✅ Headache / Stroke / Meningitis / Seizure / MG Flashcards

Question

Non-polio Enteroviral infection

Answer 1

Echoviruses and coxsackieviruses. **Hx:** Fever, severe headache, stiff neck, photophobia, drowsiness or confusion, nausea, vomiting. Most cases occur in the summer and early fall. Children are most often affected. Most frequently identified cause of aseptic meningitis. **Dx:** PCR for enterovirus is available.

Answer 2

St. Louis encephalitis virus, California encephalitis virus, West Nile virus, and eastern equine are most common. **Hx:** Most often presents as encephalitis but can present as meningitis or meningoencephalitis. Seen in patients living in or traveling to areas of arboviral activity or epidemic. Most cases occur in warmer months and when contact with mosquito vectors is most likely.

Answer 3

Herpes viruses (eg, herpes simplex, varicella, Epstein-Barr) most commonly cause encephalitis in immunocompetent adults. HSV-1 most often presents as **temporal lobe encephalitis**; HSV-2 causes **_aseptic meningitis_**. HSV meningitis is often associated with primary genital infection. **Hx:** Patients typically present with fever, altered mental status, agitation, headaches, and seizures that can rapidly progress to complete **Clinical signs** of meningeal irritation (eg, photophobia, nuchal rigidity) are usually absent in patients with pure encephalitis. unresponsiveness or coma. **Px:** can show neurologic abnormalities, including hemiparesis, cranial nerve palsies, and exaggerated deep-tendon reflexes. **Dx:** Lumbar puncture usually shows cerebrospinal fluid (CSF) findings of elevated white blood cell count **(50-1000/µL)** with lymphocytic predominance, normal glucose **(\>45 mg/dL),** and normal to slightly elevated protein concentration **\<200 mg/dL (generally 100 mg/dL)**. Most patients have an increased red blood cell count as well. Diagnosis is usually confirmed by detecting viral DNA by **polymerase chain reaction (PCR)** in the CSF. **MRI:** Usually involves (hemorrhage of) the medial temporal and inferior frontal lobes. **Tx:** HSV meningitis is often self-limiting and does not require antiviral treatment. HSV encephalitis does require antiviral treatment. Empiric treatment with intravenous **acyclovir** should be started while awaiting PCR results as encephalitis is often associated with significant morbidity and mortality.

Answer 4

**Hx:** immunosuppression or exposure history HIV-associated aseptic meningitis generally follows a mononucleosis-like syndrome. Most commonly seen in acute HIV infection. Viral load should be obtained to exclude acute HIV. Always a consideration in young adults and patients with high-risk behaviors.

Answer 5

**Hx:** Cryptococcal meningitis is usually a subacute meningitis, and patients commonly present after weeks of symptoms. It is most commonly seen in immunocompromised patients (eg, those with HIV). Symptoms are due to increased intracranial pressures (headache) from capsular swelling; almost all patients have markedly elevated opening pressure on spinal tap. **Tx:** Intravenous amphotericin (plus flucytosine) is used for induction therapy

Answer 6

**Hypocalcemia** (4.3 to 9.2 mg/dL), **hyponatremia** (sodium levels less than 120 mEq/L), **hypoglycemia** (glucose levels of 20 to 30 mg/dL), Hepatic encephalopathy. **Drug overdose:** Generalized tonic-clonic seizures are most common, but focal or multifocal partial seizures can also occur. The drugs most frequently associated with seizures are antidepressants, antipsychotics, cocaine, insulin, isoniazid, lidocaine, and methylxanthines. **Drug Withdrawl:** especially withdrawal from **ethanol** or sedative drugs, may be accompanied by one or more generalized tonic–clonic seizures that usually resolve spontaneously. **Dx:** Basic laboratory tests typically include serum electrolytes, glucose, calcium, magnesium, complete blood count, renal function tests, liver function tests, and a **toxicology screen**. In addition to laboratory screening, ECG should be obtained in patients with loss of consciousness to evaluate for possible underlying arrhythmia. Once metabolic and toxic etiologies are excluded as the cause of seizure, most patients require neuroimaging (eg, brain **MRI or CT** scan) to evaluate for structural brain abnormalities (eg, tumor, stroke, mesial temporal sclerosis) that may serve as a seizure focus. **Lumbar puncture** can be considered after neuroimaging has ruled out a space-occupying lesion, but it is typically reserved for patients with suspected meningitis (eg, fever, headache, nuchal rigidity). **Global cerebral ischemia** from cardiac arrest, cardiac arrhythmias, or hypotension. Global ischemia may also be associated with spontaneous myoclonus, Movement Disorders) or, after consciousness returns, with myoclonus recipitated by movement (action myoclonus). **Hypertensive encephalopathy** may be accompanied by generalized tonic– clonic or partial seizures. **Eclampsia** refers to the occurrence of seizures or coma in a pregnant woman with hypertension, proteinuria, and edema (preeclampsia).

Answer 7

**"Simple" Partial Seizures** begin with motor, sensory, or autonomic phenomena, depending on the cortical region affected. For example, clonic movements of a single muscle group in the face, a limb, or the pharynx may occur and may be self-limited; they may be recurrent or continuous or may spread to involve contiguous regions of the motor cortex *(Jacksonian march).* During simple partial seizures, **consciousness is preserved** unless and until the seizure discharge spreads to other areas of the brain, producing tonic–clonic seizures (secondary generalization). The aura is the portion of the seizure that precedes loss of consciousness and of which the patient retains some memory. In the postictal state, a focal neurologic deficit such as hemiparesis **(Todd paralysis)** may persist for 30 minutes to 36 hours and indicates an underlying focal brain lesion. **"Complex" Partial Seizures**, formerly called temporal lobe or psychomotor seizures and sometimes now referred to as **focal seizures with dyscognitive features**, are partial seizures in which **consciousness, responsiveness, or memory is impaired**. Episodes may begin with an aura. Epigastric sensations are most common, but affective (fear), psychic *(déjà vu)*, and sensory👄 👃🏾olfactory hallucinations) symptoms also occur. Consciousness is then impaired. Seizures generally persist for 1 to 3 minutes. The motor manifestations of complex partial seizures are characterized by coordinated involuntary motor activity, termed automatism, which takes the form of orobuccolingual movements in approximately 75% of patients and other facial or neck or hand movements in approximately 50%. Sitting up or standing, fumbling with objects, and bilateral limb movements are less common. Secondary generalization of the seizure may occur. Usually (90% of the time) originate in the temporal lobe. Auras that consist of unpleasant odors often originate in the uncus, an area at the tip of the temporal lobe that is involved in processing olfactory sensations. In the past, such seizures were called uncinate fits. **Tx:** Phenytoin, carbamazepine, oxcarbazepine, levetiraceatam, topiramate, zonisamide, sodium valproate and **_lamotrigine_** are appropriate drugs of first choice.

Answer 8

**Generalized Tonic–Clonic (Grand mal) Seizures:** are characterized by stiffening of the trunk and extremities followed by generalized symmetric jerking. **Consciousness is lost**, usually **WITHOUT aura** or other warning. **Tonic phase** —The initial manifestations are unconsciousness and tonic contraction of limb muscles for 10 to 30 seconds, producing first flexion and then extension, particularly of the back and neck. **Clonic phase** —The tonic phase is followed by a clonic (alternating muscle contraction and relaxation) phase of symmetric limb jerking that persists for an additional 30 to 60 seconds or longer. Ventilatory efforts return immediately after cessation of the tonic phase, and cyanosis clears. The mouth may **froth** with saliva. With time, the jerking becomes less frequent, until finally all movements cease and the muscles are flaccid. Sphincteric relaxation or detrusor muscle contraction may produce **urinary incontinence.** **Recovery** —As the patient regains consciousness, there is postictal confusion and often headache. Full orientation commonly takes 10 to 30 minutes or even longer in patients with status epilepticus After a generalized tonic-clonic seizure, 🍼 prolactin levels increase dramatically. **Cx: Status epilepticus** —Status epilepticus is defined arbitrarily by seizure continuing for 5 to 30 minutes without ceasing spontaneously or that recur so frequently that full consciousness is not restored between successive episodes. **Absence (Petit Mal) Seizures** are genetically transmitted seizures that always begin in childhood and rarely persist into adolescence. The spells are characterized by brief loss of consciousness (for 5-10 seconds) **without loss of postural tone.** Subtle motor manifestations, such as **eye blinking** or a **slight head turning,** are common. **Full orientation is present immediately after seizure cessation**. The spells are characteristically inducible by hyperventilation. The EEG pattern during a seizure is that of **3-Hz spike-wave activity.** **Myoclonic seizures** are characterized by sudden, **brief, shocklike contractions that may be localized to a few muscles** or one or more extremities or may have a more generalized distribution causing falls. Juvenile myoclonic epilepsy is the most common cause, with onset usually in adolescence. No loss of awareness. * *Other Types of Generalized Seizures** include tonic seizures (not followed by a clonic phase) , clonic seizures (not preceded by a tonic phase). **Atonic seizures** result from loss of postural tone, sometimes after a myoclonic jerk, leading to a fall or drop attack. They are most common in developmental disorders such as the Lennox-Gastaut syndrome. **Dx:** MRI and electrophysiologic studies are performed to identify the epileptogenic zone within the brain. Two convulsions with an EEG After a single generalized tonic–clonic seizure, recurrence of one or more seizures can be expected within 3 to 4 years in 30% to 70% of untreated adult patients (see later section on prognosis). **Tx:** Anticonvulsant medication **Lamotrigine** would likely be effective for prevention of primary generalized seizures. At this time, it *appears to have a lower incidence of inducing birth defects than other anticonvulsants.* Frequency of cognitive side effects is low. The patient has infrequent seizures so the gradual titration required for lamotrigine to decrease the risk of rash is unlikely to be a problem. **Valproic acid** is effective for all types of primary generalized seizures, but is not recommended as the initial treatment in women of childbearing age because of its potential teratogenicity. **Phenytoin** may be effective for primary generalized seizures but also has long-term side effects especially in young people and is also associated with increased risk of birth defects. **Topiramate** would likely be effective for this seizure type but may cause cognitive side effects. The incidence of teratogenic side effects of topiramate is uncertain at this time. Absence attacks of the petit mal variety are treated with **sodium valproate** or **ethosuximide.** Patients with complex partial seizures arising from a single temporal lobe are the most frequent surgical candidates; unilateral **anterior temporal lobectomy** abolishes seizures and auras in approximately 50% of these patients and significantly reduces their frequency in another 25%.

Answer 9

Generalized convulsive status epilepticus (GCSE) is defined as a seizure lasting ≥5 minutes or as ≥2 seizure events in which the patient does not completely regain consciousness (as in this patient). GCSE commonly occurs in patients with a structural brain abnormality (eg, brain tumor, stroke), metabolic abnormality (eg, hyponatremia, hypoglycemia), infection (eg, meningitis), or drug withdrawal (eg, alcohol, benzodiazepines). It is also common in epilepsy, particularly in patients who are noncompliant with antiepileptic medications, and may be the presenting feature of the disease. Regardless of underlying etiology, GCSE requires immediate treatment as prolonged seizures are associated with neuronal injury and death. * An actively seizing patient should be stabilized (ie, evaluate airway, breathing, circulation) and undergo rapid neurologic evaluation. Intravenous access and fingerstick glucose should be obtained. * Concurrently, intravenous benzodiazepines (eg, lorazepam, diazepam) should be administered for seizure termination; midazolam may be administered intramuscularly if intravenous access is unavailable. In addition, a nonbenzodiazepine antiepileptic medication should be administered to prevent seizure recurrence. Recommended medications include **fosphenytoin**, **phenytoin, levetiracetam, or valproic acid.** After this initial stabilization, neuroimaging (eg, brain MRI, head CT) should be performed to evaluate for any underlying structural abnormality, hemorrhage, or area of ischemia . Any patient who does not return to a normal state of consciousness after medical therapy should undergo continuous electroencephalography to rule out nonconvulsive status epilepticus

Answer 10

PNES is considered a type of **conversion disorder** as the clinical findings are inconsistent with seizures or other known neurological conditions. Although no single clinical finding can definitively diagnose PNES versus epileptic seizures, suggestive features include **forceful eye closure, side-to-side head or body movements, rapid alerting and reorienting, and memory recall of the event.** PNES events typically occur in front of witnesses, and these patients may model their behavior after a friend or relative with epilepsy. Unlike seizures, PNES is not associated with abnormal cortical activity during the episode. **Video-electroencephalogram monitoring is considered the gold standard** for diagnosis as it is more likely to capture an event and demonstrate lack of associated epileptiform activity. A **psychiatric assessment** is crucial as many patients with PNES have comorbid psychiatric disorders and/or a history of trauma.

Answer 11

**Benign febrile convulsions** occur in 2% to 5% of children aged 6 months to 5 years, usually during the first day of a febrile illness (temperature \> 100.4°F or 38°C), and in the absence of CNS infection (meningitis or encephalitis). **Idiopathic (cryptogenic) seizures** account for two-thirds of new-onset seizures in the general population. **Head Trauma** is a common cause of epilepsy, particularly when it occurs perinatally or is associated with a depressed skull fracture or intracerebral or subdural hematoma. **Stroke** affecting the cerebral cortex produces seizures in 5% to 15% of patients and can occur after thrombotic or embolic infarction or intracerebral hemorrhage. Even without rupturing, vascular malformations may be associated with seizures, presumably as a result of their irritative effects on adjacent brain tissue. **Mass Lesions** such as brain **tumors** or **abscesses** can present with seizures. Glioblastomas, astrocytomas, and meningiomas are the most common tumors seizures. A single brain ***abscess*** is usually the result of direct extension from an adjacent tissue infection (eg, otitis media, sinusitis, dental infection). The 2 most commonly isolated organisms are **viridans streptococci** and **Staphylococcus aureus.** **Meningitis or Encephalitis** Bacterial (eg, Haemophilus influenzae or tuberculous), viral (eg, herpes simplex), fungal, or parasitic (eg, cysticercosis) infections can also cause seizures. Meningitis is almost always associated with fever and meningeal signs. Encephalitis can have an insidious onset but is usually associated with altered mental status; a consideration only for new-onset seizures. CSF examination is always required if CNS infection is considered in the differential diagnosis **Develoipomental Anomalies** Cortical dysgenesis and neuronal migration disorders can predispose to epilepsy.

Answer 12

Orthostatic syncope is more common in elderly adults; in those taking vasoactive drugs, diuretics, or alcohol; and in the setting of volume depletion or autonomic failure, such as primary or idiopathic autonomic neuropathy **Hx:** Syncope occurs on assuming the upright position. May be caused by hypovolemia, drugs (α-adrenergic blockers), or disorders of the autonomic nervous system (idiopathic hypotension, Shy-Drager syndrome). Patients commonly have symptoms of dizziness, weakness, and fatigue, both before and after the event. Orthostasis volume down: **D/D/D/H (**Diarrhea, dehydration, diuresis, hemorrhage) ANS dysfunction: DM (autonomic neuropathy)/Parkinsons/Elderly (multiple system atrophy) **Px:** Orthostatic hypotension is characterized by an abnormal drop in blood pressure with standing (\>20 mm Hg systolic or 10 mm Hg diastolic) SBP decreases 20 DBP decreases 10 HR increases 10 **Dx:** IVF (ANS if not corrected)

Answer 13

**DDx: Spinal Cord Disorders (Myelopathy):** **Demyeinating:** Multiple sclerosis Guillain-Barré syndrome **Inflammatory:** Spinal epidural abscess Acute Transverse myelitis **Cervical spondylosis** **Vascular Myelopathies:** Spinal Cord Infarction (ASA) **Ddx: Disorders of Neuromuscular Transmission:** Myasthenia gravis Lambert-Eaton myasthenic syndrome Botulism **Ddx: Anterior Horn Cell Disorders:** Amyotrophic lateral sclerosis Polio **DDx: Myopathic Disorders:** Muscular dystrophies Inflammatory Myopathies Metabolic Myopathies Myotonic disorders **Ddx: Nerve Root and Plexus Lesions:** Intervertebral disk prolapse Brachial plexopathy Lumbosacral plexopathy

Answer 14

An autoimmune inflammatory demyelinating disorder of the central nervous system (CNS) that typically presents with neurologic deficits disseminated in space and time in women age 15-50. MS should be suspected in patients with \>2 distinctive episodes of **CNS dysfunction with at least some resolution that cannot be explained by a single lesion.** Symptoms occur over hours to days and then improve over weeks to months, although some may be permanent. Lymphocytes cross the blood-brain barrier and target myelin antigens in various parts of the nervous system causing inflammation, resulting in demyelination, neuroaxonal injury, and eventual neurodegeneration. **Hx:** Lesions may develop within the optic nerve, brain stem, cerebellum, or spinal cord, leading to well-recognized syndromes that include: 1. **Optic neuritis:** monocular visual loss, painful eye movements, and afferent pupillary defect 2. **Transverse myelitis:** motor and sensory loss below the level of the lesion with bowel and bladder dysfunction. Patients initially have flaccid paralysis (spinal shock), followed by spastic paralysis with hyperreflexia. 3. **Internuclear ophthalmoplegia:** demyelination of the medial longitudinal fasciculus resulting in impaired conjugate horizontal gaze in which the affected eye (ipsilateral to the lesion) is unable to adduct and the contralateral eye abducts with nystagmus 4. **Cerebellar dysfunction:** intention tremor, ataxia, and nystagmus **"Relapsing-remitting:** Recurrent episodes of variable frequency and severity, and may present with changes in sensation, muscle weakness, or visual problems. Over time, episodes may become more frequent and severe and encompass additional symptoms such as pain and bladder difficulties; while memory is often intact, lability in mood may be seen. **"Secondary progressive** Steady accumulation of disability with minimal recovery. A small percentage of patients will have a progressive course from the time of onset of disease. **Dx:** **MRI** is used both for initial diagnosis and to monitor progression of disease. MRI shows bright signal changes/plaques. The **McDonald criteria** (lesions separated in time and location) (eg, **trigeminal neuralgia💠,** spastic lower limb paralysis, left upper limb sensory loss) provide objective clinical and MRI findings needed to establish the diagnosis. **CSF** (in situations in which the diagnosis is **inconclusive** based on clinical presentation and neuroimaging studies)[most patients do not need LP]: changes of chronic inflammation: elevated protein, **mild lymphocytic pleocytosis** (the glucose is normal) and frequently **oligoclonal** **IgG bands (70%)** on gel electrophoresis. **Electrophysiologic studies** that measure the speed of neuronal conduction, such as visual evoked potentials, somatosensory evoked potentials, or brainstem auditory evoked responses, can provide indirect evidence of white matter lesions not evident on imaging. **Tx:** **High-dose 🌑glucocorticoids** are typically used to treat severe **acute exacerbations.** While there is no definitive cure for the underlying disease. **Plasma exchange** is indicated in those who do not respond to glucocorticoids. Other immunomodulators (eg, interferon beta, natalizumab, glatiramer) can be used for long-term disease suppression. **Disease-modifying immunomodulatory agents** reduce the relapse rate, slow disability progression, help lessen the severity of exacerbations, and improve quality of life. Disease-modifying agents include **interferon, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, and natalizumab.** Although there is no clear consensus on the use of these medications, the ***interferon-beta*** preparations (beta-1a and beta-1b) are usually considered 🥇 **first-line therapy for relapsing-remitting MS.** 💪🏽 **Refractory disease:** The addition of **other immunosuppressive agents** such as **glucocorticoids, cyclophosphamide, mitoxantrone, methotrexate, or azathioprine** may be appropriate. **Cx:** **Neurological deficits** related to an acute demyelinating plaque of MS usually last for days to weeks; in contrast, transient symptoms lasting for \<24 hours in a patient with multiple vascular risk factors (eg, hypertension, hyperlipidemia, tobacco use) are much more suggestive of TIA. **Depression** has been found in up to two-thirds of patients with MS and is the most common psychiatric complication. Depression can occur at any time and is likely caused by a combination of factors, including inflammatory changes in the brain, immune system changes, and psychological reactions to neurological deficits and the challenges of living with MS. Depression in MS is commonly underdiagnosed and undertreated. Appropriate treatment, including psychotherapy and antidepressants, can alleviate suffering and improve quality of life.

Answer 15

Epidemiology * Women: 2nd to 3rd decade * Men: 6th to 8th decade Symptoms/signs * Fluctuating & **fatigable proximal muscle weakness** that is worse later in the day * **👀 Ocular (eg, diplopia, ptosis)** * **Bulbar (eg, dysphagia, dysarthria)** * **Respiratory muscles** (myasthenic crisis) Patients typically have fluctuating, fatigable muscle weakness that worsens with repetitive motions of the same muscle groups and improves with rest. **Ocular symptoms** of binocular **diplopia and ptosis** are highly characteristic of myasthenia gravis, the latter of which may worsen with sustained upward gaze on examination. **Bulbar dysfunction** is also common and may result in dysarthria, dysphagia, and fatigable chewing. Proximal muscle involvement (eg, hip flexors, quadriceps, deltoids) can cause difficulty climbing stairs or blow-drying hair. Respiratory muscle weakness is a life-threatening complication that may lead to respiratory failure (ie, myasthenic crisis). The neurologic examination in patients with myasthenia gravis typically shows normal reflexes, sensation, coordination, and pupillary responses. Causes of exacerbations * Medications * Antibiotics: Fluoroquinolones, aminoglycosides * **Anesthetics**: Neuromuscular blocking agents * Cardiac medications: Beta blockers, procainamide * Other: **Magnesium** sulfate, penicillamine * Tapering of immunosuppressive medications * Pregnancy/childbirth * **Surgery** (especially thymectomy) * **Infection** Diagnosis * Bedside: Edrophonium (Tensilon) test, ice pack test * **Acetylcholine receptor antibodies (highly specific)** * **CT scan of chest to evaluate for thymoma** Treatment * Acetylcholinesterase inhibitors (eg, pyridostigmine) * ± Immunotherapy (eg, corticosteroids, azathioprine) * Thymectomy Myasthenia gravis is a NMJ disorder caused by autoantibodies against acetylcholine receptors in the motor end plate. Patients typically have **fluctuating and fatigable extraocular (eg, diplopia, ptosis) and bulbar (eg, dysarthria, dysphagia) muscle weakness**. They may also experience symmetric proximal **weakness involving the neck (eg, difficulty holding up the head) and upper extremities (eg, difficulty 💈 combing hair)**. Sensation, reflexes, muscle bulk/tone, and autonomic function are usually intact. Weakness can be exacerbated by various factors, including medications (eg, aminoglycosides, magnesium, beta blockers, neuromuscular blocking agents), **surgery** (particularly thymectomy), pregnancy, or **infections**. Weakness that **worsens with activity** and involves **facial and distal limb muscles in addition to proximal muscles.** IgG antibodies against AChR block neuromuscular transmission; thymus may be site of abnormal antibody production; caused by variable block of neuromuscular transmission related to an immune-mediated decrease in the number of functioning nicotinic acetylcholine receptors. **Px:** Diplopia, ptosis; slurred speech; difficulty swallowing. The diagnosis of MG can be supported with the bedside **ice pack test**, in which an ice pack is applied over the eyelids for several minutes, leading to an improvement in ptosis. **Dx:** The most commonly used pharmacologic test for patients with obvious ptosis or ophthalmoparesis is the **edrophonium (Tensilon) test.** Edrophonium is given intravenously in a dose of 10 mg (1 mL), of which 2 mg is given initially as a test dose and the remaining 8 mg approximately 30 seconds later if the test dose is well tolerated. In myasthenic patients, there is an obvious improvement in the strength of weak muscles that lasts for approximately 5 minutes. Patients with established myasthenia gravis should receive **chest imaging** (eg, **CT scan or MRI**) to evaluate for **thymoma** as thymectomy can lead to long-term improvement. Individuals with typical clinical features of myasthenia gravis should undergo confirmatory immunologic testing for **acetycholine receptor antibodies (highly specific).** Those with negative acetycholine receptor antibodies should subsequently be checked for muscle-specific tyrosine kinase antibodies. If the diagnosis remains unclear, electrophysiologic studies (eg, repetitive nerve stimulation, single-fiber electromyography) may be helpful. Impaired neuromuscular transmission can be detected electrophysiologically by a decremental response of muscle to repetitive supramaximal stimulation (at 2 or 3 Hz) of its motor nerve, but normal findings do not exclude the diagnosis. **Tx:** Anticholinesterase Drugs ***Myasthenic crisis*** is a life-threatening complication characterized by severe respiratory muscle weakness leading to **respiratory failure** (eg, accessory muscle use, hypoxemia, respiratory acidosis). Patients often have increasing generalized or bulbar weakness prior to the onset of crisis. The condition may be precipitated by infection (eg, urinary tract infection), surgery, pregnancy, or medications (eg, aminoglycosides, fluoroquinolones, macrolides, beta blockers). Patients with severe exacerbations and declining respiratory status should be monitored in the intensive care unit and **intubated** for airway protection.

Answer 16

L?ambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular disorder caused by **autoantibodies against voltage-gated calcium channels** in the presynaptic motor nerve terminal that leads to decreased acetylcholine release and subsequent weakness. Approximately 50% of cases are associated with an **underlying malignancy**, mostly **small cell lung cancer.** This patient's long smoking history and recent presentation with cough, weakness, low BMI, and a lung mass on chest CT scan are concerning for malignancy. **Hx:** Patients initially have progressive **symmetric proximal limb muscle weakness (eg, standing from a chair, combing hair, putting dishes in overhead cabinets).** Deep tendon reflexes are reduced/absent, although vigorous muscle activity can improve reflexes and muscle strength temporarily. Autonomic dysfunction (eg, dry mouth, erectile dysfunction) is also common. **Px: Proximal** muscle weakness; decreased DTRs; autonomic dysfunction. Unlike myasthenia gravis, the extraocular muscles are spared, and power steadily increases if a contraction is maintained. **Dx:** The diagnosis is confirmed electrophysiologically by the incremental response to repetitive nerve stimulation. The size of the muscle response increases remarkably to stimulation of its motor nerve at high rates—even in muscles not clinically weak. **Tx:** Immunosuppressive drug therapy (corticosteroids, mycophenolate, and azathioprine as described for myasthenia gravis) and plasmapheresis or intravenous immunoglobulin therapy may lead to symptomatic improvement. Symptomatic therapy includes **guanidine or 3,4-diaminopyridine** to increase presynaptic acetylcholine levels. Refractory symptoms may respond to immunologic therapy with intravenous immunoglobulin or oral immunosuppressants (eg, corticosteroids, azathioprine).

Answer 17

Pathophysiology * Immune-mediated demyelinating polyneuropathy * **Preceding gastrointestinal (Campylobacter) OR respiratory infection** Clinical features * Paresthesia, neuropathic pain * Symmetric, ascending weakness * **Decreased/absent deep-tendon reflexes** * Autonomic dysfunction (eg, arrhythmia, ileus) * Respiratory compromise Diagnosis * Clinical * Supportive findings * Cerebrospinal fluid: **↑ protein, normal leukocytes** * **Abnormal electromyography & nerve conduction** Management * Monitor autonomic & respiratory function * Intravenous immunoglobulin or plasmapheresis Bacterial or viral infection induces autoantibodies to motor nerves with resulting demyelination and neuropathy **Dx:** Weakness and paresthesias; ascending pattern; respiratory muscle fatigue; autonomic dysfunction; decreased DTRs Nerve conduction studies show acute peripheral polyneuropathy; **Cerebral spinal fluid (CSF) analysis** shows a **high protein** concentration with normal white blood cell (WBC) counts **(albuminocytologic dissociation)**. The CSF protein level may be elevated due to increased permeability of the blood-nerve-barrier. CSF red blood cell (RBC) and glucose levels should be normal. **Tx:** Gold standard treatment includes **intravenous immunoglobulin (IVIG)** or **plasmapheresis**. Patients should be monitored closely due to risk of respiratory failure. Most patients take several months to recover. **Cx: Neuromuscular respiratory failure** is a life-threatening complication found in up to 30% of patients. Once GBS is suspected in a hemodynamically stable patient, the next step in management is to assess pulmonary function with **spirometry**. Forced vital capacity (FVC) and negative inspiratory force monitor respiratory muscle strength, and serial pulmonary function testing should be performed **given the potential for rapid progression of disease.** **Cx: A decline in FVC (≤20 mL/kg) indicates impending respiratory failure warranting endotracheal intubation.** Additional indications for elective or emergency intubation include respiratory distress (eg, tachypnea, accessory muscle use), severe dysautonomia (eg, heart rate and blood pressure instability), or widened pulse pressure **Tx: Mechanical ventilation** is required in approximately 30% of patients who have GBS, as it can cause sudden hypercarbic respiratory failure.

Answer 18

Motor neuron disease in adults generally begins between the ages of 30 and 60 years and has an annual incidence of approximately 2 per 100,000, with a male predominance, except in familial cases. Toxic neuromodulators lead to degeneration of neurons at all levels of motor system **Dx:** Extremity weakness/**atrophy**; Bulbar (difficulty in swallowing, chewing, coughing, breathing, speaking (dysarthria) and dysphagia; **hyperreflexia; foot drop;** muscle fasciculations; respiratory failure/aspiration in 3-5 years EMG reveals acute denervation in 2 or more extremities **Tx: Riluzole** is a glutamate inhibitor that is currently approved for use in patients with amyotrophic lateral sclerosis. Although it cannot arrest the underlying pathological process, it may prolong survival and the time to tracheostomy. Its side effects are dizziness, nausea, weight loss, elevated liver enzymes and skeletal weakness.

Answer 19

**Hypokalemia:** Proximal myopathic weakness may result from chronic hypokalemia, and once the metabolic disturbance has been corrected, power usually returns to normal within a few weeks. **Periodic Paralyses:** In the **hypokalemic** form, sometimes associated with **thyrotoxicosis**, attacks tend to occur on awakening, after exercise, or after a **heavy meal,** alcohol consumption, or exposure to cold, and may last for several days. **Acetazolamide** (250-750 mg daily) or oral potassium supplements may prevent attacks, as also may a low salt and low carbohydrate diet. Attacks associated with **hyperkalemia** also tend to come on after exercise but are usually much briefer, lasting less than 1 hour. Severe attacks may be terminated by intravenous calcium gluconate (1-2 g), intravenous diuretics (furosemide 20-40 mg), or glucose, and daily acetazolamide or chlorothiazide may help prevent further episodes. **Normokalemic**: This disorder is similar clinically to the hyperkalemic variety, but the plasma potassium level is normal in attacks; treatment is with acetazolamide.

Answer 20

Sudden acute loss of motor, sensory, **autonomic**, reflex, and sphincter function below the level of the lesion. This syndrome results from a variety of infectious (bacterial, viral, fungal, parasitic) and noninfectious inflammatory disorders (**multiple sclerosis**, neuromyelitis optica, **acute disseminated encephalomyelitis**, systemic autoimmune diseases, idiopathic) that produce anatomic and functional disruption of the spinal cord. **Hx:** It manifests with weakness and various sensory disturbances below the level of the lesion. **Dx:** An inflammatory CSF profile (pleocytosis; an accompanying low CSF glucose suggests an infective cause); and an MRI showing an intrinsic spinal cord lesion that usually enhances with gadolinium administration. Characteristic **periventricular white matter changes** on T2-weighted images, and the CSF changes with oligoclonal bands, are typical of MS. **Tx:** Treatment is with corticosteroids, typically methylprednisolone (1 g intravenously daily for 3-5 days), although their benefit has not been rigorously established.

Answer 21

Peripheral neuropathy may relate to metabolic disorders such as diabetes mellitus, uremia, liver disease, myxedema, acromegaly, metachromatic leukodystrophy, or Fabry disease. That caused by diabetes is especially important and may take the form of an entrapment mononeuropathy, acute ischemic mononeuropathy, distal sensorimotor polyneuropathy, subacute proximal motor polyradiculoplexopathy (diabetic amyotrophy), thoracoabdominal radiculopathy, or autonomic neuropathy. **Diabetic Neuropathy:** Primarily axonal, symmetric sensory polyneuropathy that may have only minimal findings (such as a mild reduction in sensory nerve action potentials on nerve conduction testing) early in the course of the disease. Diabetic neuropathy typically **initially affects the distal lower extremities due to the length of these nerve fibers.** Over time, the sensory loss **ascends**, with symptoms appearing in the hands when the lower extremity sensory loss reaches the mid-calf level; this is termed the **“stocking-glove” pattern**. Motor involvement follows the same pattern, but occurs only in severe cases after sensory changes are present. Almost 20% of patients have some evidence of nerve dysfunction when their diabetes is diagnosed, indicating that nerve damage can occur before true diabetes is present, such as with impaired fasting glucose. **Diabetic lumbosacral radiculoneuropathy (diabetic amyotrophy):** Pain in proximal leg (severe) followed by weakness, with or without sensory loss (proximal), and with or without weight loss.

Answer 22

Diabetes mellitus is the most common cause of peripheral neuropathy, with the risk related to the duration of the disease and glycemic status. Neuronal injury in diabetes is due to a number of factors, including microvascular injury, demyelination, oxidative stress, and deposition of glycation end products. The use of metformin, which decreases intestinal absorption of vitamin B12, can also contribute. This leads to a length-dependent axonopathy, with clinical features occurring first in the longest nerves (eg, feet). Symmetric distal sensorimotor polyneuropathy is the most common neuropathy in patients with diabetes; the clinical features depend on the type of nerve fibers involved. * **Small fiber injury** is characterized by the predominance of positive symptoms (eg, **pain, paresthesia, allodynia**). * ****_L_**arge fiber involvement** is characterized by the predominance of negative symptoms (eg, **numbness, **_L_**oss of proprioception and vibration sense, diminished ankle reflexes**).

Answer 23

In patients with a lesion of a single peripheral nerve, sensory loss is usually less than predicted on anatomic grounds because of overlap from adjacent nerves. Compressive lesions, for example, tend to affect preferentially the large fibers subserving touch. **Hx:** Sensory loss with or without pain at onset, weakness in distribution of single nerve (such as the median or a cranial nerve). Mononeuropathy of acute onset is likely to be traumatic or ischemic in origin, whereas one evolving gradually is more likely to relate to entrapment (ie, compression by neighboring anatomic structures) or to recurrent minor trauma.

Answer 24

A peripheral neuropathy involving cranial nerve (CN) VII (facial nerve). Characteristic features include unilateral mouth drooping, **disappearance of the nasolabial fold**, and, importantly, **involvement of the _upper face_ (eg, weakness in closing the eye or raising the eyebrow).** Upper face involvement distinguishes Bell palsy from upper motor neuron disorders (eg, stroke), which spare the upper face. Other common symptoms of Bell palsy include decreased ipsilateral eye lacrimation, hyperacusis, and decreased sensation of taste over the anterior two-thirds of the ipsilateral tongue. The weakness typically develops acutely over a course of hours; however, it often occurs at night, and patients may awaken with significant facial droop. Symptoms typically progress over 2-3 weeks, with gradual improvement over the following 3-6 months. Bell palsy is thought to be due to reactivation of a neurotrophic virus, most commonly **herpes simplex virus.** Viral infection causes inflammation and edema of the facial nerve, resulting in nerve compression and degeneration of the myelin sheath. Treatment involves glucocorticoids 🌑 prednisone, 40 mg/d, preferably administered within the first 72 hours; because of the association with herpes simplex virus, some experts also recommend the addition of **valacyclovir.**

Answer 25

**Trauma:** Lifting heavy objects without adequate bracing of the spine can cause musculoskeletal pain that improves with rest. Clinical examination commonly reveals spasm of the lumbar muscles and restricted spinal movement. Management includes local heat, bed rest on a firm mattress, nonsteroidal antiinflammatory drugs or other analgesics, and musclerelaxant drugs. **Dx:** Vertebral fractures that follow more severe injury and lead to local pain and tenderness can be visualized at radiography. If spinal cord involvement is suspected—for example, because of leg weakness after injury—the patient must be immobilized until imaged to determine whether fracture dislocation of the vertebral column has occurred. **Lumbosacral radiculopathy (sciatica)⚡**, most likely due to nerve root compression by a **prolapsed Interverterbal Disk:** Protruded disk material may press on one or more nerve roots and thus produce radicular pain, a segmental motor or sensory deficit, or a sphincter disturbance in addition to a painful stiff back. The pain may be reproduced by percussion over the spine or **sciatic nerve**, by passive straight leg raising, or by extension of the knee while the hip is flexed. There is local tenderness, and **Lasègue sign** (reproduction of the patient’s pain on stretching the sciatic nerve by straight leg raising) is positive. **Tx:** Symptoms often resolve with simple analgesics, 🧯 **Nonsteroidal anti-inflammatory drugs and acetaminophen** are the preferred first-line drugs, diazepam, and bed rest on a firm mattress for 2 to 3 days, followed by gradual mobilization. Persisting pain, an increasing neurologic deficit, signs of cauda equina syndrome (eg, saddle anesthesia), or concern for epidural abscess (eg, fever, intravenous drug abuse).or any evidence of sphincter dysfunction should lead to **MRI, CT** scanning, or **CT myelography**, and surgical treatment if indicated by the results of these procedures. **Lumbar osteoarthropathy:** This tends to occur in later life and may cause low back pain that is increased by activity. **MRI** is the preferred mode of imaging. Many asymptomatic elderly subjects have degenerative changes of the lumbar spine. In patients with mild symptoms, a surgical corset is helpful, whereas in more severe cases operative treatment may be necessary. Even minor changes may cause root or cord dysfunction in patients with a congenitally narrowed spinal canal (spinal stenosis), leading to the syndrome of intermittent claudication of the spinal cord or cauda equina. Similar symptoms may result from ossification of the ligamentum flavum, epidural lipomatosis, Pott disease, osteomyelitis, rheumatoid arthritis, or post-traumatic stenosis of the spinal canal. The syndrome is characterized by pain, sometimes accompanied by weakness or radicular sensory disturbances in the legs, that occurs with activity or with certain postures and is relieved by rest. Patients with mild to moderate symptoms related to spinal stenosis should be treated conservatively with pain medication, nonsteroidal anti-inflammatory agents, and physical therapy to reduce the lumbar lordosis. Bed rest is to be avoided. If symptoms are severe, decompressive surgery is indicated when conservative treatment for 3 to 6 months has been unhelpful or there is a significant motor deficit or symptoms of cauda equina syndrome (compression of lumbosacral nerve roots in the spinal canal, below the end of the spinal cord [conus medullaris]). **Ankylosing Spondylitis:** Backache and stiffness, followed by progressive limitation of movement, characterize this disorder, which occurs predominantly in young men. Characteristic early radiologic findings consist of sclerosis and narrowing of the sacroiliac joints. Treatment is with nonsteroidal antiinflammatory agents, especially indomethacin or aspirin. Physical therapy, including postural exercises, is also important. **Neoplasm:** Extradural malignant tumors are an important cause of back pain and should be suspected if there is persistent pain that worsens despite bed rest. Neoplastic disease can also lead to a nonmetastatic (paraneoplastic) sensory or sensorimotor polyneuropathy or to Lambert-Eaton syndrome. **Infection:** Tuberculous and pyogenic infections of the vertebrae or intervertebral disks can cause progressive low back pain and local tenderness. Although there are sometimes no systemic signs of infection, the peripheral white cell count and erythrocyte sedimentation rate are elevated; osteomyelitis; **Osteoporosis:** Low back pain is a common complaint in patients with osteoporosis, and vertebral fractures may occur spontaneously or after trivial trauma. Pain may be helped by a brace to support the back. It is important that patients keep active, stop tobacco smoking, and take a diet containing adequate amounts of calories, calcium, vitamin D, and protein. Estrogen therapy may be helpful in postmenopausal women, but is less widely used than previously. The bisphosphonates alendronate and risedronate may be helpful and have reduced the incidence of fractures. **Pagets Dz:** Paget disease, which is characterized by excessive bone destruction and repair, is of unknown cause but may have a familial basis. The serum calcium and phosphorus levels are normal, but the alkaline phosphatase is markedly increased. **Congenital:** Minor spinal anomalies can cause pain because of altered mechanics or alignment or because reduction in the size of the spinal canal renders the cord or roots more liable to compression by degenerative or other changes. **Referred:** Disease of the hip joints may cause pain in the back and thighs that is enhanced by activity; examination reveals limitation of movement at the joint with a positive Patrick sign (hip pain on external rotation of the hip), and radiographs show degenerative changes. Aortic aneurysms, cardiac ischemia, visceral and genitourinary disease (especially pelvic disorders in women), and retroperitoneal masses can also cause back pain. **Nonspecific Chronic Back Pain:** Nonsteroidal anti-inflammatory drugs may provide short-term symptomatic relief. There is some controversy about the chronic use of narcotic analgesics in patients with persisting low back pain, but such agents are generally best avoided. Treatment with tricyclic antidepressant drugs is sometimes helpful, and psychiatric evaluation may be worthwhile. Bedrest is not recommended and provides no greater benefit than symptom-limited activity.

Answer 26

Radiculopathies are distinguished from peripheral neuropathies by the distribution of **motor or sensory deficits**. The presence of neck or back pain that radiates to the extremities in a radicular distribution also suggests a root lesion. Radicular pain is caused most commonly by mechanical **root compression from disk protrusion, spinal stenosis, or congenital anomalies.** **Hx:** The pain is localized to the distribution of one or more nerve roots and is often exacerbated by coughing, sneezing, and other maneuvers that cause increased intraspinal pressure. It is also exacerbated by maneuvers that stretch the affected roots. Sensory loss or pain, thoracic levels often affected, weakness in distribution of nerve roots. **Px:** Passive straight-leg raising leads to stretching of the sacral and lower lumbar roots, as does passive flexion of the neck, or extension and lateral flexion of the head to the affected side. **Tx:** Useful modes of treatment for mechanical causes include immobilization, nonsteroidal anti-inflammatory drugs or other analgesics, and surgical decompression. **Epidural steroid injections** may be helpful in radicular pain, but are not recommended in uncomplicated back pain or as initial treatment in acute radicular pain.

Answer 27

Most cases arise in older individuals when physical activity such as shoveling snow, golf, or diving from a board puts stress on the neck and results in acute cervical disc herniation or nerve root compression from underlying cervical spondylosis. Cervical spondylosis is marked by cervical spine degeneration. It is generally associated with 2 clinical syndromes: * **Cervical radiculopathy:** Degeneration and **osteophyte (CRX?)** formation in the zygapophyseal (facet) and uncovertebral joints lead to intervertebral foramen narrowing and compressive nerve root symptoms. Most patients have progressive **neck, shoulder, and/or arm pain plus weakness in a myotome (eg, axillary nerve) and sensory loss in a dermatome (eg, lateral cutaneous nerve of the arm).** * **Compressive cervical myelopathy:** Degeneration and thickening of the lateral vertebral bodies and posterior longitudinal ligament lead to spinal canal narrowing and subsequent spinal cord compression. This usually presents with neck pain, lower motor neuron signs in the upper extremities, upper motor neuron signs (eg, increased reflexes, increased tone, positive Babinski sign) in the lower extremities, and bowel/bladder dysfunction. Evaluation usually begins with **MRI of the cervical spine** to visualize anatomy; myelography is also generally required for those with symptoms of compressive myelopathy.

Answer 28

Cervical spondylosis results from chronic cervical disk degeneration, with herniation of disk material, secondary calcification, and associated osteophytic outgrowths. * **Spurling sign** (increased radicular pain by extension and lateral bending of the neck toward the side of the lesion) * **L'hermitte** sign (feeling of electrical shock with neck flexion) **Dx:** Plain x-rays show **osteophyte formation, narrowing of disk spaces, and encroachment on the intervertebral foramina.** **Tx:** A **cervical collar** to restrict neck movements may relieve severe pain. Pain may also respond to simple analgesics, nonsteroidal anti-inflammatory drugs, muscle relaxants, Tricyclic antidepressants (taken at night), or anticonvulsants.

Answer 29

From the pial vessels (around the circumference of the cord), radially oriented branches supply much of the white matter and the posterior horns of the gray matter. The remaining gray matter and the innermost portion of the white matter are supplied by the central artery (located in the anterior median fissure), which arises from the anterior spinal artery. The descending corticospinal tract is supplied by both the anterior and posterior spinal arteries. The acute onset of a flaccid, areflexic paraparesis is followed, as spinal shock wears off after a few days or weeks, by a spastic paraparesis with brisk tendon reflexes and extensor plantar responses. In addition, there is dissociated sensory impairment—pain and temperature appreciation are lost, but vibration and position sense are spared because the posterior columns are supplied by the posterior spinal arteries.

Answer 30

Causes * Spinal injury (eg, motor vehicle crash) * Malignancy (eg, lung, breast, prostate cancers; myeloma) * Infection (eg, epidural abscess) Signs & symptoms * Gradually worsening, severe local back pain * Pain worse in the recumbent position/at night * Early signs: Symmetric lower extremity weakness, hypoactive/absent deep-tendon reflexes * Late signs: Bilateral Babinski reflex, decreased rectal sphincter tone, paraparesis/paraplegia with increased deep-tendon reflexes, sensory loss Management * Emergency MRI * Intravenous glucocorticoids * Radiation-oncology & neurosurgery consultations Acute spinal cord compression (SCC) is characterized by injury to the following: * Descending corticospinal tracts (lower-extremity weakness and loss of rectal tone) * Ascending sensory spinothalamic tracts (the sensory level is often 2 spinal cord segments below the level of lesion) * Descending autonomics in the reticulospinal tract (urinary retention/bladder flaccidity/bladder shock) By contrast, lesions affecting the **conus medullaris** will typically cause back pain with bladder and rectal dysfunction, but weakness and sensory loss are less common. **Cauda equina** (spinal roots) syndrome may cause radicular pain, lower-extremity weakness, saddle anesthesia, and bowel/bladder dysfunction, but this typically affects the sacral roots. A sensory level at the umbilicus excludes cauda equina syndrome. SCC is most commonly caused by disk herniation, compression fractures, or malignancy. Immediate neurosurgical evaluation is warranted to avoid permanent neurologic dysfunction. Typically, neuroimaging (ie, MRI of the spine) is performed while awaiting surgical consultation. High-dose glucocorticoids are often used, especially in cases of suspected malignant compression.

Answer 31

Most cases arise when a large, central lumbar disc herniation at the L4-S1 level bulges into the lumbar cistern and compresses multiple spinal nerve roots in the cauda equina. Injury to the cauda equina, which is composed of nerve roots for L2-L5, S1-S5, and the coccygeal nerve, usually results in severe back pain radiating into one or both legs and loss of lower extremity motor strength, sensation, and reflexes in the affected dermatomes. **Saddle anesthesia** is highly suggestive of CES and reflects impingement of S2-S4 nerve roots; **bladder** (eg, urinary straining) **and rectal sphincter paralysis** can also occur due to damage to S3-S5 nerve roots. Loss of ankle reflex indicates damage to S1-S2 nerve roots. Straight leg raise testing (worsened sciatic pain when straight leg is raised to 30-70 degrees) is positive in \>90% of those with acute lumbar herniation and may aid diagnosis. Confirmation requires urgent **MRI of the lumbosacral spine**. Because patients with CES (particularly in the setting of bladder or rectal dysfunction) are at high risk for permanent neurologic sequelae, surgical decompression is then usually necessary.

Answer 32

**Polyneuropathies** associated with prominent pain include those related to diabetes, alcoholism, porphyria, Fabry disease, amyloidosis, rheumatoid arthritis, and acquired immunodeficiency syndrome (AIDS), as well as dominantly inherited sensory neuropathy and paraneoplastic sensory neuronopathy. In patients with polyneuropathies, **sensory loss is generally symmetric and is greater distally** than proximally **(stocking-and-glove sensory loss or length-dependent neuropathy).** The loss generally will have progressed almost to the knees before the hands are affected. Sensory loss may then be accompanied by a motor deficit and reflex changes. Diabetes mellitus, amyloidosis, and certain other metabolic disorders preferentially involve small nerve fibers subserving pain and temperature appreciation; in a pure small-fiber sensory neuropathy, the tendon reflexes are unaffected and no motor deficit occurs. **Distal axonopathies** (axonal neuropathies), the axon is the principal pathologic target; most polyneuropathies fall into this category. **_Myelinopathies_** (demyelinating neuropathies) are conditions that involve the myelin sheath surrounding the axon. These disorders include acute **idiopathic polyneuropathy** **(Guillain-Barré syndrome), chronic inflammatory demyelinating neuropathy,**diphtheria, certain paraneoplastic and paraproteinemic states, and various hereditary conditions including metachromatic leukodystrophy, Krabbe disease, and types 1 and 3 Charcot-Marie-Tooth hereditary motor and sensory neuropathy (CMT-1 and 3).

Answer 33

Nerve root involvement produces impaired cutaneous sensation in a **segmental pattern**, but because of overlap there is generally no sensory loss unless two or more adjacent roots are affected. There may be loss of tendon reflexes (C5- C6, biceps and brachioradialis; C7-C8, triceps; L3-L4, knee; S1, ankle), and if the anterior roots are also involved, weakness and muscle atrophy may occur.

Answer 34

Most cases arise when an older individual with a stenotic cervical spinal canal (eg, due to cervical spondylosis) experiences a hyperextension injury to the neck (eg, **whiplash** due to **rear-end collision🚗🚗**); this compresses the spinal cord between a hypertrophied ligamentum flavum posteriorly and a bulging disc/osteophyte complex anteriorly, leading to damage to the central spinal cord (grey matter). Patients primarily develop upper extremity manifestations, including: * **Weakness** due to damage to the alpha motor neuron cell bodies in the **anterior horn** of the spinal cord * ****_P_**ain, **_t_**emperature, and **_s_**ensory loss** in dermatomes at and surrounding the level of injury due to damage to the **posterior grey column** * Reflex loss (eg, tricep reflex) at the level of injury due to damage to fibers as they cross from the dorsal to ventral horn **Syringomyelia:** a disorder caused by disruption of cerebrospinal fluid drainage from the central canal, leading to formation of a fluid-filled cavity (syrinx) that compresses the surrounding tissue. The cavity can enlarge over time and destroy adjacent portions of the spinal cord. It is most commonly seen with Arnold-Chiari type 1 malformations (extension of the cerebellar tonsils into the foramen magnum) but can also occur as a sequela of meningitis, inflammatory disorders, tumors, and trauma. Syringomyelia can occur at any level but most commonly involves the cervical or thoracic spine, typically resulting in upper extremity symptoms. Destruction of the crossing fibers of the spinothalamic tract in the ventral white commissure results in progressive loss of **pain and temperature sensation** in dermatomes corresponding to the level of spinal cord involvement (sometimes called a **"cape-like" distribution**). Touch, vibration, and proprioception are preserved (ie, dissociated anesthesia) if the syrinx is small enough to affect only the ventral white commissure. However, expansion into the motor fibers in the ventral horns may result in progressive weakness and flaccid paralysis within the affected area. Over time, central pain, incontinence, and lower extremity manifestations may also develop. The diagnosis is confirmed by MRI, which shows an intramedullary cavity. Management usually requires surgical intervention (eg, shunt placement). Motor: **Central cord syndrome (CCS)** typically occurs with hyperextension injuries in elderly patients with pre-existing degenerative changes in the cervical spine. This type of **traumatic injury** 🚗causes selective damage to the central portion of the anterior spinal cord, specifically the central portions of the **corticospinal tracts** and the decussating fibers of the **lateral spinothalamic tract**. CCS is characterized by weakness that is more pronounced in the upper extremities than the lower. This unique motor deficit occurs because the motor fibers serving the arms are closer to the central part of the corticospinal tract. A patient with CCS may also have occasional selective loss of pain and temperature sensation in the arms due to damage to the spinothalamic tract.

Answer 35

This usually occurs when there is an injury to the **anterior spinal artery** (eg, disc retropulsion, fragments of bone from vertebral burst fracture) affecting the anterior two thirds of the spinal cord. Neurological findings include: * **Bilateral hemiparesis:** Lateral corticospinal tract; at the level of the cord injury and below * **Diminished bilateral 💥pain and 🌡temperature sensation:** Lateral spinothalamic tract (LST); 1-2 levels below the cord injury because LST decussates 1-2 levels before the corresponding level * **Intact bilateral proprioception, vibratory sensation, and light touch**: Dorsal columns; blood is supplied from the posterior spinal arteries, which are bilateral and reinforced by radicular segmental branches With destructive lesions involving predominantly the anterior portion of the spinal cord, **pain and temperature** appreciation are impaired below the level of the lesion from lateral spinothalamic tract involvement. In addition, weakness or paralysis of muscles supplied by the involved segments of the cord results from damage to anterior horn cells. With more extensive disease, involvement of the corticospinal tracts in the lateral funiculi may cause a pyramidal deficit below the lesion. There is relative preservation of posterior column function. **Motor:** Anterior (ventral) cord syndrome is characterized by bilateral spastic motor paresis distal to the lesion. It is usually due to occlusion of the **anterior spinal artery.**

Answer 36

A patient with a posterior column lesion may complain of a tight or bandlike sensation in the regions corresponding to the level of spinal involvement and sometimes also of paresthesias (like electric shocks) radiating down the extremities on neck flexion (Lhermitte sign). There is **loss of vibration and joint position** **("VIP")** sense below the level of the lesion, with preservation of other sensory modalities.

Answer 37

Lateral hemisection of the spinal cord leads to 🐻 **Brown-Séquard syndrome**. Below the lesion, there is an ipsilateral pyramidal deficit and disturbed appreciation of vibration and joint position sense, and **contralateral loss of pain and temperature** appreciation that begins two or three segments below the lesion. Hemisection of the cord, most often due to penetrating injury, may lead to Brown-Séquard syndrome, which is characterized by: **Ipsilateral: Weakness**, spasticity, loss of **vibration sense** and proprioception **Contralateral:** Loss of **pain** and **temperature** sensation This disorder usually occurs when there is an injury (eg, stab wound, cord compression) of a hemisection of the spinal cord. Findings include: * **Ipsilateral hemiparesis:** **Lateral corticospinal tract;** occurs at the level of the cord injury and below * **Ipsilateral diminished proprioception, vibratory sensation,** and light touch: **Dorsal columns**; occurs at the level of the cord injury and below * **🔀 Contralateral diminished pain and 🔥 temperature:** **Lateral sPinoThalamic tract (LST)**; tends to occur **1-2 levels below** the cord injury because the LST decussates (crosses over) 1-2 levels above the entry point for the corresponding sensory neuron

Answer 38

**SPinoThalamic** * With lesions involving the spinothalamic tract in the dorsolateral medulla and pons, pain and temperature appreciation are lost in the limbs and trunk on the 🔀 **OPPOSITE** side of the body. * When such a lesion is **medullary**, it also typically involves the **spinal trigeminal nucleus**, impairing **pain and temperature** sensation on the same side of the **face** as the lesion. The result is a **crossed sensory deficit** that affects the ipsilateral face and contralateral limbs. * Spinothalamic lesions above the spinal trigeminal nucleus affect the face, limbs, and trunk contralateral to the lesion. With lesions affecting the medial lemniscus, there is loss of touch and proprioception on the opposite side of the body. * In the upper brainstem, the spinothalamic tract and medial lemniscus run together so that a single lesion may cause loss of all superficial and deep sensation over the contralateral side of the body. **Midbrain** strokes typically present with ipsilateral oculomotor nerve palsy, ataxia (due to damage of the superior cerebellar peduncle), and contralateral hemiparesis (cerebral peduncle).

Answer 39

**Electromyography** may reveal evidence of denervation in the affected muscles and can be used to determine whether any motor units remain under voluntary control. Nerve conduction studies permit conduction velocity to be measured in motor and sensory fibers. In demyelinating neuropathies, electromyography typically reveals little or no evidence of denervation, but there is conduction block or marked slowing of maximal conduction velocity in affected nerves. In axonal neuropathies, electromyography shows that denervation has occurred, especially distally in the extremities, but maximal nerve conduction velocity is normal or slowed only slightly. Determination of a complete blood count, erythrocyte sedimentation rate, serum urea nitrogen and creatinine, fasting blood glucose, serum vitamin B12, serum protein, protein electrophoresis and immunoelectrophoresis, liver and thyroid function blood tests, and serologic test for syphilis (FTA or MHA-TP), rheumatoid factor, and antinuclear antibody may help to identify the cause of a peripheral nerve disorder, as also may chest x-ray.

Answer 40

**Trauma Prevention:** Nursing care is important in patients with severe motor or sensory deficits to prevent decubitus ulcers, joint contractures, and additional compressive peripheral nerve damage. In patients with severe dysesthesia, a cradle (metal bar frame) can be used to keep the bedclothes from touching sensitive areas of the skin. **Pain Relief:** Patients with sensory disorders may suffer from especially severe pain, which can impair quality of life. Treatment of this pain is important. **Duloxetine** (60 mg once daily) or venlafaxine (titrated up to 75 mg two to three times daily in standard formulation or as the equivalent dose once daily in the extended release formulation) is often helpful; both are selective serotonin and norepinephrine reuptake inhibitors. **Pregabalin** (150 mg increasing after 1 week to 300 mg daily in divided doses; maximum, 600 mg daily) also relieves neuropathic pain. **Phenytoin** 300 mg/d, carbamazepine up to 1200 mg/d, or mexiletine 600 to 900 mg/d can sometimes relieve the lancinating pain of certain neuropathies. If the pain is constant, burning, or dysesthetic, amitriptyline 25 to 100 mg at bedtime is often helpful as are other tricyclic agents. **Gabapentin** (300 mg three times daily, with subsequent increments depending on response and tolerance) is effective in treating various neuropathic pain disorders; pain relief may similarly occur with lamotrigine, topiramate, or sodium valproate, but this has been documented less well. Lamotrigine requires slow dose titration to avoid skin rashes and other complications. Combined gabapentin and nortriptyline may be more effective than either drug given alone for neuropathic pain (diabetic neuropathy or postherpetic neuralgia). This drug combination is therefore recommended in patients who show a partial response to either drug given alone and require additional pain relief. **Topical capsaicin** is also helpful in neuropathic pain syndromes.

Answer 41

Epidemiology * Age \>55 * Degenerative cervical spine/discs → canal stenosis → cord compression Manifestations * Gait dysfunction - usually first * Extremity weakness & numbness * LMN signs (arms) - muscle atrophy, hyporeflexia * UMN signs (legs) - **Babinski**, hyperreflexia * ↓ Proprioception/vibration/pain sensation * **Hoffman sign** (flexion and adduction of the **thumb** when **flicking the nail of the middle finger**) suggests a **corticospinal tract lesion** and supports the diagnosis of cervical myelopathy Diagnosis * MRI of cervical spine * CT myelogram Treatment * Nonsurgical - immobilization * Surgical decompression The most common cause of cervical myelopathy in older adults is **spondylosis**, a degenerative spine disease that can narrow the cervical spinal canal and compress the spinal cord. Patients usually develop slowly progressive gait dysfunction, extremity weakness, and vibratory/pain sensation changes. Neurologic examination typically shows lower motor neuron (LMN) signs such as weakness and atrophy at the level of the lesion (in the arms) and upper motor neuron (UMN) signs such as hyperreflexia below the level of the lesion (in the legs). This distribution of LMN and UMN signs should raise suspicion for cervical myelopathy. Spondylosis of the cervical spine is often diagnosed radiographically, and myelopathy is confirmed with MRI or CT myelogram. Patients may require surgical decompression.

Answer 42

Several diseases can affect both peripheral and central sensory pathways, Examples include **Friedreich ataxia, neurosyphilis (tabes dorsalis)** and combined systems disease from **vitamin B12 deficiency** **Friedreich ataxia** is an autosomal recessive disorder with onset in childhood (typically 13 y), is the most common cause of hereditary ataxia. It results from an expanded GAA trinucleotide repeat in a noncoding region of the FXN gene, which causes loss-of-function of a mitochondrial protein, frataxin.Hx **Hx:** initial symptom is usually progressive gait ataxia, followed by limb ataxia, dysarthria, and sensory gait ataxia. Neurologic examination shows knee and ankle areflexia, impaired joint position and vibration sense in the legs, leg (and sometimes arm) weakness, and extensor plantar responses. Pes cavus (high-arched feet with clawing of the toes caused by weakness and wasting of the intrinsic foot muscles) is often present, but can also occur in other neurologic disorders (eg, Charcot-Marie-Tooth disease). Severe progressive kyphoscoliosis may lead to chronic restrictive lung disease. Cardiomyopathy may result in congestive heart failure, arrhythmia, and death. Other abnormalities include visual impairment from optic atrophy and diabetes mellitus. **Tx:** There is no current treatment for the neurologic manifestations of Friedreich ataxia.

Answer 43

``` Idiopathic parkinsonism (Parkinson disease) is a proteinopathy characterized by the misfolding and aggregation of α-synuclein. It is thus also refered to as a synucleinopathy. Histopathologic examination at advanced stages shows loss of pigmentation and cells in the substantia nigra and other brainstem centers, cell loss in the globus pallidus and putamen, and filamentous eosinophilic intraneural inclusion granules (Lewy bodies) containing α-synuclein in the basal ganglia, brainstem, spinal cord, and sympa thetic ganglia. ``` The most common variety of parkinsonism occurs without obvios cause; this idiopathic form is called **Parkinson disease** or **paralysis agitans** when there are no atypical features, it is not secondary to some known cause, and there is a sustained response to treatment with dopaminergic medication. **Px:** The **cardinal features** of Parkinson disease (PD): * **Resting tremor (in a limb at rest)** A tremor at rest is perhaps the most obvious feature of Parkinson disease and is a common presenting symptom. The **tremor at rest readily disappears when sustaining a posture or during manual activities,** in contrast to an essential tremor, which is an action tremor. * **Bradykinesia** is manifested by paucity of spontaneous movement with severely affected patients sitting unnaturally still and demonstrating a lack of facial expressiveness (“facial masking”)[hyomimia]. In addition to whole-body slowness and impairment in fine motor movements [hypokinesia]. Patients assume a stooped posture, and walk in series of short, accelerating steps, such that the feet shuffle and scrape the floor. The arms remain immobile and do not swing during walking. , other _consequences of advanced bradykinesia_ include: * *Drooling of saliva* due to a lack of spontaneous swallowing * *Soft monotonous speech (hypophonia)* * *Micrographia (small, cramped handwriting)* * *Reduced arm swing* when walking, and a short, ***shuffling gait*** * **Rigidity** or increased tone (ie, increased resistance to passive movement) is characteristic of parkinsonism. * **Postural instability** (loss of postural reflexes) * Flexed axial posture * Loss of balance during turning or stopping * Loss of balance when pushed slightly from a stationary bipedal stance * Frequent falls **Gait** freezing (disturbance) flexed posture **Dx:** Diagnostic criteria for PD require **two of the four features**. In idiopathic PD, the symptoms present asymmetrically and although the contralateral side is eventually affected, the asymmetry usually persists throughout the disease course. **Tx:** **🧵Levodopa** ameliorates all the major clinical features of parkinsonism and, unlike the anticholinergic drugs, is often particularly helpful against hypokinesia. **Carbidopa** is a drug that reduces the extracerebral (peripheral) metabolism of levodopa to dopamine (causes nausea, vomiting, and hypotension) by inhibiting dopa decarboxylase but it does not cross the blood–brain barrier. Carbidopa is generally combined with levodopa in a fixed proportion (1:10 or 1:4) as carbidopa/levodopa. ❗ The most common early side effects include **hallucinations 😵, confusion, agitation, dizziness, hypotension, somnolence, and nausea.** **Involuntary movements** (eg, dyskinesia, dystonia) typically occur after **5–10 years** of therapy in nearly 50% of patients taking levodopa/carbidopa. Another late complication of levodopa therapy or consequence of advancing disease is response fluctuation such as the **wearing-off effect**, in which deterioration occurs shortly before the next dose is to be taken, or the on–off phenomenon, in which abrupt but transient fluctuations in the severity of parkinsonism occur at frequent intervals during the day, apparently without any relationship to the last dose of levodopa. **Dopamine Agonists** (pramipexole, ropinirole) ❗ are associated with a **greater risk** of **psychosis** 😵 than the dopamine precursor. **Tx:** Treatment of PD psychosis may involve a dose reduction of antiparkinson medication, medication substitution, and/or the addition of a low-potency antipsychotic medication. When antiparkinson medication adjustments fail, a **trial of an antipsychotic** is warranted. Low-potency antipsychotics with minimal dopamine-2 receptor antagonism such as **quetiapine, clozapine,** or pimavanserin are preferred. Antipsychotics with more potent dopamine-2 receptor antagonism (eg, haloperidol, risperidone) should be avoided as these medications have the highest risk of extrapyramidal symptoms and will worsen Parkinson motor symptoms **Ergot derivatives** such as bromocriptine, which stimulates dopamine D2 receptors. It is perhaps slightly less effective than levodopa in relieving the symptoms of parkinsonism but is less likely to cause dyskinesias. **Catechol-O-Methyltransferase Inhibitors** may be used to reduce the dose requirements of and any response fluctuations to levodopa. Their use leads to more sustained plasma levels of levodopa, with improved transport into the blood and across the blood–brain barrier. Tolcapone, entacapone. **Anticholinergic Drugs** (trihexyphenidyl, benztropine) are more helpful in alleviating **tremor and rigidity** than hypokinesia but are generally less effective than dopaminergic drugs. ❗Anticholinergic drugs are best avoided in the elderly because of their side effects, which include dry mouth, constipation, **urinary retention**, defective pupillary accommodation, and confusion. **Amantadine** - Unclear mechanism; ❗causes ankle edema and livedo reticularis (a mottled vascular pattern on the lower extremities) **Monoamine Oxidase Inhibitors** Selegiline, an irreversible monoamine oxidase type B (MAO-B) inhibitor, inhibits the metabolic breakdown of dopamine.

Answer 44

Multiple system atrophy (Shy-Drager syndrome) is a progressive neurodegenerative disorder (a synucleinopathy) with multisystem motor abnormalities and often a **dysautonomia**. It is more common in men and occurs usually in the sixth decade. It consists of: * Parkinsonism * **Autonomic dysfunction** (postural hypotension, abnormal sweating, disturbance of bowel or bladder control, abnormal salivation or lacrimation, impotence, gastroparesis, etc.) * Widespread neurological signs (cerebellar, pyramidal or lower motor neuron) **Hx:** When **autonomic insufficiency** is a conspicuous accompaniment, the ponymous designation of **Shy-Drager syndrome** is sometimes used. This latter syndrome is characterized by *parkinsonian features, **autonomic insufficiency*** (leading to **postural hypotension, *anhidrosis, disturbance of sphincter control, impotence,*** and signs of more widespread neurologic involvement (pyramidal or lower motor neuron signs and often a cerebellar deficit). The autonomic and multisystem—often symmetric— motor findings with marked *anterocollis* distinguish the disorder from classic Parkinson disease. **Dx:** MRI reveals a hypointense putamen with a hyperintense rim. The disease follows a progressive course leading to death over about 8 to 10 years.

Answer 45

Progressive supranuclear palsy is an idiopathic, usually sporadic, degenerative disorder, a **tauopathy** that primarily affects subcortical gray matter regions of the brain. There is much overlap clinically and pathologically with corticobasal degeneration. The principal neuropathologic finding is neuronal degeneration with the presence of neurofibrillary tangles in the midbrain, pons, basal ganglia, and dentate nuclei of the cerebellum. **Hx:** The classic clinical features are gait disturbance with early falls, supranuclear ophthalmoplegia, **pseudobulbar palsy**, axial dystonia with or without extrapyramidal rigidity of the limbs, and dementia. ***Supranuclear ophthalmoplegia*** is characterized by prominent **_failure of voluntary vertical gaze_****, with later paralysis of horizontal gaze;** oculocephalic and oculovestibular reflexes are preserved. Vertical saccades may initially be slowed. Parkinson disease differs from the classic form of progressive supranuclear palsy in that voluntary downward and horizontal gaze are not usually lost, axial posture tends to be characterized by flexion rather than extension, tremor is common, the course is less fulminant, and antiparkinsonian medications are more often effective.

Answer 46

It sometimes simulates Parkinson disease when bradykinesia and rigidity are conspicuous features. Postural-action tremor may also occur, but the usual cause of profound disability is **limb apraxia** (often leads to a useless limb) and **clumsiness** rather than extrapyramidal deficits. Other clinical features include **speech disturbances (aphasic, apraxic, or dysarthric), acalculia, cortical sensory deficits (eg, neglect syndromes)**, stimulus-sensitive myoclonus, **alien limb** **phenomenon** (the tendency for a limb to move semipurposefully, involuntarily, and without the knowledge of its owner), dysphagia, postural disturbances, dystonic features, and ultimately cognitive decline and behavioral changes. The disorder follows a progressive course, leading to increasing disability and dependence. Death typically follows within 10 years, often sooner, from aspiration pneumonia.

Answer 47

Characterized by parkinsonism that is responsive to dopaminergic therapy, **visual hallucinations**, and/or fluctuating cognition. The characteristic cognitive profile of dementia in patients with dementia with Lewy bodies includes impaired learning and attention, psychomotor slowing, constructional apraxia, and more profound visuospatial impairment but less memory impairment than in similarly staged patients with Alzheimer disease. **Dx:** Intraneuronal Lewy body inclusions in the cerebral cortex. **Tx:** Management of Lewy body disease is difficult because levodopa induces hallucinations and exacerbates the cognitive and behavioral disturbances while providing only limited benefit to the motor disturbance. Anticholinergic drugs are best avoided because they also may exacerbate cognitive dysfunction. The dementia and behavioral abnormalities often respond favorably to cholinesterase inhibitors.

Answer 48

**Parkinsonism** frequently complicates treatment with dopamine- agents such as reserpine or dopaminereceptor antagonists such as phenothiazines or butyrophenones. **Acute dystonia** or dyskinesia (such as blepharospasm, torticollis, or facial grimacing) is an occasional complication of dopamine receptor antagonist treatment, generally occurring within 1 week after introduction of such medication and often within 48 hours. **Akathisia** is a state of motor restlessness characterized by an inability to sit or stand still, which is relieved by moving about. **Tardive dyskinesia** may develop after long-term treatment with antipsychotic dopamine receptor antagonist drugs or with metoclopramide.

Answer 49

Clinical features * **Gait** instability (**wide-based**) with frequent falls * Cognitive dysfunction * Urinary urgency/incontinence * Depressed affect (frontal lobe compression) * Upper motor neuron signs in lower extremities Diagnosis * Marked improvement in gait with spinal fluid removal: Miller Fisher (lumbar tap) test * Enlarged ventricles out of proportion to the underlying brain atrophy on MRI Treatment * Ventriculoperitoneal shunting Normal pressure hydrocephalus is characterized by the accumulation of cerebrospinal fluid (CSF) leading to ventriculomegaly with **NORMAL opening pressure** on lumbar puncture. Most cases are idiopathic and occur in the **elderly**; however, **secondary disease** can occur in those with **prior neurologic insults (eg, subarachnoid hemorrhage [SAH], trauma, meningitis) that result in scarring and destruction of the arachnoid granulations responsible for CSF resorption.** Symptoms are classically described as a triad of **incontinence, cognitive impairment (eg, psychomotor retardation, apathy), and gait abnormalities**; however, all symptoms may not be present in early disease. A magnetic gait with **slow, wide-based steps that appear as though the patient's feet are stuck to the ground** is characteristic and typically appears early in the disease process. Upper motor neuron signs (eg, spasticity, hyperreflexia) may also occur. The diagnosis is confirmed with improvement of symptoms with **large-volume lumbar puncture**; **ventriculoperitoneal shunt placement** is the definitive therapy.

Answer 50

Wilson's disease is a rare, autosomal recessive disease of younger individuals that is characterized by abnormal copper deposition in tissues such as the liver, basal ganglia, and cornea. Children and adolescents tend to present with liver disease (ranging from asymptomatic aminotransferase elevations to fulminant hepatic failure), while young adults tend to demonstrate neuropsychiatric disease (ranging widely from tremor and rigidity to depression, paranoia, and catatonia). **Dx:** Classically, the diagnosis of Wilson's disease is confirmed by the presence of low serum ceruloplasmin (particularly \<20 mg/dL) in conjunction with increased urinary copper excretion or Kayser-Fleischer rings. Therefore, evaluation should include measurement of serum ceruloplasmin levels and slit lamp examination of the eyes.

Answer 51

Clinical features * Motor: chorea, delayed saccades, motor impersistince (inability to sustain grip) * Psychiatric: depression, irritability, psychosis, obsessive-compulsive symptoms * Cognitive: executive dysfunction Findings * Genetic: autosomal dominant CAG trinucleotide repeat expansion disorder * Neuropathology: loss of GABA-ergic neurons * Imaging: caudate nucleus and putamen atrophy Management/prognosis * Treatment: supportive * Survival: 10-20 years Huntington disease is a hereditary, progressive neurodegenerative disorder of the nervous system characterized by the gradual onset and subsequent progression of chorea and dementia. Characterized by increasingly severe motor impairment, cognitive decline, and psychiatric symptoms. In addition to **chorea**, other motor symptoms include **ataxia**, **dystonia**, slurred speech, impaired swallowing, and myoclonus. Various psychiatric symptoms, such as dysphoria, agitation, irritability, anxiety, apathy, disinhibition, delusions, and hallucinations, commonly occur. Deficits in sustained attention, memory retrieval, procedural memory (ability to acquire new skills), and visuospatial skills are predominant and early manifestations of the disorder. Language skills are usually preserved until the late stages of the disease. Personality changes and mood disturbances, including depression and mania, are frequent and can predate the onset of the dementia and the movement disorder. **Dx:** CT scanning or MRI often demonstrates atrophy of the cerebral cortex and caudate nucleus in established cases. Reduction in striatal metabolic rate may be demonstrated by PET. Tx: Dopamine blocking and depleting agents are effective in decreasing the involuntary movements of HD. **Haloperidol** is a dopamine receptor blocker and is commonly used for control of chorea in HD. Other neuroleptics, such as olanzapine, **risperidone**, and aripiprazole, are also effective in treating the chorea symptoms of HD.

Answer 52

The most likely diagnosis in a younger (\<50 years of age) patient with a symmetric action/postural movement disorder. Approximately one-half of all cases of ET appear to occur because of an autosomal dominant genetic mutation. **Hx:** The tremor typically involves one or both hands, the **head**, the voice, or some combination of these, but the legs tend to be spared. **Dx:** Positron emission tomography (PET) scanning shows that certain parts of the brain—including the **thalamus**—have increased activity. **Tx:** Lifestyle changes, such as getting enough sleep and reduction of caffeine, can be helpful. Essential tremor characteristically improves with alcohol intake, and patients with essential tremor are at increased risk of alcohol misuse because of this. **Rx:** If lifestyle modifications do not adequately control essential tremor symptoms, medications, including **β-blockers (such as propranolol)** 40 to 160 mg orally twice daily and anticonvulsants (such as primidone), are usually effective.

Answer 53

Sydenham chorea occurs principally in children and adolescents as a complication of a previous group A hemolytic streptococcal infection. Sydenham chorea is characterized by abnormal choreiform movements that are sometimes unilateral and, when mild, may be mistaken for restlessness or fidgetiness. **Tx:** The traditional treatment is bed rest, sedation, and prophylactic antibiotic therapy even if there are no other signs of acute rheumatism. A course of intramuscular penicillin is generally recommended, and continuous prophylactic oral penicillin daily or intramuscular benzathine penicillin G monthly until approximately age 20 years is also frequently advised to prevent streptococcal infections. PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) is the acronym used to refer to the association of obsessive compulsive or tic disorders of variable severity with streptococcal infections in children.

Answer 54

This group of disorders is characterized by **parkinsonism plus** **clinical evidence of more widespread disease from degeneration in other neuronal systems**. Depending on the disorder, they are either synucleinopathies or tauopathies. They typically respond poorly to dopaminergic medication and have a poorer prognosis than Parkinson disease. These disorders include diffuse **Lewy body disease, multisystem atrophy, progressive supranuclear palsy, and corticobasal degeneration.**

Answer 55

Common causes of vertigo Ménière disease * Recurrent episodes lasting 20 minutes to several hours * Sensorineural hearing loss * Tinnitus &/or feeling of fullness in the ear BPPV * Brief episodes triggered by head movement * Dix-Hallpike maneuver causes nystagmus Vestibular neuritis * Acute, single episode that can last days * Often follows viral syndrome * Abnormal head thrust test Migraine * Vertigo associated with headache or other migrainous phenomenon (eg, visual aura) * Symptoms resolve completely between episodes Brainstem/cerebellar stroke * Sudden-onset, persistent vertigo * Usually other neurologic symptoms

Answer 56

The syndrome is characterized by brief (seconds to minutes) episodes of severe vertigo that may be accompanied by nausea and vomiting. **Tx:** The mainstay of treatment is **repositioning (Epley) maneuvers** that use the force of gravity to move endolymphatic debris out of the semicircular canal and into the vestibule, where it can be reabsorbed. **Nystagmus** is a rhythmic oscillation of the eyes. Vestibular lesions result in a slow drift of the eyes away from the target in one direction (smooth pursuit), followed by a fast corrective movement (saccadic; fast phase) in the reverse direction that serves to bring the eye back on target. The eyes appear to "beat" in the direction of the fast phase. **Nystagmus: Periphereal Lesion** **Type:** mixed **horizontal-torsional nystagmus** results if a peripheral lesion affects all three semicircular canals on one side. The horizontal fast phases beat toward the normal ear, as do the upper poles of the eyes for the torsional fast phases. The nystagmus from peripheral disease **occasionally appears purely horizontal**, never purely torsional or vertical. **Visual fixation:** tends to suppress nystagmus that is due to a peripheral lesion, but it does not usually suppress nystagmus from a central lesion (use Frenzel lenses). The effect of fixation can also be determined during ophthalmoscopy if the examiner covers and uncovers the other eye. **Direction:** In peripheral lesions, the predominant direction of nystagmus remains the same in all directions of gaze. Deficient vestibuloocular reflex (VOR) implies a peripheral vestibular lesion (inner ear or vestibular nerve). **Nystagmus: Central Lesion** **Direction:** Nystagmus that reverses direction when the patient looks right then left suggests a central abnormality. Nystagmus that reverses direction with convergence also suggests a central lesion. **Other neurologic signs:** the presence of additional neurologic abnormalities strongly suggests the presence of a central lesion.

Answer 57

Ménière disease is a disorder of the inner ear characterized by **increased volume and/or pressure of endolymph (endolymphatic hydrops)**. The resulting distension of the endolymphatic system causes damage to both the vestibular and cochlear components of the inner ear. Ménière disease is characterized by the following triad: * **Episodic vertigo** (20 min to 24 hr), commonly associated with nausea and vomiting * **Sensorineural hearing loss**, fluctuating and varying in severity and usually worsening over time (primarily affecting low frequencies at first and progressing to permanent loss over all frequencies) * Low-frequency **tinnitus** in the affected ear, often accompanied by a feeling of fullness The diagnosis of Ménière disease is based primarily on clinical findings; however, **audiometry** should be performed to fully characterize the hearing loss and follow its course over time, and MRI should be obtained to rule out central nervous system lesions. **Tx:** Initial management includes **restriction of sodium, caffeine, nicotine, and alcohol.** Benzodiazepines, antihistamines, and antiemetics can relieve acute symptoms. Diuretics can be considered. A minority of patients may require interventional techniques (eg, endolymphatic shunt placement) for severe, intractable vertigo.

Answer 58

Caused by **immobility** of the stapes, the ear ossicle that transmits vibration of the tympanic membrane to the inner ear. **Hx:** Otosclerosis is suggested by a positive family history, a tendency toward onset at an earlier age, the presence of **conductive hearing loss**, or **bilateral** symmetric auditory impairment **Px:** Its most distinctive feature is conductive hearing loss, but sensorineural hearing loss and vertigo may also occur, whereas tinnitus is infrequent. **Tx:** Treatment with **sodium fluoride, vitamin D, or intratympanic dexamethasone** may be effective. If not, surgical stapedectomy should be considered.

Answer 59

An erosive, expansile mass of keratin debris in the middle ear. May present with unilateral hearing loss (usually **conductive**) (ie, bone conduction \> air conduction, lateralization to the affected ear), often with **otorrhea** and a **pearly white mass** in the middle ear.

Answer 60

Head trauma is the **most common** identified cause of **benign positional vertigo**. **Injury to the labyrinth** is usually responsible for posttraumatic vertigo; however, fractures of the petrosal bone may lacerate the vestibulocochlear (VIII) nerve, producing vertigo and hearing loss. **Px: Hemotympanum** or CSF otorrhea suggests such a fracture.

Answer 61

A benign tumor of CN VIII Schwann cells that forms in the internal auditory canal. Epidemiology * Median age 50 * Usually unilateral (bilateral associated with **neurofibromatosis type 2**) Clinical manifestations & pathophysiology * **Sensorineural hearing loss** (air conduction \> bone conduction, lateralization to the unaffected ear) & **imbalance** (CN VIII Schwann cell tumor) * ± **Facial numbness &/or paralysis** (CN V & VII compression) Diagnostic studies * **Audiogram** * MRI with contrast of internal auditory canal Management * Observation (eg, small tumors, minimal symptoms, older or infirm patients) * Surgery * Radiation therapy CN VIII is comprised of both the cochlear nerve and vestibular nerves. Therefore, patients with schwannoma often have unilateral hearing loss due to cochlear nerve compression. Although vertigo would generally be expected with acute vestibular nerve damage, most patients with vestibular schwannoma do not experience vertigo because the tumor's slow growth allows for central compensation of gradual unilateral loss of input; however, imbalance can still manifest when patients are deprived of visual input (eg, walking at night). As the tumor expands from the internal auditory canal into the cerebellopontine angle, it may compress CN V (causing facial numbness) and CN VII (causing facial weakness). **Hx:** Insidious **hearing loss** is usually the initial symptom. Less often, patients present with headache, vertigo, gait ataxia, facial pain, **tinnitus**, a sensation of fullness in the ear, or facial weakness. **Px: Unilateral _sensorineural_ hearing loss** is the most common finding on examination. Other frequent findings are **ipsilateral facial palsy**, depressed or absent corneal reflex, and sensory loss over the face. **Dx:** Patients require an **audiogram** and an **MRI with contrast of the internal auditory canal**. In select patients, observation may be appropriate; otherwise, treatment is with surgical resection or radiation therapy. **Tx:** Treatment is complete surgical excision

Answer 62

**Alcohol** causes acute positional vertigo because of its differential distribution between the cupula and endolymph of the inner ear. The clinical syndrome is characterized by vertigo and nystagmus in the lateral recumbent position and is accentuated when the eyes are closed. **Aminoglycoside** **antibiotics** are widely recognized ototoxins that can produce both vestibular and auditory symptoms. Streptomycin, gentamicin, and tobramycin are the agents most likely to cause vestibular toxicity, and amikacin, kanamycin, and tobramycin are associated with hearing loss. Aminoglycosides concentrate in the perilymph and endolymph and exert their ototoxic effects by destroying sensory hair cells. **Hx:** Symptoms of **vertigo**, nausea, vomiting, and gait ataxia may begin acutely; physical findings include spontaneous nystagmus and the Romberg sign. **Salicylates**, when used chronically and in high doses, can cause vertigo, tinnitus, and sensorineural hearing loss. **Hx:** Symptoms result from cochlear and vestibular end-organ damage. Salicylism is characterized by headache, tinnitus, hearing loss, vertigo, nausea, vomiting, thirst, hyperventilation, and sometimes a confusional state. **Tx:** Treatments include gastric lavage, activated charcoal, forced diuresis, peritoneal dialysis or hemodialysis, and hemoperfusion.

Answer 63

**Basilar meningitis** from **bacterial, syphilitic, or tuberculous infection or sarcoidosis** can lead to compression of the vestibulocochlear and other cranial nerves, but **hearing loss** is a more common consequence than vertigo. Metabolic disorders associated with vestibulocochlear neuropathy include hypothyroidism, diabetes, and Paget disease.

Answer 64

Epidemiology * Younger (early to mid-30s) Caucasian patients * More common in women * Autosomal dominant with incomplete penetrance Pathophysiology * Imbalance of bone resorption & deposition → stiffening of stapes Clinical manifestations * **Progressive conductive hearing loss** * **Paradoxical improvement in speech discrimination in noisy environments** * **± 🔼 Reddish hue behind tympanic membrane** Management * Amplification (eg, hearing aids) * Surgery (eg, stapes reconstruction) Otosclerosis is inherited in an autosomal dominant pattern with incomplete penetrance. It results from an **imbalance of bone resorption and deposition, causing stiffening and fixation of the ossicular chain (malleus, incus, stapes)**, primarily the stapes. Because the ossicles function as a lever connecting the tympanic membrane to the oval window to amplify sound energy, this stiffening results in CHL. As with other causes of CHL, patients with otosclerosis can have **paradoxical improvement of speech understanding in a noisy environment** (a phenomenon called the **paracusis of Willis**), possibly because CHL dampens the competing background noise, thereby allowing speech to be heard more clearly. Ear examination is generally unremarkable, although excessive bony resorption can expose underlying blood vessels, leading to a reddish hue sometimes seen behind the tympanic membrane. Management involves hearing amplification or surgical reconstruction of the stapes.

Answer 65

Presbycusis affects \>50% of adults by age 75 and is likely related to **cochlear hair cell loss** and **cochlear neuron degeneration**. Age-related brain atrophy also likely contributes (likely due to increased information processing times) and may explain the disproportionate problems with speech discrimination in older compared with younger patients with SNHL. High frequencies are affected first, making it more difficult for patients to understand **higher-pitched voices (eg, women, children). Tinnitus** often develops and is typically described as continuous ringing, rushing, or buzzing. Patients with presbycusis often hear well in one-on-one conversations in a quiet room; however, even a small amount of competing noise impairs hearing (eg, speech discrimination). Therefore, education of the patient and family is imperative. In addition to limiting background noise, families should be counseled to look directly at patients when speaking to them. Amplification (eg, **hearing aids**) may be beneficial. Presents with **bilateral, symmetric sensorineural hearing loss (SNHL).**

Answer 66

Endophthalmitis refers to a bacterial or fungal infection within the eye, particularly the vitreous. Patients usually present with pain and decreased visual acuity. Postoperative is the most common form of endophthalmitis. It usually occurs within 6 weeks of surgery. Examination reveals swollen eyelids and conjunctiva, hypopyon, corneal edema and infection. The vitreous can be sent for Gram stain and culture. Based on the severity, intravitreal antibiotic injection or vitrectomy is done.

Answer 67

Alcoholic cerebellar degeneration * \>10 years heavy alcohol use * Degeneration of Purkinje cells (cerebellar vermis) Manifestations * Usually develops over weeks to months * **Wide-based gait** * Incoordination in legs * Cognition usually intact Diagnosis * Clinical: * Impaired tandem walking/heel-knee-shin * Preserved finger-nose testing * CT/MRI - cerebellar atrophy Treatment * Alcohol cessation * Nutritional supplements * Ambulatory assistance devices (eg, walker) Cerebellar degeneration typically occurs after \>10 years of heavy alcohol use and is due to the **degeneration of Purkinje cells in the cerebellar vermis**. As these neurons are largely responsible for truncal coordination, patients with cerebellar degeneration usually develop slowly progressive **wide-based gait** and postural instability. **Px:** Physical examination typically shows evidence of postural incoordination (eg, inability to tandem walk, **abnormal heel-knee-shin testing**) with relatively preserved limb coordination (**normal finger-nose testing**). Cognitive function is usually preserved. Although alcohol cessation and nutritional supplementation prevent disease progression, ambulatory difficulties do not typically improve. Patients therefore usually benefit from ambulatory assist devices such as canes or walkers. Typical features of cerebellar degeneration include progressive gait dysfunction, truncal ataxia, **nystagmus, intention tremor or dysmetria (limb-kinetic tremor when attempting to touch a target), and impaired rapid alternating movements (dysdiadochokinesia)**. **Muscle hypotonia can also be present, leading to a pendular knee reflex - persistent swinging movements of the limb after eliciting the deep-tendon reflex (more than 4 swings is considered abnormal).** Pendular reflexes are not brisk, unlike clonus which would suggest pyramidal tract disease. **Dx:** Cerebellar atrophy on CT/MRI

Answer 68

Characterized by progressive bilaterally symmetric and predominantly high-frequency sensorineural hearing loss that occurs over many years. The condition affects more than half of all adults by age 75 and is due to degenerative changes of the inner ear or cochlear portion of the eighth cranial nerve. Patients with presbycusis will often hear well in one-on-one conversations in a quiet room; however, this ability will decline even if a small amount of competing noise is present. Subjective bilateral tinnitus can develop as the hearing loss progresses and is typically described as a steady or continuous ringing or rushing sound.

Answer 69

**Tx:** Once diagnosed with a peripheral vestibular disorder, antihistamines are the first-line therapy for symptomatic relief. They suppress the vestibular end-organ receptors and inhibit activation of the vagal response. **Meclizine (Antivert), 25 mg** orally every 4 to 6 hours **Diphenhydramine (Benadryl), 50 mg** orally every 4 to 6 hours are commonly recommended choices.

Answer 70

Perilymphatic fistulas are a rare, but debilitating, complication of **head injury** or barotrauma. They cause leakage of endolymph from the semicircular canals and cochlea into surrounding tissues, resulting in characteristic clinical features: Progressive **sensorineural hearing loss** caused by damage to cochlear hair cells from loss of endolymph. Episodic vertigo with nystagmus triggered by **pressure changes** in the inner ear (eg, Valsalvamaneuver, elevation changes [eg, riding in elevator]) due to acutely increased endolymph leakage. This can be demonstrated clinically by performing a loud clap (ie, pressure change due to sound conduction through the ossicles) near the patient's ear and observing for nystagmus **(Tullio phenomenon).** Patients are advised to limit activities that increase inner ear pressure; they also require ENT referral for further management.

Answer 71

Neurodegenerative Proteinopaties: Alzheimer disease Mild Cognitive Impairement Frontotemporal dementia Dementia with Lewy bodies Vascular dementia Normal pressure hydrocephalus Ddx: Confusional State Nutritional Inflammatory and autoimmune Infectious Endocrine Structural Toxic/metabolic/Drugs Psychiatric Vascular Disorders Head Trauma

Answer 72

Normal age-related cognitive decline involves nonprogressive, mild memory impairment and decreased rate of information processing that **does not result in interference with daily function.** Sometimes forgetting to take medication without reminders, occasional word-finding aphasia, and sleep disturbance can also occur with normal aging and are therefore less specific for dementia. In contrast, patients with age-related memory loss **will not get lost in familiar settings.**

Answer 73

Mild cognitive impairment (MCI) describes a loss of cognitive ability that **exceeds the expected age-related memory loss but does NOT interfere significantly with daily activities.** The term is sometimes used to describe the early phase of cognitive decline observed in patients who later receive a diagnosis of Alzheimer disease. There are universal age-related declines in cognition that chiefly affect memory, learning, and problem solving beginning around age 40 years, and these changes may be noticeable to patients.

Answer 74

Dementia (major neurocognitive disorder) is her impaired functioning in daily activities as demonstrated by **getting lost in familiar surroundings.** Other areas of impaired functioning in dementia can include difficulties with dressing, maintaining personal hygiene, food acquisition and intake, self-administration of medications, social interactions, and operating common appliances. Early findings * Anterograde memory loss (ie, immediate recall affected, distant memories preserved) * Visuospatial deficits (eg, lost in own neighborhood) * Language difficulties (eg, difficulty finding words) * Cognitive impairment with progressive decline Late findings * Neuropsychiatric (eg, hallucinations, wandering) * Dyspraxia (eg, difficulty performing learned motor tasks) * **Lack of insight regarding deficits** * Noncognitive neurologic deficits (eg, pyramidal & extrapyramidal motor, myoclonus, seizures) * **Urinary incontinence** **Paranoid delusions** are common and can be particularly distressing to the patient and caregivers. AD is the most common cause of dementia in the United States and usually occurs after age 65. **Death usually occurs within 10 years of diagnosis regardless of the treatment offered.** Patients experience a progressive functional decline over the course of their disease. Later findings usually include personality and behavioral changes (eg, apathy, agitation), neuropsychiatric changes (eg, delusions, paranoia), neurologic manifestations (eg, myoclonus, seizures), and apraxia (eg, difficulty with motor tasks). Urinary incontinence may develop in later stages of AD, secondary to severe cognitive dysfunction. The result of structural neuronal changes with pathologic features including deposition of insoluble, neurotoxic β-amyloid protein in extracellular parenchymal plaques and intracellular accumulation of neurofibrillary tangles composed of abnormal tau protein. **Early Manifestations:** MCI; Impairment of recent memory is typically the first sign of Alzheimer disease and may be noticed only by family members. As the memory disorder progresses over months to several years, the patient becomes **disoriented to time and then to place**. Aphasia, anomia, and acalculia may develop, forcing the patient to leave work or give up the management of family finances. The depression apparent in the earlier stages of the disorder may give way to an agitated, restless state. Apraxias and visuospatial disorientation ensue, causing the patient to become lost easily. Primitive reflexes are commonly found. A frontal lobe gait disorder may become apparent, with short, slow, shuffling steps, flexed posture, wide base, and difficulty in initiating walking. **Late Manifestations:** Late manifestations—In the late stages, previously preserved social graces are lost, and psychiatric symptoms, including psychosis with paranoia, hallucinations, or delusions, may be prominent. Seizures occur in some cases. Examination at this stage may show rigidity and bradykinesia. Rare and usually late features of the disease include myoclonus, **incontinence**, spasticity, extensor plantar responses, and hemiparesis. Mutism, incontinence, and a bedridden state are terminal manifestations. **Dx:** 🧠CT scan or **MRI** often shows **temporal and parietal** (especially **medial temporal lobe**) atrophy and **enlarged ventricles**, but such changes are nonspecific. **Tx:** Cholinesterase inhibitor **donepezil** (Aricept), **galantamine** (Reminyl), and **rivastigmine** (Exelon). They are associated with modest improvements in cognition, behavior, activities of daily living, and global measurements of functioning. However, they **do not change the progression of neurodegeneration.** **N-methyl-D-aspartate receptor antagonist** **(_memantine_)** is the only drug approved by the Food and Drug Administration as first-line treatment of moderate to advanced Alzheimer disease. **Non pharmacologic: Cognitive stimulation** included a range of activities designed to stimulate thinking, concentration, and memory. Cognitive stimulation was associated with improved cognitive function immediately after treatment. Quality of life also improved, but there was no impact on mood, overall functional level, or caregiver outcomes. **Cx: Impaired swallowing and cough reflex** are frequent abnormalities in patients with advanced dementia. Such patients have decreased recognition of food in the oropharynx as well as challenges in forming a food bolus and coordinating the complex action involved in swallowing. Such patients are also predisposed to **aspiration** of oropharyngeal secretions and inhalation of colonizing pathogenic bacteria (eg, Peptostreptococcus).

Answer 75

Progressive neuropsychiatric disorder characterized by early behavioral and **personality changes** that range from **apathy** to **social disinhibition**. Patients may fail to change their clothes, brush their teeth, pursue their former interests, or initiate many of their previous activities that constituted a normal day. They may fixate, in a seemingly idiosyncratic fashion, on a particular activity, such as going to the bathroom, sorting through a wallet, hoarding magazines, or watching television. Some patients have greater disinhibition and emotional lability (crying or laughing inappropriately). **Behavioral changes often precede memory impairments (in contrast to AD).** **Dx:** Disproportionate atrophy of the frontal and anterior temporal brain regions.

Answer 76

Dementia with Lewy bodies (DLB) presents with dementia plus **≥2 of the following features: Visual hallucinations, parkinsonism, fluctuating cognition, and REM sleep behavior disorder.** **Dx:** Intraneuronal Lewy body inclusions in the cerebral cortex. **Tx:** Treatments for DLB include carbidopa-levodopa for parkinsonism, cholinesterase inhibitors (eg, rivastigmine) for cognitive impairment, and melatonin for REM sleep behavior disorder. A trial of an antipsychotic medication (eg, risperidone) may be indicated in patients with functionally impairing visual hallucinations or delusions, but it must be prescribed with caution due to the extreme antipsychotic hypersensitivity of patients with DLB. Antipsychotics may be associated with worsening confusion, parkinsonism, and autonomic dysfunction when used in such patients. When antipsychotics are indicated in the treatment of DLB, evidence favors low-potency second-generation antipsychotics (eg, quetiapine). First-generation antipsychotics (eg, haloperidol) should be avoided entirely.

Answer 77

Consequence of progressive ischemic brain injury; **stepwise deterioration; early executive dysfunction.** **Dx:** Patients with this diagnosis may have multiple large (\>1 cm in diameter) cortical infarcts; strategic infarcts involving hippocampus or thalamus; multiple small (eg, lacunar) infarcts affecting subcortical white matter, basal ganglia, or thalamus; diffuse ischemic lesions of subcortical white matter (Binswanger disease); intracerebral hemorrhages (eg, cerebral amyloid angiopathy); or combinations of these. **Px:** The neurologic examination may show pseudobulbar palsy with dysarthria, dysphagia, and pathologic emotionality (pseudobulbar affect); focal motor and sensory deficits; ataxia; **gait** apraxia; hyperreflexia; and extensor plantar responses.

Answer 78

**♨ Hypertensive Encephalopathy :** A sudden increase in blood pressure may result in encephalopathy and headache, which develop over a period of hours to days. Impaired autoregulation of cerebral blood flow, vasospasm, and intravascular coagulation have all been proposed as causes. Stroke and subarachnoid hemorrhage also produce encephalopathy with acutely elevated blood pressure; when focal neurologic abnormalities are also present, stroke is most likely. A similar syndrome, ***Posterior Reversivle Encephalopathy Syndrome (PRES)*** can occur in normotensive individuals and may be related to autoimmune-induced endothelial dysfunction or immunosuppressive drug treatment. **Hx:** Blood pressure in excess of 250/150 mm Hg is usually required to precipitate the syndrome in patients with chronic hypertension, but previously normotensive **patients may be affected at lower pressures.** **Px:** Papilledema, retinal hemorrhages, and exudates are usually present. **Dx:** Areas of edema, located especially in parietooccipital white matter, are seen on CT scan and MRI and are reversible with treatment. The diagnosis of hypertensive encephalopathy is established when lowering the blood pressure results in rapid resolution of symptoms. **Tx:** Accomplished with 🧨**sodium nitroprusside**, given by continuous intravenous infusion at an initial rate of 0.25 μg/kg/min and increased to as much as 10 μg/kg/min as required. **Mean arterial blood pressure** should be reduced by no more than 25% in the first 2 hours of treatment, and a target of 160/100 mm Hg should be aimed for in the following 4 hours.

Answer 79

Medication side effect Primary considerations include medication toxicity, central nervous system infection (meningitis or encephalitis), alcohol withdrawal, thiamine deficiency, folate deficiency, hepatic encephalopathy, and seizures. Other CNS toxins Delirium is common at the end of life and can be caused by advanced medical conditions, the medications being used to palliate symptoms, or a combination of both. **Tx:** Evidence demonstrates that **low-dose antipsychotic agents (Haloperidol)** are effective in the treatment of delirium.

Answer 80

**CNS:** meningitis, encephalitis (CMV, HSV), subdural empyema, brain abscess **Outside CNS:** urinary tract infection, pneumonia, and sepsis most common, although can occur with other infections. Seizure (postictal state, status epilepticus)

Answer 81

Metabolic Toxic Infection Pain

Answer 82

Wernicke encephalopathy is usually a complication of chronic alcoholism, but it also occurs in other disorders associated with malnutrition, such as **anorexia nervosa**, cancer, and after bariatric surgery. It is caused by deficiency of **thiamine (vitamin B1)**. **Px:** The classic syndrome comprises the triad of **ophthalmoplegia, ataxia, and confusional state**. The most common **_ocular abnormalities:_** **nystagmus, abducens (VI) nerve palsy,** and **horizontal or combined horizontal–vertical gaze palsy**. Ataxia affects gait primarily; ataxia of the arms is uncommon, as is dysarthria. The mental status examination reveals global confusion with a prominent disorder of immediate recall and recent memory. Most patients have associated neuropathy with absent ankle jerks. Hypothermia and hypotension may occur. Pupillary abnormalities, including mild anisocoria, or a sluggish reaction to light, are occasionally seen. **Dx:** The peripheral blood smear may show macrocytic anemia, and MRI may show **atrophy of the mammillary bodies.**

Answer 83

Dehydration (**H20**) Alcohol withdrawal (delirium tremens) Hypothermia, hyperthermia (**Temp**) Hyponatremia, hypernatremia (**Na**+) Hypercalcemia (**Ca+**) Hypoglycemia, hyperglycemia (diabetic ketoacidosis or hyperosmolar syndrome) [**GLu**] Hypothyroid, hyperthyroid (**T3**) Hypoxemia, hypercarbia (**O2**, **CO2**) Malnutrition, thiamine deficiency

Answer 84

Clinical triad of **dementia, gait apraxia, and incontinence.** The dementia is often mild and insidious in onset and is typically preceded by gait disorder and incontinence. It is characterized initially by mental slowness and apathy and later by global cognitive dysfunction. **Communicating hydrocephalus** (because the lateral, third, and fourth ventricles remain in communication) or **nonobstructive hydrocephalus** (because the flow of CSF between the ventricles is not impaired). It is presumed to be caused by **impaired CSF absorption from arachnoid granulations** in the subarachnoid space over the cerebral hemispheres. **Noncommunicating** or **obstructive hydrocephalus** is caused by a **blockade of CSF circulation** within the ventricular system (eg, by an intraventricular cyst or tumor) and is associated with increased CSF pressure and often with headache and papilledema. **Urinary incontinence** is a later development, and patients may be unaware of it; fecal incontinence is uncommon. **Gait apraxia:** Characterized by unsteadiness on standing and difficulty in initiating walking (magnetic gait), even though there is no weakness or ataxia. The patient can perform the leg movements associated with walking, bicycling, or kicking a ball and can trace figures with the feet while lying or sitting but is unable to do so with the legs bearing weight. The patient typically appears to be glued to the floor; walking, once underway, is slow and shuffling. **Dementia** is manifested by psychomotor slowing, inattention, and impaired decision making and spatial recognition. Urinary incontinence is a later development, and patients may be unaware of it; fecal incontinence is uncommon. **Dx:** **Lumbar puncture** reveals normal or low opening pressure and is both diagnostic and theraputic. **Tx: LP;** Ventriculoatrial, ventriculoperitoneal, or lumboperitoneal **shunting**.

Answer 85

**Vitamin B12 deficiency** ``` Vitamin B12 (**cyanocobalamin**) deficiency produces polyneuropathy, subacute **combined degeneration** of the spinal cord (combined systems disease) affecting the **cor**_t_**icos**_p_**inal tracts and dorsal columns**, nutritional amblyopia (visual loss), and cognitive dysfunction that ranges from a mild confusional state to dementia or psychosis **(megaloblastic madness)**. The most frequent cause of vitamin B12 deficiency is **pernicious anemia**, a defect in the production of intrinsic factor associated with atrophic gastritis, anti-parietal cell antibodies, and achlorhydria. Other causes include gastric resection and vegan diet. ``` **Hx:** The presentation is usually with anemia or orthostatic lightheadedness but may also be neurologic. Distal paresthesias, gait ataxia, a bandlike sensation of tightness around the trunk or limbs, and Lhermitte sign (an electric shock–like sensation along the spine precipitated by neck flexion) may be present. **Px:** Physical examination may show low-grade fever, **glossitis (beefy red tongue)**, lemon-yellow discoloration of the skin, and cutaneous hyperpigmentation. Cerebral involvement produces confusion, depression, agitation, or psychosis with hallucinations. Spinal cord involvement causes **impaired vibratory and joint position sense, sensory gait ataxia, ataxic heel-knee-shin** and spastic paraparesis with extensor plantar responses. Associated peripheral nerve involvement may lead to loss of tendon reflexes in the legs and urinary retention. **Dx:** Because folate deficiency can produce identical changes, the diagnosis must be confirmed by measuring the **serum vitamin B12 level**. When this is low **(\<100 pg/mL)**, a Schilling test can determine whether defective intestinal absorption of vitamin B12 (as in pernicious anemia) is the cause, but the test is now rarely used. Diagnosis may be difficult when cerebral symptoms occur without anemia or spinal cord disease, so the serum vitamin B12 level should be determined routinely in patients with cognitive disorders, myelopathy, or peripheral neuropathy, regardless of whether anemia is present. **Tx:** Treatment of neurologic manifestations is by prompt intramuscular administration of **cyanocobalamin (1,000 μg),** as soon as blood is drawn to determine the serum vitamin B12 level. Daily injections are continued for 1 week, and further testing is performed to determine the cause of deficiency. If, as in pernicious anemia, deficiency is not correctable by dietary supplementation or treatment of an underlying cause (eg, intestinal malabsorption), intramuscular vitamin B12 (typically 1,000 μg) is given at weekly intervals for several months and monthly thereafter. **Wernicke Encephalopathy** Is caused by deficiency of **thiamine (vitamin B1)**. Wernicke encephalopathy is usually a complication of chronic 🍺 **alcoholism**, but it also occurs in other disorders associated with **malnutrition**, such as cancer, and after bariatric surgery. Pathologic features include neuronal loss, demyelination, and gliosis in periventricular gray matter. Proliferation of small blood vessels and petechial hemorrhages may be seen. The areas most commonly involved are the medial thalamus, mammillary bodies, periaqueductal gray matter, cerebellar vermis, and oculomotor, abducens, and vestibular nuclei. The classic syndrome comprises the triad of **ophthalmoplegia, ataxia, and confusional state.** The mental status examination reveals global confusion with a prominent disorder of immediate recall and recent memory. **Tx:** Treatment is prompt administration of **thiamine**. An initial dose of **500 mg** is given intravenously, before or with dextrose (which might otherwise precipitate or exacerbate the disorder).

Answer 86

**Upper motor neuron (UMN)** refers to anything above the anterior horn (spinal cord). Lesions to UMNs (eg, due to stroke, brain tumor) cause a combination of "pyramidal signs": spastic paralysis, clasp-knife rigidity (characterized by initial resistance to passive extension followed by a sudden release of resistance), **Spasticity** (Clasp-knife spasticity and spastic paralysis) occurs within the flexors of the upper limb and the extensors of the lower limb. There is a sudden decrease in resistance (often termed a "release") when attempting to flex a joint. **Hyperreflexia** (including **clonus**), and upgoing plantar reflexes (**Babinski** sign). This likely occurs due to loss of descending inhibition over second-order neurons in the anterior horn. **Babinski sign** indicates an upper motor neuron (UMN) lesion anywhere along the **corticospinal tract**. UMNs are thought to have inhibitory control over lower motor neurons (LMN), thus removal of UMN input causes overstimulation of LMNs and leads to unmasking of primitive reflexes, such as the Babinski reflex. **Pronator drift** is a physical examination finding that is relatively sensitive and specific for upper motor neuron or **pyramidal/corticospinal tract** disease. The pronator drift test is particularly useful in patients with subtle deficits as it can accentuate pyramidal motor weakness. It is performed by having the patient outstretch the arms with the palms up and eyes closed (so that only proprioception is used to maintain arm position). **Upper motor neuron lesions cause more weakness in the supinator muscles compared to the pronator muscles of the upper limb.** As a result, the affected arm drifts downward and the palm turns (pronates) toward the floor. Patients with an internal capsule stroke commonly have pure motor weakness affecting the contralateral arm, leg, and lower face. Contralateral spasticity or increased tone, hyperreflexia, and a positive Babinski sign are also present. Patients with multiple sclerosis often develop a spastic bladder a few weeks after developing an acute lesion of the spinal cord. Urodynamic studies show little or no residual urine after emptying as bladder contractility is normal but distensibility is poor. The bladder does not distend/relax properly due to loss of descending inhibitory control from the upper motor neuron. Supraspinal lesions: CNS lesions involving the area above the pons **Lower motor neuron (LMN)** refers to motor neurons of the anterior horn. This type of injury leads to flaccid paralysis, hypotonia, hyporeflexia, muscle atrophy, and fasciculations. **Fasciculations** are involuntary muscle contractions that arise from the spontaneous discharge of muscle fibers or motor units. They are a sign of LMN disease **Flaccid Paralysis** (ie. bladder) typically occurs in the setting of lower motor neuron lesions (cauda equina syndrome). A patient with a flaccid bladder will have a large residual volume of urine after attempted emptying and will typically experience urinary incontinence at the end of the day (pressure from a full bladder becomes greater than urinary sphincter pressure). Denervation **Atrophy** Poliomyelitis and infantile spinal muscular atrophy are examples of LMN lesions. The virus is spread via the fecal-oral route and can then cause paralysis by infecting the alpha motor neurons of the ventral horn of the spinal cord. This can result in lower motor neuron disease including (asymmetrical) flaccid paralysis, muscle atrophy, fasciculations (as seen in the media clip), and areflexia. Early prodromal symptoms include malaise, headache, fever, abdominal pain, sore throat, and nausea. Typically, sensory neurons are unaffected.

Answer 87

Because the facial/ophthalmic venous system is valveless, uncontrolled infection of the skin, sinuses, and orbit can spread to the cavernous sinus. Inflammation of the cavernous sinus subsequently results in life-threatening CST and intracranial hypertension. Headache is the most common symptom and can become intolerable. A low-grade fever and periorbital edema usually occur several days later secondary to impaired venous flow in the orbital veins. Vomiting is also a result of intracranial hypertension, and fundoscopy may reveal papilledema. Cranial nerves III, IV, V, and VI pass through the cavernous sinus, which has anastomoses crossing midline. As a result, unilateral symptoms (eg, headache, binocular palsies, periorbital edema, hypoesthesia, or hyperesthesia in V1/V2 distribution) can rapidly become bilateral. Magnetic resonance imaging with magnetic resonance venography is the imaging modality of choice for diagnosis of CST. Treatment includes broad-spectrum intravenous antibiotics and prevention or reversal of cerebral herniation.

Answer 88

The presence of EBV DNA in the CSF is specific for this condition. MRI reveals a weakly **ring-enhancing mass** that is usually solitary and **periventricular** Suspect primary CNS lymphoma in an HIV-infected patient with an altered mental status, EBV DNA in the CSF, and a solitary, weakly ring-enhancing periventricular mass on MRI.

Answer 89

**Oculomotor nerve (CN III) palsy.** The most common cause of CN III palsy in adults is ischemic neuropathy due to poorly controlled diabetes mellitus. CN III has 2 major components as follows: * Inner somatic fibers - innervate the levator muscle of the eyelid and 4 of the extraocular muscles (EOMs) (superior rectus, medial rectus, inferior rectus, inferior oblique) * Superficial parasympathetic fibers - innervate the sphincter of the iris and the ciliary muscles (controlling pupil constriction). Because the inner somatic fibers are farther from the blood supply, they are more susceptible to ischemic injury. Therefore, patients with ischemic CN III palsy typically have paralysis of the levator muscle (ptosis) and 4 EOMs **("down-and-out-gaze")** with preserved pupillary response.

Answer 90

Central retinal artery occlusion (CRAO) is characterized by a sudden painless loss of vision in one eye. Ophthalmoscopy of patients with CRAO reveals **pallor** of the optic disc, **cherry red fovea**, and **boxcar** segmentation of blood in the retinal veins. **Risk factors** include c**arotid artery disease, endocarditis, cardiac valvular disease, long bone fracture, hypercoagulable conditions, vasculitis, atrial myxoma**, etc. It occurs when a severe, abrupt diminution of blood flow through the central retinal artery causes ischemia of the inner retina. (Remember that the ophthalmic artery is the first intracranial branch of the internal carotid artery. It supplies blood to the eye via the (1) central retinal artery, which is an end artery that supplies the inner retina, and the (2) ciliary branches, which supply the choroids and anterior portion of globe). Embolism of the retinal artery is the most common cause of ocular stroke. Emboli may travel to the distal branches of the retinal artery, causing loss of only a section of the visual field. It is commonly associated with **amaurosis fugax** before the occlusion. Visual acuity is typically 20/800 (6/240) or worse. Fundoscopy reveals diffuse ischemic 💮**retinal whitening** and **cherry red spots** (typical but not specific for CRAO). ❗ CRAO is an ophthalmologic emergency. A delay in treatment may result in permanent loss of vision. Immediate intervention includes **ocular massage**, which dislodges the embolus to a point further down the arterial circulation and improves retinal perfusion. Medical management and anterior chamber paracentesis to lower the intraocular pressure may be used, but ocular massage has the most rapid action. **Carbogen therapy** (5 % CO2 and 95% O2) or **hyperbaric oxygen (HBO)** therapy have been shown to be beneficial if given early.

Answer 91

Characterized by painless, rapid, and **transient (\<10 minutes) monocular vision loss.** The description of a "**curtain descending over the visual field"** is highly suggestive of this diagnosis. The most common etiology is **retinal ischemia due to atherosclerotic emboli originating from the ipsilateral carotid artery**; therefore, patients with vascular risk factors (eg, hypertension, hyperlipidemia, smoking) should be evaluated with a **duplex ultrasound of the neck.** Funduscopic examination is often normal but may show embolic plaques and retinal **whitening (due to ischemia)**. Patients with amaurosis fugax and concomitant carotid artery disease have an increased risk of stroke.

Answer 92

Acute ACG is characterized by an acute **rise in intraocular pressure (IOP)** due to **impaired drainage of aqueous humor into the anterior chamber** (which normally occurs through the iridocorneal angle). In patients with ACG, the lens is located anatomically more forward and rests against the iris. Acute ACG is more common in women (especially age \>40), Asian and Inuit populations, and individuals with farsightedness. Patients typically develop rapid onset of severe eye pain and may see 😇**halos around lights**. The affected eye will appear injected and the pupil will be dilated and poorly responsive to light. Patients can also develop tearing and headache with subsequent nausea and vomiting as the intraocular pressure increases. Sudden angle closure typically occurs as a response to **pupillary dilation** (**mydriasis**) from **medications (eg, anticholinergics [tolterodine, trihexylphenidyl], sympathomimetics, and decongestants)** or other stimuli (eg, dim light). **Tx:** Narcotics are used to control the pain. The increased intraocular pressure is reduced with **mannitol, acetazolamide, timolol or 🐡pilocarpine.** **❌ Atropine** should be **avoided** since it can dilate the pupil and worsen the glaucoma. Sometimes, mydriatic agents such as atropine can precipitate glaucoma. **❗ Urgent ophthalmologic consultation** is indicated in patients with suspected ACG as increased IOP can damage the optic nerve and lead to **permanent vision loss.** Untreated acute ACG can lead to severe and permanent vision loss within **2-5 hours of symptom onset.** **Dx:** The gold standard for diagnosis is **gonioscopy**, in which an ophthalmologist uses a specialized prismatic lens with a slit lamp to visualize the iridocorneal angle. **Ocular** (eg, Schiotz) **tonometry** measures IOP and can provide additional information if needed or if ophthalmologic consultation is not immediately available. The device is placed against the anesthetized cornea, quantitated pressure is applied, and the resulting indentation is measured. ACG management may include pressure-lowering eye drops and laser or surgical interventions (eg, iridotomy or iridectomy).

Answer 93

**Oculomotor nerve (CN III) palsy.** The most common cause of CN III palsy in adults is ischemic neuropathy due to poorly controlled diabetes mellitus. CN III has 2 major components as follows: * **Inner somatic fibers** - innervate the levator muscle of the eyelid and 4 of the extraocular muscles (EOMs) (superior rectus, medial rectus, inferior rectus, inferior oblique) * **Superficial parasympathetic fibers** - innervate the sphincter of the iris and the ciliary muscles (controlling pupil constriction). Because the inner somatic fibers are farther from the blood supply, they are more susceptible to ischemic injury. Therefore, patients with ischemic CN III palsy typically have paralysis of the levator muscle (ptosis) and 4 EOMs **("down-and-out-gaze")** with preserved pupillary response.

Answer 94

(ie, viral or parasitic infection within the eye) presents as blurred vision with moderate pain, conjunctival injection, and constricted pupils. **Hypopyon** (cell layering within the anterior chamber) is seen in severe anterior uveitis. **Keratic precipitates ("mutton fat")** and **iris nodules** may be seen. It is associated with HLA B27-related conditions.

Answer 95

Retinal detachment refers to the separation of the layers of the retina. It usually occurs in people aged 40-70 years. Patients complain of **photopsia** (flashes of light) and **floaters** (spots in the visual field.). The most classic description is that of **"a curtain coming down over my eyes."** Usually, the inciting event occurs months before retinal detachment. Myopia or trauma can cause retinal breaks, through which fluid seeps in and separates the retinal layers. Ophthalmoscopic examination reveals a **grey, elevated retina.** Laser therapy and cryotherapy are done to create permanent adhesions between the neurosensory retina, retinal pigment epithelium, and choroid.

Answer 96

Vitreous hemorrhage typically presents as a **sudden loss of vision** and onset of **floaters**. The most common cause is **diabetic retinopathy.** An important diagnostic clue is that the fundus is hard to visualize, and even if it is visualized, details may be obscured. Immediate **ophthalmologic consultation** is required. For patients with underlying medical conditions, conservative treatment (i.e., upright position during sleep, which enhances settling of the hemorrhage) is recommended.

Answer 97

Blepharospasm is usually bilateral and symmetric. When associated with spasm of the lower face (eg, jaw, tongue), it is termed Meige syndrome. Blepharospasm is commonly affected by sensory input; **bright lights** may trigger the muscle contraction, whereas touching or brushing the skin around the eye may terminate the spasm ("sensory trick"). Blepharospasm can be caused by certain movement disorders (eg, Parkinson disease) or medications (eg, antipsychotics), but most cases are idiopathic (ie, benign essential blepharospasm). It should be differentiated from simple eyelid twitching, which causes fleeting, minor lid contractions that are unilateral and do not affect vision. Mild cases may be managed with trigger avoidance, such as wearing dark glasses to block bright lights, but botulinum toxin injection may be needed for more significant symptoms.

Answer 98

Macular degeneration typically presents as painless, progressive blurring of central vision, which can be acute or insidious. It occurs bilaterally. Testing reveals central scotoma. Ophthalmoscopy reveals growth of abnormal vessels in the retinal space.

Answer 99

Optic neuritis is commonly associated with multiple sclerosis but can be seen with other disorders as well. It typically presents as unilateral eye pain and vision loss with an associated afferent pupillary defect.

Answer 100

Pathogenesis * Neural crest origin * Involves adrenal medulla, sympathetic chain Clinical features * Median age \<2 * Abdominal mass * Periorbital ecchymoses (orbital metastases) * Spinal cord compression from epidural invasion ("dumbbell tumor”) * Opsoclonus-myoclonus syndrome Diagnostic findings * Elevated **urine and serum catecholamine** metabolites * Small, round blue cells on histology * N-myc gene amplification Neuroblastoma is a childhood malignancy derived from primitive sympathetic ganglia and may arise anywhere along the sympathetic chain or within the **adrenal medulla**. Most cases are diagnosed at age \<2, and classic presentation includes a palpable abdominal mass with systemic symptoms (eg, fever, weight loss). Patients may also present with periorbital ecchymoses **("raccoon eyes")**, which are caused by orbital metastases that obstruct palpebral blood vessels. Opsoclonus, or rapid eye movements, is a rare autoimmune paraneoplastic finding that may present in conjunction with myoclonus, or rhythmic jerking of the trunk or extremities, and is called **opsoclonus-myoclonus syndrome 👀.** Tumor involvement of the **cervical paravertebral sympathetic chain** can lead to ipsilateral **Horner syndrome (ie, ptosis, miosis, anhidrosis)**. Although sweating is often difficult to appreciate in young children, absent **facial flushing (ie, "harlequin" sign)** can be observed in anhidrotic areas.

Answer 101

A child who has a subacute disorder of the CNS that produces cranial nerve abnormalities (especially of cranial nerve VII and the lower bulbar nerves), long-tract signs, unsteady gait secondary to spasticity, and some behavioral changes is most likely to have a **pontine glioma**. These diffuse tumors are difficult to treat. Tumors of the cerebellar hemispheres can, in later stages, produce upper motor neuron signs, but the gait disturbance would be ataxia. Dysmetria and nystagmus also would be present. Supratentorial tumors are quite common in 6-year-old children; headache and vomiting likely would be the presenting symptoms and papilledema a finding on physical examination.

Answer 102

Do not cross the suture line, since they are subperiosteal hemorrhages. No discoloration of the scalp is seen, and the swelling usually progresses over the first few hours of life. Occasionally, skull fractures are present as well. Most cephalohematomas resolve within the first few weeks or months of life without residual findings.

Answer 103

**Simple, primary craniosynostosis** (simple = only one suture; primary = not because of failure of brain growth). This condition is usually sporadic (occurring in 1 in 2000 births) and more commonly affects the sagittal suture, which results in scaphocephaly (a long and narrow skull). In general, premature fusion of a single suture does not cause increased intracranial pressure or hydrocephalus; these features are more common with premature fusion of two or more sutures. The therapy for this condition is controversial, but usually involves surgery; consultation with a neurosurgeon would be indicated. Craniosynostosis is associated with genetic defects in 10% to 20% of cases. A child whose examination or history is not normal (developmental delay, polydactyly or syndactyly, unusually shaped digits or eyes, etc.) is more likely to have a genetic defect as the cause of the craniosynostosis. In these patients, chromosome evaluation for conditions such as Chotzen, Pfeiffer, Crouzon, Carpenter, or Apert syndromes is appropriate.

Answer 104

A supratentorial tumor classically presents with seizures, weakness, and sensory changes, whereas a posterior fossa tumor typically presents with cerebellar dysfunction (eg, ataxia, dysmetria). Signs of increased intracranial pressure (ICP) (eg, early-morning headache/vomiting, papilledema) can occur as the tumor enlarges, regardless of tumor location. **Pilocytic astrocytoma:** A type of low-grade glioma that typically causes symptoms due to local pressure on adjacent structures. Pilocytic astrocytomas most commonly arise in the **cerebellar** hemispheres. Lesions of the cerebellum typically affect fine motor planning and coordination, leading to dysmetria and intention tremor (eg, poor handwriting), as well as dysdiadochokinesia, which refers to the impaired ability to perform rapid, alternating movements. Given their proximity to the fourth ventricle, pilocytic astrocytomas can also present with signs of increased **ICP due to obstructive hydrocephalus** (eg, headaches, vomiting, ataxia, papilledema). **Medulloblastomas** are the second most common cerebellar tumors in children. They are high-grade tumors that occur in the cerebellar vermis or midline, leading to **truncal and gait ataxia.** **Pineal tumors** typically present with Parinaud syndrome (**limitation of upward gaze**, light-near dissociation, and eyelid retraction) and obstructive hydrocephalus given their proximity to the pretectal region of the midbrain. **Glioblastomas** are supratentorial, high-grade astrocytic tumors that typically arise in the cerebral hemispheres and present with seizures and signs of increased ICP. **Ependymomas** are glial cell tumors that arise from the ependymal cell lining of the ventricles and spinal cord. In children, the most common site is the fourth ventricle in the posterior fossa, where tumor expansion leads to obstruction of cerebrospinal fluid and increased ICP.

Answer 105

Cerebellar * Ataxic: Staggering, wide-based * Dysdiadochokinesia, dysmetria, nystagmus, Romberg sign * Cerebellar degeneration * Stroke * Drug/alcohol intoxication * Vitamin B12deficiency Gait apraxia (frontal gait) * Magnetic (freezing): * Start & turn hesitation * Dementia, incontinence, frontal lobe signs * Frontal lobe degeneration * Normal pressure hydrocephalus Parkinsonian * Short steps, shuffling * Bradykinesia, resting tremor, postural instability, decreased arm swing * Parkinson disease Steppage * **Footdrop**, excessive hip & knee flexion while walking, slapping quality, falls * Distal sensory loss & weakness * Motor neuropathy Vestibular * Unsteady, falling to one side * Normal sensation, reflexes & motor strength; nausea, vertigo * Acute labyrinthitis * Ménière disease Foot drop is due to weakness in foot dorsiflexion. To compensate for this, patients must flex the hip and knee to raise the foot and avoid dragging the toe with each step. **Steppage gait** is most commonly caused by L5 radiculopathy or neuropathy of the **common peroneal nerve**. L5 radiculopathy is typified by back pain radiating to the foot, often with weakness of foot inversion and plantar flexion. Peroneal neuropathy is due to compression of the nerve at the lateral aspect of the fibula (eg, due to prolonged crossing of the legs or squatting) and is associated with paresthesias and sensory loss over the dorsum of the foot but normal foot inversion and plantar flexion. The diagnosis can be clarified with electromyography and nerve conduction studies.