Adult neuro syndromes

Question 1

Benign fasiculation syndromes

Answer 1

Benign fasciculation syndromes presents with fasciculations in multiple muscles without associated cramps or weakness. Neurologic examination and electrodiagnostic testing are necessary to ensure that the patient does not have motor neuron disease or cramp-fasciculation syndrome. Patients can improve with withdrawal of caffeinated substances or treatment to allay anxiety.

Question 2

Type 1 Charcot-marie-tooth

Answer 2

The history and examination are consistent with type 1 Charcot-Marie-Tooth disease (CMT1), the most common form of CMT disease. CMT1 is an inherited autosomal dominant sensory and motor peripheral neuropathy with hypertrophic demyelinating pathology. The most commonly present genetic alterations are either duplications or point mutations on the PMP22 gene. Nerve conduction slowing with velocities less than 30 m/s is characteristic. The other gene alterations listed are associated with CMT2, an axonal CMT variant typically manifesting nerve conduction velocities faster than 40 m/s.

Question 3

multifocal motor neuropathy

Answer 3

Painless asymmetric weakness is a classic presentation of motor neuron disease. In patients with no evidence of upper motor neuron involvement, a diagnosis of multifocal motor neuropathy (MMN) must be excluded. Partial motor conduction blocks are a diagnostic hallmark of MMN.

Question 4

APO-e4

Answer 4

The APOE-4 gene located on chromosome 19 is associated with late-onset Alzheimer disease.

Question 5

Presenilin 1, presenilin 2 and amyloid precursor protein

Answer 5

Presenilin 1, presenilin 2 and amyloid precursor protein are associated with early-onset Alzheimer disease.

Question 6

tau

Answer 6

The protein tau is encoded by MAPT and is implicated in the pathogenesis of frontotemporal dementia.

Question 7

area postrema

Answer 7

An area postrema syndrome, characterized by intractable hiccups, nausea, and vomiting, occurs in up to 43 % of patients with Neuromyelitis Optica Spectrum Disorder.

Question 8

Adult-onset polyglucosan body disease

Answer 8

Adult-onset polyglucosan body disease is a disorder typically presenting in the fifth to seventh decades of life. Patients present with gait difficulties with lower and upper motor neuron involvement and peripheral neuropathy, with sensory deficits predominantly in the lower extremities, neurogenic bladder, and dementia. The combination of lower and upper motor neuron signs with leukoencephalopathy should lead the clinician to suspect this entity.

Question 9

dystonic reaction to reglan

Answer 9

Acute dystonic reactions are often observed after treatment with potent dopamine D2-receptor antagonists, including metoclopramide. Cervical and limb dystonia are most common. Laryngeal dystonia may be a life-threatening form of dystonic reaction in these patients. Anticholinergic medication, including diphenhydramine, is the most appropriate treatment.

Question 10

recovery following stroke

Answer 10

Although the pattern of recovery following a stroke may be variable, the earliest evidence of a return of neurologic function is usually an increase in tone. This generally occurs before improvement in strength or a return of reflexes.

Question 11

primary progressive aphasia

Answer 11

Primary progressive aphasia (PPA) is a frontotemporal dementia (frontotemporal degeneration, FTD) that is characterized initially by word-finding trouble, difficulty with naming, and comprehension. These language features are typically a dominant component of the disease in the first 2 years. Patients can later develop dysfunction in other domains, and late stage PPA patients may not appear that different from patients with other late stage dementias.

Question 12

management of toxo

Answer 12

Because of the high likelihood of toxoplasmosis empiric antibiotic therapy with pyrimethamine and sulfadiazine is appropriate. If the patient improves after 2 weeks of therapy, the drugs should be continued for at least 6 weeks. If he fails to improve after 2 weeks, then brain biopsy should be considered to rule out other disorders.

Question 13

MS drug to use during pregnancy

Answer 13

At this time glaterimer acetate is considered the safest agent to use during pregnancy and lactation. Ideally this individual should be transitioned to GA 1-2 months prior to conception.

Question 14

Spinal bulbar muscular atrophy (Kennedy disease)

Answer 14

Spinal bulbar muscular atrophy (Kennedy disease) is characterized by lower motor neuron findings, especially affecting cranial musculature associated with decreased libido and gynecomastia. Female carriers are asymptomatic. Muscle biopsy shows nondiagnostic neuropathic changes. Testicular biopsy shows diminished spermatozoids with abnormal motility and mild elevation of FSH and LH. Diagnosis is by DNA analysis which shows expanded CAG repeats translated into polyglutamine repeats.

Question 15

copper deficiency

Answer 15

This patient has subacute syndrome of pyramidal tract and dorsal column impairment due to copper deficiency. Alpha-tocopherol transfer protein gene mutation would present typically in childhood with gradual onset. A complete blood count might be abnormal, but not diagnostic. MRI of the spine might show increased T2 signal in the dorsal columns in several acquired nutritional deficiencies, but may be normal. Copper deficiency should be considered in patients with myelopathy following gastric surgery, or after zinc overdose.

Question 16

abscess v tumor on DWI/ADC

Answer 16

Cerebral abscess can be distinguished from recurrent tumor based on differences in diffusion weighted imaging and ADC maps. Both demonstrate a ring-enhancing mass with surrounding T2 hyperintensity representing brain edema. Abscesses are characterized by marked hyperintensity on DWI in the cavity and corresponding hypointensity on ADC imaging. The opposite pattern is seen with recurrent tumor.

Question 17

dopa-responsive dystonia

Answer 17

Dopa-responsive dystonia (DRD) presents in childhood as a progressive dystonia in children without a history of cerebral palsy or cognitive delay. It typically starts in a foot and progresses to become generalized. The most common inheritance pattern is autosomal dominant. The disease is unique for its robust and sustained response to low doses of levodopa. Its most notable characteristic is a diurnal variation, with symptoms usually more severe towards the end of the day and improved in the morning.

Question 18

Isoniazid neurologic side effect

Answer 18

Isoniazid (INH), used in treatment of tuberculosis, depletes pyridoxine by increasing its excretion in urine. It can produce a predominantly sensory axonal neuropathy which is largely preventable with co-administration of vitamin B6 (pyridoxine).

Question 19

cisplatin neurologic side effect

Answer 19

Cisplastin, a chemotherapeutic agent in common use for solid organ cancers, binds to and injures DNA, causing a sensory neuronopathy. There is no known preventative treatment.

Question 20

stavudine neurologic side effect

Answer 20

Stavudine is a nucleoside analog still used in some developing countries for treatment of HIV. It produces a painful neuropathy which is not preventable.

Question 21

docetaxel neurologic side effecrt

Answer 21

Docetaxel is a powerful chemotherapeutic agent which interferes with microtubule formation and disrupts axonal transport. Multiple supplements have been tried in an effort to prevent neuropathy from this agent, thus far without success.

Question 22

vincristine neurologic side effect

Answer 22

Vincristine is another common chemotherapeutic agent used primarily in the treatment of leukemias and lymphomas. It interferes with mitosis and microtubule formation, producing a neuropathy which is not preventable.

Question 23

Distal Acquired Demyelinating Symmetric Neuropathy

Answer 23

Distal Acquired Demyelinating Symmetric Neuropathy is a variant of CIDP that is slower in progression and characterized by predominantly sensory symptoms that are both symmetric and distal. Cases that are associated with an IgM paraprotein tend to be resistant to immunomodulatory therapies.

Question 24

Fingolimod (gilenya)

Answer 24

Fingolimod interacts with sphingosine-1-phosphate receptor subtypes. Potential side effects include first-dose bradyarrhythmias,macular edema, increased hepatic transaminases, blood pressure elevations and mild decrease in one second forced expiratory volume.

Question 25

elderly with acute onset vertigo

Answer 25

Cerebrovascular disease is always a concern in older individuals presenting with acute onset vertigo, especially with underlying stroke risk factors. Brain MRI may be normal within the first 48 hours in cases of posterior circulation stroke. In this setting, the presence of either skew eye deviation, normal head impulse test, or direction changing nystagmus in eccentric gaze, is highly sensitive and specific for acute brainstem or cerebellar stroke.

Question 26

acute migraine management in pregnancy

Answer 26

Of those listed, Promethazine is the recommended first line agent during pregnancy. Although ibuprofen can be used for headache management in pregnancy, it is not advisable in the 3rd trimester. Sumatriptan is probably safe but not recommended as a first line agent. Ergotamine can trigger miscarriages and should not be used.

Question 27

migraine ppx in pregnancy

Answer 27

Amitriptyline can be safely used for migraine prophylaxis during pregnancy.

Question 28

CJD diagnosis

Answer 28

The patient’s presentation is strongly suggestive of Creutzfeldt-Jakob disease (CJD). The otherwise unremarkable MRI and normal routine CSF parameters are consistent with CJD. Diffusion-weighted MRI demonstrates restricted diffusion in the cortical mantle and basal ganglia, characteristic of this disorder. Of the biomarkers listed, total CSF tau is the most specific and sensitive, followed by neuron-specific enolase and 14-3-3 protein.

Question 29

PSP

Answer 29

Progressive supranuclear palsy is a neurodegenerative disorder that begins with falls and is characterized by vertical gaze palsy, rigidity, dysarthria, cognitive decline and parkinsonian features. Pathologic features include tau positive inclusions that are most commonly found in the basal ganglia

Question 30

corticobasilar degeneration

Answer 30

Corticobasal degeneration is a progressive asymmetric movement disorder that presents with abnormalities in one limb or on one side of the body.

Question 31

MSA

Answer 31

Multiple system atrophy has parkinsonian features as well but also has dysautonomia, pyramidal signs or cerebellar symptoms.

Question 32

Want to start carbamazepine for localziation related epilepsy in an asian patient

Answer 32

This patient’s Asian descent puts her at a 5% risk of fatal skin reactions such as Stevens-Johnson syndrome if she has the HLA-B1502 allele. Therefore, she should be screened for the HLA-B1502 allele prior to starting therapy.

Question 33

amnestic MCI

Answer 33

Amnestic mild cognitive impairment (aMCI) is, neuropathologically, most often a precursor state to Alzheimer disease. As such, there is medial temporal lobe pathology demonstrated. This is reflected in MRI studies, which have shown decreased hippocampal volume as an independent predictor for the development of dementia in subjects with aMCI.

Question 34

ALS diagnosis and genetics

Answer 34

The history and examination conform to a diagnosis of probable ALS by revised El Escorial Criteria (both upper and lower motor neuron signs in at least 2 regions, and UMN signs above LMN signs). The pedigree suggests familial ALS (FALS) with an autosomal dominant inheritance. UBQLN2 has been linked to autosomal recessive FALS. All of the other genotypes are linked to autosomal dominant FALS with variable penetrance. Of these, the C9orf72 mutation is currently thought to be the most common genetic mutation found in FALS world-wide.

Question 35

Post-transplant acute limbic encephalitis (PALE)

Answer 35

Post-transplant acute limbic encephalitis (PALE) is associated with the onset of an amnestic syndrome typically within 60 days of a bone marrow transplant. The clinical picture usually progresses to an encephalitis with refractory seizures. The syndrome is usually caused by human herpes virus 6 and should be treated with anti-viral therapy.

Question 36

cataplexy

Answer 36

This patient describes cataplexy which is a disorder characterized by the sudden loss of lower limb tone with preserved consciousness. Attacks can be triggered by laughter, anger or shock. Cataplexy is associated with excessive daytime sleepiness, sleep paralysis, and hypnagogic hallucinations. Cataplectic manifestations may be subtle and consist of mild slurring of speech, buckling of knees, jaw dropping or head nodding.

Question 37

congenital myotonic dystrophy type 1

Answer 37

The patient described most likely has Congenital Myotonic Dystrophy Type 1, based on the clinical presentation of myotonic facies, hypotonia and swallowing problems. His mother, never previously diagnosed, has clinical myotonia, suggesting the phenomenon of anticipation wherein the mother has a much milder genetic defect– the CTG trinucleotide expansion –and can have a severely affected child.

Question 38

predicting neurologic outcome in hypoxic ischemic injury

Answer 38

In patients not treated with hypothermia protocols, absence of pupillary or corneal reflexes at 3 days showed a 0% false positive rate (FPR) in predicting poor neurologic outcome, while measurement of neuron-specific enolase has been shown to require much higher values than previously thought (greater than 80 micrograms/L) to achieve a 0% FPR.

Question 39

GBS v CIDP

Answer 39

Both GBS and CIDP are acquired demyelinating autoimmune neuropathies. The CSF and electrodiagnostic findings are quite similar, and cannot distinguish one from the other. The interval between onset of symptoms and disease plateau is the main distinguishing feature, with the vast majority of GBS patients reaching a plateau within four weeks of disease onset.

Question 40

JME

Answer 40

Juvenile myoclonic epilepsy is a generalized epilepsy that presents during late childhood or early adulthood. Classic presentation is often in the setting of sleep deprivation or alcohol exposure. Patients have characteristic myoclonic jerks in the early morning hours. EEG demonstrates a 6 per second spike-and-wave pattern. Treatment with valproate or lamotrigine is indicated once a diagnosis is made and is effective in most patients.

Question 41

west nile virus

Answer 41

West Nile Virus typically presents with fever, headaches and rash. Neurological manifestations include mengitis, encephalitis and in rare cases, an acute flaccid paralysis that involves the anterior horn cells similar to poliomyelitis.

Question 42

lateral medullary syndrome

Answer 42

It is characterized by ipsilateral facial anesthesia, contralateral body anesthesia, ipsilateral Horner syndrome, vertigo, dysarthria, ipsilateral cerebellar dysfunction, and hiccups. Right-sided tongue weakness would be associated with a medial medullary syndrome

Question 43

Fingolimod adverse effects

Answer 43

Fingolimod has been shown to cause bradycardia. EKG monitoring is required during the first dose. Some patients become symptomatic and may even experience syncope.

Question 44

Foster Kennedy syndrome

Answer 44

classically caused by an olfactory groove meningioma. This syndrome is characterized by a lesion involving one or both olfactory nerves and one optic nerve. This results in unilateral or bilateral reduction of olfaction, reduced visual acuity and color vision in the affected eye due to compressive optic neuropathy, and papilledema in the other eye, due to raised intracranial pressure.

Question 45

peripheral nerve hyperexcitability (PNH) or Isaac syndrome

Answer 45

The syndrome is characterized by muscle cramps and stiffness as well as the presence of marked myokymia causing undulating wave-like spontaneous muscle activity that is evident on examination. Caspr2 is an autoantigen of encephalitis and PNH previously attributed to VGKC antibodies. Antibodies are found in approximately 50% of patients.

Question 46

charles bonnet syndrome

Answer 46

The Charles Bonnet syndrome is characterized by complex visual hallucinations in the setting of significant visual deprivation. Most patients are elderly, have normal cognition, and are well aware that the images are not real.

Question 47

episodic ataxia type 2

Answer 47

This patient most likely has episodic ataxia type 2, an autosomal dominant disorder, due to a mutation in the CACNA1A gene encoding for a calcium channel protein. Acetazolamide is the recommended treatment and the response to treatment may even help confirm this disorder.

Question 48

lambert-eaton

Answer 48

The disorder is characterized by impaired release of acetylcholine from the nerve terminal at the neuromuscular junction, due to blockade of the voltage-gated calcium channel by autoantibodies directed against the channel. The potassium channel blocker, 3,4-diaminopyridine enhances the release of acetylcholine by increasing the duration of the action potential, thus improving strength.

Question 49

MELAS

Answer 49

migraines and stroke-like episodes

Question 50

Kearns-Sayre syndrome (KSS) and oculopharyngeal muscular dystrophy (OPMD)

Answer 50

KSS and oculopharyngeal muscular dystrophy (OPMD) both have ptosis, ophthalmoplegia, dysphagia, and proximal weakness. Hearing loss, cerebellar ataxia, and cardiac conduction defects are not features of OPMD but are seen with KSS.

Question 51

Distal acquired demyelinating syndrome and POEMS syndrome

Answer 51

Distal acquired demyelinating syndrome (DADS) is an insidiously progressive distal sensory predominant polyneuropathy with gait dysfunction. Nerve conduction studies classically show markedly prolonged distal motor latencies in the demyelinating range. Up to 67% of these patients have a monoclonal gammopathy, most commonly an IgM kappa paraprotein with reactivity to myelin-associated glycoprotein (MAG). Patients with this paraprotein are less responsive to treatment than patients without a paraprotein. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, m-protein, and skin changes) is another distal sensory motor demyelinating polyneuropathy associated with a paraprotein, usually an IgG lambda.

Question 52

Natalizumab black box warning

Answer 52

PML

Question 53

CADASIL

Answer 53

Cerebral autosomal dominant arteriopathy, with subcortical infarcts and leukoencephalopathy (CADASIL), due to a mutation in the NOTCH3 gene on chromosome 19. This disorder is often associated with progressive focal neurological deficits. Migraine headaches are a common clinical feature as well.

Question 54

anti-musk

Answer 54

Approximately 40% of patients with MG who are antibody-negative for the anti- acetylcholine receptor binding antibody are positive for anti-muscle-specific tyrosine kinase (MuSK) antibodies. Anti-MuSK- antibody-positive MG can clinically resemble anti-acetylcholine-antibody positive MG, but anti-MuSK MG patients may have atypical presentations with prominent facial, bulbar, and neck involvement with relative sparing of ocular muscles. Anti-MuSK- antibody postive patients are also less likely to have thymic hyperplasia or neoplasia, and do not respond to thymectomy.