Neurology Flashcards
What is the most likely diagnosis? What risk factors are associated with this condition?
- This history is consistent with Alzheimer disease, which is characterized by loss of short-term memory and general preservation of long-term memory.
- Advancing age and a family history of Alzheimer disease are two well-known risk factors. Additionally, because the amyloid precursor protein (APP) is located on chromosome 21, patients with Down syndrome (trisomy 21) have increased APP levels; these patients often develop Alzheimer disease at 30–40 years of age. Presenilin 1 is located on chromosome 14 and is noteworthy for its association with early-onset Alzheimer disease. Abnormalities in this gene result in increased β-amyloid accumulation.
How are the causes of dementia classified?
Dementia is classified into reversible and irreversible causes. Reversible causes include major depression, hypothyroidism, and chronic subdural hematoma. Other irreversible causes are vascular dementia, normal- pressure hydrocephalus, and dementia with Lewy bodies.
What are the likely gross pathology findings in Alzheimer disease?
What biochemical mechanism is likely involved in the pathogenesis of this condition?
- Neurofibrillary tangles and amyloid plaques (Figure 10-1) are commonly seen on autopsy. A high degree of cerebral atrophy in the frontal, temporal, and parietal regions is also present.
- A preferential loss of acetylcholine and choline acetyltransferase in the cerebral cortex may play a role in the development of clinical disease.
What is the most appropriate treatment for Alzheimer’s disease?
The acetylcholinesterase inhibitor class of medications, including tacrine, donepezil, rivastigmine, and galantamine, have been shown to slow the progress of memory loss. Memantine, an N-methyl-D-aspartate receptor antagonist, may protect from Alzheimer disease by blocking the excitotoxic effects of glutamate, independently of the effects of acetylcholinesterase inhibitors.
What is the prognosis for the daughter of a patient with Alzheimer’s disease ?
Onset of the familial form of Alzheimer disease, which affects approximately 10% of patients with the disease, is usually 30–60 years of age. Because this patient was older than 70 years of age at onset, she likely does not have the familial form, and the daughter is unlikely to have an increased risk on the basis of family history alone.
What is the most likely diagnosis?
Brown-Séquard syndrome due to a hemicord lesion. Brown- Séquard syndrome is characterized by ipsilateral spastic (upper motor neuron type) paralysis (1 in Figure 10-2), ipsilateral loss of vibration and position sensation (2 in Figure 10-2), and contralateral loss of pain and temperature sensation (3 in Figure 10-2).
At what level is the lesion located?
The loss of sensation up to the navel suggests that the lesion is near T10, because the dermatome that includes the navel is supplied by T10.
Damage to which tracts is causing the ipsilateral deficits in this case?
The motor deficits are due to damage to the lateral corticospinal tract (Figure 10-3), which carries motor neurons from the cortex that have decussated in the pyramids. The loss of vibration and position sense is due to damage to the dorsal columns, which carry information from sensory nerves that enter through the dorsal root, ascend to the caudal medulla (where the primary neuron synapses), and then cross to ascend to the contralateral sensory cortex. These deficits are ipsilateral because the tracts cross the midline high in the spinal cord.
Damage to which tracts is causing the contralateral deficits in this case?
The loss of pain and temperature sensation is due to damage to the spinothalamic tract (Figure 10-3). The sensory neurons that travel in the anterolateral tract enter the spinal cord through the dorsal root, synapse almost immediately, and cross the midline (within one or two levels) via the anterior commissure to ascend to the cortex.
If the lesion were above T1, how would the presentation differ?
A hemicord lesion above T1, in addition to the findings above, will present as Horner syndrome, which consists of ptosis, miosis, and anhidrosis (droopy eyelid, constricted pupil, and decreased sweating).
What is the most likely diagnosis?
Amyotrophic lateral sclerosis (ALS), or Lou Gehrig disease, is a neurodegenerative disorder that causes progressive muscle weakness. There are several ALS variants classified on the basis of their pattern of distribution. Progressive bulbar palsy affects the motor nuclei of cranial nerves, and pseudobulbar palsy describes any condition that causes bilateral corticobulbar disease. Progressive spinal muscular atrophy is a lower motor neuron deficit involving anterior horn cells of the spinal cord. Primary lateral sclerosis predominantly affects the upper motor neurons.
Where are the lesions located and how does this explain the hallmark findings?
The hallmark of this disorder is the presence of both upper motor neuron (UMN) and lower motor neuron (LMN) lesions. ALS affects anterior horn motor neurons in the spinal cord (LMN) and the lateral corticospinal tracts carrying UMNs from the cortex. Sensory and cognitive functions are generally preserved.
How is Amyotrophic lateral sclerosis (ALS) distinguished from the ascending paralysis syndromes?
ALS has both UMN and LMN findings whereas Guillain Barré syndrome (or acute inflammatory demyelinating polyradiculoneuropathy) and chronic inflammatory demyelinating polyradiculoneuropathy are solely LMN diseases and present with characteristic decreased reflex response.
What distinguishes UMN signs from LMN signs?
UMN signs include hyperreflexivity, increased tone, positive Babinski sign, and muscle spasm. LMN signs include weakness, muscle atrophy, and muscle fasciculations.
What is the course of Amyotrophic lateral sclerosis (ALS)?
ALS is currently an untreatable disease with progressive neurodegeneration and muscle weakness, resulting in death within 3–5 years of diagnosis. Riluzole can prolong survival by 2–3 months, likely by blocking glutamatergic transmission in the central nervous system (CNS). Supportive care, including dietary modification, respiratory assistance, and palliative care, is an important part of management. Neuromuscular respiratory failure is the primary cause of death.
What is the most likely diagnosis?
The student has a corneal abrasion, which typically presents with significant eye pain and a foreign body sensation. The patient will also have photophobia. This patient’s history suggests the source for his eye injury: working with machinery without wearing protective eyewear. Other etiologies of acute unilateral vision impairment are optic neuritis, retinal detachment or tear, giant cell arteritis, and amaurosis fugax.
What is the pathway of the corneal blink reflex?
The excruciating pain experienced by this patient is due to the rich innervation of the cornea by the ophthalmic branch of cranial nerve (CN) V (V1). This nerve constitutes the afferent portion of the corneal blink reflex. After synapsing in the sensory nucleus of CN V, there is bilateral projection to the nucleus of CN VII. From there, motor neurons project to the orbicularis oculi muscles, causing a consensual blink response.
What space lies between the cornea and the lens?
The space between the cornea and the lens is the anterior compartment, which is subdivided by the iris into the anterior chamber and the posterior chamber (Figure 10-4). The entire anterior compartment is filled with aqueous humor, which is secreted by the ciliary body.
What space lies behind the lens?
Behind the lens is the posterior compartment (Figure 10-4), which is filled with vitreous humor, a gelatinous substance. At the anterior aspect of the posterior compartment, the lens is held in place by the suspensory ligament, which extends from the ciliary body of the choroid to the lens.
From what embryologic structures do the cornea, iris, ciliary body, lens, and retina develop?
The optic cup is an embryologic structure derived from neuroectoderm that gives rise to the retina, iris, and ciliary body. The lens is derived from surface ectoderm. The inner layers of the cornea are derived from mesenchyme, and the outer layer derives from the surface ectoderm.
What is the most likely diagnosis?
Central cord syndrome. This syndrome is characterized by upper extremity weakness that exceeds lower extremity weakness and varying degrees of sensory loss below the level of the lesion.
What is the arterial supply to the cervical spinal cord?
The spinal cord is supplied by an anterior spinal artery (which is supplied by the vertebral arteries) that supplies the anterior two-thirds of the cord and by two posterior spinal arteries (which are supplied by the vertebral posterior inferior cerebellar arteries) that supply the dorsal columns and part of the posterior horns.
What is a vascular watershed zone?
A watershed zone is an area between two major arteries in which small branches of the arteries form anastomoses. Important watershed zones lie between the cerebral arteries (eg, middle and anterior cerebral arteries) and in the central spinal cord. These areas are susceptible to infarction during hypotension or hypoperfusion. In this case, edema and trauma impair blood flow to the cervical cord, and the predominant symptoms result from damage within the central cord watershed zone.
What is supplied by the long tracts in the areas labeled “Region A” in Figure 10-5?
Region A in Figure 10-5 indicates the most medial portions of the corticospinal tracts. These fibers supply the muscles of the upper extremity. Because they are medial structures, motor impairment of the upper extremities can occur after a smaller central cord lesion. The cross-hatched pattern in Figure 10-6 indicates the area of impairment that is associated with a central cord lesion.
What changes in the biceps, triceps, and brachioradialis reflexes are expected after damage to the anterior horn cells supplying the C6 nerve root?
The biceps reflex, which is regulated by fibers from C5 and C6, will be moderately diminished secondary to diminished lower motor neuron input. The triceps reflex is regulated primarily by C7 and should thus be unaffected by a C6 lesion. The brachioradialis reflex is primarily regulated by C6 and will thus be markedly diminished after a C6 lesion.
What is the most likely diagnosis?
What are other causes of short stature?
- The hallmark lesion for craniopharyngioma is a suprasellar, cystic, calcified mass. The differential diagnosis for a suprasellar mass includes optic gliomas, meningiomas, pituitary adenomas, and metastases.
- Other causes of short stature can arise from endocrine disorders including Cushing syndrome, growth hormone deficiency, hypothyroidism, and gastrointestinal disorders including malabsorption syndromes such as celiac disease, lactase deficiency, or inflammatory bowel disease.
From what tissue does the tumor in Craniopharyngiomas derive?
Craniopharyngiomas are rare tumors derived from the Rathke pouch. The Rathke pouch is an invagination of ectoderm lining the primitive mouth that develops into the adenohypophysis.
What tests or imaging tools may be used to confirm the diagnosis of Craniopharyngiomas?
CT scan or MRI of the head can visualize the cystic calcified suprasellar mass characteristic of craniopharyngioma. Plain radiographs of the skull can detect advanced cases. Testing of the pituitary axis and optic pathways can determine if the tumor has affected these structures.
What is the epidemiology of Craniopharyngiomas?
What are the clinical manifestations?
Craniopharyngiomas
- Epidemiology: Craniopharyngiomas exhibit a bimodal distribution, with one peak among children and the second among patients 55–65 years of age. It is the third most common intracranial tumor in children.
- Clinical manifestations: Craniopharyngiomas are slow-growing tumors with a highly variable clinical presentation. Symptoms occur because the tumor involves the pituitary gland or the optic chiasm. Patients may present with growth hormone deficiency, hypothyroidism, or central diabetes insipidus. Visual disturbances and headaches are common.
What is the cause of the patient’s hoarseness? What cranial nerve is involved in this patient? This nerve provides motor innervation to which structures?
- This patient underwent surgery for hyperthyroidism. Damage to the recurrent laryngeal nerve may occur as the surgeon is ligating the inferior thyroid artery, which is adjacent to the nerve.
- The recurrent laryngeal nerve is a branch of the vagus nerve (CN X).
- The recurrent laryngeal nerve innervates all intrinsic muscles of the larynx except for the cricothyroid, which is innervated by the external laryngeal nerve (also a branch of CN X).
What is the course of the recurrent laryngeal nerve?
The left recurrent laryngeal nerve branches off the vagus nerve at the level of the aortic arch, wraps posteriorly around the aorta, and ascends superiorly to the larynx (Figure 10-8). The right recurrent laryngeal nerve branches off the vagus at the level of the right subclavian artery and vein and wraps around the artery to ascend posteriorly to the larynx. Because the left recurrent laryngeal nerve has a long course arising from the vagus in the superior mediastinum, it is prone to injury from abnormal structures, such as enlarged lymph nodes, aneurysm of the arch of the aorta, a retrosternal goiter, or a thymoma.
What other structures can be damaged during surgery for hyperthyroidism?
What are other scenarios in which the left recurrent laryngeal nerve may be injured?
- Surgical technique focuses on preservation of the parathyroid glands, and hypoparathyroidism can occur after surgery. For this reason surgeons often remove the parathyroid gland and reimplant it elsewhere in the neck.
- Left atrial enlargement (eg, from mitral regurgitation) and tumor in the apex of the right upper lobe of the lung can impinge on and injure the recurrent laryngeal nerve. Injury of the left recurrent laryngeal nerve may also result in compression by abnormal structures in the superior mediastinum, as described above.
What is the most likely diagnosis?
Weakness of the quadriceps muscles and hip flexors (which are innervated by the femoral nerve) and lack of patellar reflex suggests femoral neuropathy (L2–L4). The cause of the neuropathy in this case is a hematoma (secondary to trauma) compressing the nerve. Because both the hip flexors (L2–L3) and the quadriceps muscles (L3–L4) are involved, the nerve is affected above the inguinal ligament. If the compression had affected the nerve distal to the inguinal ligament where the nerve branches into anterior and posterior divisions, a deficiency in either the hip flexors (anterior) or the quadriceps muscles (posterior), but not both, would be expected.
What sensory defects are expected in this patient?
The femoral nerve innervates the skin of the anterior and medial thigh; thus, light touch sensation is decreased in these areas. The lateral aspect of the thigh is innervated by the lateral femoral cutaneous nerve (L2–L3) and is spared in an isolated femoral neuropathy. The saphenous nerve is a cutaneous branch of the femoral nerve that arises from the femoral nerve in the femoral triangle. It innervates the skin of the anteromedial knee, leg, and foot to the medial side of the big toe. Because this lesion is above the femoral ligament, the saphenous nerve distribution is also involved.
What other structures are found with the femoral nerve in the femoral triangle?
The femoral nerve is the largest branch of the lumbar plexus and, after forming in the abdomen, runs posterolaterally to the inguinal ligament. It crosses under the inguinal ligament lateral to the psoas muscle and enters the femoral triangle. In the femoral triangle (bounded by the sartorius muscle, inguinal ligament, and adductor longus), it runs lateral to the femoral artery, which is lateral to the femoral vein. The vessels are enclosed within the femoral sheath and the nerve is outside it.
Why is thigh adduction spared in this patient with femoral neuropathy (L2-L4)?
The major muscles responsible for thigh adduction are the adductor longus, adductor brevis, adductor magnus, and the gracilis, which are innervated by the obturator nerve (L2–L4). Because this is a peripheral neuropathy, not pathology of the nerve root, the obturator nerve is spared and so is thigh adduction.
What are 7 other clinical scenarios that can be associated with femoral neuropathy (L2-L4)?
- Diabetic vasculitic damage.
- Direct penetrating trauma.
- Hip fracture.
- Iliac aneurysms.
- Incorrect placement of the femoral line.
- Prolonged hip flexion during gynecologic or urologic procedures.
- Tumor.
What is the most likely diagnosis? What is the pathophysiology of this condition?
- Open-angle glaucoma is the most common form of glaucoma in the United States (90%) and presents as progressive, painless visual loss. Closed-angle glaucoma is painful and can cause additional symptoms such as seeing halos around lights and red eye.
- Open-angle glaucoma is caused by elevated intraocular pressure resulting from obstruction of flow of aqueous humor through the normal outflow channels (Figure 10-9).
What are the appropriate treatments for open-angle glaucoma?
The direct cholinergic agonists pilocarpine and carbachol are used to treat open-angle glaucoma. These agents act by stimulating ciliary muscle contraction, thereby relieving tension in the suspensory ligament. Cholinomimetics also stimulate the sphincter pupillae of the iris, which widens the canal of Schlemm and constricts the pupil (miosis). Adverse effects include nausea, vomiting, diarrhea, salivation, sweating, vasodilation, and bronchoconstriction.
What effect does pilocarpine have on cardiac muscle?
Pilocarpine is an M3/M2 muscarinic receptor agonist. Cardiac cells have M2 receptors that, when activated, stimulate a G protein that inhibits adenyl cyclase and increases potassium conductance. Pilocarpine stimulation decreases the heart rate and the force of contraction (negative inotrope).
Other than direct cholinergic agonists, what are 3 additional classes of drugs that are useful in treating Open-angle glaucoma?
Other drug classes used to treat open-angle glaucoma include the following:
1. Adrenergic agonists such as epinephrine.
2. β-Blockers and acetazolamide (a carbonic anhydrase inhibitor), which decrease aqueous humorsecretion.
3. Prostaglandins, which increase the outflow of aqueous humor.
What is the most likely diagnosis? Where are these lesions typically located?
- Glioblastoma multiforme (GBM), the most common primary brain tumor. GBM represents almost 20% of all primary intracranial tumors.
- Glioblastomas are found supratentorially in the cerebral hemispheres and often cross hemispheres via the corpus callosum (“butterfly glioma”) (Figure 10-10).
What are the histologic findings in Glioblastoma multiforme (GBM)?
What is the treatment for this condition?
What is the natural history of this condition?
- Glioblastomas are composed of highly malignant astrocytes that are visualized with a glial fibrillary acidic protein stain. Histology of glioblas- tomas shows pseudopalisading tumor cells surrounding focal areas of necrosis (Figure 10-11).
- Treatment is largely palliative and only moderately increases survival time. Treatment may include surgical resection, radiation, and chemotherapy.
- Glioblastoma is an aggressive tumor; without treatment, most patients die within 3 months of diagnosis. With treatment, the median survival time is 1 year, and < 10% of patients survive 5 years.
What are other common adult brain tumors?
The most common cause of brain tumors in adults is metastases, and their presentation depends on location. Meningiomas derive from dura mater or arachnoid and are usually benign, but severity depends on location. Astrocytoma arises in brain parenchyma, has a better prognosis than GBM, and presents with seizures, headaches, and focal deficits.
What is the most likely diagnosis? What physical findings are commonly associated with this condition?
Guillain-Barré syndrome (GBS), or acute inflammatory demyelinating polyradiculoneuropathy, is characterized by symmetric ascending muscle weakness or paralysis that begins in the lower extremities. Hyporeflexia or areflexia is invariable but may not be present early in the course of disease.
In what settings does Guillain-Barré syndrome (GBS) usually occur?
GBS often occurs 1–3 weeks after a gastrointestinal or upper respiratory tract infection, vaccination, or allergic reaction. Common associated infections include Campylobacter jejuni and herpesvirus. Although a preceding event is present in most patients, approximately one third of patients with GBS report no such events during the preceding 1–4 weeks.
What is the aetiology of Guillain-Barré syndrome (GBS)?
GBS is thought to be an autoimmune reaction that develops in response to a previous infection or other medical condition. This process results in aberrant demyelination of peripheral nerves and ventral motor nerve roots. Cranial nerve roots can also be affected.
What laboratory finding is likely in Guillain-Barré syndrome?
Cerebrospinal fluid (CSF) reveals a markedly elevated protein concentration with a normal cell count, commonly referred to as albuminocytologic dissociation. This contrasts the increased cell counts typical of CNS infection. Increased CSF protein can lead to papilledema.
What is the appropriate treatment for Guillain-Barré syndrome?
The first element of GBS management is supportive care and treatment of the underlying condition with either IVIG antibody or plasmapheresis. Pulmonary function should be monitored with peak flow studies to assess for respiratory failure. Rehabilitation may be required to restore function.
If this patient’s symptoms worsen over the next few months with no signs of improvement, what alternative diagnosis should be considered other than Guillain-Barré syndrome?
Chronic inflammatory demyelinating polyradiculopathy is a chronic, progressive, or chronic progressive counterpart of GBS that often presents with similar symptoms.
What is the most likely diagnosis? What is the pathophysiology of this condition?
Horner syndrome
Horner syndrome results from a disruption in the sympathetic innervation of the face and subsequent uninhibited parasympathetic activity, which produces the classic symptoms: ipsilateral Ptosis (slight drooping of the eyelid), Anhidrosis (absence of sweating), and Miosis (pupillary constriction) (mnemonic: PAM).
What nerve pathway is disrupted in Horner syndrome?
The first neuron of the sympathetic pathway begins in the hypothalamus and synapses in the intermediolateral column of the spinal cord near T1 (Figure 10-14). The second, preganglionic, neuron travels to the superior cervical ganglion. The third and final neuron of the pathway innervates the pupil, the sweat glands of the face, and the smooth muscle of the eyelid.
If this patient presented with nystagmus to the right side and frequent falling, what acute condition should be considered?
Wallenberg syndrome results from a stroke in the lateral medullary region supplied by the posterior inferior cerebellar artery. It can present with ipsilateral Horner syndrome, nystagmus to the side of the lesion, ipsilateral limb ataxia, and vertigo. Another distinguishing feature is impaired pain and temperature sensation in the ipsilateral face and contralateral hemibody.
What are other common causes of Horner syndrome?
Any pathology that interrupts the described pathway can cause Horner syndrome. These include Pancoast tumor, neck trauma, carotid dissection, cervical cord lesions, and multiple sclerosis. Many cases of Horner syndrome are idiopathic.
What is Pancoast tumor?
Pancoast tumor is a carcinoma that usually occurs in the apex of the lung. It can cause Horner syndrome and ulnar nerve pain.
What is the most likely diagnosis?
Hydrocephalus is defined as an excessive volume of cerebrospinal fluid (CSF) within the ventricles of the brain. Because CSF is trapped within the ventricular system, this case is an example of a noncommunicating hydrocephalus. A communicating hydrocephalus can occur in states of excess CSF production. CT scan of the head shows a dilated ventricular system (Figure 10-15) with dilated atria of the lateral ventricles (arrowheads) and rounded third ventricle (arrow).
Other causes of disproportionally large head size or growth include trauma, Canavan disease, and Hurler syndrome.
Where is CSF produced? How is CSF reabsorbed?
- CSF is produced by the choroid plexus epithelium within the cerebral ventricles (Figure 10-16). The lateral ventricle communicates with the third ventricle via the foramen of Monro. The third ventricle communicates with the fourth ventricle via the aqueduct of Sylvius. The fourth ventricle communicates with the subarachnoid space via the foramen of Luschka (laterally) and the foramen of Magendie (medially).
- Arachnoid villus cells, which are located in the superior sagittal sinus, return CSF to the bloodstream within vacuoles (through a process called pinocytosis).
What forms the blood-brain barrier?
Capillary and choroid endothelial cells form the blood-brain barrier. Tight junctions of capillary endothelium within the brain impede the passage of water and solutes. Within the choroid plexus, the choroid endothelium regulates the transport of water and solutes.
What is the pathophysiology of Hydrocephalus? (3)
Hydrocephalus results from a mismatch of CSF production and reabsorption in which the rate of production exceeds reabsorption. Causes of hydrocephalus include the following:
1. Excess CSF production (eg, choroid plexus papilloma).
2. Impaired CSF reabsorption (due to obstruction or disruption of arachnoid villi).
3. Blockage of the flow of CSF.
What is the appropriate treatment for Hydrocephalus?
Treatment is surgical and involves a ventriculoperitoneal shunt, which allows for reabsorption of fluid in the peritoneum.
What condition is the patient at risk for developing?
Huntington disease is characterized by dementia, choreoathetoid movements of the face and extremities, and early death. Huntington disease has an autosomal dominant inheritance. Other causes of early-onset dementia include early-onset Alzheimer disease, multiple sclerosis, HIV infection, or Creutzfeldt-Jakob disease (much rarer).
What is the genetic basis of Huntington disease?
What neuronal pathology in patients with Huntington disease makes CT imaging useful?
- A mutation in chromosome 4 results in expansion of trinucleotide CAG repeats, which may decrease transcription of a striatal neurotrophic factor (brain-derived neurotrophic factor).
- Patients with Huntington disease have marked atrophy of the striatum, including the caudate and putamen, representing degeneration and loss of γ-aminobutyric acid–ergic and cholinergic neurons.
What 3 conditions other than Huntington disease often present with similar movement abnormalities?
- Sydenham chorea in rheumatic fever
- Tardive dyskinesia
- Wilson disease are among other diseases associated with choreoathetoid movements.
What is the prognosis for a patient with Huntington disease?
Expansion of trinucleotide repeats over successive generations leads to earlier manifestations of disease in offspring; this is called anticipation. The patient’s father died at age 45 years and likely developed Huntington disease many years earlier. If this patient had the genetic mutation, he might already be expected to show symptoms.
What conditions, other than Huntington disease are associated with trinucleotide repeats?
Fragile X syndrome, myotonic dystrophy, and spinocerebellar ataxia types I and II are also associated with trinucleotide repeats.
What is the abnormality in this patient’s vision as assessed by the Amsler grid? What is the most likely diagnosis?
- The Amsler grid assesses the degree of central vision loss (Figure 10-19A). In this assessment, patients cover one eye and, with the open eye, focus on the dot at the center of the grid. Patients with vision deficits in their macula see a distortion of the grid (Figure 10-19B).
- Age-related macular degeneration (ARMD), in which central vision is blurred, is a significant cause of vision loss in the elderly. By contrast, glaucoma typically affects peripheral vision while sparing central vision. Central vision loss can also be caused by optic neuritis and cataracts.
What are the two variants of macular degeneration?
There are dry and wet forms of macular degeneration. The dry form (85% of cases) typically progresses more slowly and occurs earlier in the disease process. The wet form, although rarer (% of cases), causes the majority of significant blindness in patients.
What are the histologic features of the retina in macular degeneration?
Drusen are extracellular protein and lipid deposits in the retina, which appear on funduscopic examination as yellow or white spots in the eye (Figure 10-18). Irregularity and, in later stages, atrophy of the retinal pigmented epithelium also occur. In wet ARMD, new vessels from the choroid may grow into the subretinal space, causing metamorphopsia (a wavy distortion of vision), hemorrhage, and scarring.
What is the macula?
The macula, which is located temporal to the optic disc, is the area of the retina that is specialized for fine- detail vision. The center of the macula is the fovea, which has the highest density of cone photoreceptor cells in the retina and the smallest amount of convergence to bipolar cells. This provides for exquisite detail in visual perception.
What is this visual field defect?
The defect is a right homonymous hemianopia likely caused by a stroke. The patient’s symptoms suggest that he has experienced a number of transient ischemic attacks (TIAs). The classical definition of a TIA is a vascular event that causes neurologic deficits that last < 24 hours. Clinically, it is defined as a neurologic deficit that lasts < 1 hour in the absence of abnormal imaging findings.
What is the pathway from photoreceptors in the retina to the visual cortex?
Photoreceptors (rods and cones) synapse on bipolar cells that synapse on ganglion cells in the retina, which form the optic nerve.
The optic nerve travels posteriorly and merges to form the optic chiasm where nasal (medial) retinal fibers from both eyes cross. The nasal hemiretina fibers are responsible for the temporal visual fields. Once past the chiasm it is known as the optic tract, which synapses on the lateral geniculate nucleus (LGN) of the thalamus.
Axons exiting the LGN fan out posteriorly through the white matter. The inferior radiations carry information from the inferior retina or superior visual field, travel through the temporal lobe, and are known as the Meyer loop. The superior radiations carry information from the superior retina or inferior visual field and travel through the parietal lobe.
The optic radiations synapse in the visual cortex of the occipital lobe near the calcarine fissure. The superior radiations synapse superior to the calcarine fissure and the inferior radiations inferior to the fissure (Figure 10-21).
Where along the optic pathway may a lesion be located to give the visual field defect of a right homonymous hemianopia
A lesion in the left optic tract, posterior to the chiasm and anterior to the lateral geniculate nucleus, may be the cause, as may a large lesion affecting the upper and lower optic radiations or a lesion in the left visual cortex.
What visual field defect does a lesion in the right temporal lobe show?
The inferior optic radiations (Meyer loop) travel through the temporal lobe. A lesion to this area shows a left upper quadrantic anopia (“pie in the sky”) as indicated by lesion J in Figure 10-21.
What is the likely diagnosis?
The history suggests medulloblastoma, a highly malignant tumor most often found in the cerebellum. The majority of patients are 4–8 years of age, and males are affected more than females. In children, 70% of intracranial tumors are infratentorial, whereas in adults 70% are supratentorial. Although medulloblastoma is the most common pediatric brain tumor, astrocytoma, brain stem glioma, and ependymomas are also common. Astrocytomas can occur anywhere in the hemispheres and the brain stem. In children, ependymomas typically occur in the fourth ventricle and are characterized by pseudorosettes, in which cells are arranged around vessels with ependymal processes directed toward the vessel wall.
How do cerebellar lesions present?
Lesions can occur in either the vermis or the hemispheres. Cerebellar lesions in the hemispheres cause ipsilateral limb ataxia and loss of muscle tone. Superior vermis lesions are characteristic of Wernicke encephalopathy and alcoholic cerebellar degeneration, presenting with the classic triad of gait or truncal ataxia, ophthalmoplegia, and confusion.
What imaging technique is used to visualize medulloblastomas?
On MRI of the head, medulloblastomas are heterogeneous enhancements located in the cerebellum, often extending into the fourth ventricle (Figure 10-22).
What is the most likely diagnosis? Where are the lesions associated with this condition typically located?
- The location of the lesion on MRI scan is typical of a meningioma. Meningiomas are usually benign, slow- growing tumors arising from the arachnoid cells penetrating the dura. They are the second most common primary brain tumor.
- Meningiomas are found along the dura, most often in the sylvian region, superior parasagittal region, and cerebellopontine angle. Other diseases that commonly involve the dura include lymphoma, metastatic carcinoma, and tuberculosis.
What is the most likely diagnosis?
Acute otitis media. The bulging, red tympanic membrane is a sign of middle ear infection. The clinical course suggests a viral upper respiratory infection leading to secondary involvement of the middle ear due to inflammation and congestion of the eustachian tube. The eustachian tube connects the middle ear to the nasopharynx.
What three bones are located in the middle ear?
The three bones located in the middle ear (auditory ossicles) are the malleus, incus, and stapes (Figure 10-25); together, they transmit sound from the tympanic membrane to the internal ear. The malleus, which articulates with the tympanic membrane, derives from the first branchial arch. The incus, which lies between the malleus and the stapes, derives from the first branchial arch. The stapes, which articulates with the oval window of the inner ear, derives from the second branchial arch.
What is the most likely diagnosis? What is the differential diagnosis for this condition?
- Metastatic brain tumor from her small cell lung cancer. Brain metastases are more prevalent than primary central nervous system tumors.
- The differential diagnosis includes a primary brain tumor, metastatic tumor from a second primary brain tumor, infection, cerebral infarct, or radiation necrosis.
What is the most likely diagnosis? What signs and symptoms are commonly associated with this condition?
Migraine headache.
How is migraine differentiated from other, more serious pathologic conditions of the head?
How can this woman’s migraine headache be differentiated from pseudotumor cerebri, cluster headaches, or tension headaches?
What is the most likely diagnosis? What are the genetics of this condition?
Neurofibromatosis type 1 (NF1), or von Recklinghausen disease, is a common neurocutaneous disorder. NF1 has complete penetrance with variable expression. Diagnosis is made on clinical criteria. Although neurofibromatosis type 2 (NF2) can present with skin lesions, NF2 most commonly causes bilateral acoustic neuromas and eye lesions; approximately 50% of affected patients develop lesions in the spinal cord, cranial nerves, and meninges.
What are the typical dermatologic findings of Neurofibromatosis type 1?
The hallmark finding is six or more hyperpigmented mac- ules called café-au-lait spots. In addition, neurofibromas, multiple soft fleshy tumors, usually develop during adoles- cence (Figure 10-27). Freckling is also present in the axilla and groin. Although NF2 often demonstrates neurofibro- mas, café-au-lait spots are rare in this condition.
What are the typical ophthalmologic findings in Neurofibromatosis type 1 (NF1)?
Patients with this condition are predisposed to what tumors?
Lisch nodules, which are raised, pigmented, hamartomas, are found on the iris (Figure 10-28).
Optic gliomas may arise anywhere along the optic tract, particularly in the optic nerve or chiasm. Patients are also at increased risk for other central nervous system tumors such as astrocytomas and other gliomas. Peripheral neurofibromas can undergo malignant transformation into neurofibrosarcomas.
What is the most likely diagnosis?
Multiple sclerosis (MS). The arrowheads in Figure 10-29 show the lesions of MS.
What anatomic feature could explain the findings on physical examination?
A medial brain stem lesion involving cranial nerves VI, VII, and XII (Figure 10-30) leads to the constellation of facial droop, tongue deviation, and lateral gaze weakness. The intention tremor indicates cerebellar involvement.
What is the most likely diagnosis? What patient characteristics are typically associated with this diagnosis?
- Myasthenia gravis. Differential includes Lambert-Eaton syndrome, which is a paraneoplastic syndrome associated with small cell lung cancer involving muscle weakness; however, strength improves if a contraction is maintained. In myasthenia gravis, symptoms worsen as activity progresses. Lambert-Eaton syndrome also typically spares the extraocular muscles.
- Myasthenia gravis is more commonly seen in women than in men, and most patients are older than 50 years of age when diagnosed.
What is the most likely diagnosis? What is the pathogenesis of this condition?
- Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral acoustic neuromas. Perforation of the eardrum, ototoxic medication, otosclerosis, or Ménière disease can also cause acquired hearing loss in children.
- Mutation of the gene merlin found on chromosome 22 (mnemonic: type 2 = 22). Merlin codes for a protein involved in cytoskeleton components responsible for contact inhibition of tumor progression.
What are the two forms of hearing loss? How do the Weber and Rinne tests distinguish between the two forms of hearing loss?
- Conductive hearing loss involves the ear canal, tympanic membrane, middle ear, and ossicles.
- Sensorineural hearing loss involves the innerear (cochlea), vestibulocochlear nerve, or central processing centers in the brain.
What is the most likely diagnosis? What neuropathologic findings are associated with this condition?
- Parkinson disease typically presents with the following symptoms: Tremor that is worse at rest, Rigidity, Akinesia or bradykinesia, and Postural instability (mnemonic: TRAP).
- Parkinson disease is marked by significant neuronal loss in the substantia nigra, which decreases dopaminergic input into the basal ganglia. Characteristic findings include depigmentation of neurons in the substantia nigra and concentric eosinophilic cytoplasmic inclusions called Lewy bodies (Figure 10-32).
How does a loss of dopamine release from the substantia nigra decrease movement?
Dopamine produced by the substantia nigra activates the direct pathway and inactivates the direct pathway in the basal ganglia. In the direct pathway, dopamine activates the caudate nucleus; this inhibits the globus pallidus internus, which in turn inhibits the ventral lateral thalamus nucleus resulting in frontal motor stimulation. In the indirect pathway, dopamine inhibits the caudate, which inhibits the globus pallidus externus, which in turn inhibits the subthalamic nucleus resulting in stimulation of the globus pallidus internus (the opposite end result as the direct pathway) (Figure 10- 33). In both, decreased dopamine results in inhibition of the frontal motor cortex and bradykinesia.
What is the most likely diagnosis? What class of drugs can cause this condition?
What is the differential diagnosis of a mass in the sella turcica?
- Hyperprolactinemia from a prolactin-secreting anterior pituitary adenoma. Classic symptoms in females are amenorrhea, infertility, and galactorrhea.
- Hyperprolactinemia also occurs in patients on antipsychotic medication. Because dopamine inhibits prolactin production, the dopamine inhibitors cause hyperprolactinemia.
- The differential diagnosis includes pituitary adenoma, pituitary hyperplasia, craniopharyngioma, meningioma, germ cell tumor, chordoma, primary lymphoma, cyst, abscess, or arteriovenous fistula of the cavernous sinus.
What visual disturbance is classically seen with pituitary adenoma?
Bitemporal hemianopia results when the growing pituitary tumor impinges on the optic chiasm (Figure 10-34).
What is the most likely diagnosis?
Seizure. Involvement of the left motor cortex is implicated because the seizure started with right-handed motor activity. In this patient a metastasis is the likely culprit. Seizures can also be caused by infection, ischemia, drug exposure or withdrawal, certain ion imbalances including hypoglycemia and hyponatremia, and trauma.
Why is the patient breathing deeply after her incident?
The patient is likely responding to acidosis. A respiratory acidosis can develop from the loss of coordinated respirations during the seizure, and a metabolic acidosis can develop as muscles contract under anaerobic conditions and produce lactic acid.
What are the most common adverse effects of antiseizure medications?
What is the most likely diagnosis? What 8 risk factors are associated with this condition?
Stroke. Figure 10-35 shows extensive hemorrhage in the thalamus (left arrow) and its extension into the third (top arrow), ipsilateral (bottom arrow), and lateral (right arrow) ventricles.
What type of aphasia does the patient exhibit? A lesion in what anatomic area causes these findings?
- The combination of fluent but nonsensical speech and poor comprehension is characteristic of Wernicke aphasia (sensory aphasia). These patients also display poor repetition and naming ability. Other findings commonly associated with Wernicke aphasia include contralateral visual field cut (due to ischemia of optic radiation) and anosognosia (unawareness of one’s deficit).
- The inferior frontal gyrus controls motor aspects of speech. A stroke in this area causes Broca aphasia (motor aphasia), which is characterized by nonfluent, agrammatic speech. Because of the proximity of the primary motor cortex for the face and arm, dysarthria (difficulty in articulating words) and right face and arm weakness are often associated with Broca aphasia. Comprehension is intact in these patients.
If the patient had nail-bed hemorrhages, nodules on her fingers and toes, and retinal hemorrhages, what diagnosis should be considered?
This constellation of symptoms suggests infective endocarditis, which is characterized by splinter hemorrhages, Osler nodes on the pads of the fingers and toes, and Roth spots on the retina. Infective endocarditis can lead to the release of thrombi from the valvular vegetations, resulting in embolic events.
What are 5 common causes of back pain?
- Musculoskeletal conditions (eg, muscle strain, osteoarthritis, compression fracture, or ankylosing spondylitis).
- Disk herniation.
- Metastases.
- Osteomyelitis.
- Referred pain from visceral disease (eg, gallstones or kidney stones, pancreatitis, or aortic aneurysm).
What is the most likely cause of this patient’s back pain?
The patient’s history of breast cancer raises concern for the development of metastases resulting in epidural spinal cord compression. Her leg weakness, hyperreflexia, and positive Babinski signs indicate upper motor neuron lesions, which are likely the cause of her weakness as well. Her pain at rest and lack of sciatica argue against disk herniation.
What is the most likely diagnosis?
Sturge-Weber syndrome is a rare neurocutaneous congenital disorder with unknown etiology. The disorder manifests vascular malformations of the skin (port-wine stain; see Figure 10-36) and leptomeninges (leptomeningeal angiomatosis).
What is the most likely diagnosis? What are some common etiologies of this condition?
- Subarachnoid hemorrhage (arrows in Figure 10-37). The classic presentation is a complaint of “the worst headache in my life” after a “thunderclap” sensation marking the onset of severe pain. Hypertension is the most common risk factor.
- Most spontaneous subarachnoid hemorrhages occur as the result of the rupture of a berry aneurysm in the circle of Willis. Other causes are trauma or an arteriovenous malformation. The risk is increased by a history of hypertension. The most common location of a berry aneurysm is the anterior communicating artery, followed by the posterior communicating artery and then the middle cerebral artery.
Given this patient’s symptoms, what is the pathophysiology of this condition?
The murmur on cardiac examination is characteristic of mitral valve prolapse, which is commonly seen in Marfan syndrome. Berry aneurysms have been associated with Marfan syndrome, Ehlers-Danlos syndrome, adult polycystic kidney disease, and coarctation of the aorta.
Why was the patient vomiting?
What is an important short-term sequela for patients with this condition?
- Vomiting is a common sign of increased intracerebral pressure, which, in this patient, is secondary to the hemorrhage.
- Patients who have recently suffered a subarachnoid hemorrhage are prone to cerebral vasospasm, especially during the first week after the hemorrhage. Prophylaxis is typically achieved with nimodipine, a calcium channel blocker that improves outcomes in SAH.
What is the most likely diagnosis? What is the source of bleeding in this type of injury?
- The temporary loss of consciousness followed by gradual mental status change over the course of days or even weeks is the classic history of a subdural hematoma. The diagnosis is confirmed by CT scan, which shows a crescent-shaped area of hemorrhage that crosses cranial suture lines (Figure 10-38).
- Subdural hematomas result from head trauma that causes venous bleeding, most commonly from rupture of bridging veins within the dura, which then bleed into the space between the arachnoid and dura mater. The elderly and alcoholics are more prone to subdural hemorrhage due to cortical atrophy and subsequent increased tension on the bridging veins.
What explains the delayed onset of symptoms?
Venous bleeding results in a slowly expanding blood accumulation and gradual compression of the cerebrum. Symptoms result from the compression of cortical and subcortical structures and therefore are variably delayed depending on when specific intracranial areas are affected by the compression.
What is a CT scan likely to show if the patient experienced no loss of consciousness, followed shortly thereafter by mental status changes?
An immediate “lucid interval,” or temporary conscious state, after a head trauma followed by rapid decline in function is more consistent with an epidural hematoma. Unlike subdural hematomas, epidural hematomas are due to arterial bleeding and thus cause a dramatic decline in mental status after an initial period of intact function. The CT scan of an epidural hematoma (Figure 10-39) shows a subosteal blood accumulation in the shape of a biconcave disk that does not cross suture lines.
What are the most common causes of syncope?
What is the most likely cause of syncope in this patient?
The primary differential for syncope is divided into cardiogenic and noncardiogenic causes. Cardiogenic causes include arrhythmias, aortic stenosis, tamponade, and aortic dissection. Noncardiogenic causes include orthostatic hypotension and vasovagal, or neurogenic, syncope, which is a reflex drop in blood pressure caused by activation of the vagus nerve.
What is the most likely diagnosis? What is the most likely cause of this patient’s condition?
Transient ischemic attack (TIA). Classically, TIA has been defined as strokelike symptoms that resolve within 24 hours. However, increasingly sensitive imaging techniques have helped refine the definition of TIA; now it is defined as focal neurologic symptoms that last < 1 hour with no evidence of ischemic changes on radiologic studies.
What is the vascular distribution of the three major vessels supplying the cerebral cortex?
The anterior cerebral, middle cerebral, and posterior cerebral arteries are the three major vessels supplying the cortex. The anterior cerebral artery branches off the internal carotid artery and supplies the medial portion of motor cortex, the sensory cortex, and the majority of the frontal lobe. The middle cerebral artery also stems from the internal carotid artery and supplies the lateral portion of the motor cortex, temporal lobe, and the somatosensory cortex. The posterior cerebral artery stems from the basilar artery and supplies the visual cortex as well as the posterior parietal lobe (Figure 10-40).
What is the most likely diagnosis?
Tuberous sclerosis, an autosomal dominant syndrome manifested by numerous benign neoplasms of the brain, skin, heart, and kidney. Tuberous sclerosis demonstrates complete genetic penetrance but highly variable expressivity. Most cases arise from a sporadic mutation, but offspring of an affected individual will inherit the mutation in an autosomal dominant pattern.
What 4 dermatologic and ophthalmic abnormalities are common in Tuberous sclerosis?
- Ash-leaf spots, which are elliptical hypopigmented macules, may develop. In fair-skinned individuals, they can be visualized with a Wood’s lamp (Figure 10-41).
- Adenoma sebaceum, which are small angiofibromas typically distributed in a malar fashion on the face, are also seen (Figure 10-42).
- Shagreen patches, which are firm, reddish, raised lesions with a leathery texture, are commonly found on the lumbar area of the back.
- Retinal hamartomas, which appear as gray or yellow lesions on funduscopic examination, may also be present.
What is the most likely diagnosis?
Ulnar neuropathy due to nerve compression. Ulnar nerve injuries often present with acute onset of numbness/tingling in the fourth and fifth digits and weakness of wrist and fourth/fifth finger flexion. If severe, ulnar injury can present as a partial clawlike deformity known as the “Pope’s blessing” (Figure 10-43).
What treatment is used to reduce the swelling at the elbow?
Anti-inflammatory agents such as corticosteroids and nonsteroidal anti-inflammatory drugs are used to treat ulnar neuropathy due to nerve compression and medial epicondylitis. Patients can also benefit from braces or casts that reduce movement at the elbow joint to decrease chronic inflammation.
What is the most likely diagnosis?
Multi-infarct dementia, also known as vascular dementia. Vascular dementia is the second most common cause of dementia after Alzheimer disease. It can be broadly categorized as either large vessel or small vessel in origin. Large-vessel disease results from recurrent infarctions or hemorrhage in the vessels that supply the cortical territories and is usually due to chronic atherosclerotic disease. It is characterized by a stepwise decline in cognitive, executive, and motor or language function. By contrast, small-vessel disease results from recurrent infarctions in subcortical and white matter regions of the brain and is usually due to poorly controlled hypertension. The stepwise decline in these patients can be subtle and may lack major defining events.
What are the causes of dementia?
The etiologies of dementia can be broadly categorized as reversible or irreversible. The irreversible causes constitute the majority of cases; however, reversible causes should be sought out since treating them can significantly improve the patient’s quality of life (Figure 10-45).
What is the most likely diagnosis?
This patient has sensorineural hearing loss. The recent hospital course suggests antibiotics, most commonly aminoglycosides, as the likely culprit. Sensorineural hearing loss is often associated with tinnitus. The otologic examination reveals a normal external ear canal and visualizes a normal tympanic membrane on the affected side. Weber testing lateralizes to the opposite ear, whereas Rinne testing in the affected ear is normal.
What is the mechanism underlying the findings on Weber and Rinne testing?
What is the primary differential diagnosis of this patient’s hearing loss?
Hearing loss can also be conductive in nature. This occurs when there is an obstruction of the ear canal (cerumen impaction) or mechanical dysfunction of the middle ear apparatus (due to an inflammatory process such as otitis media or otitis externa) that helps transmit sound waves to the cochlea.
What is the most likely diagnosis?
What organisms are most likely to cause this condition?
- This presentation likely represents a viral meningitis.
- The most common causative organism of viral meningitis is echovirus, which is part of the
Enterovirus subgroup of the Picornaviridae family. Enterovirus outbreaks tend to occur during the summer and are often associated with summer camps. Other causative organisms include coxsackievirus (another enterovirus), adenovirus, HIV, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus.
What type of cell is shown in Figure 10-47?
The cell is a lymphocyte, which is characterized by its small size; most of the cell volume is occupied by the darkly stained and round nucleus. Lymphocytes play a key role in cellular immunity, particularly in combating infection. Lymphocytosis of the CSF is common in viral meningitis.
What is the most likely diagnosis? What is the pattern of inheritance for this condition?
- Von Hippel–Lindau (VHL) disease is characterized by diffuse hemangioma formation, commonly in the retina and central nervous system, as well as by an increased incidence of renal cell carcinoma (RCC).
- VHL disease is inherited in an autosomal dominant fashion in 75% of cases. It is associated with deletion of the VHL gene, a tumor suppressor gene on the short arm of chromosome 3. Approximately 25% of cases occur sporadically. In the United States, the incidence of VHL disease is approximately 1:36,000.
What is the pathophysiology underlying the formation of hemangiomas in Von Hippel–Lindau (VHL) disease?
What is the most likely diagnosis? What type of memory deficit is likely to be seen in this condition?
- Excessive alcohol abuse is the primary culprit of Wernicke-Korsakoff syndrome. Wernicke encephalopathy presents as the triad of nystagmus, ataxia, and confusion. This may progress to Korsakoff syndrome, which consists of irreversible memory loss, confabulation, and personality changes.
- Patients with Wernicke-Korsakoff syndrome usually suffer from anterograde amnesia, which is characterized by an inability to form new memories but a general preservation of long-term memories. This is in contrast to retrograde amnesia, in which only long-term memories that precede the precipitating event are lost.
What is the pathophysiology of Wernicke-Korsakoff syndrome?
This disease is seen in alcoholics with thiamine deficiency due to poor nutrition and absorption. Thiamine deficiency results in degeneration in a symmetric pattern in multiple cerebral areas, including the cerebellum, brain stem, and bilateral mammillary bodies (Figure 10-48; arrows show abnormal enhancement of the mammillary bodies).
