USMLE Neuroscience Review

1. USMLE Neuroscience Review Mícheál Macken MD MRCPI Department of Neurology Northwestern University Feinberg School of Medicine

2. 72-year-old female patient with Alzheimer's disease, but no other medical problems, suddenly becomes comatose and dies due to an intracranial hemorrhage that caused severe damage to her entire left cerebral hemisphere. • There was no evidence or history of trauma. What is the most likely cause of this hemorrhage? • A. Epidural hematoma • B. Subdural hematoma • C. Amyloid angiopathy • D. Rupture of berry aneurysm • E. Rupture of Charcot-Bouchard aneurysm

3. The correct answer is C • Alzheimer's disease patients are prone to large "lobar" hemorrhages that are usually centered in the parietal lobe (thus the name "lobar") and may spread to totally destroy an entire cerebral hemisphere, resulting in death. • This is due to amyloid deposition into the walls of cerebral blood vessels (amyloid angiopathy), similar to the amyloid plaques seen in the parenchyma of the brain with this disease. • Amyloid makes these vessels weak and prone to rupture.

4. Rupture of a berry aneurysm (choice D) usually causes a subarachnoid hemorrhage, in which blood leaks into the space between the arachnoid membrane and the brain. The blood may also gain access to the ventricles, but does not generally damage the cerebral hemispheres. Subarachnoid hemorrhages can be sudden and deadly, but usually present with a severe headache ("the worst headache of my life"). These aneurysms are not especially associated with Alzheimer's disease. • Rupture of a Charcot-Bouchard aneurysm (choice E) might cause a sudden hemorrhage within the brain causing coma and death, but it is not especially associated with Alzheimer's disease. Charcot-Bouchard aneurysms are primarily seen in patients with severe hypertension.

5. Epidural hematoma (choice A) • A collection of blood above the dura mater, usually due to a blow to the side of the head that fractures the temporal bone of the skull and shears the middle meningeal artery. • Even though this fast-flowing arterial blood usually causes symptoms within the first 24 hours and can cause life-threatening mass effects, no traumatic event was involved in this case.

7. Subdural hematoma (choice B) • Forms when slow-flowing venous blood collects below the dura mater due to leakage from stretched cortical veins as they drain into the superior sagittal sinus. • Even though it is true that Alzheimer's patients are more susceptible to these bleeds due to brain atrophy, causing cortical veins to be maximally stretched and prone to tearing, subdural hematomas are usually associated with some sort of trauma. • Furthermore, a subdural hematoma causes gradual symptoms over time, rather than presenting as a sudden devastating event as in this case.

9. Need to know… • Different intracerebral hemorrhage patterns • ICH, SDH, Infarct, SAH, Epidural • Association of lobar h’age with AD

11. A 20-year-old man with new onset of seizures and no history of hypertension is evaluated with a contrast-enhanced CT scan of the head, which demonstrates a mixed parenchymal and subarachnoid hemorrhage. • The parenchymal hemorrhage is centered over one cerebral hemisphere. • Which of the following is the most likely source of the hemorrhage? • A. Arteriovenous malformation • B. Berry aneurysm • C. Bridging vein • D. Charcot-Bouchard aneurysm • E. Middle meningeal artery

12. The correct answer is A. • Arteriovenous malformations are composed of complex tangles of congenitally malformed vessels that typically involve the superficial or deep cerebral hemispheres. • There is a slight male predominance, and bleeding typically occurs in adolescence or young adulthood. • Symptoms may be those of subarachnoid hemorrhage (headache, increased intracranial pressure) and/or seizures. Surgical resection is usually required for therapy.

13. Berry aneurysms (choice B) can produce both subarachnoid and parenchymal hemorrhage, but are usually centered near the base of the brain. • Bleeding from bridging veins (choice C) causes subdural hematoma. • Charcot-Bouchard aneurysms (choice D) are small, intraparenchymal aneurysms that are related to hypertension. • Rupture of the middle meningeal artery (choice E) causes epidural hematoma.

14. A 33-year-old woman is brought into the emergency room by ambulance. She has been on antipsychotic medications the age of 17. Physical examination reveals a well-nourished female with a temperature of 103.2 degrees F, BP of 180/99, HR of 97, and copious perspiration. She is mute, has muscular rigidity and appears to be obtunded. Which of the following is the most likely diagnosis? • A. Acute dystonia • B. Akathisia • C. Neuroleptic malignant syndrome • D. Parkinsonism • E. Tardive dyskinesia

15. The correct answer is C • Neuroleptic malignant syndrome (NMS) is a potentially fatal condition that can occur at any time during the course of treatment with neuroleptics. • The exact etiology is unknown. Excessive muscle contraction produces muscular rigidity, and is also responsible for the high temperature. • The obtunded mental state and mutism is characteristic.

16. NEUROLEPTIC MALIGNANT SYNDROME • Rare, life-threatening • Reaction to neuroleptic medication • All anti-psychotics may precipitate - typical or atypical - potent neuroleptics most frequent

17. NEUROLEPTIC MALIGNANT SYNDROME • Classic Symptoms • Fever • Altered Mental Status • Muscle Rigidity • Autonomic Dysfunction • Heterogeneous syndrome • Average onset 4-14 days after initiation of therapy • May occur at any time

18. NEUROLEPTIC MALIGNANT SYNDROME • Pathophysiology • Dopamine D2 receptor antagonists • Nigrostriatum : muscle rigidity • Hypothalamus : altered thermoregulation • Sympathetic nervous system activation or dysfunction • J Neurol Neurosurg Psychiatry 1995 Mar 58(3) : 271-3

19. NEUROLEPTIC MALIGNANT SYNDROMEPHARMACOTHERAPY • Benzodiazepines • Dopamine Agonists • Bromocriptine • Levodopa/Carbidopa • Reverse dopamine blockade • Skeletal Muscle Relaxants • Dantrolene • Inhibits calcium release from sarcoplasmic reticulum • Neuromuscular blockade

20. Extrapyramidal side effects that occur early during neuroleptic treatment include : • Acute dystonia (choice A, prolonged contractions of muscle groups), • Akathisia (choice B, "restless legs" ), • Parkinsonism (choice D, pill-rolling tremor and rigidity) • Tardive dyskinesia (choice E) is a late-appearing complication of neuroleptic therapy characterized by perioral and athetoid movements.

21. A 60-year-old male executive with a history of angina pectoris and depression had bypass surgery the previous day. • His depression has responded well to selective serotonin reuptake inhibitors (SSRIs) and there is no history of psychosis in the past. • He now presents with confusion, agitation, irritability, and tries to remove his IV lines. • His level of consciousness fluctuates, and at times he forgets who he is. • He is given a neuroleptic drug, and appears much improved. • What is the most likely diagnosis? • A. Adjustment disorder • B. Delirium • C. Dementia • D. Exacerbation of depression with psychotic features • E. Schizophrenia

22. The correct answer is B • Delirium is a common complication of general anesthesia and surgery. • It is manifested by acute changes in mental status with waxing and waning level of consciousness, agitation, irritability, and psychosis. • Patients usually respond to low-dose neuroleptics to achieve sedation. • The course is self-limited..

23. Any psychosocial or biological stressor can lead to adjustment disorder. • This patient's surgery will restrict his level of functioning, at least in the short term. • This will be difficult for a high-functioning individual to accept. • Adjustment disorder may present with depressive mood, anxiety, and irritability, but a fluctuating level of consciousness is not a feature of this disorder • Dementia (choice C) can present with irritability, confusion, and agitation, but usually has an insidious course and affects mainly cognition. • In contrast to delirium, it does not have a fluctuating course.

24. Severe depression can present with irritability, suicidal ideation, and psychotic features (choice D). The patient has a history of depression that responded well to SSRIs and he has no prior history of psychosis. He was motivated to undergo cardiac surgery, so removing his IV lines is unlikely to be a manifestation of suicidal ideation. • Schizophrenia (choice E) presents with bizarre behavior, hallucinations, and delusions. It usually starts at a younger age than the acute symptoms in this patient, and is characterized by progressive deterioration in functioning. It is unlikely for a schizophrenic to achieve the functional level of an executive.

25. A 38-year-old woman vacationing in Connecticut is bitten by a tick. She does not seek medical treatment and eventually develops chronic arthritis of the knee and hip joints and paralysis of the left facial muscles. • A physical examination during the early stages of the disorder would most likely have revealed • A. aphthous ulcers in the mouth • B. erythema chronicum migrans • C. flaccid paralysis of limb flexors • D.purpuric lesions in a bathing trunk distribution • E. spastic paralysis of limb extensors

26. The correct answer is B • Lyme disease should be suspected in a patient who is bitten by a tick in the northeastern U.S. The disease is spread via a tick vector of the genus Ixodes, which transmits a spirochete that causes a systemic illness. • Erythema chronicum migrans is usually the first sign of the illness. This is a large red patch on the buttocks or chest that slowly expands as the center blanches. • Generally, patients also have constitutional symptoms, such as fever and chills, during this phase. • Stiff neck may develop, along with other signs of meningeal irritation, because of an aseptic meningitis.

27. Complications include Bell's palsy due to involvement of branches of the facial nerve. • Arthritis is a prominent feature in about half the patients with Lyme disease. It tends to appear several months after the infection but may persist for several years. • The course of the chronic arthritis shows exacerbations and remissions; the most commonly affected joints are the knees and hips. • Cardiac abnormalities in Lyme disease include pericarditis and heart block.

28. Erythema chronicum migrans

29. Bells palsy

30. Skin manifestations do not include aphthous ulcers (choice A). • Flaccid or spastic paralysis of limbs (choices C and E) does not accompany Lyme disease; neurologic involvement is generally limited to cranial nerves and meningitis. • Purpura (choice D) is associated with vasculitis and does not occur in Lyme disease.

31. What is the most important source of noradrenergic innervation to the cerebral cortex? • A. Basal nucleus of Meynert • B. Caudate nucleus • C. Locus coeruleus • D. Raphe nucleus • E. Substantia nigra • F. Ventral tegmental area

32. The correct answer is C. • The locus coeruleus is a dense collection of neuromelanin-containing cells in the rostral pons, near the lateral edge of the floor of the fourth ventricle. • The fact that it appears blue-black in unstained brain tissue gave rise to its name, which means "blue spot" in Latin. • These cells, which contain norepinephrine, provide the majority of noradrenergic innervation to the forebrain, including the cerebral cortex.

33. The basal nucleus of Meynert (choice A), a part of the substantia innominata, is a major collection of forebrain cholinergic neurons. • These neurons (together with neurons in septal nuclei) innervate the neocortex, hippocampal formation, and the amygdala. • The basal nucleus is one of the structures that degenerates in Alzheimer's disease.

34. The caudate nucleus (choice B) is part of the basal ganglia, located immediately lateral to the lateral ventricles. • There are at least two important cell types in the caudate. GABAergic projection neurons (the majority) innervate the globus pallidus and substantia nigra pars reticulata. • The GABAergic neurons degenerate in Huntington's disease, which leads to enlarged lateral ventricles, clearly visible on MRI. • The caudate also contains cholinergic interneurons, which provide most of the acetylcholine to the striatum (caudate and putamen). • The balance of striatal acetylcholine and dopamine is important for the treatment of patients with extrapyramidal symptoms, such as Parkinson's disease or parkinsonism accompanying therapy with antipsychotic medications

35. The raphe nuclei (choice D) are located in the midline at most levels of the brainstem. They contain serotonergic cell bodies that innervate virtually every part of the central nervous system. • The substantia nigra (choice E) is located in the midbrain, and consists of the substantia nigra pars compacta and the substantia nigra pars reticulata. • The substantia nigra pars compacta contains the nigrostriatal neurons that are the source of striatal dopamine. • This cell group degenerates in Parkinson's disease or in response to neurotoxic agents such as MPTP. • The substantia nigra pars reticulata consists predominately of GABAergic neurons that innervate the thalamus.

36. The ventral tegmental area (choice F) is located in the midbrain and is an important source of dopamine for the limbic and cortical areas. • These cells are called mesolimbic and mesocortical neurons. • Overactivity of this cell group is a popular theory of the etiology of schizophrenia, and is the basis for the administration of antipsychotic agents (dopamine receptor antagonists

37. Anatomy, Transmitters, Diseases • Locus Coeruleus Noradrenalin Depression • B. Nuc Meynert Acetylcholine Alz D • Raphe nuclei Serotonin Depression • Sub Nigra Dopamine Park D • Caudate GABA Hunt D • Ventral tegmental Dopamine Schizoph.

39. A 67-year-old male smoker presents to his physician for a routine physical examination. Chest x-ray demonstrates a 2-cm density on the left side. Laboratory studies are remarkable for a serum sodium of 128 mEq/L. The findings may be attributable to tumor cell secretion of • A. adrenocorticotrophic hormone (ACTH) • B. antidiuretic hormone (ADH) • C. melanocyte-stimulating hormone (MSH) • D. parathyroid hormone (PTH) • E. vasoactive intestinal polypeptide (VIP)

40. The correct answer is B. • All of the hormones listed can be secreted by bronchogenic carcinoma, and may cause a paraneoplastic syndrome. Of the answer choices provided, only ADH (antidiuretic hormone) causes hyponatremia. • ACTH (choice A) causes Cushing's syndrome. • MSH (choice C) causes increased skin pigmentation. • PTH (choice D) causes hypercalcemia. • VIP (choice E) causes diarrhea and hypokalemia. • Other hormones that can be produced include human chorionic gonadotropin (hCG; gynecomastia), prolactin (lactation), and calcitonin (hypocalcemia).

41. A 75-year-old woman who has not been eating because of severe gastroenteritis is admitted to the hospital. Blood chemistry demonstrates a serum sodium of 125 mEq/L. Overly vigorous correction of this electrolyte imbalance would most likely damage which of the following structures? • A. Cerebellum • B. Cortex • C. Pons • D. Spinal cord • E. Thalamus

42. The correct answer is C • Central pontine myelinolysis is a specific, and nearly always iatrogenic, condition characterized by demyelination of the central pons following overly rapid correction of severe hyponatremia. • Axons and neuronal cell bodies are relatively preserved. The lesion usually specifically involves the basis pontis and portions of the pontine tegmentum. • Clinically, patients may develop a rapidly evolving para- or quadriparesis, often accompanied by pseudobulbar symptoms such as dysarthria or dysphagia. • The specific mechanism by which the pons is damaged is unclear.

43. Need to know… • Causes of hyponatremia : • Especially small cell lung carcinoma • Danger of rapid correction – CPM • Drugs that cause hyponatremia: - • Carbamazepine (Tegretol) • Oxcarbazepine • Chlorpromazine (Thorazine) • Diuretics • Vasopressin analogs • Indapamide (Natrilix) • Selective serotonin reuptake inhibitors • Theophylline • Amiodarone (Cordarone) • Ecstasy (3,4-methylenedioxymethamphetamine)

44. A sharp instrument passing through the superior orbital fissure would most likely sever the • A. abducens nerve • B. facial nerve • C. mandibular nerve • D. maxillary nerve • E. middle meningeal artery • F. ophthalmic artery • G. optic nerve

45. The correct answer is A. • Everything that innervates the eye, other than the optic nerve, passes through this fissure. • This includes the oculomotor nerve (CN III), the trochlear nerve (CN IV), the ophthalmic nerve (V1), and the abducens nerve (CN VI).

46. The facial nerve (CN VII; choice B) passes through the internal auditory meatus. • The mandibular nerve (V3; choice C) passes through the foramen ovale. • The maxillary nerve (V2; choice D) passes through the foramen rotundum. • The middle meningeal artery (choice E) passes through the foramen spinosum. • The ophthalmic artery (choice F) passes through the optic canal. • The optic nerve (choice G) passes through the optic canal.

47. Need to know… • Foramina of skull, what travels through them: Orbital fissures Ovale Mandibular - V3 Rotundum Maxillary - V2 Spinosum Middle meningeal Artery

48. 45-year-old man presents to a physician with complaints of double vision and ptosis. • The patient has noticed that these problems are minor in the early morning, but become progressively more severe during the course of the day. • Symptoms markedly improve after a test dose of edrophonium. This condition is usually related to autoantibodies directed against which of the following? • A. Acetylcholine receptor • B. Double-stranded DNA • C. Neutrophil cytoplasmic proteins • D. SS-A (Ro) • E. TSH receptor

49. Answer A • Myasthenia gravis peaks in younger women 30’s peak in older men 60’s • Associated with thymoma: 50% of pts with thymona have MG 10% of pts with MG have thymona • Drug that causes myasthenia :Penicillamine

50. 61-year-old man with a history of hypertension has a stroke. • He is seen in neurology clinic, where his wife states that he has been having trouble getting dressed in the morning, and notes that she has seen him shaving only the right side of his face • Which of the following structures did the man's stroke most likely involve? • A. Left frontal lobe • B. Left midbrain • C. Left parietal lobe • D. Right frontal lobe • E. Right midbrain • F. Right parietal lobe