GF [PATHO] CNS

Question 1

What is the earliest morphologic marker of acute neuronal injury seen within 12–24 hours after hypoxic-ischemic insult, characterized by shrunken neurons with eosinophilic cytoplasm and pyknotic nuclei?

Answer 1

Red neurons 🟡(Red neurons are the earliest histologic sign of irreversible neuronal injury. They appear shrunken with intensely eosinophilic cytoplasm, loss of Nissl substance, and pyknotic nuclei. Commonly seen after stroke or global hypoxia. Memory anchor: “Red = dead.”)

Question 2

What is the most important pathologic marker of central nervous system injury representing reactive astrocytic proliferation and hypertrophy?

Answer 2

Gliosis (astrocytic hyperplasia and hypertrophy) 🟡(Gliosis is the CNS response to injury, characterized by proliferation of astrocytes with increased GFAP expression. Unlike peripheral tissues, the CNS does not form classic fibrotic scars; instead, it forms a glial scar. Memory anchor: “CNS scars with glia.”)

Question 3

What type of cerebral edema is caused by disruption of the blood-brain barrier leading to increased vascular permeability, commonly seen in infections, inflammation, and tumors?

Answer 3

Vasogenic edema 🟡(Vasogenic edema results from breakdown of tight junctions in the blood-brain barrier, allowing protein-rich fluid to accumulate in the extracellular space, especially in white matter. Common in tumors and abscesses. Board distinction: vasogenic = extracellular fluid.)

Question 4

What type of cerebral edema occurs in generalized hypoxic-ischemic injury due to failure of Na⁺/K⁺ ATPase and intracellular ionic imbalance?

Answer 4

Cytotoxic edema 🟡(Cytotoxic edema results from energy failure leading to intracellular accumulation of sodium and water within neurons and glial cells. It primarily affects gray matter. Memory anchor: “Cyto = cell swelling.”)

Question 5

What type of hydrocephalus results from decreased CSF resorption at the arachnoid granulations, such as after healed subarachnoid hemorrhage?

Answer 5

Communicating hydrocephalus 🟡(In communicating hydrocephalus, CSF flow within ventricles is intact, but absorption is impaired. All ventricles are enlarged. Common causes include subarachnoid hemorrhage and meningitis.)

Question 6

What type of hydrocephalus occurs when there is focal obstruction within the ventricular system preventing CSF flow between ventricles?

Answer 6

Noncommunicating hydrocephalus 🟡(Also called obstructive hydrocephalus, it results from blockage such as aqueductal stenosis or tumor. Ventricles proximal to obstruction dilate, while distal ventricles remain normal. Memory anchor: “Blocked = noncommunicating.”)

Question 7

In a patient with subfalcine (cingulate) herniation due to increased intracranial pressure, which cerebral artery is classically compressed leading to contralateral leg weakness from medial frontal lobe ischemia?

Answer 7

Anterior cerebral artery 🟡(Subfalcine herniation forces the cingulate gyrus under the falx cerebri, compressing the ACA. The ACA supplies the medial frontal and parietal lobes, which control lower extremity motor and sensory function. Classic board clue: contralateral leg weakness > arm weakness.)

Question 8

In transtentorial (uncal) herniation, which neurovascular structures are compressed resulting in ipsilateral blown pupil, contralateral homonymous hemianopia, and possible hemiparesis?

Answer 8

Ipsilateral CN III, Posterior cerebral artery (PCA), and cerebral peduncle 🟡(Uncal herniation compresses CN III causing ipsilateral fixed dilated pupil (“blown pupil”), the PCA causing contralateral homonymous hemianopia from occipital infarct, and the cerebral peduncle leading to motor deficits. Kernohan notch phenomenon is a board trap—contralateral peduncle compression may cause ipsilateral weakness.)

Question 9

Linear or flame-shaped hemorrhagic lesions seen in the midbrain and pons in the setting of downward transtentorial herniation are called what?

Answer 9

Duret hemorrhages 🟡(Duret hemorrhages are secondary brainstem hemorrhages due to tearing of penetrating arteries during rapid downward brainstem displacement. They indicate severe increased intracranial pressure and carry poor prognosis.)

Question 10

Compression of which structure during tonsillar herniation leads to respiratory arrest and cardiac dysfunction?

Answer 10

Brainstem 🟡(Tonsillar herniation forces cerebellar tonsils through the foramen magnum, compressing the medulla. The medulla contains vital respiratory and cardiovascular centers, leading to fatal cardiorespiratory depression. Memory anchor: “Foramen magnum → medulla → death.”)

Question 11

What is the most common congenital malformation of the central nervous system resulting from failure of neural tube closure?

Answer 11

Spinal dysraphism (Spina bifida) 🟡(Spinal dysraphism includes a spectrum of neural tube defects involving incomplete closure of the vertebral arches. It is more common than cranial defects. Prevention is linked to adequate folic acid intake during early pregnancy.)

Question 12

Deficiency of which vitamin during early pregnancy is strongly associated with neural tube defects such as spina bifida and anencephaly?

Answer 12

Folic acid 🟡(Folate is required for DNA synthesis and neural tube closure during weeks 3–4 of embryogenesis. Deficiency increases risk of NTDs. Supplementation before conception and during early pregnancy reduces incidence.)

Question 13

What neural tube defect is characterized by protrusion of both the spinal cord and meninges through a vertebral column defect?

Answer 13

Myelomeningocele 🟡(Myelomeningocele is the most severe form of spina bifida cystica, involving herniation of meninges and neural tissue. It is commonly associated with Chiari II malformation and hydrocephalus. Board distinction: meningocele involves only meninges; myelomeningocele includes spinal cord.)

Question 14

What is the most common anatomic location of an encephalocele?

Answer 14

Occiput 🟡(Encephalocele is herniation of brain tissue through a skull defect, most commonly in the occipital region. It results from failure of anterior neuropore closure or skull formation defects.)

Question 15

Failure of closure of the anterior (rostral) neural tube leads to which lethal cranial dysraphism characterized by absence of major portions of the brain and skull?

Answer 15

Anencephaly 🟡(Anencephaly results from failure of anterior neuropore closure, leading to absence of cerebral hemispheres and cranial vault. It is incompatible with life and associated with polyhydramnios due to impaired fetal swallowing.)

Question 16

Failure of complete separation of the cerebral hemispheres across the midline due to abnormal forebrain (prosencephalon) division during early embryogenesis results in which congenital brain malformation often associated with midline facial defects such as cyclopia or cleft lip?

Answer 16

Holoprosencephaly 🟡(Holoprosencephaly results from failure of the prosencephalon to divide into two cerebral hemispheres during weeks 3–4 of development. It is associated with midline facial anomalies and commonly linked to trisomy 13 (Patau syndrome) and SHH pathway defects. Severity ranges from alobar to lobar forms. Memory anchor: “Holo = whole brain fails to split.”)

Question 17

Absence of the major white matter commissural bundle responsible for interhemispheric cortical communication, leading to “racing car” ventricles on imaging, is called what?

Answer 17

Agenesis of corpus callosum 🟡(The corpus callosum connects the two hemispheres. Its agenesis leads to widely spaced lateral ventricles and Probst bundles (misrouted axons). It may be isolated or associated with fetal alcohol syndrome and other congenital anomalies. Board clue: inability to transfer learned information between hemispheres.)

Question 18

Which congenital malformation is characterized by a small posterior fossa causing downward herniation of the cerebellar tonsils and medulla through the foramen magnum, commonly associated with myelomeningocele and hydrocephalus?

Answer 18

Chiari II malformation (Arnold-Chiari) 🟡(Chiari II involves downward displacement of cerebellar vermis and tonsils along with the brainstem due to a small posterior fossa. Strongly associated with myelomeningocele and obstructive hydrocephalus. Distinguish from Chiari I, which is milder and not classically linked to NTDs.)

Question 19

Low-lying cerebellar tonsils extending through the foramen magnum in adolescents or adults, often presenting with occipital headaches worsened by Valsalva and possible syringomyelia, define which condition?

Answer 19

Chiari I malformation 🟡(Chiari I involves isolated tonsillar herniation without major brainstem involvement. Symptoms may include headaches and signs of syringomyelia due to CSF flow obstruction. Board trap: Chiari I = later presentation; Chiari II = neonatal + myelomeningocele.)

Question 20

Hypoplasia or agenesis of the cerebellar vermis with cystic dilation of the fourth ventricle and enlargement of the posterior fossa is characteristic of which malformation?

Answer 20

Dandy-Walker malformation 🟡(Dandy-Walker results from developmental failure of the cerebellar vermis, leading to cystic expansion of the 4th ventricle and enlarged posterior fossa. Often presents with hydrocephalus. Differentiate from Chiari malformations, which involve downward herniation.)

Question 21

A fluid-filled cavity within the central spinal cord, often associated with cape-like loss of pain and temperature due to crossing spinothalamic tract disruption, is known as what?

Answer 21

Syringomyelia 🟡(Syringomyelia involves expansion of the central canal forming a syrinx that damages decussating spinothalamic fibers, causing bilateral loss of pain and temperature over shoulders and arms. Commonly associated with Chiari I malformation. Memory anchor: “Cape-like sensory loss.”)

Question 22

What is the most common route by which infections reach the central nervous system, particularly in cases of brain abscess?

Answer 22

Hematogenous spread 🟡(Hematogenous dissemination from systemic infections, such as endocarditis or lung abscess, is the most common route of CNS infection. Other routes include direct extension from adjacent structures and traumatic implantation. Board clue: multiple abscesses at gray-white junction suggest hematogenous spread.)

Question 23

Which neurotropic viruses characteristically spread retrogradely along peripheral nerves via axonal transport to reach the central nervous system, explaining symptoms after peripheral inoculation or reactivation?

Answer 23

Rabies virus and Varicella-zoster virus (VZV) 🟡(Rabies travels via retrograde axonal transport from a bite site to the CNS using dynein motors, causing encephalitis with Negri bodies. VZV remains latent in dorsal root ganglia and reactivates, spreading along sensory nerves to cause shingles. Memory anchor: “Rabies rides the nerve back to the brain.”)

Question 24

What is the most common overall cause of acute pyogenic (bacterial) meningitis across all age groups, particularly in adults?

Answer 24

Streptococcus pneumoniae 🟡(S. pneumoniae is the leading cause of community-acquired bacterial meningitis in adults. It is a Gram-positive, lancet-shaped diplococcus and often follows otitis media, sinusitis, or pneumonia. Board clue: elderly patient with meningitis = think pneumococcus.)

Question 25

What are the most common causative organisms of acute pyogenic meningitis in newborns, reflecting vertical transmission and perinatal exposure?

Answer 25

Group B Streptococci, Streptococcus pneumoniae, Listeria monocytogenes, and Escherichia coli 🟡(In neonates, pathogens are typically acquired during delivery. Group B Strep and E. coli are classic causes; Listeria is important due to transplacental spread. Board mnemonic: “BEL” (GBS, E. coli, Listeria).)

Question 26

In teenagers and young adults living in close quarters (e.g., dormitories), which organisms are common causes of acute pyogenic meningitis?

Answer 26

Neisseria meningitidis and Streptococcus pneumoniae 🟡(N. meningitidis is a Gram-negative diplococcus spread via respiratory droplets and associated with outbreaks in crowded settings. It may cause meningococcemia with petechial rash and DIC. S. pneumoniae remains a major cause in this group as well.)

Question 27

What is the most commonly identifiable viral agent responsible for acute aseptic meningitis, especially during summer and fall?

Answer 27

Enteroviruses 🟡(Enteroviruses, including echovirus and coxsackievirus, are the leading causes of viral meningitis. They typically cause lymphocytic pleocytosis with normal glucose and mildly elevated protein. Board clue: summer viral meningitis = enterovirus.)

Question 28

Markedly elevated CSF protein with predominant mononuclear (lymphocytic) pleocytosis and low glucose is characteristic of which type of meningitis?

Answer 28

Tuberculous meningitis 🟡(TB meningitis presents with high protein, low glucose, and lymphocytic predominance due to chronic granulomatous inflammation of the meninges. It often involves the basal meninges and may cause cranial nerve palsies. Distinguish from viral meningitis, which has normal glucose.)

Question 29

What clinical conditions predispose to hematogenous spread and formation of a brain abscess?

Answer 29

Acute bacterial endocarditis, congenital heart disease with right-to-left shunts, chronic pulmonary infections, and immunosuppression 🟡(Brain abscess commonly results from hematogenous seeding, especially from endocarditis or lung infections. Right-to-left shunts bypass pulmonary filtration, increasing risk. Immunocompromised patients are at higher risk for opportunistic infections such as Nocardia or fungi.)

Question 30

What are the characteristic morphologic findings in meningovascular neurosyphilis that lead to ischemic strokes in young adults?

Answer 30

Obliterative endarteritis, perivascular plasma cells, and gummas 🟡(Meningovascular syphilis causes Heubner arteritis—obliterative endarteritis of small vessels—with dense perivascular plasma cell infiltrates. Tertiary syphilis may also produce gummas. Board clue: stroke in young adult + plasma cells = neurosyphilis.)

Question 31

A patient presents with acute hemorrhagic necrotizing encephalitis predominantly involving the temporal lobes, with fever, seizures, and altered mental status. Which virus is classically responsible for this presentation?

Answer 31

Herpes simplex virus (HSV) 🟡(HSV-1 is the most common cause of sporadic fatal encephalitis in adults. It has a predilection for the temporal lobes, causing hemorrhagic necrosis. CSF shows lymphocytic pleocytosis and elevated RBCs due to hemorrhage. Board clue: temporal lobe hemorrhagic necrosis = HSV.)

Question 32

A congenital infection characterized by microcephaly, periventricular calcifications, hepatosplenomegaly, and “owl’s eye” inclusions is caused by which virus?

Answer 32

Cytomegalovirus (CMV) 🟡(CMV is the most common congenital viral infection. It causes periventricular calcifications—distinguishing it from toxoplasmosis, which causes diffuse intracranial calcifications. Memory anchor: “CMV hugs the ventricles.”)

Question 33

Round, eosinophilic cytoplasmic inclusion bodies found in pyramidal neurons of the hippocampus and Purkinje cells of the cerebellum are pathognomonic for which viral infection?

Answer 33

Negri bodies (Rabies infection) 🟡(Negri bodies are cytoplasmic inclusions seen in rabies infection. Rabies spreads retrogradely via peripheral nerves to the CNS, causing fatal encephalitis. Classic board clue: animal bite + hydrophobia + Negri bodies.)

Question 34

What is the most common species causing cryptococcal meningitis in immunosuppressed patients, especially those with HIV/AIDS?

Answer 34

Cryptococcus neoformans 🟡(C. neoformans is an encapsulated yeast with a thick polysaccharide capsule visible on India ink preparation. It causes subacute meningitis in immunocompromised hosts. Board clue: elevated opening pressure + AIDS patient.)

Question 35

A basilar skull fracture associated with periorbital ecchymosis (“raccoon eyes”) and CSF rhinorrhea typically involves which region of the skull base?

Answer 35

Anterior skull base 🟡(Anterior skull base fractures often involve the cribriform plate of the ethmoid bone, leading to CSF rhinorrhea and periorbital ecchymosis. Distinguish from posterior skull base fractures, which cause Battle sign.)

Question 36

Basilar skull fracture causing cranial nerve III, IV, V, and VI deficits along with possible carotid artery injury typically involves which region?

Answer 36

Central skull base 🟡(Central skull base fractures affect the sphenoid region, where multiple cranial nerves traverse the cavernous sinus. Carotid artery injury may also occur. Board clue: multiple ocular motor nerve palsies + trauma.)

Question 37

What is the most common type of skull fracture overall, often resulting from lateral head trauma?

Answer 37

Temporal fracture 🟡(Temporal bone fractures are common due to the thin squamous portion. They may injure the middle meningeal artery, leading to epidural hematoma. Memory anchor: “Temporal trauma → epidural bleed.”)

Question 38

Postauricular ecchymosis (mastoid hematoma) seen after basilar skull fracture is referred to as what sign?

Answer 38

Battle sign 🟡(Battle sign indicates posterior skull base fracture involving the mastoid region. It may be associated with CSF otorrhea. Distinguish from raccoon eyes, which indicate anterior skull base fracture.)

Question 39

A patient with head trauma develops rapid neurologic deterioration after a brief lucid interval, classically following a temporal bone fracture. What is the most likely diagnosis?

Answer 39

Epidural hematoma 🟡(Epidural hematoma is typically due to arterial bleeding between the skull and dura, often after temporal bone fracture. The classic presentation includes a lucid interval followed by rapid deterioration due to expanding mass effect. It is a neurosurgical emergency.)

Question 40

Which blood vessel is most commonly lacerated in epidural hematoma following temporal bone trauma?

Answer 40

Middle meningeal artery 🟡(The middle meningeal artery runs beneath the thin temporal bone. Fracture can tear this artery, leading to rapid arterial bleeding and formation of a biconvex hematoma. Memory anchor: “Temporal trauma tears MMA.”)

Question 41

What is the characteristic CT scan appearance of an epidural hematoma?

Answer 41

Lentiform (biconvex) hyperdense lesion 🟡(Epidural hematoma appears as a lens-shaped, biconvex hyperdensity that does not cross suture lines because the dura is tightly attached at sutures. Board distinction: epidural = lens-shaped; subdural = crescent-shaped.)

Question 42

Which blood vessels are typically torn in subdural hematoma, especially in elderly patients or those with brain atrophy?

Answer 42

Bridging veins 🟡(Subdural hematoma results from tearing of bridging veins that traverse from cerebral cortex to dural sinuses. It is often seen in elderly patients or infants (shaken baby syndrome). Bleeding is slower and venous in origin.)

Question 43

What is the characteristic CT scan finding of a subdural hematoma?

Answer 43

Crescent-shaped hyperdense lesion 🟡(Subdural hematoma appears as a crescent-shaped collection that can cross suture lines but is limited by dural reflections such as the falx cerebri. Memory anchor: “Subdural spreads like a crescent.”)

Question 44

Spinal cord injury above which cervical vertebral level is associated with diaphragmatic paralysis and respiratory compromise due to phrenic nerve involvement?

Answer 44

C4 🟡(The phrenic nerve arises from C3–C5 (“C3, 4, 5 keep the diaphragm alive”). Injury above C4 can disrupt diaphragmatic function, leading to respiratory failure requiring ventilatory support.)

Question 45

Which neurons are most vulnerable to hypoxic-ischemic injury, particularly after cardiac arrest or severe hypotension?

Answer 45

Pyramidal neurons of hippocampus (CA1/Sommer sector), cerebellar Purkinje cells, and pyramidal neurons in cerebral cortex (layers III and IV) 🟡(These neurons have high metabolic demand and are highly sensitive to oxygen deprivation. CA1 hippocampal neurons are especially vulnerable, explaining memory deficits after hypoxia. Purkinje cell injury contributes to ataxia. Memory anchor: “HPC CA1 and Purkinje die first.”)

Question 46

In patients with global cerebral hypoperfusion (e.g., severe hypotension or cardiac arrest), the most common location of watershed infarcts occurs at which arterial border zone?

Answer 46

ACA–MCA border 🟡(Watershed infarcts occur in regions between major arterial territories that are most vulnerable to decreased perfusion. The ACA–MCA border zone is classically affected, leading to proximal arm and leg weakness (“man-in-the-barrel” syndrome). Memory anchor: border zones suffer first in low flow states.)

Question 47

What is the most common site of deep parenchymal (hypertensive) intracerebral hemorrhage due to rupture of Charcot-Bouchard microaneurysms?

Answer 47

Putamen 🟡(Chronic hypertension causes lipohyalinosis and microaneurysm formation in small penetrating arteries, particularly the lenticulostriate vessels supplying the basal ganglia. The putamen is the most common site. Board pattern: HTN bleed = basal ganglia.)

Question 48

What is the most common cause of spontaneous lobar intracerebral hemorrhage in elderly patients without hypertension?

Answer 48

Cerebral amyloid angiopathy (Aβ deposition in vascular walls) 🟡(Cerebral amyloid angiopathy involves deposition of β-amyloid in cortical and leptomeningeal vessel walls, leading to fragile vessels and lobar hemorrhages. It is strongly associated with Alzheimer disease. Distinguish from hypertensive hemorrhage, which is deep.)

Question 49

What is the most common type of intracranial aneurysm and the most common cause of spontaneous subarachnoid hemorrhage?

Answer 49

Saccular (“berry”) aneurysm 🟡(Berry aneurysms arise at arterial branch points due to congenital weakness of the media. Rupture causes sudden “worst headache of life” with blood in the subarachnoid space. Memory anchor: circle of Willis berry → SAH.)

Question 50

What is the most common anatomic site of berry aneurysm formation?

Answer 50

Circle of Willis – ACA–AComA junction (≈40%) 🟡(The anterior communicating artery junction is the most frequent site. Rupture may compress the optic chiasm, causing visual field defects. Other sites include PComA and MCA bifurcation.)

Question 51

Which systemic or genetic conditions are classically associated with increased risk of berry aneurysm formation?

Answer 51

ADPKD, Ehlers-Danlos (Type IV), NF1, Marfan syndrome, fibromuscular dysplasia, coarctation of the aorta 🟡(These disorders involve connective tissue or vascular wall weakness, predisposing to aneurysm formation. Board favorite: ADPKD + berry aneurysm + SAH.)

Question 52

What is the most common clinically significant vascular malformation of the brain that may present with seizures or intracerebral hemorrhage in young patients?

Answer 52

Arteriovenous malformation (AVM) 🟡(AVMs are direct connections between arteries and veins without a capillary bed, creating high-flow shunts. They can cause hemorrhage or seizures. Differentiate from berry aneurysm, which causes SAH rather than intraparenchymal hemorrhage.)

Question 53

What is the usual arterial territory in which cerebral arteriovenous malformations are most commonly located?

Answer 53

MCA territory 🟡(AVMs most frequently occur in the MCA distribution and often present with intracerebral hemorrhage in younger individuals. Memory anchor: “MCA = Most Common AVM.”)

Question 54

A young adult presents with multiple neurologic deficits separated in time and space, including optic neuritis and sensory/motor symptoms; CSF shows mild pleocytosis, mildly elevated protein, and increased IgG synthesis. What is the most likely diagnosis?

Answer 54

Multiple sclerosis 🟡(Multiple sclerosis is an autoimmune demyelinating disease of the CNS characterized by dissemination in time and space. Optic neuritis is a classic presenting feature. CSF typically shows mild lymphocytic pleocytosis, mildly elevated protein, and increased intrathecal IgG synthesis. Memory anchor: young woman + optic neuritis + relapsing neurologic deficits = MS.)

Question 55

What is the characteristic CSF electrophoresis finding in multiple sclerosis indicating intrathecal IgG production?

Answer 55

Oligoclonal IgG bands 🟡(Oligoclonal bands represent clonally expanded IgG produced within the CNS. They are detected by CSF electrophoresis and are present in the majority of MS patients. Board distinction: increased IgG index and oligoclonal bands support MS diagnosis.)

Question 56

A focal seizure that begins in one muscle group and spreads sequentially to adjacent muscle groups following the cortical homunculus pattern is called what?

Answer 56

Jacksonian march 🟡(Jacksonian march reflects focal motor seizure activity spreading along the primary motor cortex in a predictable pattern. Consciousness may be preserved initially. Memory anchor: “march” across the motor strip.)

Question 57

Rapid correction of chronic hyponatremia can cause demyelination predominantly in the pons, leading to dysarthria, dysphagia, and quadriplegia. What is this condition called?

Answer 57

Central pontine myelinolysis 🟡(Also known as osmotic demyelination syndrome, this occurs when rapid sodium correction causes osmotic injury to oligodendrocytes. Classically affects the basis pontis. Board rule: correct sodium slowly.)

Question 58

What is the most common human prion disease characterized by rapidly progressive dementia, myoclonus, and spongiform changes in the brain?

Answer 58

Creutzfeldt-Jakob disease (CJD) 🟡(CJD is caused by misfolded prion protein (PrP^Sc) leading to spongiform degeneration without inflammation. EEG may show periodic sharp wave complexes. Rapid progression distinguishes it from Alzheimer disease.)

Question 59

In prion disease such as CJD, amyloid plaques with a central core and radiating spicules found particularly in the cerebellum are called what?

Answer 59

Kuru plaques 🟡(Kuru plaques are amyloid plaques composed of prion protein with a star-like appearance. They are classically described in variant CJD and kuru. Memory anchor: prion plaques radiate like a “kuru star.”)

Question 60

What is the most common cause of progressive dementia in older adults, characterized by insidious memory loss, cortical atrophy, and accumulation of amyloid plaques and tau tangles?

Answer 60

Alzheimer disease (AD) 🟡(Alzheimer disease is the leading cause of dementia in the elderly. It features progressive memory impairment due to early involvement of the hippocampus and medial temporal lobes. Pathologically, it is characterized by extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Memory anchor: most common dementia = AD.)

Question 61

Which genetic and chromosomal associations increase the risk of developing Alzheimer disease, particularly early-onset or familial forms?

Answer 61

Trisomy 21 and ApoE ε4 allele (chromosome 19) 🟡(Individuals with trisomy 21 have an extra copy of the APP gene on chromosome 21, leading to increased Aβ deposition and early AD. The ApoE ε4 allele on chromosome 19 impairs amyloid clearance and increases late-onset AD risk. Board distinction: ApoE ε4 = risk factor, not deterministic mutation.)

Question 62

What are the focal spherical extracellular lesions composed of dilated axons and dendrites surrounding a central β-amyloid core that are specific for Alzheimer disease?

Answer 62

Neuritic plaques (Aβ) 🟡(Neuritic plaques consist of extracellular Aβ deposits surrounded by dystrophic neurites. They are specific for AD and contribute to synaptic dysfunction. Memory anchor: plaques are outside the neuron.)

Question 63

What intracellular basophilic fibrillary structures composed of hyperphosphorylated tau protein correlate more closely with severity of dementia in Alzheimer disease?

Answer 63

Neurofibrillary tangles (tau) 🟡(Neurofibrillary tangles are intraneuronal aggregates of hyperphosphorylated tau that disrupt microtubule stability. Although not specific to AD (also seen in other tauopathies), their quantity correlates with cognitive decline severity. Memory anchor: tangles track dementia severity.)

Question 64

A patient presents with masked facies (diminished facial expression), bradykinesia, stooped posture, festinating gait, rigidity, and a resting “pill-rolling” tremor. What is the most likely diagnosis?

Answer 64

Parkinson disease 🟡(Parkinson disease is characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to decreased dopamine in the striatum. The classic triad includes bradykinesia, rigidity, and resting tremor. Pathology shows Lewy bodies composed of α-synuclein. Memory anchor: “TRAP” – Tremor, Rigidity, Akinesia, Postural instability.)

Question 65

Which genetic lysosomal storage disorder due to glucocerebrosidase deficiency is considered the most important genetic risk factor for developing Parkinson disease?

Answer 65

Gaucher disease (glucocerebrosidase deficiency) 🟡(Mutations in the GBA gene, which encodes glucocerebrosidase, significantly increase the risk of Parkinson disease. Impaired lysosomal degradation promotes accumulation of α-synuclein, contributing to Lewy body formation. Board association: Gaucher mutation → ↑ risk of PD.)

Question 66

What are the cytoplasmic, eosinophilic, round to elongated neuronal inclusions with a dense core and surrounding pale halo that are pathognomonic for Parkinson disease?

Answer 66

Lewy bodies (α-synuclein) 🟡(Lewy bodies are intracytoplasmic aggregates composed primarily of α-synuclein. They are found in surviving neurons of the substantia nigra in Parkinson disease. Memory anchor: PD = α-synuclein inclusions.)

Question 67

A patient with parkinsonism accompanied by early dementia and recurrent visual hallucinations most likely has which neurodegenerative disorder?

Answer 67

Dementia with Lewy bodies 🟡(Dementia with Lewy bodies is characterized by cognitive decline preceding or occurring within one year of motor symptoms, fluctuating cognition, and visual hallucinations. It involves cortical Lewy body deposition. Distinguish from Parkinson disease dementia, where dementia develops later.)

Question 68

What trinucleotide repeat sequence is expanded in Huntington disease, leading to progressive chorea, psychiatric symptoms, and caudate atrophy?

Answer 68

CAG 🟡(Huntington disease is caused by CAG repeat expansion in the HTT gene on chromosome 4, producing mutant huntingtin protein with toxic gain of function. It shows anticipation, especially with paternal transmission. Memory anchor: “CAG = Caudate Atrophy Gene.”)

Question 69

What is the most common immediate cause of death in patients with advanced neurodegenerative diseases such as Parkinson disease and Huntington disease?

Answer 69

Pneumonia 🟡(Aspiration pneumonia is the most common immediate cause of death due to impaired swallowing, reduced cough reflex, and immobility. Board clue: neurodegeneration → dysphagia → aspiration → pneumonia.)

Question 70

Deficiency of which vitamin is responsible for the development of Wernicke encephalopathy and Korsakoff syndrome, particularly in chronic alcohol use disorder?

Answer 70

Thiamine (Vitamin B1) 🟡(Thiamine is a cofactor for enzymes in glucose metabolism such as pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. Deficiency leads to neuronal energy failure, especially in mammillary bodies and periventricular regions. Board rule: give thiamine before glucose to prevent precipitating Wernicke.)

Question 71

A patient presents with the classic triad of ataxia, confusion, and ophthalmoplegia in the setting of malnutrition or alcoholism. What is the most likely diagnosis?

Answer 71

Wernicke encephalopathy 🟡(Wernicke encephalopathy is an acute neurologic emergency due to thiamine deficiency. The triad includes confusion, ophthalmoplegia (nystagmus), and gait ataxia. MRI may show lesions in mammillary bodies. Untreated cases can progress to Korsakoff syndrome.)

Question 72

A patient with chronic alcohol use develops confabulation, hallucinations, and severe anterograde amnesia due to damage to mammillary bodies. What is the diagnosis?

Answer 72

Korsakoff syndrome 🟡(Korsakoff syndrome represents the chronic, irreversible phase of thiamine deficiency. It is characterized by profound memory impairment and confabulation due to damage to mammillary bodies and medial thalamus. Memory anchor: Wernicke = acute; Korsakoff = chronic amnesia.)

Question 73

What is the most common group of primary brain tumors overall, arising from glial cells?

Answer 73

Glioma 🟡(Gliomas include astrocytomas, oligodendrogliomas, and ependymomas. They are the most common primary brain tumor group. Board distinction: primary brain tumors ≠ metastases, which are more common overall but not primary.)

Question 74

What is the most common primary malignant brain tumor in adults, characterized by necrosis and pseudopalisading cells?

Answer 74

Glioblastoma multiforme 🟡(Glioblastoma (WHO grade IV astrocytoma) is highly aggressive and shows necrosis with pseudopalisading tumor cells and microvascular proliferation. It may cross the corpus callosum (“butterfly glioma”).)

Question 75

Which brain tumor shows “fried egg” appearance of tumor cells and “chicken-wire” capillary vasculature on histology?

Answer 75

Oligodendroglioma 🟡(Oligodendroglioma cells have round nuclei with perinuclear clearing (fried egg) and delicate branching capillaries (chicken wire). It commonly arises in frontal lobes and may present with seizures.)

Question 76

What are the characteristic genetic abnormalities associated with oligodendroglioma?

Answer 76

IDH1 or IDH2 mutation and 1p/19q codeletion 🟡(Oligodendrogliomas frequently harbor IDH mutations and combined deletion of chromosome arms 1p and 19q, which is associated with better prognosis and treatment response. Board clue: fried egg cells + 1p/19q codeletion.)

Question 77

What is the most common type of glioma overall, arising from astrocytes and encompassing a spectrum from low-grade to highly malignant tumors?

Answer 77

Astrocytoma 🟡(Astrocytomas are the most common gliomas and range from pilocytic astrocytoma (WHO grade I) to glioblastoma (WHO grade IV). They arise from astrocytes and are GFAP-positive. Memory anchor: astrocytes = most common glial origin.)

Question 78

What is the most common glioma in children, characterized histologically by Rosenthal fibers and typically arising in the cerebellum?

Answer 78

Pilocytic astrocytoma 🟡(Pilocytic astrocytoma is a WHO grade I tumor commonly seen in children, especially in the cerebellum. It shows Rosenthal fibers (elongated eosinophilic structures) and has a good prognosis. Often associated with NF1. Board clue: child + cystic cerebellar mass + mural nodule.)

Question 79

Perivascular pseudorosettes—tumor cells arranged around blood vessels with intervening processes—are characteristic of which primary brain tumor?

Answer 79

Ependymoma 🟡(Ependymomas arise from ependymal cells lining the ventricles and commonly occur in the 4th ventricle in children. They show perivascular pseudorosettes and can obstruct CSF flow, causing hydrocephalus. Distinguish from medulloblastoma, which shows Homer-Wright rosettes.)

Question 80

What is the second most common primary malignant brain tumor in children, characterized by Homer-Wright pseudorosettes and a tendency for “drop metastases” through CSF?

Answer 80

Medulloblastoma 🟡(Medulloblastoma is a malignant cerebellar tumor arising in the midline (vermis). It shows small round blue cells with Homer-Wright rosettes and frequently spreads via CSF to the spinal cord (“drop metastases”). Board clue: child + truncal ataxia + vermian mass.)

Question 81

What is the most common CNS neoplasm in adults overall?

Answer 81

Metastasis 🟡(Brain metastases are more common than primary brain tumors in adults. Common primary sources include lung, breast, melanoma, kidney, and colon. They often appear as multiple lesions at the gray-white junction.)

Question 82

What is the most common CNS neoplasm in immunocompromised individuals, particularly patients with AIDS?

Answer 82

Primary CNS lymphoma 🟡(Primary CNS lymphoma is often an EBV-associated diffuse large B-cell lymphoma seen in immunocompromised patients. It frequently involves deep brain structures and may show ring-enhancing lesions on imaging. Board clue: AIDS patient + brain mass = think CNS lymphoma.)