Neurology Pathology Flashcards
Patient presents with bilateral loss of pain and temperature sensation in cape like distribution across upper extremities. Fine touch preserved. Diagnosis?
:Syringomyelia; cystic fluid -filled cavity within the spinal cord @ C8-T1 disrupting anterior white commissar fibers = protopathic - may be congenital (Arnold Chiari malformation) or due to trauma -Can expand to involve 1. anterior horn cells = LMN in upper extremities 2. Intermedial lateral cell column = Horner syndrome (ptosis, anhidrosis, miosis) -Recall: Hypothlamospinal tract
What malformation is associated with syringomelia?
Arnold Chiari I malformation: congenital cerebellar tonsillar herniation through the foramen magum -ususally asymptomatic in childhood, presents as headaches and cerebellar symptoms
Poliomyelitis
Infection with poliovirus = fecal-oral route -presents as fever, sore throat, nausea, vomiting -damage to anterior horn cells =LMN signs
Werdnig-Hoffman disease
:Spinal muscular atrophy; congenital degeneration of anterior horn cells = LMN signs -presents in early infancy (“floppy baby”),marked hypotonia, tongue fasciculations -autosomal recessive -median age to death 7 months
UMN and LMN deficits with no sensory findings, cognitive, or oculomotor deficits. Diagnosis? Pathogenesis? Treatment?
:Amyotrophic lateral sclerosis or “Lou Gehrig Disease”; mostly sporadic -congenital forms caused by SOD = free radical injury to neurons -atrophy and weakness of hands may be early sign–> distinguish from syringomyelia b/c no sensory findings -treatment: Rilouzole
Patient: muscle weakness in the lower extremities, loss of DTRs, loss of vibratory sense and proprioception. Reports frequent falling and staggering. PE: nystagmus, dysarthria, high arches, hammer toes. Diagnosis? What is the usual cause of death?
: Fredreich ataxia; autosomal recessive trinucleotide repeat disorder (GAA) on chromosome 9 -gene encodes for frataxin (iron binding protein –> iron build up + free radical damage via fenton run) -cause of death = hypertrophic cardiomyopathy -presents in childhood with kyphoscoliosis
Tabes dorsalis. Pathogenesis? Signs/Symptoms?
:caused by tertiary syphilis; results in degeneration/demylination of dorsal columns and roots -impaired sensation and proprioception and progressive sensory ataxia (inability to sense of feel the legs -> poor coordination) -associated with charcot joints, shooting pain, argyll robertson pupil (constrict to accommodation but not light) -exam will demonstrate absence of DTRs and + Romberg
Vitamin B12 or vitamin E defeciency neurologic effects?
:subacute combined degeneration of spinal cord- demyelination of dorsal columns, lateral CST, and spinocerebellar tracts -results in ataxic gait, paresthesia, impaired position and vibration sense.
What are the microscopic changes seen in ischemic brain stroke and timeframes?
“1 day” : within 12 hrs -> red neurons
“1 week” : 24-72 hrs ->liquefactive necrosis + neutrophils; 3-5 days-> microglia (macrophages)
“1 month”: 1-2 weeks-> reactive gliosis (astrocytes) + vascular proliferation; 2 weeks or more -> fluid filled cystic cavity w/surrounding fibrotic tissue = glial scar
What are the imaging findings you expect with ischemic stroke? timeframe?
- MRI (highest sensitivity) - hyperintense (bright) area w/in 3-30 minutes
- Noncontrast CT scan- hypodense (dark) area 12-24 hrs
How can CT scan be used be used in the immediate treatment of ischemic stroke?
absence of hyperdense (bright) areas to exclude hemorrhage = can use tPA - tPA contraindicated in acute hemorrhage
Thrombotic stroke
: d/t clot formation directly at the site of infarction, usually over ruptured atherosclerotic plaque -results in pale infarct -usually in MCA territory -Risk factors: HTN, DM
Embolic stroke
:an embolus from another part of the body obstructs the vessel -results in hemorrhagic infarct -most common source of emboli is left side of heart -> atrial fibrillation
Lacunar stroke
:most commonly d/t lenticulostriate vessel, resulting in small cystic areas of infarction -secondary to hyaline arteriosclerosis –> HTN ! - internal capsule involvement = pure motor deficits - thalamus involvement = pure sensory deficits
What areas of the brain are particularly susceptible to hypoxia?
- Pyramidal neurons of cortical layers 3, 5 & 6 = cortical laminar necrosis 2. Pyramidal neurons of hippocampus 3. Purkinje layer of cerebellum 4. watershed areas
Hypoxic stroke
: due to hypoperfusion (i.e. shock) or hypoxemia. -common during cardiovascular surgeries -effects watershed areas, cortex, hippocampus, cerebellum
Difference between stroke and TIA
Transient Ischemic Attack (TIA) is a brief reversible episode of focal neurologic dysfunction lasting <24 hours without acute infarction (- MRI) -d/t focal ischemia -majority resolve in 15 minutes
Hemorrhagic stroke
: intracerebral bleeding -classically d/t Charcot-Bouchard microaneuryms of lenticulostriate vessels -often due to HTN! anticoagulation, cancer (abnormal vessels) -may be secondary to ischemic stroke followed by reperfusion -common sites: internal capsule, basal ganglia
Berry aneurysm
aka saccular aneurysm; most common site is junction of the A Comm and ACA -rupture is common complication = subarachnoid hemorrhage (WHOML) -can cause bitemporal hemianopia via compression of optic chasm -risk factors: advanced age, HTN, smoking, black race
Which diseases are associated with berry aneurysms?
Autosomal dominant polycystic kidney disease (ADPKD)
Marfan syndrome
Ehlers-Danlos
Patient complains of “worst headache of my life.” Diagnosis?
Subarachnoid hemorrhage!; rupture of berry aneurysm -rapid time course -causes= HTN, Marfan, Ehlers- Danlos, ADPKD or AVM -lumbar puncture : bloody or xanthochromatic (yellow = bilirubin breakdown)
What complication are patients with subarachnoid hemorrhage at risk for?
- Vasospasm 2-3 days afterward –> not visible on CT, treat with nimodipine
- Rebleed –> visible on CT
Diagnosis?
:epidural hematoma; d/t ruputre of the middle meningeal artery often secondary to fracture of the temporal bone
- not crossing suture lines and can cross falx, tentorium
- Presents with lucid interval but have rapid progression
- Can progress to transtentorial herniation (uncal herniation)
Recall: tentorium is extension of dura mater
Diagnosis?
: subdural hematoma= between the dura and the arachnoid mater; cresent shaped that crosses suture lines but cannot cross falx, tentorium
- d/t rupture of the bridging veins = slow venous bleeding = develops over time
- can cause midline shift
- seen in elderly, alcoholics, blunt traum, shaken baby
Tonsillar herniation
:displacment of cerebellar tonsils into the foramen magnum
-Compression of brainstem –> cardiopulmonary arrest
Subfalcine herniation
:displacement of the cingulate gyrus under the flax cerebri
-compression of the anterior cerebral artery leads to infarction
Uncal herniation
:aka transtentorial herniation; displacement of the temporal lobe uncus under the tentorium cerebelli
- compression of cranial nerve III = oculomotor palsy (down and out gaze) & dilated pupil
- compression of posterior cerebral artery leads to infarction of the occipital lobe (contralateral homonymous hemianopsia
- contralateral crus cerebri = ipsilateral paralysis (false localizing sign)
- rupture of paramedian arteries (branches of basilar) leads to Duret (brainstem) hemorrhage
Metachromatic Leukodystrophy
:autosomal recessive, lysosomal storage disease
- commonly d/t arylsufatase A deficiency–> sulfatides cannot be degreaded = accumulate in lysosome of oligodentrocytes
- central and peripheral demyelination with ataxia, dementia
Krabbe Disease
:autosomal recessive, lysosomal storage disease
- deficiency of galactocerebrosidease –> galactocerbroside and psychosine destroys myelin sheath
- peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Adrenoleukodystrophy
:X-linked, typically affecting males
- disrupts metabolism of very long chain fatty acids= accumulation in nervous system and adrenal gland, testes
- progressive disease that can lead to long-term coma/death and adrenal gland crisis
Patient- Female 25 y/o with scanning speech, incontinence , INO & nystagmus; relapsisng and remitting course.
:multiple sclerosis; autoimmune inflammation and demyelination of CNS
Presentation: optic neuritis (sudden loss of vision resulting in Marcus Gunn pupil), INO, hemiparesis, hemisensory symptoms, bladder/bowel incontinence
What do you expect to find in LP of MS patient? What findings are on MRI?
- increased lymphocytes, increased protein (IgG) in CSF; oligoclonal IgG bands on electrophoresis (diagnositc), myelin basic protein
- MRI shows periventricular plaques (oligodendryte loss and reactive gliosis)
- MRI is the gold standard
Diagnosis?
MS; dawsons fingers = specific for MS
What is the treatment for MS?
- Acute: high dose corticosteroids
- Chronic: Beta-IFN slows progression, natalizumab
- Symptomatic neurogenic bladder: catheterization, muscarinc antagonists
Spasticity: baclofen, GABA receptor agonist, pain (opoids)
Subacute Sclerosing Panencephalitis
:progressive debilitating encephalitis leading to death; d/t slowly progressing, persistent infection of the brain by measles virus
- infection occurs in infancy; neurologic signs arise in childhood
- characterized by viral inclusions within neurons (gray matter) and oligodendrocytes (white matter)
Progressive multifocal leukoencephalopathy
:JC virus infection of oligodendrocytes (white matter)
- immunosuppression (AIDS, leukemia, etc) leads to activiation of the latent virus
- presents with rapidly progressive neurologic sigsn (visual loss, weakness, dementia) leading to death
Central Pontine myelinolysis
:focal demyelination of the pons; d/t rapid correction of hyponatremia
- Presents as acute paralysis, dysarthria, dysphagia, diplopia, and LOC –> can cause locked in syndrome
- Physiology: hyponatremia causes neurons to initally swell; during rapid correction ECF becomes hypernatremic and cells shrink =CMP
- occurs in severely malnourished patients –> alcoholics, patients with liver disease, etc
- causes “locked in” syndrome
What happens in rapid correction of hypernatremia?
: cerebal edema/herniation
Physiology: hypernatremic states causes neurons to shrink as water flows out; during rapid correction ECF becomes hyponatremic inducing neuronal swelling
What are the clinical features of Alzheimers disease?
- slow onset memory loss and progression to long term memory loss and progressive disorientation
- loss of learned motor skills and language
- changes in behavior and personality
- focal neurologic deficits are not seen early in disease
What proteins are associated with early onset alzheimers disease?
presenilin-1 (chromosome 14), presenilin -2 (chromosome 1)
What increases the risk of developing Alzheimers disease ?
: E4 allele of apolipoprotein E (ApoE) on chromosome 19
Note: E2 allele is protective (decreases the risk)
What histologic findings would you expect in a patient with Alzheimers disease?
- Senile plaques: extracellular core comprosed of ABeta amyloid
- amyloid may deposit around vessels = increased risk of hemorrhage
- Neurofibrillary tangles: intracellular hyperphosphorylated tau protein = insoluble cytoskeleton elements; tangles correlate with degree of dementia
What gross findings would you expect in the brain of a patient with alzheimers?
Widespread cortical atrophy; narrowing gyri and widening sulci
What is the second most common cause of dementia in the elderly?
:multi-focal infarction injury due to HTN, atherosclerosis, or vasculitis
Pick disease
:frontotemporal dementia -> degeneration of frontal and temporal cortex; parietal and occipital lobes spared
- frontal lobe= behavioral/personality changes; temporal lobe = aphasia
- characterized by spherical tau protein aggregates in neurons of the cortex
Note: behavioral and language changes arise earlier then progresses to dementia, may have parkinsonsian aspects
Lewy Body dementia
: initially dementia and visual hallucinations followed by parkinsonian features
-Characterized by alpha-synuclein (lewy bodies) in neurons of the CORTEX
Note: In parkinsons disease dementia has LATE onset in disease
Creutzfeldt-Jacob disease
:most common spongiform encephalopathy: rapidly progressive dementia (weeks to months) with ataxia & startle myoclonus (involuntary contraction of muscle with minimal stimulus)
- Pathogenesis: Prions normally in PCP-c (alpha configuration) get converted to PCP-sc (beta-pleated sheet configuration) –> resistant to proteases and converts normal PRP-c to PRP-sc
- results in neuron and glial cell damage; characterized by intracelluar vacuoles
Parkinson’s Disease
: degeneration of the dopaniergic neurons of the substantia nigra
- characterized by lewy body (alpa-synuclein) eosinophilic inclusions in neurons & depigmenation of subtantia nigra pars compacta
- Tremor - pill-rolling,resting, Rigidity, Akinesia/bradykinesia, Postural instability [TRAP]
MPTP -a contaminant in illicit drugs is associated with which movement disorder?
Parkinson’s disease
Huntington’s disease
:autosomal dominant trinucleotide repeat CAG on chromosome 4 -> anticipation
- degeneration of caudate –> decreased GABA and ACh in brain
- presents as choreiform movements and athetosis, aggression, depression, and can progress to dementia
Note: chorea= sudden, jerky, purposeless movements; athetosis = slow writing movents, esp in fingers
Resting tremor
uncontrolled movement of distal appendages; tremor alleviated with intentional movement
Intention tremor
slow, zig-zagging motion when extending toward a target = cerebellar dysfunction
Essential tremor
:action tremor; exacerbated by holding posture/limb postion
- patients often self medicated (EtOH) which decreases tremor amplitude
- tx: B-blockers, primidone
Metastasis in the brain commonly arise from what primary tumors?
Lung, breast, kidney
Primary brain tumors in adults commonly arise in which area of the brain?
supratentorial
Primary brain tumors in children commonly arise in which areas of the brain?
Infratentorial with the exception of craniopharyngiomas
What primary brain tumor? cell lineage? Histology findings?
:Glioblastoma multiforme -adult; highly malignant -grade IV tumor of astrocytes; in cerebral hemispheres
- can cross corpus callosum = “butterfly glioma”
- Astrocytes stain from GFAP
- Pseudopalisading = tumor cells surrounded by necrosis and hemorrhage
- median survival ~ 1 year
Brain biopsy of a cerebral mass reveals the following:
:adult; pseudopallisading seen in glioblastoma multiforme; pleomorphic tumor cells surrrounding necrosis and hemorrhage
Recall: primary tumor of astrocytes
Patient- female presents with seziure, head CT reveals the following: Diagnosis? Histology?
:adult; meningioma (dural tails); benign tumor that arises from the arachnoid cells
- compresses but does not invade cortex; often asymptomatic
- treatment: resection and/or radiography
- histology: whorled pattern of spindle cells + psammoma bodies (laminted calcifications)
Schwannoma
:adult; benign tumor of schwanna cells; often localized to cerebellopontine angle= CN VIII -> acoustic schwannoma
- presents with hearing loss and tinnitus
- tumor cells are S-100 positive
- resectable or treated with sterotactic radiosurgery
- bilateral acoustic schwannoma associated with neurofibromatosis type 2
Oligodendroglioma
:adult; malignant tumor of oligodendrocytes; imaging reveals calcified tumor in white mass
-usually involves frontal lobes; may present with seizures
Histology: fried-egg appearing tumor cells + chicken wire capillary pattern
What type of brain tumor? Histology?
:Pilocytic astrocytoma -children; benign tumor of astrocytes = GFAP positive; often found in posterior fossa (ie. cerebellum)
- good prognosis
- Gross appearance: cystic + solid
histology: rosenthal fibers = brightly eosinophilic, corkscrew fibers
Medulloblastoma -what is the name of this finding?
:children; malignant tumor derived from granular cells of cerebellum ( of primative neuroectoderm)
- can compress the 4th ventricle = hydrocephalus
- can send drop metastasis to spinal cord
- histology- Homer-wright rosettes + small blue cells
Ependymoma
:children; malignant tumor of ependymal cells, most commonly in the 4th ventricle; poor prognosis
- may present as hydrocephalus
- characteristic perivasicular pseudorosettes on biopsy
Craniopharyngioma
:benign childhood tumor, arises from epithelial remnants of rathkes pouch
- may compress the optic chiasm = bitemporal hemianopsia
- only childhood supratentorial tumor
- calcification on imaging is common (tooth like
Sturge Weber syndrome
:congenital, non-inherited (somatic), developmental anomaly of neural crest derviatives (mesoderm/ectoderm) d/t activating mutation of GNAQ gene
- affects capillary sized blood vessels -> port- wine stain of the face (non-neoplastic) birthmark in V1/V2 distribution, ipsilateral leptomeningeal angioma–> seizures/epilepsy
- episcleral hemangiona –> increased IOP = early onset glaucoma
STURGE: Sporadic, port wine Stain, Tram track Ca2+, Unilateral Retardation, Glaucoma, GNAQ, Epilepsy
Tuberous sclerosis
“HAMARTOMAS”
Hamartomas in skin and CNS
Angiofibromas
Mitral regurgitation
Ash-leaf spots
cardiac Rhabdomyoma
Tuberous sclerosis
autosomal dOminant
Mental retardation
Renal angiomyolipoma
Seizures/shagreen patches
Neurofibromatosis type I
:von recklinghausen disease; cafe-au-lait spots, lisch nodules (pigments iris hamartomoas), neurofibromas in skin, optic gliomas, pheochromocytomas
- mutated NF1 tumor supressor gene (neurofibromin, a negative regulator of Ras) on chromosome 17.
- skin tumors derived from neural crest cells
Von- hippel Lindau disease
Cavernous hemangioms in skin, mucosa, organs; bilateral renal cell carcinomas; hemangioblastoma (high vascularity with hyperchromatic nuclei) in retina, brain stem, cerbellum; and pheochromocytomas
-autosomal dominant; mutated VHL tumor suppressor gene on chromosome 3, which results in constituitive expression of HIF (transcription factor) and activation of angiogenic growth factors
Cluster headaches
:repetitive brief headaches; excrutiating periorbital pain with lacrimation and rhinorrhea, May induce horner syndrome
- unilateral; 15-30 min in duration; more common in males
- tx: oxygen, sumatriptan
Tension headaches
: steady pain. no photophobia of phonophobia, no aura
>30 min (typically 4-6 hrs) or constant; bilateral
tx: analgesics, NSAIDs; acetaminophen; amytriptyline for chronic pain
Migraine
:unilateral pulsating pain with nausea, photophobia or phonophobia; may have aura
- d/t irritation of CN V, meninges, or blood vessels (release of substace P, CGRP, vasoactive peptides)
- 4-72 hr duration
tx: abortive therapy ( triptans, NSAIDs) & prophylactic (propranolol, topiramate, calcium channel blockers, amitripyline)
What are the two broad categories of seizures?
Seizures: synchronous high-frequency neuronal firing
- Partial (focal) seizures: involve one are of the brain, usually originate in the medial temporal lobe
- Generalized: diffuse
What are the types of partial seizures?
- Simple partial: conscious, may be motor, sensory, psychic
- Complex partial: same as above but LOC
What are the types of generalized seizures?
- Myoclonic: quick jerky movements
- Absence (petit mal): 3Hz “spike and wave” pattern, blank stare + no postictal state
- Atonic: “drop” seizures, commonly mistaken for fainting
- Tonic: stiffening
- Tonic-Clonic (grand mal): stiffening with entension or flexion followed by quick jerky movements + post-ictal state; often with incontinence
Epilepsy
recurrent seizures
Status epilepticus
:continuous seizure >30 min or recurrent seizures without gaining consciousness >30 min
-medical emergency
Cluster headaches
- unilateral, repetitive, 15 min-3hr
- excrutiating periorbital pain with lacrimation and rhinorrhea. may induce horner syndrome
- TX: oxygen, sumtriptan
Tension headache
- Constant, >30 min (4-6 hrs usually), bilateral
- steady pain, no photophobia, phonophobia, no aura
- tx: analgesics, NSAIDs, acetaminophen; amytriptyline for chronic pain
Migraine headache
- unilateral, 4-72 hr
- pulsating pain with nausea, photophobia or phonophobia. May have aura.
- Abortive tx: triptans, NSAIDs
- Prophylactic tx: propranolol, topiramate, CCB, amytriptyline
