Pathoma 17 Flashcards
3 things derived from 3 parts of the neural tube
Neural Crest -> PNS
Neural Tube Wall -> CNS
Lumen -> Ventricles and spinal cord canal
Detection of Neural Tube Defects during prenatal care by:
elevated alfa-fetoprotein (AFP) in amniotic fluid AND maternal blood
Disruption of cranial end of neural tube causes:
Anencephaly (absence of skull and brain)
Anencephaly effect on mother
Maternal polyhydraminos (increased amniotic fluid) impaired fetal swallowing of amniotic fluid
Disruption of caudal end of neural tube causes:
Spina bifida (vetebral defect from failure of posterior vertebral arch closure)
Spina bifida occulta presentation
Dimple or patch of hair overlying vertebral defect
What is congenital failure of cerebellar vermis to develop and how does it present?
Dandy-Walker Malformation
Presents as massively dilated 4th ventricle (posterior fossa) w/ absent cerebellum
Often accompanied by hydrocephalus
Type 2 Arnold Chiari Malformation
Congenital, downward displacement of cerebellar vermis and tonsils through foramen magnum
Obstruction of CSF flow -> hydrocephalus
Often associated w/ meningomyelocele
Where does Syringomyelia usually occur?
C8-T1
What are causes of Syringomyelia?
Arises w/ Trauma
or
Associated w/ Type 1 Arnold-Chiari malformation
Spinal Tracts affected by Syringomyelia
Anterior White Commissure (spinothalamic tract): sensory loss of pain and temperature (spares fine touch of dorsal column) in upper extremities; "cape like distribution" Anterior horn: Muscle atrophy and weakness w/ decreased tone and impaired reflexes Lateral horn (hypothalamospnial tract): Horner syndrom (ptosis, miosis, anhidrosis)
Poliomyelitis findings
Anterior motor horn damage from poliovirus Presents w/: flaccid paralysis w/ muscle atrophy fasciculations weakness w/ decreased muscle tone impaired reflexes (-) Babinski
Werdnig-Hoffman Disease
Inherited degeneration of Anterior Motor Horn
Autosomal Recessive
Presents as “floppy baby”
Death usually within a few years of birth
What is affected in Amyotrophic Lateral Sclerosis?
Upper and lower motor neurons of corticospinal tract
What is affected in Amyotrophic Lateral Sclerosis?
Upper and lower motor neurons of corticospinal tract
Anterior motor horn -> lower motor neuron signs
Lateral corticospinal tract -> upper motor neuron signs
Lower Motor Neuron Signs
- Flaccid paralysis w/ muscle atrophy
- Fasciculations
- Weakness w/ decreased muscle tone
- Impaired reflexes
- Negative Babinski
Upper Motor Neuron Signs
- Spastic paralysis w/ hyperreflexia
- Increased muscle tone
- Positive Babinski
Familial ALS sometimes has this mutation:
Zinc-copper superoxide dismutase (SOD1)
Leads to free radical injury in neurons
2 Early signs of ALS
Atrophy and weakness of hands
Distinguish ALS from Sryngomyelia
No sensory impairment in ALS
Degenerative disorder of Cerebellum and Spinal Cord?
How does it Present?
Fredreich Ataxia
Cerebellar degeneration -> Ataxia
Multiple spinal cord tract degeneration ->
-Loss of vibratory senses and proprioception
-Muscle weakness in lower extremities
-Loss of deep tendon reflexes
Early childhood presentation (wheelchair bound in few years)
Genetics of Freidreich Ataxia
Autosomal recessive
Unstable Trinucleotide repeat (GAA) expansion in Frataxin gene
What is Freidrech Ataxia associated with?
Hypertrophic cardiomyopathy
Common Infectious Agents causing meningitis in different populations
neonates: Group B strep, E. coli, Listeria monocytogenes
children and teens: N. meningitides
adults and elderly: Strep pneumoniae
non-vaccinated infants: H. influenza
Coxsackievirus in children (fecal-oral trasmission)
Fungi in immunocompromised
Presentation of Meningitis
Classic triad: headache, nuchal rigidity, fever
Also: photophobia, vomiting, altered mental status
How is Lumbar Puncture performed and why?
Stick needle between L4 and L5 (level of iliac crest)
Spinal cord ends at L2, but subarachnoid space and caudal equine continues to S2
Layers crossed includes skin, ligaments, epidural space, dura, and arachnoid
DOES NOT CROSS PIA
CSF Findings for Bacterial/Viral/Fungal Meningitis
Bacterial: neutrophils, low CSF glucose, gram stain and culture often able to identify
Viral: lymphocytes, normal CSF glucose
Fungal: lymphocytes, low CSF glucose
CSF Findings for Bacterial/Viral/Fungal Meningitis
Bacterial: neutrophils, low CSF glucose, gram stain and culture often able to identify
Viral: lymphocytes, normal CSF glucose
Fungal: lymphocytes, low CSF glucose
Why does necrosis occur within ____ after ischemia in brain?
3-5 minutes
Neurons are dependent on serum glucose as energy source -> particularly susceptible to ischemia
4 Causes of Global Cerebral Iscehmia (and examples)
- Low perfusion (atherosclerosis)
- Acute decrease in blood flow (cardiogenic shock)
- Chronic hypoxia (anemia)
- Repeated episodes of hypoglycemia (insulinoma)
Results of Severe global cerebral ischemia:
Results in diffuse necrosis
Survival leads to a ‘vegetative state’
Locations of Moderate global cerebral ischemia and effects:
Infarcts in Watershed Areas (between regions fed by anterior and middle cerebral); vulnerable area:
- Pyramidal neurons of cortex (layer 3, 5, 6): laminar necrosis
- Pyramidal neurons of hippocampus (temporal lobe): important in long-term memory
- Purkinje layer of cerebellum: integrates sensory perception w/ motor control
Difference between TIA and Ischemic Stroke
Ischemic Stroke definition: regional ischemia to the brain that results in focal neurologic deficits lasting >24 hours
Transient Ischemic Attack: symptoms last
Difference between TIA and Ischemic Stroke
Ischemic Stroke definition: regional ischemia to the brain that results in focal neurologic deficits lasting >24 hours
Transient Ischemic Attack: symptoms last
What kind of stroke causes a pale infarction in periphery of the cortex? Usually where?
Thrombotic stroke (rupture of atherosclerotic plaque) Usually at branch points
What is the most common source and location of an embolic stroke?
What does it lead to?
Most commonly from left side of heart (ex. a Fib)
Usually involves Middle Cerebral Artery
Results in hemorrhagic infarct
What causes a Lacunar stroke?
What does it usually involve?
What does it cause?
Secondary to hyaline arteriolosclerosis; Complication of HTN
Most commonly involves lenticulostriate vessels -> small cystic areas of infarction
Internal capsule involvement -> pure motor stroke
Thalamus involvement -> pure sensory stroke
What kind of stroke results in liquefactive necrosis?
What is the timeline of findings?
Ischemic stroke
12h - eosinophilic change in cytoplasm (red neurons)
24h - necrosis
1-3 days - infiltration by neutrophils
4-7 days - infiltration by microglial cells
2-3 weeks - gloss
Results in formation of fluid-filled cystic space surrounded by gliosis
What classically causes intracerebral hemorrhage?
Where and how does it present?
Rupture of Charcot-bouchard micro aneurysms of lenticulostriate vessels
Complication off HTN, treating reduces incidence by 1/2
Presents as: severe headache, nausea, vomiting, eventual coma
What presents as “worst headache of my life”?
What is it most commonly due to?
Subarachnoid hemorrhage
85% due to rupture of berry aneurysms:
-thin-walled saccular outpouchings lacking media layer
-most frequently in anterior circle of Willis branch points
-associated w/ Marfan, autosomal dominant PKD
Lumbar puncture of subarachnoid hemorrhage:
Shows xanthrochromia (yellow hue due to bilirubin)
CT of Epidural vs Subdural hematoma
Epidural: lens-shaped lesion
Subdural: crescent-shaped lesion
Classical cause of epidural hematoma:
Fracture of temporal bone w/ rupture of middle meningeal artery
Bleeding separates dura from skull
Cause of subdural hematoma:
Tearing of bridging veins between dura and arachnoid
Usually arises with trauma
Presentation of Epidural vs Subdural hematoma
Epidural:
-lucid interval may precede neurologic signs
Subdural:
-progressive neurologic signs
-inc. rate in elderly due to age-related cerebral atrophy -> stretches veins
Both: Herniation is lethal complication
Presentation of Epidural vs Subdural hematoma
Epidural:
-lucid interval may precede neurologic signs
Subdural:
-progressive neurologic signs
-inc. rate in elderly due to age-related cerebral atrophy -> stretches veins
Both: Herniation is lethal complication
2 Causes causes of herniation:
Mass effect
Increased intracranial pressure
What is Tonsilar Herniation and what can it lead to?
Displacement of cerebellar tonsils into foramen magnum
Compression of brain stem -> cardiopulmonary arrest
What is Subfalcine Herniation and what can it lead to?
Displacement of cingulate gyrus under fall cerebri
Compression of anterior cerebral artery -> infarction
What is Uncal Herniation and what 3 things can it lead to?
Displacement of temporal lobe uncut under tantrum cerebelli
- Compression of CN3 -> “down and out”, dilated pupil
- Compression of posterior cerebral artery -> occipital lobe infarction -> contralateral homonymous hemianopsia
- Rupture of paramedic artery -> Duret (brainstem) hemorrhage
Myelin cells of CNS vs PNS
CNS: Oligodendrocytes
PNS: Schwann cells
What is Leukodystrophy?
Inherited mutations in enzymes necessary for production or maintenance of myelin
Causes and Effects of 3 Leukodystrophic Diseaeses:
Metachromatic (most common)
- Deficiency of arylsulfatase (autosomal recessive)
- Sulfatides accumulate in lysosomes of oligodendrocytes
Krabbe disease
- Deficiency of galactocerebrosidase (autosomal recessive)
- galactocerebroside accumulates in macrophages
Adrenoleukodystrophy
- Impaired addition of CoA to long-chain fatty acids (x-linked)
- Accumulation of fatty acid damages adrenal glands and white matter of brain
Cause, Demographic, and Genetics of MS
- Autoimmune destruction of CNS myelin and oligodendrocytes
- Most common chronic CNS disease of young adults 20-30
- More commonly in women
- Associated w/ HLA-DR2
- More common in regions away from equator
How do you diagnose MS?
MRI: plaques (areas of white matter demyelination)
and
Lumbar puncture: increased lymphocytes, increased Ig w/ oligoclonal IgG bands on high res electrophoresis, myelin basic protein
What are 6 clinical features of MS?
- Blurred vision in one eye (CN2)
- Vertigo and scanning speech (brainstem)
- Internuclear Opthalmaplegia (MLF)
- Hemiparesis or unilateral loss of sensation (cerebral white matter, usually periventricular)
- Lower extremity loss of sensation or weakness (Cord)
- Bowel, bladder, and sexual dysfunction (ANS)
MS Treatment (Acute and Long-term):
Acute attacks: high-dose steroids (b/c it’s autoimmune)
Long-term: interferon beta (slows progression of disease
What is Subacute Sclerosing Panencephalitis?
Cause?
When?
Findings?
- Progressive, debilitating encephalitis -> DEATH
- Caused by slowly progressing, persistent infection of brain by Measles virus
- Infection in infancy —> neurologic signs years later (during childhood)
- Viral inclusions within neurons (gray matter) and oligodendrocytes (white matter)
Cause and presentation of Progressive Multifocal Leukoencephalopathy
JC virus infection of oligodendrocytes (white matter)
-Immunosuppression (AIDS or leukemia) –> reactivation of latent virus
Presents w/ rapidly progressive neurologic signs: -visual loss -weakness -dementia Leads to DEATH
Cause and presentation of Central Pontine Myelinolysis
Caused by rapid IV correction of hypoNatremia
Causes focal demyelination of Pons (anterior brain stem)
Classically presents as:
Acute bilateral paralysis (“Locked In” Syndrome)
Difference in Degeneration of Cortex vs. Brainstem/Basal ganglia
Cortex degeneration –> Dementia
Brainstem and Basal ganglia degeneration –> movement disorders
Most common cause of dementia?
Alzheimer Disease: degenerative disease of cortex
5 Clinical features of Alzheimers:
- Slow-onset memory loss (short-term progressing to long-term) and progressive disorientation
- Loss of learned motor skills and language
- Changes in behavior and personality
- Become mute and bedridden; infection common cause of death
- Focal neurologic deficits NOT seen in early disease
2 Risks for Alzheimers
- Age: doubles every 5 years after 60
2. e4 allele of APOE increases risk, e2 allele decreases
2 Associations of Early-onset Alzheimer
- Familial: associated w/ presenilin 1 and presenilin 2 mutations
- Down syndrom: commonly occurs by 40 b/c APP gene is located on chromosome 21
How is diagnosis of Alzheimers made?
By clinical and pathological correlations:
1. Presumptive diagnosis made clinically after excluding other causes
- Confirmed by histology at autopsy (when possible)
What are neurofibrillary tangles?
Found in Alzheimers
- Intracellular aggregates of fibers
- Composed of hyperphosphorylated tau protein
- tau is microtubue-associated protein
4 Morphologic features of Alzheimers
- Cerebral atrophy: gyri narrowing, sulci widening, ventricle dilation
- Neuritic plaques: AB amyloid
- Neurofibrillary tangles: hyperphosphorylated tau protein
- Loss of cholinergic neurons in nucleus basalis of Meynert
What are neuritic plaques?
What causes them?
Found in Alzheimers
- Extracellular core of AB amyloid entangled w/ neuritic processes
- AB amyloid derived from Amyloid Precursor Protein (APP)
- alpha cleavage –>degradable
- beta cleavage –> AB amyloid
- can deposit around vessels –>risk of hemorrhage
What is 2n most common cause of dementia?
Cause?
Vascular Dementia
Caused by multifocal infarction and injury
Due to HTN, atherosclerosis, or vasculitis
What is Pick Disease?
Cause?
Clinical features?
- Degenerative disease of Frontal and Temporal Cortex
- Spares Parietal and Occipital lobes
- Round aggregates of tau protein (Pick bodies) in neurons of cortex
- Early behavioral and language symptoms
- Eventually progresses to dementia
‘TRAP’ Clinical features
- Tremor:
- –Pill rolling tremor, disappears at rest
- Rigidity:
- –cogwheel rigidity in extremities
- Akinesia/bradykinesia:
- –slow voluntary movement,expressionless face
- Postural instability and shuffling gait
Pathophysiology of Parkinson Disease
Degenerative loss of Dopaminergic Neurons in Substantia Nigra of the Basal Ganglia
-Nigrostriatal pathway of basanganglia uses dopamine to initiate movement
Histology of Parkinson Disease:
- Loss of pigmented neurons in substantia nigra
- Round, eosinophilic inclusions of a-synuclein (Lewy bodies) in affected neurons (bright pink circle)
Differentiate Lewy body dementia vs. Parkinson disease
Parkinson Disease:
-late disease dementia
Lewy body dementia:
- early onset dementia, hallucinations, parkinsoninan features
- histo: CORTICAL Lewy bodies
Huntington Disease Cause
Degeneration of GABAergic neurons in the Caudate nucleus of the Basal Ganglia
Genetics of Huntington Disease
- Autosomal Dominant
- Chromosome 4
- Expanded trinucleotide repeat (CAG) in huntington gene
- Expansion during spermatogenesis
- leads to Anticipation (earlier onset every generation)
Presentation of Huntington Disease
- Chorea: random, purposeless movements
- Can progress to Dementia and Depression
- Average age of presentation is 40
- Suicide is common cause of death
What is/causes “Wet, Wobbly, Wacky”
Normal Pressure Hydrocephalus
-Triad of 1. Urinary Incontinence, 2. Gait Instability, 3. Dementia
Normal vs. disease Prion protein:
How does disease start and spread?
Prion protein normally expressed in CNS neurons
a-helix(PrPc) = normal, degradable
B-pleated (PrPsc) = diseased, not degradable, converts other normal protein into pathological form
First conversion can be: Sporadic, Inherited, Trasmitted
Histology of Spongiform Encephalopathy:
Spongy degeneration = intracellular vacuoles
-From damage to neurons and glial cells
What is the Inherited form of Prion Disease?
Familial Fatal Insomnia
- Severe insomnia
- Exaggerated startle Response
Presentation of CJD
- Rapidly progressive dementia
- Associated w/ Ataxia (cerebellar involvment)
- Associated w/ startle myoclonus
Periodic sharp waves on EEG
Death usually in
What is ‘mad cow’ disease?
Variant CJD
Special form of disease related to exposure to bovine spongiform encephalopathy
Characteristics of Metastatic CNS Tumors:
Common Sources?
Characteristically:
- Multiple, well-circumscribed lesions
- At gray-white junction
Common sources: Lung, Beast, and Kidney
Primary CNS tumor location in Adults vs. Children
Adult = usually supratentorial (above cerebellum) Children = usually infratentorial (below cortex)
Most common Adult CNS tumors:
- Glioblastoma multiforme (malignant)
- Meningioma (benign)
- Schwannoma (benign)
Most common Child CNS tumors:
- Pilocytic Astrocytoma (benign)
- Ependymoma (malignant)
- Medulloblastoma (malignant)
Glioblastoma Multiforme
- Malignant, high-grade tumor of astrocytes
- Most common primary malignant CNS tumor in Adults
- Crosses corpus callosum = ‘butterfly’ lesion
- Pseudopalisading =necrosis surrounded by tumor cells
- Endotehlial cell proliferation
- GFAP positive
- poor prognosis
Meningioma
- Benign turmor of arachnoid cells
- Most common bening CNS tumor in adults
- Common in women, rare in children
- May present as seizures
- Compresses but doesn’t invade cortex
- Imaging: round mass attached to dura
- Histo: whorled pattern; may have psamomma bodies
Schwannoma
- Benign tumor of Schwann cells
- Involves cranial or spinal nerves
- Most frequently involves CN8 at cerebellopontine angle
- –Presents as hearing loss and tinnitus
- Tumor cells S-100 positive
- Bilateral tumors seen in Neurofibromatosis Type 2
Oligodendroglioma
- Malignant tumor of oligodendrocytes
- Imaging = calcified tumor in white matter
- Usually involves frontal lobe
- May present w/ seizures
- ‘Fried-egg’ appearance of cells on biopsy
Pilocytic Astrocytoma
- Benign tumor of astrocytes
- Most common CNS tumor in children
- Usually in cerebellum
- Imaging: cystic lesion w/ a mural nodule
- Biopsy: Rosenthal fibers (thick eosinophilic processes of astrocytes), eosinophilic granular bodies
- Tumor cells GFAP positive
Medulloblastoma
- Malignant tumor derived from granular cells of cerebellum
- Neuroectoderm
- Usually in children
- Histo: small, round, blue cells, Homer-Wright rosettes
- Poor prognosis, rapidly divides, spreads via CSF, ‘drop metastasis’ = spread to cauda equina
Ependymoma
- Malignant tumor of ependymal cells (type of glial cells lining ventricles)
- Usually in children
- Common in 4th ventricle, may present w/ hydrocephalus
- Biopsy: characteristic perivascular pseudorosettes
Craniopharyngioma
- Tumor from epithelial remnants of Rathke’s pouch
- Presents as supratentorial mass in child or young adult
- Compressing optic chiasm –> biemporal hemianopsia
- Imaging: calcifications, derived from “tooth-like” tissue
- Benign, but tends to recur after resection
