Flashcards in Module 7: CNS: Alzheimer's, Park, Hunt, ALS, MS, Wernicke Deck (34):
First starting off this card deck will be Alzheimer's disease, what is the etiology?
Down syndrome b/c APP is on Chr.21
Describe early vs late onset AD
APP (Ch.21), Presenilllin (Ch1 and 14), Clusterin (Ch.8) & Complement receptor (Ch1)
Apo E genotype (Ch19) and E4 increases risk of AD and E2 decreases risk
What is the pathogenesis for Alzheimer's Disease?
Defective cleavage of transmembrane cellular proteins -- atrophy of frontal, parietal and temporal lobes
--Occipital lobe is spared
Where does Alzheimer's Disease begin?
Starts in temporal lobe aka hippocampus (which is why you have memory loss initially) the eventually generalized paralysis due to parietal lobe involvement
What is the presentation for Alzheimer's Disease?
Slowly progressive dementia (impaired cognition) but motor and sensory systems are intact
again starts in temporal (memory loss) then paralysis and bed ridden (parietal and frontal)
For Alzheimer's Disease, the dx is made on autopsy, what is seen?
Dx of exclusion (like rabies)
-Neurofibrillary tangles (TAU proteins): intracellular and hyperphosphorlyated
-Beta Amyloid Plaques, Abeta or Beta2: Extracellular, amyloid on H&E, localized (salmon pink on Congo red and apple green under polarized light)
What is seen on CT and histology and gross is Alzheimers patients?
CT: flattening of sulci and gyri with enlarged ventricles
Histology: neurofibrillary tangles + astrocyte proliferation
Gross: widening of cerebral sulci and narrowing of gyri
What complications are associated with Alzheimer's Disease?
Hydrocephalus Ex Vaco: due to atrophy of the brain
Most common cause of death = Aspiration pneumonia (bed ridden, trouble swallowing and lung abscesses)
Bed Sores/Pressure Ulcers and DVTs -- PE
Cerebral Amyloid Angiopathy: lobar hemorrhages (following a fall)
--deposition of amlyoid (homogeneous eosinophilic material) in the walls of cerebral vessels
The next topic will be Parkinson's Disease, what is the etiology?
Several fold increase in incidence of Alzheimers disease
--usually no family history: most cases are sporadic
--mutation in the synuclein gene (synuclein is component of Lewy Bodies)
-non degenerative causes = medication and cocaine abuse
What is the pathogenesis for parkinsons disease?
Atrophy of substantia nigra (nucleus of dopaminergic neurons in the midbrain) and presence of Lewy Bodies
What is the pathogenesis for Parkinson's disease?
Tremor, Rigidity, Akinesia and Shuffling Gait
Next is Huntington's Disease, what is the etiology?
CAG repeats with genetic anticipation (Earlier onset in successive generations) -- gain of function mutation that interferes with nucleic acid or protein regulations
--AD = male and females equal
What is the pathogenesis for Huntington's Disease?
Marked atrophy of caudate and putamen
Lesser atrophy of globus pallidus and cerebral cortex
What is the presentation for Huntington's Disease?
Next is ALS/Lou Gehrig's/Motor Neuron Disease, what is the etiology?
Affects middle aged
--Ch.9 hexanucleotide repeat and SOD-1
Does not affect peripheral nerves (schwann cells)
What is the pathogenesis for ALS?
Neuronal loss in spinal cord anterior horns (motor cortex)
--ubiquitin (Deposited in LMNs of brainstem to cell injury)
--TDP-43, FUS --- abnormal RNA/protein processing
What is the presentation for ALS?
Muscle weakness and atrophy
-Intellect, sensation, sphincter control and eye movements are spared
-life expectancy - 2-5 year after onset
Moving along the next big topic for discussion is Multiple Sclerosis, what is the etiology?
Multifactorial, prevalent in temperate climates
Who are at highest risk for MS?
Young White females living in temperate or colder temperatures
--other risk factors: smoking, low vit D, EBV, maternal history and move to endemic area before puberty
Autoimmune: HLA DR2 and DR15 -- antibodies destroying oligodendrocytes aka white and grey matter (genetic vulnerability to patchy demyelination of the axonal tissue)
What is the presentation for MS?
Waxes and Wanes (transient & recurrent) -- can go years without symptoms
--symptoms related to area involved and grey matter injury best correlates with disability
What is the most commonly affected nerve in MS?
CN II -- optic neuritis --- pain on eye movement and blurred vision and diplopia
Patient with MS also experience destruction of the Medial Longitudinal Fasciculus (MLF), what are the symptoms from this?
Internuclear Opthalmoplegia --- ipsilateral eye cannot adduct while contralateral eye undergoes nystagmus.
What is seen on MRI, LP and Histology in patients with MS?
MRI with contrast: periventricular demyelination of white matter
LP: oligoclonal bands of IgG in the CSF
Histology: abundant macrophages containing PAS positive debris
What are the complications of MS?
Most patients die of infections
--infections from immunosuppressive drugs
Bladder Infections from urinary retention
--damage to parasympathetics to the bladder
Very briefly patient can develop acute disseminated encephalomeylitis (ADEM), from what?
Preceding viral infection (MMR, varicella and EBV) or vaccination (for smallpox)
--multifocal perivenous encephalomyelitis with perivascular demyelination
Very briefly patients can develop acute hemorrhagic leukoencephalopathy, from what?
Fulminant form of ADEM
--extensive fibrinoid necrosis of small vessels and petechiae
Very briefly what is central pontine myelinolysis?
Monophasic demyelinating illness
Rapid Correction of Hyponatremia
-infusion of hypotonic fluids
--adrenal insufficiency, renal failure, CHF
What are some features of central pontine myelinolysis?
Affects basis points
Minimal inflammation and neurons/axons are relatively preserved
Related to Marchiafava Bignami Disease
Briefly the next topic Wernicke-Korsakoff, what is the etiology for this?
Chronic alcohol abuse --- thiamine deficiency
Wernicke Encephalopathy (acute stage) of Wernicke-Korsakoff, what is seen?
Encephalopathy, ocular palsies, ataxia
Neuronal necrosis, petechial hemorrhages
Pathogenesis; destruction of mamillary bodies
Presentation: heavy smell of alcohol, confused state, alternating movements of eye, paralysis of lateral gaze and ataxia
What is the chronic state of Wernicke-Korsakoff?
Korsakoff's Psychosis (Chronic)
--affected areas are shrunken, discolored and gliotic
What is the pathogenesis for Wernicke-Korsakoff?
Cerebellar degeneration (males greater than females)
--selective involvement of Purkinje cell layer of anterior vermis
--minor involvement of cerebellar nuclei
The last topic for this card deck is Hypoglycemia Encephalopathy, what is the etiology?
Excessive exogenous insulin (most common)
Severe liver disease