Module 7: CNS: Alzheimer's, Park, Hunt, ALS, MS, Wernicke Flashcards

1
Q

First starting off this card deck will be Alzheimer’s disease, what is the etiology?

A

Elderly ppl
Down syndrome b/c APP is on Chr.21
80% sporadic
20% familial

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2
Q

Describe early vs late onset AD

A

Early:
APP (Ch.21), Presenilllin (Ch1 and 14), Clusterin (Ch.8) & Complement receptor (Ch1)
Late:
Apo E genotype (Ch19) and E4 increases risk of AD and E2 decreases risk

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3
Q

What is the pathogenesis for Alzheimer’s Disease?

A

Defective cleavage of transmembrane cellular proteins – atrophy of frontal, parietal and temporal lobes
–Occipital lobe is spared

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4
Q

Where does Alzheimer’s Disease begin?

A

Starts in temporal lobe aka hippocampus (which is why you have memory loss initially) the eventually generalized paralysis due to parietal lobe involvement

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5
Q

What is the presentation for Alzheimer’s Disease?

A

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)

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6
Q

For Alzheimer’s Disease, the dx is made on autopsy, what is seen?

A

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)
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7
Q

What is seen on CT and histology and gross is Alzheimers patients?

A

CT: flattening of sulci and gyri with enlarged ventricles
Histology: neurofibrillary tangles + astrocyte proliferation
Gross: widening of cerebral sulci and narrowing of gyri

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8
Q

What complications are associated with Alzheimer’s Disease?

A

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

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9
Q

The next topic will be Parkinson’s Disease, what is the etiology?

A

Several fold increase in incidence of Alzheimers disease
Etiology:
–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

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10
Q

What is the pathogenesis for parkinsons disease?

A

Atrophy of substantia nigra (nucleus of dopaminergic neurons in the midbrain) and presence of Lewy Bodies

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11
Q

What is the pathogenesis for Parkinson’s disease?

A

Tremor, Rigidity, Akinesia and Shuffling Gait

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12
Q

Next is Huntington’s Disease, what is the etiology?

A

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

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13
Q

What is the pathogenesis for Huntington’s Disease?

A

Marked atrophy of caudate and putamen

Lesser atrophy of globus pallidus and cerebral cortex

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14
Q

What is the presentation for Huntington’s Disease?

A

Choreiform movements
Motor Difficulties
Dementia

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15
Q

Next is ALS/Lou Gehrig’s/Motor Neuron Disease, what is the etiology?

A

Affects middle aged
Identified mutations:
–Ch.9 hexanucleotide repeat and SOD-1
Does not affect peripheral nerves (schwann cells)

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16
Q

What is the pathogenesis for ALS?

A

Neuronal loss in spinal cord anterior horns (motor cortex)
Cytoplasmic inclusions:
–ubiquitin (Deposited in LMNs of brainstem to cell injury)
–TDP-43, FUS — abnormal RNA/protein processing

17
Q

What is the presentation for ALS?

A

Muscle weakness and atrophy

  • Intellect, sensation, sphincter control and eye movements are spared
  • life expectancy - 2-5 year after onset
18
Q

Moving along the next big topic for discussion is Multiple Sclerosis, what is the etiology?

A

Multifactorial, prevalent in temperate climates

19
Q

Who are at highest risk for MS?

A

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)

20
Q

What is the presentation for MS?

A

Waxes and Wanes (transient & recurrent) – can go years without symptoms
–symptoms related to area involved and grey matter injury best correlates with disability

21
Q

What is the most commonly affected nerve in MS?

A

CN II – optic neuritis — pain on eye movement and blurred vision and diplopia

22
Q

Patient with MS also experience destruction of the Medial Longitudinal Fasciculus (MLF), what are the symptoms from this?

A

Internuclear Opthalmoplegia — ipsilateral eye cannot adduct while contralateral eye undergoes nystagmus.

23
Q

What is seen on MRI, LP and Histology in patients with MS?

A

MRI with contrast: periventricular demyelination of white matter
LP: oligoclonal bands of IgG in the CSF
Histology: abundant macrophages containing PAS positive debris

24
Q

What are the complications of MS?

A

Most patients die of infections
–infections from immunosuppressive drugs
Bladder Infections from urinary retention
–damage to parasympathetics to the bladder

25
Q

Very briefly patient can develop acute disseminated encephalomeylitis (ADEM), from what?

A

Preceding viral infection (MMR, varicella and EBV) or vaccination (for smallpox)
–multifocal perivenous encephalomyelitis with perivascular demyelination

26
Q

Very briefly patients can develop acute hemorrhagic leukoencephalopathy, from what?

A

Fulminant form of ADEM

–extensive fibrinoid necrosis of small vessels and petechiae

27
Q

Very briefly what is central pontine myelinolysis?

A
Monophasic demyelinating illness 
Rapid Correction of Hyponatremia
-psychogenic polydipsia
-infusion of hypotonic fluids
-SIADH secretion
--adrenal insufficiency, renal failure, CHF
28
Q

What are some features of central pontine myelinolysis?

A

Affects basis points
Minimal inflammation and neurons/axons are relatively preserved
Related to Marchiafava Bignami Disease

29
Q

Briefly the next topic Wernicke-Korsakoff, what is the etiology for this?

A

Chronic alcohol abuse — thiamine deficiency

30
Q

Wernicke Encephalopathy (acute stage) of Wernicke-Korsakoff, what is seen?

A

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

31
Q

What is the chronic state of Wernicke-Korsakoff?

A

Korsakoff’s Psychosis (Chronic)

–affected areas are shrunken, discolored and gliotic

32
Q

What is the pathogenesis for Wernicke-Korsakoff?

A

Cerebral Atrophy
Cerebellar degeneration (males greater than females)
–selective involvement of Purkinje cell layer of anterior vermis
–minor involvement of cerebellar nuclei

33
Q

The last topic for this card deck is Hypoglycemia Encephalopathy, what is the etiology?

A
Excessive exogenous insulin (most common) 
Primary hyperinsulinemia 
Severe liver disease 
Adrenal insufficiency 
Nesidioblastosis (neonates)
34
Q

What is the pathogenesis for hypoglycemia encephalopathy?

A

Sustained (1-2hrs) low blood sugar level of less than 1.5mmol/L — effect on brain resembles hypoxia/ischemia
–Purkinje cells may be spared