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

Question 1

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

Answer 1

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

Question 2

Describe early vs late onset AD

Answer 2

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

Question 3

What is the pathogenesis for Alzheimer’s Disease?

Answer 3

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

Question 4

Where does Alzheimer’s Disease begin?

Answer 4

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

Question 5

What is the presentation for Alzheimer’s Disease?

Answer 5

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)

Question 6

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

Answer 6

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)

Question 7

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

Answer 7

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

Question 8

What complications are associated with Alzheimer’s Disease?

Answer 8

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

Question 9

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

Answer 9

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

Question 10

What is the pathogenesis for parkinsons disease?

Answer 10

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

Question 11

What is the pathogenesis for Parkinson’s disease?

Answer 11

Tremor, Rigidity, Akinesia and Shuffling Gait

Question 12

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

Answer 12

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

Question 13

What is the pathogenesis for Huntington’s Disease?

Answer 13

Marked atrophy of caudate and putamen

Lesser atrophy of globus pallidus and cerebral cortex

Question 14

What is the presentation for Huntington’s Disease?

Answer 14

Choreiform movements
Motor Difficulties
Dementia

Question 15

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

Answer 15

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

Question 16

What is the pathogenesis for ALS?

Answer 16

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

Question 17

What is the presentation for ALS?

Answer 17

Muscle weakness and atrophy

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

Question 18

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

Answer 18

Multifactorial, prevalent in temperate climates

Question 19

Who are at highest risk for MS?

Answer 19

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)

Question 20

What is the presentation for MS?

Answer 20

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

Question 21

What is the most commonly affected nerve in MS?

Answer 21

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

Question 22

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

Answer 22

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

Question 23

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

Answer 23

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

Question 24

What are the complications of MS?

Answer 24

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

Question 25

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

Answer 25

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

Question 26

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

Answer 26

Fulminant form of ADEM

–extensive fibrinoid necrosis of small vessels and petechiae

Question 27

Very briefly what is central pontine myelinolysis?

Answer 27

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

Question 28

What are some features of central pontine myelinolysis?

Answer 28

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

Question 29

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

Answer 29

Chronic alcohol abuse — thiamine deficiency

Question 30

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

Answer 30

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

Question 31

What is the chronic state of Wernicke-Korsakoff?

Answer 31

Korsakoff’s Psychosis (Chronic)

–affected areas are shrunken, discolored and gliotic

Question 32

What is the pathogenesis for Wernicke-Korsakoff?

Answer 32

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

Question 33

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

Answer 33

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

Question 34

What is the pathogenesis for hypoglycemia encephalopathy?

Answer 34

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