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Flashcards in Neuro- Degenerative Deck (38):

What is the characteristic progression of degenerative disorders?

• Progressive decline over decades
• Difficulties in diagnosis (only in progressed state)
• Fewer are rapid (a few years)


Generally what is Alzheimers?


progressive disease that destroys memory and other important mental functions

Alzheimer(‘s) Disease (AD)
• DAT Dementia of Alzheimer’s type (very closely associated)
o 64% of all dementia
• progressive and irreversible
• incidence increase with age
o >65 = 10-15%
o >75= 20%
o >85= 48%


Et of Alzheimers

• ~90% idiopathic (sporadic form)
o R/t apolipoprotein E gene? -> This gene forms lipoproteins. Normally after 65yrs

•~10% Familial (Genetic)
o Normally before 65yrs


Genes and Chrom involved in Alzheimers

• Chr 1, 12, 14, 19, 21 involved
• 3 genes (APP, PSI & PS2)
 APP- Amyloid precursor Gene (chr 21)
 PS- Presenilin gene (PS!= chr14) (PS2= chr 1)
 Link to down syndrome (chr 21)


Pathology of Alzheimers...

Broadly, what is happening to the brain and what areas are affected?

• Atrophy of cerebral cortex

• Prominent sulci (dips), slender gyri (ridged tissue) r/t deficiency of dec Achetyocholine (Ach)

• Amygdala and Hippocampus affected (these are specialized ganglia in the CNS)

o Amygdala is in the temporal lobe and helps us to respond to environment
o Hippocampus in temporal under floor of ventricles and associated with memory
o Sensory cortex not affected


What sort of lesions are developing with progression of Alzheimers?

Lesion development generally leads to loss of neurons

• Neuritic plaques
o Deposit of amyloid protein (sticky fragments)

• Neurofibrillary tangles
o Fibrous proteins in cytoplasm
o Fibres resistant to breakdown, but cytoplasm around them breaks down when no longer functioning (atrophy)
o Tangles Persist after necrosis

• Acetylcholine (Ach) deficiency


How are MNFTS classified and how do they progress?

(Mild, Mod, Severe)
• Insidioius onset
• Stage-based progression over ~10yrs


Mild MNFTS of Alzheimers

• Mild AD (2-4yrs)
o Memory problems (person rarely notices)
o Careless work habits
o Familiar routines are manageable


Moderate MNFTS of Alzheimers

• Moderate AD (2-10yrs)
o Decline in cognition
o Confusion
o Language problems (speech, interpretation, response)
o Some motor fx disturbance (basic daily object use)
o Indifference
o Problems with ADL’s


Severe MNFTS (terminal stage of disease)

• Severe (terminal stage of disease)
o (Resp. complications- micro aspirations)
o Severe mental impairment
o Minimal voluntary movement
o No self care
o Incontinence
o Rigid, flexor Posturing (elbows flexed, fist clenched)

Heavy Care needs make Tx very difficult
Paraphasias (using inappropriate words (foot, instead of shoe)
•*extreme challenge for family members
• difficulty with medication compliance
• Aggression (med compliance important)


Dx of Alzheimers?

• Examination of tangles only possible post mortem

• No definitive test
• Go by clinical presentation
• Could go by elimination- Dementia presentation and exclude other causes
o Vascular (stroke)
o Toxic
o Vitamin B deficiency?
o HIV, syphilis?

• Still might go through other tests for differential diagnoses (just not definitive)
o EET (ElectroEncephalogram), MRI, Labs


Tx and Management of Alzheimers

Non-pharmalogical and Pharmalogical

• No cure. Slowing progression often the goal
• Symptomatic tx (incontinence etc)
• Behavior and enviro manipulations

• Glutamate receptor blocker (Memantine)
o Glutamate is a Neurotransmitter
o Too high a level of glutamate becomes neuro toxic
o Slows progression
• Ach-esterase inhibitor (Aricept)
o EsterASE (enzyme) that breaks down ACH
o Prevents break down post receptor binding
• Low-dose anitpsychotics
• Anti depression (effexor)
• Other meds?
o Statins, ASA, and Symptomatic mngmt meds


What is Multiple Sclerosis? (MS)

Who is at higher risk?

• Autoimmune disorder of CNS
• Myelin sheath targeted (CNS only)
o oligodendrocytes also potentially damaged

• x2 inc in women (young women at risk)
• Caucasians and colder regions of the world more prevalent


MS etiology

Who is at risk?

Is there a common trigger?

• Complex trait (Some genetic + some Enviro + some idiopathic)

• Familial tendency (risk is x15 times greater if it’s in your family)
o Genetic susceptibility (see MHC/HLA)

• Viral trigger (EBV (Epstein-Barr) is the common, but not exclusive trigger)


Pathology of MS?

• Demyelination in brain and Spinal Cord-> immune & inflm damage (sclerotic patches and plaques) -> conduction problems

• Although antibodies do not target Oligodendrocytes specifically, if they are near myelin target they may be damaged or destroyed
o Necrosis of oligodendrocytes

• Lymphocytes and macropahegs infiltration in plaques (aka sclerotic patches… a lesion of sorts develops)


Which cells and locations are commonly targeted by MS?

• Locations vary (symptoms present depending on location)

• Some locations more common then others
o Optic nerve, periventricular region, cerebellum, Spinal cord, Brain stem usually affected

• Both sensory and motor effected (all myelinated cells)

What is this?
• ?Demyelination leads to neurilemma?


What is the pattern of progression for MS

• Chronic pattern of exacerbation and remission (very Characteristic!)
o Duration remission diverse (could be years)
o Relapse is exacerbation (worse)



• Vary d/t location and extent of damage
• Visual impairment, paresthesias (abnormal sensations- numbness, pins and needles, burning), fatigue
• Bowel and bladder dysfunction
• Decreased muscle strength
• Gait and coordination problems


Major barrier to dx MS

Other diseases present in a similar way as the onset symptoms of MS


Dx of MS

Dx difficult
• History and presentation
• Imaging- MRI for plaques
• Tap CSF – proteins (antibodies like IgG) will be elevated

o Why are proteins in CSF? Possibel reasons:

• Blood brain barrier (BBB) compromised
• autoimmunity
• Inflm


Tx of MS


• Steroids for acute relapse
• For delaying progression
o Methotrexate
• (immune modulatory drug- regulates IR) *key action for MS

• anitfolate (inhibits folic acid – associated in DNA/cell division)
o Interferon for those with persistent relapses
• Immune modulatory


What is Amyotrophic Lateral Sclerosis (ALS)-

AKA? Types? Who's at Risk?

Lou Gehrig disease
• Most common motor neuron disorder
• Progressive, short duration

• Middle-age male (twice the risk)
• Death in 2-5 years
o Normally respiratory failure

• Bulbar ALS – develops in brain stem
o Speech impairment and brainstem degeneration common in this form at early stages/


Et of ALS?


• Sporadic (90-95%)
o SOD1 Gene mutation, CHr 21 (~5%)
o Superoxide dismutase gene (breaks up free radicals)
o Superoxide is a freeradical

• Familial (5-10%)
o SOD1 (20%)
o Other genes (80%)

• Other factors (autoimmune, viral)


Path of ALS

• Motor neuron degeneration (irreversible) in
o Anterior horn cells in Spinal cord
o Motor nucleus in brain stem
o Upper motor Neurons (UMN) in cerebral cortex

• UMN being brain to spinal cord (LMN) is spinal to periphery
o Proposed free radical &/or glutamate toxicity
• Mechanism unclear



Key Acute issue and prognosis?

Chronic Issues?

What is left intact?

• Death in 2-5 years
o Normally respiratory failure

• Muscle atrophy (no stim, no use), weakness, fasciculations
• Dysarthria (referring to impaired speech)
• Acute complications : dysphagia & aspiration

• Intact cognition and sensory function


Dx of ALS

• Clinical presentation
• Electromyopathy (stimulating nerve and measuring conduction, stimulate muscle and measure reaction)


Tx of ALS

Pharma and Non Pharma

• Mostly supportive Mngmt
o Breathing
• PEG Tube

• Pneumonia moniter and prevention (Pharma)
• Riluzole (neuro protection?)
o Somehow works on glutamate toxicity
o Poor success rate


What parts of neural function are impacted by dementia

1) Memory
2) Language
3) Reasoning
4) judgment


What is parkinson's disease?

Slowly progressing neurologic movement disorder that eventually leads to disability. Associated with tremors and rigidity


What are the risk factors of Parkinson's

Males are more likely affected
Normally post 50yrs
**Research suggests genetics, atherosclerosis, head trauma, infections, 02 free radicals, anti psychotic meds, and environmental factors


Etiology of Parkinson's

the degenerative type is Idiopathic.

Complex trait

Alphasinuclein UCHL!-
Gene that code for Parkins protein


Pathology of Parkinson's

r/t dec levels of dopamine resulting from destruction of the substantial nigra in basal ganglia resulting in imbalance of acetylcholine (excitatory) and dopamine (inhibitory) neurotransmitters and disruption of the nigrostriatum pathway.

Causes Impairment or extrapyramidal tracts controlling complex and voluntary body movements.

Symptoms don't appear till 60% of pigmented neutrons are lost

NOTE- proteins called lewy bodies are seen on the dopamine neurons, we are not sure why


MNFTS of Parkinson's

Cardinal Signs + Extras

Tremors, rigidity, bradykinesia, postural changes,

Also depression, constipation, dementia, dysphonia (speech problems), micrographia (writing problems)


Dx of parkinson's?

Pharma Tx?

Clinical hx and the presence of 2 of the 4 cardinal signs.

No Medical or Sx tx exists to stop progression. Focus on maintaining independence.

Antiparkinsonian medications (levadopa). anticholinergic drugs, amantadine, dopamine agonists and MAO inhibitors


What areas of the brain are affect by Alzheimers?

Amygdala (environment interaction) and hippocampus (retain memory)


Which chromosome affect HLA? (MHC)



What is the prognosis for those with ALS

• Death in 2-5 years
o Normally respiratory failure


What are lewis bodies