Neuro- Degenerative Flashcards
(38 cards)
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?
Incidence?
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 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)
NOTE: 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)
MNFTS of MS
- 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
Pharmacological
• 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?
Genetic
• 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
NOTES:
• UMN being brain to spinal cord (LMN) is spinal to periphery
o Proposed free radical &/or glutamate toxicity
• Mechanism unclear
