Demyelinating Diseases Flashcards
Most common demyelinating disorder
MS
MS defined
Autoimmune demyelinating disorder = distinct episodes of neuro deficits, separated in time, attributable to white matter lesions that are separated in space
Myelin
Promotes transmission of a nerve impulse along an axon, rich in lipids & proteins, form layers around nerve fibers, produced in the CNS by oligodendrocytes
Relapsing-remitting
Attacks of worsening neuro function
MS epidemiology
2-3x more common in women than men
Genetic factors play a role
ID twin - 1 in 4 chance of developing disease
MS morphology
Lesions (plaques) spread throughout white matter
Plaques - sharply circumscribed, depressed, glassy & gray-tan, irregularly shaped lesion; commonly located @ angle of lateral ventricles (optic nerves & chiasm, brain stem, cerebellum, spinal cord)
MS symptoms
Most common: fatigue, numbness, walking, balance & coordination problems, bladder dysfunction
MS diagnosis
No specific symptom, physical finding or lab test…
Need evidence of damage in at least 2 areas of CNS, & that damage occurred at least 1 month apart
CSF Studies - MS
Mildly elevated protein, proportion of gamma globulin increased, oligoclonal bands; B-cell proliferation w/in nervous system
MS Clinical
Unilateral vision impairment, optic nerve involved
Central pontine myelinolysis
Loss of myelin in symmetrical pattern involving the basis pontis & portions of pontine tegmentum
Believed due to rapid correction of hyponatremia
What 3 groups of pts does CPM occur in
Alcoholics, severe electrolyte osmolar imbalance & orthotopic liver transplant
CPM clinical findings
Rapidly evolving quadriplegia
What is lost in degenerative diseases of the brain?
Progressive loss of neurons of gray matter
Two general characteristics of degenerative diseases of the brain
Development of protein aggregates resistant to normal degredation (recognized histologically as inclusions), aggregates usually cytotoxic
Degenerative Diseases
Alzheimers
Movement motor disorders: amyotrophic lateral sclerosis, Parkinson’s, Huntington’s
Dementia
Progressive loss of cognitive function independent of state of attention - not a part of normal aging, represents a pathologic process
What is the most common cause of dementia in the elderly?
Alzheimer’s
Delerium
The onset of mental status change, such as confusion, disorientation, agitation; often due to drugs, hypoxia, metabolic condition
Alzheimer’s
Impairment of higher intellectual functions w/alterations in mood & behavior
Later progressive disorientation, memory loss, aphasia
5-10 years patient disabled, mute & immobile
5-10% familial
1% of 60-64 y/o’s, 40% of 85-89 y/o’s
Alzheimer’s history
Memory probs, difficulty speaking, paranoia.
Died from bedsores & pneumonia
Autopsy: Cortex shrunk, dead/dying brain cells, abnormal deposits in & around cells
Entered med. literature @ 1907, in 1910 named after Dr Alzheimer
Alzheimers - cont’d
10mi baby boomers will develop
6th leading cause of death
Alzheimer’s RFs
Age, fam history, genetics: APOLIPOPROTEIN E-e4, deterministic gene - familial alzheimers disease
Alz - gross findings
Variable degree of cortical atrophy: frontal, temporal, parietal; compensatory ventricular enlargement (hydrocephalus)
Alz - 3 microscopic findings
Neurofibrillary tangles
Senile (neuritic) plaques
Amyloid angiopathy
Alz Pathogenesis
Amyloid (AB) - derived from APP
AB peptides aggregate and generate AB found in brain parenchyma & around vessels
Gene for APP is on chromo21
Development of Alz in trisomy 21
Related to gene dosage effect
Alz - Clinical
Course runs more than 10 yrs
Initially forgetfulness, other memory disturbances
Later language deficits, loss of math skills, loss of learned motor skills
FInal incontinent, mute, unable to walk
Pneumonia often terminal event
Alz - Dx
Medical history Mental status tests Phys exam & diagnostic tests Neuro exam Brain imagins
Alz - Treatment
Cholinesterase inhibitors: prevents the breakdown of acetylcholine, support communication among nerve cells by keeping acetylcholine levels high
Memantine: regulates activity of glutamate
Degenerative basal ganglia & brain stem
Movement disorders:
Rigidity, abnormal posture, chorea (involuntary jerky movements)
Reduction of voluntary or abundance of involuntary movement
Involves nigrostriatal system (dopamine pathway involved in production of movement)
Six cardinal clinical features of Parkinsonism
Clinical syndrome: Diminished facial expression Stooped posture Festinating gait Rigidity "Pill rolling" tremor Slowness of voluntary movements
What pathway in the brain is malfunctioning in the parkinsonism group of diseases
Nigrostriatal dopaminergic system
Parks - gross
Pallor of substantia nigra
Parks - micro morphology
Loss of pigmented catecholaminergic neurons w/gliosis
Lewy bodies (protein aggregates): eosinophilic, round inclusions w/dense core surrounded by paler rim
Neurofilament antigens present
IPD
Dopaminergic neurons of substantia nigra project to striatum - loss in IPD reduced striatal dopamine content
Can partially correct motor probs w/L-dopa (can cross brain barrier)
IPD - Clinical
10-15% develop dementia, increasing incidence w/increasing age
Treat w/ L-DOPA therapy
Neural transplantation
H disease: how is it genetically transmitted?
AD
H disease movement:
CHOREIFORM: involuntary jerky movements of all parts of the body, writhing movements of extremities are typical
Uncontrolled movements, chorea
H disease: Brain - gross
Small brain, marked atrophy of caudate nucleus
Severe loss of striatal neurons
H disease - affected neurons
Caudate: most severe; putamen: less
Lare & small neurons affected, small first
Medium sized - use GABA as NTs are affected
H disease - trinucleotide repeat? Age of onset?
HD of chromosome 4
CAG repeats
4th and 5th decades
H disease - natural course of disease
Early symptoms of higher cortical dysfunction include forgetfulness & thought & affected disorders
Degenerative diseases of motor neurons affect what 3 groups of neurons
LMNs - anterior horn of SC, cranial nerve nuclei: 5, 7, 8, 12
UMNs - Betz cells in motor cortex
Denervation of muscles leads to what manifestations
Muscle atrophy, hyperreflexia, eventual symmetric weakness, death from respiratory paralysis
ALS
Both UMN, LMN degenerate
Most common NM disease worldwide
Between 40-60 yrs
Men
ALS - Morphology
UMN & LMN loss
ALS - Symptoms
Muscle weakness, atrophy spread
Moving problems, swallowing (dysphagia) and speaking/forming words (dysarthria)
ALS - Dx
Signs & symptoms, tests to rule out other diseases
EMG - electromyographty
NCV - nerve conduction velocity
MRI
Thiamine deficieny
Vit B1 Beriberi Wenicke Korsakoff Common in chronic alcoholism Mamillary bodies - hemorrhage, necrosis
Neurologic manifestations of VitB12 deficiency?
Slight ataxia (coordinate muscle movement), numbness, tingling of LEs Progresses to spastic weakness, complete paraplegia may occur
Toxic & Acquired metabolic: Hypoglycemia
Hippocampus - Sommer’s sector
Cerebellum - Purkinje cells
Cortex - large pyramidal neurons
Global insult
Toxic & Acquired metabolic: Hyperglycemia
Ketoacidosis/hyperosmolar coma, dehydration
CO
Bilateral necrosis of globus pallidus
Hypoxic changes
Methanol
DEgeneration of retinal ganglion cells
Ethanol
Symptoms of cerebellar dysfunction from choric alcoholism: truncal ataxia, unsteady gait, nystagmus
Cerebellar degneration : anterior vermis (Bergman gliosis)
FAS: growth retardation, facial abnormalities, cardiac septal defects, joint probs, delayed development
Radiation
Delayed effects: months to years
Headaches, nausea, vomiting, papilledema
Coagulative necrosis w/ adjacent edema in white matter
Tumor induction possible
