Neurodegen Flashcards
What is demyelination?
Acquired loss of myelin WITH AXONAL SPARING
CNS: MS, viral (PML from JC), metabolic
PNS: Toxic, Inflammatory, Guillain-Barre
What is dysmyelination?
Inherited, myelin not formed or is abnormally formed
- Axons tend to undergo degeneration
- LEUKODYSTROPHIES
What is MS?
Autoimmune DEMYELINATING disease
Well defined episodes of neuro deficits, separated by time, white matter lesions that are separated by space
Who most often gets MS?
Young Women
What is the spectrum of MS disease?
Relentless to little progression
What are the Genetic factors of MS?
CLASS II MHC-DR2, DR4, DR15, DQ6
15-20x if 1st degree relative
MZ twins have a greater magnitude
May be environmental: Pacific theatre WII outbreak
What is the pathogenesis of MS?
CD4 T cells that attack oligos
Target: MOG (myelin oligo glycoprotein), MBP (myelin basic protein, and alpha beta crystallin
What is the mechanism of injury for MS?
Antibodies and complement
- T cell induced B cell clonal expansion in CSF
Produces IgG1, IgG3
What is the diagnostic hallmark of MS?
Oligoclonal banding of CSF
Ag-Ab complex recognized by Macrophages
What is the mechanism of injury for MS?
Antibodies and complement
- T cell induced B cell clonal expansion in CSF
Produces IgG1, IgG3
Ag-Ab complex recognized by Macrophages and is recognized by Fc receptor
Fc receptor binding with complement causes damage to myelin leading to phagocytosis
What is the diagnostic hallmark of MS?
Oligoclonal banding of CSF
Ag-Ab complex recognized by Macrophages and is recognized by Fc receptor
What is the mechanism of injury for MS?
Antibodies and complement
- T cell induced B cell clonal expansion in CSF
Produces IgG1, IgG3
Ag-Ab complex recognized by Macrophages and is recognized by Fc receptor
Fc receptor binding with complement causes damage to myelin leading to phagocytosis
Lympocyte mediated injury
- T lymph prominent in early plaque formation
- Oligos are targets of cytolytic T cells
Macrophages
-Activated macros produce ROS and NOS, proteolytic enzymes, cytokines (TNF) that damage myelin
What is the diagnostic hallmark of MS?
Oligoclonal banding of CSF
Ag-Ab complex recognized by Macrophages and is recognized by Fc receptor
What are plaques in MS?
Actively demyelinating plaques (loss of myelin, retention of axons, myelin-laden macros
-Center of plaque is Perivascular T-cells
Inactive: Axons undergo demyleination
-Leave astros to repair (GLIOSIS)
Shadow: Remyleination occurring slowly
-LFB stain
What are different types of MS?
Classic (Charcot)
Acute (Marburg)
Neuromyelitis Optica (spinal cord and optic nerves)
-Aquaporin 4 abnormalities
Schilder’s disease: Children, fulminant to remiting with steroid therapy
Concentric sclerosis (balo’s type): Very rare and diagnosed at autopsy
What is the cause of MS neuromyelitis optica?
Aquaporin 4 mutation (associated with BBB abnormalities
Who is affected by Schilder’s disease most often?
Children, young adults
Acute/subacute with symmetrical bilateral plaques
2x3cm involving central semiovale
No other lesions seen
Who is affected by Schilder’s disease most often?
Children
What is central pontine myelinolysis?
Toxic demyelination disorder
Too rapid overcorrection of hyponatremia
Due to swelling and damage to myelin sheath during the too rapid change
What is the clinical picture of CPM?
Confusion, limb weakness, conjugate gaze palsies, dysarthria, dysphagia, hypotension
What is the prognosis of CPM?
Poor most patients succumb within weeks
What is Guillain Barre syndrome?
Acute inflammatory demyelinating polyradiculopathy
Due to infectious causes (viral, campy)
Ascending paralysis
Few patients progress to MS
WHat is ADEM?
Acute disseminated encephalomyelitis
Few weeks after viral infections
HA, Vomiting, Rapid weakness, sensory loss, ataxia, visual impairment, stupor, LOC, seizures
20% succumb to disease
5-10% have relapses
What is the range of complications with alcohol and fetal development?
Binge drinking results in the severe abnormalities
Behavioral and minor learning disabilities to severe facial (ocular) and cardiac defects
What is the most common cause of Alch related death in adolescents young adults?
Alc poisoning and trauma
What are the nutritional deficiencies in the alcoholic?
Thiamine (B1)
B12
What is a consequnce of thiamine def?
Wernickes encephalopathy
- Necro encephalopathy with mamillary bodies, periaqueductal grey, pons and medulla
- Ataxia, gaze palsies, alterned mental state
Korsakoffs syndrome: Thalamic disease
- Severe antegrade amnesia with confabulation
What is a consequnce of thiamine def?
Wernickes encephalopathy
- Necro encephalopathy with mamillary bodies, periaqueductal grey, pons and medulla
- Ataxia, gaze palsies, alterned mental state
Korsakoffs syndrome: Thalamic disease
- Severe antegrade amnesia with confabulation
What is a consequence of B12 deficiency?
Subacute combined degeneration of spinal cord
Ascending and descending tract
Slow onset of ataxia, tingling of legs
paraplegia can develop
What happens to the cerebellum due to alcohol?
Atrophy
Toxic to internal granular layer of cortex (vermix) atrophy in particular
What are alcoholics also at risk for?
Central pontine myelinolysis
Hepatic encephalopathy
Stroke
Peripheral neuropathy
Optic neuropathy
Marchiafava-bignamic Disease
What is marchiafava-bignami disease?
Itatlina men who drank red wine
Toxic demyelination of corpus callosum
What happens in lead toxicity?
ALtered heme prodution
Delayed cognitive and intellectual development
Retarded growth
Learning diff and behavioral changes
What happens in lead toxicity in adults?
Neurocog disease, peripheral neuropathy IRREVERSIBLE
What happens in mercury poisoning?
Mild congnitive to psychiatric abnormalities to coma and death
Minamata disease: Hypoesthesia of hands, feet, ataxia, visual field disturbance, dysarthria, severe encephalopathy
Not reversible
Radiology effects on CNS?
Methotrexate in particular and radiation causes encephalopathy with development of learning disabilities
What does CO poisoning do?
It causes globus pallidus necrosis, survivors suffer movement and memory disorders
WHat is ADEM?
Acute disseminated encephalomyelitis
T-CELL MEDIATED HS REACTION
Few weeks after viral infections
HA, Vomiting, Rapid weakness, sensory loss, ataxia, visual impairment, stupor, LOC, seizures
20% succumb to disease
5-10% have relapses
What are characteristic lesions of MS?
Flame lesions
