Multiple sclerosis and Guillain-Barré Flashcards
Progressive neurodegenerative diseases:
main non-infectious neurodiseases / disorders
Progressive neurodegenerative diseases
Neuropsychiatric disorders
Neuropsychiatric disorders
- Depression
- Schizophrenia
Diseases of motor neurons and NMJ (properties)
Diseases of motor neurons and NMJ (examples)
Secondary neurodegenerative diseases
know cause and know not intrinsic
muscular dystrophies vs diseases of motor neurons and NMJ
not the same - issue is with muscles not with
GBS affects
Motor nerve axons, from spinal cord to muscles - PNS
Guillain-Barré syndrome
GBS is the most common
acute paralytic neuropathy
> 100,000 cases yearly
can affect anybody
GBS is a syndrome not
a disease - various subtypes
Spectrum of presentations, from very mild to very severe/fatal
GBS subtypes
Axonal subtype most severe
GBS is a reaction to
immune stimulation
- vaccines
- sickness/ infection
GBS develops
days/weeks after infection or vaccination
Molecular mimicry
Molecular mimicry is defined as
structural similarity between antigens coded by different genes
(definition in disease - Similarities between the antigens of a microbe and a host.)
GBS severity vs time
___ patients recover spontaneously in ___
Most
in 3 – 4 weeks
~70 % recover completely
~30 % retain residual weakness
___ develop into severe cases (GBS)
20 – 30 %
complete paralysis, including respiratory muscles
Rapid progression after onset, 3 – 4 days
GBS has strong evidence relating GBS with ___ bacteria
C. jejuni infection
LOS (lipooligosaccharides) in outer membrane = gangliosides in PNS axons
GBS associated with ____ viruses
flu, Zika, CMV (Cytomegalovirus), Epstein-Barr
Antibody production in GBS
is random!
Correlations seen, still it is a sporadic disorder!
GBS Immunopathology
mostly an humoral driven pathogenesis - Driven by serum (humoral - antibody- mediated) rxn. NOT cellular rxn.
antibodies against:
Against gangliosides in axonal membrane
(exposed at nodes of Ranvier)
Against broad range of myelin sheet
proteins (moesin was suggested)
GBS Humoral effects
antibody deposits
complement activation
macrophage recruitment
GBS prognosis
Potentially life-threatening disease, early diagnosis = better recovery
GBS treatments
1) IV Ig infusion: addition of normal antibodies overcomes effect of autoreactive antibodies (many mechanisms, most end up reducing inflammation)
2) Plasma exchange: removal of autoreactive antibodies and other damaging humoral factors
Severe cases ___ can achieve complete recovery
with physical therapy
GBS in low income countries
these treatments are too expensive, so unavailable - new therapeutics are urgently needed
10 – 15 % of patients die - lack of treatment and medical support (in US more like 1-3%)
MS is the most common __
also known as ___
autoimmune-mediated disease of the CNS
disseminated encephalomyelitis
Global distribution of MS
~350,000 cases in US; 2.5 – 3 million worldwide
MS age
Can strike at any age, but mostly 20 – 40 years old
Most common cause of permanent disability in young adults (stroke in older adults)
MS telltale signs
Clinical spectrum (a lot of overlap) but
(SW S N P V)
sudden-onset muscle weakness
loss of sensation
numbness
pain
vision problems - unique + CNS
MS epidemiology
geographically, diet
age (20-40)
women
Men vs Women MS
Women 3X more likely
pregnancy is protective - hormonal effect? Or immunity?
not clear why - if have MS then get pregnant symptoms go away - when pregnant immunocompromised and ms is over immune rxn.
MS Clinical presentation
- Relapsing-remitting MS
- Secondary-progressive MS
- Primary-progressive MS
- Progressive-relapsing MS
3-4 vary rare
Ultimately MS becomes
steadily progressive
After 15 – 25 years of RRMS (relapsing-remitting), it turns into SPMS (secondary- progressive)
Relapsing vs progressive MS manifestation
Relapsing - autoimmune inflammation
Progressive - neurodegeneration
MS history
important - recurrence of isolated neurological symptoms
MS MRI
best way to see lesions (an aggregation of immune cells)
Presence of lesions predicts MS development with > 80% accuracy
Size and number of lesions DO NOT correlate with severity – location most critical – however, steady increase correlates with severity
Use of contrast enhancing media shows BBB breaches due to inflammation
Why does MS occour
don’t know what initially starts it
but is due to chronic inflammation
MS progression pathology
White matter early on (mylen), then spread to grey matter
does not stop until pathogen (antigen/olog.) is gone
Why MS is such a chronic disease with months of no symptoms between attacks?
Immune does not stop until pathogen (antigen/olog.) is gone - when gone Olig can regenerate - attack again
Is permanent is because the immune response is generated against self-antigens
When myelin is destroyed in MS, the axon
redistributes the ion channels and switches to continuous signaling rather than saltatory conduction
MS remylenation ocours because
OPCs (NG2 - oligodendroyte precusor cells) can generate oligodendrocytes
As MS progresses, remission periods are
shorter and fewer
- Correlates with decline in remyelination
- With less remyelination, axon eventually dies
- OPCs ability to differentiate declines with age
- Once axonal death starts, progression into advanced MS is inevitable
MS treatments
Current disease-modifying drugs targets the immune reaction, not the actual causative pathology - axonal destruction
No cure – but increasing arsenal of drugs makes it manageable
- Sadly, one of the leading causes of death in MS is suicide
Supportive treatments
- Amelioration of acute attack symptoms
- Anti-inflammatory agents
Very expensive – average costs per single dose is $60,000!
Many make you immunosuppressed, so susceptible to infections!
MS and prions
MS excellent example that not all neurodegenerative diseases involve a prion-like component
1) Its all genetics and environment, and chance - (like) cancers
2) The 2 hits theory - applicable to many autoimmune diseases (2 hit - also in cancers)
