Demyelinating Diseases Flashcards
Parts of neurons
Cell body
Dendrites
Axons
Advatanges of myelinated neuron
Conduct impulse faster
Function of myelin on neurons
Act as insulator and help propagate signal faster
Most neuron are myelinated or unmyelinated “
Myelinated
2 cells responsible for myelinazation of neuron
Oligodendrocytes in CNS
Schwann cells in PNS
Do Schwann cells make multiple or just one myelin sheath
Just one
Importance of node of renvier
Determines rate of conduction
3 main connective tissue that bundle axons
Endoneruoem - nerve filament
Perineurium - fascicles
Épineurium -
Large diameter axons function
Light touch
Motor signal
Consequence of damage to myelin sheath
Slow nerve conduction
Condpsequence of demyelination of
Large fiber sensory dysfunction
Motor weakness
Diminished reflexes
What are demyelination disease
Acquired conditions with preferential damage to myelin
When do you have damage to axons
When there’s progression of disease as secondary damage
2 mechanism of demyelination
Damage of myelin sheath
Damage of cells that produce myelin sheath
What is dysmyelination
Formation of abnormal myelin sheath
classification of demyelination diseases
Demyelination due to inflammatory processes
Viral demyelination
Demyelination caused by acquired metabolic derangements
Hypoxic ischemic forms of demyelination
Demyelination by focal compression
Disease of inflammatory demyelination
Multiple sclerosis
Neuromyelitis optics
Acute disseminated encephalomyelitis
Acute hemorrhagic leucoencephalitis
Type of MS
Classical
acute
Concentric sclerosis
Commonest demyelination g disease
MS
Causes of MS
Polygenic defects - the higher the number of defective genes the higher severity
Environmental - high latitude zones, growing up in high prevalence areas, studies are considering EBV and HHV6
MS concordance rate higher in monozygotic or dizygotic twins
Monozygotic
MS more in women or men
Women 2x
Age of appearance of MS
15-55 yo
Clinical manifestation of MS
Muscle weakness Parenthèsia , focal sensory loss Optic neuritis, diplopia Ataxia, vertigo Autonomic motor abnormalities of bladder , bowel, sexual function Painful muscle spasms
Trigeminal neuralgia Fatigue Depression Cognitive difficulties Psychiatric disturbances Seizures
MS pathology
Autoimmune cell mediated process
T cell produce ifn gamma -> macrophages activation
TH17 -> IL17 with neutrophils and monocytes recruitment
Activated leucocytes Attach myelin and destroy it
Immune cell found in MS lesiosn
CD4
CD8
Macrophages
Possible mechanism triggering immune response in MS
Viral injury to CNS -> exposure of myelin antigens -> damage
Molecular mimicry of viral antigens and myelin -> immune rxn against virus going towards myelin
MS treatment
Agent that deplete B cells
MS morphology
MS plaques
What do you;see in macrophages at early stage of MS
Myelin fragments
Presentation of inactive plaque in MS
Gliosis with scar tissueu
Demyelinated axons
Early stage MS plaque presentation
Shadow plaque due to remyelination
Why is remyelinzation infective in advanced lesion of MS
Gliosis leading to barrier between myelin producing cells and axons
What is smouldering plaque In MS
Lesion that expand at periphery and dies down in center
Classical MS characteristics
Different size and shape of plaque , multiple, randomly distributed
Involving cortex, subcortex, cerebellar white matter, brain stem, spinal cord
Periventricular white matter
Firmer lesion than white matter -> well circumscribed , depressed, glassy grey tan, irregular shaped
Microscopy of active plaque
Perivascular infiltrates of lymphocytes and macrophages Lipid laden macrophages Myelin debris In macrophages Depletion of Oligodendrocytes Sparing of axons
Micro of inactive plaque
Hypocellular
Gliotic
Reduced ddmyelinated axons
Reduced Oligodendrocytes
PATHOphysiology MS
Concentric sclerosis MS
Alternate bands of demyelination and myelinated white matter
Rare but rapidly progressive
Neuromyelitis optica
Development of bilateral optic neuritis and acute transverse myelitis at same time or with period between them
Call presentation of neuromyelitis optica
Visual loss
paraplegia
sensory loss
Does neuromyelitis optica affect more women than men
Yes
Call vary from first attack in neuromyelitis optica good
Poor recovery
Neuromyelitis optica pathogenesis
Different from MS
Antibody dependent and complement mediated
Associated with neuromyelitis optica
Thyroiditis type one diabetes celiac disease SLE Sjogren syndrome
Inflammatory demyelination neuropathies common or uncommon ?
Uncommon
Pathogenesis o f inflammatory demyelination neuropathies
Immune disorder
Antibodies and Activated T lymphocyte react to antigens on peripheral nerves
Inflammatory and Marcrophage reaction that destroys myelin and axons
How can you strongly provide evidence of inflammatory demyelination neuropathies
By giving plasma exchange which will improve significantly clinical presentation by removing the antibodies
Two main inflammatory demyelinating neuropathies in pns
Guillard barre syndrome
Chronic inflammatory ray demyelinating disease
What is guillain barre
Demyelinating peripheral neuropathy
Counterpart fo MS in peripheral nervous system
Types of guillain barre
Acute inflammatory demyelination pooyneuropathy 90%
AMAN
MFS
Guillain barre clinical presentation
Ascending paralysis
Paresthésia -> start in the toes and fingertips
Weakness
Areflexia
Many patients completely paralyzed and unable to breathe
Mortality rate of guillain barre
5%
Guillain barre main complications leading to death
die from respiratory paralysis
Cardiac arrest
Sepsis
Other complications
Percentage of patients that recovered but have residual weakness
10%
What type of illness occurs in 2/3 of patients before developing guillain barre
Acute flu like illness
Other complications of guillain barre
Muscle atrophy
Joint weakness
Pneumonia
Type of infection or condition involved in cases guillain
Campylobacter jéjuni (20-30%) - More in AMAN Cytomegalovirus ( 20-30%) Mycoplasma pneumoniae Hepatitis E Other infections Vaccination
Guillain barre pathogenesis
Antibodies cross reaction with gangliosides
C jejuni have lipo oligosaccharides mimic carbohydrate moiety of gangliosides in human peripheral nerves
Antibodies associated with some guillain barre reflect in gangliosides inn human peripheral system
Gangliosides that have serum antibodies found in AMAN
GM1a
GM1b
GD1a
MFS gangliosides that have antibodies rxns
GD1b
GD3
GT1a
GQ1b
Manifestation happening in MFS
Ataxia
Ophtalmoplegia
Antibodies found in GBS following CMV
Anti GM2
Where rxns in guillain barre of antibodies occur
Axonal membrane of Nodes of fancier
Paranodal myelin
Morphology of GBS
Perivenular and Endoneural infiltration by lymphocytes, macrophages , plasma cells
Segmental demyelination of peripheral nerves ,
Demyelinating widespread but more severe at stromal side
Always severe axonal demyelination in GBS ?
Variable
Lab findings Hallmark of GBS
Csf protein increase
No increase in cells albuminocytological dissociation
Mortality rate
2-5%
Complications leading to death inGBS
Respiratory paralysis
Autonomic instability
Cardiac arrest
Related complications
Most common chronic acquired inflammatory peripheral neuropathy
Chronic inflammatory demyelinating polyradiculoneuropathy
What is Chronic inflammatory demyelinating polyradiculoneuropathy
Chronically progressive or relapsing symmetric sensorimotor poly neuropathy
What makes difference between CIPD and GBS
8 weeks or more symptoms in Chronic inflammatory demyelinating polyradiculoneuropathy
Chronic inflammatory demyelinating polyradiculoneuropathy presentation evolution
Start insidious
Slow evolution (slow progressive or slow relapsing )
Partial or complete recovery between recurrences
Clinical presentation of Chronic inflammatory demyelinating polyradiculoneuropathy
Preceding infection - infrequent
Initial limb weakness - proximal and distal
Sensory symptoms - tingling, numbness of hands and feet
Motor symptoms - predominant
Type of patients with more precipitous onset of symptoms in Chronic inflammatory demyelinating polyradiculoneuropathy
Children
Manifestation in Chronic inflammatory demyelinating polyradiculoneuropathy in other form of infection
Gait abnormalities
Motor deficit - symmetric weakness of both proximal and distal muscle
Sign of cranial nerve involvement - facial muscle paralysis , diplopia
Is it easy to find gangliosides involved in CIDP
No
Type of complement fixing immunoglobulin found in CIPD on myelin
IgG
IgM
CIPD pathogenesis
In blood -> APC with auto reactive T cell
Activated T cell leads to plasma cells releasing antibodies
Antibodies go to peripheral nervous system and
Sural nerve biopsy
Technique used for micros lab findings in CIDP
Sural nerve biopsy
Micro of CIDP
