6/18- Demyelinating Diseases (MS) Flashcards
What cells make myelin in the central nervous system?
Oligodendroglia
What cells make myelin in the peripheral nervous system?
Schwann cells
___ cells may invest multiple axons, while ___ invest a single axon
Oligodendroglia cells may invest multiple axons, while Schwann cells invest a single axon
Classification of Myelin Disorders:
- Central
- Peripheral
- Both
Central:
- Multiple sclerosis
- Post infectious encephalomyelitis
Peripheral:
- Guillain-Barre Syndrome
- Charcot-Marie-Tooth diseaes
Both:
- Leukodystrophies
What clinical advancement has greatly helped in the diagnosis and understanding of demyelinating diseases?
(Especially MS)
Diffusion Tensor Imaging (DTI)
- Revolutionizing our understanding of white matter tracts in health and disease
What may be seen in the gross neuropathology of MS?
- Plaques may occur anywhere there is myelin (typically periventricular, subpial, junctional [white/grey])
- Well-defined, clearly-demarcated gelatinous
- Grey due to loss of lipid in myelin
- May be symmetrical
- Acute plaque may be pink
Characteristics of lesions/plaques in MS (time)?
Lesions are disseminated in space and time (multifocal); this is required for diagnosis
- Onset typically in young adult life
What is this?
Periventricular demyelinating plaques in MS
Classic presentation of MS
- Normal white matter
- Grey area around ventricles (periventricular demyelinating plaques)
Stages of MS? Timeline?
Relapsing remitting phase
- Attacks and recovery
- All the drugs that treat MS work in this phase; this form can be favorably modified by immunomodulatory drugs
Secondary progressing phase
- Relentless, steady decline in function
- Typically occurs after a few years
Primary progressive MS
- Relentlessly progressive from the onset
- Not responsive to currently available immunomodulatory drugs
What is this?
- White matter sunken and more white than normal
- Large bilateral demyelinating plaques (MS)
If demyelination is occurring in frontal lobes, may get loss of executive function and other symptoms typically associated with dementia
What is this?
Demyelinating plaque in MS (dark spot in top right)
MRI is used for what in MS?
- Detection of asymptomatic plaques
- Aids in diagnosis
- Disease activity can be followed throughout time
- Aids in therapeutic trials and management
- Can demonstrate dissemination in space and time
Describe the criteria (for MS) of dissemination in space? In time?
Dissemination in space (DIS)
- Clinically asymptomatic lesions can be seen
- Multiple widely distributed plaques can be identified
Dissemination in time (DIT)
- Plaques show characteristics imaging feature depending on how old they are
- Lesion of differing age indicate dissemination in time
McDonald Criteria codefies diagnosis using MRI
T/F: Plaques are present when the patient with MS is asymptomatic
True
- Can have plaques that don’t result in many symptoms
- Plaques can be used to assess relative activity, though, with fewer plaques being less active
- … even at baseline, is active
What is this showing?
Left: Unstained pons
Right: Stained pons revealing MS
Normal myelin stains black or deep blue; plaques do not stain
- Not knocking out a specific system
- Not in a particular vascular territory
What is this?
Demyelination of the spinal cord: grey discoloration (right side) seen in MS
What is this?
Optic chiasm in MS
- Demyelination in chiasm (-> bitemporal binocular heminopsia field defect)
- Demyelination of optic n. (-> vision loss in one eye; optic neuritis)
Epidemiology of MS?
- Women > men
- Onset typically in early adulthood
- People who grew up far from the equator (e.g. Minneapolis native 3x greater risk than Houston)*
*Thought perhaps to be chronic VItamin D deficiency (role in bones, but also an immune regulator)
What is this? Symptoms?
Demyelination in nerve root entry zone leading to paroxysmal symptoms (abnormal synthesis of signals)
- Trigeminal neuralgia (severe episodic pain)
- Hemifacial spasm
- Radicular pain
For these symptoms in young, think MS; in mature, think vascular or mass
What is Redlich-Obersteiner’s zone?
Transition between CNS and PNS myelin
What is seen microscopically in MS?
- Perivascular lymphocytic infiltrate
- Loss of oligodendroglia
- Myelin sheath stripping
- Macrophage infiltration
- Astrogliosis
- Relative sparing of axons (especially in relapsing-remitting stage; immune system can shut down lymphocytes)
What do therapeutics target in MS?
Cellular immunity (tamp it down!)
- e.g. corticosteroids?
What is this?
Perivascular lymphocytes in MS
- Lymphocytic infiltrate around BV
What is this?
Spinal cord demyelination showing:
- Macrophages (cleaning up myelin debris or possibly stripping it off themselves)
- Denuded axons (axons relatively spared)
T/F: Oligodendroglia can divide to replace those lost in attacks of MS?
True
What is this?
Macrophages in demyelinating disease (MS)
- Cellular debris within
Therapeutics in MS?
- High dose corticosteroids for acute flares
- Numerous immune system modulators (disease modulating therapy) are now available to slow or arrest progression
These include:
- Beta-interferon
- Copolymer I
(cost is a problem)
What are some diseases of post-infectious demyelination?
Are these central or peripheral diseases?
These are central diseases
- Acute disseminated encephalomyelitis (ADE) or (ADEM)
- Acute hemorrhagic leukoencephalopathy (If you survive the attack, you will probably be okay)
Neuropathological features of acute disseminated encephalomyelitis (ADE)?
- Monophasic T-cell mediated hypersensitivity
- Perivenular lymphocytes
- Marked swelling
- Scattered small foci or hemorrhage
Neuropathological features of acute hemorrhagic leukoencephalopathy?
- Hyperacute ADE
- Swelling with multiple hemorrhages
- Fibrinoid necrosis of vessels
What is this?
Post-infectious leukoencephalopathy
- Can see various areas of demyelination scattered around
- Dissemination in space but not time (1 time event)
What is this?
Post-infectious hemorrhagic leukoencephalopathy
- Monophasic immune attack of CNS white matter
What is a disease of post-infectious inflammatory peripheral demyelination?
Guillain-Barre Syndrome with inflammatory polyradiculoneuritis
Characteristics (caused by, timeline, symptoms, treatment) of inflammatory polyradiculoneuritis in Guillain-Barre syndrome?
- May follow infection or vaccination
- Rapid progression
- May lead to respiratory failure
- Can be treated with plasma exchange (remove Abs from blood; immunosupressive)
- Recovery typically takes weeks-months
- Good outcome ultimately
- Can relapse or become recurrent (rare)
What are leukodystrophies?
Examples (3) with their deficiency and symptoms?
Genetic disorders of myelin (affect both central and peripheral myelin)
MLD- metachromatic leukodystrophy
- Arylsulfatase
- Metachromasia
Krabbe
- Galactoceramidase
- Globoid cells
ALD/AMLD
- Transporter of Lignoceroyl-CoA ligase
- Inflammation, demyelination, hypadernalism
Characteristics of metachromatic leukodystrophy?
- AR/AD/sex-linked?
- Deficiency of what?
- Result of deficiency?
- Identified how?
- Affects what population
- Symptoms?
- Diagnosis?
- Autosomal recessive
- Peripheral and central nervous system involvement
- Aryl sulfatase A deficiency (cerebroside sulfatase) with accumulation of galactosyl-3-sulfatide
- Myelin destruction with sulfatide accumulation in ECM and in macrophages
- Identified by toluidine blue or acidified cresyl violet stain- product is brown [shift from cresyl violet staining normal myelin in orthochromatic fashion to cresyl violet staining myelin brown in a metachromatic fashion; color spectral shift]
- Young children affected, also juvenile and adolescent forms
- Intellectual disability, spasticity, blindness
- Diagnosis: lack of aryl sulfatase A in urine or in culture fibroblasts
Characteristics of Krabbe’s Leukodystrophy?
- AR/AD/sex-linked?
- Deficiency
- Result of deficiency
- Autosomal recessive
- Galactocerbroside- beta-galactosidase deficiency
- “Globoid cell” leukodystrophy due to accumulation of galactocerbroside in macrophages
- Demyelination with multinucleated globoid cells
What is this?
Multinuclear macrophage (globoid cell) seen in Krabbe’s disease
Characteristics of Adrenoleukodystrophy?
- AR/AD/sex-linked?
- What regions affected?
- Mechanism
- Symptoms
- Treatment
- X-linked recessive inheritence
- Parieto-occipital demyelination
- Adult form involves spinal cord and peripheral nerves
- Peroxisomal disorder: defect in peroxisomal membrane protein that imports acyl coenzyme A synthetase into peroxisome
- Lorenzo’s oil- dietary supplement arrests progression
What is this?
Parieto-occipital demyelination in adrenoleukodystrophy
What is this?
Adrenoleukodystrophy
- Posterior predominant
What is this?
Frontal coronal section (left) and parietal coronal section (right) showing selective parieto-occipital demyelination in adrenoleukodystrophy
