myelination disorders Flashcards

1
Q

CNS myelin

A

oligodendrocyte- responsible for axon myelination in the CNS (analogous to schwann cell in the PNS), small round dark nulcei with short processes (oligo
Each oligodendrocyte provides a myelin sheath to several axons, a cytoplasmic process of the oligodendrocyte wraps around the axons and the external surfaces and cytoplasmic surfaces fuse

Myelin components- myelin basic proteins (MBP)- plasma membrane bound, proteolipid protein (PLP structural component of myelin

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2
Q

de and dys myelination

A

de myelination- destruction of myelin with relative preservation of axons- acquired disorders (ms, acute disseminated encephalomyelitis, central pontine myelinolysis, progressive multifocal leukoencephalopathy (PML), neuromyelitis optica (NMO)

Dysmyelination- failure to form myelin normally- leukodystrophy- discussed in metabolic disease session

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3
Q

MS

A

most common demyelinating disease of CNS, demyelination is multifocal (disseminated in space) and lesions are of different ages (disseminated in time), epidemiology- prevalence of approximately 1/1000 persons, W>M, peak age of onset 20-40, occurs more frequently in northern climes environmental etiology

Family twin/racial studies- familial rates, lowest in Af am, jap, chi, asians form ind pak

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4
Q

Ms classification

A

Classic type

Rapidly progressive types- Acute- marburg type, concentric sclerosis (Balos disease)

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5
Q

MS pathology

A

Grossly plaques of demyelination- depressed, irregular, firm (sclerosis- hard)

Usually occur in - periventicular white matter, optic nerves and chiasm, brainstem and spinal cord tracts, cerebellum, also occur in gray matter

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6
Q

types of MS plaques

A

active plaque- macrophages with myelin debris, perivascular lympocytes, reactive astrocytes, relative preservation of axons

Inactive plaque- few or no macrophages, few lymphocytes, myelin loss with axonal preservation, fibrillary astrocytes

Shadow plaque- partial myelin absence (either due to incomplete myelin loss or partial remyelination)

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7
Q

acute disseminated encephalomyelitis ADEM

A

monophasic demyelinating disease, acute onset, associated with recent viral illness, or immunization signs or symtoms occur 1-2 weeks following

also called perivenous encephalomyelitis and post infectious encephalomyelitis

headache lethagy and coma if diffuse brain involvement
80% complete recovery

Pathology- perivenous demyelination with axonal preservation, polymorphonuclear leukocytes PMNs early and lymphocytes later

Pathogenesis- immune response to pathogen associated antigens cross reacts to myelin ags that results in myelin damage

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8
Q

neuromyelitis optica, devic disease

A

relapsing synchronous bilaterl optic neuritis and spinal cord lesions, W>M, asians and af am >caucasians

Median age of onset is 39

path- necrosis- not just demyelination with inflammatory cells , Aquaporins (AQP4)- membrane water channels that help maintain astrocytic foot processes (autoantibodies induce complement- dependent cytotoxicity, leukocyte infiltration, cytokine release, and BBB breakdown), lead to oligodendrocyte death, myelin loss
AQP4 specific igG antibodies detectable in 60-90% of NMO pts

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9
Q

Central pontine myelinolysis (osmotic demyelination syndrome)

A

Monophasic process- loss of myelin with relative preservation of the axons and neurons in basis pontis–> limb weakness (quadriplegia), gaze / speech abn, dysphagia, hypotension, may affect extrapontine sites

Most commonly associated with too rapid correction of hyponatremia, associted with alcoholic liver damage, post liver transplant, chronic malcourishment/debilitation extensive skin burns

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10
Q

MS common problems

A

Optic neuritis is very common

Will not affect the peripheral nerves

Periventricular, juxtacortical, cortical infratentorial, sp cd invovlement are the most common

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11
Q

Autoimmunity in MS

A

Autoimmunity is a failure of an organism to recognize its own tissues as self which can lead to an immune response against its own cells and tissues

It is not known what triggers the onset of MS Genetic factors MHC, Environmental factors

B cell and T cell with blood brain disorder

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12
Q

Ms pathology

A

MS is believed to be driven by autoreactive CD4 T cells with specificity for antigens expressed by oligodendrocytes which comprise myelin, Myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), proteolipid protein (PLP)

It is generally believed that myelin specific T cells get activated in the periphery then cross the BBB, where they are reactivated and initiates destruction, activation and expansion of autoreactive CD4T cells, breakdown of the BBB, infiltration of immune cells into the CNS, De myelination and remyelination, axonal and neuronal degeneration

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13
Q

T cells in MS

A
Strongest genetic risk facotr of development of MS is the MHC class 2 DR2 DRb1 1501
During activation differentiate into effector T cells

Th1 signiture cytokine is IFNy, Th17 cytokin is IL17A

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14
Q

B cells in MS

A

ectopic germinal centers

AStocytes that mess with BBB
Microglia damage and repair

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15
Q

Axonal loss and progression

A

axons actually die along with the demyelination

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16
Q

Presenting symptoms

A

Sensory symptoms- numbness/tingling, weakness, visual loss, ataxia, diplopia, vertigo bladder and bowel

A clinical attack has to be 50 days apart

eEG cant use

17
Q

MS risk factors

A

HLA Drb1*1501, vit D deficiency, viral infections EBV, smoking

Rare in black africans and asians

Dq 6

18
Q

Environmental facotrs

A

Vitamin D- 1,25 dihydroxyvitD (calcitriul is protective on vit D
Smoking increases
Viral infections- herpetic- EBV

19
Q

Internuclear opthalmoplegia

A

Decrease sensation in the face to fine touch, Internuclear opthalmolegia

20
Q

Optic neuritis

A

acute or subacute onset of monocular visual blurring or loss, central blind spot
Pain with eye movement (90% of pts)
Loss of color vision
May have poor visual acuity but at least worse than baseline
Afferent pupillaty defect
initial symptom of MS in 13 %
Common

Relative apparent pupillary Defect (the other pupil doesnt constrict

21
Q

sensory symptoms of MS

A

dysthesias/pain

Lhermittes phenomenon- Electric sensation passing down the back and limbs upon flexion of the neck

22
Q

Brainstem symptoms of MS

A

Nystagmus, diplopia (intranuclear opthalmoplegia) facial weakness, vertigo, dysphagia, trigemina neuralgia

Nausea and vomiting (intractable), hiccupping< rare in MS but very often seen in neuromyelitis optica

23
Q

motor symptoms of MS

A

Upper motor neuron- spasticity, hyperreflexia, atrophy uncommon,

Spastic parapresis is common in primary progressive MS

24
Q

Fatigue in MS

A

Very common, (rule out thyroid)

25
Q

CSF in MS

A

White blood cells may be elevated (<50) with a lymphocytic predominance, protein may be high but usually <100

Oligoclonal bands (OCBs)- 85-95% of pts with clinically definite MS (CDMS) will have OCB in the csf, positive OCB are bands that are found in th eCSF but not identified in the corresponding serum

PTs with a clinically isolated syndrome and positive OCBs have a higher rate of conversion to CDMS (25% v 9% at 3 years) hence the inclusion in 2017 criteria for DIT
OCBs can also be seen in infections such as, subacute sclerosing panencephalitis, viral encephalitis, Lyme disease and syphilis, or other inflammatory conditions (sarcoiid) thus it is important to rule out MS mimickers, can also be seen in 7% of normal individuals

26
Q

ms treatment

A

Acute exacerbations- Steroids (typically) methylprednisolone (one gram IV) daily for 3-5 days, steroids only help speed the rate of recovery, they dont change how much a patient recovers, if very sever, can do plasma exchange

Immunomodulatory therapy or disease modifying therapy (DMT for long term
Symptom management

Healthy living abstain from smoking

27
Q

Clinically isolated syndrome

A

first neurologic episode lasting>24 hrs caused by inflammatory or demyelinating lesion of the CNS, can be unifocal or multifocal symptoms

Patients with MR showing >2 lesions are likely to progress to those with normal MRI

Multiple studies demonstate that treating CIS delays the prgression to clinically definite MS

28
Q

Radiologically isolated syndrome

A

White spots periventricular, juxtacortical infratentorial, spinal cord is seen on mri but before any symptoms

Prodrome

29
Q

balos concentric sclerosisq

A

rare variant of ms in asians

30
Q

tumefactive demyelination

A

constant headache and cant see quite right
usually cortical involvement

looks like a neoplasm

steroids

31
Q

marburg variant

A

extremely severe ms

usually results in death

32
Q

ADEM

A

pediatric, usually monophasic after an infection/vaccine

poly focal, encephalopathy

perivascular, lymphocytes and macrophages, T cell mediated

axonal sparing

steroids

33
Q

neuromyelitis optica

A

optic neuritis inNMO usually bilateral and severe, sp cd , symptoms for days

CSFwith
pmns and oligoclonal bands

IGG against aquaforins