MS Flashcards
What genetic and environmental factors predispose to MS?
Genetic Factors:
- Presence of HLADRB1*15 (HLADR2) allele increases the risk of MS especially in Northern Europeans
- Presence of HLA-A*02 allele appears to be protective against MS
- 35% disease concordance among monozygotic twins
- 3–4% disease concordance among first-degree relatives
Environmental RF:
- Pathogens: EBV, HHV6
- Cigarette smoking
- Low Vit D - sunlight exposure and vit D protective for MS
- Obesity early in life.
- Latitude - effect has decreased over years
Living further away from equator
Those who migrate before adolescence acquire the risk of the new country, those who migrate later keep risk of initial country
What does CSF oligoclonal bands mean?
Oligoclonal bands in CSF indicate antibody production in CNS
Oligoclonal bands are a form of IgG.
What does the pathophysiology of MS consist of.
Characterised by autoimmune inflammation, demyelination and axonal degeneration.
Activation of autoreactive T-lymphocytes→ inflammatory processes → focal demyelination with partial preservation of axons (acute plaques) → loss of axons and atrophy of oligodendrocytes (chronic plaques) → gliosis → inadequate remyelination
What is the function of oligodendrocytes.
Oligodendrocytes produce the myelin sheath insulating neuronal axons (analogous to Schwann cells in the peripheral nervous system),
What are the clinical types of MS?
- Clinically isolated: first clinical episode Demyelinating attack: - subacute progression of symptoms - >24-28 hours - Nadir within 2 weeks - Resolution by 4 weeks - May not return to baseline - Pseudorelapse: due to infections, electrolytes
- Radiologically Isolated MS
Presence of demyelinating lesions characteristic for MS in an asymptomatic individual - ovoid well circumscribed focus. Leads to increase risk of developing primary progressive MS - Relapsing Remitting: clearly defined attacks due to recurrent demyelination within CNS with either full/incomplete recovery - minimal disease progression during relapses though severe disability may result from a relapse.
- Secondary progressive: initially relapsing remitting followed by gradual worsening of symptoms in between exacerbations.
- Primary progressive: progressive accumulation of disability from disease onset. Diagnosis requires positive oligoclonal bands.
Definition of exacerbation in MS
- New symptoms or significant worsening of existing symptoms, both of which last at least 24 hours and preceded by at least 30 day of clinical stability.
What are the earliest clinical manifestations for MS?
Optic neuritis
- Typically unilateral
- Can be painful - pain on eye movement
- Mononuclear central vision loss
- Impaired vision and colour blindness
- Relative afferent pupillary defect
- Retrobulbar (have no optic nerve swelling)
- Will progress to optic atrophy
Pale optic disc, red desaturation/ishihara, enlarged blind spot/scotoma, visual field defects
Tx: steroids
Characteristic of internuclear ophthalmoplegia?
- Occurs due to damage to MEDIAL LONGITDUINAL FASCICULUS (the connection between the abducens nucleus, CN VI in pons and the oculomotor nucleus, CN III on the other side in the midbrain)
- Ipsilateral medial rectus weakness but an intact convergence reflex
- Disconjugate lateral gaze nystagmus in the contralateral eye - affected eye shows impairment of adduction and abducted eye shows nystagmus
- More frequently bilateral than unilateral
Internuclear ophthalmoplegia (INO) is characterized by Impaired adduction of the eye ipsilateral to the lesion and Nystagmus on the Opposite side!
Lhermitte sign
Shooting electric sensation that travels down the spine upon flexion of neck. Indicate demyelination of spinal cord tracts.
Also seen in cervical spondylosis, tranverse myelitis, b12 deficiency, chiari malformation
Uhthoff phenomenon
Reversible exacerbation of neurological symptoms following an increase in body temperature, eg: physical exertion, a warm bath or fever
Heat sensitivity: small increase in body temperature worsens signs and symptoms
What other dysfunction is common in MS?
- Bladder, bowel and sexual dysfunction.
- For bladder: urge incontinence and then overflow incontinence.
Urge incontinence develops first due to loss of CNS inhibition of detrusor contraction in the bladder. Later, detrusor muscle becomes weak, atonic and dilate and thus overflow incontinence occurs.
Most common symptom in MS?
Fatigue (90%) Walking difficulties (76%) Numbness/tingling (70%) Pain (64%) Muscle spasms (61%) Headache, depression, emotional changes (54%) Bladder dysfunction (51%) Cognitive impairment Optic neuritis Internuclear ophthalmoplegia (bilateral highly specific) Lhermittes + Uhthoof
- Cognitive impairment
- Fatigue
- Weakness
- Visual pathways: optic neuritis
- Cerebellum: ataxia, dysmetria, tremor
- Brainstem - THINK INO (BILATERALY HIGHLY SPECIFIC), ophthalmoplegia, vertigo, trigeminal neuralgia
- Spinal Cord: bladder bowel dysfunction (urge incontinence, neurogenic bladder, constipation)
- Numbness, parathesia
- Lhermitte + Uthoff
Common areas of the brain affected in MS
Periventricular
Juxtacortical/cortical
Infratentorial
Spinal cord
Dissemination in space requires lesions in at least 2/4 areas
Ix for MS
- MRI: looking for lesions separated in time and space
White matter lesions best sein on T2 FLAIR (T2 hyperintense, T1 hypointense)
Contrast enhancement on post gadolinium T1 weighted imaging - CSF: oligoclonal bands only in CSF, lymphocytic pleocytosis.
- Can also do evoked potentials
- VER (visual evoked): slow means demyelination
- SER (somatosensory)
- MER (motor)
Characteristics of neuromyelitis optica (NMO)
- Relapsing B cell mediated disease against astrocytes characterised by longitudinally extensive, centrally located necrotic spinal cord.
- Central nervous system disorder and autoimmune disorder that attacks the optic nerves (optic neuritis) and the spinal cord (myelitis)
- More severe disease than MS, individual attacks are more likely to result in a permanent neurological deficit with less chance of recovery
- Leads to bilateral optic neuritis
- Transverse myelitis: symmetric paraplegia, sensory loss, bladder dysfunction
- Antibody-mediated inflammation directed at aquaporin-4 antibody channels in the CNS that results in inflammatory demyelination in the optic nerve and spinal cord. Can be differentiated from MS by NMO lgG antibody testing and by its lack of significant brain involvement, large and longitudinally extensive spinal cord lesions, and profound CSF leukocytosis
- In people with NMO who test negative for anti-AQP4 antibodies, up to a third may be positive for auto-antibodies directed against a component of myelin called myelin oligodendrocyte glycoprotein (MOG). People with anti-MOG related NMO similarly have episodes of transverse myelitis and optic neuritis, but recovery after attacks appears to be better than anti-AQP4 related disease.
- Hanna Pearl: If MOG is negative - indicate NMO spectrum disorder which is associated with sjogrens and sarcoid
MRI Spine Findings: MS vs NMO
- MS: short segments, partial lesions
- NMO: LETM (longitudinally extensive transverse myelitis), often whole extent of cord
Longitudinally extensive, centrally located, necrotic spinal cord
Diagnosis of MS
- Dissemination of lesions in time and space
Dissemination in time: appearance of new lesions over time confirmed by one of the following
- 2 or more exacerbations occurring at least 30 days apart
- MRI showing 2 separate lesions
- Positive CSF oligoclonal bands
Dissemination in space: presence of lesions in different regions of CNS
- Presence of 2 or more lesions with objective clinical evidence
- Presence of one or more hyperintense lesions in at least 2 of the following: periventricular, juxtacortical, infratentorial, spinal
McDonalds Criteria
- 2 lesions in space and time
Time:
- 2 separate attacks or even a history of an attack
- MRI with contrast enhancement of a lesion and non enhancement of another
- Oligoclonal bands
Space
- 2 different locations in the CNS through objective clinical evidence
- 2 different locations in the CNS through MRI
Ab associate with Neuromyelitis optica (NMO)
- Anti aquaporin 4
- Anti MOG (myelin oligodendrocyte glycoprotein (MOG).
Present in chronic recurrent inflammatory optic neuritis, ADEM, NMOASD
People with anti-MOG related NMO similarly have episodes of transverse myelitis and optic neuritis, but recovery after attacks appears to be better than anti-AQP4 related disease. - Hanna Pearl: If MOG is negative - indicate NMO spectrum disorder which is associated with sjogrens and sarcoid
- Steroid responsive, may be monophasic
- Poorer response to rituximab
<30% have oligoclonal bands
Clinical features of NMO (NMO spectrum disorder)
- Optic neuritis
- Acute myelitis
- Area postrema (dorsal medulla) syndrome (episodes of intractable nausea, vomiting and/or hiccups)
- Acute brainstem syndrome
- Narcolepsy
- Cerebral syndrome with typical brain lesions
Summary of NMO
Diagnostic Criteria
- Anti aquaporin 4
- Anti MOG
- Big lesions >3 vertebrae
- Hiccups
Diagnostic Criteria
At least 2 core clinical characteristics + AQP4
- 1 of ON, myelitis or area postrema syndrome
- Dissemination in space
Isolated recurrent ON or recurrent TM do not qualify
- Additional MRI requirements
AP syndrome: dorsal medulla lesion
Myelitis: LETM
ON
