Multiple Sclerosis -Diagnostic Issues

Multiple Sclerosis -Diagnostic Issues
By:Christopher Bourque

* Manifestations due to CNS
o Slowing or failure of transmission
+ Inflammatory demyelination
+ Axonal damage
o Mostly damage of white matter tracts
+ Optic neuritis, weakness, sensory loss, ataxia nystagmus, bladder dysfunction, cognitive impairment
* Diagnosis based on clinical and laboratory evidence of
+ Dissemination in time
+ Dissemination in space
Patterns of MS
* Relapsing - remitting
o Attacks with complete/incomplete recovery
o Stable between attacks
* Secondary - progressive
o Initially relapsing-remitting
o Then progression +/- attacks
* Progressive - relapsing
o Initial gradual detioriation
o Subsequent episodes
* Primary progressive
o Gradual decline
o No attacks


Schumacher Clinical Criteria MS Diagnosis 1965
* Age (onset 10-50 years)
* CNS white matter disease
* Lesions disseminated in time and space
* Objective abnormalities on exam
* Consistent time course
o Attacks lasting > 24 hrs., spaced at least 1 month apart
o Slow or stepwise progression for > 6 months
* No better explanation
* Diagnosis by experienced clinician

Poser Criteria for the Diagnosis of MS 1983
* Widely used for last 20 years
* Definite or probable
* Laboratory supported MS
* Replaced by McDonald criteria 2001
o Technical advances enable quicker dx.
o Controversial
Additional Requirements to Make Diagnosis
Objective Lesions
Clinical (attacks)
McDonald Criteria
Positive CSFand
Dissemination in space by MRI evidence of 9 or more T2 brain lesions or 2 or more cord lesions or 4-8 brain and 1 cord lesion or positive VEP with 4-8 MRI lesions or positive VEP with less than 4 brain lesions plus 1 cord lesion and Dissemination in time by MRI or continued progression for 1 year

Clinical Manifestations
* Demographic
o Female
+ Women make up to 70%-75% MS patients
o Young age
+ Onset before age 16: 5% of cases
+ Peak onset post puberty, early 20’s
# Relapsing MS 28-30 years
* Symptoms
o Recent onset
o Frequently progressive
+ Coming on over 1-several days
+ Very acute symptoms possible
The MS Event
* Attack/relapse/exacerbation
o Acute episode of CNS dysfunction
o Lasting at least 24 hours
o In absence of fever or metabolic derangement
o All events within 30 days are unitary

MS Symptoms
* Motor
o Weakness, spasticity, ataxia
o Rarely radicular
+ lesion ant. horn, root entry zone
+ painful
+ atrophy
* Somatosensory
o 1st sx. in 43% patients
+ Includes visual
o Any anatomic distribution
o Any combination
+ Loss pain, temp, light touch, vbn, position
o Positive sx. common
+ Paresthesiae, hyperpathia, allodynia, dysesthesias
Nonspecific Associated Features That Suggest MS
* Excessive unexplained fatigue
* Temperature sensitivity
o Hot, humid weather
* Relatively recent symptoms
* History of Lhermitte’s sign
* History of bandlike sensation around the waist
* Uhthoff’s phenomenon
o eg, blurry vision with exercise or heat exposure * Fatigue
o One of the most important causes of disability
o Several sources
+ Handicap fatigue
# Increased effort to perform routine tasks
+ Secondary fatigue
# Depression, sleep disturbances, medication side-effects, other conditions
+ Systemic fatigue
# Chronic lack of energy, tirdness, malaise
# Etiology unknown

* Cognitive Disturbances
o Common, frequently overlooked
+ Estimated 50-75%
o Most common
+ Impaired attention, slow info processing, short term memory loss, reduced visuospatial skills, impaired executive function
o Impaired driving skills
o Important impact QoL, ADL
o Can occur independent
+ of disease course
+ other manifestations
MRI in MS
* Brain lesions
o Character
o Location
Evoked Potentials
* Visual evoked potentials
Principal Differential Diagnosis of Multiple Sclerosis

* Infection
* Inflammatory
* Metabolic
* Neoplastic
* Spine disease
Cerebrospinal Fluid
* Useful, not diagnostic
o Other conditions
+ Chronic CNS infections, viral syndromes, neuropathies
* Immunoglobulin abnormalities
o Production of immunoglobulin
# By plasma or B cells in CNS
+ Oligoclonal bands of immunoglobulin (IgG) (OCB)
# In CSF, not serum
# Isoelectric focusing technique
+ Elevated IgG index
# Ratio of IgG/protein in serum and CSF
# index = (csf IgG/csf albumin)
(serum IgG/serum albumin)

* First event - chance of progression to MS
o In 3 years
+ OCB +ve: 25%
+ OCB -ve: 9%
* CIS:clinically isolated syndrome
o 62.5% cases +ve OCB
* Clinically definite MS
o 90% +OCB
MRI in MS

* Spinal cord lesions
o Character
+ Asymptomatic lesions
+ Focal T2/proton density hyperintense lesions
+ Diffuse proton density abnormalities
+ Atrophy
+ Asymmetric involvement
# Multiple scattered lesions
+ Edema with acute plaques
# Often enhancing
o Location
+ Cervical and thoracic
# Especially midcervical
+ Peripheral
+ Less than 2 vertebral segments
+ Less than 50% cross-sectional area
+ Lateral, dorsal cord
Paroxysmal Symptoms in MS
* Trigeminal neuralgia (and others)
* Tonic “seizures”
* Paroxysmal dysarthria
* Hemifacial spasm
* Paroxysmal itching
* Abrupt loss of muscle tone
* Paroxysmal aphasia
* Paroxysmal kinesogenic choreoathetosis
* Lhermitte’s sign
* Visual symptoms, afferent
o Almost any pattern, related to location
o Optic neuritis
+ Central scotoma
# Mild: color desaturation
# Severe: blindness
* Vast majority have excellent return by 6 months
+ Frequent pain
# Worse on eye movement
Optic Neuritis Risk of Subsequent MS
* Other Brain Stem Structures
o Facial weakness
o Vertigo
o Loss of hearing, taste
o Dysarthria, dysphagia
+ Bulbar muscles
# Weakness, ataxia, spasticity
* Psychiatric Disturbances
o Depression
o Emotional incontinence
* Bladder dysfunction; the importance of urodynamic studies
o Failure to store: detruser hyperactivity
+ Urgency, frequency, nocturia
o Failure to empty
+ Detruser-sphincter dyssynergia
+ Poor detruser contraction
# Hesitancy, increased residual vol., retention
o Both
+ Combined
# detruser hyperactivity
# detruser-sphincter dyssynergia
o Incontinence
+ Detruser hyperactivity or
+ Overflow
+ Symptoms may not be accurate indicator of urodynamic pathology
* Bowel dysfunction
* Sexual dysfunction
o Erectile dysfunction
o Women: loss of libido, anorgasmia
o Both sexes
+ Loss of perineal sensation
+ Neuropathic pain
+ Spasticity
+ Incontinence
+ Depression, fatigue

Pain Syndromes in MS
* Primary pain
o Neuralgic
+ Trigeminal neuralgia
+ Other neuralgias
o Dysesthetic pain
+ Most often burning (legs)
+ Other dysesthesias
o Radicular pain
o Tonic seizures
o Spasticity
+ Flexor spasms
+ Extensor spasms
* Secondary pain
o Low back pain
o Osteoporosis with fractures
Neurologic Syndromes Likely for MS
* Optic neuritis
+ Unilateral eye involvement
+ Retrobulbar rather than papillitis
+ Eye pain
+ Partial vision loss, with at least some recovery
+ No retinal exudates, disc hemorrhages, macular star
o 10 years follow-up: 38% develop MS
+ MRI other lesions: risk 56%
+ MRI normal: risk 22%
o 20 years follow-up: 70% develop MS
* Transverse Myelitis
+ Incomplete
+ Sensory > motor
+ Associated
# Lhermitte’s sign
# Bandlike abdominal or chest pressure
* Internuclear Ophthalmoplegia
* Trigeminal Neuralgia
* Hemifacial Spasm
* Paroxysmal symptoms
+ Last seconds to minutes
+ Occur multiple times daily
o Tonic spasms
o Dysarthria, ataxia
o Hemiparesis, hypesthesia
Clues to a Misdiagnosis; MS
o Examination
+ Prominent
# fever, headache, uveitis, pain
+ Abrupt
# hemiparesis, hearing loss
+ No
# optic nerve/ocular involvement
# bowel/bladder involvement
+ Progressive myelopathy
# Without bowel/bladder involvement
+ Impaired level of consciousness
+ Nonscotomatous visual field defects
+ Grey matter features
# Early dementia, aphasia
# Fasciculations
# Extrapyramidal features
o MRI
+ Brain
# Normal
# Small lesions < 3 mm.
# Subcortical location (internal capsule)
# Prominent infratentorial involvement
# Prominent grey matter involvement (basal ganglia)
# Symmetric, confluent hemispheric white matter involvement
# Hydrocephalus
# Severe cerebellar/brain stem atrophy
# No callosal/periventricular lesions
* Manifestations due to CNS
o Slowing or failure of transmission
o Mostly damage of white matter tracts
o Recent appreciation of axonal/grey matter involvement
* Diagnosis based on clinical and laboratory evidence of
o Dissemination in time
o Dissemination in space
o Recent appreciation of role of MRI in assisting diagnosis
* In-office pattern recognition
o Appropriate demographic
o Appropriate clinical event

Multiple Sclerosis Diagnostic Issues.ppt