Multiple Sclerosis Diagnostic Issues

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Slide 1 : Multiple Sclerosis Diagnostic Issues Christopher Bourque
Slide 2 : Acknowledgements American Academy of Neurology Continuum series Multiple Sclerosis Vol 10, #6, Dec. 2004 Elsevier Saunders Neurologic Clinics Multiple Sclerosis Vol 23 # 1 Feb. 2005
Slide 3 : MS in 1 Slide Manifestations due to CNS Slowing or failure of transmission Inflammatory demyelination Axonal damage 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
Slide 4 : Patterns of MS Relapsing - remitting Attacks with complete/incomplete recovery Stable between attacks Secondary - progressive Initially relapsing-remitting Then progression +/- attacks Progressive - relapsing Initial gradual detioriation Subsequent episodes Primary progressive Gradual decline No attacks
Slide 5 : 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 Attacks lasting > 24 hrs., spaced at least 1 month apart Slow or stepwise progression for > 6 months No better explanation Diagnosis by experienced clinician
Slide 6 : 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 Technical advances enable quicker dx. Controversial
Slide 7 : McDonald Criteria
Slide 8 : McDonald Criteria
Slide 9 : Clinical Manifestations Demographic Female Women make up to 70%-75% MS patients Young age Onset before age 16: 5% of cases Peak onset post puberty, early 20’s Relapsing MS 28-30 years Symptoms Recent onset Frequently progressive Coming on over 1-several days Very acute symptoms possible
Slide 10 : The MS Event Attack/relapse/exacerbation Acute episode of CNS dysfunction Lasting at least 24 hours In absence of fever or metabolic derangement All events within 30 days are unitary
Slide 11 : MS Symptoms Source: Whitaker JN, Mitchell GW 1997
Slide 12 : Clinical Manifestations Motor Weakness, spasticity, ataxia Rarely radicular lesion ant. horn, root entry zone painful atrophy Somatosensory 1st sx. in 43% patients Includes visual Any anatomic distribution Any combination Loss pain, temp, light touch, vbn, position Positive sx. common Paresthesiae, hyperpathia, allodynia, dysesthesias
Slide 13 : Nonspecific Associated Features That Suggest MS Excessive unexplained fatigue Temperature sensitivity Hot, humid weather Relatively recent symptoms History of Lhermitte’s sign History of bandlike sensation around the waist Uhthoff’s phenomenon eg, blurry vision with exercise or heat exposure
Slide 14 : Clinical Manifestations Fatigue One of the most important causes of disability 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
Slide 15 : Clinical Manifestations Cognitive Disturbances Common, frequently overlooked Estimated 50-75% Most common Impaired attention, slow info processing, short term memory loss, reduced visuospatial skills, impaired executive function Impaired driving skills Important impact QoL, ADL Can occur independent of disease course other manifestations
Slide 16 : MRI in MS Brain lesions Character Large > 3 mm Ovoid Oriented perpendicular to ventricles Enhancing Open-ring enhancement Multifocal homogeneous Location Multiple white matter Brainstem, infratentorial Juxtacortical Corpus callosum Pointing away Moth eaten Callosal atrophy
Slide 17 : Evoked Potentials Visual evoked potentials Not auditory or somatosensory May point to subclinical involvement of optic nerve Quality control issues
Slide 18 : Principal Differential Diagnosis of Multiple Sclerosis Infection Lyme, Syphilis, Progressive Multifocal Leukoencephalopathy, HIV, HTLV-1 Inflammatory SLE, Sjogren syndrome, vasculitis, Sarcoidosis, Bechet’s disease Metabolic B12 deficiency, lysosomal disorders, adrenoleukodystrophy, mitochondrial disorders, other genetic diseases Neoplastic CNS lymphoma Spine disease Vascular malformations, degenerative spine disease
Slide 19 : Cerebrospinal Fluid Useful, not diagnostic Other conditions Chronic CNS infections, viral syndromes, neuropathies Immunoglobulin abnormalities 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)
Slide 20 : Cerebrospinal Fluid First event - chance of progression to MS In 3 years OCB +ve: 25% OCB -ve: 9% CIS:clinically isolated syndrome 62.5% cases +ve OCB Clinically definite MS 90% +OCB
Slide 21 : MRI in MS Spinal cord lesions 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 Location Cervical and thoracic Especially midcervical Peripheral Less than 2 vertebral segments Less than 50% cross-sectional area Lateral, dorsal cord
Slide 22 : 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
Slide 23 : MS Symptoms Source: Whitaker JN, Mitchell GW 1997
Slide 24 : Clinical Manifestations Visual symptoms, afferent Almost any pattern, related to location Optic neuritis Central scotoma Mild: color desaturation Severe: blindness Vast majority have excellent return by 6 months Frequent pain Worse on eye movement
Slide 25 : Optic Neuritis Risk of Subsequent MS Higher Risk Young adult (26-40 years) Venous sheathing Recurrent optic neuritis Female sex History of minor neurologic symptoms Brain MRI lesions CSF oligoclonal bands or intrathecal IgG production Lower Risk Age < 10 Macular star/exudates Retinal or disc hemorrhage Severe disc edema No brain MRI lesions Normal CSF
Slide 26 : Clinical Manifestations Visual symptoms, efferent Any eye movement abnormality INO Internuclear ophthalmoplegia Adductor weakness Abduction nystagmus In young adult strongly suggests MS Nystagmus Many types
Slide 27 : Clinical Manifestations Other Brain Stem Structures Facial weakness Vertigo Loss of hearing, taste Dysarthria, dysphagia Bulbar muscles Weakness, ataxia, spasticity
Slide 28 : Clinical Manifestations Psychiatric Disturbances Depression Also up to 75% of patients Major depression less frequent Suicide: 15% of adult MS deaths Risk factors Living alone FH mental illness Reporting social isolation PH major depression, anxiety, alcohol abuse Emotional incontinence Frontal lobe involvement
Slide 29 : Clinical Manifestations Bladder dysfunction; the importance of urodynamic studies Failure to store: detruser hyperactivity Urgency, frequency, nocturia Failure to empty Detruser-sphincter dyssynergia Poor detruser contraction Hesitancy, increased residual vol., retention Both Combined detruser hyperactivity detruser-sphincter dyssynergia Incontinence Detruser hyperactivity or Overflow Symptoms may not be accurate indicator of urodynamic pathology
Slide 30 : Clinical Manifestations Bowel dysfunction Constipation Can be aggrevated by fluid restriction Anticholinergic medications Urgency and incontinence Sexual dysfunction Erectile dysfunction Women: loss of libido, anorgasmia Both sexes Loss of perineal sensation Neuropathic pain Spasticity Incontinence Depression, fatigue
Slide 31 : Pain Syndromes in MS Primary pain Neuralgic Trigeminal neuralgia Other neuralgias Dysesthetic pain Most often burning (legs) Other dysesthesias Radicular pain Tonic seizures Spasticity Flexor spasms Extensor spasms Secondary pain Low back pain Osteoporosis with fractures
Slide 32 : 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 10 years follow-up: 38% develop MS MRI other lesions: risk 56% MRI normal: risk 22% 20 years follow-up: 70% develop MS
Slide 33 : Neurologic Syndromes Likely for MS Transverse Myelitis Incomplete Sensory > motor Associated Lhermitte’s sign Bandlike abdominal or chest pressure Internuclear Ophthalmoplegia Trigeminal Neuralgia Hemifacial Spasm
Slide 34 : Neurologic Syndromes Likely for MS Paroxysmal symptoms Last seconds to minutes Occur multiple times daily Tonic spasms Dysarthria, ataxia Hemiparesis, hypesthesia Polysymptomatic Syndrome Without Mental Status Changes
Slide 35 : Clues to a Misdiagnosis; MS Historical No dissemination Onset < 10 yrs. or > 55 yrs. Genetic red flags +ve FH However about 20% of MS patients have FH Early-age onset Unexplained non-CNS disease Progressive course starting before age 35 Localized disease
Slide 36 : Clues to a Misdiagnosis; MS 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
Slide 37 : Clues to a Misdiagnosis; MS 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
Slide 38 : Clues to a Misdiagnosis; MS MRI Spinal cord Large lesion, multiple segments (>2) Severe swelling Full thickness lesions Leptomenengial enhancement T1 hypointense lesions
Slide 39 : Clues to a Misdiagnosis; MS CSF Normal Disappearance of oligoclonal bands Normalization of IgG index Cell count > 50 wbc/cubic mm. Protein > 100 mg/dl
Slide 40 : MS Diagnosis; 1 Final Slide Manifestations due to CNS Slowing or failure of transmission Mostly damage of white matter tracts Recent appreciation of axonal/grey matter involvement Diagnosis based on clinical and laboratory evidence of Dissemination in time Dissemination in space Recent appreciation of role of MRI in assisting diagnosis In-office pattern recognition Appropriate demographic Appropriate clinical event

 


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