Multiple Sclerosis Diagnostic Issues Christopher Bourque
Acknowledgements <ul><li>American Academy of Neurology </li></ul><ul><ul><li>Continuum series </li></ul></ul><ul><ul><ul><...
MS in 1 Slide <ul><li>Manifestations due to CNS  </li></ul><ul><ul><li>Slowing or failure of transmission </li></ul></ul><...
Patterns of MS <ul><li>Relapsing - remitting </li></ul><ul><ul><li>Attacks with complete/incomplete recovery </li></ul></u...
Schumacher Clinical Criteria MS Diagnosis 1965 <ul><li>Age (onset 10-50 years) </li></ul><ul><li>CNS white matter disease ...
Poser Criteria for the Diagnosis of MS 1983 <ul><li>Widely used for last 20 years </li></ul><ul><li>Definite or probable <...
McDonald Criteria Next slide 1 0 (progression from onset) Dissemination in space by MRI  or  positive CSF and 2 or more MR...
McDonald Criteria Positive CSF  and  Dissemination in space by MRI evidence of 9 or more T2 brain lesions or  2 or more co...
Clinical Manifestations <ul><li>Demographic </li></ul><ul><ul><li>Female </li></ul></ul><ul><ul><ul><li>Women make up to 7...
The MS Event <ul><li>Attack/relapse/exacerbation </li></ul><ul><ul><li>Acute episode of CNS dysfunction </li></ul></ul><ul...
MS Symptoms Source: Whitaker JN, Mitchell GW  1997 100 88 87 82 63 39 49 42 41 23 10 4 Visual/oculomotor Paresis Paresthes...
Clinical Manifestations <ul><li>Motor </li></ul><ul><ul><li>Weakness, spasticity, ataxia </li></ul></ul><ul><ul><li>Rarely...
Nonspecific Associated Features That Suggest MS <ul><li>Excessive unexplained fatigue </li></ul><ul><li>Temperature sensit...
Clinical Manifestations <ul><li>Fatigue </li></ul><ul><ul><li>One of the most important causes of disability </li></ul></u...
Clinical Manifestations <ul><li>Cognitive Disturbances </li></ul><ul><ul><li>Common, frequently overlooked </li></ul></ul>...
MRI in MS <ul><li>Brain lesions </li></ul><ul><ul><li>Character </li></ul></ul><ul><ul><ul><li>Large  >  3 mm </li></ul></...
Evoked Potentials <ul><li>Visual evoked potentials </li></ul><ul><ul><li>Not auditory or somatosensory </li></ul></ul><ul>...
Principal  Differential Diagnosis of Multiple Sclerosis <ul><li>Infection </li></ul><ul><ul><ul><li>Lyme, Syphilis, Progre...
Cerebrospinal Fluid <ul><li>Useful, not diagnostic </li></ul><ul><ul><li>Other conditions </li></ul></ul><ul><ul><ul><li>C...
Cerebrospinal Fluid <ul><li>First event - chance of progression to MS </li></ul><ul><ul><li>In 3 years </li></ul></ul><ul>...
MRI in MS <ul><li>Spinal cord lesions </li></ul><ul><ul><li>Character </li></ul></ul><ul><ul><ul><li>Asymptomatic lesions ...
Paroxysmal Symptoms in MS <ul><li>Trigeminal neuralgia (and others) </li></ul><ul><li>Tonic “seizures” </li></ul><ul><li>P...
MS Symptoms Source: Whitaker JN, Mitchell GW  1997 100 88 87 82 63 39 49 42 41 23 10 4 Visual/oculomotor Paresis Paresthes...
Clinical Manifestations <ul><li>Visual symptoms, afferent </li></ul><ul><ul><li>Almost any pattern, related to location </...
Optic Neuritis Risk of Subsequent MS <ul><ul><li>Higher Risk </li></ul></ul><ul><ul><ul><ul><li>Young adult (26-40 years) ...
Clinical Manifestations <ul><li>Visual symptoms, efferent </li></ul><ul><ul><li>Any eye movement abnormality </li></ul></u...
Clinical Manifestations <ul><li>Other Brain Stem Structures </li></ul><ul><ul><li>Facial weakness </li></ul></ul><ul><ul><...
Clinical Manifestations <ul><li>Psychiatric Disturbances </li></ul><ul><ul><li>Depression </li></ul></ul><ul><ul><ul><li>A...
Clinical Manifestations <ul><li>Bladder dysfunction; the importance of urodynamic studies </li></ul><ul><ul><li>Failure to...
Clinical Manifestations <ul><li>Bowel dysfunction </li></ul><ul><ul><li>Constipation </li></ul></ul><ul><ul><ul><li>Can be...
Pain Syndromes in MS <ul><li>Primary pain </li></ul><ul><ul><li>Neuralgic </li></ul></ul><ul><ul><ul><li>Trigeminal neural...
Neurologic Syndromes Likely for MS  <ul><li>Optic neuritis </li></ul><ul><ul><ul><li>Unilateral eye involvement </li></ul>...
Neurologic Syndromes Likely for MS <ul><li>Transverse Myelitis </li></ul><ul><ul><ul><li>Incomplete </li></ul></ul></ul><u...
Neurologic Syndromes Likely for MS <ul><li>Paroxysmal symptoms </li></ul><ul><ul><ul><li>Last seconds to minutes </li></ul...
Clues to a Misdiagnosis; MS <ul><li>Historical </li></ul><ul><ul><li>No dissemination </li></ul></ul><ul><ul><li>Onset < 1...
Clues to a Misdiagnosis; MS <ul><ul><li>Examination </li></ul></ul><ul><ul><ul><li>Prominent  </li></ul></ul></ul><ul><ul>...
Clues to a Misdiagnosis; MS <ul><ul><li>MRI </li></ul></ul><ul><ul><ul><li>Brain </li></ul></ul></ul><ul><ul><ul><ul><li>N...
Clues to a Misdiagnosis; MS <ul><ul><li>MRI </li></ul></ul><ul><ul><ul><li>Spinal cord </li></ul></ul></ul><ul><ul><ul><ul...
Clues to a Misdiagnosis; MS <ul><ul><li>CSF </li></ul></ul><ul><ul><ul><li>Normal </li></ul></ul></ul><ul><ul><ul><li>Disa...
MS Diagnosis; 1 Final Slide <ul><li>Manifestations due to CNS  </li></ul><ul><ul><li>Slowing or failure of transmission </...
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Multiple Sclerosis Diagnostics Dr C Bourque

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  • Multiple Sclerosis Diagnostics Dr C Bourque

    1. 1. Multiple Sclerosis Diagnostic Issues Christopher Bourque
    2. 2. Acknowledgements <ul><li>American Academy of Neurology </li></ul><ul><ul><li>Continuum series </li></ul></ul><ul><ul><ul><li>Multiple Sclerosis </li></ul></ul></ul><ul><ul><ul><ul><li>Vol 10, #6, Dec. 2004 </li></ul></ul></ul></ul><ul><li>Elsevier Saunders </li></ul><ul><ul><li>Neurologic Clinics </li></ul></ul><ul><ul><ul><li>Multiple Sclerosis </li></ul></ul></ul><ul><ul><ul><ul><li>Vol 23 # 1 Feb. 2005 </li></ul></ul></ul></ul>
    3. 3. MS in 1 Slide <ul><li>Manifestations due to CNS </li></ul><ul><ul><li>Slowing or failure of transmission </li></ul></ul><ul><ul><ul><li>Inflammatory demyelination </li></ul></ul></ul><ul><ul><ul><li>Axonal damage </li></ul></ul></ul><ul><ul><li>Mostly damage of white matter tracts </li></ul></ul><ul><ul><ul><li>Optic neuritis, weakness, sensory loss, ataxia nystagmus, bladder dysfunction, cognitive impairment </li></ul></ul></ul><ul><li>Diagnosis based on clinical and laboratory evidence of </li></ul><ul><ul><ul><li>Dissemination in time </li></ul></ul></ul><ul><ul><ul><li>Dissemination in space </li></ul></ul></ul>
    4. 4. Patterns of MS <ul><li>Relapsing - remitting </li></ul><ul><ul><li>Attacks with complete/incomplete recovery </li></ul></ul><ul><ul><li>Stable between attacks </li></ul></ul><ul><li>Secondary - progressive </li></ul><ul><ul><li>Initially relapsing-remitting </li></ul></ul><ul><ul><li>Then progression +/- attacks </li></ul></ul><ul><li>Progressive - relapsing </li></ul><ul><ul><li>Initial gradual detioriation </li></ul></ul><ul><ul><li>Subsequent episodes </li></ul></ul><ul><li>Primary progressive </li></ul><ul><ul><li>Gradual decline </li></ul></ul><ul><ul><li>No attacks </li></ul></ul>
    5. 5. Schumacher Clinical Criteria MS Diagnosis 1965 <ul><li>Age (onset 10-50 years) </li></ul><ul><li>CNS white matter disease </li></ul><ul><li>Lesions disseminated in time and space </li></ul><ul><li>Objective abnormalities on exam </li></ul><ul><li>Consistent time course </li></ul><ul><ul><li>Attacks lasting > 24 hrs., spaced at least 1 month apart </li></ul></ul><ul><ul><li>Slow or stepwise progression for > 6 months </li></ul></ul><ul><li>No better explanation </li></ul><ul><li>Diagnosis by experienced clinician </li></ul>
    6. 6. Poser Criteria for the Diagnosis of MS 1983 <ul><li>Widely used for last 20 years </li></ul><ul><li>Definite or probable </li></ul><ul><li>Laboratory supported MS </li></ul><ul><li>Replaced by McDonald criteria 2001 </li></ul><ul><ul><li>Technical advances enable quicker dx. </li></ul></ul><ul><ul><li>Controversial </li></ul></ul>
    7. 7. McDonald Criteria Next slide 1 0 (progression from onset) Dissemination in space by MRI or positive CSF and 2 or more MRI lesions consistent with MS and dissemination in time by MRI or second clinical attack 1 1 monosymptomatic Dissemination in time by MRI or second clinical attack 2 or more 1 Dissemination in space by MRI or positive CSF and 2 or more MRI lesions consistent with MS or further clinical attack involving different site 1 2 or more None 2 or more 2 or more Additional Requirements to Make Diagnosis Objective Lesions Clinical (attacks)
    8. 8. McDonald Criteria Positive CSF and 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 1 0 (progression from onset) Additional Requirements to Make Diagnosis Objective Lesions Clinical (attacks)
    9. 9. Clinical Manifestations <ul><li>Demographic </li></ul><ul><ul><li>Female </li></ul></ul><ul><ul><ul><li>Women make up to 70%-75% MS patients </li></ul></ul></ul><ul><ul><li>Young age </li></ul></ul><ul><ul><ul><li>Onset before age 16: 5% of cases </li></ul></ul></ul><ul><ul><ul><li>Peak onset post puberty, early 20’s </li></ul></ul></ul><ul><ul><ul><ul><li>Relapsing MS 28-30 years </li></ul></ul></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Recent onset </li></ul></ul><ul><ul><li>Frequently progressive </li></ul></ul><ul><ul><ul><li>Coming on over 1-several days </li></ul></ul></ul><ul><ul><ul><li>Very acute symptoms possible </li></ul></ul></ul>
    10. 10. The MS Event <ul><li>Attack/relapse/exacerbation </li></ul><ul><ul><li>Acute episode of CNS dysfunction </li></ul></ul><ul><ul><li>Lasting at least 24 hours </li></ul></ul><ul><ul><li>In absence of fever or metabolic derangement </li></ul></ul><ul><ul><li>All events within 30 days are unitary </li></ul></ul>
    11. 11. MS Symptoms Source: Whitaker JN, Mitchell GW 1997 100 88 87 82 63 39 49 42 41 23 10 4 Visual/oculomotor Paresis Paresthesias Incoordination Genitourinary/bowel Cerebral During course % Presenting % Deficit reported
    12. 12. Clinical Manifestations <ul><li>Motor </li></ul><ul><ul><li>Weakness, spasticity, ataxia </li></ul></ul><ul><ul><li>Rarely radicular </li></ul></ul><ul><ul><ul><li>lesion ant. horn, root entry zone </li></ul></ul></ul><ul><ul><ul><li>painful </li></ul></ul></ul><ul><ul><ul><li>atrophy </li></ul></ul></ul><ul><li>Somatosensory </li></ul><ul><ul><li>1st sx. in 43% patients </li></ul></ul><ul><ul><ul><li>Includes visual </li></ul></ul></ul><ul><ul><li>Any anatomic distribution </li></ul></ul><ul><ul><li>Any combination </li></ul></ul><ul><ul><ul><li>Loss pain, temp, light touch, vbn, position </li></ul></ul></ul><ul><ul><li>Positive sx. common </li></ul></ul><ul><ul><ul><li>Paresthesiae, hyperpathia, allodynia, dysesthesias </li></ul></ul></ul>
    13. 13. Nonspecific Associated Features That Suggest MS <ul><li>Excessive unexplained fatigue </li></ul><ul><li>Temperature sensitivity </li></ul><ul><ul><li>Hot, humid weather </li></ul></ul><ul><li>Relatively recent symptoms </li></ul><ul><li>History of Lhermitte’s sign </li></ul><ul><li>History of bandlike sensation around the waist </li></ul><ul><li>Uhthoff’s phenomenon </li></ul><ul><ul><li>eg, blurry vision with exercise or heat exposure </li></ul></ul>
    14. 14. Clinical Manifestations <ul><li>Fatigue </li></ul><ul><ul><li>One of the most important causes of disability </li></ul></ul><ul><ul><li>Several sources </li></ul></ul><ul><ul><ul><li>Handicap fatigue </li></ul></ul></ul><ul><ul><ul><ul><li>Increased effort to perform routine tasks </li></ul></ul></ul></ul><ul><ul><ul><li>Secondary fatigue </li></ul></ul></ul><ul><ul><ul><ul><li>Depression, sleep disturbances, medication side-effects, other conditions </li></ul></ul></ul></ul><ul><ul><ul><li>Systemic fatigue </li></ul></ul></ul><ul><ul><ul><ul><li>Chronic lack of energy, tirdness, malaise </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Etiology unknown </li></ul></ul></ul></ul>
    15. 15. Clinical Manifestations <ul><li>Cognitive Disturbances </li></ul><ul><ul><li>Common, frequently overlooked </li></ul></ul><ul><ul><ul><li>Estimated 50-75% </li></ul></ul></ul><ul><ul><li>Most common </li></ul></ul><ul><ul><ul><li>Impaired attention, slow info processing, short term memory loss, reduced visuospatial skills, impaired executive function </li></ul></ul></ul><ul><ul><li>Impaired driving skills </li></ul></ul><ul><ul><li>Important impact QoL, ADL </li></ul></ul><ul><ul><li>Can occur independent </li></ul></ul><ul><ul><ul><li>of disease course </li></ul></ul></ul><ul><ul><ul><li>other manifestations </li></ul></ul></ul>
    16. 16. MRI in MS <ul><li>Brain lesions </li></ul><ul><ul><li>Character </li></ul></ul><ul><ul><ul><li>Large > 3 mm </li></ul></ul></ul><ul><ul><ul><li>Ovoid </li></ul></ul></ul><ul><ul><ul><li>Oriented perpendicular to ventricles </li></ul></ul></ul><ul><ul><ul><li>Enhancing </li></ul></ul></ul><ul><ul><ul><ul><li>Open-ring enhancement </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Multifocal homogeneous </li></ul></ul></ul></ul><ul><ul><li>Location </li></ul></ul><ul><ul><ul><li>Multiple white matter </li></ul></ul></ul><ul><ul><ul><li>Brainstem, infratentorial </li></ul></ul></ul><ul><ul><ul><li>Juxtacortical </li></ul></ul></ul><ul><ul><ul><li>Corpus callosum </li></ul></ul></ul><ul><ul><ul><ul><li>Pointing away </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Moth eaten </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Callosal atrophy </li></ul></ul></ul></ul>
    17. 17. Evoked Potentials <ul><li>Visual evoked potentials </li></ul><ul><ul><li>Not auditory or somatosensory </li></ul></ul><ul><ul><li>May point to subclinical involvement of optic nerve </li></ul></ul><ul><ul><ul><li>Quality control issues </li></ul></ul></ul>
    18. 18. Principal Differential Diagnosis of Multiple Sclerosis <ul><li>Infection </li></ul><ul><ul><ul><li>Lyme, Syphilis, Progressive Multifocal Leukoencephalopathy, HIV, HTLV-1 </li></ul></ul></ul><ul><li>Inflammatory </li></ul><ul><ul><ul><li>SLE, Sjogren syndrome, vasculitis, Sarcoidosis, Bechet’s disease </li></ul></ul></ul><ul><li>Metabolic </li></ul><ul><ul><ul><li>B12 deficiency, lysosomal disorders, adrenoleukodystrophy, mitochondrial disorders, other genetic diseases </li></ul></ul></ul><ul><li>Neoplastic </li></ul><ul><ul><ul><li>CNS lymphoma </li></ul></ul></ul><ul><li>Spine disease </li></ul><ul><ul><ul><li>Vascular malformations, degenerative spine disease </li></ul></ul></ul>
    19. 19. Cerebrospinal Fluid <ul><li>Useful, not diagnostic </li></ul><ul><ul><li>Other conditions </li></ul></ul><ul><ul><ul><li>Chronic CNS infections, viral syndromes, neuropathies </li></ul></ul></ul><ul><li>Immunoglobulin abnormalities </li></ul><ul><ul><li>Production of immunoglobulin </li></ul></ul><ul><ul><ul><ul><li>By plasma or B cells in CNS </li></ul></ul></ul></ul><ul><ul><ul><li>Oligoclonal bands of immunoglobulin (IgG) (OCB) </li></ul></ul></ul><ul><ul><ul><ul><li>In CSF, not serum </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Isoelectric focusing technique </li></ul></ul></ul></ul><ul><ul><ul><li>Elevated IgG index </li></ul></ul></ul><ul><ul><ul><ul><li>Ratio of IgG/protein in serum and CSF </li></ul></ul></ul></ul><ul><ul><ul><ul><li>index = (csf IgG/csf albumin) </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li> (serum IgG/serum albumin) </li></ul></ul></ul></ul></ul>
    20. 20. Cerebrospinal Fluid <ul><li>First event - chance of progression to MS </li></ul><ul><ul><li>In 3 years </li></ul></ul><ul><ul><ul><li>OCB +ve: 25% </li></ul></ul></ul><ul><ul><ul><li>OCB -ve: 9% </li></ul></ul></ul><ul><li>CIS:clinically isolated syndrome </li></ul><ul><ul><li>62.5% cases +ve OCB </li></ul></ul><ul><li>Clinically definite MS </li></ul><ul><ul><li>90% +OCB </li></ul></ul>
    21. 21. MRI in MS <ul><li>Spinal cord lesions </li></ul><ul><ul><li>Character </li></ul></ul><ul><ul><ul><li>Asymptomatic lesions </li></ul></ul></ul><ul><ul><ul><li>Focal T2/proton density hyperintense lesions </li></ul></ul></ul><ul><ul><ul><li>Diffuse proton density abnormalities </li></ul></ul></ul><ul><ul><ul><li>Atrophy </li></ul></ul></ul><ul><ul><ul><li>Asymmetric involvement </li></ul></ul></ul><ul><ul><ul><ul><li>Multiple scattered lesions </li></ul></ul></ul></ul><ul><ul><ul><li>Edema with acute plaques </li></ul></ul></ul><ul><ul><ul><ul><li>Often enhancing </li></ul></ul></ul></ul><ul><ul><li>Location </li></ul></ul><ul><ul><ul><li>Cervical and thoracic </li></ul></ul></ul><ul><ul><ul><ul><li>Especially midcervical </li></ul></ul></ul></ul><ul><ul><ul><li>Peripheral </li></ul></ul></ul><ul><ul><ul><li>Less than 2 vertebral segments </li></ul></ul></ul><ul><ul><ul><li>Less than 50% cross-sectional area </li></ul></ul></ul><ul><ul><ul><li>Lateral, dorsal cord </li></ul></ul></ul>
    22. 22. Paroxysmal Symptoms in MS <ul><li>Trigeminal neuralgia (and others) </li></ul><ul><li>Tonic “seizures” </li></ul><ul><li>Paroxysmal dysarthria </li></ul><ul><li>Hemifacial spasm </li></ul><ul><li>Paroxysmal itching </li></ul><ul><li>Abrupt loss of muscle tone </li></ul><ul><li>Paroxysmal aphasia </li></ul><ul><li>Paroxysmal kinesogenic choreoathetosis </li></ul><ul><li>Lhermitte’s sign </li></ul>
    23. 23. MS Symptoms Source: Whitaker JN, Mitchell GW 1997 100 88 87 82 63 39 49 42 41 23 10 4 Visual/oculomotor Paresis Paresthesias Incoordination Genitourinary/bowel Cerebral During course % Presenting % Deficit reported
    24. 24. Clinical Manifestations <ul><li>Visual symptoms, afferent </li></ul><ul><ul><li>Almost any pattern, related to location </li></ul></ul><ul><ul><li>Optic neuritis </li></ul></ul><ul><ul><ul><li>Central scotoma </li></ul></ul></ul><ul><ul><ul><ul><li>Mild: color desaturation </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Severe: blindness </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Vast majority have excellent return by 6 months </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Frequent pain </li></ul></ul></ul><ul><ul><ul><ul><li>Worse on eye movement </li></ul></ul></ul></ul>
    25. 25. Optic Neuritis Risk of Subsequent MS <ul><ul><li>Higher Risk </li></ul></ul><ul><ul><ul><ul><li>Young adult (26-40 years) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Venous sheathing </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Recurrent optic neuritis </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Female sex </li></ul></ul></ul></ul><ul><ul><ul><ul><li>History of minor neurologic symptoms </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Brain MRI lesions </li></ul></ul></ul></ul><ul><ul><ul><ul><li>CSF oligoclonal bands or intrathecal IgG production </li></ul></ul></ul></ul><ul><ul><li>Lower Risk </li></ul></ul><ul><ul><ul><ul><li>Age < 10 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Macular star/exudates </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Retinal or disc hemorrhage </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Severe disc edema </li></ul></ul></ul></ul><ul><ul><ul><ul><li>No brain MRI lesions </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Normal CSF </li></ul></ul></ul></ul>
    26. 26. Clinical Manifestations <ul><li>Visual symptoms, efferent </li></ul><ul><ul><li>Any eye movement abnormality </li></ul></ul><ul><ul><li>INO </li></ul></ul><ul><ul><ul><li>Internuclear ophthalmoplegia </li></ul></ul></ul><ul><ul><ul><ul><li>Adductor weakness </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Abduction nystagmus </li></ul></ul></ul></ul><ul><ul><ul><ul><li>In young adult strongly suggests MS </li></ul></ul></ul></ul><ul><ul><li>Nystagmus </li></ul></ul><ul><ul><ul><li>Many types </li></ul></ul></ul>
    27. 27. Clinical Manifestations <ul><li>Other Brain Stem Structures </li></ul><ul><ul><li>Facial weakness </li></ul></ul><ul><ul><li>Vertigo </li></ul></ul><ul><ul><li>Loss of hearing, taste </li></ul></ul><ul><ul><li>Dysarthria, dysphagia </li></ul></ul><ul><ul><ul><li>Bulbar muscles </li></ul></ul></ul><ul><ul><ul><ul><li>Weakness, ataxia, spasticity </li></ul></ul></ul></ul>
    28. 28. Clinical Manifestations <ul><li>Psychiatric Disturbances </li></ul><ul><ul><li>Depression </li></ul></ul><ul><ul><ul><li>Also up to 75% of patients </li></ul></ul></ul><ul><ul><ul><li>Major depression less frequent </li></ul></ul></ul><ul><ul><ul><li>Suicide: 15% of adult MS deaths </li></ul></ul></ul><ul><ul><ul><ul><li>Risk factors </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Living alone </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>FH mental illness </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Reporting social isolation </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>PH major depression, anxiety, alcohol abuse </li></ul></ul></ul></ul></ul><ul><ul><li>Emotional incontinence </li></ul></ul><ul><ul><ul><li>Frontal lobe involvement </li></ul></ul></ul>
    29. 29. Clinical Manifestations <ul><li>Bladder dysfunction; the importance of urodynamic studies </li></ul><ul><ul><li>Failure to store: detruser hyperactivity </li></ul></ul><ul><ul><ul><li>Urgency, frequency, nocturia </li></ul></ul></ul><ul><ul><li>Failure to empty </li></ul></ul><ul><ul><ul><li>Detruser-sphincter dyssynergia </li></ul></ul></ul><ul><ul><ul><li>Poor detruser contraction </li></ul></ul></ul><ul><ul><ul><ul><li>Hesitancy, increased residual vol., retention </li></ul></ul></ul></ul><ul><ul><li>Both </li></ul></ul><ul><ul><ul><li>Combined </li></ul></ul></ul><ul><ul><ul><ul><li>detruser hyperactivity </li></ul></ul></ul></ul><ul><ul><ul><ul><li>detruser-sphincter dyssynergia </li></ul></ul></ul></ul><ul><ul><li>Incontinence </li></ul></ul><ul><ul><ul><li>Detruser hyperactivity or </li></ul></ul></ul><ul><ul><ul><li>Overflow </li></ul></ul></ul><ul><ul><ul><li>Symptoms may not be accurate indicator of urodynamic pathology </li></ul></ul></ul>
    30. 30. Clinical Manifestations <ul><li>Bowel dysfunction </li></ul><ul><ul><li>Constipation </li></ul></ul><ul><ul><ul><li>Can be aggrevated by </li></ul></ul></ul><ul><ul><ul><ul><li>fluid restriction </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Anticholinergic medications </li></ul></ul></ul></ul><ul><ul><li>Urgency and incontinence </li></ul></ul><ul><li>Sexual dysfunction </li></ul><ul><ul><li>Erectile dysfunction </li></ul></ul><ul><ul><li>Women: loss of libido, anorgasmia </li></ul></ul><ul><ul><li>Both sexes </li></ul></ul><ul><ul><ul><li>Loss of perineal sensation </li></ul></ul></ul><ul><ul><ul><li>Neuropathic pain </li></ul></ul></ul><ul><ul><ul><li>Spasticity </li></ul></ul></ul><ul><ul><ul><li>Incontinence </li></ul></ul></ul><ul><ul><ul><li>Depression, fatigue </li></ul></ul></ul>
    31. 31. Pain Syndromes in MS <ul><li>Primary pain </li></ul><ul><ul><li>Neuralgic </li></ul></ul><ul><ul><ul><li>Trigeminal neuralgia </li></ul></ul></ul><ul><ul><ul><li>Other neuralgias </li></ul></ul></ul><ul><ul><li>Dysesthetic pain </li></ul></ul><ul><ul><ul><li>Most often burning (legs) </li></ul></ul></ul><ul><ul><ul><li>Other dysesthesias </li></ul></ul></ul><ul><ul><li>Radicular pain </li></ul></ul><ul><ul><li>Tonic seizures </li></ul></ul><ul><ul><li>Spasticity </li></ul></ul><ul><ul><ul><li>Flexor spasms </li></ul></ul></ul><ul><ul><ul><li>Extensor spasms </li></ul></ul></ul><ul><li>Secondary pain </li></ul><ul><ul><li>Low back pain </li></ul></ul><ul><ul><li>Osteoporosis with fractures </li></ul></ul>
    32. 32. Neurologic Syndromes Likely for MS <ul><li>Optic neuritis </li></ul><ul><ul><ul><li>Unilateral eye involvement </li></ul></ul></ul><ul><ul><ul><li>Retrobulbar rather than papillitis </li></ul></ul></ul><ul><ul><ul><li>Eye pain </li></ul></ul></ul><ul><ul><ul><li>Partial vision loss, with at least some recovery </li></ul></ul></ul><ul><ul><ul><li>No retinal exudates, disc hemorrhages, macular star </li></ul></ul></ul><ul><ul><li>10 years follow-up: 38% develop MS </li></ul></ul><ul><ul><ul><li>MRI other lesions: risk 56% </li></ul></ul></ul><ul><ul><ul><li>MRI normal: risk 22% </li></ul></ul></ul><ul><ul><li>20 years follow-up: 70% develop MS </li></ul></ul>
    33. 33. Neurologic Syndromes Likely for MS <ul><li>Transverse Myelitis </li></ul><ul><ul><ul><li>Incomplete </li></ul></ul></ul><ul><ul><ul><li>Sensory > motor </li></ul></ul></ul><ul><ul><ul><li>Associated </li></ul></ul></ul><ul><ul><ul><ul><li>Lhermitte’s sign </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Bandlike abdominal or chest pressure </li></ul></ul></ul></ul><ul><li>Internuclear Ophthalmoplegia </li></ul><ul><li>Trigeminal Neuralgia </li></ul><ul><li>Hemifacial Spasm </li></ul>
    34. 34. Neurologic Syndromes Likely for MS <ul><li>Paroxysmal symptoms </li></ul><ul><ul><ul><li>Last seconds to minutes </li></ul></ul></ul><ul><ul><ul><li>Occur multiple times daily </li></ul></ul></ul><ul><ul><li>Tonic spasms </li></ul></ul><ul><ul><li>Dysarthria, ataxia </li></ul></ul><ul><ul><li>Hemiparesis, hypesthesia </li></ul></ul><ul><li>Polysymptomatic Syndrome Without Mental Status Changes </li></ul>
    35. 35. Clues to a Misdiagnosis; MS <ul><li>Historical </li></ul><ul><ul><li>No dissemination </li></ul></ul><ul><ul><li>Onset < 10 yrs. or > 55 yrs. </li></ul></ul><ul><ul><li>Genetic red flags </li></ul></ul><ul><ul><ul><li>+ve FH </li></ul></ul></ul><ul><ul><ul><ul><li>However about 20% of MS patients have FH </li></ul></ul></ul></ul><ul><ul><ul><li>Early-age onset </li></ul></ul></ul><ul><ul><ul><li>Unexplained non-CNS disease </li></ul></ul></ul><ul><ul><li>Progressive course starting before age 35 </li></ul></ul><ul><ul><li>Localized disease </li></ul></ul>
    36. 36. Clues to a Misdiagnosis; MS <ul><ul><li>Examination </li></ul></ul><ul><ul><ul><li>Prominent </li></ul></ul></ul><ul><ul><ul><ul><li>fever, headache, uveitis, pain </li></ul></ul></ul></ul><ul><ul><ul><li>Abrupt </li></ul></ul></ul><ul><ul><ul><ul><li>hemiparesis, hearing loss </li></ul></ul></ul></ul><ul><ul><ul><li>No </li></ul></ul></ul><ul><ul><ul><ul><li>optic nerve/ocular involvement </li></ul></ul></ul></ul><ul><ul><ul><ul><li>bowel/bladder involvement </li></ul></ul></ul></ul><ul><ul><ul><li>Progressive myelopathy </li></ul></ul></ul><ul><ul><ul><ul><li>Without bowel/bladder involvement </li></ul></ul></ul></ul><ul><ul><ul><li>Impaired level of consciousness </li></ul></ul></ul><ul><ul><ul><li>Nonscotomatous visual field defects </li></ul></ul></ul><ul><ul><ul><li>Grey matter features </li></ul></ul></ul><ul><ul><ul><ul><li>Early dementia, aphasia </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Fasciculations </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Extrapyramidal features </li></ul></ul></ul></ul>
    37. 37. Clues to a Misdiagnosis; MS <ul><ul><li>MRI </li></ul></ul><ul><ul><ul><li>Brain </li></ul></ul></ul><ul><ul><ul><ul><li>Normal </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Small lesions < 3 mm. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Subcortical location (internal capsule) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Prominent infratentorial involvement </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Prominent grey matter involvement (basal ganglia) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Symmetric, confluent hemispheric white matter involvement </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Hydrocephalus </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Severe cerebellar/brain stem atrophy </li></ul></ul></ul></ul><ul><ul><ul><ul><li>No callosal/periventricular lesions </li></ul></ul></ul></ul>
    38. 38. Clues to a Misdiagnosis; MS <ul><ul><li>MRI </li></ul></ul><ul><ul><ul><li>Spinal cord </li></ul></ul></ul><ul><ul><ul><ul><li>Large lesion, multiple segments (>2) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Severe swelling </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Full thickness lesions </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Leptomenengial enhancement </li></ul></ul></ul></ul><ul><ul><ul><ul><li>T1 hypointense lesions </li></ul></ul></ul></ul>
    39. 39. Clues to a Misdiagnosis; MS <ul><ul><li>CSF </li></ul></ul><ul><ul><ul><li>Normal </li></ul></ul></ul><ul><ul><ul><li>Disappearance of oligoclonal bands </li></ul></ul></ul><ul><ul><ul><ul><li>Normalization of IgG index </li></ul></ul></ul></ul><ul><ul><ul><li>Cell count > 50 wbc/cubic mm. </li></ul></ul></ul><ul><ul><ul><li>Protein > 100 mg/dl </li></ul></ul></ul>
    40. 40. MS Diagnosis; 1 Final Slide <ul><li>Manifestations due to CNS </li></ul><ul><ul><li>Slowing or failure of transmission </li></ul></ul><ul><ul><li>Mostly damage of white matter tracts </li></ul></ul><ul><ul><li>Recent appreciation of axonal/grey matter involvement </li></ul></ul><ul><li>Diagnosis based on clinical and laboratory evidence of </li></ul><ul><ul><li>Dissemination in time </li></ul></ul><ul><ul><li>Dissemination in space </li></ul></ul><ul><ul><li>Recent appreciation of role of MRI in assisting diagnosis </li></ul></ul><ul><li>In-office pattern recognition </li></ul><ul><ul><li>Appropriate demographic </li></ul></ul><ul><ul><li>Appropriate clinical event </li></ul></ul>
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