1st interactive course in MS advanced managment

Transcription

1 6-7 December - Toronto, Canada 1st interactive course in MS advanced managment IMPROVING THE PATIENT S LIFE THROUGH MEDICAL EDUCATION

2 Liesly Lee Sunnybrook Health Sciences Centre. Department of Medicine Division of Neurology University of Toronto Toronto, Canada Receipt of grants and contracts: Novartis, Genzyme, Roche; Receipt of honoraria and consultation fee: Novartis, Genzyme, Roche; Member of a company advisory board, board of directors or other similar group: Novartis, Genzyme

3 Clinical Cases in MS mimics Liesly Lee Associate Professor of Medicine (Neurology) Sunnybrook Health Sciences Centre University of Toronto

4 Objectives Recognize red flags that suggest for mimics Identify different parameters red flags Review of cases using these red flags

5 Multiple Sclerosis Inflammatory demyelinating disease of the CNS Diagnosis is a clinical one, although ancillary testing is often used The McDonald Criteria is also used: Dissemination in space Dissemination in time

6 Polmanet al, Annals of Neurology 2011;69:

7 Realistic practical approach to diagnosis History of clinical presentation: Optic neuritis, INO Epidemiological likelihood: Caucasian, gender Neurological exam findings: Upper motor neuron findings, INO Accompanying neuroimaging results: MRI showing typical changes

8 Different approaches to MS mimics By virtue of atypical clinical presentations: Optic neuropathy Myelopathy By virtue of atypical neuroimaging: White vs gray matter involvement lesion characteristics in terms of location, appearance By virtue of accompanying laboratory results: Abnormal inflammatory/infectious indices

9 Katz Sand et al; AAN Continuum 2013; 19(4)

10 Katz Sand et al; AAN Continuum 2013; 19(4)

11 Katz Sand et al; AAN Continuum 2013; 19(4)

12 Katz Sand et al; AAN Continuum 2013; 19(4)

13 Katz Sand et al; AAN Continuum 2013; 19(4)

14 Clinical Case # 1 Young male (now 41yo), previously well admitted for ACL repair, course complicated with superimposed infection post-op; became acutely confused and unstable gait; MRI Brain at that time consistent with ADEM -Treated with IV Steroids Recurrence of symptoms again in 1996 (with accompanying right hemiparesis) readmitted to hospital; MRI Brain similar lesions and treated with steroids again; CSF exam positive for oligoclonal banding Jan 1997 recurrence; no treatment June 1997 recurrence again mainly slurred speech; treated with Methyl-prednisolone Residual deficits in 1997 on assessment mildly slurred speech and occasional word finding difficulties

15 Clinical Case # Completed college noted difficulties completing tasks worked in different jobs unable to maintain them however 2009 in church at carol singing difficulty speaking and numbness of his left upper extremity lasting 45 minutes July 2010 I took over his care for presumed MS and first examined him identified cognitive issues -MMSE 20/30; slurred speech; cerebellar findings but could walk

16 Clinical Case # 1 Family History has a paternal first cousin with an undiagnosed condition wheelchair bound with cognitive impairment and muscle weakness Cognitive domains compromised particularly executive function and memory But based on previous history of events, progression and imaging thought to have Cortical Variant of MS In addition to this the patient noted 2-3 migraines per week MRI Brain 2010 performed

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19 Clinical Case # developed right foot weakness course of steroids given the right foot weakness resolved. In view of events, glatiramer acetate started. But then repeat MRI revealed:

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21 Clinical Case # 1 Evoked potentials were normal CSF oligoclonalbanding pattern noted again

22 Given atypical presentation Migraines Cognitive Impairment Imaging Clinical Case # 1 Any thoughts on diagnosis? Any further tests?

23 Clinical Case # 1 Positive NOTCH 3 mutation Diagnosis: CADASIL (Cerebral Autosomal Dominant Arteriopathywith Subcortical Infarct and Leukoencephalopathy) Change in management: Secondary Stroke Prevention Symptomatic management of migraines Genetic counselling Glatiramer Acetate stopped

24 RED FLAGS: Atypical presentation for multiple sclerosis Involvement of bilateral temporal lobes on imaging Questionable lacunar infarcts in deep white matter not particularly a common location for MS Migraines Family History

25 Recurrent bouts of neurological dysfunction Presence of oligoclonal banding Family hx But Bilateral temporal lobe involvement was more specific External capsules would be involved earlier in the disease course

26 Charilet al, Lancet Neurol2006; 5:

27 Clinical Case 2 63 year old asianman Onset history is poorly documented as he was seen at more than one hospital Late August 2010 Loss of vision in left eye diagnosed as L CRAO September 2010 frontal headache, unsteady gait, nausea, vertigo.. MRI Brain with vascular imaging was unremarkable diagnosed as posterior circulation ischemia November 2010 admitted with back pain radiating into his legs, urinary retention, fecal incontinence and saddle anesthesia; on exam had decreased acuity in his left eye, left gaze evoked nystagmus, abnormal eye movements, ataxic gait, lower extremity weakness and saddle anesthesia with decreased rectal tone

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31 Other investigations: Clinical Case 2 CSF testing: normal cell counts, positive oligoclonal banding CT Chest and Abdomen: no malignancy NMO antibody: negative Treated with trial of pulse steroids Improved clinically and discharged to rehabilitation

32 Clinical Case #2 Feb 2011 seen in follow up; continued to have gaze evoked nystagmus with plantar flexion weakness (4+/5) and impaired vibration in the toes April 2011 MRI brain and spine repeated improving signal changes; evoked potentials showed impaired left visual function but otherwise normal DDX: Opticospinalvariant of MS vs ADEM In the meantime, was started on Glatiramer Acetate

33 Clinical Case #2 From 2011 to 2012.worsening leg spasms helped with baclofen Repeat imaging in stable Then on October 2012 had been stable with no recurrences; new history yielded an episode of intractable hiccups and nausea/vomiting in 2008 and again in 2010 NMO antibody repeated POSITIVE (new testing parameters)

34 RED FLAGS: The diagnosis of NMO vsopticospinalvariant of MS controversial if these are separate entities versus if they fall within the same spectrum In addition, in this case the initial testing for NMO was negative New laboratory parameters were able to identify the seropositivity However, given the history of intractable nausea, area postremahad to be noted as a target for NMO Importance: it possibly changes the course of management

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36 Clinical Case #3 50 yowoman presented with chronic history of bilateral leg weakness ( foot slapping as she walks) comes and goes, last episode in early 2010 (weaker right foot) Remote bouts of dizzy with abnormal eye movements that resolved Hx of asthma, irritable bowel syndrome, hypertension Symptoms fully resolved in late 2010

37 Sep 2010 dysconjugateeye movements at times; extensor plantars; impaired vibration in feet Evoked potentials bilateral slowing of both optic nerves MRI:

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40 Late 2010 Discussion of disease modifying therapy held was deferred December, Bouts of syncope with diaphoresis Cardiology work up started -large mobile mass on the aortic valve

41 Late 2010 February 2011 right hand paraesthesia, speech slurring and decreased grip strength Repeat MRI revealed increased white matter lesions with some diffusion weighed changes more in keeping with infarcts

42 Laboratory workup ANA positive (1/640) Elevated PTT Significant livedo reticularis was seen Any thoughts?

43 Outcome Positive anti-phospholipid antibody -Diagnosis of Antiphospholipid antibody syndrome Started on anti-coagulation Subsequently diagnosed as SLE started on Hydroxychloroquine Cardiac mass resolved; clinically stable

44 Katz Sand et al; AAN Continuum 2013; 19(4)

45 Take-home message Take into consideration of typical clinical presentations Look at the imaging findings Guided by the history, exam findings, radiology, pursue other laboratory investigations to avoid misdiagnosis

46 References: Polmanet al, Diagnostic Criteria for Multiple Sclerosis: 2010 Revisions to the McDonald Criteria; Annals of Neurology 2011;69: Scottiet al; Diagnosis and differential diagnosis of acute transverse myelopathy. The role of neuroradiological investigations and review of the literature; Neurol Sci(2001) 22:S69 S73 Charilet al,mri and the diagnosis of multiple sclerosis: expanding the concept of no better explanation ; Lancet Neurology 2006; 5: Katz Sand et al; Diagnosis and the differential diagnosis of Multiple Sclerosis; AAN Continuum 2013; 19(4) Miller et al, Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis; Lancet Neurology 2005; 4: O Riordan et al, CADASIL imitating multiple sclerosis: the importance of MRI markers; Multiple Sclerosis 2002; 8: 430 ± 432 Apiwattanakulet al, Vomiting as the Initial Presentation of NMO; ANN NEUROL 2010;68: