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Multiple Sclerosis

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Abdullah Albishri

on 20 October 2015

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Transcript of Multiple Sclerosis

CASE 2
CASE 1

Thank You

Questions?

Take Home

Exacerbations do not necessarily require treatment with corticosteroids

There is NO role for low dose corticosteroids in the treatment of MS relapses

Treatment of symptoms will improve quality of life

Treating PPMS

PROMiSe trial post-hoc analysis Glatiramer Acetate slowed progression of disease in men with earlier disease

IVIG
Delayed progression by 12 wks vs PCB (Pohlau, 2007)
Results need to be confirmed

Consider challenge with steroids or IIS if relatively rapid decline in ADLs

CASE 4
Pulsed IVMP

May attempt to “stabilize” disease course

1gram IVMP q15-30 days x 3-6 months

CRITICAL to have close follow-up and document objective changes on exam


GOOD IIS CANIDATE

Active progression over past several months or frequent severe relapses
Age < 40
Ambulatory
Earlier disease course (RRMS or early SPMS)
Incomplete recovery from relapses
Frequent relapses leading to disability
Persistence of multiple Gd+ MRI lesions

CASE 3
TREATMENT OF RELAPSE

For patients with acute, severe neurologic deficits caused by multiple sclerosis who have a poor response to treatment with high-dose glucocorticoids, we suggest treatment with plasma exchange (Grade 2B).

Diagnostic Criteria

Dawson criteria: 1916
Schumacher criteria: 1965
Poser criteria: 1983
McDonald criteria: 2001
Revised McDonald criteria: 2005
Revised McDonald criteria: 2010

All criteria require dissemination in time and space

MS Diagnosis

“Dissemination in space and time”
Objectives

1. Learn to diagnosis MS

2. Learn to assess the risk of developing MS after a Clinically Isolated Syndrome

3. Become more familiar with MS therapeutics and treatment algorithms

Take Home

There is no specific diagnostic test (imaging, blood, CSF) for MS

There is a differential diagnosis for white matter lesions on MRI

Neurological symptoms in MS patients are not always related to MS activity

MS patients can develop other diseases that may impact their MS symptoms

Pregnancy

Seems to protect from relapses (2nd & 3rd trimester); likely related to hormone levels
Fertility treatments may increase risk of relapse

Increased relapse rate during 1st trimester post-partum

First-line injectable DMTs (GA, IFN-β) considered safe in breast-feeding



Treating SPMS

No treatment has been shown to be helpful UNLESS the patient still has superimposed relapses

SPMS

CASE 4

45yo RH M with 13yr history of MS
DMT with Glatiramer Acetate
Last MS relapse 7 years ago
Ambulation:
Cane 4 years ago
Walker 3 years ago
Wheelchair 1 year ago

MITOXANTRONE

Chemotherapy drug used to treat a variety of cancers since 1987

FDA approved for progressive forms of MS or worsening RRMS

12 mg/m2 q 3 months, many other regimens

POOR IIS CANIDATE
Age > 50
Long-standing, stable disability
-Predominantly motor or cerebellar deficits
-Non-ambulatory status
Significant spinal cord atrophy
Significant other medical problems
Rationale for Intense Immunosuppression (IIS) in Rapidly Worsening MS

Inflammatory damage occurs during early RRMS

Permanent tissue damaged from recurrent bouts of inflammation, even during the silent periods of so-called remission

Accumulated disability is at least in part secondary to early active inflammatory disease

We can treat inflammation

During later disease stages, there
is no / less inflammation and our
treatments are not effective

TREATMENT OF RELAPSE:
For patients with an acute multiple sclerosis (MS) exacerbation that results in neurologic symptoms and increased disability or impairments in vision, strength, or cerebellar function, we recommend treatment with glucocorticoids (Grade 1B).


Our preferred regimen is IV methylprednisolone 1000 mg daily for five days without an oral taper. However, the data suggest that oral regimens are just as effective.



HOW TO IDENTIFY A RELAPSE?
CRITICAL, compare with previous examinations (history and examination), when ever possible

Relapses can be precipitated by infections and fever
Check U/A for occult UTI

ACUTE MS RELAPSE

CASE 2

IO & FE 4/5 on left hand
Hyper reflexia of left arm
Ataxic FFM & dysmetric FNF on left
Decreased LT on left face, arm, leg



CASE 2

26yo F with RRMS diagnosed 2yrs ago,
3 day history of difficulty writing, clumsy and numb left hand

No signs/symptoms of infection
No prior history of similar symptoms

Humanized monoclonal Antibody against alpha4 beta1 integrin
Selective adhesion-molecule inhibitor (SAM)
Prevents transendothelial migration of activated leukocytes from small venules into CNS
Natalizumab

Differential Diagnosis

Metabolic: SCD (B12 def), Adrenomyeloneuropathy

Connective Tissue Diseases: Sjogren’s, SLE

Infectious: HIV, HTLV1, Lyme disease, Syphillis

Structural: Chiari malformation, spinal cord compression

Genetic: ataxias, paraplegias, mitochondrial

Neoplastic: CNS lyphoma, paraneoplastic

“MS variants”: ON, TM, ADEM, NMO

Other: Neurosarcoidosis, CNS vasculitis

Psychiatric

History & Physical Exam
Brain and Spinal Cord MRI
Labs: rule out mimics of MS
Connective tissue diseases, infections, metabolic disorders

Cerebrospinal Fluid (when clinical and MRI evidence inconclusive)

Evoked Potentials:
Identify damage to visual, auditory, & touch perception systems
Less sensitive than MRI or cerebrospinal fluid

DIAGNOSTIC WORK UP

Diagnosis of MS requires elimination of more likely diagnoses and demonstration of dissemination of lesions in space (DIS) and time (DIT)
CASE 1

Does she have MS?
How do we diagnose MS?

Left intranuclear ophthalmoplegia

Hyper-reflexia of the bilateral legs

Bilateral upgoing toes (+ babinski)

Absent vibration, poor proprioception in feet

Mildly dysmetric finger-nose-finger and ataxic fine finger movements R>L

+ Romberg and Ataxic gait

CASE 1 EXAM

1year ago, 3 week history of urinary urgency & frequency, one episode of fecal incontinence and bilateral foot numbness with frequent tripping

6 months ago, 2 week history of clumsy gait and poor balance, tremors of the right hand

1 month history of blurry vision with right gaze only

CASE 1 30yo Science teacher

MS Signs and Symptoms

Fatigue
Heat intolerance
Visual symptoms (e.g. visual loss, Internuclear ophthalmoplegia,)
Numbness, tingling, loss of sensation
Weakness, Incoordination
Imbalance, Vertigo, Nystagmus
Urinary and sexual dysfunction
Cognitive deficits
Lhermitte phenomenon
Depression
Epilepsy
Questions:

1. When faced with a clinically isolated syndrome, which tests can help delineate the risk to develop MS? 

2. True or False: Starting MS therapies early improves long term outcome.

3. True or False: MS patients have high risk pregnancies.

Treatment: Intense Immunosuppression

Rapidly Worsening MS

Documented worsening corresponding to >3 point EDSS increase in previous 12 months despite at least 6 months of IMT and at least 2 courses of IVMP

Rapidly Worsening MS

CASE 3

27yo F diagnosed with RRMS 5 years ago
DMT with Rebif since diagnosis

Suffered 3 MS relapses in past 15 months
each treated with Methylprednisolone
Incomplete recovery of cerebellar and pyramidal function

EDSS 1 year ago was 2.5, now 5.5

Interferons
Flu-like symptoms
Liver dysfunction
Bone marrow
Endocrine abnormalities
Other:
Depression
Spasticity
Headaches

Glatiramer Acetate
Injection Site Reactions
Idiopathic Injection Reactions


DMT Side Effects



Peak age 15 to 45
Women : Men 2.5 : 1
Geographic variation

USA prevalence 0.1%
Approx ½ million MS patients in USA

Life expectancy essentially normal

Epidemiology

An chronic inflammatory demyelinating disorder of the CNS of uncertain etiology, likely autoimmune, associated with destruction of myelin sheaths and axons

What Is MS?

Abdullah Al-Bishri

What Residents Should Know

Multiple Sclerosis

EDSS=0 last 3 visits
CASE 2

Expanded Disability Status Scale
NEWLY DIAGNOSED RRMS

> 2 historical events with objective findings on examination

MRI consistent with MS

Normal “rule out labs”

CXR normal

CASE 1

Syphillis
CJD
Whipple’s disease
Lyme disease
Vaculitidies
Devic’s disease
Healthy siblings of MS patients

Lupus 25%
Sarcoidosis 51%
Behcet’s dz 8%


CSF OCB are not specific to MS!

• Most helpful for suggesting an alternative Dx
-high protein, marked pleocytosis, PMNs
Oligoclonal Bands
Presence of 2 or more distinct bands in CSF is consistent with MS
CSF Analysis
Current EDSS=3
CASE 2
Expanded Disability Status Scale

November

August

1. Dissemination in space: Objective evidence of neurological deficits localized to two separate parts of the CNS

2. Dissemination in Time:
Onset of neurological deficits separated by at least one month

3. Rule out other explanations!

Summarized Diagnostic Criteria

MRI - Dissemination in Space

3 of the following:
9 T2 or 1 Gd+
3 Periventricular
1 Infratentorial
1 Juxtacortical lesion



Natural History of Multiple Sclerosis

T2

Gd

> 3 months

Gd

> 1 month

> 1 month

CIS

MRI - Dissemination in Time

T2

Natural History of RRMS and PPMS

2010 Revised McDonald
MS Diagnostic Criteria
CYCLOPHOSPHAMIDE
Chemotherapy agent

Also used in other autoimmune disease

Monthly IV infusion
Full transcript