TEST #3 Hon Multiple Sclerosis

Question 1

Definition of MS

Answer 1

– A disorder of the brain and spinal cord characterized by a tendency for periods of increasing and decreasing symptoms and signs (exacerbations & remissions), which RESULT FROM LOSS OF NERVE TRACT INSULATION (myelin) at multiple sites in the CNS.

Question 2

M.S. Patients can present with almost any Neurologic Symptom, however, the following as some COMMON Ones:

Answer 2

– Paresthesias
– Gait disturbance (e.g. transverse myelitis) 
– Weakness
– Visual loss (e.g. optic neuritis)
– Urinary difficulty
– Dysarthria
– Hemiparesis

Question 3

There are four types of M.S.:

Answer 3

1) RELAPSING REMITTING (45-50%)
2) SECONDARY PROGRESSIVE (20-25%) – note that these patients BEGIN their disease process in the RELAPSING REMITTING category.
3) PRIMARY PROGRESSIVE (15-20%)
4) BENIGN (10-15%)

Question 4

The following can be said about MS:

Answer 4

– M.S. is a disorder of the central nervous system.

– Most M.S. patients are diagnosed in their 20’s and 30’s.

– This disorder is generally characterized by PERIODS of EXACERBATION and REMISSION.

– NO SINGLE TEST CAN CONFIRM THE DIAGNOSIS of M.S., however multiple studies can be
used to help make the diagnosis.

Question 5

What causes MS?

Answer 5

– Essentially unknown

– Probably some GENETIC SUSCEPTIBILITY (3-5% lifetime risk of developing M.S. if you
have a first degree relative with M.S.)

– Perhaps a childhood event or illness that sensitizes the immune system to attack CNS myelin, followed by an adult event triggering the disease process – e.g. viral infection, post-partum period.

Question 6

Epidemiology of MS

Answer 6

– Affects women more than men (1.5:1), with women generally having a more
favorable course

– Onset of disease between age 15-50 (average age of onset 29) years. In general,
earlier onset is a more favorable prognostic feature.

– Geographic distribution:
a) TROPICAL ZONES: 5-10 per 100,000

b) TEMPERATE ZONES: 50 per 100,000!!!!!!!!!!!
i) Risk determined BEFORE AGE 14!!!!!!!!!!!!!!!!!!

Question 7

Studies used to make the Diagnosis of MS

Answer 7

– MRI of the head, C & T spine!!!!!!!!!
a) Typically see OVOID LESIONS of HIGH SIGNAL on T2WI in the PERIVENTRICULAR WHITE MATTER and in the spinal cord. Acute lesions may enhance.

– Multimodality evoked potentials (SSEP’s, VEP’s, BAER)

– Lumbar puncture for CSF analysis:
• **Presence of OLIGOCLONAL BANDS &/or INCREASED IgG ——-> index/synthesisratearethetypical findings in ——-> M.S. patients

Question 8

Description of MS

Answer 8

• M.S. is diagnosed by MULTIPLE LESIONS OVER SPACE AND TIME!!!!!

Question 9

Drugsusedfor“maintenance”inM.S.(todecreasethefrequencyand severity of exacerbations and slow the progression of the disease):

Answer 9

• Avonex, Rebif (Interferon Beta-1A)
• Betaseron (Interferon Beta-1B)
• Copaxone (Glatirimer Acetate)
• Tysabri (natalizumab)
• Gilenya (fingolimod)
• Aubagio (Teriflunomide)
• Tecfidera (Dimethyl fumarate)
• Lemtrada (Alemtuzumab)

*** In general, these medications are used in patients with RELAPSING FORMS of M.S. (NOT Primary Progressive)!!!!!!

Question 10

Medication used to treat an acute exacerbation in MS

Answer 10

– High dose CORTICOSTEROIDS (Solumedrol – 1 gram I.V. daily for 3-5 days followed by PREDNISONE TAPER)

– This generally REDUCES the length of the exacerbation, but is not thought to change the overall outcome of it.

Question 11

Differential Diagnosis

Answer 11

– It is nearly impossible to differentiate a first time M.S. attack from a post-infectious or post-immunization encephalomyelopathy (A.D.E.M.
– Acute Disseminated Encephalomyelitis).

– ADEM should never recur, however. If the patient develops future symptoms or new lesions on neuroimaging (MRI), M.S. is the more likely diagnosis.

– AUTOIMMUNE DISEASE – e.g. SLE with cerebritis or CNS vasculitis or
Polyarteritis Nodosa with transverse myelitis

– Devic’s disease (Neuromyelitis Optica)

– B12 deficiency

– Lymphoma or Leukemia with CNS involvement

– Spinocerebellar ataxias

– Vascular malformations – e.g. spinal cord AVM

– Infections – e.g. HIV, HTLV-1, EBV, CMV, West Nile Virus, Lyme
Disease, Syphilis

– Granulomatous Disease – e.g. Sarcoidosis

– Metachromatic leukodystrophy, adrenomyeloleukodystrophy

Question 12

MS and Medications

Answer 12

• Although immunomodulatory medications are helpful in improving the overall disease progression, there is NOTHING TO STOP THE DISEASE PROCESS.
• Much effort must be made to treat the symptoms of M.S.

Question 13

Things used for Symptom Treatment

Answer 13

• SPASTICITY:
– Baclofen (oral or intrathecal), tizanadine, diazepam, carbamazepine, BoTox
injections, dantrolene

• INTENTION TREMOR:
– Propranolol, primidone, clonazepam

• URINARY URGENCY (Spastic Bladder)
– Oxybutinin, Petrol LA

• URINARY RETNETION/ HESITANCY:
– bethanechol

• PAINFUL DYSESTHESIAS:
– Carbamazepine, oxcarbamazepine, gabapentin, phenytoin, baclofen

• FATIGUE:
– Amantadine, modafinil, armodafinil, fluoxetine, bupropion, methylphenidate, pemoline, exercise

*** Although there is no cure for M.S., most patients can be MANAGED WELL with early, aggressive intervention.

Question 14

Devices Disease

Answer 14

AKA Neuromyelitis Optica (NMO)!!!!!!!!!

• Sometimes considered a “variant” of M.S., but probably a different entity.
• Characterized by INFLAMMATION and DEMYELINATION of Optic Nerves and Spinal Cord (often long segments of spinal cord) with relative sparing of brain.
• Can use fairly sensitive and specific testing for NMO (Aquaphorin) antibodies in blood and CSF.
• Treatment is generally STEROIDS &/or plasma exchange, followed by immunosupression (e.g. azothiaprine, mycophenolate mofetil, or rituxumab).