Multiple sclerosis cases

1. Multiple sclerosis and other
demyelinating diseases of CNS
Dr.Shahnaz Shah
Dept. Of Neurology,
JPMC/JSMU
What does MS look like?
🠶 Mrs. XYZ – a 35yo, married, mother of 3 who is exhausted all the time and
can’t drive because of vision problems and numbness in her feet
🠶 Mr. ABC – a 25yo African-American man who stopped working because he
can’t control his bladder or remember what he read in the morning paper
🠶 – a 14yo Hispanic girl who falls down a lot and whose parents just told her

2. she has MS
🠶 – a 47yo single woman who moved into a nursing home because she can no
longer care for herself
19th Century Highlights
MS-related central nervous system
pathology—Jean Cruveilhier, c 1841
Jean-Martin Charcot (1825–1893)
described features of MS

3. What MS Is:
🠶 thought to be a disease of the immune system – perhaps
autoimmune.
🠶 The immune system attacks the myelin coating around the nerves
in the central nervous system (CNS – brain, spinal cord, and optic
nerves) and the nerve fibers themselves.
🠶 Its name comes from the scarring caused by inflammatory attacks
at multiple sites in the central nervous system.
What MS Is Not:
🠶 MS is not:
🠶Contagious
🠶Directly inherited

4. 🠶Always severely disabling
🠶Fatal—except in fairly rare instances 🠶
Being diagnosed with MS is not a reason to:
🠶Stop working
🠶Stop doing things that one enjoys
🠶Not have children
Who gets MS?
🠶 Usually diagnosed between 20 and 50
🠶Occasionally diagnosed in young children and older adults
🠶 More common in women than men (2-3:1)
🠶 Most common in those of Northern European ancestry

5. 🠶More common in Caucasians than Hispanics or African
Americans; rare among Asians
🠶 More common in temperate areas (further from the equator)
What Causes MS?
Genetic
Predisposition
Autoimmunity
Loss of myelin
& nerve fiber
Environmental Trigger

6. Pathogenesis of MS
🠶 Immune-mediated inflammatory disease of the CNS
🠶 Previously thought to be mainly T-cell mediated (CD-4), now known
to involve B-cells, macrophages, cytokines, etc.
🠶 May develop in genetically susceptible triggers (many thoughts:
viruses, bacteria, etc.)
🠶 Results in: demyelination, axonal loss, brain atrophy
What is the genetic factor?
• The risk of getting MS is approximately:
🠶1/750 for the general population (0.1%)
🠶1/40 for person with a close relative with MS (3%)

7. 🠶1/4 for an identical twin (25%)
🠶 20% of people with MS have a blood relative with MS
The risk is higher in any family in which there are several family
members with the disease (aka multiplex families)
What happens in MS?
“Activated” T cells...
...cross the blood-brain barrier…
…launch attack on myelin & nerve fibers...

8. …to obstruct nerve signals.
myelinated nerve fiber myelinated nerve fiber
What happens to the myelin and nerve
fibers?
What are the possible symptoms? ∙ MS
symptoms vary between individuals and are unpredictable
🠶 Fatigue (most common)
🠶 Decreased visual acuity,
diplopia
🠶 Bladder and/or bowel
dysfunction
🠶 Sexual dysfunction
🠶 Paresthesias (tingling,
(numbness, burning)
• Cognitive difficulties

9. • Pain (neurogenic)
• Heat sensitivity
• Spasticity
• Gait difficulties
• Speech/swallowing problems
• Emotional disturbances
Presenting Symptoms of MS
Symptom Approximate Prevalence Weakness in one or more limbs
40-50% Sensory loss/paresthesias 40-45% Visual loss (sec. to optic
neuritis) 16-36% sphincter dysfunction 20% Gait disturbance/ataxia
5-15% Diplopia 7-15% Dizziness/vertigo 5% Pain 3% Sensory in face
3%
Multiple sclerosis Clinical Features

10. 🠶 certain patterns of neurologic symptoms and signs are commonly observed:
🠶 Optic neuritis
🠶 Unilateral visual impairment
🠶When this occurs as the first event, only a minority (10% to 50%) go on to
develop full-blown MS
Clinical Features
Internuclear ophthalmoplegia
With a lesion of the left MLF, the left eye fails to adduct when

11. the patient looks to the right, and there is nystagmus in the
abducting eye this condition is referred to as left internuclear
ophthalmoplegia.
Internuclear Ophthalmoplegia
Defective adduction of the
ipsilateral eye
Nystagmus of the
contralateral (abducting)
eye
NORMAL CONVERGENCE
Contd….

12. 🠶Involvement of the brain stem produces cranial nerve signs and
ataxia
🠶Spinal cord lesions give rise to motor and sensory impairment of
trunk and limbs, spasticity, and difficulties with the voluntary
control of bladder function
🠶Lhermitte’s sign
Contd…
🠶 Changes in cognitive function can be present, but are often much
milder than the other findings
🠶 In any individual patient it is hard to predict when the next relapse
will occur;

13. 🠶 current treatments aim at decreasing the rate and severity of
relapses
Diagnostic work up
🠶 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

14. 🠶 Less sensitive than MRI or cerebrospinal fluid
CSF Analysis
• Most helpful for suggesting an alternative Dx
-high protein, marked pleocytosis, PMNs
🠶 Elevated IgG Index >0.7
🠶Increased CNS IgG synthesis, with normal serum IgG consistent
with MS
🠶Oligoclonal Bands
🠶Presence of ≥2 distinct bands in CSF is consistent with
MS
CSF OCB are not specific to MS!

15. 🠶 Lupus 25%
🠶 Sarcoidosis 51% 🠶 Behcet’s
dz 8%
🠶 Syphillis
🠶 CJD
🠶 Whipple’s disease 🠶 Lyme
disease
🠶 Vaculitidies
🠶 Devic’s disease
🠶 Healthy siblings of MS
patients
MRI changes in MS
MRI changes in MS
🠶 Lesions may occur anywhere in WM but are most commonly seen
in
🠶Periventricular regions

16. 🠶Cortical/juxtacortical
🠶Optic nerves
🠶Infratentorial (Brain stem, Cerebellum)
🠶Spinal cord
Wingerchuk DM, et al. Lab Invest. 2001;81:263-281.
MRI changes in MS
Differential
Diagnosis
🠶 Metabolic: SCD (B12 def),
Adrenomyeloneuropathy
🠶 Connective Tissue Diseases:
Sjogren’s, SLE
🠶 Infectious: HIV, HTLV1, Lyme
disease, Syphillis

17. 🠶 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
Treatment of acute exacerbations
🠶Treat or remove inciting stimulants (infections, stress)

18. 🠶Mild: observation, treat symptoms
🠶Moderate: oral prednisone, outpatient Physiotherapy, treat
symptoms
🠶Severe: IV Solumedrol, intensive Physiotherapy, treat
symptoms
Disease modifying drugs
🠶Monoclonal antibodies (Ocrelizumab, Natalizumab,
Alemtuzumab, Rituximab)
🠶Beta-interferon (s/c, I/M)
🠶Glatiramer acetate
Oral drugs

19. 🠶 Fingolimod
🠶 Dimethyl fumarate
🠶 Terifluonamide
Multiple Sclerosis
🠶 Symptomatic treatment: pharmacologic Rx of the symptoms- 🠶Bladder
dysfunction: oxybutynin (ditropan), propantheline, Solifenacin
🠶Constipation: psyllium hydromucilloid, bisacodyl
🠶Fatigue: amantadine, modafinil
🠶Muscle spascity: baclofen diazepam, dantrolene
🠶Tremors: propranolol, clonazepam
🠶Trigeminal neuralgia: carbamazepine, pregabalin
🠶Dysesthesia: TENS transcutaneous electrical nerve stimulation
Benefits of Therapy

20. 🠶 About 30-60% reduction in relapse
🠶 Delay disease progression
🠶 Reduction in lesions on MRI
🠶 Slow cognitive decline
🠶 No significant benefit in secondary progressive disease without
relapses
What is the prognosis?
🠶 One hallmark of MS is its unpredictability.
🠶Approximately 1/3 will have a very mild course
🠶Approximately 1/3 will have a moderate course

21. 🠶Approximately 1/3 will become more disabled
Contd….
• Certain characteristics predict a better outcome:
🠶Female
🠶Onset before age 35
🠶Sensory symptoms
🠶Monofocal rather than multifocal episodes
🠶Complete recovery following a relapse
Acute disseminated encephalomyelitis (ADEM)

22. 🠶 Mostly in children and adolescents
🠶 Presents with
🠶Altered mental status/encephalopathy (irritability to obtunded)
🠶Acute/subacute onset of focal symptoms based on lesions (maximum
neurological symptoms over 4-7 days)
🠶Typically still during febrile illness
🠶1/3 with seizures
ADEM
🠶 Workup
🠶Labs: none are diagnostic

23. 🠶CSF: pleocytosis, elevated protein, elevated IgG index; rule out
infection!
🠶Imaging: MRI brain with contrast
🠶 Treatment: IV high dose steroids > IVIg > PLEX; PT
🠶 Outcome
🠶Recovery over 4-6 weeks- 60-90% with no residual defecits
🠶Repeat MRI 6-12 months later to assess for lesion resolution
ADEM MRI findings
Neuromyelitis Optica spectrum disorder (NMOSD)
🠶 Previously known as, Devic’s Disease
🠶 Clinical syndromes

24. 1. Optic neuritis
2. Longitudinally extensive Transverse myelitis
3. Area postrema syndrome (hiccups, vomiting)
4. Brainstem syndrome
5. Diancephalic syndrome
6. Cerebral syndrome
-NMO-IgG + (aquaporin 4, found in serum and CSF)
LETM in NMOSD
Neuromyelitis Optica spectrum disorder
(NMOSD)
Treatment
🠶Acute attacks: high dose iv methylprednsolone , can be

25. combined with plasmapheresis
🠶Disease modifying drugs: Azathioprine, Mycophenolate
Mofetil, Rituximab