1. SCLEROSIS MULTIPLE Ahmed Salam Lectures Medical Student “TSU”

2. MULTIPLE SCLEROSIS G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
MULTIPLE
is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms
SCLEROSIS

3. Pathological Hallmarks:
G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
Pathological Hallmarks:
MS involves the loss of oligodendrocytes the cells responsible for creating and maintaining a fatty layer—known as the myelin sheath—which helps the neurons carry electrical signals (action potentials).This results in a thinning or complete loss of myelin and, as the disease advances, the breakdown of the axons of neurons. When the myelin is lost, a neuron can no longer effectively conduct electrical signals.A repair process, called remyelination takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell's myelin sheath.Repeated attacks lead to successively less effective remyelinations, until a scar-like plaque is built up around the damaged axons.These scars are the origin of the symptoms and during an attack magnetic resonance imaging (MRI) often shows more than ten new plaques.This could indicate that there are a number of lesions below which the brain is capable of repairing itself without producing noticeable consequences.Another process involved in the creation of lesions is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons.

4. What is Multiple Sclerosis (MS)?
G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
What is Multiple Sclerosis (MS)?
MS is a autoimmune disease where the myelin surrounding the nerve pathways, which transmit signals through the brain and spinal cord, are slowly diminishing. This is a process called demyelization. After this occurs the body produces scar tissue or plaque around these nerve pathways. Due to this, the body is unable to transmit information quickly if at all.

5. Pathophysiology: G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
Pathophysiology:
Blood-brain barrier breakdown
The BBB prevent entrance of T cells into the nervous system. The blood–brain barrier is normally not permeable to these types of cells, unless triggered by infection or a virus, which decreases the integrity of the tight junctions. When the blood–brain barrier regains its integrity, usually after infection or virus has cleared, the T cells are trapped inside the brain.
Autoimmunology
The immune system attacks the nervous system, forming plaques or lesions. Commonly involves white matter. Destroys oligodendrocytes- causing demyelination Remyelination occurs in early phase but not completely. Repeated attacks lead to fewer remyelination.
Inflammation
T-cells attacks on myelin triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Leaks form in the BBB cause swelling, activation of macrophages, and more activation of cytokines and other destructive proteins

6. Clinical course: G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
Clinical course:
Relapsing/Remitting: In this stage the pt experience acute attacks. Between these attacks the disorder is not progressing. During this time, pt may be admitted to hospital for three to five days to get intravenous corticosteroids. Some side effects may include: osteoporosis and impaired memory. The impaired memory can be reversed.
Secondary Progressive: In this stage the disorder is progressing at a variable rate. This stage normally takes many years to form; approximately years.
Primary Progressive: Progression of disease WITHOUT REMISSION. (Relates to 10% of those diagnosed with MS)
Progressive Relapsing: Progressive from the onset with clear acute relapses. (Relates to 5% of those diagnosed with MS)

7. Signs and symptoms: The most common initial symptoms
G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
Signs and symptoms:
The most common initial symptoms
changes in sensation in the arms, legs or face (33%)
Optic neuritis (20%)
weakness (13%)
double vision- internuclear opthalmoplegia (7%)
unsteadiness when walking (5%)
and balance problems (3%)

8. G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT

9. Lhermitte's sign: G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
Lhermitte's sign:
is an electrical sensation that runs down the back and into the limbs and is produced by bending the neck forwards. The sign suggests a lesion of the dorsal columns of the cervical cord or of the caudal medulla

10. Uhthoff's phenomenon: G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
Uhthoff's phenomenon:
is the worsening of neurologic symptoms in multiple sclerosis and other neurological, demyelinating conditions when the body gets overheated from hot weather, exercise, fever, or saunas and hot tubs

11. Expanded Disability Status Scale (EDSS):
G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
Expanded Disability Status Scale (EDSS):
EDSS is a method of quantifying disability in multiple sclerosis based on eight Functional Systems (FS):
Pyramidal (ability to walk)
Cerebellar (coordination)
Brain stem (speech and swallowing)
Sensory (touch and pain)
Bowel and bladder functions
Visual
Mental
Other (any other neurological findings)

12. Diagnosis is based on McDonald’s Criteria
G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
INVESTIGATION:
CSF
oligoclonal bands, abnormal colloidal gold curve, elevated γ-globulin IgG, mild mononuclear pleocytosis (<40 cells/mL), myelin debris, normal or slightly elevated protein. (Myelin basic Protein)
Blood test
B-12 and folate levels or antinuclear antibody (ANA) titers.
Antiphospholipid antibody syndrome must be undertaken in patients with evidence of blood dyscrasia and in women with unexplained miscarriages or history of deep venous thrombosis.
elevated erythrocyte sedimentation rate (ESR) and positive titers of rheumatoid factor (RF) should help identify the presence of a vasculitic disorder that may be mimicking MS.
MRI
MRI of the head and spine (more sensitive than CT): May show many plaques. MRI reveals multiple lesions with high T2 signal intensity and one large white matter lesion. These demyelinating lesions may sometimes mimic brain tumors because of the associated edema and inflammation.
Diagnosis is based on McDonald’s Criteria

13. G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
"Dawson's Fingers” is the name for the multiple sclerosis lesions around the ventricle-based brain veins of Multiple Sclerosis patients seen on MRI

14. DISEASE MODIFYING TREATMENT
G.S.M MEDICAL LECTURES/ Multiple Sclerosis
AHMED SALAM
MD STUDENT
MANAGEMENT:
Steroids: methylprednisolone (MP) 500–1,000 mg/d IV for 5 days
followed by tapered oral prednisone or MP 1 g/d IV for 3 days
± oral taper
ACUTE
ATTACK
Interferon beta-1a (Avonex, CinnoVex,ReciGen and Rebif)
Interferon beta-1b (Betaseron )
Glatiramer acetate (Copaxone), a non-steroidalimmunomodulator.
Mitoxantrone, is an immunosuppressant 
Natalizumab (Tysabri)
Fingolimod (Gilenya)
The interferons (side effects include flulike symptoms, injection-site reactions, mild liver dysfunction) and glatiramer acetate are delivered by frequent injections, varying from once-per-day for glatiramer acetate to once-per-week (but intra-muscular) for Avonex. Natalizumab and mitoxantrone are given by IV infusion at monthly intervals.
DISEASE MODIFYING TREATMENT

15. MANAGEMENT: G.S.M MEDICAL LECTURES/ Multiple Sclerosis AHMED SALAM
MD STUDENT
MANAGEMENT:
Spasticity
Baclofen 5 mg PO 1–3 t.i.d. and increase as needed Diazepam 2–5 mg PO at bedtime
Pain
NSAIDs Gabapentin effective vs. MS pain syndromes at 300 mg/d PO, may increase to 1,800 mg/d within 1 week, max dose 3,600 mg/d
Bladder dysfunction
Propantheline 7.5 mg PO q3–4h to start, increase to 15 mg t.i.d. to q.i.d. plus 15–30 mg at bedtime Oxybutynin chloride 5 mg PO t.i.d.–q.i.d. Prophylactic antibiotics for urinary infections Self-catheterizations  for inadequate bladder emptying
Constipation:
Stool softeners, bulk-producing agents, laxative suppositories
Incoordination or tremors:
Depression and emotional lability
Antidepressant agents such as SSRIs. Psychotherapy and support
Paranoia or mania
Haloperidol lithium or atypical antipsychotic
Hemifacial and dysesthesias
Carbamazepine 100–200 mg PO once or twice a day to start; increase to total daily dosage of 600–1,600 mg t.i.d.–q.i.d. Must monitor serum levels
MANAGE MS SYMPTOMS