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DRKUPE’S  NOTE ON drkupe MULTIPLE SCLEROSIS Irfan Ziad MD UCD
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 M U L T I P L E SCLEROSIS
> Predominant age:  20-40 MULTIPLE SCLEROSIS AFFECT: 0.1% Worldwide incidence Higher incidence in  Northern European  descent and in temperate climate, but the latitude gradient is  decreasing The ratio is increasing now people in US have MS 400, 000  1–3%   risk of MS among 1st-degree relatives worse prognosis Highly variable and unpredictable
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
PRMS   Progressive Relapsing MS SPMS   Secondary Progressive MS PPMS   Primary Progressive MS  RRMS   Relapsing/ Remitting MS  CLASSIFICATION OF MULTIPLE SCLEROSIS Gradual progression of the disease from its onset with no relapses or remissions Unpredictable attacks which may or may not leave permanent deficits followed by periods of remission Initial RRMS that suddenly begins to decline without periods of remission and relapses. Steady decline since onset with super-imposed attacks.
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Lhermitte's sign   (25-40%) 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. 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.
EDSS is a method of quantifying disability in multiple sclerosis based on eight Functional Systems (FS) Expanded Disability Status Scale (EDSS) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Normal Neurological Exam 0.0 Death due to MS 10.0 1.0 4.5 5.0 9.5 Fully ambulatory Ambulation impairment A graph showing the average time a person spends in each EDSS level.
Diagnosis is based on  McDonald’s Criteria  (Revised 2010) 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 ,[object Object],[object Object],[object Object],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.
&quot;Dawson's Fingers” is the name for the multiple sclerosis lesions around the ventricle-based brain veins of Multiple Sclerosis patients seen on MRI
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 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],DISEASE MODIFYING TREATMENT
MANAGEMENT MANAGE MS SYMPTOMS 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:  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

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Multiple sclerosis

  • 1. DRKUPE’S NOTE ON drkupe MULTIPLE SCLEROSIS Irfan Ziad MD UCD
  • 2. 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 M U L T I P L E SCLEROSIS
  • 3. > Predominant age: 20-40 MULTIPLE SCLEROSIS AFFECT: 0.1% Worldwide incidence Higher incidence in Northern European descent and in temperate climate, but the latitude gradient is decreasing The ratio is increasing now people in US have MS 400, 000 1–3% risk of MS among 1st-degree relatives worse prognosis Highly variable and unpredictable
  • 4. 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
  • 5. PRMS Progressive Relapsing MS SPMS Secondary Progressive MS PPMS Primary Progressive MS RRMS Relapsing/ Remitting MS CLASSIFICATION OF MULTIPLE SCLEROSIS Gradual progression of the disease from its onset with no relapses or remissions Unpredictable attacks which may or may not leave permanent deficits followed by periods of remission Initial RRMS that suddenly begins to decline without periods of remission and relapses. Steady decline since onset with super-imposed attacks.
  • 6.
  • 7.
  • 8.
  • 9. &quot;Dawson's Fingers” is the name for the multiple sclerosis lesions around the ventricle-based brain veins of Multiple Sclerosis patients seen on MRI
  • 10.
  • 11. MANAGEMENT MANAGE MS SYMPTOMS 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: 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