Multiple+Sclerosis

• Typically a dz of young adults (20-45yrs) • Almost twice as common in women; Northern Europeans at highest risk • Immune-mediated destruction of myelin coating on axons à degeneration of nerve fibers • Demyelinated or sclerotic patches develop throughout white matter of CNS • Significant lymphocyte invasions of lesions: – CD8+T-lymphocytes and macrophages (CD4+ T-cells also in plaque infiltrate, but the other two are thought to induce oligodendrocyte injury) • Oligodendrocytes: myelin-producing cells of the CNS • Decreased conduction velocity results • Marked by exacerbations and remissions in neurological dysfunction • Commonly affects the following areas: – Optic nerve (visual field) – Corticobulbar tracts (speech & swallowing) – Corticospinal tracts (muscle strength) – Cerebellar tracts (gait & coordination) – Spinocerebellar tracts (balance) – Medial longitudinal fasciculus (conjugate gaze of EOMs) –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Posterior cell columns of the spinal cord (position & vibratory sensation) •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Clinical Features (last from weeks to days and then completely or partially resolve) –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Paresthesias (numbness, tingling, burning, pressure on face or involved extremity) –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> //Lhermitte symptom//: an electric shock produced by flexion of the neck –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Pain from spasticity •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Treated w/ stretching exercises –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Abnormal gait –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Bladder dysfunction –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Sexual dysfunction –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Vertigo –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Nystagmus –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> **Fatigue** –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Speech disturbances –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Psychological manifestations •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Represent either an emotional reaction to the dz __or__ involvement of the white matter of the cerebral cortex (more likely) •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Depression •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Euphoria •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Inattentiveness •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Apathy •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Forgetfulness •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Loss of memory •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Diagnosis –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Cerebrospinal fluid analysis •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Large percentage of pts w/ MS have elevated IgG levels •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Some have oligoclonal patterns –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> MRI •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Detects multiplicity of lesions •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Treatment –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Non-pharm •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Encourage healthy lifestyle •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> PT may help maintain muscle tone •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Every effort should be made to avoid: •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Excessive fatigue •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Physical deterioration •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Emotional stress •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Viral infections •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Extremes of environmental temperatures –<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Pharmacological •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Treat acute relapse of the dz •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> __Corticosteroids__: reduce inflammation, improve nerve conduction, have important immunologic effects •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Long term use not recommended •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Modify the course of the dz •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> __Interferon β__ (cytokine; immune enhancer) •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> __Glatiramer acetate__ (synthetic polypeptide; simulates parts of the myelin basic protein; blocks myelin-damaging T cells) •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> __Mitoxantone__ (anticancer drug) •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Interrupt the progression of the dz •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Immunosuppressants (methotrexate; cyclophosphaminde; mitoxantrone; cyclosporine •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Treat symptoms of the disorder •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> **Dantrolene (Dantrium)- (P) direct-acting skeletal muscle relaxant** •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Botulinum toxins A and B bind __directly__ to the receptors of motor nerve terminals and inhibit the release of Ach à local paralysis •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Long term use justified when reducing pain and disabling spasticity •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> __Indications__: control of clinical spasticity from upper motor neuron disorders; preoperatively to prevent or attenuate the devlopement of malignant hyperthermia in susceptible pts; IV for mgmt of fulminant malignant hyperthermia •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> __Actions__: interferes w/ the release of Ca2+ from the sarcoplasmic reticulum w/in skeletal muscles, preventing muscle contraction; doesn’t interfere w/ neuromuscular transmission •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> __PK__: •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> __Half-life__: 9h (oral); 4-8h (IV); excreted in urine •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> __Adverse effects__: drowsiness, dizziness, weakness, fatigue, diarrhea, hepatitis, myalgia, tachycardia, transient blood pressure changes, rash, urinary frequency •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Baclofen (Lioresal) for spasticity •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Diazepam (Valium) for spasticity •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Cholinergic drugs for bladder problems •<span style="font: normal normal normal 7pt/normal 'Times New Roman';"> Antidepressants for depression
 * Multiple Sclerosis**
 * **Route** || **Onset** || **Peak** || **Duration** ||
 * Oral || Slow || 4-6 h || 8-10h ||
 * IV || Rapid || 5h || 6-8h ||