"Multiple Sclerosis" PDF

Multiple Sclerosis Epidemiology Pathology-Plaques - Onset: - Development of focal, often perivenular, scattered ➔ Females aged 20 to 35 years....

Multiple Sclerosis Epidemiology Pathology-Plaques - Onset: - Development of focal, often perivenular, scattered ➔ Females aged 20 to 35 years. areas of demyelination. ➔ Males aged 35 to 45 years. - Together with reactive gliosis, axonal damage, and - Female: male ratio is 2:1. neuronal degeneration. - MC in Caucasians. - These lesions occur in: - First-degree relatives: 10-20X. ➔ Both white and gray matter of the brain and spinal cord. ➔ The optic (II) nerve. Etiology Presentation - Unknown. - Genetic factors: Paresthesia is the MC symptom. ➔ HLA alleles, IL2RA and IL7RA. Bilateral hand numbness is least ➔ Unlike other diseases, no Mendelian inheritance so far. likely symptom. - Environmental factors: viruses, geography, diet, smoking. If you have a young patient and you can't localize the lesion to ➔ Prevalence of the disease rises with increasing distance one site, then think of MS from the equator. ➔ Residence: 1st 15 years of life determines risk. - Both T lymphocytes and B lymphocytes, as well as innate immune mechanisms, participate in MS pathogenesis. UMNL: hyperreflexia, spasticity, +ve babiniski, absent - No single autoantigen, autoantibody, or infectious abdominal reflexes (MC). agent has thus far been unequivocally associated with MS. Cerebellum: lower extremity - More than 200 genetic variants have been discovered ataxia, impaired rapid to be associated with modifying the risk of MS. alternating movement (dysdiadochokinesia), nystagmus (also brainstem), intentional tremor, dysmetria. Nerve demyelination: impaired vibratory/joint position sense  Multiple Sclerosis Physical Examination Course - S&S typically develop over hours to days. - Relapsing-remitting: - S&S highly variable based on the lesions. ➔ MC form; affects about 85% of patients. ➔ Characterized by relapses lasting from days to weeks, - Optic neuritis: followed by complete or partial remission over ➔ ↓ visual acuity. months or years. ➔ Central scotoma. ➔ No progression (stable) between attacks= attacks + recovery. ➔ Red desaturation. ➔ Marcus-Gunn pupil: AKA relative afferent pupillary - Secondary progressive: defect (RAPD), paradoxical dilatation. ➔ Approximately 75% of RRMS cases will transition to SPMS within 15 years of the initial diagnosis. - Depression: ➔ Symptoms often worsen gradually following initial ➔ Either from the disease itself or from medications. relapse or have no acute exacerbations. ➔ Should be treated because it causes more relapses. ➔ No clear ability to know the transition point from RRMS to SPMS. ➔ Progression independent of relapse (can decline without relapse). - Uthoff's phenomenon (heat sensitivity): ➔ Gradually progressive course after being R-R= attacks + decline. ➔ Happens when taking a hot shower or sauna. ➔ Try to treat it in early phases. ➔ Core body temperature should increase. ➔ Causing worsening and recurrence of symptoms. - Primary progressive: ➔ Usually spasticity. - Lhermitte's sign: ➔ Late diagnosis. ➔ Electric shock like condition with sudden ➔ Characterized by progressive accumulation of disability flexion of the neck. after initial relapsing course of the disease. ➔ Not specific for MS. ➔ Steady, functional worsening from the onset of the ➔ Caused by spinal pathologies: abscess, tumor, disease with no relapses or remissions. spondylosis. ➔ Gradual progression from onset= decline only. ➔ Affects approximately 10% of patients with MS. - Fatigue, euphoria. ➔ More resistant to drug therapy. - Trigeminal neuralgia. - Uninhibited neurogenic bladder: frequent urination - Progressive-relapsing: progression from onset with clear relapses. - Flaccid neurogenic bladder: urinary retention. - Rubral tremor (Severe Holmes tremor).  Multiple Sclerosis Note: what really helps us is knowing if it’s active or not because  Clinical: drugs work on active lesions. ▪ Objective evidence means radiological findings go New lesions. with clinical ones→ the most helpful for diagnosis New attacks. Enhancing lesions on MRI. and can be diagnosed with only one attack. Enlarging lesions on MRI.  Paraclinical: Diagnosis ▪ CSF electrophoresis: ❖ Not mandatory for diagnosis. - Schumacher Criteria: ❖ Predicts future relapses. ➔ The identification of a syndrome “typical” of MS- ❖ Opening pressure is normal. related demyelination. ❖ WBC usually 50 to 100 rare. ❖ Protein mildly elevated at 50 to 60, >100 rare. ❖ Myelin basic protein is high for first 2 weeks of exacerbation. ❖ Oligoclonal bands: Predicts future relapses. More than 2 bands. Optic neuritis: acute, unilateral, improves (if bilateral or Means dissemination in time. doesn’t improve→ not MS) ❖ IgG index: (CSF IgG/serum IgG)/(CSF albumin/serum albumin) Transverse myelitis: should be partial TM. >0.7 in 90% of MS cases. Brainstem syndromes: internuclear ophthalmoplegia. Cerebellar syndrome: intentional tremor. ▪ Evoked potential: ❖ Visual evoked potentials. ➔ Objective evidence of CNS involvement: ❖ Somatosensory evoked potentials.  Radiological (MRI): ❖ Brain stem auditory evoked potentials. ▪ Not mandatory for diagnosis. ▪ T2, FLAIR high sensitivity. ➔ Demonstration of dissemination in space and time: ▪ Multiple periventricular white matter lesions. ▪ Ovoid-shaped lesions that are > 3 mm (Dawson's Dissemination Radiological: in time Presence of enhancing and non-enhancing lesions fingers). Appearance of a new lesion a follow-up MRI ▪ Corpus callosum thinning or scalloping. Clinical: ▪ Atrophy in chronic disease. A second clinical attack ▪ Enhancement with active lesions. Dissemination Radiological: in space At least one lesion in two of four areas: periventricular, juxtacortical, infrenatorial, spinal cord Clinical: A further attack in a different area of the brain.  Multiple Sclerosis - In general patients with mild disease (EDSS score 0-3) 5 years after diagnosis only uncommonly progress to severe disease. - EDSS score 6: 10, 15 years: 7.5%, 11.5% of patients respectively. - Most important factor that determines prognosis: ➔ Duration of recovery and if she recovered completely or not. ➔ MRI load (number of lesions on MRI). Differential Diagnosis Periventricular: should be in contact with ventricles NOT beside them. Spinal: lesion facing not more than 3 vertebrae. - Acute disseminated encephalomyelitis (ADEM). ➔ In pediatrics, febrile illness. ➔ No better explanation other than MS. ➔ Monophasic illness (not lifelong). ➔ Steroids are enough. - McDonald Criteria 2017 for PPMS: - NMOSD. ➔ Severe optic neuritis with severe transverse myelitis. ➔ MS drugs make it worse. ➔ Long spinal lesion > 3 vertebrae. - Longitudinal extensive spinal cord lesion. Prognosis - Optic neuritis. - B12 def. Favorable Unfavorable Early age of onset Later age of onset - Rh A., SLE, Sjögren’s dis. Female sex Male sex. - HIV, HTLV-1. Optic neuritis as presenting Presentation other than optic - Sarcoidosis. episode neuritis - Tumors. Sensory symptoms as presenting Involvement of cerebellar and/or episode motor functions. Acute onset of symptoms Progressive course from onset. Treatment Excellent recovery from attacks Poor recovery from exacerbations. - Acute: IV methylprednisolone, plasma exchange. Long inter-exacerbation period Frequent exacerbations. Minimal dysfunction at 5 yrs= min. Spinal cord lesions. dysf. At 15 (most important one)  Multiple Sclerosis - Steroids: Internuclear Ophthalmoplegia ➔ "Slam and Taper". - Highly suggestive of a lesion affecting the medial longitudinal ➔ High-dose steroids followed by slow taper. ➔ Reduces duration and severity of exacerbations. fasciculus within the brainstem, which is involved in conjugate gaze. - MC causes: stroke in elderly, MS in young patients. ➔ Does not change the outcome or frequency. - Inability to adduct one eye, with nystagmus in the other eye. ➔ Methylprednisolone 1000 mg qd for 5d. - Rt MLF lesion: ➔ Monitor for S/E: sugar, infection, ulcer. ➔ Right eye: cannot adduct (medial rectus muscle). ➔ Left eye: nystagmus (lateral rectus muscle). - Symptomatic: ➔ Fatigue: amantadine, pemoline. ➔ Spasticity: baclofen, benzodiazepines, dantrolene, botulinum toxin injection. ) ‫ِيرا‬ ً ‫صغ‬َ ‫ارح َْم ُه َما َك َما َربَّيَانِي‬ ْ ‫ب‬ ِِّ ‫( َوقُ ْل َر‬ ➔ Depression: TCA, SSRIs. ➔ Uninhibited neurogenic bladder: anticholinergics. - Immune modulation. - Relapse prevention: ➔ Interferons are relatively safe during pregnancy. ➔ Oral fingolimod. ➔ IV high disease activity drugs (monoclonal Abs): natalizumab, rituximab, ocrelizumab, alemtuzumab. ➔ Natalizumab can cause PML (reactivation of JC virus).