MS

**MULTIPLE SCLEROSIS (most likely meaning)**

**Pathophysiology:** Autoimmune, T-cell (Th1/Th17)-mediated attack on CNS myelin, with loss of oligodendrocytes, plaque formation, and later axonal loss. Peripheral myelin (Schwann cells) is spared. Risk factors: female sex (about 2-3:1), northern latitude, low vitamin D, prior EBV infection, smoking, and HLA-DR2 (DRB1*1501).

**Clinical features:** - Optic neuritis: painful monocular vision loss and a relative afferent pupillary defect (RAPD). It is often the presenting symptom. - Internuclear ophthalmoplegia (MLF lesion): impaired adduction of the ipsilateral eye, with nystagmus of the abducting contralateral eye. Bilateral INO in a young adult is classic for MS. - Spinal cord lesions: spastic weakness, hyperreflexia, and Babinski sign. Sensory loss and bladder dysfunction can also occur. - Cerebellar signs: scanning speech, intention tremor, and ataxia (Charcot triad: scanning speech, intention tremor, nystagmus). - Lhermitte sign: electric shock down the spine with neck flexion. - Uhthoff phenomenon: symptoms worsen with heat. - Other features: fatigue, depression, and trigeminal neuralgia in a young patient.

**Subtypes:** Relapsing-remitting (about 85% at onset), secondary progressive, primary progressive, and progressive-relapsing.

**Diagnosis:** - MRI: periventricular white matter plaques (Dawson fingers, perpendicular to the ventricles), plus lesions in the corpus callosum, brainstem, cerebellum, and spinal cord. Gadolinium enhancement indicates active lesions. - CSF: oligoclonal IgG bands, elevated IgG index, and mild lymphocytic pleocytosis. Myelin basic protein may be elevated. - McDonald criteria: lesions disseminated in time and space. - Evoked potentials (for example, delayed visual evoked potentials) can be supportive.

**Management:** - Acute relapse: high-dose IV methylprednisolone. Use plasmapheresis if steroid-refractory. - Disease-modifying therapy: - Interferon-beta - Glatiramer acetate - Natalizumab (anti-α4 integrin; risk of PML with JC virus) - Ocrelizumab and rituximab (anti-CD20) - Fingolimod and siponimod (S1P modulators) - Dimethyl fumarate - Teriflunomide - Symptomatic treatment: - Baclofen or tizanidine for spasticity - Oxybutynin for bladder urgency - Amantadine or modafinil for fatigue - Dalfampridine (K+ channel blocker) for walking

**Key differentials:** - Neuromyelitis optica: anti-aquaporin-4 antibodies; optic neuritis plus longitudinally extensive transverse myelitis. - Guillain-Barré: PNS demyelination, ascending weakness, and albuminocytologic dissociation. - Acute disseminated encephalomyelitis (ADEM): monophasic, post-infectious or post-vaccine, more common in children. - PML: JC virus in immunosuppressed patients. - Central pontine myelinolysis: rapid sodium correction.

**OTHER COMMON "MS" ABBREVIATIONS:** - **Mitral stenosis:** Usually caused by rheumatic heart disease. Findings are an opening snap followed by a low-pitched diastolic rumble with presystolic accentuation, which is loudest at the apex in left lateral decubitus. Left atrial enlargement can cause atrial fibrillation, and the patient may have dysphagia or hoarseness (Ortner syndrome). Treat with diuretics, rate control, and anticoagulation if AF is present; use balloon valvuloplasty or valve replacement for severe symptomatic disease. - **Morphine sulfate:** An opioid μ-receptor agonist. Side effects include respiratory depression, miosis, constipation, and sedation. Naloxone reverses it. - **Musculoskeletal:** Used in exam documentation. - **Mental status:** As in "altered MS" or "MS exam."