Case A 32 year old woman comes with complaint of numbness and tingling sensation in her right hand. Her symptoms began several days ago and have progressively worsened over the last several hours. When asked, she states that 3 years ago she had an episode of “seeing double” that lasted for 2 days and resolved on its own. Physical examination is significant for hyperreactive reflexes bilaterally in her lower extremities. Increased spasticity is also noted in her lower extremities. What is the Most Likely diagnosis? 10/13/2015Dr. Alka Stoelinga1

MULTIPLE SCLEROSIS 10/13/20152Dr. Alka Stoelinga

MULTIPLE SCLEROSIS Multiple sclerosis is an inflammatory disease of CNS white matter characterized by relapsing or progressive course Multiple sclerosis is a common disease of unknown cause in which there are multiple areas of Demyelination within brain and the spinal cord.  Peak incidence: years Male: Female = 1:2 10/13/20153Dr. Alka Stoelinga

Etiology: Multifactorial causation : – Genetic, environmental (Infectious, dietary, climatic), immunologic MS lesions most commonly involve white matter areas close to the ventricles of the cerebellum, brain stem, basal ganglia, spinal cord; and the optic nerve. Immune mechanism against CNS myelin sheath is suggested due to presence of increased levels of activated T-Lymphocytes in the CSF, and increased immunoglobulin synthesis within the CNS 10/13/2015Dr. Alka Stoelinga4

Pathology – Activation of lymphocytes in response to myelin proteins (auto antigen). – Destruction of the myelin. – Initiation of inflammation and infiltration of the macrophage and lymphocytes – Later on healing by gliosis, loss of neuronal function – Initially inflammation leads to transient loss of function but later permanent deficit occur due to disruption of axonal integrity – Demyelination may impair nerve conduction that lowers the efficiency of CNS function – It also causes ectopic impulse generation that causes Paresthesia. 10/13/20155Dr. Alka Stoelinga

Nerve 10/13/20156Dr. Alka Stoelinga

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Clinical features Presentation- – Weakness, numbness, tingling or unsteadiness of a limb. – Urinary urgency or retention – Blurry vision – Double vision 1.Relapsing and remitting MS:80% of patients have a relapsing and remitting course of neurological deficit 1.Characterized by recurrent attacks of neurologic dysfunction. The attacks generally evolve over days to weeks and may be followed by complete, partial or no recovery. Recovery occurs usually spontaneously within weeks to several months 2. 20% follow a slowly progressive :  Secondary progressive MS  The disease has relapsing-remitting course at first but evolves to be progressive and this phase may begin shortly after disease onset or delayed for several months or years.  Primary progressive MS  Characterized by gradual progression of disability from the onset of disease 3. And minority have fatal disease causing early death Peak age of onset is in the fourth decade Frequent relapse and incomplete recovery indicate poor prognosis. Physical signs observed in multiple sclerosis depend on the anatomical site of Demyelination 10/13/20158Dr. Alka Stoelinga

Scenario Young patient (Usually <55years) H/O multiple neurological complaints that cannot be explained by presence of one CNS lesion 10/13/2015Dr. Alka Stoelinga9

Initial presenting features of Multiple sclerosis: Blurring of vision due to optic neuritis Diplopia Weakness in one or more limbs Paresthesia Ataxia Urinary symptoms 10/13/201510Dr. Alka Stoelinga

End stage multiple sclerosis: Patient is severely disabled with spastic paraparesis, ataxia, optic atrophy, nystagmus, pseudobulbar palsy, incontinence of urine, dementia Death occurs usually due to bronchopneumonia and renal failure. 10/13/201511Dr. Alka Stoelinga

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MRIMRI scans (post-contrast) of the same brain slice at monthly intervals. Bright spots indicate active lesions. 10/13/201516Dr. Alka Stoelinga

Investigations Clinical picture Identify multiple sites of neurological involvement i.e., plaques of Demyelination by imaging: MRI and Myelography Provide evidence for an inflammatory disorder: CSF examination(cell count and protein electrophoresis) Demonstrate other sites of involvement by: Visual and other evoked potentials Exclude other conditions: CXR, Serum ACE and serum B12 antibodies 10/13/201517Dr. Alka Stoelinga

Differential diagnosis: 1.SLE 2.Stroke 3.Friedreich’s ataxia 4.CNS sarcoidosis 5.Bechcet’s syndrome 6.Sjogren’s syndrome 10/13/201518Dr. Alka Stoelinga

Treatment Acute relapse – High-dose intravenous steroids (Methylprednisolone 1 g daily for 3 days followed by tapering dosage of oral Prednisolone for next 4 weeks) Preventing relapses – Immunosuppressive agents including Azathioprine have a marginal effect in reducing relapses and improving long-term outcome – Interferon Beta-1A – Interferon Beta 1B reduces the number of relapses – Glatiramer acetate(Immune modulator) 10/13/201519Dr. Alka Stoelinga

Treatment of complications  Spasticity: Regular Physiotherapy Baclofen (most effective)  Painful Paresthesia: Carbamazepine Amitriptyline  Ataxia: Isoniazid and clonazepam  Care of bowel and bladder 10/13/201520Dr. Alka Stoelinga

Treatment MS and fatigue  Amantidine MS with Urinary incontinence  Oxybutanine MS and urinary retention  Bethanicol 10/13/2015Dr. Alka Stoelinga21

Prognosis About 15% of those having one attack of Demyelination do not suffer any more events Approximately 5% of patients die within 5 years of onset After 10 years, about one-third of patients are disabled to the point of needing help with walking 10/13/201522Dr. Alka Stoelinga

Cavernous sinus thrombosis Cavernous sinus thrombosis (CST) is the formation of a blood clot within the cavernous sinus, a cavity at the base of the brain which drains deoxygenated blood from the brain back to the heart. The cause is usually from a spreading infection in the sinuses, ears, or teeth. Staphylococcus aureus and Streptococcus are often the associated bacteria. Cavernous sinus thrombosis causes decrease or loss of vision drooping or bulging eyes Headaches paralysis of the cranial nerves which courses/runs through the cavernous sinus. This infection is life-threatening and requires immediate treatment, which usually includes antibiotics and sometimes surgical drainage. 10/13/201523Dr. Alka Stoelinga

Cavernous sinus thrombosis 10/13/201524Dr. Alka Stoelinga

WERNICKE-KORSAKOFF DISEASE Due to a deficiency of thiamine Causes are: 1. Malnutrition 2.Alcoholism 3. Malabsorption 4.Protracted vomiting. There is failure of carbohydrate metabolism (because thiamin is a co- factor in many enzymes of the citric acid cycle) and accumulation of glutamate. Clinical triad is that of Ophthalmoplegia, ataxia, and global confusion Patients are profoundly disoriented, If the disease is not treated  stupor, coma, and death may ensue. 10/13/201525Dr. Alka Stoelinga

Approximately half recover incompletely, ataxia is very slow to recover or may not recover. Later on Korsakoff’s psychosis may occur (characterized by loss of recent memory, confabulation, impaired temporal sequencing of events) Treatment – Administer to all chronic alcoholic patients especially before giving intravenous glucose for suspected hypoglycemia. – Intravenous or intramuscular thiamin 50 mg TDS – Later on switched over oral therapy 100 mg TDS 10/13/201526Dr. Alka Stoelinga

Qs 1.Difference between UMNL and LMNL 2.Causes of spinal cord injury and its C/F 3.Clinical features and causes of spinal cord compression 4.Management of Spinal cord compression 5.Short notes on 1.Cervical Spondylosis 2.Brown sequard syndrome 3.Syringomyelia 10/13/2015Dr. Alka Stoelinga27