Multiple Sclerosis Lecture Notes PDF

Multiple sclerosis ❑ Multiple sclerosis (MS) is an inflammatory, autoimmune disorder with areas of CNS demyelination and axonal transection and variable symptoms and presentation. ❑ Multiple describes the number of CNS lesions, and sclerosis refers to the demyelinated lesions, today called...

Multiple sclerosis ❑ Multiple sclerosis (MS) is an inflammatory, autoimmune disorder with areas of CNS demyelination and axonal transection and variable symptoms and presentation. ❑ Multiple describes the number of CNS lesions, and sclerosis refers to the demyelinated lesions, today called plaques. ❑ Although MS was first described almost 140 years ago, the cause remains a mystery, and a cure is still unavailable. Epidemiology and etiology ❑ Approximately 2.3 million people worldwide have MS. ❑ Diagnosis usually occurs between 20 and 50 years; peak incidence occurs in the fourth decade, rarely seen in pediatrics. ❑ Women are affected about 3 times more often than men Etiology and Risk Factors for Multiple Sclerosis (MS) 1. Genetic Factors Family history of MS or other autoimmune diseases. Family history of migraines. 2. Personal Health History Personal history of autoimmune diseases. Personal history of migraines. 3. Environmental Factors Vitamin D deficiency. Geographic location (farther from the equator). Viral infections (e.g., Epstein-Barr Virus which mimics myelin sheath antigens). 4. Lifestyle Factors Obesity (especially in adolescence). Poor diet (low in omega-3, high in saturated fats). Cigarette smoke exposure (increases the risk of MS and worsens disability progression).  Epidemiology and etiology Inheritance Theory ❑ Genetics cannot fully explain the etiology of MS because only The exact a small proportion of patients report a family member with cause is MS; however, genetic risks may explain up to 35% of cases. unknown  Epidemiology and etiology Environment theory ❑ Epstein-Barr virus, CMV and Human Herpesvirus (HHV)-6, are thought to be a possible infectious etiologic agent. ❑ Antibody titers to Epstein–Barr nuclear antigen (EBNA) The exact complex are higher in MS patients versus controls. cause is ❑ Infection cannot fully explain MS because there is a high rate unknown of seropositivity in the population, but MS is much less common. A. Initial loss of myelin sheath without affecting nerve axons leading to slowing down of nerve impulses B. Destruction of axons (transection): impulses are totally blocked resulting in permanent loss of nerve function. Axonal loss is likely responsible for MS progression. How does EBV contribute to MS Molecular Mimicry: EBV proteins may share structural similarities with CNS antigens (e.g., myelin basic protein), triggering an autoimmune response where the immune system mistakenly attacks myelin. Activation of Autoreactive T-cells: EBV infection may activate T-cells that target both viral antigens and myelin components, contributing to demyelination.  Typical syndromes at presentation include, but are not limited to, monocular visual loss due to optic neuritis, limb weakness or sensory loss, double vision due to brain-stem dysfunction, or ataxia due to a cerebellar lesion. Clinical presentation Tertiary Symptoms: Financial problems, Personal/social problems Educational problems, Emotional problems Course of illness Radiologically isolated syndrome A radiologically isolated syndrome (RIS), refers to individuals who have clinical scenarios not typical of MS, yet obtain MRI scans for other reasons (eg, headache) and have radiological signs suggestive of MS. Some percentage of these patients RIS convert to RRMS over time. Course of illness Clinically isolated syndrome At the onset of symptoms, about 85% of patients have exacerbations—new symptoms lasting at least 24 hours and separated from other new symptoms—followed by remissions (complete or incomplete). The first clinical presentation is typically Clinically isolated syndrome (CIS) (the criterion of dissemination in time has not been met to diagnose MS). Patients younger than 40 years old are more likely to convert from CIS to clinically definite MS than those ≥40 years. Patients with optic neuritis as the presenting diagnosis are less likely than those with other symptoms to develop clinically definite MS. Course of illness Relapsing remitting MS It is characterized by exacerbations (relapses/attacks) or periods of new or worsening neurological symptoms, followed by remissions (periods of recovery or partial improvement where symptoms decrease or resolve). Neurologic recovery following an exacerbation is often quite good early in the disease course, but following repeated relapses, recovery tends to be less complete. Secondary-progressive MS Most RRMS patients eventually enter a progressive phase in which attacks and remissions are difficult to identify. This is referred to as secondary- progressive multiple sclerosis (SPMS). Course of illness Primary progressive MS Approximately 15% of patients never have discrete phases of attacks and remissions but have progressive disease from the outset, known as primary-progressive multiple sclerosis (PPMS). These patients will have symptoms, especially spastic paraparesis that may worsen rapidly or relatively slowly over time and accrue progressively more disability. Progressive relapsing MS Finally, a small percentage of patients may have a mixture of both progression and relapses, referred to as progressive-relapsing multiple sclerosis (PRMS). These patients are generally treated as relapsing patients.  Diagnosis: ❑ To date, there are no tests specific for MS. ❑ MRI, the most valuable diagnostic tool, produces images of the brain and spine that reflect damage that is characteristic of MS plaques in multiple areas of the CNS. ❑ Lesions that enhance after injection of the contrast media gadolinium indicate new lesions  Diagnosis: ❑ The key requirement for a diagnosis of MS is evidence of damage to the central nervous system that is : ✓disseminated in time (DIT) ✓disseminated in space (DIS) ❑ This means showing that damage has occurred at different dates (DIT) and to different parts (DIS) of the central nervous system. ❑ An attack is defined as a patient-reported or objectively observed event typical of an acute inflammatory demyelinating event in the CNS with a duration of at least 24 hours in the absence of fever or infection.  Diagnosis: DIT: Patient has had more than one attack of neurological dysfunction that occurred at different times ❑ 2 clinical relapses (S&S) separated by at least 30 days ❑ MRI evidence of dissemination over time ✓ a new T2-weighted lesion after the initial event ✓or the simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions at any time. DIS: ❑ 2 attacks representing different anatomical lesions ❑ by MRI evidence of one or more T2-weighted lesions in at least two of the following areas: periventricular, juxtacortical, infratentorial, spinal cord.  Diagnosis: ❑ The presence of oligoclonal immunoglobulin G bands in the spinal fluid is also a good marker for MS. ❑ Elevated immunoglobulin G index ❑ It shows that there has been disease activity in the past, and so can be used as evidence of DIT.  Diagnosis: Evoked potentials: ❑ Evoked potential (EP) tests measure the electrical activity of the brain in response to stimulation of specific sensory nerve pathways. They can detect the slowing of electrical conduction caused by damage (demyelination) along these pathways even when the change is too subtle to be noticed by the person or to show up on neurologic examination. ❑ EP testing has been eliminated from the 2017 Revised McDonald Criteria for the Diagnosis MS. https://www.youtube.com/watch?v=4LCkDwcXMHE  Diagnosis: Optic coherence tomography: ❑ Optical Coherence Tomography (OCT) is a scan that measures the thickness of the nerve fibers in the optic neve. ❑ OCT is able to capture and measure atrophy (thinning) of the optic nerve, common in MS.  Assessment: The most widely used clinical rating scale is the Expanded disability status scale EDSS, which uses a numerical value ranging from 0 (no disability) to 10 (death) to evaluate neurologic functions. The limitations of this scale are the relative insensitivity to clinical changes not involving impairment of ambulation, such as changes in cognition, fatigue, and affect.  Aggravating factors The unpredictable nature of MS makes it impossible to anticipate when an exacerbation will occur. Certain factors may aggravate symptoms or lead to an attack including ✓infections, ✓sleep deprivation, ✓stress, ✓malnutrition, anemia, ✓concurrent organ dysfunction, ✓exertion, and ✓Childbirth. Many patients experience a significant reduction in relapses during the third trimester of pregnancy, followed by a relative increase postpartum ✓increased body temperature  Prognostic factors MS reduces life expectancy by 10 to 12 years. Multiple sclerosis usually does not directly diminish life expectancy, although the development of secondary complications such as pneumonia or septicemia (secondary to aspiration in those with swallowing difficulties, decubitus ulcers, or UTIs) or rapid progression of primary lesions affecting respiratory function can lead to a shorter than expected life span. Suicide rates as high as seven times that seen in the general population have been reported. Practical exam II Epilepsy Alzheimer Parkinson’s Migraine