Multiple Sclerosis
Clinical Features
- Bladder dysfunction - failure to empty, failure to store or combination dysfunction (occurs in 80% of people with MS) - Constipation or loss of control of the bowels, diarrhoea and other bowel issues. - Fatigue (occurs in 80% of people with MS). - Pain (in one study 55% of people with MS had clinically significant pain and can lead to chronic pain). - Spasticity - feelings of stiffness and wide range of involuntary muscle spasms. - Dysarthria (slurring, unclear articulation of words, difficulty controlling loudness), dysphonia (hoarseness, breathiness, nasality, poor control of pitch), swallowing problems (dysphagia). - Difficulty to concentrate and poor memory (difficulty to organize, plan, focus, shift attention as necessary, understand and use language, perform calculations, etc.) - Visual - sudden onset of double vision, poor contrast, eye pain, heavy blurring. - Emotional changes - severe depression, mood swings, irritability, episodes of uncontrollable laughing and crying. Heat sensitivity - elevated core temperature can alter effective conduction of nerve impulses causing fatigue.
Lesion Location
- Lesions located at the grey white junction of associative, limbic, and prefrontal cortex are correlated with cognitive dysfunction - Lesions located in the frontal lobes, dorsal midbrain, pons, parietal and temporal lobes are associated with bowel and bladder dysfunction - Lesions located at the corpus callosum (and adjacent white matter), inferior/ superior longitudinal fascicles, occipitofrontal fascicles and corticospinal tracts are correlated with coordination impairment - Cerebellum motor and sensory cortic and sometimes spinal cord - Basal ganglia is uncommon
Epidemiology
- prevalence is approx 1 per 1000 in NZ (just over 4000 people with it in NZ) - incidence around 134 people per year - female to male ratio 3:1 in NZ
Causes of MS
- thought to be an autoimmune disorder where the bodies immune system attacks its own healthy tissue - autoimmune response destroys the myelin sheath that sorrounds the CNS nerves - the reason this occurs is unknown - myelin sheath assists with conduction of messages from the brain along the nerves. - with MS the myelin sheaths are scarred, causing messages from the brain to become slowed or blocked.
Risk Factors
1. Age - Can occur at any age but most common between 20-50. NZ average age of diagnosis is 37 2. Gender - women twice as likely to develop MS as men 3. Family History - if one of your parents or siblings has had MS, you are at higher risk of developing the disease 4. Climate - MS becomes more common the further you are from the equator > cooler climates = more at risk 5. Certain Infections - A variety of viruses have been linked to MS, including Epstein-Barr, the virus that causes infectious mononucleosis 6. Certain Auto-immune diseases - You have a slightly higher risk of developing MS if you have thyroid disease, type 1 diabetes or inflammatory bowel disease. 7. Smoking: -Smokers who experience an initial event of symptoms that may signal MS are more likely than nonsmokers to develop a second event that confirms relapsing-remitting MS.
Outcome Measures
1. Expanded Disability Status Scale (EDSS) (Gold Standard) A nonlinear scale ranging from 0 (normal neurologic examination to 10 (death due to MS) Widely incorporated in MS clinical trials Provides a critical framework for quantifying the toll that MS takes on those who suffer from it Scoring goes up in 0.5 increments and is scored by the neurologist Consists of assessments of 8 independent functional systems and overall disability status Good validity and reliability (Bermel, Waldman, & Mowry, 2014) 2. Neurologic Rating Scale (NRS) 8 categories consisting of 22 parameters; Mentation, mood, related cranial nerves, lower cranial nerves, motor function in each extremity, deep tendon reflexes, sensory function in each extremity, gait trunk and balance, eyes, cerebellar signs. Score system rating: Min = -10, Max = 100 (the higher the score, the greater the patients function) (C Sipe et al., 1984) Other outcome measures include: Multiple sclerosis Impact Scale (MSIS), fatigue, Qol, ROM, cardiorespiratory fitness, gait assessment, cognitive assessment
Progression
1. Relapsing- Remitting (85% of cases) - Most common form of the disease. It is characterized by clearly defined acute attacks with full recovery or with residual deficit upon recovery. Periods betweeen disease relapses are characterized by a lack of disease progression 2. Primary progressive (10-15% of cases) - Characterized by progression of disability from onset, without plateaus or remissions or with occasional plateaus and temporary minor improvements. A person with PPMS, by definition, does not experience acute attacks 3. Secondary-progressive MS- Begins with an initial relapsing-remitting disease course, followed by a progression of disability that mey include occasional relapses and minor remissions and plateaus. Typicaly, secondary-progressive disease is characterized by: less recovery following attacks, persistently worsening functioning during and between attacks, and/or fewer and fewer attacks (or none at all) accompanied by progressive disability. 4. Progressive relapsing - is the least common disease course. PRMS shows progression of disability form onset but with clear acute relapses, with or without full recovery. Aproximately 5%of people with MS appear to have PRMS at diagnosis. 5. Benign MS- One or two relapses and remission resulting in full recovery and no disability
What types of MS are there?
1. Relapsing-Remitting (RRMS): - 85% of MS cases. Suffer distinct attack of symptoms which then fade either partially or completely 2. Primary Progressive (PPMS): - 5-10% of MS cases. Symptoms gradually get worse over time 3. Secondary Progressive (SPMS): - stage of MS that follows RRMS. It is a sustained build up of disability, without any relapse. Occurs in 65% of RRMS, and will develop into SPMS after 15 years of being diagnosed with MS 4. Progressive Relapsing: - charecterised by a gradual progression of disability from the onset of the disease and is accompanied by one or more relapse
Diagnosis
At present, there is no single set of symptoms, clinical tests or presentations that determine whether a person has MS. Therefore, multiple strategies are used collectively to determine whether a person meets the criteria for diagnosis and to rule out other possible causes of what might be contributing to symptoms the patient might be experiencing. Diagnosis Tests include: 1. Medical history and neurological exam Gather information about birthplace, family history and places travelled. Ask about medical history to identify any other signs and symptoms that could be caused by MS. Tests to evaluate: mental, emotional and language functions, movement and coordination, balance, vision, and other four senses. 2. MRI Detects the presence of MS plaques or scarring. Can differentiate between old and new lesions. MS cannot be confirmed by MRI alone as other conditions also present with spots on MRI and 5% of people who are confirmed to have MS did not initially have brain lesions. 3. Visual Evoked Potential (VEP) Recordings of the nervous systems electrical response to the stimulation of specific sensory pathways. Demyelination will cause slower response time. 4. Lumbar puncture Analysis of cerebrospinal fluid can detect the levels of certain immune system proteins and the presence of oligoclonal bands. These bands indicate an immune response within the CNS (found in 90-95% of people with MS). However, they are present in other diseases as well. 5. Blood tests Can rule out other conditions.
Pathophysiology
Demyelination of the CNS. Destruction of oligodendrocytes (responisble for myelinating the CNS) and reactive astrogliosis Immune cell infiltration across the blood brain barrier Promotes inflammation, demyelination, gliosis and neuroaxonal degeneration Disrupts neronal signalling Activated T helper cells recruit additional immune cells which increases the immune response These destroy the lymphotoxin and TNF alpha that damage the oligodendrocytes B cells, auto anti bodies and complement factors enter the CNS once the inflammation process has started causing additional damage to the CNS T cells are part of the immune system however sometimees they do more harm than good They begin to attack our CNS The T cell secrete cytokines which recruits B cells and macrophages B cells transform into plasma cells and release antibodies that attack the myelin Macrophages release nitric oxide chemicals onto the melin causing further damage to the CNS The longer this occurs, the more difficult it is for our nerve cells to carry nerve signals
Interdisciplinary Management
First line treatments for relapsing & remitting MS (RRMS) = Medicine 1. Gilenya take 1 capsule per day: Gilenya is a disease modifying treatment available as a tablet shown to reduce relapses and disability progression in people with relapsing remitting MS. 2. Aubagio teriflunomide take 1 tablet per day. The active ingredient is teriflunomide. Aubagio works by selectively interfering with the ability of white blood cells (lymphocytes) to produce the disease response and nerve damage that ultimately leads to relapses. 3. Tecfidera dimethyl fumerate take one capsule 2x daily: The active ingredient in Tecfidera® is dimethyl fumerate, which works to reduce MS relapses and slow the progression of RRMS. Tecfidera reduces the inflammation in the brain caused by MS and helps to protect the cells that form the myelin against attacks which may damage it. 4. Tysabri Natalizumab IV administrated: Natalizumab is a synthetic antibody which locks onto certain immune cells, called T-cells. Once the natalizumab is attached to the T- Cells, they cannot cross the blood brain barrier to attack the myelin or nerves in the brain and spinal cord where inflammation and damage is caused in MS 5. Stem cell transplant . Stem cell therapy is any treatment that uses or targets stem cells. This is usually to help replace or repair damaged cells or tissues, but can also be used to prevent damage from happening in the first place. 6. Stem cell transplant autologous haematopoietic stem cell transplant (AHSCT) The aim of this treatment is to "reset" the immune system, so that it will stop attacking the person's own central nervous system. 7. Diet and nutrition Ensure the patient has an adequate diet and nutritional intake alongside treatment 8. Exercise. Research has suggested that exercise can improve the overall health of people with milder MS and help people with more severe MS to stay as mobile and active as possible. Exercise can also help some people manage their MS symptoms, such as fatigue, muscle stiffness, balance difficulties, anxiety, depression, bladder and bowel problems and decrease the risk of heart disease. 9. Medicinal cannabis
Definition
Multiple sclerosis is a chronic progressive disease of the central nervous system (brain, spinal cord, and optic nerves) that affects sensation, movement and body functions.
Prognosis
Research suggests that there are numerous factors that may influence how MS may develop. The longer you can maintain a healthy brain the better the prognosis. 1. Prognosis and Relapsing remitting MS (88%) - For those with relapsing forms of MS there is no predictor as to the frequency or timing of relapses. In some cases, people have been known to go for many years, or decades without new relapses. A relapse does not mean that your disability will progress as in most cases following a relapse and a period of recovery there will be no lasting damage. In some cases, depending on the severity and localisation of new brain lesions disability progression may occur. You should keep a record of any relapses and ensure that you discuss these with your health professional. Disease modifying treatments available in New Zealand, in most cases, effectively help to minimise the relapse rate and disability progression. Currently in New Zealand disease modifying treatments (DMTs) are only available for those with relapsing remitting forms of MS. Where treatments aren't available not wanted it is important to work with your health professionals and community supports and address lifestyle changes such as diet, sunlight, exercise, and meditation. 2. Prognosis and Progressive MS (12%) - The nature of progressive MS means that disability will occur much faster however there is no definitive research to predict how this will occur and over what time period. According to a 2005 study a quarter participants with primary progressive MS required a walking cane within 7.5 years however a quarter still did not require one after 25 years. Research also shows that men tend to progress faster than women by 38%. Other studies have shown that from diagnosis to an EDSS score of 6, the median time for secondary progressive groups was 10 years, while it was just three years for the primary progressive group. Influencing factors for prognosis (factors below suggest a better disease course): 1. Diagnosed at a young age in 20-30's 2. Few relapses in the first years after diagnosis 3. Complete recovery from relapses with no long-term damage 4. Long intervals between relapses 5. Symptoms that are sensory in nature (Numbness & tingling)
Differential Diagnosis
When a patient has a first attack of demyelination - the physician should not rush to diagnose MS because the differential diagnosis includes a number of other diseases which include: - Spinal cord neoplasms Acute disseminated encephalomyelitis (ADEM) - Schilder disease (young children and adolescence - massive demyelination) - Baló concentric sclerosis - Sarcoidosis - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) - Transverse myelitis - Infarction of the spinal cord - Vasculitis - Radiation myelitis - Arteriovenous fistula - Progressive multifocal leukoencephalitis - Subacute combined degeneration of the spinal cord (vitamin B 12 deficiency) - Small-vessel ischemic disease (affecting the brain primarily, and caused by diseases with vascular risk factors, such as diabetes, hypertension, hyperlipidemia, old age) - Non-MS Idipathic Inflammatory Demyelinating Disease (IIDD) The ability to make an accurate diagnosis as early as possible is important for patient management, counselling and optimal therapy