Multiple Sclerosis - N. 302 Spring 2024-2025 PDF

MULTIPLE SCLEROSIS N. 302 Spring 2024-2025 Prepared by Dr. M. Adra Revised by S. DS. Outline Prevalence Pathophysiology Clinical Presentation Management MULTIPLE SCLEROSIS Is the most common chronic, progressive, immune-mediated inflammatory disease in which the fatty myelin sheaths ar...

MULTIPLE SCLEROSIS N. 302 Spring 2024-2025 Prepared by Dr. M. Adra Revised by S. DS. Outline Prevalence Pathophysiology Clinical Presentation Management MULTIPLE SCLEROSIS Is the most common chronic, progressive, immune-mediated inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. Snapshot! A 32-year-old women presents to her physician complaining of double vision. This has been very distressing for her. She has a past medical history significant for type 1 diabetes, treated with a continuous subcutaneous insulin pump. Upon further questioning, she mentions she experienced arm weakness and numbness that resolved spontaneously over the course of a couple weeks. Physical examination is notable for impaired adduction of the right eye, and nystagmus on abduction of the left eye on left lateral gaze.  Incidence Worldwide Higher incidence in the US & Northern European- incidence is Germany descent and in 0.1% temperate climate. Epidemiology: ↑ in women ( 2-3 X) ↑ in whites onset commonly between 20- 40 years ↑ in temperate climates associated with HLA-DR2 ( genetic predisposition) Prevalence is increasing globally. Myelin is an insulating layer, or sheath that forms around nerves, including those in the brain and spinal cord. It is made up of protein and fatty substances. It allows electrical impulses to transmit quickly and efficiently along the nerve cells In MS, the immune system destroys the myelin and causes scarring, or sclerosis, ( Gliosis) of the nerves in the brain and the spinal cord. Oligodendrocytes ( myelinating cells of the central nervous system (CNS)) are destroyed by T cells that pass the BBB. High protein levels ( antibodies) and inflammatory markers can be found in the CSF This disseminated scarring of the brain and the spinal cord interferes with the ability of nerves to conduct an electrical signal to other nerves or muscles. What happens to the myelin and nerve fibers? Autoimmune response- Immune cells entering the CNS Focal inflammation resulting in macroscopic plaques and injury to the blood-brain barrier (BBB) Neurodegeneration with microscopic injury involving different components of the CNS including axons, neurons, and synapse  Steps involved in the damage to the myelin and axons. One area of myelin has been The immune attack Once the axons are damaged, the myelin has been becomes directed damaged, they cannot severed toward the axon itself. be repaired. The yellow segments represent the myelin coating. Myelin has some ability to repair itself, and the potential of myelin repair is an area of intensive research currently. Once the axons are damaged, however, they cannot be repaired. Because axonal damage can occur even in the earliest stages of the disease, early treatment with a disease-modifying medication should be considered by anyone with a confirmed MS. Risk factors of MS? Genetic predisposition Environmental factors Vitamin D deficiency ? Living further from the equator, Infections, Epstein Bar Virus, Smoking, obesity Other Autoimmune diseases  Symptoms: vary between individuals and are unpredictable Paresthesia Bladder Fatigue Decreased (tingling, and/or Sexual (most visual acuity, (numbness, common) diplopia bowel dysfunction burning) dysfunction Emotional disturbances Cognitive Pain difficulties Heat (depression, (neurogeni Spasticity mood (memory, sensitivity attention,) c) swings) Gait, Speech/ balance, and Intention Hearing swallowing Vertigo coordination problems al Tremor loss problems  Relapsing-remitting MS RRMS is the most common form of MS, with 85% of people initially experiencing episodes of acute symptoms followed by partial or MS usually complete recovery periods when symptoms do not progress. takes one Primary-progressive MS PPMS is a progressive form of the disease that worsens over time without any of four remission; however, the rate of progression is variable. The incidence of PPMS is approximately 15% of MS cases. courses: Secondary-progressive MS SPMS is a RR course that becomes steady progressive worsening of symptoms Progressive-relapsing MS PRMS is the rarest type, marked by bouts of relapses in between progressive worsening of symptoms and only occurs in approximately 5% of people with MS.  Progressio n of MS subtypes RRMS most common PPMS 15% of all cases SPMS PRMS rare Symptoms vs. Relapses MS symptoms are chronic or ongoing. MS is the most common cause of disability in young adults. Onset of the disease is often insidious and gradual, with vague symptoms occurring intermittently over months or years. 1in 4 people with MS regularly use a wheelchair. MS relapses are sudden flare-ups of disease activity (including new or worsening symptoms) that typically last at least 24 hrs, several days to several weeks or months; And it is not caused by infection or other cause. That happens at least 30 days after any previous episode began. New symptoms can appear, or old symptoms re-appear, either gradually or suddenly.  Primary Secondary Tertiary symptoms symptoms symptoms Fatigue Infections Job loss Sensory or Falls Loss of intimacy motor problems Injury Role Cognitive Skin breakdown changes/family Problems disruption Bladder and Social isolation Bowel Depression Dysfunction Sexual Dysfunction Spasticity/ Altered Mobility Visual  Most common initial symptoms Changes in sensation in the arms, legs or face (33%) Optic neuritis (20%) Weakness (13%) Double vision (7%) Unsteadiness when walking (5%) balance problem (3%) Lhermitte's sign (25- Uhthoff's 40%) is an electrical phenomenon sensation that runs down is the worsening of the back and into the neurologic symptoms in limbs and is produced by MS when the body gets bending the neck overheated from hot forwards. The sign weather, exercise, fever, suggests a lesion of the or saunas and hot tubs. dorsal columns of the cervical cord or of the caudal medulla.  Assessment Assess mobility Assess disability and track progression and remission over time Assess fatigue – diminishes QOL, associated with pain, poor sleep or depression Assess bladder function- loss of independence Difficulty swallowing ? High risk for aspiration and airway obstruction Assess for reduced nutritional intake Assess for pain Assess for depression Diagnosis of MS MRI remains the golden standard. MRI may be helpful because sclerotic plaques as small as 3 to 4 mm in diameter can be detected. No single test exists for the diagnosis of MS. Diagnosis is made by weighing the history and physical, MRI, evoked potentials, and CSF/blood studies ( high antibody IgG levels) and excluded other causes of the patient's symptoms. Currently there is no cure for MS. Management- Interdisciplinary Early treatment is very important The treatment should be considered as soon as a dx of relapsing MS has been confirmed. Tx is most effective during early, inflammatory phase. Irreversible damage to axons occurs even in the earliest stages of the illness. Tx is least effective during later, neurodegenerative phase  Management Management of MS falls into five general categories:  Treatment of relapses (aka-also known as- exacerbations, flare-ups, attacks— that last at least 24 hours)  Symptom management  Disease modification  Rehabilitation (maintain/improve function)  Psychosocial support  Treatment of relapses Not all relapses require treatment 3–5-day course of IV methylprednisolone —Methylprednisolone orally or intravenously, 500mgs a day for 5 days or 1g a day for 3 days. Stomach cover should be given e.g Omeprazole 20mg daily. Depending on the nature of the relapse, referral to physiotherapy / Rehabilitation can be beneficial to restore/maintain function Psychosocial support  Given intravenously once a day for three-to-five days. Sometimes the IV steroid is followed with steroid pills (prednisone) given in a tapering dose for an additional 1-2 weeks. Methylprednis Has the capacity to close the damaged olone blood-brain barrier and reduce inflammation in the central nervous system. Mechanism of action: It acts in various ways to decrease the inflammatory cycle in 1) dampening the inflammatory cytokine cascade, 2) inhibiting the activation of T cells, 3) decreasing the extravasation of immune cells into the CNS. 4) facilitating the apoptosis of activated immune cells, and indirectly decreasing the cytotoxic effects of nitric oxide and tumor necrosis factor alpha.  Treating Multiple Sclerosis (MS) Disease modifying Symptomatic Abortive therapies therapies therapies Methylprednisolone Interferon beta-1a The major goals of given once a day IV for Interferon beta-1b symptom management three-to-five days. T Cell targeted drugs are to maintain Sometimes the IV (Tecfidera) independent function steroid is followed with IV and improve quality steroid pills, given in a Immunomodulators of life. tapering dose for an (Lemtrada) A coordinated, additional 1-2 weeks. CD 20s (Ublituximab) comprehensive, Mitoxantrone – a interdisciplinary approach to MS care is chemotherapy drug the best approach for the long-term management.  Interferons Interferon beta (IFNβ) was the first disease-modifying therapy available to treat multiple sclerosis (MS), providing patients with a treatment that resulted in reduced relapse rates and delays in the onset of disability. They are proteins that dampen the inflammation. Four IFNβ drugs are currently approved to treat relapsing forms of MS: subcutaneous (SC) IFNβ-1b, SC IFNβ-1a, intramuscular IFNβ-1a, and, most recently, SC peginterferon beta-1a. Peginterferon beta-1a has an extended half-life and requires less frequent administration than other available treatments (once every 2 weeks vs every other day, 3 times per week, or weekly).  Trade Year of FDA Route of Drug Interferon name Betaseron approval 1993 administration Subcutaneous Dosing 0.25 mg Frequency Every other Pharmacokinetics t½: 5 h INTERFERON beta-1b day Tmax: 1–8 h BETA THERAPIES Interferon Extavia 1993 Subcutaneous 0.25 mg Every other t½: 5 h FDA beta-1b day Tmax : 1–8 h APPROVED FOR Interferon beta-1a Avonex 1996 Intramuscular 30 μg Once weekly t½: 10 h TREATMENT Tmax: 5–15 h OF RELAPSING- Interferon Rebif 2002 Subcutaneous 22 or 44 3 times t½: 50–60 h beta-1a μg weekly Tmax: 8 h REMITTING MULTIPLE Peginterferon Plegridy 2014 Subcutaneous 125 μg Once every t½: mean ± SD 78 ± SCLEROSIS beta-1a 2 wk 15 h T max: 1–1.5 d  Eliminate or reduce symptoms that Eliminate impair functional abilities. or reduce Maintain independence in activities of daily living for as long as possible. Improve Improve quality of life, Maximize Symptom neuromuscular function. Management: Goals Avoid Avoid secondary complications ↓ factors that precipitate exacerbations Use targeted and individualized treatment of symptoms (essential in Use management of MS) Optimize psychosocial well-being. Adjust to the illness.  Symptom Management Muscle relaxants for spasticity- for spasticity ( Baclofen- GABA agonist) watch for sedation; diazepam ( Valium). CNS stimulants for fatigue Amantadine (Symmetrel) for dyskinesia; methylphenidate [Ritalin], are used to treat fatigue. Also, SSRIs: eg, fluoxetine Anticholinergics- used to treat bladder symptoms - oxybutynin ( Dotropan) used to treat overactive bladder Tricyclic antidepressants & Antiseizure drugs used for chronic pain syndromes. Gabapentin is used to treat epilepsy. It's also taken for nerve pain Selective potassium channel blocker Dalfampridine (Ampyra) is used to improve walking speed in MS patients. It is a selective potassium channel blocker and improves nerve conduction in damaged nerve segments. Encourage the use of assistive devices Collaborative multi- disciplinary approach Physical therapy: Relieve spasticity; Improve coordination. Train patient to substitute unaffected muscles for impaired muscles. Exercise improves daily functioning for patients with MS who are not experiencing an exacerbation Water therapy provides exercise and recreation for the patient with a chronic neurologic disease. Water gives buoyancy to the body and allows the patient to perform activities that would normally be impossible because it gives the patient greater control over the body. Nursing Interventions Exacerbations of MS are triggered by infection (especially upper respiratory and urinary tract infection), trauma, immunization, delivery after pregnancy, stress, and change in climate. Each person responds differently to these triggers. During an acute exacerbation, the patient may be immobile and confined to bed. The focus of nursing intervention at this phase is to prevent major complications of immobility, such as respiratory and urinary tract infections and pressure ulcers. Help patient identify triggers and develop ways to avoid them or minimize their effects. Reassure patient. Assist patient in dealing with anxiety and grief caused by diagnosis. Teach patient about- medication regimen, balance between rest and exercise, self catheterization, intake of fiber to prevent constipation, lifestyle changes. What is the outlook for MS patients? Life expectancy for people with MS has increased considerably in the last 25 years. The average life expectancy for people with MS is around 5 to 10 years lower than average. MS itself is rarely fatal, but complications may arise from severe MS, such as chest or bladder infections, or swallowing difficulties., Case study: A 29 year-old graphic designer, Betty Jackson first noticed her symptoms in the summer of 2019 while she was biking along the lake with her husband. She was experiencing difficulty reading signage and clumsiness using her arms while steering her bike. Upon completing her route, she felt excessively fatigued. These symptoms persisted for a few days, eventually affecting her productivity at work, prompting a visit to her family physician. MRI findings revealed demyelination and plaques in the corpus callosum; the physician classified her event as a “clinically isolated syndrome” of MS. Approximately 10 months later, Betty’s symptoms resurfaced: she experienced the same fatigue, vision disturbances and arm issues. A secondary MRI revealed more distal demyelination & plaques; prompting a diagnoses of relapsing-remitting MS (RRMS). The physician referred her to a private physiotherapy clinic in the community for motor control training and gait safety education. Betty's recent diagnosis has caused her considerable stress and she is fearful of losing her job, or becoming unable to support her children because of considerable fatigue and/or potential progression of gait impairment in the future.  Fatigue is of great importance to Betty’s participation as a worker and a parent. Regular exercise has been cited widely in the literature as beneficial for promoting restful sleep and reducing fatigue in individuals with MS. a 3 month locomotor training program involving a combination of virtual-reality based and overground balance interventions, and body-weight-supported/treadmill training twice a week, improvements were observed both at post-intervention and 2-month follow-up in gait speed, endurance and balance. A challenging aspect of this case is the significant occupational modification that would likely be necessary for the patient. Graphic design requires a high level of upper extremity motor function, and without considerable workplace modification, ergonomic intervention, or additional support from the employer, continuing to pursue this line of work may prove unrealistic. For this reason the involvement of an occupational therapist and/or social worker may be warranted. Subjective Assessment: Assessment Date: May 12, 2020 Demographics: Name: Betty Jackson Age: 29 Sex: Female History (Hx) of Present Illness: Medical diagnosis: Relapsing Remitting Multiple Sclerosis Diagnosed in April 2020 following MRI imaging ordered by her family physician 2 previous relapses (first relapse in June 2019, second relapse in March 2020) in the last year both of which presented with excessive fatigue, blurry vision, impaired upper extremity function Rehabilitation History: Previously attended physiotherapy regarding rehabilitation of a sprained left ankle following a sports injury approximately 10 yrs ago, but has not been to physiotherapy regarding current condition previously Current symptoms or status: Primary Complaints: Patient reports following her last relapse-remission episode, she has experienced uncoordinated, difficult arm and hand movements especially with her right arm which is her dominant side. In addition, the patient complains of occasional experiences of unsteadiness when taking a step, greater than normal fatigue following a work day and/or ADLs, and feeling “clumsier than usual”. Patient also reported occasional difficulty focusing on tasks at work. Aggravating Factors: warm weather, stressful work life Easing Factors: cooler weather, rest Social History: Lives in an apartment with husband and two children (aged 4 and 5). Apartment building has 4 steps to the front entrance, and elevators to the patient's unit floor. Apartment unit has no stairs within. Husband works as an arborist (part-time to full-time depending on season). Patient also mentioned that her husband is a life-time indoor smoker and has no intention of quitting. Hobbies: Enjoys biking with her husband, and playing with her kids Occupation: Graphic designer, full-time Functional status/Activity – current and previous Previously high activity level with complete independence No prior fall history but experiences occasional instability during longer periods of walking Currently reports difficulty with completing previously tolerable biking routes, and playing with her children for prolonged periods. Occasionally needs assistance from husband with work around the house and errands. Other information: Medications: Rebif (self-administered subcutaneously 3x per week) Diagnostic Tests/Investigations: MRI Imaging identifying both active and inactive demyelination plaques within the corpus callosum and in the periventricular white matter Hand dominance: Right-handed Health Habits: non-smoker, 1-2 wine glasses per week, no recreational drug use Patient’s goals and concerns: Maintain and prevent decline of as much upper extremity function and balance in walking as possible Manage fatigue symptoms as patient feels she no longer is able to participate in biking routes with her husband and friends Patient expressed serious concerns about future potential decreases in her own function and mobility and how it will affect her ability to work and take care of her children. This is especially a concern as her husband’s occupation is busiest during the summer when the temperature is higher, and the symptoms seem to be worse. Another area of concern for the patient is the recently noticed decline in her right arm and hand function which will greatly impact her occupation. Problem List: Bilateral upper extremity weakness Decreased upper extremity motor coordination affecting occupation and activities of daily living Increased right dominant hand dexterity affecting occupation Decreased tolerance to activity due to fatigue Decreased balance Altered gait pattern Decreased participation in hobbies Decreased productivity at work Interventions Gait aid Aerobic Training: Taking into consideration the patient's hobbies, she can potentially seek out a bicycle with pedal assist (i.e., e-bike). An e-bike would allow her to pedal normally and if needed she can use the pedal assist (e.g., uphill or once fatigue begins to set in). Dexterity and Upper Limb Training: Upper Limb Strengthening: Banded resistance training for shoulders and upper arms (Shoulder Flexion, Horizontal Abduction, Elbow Extension, Elbow Flexion). Vestibular and Coordination Training (PT supervised):