​Kembara Xtra - Medicine - Multiple Sclerosis

​Kembara Xtra - Medicine - Multiple Sclerosis 
An inflammatory disorder that targets elements of the neuronal myelin sheath and causes demyelination, which frequently results in progressive axonal loss and ultimately CNS atrophy It mostly affects the white matter but can also harm the grey matter and meninges underneath
Multiple sclerosis (MS) has four distinct clinical subtypes:
Clinically isolated syndrome (CIS) is the initial symptom of CNS demyelination in a patient that may be caused by MS but does not meet the criteria for dissemination at that time. 60% of people who are first diagnosed with CIS will eventually relapse and develop MS.
- Relapsing-remitting Multiple Sclerosis (RRMS): episodic flare-ups that last for days to weeks and are interspersed with times of neurologic stability. Attacks might bring on new symptoms while also making old ones worse.
Following each bout, there may be a complete recovery of any remaining impairments (90% of patients).
After an initial relapsing-remitting disease history, secondary progressive MS (SPMS) refers to a gradual deterioration in disease state. Acute flare-ups may be linked to the progressive phase. Retrospective diagnoses of SPMS are common.
With no initial relapsing-remitting disease course, primary progressive MS (PPMS) is characterized by a gradual decrease in disease status and accumulation of disability from the time of illness onset (10% of patients).


pregnant women's issues
In most circumstances, it is advisable to stop taking MS medication while pregnant. Interferon and glatiramer acetate are chosen treatments if they are clinically required during pregnancy.
Most patients suffer fewer disease exacerbations throughout pregnancy, although postpartum relapse frequency usually rises. For individuals with a high risk of symptom recurrence, natalizumab may be continued until 34 weeks.
All medications approved for MS treatment are prohibited during breastfeeding, especially for people with extremely active illness before to conception. MS therapy should be promptly continued following birth, especially for people with very active disease. Patients should carefully weigh the risk of delaying MS therapy when deciding whether or not to breastfeed.

Epidemiology 

Although improvements in genetics and immunology have advanced our understanding of the disease process, there is still much to learn about the multifaceted complexity of MS. Caucasian women in their second and third generations are most frequently affected, and the condition is more prevalent in individuals who have first-degree relatives who have the illness.
Men globally experience 2.0 cases per 100,000 person-years compared to women, who experience 3.6 cases per 100,000 person-years.
Prevalence: 35.9 per 100,000 individuals worldwide and 117.49 per 100,000 persons in the Americas.


Pathophysiology and Etiology 

primarily an autoimmune response against the myelin sheath, driven by T cells and B cells. CD4 T lymphocytes pass the blood-brain barrier and detect proteins on the surface of the myelin sheath due to dysregulation and the identification of an incorrect antigen. Myelin and oligodendrocytes are destroyed as a result of the release of cytokines, interferon, and tumor necrosis factor, as well as the activation of macrophages and B cells. After demyelination, faster salutatory nerve conduction velocities (impulses jumping between nodes of Ranvier) are changed to much slower continuous nerve velocities. The focused neurologic impairments associated with MS are brought on by these alterations in the acute setting.
The ability of surviving oligodendrocytes or those created from precursor cells to partially remyelinate stripped axons results in scars that over time may cause irreversible axonal loss and brain atrophy.
The lateral corticospinal (motor) tracts of the spinal cord normally lose the bulk of their axons. MS was traditionally believed to just affect the white matter tracts; however, there is growing evidence of inflammation-related damage to the meninges and cortical grey matter beneath.


MS is polygenic and does not have a mendelian pattern of inheritance. Five to seven times more likely to receive a diagnosis are those with first-degree relatives who are afflicted.
● MS has been linked to more than 100 genetic loci, indicating that it is primarily an immunological reaction to an antigen. These are often assigned to the HLA gene cluster's class II region. The locus on chromosome 6 known as HLA-DRB1 is the most prevalent.
Although their participation in the MS disease process is not fully known, natural killer cell variants and their polymorphic killer-immunoglobulin-like receptors are considered to play a significant impact. These form major histocompatibility complexes with high binding affinity for myelin basic proteins.


Risk Factors: Caucasian > Afro-Caribbean > East Asian; peak incidence ages 15 to 45; mean age 28 to 31 (significantly earlier in women than males); gender: 2 to 3 times more common in women.
Smoking is a substance, while prior Epstein-Barr virus infections and a history of infectious mononucleosis are infectious factors. Geographically, MS incidence has historically been inversely correlated with distance from the equator and its link with greater vitamin D exposure. Recently, however, this link has become less pronounced, which may be related to lifestyle changes that have reduced solar exposure in certain areas.


Accompanying Conditions 

Internuclear ophthalmoplegia: Impaired adduction of the afflicted eye results from injury to the medial longitudinal fasciculus.
Optic neuritis, an inflammation of the optic nerve that causes blindness, is linked to a number of other autoimmune disorders.

Diagnosis 

Depending on where the lesions are, a person with MS may have a variety of neurologic signs and symptoms. The key to making a diagnosis is to show that CNS lesions with distinct temporal and spatial separations are not more likely the result of a different disease process.
HISTORY
Fatigue, epilepsy, disorientation, visual abnormalities, facial palsy, dysphagia, muscle weakness or spasms, hyperesthesia or paresthesia, discomfort, bowel or bladder incontinence, urine frequency or retention, and impotence are just a few of the symptoms that might occur.


clinical assessment 

 Weakness, foot drop, abnormal gait, and internuclear ophthalmoplegia
 Paresthesia or hyperesthesia, scanning speech (cerebellar dysarthria), and stiffness (particularly in the lower extremities)
Uhthoff phenomenon: Symptoms get worse when exposed to temperatures that are greater than usual.
Lhermitte sign: electric-like impulses that run down the spine in response to neck flexion

Differential diagnoses include infectious conditions such as Lyme disease, neurosyphilis, acute disseminated encephalomyelitis, progressive multifocal leukoencephalopathy, and primary cerebral angiitis, as well as autoimmune conditions such as systemic lupus erythematosus, antiphospholipid antibody syndrome, neurosarcoidosis, and Behçet disease.
 CNS: stroke, normal pressure hydrocephalus, neuromyelitis optica, epilepsy, CNS neoplasms
Metachromatic leukodystrophy is a genetic disorder. A vitamin B12 deficiency is another.

Laboratory Results 

 MRI of the head and spine: Callosal and periventricular lesions are comparatively specific for MS. Gadolinium additions can aid in locating active lesions.
Cerebrospinal fluid from a lumbar puncture might show high or normal levels of total protein. 90% of MS patients have oligoclonal immunoglobulin G bands, albeit they may not be present at the beginning of the disease. Positive results do not rule out MS, but they may be helpful if other diagnostic criteria are unclear.
Blood tests can be used to rule out alternative diagnoses. These include tests for antinuclear antibodies, antineutrophil cytoplasmic antibodies, anti-double-stranded DNA antibodies, extractable nuclear antigen antibodies, antiphospholipid antibodies, complement, erythrocyte sedimentation rate, immunoglobulin G, immunoglobulin M, rheumatoid factor, and Lyme disease antibodies.
McDonald criteria for diagnosing MS: must show spatial and temporal spread of CNS lesions 1 T2 lesion on an MRI in at least two of the four CNS regions that are frequently damaged by MS: the periventricular zone, the juxtacortical region, the infratentorial region, or the spinal cord, or by waiting for another clinical episode that suggests a different CNS site.
- The simultaneous appearance of asymptomatic gadolinium-enhanced and nonenhancing lesions at any time, or a new T2 and/or gadolinium-enhanced lesion on an MRI when compared to baseline scans, are examples of dissemination in time.
Diagnostic Techniques/Additional Evoked Potentials: Assess the electrical activity of the CNS in response to neural stimulation to determine how well the visual, auditory, and somatosensory motor pathways are functioning. A demyelinating illness may be indicated by a significant delay without a clinical presentation. In 80–90% of MS patients, delayed visual evoked potentials are present.


A holistic, multidisciplinary team approach to management is crucial.
Treatment for acute relapses, symptomatic therapy, and disease-modifying drugs are the three primary types of MS treatment now available.
Early use of disease-modifying therapies has the potential to decrease the progression of the disease generally, and should be controlled by an MS expert.


Methylprednisolone 0.5 g PO daily for 5 days or 1 g IV daily for 3 to 5 days is the medication used to treat acute relapses; a second round of treatment is possible.
 Adrenal insufficiency, Cushing syndrome, fluid retention, hypokalemia, GI problems, headache, and emotional lability are a few of the side effects.
- Plasmapheresis - Disease-modifying therapy (1) - ACTH gel 80 U IM or SC daily for 5 to 15 days - Side effects comparable to methylprednisolone[B]
- IFN-1a (Avonex) 30 g IM once a week, IFN-1a (Rebif) 22 or 44 g SC three times a week, or IFN-1b (Betaseron/Betaferon/Extavia) 250 g SC every other day.
 Adverse reactions include flu-like symptoms, depression, skin site reactions, thyroid malfunction, and abnormal liver enzyme levels.
- Dimethyl fumarate (Tecfidera) 120 to 240 mg PO twice daily Monitoring: CBC, LFTs Side effects: diarrhea, cramps, LFT elevation, nausea, flushing. - Glatiramer acetate (Copaxone) 20 mg SC daily Monitoring: none Side effects: skin site responses, acute postinjection reaction, lipoatrophy.
- Monitoring: CBC, LFTs, and UA Teriflunomide (Aubagio) 7 to 14 mg PO daily
Natalizumab (Tysabri) 300 mg IV every 28 days Side effects: nasopharyngitis, headache, diarrhea, exhaustion, back pain, influenza, hair thinning, LFT elevation, nausea, UTI Monitoring: CBC, LFTs Side effects: headache, fatigue, UTI, hypersensitive reaction
Alemtuzumab (Lemtrada) 12 to 24 mg IV for 5 days, then 3 days 12 months after the initial treatment. Monitoring: CBC, LFTs, TSH. Side effects: immune thrombocytopenic purpura, autoimmune thyroid-related issues, headaches, flushing. Fingolimod (Gilenya) 0.5 mg PO daily. Monitoring: ECG, CBC, LFTs, eye exam. Side effects: 1st-degree AV
Bladder dysfunction is treated with oxybutynin, tolterodine, cannabis extract (nabiximols), catheterization, and intravesical botulinum toxin. Pain is treated with amitriptyline, pregabalin, gabapentin, and cannabis extract (nabiximols).
Amantadine and modafinil are used to treat fatigue, tremors, and depression. Clonazepam, primidone, and -blockers are used to treat tremors and depression. Fampridine is used to treat walking problems.

Patient Follow-Up Monitoring
The Kurtzke Expanded Disability Status Scale (EDSS) can be used to gauge the degree of neurologic impairment caused by MS: Eight functional systems (FS)—pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral—are used by the EDSS to measure the degree of a disability.
EDSS rating scale:
No disability and little indications in 1 FS at 1.0; minimal disability in 1 FS at 2.0
3.0—moderate disability in one FS or mild disability in three to four FS, yet totally ambulatory
4.0 – ambulatory without assistance or rest for at least 500 meters 5.0 – ambulatory without assistance or rest for at least 200 meters 6.0 – intermittent or continuous unilateral assistance (cane, crutch, or brace); must be able to walk 100 meters 7.0 – unable to walk beyond 5 meters even with assistance; essentially restricted to wheelchair, wheels self and transfers alone; active in wheelchair for at least 12 hours per day 8.0 – essentially restricted to bed, chair, or wheelchair;
9.0 — bedridden, useless, but able to talk and eat; 10.0 — MS-related death

Average life expectancy is 5 to 10 years less than in the unaffected group, according to the prognosis.
Using optical coherence tomography (OCT) to measure the thinning of the peripapillary retinal nerve fiber layer or the ganglion cell layer plus the inner plexiform layer in patients without prior optic neuritis has revealed an association with accelerated disability progression in MS patients; however, the clinical significance of this association is unclear at this time.


Complications 
It is uncommon for death to result from an MS relapse; instead, complications from MS, like infection in a disable person, are more frequently linked to death.

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