Definition and Overview
Multiple sclerosis (MS) is a chronic inflammatory nervous system disease in which myelin is damaged and axon degeneration occurs due to an autoimmune mechanism in the central nervous system (brain, spinal cord, and optic nerve). The name ‘multifocal’ implies that several parts of the central nervous system are affected at different times.
Approximately 2.8 million people worldwide are affected, and in Korea, the rate is reported to be approximately 3.5 to 5 per 100,000 people. It mainly occurs between the ages of 15 and 50, and is approximately 2 to 3 times more common in women than in men. It is a major cause of non-traumatic neurological disorders and has a significant impact on the quality of life and vocational ability of young adults.
Classification
It is classified into four types depending on the clinical course.
Relapsing-remitting MS (RRMS) accounts for approximately 85% of all cases. Neurological symptoms appear for a few days to several weeks, and then repeat recurrence and remission with partial or complete recovery.
Secondary progressive MS (SPMS) occurs in about 50% of patients who start with relapsing-remitting MS within about 10 to 15 years after diagnosis. The disorder progresses slowly without recurrence, or progresses on top of recurrence.
Primary progressive MS (PPMS) accounts for approximately 10-15% of all cases, and the disorder progresses without recurrence from the beginning. The response to treatment is relatively low.
Progressive-relapsing MS (PRMS) is a rare form that progresses from the beginning and is accompanied by clear recurrences.
Causes and Pathogenesis
The exact cause of multiple sclerosis has not been identified, but it is understood to be a combination of genetic predisposition and environmental factors.
Immunologically, autoreactive T lymphocytes pass through the blood-brain barrier, infiltrate the central nervous system, and target and attack myelin basic protein, which makes up myelin sheath. B cells and antibodies are also involved in lesion formation.
Genetically, the HLA-DRB1*1501 genotype is the strongest risk factor. Environmental factors such as vitamin D deficiency, history of Epstein-Barr virus infection, and smoking are known to increase the risk of developing the disease.
If myelin damage is repeated, myelin regeneration ability decreases and axonal degeneration progresses, resulting in irreversible loss of nerve function.
Autonomic nervous system invasion
Approximately 30-50% of patients with multiple sclerosis are accompanied by autonomic dysfunction. This is because demyelinating lesions are formed in the autonomic nerve cells of the lateral horn of the spinal cord and the descending autonomic nerve pathway.
Major autonomic symptoms include orthostatic hypotension, heart rate dysregulation (tachycardia, bradycardia), sweating abnormalities (hyperhidrosis or anhidrosis), bladder dysfunction (frequent urination, urinary incontinence, residual urine), bowel dysfunction (constipation, fecal incontinence), and sexual dysfunction.
In heart rate variability (HRV) tests, patients with multiple sclerosis are objectively confirmed to have a decline in autonomic nervous control, and this shows a correlation with disease severity.
symptoms
Optic neuritis is a common early symptom that occurs over several days, including decreased vision in one eye and pain during eye movements. In approximately 15-20% of patients with multiple sclerosis, optic neuritis is the first symptom.
Motor symptoms include hemiplegia, paralysis of the lower body, muscle weakness, and stiffness. Sensory symptoms include numbness, abnormal sensations, and pain. Lhermitte's sign (a feeling of an electric shock running down the back when the neck is bent forward) suggests damage to the cervical myelin sheath.
Cerebellar symptoms may include ataxia, intention tremor, gait instability, and dizziness. Cognitive decline (particularly processing speed, attention, and memory) is reported in approximately 40-65% of patients. Depression and fatigue are among the symptoms that most significantly reduce quality of life.
diagnosis
Diagnosis is made according to the 2017 McDonald criteria. The key is to identify ‘dissemination in time’ and ‘dissemination in space’.
MRI is the most important tool for diagnosis. In brain MRI, characteristic T2 hypersignal lesions are observed in the periventricular, juxtacortical, and infratentorial regions. Spinal cord MRI reveals a short-segment T2 lesion. Contrast-enhancing lesions indicate active inflammation.
In cerebrospinal fluid (CSF) tests, oligoclonal antibodies (oligoclonal bands) appear positive in approximately 90-95% of patients. An increase in the IgG index is also used as an auxiliary indicator.
Prolongation of P100 latency in visual evoked potentials (VEP) is useful for detecting asymptomatic optic nerve lesions.
treatment
relapse treatment
In case of acute recurrence, 1 g of methylprednisolone is administered intravenously for 3 to 5 days to shorten the recovery period. Steroids accelerate recovery from recurrence but do not change the long-term prognosis.
Disease control treatment
Interferon beta-1a, -1b and glatiramer acetate are first-line treatments that reduce the recurrence rate by about 30%. Highly effective drugs such as natalizumab, ofatumumab, and ocrelizumab have been reported to reduce the recurrence rate by approximately 50-70%. Ocrelizumab, approved in 2018, is the first DMT recognized to be effective in primary progressive MS.
symptomatic treatment
Baclofen, tizanidine, and cannabinoids are used for spasticity. Anticholinergics or mirabegron are used for bladder dysfunction. Gabapentin and pregabalin are effective for neuropathic pain. Amantadine and modafinil are used for fatigue.
prognosis
Patients with relapsing-remitting multiple sclerosis can maintain good function for a considerable period of time with appropriate DMT treatment. At 10 years after diagnosis, approximately 50-60% of patients are able to lead independent daily lives. Poor prognostic factors include male sex, older age at onset, motor and cerebellar symptoms from the beginning, multiple lesions and spinal cord lesions on MRI, and incomplete recurrence recovery.