1. Acute treatment of MS
(1) Glucocorticoids
The principle of hormone therapy is high-dose, short-course shock therapy, and it is not advocated to apply hormones in small doses for a long time.
i. Glucocorticoid therapy can promote the recovery of neurological function in MS patients with acute onset in the short term (Grade A recommendation). Li Hongzeng, Department of Neurology, Tangdu Hospital, Fourth Military Medical University
ii. Any form of prolonged glucocorticoid administration has no long-term benefit on neurological recovery (Grade B recommendation).
iii. Based on the results of a level II evidence study, regular hormone shocks may be beneficial in the long-term treatment of patients with RRMS, slowing disease progression and brain atrophy (level C recommendation).
The corticosteroid indicated for MS is methylprednisolone. The recommended method: The conventional usage is to start with 1g/d for 3-4 h intravenously for 3 d; then the dose is reduced by half and each dose is used for 3 d until it is reduced, usually for 24 d. Specifically if the application of methylprednisolone 1 g / d intravenous shock treatment for 3 d, changed to 500 mg / d with 3 d, 240 mg / d × 3 d, 120 mg / d × 3 d, followed by a change to prednisone oral 60 mg / d × 3 d, 30 mg / d × 3 d, 15 mg / d × 3 d, 5 m g / d × 3 d, and finally reduce the stop. In case of recurrence during hormone reduction, patients with new signs and/or new lesions on MRI may be treated with methylprednisolone shock therapy again. Overall, hormone therapy is highly effective, with an efficiency of about 80% for the acute phase of MS. Generally speaking, hormones are more effective when the acute attack is obvious, but the effect is not obvious when the attack is not obvious. The onset of action of hormone is usually from 24 to 72 h. The effect is usually seen in 24 h. Patients feel better soon after using hormone, and different degrees of improvement can be seen in evoked potentials and MRI.
In general, the relapse rate decreases during pregnancy, but the period after delivery (especially the first 3 months) is the time when the relapse rate is higher. One study compared the effect of postpartum treatment without hormone therapy in 22 patients with that of postpartum treatment with hormone therapy in 20 patients, and concluded that postpartum application of hormone therapy could reduce and prevent acute recurrence.
Most of the side effects of hormone therapy, such as electrolyte disorders, blood sugar, blood pressure and lipid abnormalities, can be prevented, but there is still no effective method to prevent arrhythmias caused by high doses of hormones, so clinicians must pay close attention to the arrhythmias once they occur and deal with them promptly, or even stop the medication. In addition, the amount and duration of hormone therapy should be controlled as much as possible to prevent hormone-induced complications such as osteoporosis, femoral head necrosis and severe fractures.
(2) Plasma exchange
Plasma exchange, also known as blood purification, includes lymphocyte removal, specific lymphocyte removal, immunoreactive substance removal, etc.
i. Based on consistent Level I, II and III evidence studies, plasma exchange has little or no effect on the treatment of progressive MS (Level A recommendation).
ii. Plasma replacement is therapeutically effective for severe demyelination in the acute phase of type II pathology (humoral immune significant) and ineffective for common MS (Grade C recommendation).
Overall, the efficacy of plasma replacement in MS is uncertain and is generally not used as the treatment of choice in the acute phase, but only as an alternative treatment when no other approach is available. m S is primarily a cellular immune-mediated immune disease, so plasma replacement may be less effective, and doing specific cellular immune component removal may have a better efficacy.
(3) Intravenous immunoglobulin (IVIg)
From the current data, the overall efficacy of IVIg is still unclear and is only used as an optional treatment. The dosage is 0.4 g per kg of body weight, and 5 d of continuous use is a course of treatment. After 5 d, if there is no efficacy, patients are not recommended to use it again; if there is efficacy but the efficacy is not particularly satisfactory, it can continue to be used for 1 d per week for 3 to 4 weeks.
Therefore, the preferred regimen for the acute phase of MS is high-dose methylprednisolone shock therapy, with IVIg or plasma exchange available for severe intractable attacks (poor response to hormones).
2. Disease modifying therapy (DMT) in the remission phase of MS
(1) Interferon beta (IFNβ)
IFNβ-1a is a glycosylated recombinant mammalian cell product with identical amino acid sequence to natural interferon; IFNβ-1b is a non-glycosylated bacterial cell product produced by Escherichia coli, in which the serine at position 17 is replaced by cysteine. The structural differences with and without the glycosyl group lead to differences in the clinical properties of the two: (i) the activity is different, and the activity of IFNβ-1a with the glycosyl group is much greater than that of IFNβ-1b; (ii) compared with IFNβ-1b, IFNβ-1a takes longer to produce neutralizing antibodies after use and has a lower antibody titer, which may be related to the protective effect of the glycosyl group on some immune loci. Rebif is the only IFNβ-1a approved by the State Food and Drug Administration (SFDA) of China for the treatment of MS. Interferon treats MS through its immunomodulatory effects, which are achieved through multiple mechanisms, including regulation of cytokines, inhibition of cell migration into the brain, inhibition of T cell activation, and suppression of other inflammatory T cells.
i. IFNβ reduces the number of seizures in patients with RRMS or CIS at high risk of developing MS (Class A recommendation). iFNβ treatment reduces MRI lesions and delays the progression of physical disability (Class B recommendation).
IFNβ treatment should be used when available in patients at high risk of developing clinically confirmed MS or diagnosed RRMS or SPMS (Grade A recommendation). i. The efficacy of IFNβ in patients with recurrence-free PPMS is uncertain (Grade U? recommended).
iii. There is a dose-effect curve associated with IFN usage in the treatment of MS with IFNβ (Grade B recommendation), and the efficacy of high-dose IFNβ-1a (44 μg subcutaneously, 3 times per week) is significantly better than low-dose IFNβ-1a (22 μg subcutaneously, 3 times per week).
iv. MS patients treated with IFNβ produced neutralizing antibodies (Grade A recommendation), the incidence of neutralizing antibody production was lower with IFNβ-1a than with IFNβ-1b (Grade B recommendation), and the presence of neutralizing antibodies may be associated with a decline in clinical treatment with IFN-β (Grade C recommendation).
(2) Glatiramer acetate (GLA)
is a synthetic polypeptide chain consisting of four amino acids (L-glutamic acid, L-lysine, L-alanine and L-tyrosine) in a specific molar ratio (1.4:3.4:4.2 :1.0), whose mechanism of action is not yet clear and may be related to immunomodulation. Gliemer acetate reduces the number of seizures in patients with RRMS (Class A recommendation).
(3) Mitoxantrone
It is an antineoplastic drug and an immunosuppressant. It was approved by the FDA in 2000 for patients with severe RRMS or SPMS, PRMS, and was the first immunosuppressant approved by the FDA for the treatment of MS. It should be used with attention to its cardiotoxicity and should not be applied for more than two years as a second-line drug for the treatment of MS.
i. Mitoxantrone may reduce the relapse rate in patients with RRMS (Grade B recommendation), but the potential toxicity of mitoxantrone in the early stages of the disease outweighs the clinical benefit.
ii. Mitoxantrone may have some efficacy in disease progression in SPMS (Grade C recommendation).
(4) Natalizumab
A recombinant α4-integrin monoclonal antibody that prevents activated T lymphocytes from crossing the blood-brain barrier into the central nervous system to cause an immune response. It has shown significant efficacy in the treatment of MS, reducing the relapse rate of MS by 68% and the number of new MR I lesions by 83%, and is currently the more efficacious drug for RRMS (Class A recommendation). To date, five patients with progressive multifocal leukoencephalopathy have been reported with natal monoclonal antibody, which is a second-line drug for the treatment of RRMS.
(5) Immunosuppressants
Patients who are not eligible for IFNβ and have a tendency to relapse can be treated with immunosuppressants judiciously, but the efficacy of immunosuppressants is poorer than that of drugs such as IFNβ mentioned above, the evidence of relapse prevention effect is not sufficient, and all long-term applications have certain side effects. However, since the immune activity is still ongoing during MS remission, the application of immunosuppressive drugs can be carefully considered and their efficacy/risk ratio can be fully evaluated. Azathioprine and cyclosporine A are commonly used clinically, as well as cyclophosphamide and methotrexate.
Azathioprine may reduce relapses in MS patients (Class C recommendation) and is not effective for disability progression (Class U recommendation). The usual dosage is 2 mg/d per kg of body weight, increasing gradually from small doses to a total of 10 g/kg of body weight, and blood count, liver and renal function should be monitored closely during administration. Immunosuppressants other than azathioprine are not recommended for remission treatment of RRMS due to lack of evidence, but can be tried in SPMS.
Cyclosporine has some therapeutic effect in progressive MS (Grade C recommendation), but attention should be paid to its nephrotoxicity.
(7) Intravenous high-dose immunoglobulin
To date, the number of studies on intravenous immunoglobulin is generally small and complete information on clinical and MRI prognosis is lacking; therefore, it can only be assumed that intermittent intravenous immunoglobulin may reduce the number of episodes of relapsing-remitting MS (Grade C recommendation), and the available evidence suggests that intravenous immunoglobulin has little effect in delaying disease progression (Grade C recommendation).
3. Symptomatic treatment of MS
(1) For painful spasms, drugs such as carbamazepine, gabapentin and baclofen can be applied. For more intense trigeminal neuralgia and nerve root pain, other anti-epileptic drugs can also be applied.
(2) Chronic pain and abnormal sensation can be treated with amitriptyline and duloxetine.
(3) Depression and anxiety can be treated with SSRI, SNRI and NaSSA drugs as well as psychological counseling.
(4) Weakness and fatigue, which are the more obvious symptoms of MS patients, can be treated with amantadine 0.1g 3 times a day.
(5) Tremor, benzhexol hydrochloride and aurolol hydrochloride can be applied.
(6) Vesicorectal dysfunction: with the treatment of drugs or with the help of catheterization.
(7) Sexual dysfunction: Apply drugs such as Viagra, etc.
(8) Physical and speech dysfunction, functional rehabilitation.