What Is Multiple Sclerosis Numbness?
Multiple sclerosis (MS) is an autoimmune disease characterized by central nervous system white matter inflammatory demyelinating disease. The most frequently affected parts of the disease are white matter around the ventricle, optic nerve, spinal cord, brain stem, and cerebellum. The main clinical features are the recurrence of multiple lesions and the course of the white matter scattered in the central nervous system. The course of the disease is multiple.
| Dong Huiqing | (Chief physician) | Department of Neurology, Xuanwu Hospital, Capital Medical University |
| Wei Xin | (Attending physician) | Department of Neurology, Xuanwu Hospital, Capital Medical University |
Multiple sclerosis (MS) is an autoimmune disease characterized by central nervous system white matter inflammatory demyelinating disease. The most frequently affected parts of the disease are white matter around the ventricle, optic nerve, spinal cord, brain stem, and cerebellum. The main clinical features are the recurrence of multiple lesions and the course of the white matter scattered in the central nervous system, and the recurrence of the disease. The course of the disease is multiple.
On May 11, 2018, the National Health Commission and other five departments jointly formulated the "First Batch of Rare Diseases", and multiple sclerosis was included. [1]
- Western Medicine Name
- Multiple sclerosis
- English name
- multiple sclerosis, MS
- Affiliated Department
- Internal Medicine-Neurology
- Main cause
- Viral infection, immune factors, genetic predisposition, environmental factors, etc.
The etiology and pathogenesis of multiple sclerosis
The etiology and pathogenesis have not been fully clarified so far. Studies in recent years have proposed a multifactorial etiology theory that combines the effects of autoimmunity, viral infection, genetic predisposition, environmental factors, and individual susceptibility factors.
Multiple sclerosis virus infection and molecular simulation theory
Studies have found that the disease initially recurs or later recurs. There is often an acute infection. In patients with multiple sclerosis, not only the antibody titer of measles virus increased, but also the antibody titer of other viruses increased. The infected virus may have a common antigen with the central nervous system (CNS) myelin protein or oligodendrocytes, that is, the amino acid sequence of the virus is the same as or very similar to the amino acid sequence of a certain polypeptide of a neuromyelin component such as MBP. It is speculated that the virus is infected. T cells in the hind body activate and generate viral antibodies, which can cross-react with neuromyelin polypeptide fragments, leading to demyelinating lesions.
Multiple sclerosis autoimmune theory
Experimental allergic encephalomyelitis (EAE), its immune pathogenesis and lesions are similar to those of MS, such as targeting myelin basic protine (MBP) myelin basic protein protein (MBP) immune attack, leading to the loss of white matter myelin sheath of the central nervous system, a variety of neurological disorders. At the same time, the clinical application of immunosuppressive drugs or immunomodulatory drugs has a significant relief effect on MS treatment, which suggests that MS may also be a disease related to autoimmunity.
Multiple sclerosis genetics
The study found that about 10% of patients with multiple sclerosis have a family history. The incidence of multiple sclerosis in the first-generation relatives of patients is 5 to 15 times higher than that of the general population. In monozygotic twins, the incidence of disease can reach 50%.
Multiple sclerosis
Epidemiological data show that countries close to the Earth's polar regions, especially in the northern high latitudes of the northern hemisphere, have a higher incidence of this disease. High-risk areas for MS include the northern United States, Canada, Iceland, the United Kingdom, Northern Europe, Tasmania, Australia and southern New Zealand, with prevalence rates of 40 / 100,000 or more. The incidence in equatorial countries is less than 1 in 100,000, and the incidence in Asian and African countries is lower, at about 5 in 100,000. China is a low-incidence area, similar to Japan.
Multiple sclerosis other
Predisposing factors infection, overwork, trauma, emotional excitement, and drug withdrawal during hormonal therapy can all trigger the disease or cause the disease to recur or worsen.
Multiple sclerosis pathology
Characteristic pathological changes are multiple demyelinating plaques in the white matter of the central nervous system, mostly located around the lateral ventricle, with reactive glial hyperplasia, and may also have axonal damage. Lesions can affect the white matter of the brain, spinal cord, brain stem, cerebellum, and optic nerve. Cerebral and spinal coronal sections can be seen by the naked eye with more gray-gray scattered demyelinating lesions of different shapes, varying in size, 1-20 mm in diameter, with semi-oval centers and around the ventricles, especially the lateral ventricle anterior horns. Microscopy showed acute myelin disintegration and loss, axons were relatively intact, oligodendrocytes degenerate and proliferated slightly, and inflammatory cells (mononuclear, lymph, and plasma cells) infiltration around the small veins were seen. In the late stage of the disease, the axons disintegrated, and the number of nerve cells was reduced, replaced by sclerotic plaques formed by glial cells.
Clinical manifestations of multiple sclerosis
1. Age and gender The age of onset is mostly 20 to 40 years old. Patients under 10 years old and over 50 years old are rare. The ratio of male to female is about 1: 2.
2. Onset forms are more common in subacute onset, and acute and insidious onset are only seen in a few cases.
3. Clinical characteristics The vast majority of patients are clinically manifested as multiple spatial and temporal. Spatial multipleness refers to multiple occurrences of lesions, and temporal multipleness refers to remission-relapse course. A few cases present with single lesions throughout the course of the disease. The monophasic course is more common in slowly progressive multiple sclerosis that develops with spinal cord signs and clinically rare acute multiple sclerosis.
4. Clinical symptoms and signs Because the brain, brain stem, cerebellum, and spinal cord of multiple sclerosis patients can be affected simultaneously or successively, their clinical symptoms and signs are diverse. Signs of multiple sclerosis often have more symptoms than symptoms. For example, patients with complaints of weakness in one side of the lower extremity and numbness and tingling may have signs of bilateral corticospinal tract or posterior cord involvement on examination. The clinical features of multiple sclerosis and its main features are summarized as follows:
Multiple sclerosis limb weakness
Most commonly, about 50% of patients have first symptoms including weakness in one or more limbs. Dyskinesia is generally more pronounced in the lower limbs than in the upper limbs, and can be hemiplegia, paraplegia, or quadriplegia, with asymmetric paralysis being the most common. The tendon reflex is normal in the early stage and can develop into hyperthyroidism later, the abdominal wall reflex disappears, and the pathological reflex is positive.
Multiple sclerosis paresthesia
Superficial sensory disturbances are characterized by acupuncture numbness in the limbs, trunk, or face, abnormal limb coldness, ants walking, itching, and sharp, burning-like pain and unclear positioning. Pain may be related to demyelinating lesions of the spinal nerve roots, which has significant characteristics. May also have deep sensory disturbances.
Multiple Sclerosis Eye Symptoms
Often manifested as acute optic neuritis or retrobulbar optic neuritis, most of which are acute onset of vision loss in one eye, and sometimes both eyes are affected at the same time. Fundus examination showed edema or normal optic nipples, and optic nerve atrophy later. Ophthalmoplegia and diplopia occur in about 30% of cases. Nystagmus is mostly horizontal or horizontal plus rotation. Lesions invading the medial longitudinal bundle cause internucleus ophthalmoplegia, invading the paramedian pontine reticular formation (PPRF) and causing a hemi-syndrome.
Multiple sclerosis ataxia
30% to 40% of patients have varying degrees of ataxia, but the three main signs of Charcot (nystagmus, intentional tremor, and bard-like language) are only seen in some patients with advanced multiple sclerosis.
Seizure symptoms of multiple sclerosis
It is a sensory or motor abnormality that is short in duration and can be induced by special factors. Paroxysmal neurological dysfunction lasts from a few seconds to several minutes at a time. Frequent, excessive ventilation, anxiety, or maintaining a certain posture of the limb can be induced, which is one of the symptoms characteristic of multiple sclerosis. Tonic spasm, paresthesia, dysarthria, ataxia, epilepsy, and pain and discomfort are the more common multiple sclerotic episodes. Among them, tonic spasm confined to the limb or face, often accompanied by abnormal radiation pain, also known as painful spasm, generally unconscious loss and abnormal EEG during the onset. Passive neck flexion induces tingling or lightning-like sensations, which are released from the neck along the spine to the thighs or feet, called the Lhermitte sign. The Lhermitte sign is due to neck flexion. At the same time, the local traction and pressure of the spinal cord increased, and the posterior cord of the demyelinated spinal cord was stimulated.
Multiple sclerosis
It is more common in patients with multiple sclerosis, and it often manifests as depression, irritability and irritability. Some patients appear euphoria and excitement. They may also appear indifferent, lethargy, crying and laughing, slow response, low intelligence, repeated language, Suspicion and delusion of murder, etc. Memory loss and cognitive impairment can occur.
Other symptoms of multiple sclerosis
Bladder dysfunction is one of the main pains of patients with multiple sclerosis, including frequent urination, urgency, urinary retention, urinary incontinence, and it is often combined with spinal dysfunction. In addition, primary or secondary sexual dysfunction may occur in male patients with multiple sclerosis.
Multiple sclerosis can be accompanied by peripheral nerve damage and a variety of other autoimmune diseases, such as rheumatism, rheumatoid syndrome, Sjogren's syndrome, and myasthenia gravis. Multiple sclerosis combined with other autoimmune diseases is the result of multiple target involvement due to the body's immune regulation disorders.
Clinical classification of multiple sclerosis
The American Society for Multiple Sclerosis classified the disease into the following four types (Table 1) according to the course of the disease in 1996, which is related to the decision to treat multiple sclerosis.
Table 1 Clinical classification of multiple sclerosis
Relapsing r emitting (RR) | It is the most common clinical disease, accounting for about 85%. There are multiple relapses and remissions in the early stages of the disease, which can be acute onset or worsen, and can recover afterwards. The condition is stable between relapses. |
Secondary-progressive (SP) | RR patients can be changed to this type after a period of time. 80% of patients will be changed to this type after 25 years of disease. Progressive aggravation of the disease will not be relieved, with or without acute recurrence. |
Primary-progressive (PP) | About 10%, the age of onset is too large (40-60 years old), after the onset of hemiplegia or paresis slowly progress for a long time, after the onset of neurological dysfunction, cerebellum or brain stem symptoms appear |
Progressive relapse (primary-relapsing, PR) | Clinically rare, with concurrent acute relapse on the basis of the primary progressive course |
Multiple sclerosis assistant examination
Cerebrospinal fluid examination, evoked potential and magnetic resonance imaging are of great significance for the diagnosis of multiple sclerosis.
1. Cerebrospinal fluid (CSF) examination can provide important evidence for clinical diagnosis of MS.
(1) Number of CSF mononuclear cells (MNC): slightly increased or normal, generally within 15 × 106 / L, about 1/3 of cases with acute onset or deterioration can be mildly to moderately increased, It usually does not exceed 50 × 106 / L. Beyond this value, other diseases should be considered instead of MS. CSF protein increased slightly in about 40% of MS cases.
(2) Detection of IgG intrathecal synthesis: MS CSF-IgG increase is mainly CNS synthesis, which is an important immunological examination of CSF. CSF-IgG index: It is a quantitative indicator of IgG intrathecal synthesis. It is found in about 70% of MS patients. The measurement of this group of indicators can also calculate the CNS 24-hour IgG synthesis rate, which is similar to the IgG index; (OB) CSF-IgG oligoclonal bands (OB): It is a qualitative indicator of IgG intrathecal synthesis, and the OB positive rate can reach more than 95%. However, CSF and serum should be tested at the same time. Only the presence of OB in CSF and the absence of serum support the diagnosis of MS.
2. Evoked potentials include visual evoked potentials (VEP), brainstem auditory evoked potentials (BAEP), and somatosensory evoked potentials (SEP). 50% to 90% of MS patients may have one or more abnormalities.
3. The high resolution of MRI can identify asymptomatic lesions, so that the diagnosis of MS no longer depends on clinical criteria. It can be seen that the round T1 low signal and T2 high signal of different sizes are common in the anterior and posterior angles of the lateral ventricle, the center of the semioval circle and the corpus callosum, or the fusion spots, which are mostly located in the lateral ventricle body; Spotted irregular T1 low-signal and T2 high-signal plaques can be seen in the spinal cord. Most patients with long course of disease can be accompanied by signs of atrophy of the white matter such as dilatation of the ventricular system and widening of the sulci.
Diagnosis and differential diagnosis of multiple sclerosis
Multiple sclerosis diagnosis
The essence of diagnosis is the multiplicity of time and space. In the past, the diagnostic standards commonly used at home and abroad were formulated at the special conference on multiple sclerosis diagnosis held in Washington in 1983, that is, the Poser diagnostic standard [2] (Table 2) (in line with one of them).
Table 2 Diagnostic criteria for Poser (1983)
Clinical definite MS (clinical definite MS, CDMS) | clinical evidence of two episodes and two isolated lesions in the course of the disease; clinical manifestation of one lesion and subclinical evidence of another in the course of two episodes |
Laboratory supported definite MS (LSDMS) | Two episodes during the course of disease, one clinical evidence of lesion, CSF OB / IgG (+); One episode during the course of disease, clinical evidence of two isolated lesions, CSF OB / IgG (+); One episode during the course of disease, one location Clinical evidence of disease and subclinical evidence of another disease, CSF OB / IgG (+) |
Clinically probable MS (CPMS) | Two episodes in the course of disease, clinical evidence of one lesion; One episode in the course of disease, clinical evidence of lesions in two different parts; One episode in the course of disease, clinical evidence of one lesion and subclinical evidence of another site |
Laboratory supported probable MS (LSPMS) | Two episodes in the course of the disease, CSF OB / IgG, two episodes involving different parts of the CNS, at least one month apart, each episode lasting 24 hours. It should be noted that MS cannot be diagnosed based on any single symptom or sign, and the central nervous system should be prompted. All the clinical manifestations of the lesions at different times and in different parts of the system were used as the basis for diagnosis. |
With the development of imaging technology, people's comprehensive and in-depth research on the disease, and the necessity of early diagnosis and treatment, the diagnostic criteria of MS have been continuously updated. The 2001 McDonald diagnostic standard [2] had a major breakthrough, simplifying the diagnosis of MS in the Poser diagnostic standard from four categories (clinical diagnosis, laboratory support confirmation, clinical possibility, laboratory possibility) to two types (confirmed, possible) The results of MRI were introduced and the diagnostic criteria of primary progressive multiple sclerosis (PPMS) were proposed. The 2005 revised McDonald diagnostic criteria [3] emphasized the importance of MRI lesions in time multipleness, further explained the significance of spinal cord disease in the diagnosis, and simplified the diagnosis of PPMS. This diagnostic standard has been widely used worldwide in recent years. From the perspective of the development of MS diagnostic criteria, the development trend is early diagnosis, which increases the sensitivity of the diagnosis without reducing the specificity, clarifies the concept of diagnosis, and simplifies the diagnosis process.
In May 2010 in Dublin, Ireland, the International Expert Group on the Diagnosis of Multiple Sclerosis (referred to as the International Expert Group) discussed the need for further elaboration of the spatiotemporal nature based on recent studies and expert opinions on MS diagnosis. The standard applies to children, Asians, and Latin Americans, and the McDonald diagnostic criteria [4] was revised for the second time (Table 3).
Table 3 2010 revised diagnostic criteria for MS
Clinical manifestation | Additional evidence needed to diagnose MS |
2 clinical episodes a; objective clinical evidence of 2 lesions or objective clinical evidence of 1 lesion with reasonable evidence of 1 previous episode b | No c |
2 clinical episodes a; objective clinical evidence of 1 lesion | The multiplicity of spaces requires any of the following two items: There are 1 T2 lesions in at least 2 of the 4 typical CNS lesion areas (paraventricular, near cortex, sub-occipital, and spinal cord) in MS; Waiting for another clinical attack involving different parts of the CNSa ; |
1 clinical episode a; objective clinical evidence of 2 lesions | The multiplicity of time requires any of the following 3 items: MRI examination at any time has both asymptomatic enhanced and non-enhanced lesions; Follow-up MRI examinations have new T2 lesions and / or thoracic enhancement lesions, regardless of the time interval from the baseline MRI scan; Waiting for another clinical episode a ; |
1 clinical episode a; objective clinical evidence of 1 lesion (clinical isolated syndrome) | The multiplicity of spaces requires any of the following two items: There are 1 T2 lesions in at least 2 of the 4 typical CNS lesion areas (paraventricular, near cortex, sub-occipital, and spinal cord) in MS; Waiting for another clinical attack involving different parts of the CNSa ; The multiplicity of time requires any of the following 3 items: MRI examination at any time has both asymptomatic enhanced and non-enhanced lesions; Follow-up MRI examinations have new T2 lesions and / or thoracic enhancement lesions, regardless of the time interval from the baseline MRI scan; Waiting for another clinical episode a ; |
Implicit Progressive Neurological Dysfunction (PPMS) in MS | Retrospective or prospective studies have proven that the disease has progressed for 1 year and has 2 of the following 3 items: There are 1 T2 lesions in the typical lesion area of MS (near the ventricle, near the cortex or under the curtain) to prove the spatial multipleness of brain lesions; There are 2 T2 lesions in the spinal cord to prove the spatial multipleness of the spinal cord lesions; CSF positive results (isoelectric focus electrophoresis evidence of oligoclonal bands and / or increased IgG index); |
When the clinical manifestations meet the above diagnostic criteria and there is no other more reasonable explanation, it can be clearly diagnosed as MS; when MS is suspected but does not fully meet the above diagnostic criteria, it is diagnosed as "possible MS"; other diagnoses can explain the clinical manifestation more reasonably , The diagnosis is "non-MS". a A seizure (relapse, exacerbation) is defined as a current or past event with CNS acute inflammatory demyelinating disease characteristics found by subjective narrative or objective examination of the patient, lasting at least 24 hours, and no fever or infection signs. Clinical seizures need to be confirmed by a concurrent neurological examination. In the absence of neurological examination evidence, certain past events with typical symptoms and progression characteristics of MS can also provide reasonable evidence for previous demyelination events. The subjective narrative symptoms (previous or present) of the patient should be multiple episodes that last at least 24 h. Before confirming the diagnosis of MS, it is necessary to confirm: at least one attack must be confirmed by neurological examination; patients with previous visual impairment have positive visual evoked potentials; or MRI examination reveals demyelination changes in the CNS area consistent with previous neurological symptoms. b The most reliable clinical diagnosis is based on objective evidence of 2 episodes. In the absence of objective evidence confirmed by neurological examination, reasonable evidence for a previous episode includes: past events with typical symptoms and progression of inflammatory demyelinating disease; at least 1 clinical episode supported by objective evidence . c No additional evidence is required. However, the diagnosis of MS still needs to meet the imaging requirements of diagnostic criteria. When the results of imaging or other tests (such as CSF) are negative, the diagnosis of MS should be taken with caution, and other diagnoses need to be considered. It must be satisfied before the diagnosis of MS: there is no more reasonable explanation of clinical manifestations, and there must be objective evidence supporting MS. d No need to strengthen the lesion. For patients with brainstem or spinal cord syndrome, the responsible lesions are not included in the statistics of MS lesions. |
Differential diagnosis of multiple sclerosis
MS needs to be distinguished from the following types of white matter lesions:
1. Infection: including HIV, tuberculosis, syphilis, Whipple, etc., can be identified based on medical history, accompanying performance of other systems, and laboratory test results of cerebrospinal fluid
2. Inflammation: ADEM, NMO, Hashimoto's encephalopathy, Behcet's disease, and sarcoidosis of the nervous system.
3. Metabolic / nutritive: Wernike encephalopathy, subacute combined degeneration, white matter malnutrition.
4. Mitochondrial disease: MELAS, Leigh disease, Leber disease; can be further identified by mitochondrial genetic examination.
5. Vascular disease: Vasculitis, spinal arteriovenous fistula and malformations need to be further diagnosed by biopsy, angiography, etc.
6. Tumor-related: primary central nervous system lymphoma, paraneoplastic syndrome; the clinical and imaging manifestations of these diseases can be similar to MS, and need to be further identified through tumor-related examination.
7. Others: SCA, CO poisoning, reversible encephalopathy, cervical spondylosis, spinal cord compression, tropical spastic paraplegia (TSP).
Among them, the identification with ADEM and NMO is required, as shown in Table 4 and Table 5.
Table 4 Identification points of MS and ADEM
| Identification characteristics | MS | ADEM |
1 | Age of onset | Older (Juvenile) Female> Male | Younger (<10 years), no gender difference |
2 | "Cold-like" precursor | Not necessarily | Very often |
3 | Encephalopathy symptoms | Early disease rarely | Must |
4 | Convulsions | Rarely | Not necessarily |
5 | Seizure periodicity | Seizures at least 4 weeks apart | Single, lasting up to 12 weeks |
6 | Large gray matter lesions on MRI | Rarely | After common |
7 | MRI image enhancement map | After common | After common |
8 | MRI tracking changes | Relapse and new lesions appear | Lesions can disappear or have only a few sequelae |
9 | CSF leukocytosis | Rare (if any, no more than 50) | Varying degrees |
10 | Oligoclonal band | Often positive | Positive to varying degrees |
11 | Response to corticosteroids | well | very good |
Table 5 Identification points of MS and NMO
| Identification characteristics | MS | NMO |
1 | Epidemiology | | |
| Male: Female ratio | 1: (2-3) | 1: (5-10) |
| Age of onset | 2040 years | 30-40 years old |
2 | Course of disease | | |
| Types of | Relapsing-remitting | Recurrent type with high early recurrence rate |
| Condition | Lighter and better recovery | Severe, incomplete recovery |
| Permanent disability | Usually in progress | Related to relapse |
3 | Clinical manifestation | | |
| Affected area | Optic nerve, spinal cord, cerebellum, brain stem, hemisphere | Optic nerve and spinal cord |
| Myelitis | APTM | ACTM, involving the medulla oblongata, resulting in stubborn nausea, hiccups, or respiratory failure |
| Optic neuritis | Light or moderate | Severe, can occur quickly on both sides simultaneously or sequentially |
| Brain symptoms | Common (diplopia, internuclear ophthalmoplegia, anaesthesia, or weakness) | Yes (encephalopathy, hypothalamic dysfunction) |
4 | Auxiliary inspection | | |
| Spinal MRI | Less than 2 spinal cord segments | More than 3 or more spinal cord segments |
| Asymmetric eccentric distribution involving the posterior spinal cord | Central gray matter or whole spinal cross section |
| No or little swelling | With swelling and palate enhancement |
| Brain MRI | Near ventricle, near cortex, under the curtain | MRI is normal or does not meet MS characteristics (Circumventricular area around the ventricle) |
| Round structure with long axis perpendicular to ventricle wall | Fusion, linear lesions |
| CSF | Leukocytosis <15 × 106 / L Predominant monocytes; | Cell proliferation can be> 50 × 106 / L Neutrophils |
| Uncommon protein elevations (<100 mg / dl) | Elevated protein is common (> 150 mg / dl) |
| OCB positive | OCB negative |
| Serum MO-IgG | rare | common |
5 | Concomitant autoantibodies or systemic inflammatory diseases | rare | common |
Multiple Sclerosis Treatment
Multiple Sclerosis Treatment Principles
The main purpose of multiple sclerosis treatment is to inhibit the progression of inflammatory demyelinating lesions, prevent the deterioration of the acute stage and relapse in the remission stage, and adopt symptomatic and supportive therapy at the later stage to reduce the pain caused by neurological dysfunction. Its main treatment principles are as follows:
1. Patients with recurrence and severe injury should use large-dose glucocorticoid intravenous drip;
2. All patients with RR-type MS should be given immunomodulatory therapy for a long time;
3. SP type MS patients need to be given early treatment;
4. PP patients with poor response to treatment to improve the condition;
5. MS is a lifelong disease and there have been no recent cases of discontinuation of treatment. If the patient cannot tolerate one treatment or fails, another treatment is needed;
6. The disease activity of the patient needs to be detected clinically and / or by MRI. Changes or additions to treatment should be initiated before irreversible functional impairment occurs.
Specific treatments for multiple sclerosis
as follows:
1. Relapsing-remitting (RR) multiple sclerosis
(1) Acute treatment
Corticosteroids: It is the main therapeutic drug for the onset and relapse of multiple sclerosis. It has anti-inflammatory and immunomodulatory effects, can promote the recovery of acute relapse and shorten the course of relapse, but it can not improve the degree of recovery. Long-term application cannot prevent recurrence, and serious adverse reactions can occur. Methylprednisolone (methylprednisolone, MPL): can reduce inflammation and edema, currently advocated for use in the acute active phase of multiple sclerosis, large-dose short-course therapy: the most commonly used, 1g / d was added to 500ml of 5% glucose intravenously for 3 to 5 days, and then the oral prednisone 60 mg / d was changed, and gradually reduced to 4 to 6 weeks until the drug was discontinued. It is usually used in patients with less severe attacks. During treatment with corticosteroids, pay attention to check electrolytes, blood sugar, blood pressure regularly, routine potassium and calcium supplements, and use gastric antacids to protect the gastric mucosa.
Intravenous immunoglobulin (IVIG): 0.4g / (kg · d) for 3 to 5 days. It has a certain effect on reducing the recurrence rate of patients with RR type, but it is best to apply it early. The treatment can be strengthened once a month according to the condition, and the dosage is still 0.4g / (kg · d) for 3 to 6 consecutive months.
Plasma exchange (PE) PE is mainly used for MS patients who are not sensitive to high-dose corticosteroid treatment. At present, the exact mechanism of PE treatment, the duration of efficacy and the effect on relapse are not clear. The possible mechanism is related to the elimination of autoantibodies.
(2) Treatment in remission
Four major FDA-approved drugs are used in the RRMS stabilization phase, interferon, glatiramer acetate, natalizumab, and fingolimod.
-interferon (interferon-, IFN-) -interferon (interferon-, IFN-) therapy: IFN- has immunomodulatory effects, can inhibit lymphocyte proliferation, antigen presentation, and regulate cytokine Produces, inhibits T cells from crossing the blood-brain barrier by down-regulating the expression of adhesion molecules and inhibiting T cell metal matrix proteases. Two types of recombinant preparations, IFN-1a and IFN-1b, have been approved for marketing in the United States and Europe as recommended drugs for the treatment of RR-type MS. The structure of IFN-1a is basically the same as that of human physiological IFN-. IFN-1b lacks a glycosyl group, and serine is substituted for cysteine at position 17. IFN-1a and IFN-1b have obvious effects on acute exacerbation, and IFN-1a is effective in maintaining stable conditions.
IFN-1a can be used in the treatment of MS in the first episode of 22 g or 44 g, subcutaneous injection, 1 or 2 times / week; confirmed R-RMS, 22 g, 2 or 3 times / week. It is well tolerated and has less disability. IFN-1b was 250 g and was injected subcutaneously every other day. Both IFN-1a and IFN-1b need to be continuously administered for more than 2 years, and the efficacy generally decreases after 3 years of administration.
A common adverse reaction is flu-like symptoms that last 24 to 48 hours and usually do not occur after 2 to 3 months. IFN-1a can cause swelling and pain at the injection site, liver damage, and severe allergic reactions. IFN-1b can cause swelling and tenderness at the injection site, occasionally local necrosis, mild increase in serum transaminase, leukopenia, or anemia.
An analogue of artificial myelin basic protein synthesized by Glatiramer acetate (GA). The possible mechanism of action is to transform T cells from Th1 phenotype to Th2 phenotype, thereby promoting the anti-inflammatory cytokine. produce. Induces immune tolerance in myelin-reactive T cells. Subcutaneous injection, 20mg / day.
Natalizumab (natalizumab): Recombinant 4-integrin (lymphocyte surface protein) monoclonal antibody, can prevent activated T lymphocytes from crossing the blood-brain barrier. More than 2 relapses within 1 year, and more than 1 MRI enhanced lesions. Try to avoid PML in monotherapy.
Fingolimod (FTY270): It is a new type of immunosuppressant synthesized by chemical modification of antibiotic components extracted from culture medium of ascomycetes of cicada larvae. ) -2-Aminopropanediol hydrochloride, a sphingosine-1-phosphate (s1P) receptor modulator, binds to the s1P receptor on the surface of lymphocytes after phosphorylation in vivo, changes the migration of lymphocytes and promotes cells Enters the lymphatic tissue and reduces LC infiltration in the CNS.
2. Treatment of secondary progressive (SP) and progressive recurrent (PR) MS:
(1) In 2000, the US FDA approved mitoxantrone for SP-type MS. The recommended dose is 12 mg / m2. Intravenous infusion. The total dose of mitoxantrone used to treat MS should not exceed 140 mg (excessive drugs may cause poisoning). It can reduce the recurrence rate of MS by 60% and ease the progress of MS.
Common side effects include: nausea, baldness, leukocytopenia, and anemia. Myocardial toxicity is another common side effect of mitoxantrone. Therefore, the use of mitoxantrone in the treatment of MS requires close monitoring of the left ventricular ejection fraction and regular measurement of blood routine and liver function.
Other immunosuppressants such as methotrexate, cyclophosphamide, and cyclosporine A can also be used to reduce the symptoms of multiple sclerosis, but there is no reduction in the demyelinating lesions shown by MRI, only for adrenal glucose Patients who did not respond to corticosteroids.
Methotrexate (MTX) Methotrexate (MTX): Can inhibit cellular and humoral immunity, and has anti-inflammatory effects. Chronic progressive MS patients with moderate to severe disability are treated with MTX 7.5mg per week for 2 years orally, which can significantly reduce the deterioration of the disease, and is especially effective for secondary progressive patients.
cyclophosphamide (cyclophosphamide): should be used for rapid progress of MS ineffective in MTX treatment. Advocate long-term low-dose oral administration, 50mg / time, twice daily for one year. Leukopenia and hemorrhagic cystitis are common adverse reactions to the drug.
Azathioprine: It can alleviate the progress of the disease course and reduce the recurrence rate of multiple sclerosis. 2 mg / (kg · d) orally for two years.
cyclosprine A (cyclosprine A): Cyclosporine A (cyclosprine A): is a powerful immunosuppressive drug, medication for 2 years can delay the disability time. The dose should be within 2.5mg / (kg · d), and> 5mg / (kg · d) is prone to renal poisoning. The serum creatinine level (<1.3mg / dl) needs to be monitored. To reduce the toxicity, it can be divided into two or three times orally . Renal toxicity occurs in 84% of patients, and hypertension is common.
(2) Recent clinical and MRI studies suggest that IFN-1a and IFN-1b can reduce the rate of progression of secondary progressive multiple sclerosis. The confirmed SPMS can be subcutaneously injected with 44 g of IFN-1a 2 to 3 times / week.
(3) Hematopoietic stem cell transplantation: The principle of hematopoietic stem cell transplantation is to perform immune reconstruction to make the central nervous system immune tolerant, so as to achieve the purpose of treatment, but it should be considered only when other treatment methods are ineffective.
3. Specific immunomodulatory therapy is not effective for primary progressive multiple sclerosis, mainly symptomatic treatment. Plasma exchange may be useful for outbreaks, but randomized controlled trials have shown poor efficacy in chronic cases.
4. Symptomatic treatment
(1) Fatigue symptoms: adequate bed rest should be guaranteed to avoid overwork, especially in the acute relapse period. Fatigue is a common complaint in many patients, and sometimes it may be effective with amantadine (100 mg taken orally at morning and noon) or selective serotonin reuptake inhibitors such as fluoxetine, citalopram, and the like.
(2) Bladder and rectal dysfunction: bethanechol chloride (bethanechol chloride) may be useful for urinary retention, and it can be used for intermittent catheterization when ineffective. Monitoring residual urine volume is an important measure to prevent infection. Bromamphetamine can be used for urinary incontinence.
(3) Severe spastic paraplegia and thigh pain flexor spasm: oral baclofen or baclofen or placement of a micropump and an intrathecal catheter may be effective. Orthostatic tremor is orally treated with isoniazid 300mg / d, which is increased by 300mg per week up to 1200mg / d. Combining with pyridoxine 100mg / d can improve; carbamazepine or clonazepam is effective in a few cases.
Prognosis of multiple sclerosis
Patients can recover at least partially after an acute attack, but the frequency and severity of relapses is difficult to predict. Factors suggesting a good prognosis include women, onset before the age of 40, visual or somatosensory clinical manifestations, and the appearance of a cone system or cerebellar dysfunction indicates a poor prognosis. Although it may eventually lead to some degree of dysfunction, the prognosis of most patients with MS is more optimistic. About half of patients have only mild or moderate dysfunction after 10 years of onset, and the survival time after disease can be as long as 20-30 years, but a few Can die within a few years.
Multiple Sclerosis Care
Intervention for multiple sclerosis anxiety and depression
(1) Establish a good family support system
MS has a long course, recurrent conditions, and long treatment time, which brings tremendous mental and economic stress to the family and patients. Long-term stress causes patients with emotional abnormalities. Anxiety and depression affect the treatment and rehabilitation of patients. A good social support system can reduce the occurrence of adverse emotions in patients, ensure timely treatment of patients, and delay the illness. [5]
(2) Self-decompression and maintain a good attitude
Patients should self-adjust their mentality and choose the decompression method that suits them. You can talk to your friends and classmates and find ways to vent your dissatisfaction and anger. Choose your favorite exercise method and stick to it.
People can choose to jog, swim and play Tai Chi, or relax themselves and listen to some brisk music.
Multiple Sclerosis Diet Guide
Ensure a nutritionally balanced diet
Eat less fat, oil, sugar, salt, eat lean meat, fish, soy products, fruits, vegetables, and calcium-rich foods. O When you are in a good state, you can increase your appetite, eat in small mouths, chew slowly, and eat a small number of meals.
Guidance for those with difficulty swallowing or chewing
In the advanced symptoms of MS, it can be manifested as bulbar paralysis, coughing with drinking water, and difficulty eating.
1) People with swallowing disorders should prefer pasty foods or use thickeners.
2) Select a thick spoon with a small handle and a long handle.
3) Choose a cup that does not touch the nose.
4) A wide-mouth flat-bottomed porcelain bowl should be selected and non-slip mats can be used at the same time.
Difficulty swallowing should also pay attention to the position of eating. Patients who can sit up should eat in the sitting position. Patients who can't sit up should raise the bed head at least 30 ° and bend forward. The feeder should stand on the affected side of the patient and swallow on the healthy side. It is contraindicated to feed in a flat position. Gastric tube insertion should choose thin liquid or thick liquid, milk custard broth baby rice paste can be, go to the hospital once a month to change the gastric tube, every time before feeding liquid, the gastric juice should be pumped back to the stomach.
, Multiple sclerosis actively cooperates with treatment, and do good self-observation of drugs
Hormones are the most common and important drugs for the treatment of MS. When taking them, they must be gradually reduced to discontinuation according to the doctor's order, and can not be increased or decreased at will, or even discontinued. Common side effects of hormones include obesity, hypertension, osteoporosis, gastric duodenal ulcers, etc. Patients should pay attention to observe blood pressure, stool color, stomach discomfort, and seek medical attention if there are abnormalities.
The systemic side effects of -interferon are similar to flu-like symptoms. Headaches, fever, chills, joint or muscle pain are generally the most obvious at the beginning of medication, and gradually decrease in the first or second month of treatment. -4 hours appear. Local side effects include focal flushing at the injection site, which can last for several weeks. Necrosis can occur in severe cases, but it is rare. These symptoms are usually not severe, so don't worry, they will gradually decrease and disappear. Interferon injections are administered subcutaneously or intramuscularly by family members or patients, and each injection requires a change of site.
Multiple sclerosis prevents urinary tract infections and constipation
Patients with MS have obvious defecation disorders. Adequate water intake should be ensured. Drink at least 1500-2000 ml of water a day, and should not drink water O 2 hours before bedtime. Urinary incontinence can be replaced in time with a urine pad, and the perineum can be cleaned twice a day. Urinary storage patients can use intermittent urinary catheterization (interval 4-6 h). If the urine is cloudy, drink plenty of water and seek medical attention. Recognize the symptoms and signs of early urinary tract infections: frequent urination, urgency, and dysuria.
Prevent constipation: Eat high-fiber foods such as plantains and massage clockwise on the abdomen to promote bowel movements. [5]
Multiple sclerosis limb exercise
Objective To delay disease progression and reduce recurrence, maintain and improve various functions, and maximize the quality of life of patients.
(1) Principle Early start: Rehabilitation treatment should be started at the early stage of the disease and when the condition has eased.
Step by step: The treatment content should be planned. Continuous and regular rehabilitation can help patients restore muscle tension, increase muscle endurance and bone strength, help patients adjust mood swings, sleep well, and prevent and treat depression.
Varies from person to person: The treatment method and intensity depend on the location and severity of the disease.
Targeted treatment: one side limb dysfunction, can use the healthy side limb to help the affected limb activity, upper limb dysfunction, you can use lower limb activities to drive upper limb exercise; lower limb dysfunction, you can use upper limb activities, such as wheelchair and bed activities to help the lower limb work out. The intensity should be small at the beginning and gradually increase the amount of exercise.
(2) Rehabilitation assessment
Nerve dysfunction. Evaluation of motor function (assessment of joint range, muscle prescription, muscle tension). Evaluation of self-care ability in daily life. nerve function assessment.
(3) Improve motor function
joint function training: the focus is to maintain normal range of joint movements and correct deformed posture. Generally, active and passive movement methods are adopted. Joint loosening techniques should be applied to those with tight joint capsules. If contracture occurs, continuous stretching can be considered. Splints can also be used to help patients maintain the most ideal posture. Exercise and aerobic endurance training, but the intensity, type and frequency of training should be determined according to the specific physical condition of the patient. Because patients are prone to fatigue and heat intolerance, exercise is often restricted. The method to overcome is to add 1 to 5 minutes of rest during exercise, and arrange physical activities in a cold environment that rarely raises the body temperature as much as possible; Relieve muscle spasm: mainly extensor spasm, can perform trunk flexion Rotating activities, spiral or diagonal limb movement patterns are the focus of training. Other antagonist muscles, such as flapping, shaking, or tapping on the spastic muscles, can reduce muscle spasms. Persistence of passive movement of the joint every day, continuous stretching or compression of the long tendon of the spastic muscle can also reduce spasm; ataxia gait training: mainly correct the ataxia by improving the stability of the patient's proximal end; feeling Handling of obstacles: Superficial sensory loss can increase sensory response of the limb through sensory stimulation such as vigorous brushing and rubbing; proprioceptive loss can be improved or compensated by sensory feedback treatments such as verbal instructions and audiovisual feedback. [6]
Multiple sclerosis safety protection
Anti-aspiration: those who have difficulty swallowing carefully feed and shake the bed head high.
Fall prevention: The home is non-slip and removes obstacles from the home.
Anti-scald: For those with numbness and numbness, use hot water bottle with caution. The water temperature should not exceed 50C.
Anti-decubitus: Long-term bedridden people pay attention to the mattress should be soft, often turn over, keep the skin dry and clean, to prevent skin pressure caused by pressure sores. [5]
