Overview
多发性硬化是中枢神经系统炎性脱髓鞘疾病
发病与自身免疫相关，遗传和环境也参与
以药物治疗为主
临床类型不同，预后不同
What is Multiple Sclerosis?
Definition.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system.
Myelin is a membrane that wraps around the outside of nerve fibers and serves as an insulator. Loss of the myelin sheath affects nerve function, and appropriate clinical symptoms can occur.
It is an autoimmune disease, and genetic and environmental factors are also involved in its pathogenesis.
Types
Relapsing-remitting type (RRMS): characterized by recurrent attacks and remissions, it is the most common type.
Secondary progressive type (SPMS): develops from RRMS and is characterized by a gradual decrease in the number of episodes but a gradual increase in neurological disability.
Primary progressive type (PPMS): slow progressive exacerbation from the outset with no remitting relapsing course.
Progressive relapsing type (PRMS): gradual progression of neurological disability with a small number of acute attacks in the process.
Incidence
The incidence rate in China is low, about 0.288 per 100,000 adults and 0.055 per 100,000 children.
Residents of high latitude and high altitude areas are susceptible to multiple sclerosis.
The disease is most common in young adults, with the peak incidence between the ages of 40 and 49.
The proportion of women with the disease is 1.5 to 2 times that of men.
Questions you may be concerned about
Can multiple sclerosis be cured?
Multiple sclerosis can be treated to relieve symptoms, but it cannot be cured.
Multiple sclerosis is an autoimmune-related disease.
The main manifestations are limb weakness, sensory abnormalities, visual impairment, ataxia, etc. Most of them show the process of attack-remission-relapse, which is repeated many times.
If diagnosed in time and treated with standardized medication, the symptoms can be relieved and relapses can be reduced and progress can be slowed down.
Does MS always cause disability?
Most people with multiple sclerosis will be disabled.
A small number of MS patients have few neurological symptoms and signs for more than 10 years after the onset of the disease.
However, most patients will have some residual neurological deficits after each relapse, and as the disease progresses, the residual symptoms gradually increase, which can eventually lead to disability.
Patients with multiple sclerosis can delay the process of disability through active treatment and rehabilitation exercises.
Is there a cure for multiple sclerosis?
Currently, there is no cure for multiple sclerosis.
Multiple sclerosis is mainly treated with medication to control the relapse and progression of the disease.
Glucocorticoids, immunoglobulin, plasma exchange and other treatments are used in the acute stage, and disease-modifying drugs, such as teriflunomide, sinimod, fingolimod, etc., as well as targeted B-cell immunotherapy, such as rituximab, ofatumumab, etc., are used in the remission stage.
Etiology
Causes
The exact cause of multiple sclerosis is unclear and may be related to factors such as genetics, viral infections, and autoimmune reactions.
Genetic factors
Multiple sclerosis has a clear tendency to develop in families. The probability of one identical twin having the disease is 30%, while the probability of the other twin having the disease is 3% to 5% for fraternal twins.
Parents or siblings of multiple sclerosis patients have a prevalence rate 12 to 15 times higher than that of the general population.
Viral infection
Associated with the induction of an autoimmune response following viral infections, such as measles virus, human herpes virus type 4 (EBV), and human herpes virus type 6 (HHV-6).
Autoimmune reaction
Associated with abnormal antibodies in the body attacking its own normal tissues.
Predisposing factors
Decreased sun exposure and vitamin D deficiency: can increase the risk of MS onset and relapse.
Poor diet: a high-fat diet may increase the probability of developing MS.
Smoking: Smoking or secondhand smoke can significantly increase the likelihood of developing multiple sclerosis and worsen the condition.
High temperatures: Hot weather, hot baths or fever may cause exacerbation of the disease.
Pathogenesis
The myelin sheath that surrounds the nerve fibers is attacked by abnormal antibodies in the body and undergoes a pathological change that separates it from the nerve fibers, resulting in what is called “demyelination” (if you think of a nerve as a piece of electrical wire, the demyelination change is the peeling off of the skin on the outside of the wire).
When a nerve is “demyelinated”, the membrane potential of the nerve cell is altered and information is not transmitted, leading to a range of sensory, motor and cognitive impairments.
Symptoms
Multiple sclerosis is characterized by a wide range of clinical symptoms, which can be recurrent.
Most patients present with Clinically Isolated Syndrome (CIS) at the first attack, which often involves the spinal cord, brainstem, optic nerves and other parts of the body, with visual loss, numbness of the limbs, weakness of the limbs, and urinary and defecation disorders. The lesions are characterized by temporal isolation and clinical symptoms lasting more than 24 hours.
Most patients with CIS can progress to multiple sclerosis after experiencing a first attack.
Main manifestations
Limb weakness
Most common, first symptoms include weakness of one or more limbs in about 50% of patients. It is usually more pronounced in the lower limbs than in the upper limbs, and may be hemiplegic (weakness in one limb), paraplegic (weakness in both lower limbs), or quadriplegic (weakness in all four limbs).
Varying degrees of physical fatigue are present, sometimes feeling extremely tired with a little activity.
Sensory abnormalities
Tingling sensation, numbness, ants, itching or burning pain in the limbs, trunk or face.
Deep sensory disturbances may be present. Deep sensations include muscle and joint positional, kinesthetic, and vibratory sensations. For example, if the patient closes his eyes and the examiner touches one of his fingers or toes and asks him to answer which one he is touching, an incorrect answer is a positional sensory disorder.
Visual impairment
Sharp decrease in vision in one eye, sometimes both eyes are involved at the same time, which may be accompanied by eye pain.
About 30% of patients have ocular muscle paralysis (inability to rotate the eye at will, double vision), diplopia (seeing one thing as two or three).
Visual field defects.
Ataxia.
Chanting-like speech: speech that is intonated as if reciting old-fashioned poetry.
Nystagmus: uncontrollable wobbling of the eyeballs.
Intentional Nystagmus: A tremor that occurs when the limb is moving toward a target, but not when it is stationary. For example, when fingering the nose, the hand shakes uncontrollably, but stops shaking when it reaches the tip of the nose.
Unsteady walking.
Psychiatric symptoms and cognitive dysfunction
Most often manifested as depression, irritability and short temper.
Some patients present with euphoria and excitement, but may also present with apathy, lethargy, forceful crying and laughing, repetitive speech, suspicion and delusions of victimization.
About half of the patients may have cognitive dysfunction, which usually manifests as memory loss, slow reaction time, decreased judgment and reduced abstract thinking ability.
Seizure symptoms
More common are tonic spasms (rigidity), sensory abnormalities, dysarthria (difficulty or slurring of speech, slowing of speech), ataxia, seizures, and pain and discomfort.
Episodic neurologic dysfunction lasts from a few seconds to several minutes at a time and can be triggered by frequent hyperventilation, anxiety, or prolonged holding of the limb in a certain position.
Tonic spasms limited to the limbs or face, often accompanied by radiating abnormal pain, are also known as nociceptive spasms.
Other symptoms
Bladder and rectal dysfunction: including urinary frequency, urinary urgency, urinary retention, urinary incontinence and constipation.
Sexual dysfunction may also occur in male patients.
Complications
Some patients may be bedridden for a long period of time due to limb motor and sensory disorders, and the following complications may occur.
Pressure sores: prolonged bed rest can lead to ulceration and necrosis of the skin at the place of pressure.
Double lower extremity deep vein thrombosis: due to the impaired movement of the lower extremities, there may be venous thrombosis, manifested as lower extremity edema.
Pulmonary embolism: the lower limb thrombus dislodged, with the blood flow into the lungs, can lead to pulmonary embolism, the light only manifested as chest tightness, the heavy can cause dyspnea, pulmonary edema, and even life-threatening.
Consultation
Department of Medicine
Neurology
If symptoms such as loss of vision, numbness of the limbs, weakness of the limbs and difficulty in speaking occur, you should consult a doctor promptly.
Preparation for medical treatment
Preparing for your visit: registering, preparing your documents, and frequently asked questions
Tips for seeking medical treatment
Try to keep a record of the symptoms you have experienced and how long they have lasted, so that you can give your doctor more reference.
Special tips: Family members are recommended to accompany you to the doctor, avoid driving or riding to the doctor by yourself.
Preparation Checklist
症状清单
Are there any visual disturbances, limb weakness, sensory abnormalities, unsteady gait, urinary or bowel problems?
Is this the first time you are experiencing these symptoms?
病史清单
Is there a family history of multiple sclerosis?
Is there any history of infection with measles virus, EBV, human herpes virus type 6, etc.?
检查清单
Imaging tests: CT head, MRI head
Other tests: cerebrospinal fluid test, electrophysiologic test
用药清单
Teriflunomide, alemtuzumab, mitoxantrone, carbamazepine, sildenafil, amitriptyline, pregabalin, amantadine, phenelzine hydrochloride, oxybutynin
Diagnosis
Diagnosis is based on
medical history
There is a family history of multiple sclerosis.
There may be a history of autoimmune disease.
Clinical manifestations
症状
Numbness of the limbs, weakness of the limbs, loss of vision, difficulty in speaking, urinary frequency and urgency.
体征
Nystagmus: uncontrollable wobbling of the eyeballs, mostly horizontal or horizontal plus rotation.
Intentional Tremor: If the arm is stretched out and the finger is pointed to the tip of the nose, the hand will shake uncontrollably, but it will stop shaking after pointing to the tip of the nose; or it will shake uncontrollably when reaching for an object, but it will stop shaking once the object is reached.
Lhermitte’s sign (Lhermitte’s sign): a tingling or lightning-like sensation induced by passive flexion of the neck (bowing of the head) that radiates from the neck down the spine to the thighs or feet.
Deep reflex hyperreflexia: e.g., knee hyperreflexia, ankle hyperreflexia.
Other signs: Pathologic reflexes are often present, such as a positive Hoffman’s sign and Babinski’s sign.
Imaging
颅脑CT
Routine CT scans of patients with multiple sclerosis are often normal, with hypodense areas seen only in larger lesions.
It is less sensitive for lesions in the optic nerve, brainstem and spinal cord.
颅脑磁共振（MRI）
It is the most effective auxiliary diagnostic means for detecting multiple sclerosis, and the positive rate can reach 62%～94%, which is significantly better than that of CT, and it can find demyelinating foci in the cerebellum, brainstem and spinal cord, which are difficult to be shown by CT.
Cerebrospinal fluid examination
Cerebrospinal fluid examination can provide an important basis for the clinical diagnosis of primary progressive multiple sclerosis and differential diagnosis of multiple sclerosis.
Cerebrospinal fluid is obtained by lumbar puncture and examined.
Precautions for examination
检查时按照医生要求调整体位。
一旦穿刺针进入体内后，不要咳嗽和移动身体。
做完穿刺后，要去掉枕头平卧6小时左右，防止因颅内压力改变引起头痛。
保持局部皮肤的清洁、干燥，防止穿刺处感染。
Electrophysiologic examination
Electrophysiologic examination is sensitive in detecting subclinical lesions and can assist in early diagnosis, as well as observing changes in the condition of multiple sclerosis.
Electrophysiologic tests include visual, auditory, and somatosensory evoked responses. Visual evoked potentials are more sensitive in diagnosing patients with MS who do not have an exact intracranial lesion (e.g., only a spinal cord lesion).
Examination Considerations
应于检查前一天洗头，以免头皮污垢影响检查结果。
检查前按照医生要求停用或使用相关药物。
放松心情，应避免精神紧张影响检查结果。
Differential Diagnosis
Acute disseminated encephalomyelitis
Similarities: motor deficits, sensory abnormalities, visual deficits.
Differences: Acute disseminated encephalomyelitis (ADEM) is difficult to distinguish from first-onset multiple sclerosis and is usually differentiated from the following.
Acute disseminated encephalomyelitis can occur in children and adults. Multiple sclerosis is less common in children and more common in adults.
Patients with acute disseminated encephalomyelitis tend to have a clear history of antecedent infections or vaccinations, while patients with multiple sclerosis are rare.
When lesions involve the optic nerve, multiple sclerosis usually involves one side first, whereas acute disseminated encephalomyelitis usually involves both sides.
The vast majority of acute disseminated encephalomyelitis has a monophasic course, and the majority of patients with multiple sclerosis have a temporally polyphasic course.
Imaging tests, such as magnetic resonance imaging, are helpful in differentiating.
Optic nerve myelitis
Similarities: loss of vision, eye pain, sensory deficits, motor deficits.
Differences: Optic neuromyelitis optica (NMO) and multiple sclerosis can be differentiated by the following points.
Optic neuromyelitis is more common in Asians and multiple sclerosis is more common in Westerners.
Optic neuromyelitis optica is more common in people between the ages of 5 and 50, and multiple sclerosis is less common in children.
Patients with optic neuromyelitis optica tend to have a clear history of antecedent infection or immunization, while patients with multiple sclerosis are rare.
Magnetic resonance imaging and cerebrospinal fluid examination are helpful in differentiation.
Wernicke’s encephalopathy (Wernicke’s disease)
Similarities: Diplopia, eye movement disorders, mental abnormalities and unsteady walking.
Differences: Wernicke’s encephalopathy is caused by vitamin B1 deficiency and is more common in middle-aged men, especially in alcoholics. Cranial CT or magnetic resonance examination can help to differentiate.
Multiple lacunar cerebral infarcts
Similarities: Sensory abnormalities, dysarthria, visual field changes, ataxia.
Differences: Magnetic resonance examination shows similar morphology of both lesions in supratentorial, but multiple sclerosis shows spatial multiplicity on imaging. The temporal multiplicity of multiple sclerosis also helps in differentiation.
Primary central nervous system lymphoma
Similarities: limb weakness, visual field changes, ataxia, and mental behavioral abnormalities.
Differences: a rare highly malignant non-Hodgkin’s lymphoma. Cranial magnetic resonance examination helps to differentiate. Cerebrospinal fluid cytology sometimes detects lymphoma cells.
Treatment
Treatment in the acute phase is aimed at reducing symptoms, shortening the course of the disease, improving disability, and preventing complications.
Treatment is required in the acute phase for symptoms of functional disability with evidence of objective neurologic deficits, such as vision loss, motor deficits, and cerebellar/brainstem symptoms. Minor sensory deficits do not require treatment and usually resolve with rest or symptomatic management.
Treatment in remission is aimed primarily at controlling disease progression.
Medication
Acute phase
糖皮质激素
Helps to promote neurologic recovery in patients with acute onset of the disease, but prolonged hormone dosing has no long-term benefit for neurologic recovery.
Recommended Use: Intravenous high-dose methylprednisolone shock therapy, or oral prednisone acetate or prednisolone.
Adverse reactions: electrolyte disorders, abnormalities of blood glucose, blood pressure, blood lipids, upper gastrointestinal bleeding, osteoporosis, femoral head necrosis.
静脉注射用丙种球蛋白
Used for pregnant or lactating women, adults who cannot apply hormone therapy or children who are ineffective on hormone therapy.
Recommended Use: Intravenous infusion, use 5 consecutive days as a course of treatment.
Remission
特立氟胺
First-line oral therapy in the treatment of remission.
Teriflunomide may be given to patients with confirmed relapsing forms.
Adverse reactions: diarrhea, vomiting, thinning hair, elevated alanine aminotransferase levels.
Precautions: Teriflunomide is contraindicated in pregnant women or women preparing for pregnancy.
注射用重组人β-1b干扰素
First-line treatment in remission therapy
Adverse reactions: redness, swelling, and pain at the injection site, flu-like symptoms (fatigue, chills and fever, muscle aches, sweating), asymptomatic liver function abnormalities, leukopenia, and thyroid function abnormalities.
Precautions: Contraindicated in pregnant or lactating women.
阿仑珠单抗
Patients with confirmed relapsing forms may be treated with intravenous alemtuzumab.
ADVERSE REACTIONS: Infusion reactions, infections and autoimmune disorders.
米托蒽醌
May reduce relapse rate in patients with relapsing-remitting forms; delays progression in patients with relapsing-remitting, secondary-progressing, and primary-progressing forms.
Adverse reactions: nausea, vomiting, anorexia, diarrhea; cardiac arrhythmias, myocardial infarction; hematopenia due to bone marrow suppression.
Symptomatic treatment
Painful spasms: can be treated with carbamazepine, tizanidine, gabapentin, baclofen and other drugs.
Chronic pain, sensory abnormalities, etc.: can be treated with amitriptyline, pregabalin, selective 5-hydroxytryptamine and norepinephrine reuptake inhibitors (SNRI), norepinephrine-ergic and specific 5-hydroxytryptamine-ergic antidepressant (NaSSA) class of drugs.
Depression, anxiety: can be treated with selective 5-hydroxytryptamine reuptake inhibitors, SNRI, NaSSA analogs, and counseling.
Weakness and fatigue (when more pronounced): can be treated with amantadine and others.
Tremor: can be treated with medications such as Benzhexol hydrochloride and Arotinolol hydrochloride.
Vesico-rectal dysfunction: treated with medication or with the help of catheter, etc. For example, urinary incontinence can be treated with medication such as oxybutynin and tamsulosin.
Sexual dysfunction: can be applied to improve sexual function drugs (such as sildenafil) and other treatments.
Cognitive impairment: cholinesterase inhibitors and other drugs can be applied to treat.
Precautions on the use of drugs for special groups
妊娠期和计划妊娠患者
Any remission therapy drugs are not recommended to be applied during pregnancy.
For patients who are planning a pregnancy but are at high risk of relapse, treatment with glimer acetate or interferon may be used until pregnancy is confirmed.
For patients who are planning a pregnancy but are at very high risk of relapse, treatment with glimer acetate or interferon may be considered throughout the pregnancy.
For patients with persistent highly active disease, delayed pregnancy is recommended. In patients who insist on pregnancy, treatment with natalizumab throughout pregnancy may be considered after a full discussion of the potential risks.
哺乳期患者
Breastfeeding is not recommended, and remission therapy should be initiated as early as possible after delivery to prevent relapse.
Plasma exchange
Treatment with plasma exchange may be attempted in patients with acute severe disease or those who are refractory to hormonal therapy.
Hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation may be effective for patients with severe and refractory multiple sclerosis.
Traditional Chinese Medicine (TCM)
Some Chinese medicines may have the effect of improving multiple sclerosis, such as Astragalus Methyloside, Kidney and Medulla Supplement Tablets. Specific Chinese medicine treatments should be consulted with a specialized Chinese medicine practitioner.
Rehabilitation therapy
Rehabilitation therapy is effective in improving fatigue, movement disorder, gait abnormality, cognitive impairment, etc. It can minimize the disability and improve the motor ability and quality of life of patients.
Patients should receive rehabilitation therapy under the guidance of professional rehabilitation doctors as soon as possible.
Rehabilitation treatment for limb weakness
训练方式
Aerobic exercise: limb linkage training, treadmill walking training, home walking training, lower limb assisted linkage training.
Resistance training: weight-bearing training, elastic band flexibility resistance training, muscle strength enhancement training.
Aerobic exercise combined resistance training.
Balance function and stability training.
作用
Exercise training can significantly improve walking endurance and speed, as well as improve balance function, relieve fatigue and depression symptoms, and reduce the patient’s fear of falling.
Rehabilitation of muscle spasms
Aquatic exercise training is an effective way to relieve muscle spasms.
Adherence to active/passive joint movement and manipulative massage therapy can suppress muscle tension.
If severe spasticity or joint contractures occur, braces or orthotics may be used.
Rehabilitation of tremor and ataxia
Currently, the Frenkel training method is mainly used, with repetitive training in four areas: lying, sitting, standing and walking.
Rehabilitation for dysarthria
Speech is slowed down to allow time for the tongue muscles to compensate for the loss of control of the other organs of articulation.
Communication skills can also be improved by looking at pictures and repeatedly reading aloud the alphabet, single words and words.
Rehabilitation for cognitive dysfunction
Gradually get used to changes and adapt some new methods to improve cognitive function, such as using notepads and calendar cards to record life and work chores, and reciting repeatedly to enhance memory.
Precautions during rehabilitation
During exercise training, you need to be accompanied by family members to prevent accidents such as falls and falling out of bed.
Ensure that the training environment is safe, and remove sharp objects from the surrounding area during training to prevent debris from obstructing the route.
Choose the right time for training. It is not advisable to train on an empty stomach or on a full stomach after a meal.
If spasms (stiffness) or painful spasms (stiffness with pain) occur during training, stop training immediately and relax at the right time.
Ensure that the training intensity is appropriate, and gradually increase the training intensity.
Prognosis
Cure
The prognosis for multiple sclerosis varies greatly depending on the clinical type and course of the disease.
Benign type of multiple sclerosis has a better prognosis, and there is no obvious dysfunction after 15 years of disease onset.
The malignant form of MS may worsen, become disabled, or die within a relatively short period of time after disease onset.
Hazards
In severe cases, the disease may leave severe functional disability, affecting daily life and work.
Repeated attacks of multiple sclerosis can easily leave sequelae, such as limb paralysis, vision loss, blindness, urination or defecation disorders, and so on.
Daily
Daily Management
Dietary management
A diet high in fiber, high in protein, low in fat, low in oil and low in cholesterol is the mainstay.
Eggs, milk, beans and their products, fish, poultry and lean meat are recommended to supplement protein.
Consume plenty of fresh vegetables, fruits and whole grains, such as cooking oats, quinoa, millet, red beans and others with rice.
Eat a light diet and animal fats such as lard should be avoided. Limit your intake of foods high in cholesterol such as egg yolks, organ meats, and excessive amounts of seafood.
Avoid fatty, fried and deep-fried foods such as desserts, cakes, ice cream or sugary drinks.
Ensure adequate water intake.
Life management
When the vision is unclear or diplopia, try to close the eyes to rest or rest both eyes alternately, use reading materials with larger font size, etc.
Family members should create a convenient environment for the patient to move around, such as placing daily necessities on the side with better vision.
Keep the vulva clean and dry, wash and dry it in time after bowel movement, and perform daily vulvar douching to prevent urinary tract infection.
Avoid triggers, such as avoiding high water temperature when bathing and staying away from excessively warm or cold environments.
Prevent colds and other infections, trauma.
Avoid emotional excitement, excessive stress and exertion.
Maintain normal activities, stay active and exercise moderately as much as possible to prevent myasthenia gravis.
Psychological support
Patients and family members can learn and understand more about the disease, correctly recognize the disease, understand the nature and development of the disease, and establish confidence in overcoming the disease.
Family members must be concerned, communicate more with the patient and pacify the patient. Family members or friends must respect the patient and must listen patiently when talking to them. Family and friends should also visit the patient from time to time to reduce their sense of isolation.
In life, try to take care of the patient’s habits. Encourage the patient to participate in social and family activities. Let the patient do things that he or she can accomplish by himself or herself. Family members should praise and encourage his or her success in self-care, which will help enhance the patient’s self-confidence.
Patients can also listen to soft music, take deep breaths, watch entertainment programs and other methods to relax their body and mind and relieve their bad moods.
Prevention
The cause of multiple sclerosis is still unclear and there are no specific and effective preventive measures for the time being. Staying away from risk factors can help minimize the occurrence, aggravation or relapse of the disease.
Avoid high water temperature when bathing.
Quit smoking.
Enhance nutrition, exercise properly, and strengthen the resistance of the body.
Reasonable arrangement of life and work, ensure sufficient sleep.
Follow the doctor’s instructions to adhere to the medication, can not stop the medication without authorization.
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