Multiple sclerosis (MS) is characterized by a scattered, rag-like demyelination in the brain and spinal cord. Common symptoms may include visual and oculomotor abnormalities, paresthesias, weakness, spasticity, voiding dysfunction and mild cognitive symptoms. Typically, neurologic deficits are varied, with remissions and exacerbations gradually cause disability. Diagnosis requires clinical or MRI evidence of ? 2 characteristic neurological lesions in time and space (location in the CNS) are separated. Treatment includes corticosteroids in acute exacerbations, immunomodulatory drugs for the prevention of attacks and supportive measures.
(See also Overview of demyelinating diseases.)
Multiple sclerosis (MS) is characterized by a scattered, rag-like demyelination in the brain and spinal cord. Common symptoms may include visual and oculomotor abnormalities, paresthesias, weakness, spasticity, voiding dysfunction and mild cognitive symptoms. Typically, neurologic deficits are varied, with remissions and exacerbations gradually cause disability. Diagnosis requires clinical or MRI evidence of ? 2 characteristic neurological lesions in time and space (location in the CNS) are separated. Treatment includes corticosteroids in acute exacerbations, immunomodulatory drugs for the prevention of attacks and supportive measures. (See also Overview of demyelinating diseases.) The cause of MS, an immunological mechanism is adopted. A postulated cause is an infection with a latent virus (possibly with a human herpes virus such as Epstein-Barr virus) which, when activated, triggers a secondary autoimmune response. An increased incidence within certain families and the presence of allotypes (HLA-DR2) of human leukocyte antigen (HLA) suggests a genetic predisposition. MS is more common in people who have spent their first 15 years of life in a temperate climate (1/2000) than in people who have stayed at this time in the tropics (1 / 10,000). One explanation is that lower vitamin D levels are associated with an increased risk of MS. The vitamin D levels correlate with the degree of sunlight, which is lower in moderate climates. Smoking also appears to increase the risk. The age at onset varies between 15 and 60 years, typically it is 20-40 years; Women are affected slightly more often. Neuromyelitis optica (Devic’s syndrome), which has been viewed as a variant of MS is now recognized as a separate disorder. Pathophysiology occur localized demyelinated areas (plaques) which with destruction of oligodendroglia, perivascular inflammation, and chemical changes in lipid and protein constituents of myelin in and around the plaques. Destruction of axons is possible, however, remain cell bodies rather relatively well preserved. A fibrous gliosis develops in plaques that are scattered throughout the CNS, primarily in white matter, particularly in the lateral and posterior column of the spinal cord (v. A. In cervical sections) in the optic nerve and in the periventricular areas. Railways in the midbrain, pons and cerebellum are also affected. The gray matter in the brain and spinal cord may be affected, but to a much lesser extent. Symptoms and complaints Multiple sclerosis is characterized by several CNS deficits, with remissions and recurring exacerbations (relapses). These relapses occur with a frequency of an average of 1 every 2 years, but the frequency varies considerably. Although MS can progress unpredictable and go back, there are typical historical pattern: Relapsing remittent pattern: thrusts alternating with remissions, while a partial or complete involution occurs or the symptoms are stable. Remissions can last months or years. Relapses may occur spontaneously or be triggered by an infection such as influenza. Primary progredientes pattern: The disease progresses slowly and without remissions, although there may be plateaus temporarily, where the disease does not progress. Unlike the relapsing-remitting pattern there are no clear exacerbations. Secondary progredientes pattern: This pattern begins with relapses alternating with remissions (relapsing-shaped pattern), followed by a gradual progression of the disease. Progredientes relapsing-shaped pattern: The disease progresses slowly, the progression but is interrupted by sudden, significant relapses. This pattern is rare. The most common initial symptoms are paresthesias in one or more extremities, in the trunk or on one side of the face weakness or clumsiness of a leg or a hand visual disturbances (eg, partial loss of vision and pain in one eye because of retrobulbar neuritis, diplopia due. an internuclear ophthalmoplegia, scotoma) Other common early symptoms include a slight stiffness or unusual fatigability of a limb, minor gait disturbances, difficulty with bladder control, vertigo, and mild mood disorders; all indicate a mostly disseminated CNS involvement and can be discreet. Fatigue is common. Extreme Heat (. As warm weather, a hot bath, fever) symptoms may temporarily worsen (Uhthoff phenomenon). There are often mild cognitive symptoms apathy, limited (self-) assessment or inattention may occur. Mood disorders, incl. Emotional lability, euphoria or, most common, depression, occur frequently. Depression can be reactive or partly be due to cerebral lesions in MS. Some patients have seizures. Cranial nerves The unilateral or asymmetric optic neuritis and bilateral internuclear ophthalmoplegia (INOP) are typical. The optic neuritis caused vision loss (blindness of scotomas to rich), Bulbusschmerzen during eye movement and sometimes abnormal visual fields, papilledema or a partial or complete afferent pupillary defect. The internuclear ophthalmoplegia (INO) occurs when lesions of the medial longitudinal fasciculus (MLF) of the III., IV., And VI. Cranial nerve nucleus connects. While a lateral view abduction movement of one eye is lowered, the other with a nystagmus of (abduzierenden) eye; the convergence is intact. MS INO is typically bilateral; unilateral INO is often caused by ischemic stroke. Fast, kleinamplitudige Augenoszillationen at (primary) straight-ahead (Pendular) are rare, but characteristic of MS. Dizziness occurs frequently. Intermittent one-sided facial weakness or pain (similar to a trigeminal neuralgia), paralysis or spasm may occur. A slight dysarthria can be adjusted, which is caused by a Bulbärparese, cerebellar damage or disruption of cortical control. Other cranial nerve deficits are unusual, but may secondarily Motorized by a brain stem injury entstehen.Motorik weakness is common. They mostly reflected damage to the corticospinal tracts in the spinal cord, preferably to the lower extremities and is bilateral and spastic. Deep tendon reflexes (Patellarsehnen- and Achilles tendon reflex) are usually increased, and often are a positive Babinski sign and clonus ago. The spastic paraplegia resulting in a stiff, poorly balanced gait; in advanced cases, patients may be wheelchair-bound. Painful Beugespasmen in response to sensory stimuli (eg. B. linens) may occur in the late history. The damage to the brain or spinal cord can lead to hemiparesis, which is sometimes standing in the foreground symptom. Limited mobility increases the risk of Osteoporose.Kleinhirn In advanced MS cerebellar ataxia may cause along with a spasticity serious disability; other cerebellar symptoms include slurred, halting speech (slow debate with the tendency at the beginning of a word or syllable hesitation) and the Charcot triad (intention tremor, faltering speech and nystagmus) .Sensorik paresthesia and partial loss of sensory perceptions of any kind are common and often circumscribed (eg., one or both hands or legs). Various painful sensory disturbances (z. B. burning or pain, which feel like an electric shock) can occur spontaneously or as a result of contact, v. a. if the spinal cord is affected. One example is the Lhermitte’s sign, a sudden, like an electric shock occurring pain that propagates along the spinal cord to the legs when the neck is bent. Objective changes of the sensor are often temporary, and in the early stages of the disease difficult to zeigen.Rückenmark The involvement of the spinal cord usually caused bladder dysfunction (eg. As stress incontinence or urinary retention, high Restharnanteil, light urinary incontinence). Constipation, erectile dysfunction in men and genital anesthesia in women may occur. A complete urinary and fecal incontinence may occur in advanced MS. Progressive myelopathy, a variant of the MS caused to the spinal cord level motor weakness but no other deficits. Diagnosis Clinical criteria MRI of the brain and spinal cord Sometimes CSF IgG levels and evoked potentials multiple sclerosis is suspected in patients with optic neuritis, INO or other symptoms that indicate a MS, v. a. if the deficits are multifocal or intermittently occur. If MS is suspected, MRI of the brain and spine are performed. MRI is the most sensitive imaging methods in MS and may exclude other treatable disorders that may mimic MS such. B. nichtdemyelinisierende lesions in the transition area between the spinal cord and medulla oblongata (z. B. subarachnoid cyst foramen magnum tumors). A reinforcement by gadolinium contrast agent can distinguish between active and inflamed older plaques. The sensitivity of MRI is increased by twice the contrast dose given (this is standard procedure) and the scan is delayed (double-dose delayed-scanning). Also MRI magnet with wider angles (3-7 Tesla) may differ perivenular MS plaques of nonspecific white matter lesions. An MS must be distinguished from: Clinically isolated syndrome (consisting of only one clinical manifestation typical of MS) ??Radiological isolated syndrome (MRI findings typical of MS that found by chance in patients without clinical manifestations, be). MS can be distinguished because a diagnosis of MS detection of CNS lesions in time and space (location in the CNS) are separated requires. For example, any of the following points may indicate a temporal separation: Earlier chronic exacerbations and remissions are frequent. MRI showing reinforcing and non-reinforcing lesions at the same time, even if patients are asymptomatic a new lesion in a subsequent MRI in patients with a previous lesion Each of the following information may indicate a spatial separation: development of MRI lesions in ? 2 areas in are affected generally by MS (z. B. the periventricular, juxtacortikalen or infratentorial areas or spinal cord) clinical evidence of a lesion at a different time, as a preceding or subsequent deficit additional laboratory tests If MRI and clinical findings are not diagnostic typical of MS, but do not match it, additional tests may be needed to separate neurological Anoma lien to objectify. Such an investigation can evoked potentials and occasionally include CSF or blood tests. Evoked potentials (delayed electrical response to sensory stimulation) are often more sensitive to MS as clinical symptoms. Visual evoked potentials are sensitive and particularly useful in patients without a confirmed cranial lesions (z. B. with lesions only in the spinal cord). Somatosensory evoked potential and auditory brainstem response are usually also measured. CSF examination is performed less frequently (because the diagnosis can usually be based on MRI), but can be useful if MRI and clinical findings are inconclusive or if an infection (eg. As CNS disease) must be excluded. It is a CSF, incl. Opening pressure, cell count and Zelldiferenzierung, determination of protein, glucose, immunoglobulins, oligoclonal bands and basic usually myelin protein and albumin performed. IgG is usually (typically <11%) (typically <27%) increased or Liquoralbumin in relation to Liquorkomponenten like protein. IgG levels correlate with the severity of the disease. Oligoclonal bands can usually be detected by electrophoresis of cerebrospinal fluid. During an active demyelination myelin basic protein can be increased. The lymphocyte count in the cerebrospinal fluid and total protein may be slightly increased. Blood tests may be needed. Sometimes systemic diseases (. Eg SLE) and infections (. Eg Lyme disease) can mimic an MS; they should be excluded by specific blood tests. Blood tests for the detection of an optica specific IgG antibody for Neuromyelitis (Aquaporin-4 Antibodies [also known as NMO-IgG]) can be carried out in order to distinguish the interference from an MS. Prognosis The course is highly variable and unpredictable. In most patients, v. a. when the MS begins with an optic neuritis, the remissions can last months for 10 years to>. Most patients who have a clinically isolated syndrome eventually develop MS, with a second become distinct lesion or MRI that detects a lesion, 2 to 4 years after the first symptoms have usually started. Treatment with disease-modifying drugs can delay this progression. If patients have a radiologically isolated syndrome, the progression of MS is a risk, but further studies of this risk is necessary. When the initial brain or spinal MRI shows more extensive disease, patients may have the risk of an earlier disability, as well as patients who are motorized, bowel and / or bladder symptoms when they imagine. Some patients, such as men with onset in middle age and with frequent relapses can quickly learn an increase in disability. Smoking can accelerate the course of Krnakheit. Life expectancy is shortened only in very severe cases. Treatment corticosteroids in acute attacks immune modulators for the prevention of relapses baclofen or tizanidine in spasticity gabapentin or tricyclic antidepressants in pain Supportive treatment to the treatment goals of multiple sclerosis include the following: reduction of acute exacerbations Decreasing frequency of exacerbations symptom relief Maintaining the patient’s ability to go (which is especially important) Disease modifying drugs Acute flare-ups that cause objective, limit its function deficits (eg. B. limitations of vision, strength or coordination) are short-term corticosteroid treatment (eg. prednisone 60-100 mg / Tag po once a day, consisting of about 2-3 weeks Methylprednisolone is slipped, 500-1000 mg / day i.v. about once a day 3-5 days). There are some indications that i.v. administered corticosteroids reduce acute relapses, slow the progression, and improve MRI scans of the disease. An immunomodulatory therapy, such as interferons (IFN) or glatiramer, the shear rate decreases and delays any possible disability. Typical treatments include the following: Interferon beta-1b 8 million IU s.c. every other day interferon beta-1a 6 million IU (30 mcg) i. m. weekly interferon beta-1a 44 mcg s. c. 3 times a week Frequent adverse effects of interferons are flu-like symptoms and depression (rather decrease over the treatment time), the development of neutralizing antibodies after months of therapy and cytopenias. It can glatiramer acetate 20 mg s.c. once daily or 40 mg sc 3 times / week (h difference with ? 48) are used. The orally applicable immunomodulatory drugs Fingolimod 0.5 mg p.o. 1 time / day, 14 mg p.o. Teriflunomide 1 time / day, and 240 mg of dimethyl fumarate p.o. 2 times / day, are more recently for the treatment of relapsing forms of MS. There is no consensus regarding the selection of disease-immunomodulatory therapy; many experts recommend patient education and shared decision making. Treatment with disease modifying drugs is a clinically isolated syndrome (z. B. optic neuritis) and displayed for certain MS. The immunosuppressant mitoxantrone 12 mg / m2 i.v. every 3 months for 24 months may be helpful v. a. with progressive MS, which is refractory to other treatments. Natalizumab, an anti-alpha-4 integrin antibody, inhibits the passage of leukocytes through the blood-brain barrier; as a monthly infusion given, it reduces the number of relapses and new lesions in the brain, but it can increase the risk of progressive multifocal leukoencephalopathy. Recently it has been shown that alemtuzumab, an anti-CD52 humanized monoclonal antibody administered i.v. administered is effective in the treatment of MS. However, since it increases the risk of autoimmune diseases, severe infusion reactions and certain cancers, Alemtuzumab is usually used only if treatment with ? 2 other drugs is ineffective. If immunomodulatory drugs are ineffective, a monthly i.v. administration of immunoglobulin may help. Other immunosuppressants next mitoxantrone (eg., Methotrexate, azathioprine, mycophenolate, cyclophosphamide, cladribine) have been used for more severe progressive MS courses, but they are controversial. Plasmapheresis and hematopoietic stem cell transplantation may be a little useful in severe, persistent symptoms Erkrankung.Kontrolle Other treatments can be set to control specific symptoms: The spasticity is treated with gradually increased doses of baclofen 10-20 mg po 3 to 4 times daily, or tizanidine, 4-8 mg p.o. 3 times a day. Walking exercise and general physical training can help with hemiplegic spastic limbs. Painful paresthesias are usually 100-800 mg p.o. gabapentin 3 times daily or pregabalin 25 to 150 mg p.o. treated 2 times a day; Alternatives are tricyclic antidepressants (eg. As amitriptyline 25-50 mg p.o. evening, desipramine 25-100 mg p.o. evening when amitriptyline intolerable has anticholinergic side effects), carbamazepine 200 mg p.o. 3 times a day just like other anticonvulsants and opioids. The depression is treated with psychotherapy and antidepressants measures. Bladder dysfunction are treated depends on the underlying mechanism. Fatigue can amantadine 100 mg po 3 times / day, modafinil 100 to 300 mg p.o. 1 time / day, armodafinil 150 to 250 mg p.o. 1 time / day, or depot-amphetamine 10 to 30 mg 1 time / day treated. Supportive treatment encouragement and affirmation to help the patient. Regular exercise treatments (eg. As ergometer training, bed bike, swimming, stretching, balance exercises) with or without physical therapy are recommended, even for patients with advanced MS, because this training strengthens the heart and muscles, spasticity reduced contractures preventing and has psychological benefits. Vitamin D supplements (800-1000 units / d) may reduce the risk of progression of the disease. Serum vitamin D levels should be monitored to ensure that the dosage is sufficient. Vitamin D lowers the risk of osteoporosis, especially in patients at increased risk because their mobility is restricted or they are taking corticosteroids. Patients should make their lives as normal and as active as possible, but avoid overexertion, fatigue and heat exposure. Smoking should be stopped. Vaccination does not seem to increase the risk of relapse. Severely disabled patients require nursing measures for the prevention of urinary tract infections Druckulzeraund; an intermittent self may be necessary. Key points Multiple sclerosis involves demyelination of the CNS. Although MS can progress unpredictable, there are typical historical pattern: The most common symptoms are paresthesias, weakness or clumsiness and visual symptoms, but a variety of symptoms are possible. MS is confirmed when MRI and clinical findings establish characteristic lesions that are separated in time and space; But the progression of MS is likely if patients also have only one characteristic clinical deficit or possibly a single radiological lesion. Treat patients with corticosteroids (severe flares) and immunomodulatory drugs (to delay relapses and the prevention of attacks). Treatment of patients takes place supportive, with drugs to treat the symptoms (eg. As spasticity, painful paresthesias, depression, bladder dysfunction, fatigue) when justified.