Acute disseminated encephalomyelitis

Japanese: 急性散在性脳脊髄炎

Concept Acute disseminated encephalomyelitis is an acute-onset inflammatory demyelinating disease that diffusely invades the brain and spinal cord. Its course is monophasic, and relapses and remissions are extremely rare. It is usually classified into three types based on the cause: 1) postvaccinal ADEM, 2) postinfectious ADEM, and 3) idiopathic ADEM.
The epidemiological prevalence is unclear, but it occurs regardless of race, age, or gender. Postinfectious cases are more common in children, while idiopathic cases tend to be more common in young adults.
Etiology Postinfectious acute disseminated encephalomyelitis develops 2 to 15 days after viral infection such as measles, rubella, chickenpox, mumps, or influenza, or after infection with whooping cough or dengue fever. It is thought that the mechanism of onset is not direct infection of the nervous tissue by the virus, but rather an allergic reaction. Postvaccination acute disseminated encephalomyelitis develops 2 to 15 days after vaccination against rabies, smallpox, typhoid, etc. It is thought to be caused by an allergic reaction to brain antigens or cross-antigens contained in the vaccine. As the pathological findings are similar to those of experimental allergic encephalomyelitis (EAE), it is thought that an allergic mechanism due to delayed hypersensitivity is involved.
PathologyPerivenous encephalomyelitis is characterized by the infiltration of mononuclear cells, mainly lymphocytes, around the small veins, and lesions are observed scattered throughout the white matter of the cerebrum, brain stem, cerebellum, and spinal cord. Demyelination is observed around the small veins, and is milder than in multiple sclerosis.
Clinical symptoms: The disease develops acutely several days to several weeks (mainly 1-2 weeks) after viral infection or vaccination. Symptoms such as fever, general malaise, headache, nausea, and vomiting appear before the neurological symptoms. Meningeal irritation symptoms such as neck stiffness and convulsions may occur. In general, neurological symptoms suggesting lesions in the cerebrum (hemiplegia, hemianopsia, aphasia), brainstem (nystagmus, ocular movement disorder), cerebellum (ataxia, dysarthria), and spinal cord (quadriplegia, bladder-rectum disorder) progress rapidly. Clinically, it is divided into three types: encephalitis, myelitis, and encephalomyelitis. The prognosis is poor if the patient falls into a lethargic or coma.
Test results: There are no test abnormalities specific to this disease, but there is sometimes a mild increase in peripheral blood white blood cell count. Cerebrospinal fluid pressure is mildly increased, and protein content is also elevated, but rarely exceeds 100 mg/dL. Cerebrospinal fluid cells are primarily lymphocytes, showing an increase of several tens to several hundred cells/μL. MRI reveals widespread, often symmetrical lesions in the white matter of the central nervous system, which are enhanced by gadolinium-DTPA. Electroencephalograms often show widespread, nonspecific abnormalities.
Treatment: Pulse therapy with corticosteroids (methylprednisolone, 500-1000 mg per day, intravenous infusion for three days) is considered effective. Symptomatic treatment is similar to that for multiple sclerosis. [Itoyama Yasuto]
■ References
Compston A, et al eds: McAlpine's Multiple Sclerosis, 4th ed, Churchill Livingstone Elsevier, Philadelphia, 2006.
Yasuto Itoyama: Changing concepts of disease: Opticospinal multiple sclerosis (OSMS) and optic neuritis (NMO). Annual Review, Nerve, 2008: 238-245, 2008.
Misu T, Fujihara K, et al: Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis. Brain, 130: 1224-1234, 2007.
Vinken PJ, Bruyn GW, et al eds: Handbook of Clinical Neurology: Demyelinating Disease 47, Elsevier Science Publishers, Amsterdam, 1985.

Acute disseminated encephalomyelitis (non-infectious inflammatory disease)

(1)
Acute disseminated encephalomyelitis (ADEM)
[⇨15-9-4)] [Takashi Inuzuka]
■ References <br /> Matsui, M.: Transverse myelitis. Clinical Neuroscience, 28: 108-109, 2010.

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

概念
　急性散在性脳脊髄炎は急性に発症する炎症性脱髄疾患で，脳や脊髄を散在性に侵す．その経過は単相性で，再発・寛解を示すものは，きわめてまれである．通常，原因別に，①ワクチン接種後（postvaccinal ADEM），②感染後（postinfectious ADEM），③特発性（spontaneous ADEM）の3型に分類される．
疫学
　有病率は明らかではないが，人種，年齢，性差にかかわりなく起こる．感染後のものは小児に多く，特発性のものは若年成人に多い傾向がある．
病因
　感染後急性散在性脳脊髄炎は麻疹，風疹，水痘，流行性耳下腺炎，インフルエンザなどのウイルス感染，または百日咳やデング熱の感染後2～15日ほどして発症する．発症機序としてはウイルスが直接神経組織へ感染するのではなく，アレルギー反応により起こるものと考えられている．ワクチン接種後急性散在性脳脊髄炎は狂犬病，痘瘡，腸チフスなどのワクチン接種2～15日後に発症する．ワクチンに含まれていた脳抗原や交叉抗原に対するアレルギー反応が原因と考えられている．実験的アレルギー性脳脊髄炎（EAE）の病理像に類似していることより，遅延型過敏症によるアレルギー機序の関与が考えられる．
病理
　リンパ球を主体とする単核細胞が小静脈周囲性に浸潤する静脈周囲性脳脊髄炎（perivenous encephalomyelitis）であり，病変は大脳，脳幹，小脳，脊髄の白質に散在して観察される．脱髄は小静脈周囲性に認められ，その程度は多発性硬化症に比べると軽度である．
臨床症状
　ウイルス感染やワクチン接種後数日から数週間後（おもに1～2週）に急性に発症する．神経症状に先行して発熱，全身倦怠感，頭痛，悪心・嘔吐などの症状が出現する．項部硬直などの髄膜刺激症候や，痙攣をきたすことがある．一般に大脳（片麻痺，半盲，失語），脳幹（眼振，眼球運動障害），小脳（運動失調，構音障害），脊髄（四肢麻痺，膀胱直腸障害）の病変を示唆する神経症状が急速に進展してくる．臨床的に脳炎型，脊髄炎型，脳脊髄炎型の3型に分けられる．嗜眠状態や昏睡状態に陥る場合は予後不良である．
検査成績
　本症に特異的な検査異常はないが，ときに末梢血白血球数の軽度増加がある．髄液圧は軽度亢進し，蛋白量も上昇するが，100 mg/dLをこえることは少ない．髄液細胞はリンパ球を主体として数十～数百/μLの増加を示す．MRIでは中枢神経白質に多くは左右対称に広範な病変がみられ，ガドリニウムDTPAにより増強される．脳波は広範に非特異的な異常を示すことが多い．
治療
　副腎皮質ステロイドのパルス療法（メチルプレドニゾロンで1日量500～1000 mg点滴静注を3日間）が有効とされている．対症療法は多発性硬化症に準じる．［糸山泰人］
■文献
Compston A, et al eds: McAlpine’s Multiple Sclerosis, 4th ed, Churchill Livingstone Elsevier, Philadelphia, 2006.
糸山泰人：変わりつつある疾患の概念－視神経脊髄型多発性硬化症（OSMS）と視神経炎（NMO）－．Annual Review神経，2008: 238-245, 2008．
Misu T, Fujihara K, et al: Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis. Brain, 130: 1224-1234, 2007.
Vinken PJ, Bruyn GW, et al eds: Handbook of Clinical Neurology: Demyelinating Disease 47, Elsevier Science Publishers, Amsterdam, 1985.