Alcoholism

Japanese: アルコール中毒

Most cases are caused by ethyl alcohol (ethanol) poisoning due to drinking alcohol, but methyl alcohol can also occur in rare cases. Ethanol has a strong depressant effect on the reticular activating system and the cerebrum, suppressing the thermoregulatory center, vasomotor center and antidiuretic hormone secretion, causing damage to the nervous system as well as the digestive system, respiratory system and circulatory system. In addition to ethanol, alcoholism can also cause various neurological and muscular disorders due to vitamin deficiencies associated with nutritional disorders. Side effects can also occur due to interactions with other drugs.
1) Acute alcohol intoxication:
Acute alcohol poisoning occurs when a large amount of ethanol is suddenly ingested, resulting in an intoxicated state and various central nervous system symptoms (Table 15-11-2), but the onset of symptoms varies greatly from person to person and depends on gender, age, mental and physical condition, and ethnicity. Ethanol is mainly absorbed in the small intestine, then converted to acetaldehyde by alcohol dehydrogenase (ADH) in the liver, and is further metabolized by acetaldehyde dehydrogenase (ALDH). There are polymorphisms in the ADH and ALDH genes, and people who have the ADH2* ₂ gene, which codes for the highly active ADHβ2 enzyme, and the ALDH2*2 gene, which codes for the inactive ALDH2, have a reduced ability to metabolize acetaldehyde, resulting in high blood levels. Compared to whites and blacks, more Japanese people have this condition, and are more likely to experience acute poisoning symptoms, including intoxication.
2) Major neurological and muscular disorders caused by chronic alcoholism:
a) Alcoholism and withdrawal syndrome (delirium tremens): Compared to non-drinkers, the brain shrinks in alcoholics. Withdrawal syndrome occurs within 48 hours of abstinence from alcohol. Symptoms include finger tremors, insomnia, anxiety, restlessness, hallucinations, convulsions, nausea/vomiting, sweating, and tachycardia. Seizures consist of one or two generalized tonic-clonic convulsions, which rarely progress to status epilepticus. Electroencephalograms are normal in 90% of cases. Symptoms improve within a few days, but some progress to delirium tremens. Delirium tremens appears 48 to 72 hours after abstinence from alcohol. Symptoms are similar to those of withdrawal syndrome, but are more severe, with impaired consciousness such as delirium, coarse tremors throughout the body, and hyperexcitability of the autonomic nervous system. Symptoms persist for a few hours to a few weeks before recovery, but may also lead to death. Treatment involves administering benzodiazepines, adequate fluid and electrolyte replacement, vitamins, and anticonvulsants.
b) Wernicke-Korsakoff encephalopathy: Wernicke encephalopathy is often accompanied by Korsakoff syndrome, but clinically and pathologically, they are the same disease, caused by thiamine (vitamin _B1 : _VB1 ) deficiency. Pathological examination reveals necrotic foci in the third ventricle, periaqueductal gray matter, thalamus, mammillary bodies, corpus tetragamum, cerebellum and brain stem, as well as vascular proliferation, neuronal loss and gliosis.
Wernicke's encephalopathy develops acutely or subacutely and is characterized by the triad of impaired consciousness, ophthalmoplegia, and truncal ataxia, although there are few cases that present all three symptoms. Patients are confused, disoriented, and have impaired memory, and those who fall into a coma have a poor prognosis. Korsakoff syndrome causes cognitive impairment and an amnesic syndrome. Patients become confused, with impaired memory and severe short-term memory impairment. Anterograde amnesia, retrograde amnesia, disorientation, and confabulation can also be seen.
MRI shows high signal areas in the above areas on diffusion weighted imaging (DWI) and _T2 weighted images. Diffusion coefficient imaging (ADC) maps show low or high signal. Blood _VB1 and red blood cell transketolase activity decrease. Treatment is administration of _VB1 . c) Pellagra: This is caused by alcohol-induced nicotinic acid deficiency. Erythema, pigmentation, and thickened skin (pellagra rash) are observed on the face, hands, dorsum of the feet, and other areas exposed to sunlight. Gastrointestinal symptoms such as diarrhea, glossitis, and gastric juice deficiency, as well as anemia, are followed by mental symptoms such as amnesia, delirium, confusion, hallucinations, and delusions, and sometimes dementia. Peripheral neuropathy, spastic paralysis, ataxia, tremors, and muscle stiffness also appear. Blood niacin levels decrease. Treatment is administration of niacin and vitamin supplements.
d) Marchiafava-Bignami disease: Demyelination and necrosis of the central part of the corpus callosum occurs in association with alcohol, and the lesion spreads symmetrically to the anterior commissure, posterior commissure, centrum semiovale, subcortical white matter, and middle cerebellar peduncle, but does not affect the upper and lower outermost layers of the corpus callosum or gray matter. The cause is unknown. Pathological examination reveals thinning and vacuolation of the corpus callosum. Demyelination is observed, but gliosis is not prominent. Acute cases present with impaired consciousness and convulsions, and sometimes death. Subacute cases present with higher-order functional disorders and gait disturbance due to cerebral hemispheric detachment, and chronic cases present with progressive dementia and symptoms of corpus callosum detachment (apraxia of the left hand, agraphia, tactile naming disorder, etc.). MRI reveals bilaterally symmetric low signal areas on _T1- weighted images and high signal areas on T2 _- weighted images corresponding to the lesion, as well as central necrosis and thinning with relatively preserved outermost layers of the corpus callosum. Treatment involves the administration of vitamin supplements and high-dose corticosteroids. The prognosis is relatively poor.
e) Central pontine myelinolysis: This condition is common in cases of electrolyte abnormalities, especially hyponatremia, and during rapid correction of hyponatremia, as well as in burns and liver transplant patients. The incidence is reduced if the rate of hyponatremia correction is kept to 8 mmol/L/day or less. The cause is unknown, but osmotic demyelination due to angioedema is thought to be one factor. Symmetric demyelinating lesions are seen not only in the base of the pons, but also in half of the cases in the cerebellum, lateral geniculate body, internal capsule, hippocampus, cerebral white matter, thalamus, and basal ganglia (extrapontine myelinolysis).
Hyponatremia causes impaired consciousness and convulsions, and after correction, symptoms such as dysarthria, dysphagia, quadriplegia, external ophthalmoplegia, behavioral abnormalities, mutism, and locked-in syndrome appear. Extrapontine myelinolysis causes involuntary movements such as parkinsonism, choreoathetosis, and dystonia, as well as cerebellar symptoms.
MRI reveals symmetrical circular or triangular low absorption areas on _T1- weighted images and high signal areas on _T2- weighted images in the center of the pontine tegmentum 1 to 2 weeks after the onset of the disease.
Early and appropriate systemic management will result in improvement, but death or sequelae may occur. _{VB 1} is ineffective.
f) Alcoholic cerebellar atrophy: This condition is caused by nutritional disorders associated with alcohol consumption. It develops subacutely, and in rare cases, it develops acutely or takes a transient course. Pathological examination reveals greater damage to the superior vermis of the cerebellum, and MRI reveals atrophy of the vermis. Patients are also affected by ataxic gait and severe impaired coordination of the lower limbs. Treatment involves administration of _VB1 .
g) Alcoholic neuropathy: There are cases where it is accompanied by nutritional disorders or vitamin _B1 deficiency, and cases where it is not. The former is a rapidly progressing, motor-dominant sensory-motor neuropathy similar to beriberi. It is often associated with alcohol-related diseases. It shows axonal degeneration and segmental demyelination, mainly in large-diameter fibers. The latter is a pure alcoholic neuropathy, but it is a slowly progressing neuropathy with a sensory-dominant tendency, characterized by pain, burning pain, and superficial sensory disorders, and is mainly affecting small-diameter fibers.
Symptoms include muscle weakness and sensory impairment, primarily in the distal parts of the lower limbs, as well as decreased vibration sense, muscle weakness in proximal muscles, and autonomic nerve disorders (rectal bladder dysfunction, hypotension, hypothermia, abnormal sweating, and gastrointestinal peristalsis disorders). Slowed nerve conduction velocity and neurogenic changes are observed on electromyograms. Occasionally, cerebrospinal fluid protein levels increase. Conditions improve with cessation of alcohol consumption and administration of _VB1 .
h) Alcoholic myopathy: Acute and chronic alcoholic myopathy, hypokalemic (K) myopathy, and cardiomyopathy occur.
Acute myopathy ranges from asymptomatic, where there are no muscular symptoms and only an increase in serum creatine kinase (CK), to necrotizing myopathy and rhabdomyolysis. Rhabdomyolysis develops suddenly after drinking alcohol, with symptoms such as muscle pain, muscle swelling, knee bending, and brown urine, and also leads to muscle weakness. Chronic myopathy is accompanied by gradual onset of generalized muscle weakness and muscle atrophy, mainly in the pelvic girdle muscles. In many cases, serum CK levels are normal, but electromyograms and muscle biopsies show myogenic changes. Hypokalemic myopathy occurs when hypokalemia is caused by insufficient intake and increased excretion of potassium due to alcohol. The proximal muscles of the limbs are primarily affected, and hypercreatine kinaseemia is observed. Potassium replacement therapy improves the condition within a few days. i) Methanol intoxication: Most poisonings are caused by accidental ingestion or oral ingestion for suicidal purposes. It is broken down in the liver into formaldehyde and formic acid, and the formic acid damages the nervous system and cardiovascular system. The metabolic rate is slow, and although initial symptoms are mild, severe symptoms can occur with a delayed course. Pathological findings include necrosis and hemorrhage in the bilateral putamen, caudate nucleus, and cerebral white matter. Initial symptoms are primarily gastrointestinal (nausea, vomiting, abdominal pain, gastritis, pancreatitis), but 6 to 30 hours after ingestion, neurological symptoms such as intoxication, convulsions, impaired consciousness, impaired vision, and ataxia, as well as pulmonary edema, circulatory failure, and metabolic acidosis appear. MRI shows low absorption areas in _T1- weighted images and high signal areas in _T2- weighted images in the basal ganglia and cerebral white matter. Treatment involves correction of acidosis and, if necessary, hemodialysis and ethanol therapy. [Kumamoto Toshihide]
■ References
Harris J, Chimelli L, et al: Nutritional deficiencies, metabolic disorders and toxins affecting the nervous system. In: Greenfield's Neuropathology, 8th ed (Love S, Louis DN, et al eds), pp 675-731, Hodder Arnold, London, 2008. Toshihide Kumamoto: Blood ethanol concentration. Comprehensive blood and urine chemical tests and immunological tests (2), 7th edition, pp 522-525, Nippon Rinsha, Tokyo, 2010. McLean DR, Jacobs H, et al: Methanol poisoning: a clinical and pathological study. Ann Neurol, 8: 161-167, 1980.

Table 15-11-2
"Correlation between blood ethanol concentration and central nervous system symptoms (Brust JCM: Merritt's Neurology, 11th ed, p1151, Lippincott Williams & Wilkins, Philadelphia, 2005, partially modified)"

Table 15-11-2

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

Japanese:

ほとんどが飲酒によるエチルアルコール（エタノール）中毒であるが，まれにメチルアルコールでも起こる．エタノールは網様体賦活系や大脳に対する強い抑制作用をもち，体温調節中枢，血管運動中枢，抗利尿ホルモン分泌を抑制し，神経系を中心に消化器系，呼吸器系，循環器系などに障害を起こす．アルコール依存症ではエタノールのほかに，栄養障害に伴うビタミン類欠乏による種々の神経・筋障害を生じる．ほかの薬物との相互作用による副作用も出現する．
1）急性アルコール中毒（acute alcohol intoxication）：
急性アルコール中毒は，急激な大量のエタノール摂取により酩酊状態になり，種々の中枢神経症状を生じるが（表15-11-2），症状出現には個人差が大きく，性，年齢，心身状態，民族により異なる．エタノールはおもに小腸で吸収後，肝臓でアルコール脱水素酵素（ADH）によりアセトアルデヒドに変換され，さらにアセトアルデヒド脱水素酵素（ALDH）により代謝される．ADH，ALDH遺伝子には多型性があり，酵素活性の高いADHβ₂をコードするADH2＊2遺伝子，不活性型のALDH2をコードするALDH2＊2遺伝子を有する人はアセトアルデヒド代謝能が低下するため，血中濃度が高くなる．白人や黒人に比べ，日本人にはこれを有する人が多く，酩酊をはじめ急性中毒症状を生じやすい．
2）慢性アルコール中毒（chronic alcoholism）によるおもな神経・筋障害：
　a）アルコール依存症（alcoholism）と離脱症候群（振戦譫妄）：アルコール依存症では非飲酒者に比べ，脳が萎縮する．離脱症候群は，断酒後48時間以内に起こる．手指振戦，不眠，不安，不穏，幻覚，痙攣，悪心・嘔吐，発汗や頻脈などが出現する．痙攣発作は1～2回の全般性強直性間代性痙攣で，まれに重積する．脳波は90％で正常である．症状は数日で改善するが，一部は振戦譫妄に移行する．　振戦譫妄は，断酒後48～72時間に出現する．離脱症候群と同様の症状だが，より重篤で，譫妄などの意識障害，全身の粗大振戦，自律神経の過興奮状態を認める．症状は数時間から数週間持続後，回復するが，死に至ることもある．　治療はベンゾジアゼピンを投与し，十分な補液と電解質管理を行い，ビタミン剤，抗痙攣薬を投与する．
　b）Wernicke-Korsakoff脳症：Wernicke脳症にKorsakoff症候群がしばしば合併するが，臨床病理学的には同一疾患であり，原因もチアミン（ビタミンB₁：VB₁）欠乏による．病理では，第3脳室や中脳水道周囲の灰白質，視床，乳頭体，四丘体，小脳や脳幹に壊死巣を認め，血管増生，神経細胞脱落とグリオーシスを認める．
　Wernicke脳症は急性，亜急性に発症し，意識障害，眼筋麻痺，体幹失調を3徴とするが，すべてそろう例は少ない．錯乱，失見当識，記銘力障害などを認め，昏睡例は予後が悪い．Korsakoff症候群は認知機能障害と健忘症候群をきたす．錯乱状態となり，記銘力障害，短期記憶が高度に障害される．前向性健忘，逆行性健忘，失見当識や作話もみられる．
　MRIでは上記部位に拡散強調画像（DWI），T₂強調画像で高信号域を認める．拡散係数画像（ADC）マップでは低，または高信号を示す．血中VB₁や赤血球中トランスケトラーゼ活性が低下する．治療はVB₁を投与する．　c）ペラグラ（pellagra）：アルコールによるニコチン酸欠乏で起こる．顔面，手・足背など日光露出部に紅斑，色素沈着，皮膚肥厚（ペラグラ疹）を認める．下痢，舌炎，胃液分泌欠乏などの胃腸症状や貧血に続いて健忘，譫妄，錯乱，幻覚，妄想などの精神症状，ときに認知症を認める．末梢神経障害，痙性麻痺，失調，振戦，筋硬直なども出現する．血中ナイアシン値は低下する．治療にはナイアシン，ビタミン剤を投与する．
　d）Marchiafava-Bignami病：アルコールに関連して脳梁の中心部の脱髄壊死を生じ，病変は前交連，後交連，半卵円中心，皮質下白質，中小脳脚へと左右対称性に広がるが，脳梁の上下最外層や灰白質は侵されない．成因は不明である．病理では，脳梁の菲薄化，空胞化を認める．脱髄を認めるがグリオーシスは目立たない．　急性例では意識障害と痙攣で発症し，ときに死亡する．亜急性例では大脳半球離断による高次機能障害，歩行障害をきたし，慢性例では進行性の認知症や脳梁離断症状（左手の失行，失書と触覚性呼称障害など）を認める．　MRIでは病巣に一致して左右対称性にT₁強調画像で低信号域，T₂強調画像で高信号域および脳梁の最外層が比較的保たれた中心性壊死，菲薄化を認める．治療はビタミン剤投与や副腎皮質ステロイドの大量療法を行う．予後は比較的悪い．
　e）橋中心髄鞘崩壊症（central pontine myelinolysis）：電解質異常，特に低ナトリウム血症やその急激な補正中に発症する例や火傷，肝移植例に多い．低ナトリウム血症の補正速度を8 mmol/L/日以下に抑えると発症が減少する．成因は不明だが，血管性浮腫による浸透圧性脱髄が一因と考えられる．左右対称性の脱髄病変は橋底部のほか，半数に小脳，外側膝状体，内包，海馬，大脳白質，視床，基底核にもみられる（橋外髄鞘崩壊症）．
　低ナトリウム血症による意識障害と痙攣が生じ，補正後に構音障害，嚥下障害，四肢麻痺，外眼筋麻痺，行動異常，無言症，閉じ込め症候群などがみられる．橋外髄鞘崩壊症ではパーキンソニズム，舞踏アテトーゼ，ジストニアなどの不随意運動や小脳症状などを認める．
　MRIでは，発症後1～2週間目に橋被蓋部中心にほぼ左右対称性の円形や三角形のT₁強調画像で低吸収域，T₂強調画像で高信号域を認める．
　早期の適切な全身管理により改善するが，死亡や後遺症を残すこともある．VB₁は無効である．
　f）アルコール性小脳萎縮症（alcoholic cerebellar atrophy）：飲酒に伴う栄養障害で起こる．亜急性に発症し，まれに急性発症や一過性の経過をとる．病理では小脳の上虫部がより障害され，MRIでは虫部の萎縮を認める．失調性歩行や下肢に強い協調運動障害を認める．治療はVB₁を投与する．
　g）アルコール性ニューロパチー（alcoholic neuropathy）：栄養障害やVB₁欠乏を伴うものと伴わないものがある．前者は急速に進行し，運動優位の脚気に類似した感覚・運動性ニューロパチーである．アルコール関連疾患によく合併する．大径線維を中心に軸索変性と節性脱髄を示す．後者は純粋のアルコール性ニューロパチーであるが，疼痛や灼熱痛，表在感覚障害を主体とする感覚優位の緩徐進行性のニューロパチーで，おもに小径線維優位に障害される．
　四肢，特に下肢の遠位部優位の筋力低下，感覚障害を認め，振動覚低下，近位筋の筋力低下，自律神経障害（直腸膀胱障害，低血圧，低体温，発汗異常，消化管蠕動障害）などもみられる．神経伝導速度の遅延や筋電図で神経原性変化を認める．ときに髄液蛋白が増加する．飲酒中止やVB₁の投与で改善する．
　h）アルコール性ミオパチー（alcoholic myopathy）：急性および慢性アルコール性ミオパチー，低カリウム（K）性ミオパチー，心筋症が生じる．
　急性ミオパチーには筋症状がなく，血清クレアチンキナーゼ（CK）上昇のみを認める無症候性から壊死性ミオパチーや横紋筋融解症まで存在する．横紋筋融解症は飲酒後に急激に筋肉痛，筋腫脹，腓返り，褐色尿などで発症し，筋力低下をきたす．慢性ミオパチーでは，徐々に発症する腰帯筋中心の全身の筋力低下，筋萎縮を認める．多くは血清CK値は正常だが，筋電図，筋生検では筋原性変化を示す．低カリウム性ミオパチーは，アルコールによるKの摂取不足や排泄の増大による低カリウム血症で起こる．おもに四肢近位筋が障害され，高クレアチンキナーゼ血症を認める．Kの補充療法により数日で改善する．　i）メチルアルコール中毒（メタノール中毒）（methanol intoxication）：中毒の多くは誤飲や自殺目的などの経口摂取による．肝でホルムアルデヒドとギ酸に分解され，ギ酸が神経系，心循環器系を障害する．代謝速度は遅く，初期症状は軽微でも，遅延性に重篤な症状が生じる．病理では両側被殻，尾状核や大脳白質に壊死や出血をきたす．初期はおもに消化器症状（悪心・嘔吐，腹痛，胃炎，膵炎）だが，摂取後6～30時間経って酩酊，痙攣，意識障害，視力障害，運動失調などの神経症状，肺水腫，循環不全，代謝性アシドーシスが出現する．MRIでは基底核や大脳白質にT₁強調画像で低吸収域，T₂強調画像で高信号域を示す．治療はアシドーシスの補正や必要に応じ血液透析・エタノール療法を行う．［熊本俊秀］
■文献
Harris J, Chimelli L, et al: Nutritional deficiencies, metabolic disorders and toxins affecting the nervous system. In: Greenfield’s Neuropathology, 8th ed (Love S, Louis DN, et al eds), pp 675-731, Hodder Arnold, London, 2008.熊本俊秀：血中エタノール濃度．広範囲血液・尿化学検査免疫学的検査（2），第7版，pp 522-525，日本臨牀社，東京，2010.McLean DR, Jacobs H, et al: Methanol poisoning: a clinical and pathological study. Ann Neurol, 8: 161-167, 1980.

表15-11-2
"血中エタノール濃度と中枢神経症状との相関(Brust JCM:Merritt's Neurology,11th ed, p1151, Lippincott Williams & Wilkins, Philadelphia, 2005 を一部改変）"">

表15-11-2

出典　内科学第10版内科学第10版について　情報

<<: Alcohol dehydrogenase

>>: Algol - Algol (English spelling)