Leukodystrophyの病理

Pathology of leukodystrophies.

　leukodystrohy（LD）とは先天性障害のため，中枢神経系の髄鞘が広範囲に脱落する慢性進行性疾患の総称である。換言すれば，先天的な髄鞘形成グリアの障害のため，髄鞘が形成されないかまたは形成が不充分であり，あるいは形成された髄鞘も化学的構成異常のために変性しやすく，その構造を保持できない状態である。多発性硬化症のごとき，完成した髄鞘が破壊される脱髄性疾患とは異なる。

　LDには種々の疾患および亜型が含まれ，Seitelberger（1984）は形態と病理発生を基にした分類を提唱している。これに疾患名を追加したのがTable1である。すなわちLDを代謝異常によるものと発生異常によるものに大別し，前者にはミエリン脂質の代謝に関与する酵素異常症と，アミノ酸代謝障害による疾患が属する。ミエリン脂質の酵素異常症には，障害酵素の明らかなmetachromatic LD（MLD）とgioboid cell LD（GLD），および酵素異常の疑われるsudanophilic LD（SLD）が含まれる。その代表は伴性劣性の遺伝形式をとるadrenoleukodystrophyであるが，そのほかに原因不明の種々のLDがある。たとえば常染色体性劣性遺伝のSLD，pigment typeのSLD，那須病などである。アミノ酸の代謝異常による群にはvan Bogaert-Bertlandの海綿状変性症が入れられている。

　Leukodystrophies (LDs) are hereditary, chronic progressive diseases with widespread demyelination of the central nervous system (CNS), where formation or maintenance of the myelin sheath is disordered by metabolic or dysgenetic etiologies. In the course of a series of morphologic studies on LDs, various types of adrenoleukodystrophy (ALD), other sudanophilic LDs (SLD), Nasu disease and Pelizaeus-Merzbacher (P-M) syndrome were examined, and the obtained facts were reported by etiology.

　LDs of metabolic genesis commonly had diffuse demyelination of bilateral cerebral white matter with relatively spared subcortical arcuate fibers ; loss of axons equal to demyelination ; glial substitution of affected areas ; and neuronal degeneration in the basal ganglia and cerebellar cortex due to secondary and anoxic processes. This pattern of demyelination, however, involves some cerebrovascular disorder and severe carbon monoxide poisoning. The genesis of ALD is presumably related with immunologic processes partly, because mononuclear inflammatory cells were considerably infiltrated in demyelinated areas of ALD. Contrary to reported findings, the demyelinated white matter of an adult with ALD presented remarkable reduction of longer-chain fatty acids of galactolipids and conversely significant increase of shorter-chain fatty acids. A 58-year-old female with ALD showed akinetic mutism with widespread demyelination of the cerebral hemisphere : after her menopause, the advantage of the mutant gene might have accelerated. In a patient with neonatal ALD, a peroxisomal enzymatic disorder, sural nerve biopsy disclosed frequently curved lamellar profiles in the cytoplasm of fibroblasts and Schwann cells, especially of unmyelinated fibers. In postnatal SLD and Nasu disease, myelin basic protein (MBP) immunostain of subcortical arcuate fibers suggested abnormality of myelin lipids, through better stainability than luxol fast blue stain did. Axonal spheroids were abundant in demyelinated areas in childhood ALD, female ALD, Nasu disease and SLD of the pigment type. The spheroids may be the secondary products of myelin disintegration accompanied by the disturbed axonal flow.