筋萎縮性側索硬化症における肝微細構造の電顕的研究

HEPATIC ULTRASTRUCTURAL STUDY IN AMYOTROPHIC LATERAL SCLEROSIS (ALS)

I．はじめに

　著者らは，さきに筋萎縮性側索硬化症（ALS）につき，生検肝の電顕的検索を行ない，ALSの全例（7例）に代謝障害を示唆する肝細胞内微小器官（糸粒体および小胞体）の異常を認め，中間報告^3）をした。これらは，従来本症においてあまり注目されたことのない所見である。

　本報告は2部から成り，第I部は，（1）さきに得られた肝所見を，さらに多くのALS症例で観察し，その特殊性を再確認するとともに，（2） ALSにおける肝電顕所見が筋萎縮による二次的なものである可能性の有無を含めて，他の神経疾患における肝電顕所見と比較検討した。第II部では，ALS例での微小器官異常の分布を，肝小葉を構成する3つの帯（zone）べつに定量的に検討した。

Biopsied liver specimens from sixteen cases withALS, seven cases with other neurological diseases,namely three cases of polyradiculoneuritis associatedwith moderate or severe amyotrophy in limb andtrunk, three cases of myelopathy and one case ofjuvenile parkinsonism and from three normaI (non-neurological) control cases of duodenal ulcer wereexamined. Age of ALS ranged from thirty sevento seventy year old and the period from onset tobiopsy was five to thirty eight months. Medicationwas discontinued for one month before biopsy inall subjects. All subjects had no habit of drinkingalcohol Except one case of ALS, detailed Iaboratorytests for Liver function remained within almostnormal range in all examined cases, but the valueofα₁-, α₂-, β-globulin, TTT, CCF, ICG (R₁₅), GTTand IRI were slightly abnormal, as shown Table land 2 in each cases, which however were notspecific for any hepatic diseases. In one case ofALS, liver function tests showed severe abnormalfindings with TTT and CCF.

Light microscopic findings;

There was no evidence of inflarnmatory changes,fatty degeneration or pigmentation in hepatocytes,increased Kupffer cell or dilated Glisson's capsule(microscopic normal liver) in nine of sixteen casesof ALS. Brown pigment in hepatocyte in fourcases and slight fatty degeneration (lesser than10%) in two were observed, which were thoughtto be non-specific and non-pathological. In onecase with high value of colloidal reactions, chronicinactive hepatitis was shown. There were nopathological and specific changes in seven cases ofother neurological diseases.

Electron microscopic findings;

In all sixteen cases with ALS, changes oforganelle in hepatocytes were observed as following;

1) increased smooth-surfaced endoplasmic retic-ulum,

2) destroyed and dilated rough-surfaced endoplasmic reticulum,

3) enlarged and deformed mitochondria, giantmitochondria and

4) appearance of intramitochondrial paracrys-talline inclusions (intramitochondrial crystalloids).

Bile canaliculi, Disse's space and nucleus ofhepatocyte were almost normal. On the otherhand, there were no abnorrnal changes of hepaticultrastructure in all cases with other neurologicaldiseases (polyradiculoneuritis, myelopathy andjuvenile parkinsonisrn).

In three ALS cases and one control case, thepercentage of deformed mitochondria and intra-mitochondrial paracrystalline inclusions in a hepato-cyte were studied in about twenty hepatocyteswith peripheral, intermediate and central zone ofliver lobules separately. These two abnormalitiesin mitochondria with ALS were almost equal inthree zones of liver lobules and in three cases.

These ultrastructural changes, which were fonndcommon to ALS and had not been described in theliterature, suggest some metabolic abnormality inALS liver.