正常圧水頭症の病態に関する生化学的アプローチ—特にシャント有効性について

BIOCHEMICAL INVESTIGATION OF NORMAL PRESSURE HYDROCEPHALUS IN THE ASSESSMENT OF SHUNT EFFECTIVENESS

　抄録　正常圧水頭症（NPH）のシャント手術有効性を術前に予測する目的で，髄液中尿酸値，γ-アミノ酪酸（GABA）値を測定し，生化学的側面からNPHの病態を検討した。正常人66例より年齢別の正常値を求め，NPH 18例ではシャント手術の前後で髄液を採取した。他にNPH類似の病態として多発梗塞性痴呆（MID）についても検索した。NPHにおいて，術前GABAは全例が高値を示し，術後低下した。尿酸は術前低値で，術後シャント有効例でのみ上昇した。年齢別正常値の推移，あるいはMIDを含め各疾患での髄液中尿酸値，GABA値の変化を考慮した場合，シャント有効例でのシャント前後の測定値の変化は，可逆性のある脳機能の低下で説明が可能と思われ，これを脳の機能的代償能力と呼んだ。また，術前のGABA値はシャント有効例と無効例で有意の差を示し，300pmol／mlが境界値であった。この事は髄液中のGABA値の測定により，術前にシャント有効性を予知できる可能性を示唆した。

It is well known that, among patients of normal pressure hydrocephalus (NPH), there is a group in which a shunting procedure had no effect on improving clinical signs (shunt-ineffective group). To differentiate the shunt-effective group from the shunt-ineffective group, we performed measure-ments of cerebrospinal fluid (CSF) levels of uric acid (UA) and gamma-aminobutyric acid (GABA) in patients of NPH.

We investigated the age-related CSF levels of UA and GABA in the normal subjects and com-pared them with those in the patients of NPH including the shunt-ineffective group and other related states, that is, multi-infarct dementia (MID) and patients with full recovery after subarachnoid hemorrage (SAH) due to the ruptured aneurysm.

In the normal subjects, CSF UA levels of second and over seventh decades were significantly higher than those of third, fourth, and fifth decades. On the other hand, CSF GABA levels of second and over seventh decades were significantly lower than those of the others. In the patients of MID, CSF UA levels were much higher and CSF GABA levels were much lower in comparison with the normal controls. These results suggested that, in the aged normal subjects, some degree of braindamage is responsible for high CSF UA levels and low CSF GABA levels.

There was no difference in the values of CSF UA and GABA between normal subjects and the patients with full recovery after SAH.

In the patients of NPH, CSF UA levels were low in general, while CSF GABA levels were all high. After the shunting operation, CSF UA and GABA levels became normal in the shunt-effective group. On the other hand, in the shunt-ineffective group, CSF GABA levels were lowered but CSF UA levels were remaind low or lowered further. And it should be noted that preoperative CSFGABA levels of the shunt-effective group were significantly higher than those of the shunt-ineffective group.

These results showed that a lowered brain func-tion was reversible not only clinically, but also biochemically in the shunt-effective group, which seemed to be similar to a penumbra of cerebral ischemia, and suggested that the measurement of CSF GABA levels might provide a possibile way to differentiate the shunt-ineffective group from shunt-effective group.