Neurological Surgery 脳神経外科45巻12号

2017年12月発行

総説

結節性硬化症に伴う脳病変に対する外科治療

著者： 菅野秀宣¹

所属機関： ¹順天堂大学脳神経外科

ページ範囲：P.1039 - P.1049

Ⅰ．はじめに
　結節性硬化症（tuberous sclerosis complex：TSC）は，TSC1またはTSC2遺伝子の欠損を原因とする神経皮膚症候群の1つである．TSC1およびTSC2遺伝子にそれぞれコードされるhamartinとtuberinは複合体を形成し，Ras homolog enriched in brain（Rheb）のGTPase activating protein（GAP）として作用し，Rhebを不活性化することで，下流に位置するmammalian target of rapamycin（mTOR）を抑制し，細胞増殖を制御している⁶⁾．そして，その機構の崩壊がTSCにおける腫瘍性増殖のメカニズムと考えられる．また，mTORが活性化されると神経細胞は興奮性を示すことも知られており，それがTSCに伴うてんかんや精神症状出現のメカニズムの1つであると推定されている．
　TSCは，顔面血管線維腫，難治性てんかん，精神発達遅滞が古典的三徴とされるが，これら以外に上衣下巨細胞性星細胞腫（subependymal giant cell astrocytoma：SEGA）による水頭症，腎血管筋脂肪腫（angiomyolipoma：AML）による腹部膨満や腫瘍からの出血，心横紋筋腫，白斑やshagreen patchに代表される皮膚病変，肺リンパ脈管筋腫症による呼吸不全などが，さまざまな組み合わせで，かつ異なる時期に発症してくる．これらの多様な表現形は，遺伝子型の違いによるものと考えられているが，体細胞変異も報告されており，遺伝子変化と症状・症候との関連は依然研究段階にある．
　TSCに伴う神経系の症状・症候で問題になるのは，てんかん，発達遅滞，行動異常，自閉症のほかにSEGAに伴う水頭症などである^4,6)．これらの症状・症候は難治性に経過することが多く，適確な治療法の確立が求められてきた．このような中，TSCに伴う種々の病態に対するmTOR阻害薬の治療効果が明らかとなり，本疾患の治療は新たな局面を迎えたといえる．本稿では，TSCの治療全般について解説するとともに，その中での脳神経外科治療の位置づけと，今後の方向性について述べる．

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