Pikielny R T
Departamento de Neurología, Instituto de Investigaciones Neurológicas Raul Carrea (FLENI), Buenos Aires, Argentina.
Medicina (B Aires). 1997;57(1):104-10.
Until the introduction of L-dopa in the therapeutics of idiopathic Parkinson's disease (IPD) at the end of the 60's, treatment was essentially limited to anticholinergic drugs and surgical procedures devised to produce discrete lesions in the pallidum, ansa lenticularis and thalamus. L-dopa, associated with dopa decarboxylase inhibitors and dopaminergic agonists, gave rise to an almost complete standstill of surgical procedures. Nevertheless, natural progression of IPD with motor fluctuations and the appearance of L-dopa related abnormal involuntary movements caused surgery to reappear as a primary treatment option. The MPTP epidemic in heroin addicts was responsible for obtaining an experimental model of IPD and became the starting point for a wealth of information concerning the physiopathology of basal ganglia circuitry, neurotransmitters and specific dopaminergic, gabaergic and glutamaergic receptor subtypes involved in motor control. This information, in the context of new stereotactic techniques with modern neuroimaging, enabled old surgical procedures on the internal globus pallidus (Gpi) and thalamus to be reformulated. Additional neurophysiological guidance further improved accuracy in target finding thereby giving rise to impressive results in the symptomatic improvement of IPD including L-dopa induced dyskinesias.
直到20世纪60年代末左旋多巴被引入特发性帕金森病(IPD)的治疗中,此前的治疗基本上局限于抗胆碱能药物以及旨在在苍白球、豆状核袢和丘脑产生离散性损伤的外科手术。左旋多巴与多巴脱羧酶抑制剂和多巴胺能激动剂联合使用,导致外科手术几乎完全停滞。然而,IPD伴运动波动的自然进展以及左旋多巴相关异常不自主运动的出现,使得手术再次成为主要的治疗选择。海洛因成瘾者中的MPTP流行导致了IPD实验模型的获得,并成为有关基底神经节回路、神经递质以及参与运动控制的特定多巴胺能、γ-氨基丁酸能和谷氨酸能受体亚型的生理病理学大量信息的起点。在具有现代神经影像学的新立体定向技术背景下,这些信息使得对内侧苍白球(Gpi)和丘脑的旧有外科手术得以重新制定。额外的神经生理学引导进一步提高了靶点定位的准确性,从而在IPD的症状改善(包括左旋多巴诱发的运动障碍)方面产生了令人瞩目的结果。