Kronenbuerger M, Tronnier V M, Gerwig M, Fromm C, Coenen V A, Reinacher P, Kiening K L, Noth J, Timmann D
Department of Neurology, University Hospital Aachen, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Exp Neurol. 2008 Jun;211(2):387-96. doi: 10.1016/j.expneurol.2008.02.002. Epub 2008 Feb 21.
Several lines of evidence point to a disturbance of olivo-cerebellar pathways in essential tremor (ET). For example, subjects with ET exhibit deficits in eyeblink conditioning, a form of associative learning which is known to depend on the integrity of olivo-cerebellar circuits. Deep brain stimulation (DBS) of the ventrolateral thalamus is an established therapy for ET. If tremor in ET is related to the same pathology of the olivo-cerebellar system as impaired eyeblink conditioning, one may expect modulation of eyeblink conditioning by DBS. Delay eyeblink conditioning was assessed in 11 ET subjects treated with DBS (ET-DBS subjects) who were studied on two consecutive days with DBS switched off (day 1) and on (day 2). For comparison, 11 age-matched ET subjects without DBS (ET subjects) and 11 age-matched healthy controls were studied. On day 1, eyeblink conditioning was diminished in ET-DBS subjects and in ET subjects compared with controls. When DBS was switched on ET-DBS subjects exhibited conditioning rates within the range of controls on day 2, while ET subjects improved only minimally. Improved eyeblink conditioning in ET-DBS subjects suggests that thalamic DBS counteracts a functional disturbance of olivo-cerebellar circuits which is thought to be responsible for eyeblink conditioning deficits in ET. Modulation of cerebello-thalamic and/or thalamo-cortico-cerebellar pathways by DBS may play a role.
多条证据表明，特发性震颤（ET）存在橄榄小脑通路紊乱。例如，ET患者在眨眼条件反射方面表现出缺陷，眨眼条件反射是一种已知依赖于橄榄小脑回路完整性的联想学习形式。丘脑腹外侧核的深部脑刺激（DBS）是ET的一种既定治疗方法。如果ET中的震颤与眨眼条件反射受损的橄榄小脑系统的相同病理相关，那么人们可能预期DBS会调节眨眼条件反射。对11名接受DBS治疗的ET患者（ET-DBS患者）进行了延迟眨眼条件反射评估，这些患者连续两天接受研究，第一天关闭DBS，第二天开启DBS。作为对照，研究了11名年龄匹配的未接受DBS的ET患者（ET患者）和11名年龄匹配的健康对照者。在第一天，与对照组相比，ET-DBS患者和ET患者的眨眼条件反射减弱。当开启DBS时，ET-DBS患者在第二天的条件反射率在对照组范围内，而ET患者仅略有改善。ET-DBS患者眨眼条件反射的改善表明，丘脑DBS抵消了橄榄小脑回路的功能障碍，这种功能障碍被认为是ET患者眨眼条件反射缺陷的原因。DBS对小脑丘脑和/或丘脑皮质小脑通路的调节可能起了作用。
