Animal Models of Action Tremor

Abstract

Summary: This article is devoted to animal models of tremors that emerge from lesions in the Guillain-Mollaret triangle. Cerebellar intention tremor is caused by lesions in the brachium conjunctivum or i n the interpositus nucleus. possibly in combination with damage to the dentate nucleus. Impaired feedforward motor control delays the braking of rapid movements, resulting in target overshoot and subsequent oscillation. Transcortical and transcerebellar sensorimotor loops undergo oscillation at a frequency that depends on the mechanical properties of the limb and the length of the sensorimotor loop (mechanical retlex oscillation). The crcscendo quality of intention tremor may be ;I result of amplification of tremor in reverberating brain stem-cerebellar or thalamocortical loops. So-called rubral or midbrain tremor is caused by a combination of damage to the brachium conjunctivum and nigrostriatal pathways in the vicinity of the red nucleus. Secondary compensatory changes in the motor system are probably involved because midbrain tremor in people usually begins weeks or months after a midbrain stroke or trauma. Harmaline causes enhanced neuronal synchrony and rhythmicity in the inferior olive; this animal model, although as yet unproven, is the most popular one for essential tremor (ET). Additional studies in laboratory animals are needed to define the seemingly universal involvement of the cerebellum and ventrolateral thalamus (ventralis intermedius [Vim]) in virtually all human tremor disorders. Key Words: Tremor-Movement disorders-CerebellumInferior olive-Red nucleus.Action tremor is any physiologic or pathologic tremor that occurs during voluntary muscle contraction. Postural tremor. kinetic tremor, and intention tremor are all forms of action tremor. This article is devoted to the tremors in laboratory animals that emerge from impairment of the Guillain-Mollaret triangle, with emphasis on the relevance of these animal models to human cerebellar tremor, midbrain tremor, and essential tremor (ET). CEREBELLAR TREMORCerebellar tremor will be restricted to designation of tremors that result from damage 10 the cerebellum or its nuclear output in the brachium conjunctivum. Gordon Holmes' noted that cerebellar "tremor, which is sometimes apparent during the whole range of movement, is usually more prominent toward its end," and observed that ''the irregular oscillations in the intended direction result from failure of uniform deceleration, but this is complicated by secondary or correcting jerks when the object has not been accurately reached in the first attempt." Consequently, distinguishing tremor from ataxia is difficult and somewhat arbitrary in people and monkeys with cerebellar lesions. The rhythm and amplitude of cerebellar tremor are usually irregular, and proximal limb muscles are often involved as much or more than distal ones. Frequencies ranging from 1-7 Hz have been observed, and the lower frequencies typically emerge from proximal joints with greater inertial loads2Action tremor in the ipsilateral uppe...

Posturographic analysis of balance control in patients with essential tremor

“…Converging evidence favors the idea that ET originates from an oscillating source feeding into the cerebellum, 20 and the inferior olive has been indicated as the possible origin of such oscillating activity. 21,22 The olivocerebellar circuit seems to be implicated in this role. 23 Similar to our ET patients, subjects with neocerebellar (lateral) lesions tend to have only slight postural instability that is indistinguishable from control subjects.…”

Linking Essential Tremor to the Cerebellum: Neuropathological Evidence

“…Yet one of the challenges to studies of disease pathogenesis is the absence of a robust animal model for ET. As reviewed elsewhere [15,67], the traditional animal model for ET is the harmaline model. It is important to point out that this is an animal toxin model of action tremor and not a model of the human disease, ET, which occurs in nature [15].…”

“…Also, harmaline-exposed animals develop an acute, total body tremor of high frequency that resolves after a few hours. Hence, it is a model of acute tremor rather than chronic tremor [15,67]. With the absence of any identified major susceptibility genes for ET [68,69], there are no genetically modified animal models for ET.…”

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

“…There is an ongoing debate on whether a cerebellar dysfunction in essential tremor is caused by disease progression and neurodegeneration (Louis et al, 2007) or a functional disruption of the cerebello-thalamo-cortical network through the interference of tremor-related neuronal oscillations with normal cerebellar timing function (Solomon et al, 1994;Elble, 1998;Deuschl et al, 2000;Blangero et al, 2009;Elble, 2009).…”