The Parkinson's-Reversing Breakthrough

Parkinson Disease Causes

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Tremor, although less specific than bradykinesia, is one of the most recognizable symptoms of PD. However, only half of all patients present with tremor as the initial manifestation of PD, and 15% never have tremor (45). Although tremor at rest (4-6 Hz) is the typical parkinsonian tremor, most patients also have tremor during activity, and this postural tremor (5-8 Hz) may be more disabling than the resting tremor. Postural tremor without parkinsonian features and without any other known etiology is often diagnosed as essential tremor (ET) (Table 2). However, isolated postural tremor clinically identical to ET may be the initial presentation of PD and may be found with higher-than-expected frequency in relatives of patients with PD (46,47). The two forms of postural tremors can be differentiated by a delay in the onset of tremor when arms assume an outstretched position. Although most patients with PD have a latency of a few seconds (up to a minute) before the tremor reemerges during postural holding, hence reemergent tremor, postural tremor of ET usually appears immediately after arms assume a horizontal posture (48). Since the reemer-gent tremor has similar frequency to that of rest tremor and both tremors generally respond to dopaminergic drugs, it is postulated that the reemergent tremor represents a variant of the more typical rest tremor. It has been postulated that the typical tremor at rest results from nigrostriatal degeneration and consequent disinhibition of the pacemaker cells in the thalamus (49). These thalamic neurons discharge rhythmically at 5 to 6 Hz, a frequency similar to the typical parkinsonian tremor at rest (50,51). Some support for the thalamic pacemaker theory of PD tremor also comes from the studies of Lee and Stein (52), which show that the resting 5 Hz tremor is remarkably constant and relatively resistant to resetting by mechanical perturbations. Furthermore, during stereotactic thalamotomy, 5 Hz discharges are usually recorded in the nucleus ventralis intermedius of the thalamus in parkinsonian subjects, even in the absence of visible tremor (53). This rhythmic bursting is not abolished by deafferentation or paralysis. Because the frequency (6 Hz) of the postural (action) tremor is the same as the frequency of the cogwheel phenomenon elicited

TABLE 2 Differential Diagnosis of Parkinsonian and Essential Tremor

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