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ARTICLES: Alexander Rajput, Christopher A. Robinson, and Ali H. Rajput Essential tremor course and disability: A clinicopathologic study of 20 cases Neurology 2004; 62: 932-936 [Abstract] [Full text] [PDF]

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Essential tremor course and disability: A clinicopathologic study of 20 cases

Joseph Jankovic   (20 May 2004)

Reply to Jankovic

Alexander H. Rajput, Christopher A. Robinson and Ali H. Rajput   (20 May 2004)

Essential tremor course and disability: A clinicopathologic study of 20 cases 20 May 2004
Joseph Jankovic, Baylor College of Medicine 6550 Fannin #1801, Houston, Texas 77030 Send Correspondence to journal: Re: Essential tremor course and disability: A clinicopathologic study of 20 cases josephj{at}bcm.tmc.edu Joseph Jankovic	I read with interest the recent article by Rajput et al [1] of clinicopathological study of 20 cases clinically diagnosed with essential tremor (ET). Although six (30%) of their cases had parkinsonian features and one (5%) had autopsy-proven Parkinson’s disease (PD), they concluded that “The risk of PD in ET cases was comparable with that in the general population”. The data presented in this paper, however, do not support this conclusion. The statement is based on flawed methodology as patients who at initial assessment had rest tremor, rigidity and bradykinesia (e.g. any evidence of PD) were excluded. Therefore, individuals with long- standing ET who later developed PD would not have been included in this study. Over the last 25 years, I have followed a large number of patients who (during the period of observation) evolved from typical, isolated, ET to a PD-like, levodopa-responsive, disorder. In addition, I and others [2] found a significantly greater prevalence of isolated tremor in relatives of patients with PD and described several large ET families in which some members later developed PD [3]. In contrast, the frequency of co-existent PD in patients with disorders other than ET, such as dystonia, followed longitudinally in our Movement Disorders Clinic is relatively rare and consistent with the expected incidence in general population. There is other evidence to suggest that patients with ET have higher-than-expected risk for PD. Positron emission tomography (PET) studies have shown a 10-13% reduction in 18F-dopa uptake in the striatum of patients with ET as compared to controls, suggesting a physiologically important compromise of the dopaminergic system in patients with ET [4]. Furthermore, using 123I-IPT SPECT to image the striatal dopamine transporter, Lee et al [5] found mean bilateral uptake in nine patients with isolated postural tremor (ET) to be lower than in normal control subjects and concluded that “some patients with postural tremor may acquire rest tremor in association with mild substantia nigra neuronal loss”. These and other findings confirm the notion that a subset of patients with ET carries a high risk for subsequent development of PD or PD-like disorder. Further clinical, physiological, pathological, and genetic studies are needed to determine which patients with ET evolve into ET-parkinsonism syndrome. References 1. Rajput A, Robinson CA, Rajput AH. Essential tremor course and disability: A clinicopathologic study of 20 cases. Neurology 2004;62:932-936. 2. Louis ED, Levy G, Mejia-Santana H, et al. Risk of action tremor in relatives of tremor-dominant and postural instability gait disorder PD. Neurology 2003;61:931-936. 3. Jankovic J. Essential tremor: A heterogenous disorder. Mov Disord 2002;17:638-644. 4. Jankovic J, Contant C, Perlmutter J. Essential tremor and Parkinson's disease. Neurology 1993; 43:1447-1448. 5. Lee MS, Kim YD, Im JH, et al. 125I-IPT brain SPECT study in essential tremor and Parkinson’s disease. Neurology 1999;52:1422-1426.
Reply to Jankovic 20 May 2004
Alexander H. Rajput, University of Saskatchewan Division of Neurology, Royal University Hospital, Saskatoon, SK, S7N0W8, Canada, Christopher A. Robinson and Ali H. Rajput Send Correspondence to journal: Re: Reply to Jankovic rajputa{at}sask.usask.ca Alexander H. Rajput, et al.	We thank Dr. Jankovic for his comments.[1] We used his recommended essential tremor (ET) diagnostic criteria [3] and are surprised by the comment that we should have included Parkinson’s disease (PD) cases in our study. Risk of developing a disease implies that the individual does not have that disorder when the study commences. It would be a mistake to include patients presenting to our clinic with both ET and PD, as suggested by Dr. Jankovic, since we can not be certain which came first. We have used the best available methods to examine the risk of patients with ET subsequently developing PD. Dr. Jankovic is concerned that we focused on one PD case, though six cases had parkinsonism (PS). In the past, he reported marked increased risk of PD in ET patients. [6] Unlike clinical studies, we provide precise information on the PS variants. He has observed “a large number of patients who … evolved from typical, isolated, ET to a PD-like, levodopa- responsive, disorder.” While most PD cases improve on levodopa, all who benefit do not necessarily have PD. [7] Our two PSP cases had no evidence of ophthalmoplegia and without autopsy, verification would have been misdiagnosed as PD. Pathology remains the gold standard of PD diagnosis. Dr. Jankovic refers to a greater prevalence of isolated tremor in relatives of PD cases. However, Louis et al conclude “whether the tremor … represents essential tremor or an isolated manifestation of PD requires further investigation” . [2] The functional imaging studies of ET are controversial. Brooks et al [8] observed a 10 to 13% reduction in mean putamen fluorodopa uptake in PET studies of ET and interpreted this as not significant. Jankovic et al [4] re-analyzed the published data and criticized the conclusion that the findings were not significant. Brooks et al [9] disagreed with that criticism. Lee et al [5] found abnormal SPECT in four of six ET plus resting tremor cases and noted that “many of them had mild parkinsonian feature.” Taking all available evidence into consideration, the risk of PD is not exaggerated in ET. References 6. Geraghty JJ, Jankovic J, Zetusky WJ. Association Between Essential Tremor and Parkinson's Disease. Annals of Neurology 1985; 17:329-333. 7. Rajput AH, Rozdilsky B, Rajput A, Ang L. Levodopa Efficacy and Pathological Basis of Parkinson Syndrome. Clinical Neuropharmacology 1990; 13:553-558. 8. Brooks DJ, Playford ED, Ibanez V, et al. Isolated tremor and disruption of the nigrostriatal dopaminergic system: An 18F-dopa PET study. Neurology 1992; 42:1554-1560. 9. Brooks DJ, Playford ED, Ibanez V, et al. Essential tremor and PD. Reply. Neurology 1993; 43:1448-1449.