Abstract
Background
Parkinson's Disease (PD) can present with dystonia or essential tremor but task specific tremor (TST) preceding PD has been only rarely reported. The relationship between TST and PD is unclear. We report a series of 12 patients with TST who later developed PD.
Cases
Patients with TST and PD were identified from our database. Records and imaging were reviewed and descriptive statistics presented. Twelve patients were identified. All 11 patients who had TST of arm developed rest tremor ipsilateral to the TST arm. DaTscan showed reduced dopaminergic uptake in all 11 patients who were scanned. The TST improved with STN and VIM DBS (3/12) and partially to dopaminergic medications (N = 3) and trihexyphenidyl (N = 2).
Conclusion
Rest tremor consistently occurring ipsilateral to TST, positive DaTscan, and partial response to dopaminergic medications but not to ET medications suggests TST is a precursor to PD in this population rather than chance occurrence.
Keywords: task specific tremor, Parkinson's disease, rest tremor, DaTscan, DBS
Task specific tremor (TST) is a poorly understood phenotype of action tremor occurring only with specific tasks, such as writing, which shares some features of tremor and some of dystonia. Pure TST is not considered a sub‐type of essential tremor (ET) in the latest tremor classification system, but it is clear that TST patients can develop postural tremor, which would then meet criteria for ET. 1 The relationship between ET and Parkinson's disease (PD) is greatly debated but multiple studies show some association. 2 , 3 Pure dystonia, typically of the foot and L‐dopa responsive, is a well‐recognized initial symptom in young onset PD. However, only a few cases of TST later developing PD have been reported. 4 , 5 , 6 Herein, we report a case series of 12 subjects with TST who later developed PD.
Objective
The objective of the study is to report the association of TST with PD based on history, physical examination and DaTscan abnormalities.
Methods
We queried for patients with TST and PD from our database and through chart review at the Methodist Neurological Institute Movement Disorder Clinic, and collected demographics, disease characteristics, and DaTscan results. Descriptive statistics are provided.
Results
We identified 12 subjects, seven male, with a mean age of TST onset of 54.08 ± 15.28 [Table 1]. Seven patients had tremor with writing, one when applying mascara, one when holding a microphone, one with typing, one when holding glass; and one had jaw tremor only while drinking from a cup. All 11 patients with arm tremor later developed rest tremor on the arm ipsilateral to the TST arm. The first PD sign to appear was rest tremor in 10 and bradykinesia in two. Dopamine loss consistent with PD was confirmed by DaTscan in all patients who were scanned (N = 11). DaTscans was obtained at a mean duration of 14.81 ± 16.38 years from the onset of TST [range: 2–45 years] and 5 ± 5.16 from the onset of PD [range: 0.2–15 years], [Table 1]. All patients were scanned after onset of PD signs. Seven of the 10 patients with TST of the limb and who had DaTscans showed decreased uptake predominantly on the side contralateral to the tremor. Two patients showed decreased uptake on the side ipsilateral to the tremor and one patient had symmetrical bilateral decreased uptake. The woman with TST of jaw with drinking later developed mostly right body PD signs and reduced DaTscan signal in the left striatum. Mean age for PD onset was 67.66 ± 8.40. The mean duration between onset of TST and onset of PD is 13.66 ± 14.36 years [range: 2–35 years]. Family history was positive for ET in only patient 1 [Table 1] and none had a family history of PD. The TST responded well to STN DBS in two patients, and VIM DBS in one patient. Improvement in the TST tremor component was noted with dopaminergic medications in only three patients and with trihexyphenidyl in two. Among the subjects who took levodopa, the subjects tried at least 200 mg three times per day. ET medications were generally ineffective [Table S1]. Mean follow up period after diagnosis of PD was 2.04 ± 0.86 years. Only one of six patients with a long duration of levodopa use developed dyskinesia.
TABLE 1.
Patient Summary
| Sex | TST pheno‐type | Arm involved with TST | Age of onset of TST | Age of onset of PD signs | First PD sign | Main current PD side | Age at DaT‐scan | DaTscan abnormal | TST still present? | TST responded to DM? | TST responded best to treatment with? | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | M | Writing | R | 48 | 51 | RT | R | 60 | 3# Bl P, 1# L > R C | Yes | Yes | Trihexyphenidyl, Levodopa, ropinirole |
| 2 | F | Mascara | R | 60 | 66 | RT | Bl | 68 | 2# L > R PS | Yes | No | None |
| 3 | M | Holding a microphone | R | 59 | 67 | RT | R | 69 | 1# L C,P | Yes | No | L VIM DBS |
| 4 | M | Writing | R | 30 | 63 | RT | R | NA | NA | Yes | Yes | Rotigotine |
| 5 | M | Writing | R | 45 | 60* | RT | R | 64 | 3# Bl P, L C | No | No | L STN DBS |
| 6 | F | Holding glass | R | 30* | 63* | RT | R | 78 | 1# Bl PS | Yes | No | Trihexyphenidyl |
| 7 | F | Typing | R | 67 | 68 | RT | R | 69 | 1# L > R P | Yes | Yes | Pramipexole |
| 8 | F | Writing | R | 60 | 67 | RT | R | 74 | L P | No | No | L STN DBS |
| 9 | M | Writing | R | 70 | 72 | B | R | 72 | 3# R C | Yes | No | None |
| 10 | M | Writing | R | 70 | 74 | B | R | 74 | 1# Bl P, 3# R C | Yes | No | Amantadine |
| 11 | F | Jaw drinking tremor | Not applicable | 74 | 82 | RT | R | 82 | L > R PS | Yes | No | Botulinum Toxin‐ A |
| 12 | M | Writing | R | 36 | 79 | RT | R | 81 | 2# L > R P | Yes | No | Propranolol |
Patient could provide only a rough estimate.
M, male; F, female; R, right; L, left; Bl, bilateral; RT, rest tremor; B, bradykinesia; P, putamen; C, caudate; PS, posterior striatum; 1#, mild decrease; 2#, moderate decrease; 3#, marked decrease; DM, dopaminergic medications; NA, not available.
Discussion
We report 12 subjects with TST who developed PD after a highly variable amount of time, confirmed by DaTscan in 11, manifest with rest tremor on the same side of the TST. In most, the TST was not very L‐dopa responsive, nor responsive to ET medications, but did respond well to STN and VIM DBS in the three subjects who had surgery. The above mentioned findings of TST, ipsilateral rest tremor and response to DBS can be appreciated in Video S1.
All of our patients who were scanned showed decreased uptake on the DaTscan. DaTscan is used to assist in distinguishing Parkinsonian syndromes including PD from ET, dystonic tremor, and drug induced tremors. Sensitivity of DaTscan for detection of PD is about 92% as shown by Gayed et al. 7 and 88.7% on a pooled analysis by O'Brien JT et al. 8 The reduction of tracer uptake is largely contralateral to the side of greater clinical PD signs, but can be ipsilateral in about 5%. 7 However, DaTscan correlates less with tremor compared to bradykinesia and rigidity. 9 In our study, the tracer uptake was reduced on the side contralateral to TST in seven subjects and was ipsilateral in 2, although clinical rest tremor corresponded to the site of TST in all 10 cases. The clinical and imaging findings on the same side as their TST suggest a pathophysiological association between TST and PD rather than coincidental co‐occurrence. We cannot determine what percentage of TST develop parkinsonism and do not routinely obtain DaTscans on patients with isolated TST, so have not seen an abnormal DaTscan in pure TST. We do have two additional subjects who probably had TST and also have mild parkinsonism and abnormal DaTscans, but at the time of initial evaluation by us both also had kinetic tremor of at least 1 cm amplitude, although no postural tremor.
There are a few other reports of TST and persistent unilateral tremor progressing to PD. 4 , 5 , 6 One study of 56 patients with task specific writing tremor provided a detailed description of the phenomenology of TST in which 12 of the 56 patients demonstrated rest tremor, mostly ipsilateral to the TST, and eight had re‐emergent tremor. However, only two patients met clinical criteria for PD. 4 Smith et al. presented an abstract of five patients with TST who progressed to PD. 5 In all five patients, bradykinesia, rigidity and rest tremor developed on the side of the TST. The tremor was less responsive to tremor medications and responded to carbidopa‐levodopa. DaTscan was abnormal in three patients who were scanned. Similarly, Battista et al. reported a single 63 year old patient with TST who progressed to PD. 6 The tremor in this patient was responsive to levodopa. In a follow up study of 13 patients with asymmetrical postural tremor by Chaudhuri et al., all patients developed tremor predominant PD by a follow‐up interval of an average of 19.2 years. 10 The rest tremor was ipsilateral to the arm with the postural tremor. The tremor in this study group generally responded to beta blockers and alcohol but the tremor here was postural and not TST.
Our report suffers all the short‐comings of any retrospective series that relies on patient recall. Most subjects were seen initially with only their TST and followed as they developed PD but a few were seen after mild PD signs were present and those are more subject to recall bias. Most subjects were seen after we started data collection to fill any missing datapoint. Despite these issues, we feel that long standing TST is a precursor to PD.
Conclusion
Rest tremor and bradykinesia can occur in patients with isolated TST after a variable period of time, consistent with evolution into PD, confirmed by DaTscan. The TST tremor is not generally responsive to tremor medications, occasionally responsive to dopaminergics and anti‐cholinergic, but very responsive to STN and VIM DBS. This suggests a pathophysiological association between the two entities.
Author Roles
(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique;
(3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.
W.O.: 1A, 2A, 2B, 2C, 3B
V.K.: 1B, 1C, 2A, 2B, 3A
Disclosures
Ethical Compliance Statement: This was a retrospective chart review trial with waiver from Methodist Research Institute IRB. Consent for videotaping was obtained on an IRB approved consent form for videotaping. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflicts of Interest: No specific funding was received for this project. The authors declare that there are no conflicts of interest relevant to this work.
Financial disclosures for previous 12 months: W.O. is employed in Houston Methodist Hospital. He has received Speaking/Consulting fee from USWorldMeds, Neurocrine, TEVA, Sunovion, Acorda, ACADIA, IMPAX, and Grant support from Lundbeck, Biogen, Revance, IMPAX, Sun.
V.K. has no disclosures to report.
Supporting information
Table S1. All non‐surgical treatments tried by patients.
Video S1. This video shows a patient with task specific writing tremor who later developed PD. For the first part of the video, the patient is off STN DBS and is shown to have bradykinesia and re‐emergent tremor of the right arm. No postural arm tremor is noted but a severe task specific writing tremor is seen with the right arm, slightly less if asked to draw a straight line as opposed to letters. The subsequent portion shows improvement in bradykinesia, re‐emergent tremor and TST when the STN DBS is activated.
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Associated Data
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Supplementary Materials
Table S1. All non‐surgical treatments tried by patients.
Video S1. This video shows a patient with task specific writing tremor who later developed PD. For the first part of the video, the patient is off STN DBS and is shown to have bradykinesia and re‐emergent tremor of the right arm. No postural arm tremor is noted but a severe task specific writing tremor is seen with the right arm, slightly less if asked to draw a straight line as opposed to letters. The subsequent portion shows improvement in bradykinesia, re‐emergent tremor and TST when the STN DBS is activated.