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Year : 2018  |  Volume : 1  |  Issue : 1  |  Page : 2-7

Dystonic tremor: Definition, clinical spectrum, pathophysiology, and treatment

Department of Neurology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India

Date of Web Publication24-Dec-2018

Correspondence Address:
Prof. Sanjay Pandey
Department of Neurology, Academic Block, Room No. 507, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi 110002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AOMD.AOMD_6_18

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Tremor is now considered an important phenotypic feature of dystonia. Tremor in dystonia is of two types: dystonic tremor, where tremor occurs at the same site that involves dystonia, and tremor associated with dystonia, where tremor occurs at a site other than that involving the dystonic region. A patient may be found to have both the conditions together, and different syndromes are separated on clinical grounds. The aim of this review was to discuss the definition, clinical spectrum, pathophysiology, and treatment of dystonic tremor.

Keywords: Dystonia, scans without evidence of dopaminergic deficit, tremor

How to cite this article:
Sarma N, Pandey S. Dystonic tremor: Definition, clinical spectrum, pathophysiology, and treatment. Ann Mov Disord 2018;1:2-7

How to cite this URL:
Sarma N, Pandey S. Dystonic tremor: Definition, clinical spectrum, pathophysiology, and treatment. Ann Mov Disord [serial online] 2018 [cited 2023 May 30];1:2-7. Available from: https://www.aomd.in/text.asp?2018/1/1/2/248388

  Introduction Top

The 2013 consensus update has defined dystonia as “a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both.”[1] Dystonic movements have been described to be patterned, twisting, and tremulous.[1] Dystonia has been classified according to two main axes: axis 1 includes clinical characteristics, whereas axis 2 consists of etiology.[1] Besides describing dystonic movements to have a tremulous component, they have also described dystonic tremor has also been described as an oscillatory, rhythmical, although often inconstant, patterned movement produced by contractions of dystonic muscles.[1] However, it has not been delineated whether tremor accompanying dystonia is an extension of the phenotypic presentation or is it a separate entity in itself.

The 2017 consensus statement on tremor defines tremor as “an involuntary, rhythmic, oscillatory movement of a body part.”[2] Similar to dystonia, this consensus statement has classified tremor in two main axes: axis 1 includes clinical features, whereas axis 2 comprises etiology.[2] Tremor is classified based on activation conditions as rest or action. The latter includes postural, kinetic (simple and intention), task-specific, and isometric tremors.[2] Though tremor in dystonia can be differentiated from essential tremor in isolation clinically, dystonia can be present in 12%–47% of patients with essential tremor.[3],[4] The recent consensus statement by the Movement Disorder Society has defined essential tremor with questionable dystonic posturing as essential tremor plus syndrome.[2] However, it might also be prudent to also define when not to call a dystonic posturing questionable because until then there shall always be situation where there will be difficulty in distinguishing essential tremor plus and dystonic tremor syndromes.

  Classification of Tremor in Dystonia Top

According to the 2017 consensus statement by the Movement Disorder Society,[2] dystonic tremor syndromes are tremor syndromes combining tremor and dystonia as the leading neurological signs. Tremor in dystonia is of two types: dystonic tremor, where tremor occurs at the same site that involves dystonia, and tremor associated with dystonia (TAD), where tremor occurs at a site other than that involving the dystonic region. A patient may be found to have both the conditions together, and different syndromes are separated on clinical grounds.[2]

  Epidemiology Top

The prevalence of tremor in dystonia has been described to lie between 14% and 86.67% across various studies.[5] Tremor has been found to be more common in patients with late-onset dystonia, those with cervical dystonia, and those with segmental/multifocal dystonia.[6] It has been found in studies that up to four-fifths of the patients of tremor with dystonia have dystonia preceding tremor.[7] Tremor in dystonia is predominantly of action type (usually postural or kinetic), and rest tremor is regarded as the least prevalent.[7],[8] However, a recent Italian study has found rest tremor to be present in around 32% patients who have tremor in dystonia.[9] To provide an Indian perspective, we examined 90 patients of dystonia and found tremor to be present in around 45.5% (41) patients. Tremor was most prevalent in multifocal and segmental dystonia, and the majority of patients had a combination of dystonic tremor and tremor in dystonia. Rest tremor was found in 9 of those 41 patients.[10]

  Clinical Features Top

Tremor in dystonia tends to be coarse, irregular, and asymmetric; having a jerky component; and is usually unilateral. The phenotypic manifestation of tremor in dystonia may sometimes confuse the physicians with certain other conditions [Figure 1]. As mentioned earlier, dystonia in essential tremor is a fairly common phenomenon and a physician may confuse this with TAD. Essential tremor is usually bilateral and symmetric. Features of tremor in dystonia such as sensory trick, null point phenomenon, directional quality, and irregularity are useful in differentiating it from essential tremor.[11] Head tremor in essential tremor can be distinguished from tremor in dystonia by observing the persistence of tremor in lying down position, which is more likely to occur in the latter.[12] Voice tremor in dystonia can be distinguished from that of essential tremor by its disappearance during singing and emotional speech.[13]
Figure 1: Differential diagnosis of dystonic tremor and tremor associated with dystonia. SWEDD = Scan without evidence of dopaminergic deficit

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Dystonia myoclonus is a condition consisting of dystonia in the form of cervical dystonia and writer’s cramp along with myoclonus involving the trunk and arm. The patients with these conditions may develop fine myoclonic jerks while writing, thus making it similar to either TAD or dystonic tremor.[14] Although this condition is alcohol responsive, it might sometimes be difficult to distinguish between the two. Surface electromyography reveals longer bursts in TAD when compared to dystonia myoclonus.[15]

Patients with Parkinson’s disease who have focal dystonia along with rest tremor may be confused clinically with those who have tremor in dystonia. In addition, the slowness caused by dystonia may mimic bradykinesia of Parkinson’s disease. As mentioned earlier, tremor in dystonia is more prominent during action, whereas tremor of Parkinson’s disease is predominantly at rest. Reemergence of tremor is found particularly in Parkinson’s disease; however, the same may also be found rarely in tremor in dystonia.[16] Isolated head tremor suggests more of tremor in dystonia, whereas the presence of lip and jaw tremor suggests Parkinson’s disease.[14] Patients with Parkinson’s disease have micrographia, whereas patients with tremor in dystonia have macrographia. Other associated factors of tremor in dystonia such as null point and sensory trick are absent in patients with Parkinson’s disease.

A certain group of patients may present with an asymmetric resting arm tremor, impaired arm swing, and facial hypomimia or a jaw tremor, but without evidence of bradykinesia. They can be initially misdiagnosed as cases of Parkinson’s disease; however, dopamine transporter single-photon emission computed tomography (DaT-SPECT) scans are normal in these patients and such a state is described as SWEDDs (scans without evidence for dopaminergic deficit).[17] Patients labeled, as SWEDDs should not be always considered the same as those with tremor in dystonia. A recent retrospective study reevaluated the SPECT scans of 10 patients who were earlier labeled as SWEDDs and found 9 of 10 scans to be outside the normal limits.[18] The diagnosis of SWEDDs should be hence made after a thorough clinical and imaging evaluation.

  Pathophysiology Top

The pathogenesis of dystonic tremor has been implicated to occur as a result of loss of inhibition at cortical, subcortical, and spinal levels, similar to that of dystonia.[8] This loss of inhibition results in an imbalance in the direct and indirect pathways in basal ganglia, leading to excessive stimulatory output. The cerebellum has also been hypothesized to play a role in the pathogenesis of tremor in dystonia. It has been hypothesized that the cerebellum may have influence on cortical excitability and somatosensory functions.[19] Defazio et al.[6] have proposed a dysfunction in the burst of cerebellar neurons to be responsible for patients with tremor in dystonia. Involvement of cerebellar circuit has been demonstrated electrophysiologically using blink reflex. A study conducted blink reflex recovery curve in patients of cervical dystonia with and without tremor. Patients of cervical dystonia with tremor showed a decreased number of conditioned responses in the eyeblink classical conditioning paradigm, which was mediated by cerebellum.[20] This suggests that cerebellar dysfunction may determine the presence of tremor in dystonia. On the basis of observations in patients, the thalamus is also considered an important center in tremor in dystonia. The cerebello-ponto-thalamic pathway and cortico-striato-ponto-thalamic loop dysfunction have also been found to cause tremor in dystonia, probably by increasing the thalamocortical drive.[21],[22] A study comprising functional magnetic resonance imaging (MRI), voxel morphometry, and diffusion-weighted imaging was conducted in patients of spasmodic dysphonia with and without dystonic voice tremor.[23] They found patients of spasmodic dysphonia with voice tremor to have additional abnormalities in middle frontal gyrus and cerebellum when compared to patients of spasmodic dystonia without voice tremor. Inferior frontal gyrus and putaminal abnormalities were common in both the groups. This suggests that tremor in dystonia is an extended spectrum of the same disease process.

There can be difficulty in differentiating tremor in dystonia from early Parkinson’s disease that present with tremor and posturing with no abnormality on MRI. DaT-SPECT helps us in this situation as it reveals asymmetrical reduced uptake in the striatum in Parkinson’s disease and is normal in patients of tremor in dystonia.[24],[25] There are a certain group of patients, however, as mentioned in “Clinical Features” section as SWEDDs, who present with tremor and reduced arm swing but have normal DaT scans. However, it is not clear whether SWEDDs patients are the same as tremor in dystonia. A long-term follow-up study of 16 patients of SWEDDs found abnormal DaT scans in two patients after a gap of 5 years.[26] This may suggest the term “SWEDDs” contains a heterogeneous group of patients, of which some constitute Parkinson’s disease; whether the rest patients are same as tremor in dystonia is something that needs further evaluation.

A cross-sectional imaging study was conducted by comparing patients of dystonic tremor with those of essential tremor. Thickening and increased gray matter volume of the left sensorimotor cortex was found in patients of dystonic tremor as compared to those of essential tremor.[27] It can be concluded that tremor in dystonia involves multiple levels of the neuraxis, including the cortex, subcortex, and cerebellum.

Besides structural imaging, tremor in dystonia also bears electrophysiological differences, differentiating it from essential tremor. Blink reflex studies have shown abnormalities in R2 response in patients of tremor in dystonia when compared to patients of essential tremor.[28] Patients with tremor in dystonia were found to have higher temporal discrimination threshold and a lower temporal discrimination movement threshold when compared to those with essential tremor.[29] Similarly patients with tremor in dystonia were found to have abnormal somatosensory temporal discrimination threshold when compared to those with essential tremor.[30]

  Genetic Forms of Tremor in Dystonia Top

Certain genetic forms of dystonia were found to have tremor as a prominent clinical feature. Dystonic head tremor was described in patients having DYT24 (ANO3) and DYT25 (GNAL) mutations.[31],[32] Certain patients with DYT24 mutations may have tremor as the only clinical manifestation.[31] A recent genetic study conducted in patients of cervical dystonia found tremor in THAP1, TOR1, and GNAL mutations.[33] Also patients with TOR1 and GNAL mutations had positive family history of tremor with absence of dystonia in family members.[33] This may suggest a hypothesis that tremor and dystonia are part of a single phenotypic spectrum of one pathologic process.

  Secondary Forms of Tremor in Dystonia Top

Tremor in dystonia has been described because of various etiologies. The Lausanne Stroke Registry described three patients with dystonic tremor of hand following stroke.[34] All the three patients had thalamic infarct. Dystonic tremor has also been described following striatopallidal and thalamic strokes.[22] Secondary cervical dystonic tremor has also been described in a patient following Japanese encephalitis.[35] MRI of that patient revealed thalamic and pontine lesions. There is also a case report of development of Holmes tremor and focal dystonia of right upper limb following gamma knife surgery of the left thalamus for arteriovenous malformation.[36]

  Treatment Top

Therapeutic options available for tremor in dystonia include drugs, botulinum toxin, deep brain stimulation (DBS), MRI-guided focused ultrasound (MRgFUS), and other procedures such as transcutaneous electrical nerve stimulation.[5] However, no randomized trials on the efficacy of drugs are available, and the algorithm to treatment is based on case reports and expert consensus. Oral drugs available for treatment include trihexyphenidyl, clonazepam, propranolol, and tetrabenazine. A study of 25 patients of dystonic tremor treated with drugs found response only in 40% of the patients, with the best response shown by anticholinergics followed by propranolol.[37]

Tremor in dystonia may have a good response to botulinum toxin, especially when involving the head, jaw, and vocal cords.[5] Botulinum toxin has also been found to be useful in primary writing tremor.[38] A comparative study of patients with cervical dystonia found better response with botulinum toxin in those patients who also had tremor.[39]

DBS is an important modality of treatment in tremor in dystonia, especially in cases that are not responsive to conservative measures. It involves electrical stimulation of specific regions of the brain through electrodes with a subcutaneously placed pulse generator. The sites that have been tried for electrical stimulation include ventrointermediate (Vim) nucleus of thalamus, globus pallidus internus (GPi), and zona incerta. A retrospective study evaluating the outcome of DBS in 10 patients found best tremor control with Vim stimulation, however, with persisting mild dystonia, whereas those with GPi stimulation had marked improvement in dystonia and around 50% improvement in tremor.[40],[41]

MRgFUS is a novel, incision-free ablative technique used successfully in patients with essential tremor. Encouraging results of using this technique are reported in the treatment of patients with dystonic tremor also. Recently, Fasano et al. published results of a 6-month single-blinded study reporting unilateral thalamotomy (Vim nucleus of the dominant hemisphere) with MRgFUS in six patients with tremor (three with dystonic tremor and three with Parkinson’s disease) other than essential tremor.[42] All patients achieved sustained improvement of contralateral tremor score.

Although there no clear-cut guidelines for the treatment of tremor in dystonia, it is suggested that a patient with arm tremor may be first treated with oral agents, whereas patients with jaw, head, and vocal cord tremor may be treated with botulinum toxin.[41] Response failure with these approaches should warrant a consideration for DBS.[41][Table 1] summarizes the therapeutic modalities for tremor in dystonia.
Table 1: Treatment of tremor in dystonia

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  Conclusion Top

Tremor in dystonia is a fairly prevalent condition and is primarily classified as whether it occurs at the same site as of dystonia or elsewhere. It tends to be more commonly postural or kinetic and sometimes at rest. Clinicians must be able to identify this entity and separate it from other common causes of tremor such as essential tremor and Parkinson’s disease. Although various treatment modalities are available, the response is still far from satisfactory. Further research is required for better understanding of pathophysiological process and for the development of treatment modalities, which can be made easily available to all patients.

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  References Top

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