A clinical study of non-parkinsonian tremor in Moroccan patients

Objective

To report the characteristics of the most frequent tremors in a population of Moroccan patients.

Background

Tremor is the most common movement disorder. It implies a wide variety of disorders with Parkinson's disease and essential tremor being the most frequent.

Methods

A retrospective study of 148 patients with tremor referred to our movement disorders outpatient clinic was performed. Clinical features and treatment regimens were analyzed. Patients with parkinsonian tremor were excluded.

Results

We included 62 patients with non-parkinsonian tremor. The etiologies were as follows: essential tremor (54.8%), dystonic tremor (19.4%), tremor associated with dystonia (14.5%), enhanced physiological tremor (3.2%), cerebellar tremor (3.2%), psychogenic tremor (3.2%) and Holmes’ tremor (1.6%). The characteristics of essential tremor patients were analyzed. Female patients accounted for 67.6% of patients. Mean age at the onset of tremor was 52.2 ± 16.4 years. Family history of tremor was reported in 17.6% of cases. Tremor affected the arms (94.1%), head (52.9%), voice (35.3%) and legs (8.8%). Tremor was bilateral in 87.5% but was asymmetrical in 50% of patients. Patients had postural tremor (76.5%), kinetic tremor (79.4%) and rest tremor (associated in 11.8%). Treatment relied on propranolol (88.3%), primidone (14.7%), gabapentin (14.7%), clonazepam (14.7%), alprazolam (11.8%), topiramate (5.9%) and, in one patient, radiosurgery.

Conclusions

Essential tremor was the predominant diagnosis, confirming its high prevalence. There was a predominance of female patients and a peak of age at onset in the fifth and sixth decades. Asymmetry of the disease was noted in half of patients.     

Deep Brain Stimulation of the Subthalamic Area for Dystonic Tremor

The stereotactic surgical target for dystonic tremor is the subject of ongoing debate. Targeting the subthalamic area using deep brain stimulation has been regaining interest as a therapy for various types of involuntary movements. We describe the efficacy of stimulation of the subthalamic area in a patient with intractable dystonic tremor. Excellent control without neurological complications was achieved. This case report demonstrates that the subthalamic area is a valuable target for the control of dystonic tremor.     

Motor outcomes and adverse effects of deep brain stimulation for dystonic tremor: A systematic review

Dystonic tremor (DT) is defined as the tremor in body parts affected by dystonia. Although deep brain stimulation (DBS) has been used to manage medically-refractory DT patients, its efficacy has not been well established. The objective of this study is to provide an up-to-date systematic review of DBS outcomes for DT patients. We conducted a literature search using Medline, Embase, and Cochrane Library databases in February 2020 according to the PRISMA guidelines. From 858 publications, we identified 30 articles involving 89 DT patients who received DBS of different targets. Thalamic DBS was the most common (n = 39) and improved tremor by 40–50% potentially in the long-term over five years with variable effects on dystonic symptoms. Globus pallidus internus (GPi), subthalamic, and subthalamic nucleus (STN) DBS improved both tremor and dystonic symptoms; however, data were limited. A few studies have reported better tremor and dystonia outcomes with combinations of different targets. Concerning adverse effects, gait/balance disorders, and ataxia seemed to be more common among patients treated with thalamic or subthalamic DBS, whereas parkinsonian adverse effects were observed only in patients treated with subthalamic or GPi DBS. Comparative benefits and limitations of these targets remain unclear because of the lack of randomized controlled trials. In conclusion, DBS of these targets may improve tremor with a variable effect on dystonia with different adverse effect profiles. The shortcomings in the literature include long-term motor outcomes, quality of life outcomes, optimal DBS targeting, and DBS programming strategy.     

Tremor associated with Klinefelter syndrome – A case series and review of the literature

BackgroundPrevious case series suggested a link between Klinefelter syndrome (KS) and essential tremor (ET) or an ET-like syndrome.MethodsWe investigated three KS-patients with tremor including tremor-analyzes and discuss our data in context to findings from a literature review. The clinical outcome after deep brain stimulation (DBS) is also reviewed.ResultsTremor in KS is predominantly a postural and kinetic tremor that resembles ET. Our patients were further characterized by absent family history for tremor in first degree relatives, lack of subjective alcohol responsiveness inquired by history, and tremor onset in childhood. One of our patients and two cases from literature improved after DBS of the ventral intermediate nucleus (VIM) of the thalamus.ConclusionsTremor in KS shares several features with ET. If other characteristics such as family history, alcohol responsiveness, and age at tremor onset may serve as discriminating factors from ET, needs to be further investigated. First observations suggest that VIM-DBS may be efficacious.     

Effects of thalamic stimulation frequency on intention and postural tremor

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus improves essential tremor. Suppression of the amplitude of the postural tremor component with VIM DBS depends on stimulation frequency. The purpose of this study was to determine the effect of DBS frequency on the intention tremor component, that is, tremor that is enhanced by target-directed movement, and to compare it to the effect of DBS frequency on postural tremor in people with essential tremor. We measured tremor frequency and amplitude during trials of postural holding and voluntary reaching between two targets at 10 different stimulation frequency settings between 0 and 185 Hz. Tremor frequency did not change with changes in stimulation frequency. Amplitude suppression of both intention and postural tremor depended on stimulation frequency. Maximal tremor reduction occurred at approximately 130 Hz for both forms of tremor. However, at optimal frequencies, the percent reduction in tremor amplitude relative to the DBS OFF condition was greater for postural than for intention tremor. These results suggest that VIM DBS stimulation frequencies near 130 Hz may provide maximal control of intention and postural tremor. Identification of optimal stimulation settings should consider assessment of intention tremor, not just postural tremor, as intention tremor may not be as well controlled as postural tremor but may be a better gauge for functional benefit.     

Primidone and essential tremor

Summary To clarify whether primidone itself, and not only its metabolite phenobarbitone, suppresses essential tremor, the effect of a high single dose of primidone was tested. Of 11 patients, 8 showed a reduction of their tremor by 54%–69% for up to 28h. The serum concentration of primidone was as expected, whereas those of the metabolites phenyl-ethylmalonamide and phenobarbitone were very low. The tremor suppression can thus be considered to be an effect of primidone. Three of the 11 patients did not show a reduction of tremor.     

Objective predictors of ‘early tolerance’ to ventral intermediate nucleus of thalamus deep brain stimulation in essential tremor patients

Objective

To identify pre-operative clinical and computerized spiral analysis characteristics that may help ascertain which patients with Essential Tremor (ET) will exhibit ‘early tolerance’ to ventral intermediate nucleus of thalamus (Vim) deep brain stimulation (DBS).

Surgical targets for dystonic tremor: Considerations between the globus pallidus and ventral intermediate thalamic nucleus

Dystonic tremor (DT) is characterized by coexisting tremor and abnormal dystonic posturing in the same segment. DT is often medically refractory and DBS is an important therapeutic option. However, the optimal surgical target for DT remains uncertain with Vim, GPi and zona incerta previously reported as effective. We retrospectively reviewed the outcome data from all patients with DT involving at least one upper extremity who underwent DBS at Vanderbilt University from July 2006 to July 2010. We evaluated the improvement of tremor and dystonia after their response to DBS was judged to be maximal. Ten patients met the inclusion criteria. Vim was targeted in four patients and three had unilateral procedure and one bilateral Vim DBS. GPi was targeted in four patients with bilateral DBS procedure in every patient from this subgroup. A combined bilateral GPi and unilateral Vim DBS was performed in two patients. The best results for tremor control were observed in patients with Vim DBS but they had persisting mild dystonia. Patients with GPi DBS had average DT improvement by approximately 50% but their dystonia symptoms were markedly improved. We propose that the patients with DT with a mild dystonia should be considered for Vim DBS procedure and the coexistence of severe DT and dystonia may be successfully controlled by combined GPi and Vim DBS surgeries.     

Use of efficacy probability maps for the post-operative programming of deep brain stimulation in essential tremor

IntroductionPost-operative programming of deep brain stimulation for movement disorders can be both time consuming and difficult, which can delay the optimal symptom control for the patient. Probabilistic maps of stimulation response could improve programming efficiency and optimization.MethodsThe clinically selected contacts of patients who had undergone ventral intermediate nucleus deep brain stimulation for the treatment of essential tremor at our institution were compared against contacts selected based on a probability map of symptom reduction built by populating data from a number of patients using non-rigid image registration. A subgroup of patients whose clinical contacts did not match the map-based selections prospectively underwent a tremor rating scale evaluation to compare the symptom relief achieved by the two options. Both the patient and video reviewer were blinded to the selection.Results54% of the map-based and clinical contacts were an exact match retrospectively and were within one contact 83% of the time. In 5 of the 8 mismatched leads that were evaluated prospectively in a double blind fashion, the map-based contact showed equivalent or better tremor improvement than the clinically active contact.ConclusionsThis study suggests that probability maps of stimulation responses can assist in selecting the clinically optimal contact and increase the efficiency of programming.     

Effects of chronic alcohol consumption on long-term outcomes of thalamic deep brain stimulation for essential tremor

The prevalence of essential tremor (ET) is about 4% above 40 years of age. Chronic alcohol consumption is present in around 20% of patients with ET. Our objective was to identify whether chronic alcohol consumption was associated with a negative effect on tremor outcome after thalamic deep brain stimulation (DBS) in ET patients. We conducted a retrospective chart review, from January 2005 to December 2012, from which 23 patients who had ventral intermediate nucleus (Vim)-DBS surgery for ET were identified. Seven patients had a positive history of chronic alcohol consumption. We defined as chronic alcohol users those patients with a habit of drinking alcohol every day in order to suppress tremor. In the overall group of 23 patients, there was a reduction in the median tremor score from 8 pre-operatively, to 1 post-operatively (p < 0.0001). The alcohol consumers group experienced a reduction in the median tremor score from 6 pre-operatively to 0 post-operatively (p = 0.03). The non-alcohol consumers group had a reduction in the median tremor score from 8 pre-operatively to 1.7 post-operatively (p < 0.0001). Both groups of patients experienced significant benefit from thalamic DBS. A larger study may reveal statistically significant differences between subgroups.     

Loss of benefit in VIM thalamic deep brain stimulation (DBS) for essential tremor (ET): How prevalent is it?

Ventralis intermedius (Vim) thalamic deep brain stimulation for medication-refractory essential tremor (ET) has been shown to significantly improve severity of limb tremor in several large case series with significant reduction in objective motor scores. A variable proportion of patients experience decline in benefit over time, however, most studies have not been designed to describe the phenomenon of waning benefit in terms that are helpful for patient counseling. In this retrospective single center study, we define waning benefit as a phenomenon that occurs after patients begin to require reprogramming visits to optimize DBS benefit on tremor. We employed a survival analysis with time to escape (TTE) as a quantitative measure of time elapsed between implantation and the need for subsequent reprogramming. In our cohort of ET patients operated on with Vim DBS from 1994 to 2009, among 45 subjects who met inclusion criteria, 73% reported waning benefit at some point during a mean follow-up period of 56 months (range 12–152 months). The mean TTE from implantation date was 18 months (range 3–75 months). We conclude that loss of benefit over time from Vim DBS for ET is more prevalent than previously published estimates have indicated and should be discussed during patient counseling regarding durability of expected benefit. In addition, this data suggests that a disease-based explanation rather than technical factors are more likely to explain the decline in benefit.     

Thalamic stimulation for primary writing tremor

We report a patient with primary writing tremor whose tremor was treated with thalamic stimulation. He had undergone trials of multiple oral medications with no benefit for his tremor. An electrode lead was implanted in the thalamic nucleus ventralis intermedius with nearly complete control of his tremor and no postoperative complications. We conclude that nucleus ventralis intermedius thalamic stimulation is safe and effective for primary writing tremor. Received: 30 March 2000 / Received in revised form: 31 October 2000 / Accepted: 13 November 2000     

Effects of ventral intermediate nucleus deep brain stimulation across multiple effectors in essential tremor

ObjectiveEssential tremor (ET) prominently affects the upper-limbs during voluntary movements, but can also affect the lower-limbs, head, and chin. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of thalamus improves both clinical ratings and quantitative measures of tremor, no study has quantified effects of DBS on tremor across multiple body parts. Our objective was to quantify therapeutic effects of DBS across multiple body parts in ET.MethodsWe performed quantitative assessment of tremor in ET patients who had DBS for at least one year. We assessed tremor on and off VIM-stimulation using triaxial accelerometers on the upper-limbs, lower-limbs, head and chin during seated and standing tasks.ResultsVIM-DBS significantly reduced tremor, but there was no statistical difference in degree of tremor reduction across the measured effectors. Compared to healthy controls, ET patients treated with DBS showed significantly greater tremor power (4–8 Hz) across all effectors during seated and standing tasks.ConclusionsVIM-DBS reduced tremor in ET patients. There was no significant difference in the degree of tremor reduction across the measured effectors.SignificanceThis study provides new quantitative evidence that VIM-DBS is effective at reducing tremor across multiple parts of the body.     

Effects of Electrode Implantation Angle on Thalamic Stimulation for Treatment of Tremor

Introduction. Chronic thalamic stimulation has been confirmed as an effective treatment for tremor. The optimal target has been commonly accepted to be situated within the ventral thalamus, but a standard trajectory of the deep brain stimulation (DBS) electrode has not yet been established. Materials and Methods. A 53‐year‐old man with an 11‐year history of essential tremor was treated by DBS of the thalamus. In this patient, we had a chance to compare the effects of different trajectory angles of the DBS electrode on tremor. Results. Intraoperative stimulation with the DBS electrode temporarily inserted at a high angle to the horizontal plane of the anterior commissure–posterior commissure (AC–PC) line to cover only the nucleus ventralis intermedius (Vim) was not effective. In contrast, stimulation with the DBS electrode permanently implanted at a low angle, covering a wide area extending from the nucleus ventralis oralis (Vo) to the Vim, reduced the tremor. Conclusion. We report on the case of a patient who showed different effects on tremor depending on the trajectory angle of the DBS electrode to the AC–PC line. The insertion trajectory of the DBS electrode may be an important factor for the treatment of tremor.     

脑深部电刺激术治疗震颤

目的探讨脑深部电刺激术（brain deep stimulation,DBS）治疗各种震颤的疗效、术中手术靶点确定以及术后程控策略.方法采用微电极记录下丘脑腹中间核和丘脑底核电刺激术,对4例原发性震颤（essentialtremor,ET）（其中1例合并帕金森病患者靶点选择丘脑底核）和1例窒息后震颤症患者进行治疗.结果4例ET患者经过2～4次调试,双侧上肢症状控制满意（改善率在75%～90%）,其中1例头部震颤和发音震颤患者症状显著改善（改善率分别为82%和84%）.1例缺氧后震颤患者经多次调试症状改善不明显.其中1例行双侧DBS治疗的ET患者,手术后2个月出现慢性硬膜下血肿,经手术清除后痊愈,且开启DBS后症状控制满意.5例患者均没有出现永久性并发症.结论DBS是治疗ET双侧症状的首选方法,相对于丘脑毁损术（尤其是双侧）有较高的安全性.