Tremor Syndrome Research Articles

Reader response: MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes.

Fasano et al.1 reported a noninvasive therapeutic option for patients with disabling tremor. It is heartening that the patients had a more than 50% improvement in tremor score sustained over 6 months after the procedure.

Author response: MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes

We thank Dr. Venketasubramanian for the interest in our article,1 and for highlighting the safety concerns of focused ultrasound (FUS) as well as the need for more studies, which we agree on. Temporal bone window applies to standard brain diagnostic ultrasound whereas FUS uses over 1,000 ultrasound beams directed towards a deep target from all directions surrounding the patient's head.2 Therefore, the problem of temporal bone window does not apply to FUS. However, it is estimated that roughly 15% of FUS candidates cannot receive the treatment due to the high bone density of their skull.3

Editors' note: MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes

In “MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes,” Fasano et al. studied unilateral thalamotomy with MRI-guided focused ultrasound (MRgFUS) in patients with tremors other than essential tremor (ET). They found that MRgFUS targeting the ventro-intermedius nucleus (Vim) of the dominant hemisphere improved the tremor of the contralateral hemibody at 6 months. Commenting on the article, Dr. Venketasubramanian is concerned about the potential side effect of the procedure, noting that 2 patients had persistent neurologic symptoms and deficits. He also mentions the absence of an adequate temporal bony window, seen in some individuals, which may limit use of MRgFUS. Authors Fasanol et al. agree with the safety concerns and that more studies are needed. They also explain that the problem of temporal bone window does not apply to focused ultrasound (FUS). However, they clarify that 15% of FUS candidates cannot receive the treatment due to the high bone density of their skull. In “MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes,” Fasano et al. studied unilateral thalamotomy with MRI-guided focused ultrasound (MRgFUS) in patients with tremors other than essential tremor (ET). They found that MRgFUS targeting the ventro-intermedius nucleus (Vim) of the dominant hemisphere improved the tremor of the contralateral hemibody at 6 months. Commenting on the article, Dr. Venketasubramanian is concerned about the potential side effect of the procedure, noting that 2 patients had persistent neurologic symptoms and deficits. He also mentions the absence of an adequate temporal bony window, seen in some individuals, which may limit use of MRgFUS. Authors Fasanol et al. agree with the safety concerns and that more studies are needed. They also explain that the problem of temporal bone window does not apply to focused ultrasound (FUS). However, they clarify that 15% of FUS candidates cannot receive the treatment due to the high bone density of their skull.

Occurrence of thalamic high frequency oscillations in patients with different tremor syndromes

ObjectiveTo assess whether high frequency oscillations (HFOs, >150 Hz), known to occur in basal ganglia nuclei, can be observed in the thalamus. MethodsWe recorded intraoperative local field potentials from the ventral intermediate nucleus (VIM) of the thalamus in patients with Essential Tremor (N = 16), Parkinsonian Tremor (3), Holmes Tremor (2) and Dystonic Tremor (1) during implantation of electrodes for deep brain stimulation. Recordings were performed with up to five micro/macro-electrodes that were simultaneously advanced to the stereotactic target. ResultsThalamic HFOs occurred in all investigated tremor syndromes. A detailed analysis of the Essential Tremor subgroup revealed that medial channels recorded HFOs more frequently than other channels. The highest peaks were observed 4 mm above target. Macro- but not microelectrode recordings were dominated by peaks in the slow HFO band (150–300 Hz), which were stable across several depths and channels. ConclusionHFOs occur in the thalamus and are not specific to any of the tremors investigated. Their spatial distribution is not homogeneous, and their appearance depends on the type of electrode used for recording. SignificanceThe occurrence of HFOs in the thalamus of tremor patients indicates that HFOs are not part of basal ganglia pathophysiology.

Rare tremor syndromes

There is a group of uncommon sporadic tremor syndromes, which are only partially taken into account in the current classification of tremor. Their knowledge is of diagnostic and therapeutic relevance and they should be considered in the differential diagnosis of frequent tremor syndromes. Differential diagnostics and treatment of uncommon tremor syndromes. Literature search (PubMed, Google Scholar). Holmes tremor, myorhythmia, palatal tremor, limb-shaking transient ischemic attack (TIA), tardive tremor, neuropathic tremor, tremor induced by peripheral trauma and orthostatic tremor syndrome are described. Uncommon sporadic tremor syndromes are mainly symptomatic with various underlying neurological or systemic pathologies. Their recognition accelerates the diagnostic process and has therapeutic relevance.

Movement disorders in mitochondrial disease.

Mitochondrial disease presents with a wide spectrum of clinical manifestations that may appear at any age and cause multisystem dysfunction. A broad spectrum of movement disorders can manifest in mitochondrial diseases including ataxia, Parkinsonism, myoclonus, dystonia, choreoathetosis, spasticity, tremor, tic disorders and restless legs syndrome. There is marked heterogeneity of movement disorder phenotypes, even in patients with the same genetic mutation. Moreover, the advent of new technologies, such as next-generation sequencing, is likely to identify novel causative genes, expand the phenotype of known disease genes and improve the genetic diagnosis in these patients. Identification of the underlying genetic basis of the movement disorder is also a crucial step to allow for targeted therapies to be implemented as well as provide the basis for a better understanding of the molecular pathophysiology of the disease process. The aim of this review is to discuss the spectrum of movement disorders associated with mitochondrial disease.

Thalamic Directional Deep Brain Stimulation for tremor: Spend less, get more

BackgroundDirectional Deep Brain Stimulation (D-DBS) allows axially asymmetric electrical field shaping, away from structures causing side-effects. However, concerns regarding the impact on device lifespan and complexity of the monopolar survey have contributed to sparing use of these features. ObjectiveTo investigate whether chronically implanted D-DBS systems can improve the therapeutic window, without a negative impact on device lifespan, in thalamic deep brain stimulation (DBS). MethodsWe evaluated stable outcomes of initial programming sessions (4–6 weeks post-implantation) retrospectively in 8 patients with drug-resistant disabling tremor syndromes. We assessed the impact of directional stimulation on the Therapeutic Window (TW), Therapeutic Current Strength (TCS), tremor scores, disability scores and total electrical energy delivered. Finally, we performed Volume of Tissue Activation (VTA) modelling, based on a range of parameters. ResultsWe report significant gains in TW (91%) and reductions in TCS (31%) with stimulation in the best direction compared to best omnidirectional stimulation alternative. Tremor and ADL scores improvements remained unchanged at six months. There was no increase in averaged IPG power consumption (there is a 6% reduction over the omnidirectional-only alternative). Illustrative VTA modelling shows that D-DBS achieves 85% of the total activation volume at just 69% of the stimulation amplitude of non-directional configuration.Conclusions: D-DBS can improve the therapeutic window over non-directional DBS, leading to significant reduction in disability that may be sustained without additional reprogramming visits. When averaged across the cohort, power output and predicted device lifespan was not impacted by the use of directional stimulation in this study.

A role for accelerometry in the differential diagnosis of tremor syndromes.

Accelerometry is a reliable tool for gauging the occurrence, amplitude and frequency of tremor. However, there is no consensus on criteria for accelerometric diagnosis of tremor syndromes. We enrolled 20 patients with essential tremor (ET), 20 with dystonic tremor (DT), and 20 with classic parkinsonian tremor (PD-T), all meeting accepted clinical criteria. All the patients underwent dopamine transporter imaging (by means of single-photon emission computed tomography) and triaxial accelerometric tremor analysis. The latter revealed groupwise differences in tremor frequency, peak dispersion, spectral coherence, unilaterality and resting vs action tremor amplitude. From the above, five diagnostic criteria were extrapolated for each condition. Receiver operating characteristic curves, depicting criteriabased scoring of each tremor type, showed negligible declines in specificity for scores ≥4 in patients with ET or DT and scores ≥3 in patients with PD-T, thus providing a simple scoring method (accelerometrically derived) for differential diagnosis of the principal tremor syndromes.

Cranial Neuroimaging in Infantile Tremor Syndrome: The Road Ahead

Cranial Neuroimaging in Infantile Tremor Syndrome: The Road Ahead

Movement Disorders in Women.

Movement disorders such as Parkinson's disease (PD), restless legs syndrome (RLS), chorea, essential tremor, and Tourette syndrome, occur in men and women of all ages. Yet, considerable sex differences in epidemiology, clinical features, and treatment exist in these disorders. In this review, we highlight key differences in the evaluation and management of women with movement disorders, addressing sex-specific complications of treatment and unique challenges surrounding the management of movement disorders during pregnancy. We review the complex relationship between estrogen and movement disorders, including the putative neuroprotective effects of estrogen in PD and the modulatory effects on RLS and chorea associated with autoimmune disease. Further understanding of sex-specific and hormonal effects on clinical features will be important to optimize the management of women with movement disorders in the future.

Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society.

Consensus criteria for classifying tremor disorders were published by the International Parkinson and Movement Disorder Society in 1998. Subsequent advances with regard to essential tremor, tremor associated with dystonia, and other monosymptomatic and indeterminate tremors make a significant revision necessary. Convene an international panel of experienced investigators to review the definition and classification of tremor. Computerized MEDLINE searches in January 2013 and 2015 were conducted using a combination of text words and MeSH terms: "tremor", "tremor disorders", "essential tremor", "dystonic tremor", and "classification" limited to human studies. Agreement was obtained using consensus development methodology during four in-person meetings, two teleconferences, and numerous manuscript reviews. Tremor is defined as an involuntary, rhythmic, oscillatory movement of a body part and is classified along two axes: Axis 1-clinical characteristics, including historical features (age at onset, family history, and temporal evolution), tremor characteristics (body distribution, activation condition), associated signs (systemic, neurological), and laboratory tests (electrophysiology, imaging); and Axis 2-etiology (acquired, genetic, or idiopathic). Tremor syndromes, consisting of either isolated tremor or tremor combined with other clinical features, are defined within Axis 1. This classification scheme retains the currently accepted tremor syndromes, including essential tremor, and provides a framework for defining new syndromes. This approach should be particularly useful in elucidating isolated tremor syndromes and syndromes consisting of tremor and other signs of uncertain significance. Consistently defined Axis 1 syndromes are needed to facilitate the elucidation of specific etiologies in Axis 2. © 2017 International Parkinson and Movement Disorder Society.

Infantile tremor syndrome

Infantile tremor syndrome (ITS) is defined by the tetrad of pallor, developmental delay/regression, skin pigmentation, and brown scanty scalp hair. Involuntary movements in the form of tremors supervene in the natural course of the illness in a significant number of cases. The disorder is common in exclusively breast-fed infants of vegetarian mothers. Most of the children eventually recover but are frequently left with long-term cognitive and language neurodeficits. This review attempts to provide comprehensive and up-to-date information on the subject incorporating recently published studies.

Study of serum folate and ferritin levels in patients of infantile tremor syndrome

Background: Infantile tremor syndrome (ITS) is a very common clinical entity. The etiology of ITS remains obscure. Various hypothesis has been proposed including vitamin B12 deficiency. But it remains to be seen whether there are other contributory factors also. So, this study was conducted to study serum folate levels, serum ferritin levels and type of anemia in patients with infantile tremor syndrome.Methods: The study was a prospective study carried out in the inpatients of department of pediatrics, SSG hospital. Those patients who had clinical features of infantile tremor syndrome but had not received any hematinics or blood transfusion in the past were included in the study. A total of 40 patients were studied. These patients were studied according to the set proforma and were subjected to routine hematological investigations like complete blood count, peripheral smear, blood indices, CRP and serum ferritin and folate levels.Results: Anemia of varying degree was present in all the patients. None of the patients showed low serum folate levels. Serum ferritin levels were low in 2 patients (5%).Conclusions: Folic acid deficiency does not occur and play any role in the etiology of ITS. Iron deficiency is seen in a very small proportion of patients with ITS.

Non-contact measurement of tremor for the characterisation of Parkinsonian individuals: comparison between Kinect and Laser Doppler vibrometer

Parkinson’s disease is a progressive neurodegenerative disorder affecting the central nervous system. One of its main and most evident symptoms is the tremor, which usually manifests at rest with varying intensity during time. An important diagnostic challenge is the differential diagnosis between Parkinson’s disease and the other most widely represented tremor syndrome, i.e. Essential (or senile) tremor. At present there are no standard methods for the quantification of tremor and the diagnosis of both Parkinson’s disease and Essential tremor is mainly done on the base of clinical criteria and by using rating scales. The aim of this work is to objectively and non-invasively assess the tremor linked to the quoted diseases, using non-contact techniques: Laser Doppler Vibrometer (LDV) and Kinect for Windows device. Two subjects with Parkinson’s disease and one with Essential tremor were tested in different conditions: at rest, during a cognitive task, with forward stretched arms and in “Wing position”. The results from data processing in terms of tremor frequency seem to be comparable, with a mean deviation of 0.31 Hz. Furthermore, the values computed are consistent with what is stated in the literature (i.e. 4-12 Hz). So, both LDV and Kinect device can be considered suitable to be used as an objective means for the assessment and monitoring of Parkinson’s disease tremor, helping the clinician in the choice of the most suitable treatment for the patients.

Case Series of Infantile Tremor Syndrome in Tertiary Care Paediatric Centre from Southern India.

Infantile tremor syndrome (ITS) is characterized by anaemia, skin depigmentation, tremors and developmental delay. The lack of sufficient literature on ITS and its conflicting association with vitamin B12 deficiency made us present this article. The objective of this study is to describe demographic, clinical and laboratory profile and outcome of ITS. This is a retrospective chart review of all children presenting with typical features of ITS attending a tertiary paediatric centre in southern India between January 2014 and January 2017. All children with pallor, skin depigmentation and developmental delay, with/without tremors, were included. Anaemia, developmental delay and tremors secondary to non-nutritional causes like metabolic causes were excluded. Of 70 children, 66 were exclusively breastfed and 46 mothers were vegetarians. Mean age of presentation was 13.2 months. Developmental delay was noted in 64, regression in 6 and tremors in 40. Vitamin B12 levels were low in 62 cases. ITS should be considered in children <3 years with anaemia, developmental delay/regression and skin depigmentation, with/without tremors. ITS can be seen in < 3 months of age and in high socio-economic status.

MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes.

To report the 6-month single-blinded results of unilateral thalamotomy with MRI-guided focused ultrasound (MRgFUS) in patients with tremors other than essential tremor. Three patients with tremor due to Parkinson disease, 2 with dystonic tremor in the context of cervicobrachial dystonia and writer's cramp, and 1 with dystonia gene-associated tremor underwent MRgFUS targeting the ventro-intermedius nucleus (Vim) of the dominant hemisphere. The primary endpoint was the reduction of lateralized items of the Tremor Rating Scale of contralateral hemibody assessed by a blinded rater. All patients achieved a statistically significant, immediate, and sustained improvement of the contralateral tremor score by 42.2%, 52.0%, 55.9%, and 52.9% at 1 week and 1, 3, and 6 months after the procedure, respectively. All patients experienced transient side effects and 2 patients experienced persistent side effects at the time of last evaluation: hemitongue numbness and hemiparesis with hemihypoesthesia. Vim MRgFUS is a promising, incision-free, but nevertheless invasive technique to effectively treat tremors other than essential tremor. Future studies on larger samples and longer follow-up will further define its effectiveness and safety. NCT02252380. This study provides Class IV evidence that for patients with tremor not caused by essential tremor, MRgFUS of the Vim improves the tremor of the contralateral hemibody at 6 months.

Hypertrophic Olivary Degeneration and Palatal or Oculopalatal Tremor.

Hypertrophic degeneration of the inferior olive is mainly observed in patients developing palatal tremor (PT) or oculopalatal tremor (OPT). This syndrome manifests as a synchronous tremor of the palate (PT) and/or eyes (OPT) that may also involve other muscles from the branchial arches. It is associated with hypertrophic inferior olivary degeneration that is characterized by enlarged and vacuolated neurons, increased number and size of astrocytes, severe fibrillary gliosis, and demyelination. It appears on MRI as an increased T2/FLAIR signal intensity and enlargement of the inferior olive. There are two main conditions in which hypertrophic degeneration of the inferior olive occurs. The most frequent, studied, and reported condition is the development of PT/OPT and hypertrophic degeneration of the inferior olive in the weeks or months following a structural brainstem or cerebellar lesion. This “symptomatic” condition requires a destructive lesion in the Guillain–Mollaret pathway, which spans from the contralateral dentate nucleus via the brachium conjunctivum and the ipsilateral central tegmental tract innervating the inferior olive. The most frequent etiologies of destructive lesion are stroke (hemorrhagic more often than ischemic), brain trauma, brainstem tumors, and surgical or gamma knife treatment of brainstem cavernoma. The most accepted explanation for this symptomatic PT/OPT is that denervated olivary neurons released from inhibitory inputs enlarge and develop sustained synchronized oscillations. The cerebellum then modulates/accentuates this signal resulting in abnormal motor output in the branchial arches. In a second condition, PT/OPT and progressive cerebellar ataxia occurs in patients without structural brainstem or cerebellar lesion, other than cerebellar atrophy. This syndrome of progressive ataxia and palatal tremor may be sporadic or familial. In the familial form, where hypertrophic degeneration of the inferior olive may not occur (or not reported), the main reported etiologies are Alexander disease, polymerase gamma mutation, and spinocerebellar ataxia type 20. Whether or not these are associated with specific degeneration of the dentato–olivary pathway remain to be determined. The most symptomatic consequence of OPT is eye oscillations. Therapeutic trials suggest gabapentin or memantine as valuable drugs to treat eye oscillations in OPT.

Infantile tremor syndrome of the tropics: A neurocutaneous syndrome of infantile B12 deficiency?

Infantile tremor syndrome of the tropics: A neurocutaneous syndrome of infantile B12 deficiency?

Troubles moteurs tardifs induits par antipsychotiques : mise au point

Antipsychotic-induced tardive movement disorders (ATMDs) constitute a set of late-onset involuntary movements, resulting from the blocking of dopamine receptors. ATMDs are generally underscreened by health professionals, though they may also occur with new generation antipsychotics. ATMDs encompass several specific clinical types: tardive dyskinesia, tardive dystonia, tardive akathisia, tardive tremor, tardive myoclonus, tardive stereotypy, tardive tourettism, tardive parkinsonism, and withdrawal emergent syndrome. The prevalence rates of ATMDs are high, and the outcome may be variable. The most evidenced risk factor for ATMDs is age. Primary and secondary prevention rely on systematically assessing the clinical risk factors before prescribing an antipsychotic medication, and regularly undertaking a neurological examination. Managing ATMDs requires decreasing, stopping, or changing the antipsychotic treatment. Specific reversing drugs, such as reserpine, can be used, though the levels of evidence of these drugs are low. Surgery can be considered in the case of severe and resistant ATMDs.

Tremor stability index: a new tool for differential diagnosis in tremor syndromes

Misdiagnosis among tremor syndromes is common, and can impact on both clinical care and research. To date no validated neurophysiological technique is available that has proven to have good classification performance, and the diagnostic gold standard is the clinical evaluation made by a movement disorders expert. We present a robust new neurophysiological measure, the tremor stability index, which can discriminate Parkinson’s disease tremor and essential tremor with high diagnostic accuracy. The tremor stability index is derived from kinematic measurements of tremulous activity. It was assessed in a test cohort comprising 16 rest tremor recordings in tremor-dominant Parkinson’s disease and 20 postural tremor recordings in essential tremor, and validated on a second, independent cohort comprising a further 50 tremulous Parkinson’s disease and essential tremor recordings. Clinical diagnosis was used as gold standard. One hundred seconds of tremor recording were selected for analysis in each patient. The classification accuracy of the new index was assessed by binary logistic regression and by receiver operating characteristic analysis. The diagnostic performance was examined by calculating the sensitivity, specificity, accuracy, likelihood ratio positive, likelihood ratio negative, area under the receiver operating characteristic curve, and by cross-validation. Tremor stability index with a cut-off of 1.05 gave good classification performance for Parkinson’s disease tremor and essential tremor, in both test and validation datasets. Tremor stability index maximum sensitivity, specificity and accuracy were 95%, 95% and 92%, respectively. Receiver operating characteristic analysis showed an area under the curve of 0.916 (95% confidence interval 0.797–1.000) for the test dataset and a value of 0.855 (95% confidence interval 0.754–0.957) for the validation dataset. Classification accuracy proved independent of recording device and posture. The tremor stability index can aid in the differential diagnosis of the two most common tremor types. It has a high diagnostic accuracy, can be derived from short, cheap, widely available and non-invasive tremor recordings, and is independent of operator or postural context in its interpretation.