Intention Tremor Research Articles

Intracellular FMRpolyG-Hsp70 complex in fibroblast cells from a patient affected by fragile X tremor ataxia syndrome

BackgroundFragile X-associated tremor/ataxia syndrome is a late-onset neurodegenerative disorder that affects about 40% of carriers of CGG-repeat expansions in the premutation range within the fragile X gene (FMR1). Main clinical features include intention tremor, cerebellar ataxia, and parkinsonism. Recently, great emphasis on the deposition of soluble aggregates produced by a RAN translation process, as main pathogenic mechanism, has been given. These aggregates contain a small protein with a polyglycine stretch on the aminoterminal end named FMRpolyG and, so far, have been isolated and characterized in drosophila and mouse models, in post mortem brain of fragile X-associated tremor/ataxia syndrome patients, in fibroblasts of fragile primary ovarian insufficiency patients, but never in fibroblasts from a fragile X-associated tremor/ataxia living patients. In adult carriers the syndrome is frequently misdiagnosed due to the lack of specific markers. MethodsWe standardized immunocytochemistry, immunoprecipitation and western blot procedures to study and biochemically characterize the FMRpolyG protein in fibroblasts from human skin biopsy. ResultsWe demonstrate for the first time, in fibroblasts from a patient affected by Fragile X-associated tremor/ataxia syndrome, the presence ex vivo of inclusions consisting of FMRpolyG- Hsp70 soluble aggregates. ConclusionThese observations can pave the way to develop a cellular model for studying ex vivo and in vitro the mechanisms involved in the production of FMRpolyG aggregates, their toxicity, and the role of the FMRpolyG-Hsp70 interaction in the pathogenesis of fragile X-associated tremor/ataxia syndrome.

Immunologic adverse reactions of β-blockers and the skin.

β-Blockers are a widely utilised class of medication. They have been in use for a variety of systemic disorders including hypertension, heart failure and intention tremors. Their use in dermatology has garnered growing interest with the discovery of their therapeutic effects in the treatment of haemangiomas, their potential positive effects in wound healing, Kaposi sarcoma, melanoma and pyogenic granuloma, and, more recently, pemphigus. Since β-blockers are deployed in a variety of disorders, which have cutaneous co-morbidities such as psoriasis, their pertinence to dermatologists cannot be overstated. Likewise, β-blockers, like any other drug category, carry risks of side effects, some of which are dermatologic. These include triggering and exacerbation of psoriasis, psoriatic and rheumatoid arthritis, anaphylaxis, contact dermatitis, occupational contact dermatitis, Raynaud's disease, alopecia, lichen planus-like drug eruption, hyperhydrosis and vitiligo. While recent articles have focussed on the positive uses of β-blockers, it may also be wise to call our attention to the potential dermatologic adverse effects that may follow β-blocker use, as well as possible therapeutic approaches to these. This short review will focus on those dermatoses resulting from β-blocker use, which have an immunologic basis.

Characteristics of Tremor Induced by Lesions of the Cerebellum.

It is a clinical experience that acute lesions of the cerebellum induce pathological tremor, which tends to improve. However, quantitative characteristics, imaging correlates, and recovery of cerebellar tremor have not been systematically investigated. We studied the prevalence, quantitative parameters measured with biaxial accelerometry, and recovery of pathological tremor in 68 patients with lesions affecting the cerebellum. We also investigated the correlation between the occurrence and characteristics of tremor and lesion localization using 3D T1-weighted MRI images which were normalized and segmented according to a spatially unbiased atlas template for the cerebellum. Visual assessment detected pathological tremor in 19% while accelerometry in 47% of the patients. Tremor was present both in postural and intentional positions, but never at rest. Two types of pathological tremor were distinguished: (1) low-frequency tremor in 36.76% of patients (center frequency 2.66 ± 1.17Hz) and (2) normal frequency-high-intensity tremor in 10.29% (center frequency 8.79 ± 1.43Hz). The size of the lesion did not correlate with the presence or severity of tremor. Involvement of the anterior lobe and lobule VI was related to high tremor intensity. In all followed up patients with acute cerebellar ischemia, the tremor completely recovered within 8weeks. Our results indicate that cerebellar lesions might induce pathological postural and intentional tremor of 2-3Hz frequency. Due to its low frequency and low amplitude, quantitative tremorometry is neccessary to properly identify it. There is no tight correlation between lesion localization and quantitative characteristics of cerebellar tremor.

Clinical Characteristics of Essential Tremor in South India: A Hospital-Based Cohort Study.

Introduction:Essential tremor (ET) is the most common adult movement disorder. Classic ET is characterized by action tremor of hands (95% cases), and tremor involving other regions is less common. Recent studies have revealed a few patients exhibiting nontremor features that include cognitive disorders, tandem gait abnormality, mood fluctuations, olfactory abnormality, hearing impairment, and sleep disorders. Very few studies on ET have so far been conducted in India, and the present study is a pioneering attempt to evaluate the clinical characteristics of patients diagnosed with ET.Materials and Methods:A standardized assessment protocol was used to collect data. Diagnosis of ET was established using consensus criteria established by the Movement Disorder Society. Tremor Research Group Essential Tremor Rating Assessment Scale was used to evaluate tremor impact. The severity of hand tremor was assessed by Glass Scale, and cognitive function was assessed by Mini–Mental Status Examination.Results:Out of the 45 patients enrolled, 73.3% were male and 26.6% were female, with a mean age of 44 ± 15 years. Postural tremor was observed in all, followed by intention tremor in 9 and rest tremor in 6 patients. Tremor of the hand was identified to be most predominant (100%). Voice tremor was observed in 15 (33.3%) patients and head tremor in 12 patients (26.6%) who were all females. Leg tremor was observed in 12 patients (26.6% of patients) and tongue tremor in 6 (13%) patients. Baseline asymmetry of tremor was observed in 60% of patients and positive family history in 35% of patients. The most common nontremor feature was tandem gait abnormality (40%). Moreover, most of the patients had Glass Scale II.Conclusion:Baseline asymmetry of tremor and male predominance were observed in the study. While hand tremor was the most common form of tremor, tandem gait abnormality was the most common nontremor feature as observed in patients with ET.

Neurological diseases in cattle caused by plants and mycotoxins in Santa Catarina state, Brazil

ABSTRACT: This study described the epidemiological and clinical-pathological aspects of 25 outbreaks of neurological diseases in cattle caused by plants and mycotoxins in Santa Catarina state. Six of them were due to Sida carpinifolia poisoning, five to Solanum fastigiatum, five to Phalaris angusta, three to Claviceps paspali, three to Claviceps purpurea, and three outbreaks were of unknown etiology. The clinical signs observed in the affected cattle were mild to severe and characterized by generalized muscle tremors, incoordination, hypermetria, wide-based stance, intentional head tremors, dull staring eyes, and frequent ear twitching, with convulsions in some cases. At necropsy, lesions were observed only for P. angusta poisoning, characterized by gray-greenish discoloration in thalamus and midbrain. Microscopically, rarefaction and/or disappearance of Purkinje neurons with substitution by Bergmann cells were observed for S. carpinifolia and S. fastigiatum poisoning. For P. angusta poisoning, thin granular brown-yellowish pigment was observed in the cytoplasm of some neurons. Gross and microscopic findings were not observed in three outbreaks of tremorgenic disease of unknown etiology. Experiments conducted with leaves, flowers and seeds of Ipomoea indivisa and Ipomoea triloba, as well as with maize and soybean residues contaminated with Ipomoea spp. did not reproduced clinical signs.

The Discovery of a LEMD2-Associated Nuclear Envelopathy with Early Progeroid Appearance Suggests Advanced Applications for AI-Driven Facial Phenotyping

Over a relatively short period of time, the clinical geneticist's "toolbox" has been expanded by machine-learning algorithms for image analysis, which can be applied to the task of syndrome identification on the basis of facial photographs, but these technologies harbor potential beyond the recognition of established phenotypes. Here, we comprehensively characterized two individuals with a hitherto unknown genetic disorder caused by the same de novo mutation in LEMD2 (c.1436C>T;p.Ser479Phe), the gene which encodes the nuclear envelope protein LEM domain-containing protein 2 (LEMD2). Despite different ages and ethnic backgrounds, both individuals share a progeria-like facial phenotype and a distinct combination of physical and neurologic anomalies, such as growth retardation; hypoplastic jaws crowded with multiple supernumerary, yet unerupted, teeth; and cerebellar intention tremor. Immunofluorescence analyses of patient fibroblasts revealed mutation-induced disturbance of nuclear architecture, recapitulating previously published data in LEMD2-deficient cell lines, and additional experiments suggested mislocalization of mutant LEMD2 protein within the nuclear lamina. Computational analysis of facial features with two different deep neural networks showed phenotypic proximity to other nuclear envelopathies. One of the algorithms, when trained to recognize syndromic similarity (rather than specific syndromes) in an unsupervised approach, clustered both individuals closely together, providing hypothesis-free hints for a common genetic etiology. We show that a recurrent de novo mutation in LEMD2 causes a nuclear envelopathy whose prognosis in adolescence is relatively good in comparison to that of classical Hutchinson-Gilford progeria syndrome, and we suggest that the application of artificial intelligence to the analysis of patient images can facilitate the discovery of new genetic disorders.

Differential impact on speech production from chronic thalamic DBS in Essential Tremor and that from STN DBS in Parkinson's disease

Essential Tremor (ET) is the most common tremor syndrome seen in adults. The characteristic tremor in ET is postural and action tremors, with a frequency of 4–7 Hz; while in patients with Parkinson’s disease (PD), the dominant tremor is resting tremor with a typical frequency of 5 Hz. Deep brain stimulation (DBS) in the ventral intermediate nuclei (Vim) has been shown effective in treating action or intention tremors in medically resistant ET, while DBS in the subthalamic nucleus (STN) has been shown effective in treating rigidity, rest tremor and Dopa-induced dyskinesias in PD. However, chronic bilateral DBS, whether in Vim or STN, may have negative impact on speech production. We report two cases where both patients received DBS greater than one year and developed speech impairment. When the stimulation in Vim was turned off for 30 min in ET, the patient's speech returned to the baseline while turning the STN stimulation off for 30 min in PD, minimal changes were observed and 12 h with stimulation-off were required for speech to return to the non-stimulated state.Essential Tremor (ET) is the most common tremor syndrome seen in adults. The characteristic tremor in ET is postural and action tremors, with a frequency of 4–7 Hz; while in patients with Parkinson’s disease (PD), the dominant tremor is resting tremor with a typical frequency of 5 Hz. Deep brain stimulation (DBS) in the ventral intermediate nuclei (Vim) has been shown effective in treating action or intention tremors in medically resistant ET, while DBS in the subthalamic nucleus (STN) has been shown effective in treating rigidity, rest tremor and Dopa-induced dyskinesias in PD. However, chronic bilateral DBS, whether in Vim or STN, may have negative impact on speech production. We report two cases where both patients received DBS greater than one year and developed speech impairment. When the stimulation in Vim was turned off for 30 min in ET, the patient's speech returned to the baseline while turning the STN stimulation off for 30 min in PD, minimal changes were observed and 12 h with stimulation-off w...

Neurofascin (NFASC) gene mutation causes autosomal recessive ataxia with demyelinating neuropathy

IntroductionNeurofascin, encoded by NFASC, is a transmembrane protein that plays an essential role in nervous system development and node of Ranvier function. Anti-Neurofascin autoantibodies cause a specific type of chronic inflammatory demyelinating polyneuropathy (CIDP) often characterized by cerebellar ataxia and tremor. Recently, homozygous NFASC mutations were recently associated with a neurodevelopmental disorder in two families. MethodsA combined approach of linkage analysis and whole-exome sequencing was performed to find the genetic cause of early-onset cerebellar ataxia and demyelinating neuropathy in two siblings from a consanguineous Italian family. Functional studies were conducted on neurons from induced pluripotent stem cells (iPSCs) generated from the patients. ResultsGenetic analysis revealed a homozygous p.V1122E mutation in NFASC. This mutation, affecting a highly conserved hydrophobic transmembrane domain residue, led to significant loss of Neurofascin protein in the iPSC-derived neurons of affected siblings. ConclusionsThe identification of NFASC mutations paves the way for genetic research in the developing field of nodopathies, an emerging pathological entity involving the nodes of Ranvier, which are associated for the first time with a hereditary ataxia syndrome with neuropathy.

Chronic, low-level oral exposure to marine toxin, domoic acid, alters whole brain morphometry in nonhuman primates

Domoic acid (DA) is an excitatory neurotoxin produced by marine algae and responsible for Amnesiac Shellfish Poisoning in humans. Current regulatory limits (˜0.075-0.1 mg/kg/day) protect against acute toxicity, but recent studies suggest that the chronic consumption of DA below the regulatory limit may produce subtle neurotoxicity in adults, including decrements in memory. As DA-algal blooms are increasing in both severity and frequency, we sought to better understand the effects of chronic DA exposure on reproductive and neurobehavioral endpoints in a preclinical nonhuman primate model. To this end, we initiated a long-term study using adult, female Macaca fascicularis monkeys exposed to daily, oral doses of 0.075 or 0.15 mg/kg of DA for a range of 321–381, and 346–554 days, respectively. This time period included a pre-pregnancy, pregnancy, and postpartum period. Throughout these times, trained data collectors observed intentional tremors in some exposed animals during biweekly clinical examinations. The present study explores the basis of this neurobehavioral finding with in vivo imaging techniques, including diffusion tensor magnetic resonance imaging and spectroscopy. Diffusion tensor analyses revealed that, while DA exposed macaques did not significantly differ from controls, increases in DA-related tremors were negatively correlated with fractional anisotropy, a measure of structural integrity, in the internal capsule, fornix, pons, and corpus callosum. Brain concentrations of lactate, a neurochemical closely linked with astrocytes, were also weakly, but positively associated with tremors. These findings are the first documented results suggesting that chronic oral exposure to DA at concentrations near the current human regulatory limit are related to structural and chemical changes in the adult primate brain.

IMPROVEMENTS IN A CASE OF SENSORY ATAXIA THROUGH CELL TRANSPLANTATION

Sensory ataxia is a type of ataxia that is caused by the loss of sensory input to control the movement of the body. It is both a sign and a symptom. There have been no curative modalities for treating sensory ataxia. Cellular therapy has gained significant attention as a therapeutic option for various neurological disorders. We present a case of an 18-year-old female diagnosed with sensory ataxia who was intrathecally administered with autologous bone marrow mononuclear cells (BMMNCs) along with neurorehabilitation. Twelve months after cellular therapy, signs such as ataxia, postural tremors, intention tremors and dysmetria improved. Functional Independence Measure score improved from 106 to 107. Berg Balance Scale improved from 18 to 34. Brief Ataxia Rating Scale improved from 7 to 5. Modified International Cooperative Ataxia Rating Scale improved 26 to 24. Comparison of the Positron Emission Tomography Computed-Tomography (PET CT) image before and 12 months after cellular therapy showed improved metabolism in bilateral sensory motor cortex, thalamus and cerebellum. These PET findings correlated with symptomatic improvements. The clinical improvements along with PET CT findings suggest that cellular therapy is a beneficial therapeutic modality for sensory ataxia. No major adverse effects were seen. Further clinical studies should be conducted to understand the efficacy of cellular therapy in sensory ataxia. 
 Keywords: Sensory ataxia; Cellular therapy; Autologous Bone Marrow Mononuclear Cells; Positron Emission Tomography Computed Tomography.

Ataxia with novel compound heterozygous PEX10 mutations and a literature review of PEX10-related peroxisome biogenesis disorders

ObjectivesTo describe the clinical and genetic features of a Chinese peroxisome biogenesis disorder 6B patient with PEX10 mutations and review PEX10–related peroxisomal disorders. Patients and methodsThe proband is a 7-year-old boy with mild mental retardation and gait instability, intention tremor and nystagmus. An extensive clinical and laboratory evaluation including molecular genetic studies was performed. Genomic DNA was extracted from peripheral blood using the standardized phenol/chloroform extraction method, and the coding region of the PEX10 gene was sequenced in three family members. ResultsCerebral MRI showed cerebellar atrophy. Magnetic resonance spectroscopy revealed a decreased N-acetyl aspartate peak in the cerebellum. Nerve conduction velocity examination found prolonged motor and sensory nerve potential latencies (proximal obvious), decreased potential amplitude, and slow nerve conduction velocity. Routine blood tests and biochemistries were abnormal. The PEX10 gene test showed compound heterozygous mutations (c.209 G > A, p. G70E and c.830 T > C, p. L277 P). The mutation c.830 T > C, p. L277 P has been previously reported, whereas c.209 G > A, p. G70E is novel. ConclusionWe identified an ataxia case of peroxisome biogenesis disorder 6B caused by novel compound heterozygous mutations of the PEX10 gene. Peroxisome biogenesis disorders should be considered in the differential diagnosis of autosomal recessive ataxia, especially cases with early onset.

Effects of oral domoic acid exposure on maternal reproduction and infant birth characteristics in a preclinical nonhuman primate model

Domoic Acid (DA) is a naturally-occurring excitotoxin, produced by marine algae, which can bioaccumulate in shellfish and finfish. The consumption of seafood contaminated with DA is associated with gastrointestinal illness that, in the case of high DA exposure, can evolve into a spectrum of responses ranging from agitation to hallucinations, memory loss, seizures and coma. Because algal blooms that produce DA are becoming more widespread and very little is known about the dangers of chronic, low-dose exposure, we initiated a preclinical study focused on the reproductive and developmental effects of DA in a nonhuman primate model. To this end, 32 adult female Macaca fascicularis monkeys were orally exposed to 0, 0.075 or 0.15 mg/kg/day DA on a daily basis, prior to and during pregnancy. Females were bred to non-exposed males and infants were evaluated at birth. Results from this study provided no evidence of changes in DA plasma concentrations with chronic exposure. DA exposure was not associated with reproductive toxicity or adverse changes in the physical characteristics of newborns. However, in an unanticipated finding, our clinical observations revealed the presence of subtle neurological effects in the form of intentional tremors in the exposed adult females. While females in both dose groups displayed increased tremoring, the effect was dose-dependent and observed at a higher rate in females exposed to 0.15 mg/kg/day. These results demonstrate that chronic, low-level exposure to DA is associated with injury to the adult CNS and suggest that current regulatory guidelines designed to protect human health may not be adequate for high-frequency shellfish consumers.

Fragile X associated tremor/ataxia syndrome: its clinical presentation, pathology, and treatment

The fragile X associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease associated with the repetition of CGG triplets (55-200 CGG repetitions) in the FMR1 gene. The premutation of the FMR1 gene, contrasting with the full mutation (more than 200 CGG repetitions), presents an increased production of messenger and a similar or slightly decreased production of FMRP protein. FXTAS affects 40% of men and 16% of women carriers of the premutation. It presents with a wide constellation of neurological signs such as intention tremor, cerebellar ataxia, parkinsonism, executive function deficits, peripheral neuropathy and cognitive decline leading to dementia among others. In this review, we present what is currently known about the molecular mechanism, the radiological findings and the pathology, as well as the complexity of the diagnosis and management of FXTAS.

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS).

Individuals carrying an FMR1 expansion between 55 and 200 CGG repeats, are at risk of developing the Fragile X-associated tremor/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder characterized by cerebellar gait ataxia, intentional tremor, neuropathy, parkinsonism, cognitive decline, and psychological disorders, such as anxiety and depression. In addition, brain atrophy, white matter disease, and hyperintensities of the middle cerebellar peduncles can also be present. The neuropathological distinct feature of FXTAS is represented by the presence of eosinophilic intranuclear inclusions in neurons and astrocytes throughout the brain and in other tissues. In this chapter, protocols for available diagnostic tools, in both humans and mice, the clinical features and the basic molecular mechanisms leading to FXTAS and the animal models proposed to study this disorder are discussed.

Lamotrigine Induces Tremor among Epilepsy Patients Probably via Cerebellar Pathways.

Lamotrigine, a frequently used antiepileptic drug, inhibits voltage-gated sodium-channels. By suppressing the release of glutamate and aspartate, lamotrigine acts as a membrane stabilizer, and it is also effective in bipolar disorder and migraine. However, lamotrigine is known to induce tremor among 4-10% of patients. We examined the lamotrigine-induced tremor in 28 epilepsy patients (age: 38.06 ± 13.56 years; 24 females and 4 males) receiving lamotrigine monotherapy and compared the data to 30 age- and sex-matched controls (age: 33.06 ± 10.71 years; 25 females and 5 males). Tremor was visually assessed by clinical tremor rating scales. Quantitative characteristics (intensity, center frequency and frequency dispersion) which are regularly used to differentiate various tremor syndromes were measured by validated, sensitive biaxial accelerometry in resting, postural and intentional positions. Regularity of repetitive finger and hand movements and reaction time were also determined. Data were statistically analyzed. Clinical tremor rating scales detected pathological tremor in three patients (10%), while accelerometry revealed tremor in seven patients (25%). Center frequency of patients with pathological tremor was similar to controls, but the frequency dispersion was significantly lower and tremor intensity was significantly higher in both postural and intentional positions. Rhythmic movements and reaction time were normal. Our results show that objective measurements detect pathological intention tremor in 25% of epilepsy patients receiving lamotrigine monotherapy. Quantitative characteristics suggest the involvement of the cerebellum in the pathomechanism of lamotrigine-induced tremor. Determining the parameters of drug-induced tremor syndromes might help to understand the complex action of tremor generator networks.

50 YOM with Shoulder Impingement Syndrome Improves with Neuro-Rehabilitation

50 YOM with Shoulder Impingement Syndrome Improves with Neuro-Rehabilitation

Revisiting the Clinical Phenomenology of "Cerebellar Tremor": Beyond the Intention Tremor.

Tremor is an involuntary, rhythmic, oscillatory movement of a body part. It is a central feature of a range of diseases resulting from pathological changes in the cerebellum. Interestingly, in modern times, the terms "cerebellar tremor" and "intention tremor" are often used synonymously and interchangeably. However, "cerebellar tremor" (i.e., tremors of cerebellar origin) do not always present exclusively as intention tremor. In this article, we comprehensively revisit the clinical phenomenology of tremors observed in various diseases that are based in the cerebellum. By this, we mean diseases for which the cerebellum and its various connections are often seen as playing a central and defining role. These include spinocerebellar ataxias, essential tremor, orthostatic tremor, dystonia, acute cerebellitis, cerebellar tumors, paraneoplastic cerebellar degeneration, and cerebellar strokes. The theme of this article is to highlight, through published data available in the current literature, that the clinical phenomenology of tremor of cerebellar origin is heterogeneous, and it extends beyond that of intention tremor to include postural tremors, kinetic tremor, rest tremor, and orthostatic tremor. This heterogeneity is consistent with the seminal work of Gordon Holmes, in which he described a variety of tremors aside from intention tremor in the setting of cerebellar lesions. In the end, it would seem that the notion that intention tremor is the sole signature of cerebellar lesions is an over-simplification and is not correct. Future studies are warranted to identify and further characterize the heterogeneity of tremors arising from the various cerebellar etiologies.

Microglial cell activation and senescence are characteristic of the pathology FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with premutation alleles of the FMR1 gene. Expansions of more than 200 CGG repeats give rise to fragile X syndrome, the most common inherited form of cognitive impairment. Fragile X-associated tremor/ataxia syndrome is characterized by cerebellar tremor and ataxia, and the presence of ubiquitin-positive inclusions in neurons and astrocytes. It has been previously suggested that fragile X-associated tremor/ataxia syndrome is associated with an inflammatory state based on signs of oxidative stress-mediated damage and iron deposition. Determine whether the pathology of fragile X-associated tremor/ataxia syndrome involves microglial activation and an inflammatory state. Using ionized calcium binding adaptor molecule 1 and cluster differentiation 68 antibodies to label microglia, we examined the number and state of activation of microglial cells in the putamen of 13 fragile X-associated tremor/ataxia syndrome and 9 control postmortem cases. Nearly half of fragile X-associated tremor/ataxia syndrome cases (6 of 13) presented with dystrophic senescent microglial cells. In the remaining fragile X-associated tremor/ataxia syndrome cases (7 of 13), the number of microglial cells and their activation state were increased compared to controls. The presence of senescent microglial cells in half of fragile X-associated tremor/ataxia syndrome cases suggests that this indicator could be used, together with the presence of intranuclear inclusions and the presence of iron deposits, as a biomarker to aid in the postmortem diagnosis of fragile X-associated tremor/ataxia syndrome. An increased number and activation indicate that microglial cells play a role in the inflammatory state present in the fragile X-associated tremor/ataxia syndrome brain. Anti-inflammatory treatment of patients with fragile X-associated tremor/ataxia syndrome may be indicated to slow neurodegeneration. © 2018 International Parkinson and Movement Disorder Society.

Botulinum toxin for the treatment of hand tremor

The aim of this study is to review our longitudinal experience with onabotulinumtoxinA (onaBoNT-A) injections for medically refractory hand tremor. We performed a retrospective review of our database of patients treated with onaBoNT-A for hand tremor evaluated between 2010 and 2018 in at least 2 sessions with follow-up. The majority were injected into the forearm flexors (FF), although treatment was individualized. During the specified period, 91 patients (53 essential tremor, 31 dystonic tremor, 6 Parkinson’s disease tremor, and 1 cerebellar outflow tremor) met our inclusion criteria. The mean age (SD) was 64.8 years (12.8), and mean duration of follow-up was 29.6 months (25.1) with mean of 7.7 (6.3) treatment visits. FF were injected in 89 (97.8%) patients, exclusively in 74 (81.3%), and 15 (16.5%) were injected in FF and other muscles. EMG guidance was used in 5 patients (5.5%). On a 0–4 “peak effect” rating scale (0 = no effect, 4 = marked improvement in severity and function), 80.2% and 85.7% of patients reported moderate or marked improvement (score 3 or 4) at their first and last follow-up visit, respectively. There was no statistically significant difference in the outcomes between first and last visit: average “peak effect” rating score (3.2 versus 3.4), “global” rating score (3.0 versus 3.2), latency of response (4.5 versus 3.8 days), and total duration of response (12.7 versus 12.8 weeks), except onaBoNT-A dose (65.0 versus 78.6 U/limb, p = 0.002). Of 1095 limb injections, there were 134 (12.2%) non-disabling and transient (mean 36 days) adverse events (132 limb weakness, 2 pain). OnaBoNT-A injections are safe and effective in the treatment of hand tremor.

Deep brain stimulation of the ventralis intermedius nucleus of the thalamus and posterior subthalamic area for Holmes’ tremor secondary to brainstem hemorrhage: A case report

Holmes’ tremor is a rare but severely disabling movement disorder characterized by a combination of resting, action, and intention tremor. Because Holmes’ tremor is usually resistant to pharmacotherapy, surgical treatment is required for symptom control in most cases. We report the case of a 56-year-old man who was diagnosed with Holmes’ tremor and treated with stimulation of the ventralis intermedius nucleus of the thalamus and posterior subthalamic area. Deep brain stimulation alleviated the patient’s tremor over a 3-year follow-up period.