Ataxia and tolerance after thalamic deep brain stimulation for essential tremor

BackgroundDeep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) thalamus is highly effective to treat medication-refractory essential tremor (ET). Complications of stimulation-induced ataxia and tolerance have been reported in limited series, ranging from 5 to 40%.ObjectiveWe analyzed a large single-center cohort of ET patients treated with thalamic DBS to assess rates of ataxia and tolerance.MethodsRetrospective study of all ET patients that underwent VIM DBS at Mayo Clinic from 2010 to 2014. Demographic, clinical and DBS data were extracted. Risk factors, complications and time to onset of tolerance and ataxia were examined.ResultsOne hundred and thirteen ET patients (51% male) of mean age 68 ± 10 years and mean ET duration 27 ± 18 years underwent DBS during the study period. Of these, 98 (87%) had follow-up of ≥6 months (mean 4.0 ± 1.5 years) and were included for analysis. Complications of isolated ataxia (26%), isolated tolerance (4%), both tolerance and ataxia (9%), or neither (61%) were identified. Development of ataxia was about 3 times more common than tolerance (35% vs. 13%). The mean time to ataxia was 5.5 ± 0.3 years postoperatively. Risk factors for ataxia were baseline ataxic features, older age, and shorter ET disease duration. Small sample size limited calculation of risk factors and onset time for tolerance.ConclusionsStimulation-related ataxia occurred in one-third of ET patients, while tolerance was less common. Presence of baseline ataxia, age, and disease duration may aid counseling of stimulation-related ataxia risk. Larger studies are warranted to confirm these findings and further assess risk factors for tolerance.     

The cerebellar form of acquired hepatocerebral degeneration: The hepatic ataxia

This article reports a patient with acquired hepatocerebral degeneration that presented with progressive cerebellar ataxia, cerebellar atrophy, and middle cerebellar peduncle lesions. He had a marked improvement after liver transplantation. We reinforce that hepatic failure should be investigated in patients with pure cerebellar syndrome, resembling neurodegenerative diseases.     

帕金森病震颤研究进展

帕金森病是一种常见的由神经系统退行性病变所引起的疾病,其以运动症状为主要临床表现。震颤作为常见的运动症状之一,极大困扰帕金森病患者,并严重影响其生活质量。临床治疗中,震颤也是帕金森病最难治疗的症状。有关震颤的发病机制,国内、外尚无定论,本文将对帕金森病震颤的发生机制作相应评述,冀望能为帕金森病震颤的诊疗提供一定思路。     

Profile of extrapyramidal manifestations in 85 patients with spinocerebellar ataxia type 1, 2 and 3

This study aimed to determine the prevalence and type of extrapyramidal signs (EPS) in spinocerebellar ataxia (SCA) type 1, 2 and 3. Eighty-five patients with genetically confirmed SCA (SCA1 = 40, SCA2 = 28, SCA3 = 17) were evaluated for the prevalence and types of EPS. Forty-one SCA patients (48.2%) had one or more types of EPS. The prevalence of EPS was 60.7% in SCA2, 52.9% in SCA3, and 37.5% in SCA1. Among SCA2 patients, bradykinesia was the most frequent (35.3%), followed by reduced facial expression, postural tremor and dystonia (29.4% each), rest tremor, titubation and rigidity (23.5% each), and lip/jaw tremor and chorea (11.8% each). In SCA3 the common EPS were bradykinesia (44.4%), staring look, postural tremor and dystonia (33.3% each), and reduced facial expression and rigidity (22.2% each). In SCA1, staring look was the most common (53.3%), followed by dystonia and bradykinesia (33.3% each), and postural tremor (26.7%). In all three groups, there was no significant difference in the mean length of repeat of the abnormal allele between those with and without EPS. To conclude bradykinesia, staring look, dystonia and postural tremor were the most frequent EPS observed in SCA. In SCA1, these signs were seen more often in younger patients with early onset of symptoms.     

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.     

Thalamic stimulation alleviates levodopa-resistant rigidity in a patient with non-Parkinson’s disease parkinsonian syndrome

Deep brain stimulation (DBS) to the thalamic ventrointermediate nucleus (Vim) is a useful treatment in patients with tremor-dominant Parkinson’s disease (PD). Efficacy to alleviate rigidity remains controversial. We report a 65-year-old right-handed man with persistent severe rigidity and bradykinesia on the right side despite daily administration of levodopa/carbidopa (600/60 mg). His right-hand tremor was continuous at rest and present at action. His antiparkinsonian medications appeared ineffective and he reported difficulties with writing and eating. Repeated ¹²³I-meta-iodobenzylguanidine myocardial scintigraphy studies demonstrated a non-PD pattern. He underwent the stereotactic implantation of a DBS electrode into the left Vim. Using contacts 1 and 2 we started continuous unipolar stimulation with a pulse generator implanted in a subclavian pocket. This improved the tremor and the rigidity and bradykinesia of his right hand. Postoperative image analysis revealed the likelihood of simultaneous stimulation of the Vim and the nucleus ventralis oralis posterior. Our findings suggest thalamic stimulation as a therapeutic option for drug-resistant rigidity (and tremor) in patients with parkinsonian syndromes ineligible for DBS targeted at the globus pallidus internus or subthalamic nucleus.     

A mechanistic study of the tremor associated with epidural anaesthesia for intrapartum caesarean delivery

BackgroundIt is not known if the tremor associated with an epidural top-up dose for intrapartum caesarean delivery is thermoregulatory shivering. A tremor is only shivering if it has the same frequency profile as cold stress-induced shivering. Thermoregulatory shivering is a response to a reduction in actual body temperature, whereas non-thermoregulatory shivering may be triggered by a reduction in sensed body temperature. This mechanistic study aimed to compare: 1. the frequency profiles of epidural top-up tremor and cold stress-induced shivering; and 2. body temperature (actual and sensed) before epidural top-up and at the onset of tremor.MethodsTwenty obstetric patients received an epidural top-up for intrapartum caesarean delivery and 20 non-pregnant female volunteers underwent a cold stress. Tremor, surface electromyography, core temperature, skin temperature (seven sites) and temperature sensation votes (a bipolar visual analog score ranging from −50 to +50 mm) were recorded.ResultsThe mean (SD) primary oscillation (9.9 (1.9) Hz) frequency of epidural top-up tremor did not differ from that of cold stress-induced shivering (9.0 (1.6) Hz; P=0.194), but the mean (SD) burst frequency was slower (6.1 (1.2) × 10⁻² Hz vs 6.9 (0.7) × 10⁻² Hz, respectively; P=0.046). Before the epidural top-up dose, the mean (SD) core temperature was 37.6 (0.6) °C. Between the epidural top-up dose and the onset of tremor the mean (SD) core temperature did not change (–0.1 (0.1) °C; P=0.126), the mean (SD) skin temperature increased (+0.4 (0.4) °C; P=0.002) and the mean (SD) temperature sensation votes decreased (−12 (16) mm; P=0.012).ConclusionThese results suggest that epidural top-up tremor is a form of non-thermoregulatory shivering triggered by a reduction in sensed body temperature.     

Investigating the role of FUS exonic variants in Essential Tremor

Essential Tremor is the most common form of movement disorder. Aggregation in families suggests a strong genetic component to disease. Linkage and association studies have identified several risk loci but the specific causal variants are still unknown. A recent study using whole exome sequencing identified a rare nonsense variant in the FUS gene (p.Q290X) that segregated with Essential Tremor in a large French Canadian family. In addition, two other rare FUS variants were identified (p.R216C and p.P431L) in Essential Tremor patients however co-segregation analysis with disease was not possible. In the present study, we sequenced all 15 exons of FUS in 152 familial probands with Essential Tremor and genotyped three reported FUS variants in 112 sporadic Essential Tremor patients and 716 control subjects recruited at Mayo Clinic Florida. Only known synonymous SNPs unlikely to be pathogenic were detected in our sequencing and not any of the recently identified mutations or novel ones. We conclude that the FUS mutations associated with risk of Essential Tremor are probably a rare occurrence.     

Differential diagnosis of tremor syndromes using MRI relaxometry

Differential diagnosis of the most common tremor syndromes – essential tremor (ET) and Parkinson's disease (PD) is burdened with high error rate. However, diagnostic MRI biomarkers applicable in this clinically highly relevant scenario remain an unfulfilled objective.The presented study was designed in search for possible candidate MRI protocols relevant for differential diagnostic process in tremor syndromes.10 non-advanced tremor-dominant PD patients meeting diagnostic criteria for clinically established PD, 12 isolated ET patients and 16 healthy controls were enrolled into this study. The study focused on relaxation MRI protocols – T1, T2, adiabatic T1ρ and adiabatic T2ρ due to their relatively low post-processing requirements enabling implementation into routine clinical practice.Compared to ET, PD patients had significantly longer T2 relaxation times in striata with dominant findings in the putamen contralateral to the clinically more affected body side. This difference was driven by alterations in the PD group as confirmed in the complementary comparison with healthy controls. According to the receiver operating characteristic analysis, this region provided a reasonable sensitivity of 0.91 and specificity of 0.89 in the differential diagnosis of PD and ET. In PD patients, we further found prolonged T1ρ in the substantia nigra compared to ET and healthy controls, and shorter T2 and T2ρ in the cerebellum compared to healthy controls.T2 relaxation time in the putamen contralateral to the clinically more affected body side is a plausible candidate diagnostic marker for the differentiation of PD and ET.