Double lesion MRgFUS thalamotomy for essential tremor: 4.5-year outcomes and framework for assessing loss of efficacy and tremor progression.

BACKGROUND: The essential tremor (ET) course to 54 months post-unilateral VIM/PSA magnetic resonance-guided focused ultrasound (MRgFUS) in the treated arm (TA) and non-treated arm (NTA) of 12 patients is reported. METHODS: Tremor severity was rated using Bain Findley spirography (BFS) scores in the TA and NTA. We divided follow-up into 'Early' (0-6 months) and 'Late' (6-54 months) phases, to minimise the effect of peri-lesion oedema resolution on the latter. RESULTS: The mean baseline BFS score was 6.2 in TA and 5.7 in the NTA. After unilateral VIM/PSA MRgFUS, mean BFS improved in TA at all subsequent time points (p < 0.001), with no significant differences between BFS scores at consecutive assessments or between 1 and 54 months, while the NTA BFS scores worsened between 12 and 24 months (p < 0.003). Three patients showed worsening of their TA BFS scores and an increasing NTA-TA BFS difference, indicating slower tremor worsening in TA compared to NTA, whilst one patient showed a greater rate of worsening in the TA compared to NTA BFS. CONCLUSION: After 54 months, the beneficial effect of MRgFUS is usually maintained with any worsening of BFS scores in TA slower than in NTA. Loss of treatment benefit is rare.

Mitochondrial complex I NUBPL mutations cause combined dystonia with bilateral striatal necrosis and cerebellar atrophy.

BACKGROUND AND PURPOSE: The recent advances in genetics have helped to unravel the cause of many dystonia syndromes. With the broadening spectrum of genetically defined dystonia syndromes, distinct clinico-radiological phenotypes are a welcome handle to guide the diagnostic work-up. METHODS: Exome sequencing was used to elucidate the genetic cause of a syndrome characterized by generalized dystonia, pyramidal and cerebellar involvement, with bilateral striatal necrosis (BSN) and cerebellar atrophy on magnetic resonance imaging. Homozygosity mapping and linkage analysis were used in a supportive role. Known genetic causes of BSN were excluded by use of exome data or Sanger sequencing. RESULTS: Compound heterozygous mutations were identified in the NUBPL gene in a small UK kindred. The gene lay in a region of positive linkage and segregated with disease in a family of six individuals. CONCLUSION: NUBPL mutations cause early onset, autosomal recessive generalized dystonia with cerebellar ataxia, pyramidal signs, preserved cognition and a distinct magnetic resonance imaging appearance with BSN and cerebellar atrophy.

Tremulous cervical dystonia is likely to be familial: clinical characteristics of a large cohort.

BACKGROUND: Primary cervical dystonia is the most common form of adult-onset focal dystonia. Although most frequently sporadic, 15-20% of patients report a positive family history, suggesting a possible genetic cause. Head tremor is often present in patients with cervical dystonia and may be a prominent symptom. OBJECTIVE: To describe the clinical characteristics of patients with tremulous cervical dystonia. METHODS: Patients with primary cervical dystonia attending our botulinum toxin clinic were assessed with an interview and neurological examination and their notes reviewed. Patients were classified as having either tremulous or non-tremulous cervical dystonia, according to the presence or absence of head tremor on examination. Clinical and demographic data were compared between groups. RESULTS: From 273 patients included (190 females, 83 males), 125 (46%) were classified as tremulous and 148 (54%) as non-tremulous. Tremulous patients were more likely to have a segmental distribution (61% vs. 25%), often involving the arms (48%), and had more frequently associated arm tremor (55% vs. 10%). A positive family history of dystonia and/or tremor was more frequent in tremulous patients (50% vs. 18%). CONCLUSIONS: Patients with cervical dystonia with associated head tremor are more likely to have a segmental distribution (with frequent arm involvement), associated arm tremor and a positive family history, suggesting a genetic etiology in this subgroup of patients.

Does befriending by trained lay workers improve psychological well-being and quality of life for carers of people with dementia, and at what cost? A randomised controlled trial.

OBJECTIVES: To determine whether a social support intervention (access to an employed befriending facilitator in addition to usual care) is effective compared with usual care alone. Also to document direct and indirect costs, and establish incremental cost-effectiveness. DESIGN: The Befriending and Costs of Caring (BECCA) trial was a cost-effectiveness randomised controlled trial. Data on well-being and resource use were collected through interviews with participants at baseline and at 6, 15 and 24 months. SETTING: This research was carried out in the English counties of Norfolk and Suffolk, and the London Borough of Havering. It was a community-based study. PARTICIPANTS: Participants were family carers who were cohabiting with, or providing at least 20 hours' care per week for, a community-dwelling relative with a primary progressive dementia. INTERVENTIONS: The intervention was 'access to a befriender facilitator' (BF). BFs, based with charitable/voluntary-sector organisations, were responsible for local befriending schemes, including recruitment, screening, training and ongoing support of befriending volunteers, and for matching carers with befrienders. The role of befrienders was to provide emotional support for carers. The target duration for befriending relationships was 6 months or more. MAIN OUTCOME MEASURES: Depression was measured by the Hospital Anxiety and Depression Scale (HADS) at 15 months postrandomisation. The health-related quality of life scale EQ-5D (EuroQol 5 Dimensions) was used to derive utilities for the calculation of quality-adjusted life-years (QALYs). RESULTS: A total of 236 carers were randomised into the trial (116 intervention; 120 control). At final follow-up, 190 carers (93 intervention; 97 control) were still involved in the trial (19% attrition). There was no evidence of effectiveness or cost-effectiveness from the primary analyses on the intention-to-treat population. The mean incremental cost per incremental QALY gained was in excess of 100,000 pounds, with only a 42.2% probability of being below 30,000 pounds per QALY gained. Where care-recipient QALYs were included, mean incremental cost per incremental QALY gained was 26,848 pounds, with a 51.4% probability of being below 30,000 pounds per QALY gained. Only 60 carers (52%) took up the offer of being matched with a trained lay befriender, and of these only 37 (32%) were befriended for 6 months or more. A subgroup analysis of controls versus those befriended for 6 months or more found a reduction in HADS-depression scores that approached statistical significance (95% CI -0.09 to 2.84). CONCLUSIONS: 'Access to a befriender facilitator' is neither an effective nor a cost-effective intervention in the support of carers of people with dementia, although there is a suggestion of cost-effectiveness for the care dyad (carer and care recipient). In common with many services for carers of people with dementia, uptake of befriending services was not high. However, the small number of carers who engaged with befrienders for 6 months or more reported a reduction in scores on HADS depression that approached statistical significance compared with controls (95% CI -0.09 to 2.84). While providing only weak evidence of any beneficial effect, further research into befriending interventions for carers is warranted.

Carers Assessment of Difficulties Index (CADI): psychometric properties for use with carers of people with dementia.

Burden is a commonly recognised phenomenon in family caring. The Carers Assessment of Difficulties Index (CADI) was developed as a clinical tool for assessing the multiple dimensions of carer burden. It has been used with a number of caring cohorts, but its psychometric properties have not been explored specifically with carers of people with dementia. The 30-item CADI was administered to 232 carers of people with dementia with the aim of assessing the suitability of the frequency scale for clinical and research use with this population. The psychometric properties were examined, including descriptive data, a principal components analysis (PCA), and a reliability analysis on the resultant components. All items were experienced by some participants, but no item was experienced by all. An 8- factor solution from the PCA explained 59% of the variance. Eight subscales were established with good internal consistency. It is concluded that the CADI is suitable for both clinical and research use with carers of people with dementia.

The use of the rat isolated vagus nerve for functional measurements of the effect of drugs in vitro.

In this article we describe how to dissect, set up and use the rat isolated vagus nerve in a 'grease gap' apparatus which provides a simple and practical method for measuring the effects of drugs on the membrane potential of axons in the nerve in vitro. Some discussion of the origins and development of the technique as well as the strengths and disadvantages of the preparation as a neuropharmacological tool are included. The vagus nerve conducts action potentials in at least three distinct types of axons that can be measured extracellularly as compound action potentials and distinguished on the basis of their conduction velocity and excitability. Activity in myelinated A fibres and unmyelinated C fibres can be measured separately easily. The axons express receptors for a wide range of putative neurotransmitter agents including 5-HT, GABA and ATP as well as other agents such as capsaicin, anandamide, bradykinin and prostanoids. Responses to all of these chemicals can be measured as a depolarization of the nerve fibres. The vagus nerve is an important target for a wide range of drugs and the isolated preparation provides a fairly simple preparation for studying their effects. The isolated vagus nerve is also a convenient system in which the effects of drugs that have been discovered using heterologous expression systems can be assayed on receptors and ion channels that are expressed in a native neural system.

Unit discharge planning model.

THE UNIT DISCHARGE coordination model was implemented in January 1993 at the Children's Seashore House in Philadelphia, Pennsylvania, a 77-bed inpatient pediatric specialized care and rehabilitation institution. The model, which identifies staff nurses as primary discharge coordinators, has shown remarkable outcomes, evidenced by decreased lengths of stay, improved staff development, and better coordination of discharge resources. CNSs and nursing administrators will find this model cost effective, economically sound, and quality focused to enhance professional development at the staff level.