A retrospective study to assess resource utilization and costs in patients with post-stroke spasticity in the United Kingdom.

OBJECTIVE: Post-stroke spasticity (PSS) is a common complication following stroke. This study describes the differences in healthcare resource utilization between patients who do and do not develop PSS in the UK. METHODS: Adults registered in The Health Improvement Network database with a recorded stroke between 2007 and 2011 were included. PSS was identified through Read codes; machine learning was used to retrospectively identify unrecorded PSS events. Patients with diagnosed or predicted PSS in the 12 months after stroke were matched to those with no PSS on age, sex, number of strokes, socioeconomic status, and comorbidities using the nearest neighbor algorithm. Utilization and costs associated with general practitioner visits, nurse visits, hospitalizations, referrals to specialists, laboratory tests, and medications in the 12 months after stroke were compared. RESULTS: Overall, 2,951 PSS cases were matched to 37,753 controls. During the first year, more PSS cases visited a physiotherapist (19% vs 7%) and occupational therapist (12% vs 5%) compared to controls. A greater proportion of cases were also referred to specialists (76% vs 64%) and hospitalized (33% vs 9%) compared to controls. Medication for spasticity was, on average, 14.68 prescriptions for cases and 5.64 for controls. Total mean costs per patient were £1,270 (standard deviation [SD] = 772) and £635 (SD = 273) for cases and controls, respectively. CONCLUSION: Costs after stroke for patients developing PSS are twice as high compared to patients who do not develop it, with the major driver being the number of hospital admissions. This highlights the need for better recording and closer management of PSS.

Botulinum toxin type B for cervical dystonia.

BACKGROUND: This is an update of a Cochrane review first published in 2004, and previously updated in 2009 (no change in conclusions). Cervical dystonia is a frequent and disabling disorder characterised by painful involuntary head posturing. Botulinum toxin type A (BtA) is usually considered the first line therapy for this condition, although botulinum toxin type B (BtB) is an alternative option. OBJECTIVES: To compare the efficacy, safety and tolerability of botulinum toxin type B (BtB) versus placebo in people with cervical dystonia. SEARCH METHODS: We identified studies for inclusion in the review using the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of articles and conference proceedings, last run in October 2015. We ran the search from 1977 to 2015. The search was unrestricted by language. SELECTION CRITERIA: Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtB versus placebo in adults with cervical dystonia. DATA COLLECTION AND ANALYSIS: Two independent authors assessed records, selected included studies, extracted data using a paper pro forma and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third author. We performed one meta-analysis for the comparison BtB versus placebo. We used random-effects models when there was heterogeneity and fixed-effect models when there was no heterogeneity. In addition, we performed pre-specified subgroup analyses according to BtB doses and BtA previous clinical responsiveness. The primary efficacy outcome was overall improvement on any validated symptomatic rating scale. The primary safety outcome was the number of participants with any adverse event. MAIN RESULTS: We included four RCTs of moderate overall methodological quality, including 441 participants with cervical dystonia. Three studies excluded participants known to have poorer response to Bt treatment, therefore including an enriched population with a higher probability of benefiting from Bt treatment. None of the trials were independently funded. All RCTs evaluated the effect of a single Bt treatment session using doses between 2500 U and 10,000 U. BtB was associated with an improvement of 14.7% (95% CI 9.8% to 19.5) in the patients' baseline clinical status as assessed by investigators, with reduction of 6.8 points in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-total score) at week 4 after injection (95% CI 4.54 to 9.01). Mean difference (MD) in TWSTRS-pain score at week 4 was 2.20 (95% CI 1.25 to 3.15). Overall, both participants and clinicians reported an improvement of subjective clinical status. There were no differences between groups in the withdrawals rate due to adverse events or in the proportion of participants with adverse events. However, BtB-treated patients had a 7.65 (95% CI 2.75 to 21.32) and a 6.78 (95% CI 2.42 to 19.05) increased risk of treatment-related dry mouth and dysphagia, respectively. Statistical heterogeneity between studies was low to moderate for most outcomes. All tested dosages were efficacious against placebo without clear-cut evidence of a dose-response gradient. However, duration of effect (time until return to baseline TWSTRS-total score) and risk of dry mouth and dysphagia were greater in the subgroup of participants treated with higher BtB doses. Subgroup analysis showed a higher improvement with BtB among BtA-non-responsive participants, although there were no differences in the effect size between the BtA-responsive and non-responsive subgroups. AUTHORS' CONCLUSIONS: A single BtB-treatment session is associated with a significant and clinically relevant reduction of cervical dystonia impairment including severity, disability and pain, and is well tolerated, when compared with placebo. However, BtB-treated patients are at an increased risk of dry mouth and dysphagia. There are no data from RCTs evaluating the effectiveness and safety of repeated BtB injection cycles. There are no RCT data to allow us to draw definitive conclusions on the optimal treatment intervals and doses, usefulness of guidance techniques for injection, and impact on quality of life.

Deep brain stimulation in the ventrolateral thalamus/subthalamic area in dystonia with head tremor.

BACKGROUND: Pallidal deep brain stimulation (GPi-DBS) effectively ameliorates idiopathic dystonia, although approximately 15% of patients respond insufficiently. Although various thalamic and subthalamic targets have been suggested for dystonic tremor, no systematic studies have been published on thalamic DBS in dystonic tremor. We assessed the effect of thalamic/subthalamic area DBS (Th-DBS) on dystonic head tremor and dystonia in a single-blind design. METHODS: Dystonic head tremor and dystonia before and 3 months after surgery were quantified via blinded video-ratings using the Fahn-Tolosa-Marin-Tremor-Scale and the Burke-Fahn-Marsden-Dystonia-Rating-Scale in seven patients with idiopathic cervical or segmental dystonia, dystonic head tremor, and bilateral Th-DBS. Pain, side effects, adverse events, and stimulation parameters were assessed. RESULTS: Th-DBS improved dystonic tremor and dystonia (P < 0.05; 57.1% and 70.4%, respectively). Head tremor amplitude and pain were also improved (P < 0.05; 77.5% and 90.0%, respectively). Side effects included dysarthria, gait disturbance, slowness of movement, and weight gain. CONCLUSION: Dystonic head tremor and dystonia can be improved with Th-DBS.

Parkinson's disease.

INTRODUCTION: Around 1% of adults have Parkinson's disease, with a median time of 9 years between diagnosis and death. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in people with early-stage Parkinson's disease? What are the effects of adding other treatments in people with Parkinson's disease who have motor complications from levodopa? What are the effects of surgery in people with later Parkinson's disease? What are the effects of nursing and rehabilitation treatments in people with Parkinson's disease? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding a catechol-methyl transferase inhibitor, or dopamine agonist to levodopa; amantadine; dopamine agonists; levodopa (immediate-release, modified-release); monoamine oxidase B inhibitors; occupational therapy; pallidal deep brain stimulation; pallidotomy; Parkinson's disease nurse specialist interventions; physiotherapy; speech and language therapy; subthalamic nucleus deep brain stimulation; subthalamotomy; swallowing therapy; thalamic deep brain stimulation; and thalamotomy.

Movement, visceral and autonomic disorders: use of botulinum toxin.

This article reviews the development of botulinum toxin treatment, how it works, the range of conditions it can treat and the benefits and side effects. It sets out how it is used in practice in specialist units.

Orienting of attention and Parkinson's disease: tactile inhibition of return and response inhibition.

There is growing evidence for cognitive impairments in Parkinson's disease (PD), including in the orienting of attention and inhibition of return (IOR). IOR refers to the slowing of a response to a target stimulus presented in the same location as a previous stimulus. While some researchers have reported normal levels of visual IOR in PD patients using cue-target tasks, others have reported significant reductions in IOR in this patient group. However, the inhibitory effects observed in cue-target tasks may reflect non-ocular response inhibition associated with withholding a response from the cue stimulus, rather than attentional or oculomotor processes. Many researchers working with normal participants have circumvented this confound by using a target-target task, in which a response is made to all peripheral stimuli. Here, we compared IOR measured in cue-target and target-target tasks, using tactile rather than visual stimuli. Both the PD and the control groups exhibited significant inhibitory effects in the cue-target task, but only the control group exhibited significant IOR in the target-target task. Our results demonstrate a reduction, or elimination, of IOR in PD and this change may have been underestimated in previous studies, in which methodologically flawed cue-target tasks were used. This reduction in IOR may reflect impaired inhibitory processes or hyper-reflexive orienting in parkinsonian patients.

Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia.

Cannabis may have medicinal uses in a variety of diseases. The neural mechanisms underlying dystonia involve abnormalities within the basal ganglia-in particular, overactivity of the lateral globus pallidus (GPl). Cannabinoid receptors are located presynaptically on GABA terminals within the GPi, where their activation reduces GABA reuptake. Cannabinoid receptor stimulation may thus reduce overactivity of the GPl and thereby reduce dystonia. A double-blind, randomised, placebo-controlled, crossover study using the synthetic cannabinoid receptor agonist nabilone in patients with generalised and segmental primary dystonia showed no significant reduction in dystonia following treatment with nabilone.