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Disease outcomes are heterogeneous in Parkinson’s disease and may be predicted by gene variants. This study investigated if the BDNF rs6265 single nucleotide polymorphism (SNP) is associated with differential outcomes with specific pharmacotherapy treatment strategies in the “NIH Exploratory Trials in PD Long-term Study 1” (NET-PD LS-1, n = 540). DNA samples were genotyped for the rs6265 SNP and others (rs11030094, rs10501087, rs1491850, rs908867, and rs1157659). The primary measures were the Unified Parkinson’s Disease Rating Scale (UPDRS) and its motor component (UPDRS-III). Groups were divided by genotype and treatment regimen (levodopa monotherapy vs levodopa with other medications vs no levodopa). T allele carriers were associated with worse UPDRS outcomes compared to C/C subjects when treated with levodopa monotherapy (+ 6 points, p = 0.02) and to T allele carriers treated with no levodopa treatment strategies (UPDRS: + 8 points, p = 0.01; UPDRS-III: + 6 points, p = 0.01). Similar effects of worse outcomes associated with levodopa monotherapy were observed in the BDNF rs11030094, rs10501087, and rs1491850 SNPs. This study suggests the levodopa monotherapy strategy is associated with worse disease outcomes in BDNF rs6265 T carriers. Pending prospective validation, BDNF variants may be precision medicine factors to consider for symptomatic treatment decisions for early-stage PD patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-020-00965-9.

Introduction The efficacy of pharmacotherapy and deep brain stimulation of the subthalamic nucleus in treating Parkinson's disease motor symptoms is highly variable and may be influenced by patient genotype. The relatively common (prevalence about one in three) and protein-altering rs6265 single nucleotide polymorphism (C > T) in the gene BDNF has been associated with different clinical outcomes with levodopa. Objective We sought to replicate this reported association in early-stage Parkinson's disease subjects and to examine whether a difference in clinical outcomes was present with subthalamic nucleus deep brain stimulation. Materials and methods Fifteen deep brain stimulation and 13 medical therapy subjects were followed for 24 months as part of the Vanderbilt DBS in Early Stage PD clinical trial (NCT00282152, FDA IDE #G050016). Primary outcome measures were the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire-39. Results Outcomes with drug therapy in subjects carrying the rs6265 T allele were significantly worse following 12 months of treatment compared to C/C subjects (UPDRS: +20 points, p = 0.019; PDQ-39: +16 points, p = 0.018). In contrast, rs6265 genotype had no effect on overall motor response to subthalamic nucleus deep brain stimulation at any time point; further, rs6265 C/C subjects treated with stimulation were associated with worse UPDRS part II scores at 24 months compared to medical therapy. Conclusions Genotyping for the rs6265 polymorphism may be useful for predicting long-term response to drug therapy and counseling Parkinson's disease patients regarding whether to consider earlier subthalamic nucleus deep brain stimulation. Validation in a larger cohort of early-stage Parkinson's disease subjects is warranted.

Objectives Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in advanced Parkinson's disease. STN DBS may also affect emotion, possibly by impacting a parallel limbic cortico-striatal circuit. The objective of this study was to investigate changes in prefrontal cortical activity related to DBS during an emotion induction task. Materials and Methods We used near infrared spectroscopy to monitor prefrontal cortex hemodynamic changes during an emotion induction task. Seven DBS patients were tested sequentially in the stimulation-on and stimulation-off states while on dopaminergic medication. Patients watched a series of positive, negative, and neutral videos. The general linear model was used to compare prefrontal oxygenated hemoglobin concentration between DBS states. Results Deep brain stimulation was correlated with prefrontal oxygenated hemoglobin changes relative to the stimulation off state in response to both positive and negative videos. These changes were specific to emotional stimuli and were not seen during neutral stimuli. Conclusions These results suggest that STN stimulation influences the prefrontal cortical representation of positive and negative emotion induction.

Statement of Problem: The osseointegration of dental implant is related to their composition and surface treatment. Titanium zirconium (TiZr) has been introduced as an alternative to the commercially pure titanium and its alloys as dental implant material, which is attributed to its superior mechanical and biological properties. Surface treatments of TiZr have been introduced to enhance their osseointegration ability; however, reliable, easy to use surface modification technique has not been established. Purpose: The purpose of this study was to evaluate and compare the effect of neodymium-doped yttrium aluminum garnet (Nd-YAG) laser surface treatment of TiZr implant alloy on their osteogenic potential. Materials and Methods: Twenty disc-shaped samples of 5 mm diameter and 2 mm height were milled from the TiZr alloy ingot. The polished discs were ultrasonically cleaned in distilled water. Ten samples each were randomly selected as Group A control samples and Group B consisted of Nd-YAG laser surface etched and conditioned test samples. These were evaluated for cellular response. Cellular adhesion and proliferation were quantified, and the results were statistically analyzed using nonparametric analysis. Cellular morphology was observed using electron and epiflurosence microscopy. Results: Nd-YAG laser surface modified and conditioned TiZr samples increased the osteogenic potential. Conclusion: Nd-YAG laser surface modification of TiZr, improves the cellular activity, surface roughness, and wettability, thereby increasing the osteogenic potential.

Background Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may have a disease modifying effect in early Parkinson9s disease (PD). A randomised, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. Objectives/methods 15 of 30 early PD patients were randomised to receive STN-DBS implants in an institutional review board approved protocol. Operative technique, location of DBS leads and perioperative adverse events are reported. Active contact used for stimulation in these patients was compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. Results 14 of the 15 patients did not sustain any long term (>3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior −1.1±1.7 mm, lateral 10.7±1.7 mm and superior −3.3±2.5 mm (anterior and posterior commissure coordinates). This location is statistically no different (0.77 mm, p>0.05) than the optimal contact used in the treatment of 47 advanced PD patients. Conclusions The perioperative adverse events in this trial of subjects with early stage PD are comparable with those reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomised, surgical versus best medical therapy trial for the early treatment of PD.

Parkinson's disease is a neurodegenerative disorder characterized by progressive loss of dopaminergic cells in the central nervous system, in particular the substantia nigra, resulting in an unrelenting loss of motor and nonmotor function. Animal models of Parkinson's disease reveal hyperactive neurons in the subthalamic nucleus that have increased firing rates and bursting activity compared with controls. Although subthalamic nucleus activity has been characterized in patients with advanced-stage Parkinson's disease, it has not been described in patients with early-stage Parkinson's disease. Here we present the results of subthalamic nucleus neuronal recordings from patients with early-stage Parkinson's disease (Hoehn and Yahr stage II) enrolled in an ongoing clinical trial compared with recordings from age- and sex-matched patients with advanced Parkinson's disease. Subthalamic nucleus neurons had a significantly lower firing rate in early versus advanced Parkinson's disease (28.7 vs 36.3 Hz; P

Many adults with intellectual disabilities (ID) have spasticity, where increased muscle tone impairs activities of daily living (ADL) self-performance and care delivery. There are few reports of spasticity treatment for people with ID, and none of functionally meaningful outcomes. Our objective is to determine the effect of comprehensive spasticity management on ADL self-performance and care delivery. Baseline evaluation included repeated modified Ashworth and range of motion assessments, and timed and videotaped care task observations. Spasticity treatment was initiated immediately thereafter. Follow-up evaluation was conducted after spasticity management was optimized, one year after initiation. All individuals with spasticity at a single developmental center for whom treatment goals could be identified were included. Treatment was recommended by a neurologist from any accepted treatment for spasticity except oral medications, including botulinum neurotoxin A, intrathecal baclofen and orthopedic procedures. The main outcome measure is comparison of ease of videotaped care delivery, rated by direct caregivers blinded to participant treatment status. Spasticity treatment resulted in significant improvement across all outcome measures. Range of motion improved by 9 degrees (P = 0.005) and MAS by 0.4 (P = 0.022). Participants took 14% percent less time to complete tasks post-treatment (P = 0.01). Thirteen caregivers completed evaluations of 35 video pairs with an intra-class correlation of 0.9. After treatment, undergarment change (P = 0.031) and shirt change (P = 0.017) were rated easier, and all goals (P = 0.0006). Transfers trended toward improvement (P = 0.053). This study shows comprehensive spasticity management provides meaningful improvement in ADL care for patients with ID, which may improve quality of life and reduce caregiver burden.

Previous reports have suggested that essential tremor (ET) represents a risk factor for the development of Parkinson's disease (PD). Patients with long-standing ET who develop PD tend to have a tremor-dominant subtype. To further clarify this association, we examined patients from kindreds with autosomal dominant ET who had signs of isolated PD but did not meet criteria for overlapping ET. We identified 22 patients with PD meeting these diagnostic criteria, and 90% (20 of 22) had tremor-predominant subtype of PD. Unilateral rest tremor was the presenting symptom in 15 of 22 patients, bradykinesia or rigidity in 5 of 22, and gait problems in 2 of 22. Postural tremor was relatively mild, and the severity of kinetic tremor tightly correlated with rest tremor (r = 0.83, P < 0.001). Tremor-dominant subtype of PD in patients with a positive family history of ET suggests that these patients have inherited a genetic susceptibility factor for tremor, which affects the motor phenotype of PD.

Aim: This study aimed to evaluate whether the extract of Morinda citrifolia L. mixed with irreversible hydrocolloid powder decreases microbial contamination during impression making without affecting the resulting casts. Materials and Methods: Twenty volunteers were randomly divided into two groups (n = 10). Group A 30 ml extract of M. citrifolia L diluted in 30 ml of water was mixed to make the impression with irreversible hydrocolloid material. Group B 30 ml deionized water was mixed with irreversible hydrocolloid material to make the impressions following which the surface roughness and dimensional stability of casts were evaluated. Results: Extract of M. citrifolia L. mixed with irreversible hydrocolloid decreased the percentage of microorganisms when compared with water (P < 0.001) but did not affect the surface quality or dimensional stability of the casts. Conclusion: Mixing the extract of M. citrifolia L. with irreversible hydrocolloid powder is an alternative method to prevent contamination without sacrificing impression quality.

Background Pain is a prevailing feature of cervical dystonia (CD), the most common form of focal dystonia. This analysis examined pain relief after onabotulinumtoxinA treatment in CD subjects with moderate/severe pain from the Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE). Methods CD PROBE was a prospective, multicenter, observational registry of CD subjects who were naive to botulinum toxin (BoNT), new to physician, or had not received BoNT within ≥ 16 weeks if in a clinical trial. Subjects were eligible for 3 treatments, with variable session intervals. Descriptive and inferential statistics were utilized to evaluate the change in pain scores in the population with moderate/severe neck pain at baseline (Pain Numeric Rating Scale [PNRS] score 4 to 10). Results Of 1046 enrolled, 733 (70.7%) had moderate/severe neck pain at baseline. Postinjection pain questionnaire responses 4 to 6 weeks after each of the 3 treatments revealed that a majority of subjects (67.1%, 72.4%, and 76.4%) reported pain relief; mean time to pain relief was 7.1, 7.4, and 7.6 days. All pain scales showed significant improvements from baseline to final visit (all P < 0.0001): PNRS, mean 6.6 to 3.8; CD Impact Profile-58 Pain and Discomfort subscale, mean 78.7 to 56.5; and Toronto Western Spasmodic Torticollis Rating Scale Pain subscale, mean 12.6 to 8.5. Multivariable regression models showed that initial pain score significantly contributed to the final pain score for all scales. Conclusion Results from this real-world clinical registry indicate that a majority of CD subjects with moderate/severe neck pain experience significant relief following onabotulinumtoxinA treatment.

Botulinum toxin type A (Dysport) has been shown in European studies to be a safe and effective treatment for cervical dystonia. This multicenter, double-blind, randomized, controlled trial assessed the safety and efficacy of Dysport in cervical dystonia patients in the United States. Eighty patients were randomly assigned to receive one treatment with Dysport (500 units) or placebo. Participants were followed up for 4 to 20 weeks, until they needed further treatment. They were assessed at baseline and weeks 2, 4, 8, 12, 16, and 20 after treatment. Dysport was significantly more efficacious than placebo at weeks 4, 8, and 12 as assessed by the Toronto Western Spasmodic Torticollis Rating Scale (10-point vs. 3.8-point reduction in total score, respectively, at week 4; P < or = 0.013). Of participants in the Dysport group, 38% showed positive treatment response, compared to 16% in the placebo group (95% confidence interval, 0.02-0.41). The median duration of response to Dysport was 18.5 weeks. Side effects were generally similar in the two treatment groups; only blurred vision and weakness occurred significantly more often with Dysport. No participants in the Dysport group converted from negative to positive antibodies after treatment. These results confirm previous reports that Dysport (500 units) is safe, effective, and well-tolerated in patients with cervical dystonia.

The genetic etiology of essential tremor remains unknown despite the significant proportion of familial cases. The search for monogenic causes has repeatedly failed until recent identification of three disease-causing mutations in FUS (fused in sarcoma), a gene previously linked to a rare forms of familial amyotrophic lateral sclerosis with frontotemporal dementia. The genetic epidemiology of FUS in ET is unknown. Herein, we screened 104 patients from 52 pedigrees for mutations in the coding sequence of FUS. Two of the most genetically distant affected individuals from each pedigree were selected for Sanger sequencing to potentially increase the success of genetic analysis. We did not identify a single pathogenic mutation. Our data suggest that FUS mutations are a rare cause of familial ET.

Pfister AA, Roberts AG, Taylor HM, Noel-Spaulding S, Damian MM, Charles PD. Spasticity in adults living in a developmental center. Arch Phys Med Rehabil 2003;84:1808–12. Objectives To ascertain the prevalence of spasticity among adults living in a developmental center and to document the development of spasticity treatment plans for this population. Design Descriptions of the clinical features of medical disorders and a prevalence survey. Setting Residential developmental center. Participants One hundred three adults. Interventions Not applicable. Main outcome measures Characteristics described included the prevalence of spasticity in this population, the specific spasticity diagnosis, functional goals for spasticity treatment identified by the participants' multidisciplinary teams, and the specific treatment indicated by the neurologist. Results Of the 103 people diagnosed by the neurologist, 24 had diplegic spasticity, 4 had hemiplegic spasticity, 44 had quadriplegic spasticity, and 31 had no spasticity. Functional goals identified by multidisciplinary teams were undergarment change (46.3% of the persons for whom goals were identified), splinting hands (11%), dressing (57.4%), hygiene (20.4%), wheelchair positioning (25.9%), ambulation improvement (14.8%), and transfers (9.3%). After physical and occupational therapy, the first invasive treatments indicated for people with spasticity included botulinum toxin injections (60%), intrathecal baclofen (26.4%), orthopedic surgery (5.6%), and medication (1.4%). No treatment was recommended for 25% of the spasticity patients. Conclusions The prevalence of spasticity was 35% in this developmental center population of 205 individuals. A multidisciplinary team approach to the evaluation of adults with spasticity who live in a developmental center makes it possible to identify functional goals that are amenable to spasticity treatment and minimizes treatment that does not target specific functional goals.

Disjointed patient care is a well-documented problem in health care systems, often stemming from poor communication between providers, services, and follow-up care resources. A multidisciplinary discharge huddle, augmented with cellular and tablet technology, was implemented on the Neurology Stroke Service to facilitate multidisciplinary communication, improve transition of patients, and increase referrals into affiliated follow-up care. After initiating the huddle, patient length of stay decreased by 1.4 days (25%), patient flow into continuum partners increased by 10%, and the number of patients going without services after their hospital stay decreased by more than 12%. Huddle members reported that the technology was helpful, heavily utilized, and made their work more efficient. This pilot suggests that utilizing modern mobile technologies can help improve efficiency and referrals within the health care system and reduce patient length of stay.

Dystonic tremor (DT) is characterized by coexisting tremor and abnormal dystonic posturing in the same segment. DT is often medically refractory and DBS is an important therapeutic option. However, the optimal surgical target for DT remains uncertain with Vim, GPi and zona incerta previously reported as effective. We retrospectively reviewed the outcome data from all patients with DT involving at least one upper extremity who underwent DBS at Vanderbilt University from July 2006 to July 2010. We evaluated the improvement of tremor and dystonia after their response to DBS was judged to be maximal. Ten patients met the inclusion criteria. Vim was targeted in four patients and three had unilateral procedure and one bilateral Vim DBS. GPi was targeted in four patients with bilateral DBS procedure in every patient from this subgroup. A combined bilateral GPi and unilateral Vim DBS was performed in two patients. The best results for tremor control were observed in patients with Vim DBS but they had persisting mild dystonia. Patients with GPi DBS had average DT improvement by approximately 50% but their dystonia symptoms were markedly improved. We propose that the patients with DT with a mild dystonia should be considered for Vim DBS procedure and the coexistence of severe DT and dystonia may be successfully controlled by combined GPi and Vim DBS surgeries.

Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated.

Publisher Summary Neuroleptic malignant syndrome (NMS) is a rare and potentially fatal syndrome of hyperthermia, rigidity, autonomic instability, and mental status derangement. The primary morbidity and mortality associated with NMS are irreversible brain injury from hyperthermia and renal failure from myoglobinuria secondary to rigidity-induced skeletal muscle necrosis. Neuroleptics are commonly prescribed drugs in the United States. Phenothiazines, thiothixine, and butyrophenones are the agents most commonly implicated in causing NMS, with haloperidol being the most commonly associated, most likely because it was one of the most commonly prescribed neuroleptics. The differential diagnosis of NMS includes other syndromes with hyperthermia as a prominent feature, fever complicating Parkinson's disease or other extrapyramidal syndromes, and lethal catatonia. Malignant hyperthermia and NMS have similar clinical features but are distinguishable because malignant hyperthermia is inherited as an autosomal dominant condition and is only triggered by the administration of anesthetic agents. Patients with NMS should be treated in an intensive care unit. Treatment begins with the immediate withdrawal of the offending neuroleptic or the reintroduction of the antiparkinson agent that was discontinued. The average time for recovery from NMS is 10 days.

Research on individuals with intellectual and developmental disabilities continues to be an underinvestigated area of medicine. Even after the Surgeon General’s report (Office of the Surgeon General, 2002) emphasizing the need to develop specific, achievable goals to improve the quality of life of people with intellectual and developmental disabilities, there is insufficient research with these individuals. Now more than ever, it is imperative that adequate research efforts be focused on the population of individuals with intellectual and developmental disabilities in order to better understand and define their specific needs, and, ultimately, to improve their quality of life. With the evolution of modern medicine and the introduction of novel medical concepts and treatments, these individuals are living longer (McCausland et al., 2010), but they continue to face clear challenges in maintaining good health because they have poor health status compared to individuals in the general population (Lennox, Beange, & Edwards, 2000). Researchers have shown that the needs of this population differ significantly from those of the general population and that they are at an increased risk of developing comorbidities. However, their specific needs have not been well-defined (Parish, Moss, & Richman, 2008). To date, few large epidemiological studies have been conducted to assess the prevalence of specific medical conditions in individuals with intellectual and developmental disabilities (Beange, McElduff, & Baker, 1995). Furthermore, only 14% of individuals with intellectual and developmental disabilities currently live in public or private institutions (Smith, Lakin, Larson, & Salmi, 2011), making community-based research increasingly important.

Background A registry of patients with cervical dystonia (Cervical Dystonia Patient Registry for Observation of onaBotulinumtoxinA Efficacy [CD PROBE]) was initiated to capture data regarding physician practices and patient outcomes with onabotulinumtoxinA (BOTOX®, Allergan, Inc., Irvine, CA, USA). Methods and baseline demographics from an interim analysis are provided. Methods/Design This is a prospective, multicenter, clinical registry in the United States enrolling subjects with cervical dystonia (CD) who are toxin naïve and/or new to the physicians' practices, or who had been in a clinical trial but received their last injection ≥ 16 weeks prior to enrollment. Subjects are followed over 3 injection cycles of onabotulinumtoxinA, with assessments at time of injection and 4-6 weeks later. Information on physician's practice, patient demographics, CD disease history, duration of treatment intervals and neurotoxin dose, dilution, use of electromyography, and muscles injected are collected. Outcomes are assessed by physicians and subjects using various questionnaires. Discussion This ongoing registry includes 609 subjects with the following baseline data: 75.9% female, 93.6% Caucasian, mean age 57.6 ± 14.3, age at symptom onset 48.3 ± 16.2, and time to diagnosis 5.4 ± 8.6 years, with an additional 1.0 ± 3.5 years before treatment. Of those employed at the time of diagnosis, 36.6% stopped working as a result of CD. CD PROBE, the largest clinical registry of CD treatment, will provide useful data on current treatment practices with onabotulinumtoxinA, potentially leading to refinements for optimization of outcomes. Trial registration NCT00836017

The purpose of this study was to assess and evaluate the role of transforming growth factor-beta(1), epidermal growth factor, and their respective carriers (collagen and liposomes) in the early phases of the wound-healing process in linear incision wounds; we used an in vivo biomechanical testing system. One hundred twenty specific pathogen-free male Sprague-Dawley rats were divided into five experimental groups (n = 24), including one group receiving no treatment at all. Each animal received one abdominal midline incision. At 3 and 5 days after wounding, 12 animals per group were randomly selected for in vivo biomechanical evaluation. Specimens were also randomly obtained from nondisrupted tissues for histologic analysis. Statistical analysis comparing groups revealed that transforming growth factor-beta(1) significantly increased wound strength at day 5, and liposomes decreased wound strength at day 3. There were no other significant differences among groups for each of the time intervals studied. Our results suggest that in vivo biomechanical evaluation of tissue response to injury and treatments will add new dimension to future studies of skin and wound healing.

This Viewpoint contributes to the topical debate on the therapeutic benefits of deep brain stimulation in Parkinson's disease (PD). The authors argue that there is more to this treatment approach than just providing symptomatic benefits, and suggest that it may actually become the first therapy proven to slow the progression of PD.

Comparative studies of botulinum neurotoxin preparations to date have generally examined 2 preparations at prespecified dose ratios in relatively homogeneous groups of patients under controlled study conditions. It is unclear whether the differences in adverse-event rates that have been noted under these controlled conditions can be generalized to the broader population of cervical dystonia patients, who are treated with a wider range of doses in a variety of settings.We conducted a systematic review and analysis of the published literature to compare rates of dysphagia and dry mouth in studies of botulinum neurotoxin products.We searched the MEDLINE, EMBASE, Biosis, SciSearch, JICST (Japan Science and Technology Center), and Pascal databases from 1985 through 2006 using the terms cervical dystonia, spasmodic torticollis, and botulinum toxin for original English-language studies of Botox, Dysport, or Myobloc in the treatment of cervical dystonia (or spasmodic torticollis) that documented adverse events by treatment or patient. Studies that involved patients with various types of dystonias or movement disorders were included as long as adverse events were reported separately for those with cervical dystonia. Rates of dysphagia with the original preparation of Botox were considered separately from those with the current preparation of Botox.Seventy published articles were included in the analysis (30 Botox, 24 Dysport, 3 Botox + Dysport, 11 Myobloc, 2 Botox + Myobloc). Mean total doses per treatment ranged from 60 to 374 U for Botox, 125 to 1200 U for Dysport, and 579 to 19,853 U for Myobloc. Botox was associated with a significantly lower rate of dysphagia than Dysport, with mean dysphagia rates of 10.5% for original Botox, 8.9% for current Botox, and 26.8% for Dysport (both, P0.05). Myobloc was associated with dry mouth (3.2%-90.0%) in 9 of 13 studies, but this adverse event was not reported in a sufficient number of studies of botulinum toxin type A preparations (Botox, n = 2; Dysport, n = 6) to permit statistical comparison. In the weighted analysis, the duration of effect differed between botulinum neurotoxin products (current BotoxMyoblocoriginal BotoxDysport; all, P0.001), but only 43 (61.4%) of the 70 studies reported duration, and the definitions varied.The results of this analysis indicate differences in adverse-event rates between botulinum neurotoxin preparations, suggesting that use of these products should be based on their individual dosing, efficacy, and safety profiles.

Tremor is often a disabling primary condition or secondary to another disorder. No universally effective pharmacological agent exists for the treatment of essential tremor, and patients differ greatly in their response to therapies, thus requiring individualised regimens. Deep brain stimulation is the best option for patients with disabling, drug-resistant essential tremor. Resting tremor in Parkinson's disease is usually not the primary disabling feature, and in most cases, levodopa/carbidopa is satisfactory for many years. Young Parkinson's patients with dominant, disabling tremor benefit from anticholinergics in addition to dopaminergic therapies. However, older Parkinson's patients with more disabling tremor may suffer from dose-dependent side effects, and deep brain stimulation should be considered. This article outlines the available pharmacological agents and treatment considerations for various disabling tremors, including essential tremor and Parkinson's disease.

This study reports a retrospective analysis of 16 patients to determine changes in medication costs associated with deep brain stimulation of the bilateral subthalamic nucleus (DBS B-STN). Antiparkinsonian medication (APMED) costs were evaluated pre- and post-operatively at 1 and 2 years, based on prescribed dosages. After treatment with DBS, patients experienced a 32% reduction in APMED costs after 1 year and a 39% reduction after 2 years. Hypothetical projections of total potential savings are presented, accounting for increasingly complex medication regimens and medication cost inflation. DBS patients may experience a significant long-term reduction in the cost of their pharmacologic treatment.

Background: Although dry mouth (xerostomia) has been reported with botulinum toxin type B used as treatment for cervical dystonia, the impact of this adverse effect (AE) on patients' activities of daily living (ADLs) has not been assessed. tObjective: The aim of this study was to examine the severity, duration, and impact of xerostomia in patients with cervical dystonia who reported this AE in routine clinical practice following treatment with botulinum toxin type B. Methods: In this uncontrolled study, investigators at 5 study centers across the United States retrospectively identified patients who were diagnosed with cervical dystonia and had received ≥ 1 treatment with botulinum toxin type B injection and who had reported xerostomia, based on patients' charts. These patients were mailed a survey that included questions about their treatment history, disease severity, and xerostomia (severity, onset, duration, change with subsequent injections, and effects on dental and oral health), as well as an 8-item Patient Benefit Questionnaire (PBQ), which was designed to assess the impact of xerostomia symptoms on patients' ADLs. Results: A total of 45 patients received a mean of 2.91 injections with botulinum toxin type B (mean dose per injection, 11,958 U), with a total of 131 injections. The mean severity of patient-rated xerostomia following the first injection of botulinum toxin type B was 3.88 on a scale of 1 (mild) to 5 (severe), and this rating did not change for patients who received subsequent injections (mean, 3.76). Following atypical injection of botulinum toxin type B, xerostomia began a mean (SD) of 4.82 (3.32) days later and persisted for a mean (SD) duration of 5.56 (3.57) weeks. The overall mean score on the 10-point PBQ prior to botulinum toxin treatment was 8.89, which decreased to 5.42 following botulinum toxin type B injection (lower scores indicate more severe xerostomia). Conclusions: This study of patients with cervical dystonia suggests that patients who experience xerostomia following treatment with botulinum toxin type B injection, on average, rate their symptoms as moderate to severe and exhibit reduced scores on the PBQ—a questionnaire on which lower scores indicate greater negative impact of xerostomia on patients' ADLs.

Injection with botulinum toxin type A (Botox) is a safe and efficacious treatment for idiopathic cervical dystonia. We present the first case report of clinical Botox treatment during pregnancy. This patient underwent four apparently uncomplicated full-term pregnancies while receiving regular Botox treatments.

A child suffered bilateral thalamic infarction secondary to Sneddon and antiphospholipid antibody syndromes. Her initial findings of hypersomnolence, mood disturbance, and amnesia are characteristic of bilateral thalamic infarction. Clinical and laboratory evaluation confirmed the diagnosis of both Sneddon and antiphospholipid antibody syndromes as the cause of her unusual stroke. The treatment of this patient, based on experience with adult patients, was long-term, high-intensity warfarin anticoagulation.

This placebo-controlled crossover trial investigate the safety and efficacy of onabotulinumtoxinA (BOTOX, Allergan, Inc.) for the treatment of cervical myofascial pain syndrome (CMPS). A group of subjects with Cervical Dystonia (CD) served as additional controls. A change in diary pain score from baseline to week 3 in placebo vs. onabotulinumtoxinA was the primary outcome measure. Both CMPS and CD subjects showed a trend towards significant pain relief from onabotulinumtoxinA. This suggests that the study was underpowered and that a larger sample size would be necessary in future trials of onabotulinumtoxinA for CMPS.

Background There is an ongoing debate whether essential tremor (ET) represents a monosymptomatic disorder or other neurologic symptoms are compatible with the diagnosis of ET. Many patients with clinically definite ET develop dystonia. It remains unknown whether tremor associated with dystonia represent a subtype of ET. We hypothesized that ET with dystonia represents a distinct subtype of ET. Methods We studied patients diagnosed with familial ET and dystonia. We included only those patients whose first-degree relatives met diagnostic criteria for ET or dystonia with tremor. This cohort was ascertained for the presence of focal, segmental, multifocal, hemidystonia or generalized dystonia, and ET. Results We included 463 patients from 97 kindreds with autosomal dominant mode of inheritance (AD), defined by the vertical transmission of the disease. ET was the predominant phenotype in every ascertained family and each was phenotypically classified as AD ET. "Pure" ET was present in 365 individuals. Focal or segmental dystonia was present in 98 of the 463 patients; 87 of the 98 patients had ET associated with dystonia, one had dystonic tremor and ten had isolated dystonia. The age of onset and tremor severity did not differ between patients with "pure" ET and ET associated with dystonia. We did not observe a random distribution of dystonia in AD ET pedigrees and all patients with dystonia associated with ET were clustered in 28% of all included pedigrees (27/97, p < 0.001). Conclusions Our results suggest that familial ET associated with dystonia may represent a distinct subtype of ET.

In the setting of a spasticity management program, 26 adults with Intellectual Disability (ID) and spasticity were treated with injections of Botulinum Toxin type A. After a series of regular injections (range: 4-7 injections), three patients experienced dramatically lengthened benefit lasting an average of 22.3 months (range: 19-29). None of the patients exhibit characteristics that have been suggested to explain this phenomenon in other disorders, such as duration of illness or toxin dose. Future studies should identify which characteristics or treatment parameters predict lengthened response.

The original article to which this Erratum refers was published in Movement Disorders (2004) 19(11)1384–1385.

Reply from the Authors: We appreciate the comments by Dr. Foundas concerning the relation of language dominance and brain asymmetries identified on MRI. The work she describes is exciting and carries great significance. The ability to predict language dominance reliably by a noninvasive investigation of brain asymmetries on MRI would certainly be a great advance in evaluating patients being considered for surgical treatment of epilepsy. We have three primary concerns regarding the work described by Dr. Foundas. First, the number of subjects is very small in …