Several single-center studies and one large multicenter clinical trial demonstrated that directional deep brain stimulation (DBS) could optimize the volume of tissue activated (VTA) based on the ...individual placement of the lead in relation to the target. The ability to generate axially asymmetric fields of stimulation translates into a broader therapeutic window (TW) compared to conventional DBS. However, changing the shape and surface of stimulating electrodes (directional segmented vs. conventional ring-shaped) also demands a revision of the programming strategies employed for DBS programming. Model-based approaches have been used to predict the shape of the VTA, which can be visualized on standardized neuroimaging atlases or individual magnetic resonance imaging. While potentially useful for optimizing clinical care, these systems remain limited by factors such as patient-specific anatomical variability, postsurgical lead migrations, and inability to account for individual contact impedances and orientation of the systems of fibers surrounding the electrode. Alternative programming tools based on the functional assessment of stimulation-induced clinical benefits and side effects allow one to collect and analyze data from each electrode of the DBS system and provide an action plan of ranked alternatives for therapeutic settings based on the selection of optimal directional contacts. Overall, an increasing amount of data supports the use of directional DBS. It is conceivable that the use of directionality may reduce the need for complex programming paradigms such as bipolar configurations, frequency or pulse width modulation, or interleaving. At a minimum, stimulation through directional electrodes can be considered as another tool to improve the benefit/side effect ratio. At a maximum, directionality may become the preferred way to program because of its larger TW and lower energy consumption.
Tardive dystonia (TD) is a disabling complication of pharmacological therapy with dopaminergic receptor antagonists, usually resistant to oral medications. Several reports have shown that deep brain ...stimulation (DBS) of the globus pallidus pars interna (GPi) might be effective in TD, but the overall level of evidence remains limited to case reports or small case series.
We sought to summarize the collective evidence in support of GPi-DBS for TD using a meta-analytic approach.
We searched PubMed for human studies reporting tardive dystonia cases treated with GPi-DBS that reported the validated Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) as outcome measure. Data extracted were reviewed for risk of bias. Then, through linear mixed effects modeling of the percent improvement seen on an individual level, we estimated the average improvement effect varying by study.
The searching strategy resulted in a total of n = 78 studies, which were screened for eligibility criteria resulting in the inclusion of n = 14 studies, yielding 134 TD patients for the final analyses. The overall estimate improvement in the BFMDRS after GPi-DBS was 66.88 ± 11.96%. The review of individual case reports indicated rare worsening (n = 4) or lack of improvement (n = 3) following GPi-DBS.
Bilateral GPi-DBS can be an effective therapeutic option for severe cases of TD resistant to oral pharmacological therapies, even though rare cases of symptom worsening or lack of improvement have also been reported.
Objective. This cross-sectional study analyzes the pattern of ultrasound peripheral nerve alterations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal ...motor neuropathy (MMN) at different stages of functional disability. Material and Methods. 22 CIDP and 10 MMN patients and a group of 70 healthy controls were evaluated with an ultrasound scan of the median, ulnar, peroneal, tibial, and sural nerves. Results were correlated with clinical disability scales and nerve conduction studies. Results. Patients with intermediate functional impairment showed relatively larger cross-sectional areas than subjects with either a milder ( p < 0.05 ) or more severe impairment ( p < 0.05 ), both in CIDP and in MMN. In addition, MMN was associated with greater side-to-side intranerve variability ( p < 0.05 ), while higher cross-sectional areas were observed in CIDP ( p < 0.05 ) and in nerve segments with predominantly demyelinating features ( p < 0.05 ). Higher CSA values were observed in nerves with demyelinating features versus axonal damage ( p < 0.05 for CIDP; p < 0.05 for MMN). Discussion and Conclusions. Greater extent of quantitative and qualitative US alterations was observed in patients at intermediate versus higher functional disability and in nerves with demyelinating versus axonal damage. CIDP and MMN showed differential US aspects, with greater side-to-side intranerve variability in MMN and higher cross-sectional areas in CIDP.
Introduction
Tardive dystonia (TD) is a disabling complication of pharmacological therapy with dopaminergic receptor antagonists, usually resistant to oral medications. Several reports have shown ...that deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) might be effective in TD, but the overall level of evidence remains limited to case reports or small case series.
Objectives
We sought to summarize the collective evidence in support of GPi-DBS for TD using a meta-analytic approach.
Methods
We searched PubMed for human studies reporting tardive dystonia cases treated with GPi-DBS that reported the validated Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) as outcome measure. Data extracted were reviewed for risk of bias. Then, through linear mixed effects modeling of the percent improvement seen on an individual level, we estimated the average improvement effect varying by study.
Results
The searching strategy resulted in a total of
n
= 78 studies, which were screened for eligibility criteria resulting in the inclusion of
n
= 14 studies, yielding 134 TD patients for the final analyses. The overall estimate improvement in the BFMDRS after GPi-DBS was 66.88 ± 11.96%. The review of individual case reports indicated rare worsening (
n
= 4) or lack of improvement (
n
= 3) following GPi-DBS.
Conclusions
Bilateral GPi-DBS can be an effective therapeutic option for severe cases of TD resistant to oral pharmacological therapies, even though rare cases of symptom worsening or lack of improvement have also been reported.
Highlights ► A technique to achieve non invasive, well tolerated maximal stimulation of lumbosacral motor nerve roots. ► A method to obtain a simultaneous, bilateral and balanced maximal activation ...of several lumbosacral motor roots. ► A tool to detect conduction slowing and block in proximal tracts of peripheral motor nerves.
Cases of chronic inflammatory demyelinating poliradiculoneuropathy (CIDP) have been reported in hematopoietic stem cells transplantation complicated by graft versus host disease (GVHD). A systematic ...review of the CIDP‐like neuropathies associated with GVHD was conducted until January 2015, analyzing the clinical presentation and the response to different therapeutic regimens. Nineteen patients have been reported in literature including the present one. Fourteen subjects fulfilled the criteria for CIDP, whereas two cases presented with an asymmetric motor onset and one showed motor involvement only associated with anti‐ganglioside antibodies. In addition, two subjects already affected by CIDP developed a significant relapse after GVHD. This study reviews the literature data and reports one additional case of CIDP and GVHD, suggesting that the two clinical entities might share a similar immunological background.
•In APD, fluctuations between patients’ motor states develop as disease progresses.•Evidence on long-term impact of CLES on motor fluctuations across the day is limited.•CLES was associated with ...fewer motor fluctuations and increased symptom control.•Patients taking CLES had faster onset to good ON time after waking.•CLES may improve patients’ quality of life by reducing unpredictable OFF periods.
Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson’s disease patients across 54 weeks. Evidence on CLES’s long-term effectiveness on patterns of motor-symptom control throughout the day remains limited.
We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289). Diary data recorded patients’ motor states at 30-minute intervals over 3 days at baseline and weeks 4, 12, 24, 36, and 54. Adjusted generalized linear mixed models assessed changes from baseline at each timepoint for four outcome measures: time to ON without troublesome dyskinesia (ON-woTD) after waking, motor-symptom control as measured by motor states’ durations throughout the day, number of motor-state transitions, and presence of extreme fluctuations (OFF to ON with TD).
Patients demonstrated short-term (wk4) and sustained (wk54) improvement in all outcomes compared to baseline. At weeks 4 and 54, patients were more likely to reach ON-woTD over the course of their day (HR: 1.86 and 2.51, both P < 0.0001). Across 4-hour intervals throughout the day, patients also experienced increases in ON-woTD (wk4: 58–65 min; wk54: 60–78 min; all P < 0.0001) and reductions in OFF (wk4: 50–61 min; wk54: 56–68 min; all P < 0.0001). At weeks 4 and 54, patients’ motor-state transitions were reduced by about half (IRR: 0.53 and 0.49, both P < 0.0001), and fewer patients experienced extreme fluctuations (OR: 0.22 and 0.15, both P < 0.0001).
CLES monotherapy was associated with significant long-term reductions in motor-state fluctuations, faster time to ON-woTD upon awakening, and increased symptom control throughout the day.
Introduction. This study evaluates the efficacy of palmitoylethanolamide ultramicronized (PEA-um) as an add-on treatment in patients with diabetic or traumatic neuropathic pain (NP). Methods. 30 ...patients with chronic NP were assessed with Visual Analogue Scale (VAS), NP Symptom Inventory (NPSI), and Health Questionnaire Five Dimensions (EQ-5D), both at baseline and after 10 and 40 days of treatment with 1200 mg/die of PEA-um. All other therapies were maintained stable during the follow-up period. Results. VAS mean score significantly improved within the first 10 days, ranging from 8.20 ± 1.53 to 6.40 ± 1.83 ( P < 0.002 ), with a further decrease to 5.80 ± 2.04 ( P < 0.001 ) after 40 days of PEA-um administration. Moreover, NPSI total score improved from 5.2 ± 1.5 to 3.8 ± 2.1 ( P : 0.025) and EQ-5D ranged from −0.30 ± 0.65 to 0.5 ± 0.34 ( P < 0.001 ) between T0 and T2. Conclusions. This study reports the prospective short-term efficacy data of oral PEA-um in patients with diabetic or traumatic NP. A significant improvement was observed both in VAS and NPSI scores and in quality of life scales after 40 days of treatment, although some limitations should be considered, including the short followup and the open-label study design.
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