Best Practice Guidelines for the Management of Patients with Post-Stroke Spasticity: A Modified Scoping Review.

This article aims to provide a concise overview of the best available evidence for managing post-stroke spasticity. A modified scoping review, conducted following the PRISMA guidelines and the PRISMA Extension for Scoping Reviews (PRISMA-ScR), involved an intensive search on Medline and PubMed from 1 January 2000 to 31 August 2023. The focus was placed on high-quality (GRADE A) medical, rehabilitation, and surgical interventions. In total, 32 treatments for post-stroke spasticity were identified. Two independent reviewers rigorously assessed studies, extracting data, and evaluating bias using GRADE criteria. Only interventions with GRADE A evidence were considered. The data included the study type, number of trials, participant characteristics, interventions, parameters, controls, outcomes, and limitations. The results revealed eleven treatments supported by GRADE A evidence, comprising 14 studies. Thirteen were systematic reviews and meta-analyses, and one was randomized control trial. The GRADE A treatments included stretching exercises, static stretching with positional orthosis, transcutaneous electrical nerve stimulation, extracorporeal shock wave therapy, peripheral magnetic stimulation, non-invasive brain stimulation, botulinum toxin A injection, dry needling, intrathecal baclofen, whole body vibration, and localized muscle vibration. In conclusion, this modified scoping review highlights the multimodal treatments supported by GRADE A evidence as being effective for improving functional recovery and quality of life in post-stroke spasticity. Further research and exploration of new therapeutic options are encouraged.

Continuous speech with pauses inserted between words increases cortical tracking of speech envelope.

The decoding multivariate Temporal Response Function (decoder) or speech envelope reconstruction approach is a well-known tool for assessing the cortical tracking of speech envelope. It is used to analyse the correlation between the speech stimulus and the neural response. It is known that auditory late responses are enhanced with longer gaps between stimuli, but it is not clear if this applies to the decoder, and whether the addition of gaps/pauses in continuous speech could be used to increase the envelope reconstruction accuracy. We investigated this in normal hearing participants who listened to continuous speech with no added pauses (natural speech), and then with short (250 ms) or long (500 ms) silent pauses inserted between each word. The total duration for continuous speech stimulus with no, short, and long pauses were approximately, 10 minutes, 16 minutes, and 21 minutes, respectively. EEG and speech envelope were simultaneously acquired and then filtered into delta (1-4 Hz) and theta (4-8 Hz) frequency bands. In addition to analysing responses to the whole speech envelope, speech envelope was also segmented to focus response analysis on onset and non-onset regions of speech separately. Our results show that continuous speech with additional pauses inserted between words significantly increases the speech envelope reconstruction correlations compared to using natural speech, in both the delta and theta frequency bands. It also appears that these increase in speech envelope reconstruction are dominated by the onset regions in the speech envelope. Introducing pauses in speech stimuli has potential clinical benefit for increasing auditory evoked response detectability, though with the disadvantage of speech sounding less natural. The strong effect of pauses and onsets on the decoder should be considered when comparing results from different speech corpora. Whether the increased cortical response, when longer pauses are introduced, reflect improved intelligibility requires further investigation.

The role of the capsaicin 8% patch in the treatment of painful diabetic peripheral neuropathy.

Treatment of painful diabetic peripheral neuropathy (PDPN) is challenging and often limited by drug tolerability and adverse effects. This review article focuses on the high-dose (8%) capsaicin patch that allows for improved efficacy and reduced application frequency in comparison to low-dose capsaicin formulations. Systemic absorption is minimal resulting in fewer systemic side effects than first-line oral medications. There is evidence that capsaicin patch treatment is well-tolerated, safe and provides effective pain relief maintained for several weeks; well-powered studies are needed to confirm these findings. The capsaicin 8% patch may benefit patients at high risk for adverse effects from oral medication, polypharmacy or inadequate pain relief from first-line therapies.

Treatment of nerve pain in the feet and other regions due to nerve damage from diabetes is challenging, often due to the unwanted side effects of medications. This review article focuses on the high-dose (8%) capsaicin patch, which can be applied directly to the feet. It is more potent than the low-dose formulations, allowing patients to apply it less often while also working more effectively compared with low-dose capsaicin creams. Because it acts directly on the skin, there are fewer systemic side effects such as drowsiness or urinary retention. There is evidence that capsaicin patch treatment is safe and provides pain relief for several weeks. More large studies are needed to confirm these findings. The capsaicin 8% patch may benefit patients at high risk for side effects from oral medications or inadequate pain relief from first-line medications.

Botulinum Toxin Therapy in Writer's Cramp and Musician's Dystonia.

Task-specific focal dystonia is characterized by muscle contraction(s) during a specific task, resulting in abnormal postures or movements. Specifically, writer's cramp involves the upper extremity during the act of writing. Musician's dystonia has a highly variable presentation, and thus makes therapeutic options more limited. Treatments include oral pharmacologic agents, neuromodulation, surgery and, most often, botulinum toxin (BoNT) injection. Selection of target muscles for toxin injection continues to be an area of active research for these task-specific movements. We present a review of the literature selected from a predefined search of the MEDLINE and ClinicalTrials.gov databases. We include six controlled studies of botulinum toxin for the management of writer's cramp and focal task-specific dystonia (FTSD), including musician's dystonia. Overall, 139 patients were included across all studies, with 99 individuals injected for writer's cramp and the remaining 40 individuals with FTSD. The age range of all patients was 18-80 years old. We included studies that utilized only the BoNT-A serotype. These studies utilized various severity scales to quantify response to toxin injection, with ratings of instrument or pen control included as subjective ratings. Of the included 139 patients in this review, pooled data for toxin response show that 73% of patients who received the drug demonstrated improvement. Specific techniques for muscle localization and targeting were difficult to study as variable methods were employed. This remains an area of ongoing exploration.

Management of Neuropathic Pain in the Geriatric Population.

Neuropathic pain is common in the geriatric population. Diagnosis requires a thorough history and physical examination to differentiate it from other types of pain. Once diagnosed, further workup is required to elucidate the cause, including potential reversible causes of neuropathy. When treating neuropathic pain in the elderly, it is important to consider patients' comorbidities and other medications to avoid drug-drug interactions and iatrogenic effects given the physiologic changes of drug metabolism in the elderly. Nonsystemic therapies and topical medications should be considered. Systemic medications should be started at low dose and titrated up slowly with frequent monitoring for adverse effects.

A critical review of the capsaicin 8% patch for the treatment of neuropathic pain associated with diabetic peripheral neuropathy of the feet in adults.

INTRODUCTION: Diabetes is an increasingly prevalent disorder affecting nearly 1-in-5 adults, of which half will experience diabetic peripheral neuropathy (DPN) and a quarter will suffer from diabetic peripheral nerve pain (DPNP), severely impacting quality of life. The currently approved treatment options are typically centrally acting agents whose use is limited by systemic effects and drug interactions. The capsaicin 8% dermal patch was recently approved by the U.S. FDA for the treatment of DPNP. AREAS COVERED: The authors review the available literature regarding the use of high-concentration capsaicin 8% patch for the treatment of diabetic peripheral neuropathy and neuropathic pain and discuss implementing its use in clinical practice. EXPERT OPINION: The high-concentration capsaicin 8% patch is an effective and well-tolerated treatment option for treating DPNP. Capsaicin 8% patch may be used alone or in combination with other oral therapies and can provide rapid and sustained neuropathic pain relief following a single application and is safe and effective when used long term.

Biokinetic Analysis and Metabolic Fate of 2,4-D in 2,4-D-Resistant Soybean (Glycine max).

The Enlist weed control system allows the use of 2,4-D in soybean but slight necrosis in treated leaves may be observed in the field. The objectives of this research were to measure and compare uptake, translocation, and metabolism of 2,4-D in Enlist (E, resistant) and non-AAD-12 transformed (NT, sensitive) soybeans. The adjuvant from the Enlist Duo herbicide formulation (ADJ) increased 2,4-D uptake (36%) and displayed the fastest rate of uptake (U50= 0.2 h) among treatments. E soybean demonstrated a faster rate of 2,4-D metabolism (M50= 0.2 h) compared to NT soybean, but glyphosate did not affect 2,4-D metabolism. Metabolites of 2,4-D in E soybean were qualitatively different than NT. Applying 2,4-D-ethylhexyl ester instead of 2,4-D choline (a quaternary ammonium salt) eliminated visual injury to E soybean, likely due to the time required for initial de-esterification and bioactivation. Excessive 2,4-D acid concentrations in E soybean resulting from ADJ-increased uptake may significantly contribute to foliar injury.

NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: results of a 52-week open-label study.

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of repeated NGX-4010 treatments in the open-label extension phase of a 52-week study in patients with neuropathic pain due to HIV-associated distal sensory polyneuropathy (HIV-DSP). METHODS: Patients completing the 12-week, randomized, double-blind phase of the study could enter a 40-week, open-label phase, and receive up to 3, 60-minute NGX-4010 treatments. Patients recorded their "average pain for the past 24 hours" daily using the Numeric Pain Rating Scale (NPRS). Efficacy assessment included the percentage NPRS score reduction from baseline to weeks 2 to 12 after the final treatment, and Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) questionnaires at study termination. RESULTS: Of 307 patients randomized, 272 entered the open-label phase; 81, 90, 55, and 46 received 0, 1, 2, and 3 retreatments, respectively. The mean percentage decrease in NPRS score from baseline to weeks 2 to 12 after the final treatment was similar in patients receiving single or multiple NGX-4010 treatments (-25.8%, -27.1%, -24.6%, and -22.7% for 1, 2, 3, and 4 NGX-4010 treatments, respectively). PGIC and CGIC results demonstrated a benefit of NGX-4010 treatment through to the end of the study regardless of the number of treatments received. Transient local application site reactions were the most frequently reported adverse events, and were mainly mild to moderate, nonserious, and did not increase with repeated treatment. DISCUSSION: Repeated NGX-4010 treatments were generally well tolerated and resulted in consistent reductions in HIV-DSP-associated pain and improvement in patient-reported outcomes.

Hypnosis for treatment of HIV neuropathic pain: a preliminary report.

OBJECTIVE: Painful HIV distal sensory polyneuropathy (HIV-DSP) is the most common nervous system disorder in HIV patients. The symptoms adversely affect patients' quality of life and often diminish their capacity for independent self-care. No interventions have been shown to be consistently effective in treating the disorder. The purpose of the present study was to determine whether hypnosis could be a useful intervention in the management of painful HIV-DSP. METHOD: Participants were 36 volunteers with HIV-DSP who received three weekly training sessions in self-hypnosis. Participants were followed for pain and its sequelae for 7 weeks prior to the intervention, and for 7 weeks postintervention. Participants remained on the same standard-of-care pain regimen for the entire 17 weeks of the protocol. The primary outcome measure was the Short Form McGill Pain Questionnaire cale (SFMPQ) total pain score. Other outcome measures assessed changes in affective state and quality of life. RESULTS: Mean SFMPQ total pain scores were reduced from 17.8 to 13.2 (F[1, 35] = 16.06, P < 0.001). The reductions were stable throughout the 7-week postintervention period. At exit, 26 out of 36 (72%) had improved pain scores. Of the 26 who improved, mean pain reduction was 44%. Improvement was found irrespective of whether or not participants were taking pain medications. There was also evidence for positive changes in measures of affect and quality of life. CONCLUSION: Brief hypnosis interventions have promise as a useful and well-tolerated tool for managing painful HIV-DSP meriting further investigation.

A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy.

INTRODUCTION: Effective treatment of HIV-associated distal sensory polyneuropathy remains a significant unmet therapeutic need. METHODS: In this randomized, double-blind, controlled study, patients with pain due to HIV-associated distal sensory polyneuropathy received a single 30-minute or 60-minute application of NGX-4010--a capsaicin 8% patch (n = 332)--or a low-dose capsaicin (0.04%) control patch (n = 162). The primary endpoint was the mean percent change from baseline in Numeric Pain Rating Scale score to weeks 2-12. Secondary endpoints included patient global impression of change at week 12. RESULTS: Pain reduction was not significantly different between the total NGX-4010 group (-29.5%) and the total control group (-24.5%; P = 0.097). Greater pain reduction in the 60-minute (-30.0%) versus the 30-minute control group (-19.1%) prevented intended pooling of the control groups to test individual NGX-4010 treatment groups. No significant pain reduction was observed for the 30-minute NGX-4010 group compared with 30-minute control (-26.2% vs.-19.1%, respectively, P = 0.103). Pain reductions in the 60-minute NGX-4010 and control groups were comparable (-32.8% vs. -30.0%, respectively; P = 0.488). Posthoc nonparametric testing demonstrated significant differences favoring the total (P = 0.044) and 30-minute NGX-4010 groups (P = 0.035). Significantly, more patients in the total and 30-minute NGX-4010 group felt improved on the patient global impression of change versus control (67% vs. 55%, P = 0.011 and 65% vs. 45%, P = 0.006, respectively). Mild to moderate transient application site pain and erythema were the most common adverse events. CONCLUSIONS: Although the primary endpoint analyses were not significant, trends toward pain improvement were observed after a single 30-minute NGX-4010 treatment.

Long-term safety of NGX-4010, a high-concentration capsaicin patch, in patients with peripheral neuropathic pain.

CONTEXT: Postherpetic neuralgia (PHN) and painful human immunodeficiency virus-associated distal sensory polyneuropathy (HIV-DSP) are peripheral neuropathic pain syndromes that are difficult to treat. Current treatment options are often limited by poor tolerability. OBJECTIVES: The objective of the current open-label study was to assess the safety of repeated applications of NGX-4010, a high-concentration capsaicin patch (capsaicin 8%), over one year, in patients with moderate to severe PHN or HIV-DSP. METHODS: Patients had successfully completed a previous NGX-4010 study and had a pain level appropriate for further treatment. Eligible patients had not been treated with NGX-4010 within 12 weeks of study initiation. Patients received pretreatment with a topical local anesthetic (lidocaine 4%) for 60 minutes followed by either a 60-minute (PHN and HIV-DSP patients) or a 90-minute (HIV-DSP patients) treatment with NGX-4010. Patients could receive up to three additional treatments at intervals of > or = 12 weeks. Regardless of the number of treatments received, all patients were followed up for 48 weeks except for those withdrawing early. RESULTS: A total of 106 patients were enrolled and received a total of 293 NGX-4010 treatments. The most frequently reported treatment-emergent adverse events were transient, mild-to-moderate application site erythema, pain, edema, and papules. Small, transient pain-related increases in blood pressure during and immediately after NGX-4010 application were observed. There was no evidence of an increased incidence of adverse events, dermal irritation, intolerability, or impaired neurological function with repeated treatments. CONCLUSION: It is concluded that repeated treatments with NGX-4010 administered over a one-year period are generally safe and well tolerated.

Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy.

BACKGROUND: HIV-associated distal sensory polyneuropathy (HIV-DSP) is a painful condition with limited effective treatment. Capsaicin desensitizes cutaneous nociceptors resulting in reduced pain. We report a placebo-controlled study of a high-concentration capsaicin dermal patch (NGX-4010) for the treatment of painful HIV-DSP. METHODS: This double-blind multicenter study randomized 307 patients with painful HIV-DSP to receive NGX-4010 or control, a low-concentration capsaicin patch. After application of a topical anesthetic, NGX-4010 or control was applied once for 30, 60, or 90 minutes to painful areas on the feet. The primary efficacy endpoint was percent change in Numeric Pain Rating Scale (NPRS) from baseline in mean "average pain for past 24 hours" scores from weeks 2 to 12. RESULTS: A single NGX-4010 application resulted in a mean pain reduction of 22.8% during weeks 2 to 12 as compared to a 10.7% reduction for controls (p = 0.0026). Following a transient treatment-related pain increase, pain was reduced; significant improvement was apparent by week 2 and continued throughout the controlled 12-week observation period. Mean pain reductions in the NGX-4010 30-, 60- and 90-minute groups were 27.7%, 15.9%, and 24.7% (p = 0.0007, 0.287, and 0.0046 vs control). One third of NGX-4010-treated patients reported >or=30% pain decrease from baseline as compared to 18% of controls (p = 0.0092). Self-limited, mild-to-moderate local skin reactions were commonly observed. CONCLUSIONS: A single NGX-4010 application was safe and provided at least 12 weeks of pain reduction in patients with HIV-associated distal sensory polyneuropathy. These results suggest that NGX-4010 could provide a promising new treatment for painful HIV neuropathy.

Safety profile of treatment in diabetic peripheral neuropathic pain.

New treatment options for diabetic peripheral neuropathic pain (DPNP) have recently been developed, including two Food and Drug Administration (FDA) approved agents, duloxetine and pregabalin. As clinicians face a broader spectrum of efficacious treatments, side-effect profiles play an increasingly important role in the development of a pain management regimen. In this article we review the safety profile of agents commonly used in the treatment of DPNP.