BMC Neurology

BackgroundComplex Regional Pain Syndrome (CRPS) presents as chronic, continuous pain and sensory, autonomic, and motor abnormalities affecting one or more extremities. People with CRPS can also show changes in their perception of and attention to the affected body part and sensory information in the affected side of space. Prism Adaptation (PA) is a behavioural intervention targeted at reducing attention deficits in post-stroke hemispatial neglect. PA also appears to reduce pain and other CRPS symptoms; however, these therapeutic effects have been demonstrated only in small unblinded studies. This paper describes the protocol for an ongoing double-blind, randomized, sham-controlled clinical trial that will evaluate the efficacy of PA treatment for CRPS. The secondary aims of the study are to examine the relationships between neuropsychological changes (such as spatial attention, space and body representation, and motor spatial performance) and clinical manifestations of CRPS, as well as symptom improvement. MethodsForty-two participants with upper-limb CRPS type I will undergo two weeks of twice-daily PA treatment or sham treatment. The primary outcome measures are current pain intensity and CRPS severity score, measured immediately before and after the treatment period. Secondary outcome measures include the results of self-report questionnaires about pain, movement, symptoms interference, and body representation; clinical assessments of sensory, motor, and autonomic functions; and computer-based psychophysical tests of neuropsychological functions. Data are collected in four research visits: four weeks and one day before treatment, and one day and four weeks after the end of treatment. Additional follow-up through postal questionnaires is conducted three and six months post-treatment. DiscussionIt is hypothesised that participants undergoing PA treatment, compared to those receiving sham treatment, will show greater reduction in pain and CRPS severity score, and improvements on other clinical and neuropsychological measures. Also, more pronounced neuropsychological symptoms are predicted to correlate with more severe clinical CRPS symptoms. This study will provide the first randomized double-blind evaluation of the therapeutic effects of PA that could be implemented as a rehabilitation method for CRPS, and will contribute to the understanding of how neuropsychological changes in body representation and attention pertain to the manifestation and treatment of CRPS.

Over 400,000 U.S. military personnel have been diagnosed with a mild or moderate traumatic brain injury (TBI) since the year 2000. Posttraumatic headache (PTH) is one of the most common and bothersome sequela after a mild or moderate head injury. Persistent posttraumatic headache are headaches due to the head injury lasting longer than 3 months. About 40% of military personnel who develop PTH after a TBI have persistent PTH and about 20% have PTH lasting longer than a year after the original injury. Persistent PTH has a negative impact on daily activities, including work and social functioning. There are no available guidelines for treating posttraumatic headache, and there is extraordinary variability in treatment practices as a result. The present study aims to identify predictive factors that account for heterogeneity in response to behavioral intervention for posttraumatic headache attributable to mild to moderate TBI. We intend to create a predictive model of PTH through the adoption of the Predictive Approaches to Treatment effect Heterogeneity Statement (PATH Statement). This rigorous, guided approach will be used to develop and validate a predictive model of psychosocial factors related to PTH treatment outcomes, thereby improving individualized treatment of PTH. This protocol provides an overview of the research design and methods for this study.

ObjectiveRecent studies regarding the effects of erythropoietin (EPO) for treating traumatic brain injury (TBI) have been inconsistent. This study conducts a meta-analysis of randomized controlled trials (RCTs) to assess the safety and efficacy of EPO for TBI patients at various follow-up time points. MethodsA literature search was performed using PubMed, Web of Science, MEDLINE, Embase, Google Scholar and the Cochrane Library for RCTs studying EPO in TBI patients published through March 2019. Non-English manuscripts and non-human studies were excluded. The assessed outcomes include mortality, neurological recovery and associated adverse effects. Dichotomous variables are presented as risk ratios (RR) with a 95% confidence interval (CI). ResultsA total of seven RCTs involving 1197 TBI patients were included in this study. Compared to the placebo arm, treatment with EPO did not improve acute hospital mortality or short-term mortality. However, there was a significant improvement in mid-term (6 months) follow-up survival rates. EPO administration was not associated with neurological function improvement. Regarding adverse effects, EPO treatment did not increase the incidence of thromboembolic events or other associated adverse events. ConclusionsThis meta-analysis indicates a slight mortality benefit for TBI patients treated with EPO at mid-term follow-up. EPO does not improve in-hospital mortality, nor does it increase adverse events including thrombotic, cardiovascular and other associated complications. Our analysis did not demonstrate a significant beneficial effect of EPO intervention on the recovery of neurological function. Future RCTs are required to further characterize the use of EPO in TBI.

IntroductionHeadaches significantly impair quality of life, and primary headaches are among the most common neurological complaints. Stimulating carotid baroreceptors via carotid sinus massage (CSM) combined with modified Trendelenburg positioning may modulate autonomic activity and alleviate acute headache symptoms. Thus, this study evaluated the effectiveness and safety of this combined approach (CSM+T). MethodsSeventeen patients (14 females; ages 16-64) with tension-type headaches (6), chronic migraines (10), or mixed-headaches (1) and various comorbidities received up to three 15-second CSM+T applications at one-minute intervals. Pain was assessed using a 10-point visual analog scale (VAS), while heart rate (HR), blood pressure (BP), and oxygen saturation (SpO2) were recorded before and after the intervention. A 24-hour follow-up evaluated headache recurrence and adverse effects. ResultsSixteen patients experienced significant pain reduction (median decrease: 9 VAS points; p < 0.0001) without complications. Pain relief persisted 24 hours without the need for additional medication or adverse effects. HR, BP, and SpO2 decreased following CSM+T. A negative correlation was observed between HR reduction and pain relief. Among responders, migraine patients had a smaller mean HR decrease than tension-type headache patients, yet both groups achieved similar median pain relief. These results suggest that a more pronounced cardiovagal response does not necessarily confer greater analgesia, implying additional central or multifactorial mechanisms. ConclusionCSM+T appears to be a safe and effective non-pharmacological intervention for rapid headache relief in a heterogeneous patient population. Larger, controlled trials are warranted to confirm these findings and refine clinical protocols.

IntroductionTemporomandibular joint (TMJ) disorders are associated with severe pain and functional impairment. Although thread embedding acupuncture (TEA) is commonly used for the management of temporomandibular disorders (TMD) at clinical sites, evidence supporting its use remains insufficient. This study aimed to evaluate the efficacy, safety, and cost-effectiveness of TEA for the treatment of chronic TMJ disorders. MethodsThis randomized, assessor-blinded, controlled clinical trial included 76 patients with chronic TMD. Participants will be randomly allocated to either the TEA or the usual care group. The TEA group will receive treatment administered at eight bilateral predefined acupoints for six weeks. The usual care group will receive transcutaneous electrical nerve stimulation (TENS) and infrared therapy. The primary outcome was average pain intensity measured using the Visual Analog Scale (VAS). The secondary outcomes will include maximum pain intensity (VAS), vertical TMJ opening, Graded Chronic Pain 2.0, Jaw Functional Limitation Scale-20, Patient Global Impression of Change, EuroQol 5-Dimension 5-level (EQ-5D-5L), adverse events, and medical costs for economic evaluation. DiscussionThis study provides evidence for the efficacy and safety of TEA for chronic TMJ disorders and explores its potential as a cost-effective treatment. Trial registrationThis study was registered with the Clinical Research Information Service of the Republic of Korea (Registration Number: KCT0009946).

IntroductionMusculoskeletal pain is a common affection due to ageing, sedentarism and injuries. The objective of this trial is to prove efficacy of a natural topical composition containing Arnica montana, Hypericum perforatum, Calendula officinalis, Melaleuca sp. and menthol in pain management in adults with acute or chronic pain. MethodsThis randomized, double-blinded and placebo-controlled trial included 200 patients with musculoskeletal pain, 100 in the intervention group receiving the topical formula and 100 in the placebo group, receiving a similar formula without active ingredients. The products were applied topically twice daily for 14 days in affected areas. Immediate pain alleviation and stiffness perception were monitored for two hours at days 0, 7 at 14. Pain reduction and recovery perception upon sustained application were assessed after 7 and 14 days. ResultsIntervention immediately reduced pain and stiffness at rest and in motion 30 minutes after application and kept being superior to placebo in all short-term timepoints (p < 0.05). Immediate pain reduction was maintained even at late stages of recovery. A two-week sustained intervention resulted in significant pain reduction and improvement in recovery perception. Even if both groups reached statistical significance with respect to baseline due to spontaneous lesion recovery, a significantly improved recovery was reported in the intervention group with respect to placebo. ConclusionsIntervention was found to reduce pain and stiffness upon minutes of its application and to improve pain and mobility over the 14 days of treatment, showing benefits both for immediate alleviation and for longer term recovery. Level of EvidenceTherapeutic Level I

IntroductionAdequate postoperative pain management following lumbar spinal decompression surgery is important as it will lead to early mobilization, less complications and shorter hospital stay. Opioid consumption should be limited due to their frequently accompanied side effects and their addictive nature. During the final phase of lumbar decompression surgery, the epidural space becomes easily accessible. This might be an ideal moment for surgeons to administer an epidural bolus of analgesia, as a safe and effective method for post-operative pain relief. MethodsThis is a double blind randomized controlled trial comparing a single intraoperative bolus of epidural analgesia using bupivacaine 0.25% to placebo (NaCl 0,9%) and its effect on postoperative pain following lumbar spinal decompression surgery. The primary outcome was the difference in NRS pain between the intervention and placebo groups during the first 48h after surgery. It was hypothesized that the intervention group will have lower postoperative NRS pain scores. ResultsBoth the intervention group and the placebo group consisted of 20 randomized patients (N=40). We observed statistically significant lower NRS pain scores in the intervention group in comparison with the control group, with a difference of -1.9 ({+/-}1.1). The average pain score was lower in the intervention group at all postoperative time-points. Opioid consumption, quality of life and satisfaction were similar between study groups. No study related complications occurred, and complications rate did not differ between study groups. ConclusionThis randomized controlled trial shows that administrating a bolus of intraoperative epidural bupivacaine is a safe and effective method in reducing early postoperative pain following lumbar decompression surgery.

IntroductionNeuropathic pain (NP) remains difficult to manage because conventional pharmacological therapies often have limited efficacy and intolerable side effects. Non-invasive neuromodulation techniques have emerged as potential alternatives with fewer adverse effects. Meta-analyses of randomised controlled trials suggest that high-frequency repetitive transcranial magnetic stimulation over the primary motor cortex has analgesic effects; however, its efficacy is modest and restricted by the inability to stimulate deeper brain regions. Low-intensity transcranial focused ultrasound stimulation (TUS) is a novel approach that enables precise targeting of deep brain structures and modulation of neural activity. Although promising in preclinical and preliminary human studies, its long-term therapeutic efficacy for NP remains unknown. This trial aims to evaluate the therapeutic effects and safety of repeated TUS sessions in patients with NP. Methods and analysisThis randomised, participant-blinded, placebo-controlled, three-arm, parallel-group clinical trial will enrol 39 participants with NP (pain duration [&ge;] 3 months; pain intensity [&ge;] 4 on the Numerical Rating Scale). Participants will be randomly allocated to one of three groups: (1) TUS targeting the primary motor cortex, (2) TUS targeting the posterior superior insula, or (3) sham stimulation. Each participant will undergo weekly sessions for eight weeks. The primary outcome is change in weekly average pain intensity scores recorded in a pain diary. Secondary outcomes include additional pain scales, quality of life measures, psychological assessments, quantitative sensory testing, motor cortical excitability, and adverse events. Ethics and disseminationThe protocol has been approved by the University of Osaka Clinical Research Review Board. Written informed consent will be obtained from all participants. Findings will be disseminated via scientific presentations and peer-reviewed publications. Trial registration numberjRCTs052240227 STRENGTHS AND LIMITATIONS OF THIS STUDY{Rightarrow} This is the first randomised, participant-blinded, placebo-controlled clinical trial evaluating the long-term effects of transcranial focused ultrasound stimulation (TUS) for neuropathic pain. {Rightarrow}TUS is a novel, non-invasive technique that can precisely target deep brain areas using a navigation system, offering the potential to modulate brain function. {Rightarrow}The single-blind design (participants only) may introduce a risk of performance bias, as operators cannot be blinded owing to technical constraints. {Rightarrow}The small sample size may limit statistical power to detect subtle between-group differences.

ObjectiveTo examine the change over time in sleep quality and psychosocial outcomes from the MRI Outcomes for Mindfulness Meditation Clinical Trial, assess how these mediated treatment response (50% reduction in headache frequency post-intervention) and examine the relationship between baseline values and treatment response. MethodsThis is a secondary analysis of a randomized placebo-controlled trial with single masking. Patients were recruited from the community, headache clinics and primary care offices in Baltimore Maryland. Eligible patients were aged 18-65 and met the International Classification of Headache Disorders criteria for episodic migraine (4-14 headache days in 28 days).The trial (primary outcomes previously reported) included 98 episodic migraine patients randomized to either enhanced (MBSR+) or stress management for headache (SMH). Follow-up visits occurred at 10, 20 and 52 weeks post baseline. Intervention groups met separately for two hours weekly for 8 weeks and then biweekly for an additional 8 weeks. MBSR+ had an additional half-day retreat held between weeks 6 and 8. ResultsThere was a significant improvement in sleep quality from baseline to post-intervention (p=0.0025), in both groups. There were no significant change from baseline or between groups in anxiety, depression and stress. There was also no significant association between baseline scores and treatment response. Mediation analysis showed a significant indirect effect for sleep, anxiety, stress, and depression on treatment response, ranging from 6-8%. ConclusionsThe findings indicate that in episodic migraine, treatment response to MBSR+ compared to SMH was mediated by small, but significant improvements in sleep, anxiety, stress, and depression.

We tested two low-dose naltrexone and acetaminophen combinations and each component in the acute treatment of migraine. The patients use a single-dose of the study medication for a moderate or severe pain intensity migraine attack. Patients were adults with migraine with or without aura experiencing 2 to 20 (average 6.4) monthly migraine days. The co-primary endpoints were pain-freedom and absence of prospectively-identified most bothersome migraine-associated symptom 2 hours after dosing. We randomized 92 patients; 72 completed the study (mean age, 43 years; 75% women). Pain-freedom at 2 hours was 10.2% higher than placebo with naltrexone 2.25 mg/acetaminophen 325 mg, 10.9% with naltrexone 3.25 mg/acetaminophen 325 mg, 17.3% with naltrexone 2.25 mg, and 31.3% with acetaminophen 325 mg. The treatment groups migraine burden at baseline was unbalanced due to randomized patients uneven study completion. The acetaminophen group had the lowest migraine burden, giving its results lower credibility. Saliently, Low-dose naltrexone alone (n=19) had a 17.3% higher response rate for headache pain-freedom at 2 hours than placebo (n=17). The naltrexone and the placebo groups were the largest and had a balanced disease burden, implying higher credibility to the naltrexone group results. We found low-dose naltrexone and acetaminophen combination, low-dose naltrexone, and acetaminophen had higher response rates than placebo in treating headache pain. The most commonly reported adverse events were sedation, nausea, and dizziness. We postulate that naltrexones toll-like receptor (TLR4) antagonism properties prevent pro-inflammatory cytokines production in the trigeminal ganglion averting "overactive nerves" (laymans term) and migraine. Although this trial used low-dose naltrexone (defined as 1 - 5 mg/day), future phase 3 studies will test a range of naltrexone and acetaminophen combination doses.

IntroductionVentriculoperitoneal (VP) and Lumboperitoneal (LP) shunts are the most common treatments for Idiopathic Normal Pressure Hydrocephalus (iNPH). Shunt procedure choice is generally based on surgeon on preference rather than evidence. We performed a systematic review and meta-analysis to address this gap for evidence-based shunt selection in iNPH treatment. MethodsPublications on post-operative outcomes for LP and VP shunts in iNPH were identified in MEDLINE and EMBASE. Papers were selected based on pre-specified inclusion and exclusion criteria and meta-analysis was conducted for outcome measures after shunt procedure. Results17 papers were included. LP Shunt patients showed greater cognitive improvement with an average increase of 2.00 points (95% CI: 1.08; 2.93, p < 0.0001) on their MMSE score post-operatively compared to VP shunt patients who improved on average by 1.30 points (95% CI: 0.81; 1.79, p < 0.0001). The LP group had considerable heterogeneity (I2 = 66.42%, p = 0.0003) whereas the VP shunt group had minimal heterogeneity (I2 = 0.00%, p = 0.8447) reflecting more uniformity across its included studies. For overall symptomatic improvement measured by the iNPHGS, VP shunts patients demonstrated a larger reduction in overall symptom scores with an average decrease of 2.91 points (95% CI: -3.78; -2.05, p < 0.0001) but with a high heterogeneity (I2 = 79.12%, p = 0.0012) compared to LP shunt patients with an average reduction of 1.91 points (95% CI: -2.31; -1.51, p < 0.0001) with no detected heterogeneity (I2 = 0.00%, p = 0.8454). ConclusionsOur findings demonstrate that LP and VP shunts show differing patterns of improvement across the cognitive domain and the broader iNPH triad, with LP shunting showing greater cognitive improvement and VP shunting showing greater overall symptomatic improvement. These differences represent a signal warranting further investigation, specifically whether symptom profiles should inform shunt selection.

Black and Hispanic/Latino communities experience disproportionate chronic pain and are underrepresented in pain research. Transcutaneous auricular vagus nerve stimulation (taVNS) and transcranial magnetic stimulation (TMS) are promising tools for pain management. Therefore, it is critical to ensure that research using these tools engages underrepresented communities to make research findings more generalizable and reach all who may benefit. Lack of diversity in the research workforce itself is a key barrier to improving Black and Hispanic/Latino representation in pain research, and video-enhanced recruitment and consenting may be a useful tool to better engage minoritized communities. Using community participatory research principles in an iterative process, we engaged key stakeholders, including neuromodulation researchers and minoritized community members, to create and test informational videos on taVNS and TMS. These videos were designed for Black English-speaking, Hispanic/Latino Spanish-speaking, and Haitian-Creole speaking people with chronic pain. Study 1 involved iterative feedback from stakeholders to develop test videos, which were then refined based on community member input. Study 2 was a pilot randomized controlled trial assessing the impact of these videos on participant expectations for pain relief with taVNS. Results indicated that the videos were well-received, and there was no significant difference in expectancy scores between those who viewed the videos and those who received traditional brochures. This suggests that while videos may improve engagement, they do not unduly influence expectations, potentially making them valuable tools for improving research participation in underrepresented populations. These videos will be freely available to help researchers to engage people from minority communities. PERSPECTIVEThis article presents the process of developing culturally sensitive informational videos on taVNS and TMS, and provides the field with these videos in English, Spanish, and Haitian-Creole language. These videos could potentially help researchers to engage people from minority communities to enhance the diversity and reach of research using noninvasive brain stimulation for pain.

BackgroundTraumatic brain injury (TBI) is a critical problem which portends an intensive burden with increased mortality and disability affecting more the young population worldwide. The primary goal of TBI treatment is to control intracranial pressure (ICP) and to prevent he devastating effect of secondary brain insult. For over a hundred years decompressive craniectomy has been a standard surgical intervention for treatment of TBI, however it is not without harm since it causes serious complications including meningitis, subdural hygroma, hydrocephalous and increased reoperation rate. Cisternostomy is the most recently introduced intervention for management of cerebral edema Cisternostomy has proven its efficiency a standalone treatment as an adjunctive to decompressive craniectomy in treatment of severe traumatic brain injury. This review aims at investigating the therapeutic effects of cisternostomy when used independently or as an adjunctive to decompressive craniectomy (DC) across the available randomized clinical trials (RCTs) and non randomized studies of effect intervention (NRSI) sectional studies to optimize the strength of evidence for underpinning the strategy for treatment of traumatic brain injury. Methods and AnalysisWe will conduct the systematic review and meta-analysis by employing the provisions of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 guideline and the review protocol has been submitted to International Prospective Register of Systematic Reviews (PROSPERO) for registration before commencement of the study. We will construct the search strategy using the all field terms, medical subheading terms [MeSH Terms] with all permutations combined with Boolean operators such as AND and OR. PubMed, EMBASE, Scopus, COCHRAINE, Web Of Science, Global Index Medicus, Semantic Scholar and Google Scholar electronic databases will be searched. Ethical Consideration and DisseminationThis review will not include any human participant such that the ethical clearance approval is not applicable. The protocol of this review has been registered at PROSPERO ID CRD42023400894. We will disseminate the final report of this review to local and international scientific conferences and The results of this review will be submitted for publication in the Journal of Neurotrauma.

We tested a low-dose naltrexone and acetaminophen combination for episodic migraine prevention. We randomly assigned patients to naltrexone and acetaminophen combination (n=6) or placebo (n=6) for a 12-week double-blind treatment. Non-responders continued into open-label treatment with naltrexone and acetaminophen combination (n=5) for additional 12 weeks. Patients were adults who experienced 5 to 17 (average 9.7) migraine days at baseline. The primary endpoint was the mean change in the monthly migraine days during the last 4 weeks of the double-blind treatment period. The key secondary endpoint was the mean change in the monthly migraine days from the 4-week double-blind follow-up (2nd baseline) to the last 4 weeks of the open-label treatment period. The magnitude of the treatment effect for the naltrexone and acetaminophen combination observed in the double-blind period was 2.2 fewer monthly migraine days than placebo (p=0.43). Four out of 6 (66.7%) naltrexone and acetaminophen-treated patients experienced 75% reduction in migraine days compared to 1 out of 6 (16.7%) placebo-treated patients (p=0.09). In the open-label phase, treatment with the naltrexone and acetaminophen combination (n=5) led to 8.2 fewer mean monthly migraine days (from 11.8 to 3.6), representing 69.5% improvement (p=0.03), and 100% of the patients experienced a 50% reduction in monthly migraine days. Adverse events were mild to moderate and transient, included dry mouth, fatigue, sedation, nausea, and feeling jittery. We postulate that naltrexones toll-like receptor (TLR4) antagonism properties prevent pro-inflammatory cytokines production in the trigeminal ganglion averting "overactive nerves" (laymans term) and migraine. Although this trial used low-dose naltrexone (defined as 1 - 5 mg/day), in future phase 3 studies we will test a range of naltrexone and acetaminophen combination doses.

BackgroundNon-specific low back pain(NS-LBP) is related to disability and work absence and accounts for high economical costs of global.It is a problem that has a negative impact on physical, mental health of patients and quality of life. At present, acupoint herbal patching(AHP) as an adjuvant therapy is currently undergoing clinical trials in different medical centers. This study aimed to design a systematic review and meta-analysis to explore the effects of AHP on non-specific low back pain(NS-LBP). MethodsWe will search the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, the Chinese Biomedical Literature Database,the Chinese Scientific Journal Database, the Wan-Fang Database and the China National Knowledge Infrastructure. The primary outcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software. Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. We will use the GRADE approach to assess the overall quality of evidence supporting the primary outcomes. We will also use Spass software (Version19.0) for complex network analysis to explore the potential core prescription of acupoint herbal patching for functional constipation. ResultsThis systematic review protocol will analyze the effectiveness, quality of life, improvement of the symptom and safety of acupoint herbal patching therapy for non-specific low back pain. ConclusionThe findings of this systematic review will provide evidence to evaluate the effectiveness and safety of acupoint herbal patching for non-specific low back pain.

BackgroundPersistent Postural-Perceptual Dizziness (PPPD) is a prevalent long-term functional neurological disorder characterised by non-spinning vertigo, perceived instability, and visual motion sensitivity. Current diagnostic criteria inadequately incorporate psychological variables widely associated with PPPD symptom onset and maintenance. ObjectivesThis study explored PPPD-specific psychological variables to differentiate PPPD patients from healthy controls and, exploratorily, from Bilateral Vestibulopathy (BVP) patients. We evaluated these variables as potential treatment targets through mediation analysis. Our aim was to inform more precise diagnostic criteria and guide targeted interventions for PPPD. MethodsWe conducted a cross-sectional study with 164 participants, including 59 diagnosed cases of PPPD, 16 cases of BVP, and 89 healthy controls. Participants completed a series of questionnaires assessing negative illness perception, balance vigilance, anxiety, visual sensitivity, dizziness and other related metrics. ResultsPsychological variables, particularly anxiety, cognitive fusion, and justice appraisal significantly mediated the relationship between key PPPD symptoms (dizziness, visual sensitivity, and balance vigilance) and PPPD diagnosis compared to healthy controls. Logistic regression suggested psychological differences between PPPD and BVP, but limited BVP sample size constrained generalisability. Between PPPD and healthy controls, psychological variables significantly improved classification accuracy compared to measures of dizziness alone. ConclusionIncorporating psychological variables in the diagnosis and management of PPPD could enhance the understanding of the disorder and may aid in developing better-targeted interventions. The study supports revising existing diagnostic criteria to include validated psychological assessments and highlights the potential of treatments addressing cognitive and emotional aspects of PPPD to improve patient outcomes.

BackgroundPost-stroke aphasia is a common but intractable sequela which still needs new and more effective treatments. Evidence from follow-ups after contralateral seventh cervical nerve transfer surgery indicated that nerve transection leads to immediate language improvements in patients with right post-stroke aphasia. ObjectiveThrough a prospective cohort design, this study aims to prove that C7 neurotomy at the intervertebral foramen (NC7) combined with a 3-week intensive speech and language therapy (iSLT) can improve the language function in post-stroke aphasia patients. MethodsIn this study, patients aged over 18 years old and had been diagnosed with post-stroke aphasia for 1 year or longer were included. Primary outcomes were the change in the ability to retrieve personally relevant words in Boston Naming Test (BNT) with follow-up assessment after three-weeks iSLT post-operatively. As well as several secondary outcome measures including the Western Aphasia Battery (WAB), daily communication abilities (measured by the Communication Activities of Daily Living Third Edition [CADL-3]) and Fugl-Meyer of upper limb part (UEFM). ResultsThe average increase of BNT score was 11.2 points from baseline to 3 weeks post-operatively (P=0.001, 95%CI: 8.1-14.1). The WAB and CADL-3 assessment showed 9.4, 10.4 points increasing in average (P<0.005, 95%CI: 4.6 to 14.1; P<0.001, 95%CI:6.7 to 14.1) from baseline to 4-week follow-up, respectively. The mean difference from baseline to 3 weeks post-operatively in UEFM score decreased 0.8 points (95% CI: -3.2 to 1.6; p<0.405). ConclusionsNC7 plus iSLT significantly improved the language function in patients with post-stroke aphasia, and did not significantly affect the motor function of the right limb. The mechanism of this surgery needs to be further explored.

BackgroundThe Neuropathic Pain Symptom Inventory (NPSI) is a commonly used assessment in neuropathic pain (NP) trials, yet a Minimal Clinically Important Difference (MCID) has not been established. An MCID would enhance the interpretability of NPSI scores, guiding clinicians and researchers in assessing clinically important improvements in NP symptoms. The aim of this study was to calculate an MCID from the available scientific research that used the NPSI. MethodsWe conducted a systematic review and meta-analysis of NP trials reporting the NPSI. Four distributional approaches were applied to estimate the MCID: 1) meta-regression on the set of standard deviation (SD) of change scores, 2) meta-regression on the set of baseline SD scores, 3) simple aggregation on the set of SD of change scores, and 4) simple aggregation on the set of baseline SD scores. Only treatment arms within Randomized Controlled Trials (RCTs) were examined for MCID estimation. Control arms were examined separately in a sensitivity analysis using the simple aggregation method for both SD of change and baseline SD sets. Bias for each included study was assessed using the Cochrane tool for quality assessment of randomized controlled trials. Results323 trials were examined, 12 were selected for inclusion with a total of 17 treatment arms. The calculated MCID estimates for the NPSI total score (range 1-100) were 6.21 for the SD of change meta-regression and 7.1 for baseline SD meta regression. The MCID values aggregated using simple aggregation methods were 7.95 using pooled SD of change scores, 7.8 using pooled baseline SD. Control arms had a MCID of 8.04 for SD of Change and 8.71 for Baseline SD. ConclusionThis study provides preliminary MCID estimates for the NPSI. Limitations include limited data for NP subtypes, highlighting the need for additional anchor-based and etiology-specific MCID research to refine these estimates. These findings can aid in future NP trial design and the interpretation of results.

Subanesthetic ketamine infusion has been used for managing refractory headache in inpatient or outpatient infusion settings. Intranasal (IN) ketamine may be an alternative option for outpatient care. We performed a retrospective study at a single tertiary headache center to assess the clinical effectiveness and tolerability of IN ketamine in patients with refractory chronic migraine (rCM). Candidates who received IN ketamine between January 2019 and February 2020 were screened through an electronic medical record query. Manual chart reviews and structured phone interviews were conducted upon obtaining informed consent. Among 242 subjects screened, 169 (age 44.3{+/-}13.8; female 79.9%) were interviewed. They reported 25.0{+/-}8.7 monthly headache days and tried 6.9{+/-}3.1 preventive medications. Overall, they used roughly 7.8{+/-}7.0 sprays (ie., 78 mg) per day and 11.6{+/-}8.9 days per month. Intranasal ketamine was reported as "very effective" in 49.1% and quality of life (QOL) was considered "much better" in 35.5%. However, 74.0% reported at least one adverse event (AE). In this retrospective study, IN ketamine can serve as an acute treatment for rCM by reducing headache intensity and improving QOL with relatively tolerable AEs. Most patients found IN ketamine effective and continued to use it despite these AEs. The study is limited by its single-center design and selection/recall biases. Well-designed prospective placebo-controlled trials are necessary to demonstrate the efficacy and safety of IN ketamine in patients with migraine. O_LIWhat is already known on this topic - Intravenous ketamine, although has been used for chronic pain and refractory headache, is limited to infusion settings. Intranasal ketamine, a more convenient alternative, has not been well-studied for refractory headache. C_LIO_LIWhat this study adds - This real-world study describes the usage pattern, effectiveness, and adverse event profiles of intranasal ketamine in patients with refractory chronic migraine. C_LIO_LIHow this study might affect research, practice or policy - Intranasal ketamine is probably effective with minimal adverse events for refractory chronic migraine, but more well-designed studies are needed. C_LI

ObjectivePhantom limb pain (PLP) is debilitating and affects over 70% of people with lower-limb amputation. Other neuropathic pain conditions correspond with increased spinal excitability, which can be measured using reflexes and F-waves. Spinal cord neuromodulation can be used to reduce neuropathic pain in a variety of conditions and may affect spinal excitability, but has not been extensively used for treating phantom limb pain. Here, we propose using a non-invasive neuromodulation method, transcutaneous spinal cord stimulation (tSCS), to reduce PLP and modulate spinal excitability after transtibial amputation. ApproachWe recruited three participants, two males (5- and 9-years post-amputation, traumatic and alcohol-induced neuropathy) and one female (3 months post-amputation, diabetic neuropathy) for this 5-day study. We measured pain using the McGill Pain Questionnaire, visual analog scale, and pain pressure threshold test. We measured spinal reflex and motoneuron excitability using posterior root-muscle (PRM) reflexes and F-waves, respectively. We delivered tSCS for 30 minutes/day for 5 days. Main ResultsAfter 5 days of tSCS, pain scores decreased by clinically-meaningful amounts for all participants from 34.0{+/-}7.0 to 18.3{+/-}6.8. Two participants had increased pain pressure thresholds across the residual limb (Day 1: 5.4{+/-}1.6 lbf; Day 5: 11.4{+/-}1.0 lbf). F-waves had normal latencies but small amplitudes. PRM reflexes had high thresholds (59.5{+/-}6.1 {micro}C) and low amplitudes, suggesting that in PLP, the spinal cord is hypoexcitable. After 5 days of tSCS, reflex thresholds decreased significantly (38.6{+/-}12.2 {micro}C; p<0.001). SignificanceOverall, limb amputation and PLP may be associated with reduced spinal excitability and tSCS can increase spinal excitability and reduce PLP.