Transcranial direct current stimulation (tDCS) is a non-invasive and painless technique of brain neuromodulation that applies a low-intensity galvanic current to the scalp with the aim of stimulating specific areas of the brain. Preliminary investigations have indicated the potential therapeutic efficacy of multisession tDCS applied to the auditory cortex (AC) in the treatment of chronic tinnitus. The aim of this study was to explore the therapeutic effects of repeated sessions of bilateral tDCS targeting the AC on chronic tinnitus. A double-blinded randomized placebo-controlled trial was conducted on patients (n = 48) with chronic intractable tinnitus (>2 years duration). Participants were randomly allocated to two groups: one receiving tDCS (n = 26), with the anode/cathode placed over the left/right AC, and the other receiving a placebo treatment (n = 22). A 20 min daily session of 2 mA current was administered for five consecutive days per week over two consecutive weeks, employing 35 cm2 electrodes. Tinnitus handicap inventory (THI) scores, tinnitus loudness, and tinnitus distress were measured using a visual analogue scale (VAS), and were assessed before intervention, immediately after, and at one-month follow-up. Anodal tDCS significantly reduced THI from 72.93 ± 10.11 score to 46.40 ± 15.36 after the last session and 49.68 ± 14.49 at one-month follow-up in 18 out of 25 participants (p < 0.001). The risk ratio (RR) of presenting an improvement of ≥20 points in the THI after the last session was 10.8 in patients treated with tDCS. Statistically significant reductions were observed in distress VAS and loudness VAS (p < 0.001). No statistically significant differences in the control group were observed. Variables such as age, gender, duration of tinnitus, laterality of tinnitus, baseline THI scores, and baseline distress and loudness VAS scores did not demonstrate significant correlations with treatment response. Repeated sessions of bilateral AC tDCS may potentially serve as a therapeutic modality for chronic tinnitus.

UNASSIGNED: The study aimed at investigating functional connectivity strength (FCS) changes in children with MRI-negative intractable epilepsy (ITE) and evaluating correlations between aberrant FCS and both disease duration and intelligence quotient (IQ).
UNASSIGNED: Fifteen children with ITE, 24 children with non-intractable epilepsy (nITE) and 25 matched healthy controls (HCs) were subjected to rs-fMRI. IQ was evaluated by neuropsychological assessment. Voxelwise analysis of covariance was conducted in the whole brain, and then pairwise comparisons were made across three groups using Bonferroni corrections.
UNASSIGNED: FCS was significantly different among three groups. Relative to HCs, ITE patients exhibited decreased FCS in right temporal pole of the superior temporal gyrus, middle temporal gyrus, bilateral precuneus, etc and increased FCS values in left triangular part of the inferior frontal gyrus, parahippocampal gyrus, supplementary motor area, caudate and right calcarine fissure and surrounding cortex and midbrain. The nITE patients presented decreased FCS in right orbital superior frontal gyrus, precuneus etc and increased FCS in bilateral fusiform gyri, parahippocampal gyri, etc. In comparison to nITE patients, the ITE patients presented decreased FCS in right medial superior frontal gyrus and left inferior temporal gyrus and increased FCS in right middle temporal gyrus, inferior temporal gyrus and calcarine fissure and surrounding cortex. Correlation analysis indicated that FCS in left caudate demonstrated correlation with verbal IQ (VIQ) and disease duration.
UNASSIGNED: ITE patients demonstrated changed FCS values in the temporal and prefrontal cortices relative to nITE patients, which may be related to drug resistance in epilepsy. FCS in the left caudate nucleus associated with VIQ, suggesting the caudate may become a key target for improving cognitive impairment and seizures in children with ITE.

The general anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. This study was aimed to compare the analgesic effectiveness and safety of systemic analgesics alone or plus at-home topical sevoflurane for the management of patients with painful nonrevascularizable leg ulcers who were referred to a Pain Clinic by their attending vascular surgeons. We reviewed charts of patients treated in a single Pain Clinic with analgesic Standard of Care either alone (group SoC) or plus at-home topical sevoflurane (group SoC + Sevo), according to safety criteria. The area under the curve of pain over a year (AUC-Pain) was the primary outcome for analgesic effectiveness. Opioids were converted into Oral Morphine Milligram Equivalents. Groups SoC (n = 26) and SoC + Sevo (n = 38) were similar in baseline characteristics. Compared to SoC, median values [interquartile range] of area under the curve of pain for one-year follow-up were markedly lower for SoC + Sevo (54 [35-65] vs. 15 [11-23]; p < 0.000001, U Mann-Whitney test). Oral Morphine Milligram Equivalents were similar at baseline (SoC: 78.5 [22.5-135] vs. SoC + Sevo: 101.3 [30-160]; p = 0.753), but significantly lower for SoC + Sevo at three (120 [22.5-202.5] vs. 30 [0-80]; p = 0.005), six (120 [11.3-160] vs. 20 [0-67.5]; p = 0.004), nine (114.4 [0-154] vs. 0 [0-37]; p = 0.018), and 12 months (114.4 [0-154] vs. 0 [0-20]; p = 0.001). Multiple linear regression analysis revealed the addition of sevoflurane to be the most likely variable to explain this difference in outcome (ß:-33.408; p < 0.000001). Nine patients (24%) in SoC + Sevo had adverse effects attributed to sevoflurane, but only one patient needed to stop using sevoflurane due severe dermatitis. In conclusion, the addition of topical sevoflurane to the analgesic standard of care in patients with painful nonrevascularizable leg ulcers was a well-tolerated therapy that significantly improved pain control and allowed for a significant reduction in opioid consumption.

Focal onset epilepsy carries a higher risk of intractability than generalized onset epilepsy. Knowledge of the risk factors of intractability will help guide the treatment of children with focal epilepsy. In addition to risk factors present at initial diagnosis, the evolution of clinical and electroencephalographic features may also play a role in predicting intractability.
A prospective cohort study was done on children aged one month to three years with newly diagnosed focal epilepsy. Initial treatment of carbamazepine was given according to a standard protocol after assessment of clinical manifestations, neurologic and developmental status, EEG, and brain MRI. Depending on response to therapy, subjects may also receive valproic acid or phenobarbitone following the protocol. Follow-up was done in the second week and every month thereafter. At the end of the study period, seizure type was re-assessed and a repeat neurological and developmental examination and EEG was obtained to evaluate the role of clinical and EEG evolution in predicting intractability.
Out of 71 subjects, 21 (29.6%) had intractable epilepsy at the end of the study period. Age of onset (p = 0.216) and neurological status (p = 0.052) were not associated with intractable epilepsy. On logistic regression analysis, evolution of seizure type (p < 0.001; RR 56.45; 95%CI 6.56 to 485.85) and evolution of background EEG rhythm (p < 0.001; RR 56.51; 95%CI 2.77 to 1152.16) were significantly associated with intractable epilepsy.
Changes in seizure type and baseline EEG rhythm may predict intractability in children one month to three years of age with focal epilepsy.

OBJECTIVE: To evaluate the safety and efficacy of superselective vesical artery embolization (SVAE) in the treatment of intractable hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HSCT).
METHODS: From January 2010 to December 2018, 26 patients with hematologic malignancy who underwent SVAE for treatment of intractable HC following HSCT were retrospectively reviewed. SVAE was performed with 300-500 μm gelatin-sponge particles initially. Technical success was defined as achieving bilateral SVAE for all the prominent vesical arteries. Therapeutic efficacy was defined as: Complete response (CR): macroscopic hematuria completely disappeared on more than 2 consecutive days after SVAE; Partial response (PR): macroscopic hematuria reduced after SVAE or briefly disappeared after SVAE but reappeared soon within 2 days; No response: no response to SVAE or hematuria aggravated after SVAE; Recurrence: macroscopic hematuria relapsed on follow-up after achieving an initial CR. Adverse events were also registered.
RESULTS: There was a mean follow-up of 11.4 months (range, 0.5-83.7). The mean interval for the onset of HC after HSCT was 39.7 ± 19.0 days, and mean duration of hematuria before embolization was 14.9 ± 15.7 days. SVAE was technically successful in all patients. After embolization, macroscopic hematuria regressed within 48 h for all patients. The mean urine erythrocyte counts dropped from 14,213.2 ± 20,999.0/uL before SVAE to 6072.9 ± 12,720.7/uL on 3d after SVAE (P = 0.002) and 3720.2 ± 8988.9/uL on 7 d after SVAE (P = 0.001), respectively. Hematuria completely disappeared prior to discharge in 23 (88.5%) patients (including 20 with one embolization and 3 with 2 embolizations) and remainder 3 patients had PR. No major procedure-related complications were noted, except for post-embolization syndrome in 8 patients, which resolved with symptomatic treatment. On follow-up monthly, hematuria recurrence was seen in 4/23 patients (17.4%) and was managed conservatively in 2 patients and with repeat embolization in the remainder 2 patients.
CONCLUSIONS: For fragile patients with hematologic malignancy, SVAE is safe and effective to treat HC following HSCT, even though repeat embolization may be required to achieve a sustained complete remission of the hematuria.

UNASSIGNED: Recruitment into trials in rare chronic pain conditions can be challenging, so such trials consequently are underpowered or fail.
UNASSIGNED: Drawing from our experience in conducting, to date, the largest academic trial in a rare chronic pain condition, complex regional pain syndrome, we have identified recruitment and retention strategies for successful trial conduct.
UNASSIGNED: We present 13 strategies grouped across the categories of \'setting the recruitment rate\', \'networking\', \'patient information\', \'trial management\' and \'patient retention\'. Moreover, six recruitment risks are also discussed. A conservative recruitment estimate, based on audits of newly referred patients to the trial centres without taking into account availability of \'old\' patients or recruitment from outside centres, and assuming a 55% patient refusal rate yielded accurate numbers.
UNASSIGNED: Appreciation of these identified recruitment challenges and opportunities may contribute to supporting prospective investigators when they design clinical trials for chronic pain patient population groups where it has been historically difficult to conduct high-quality and robust clinical trials.

OBJECTIVE: To evaluate the potential risk factors associated with seizure recurrence in different periods after epilepsy surgery.
METHODS: A total of 303 patients with refractory epilepsy after epilepsy surgery were included. The Kaplan-Meier method with log-rank test and univariate and multivariate Cox proportional hazards model were performed to calculate the comparison of survival curves between groups and identify the risk factors associated with seizure recurrence in different periods after surgery.
RESULTS: The significant predictors of seizure recurrence were determined, including duration of epilepsy (P = 0.018), seizure types (P = 0.009), magnetic resonance imaging findings (P = 0.007), intracranial electroencephalographic recordings (P = 0.002), sides of epileptogenic zone (P = 0.025), and types of surgery (P = 0.002). Moreover, the significant predictors of seizure recurrence within 12 months after surgery were also included, such as gender (P = 0.007), duration of epilepsy (P = 0.013), intracranial electroencephalographic recordings (P = 0.003), and types of surgery (P < 0.001). Our results indicated that the variables of magnetic resonance imaging findings (P = 0.015), sides of epileptogenic zone (P = 0.004), and seizure relapse within 12 months after surgery (P < 0.001) were significantly associated with seizure recurrence in 12-36 months after surgery. Seizure relapse within 12 months after surgery (P < 0.001) was also associated with seizure recurrence >36 months after surgery.
CONCLUSIONS: We reconfirmed the well-known risk factors associated with seizure recurrence and also identified the controversial variables. In addition, we found that the risk factors associated with seizure recurrence were different in different periods after epilepsy surgery.

Background Occipital nerve stimulation (ONS) has been proposed to treat chronic medically-intractable cluster headache (iCCH) in small series of cases without evaluation of its functional and emotional impacts. Methods We report the multidimensional outcome of a large observational study of iCCH patients, treated by ONS within a nationwide multidisciplinary network ( https://clinicaltrials.gov NCT01842763), with a one-year follow-up. Prospective evaluation was performed before surgery, then three and 12 months after. Results One year after ONS, the attack frequency per week was decreased >30% in 64% and >50% in 59% of the 44 patients. Mean (Standard Deviation) weekly attack frequency decreased from 21.5 (16.3) to 10.7 (13.8) ( p = 0.0002). About 70% of the patients responded to ONS, 47.8% being excellent responders. Prophylactic treatments could be decreased in 40% of patients. Functional (HIT-6 and MIDAS scales) and emotional (HAD scale) impacts were significantly improved, as well as the health-related quality of life (EQ-5D). The mean (SD) EQ-5D visual analogic scale score increased from 35.2 (23.6) to 51.9 (25.7) ( p = 0.0037). Surgical minor complications were observed in 33% of the patients. Conclusion ONS significantly reduced the attack frequency per week, as well as the functional and emotional headache impacts in iCCH patients, and dramatically improved the health-related quality of life of responders.

OBJECTIVE: Up to 14% of children with epilepsy continue to experience seizures despite having appropriate medical therapy and develop medically refractory epilepsy (MRE). Assessing clinical outcomes and therapeutic efficacy in children with MRE undergoing palliative epilepsy surgery has been challenging because of the lack of a quantitative instrument capable of estimating the clinical status of these patients. The ideal instrument would at once consider seizure control, neurodevelopment, caregiver burden, and quality of life. The purpose of this study was to develop and pilot the Pediatric Refractory Epilepsy Questionnaire (PREQ), a quantitative instrument to assess the severity and individual burden of epilepsy in children with MRE undergoing palliative epilepsy treatments.
METHODS: The caregivers of 25 patients with MRE completed the PREQ and the Quality of Life in Childhood Epilepsy (QOLCE) measure and participated in a semistructured interview. Medical records of the patients were reviewed, an Early Childhood Epilepsy Severity Scale (E-CHESS) score was calculated, and a Global Assessment of Severity of Epilepsy (GASE) score was obtained for each patient.
RESULTS: The initial PREQ was modified based on the analysis of responses, association with previously validated scales, comments from caregivers, and expertise of the PREQ panelists. Pediatric Refractory Epilepsy Questionnaire subscale scores were calculated based on clinical paradigm and compared with independent measures of seizure severity and quality of life. Significant correlations were observed between the seizure severity subscale and the GASE score (r=0.55) and between the mood subscale and the well-being score (r=0.61) on the QOLCE. Significant correlations were also observed between the caregiver rating of seizure severity and the GASE score (r=0.53), the social activity score (r=0.57), and the behavior score (r=0.43) on the QOLCE. Correlations between the caregiver rating of quality of life and the quality of life score (r=0.58) and the number of AEDs used (r=0.45) were also significant.
CONCLUSIONS: This pilot study is an initial, critical step in the development of the PREQ. The significant correlations between the PREQ subscales and the external epilepsy severity and quality of life measures lend preliminary support to our hypothesis that the PREQ is assessing the severity of epilepsy along with other important domains, such as mood, neurodevelopment, and quality of life. A larger prospective study of this modified PREQ is currently underway to further develop the PREQ.