Tolerability of clobazam as add-on therapy in patients aged 50 years and older with drug-resistant epilepsy.

OBJECTIVE: To evaluate the tolerability of clobazam in patients with drug-resistant epilepsy aged 50 years and older. METHODS: We performed a single center, retrospective chart review of patients at least 50 years of age with drug resistant epilepsy of any type who started clobazam as an add on therapy. Retention rate, safety, and tolerability at 6 and 12 months and last follow-up, and the discontinuation rate due to side effects were analyzed. RESULTS: A total of 26 patients met inclusion criteria. Mean age was 62 ± 7.1 years, and 69.2% of patients were female. The mean baseline seizure frequency before initiation of clobazam was 2 (range 1-30) seizures per month. The mean total daily dose of clobazam administered was 13 (range 5 to 30) mg/day. At the 12-month follow-up visit after clobazam initiation, 40% of patients were seizure-free and an additional 45% of patients had > 50% reduction in seizure frequency. The mean seizure frequency at 12-month follow-up was 1.5 (range 0-24) seizures per month. The mean total dose of clobazam at 12-month follow-up was 14.25 (range 5 to 25) mg/day. The mean duration of clobazam at last follow was 55.2 ± 27.02 (mean ± SD months) and 18 (69.2%) patients remained on clobazam. Twenty out of 26 (76.9%) patients reported at least one side effect and 6/26 (23%) discontinued the medication within a month of initiation. At last follow-up, 40% remained seizure free on stable dosing. CONCLUSION: Clobazam can be a safe and tolerable, add-on treatment older adults with drug-resistant epilepsy. Those who responded tolerated the medication well. Discontinuation due to side effects occurred soon after initiation of therapy.

Immune landscapes associated with different glioblastoma molecular subtypes.

Recent work has highlighted the tumor microenvironment as a central player in cancer. In particular, interactions between tumor and immune cells may help drive the development of brain tumors such as glioblastoma multiforme (GBM). Despite significant research into the molecular classification of glioblastoma, few studies have characterized in a comprehensive manner the immune infiltrate in situ and within different GBM subtypes.In this study, we use an unbiased, automated immunohistochemistry-based approach to determine the immune phenotype of the four GBM subtypes (classical, mesenchymal, neural and proneural) in a cohort of 98 patients. Tissue Micro Arrays (TMA) were stained for CD20 (B lymphocytes), CD5, CD3, CD4, CD8 (T lymphocytes), CD68 (microglia), and CD163 (bone marrow derived macrophages) antibodies. Using automated image analysis, the percentage of each immune population was calculated with respect to the total tumor cells. Mesenchymal GBMs displayed the highest percentage of microglia, macrophage, and lymphocyte infiltration. CD68+ and CD163+ cells were the most abundant cell populations in all four GBM subtypes, and a higher percentage of CD163+ cells was associated with a worse prognosis. We also compared our results to the relative composition of immune cell type infiltration (using RNA-seq data) across TCGA GBM tumors and validated our results obtained with immunohistochemistry with an external cohort and a different method. The results of this study offer a comprehensive analysis of the distribution and the infiltration of the immune components across the four commonly described GBM subgroups, setting the basis for a more detailed patient classification and new insights that may be used to better apply or design immunotherapies for GBM.

A quantitative method for evaluating cortical responses to electrical stimulation.

BACKGROUND: Electrical stimulation of the cortex using subdurally implanted electrodes can causally reveal structural connectivity by eliciting cortico-cortical evoked potentials (CCEPs). While many studies have demonstrated the potential value of CCEPs, the methods to evaluate them were often relatively subjective, did not consider potential artifacts, and did not lend themselves to systematic scientific investigations. NEW METHOD: We developed an automated and quantitative method called SIGNI (Stimulation-Induced Gamma-based Network Identification) to evaluate cortical population-level responses to electrical stimulation that minimizes the impact of electrical artifacts. We applied SIGNI to electrocorticographic (ECoG) data from eight human subjects who were implanted with a total of 978 subdural electrodes. Across the eight subjects, we delivered 92 trains of approximately 200 discrete electrical stimuli each (amplitude 4-15 mA) to a total of 64 electrode pairs. RESULTS: We verified SIGNI's efficacy by demonstrating a relationship between the magnitude of evoked cortical activity and stimulation amplitude, as well as between the latency of evoked cortical activity and the distance from the stimulated locations. CONCLUSIONS: SIGNI reveals the timing and amplitude of cortical responses to electrical stimulation as well as the structural connectivity supporting these responses. With these properties, it enables exploration of new and important questions about the neurophysiology of cortical communication and may also be useful for pre-surgical planning.

Improvement in Bilateral Carpal Valgus Deviation in 9 Foals After Unilateral Distolateral Radial Periosteal Transection and Elevation.

OBJECTIVES: To evaluate the effect of periosteal transection and elevation in foals with naturally occurring carpal valgus deviation. STUDY DESIGN: Prospective clinical study. ANIMALS: Foals (n = 9) with bilateral carpal valgus. METHODS: Foals with bilateral carpal valgus had distolateral radial periosteal transection and elevation (PE) including distal ulnar transection on 1 limb. Foals were stall confined until the skin incisions healed, and then allowed free exercise in a small paddock or round pen. Dorsopalmar carpal radiographs were obtained at 14 day intervals to determine the carpal valgus angle (CVA) until it was <5°. RESULTS: All limbs had a reduction in CVA and there was no significant difference in total carpal valgus angular correction or the rate at which the correction occurred between the surgical and control limb. CONCLUSIONS: Unilateral distolateral radial PE had no effect on carpal angulation in 9 foals with naturally occurring bilateral carpal valgus deviation when performed between 19 and 43 days.

Outcome of medial patellar ligament desmoplasty for treatment of intermittent upward fixation of the patella in 24 horses (2005-2012).

This retrospective study provides long-term results of medial patellar ligament (MPL) desmoplasty in horses with intermittent upward fixation of the patella (UFP) that were treated at a single referral hospital over a 7-year period. Follow-up interviews were conducted with owners, trainers, or referring veterinarians using a standardized questionnaire. Overall, 71% of horses returned to their intended use with only 18% at a higher level. Recurrence of UFP was noted in 33% of cases. Satisfaction with the procedure was generally low, with only 50% of owners being completely satisfied. Further investigation is warranted to determine appropriate medical and/or surgical therapy.

Résultat de la desmoplastie du ligament superficiel interne pour le traitement de l'accrochement supérieur intermittent de la rotule chez 24 chevaux (2005­2012). Cette étude rétrospective présente les résultats à long terme de la desmoplastie du ligament superficiel interne (LSI) chez des chevaux atteints d'un accrochement supérieur intermittent de la rotule (ASI) qui ont été traités dans un seul hôpital spécialisé pendant une période de 7 ans. Des entrevues de suivi ont été réalisées auprès des propriétaires, des dresseurs ou des vétérinaires traitants à l'aide d'un questionnaire standardisé. Dans l'ensemble, 71 % des chevaux sont retournés à leur utilisation attitrée et seulement 18 % des chevaux ont réussi à mieux performer. La récurrence de l'ASI a été notée dans 33 % des cas. La satisfaction à l'égard de l'intervention était généralement faible, et seulement 50 % des propriétaires étaient entièrement satisfaits. De nouvelles études sont justifiées afin de déterminer le traitement médical et/ou chirurgical approprié.(Traduit par Isabelle Vallières).

The influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion in the standing horse.

This study investigated the influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion (IVRLP) and assessed the efficacy of low volume IVRLP. The front limbs of 9 horses were randomly assigned to 1 of 3 volume groups: 10 mL (Group 1), 30 mL (Group 2), or 60 mL (Group 3). A tourniquet was applied distal to the carpus and the limbs were perfused with 500 mg genta-micin diluted to the assigned volume via a catheter placed in the lateral palmar digital vein at the level of the proximal sesamoid bones. Synovial fluid samples were collected from the metacarpophalangeal joint at 30 minutes, followed by removal of the tourniquet. Gentamicin concentration in synovial fluid was detected using a fluorescence polarization immunoassay. There were no statistically significant differences among gentamicin concentrations in synovial fluid among perfusate volume groups. Mean gentamicin concentration in Group 1 (125.9 µg/mL) was higher than Group 2 (82.7 µg/mL) and Group 3 (56.1 µg/mL).

Influence du volume perfusé sur la concentration antimicrobienne dans le liquide synovial après la perfusion intraveineuse régionale d'un membre chez un cheval debout. Cette étude a étudié l'influence du volume perfusé sur la concentration antimicrobienne dans le liquide synovial après la perfusion intraveineuse régionale d'un membre (PIRM) et a évalué l'efficacité d'un faible volume de PIRM. Les membres antérieurs de 9 chevaux ont été assignés au hasard à 1 de 3 groupes de volume: 10 ml (Groupe 1), 30 ml (Groupe 2) ou 60 ml (Groupe 3). Un tourniquet a été appliqué en aval du carpe et les membres ont été perfusés avec 500 mg de gentamicine diluée au volume assigné par un cathéter placé dans la veine digitale palmaire latérale au niveau des os sésamoïdes proximaux. Les échantillons de liquide synovial ont été prélevés de l'articulation métacarpo-phalangienne à 30 minutes, suivis de l'enlèvement du tourniquet. La concentration de gentamicine dans le liquide synovial a été détectée à l'aide d'un immuno-essai par fluorescence polarisée. Il n'y avait pas de différences statistiquement significatives entre les concentrations de gentamicine dans le liquide synovial parmi les groupes de volume perfusé. La concentration médiane de gentamicine du Groupe 1 (125,9 µg/ml) était supérieure à celle du Groupe 2 (82,7 µg/ml) et du Groupe 3 (56,1 µg/ml).(Traduit par Isabelle Vallières).

Tenosynoviotomy for sepsis of the digital flexor tendon sheath in 9 horses.

OBJECTIVE: To describe a tenosynoviotomy technique for treatment of sepsis of the digital flexor tendon sheath (DFTS) in horses and report long-term outcome. STUDY DESIGN: Case series. ANIMALS: Horses (n = 9). METHODS: Horses were positioned in lateral recumbency with the affected limb uppermost. A linear incision was made just lateral to the mesotenon beginning 5 cm proximal to the apices of the proximal sesamoid bones, extending 2 cm distal to the bifurcation of the superficial digital flexor tendon (SDFT). The incision was continued through the skin, subcutaneous tissue, palmar/plantar annular ligament, and DFTS. Tenotomy of the distal lateral branch of the SDFT was also performed. The site was thoroughly debrided, lavaged, and packed with gauze and allowed to heal by second intention. Follow-up was obtained via owner telephone interview. RESULTS: Mean surgery time was 32 minutes (range, 10-64 minutes). Systemic antibiotics were administered postoperatively (range, 11-46 days; mean, 23 days). Mean hospitalization was 11 days (range, 0-49 days). Follow-up was available for 7 (70%) horses. One year postoperatively, 5 (71%) horses were serviceable for their intended use, and 2 (29%) had been euthanatized. Of 5 survivors, 3 returned to ridden exercise, 1 was retired as a broodmare, and 1 was a broodmare. All owners were satisfied with the cosmetic appearance of the surgery site. CONCLUSION: Open drainage via tenosynoviotomy, performed as a salvage procedure, represents a feasible treatment for DFTS sepsis.

Reevaluation of the effect of phenylephrine on resolution of nephrosplenic entrapment by the rolling procedure in 87 horses.

OBJECTIVE: To evaluate the outcome in horses treated with a rolling technique or surgically for nephrosplenic entrapment of the large colon (NSE) and to examine the benefit of phenylephrine (PE) HCl on the efficacy of nonsurgical (rolling) management of NSE. STUDY DESIGN: Case series. ANIMALS: Horses (n = 211) diagnosed with NSE by rectal palpation with or without ultrasonography, or at the time of exploratory celiotomy or necropsy. METHODS: Medical records (January 1, 2001-September 1, 2008) were collected from horses diagnosed with NSE at 2 referral centers. Records were used to obtain signalment, physical exam findings, laboratory results, ultrasonographic findings, the use of PE HCl, the specific treatment used, and outcome. Rectal findings indicative of NSE were: (1) palpation of large colon within the nephrosplenic space or (2) palpation of colonic bands coursing dorsally toward the nephrosplenic space in association with ultrasonographic findings suggestive of NSE. RESULTS: Rolling was successful in 50 of 87 (58%) horses, 85 horses (98%) survived to discharge. Horses (n = 155) that were treated surgically (42 of which had previously undergone the rolling procedure) had a 94% short-term survival rate. Premedication with PE resulted in no significant difference (P = .91) in resolution of NSE by rolling. CONCLUSIONS: Resolution of NSE by rolling was not significantly affected by premedication with PE in the population studied.

Use of a suprapatellar pouch portal and laparoscopic cannula for removal of debris or loose fragments following arthroscopy of the femoropatellar joint of 168 horses (245 joints).

OBJECTIVE: To validate the safety of a suprapatellar pouch (SPP), approach to the femoropatellar joint (FPJ), and describe use of a laparoscopic cannula to remove debris or loose bodies. STUDY DESIGN: Retrospective case series ANIMALS: Horses (n = 168) with osteochondritis dissecans (OCD) of the FPJ. METHODS: Arthroscopy was performed on 245 FPJ with OCD. Two subpatellar portals were created, 1 axial and 1 abaxial to the lateral patellar ligament. Additionally, a SPP egress portal for lavage, was created 2 cm proximal to the most palpable dorsolateral eminence of the patellar base. A 10-mm laparoscopic cannula and trocar unit was used in all SPP portals. The SPP portal was closed in 2 layers in the first 121 horses and the skin only in the remaining 47 horses. Medical records were reviewed for complications and surgical time and owner satisfaction with cosmesis obtained. RESULTS: No complications were recorded for the SPP portal regardless of closure technique. All owners were satisfied with the cosmetic outcome of the procedure once the hair had grown back and felt the additional incision did not negatively impact horses presented for sale at public auction. Mean surgery time was 27.7 min/joint. CONCLUSION: No complications were recorded using a SPP portal and laparoscopic cannula, and owner satisfaction was high.

Racing and sales performance after unilateral or bilateral single transphyseal screw insertion for varus angular limb deformities of the carpus in 53 thoroughbreds.

OBJECTIVE: To evaluate the racing and sales performance of Thoroughbred horses with varus angular limb deformities of the carpus treated by unilateral or bilateral single transphyseal screw (STS) placement. STUDY DESIGN: Case series. ANIMALS: Thoroughbred horses (n=53). METHODS: Medical records (January 1, 2005-December 31, 2006) of yearling Thoroughbreds treated for carpal angular limb deformity by transphyseal screw insertion in the distal aspect of the radius were reviewed. Retrieved data were sex, surgery, and screw removal dates, surgical site, appearance, limb(s) affected, type of angular limb deformity, and degree of angular deviation measured by a goniometer. Racing and sales data were collected for analysis from an online racing site for all treated horses and their maternal siblings. RESULTS: No significant differences were identified between treated horses and their maternal siblings in yearling sale price, 2-year-olds in training sale price, percent starters, percent winners, and starts, earnings, and earnings/start made during the 2- and 3-year old years. CONCLUSIONS: No deleterious effects on sales or racing performance were identified after use of STS in the distal aspect of the radius of Thoroughbreds for the treatment of varus angular limb deformities of the carpus.

A practical procedure for real-time functional mapping of eloquent cortex using electrocorticographic signals in humans.

Functional mapping of eloquent cortex is often necessary prior to invasive brain surgery, but current techniques that derive this mapping have important limitations. In this article, we demonstrate the first comprehensive evaluation of a rapid, robust, and practical mapping system that uses passive recordings of electrocorticographic signals. This mapping procedure is based on the BCI2000 and SIGFRIED technologies that we have been developing over the past several years. In our study, we evaluated 10 patients with epilepsy from four different institutions and compared the results of our procedure with the results derived using electrical cortical stimulation (ECS) mapping. The results show that our procedure derives a functional motor cortical map in only a few minutes. They also show a substantial concurrence with the results derived using ECS mapping. Specifically, compared with ECS maps, a next-neighbor evaluation showed no false negatives, and only 0.46 and 1.10% false positives for hand and tongue maps, respectively. In summary, we demonstrate the first comprehensive evaluation of a practical and robust mapping procedure that could become a new tool for planning of invasive brain surgeries.

Survival and complications after large colon resection and end-to-end anastomosis for strangulating large colon volvulus in seventy-three horses.

OBJECTIVE: To report complications and survival after large colon resection and end-to-end anastomosis in horses with strangulating large colon volvulus. STUDY DESIGN: Retrospective case series. ANIMALS: Horses (n=73) with strangulating large colon volvulus. METHODS: Records (January 1995 to December 2005) of horses that had large colon resection and anastomosis for strangulating large colon volvulus were reviewed for complications. Follow-up data were obtained by telephone questionnaire at least 1 year postoperatively. Cox proportional hazards model was used for multivariate association with survival time. Variables included admission date, age, temperature, heart rate, packed cell volume, total plasma protein concentration, white blood cell count, breed, and sex. Significance was set at P<.05. RESULTS: The most common postoperative complication was diarrhea. None of the 9 variables of interest were significant for survival. Short-term survival rate (to discharge) was 74%. Overall survival rates at 1, 2, and 3 years postoperatively were 67.8%, 66.0%, and 63.5%, respectively. Four horses died of colic in the first year after surgery. All horses surviving long-term (>1 year) returned to their intended use (37 brood mares, 2 racehorses, and 1 show horse) with no chronic problems related to the surgical procedure. CONCLUSION: None of the variables examined were associated with survival. Outcomes were similar to other large studies of surgical colic in the horse. Self-limiting diarrhea is common after large colon resection and the prognosis for survival after hospital discharge is favorable. CLINICAL RELEVANCE: Horses that survive the early postoperative period and are discharged after large colon resection and anastomosis have a good chance for long-term survival with minimal negative impact on quality of life and use.

Fertility and complications after fetotomy in 20 brood mares (2001-2006).

OBJECTIVE: To report fertility (foals conceived, live foal births) of mares after partial fetotomy to resolve dystocia and complications associated with fetotomy. STUDY DESIGN: Retrospective study. ANIMALS: Horses (n=20). METHODS: Medical records (2001-2006) of mares that had partial fetotomy (1-3 cuts) for dystocia were reviewed. Complications and subsequent fertility were obtained by interview and live foal data were recorded by the Jockey Club. Postfetotomy conception and live foals produced over 21 breeding seasons (defined as years each mare was bred regardless of conception) were recorded. RESULTS: Twenty mares were identified. Bilateral carpal flexion alone (3 mares) or in combination with another deformity (7 mares) was the most common presentation for dystocia. From 2001 to 2006, there were 24 breeding seasons for which 20 mares conceived (83%). Eighteen mares conceived before 2006 and all produced live foals. Three mares were bred in 2006; 2 became pregnant, 1 was electively aborted, and 1 is pregnant. Eight of 19 (42%) mares had retained placenta, which were expelled within 24 hours after medical therapy. CONCLUSION: Partial fetotomy performed with 1-3 cuts does not impede a successful reproductive future. CLINICAL RELEVANCE: In selected equine dystocia cases, partial fetotomy should be given primary consideration when the foal is dead and vaginal delivery cannot be readily achieved. Fetotomy should not adversely affect the future fertility of the mare.

Use of colonic luminal pressure to predict outcome after surgical treatment of strangulating large colon volvulus in horses.

OBJECTIVE: To evaluate the relationship of colonic luminal pressure (CLP) measurements to outcome in horses with large colon volvulus (LCV) after either manual correction or large colon resection and anastomosis (LCRA). STUDY DESIGN: Retrospective study. ANIMALS: Horses (n=57) that had LCV. METHODS: Records for horses with LCV (March 1997-December 2003) were reviewed. Inclusion criteria were strangulating LCV proximal to the cecocolic ligament (>270 degrees), recorded CLP, and successful recovery from anesthesia. CLP measurements and survival/mortality rates were compared between horses that had manual correction (M) or LCRA (R). RESULTS: Of 57 horses, 27 had M and 30 had LCRA. For group M, CLP measurements had a sensitivity of 0.60 and specificity of 0.77 for predicting survival, whereas for group R, sensitivity was 0.50 and specificity was 0.54. CONCLUSION: In our LCV population, elevated CLP measurements had poor accuracy for predicting outcome in horses after surgical correction, especially after LCRA. CLINICAL RELEVANCE: CLP measurements based on a single hospital population of horses with LCV should be used with caution for other hospital populations of LCV. CLP may be only one of many variables needed for predicting outcome of horses with strangulating LCV, especially after LCRA.

Neurofibromatosis 1.

Neurofibromatosis 1 is one of the most common genetic conditions affecting the nervous system. Individuals with NF1 are predisposed to the development of peripheral nerve sheath tumors (neurofibromas and MPNSTs), astrocytomas (optic pathway gliomas), learning disabilities, seizures, strokes, macrocephaly, and vascular abnormalities. The NF1 tumor suppressor gene encodes a large protein (neurofibromin) that functions primarily as a RAS negative regulator, suggesting that targeted therapy for NF1 might derive from inhibition of the RAS signaling pathway.