Spatial and temporal profile of high-frequency oscillations in posttraumatic epileptogenesis.

We studied the role of temporal and spatial changes in high-frequency oscillation (HFO, 80-500 Hz) generation in epileptogenesis following traumatic brain injury (TBI). Experiments were conducted on adult male Sprague Dawley rats. For the TBI group, fluid percussion injury (FPI) on the left sensorimotor area was performed to induce posttraumatic epileptogenesis. For the sham control group, only the craniotomy was performed. After TBI, 8 bipolar micro-electrodes were implanted bilaterally in the prefrontal cortex, perilesional area and homotopic contralateral site, striatum, and hippocampus. Long-term video/local field potential (LFP) recordings were performed for up to 21 weeks to identify and characterize seizures and capture HFOs. The electrode tip locations and the volume of post TBI brain lesions were further estimated by ex-vivo MRI scans. HFOs were detected during slow-wave sleep and categorized as ripple (80-200 Hz) and fast ripple (FR, 250-500 Hz) events. HFO rates and the HFO peak frequencies were compared in the 8 recording locations and across 8-weeks following TBI. Data from 48 rats (8 sham controls and 40 TBI rats) were analyzed. Within the TBI group, 22 rats (55%) developed recurrent spontaneous seizures (E+ group), at an average of 62.2 (+17.1) days, while 18 rats (45%) did not (E- group). We observed that the HFOs in the E+ group had a higher mean peak frequency than the E- group and the sham group (P < 0.05). Furthermore, the FR rate of the E+ group showed a significant increase compared to the E-group (P < 0.01) and sham control group (P < 0.01), specifically in the perilesional area, homotopic contralateral site, bilateral hippocampus, and to a lesser degree bilateral striatum. When compared across time, the increased FR rate in the E+ group occurred immediately after the insult and remained stable across the duration of the experiment. In addition, lesion size was not statistically different in the E+ and E- group and was not correlated with HFO rates. Our results suggest that TBI results in the formation of a widespread epileptogenic network. FR rates serve as a biomarker of network formation and predict the future development of epilepsy, however FR are not a temporally specific biomarker of TBI sequelae responsible for epileptogenesis. These results suggest that in patients, future risk of post-TBI epilepsy can be predicted early using FR.

Spike and wave discharges and fast ripples during posttraumatic epileptogenesis.

OBJECTIVE: The goal of the present study was to determine whether spike and wave discharges (SWDs) and SWDs with superimposed fast ripples (SWDFRs) could be biomarkers of posttraumatic epileptogenesis. METHODS: Fluid percussion injury was conducted on 13-14-week old male Sprague Dawley rats. Immediately after traumatic brain injury (TBI), they were implanted with microelectrodes in the neocortex, hippocampus, and striatum bilaterally. Age-matched sham rats with the same electrode implantation montage acted as controls. Wideband brain electrical activity was recorded intermittently from Day 1 of TBI, and continued from 2 to 21 weeks after TBI. SWD and SWDFR analysis was performed during the first 2 weeks to investigate whether the occurrence of this pattern predicted development of epilepsy. The remaining 3-21 weeks were used for identifying which rats became epileptic (E+ group) and which did not (E- group). RESULTS: The E+ group (n = 9) showed a significant increase in SWD rate in prefrontal cortex during Weeks 1 and 2 after TBI. The E- group showed a significant increase in SWD rate only in the second week. One hundred percent of rats in the E+ group displayed SWDFRs beginning from the first week after TBI. The SWDFR pattern was observed in all recorded brain areas: prefrontal and perilesional cortices, hippocampus, and striatum. None of rats in the E- group showed coexistence of fast ripples with SWDs. SIGNIFICANCE: Occurrence of SWDFRs after TBI, but not an increase in the rate of SWDs, could be a noninvasive electroencephalographic biomarker of posttraumatic epileptogenesis.

Immunolocalization of Gas7 in the Subgranular Zone of Mice Hippocampus.

It is established that neural stem cells (NSC) reside in the hippocampal subgranular zone (SGZ) and contribute to neurogenesis throughout life. Although the molecular events that regulate hippocampal neural stem cell differentiation are known, the precise mechanism is undefined. Here, the role of growth arrest specific 7 (Gas7) protein in SGZ neural progenitor cell differentiation was studied. Immunoblotting and immunohistochemistry for Gas7 were performed on 12 weeks old mice hippocampus. The results displayed a strong signal for Gas7 protein in the mice hippocampal tissue and SGZ cells, therefore suggesting that Gas7 might have a role in neural progenitor cell differentiation in SGZ.

Effects of selective serotonin and norepinephrine reuptake inhibitors on depressive- and impulsive-like behaviors and on monoamine transmission in experimental temporal lobe epilepsy.

OBJECTIVE: Examine therapeutic potential of a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor (NERI) in an animal model of comorbidity between epilepsy, depression-like, and impulsive-like impairments. METHODS: Epilepsy was induced in male Wistar rats by LiCl and pilocarpine. An SSRI fluoxetine (FLX), and an NERI reboxetine (RBX) were administered either alone or as a combination over 1 week. Depressive-like and impulsive-like behaviors were examined using the forced swim test. Fast scan cyclic voltammetry was used to analyze serotonergic transmission in the raphe nucleus (RN)-prefrontal cortex (PFC) pathway, and noradrenergic transmission in locus coeruleus (LC)-PFC, and LC-RN projections. Monoamine levels in PFC were measured using high-performance liquid chromatography (HPLC). Functional capacities of 5-HT1A receptors and α2A adrenoreceptors in PFC were analyzed by autoradiography. RESULTS: Epileptic rats showed behavioral signs of depression and hyperimpulsivity, suppressed serotonergic and noradrenergic tones, decreased levels of serotonin (5-HT), and norepinephrine (NE); 5-HT1A receptor and α2A adrenoreceptors functions remained intact. FLX failed to improve behavioral deficits, but effectively raised 5-HT level and marginally improved RN-PFC serotonergic transmission. RBX reversed impulsive-like behavior, normalized content of NE and noradrenergic tone in LC-PFC and LC-RN. FLX-RBX combination fully reversed depressive-like behavior, and normalized RN-PFC serotonergic transmission. None of the treatment modified the function of 5-HT and NE receptors. SIGNIFICANCE: Depressive- and impulsive-like behaviors in the pilocarpine model of epilepsy stem respectively from dysfunctions of serotonergic and noradrenergic ascending pathways. At the same time, epilepsy-associated depression is SSRI resistant. The finding that an SSRI-NERI combination exerts antidepressant effect, along with RBX-induced improvement of LC-RN noradrenergic transmission point toward the involvement of LC-RN noradrenergic input in enabling therapeutic potential of FLX. Medications that improve serotonergic and noradrenergic transmission, such as serotonin-norepinephrine reuptake inhibitors may be effective in treating epilepsy-associated SSRI-resistant depression, as well as concurrent depression and attention-deficit/hyperactivity disorder (ADHD).

Cytokine-dependent bidirectional connection between impaired social behavior and susceptibility to seizures associated with maternal immune activation in mice.

Maternal immune activation (MIA) results in the development of autism in the offspring via hyperactivation of IL-6 signaling. Furthermore, experimental studies showed that the MIA-associated activation of interleukin-1ß (IL-1ß) concurrently with IL-6 increases the rate and the severity of hippocampal kindling in mice, thus, offering an explanation for autism-epilepsy comorbidity. We examined whether epileptic phenotype triggered by prenatal exposure to IL-6 and IL-1ß combination is restricted to kindling or whether it is reproducible in another model of epilepsy, whereby spontaneous seizures develop following kainic acid (KA)-induced status epilepticus. We also examined whether in mice prenatally exposed to IL-6 and IL-6+IL-1ß, the presence of spontaneous seizures would exacerbate autism-like features. Between days 12 and 16 of pregnancy, C57BL/6J mice received daily injections of IL-6, IL-1ß, or IL-6+IL-1ß combination. At postnatal day 40, male offspring were examined for the presence of social behavioral deficit, and status epilepticus was induced by intrahippocampal KA injection. After 6weeks of monitoring for spontaneous seizures, sociability was tested again. Both IL-6 and IL-6+IL-1ß offspring presented with social behavioral deficit. Prenatal exposure to IL-6 alleviated, while such exposure to IL-6+IL-1ß exacerbated, the severity of KA-induced epilepsy. Increased severity of epilepsy in the IL-6+IL-1ß mice correlated with the improvement of autism-like behavior. We conclude that complex and not necessarily agonistic relationships exist between epileptic and autism-like phenotypes in an animal model of MIA coupled with KA-induced epilepsy and that the nature of these relationships depends on components of MIA involved.

Melanoma metastasis to the bladder: A case report.

Metastasis of malignant melanoma to the bladder is rarely seen clinically with only 29 cases reported in English-language literature. However, autopsy series of melanoma patients have shown that metastasis to the bladder could be as high as 37%, implying that numerous cases remain undiagnosed. This report details a case of malignant melanoma metastasis to the bladder. Patient presented with severe anemia and history of gross hematuria. Computerized tomography (CT) revealed a 2.7 cm mass in the bladder. Cystoscopy confirmed presence of a mass. Patient underwent cystoscopy and transurethral resection of the tumor, revealed to be melanoma on pathology.

Succinate dehydrogenase deficient renal cell carcinoma: A case report.

Succinate dehydrogenase (SDH) deficient renal cell carcinoma (RCC) are uncommon renal tumors that typically present in relatively younger patients. SDH mutations are known to cause cancer, but often presents with hereditary paragangliomas, pheochromocytomas, and gastrointestinal stromal tumors. This report details a case of SDH deficient RCC in a patient with no know contributing family history. Patient presented with recurrent urinary tract infections and groin pain. Computerized tomography (CT) revealed a 4 cm mass in the right kidney. Partial nephrectomy was performed, and the patient had an uneventful recovery. Immunohistochemical staining revealed the tumor was SDH negative.

Ureteral fibroepithelial polyp: A diagnostic challenge.

Ureteral fibroepithelial polyps (UFP) are relatively rare, benign tumors. A total of 236 total cases were documented between 1932 and 2013. Notably, imaging studies, including computerized tomography (CT) and magnetic resonance imaging (MRI) are often negative. This report details a case of a patient with a UFP who presented with hematuria. CT suggested a possible 1.8 cm mass, but subsequent MRI was negative. Cystoscopy showed a polyp that prolapsed out of the left ureter and into the bladder with peristalsis. The patient subsequently underwent retrograde ureteroscopy and holmium laser excision of the polyp.

Inverted urothelial papilloma: A case report.

Inverted urothelial papilloma (IUP) is an unusual tumor that typically presents as a non-invasive, endophytic urothelial neoplasm. Though fairly well described in the bladder, IUP of the upper urinary tract is fairly rare, with only 68 cases documented in English language literature. Our patient presented with an IUP of the distal left ureter and was treated with a distal ureterectomy and reimplant of the ureter with a psoas hitch.

An approach for reliably identifying high-frequency oscillations and reducing false-positive detections.

OBJECTIVE: Aiming to improve the feasibility and reliability of using high-frequency oscillations (HFOs) for translational studies of epilepsy, we present a pipeline with features specifically designed to reject false positives for HFOs to improve the automatic HFO detector. METHODS: We presented an integrated, multi-layered procedure capable of automatically rejecting HFOs from a variety of common false positives, such as motion, background signals, and sharp transients. This method utilizes a time-frequency contour approach that embeds three different layers including peak constraints, power thresholds, and morphological identification to discard false positives. Four experts were involved in rating detected HFO events that were randomly selected from different posttraumatic epilepsy (PTE) animals for a comprehensive evaluation. RESULTS: The algorithm was run on 768-h recordings of intracranial electrodes in 48 PTE animals. A total of 453 917 HFOs were identified by initial HFO detection, of which 450 917 were implemented for HFO refinement and 203 531 events were retained. Random sampling was used to evaluate the performance of the detector. The HFO detection yielded an overall accuracy of 0.95 ± 0.03 , with precision, recall, and F1 scores of 0.92 ± 0.05 , 0.99 ± 0.01 , and 0.94 ± 0.03 , respectively. For the HFO classification, our algorithm obtained an accuracy of 0.97 ± 0.02 . For the inter-rater reliability of algorithm evaluation, the agreement among four experts was 0.94 ± 0.03 for HFO detection and 0.85 ± 0.04 for HFO classification. SIGNIFICANCE: Our approach shows that a segregated pipeline design with a focus on false-positive rejection can improve the detection efficiency and provide reliable results. This pipeline does not require customization and uses fixed parameters, making it highly feasible and translatable for basic and clinical applications of epilepsy.

Prospective randomized trial comparing shock wave lithotripsy and ureteroscopy for lower pole caliceal calculi 1 cm or less.

PURPOSE: The optimal management of lower pole renal calculi is controversial. We compared shock wave lithotripsy (SWL) and ureteroscopy (URS) for the treatment of patients with small lower pole stones in a prospective, randomized, multicenter trial. MATERIALS AND METHODS: A total of 78 patients with 1 cm or less isolated lower pole stones were randomized to SWL or URS. The primary outcome measure was stone-free rate on noncontrast computerized tomography at 3 months. Secondary outcome parameters were length of stay, complication rates, need for secondary procedures and patient derived quality of life measures. RESULTS: A total of 67 patients randomized to SWL (32) or URS (35) completed treatment. The 2 groups were comparable with respect to age, sex, body mass index, side treated and stone surface area. Operative time was significantly shorter for SWL than URS (66 vs 90 minutes). At 3 months of followup 26 and 32 patients who underwent SWL and URS had radiographic followup that demonstrated a stone-free rate of 35% and 50%, respectively (p not significant). Intraoperative complications occurred in 1 SWL case (unable to target stone) and in 7 URS cases (failed access in 5 and perforation in 2), while postoperative complications occurred in 7 SWL and 7 URS cases. Patient derived quality of life measures favored SWL. CONCLUSIONS: This study failed to demonstrate a statistically significant difference in stone-free rates between SWL and URS for the treatment of small lower pole renal calculi. However, SWL was associated with greater patient acceptance and shorter convalescence.

Ureteroscopic holmium laser lithotripsy in patients with renal impairment.

OBJECTIVES: In this study, we try to evaluate the efficacy and safety of holmium lasers for treatment of ureteric stones in patients with renal impairment or obstructive anuria. PATIENTS AND METHODS: Twenty-six patients were included in this study, of which 20 patients presented with elevated blood urea and serum creatinine (2.1-7.6 mg%), and six patients presented with calcular anuria (mean serum creatinine 22 mg%). None of the patients had a ureteric stent or nephrostomy tube before the ureteroscopy. All patients were treated with holmium laser. A stone basket or grasper was used to remove significant stone fragments at the end of the procedure in seven patients. In these seven patients, ureteric stents were placed at the end of the procedure. RESULTS: All patients were free of any stone fragments at 1 week and at 3 months postoperatively. In all patients, including the six with obstructive anuria, the renal impairment resolved or improved as evidenced by normalization or fall in blood urea and creatinine. Thus, in this small group of uremic patients, the success rate for treatment of ureteral stone was 100%. CONCLUSIONS: A holmium laser is a safe and effective modality of ureteroscopic lithotripsy in patients with significant renal impairment or even obstructive anuria. The use of holmium laser with ureteroscopy may be considered in this group of patients as long as the general condition of the patient permits the safe administration of anesthesia.

A varied presentation of hydatid cyst: a report of four cases with review of literature.

Contrary to the popular perception, hydatosis does not remain restricted to certain geographical locales but is a global health concern, particularly in the rural countryside. Although liver and lung involvement account for the majority of the lesions, primary breast, bone, kidney and soft tissue hydatosis with features of cystic echinococcosis are extremely rare. We report four such rare cases of cystic echinococcosis which were diagnosed and treated in our institute.

A Prospective Study of Herpes Zoster in Children.

BACKGROUND: Herpes zoster (HZ) is a dermatomal viral infection, caused by reactivation of varicella zoster virus (VZV) that persists in the posterior root ganglion. HZ is uncommonly reported in immunocompetent children. It may be due to intrauterine VZV infection or secondary to postnatal exposure to VZV at an early age. AIMS: Our study was to review clinico-epidemiological data for HZ in children for early diagnosis and treatment to prevent complications. MATERIALS AND METHODS: A prospective observational study was conducted from January 2013 to December 2014. Consecutive cases clinically diagnosed as HZ in the pediatric age group were taken up. RESULTS: We report the clinico-epidemiological study of 26 cases of HZ, their benign course and recovery among children. CONCLUSIONS: HZ is a rare disease in childhood. Varicella in early childhood is a risk factor of HZ in immunocompromised and immunocompetent children. Childhood zoster occurs in either healthy or underlying immunodeficient children. The appearance of HZ in a young child does not always imply an underlying immunodeficiency or malignancy. But the identification of HZ with or without immunodeficiency is of prime importance from the treatment and prognostic point of view and should be considered in the differential diagnosis of vesicular eruptions. The prognosis is generally good in healthy children.

Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy.

Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals' behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino-N-[(1S,2S,4R)-7,7-dimethyl-1-[[[4-(2-methylphenyl)-1-piperazinyl]sulfonyl]methyl]bicyclo[2.2.1]hept-2-yl]-4-(methylsulfonyl)butanamide hydrochloride abolished ECT-induced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.

Increased distributional variance of mitochondrial DNA content associated with prostate cancer cells as compared with normal prostate cells.

BACKGROUND: Mitochondria are key organelles for apoptosis, and mitochondrial DNA (mtDNA) content can regulate cancer progression. Increases in mtDNA mutations and deletions have been reported in cancer; however, a detailed investigation of mtDNA content in cancer cells has not yet been conducted. METHODS: Quantitative real-time PCR and improved extraction method were established to investigate the mtDNA content in a single prostate cell. RESULTS: The heterogeneity of mtDNA content was demonstrated between the clones of prostate cancer cell line LNCaP and individual cells in each clone. To investigate whether large distributional variance of mtDNA content is associated with cancer initiation and/or progression, we first compared PZ-HPV-7, an HPV-transformed normal prostate epithelial cell line, with CA-HPV-10, transformed from prostate cancer cells derived from the same donor. We found an enhanced distributional variance of mtDNA content in CA-HPV-10. Then, we investigated mtDNA content in individual cells in laser microdisssected cancer and adjacent normal cells from prostate cancer tissue specimens using quantitative real-time PCR method. Results showed that the mtDNA content per cell follows a higher skewed distribution in cancer cells as compared in normal cells. We also observed that mtDNA content was increased in seven of nine (78%) of prostate cancers compared to normal prostate tissue. CONCLUSIONS: These results indicate that prostate carcinogenesis may involve dysregulation of mtDNA content.

Experience with ureteroscopic holmium laser lithotripsy in children.

The purpose of the study was to evaluate the outcome of ureteroscopic holmium laser lithotripsy (UHLL) in children, taking into consideration different stone locations. Records of 15 children with ureteral calculi managed with UHLL were reviewed. All patients were evaluated with history, clinical, radiological and laboratory assessment prior to treatment. All patients were managed on an outpatient basis. After stone disintegration, if sizable fragments remained, they were retrieved using grasping forceps or stone basket extraction. Patient records were reviewed for age, sex, stone laterality, location, number and size, need for ureteral dilation, stenting and residual fragment extraction. Of the 15 children, 11 were female and 4 were male. Mean age was 8.5 years (age range 2-15 years). There was no significant difference in stone laterality (eight left and seven right ureteral stones). Main presenting symptoms were renal colic, hematuria and urinary tract infection or a combination of these symptoms. The 15 children harbored 15 ureteral stones (range 5-11 mm, mean 7.8 mm) and underwent 15 UHLL procedures. Ureteral dilation was performed in 14 patients using balloon dilators. Stone retrieval was done in all patients. DJ stents were placed at the conclusion of the procedure in 11 patients. Complete stone clearance was achieved at the end of the procedure in all patients (success rate 100%). No complications were encountered during or after the procedure. This study confirms the effectiveness and safety of ureteroscopy and holmium laser in the treatment of ureteral stones in children regardless of stone location.