Non-invasive therapeutic brain stimulation for treatment of resistant focal epilepsy in a teenager

A 13-year-old boy with symptomatic focal epilepsy due to a right parietal dysembryoplastic neuroepithelial tumor (DNET) presented pre- and post-operatively fluctuating tinnitus and sensory symptoms which became persistent after incomplete tumor resection. He received low-frequency rTMS treatment and cathodal tDCS treatment.Case report with clinical details and pictures from rTMS and tDCS stimulation targets.The patient became symptom free with an initial low-frequency rTMS treatment series targeted to the EEG-verified epileptic zone followed by maintenance therapy at the same region with cathodal tDCS at home.Both rTMS and tDCS could be more often used in adolescents when drug treatment and surgery do not cease focal epilepsy, here with fluctuating tinnitus.\nAims\nMethods\nResults\nConclusions</div

Successful suppression of musical hallucinations with low-frequency rTMS of the left temporo-parietal junction: A case report

Background: Inhibitory low frequency repetitive transcranial magnetic stimulation (rTMS) of the temporo-parietal area has been applied to treat both auditory verbal hallucinations as well as tinnitus.Objective: We hypothesized that 1 Hz rTMS to the left temporoparietal junction (TPJ) may be beneficial in alleviating musical hallucinations (MH), another condition with auditory experiences in the absence of an external source.Methods: Here we describe a patient with almost insufferable life-long MH with comorbid depression, who received inhibitory rTMS to the left TPJ as well as the right dorsolateral prefrontal cortex (DLPFC).Results: The intrusiveness and frequency of her MH as well as her depressive symptoms alleviated quickly and substantially, and once-a-week maintenance therapy with rTMS seemed to preserve this amelioration. Future studies will hopefully reveal whether this is a viable treatment approach for other patients suffering from MH with or without comorbid depression.(c) 2021 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).</p

Mapping Lesion-Related Epilepsy to a Human Brain Network

Importance: It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions. Objective: To assess whether lesion locations associated with epilepsy map to specific brain regions and networks. Design, setting, and participants: This case-control study used lesion location and lesion network mapping to identify the brain regions and networks associated with epilepsy in a discovery data set of patients with poststroke epilepsy and control patients with stroke. Patients with stroke lesions and epilepsy (n = 76) or no epilepsy (n = 625) were included. Generalizability to other lesion types was assessed using 4 independent cohorts as validation data sets. The total numbers of patients across all datasets (both discovery and validation datasets) were 347 with epilepsy and 1126 without. Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data were analyzed from September 2018 through December 2022. All shared patient data were analyzed and included; no patients were excluded. Main outcomes and measures: Epilepsy or no epilepsy. Results: Lesion locations from 76 patients with poststroke epilepsy (39 [51%] male; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2.0] years) and 625 control patients with stroke (366 [59%] male; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the discovery data set. Lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity to the basal ganglia and cerebellum. Findings were validated in 4 independent cohorts including 772 patients with brain lesions (271 [35%] with epilepsy; 515 [67%] male; median [IQR] age, 60 [50-70] years; follow-up range, 3-35 years). Lesion connectivity to this brain network was associated with increased risk of epilepsy after stroke (odds ratio [OR], 2.82; 95% CI, 2.02-4.10; P \u3c .001) and across different lesion types (OR, 2.85; 95% CI, 2.23-3.69; P \u3c .001). Deep brain stimulation site connectivity to this same network was associated with improved seizure control (r, 0.63; P \u3c .001) in 30 patients with drug-resistant epilepsy (21 [70%] male; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months). Conclusions and relevance: The findings in this study indicate that lesion-related epilepsy mapped to a human brain network, which could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies

Systemic Analysis of Gene Expression Profiles Identifies ErbB3 as a Potential Drug Target in Pediatric Alveolar Rhabdomyosarcoma

Peer reviewe

Expression profile of <i>ERBB3</i> in pediatric healthy and cancer tissues.

<p><b>A</b>) Body-wide expression profile of the <i>ERBB3</i> gene across the database. Each dot represents the expression of <i>ERBB3</i> in one sample. Anatomical origins of each sample are marked in color bars below the gene plot. The <i>ERBB3</i> gene is highly expressed in malignant connective and muscular tissue samples (green dots). <b>B</b>) Box plot analysis of the <i>ERBB3</i> gene expression levels across a variety of pediatric cancer samples. <i>ERBB3</i> is particularly highly expressed in alveolar rhabdomyosarcomas. NOS, not otherwise specified.</p

Expression and function of ErbB3 in rhabdomyosarcoma.

<p>(<b>A</b>) Western analysis of ErbB3 expression in RD cells transfected or not with a plasmid encoding ErbB3 or an empty vector control (lanes 1–3), or with <i>ERBB3</i>-targeting or control siRNA (lanes 4–5). Membranes were reblotted with anti-actin to control loading. (<b>B–D</b>) Immunohistochemical analysis of ErbB3 expression in normal adult human stomach (<b>B</b>) and in two samples representing pediatric alveolar rhabdomyosarcoma (<b>C</b>,<b>D</b>). (<b>E</b>,<b>F</b>) MTT proliferation analysis of the effect of <i>ERBB3</i> overexpression (<b>E</b>) or siRNA-mediated <i>ERBB3</i> down-regulation on the growth of RD cell transfectants. Expression of ErbB3 in the transfectants is shown in (<b>A</b>). *, <i>P</i><0.001 when compared to control. Scale bar in (<b>B–D</b>), 100 µm.</p

Expression profile of <i>VEGFC</i> in pediatric healthy and cancer tissues.

<p><b>A</b>) Body-wide expression profile of the <i>VEGFC</i> gene across the database. Each dot represents the expression of <i>VEGFC</i> in one sample. Anatomical origins of each sample are marked in color bars below the gene plot. The <i>VEGFC</i> gene is highly expressed in samples originating from malignant connective or muscular tissue (green dots). The ten green dots forming a separate group with high <i>VEGFC</i> expression all represent samples from Ewing’s sarcoma. <b>B</b>) Box plot analysis of the <i>VEGFC</i> gene expression levels across a variety of pediatric cancer samples. <i>VEGFC</i> is particularly highly expressed in Ewing’s sarcoma. NOS, not otherwise specified.</p

Hierarchial clustering of validated therapeutic target genes in rhabdomyosarcomas and Ewing’s sarcomas.

<p>The red boxes illustrate mRNA expression levels exceeding the mean expression per gene in the analyzed tissues, whereas the blue boxes illustrate mRNA expression levels lower than the mean expression per gene. The number of samples analyzed per tissue type is given in parentheses.</p

Expression profile of <i>EPHA2</i> in pediatric healthy and cancer tissues. A

<p>) Body-wide expression profile of the <i>EPHA2</i> gene across the database. Each dot represents the expression of <i>EPHA2</i> in one sample. Anatomical origins of each sample are marked in color bars below the gene plot. The <i>EPHA2</i> gene is highly expressed in malignant connective and muscular tissue samples (green dots). <b>B</b>) Box plot analysis of the <i>EPHA2</i> gene expression levels across a variety of pediatric cancer samples. <i>EPHA2</i> is particularly highly expressed in osteosarcoma and Ewing’s sarcoma. NOS, not otherwise specified.</p

Mapping Lesion-Related Epilepsy to a Human Brain Network

IMPORTANCE It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions. OBJECTIVE To assess whether lesion locations associated with epilepsy map to specific brain regions and networks. DESIGN, SETTING, AND PARTICIPANTS This case-control study used lesion location and lesion network mapping to identify the brain regions and networks associated with epilepsy in a discovery data set of patients with poststroke epilepsy and control patients with stroke. Patients with stroke lesions and epilepsy (n = 76) or no epilepsy (n = 625) were included. Generalizability to other lesion types was assessed using 4 independent cohorts as validation data sets. The total numbers of patients across all datasets (both discovery and validation datasets) were 347 with epilepsy and 1126 without. Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data were analyzed from September 2018 through December 2022. All shared patient data were analyzed and included; no patients were excluded. MAIN OUTCOMES AND MEASURES Epilepsy or no epilepsy. RESULTS Lesion locations from 76 patients with poststroke epilepsy (39 [51%] male; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2.0] years) and 625 control patients with stroke (366 [59%] male; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the discovery data set. Lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity to the basal ganglia and cerebellum. Findings were validated in 4 independent cohorts including 772 patients with brain lesions (271 [35%] with epilepsy; 515 [67%] male; median [IQR] age, 60 [50-70] years; follow-up range, 3-35 years). Lesion connectivity to this brain network was associated with increased risk of epilepsy after stroke (odds ratio [OR], 2.82; 95% CI, 2.02-4.10; P <.001) and across different lesion types (OR, 2.85; 95% CI, 2.23-3.69; P <.001). Deep brain stimulation site connectivity to this same network was associated with improved seizure control (r, 0.63; P <.001) in 30 patients with drug-resistant epilepsy (21 [70%] male; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months). CONCLUSIONS AND RELEVANCE The findings in this study indicate that lesion-related epilepsy mapped to a human brain network, which could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies