scholarly journals P.039 mTOR inhibitors as a new therapeutic strategy in treatment resistant epilepsy in hemimegalencephaly: a case report

2017 ◽  
Vol 44 (S2) ◽  
pp. S23-S23
Author(s):  
Q Xu ◽  
H Sarnat ◽  
S Uliel-Sibony ◽  
C Boelman ◽  
M Connolly ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Refractory Epilepsy ◽  
Focal Cortical Dysplasia ◽  
Mtor Inhibitors ◽  
Response To Treatment ◽  
Definitive Treatment ◽  
High Morbidity ◽  
Treatment Resistant ◽  
Integral Role ◽  
First Time

Background: Hemimegalencephaly (HME) is a hamartomatous malformation of one cerebral hemisphere, resulting in refractory epilepsy, intellectual disability, and autistic features. Hemispherectomy is the definitive treatment, but there is risk of high morbidity and mortality, especially when done in early infancy. Various preclinical studies have shown that dysregulation of the mTOR pathway has an integral role in the development of various epilepsy syndromes, including tuberous sclerosis complex (TSC), focal cortical dysplasia and HME. Recently, mTOR inhibitors were proven to be effective in treating seizures in TSC. Methods: We present a case of a 6 day old female with refractory epilepsy despite the trial of 9 anti-seizure medications and the ketogenic diet. As the patient was awaiting epilepsy surgery, an mTOR inhibitor, rapamycin was initiated. Results: After 1 week of the initiation, she had over a 50% reduction in seizures. At two weeks, the parents felt that for the first time, she was making developmental gains. She also appeared brighter and more interactive. Due to her response to treatment, her hemispherectomy was deferred to when she is older, so there will be a decreased risk of complications from the surgery. Conclusions: This case exemplifies how mTOR inhibitors should be considered as a treatment option for patients with HME and refractory epilepsy.

mTOR Inhibitors as a New Therapeutic Strategy in Treatment Resistant Epilepsy in Hemimegalencephaly: A Case Report

2018 ◽  
Vol 34 (3) ◽  
pp. 132-138 ◽  
Author(s):  
Qi Xu ◽  
Shimrit Uliel-Sibony ◽  
Christopher Dunham ◽  
Harvey Sarnat ◽  
Laura Flores-Sarnat ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Mtor Inhibitor ◽  
De Novo ◽  
Mtor Inhibitors ◽  
Mtor Pathway ◽  
Definitive Treatment ◽  
Malformations Of Cortical Development ◽  
Treatment Resistant ◽  
Seizure Reduction ◽  
Functional Hemispherectomy

Hemimegalencephaly is a hamartomatous malformation of one hemisphere. Functional hemispherectomy, the definitive treatment, is associated with significant morbidity and mortality in early infancy. Dysregulation of the mTOR pathway can result in malformations of cortical development, and mTOR inhibitors can effectively reduce seizures in tuberous sclerosis complex. We report a 6-day-old female with hemimegalencephaly and frequent seizures despite 9 antiseizure medications. At 3 months of age, while awaiting hemispherectomy, an mTOR inhibitor, rapamycin, was initiated by the neurologist. After 1 week of treatment, there was >50% reduction in seizures and total seizure burden, and after 2 weeks, development improved, resulting in deferral of surgery by 2.5 months with an increased body weight. Pathology demonstrated cortical dysplasia with upregulation of the mTOR pathway. Deep-sequencing of brain tissue demonstrated 16% mosaicism for a pathogenic de novo MTOR gene mutation. This case exemplifies how mTOR inhibitors could be considered for seizure reduction in patients with hemimegalencephaly while awaiting surgery.

A case of linear epidermal naevus presenting as genital warts – a cautionary tale

2005 ◽  
Vol 16 (3) ◽  
pp. 267-269
Author(s):  
M Mahto ◽  
J Ashworth ◽  
D M Vickers
Keyword(s):  
Unusual Case ◽  
Adult Life ◽  
Genital Warts ◽  
Definitive Treatment ◽  
Cautionary Tale ◽  
Surgical Ablation ◽  
Genital Area ◽  
Organ Systems ◽  
First Time ◽  
Epidermal Naevus Syndrome

Linear epidermal naevus (LEN) in the genital area is quite rare. It may present at birth or appear later on in life, in infancy or childhood and occasionally for the first time in adult life. There are several variants of epidermal naevi (EN), which, to the less experienced, can be mistaken for warts. When extensive, it can be associated with abnormalities in other organ systems (epidermal naevus syndrome). The definitive treatment of LEN is surgical ablation with excision of underlying dermis, but this frequently leads to scarring. Laser therapy is an alternative treatment modality and good results have been shown. We report an unusual case of LEN in the genital area in a 60-year-old man presenting as genital warts.

Phosphorylation of S6 Protein as a Potential Biomarker in Surgically Treated Refractory Epilepsy

2020 ◽  
Vol 42 (5-6) ◽  
pp. 230-236
Author(s):  
Felipe I. Chodraui ◽  
Camila Araújo B. Garcia ◽  
Niele D. Mendes ◽  
Marcelo V. Santos ◽  
Pâmela S. Beggiora ◽  
...  
Keyword(s):  
Refractory Epilepsy ◽  
Focal Cortical Dysplasia ◽  
Clinical Aspects ◽  
Control Group ◽  
Type I ◽  
Phosphorylated Protein ◽  
Downstream Target ◽  
Molecular Features ◽  
Brain Anomalies ◽  
Potential Biomarker

The tuberous sclerosis complex (TSC), focal cortical dysplasia IIB (FCD IIB), and hemimegalencephaly (HME) exhibit similar molecular features that are dependent on the hyperactivation of the mTOR pathway. They are all associated with refractory epilepsy and the need for surgical resection with varying outcomes. The phosphorylated protein S6 (pS6) is a downstream target of mTOR, whose increased expression might indicate mTOR hyperactivation, but which is also present when there is no alteration in the pathway (such as in FCD type I). We have performed immunohistochemical marking and quantification of pS6 in resected brain specimens of 26 patients clinically and histologically diagnosed with TSC, FCD IIB, or HME and compared this data to a control group of 25 patients, to measure the extent of pS6 positivity and its correlation with clinical aspects. Our results suggest that pS6 may serve as a reliable biomarker in epilepsy and that a greater percentage of pS6 marking can relate to more severe forms of mTOR-dependent brain anomalies.

scholarly journals Prolonged efficacy of pembrolizumab in a patient presenting a multi-treated metastatic hepatocholangiocarcinoma

2020 ◽  
Vol 13 ◽  
pp. 175628482093518 ◽  
Author(s):  
Angélique Saint ◽  
Maxime Benchetrit ◽  
Sébastien Novellas ◽  
Denis Ouzan ◽  
Alexander Tuan Falk ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Complete Response ◽  
It Management ◽  
Tumor Control ◽  
Line Treatment ◽  
Viral Hepatitis C ◽  
Programmed Cell Death 1 ◽  
First Time ◽  
Inhibitor Treatment ◽  
Over Time

Introduction: Hepatocholangiocarcinoma (HCC-ICC) is a rare tumor presenting the histologic characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). As there is no consensus on it management, the therapeutic strategy rests on the specific treatments for HCC or ICC. Programmed cell death 1 (PD-1) inhibitors showed encouraging results in the second line treatment of HCC after sorafenib but it efficacy in HCC-ICC has never been reported. Methods and results: We present the case of a 72-year-old male patient treated for metastatic HCC-ICC due to a viral hepatitis C cirrhosis in progression after two lines of treatment. Tumor was characterized by a PDL-1 status of 85%. Patient received pembrolizumab at doses of 200 mg every 21 days by intravenous infusion. After one injection he was presented an immediate clinical benefit, a partial response was observed after two months of treatment and a complete response two months later. This response was maintained over time along with toxicity-free tumor control after 18 months treatment. Conclusion: To our knowledge, we reported for the first time the efficacy of a PD1 inhibitor treatment in a patient presenting metastatic HCC-ICC due to viral cirrhosis and overexpressing PDL-1 after failure of two lines of treatment.

Treatment Resistant Mood Disorders Among LGBTQ People: Clinical Features and Response to Treatment

2021 ◽  
Vol 89 (9) ◽  
pp. S160-S161
Author(s):  
Fumie Oka ◽  
Kamile Weischedel ◽  
Amanda Bakian ◽  
Brian Mickey
Keyword(s):  
Mood Disorders ◽  
Clinical Features ◽  
Response To Treatment ◽  
Treatment Resistant

scholarly journals Indolent peritoneal mesothelioma: PI3K-mTOR inhibitors as a novel therapeutic strategy

ESMO Open ◽  
2017 ◽  
Vol 2 (1) ◽  
pp. e000101 ◽  
Author(s):  
Saoirse O Dolly ◽  
Cristina Migali ◽  
Nina Tunariu ◽  
Chiara Della-Pepa ◽  
Shelize Khakoo ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Mtor Inhibitors ◽  
Peritoneal Mesothelioma ◽  
Novel Therapeutic

scholarly journals Serum CEACAM1 Elevation Correlates with Melanoma Progression and Failure to Respond to Adoptive Cell Transfer Immunotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
R. Ortenberg ◽  
S. Sapoznik ◽  
D. Zippel ◽  
R. Shapira-Frommer ◽  
O. Itzhaki ◽  
...  
Keyword(s):  
Strong Predictor ◽  
Xenograft Model ◽  
Tumor Burden ◽  
Adoptive Cell Transfer ◽  
Screening Tools ◽  
Response To Treatment ◽  
Tumor Biomarker ◽  
Melanoma Patients ◽  
First Time

Malignant melanoma is a devastating disease whose incidences are continuously rising. The recently approved antimelanoma therapies carry new hope for metastatic patients for the first time in decades. However, the clinical management of melanoma is severely hampered by the absence of effective screening tools. The expression of the CEACAM1 adhesion molecule on melanoma cells is a strong predictor of poor prognosis. Interestingly, a melanoma-secreted form of CEACAM1 (sCEACAM1) has recently emerged as a potential tumor biomarker. Here we add novel evidences supporting the prognostic role of serum CEACAM1 by using a mice xenograft model of human melanoma and showing a correlation between serum CEACAM1 and tumor burden. Moreover, we demonstrate that serum CEACAM1 is elevated over time in progressive melanoma patients who fail to respond to immunotherapy as opposed to responders and stable disease patients, thus proving a correlation between sCEACAM1, response to treatment, and clinical deterioration.

scholarly journals Epilepsy in children with perinatal arterial ischemic stroke

2021 ◽  
Author(s):  
Fabienne Kühne ◽  
Alexander Jungbluth ◽  
Joanna Schneider ◽  
Christoph Bührer ◽  
Christine Prager ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Ischemic Stroke ◽  
Neonatal Period ◽  
Refractory Epilepsy ◽  
Late Onset ◽  
Cognitive Outcome ◽  
Response To Treatment ◽  
Arterial Ischemic Stroke ◽  
Structural Epilepsy ◽  
Drug Refractory Epilepsy

Purpose: Perinatal ischemic stroke (PIS) is a frequent cause for perinatal brain structure defects resulting in epilepsy, cerebral palsy and disability. Since the severity of symptoms is variable, the aim of this study was to evaluate the outcome of children with PIS and seizures/epilepsy to aid parental counseling and therapy decisions. Material: We studied retrospectively patients with arterial PIS and structural epilepsy or seizures in the newborn treated at a single center in 2000-2019. Specifically, signs and symptoms of cerebral palsy (CP), developmental and motor delay, epilepsy and thrombophilia were assessed. Results: From the identified 69 individuals with arterial PIS, we only included the 50 patients (64% male) who had structural epilepsy at the time of investigation or previously in their medical history.The mean age of the included patients was 7.1 years (range 0.08-22) at last consultation. Infarct localisation was predominantly unilateral (86%), left sided (58%) and affecting the middle cerebral artery (94%). Genetic thrombophilia was identified in 52% of the patients examined with genetic testing. More than half of the individuals had CP (52%), and 38.5% had a cognitive outcome below average. First seizures occurred in the neonatal period in 58% of patients and developed into drug-refractory epilepsy in 24.1%. Children with late-onset of epilepsy were twice as likely to develop drug-refractory epilepsy (52.4%). Discussion: Our study shows that patients with PIS and seizures as common sequela often also develop CP. Children with later onset of epilepsy have a worse outcome. Patients with seizure onset in the neonatal period and reccuring seizures have a good response to treatment. Therefore, early diagnosis, follow-up examination and adequate therapy are important. Most children need intensive physiotherapy and speech therapy; however, participation in life is usually age-appropriate.

Multinodular and vacuolating neuronal tumor associated with focal cortical dysplasia in a child with refractory epilepsy: a case report and brief review of literature

2020 ◽  
Vol 36 (7) ◽  
pp. 1557-1561 ◽  
Author(s):  
Lídia Nunes Dias ◽  
Santiago Candela-Cantó ◽  
Cristina Jou ◽  
Javier Aparicio Calvo ◽  
Sergio García-García ◽  
...  
Keyword(s):  
Case Report ◽  
Refractory Epilepsy ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Review Of Literature ◽  
Neuronal Tumor

Enhanced MR conspicuity of Type IIb focal cortical dysplasia by T1WI with CHESS: Two case reports

2020 ◽  
pp. 10.1212/CPJ.0000000000000987
Author(s):  
Midori Kusama ◽  
Noriko Sato ◽  
Zen-ichi Tanei ◽  
Yukio Kimura ◽  
Masaki Iwasaki ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Chemical Shift ◽  
Refractory Epilepsy ◽  
Focal Cortical Dysplasia ◽  
Case Reports ◽  
Cortical Dysplasia ◽  
Fat Suppression ◽  
Developmental Anomaly ◽  
Mri Findings ◽  
Mr Sequences

Focal cortical dysplasia (FCD) is a congenital developmental anomaly that is one of the leading causes of refractory epilepsy. MRI is an essential examination and T1WI, T2WI, and FLAIR images are commonly used MR sequences for delineating FCD.1 However, these MRI findings are often insufficiently clear. We experienced two FCD cases that were much better visualized by using T1WI with chemical shift selective (CHESS) than with T2WI and FLAIR images. CHESS is the most frequently used fat suppression pulse in clinical practice. We report two cases in which CHESS clearly demonstrated FCD, and compare the cases' pathology and MRI findings.

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