scholarly journals Clinical and histopathological outcomes in patients with SCN1A mutations undergoing surgery for epilepsy

2015 ◽  
Vol 16 (6) ◽  
pp. 668-674 ◽  
Author(s):  
Karen L. Skjei ◽  
Ephraim W. Church ◽  
Brian N. Harding ◽  
Mariarita Santi ◽  
Katherine D. Holland-Bouley ◽  
...  
Keyword(s):  
Molecular Layer ◽  
Genetic Defect ◽  
Case Series ◽  
Intractable Epilepsy ◽  
Surgical Pathology ◽  
Dravet Syndrome ◽  
Pathophysiological Mechanism ◽  
Age At Surgery ◽  
Wide Range ◽  
Neuropathological Finding

OBJECT Mutations in the sodium channel alpha 1 subunit gene (SCN1A) have been associated with a wide range of epilepsy phenotypes including Dravet syndrome. There currently exist few histopathological and surgical outcome reports in patients with this disease. In this case series, the authors describe the clinical features, surgical pathology, and outcomes in 6 patients with SCN1A mutations and refractory epilepsy who underwent focal cortical resection prior to uncovering the genetic basis of their epilepsy. METHODS Medical records of SCN1A mutation-positive children with treatment-resistant epilepsy who had undergone resective epilepsy surgery were reviewed retrospectively. Surgical pathology specimens were reviewed. RESULTS All 6 patients identified carried diagnoses of intractable epilepsy with mixed seizure types. Age at surgery ranged from 18 months to 20 years. Seizures were refractory to surgery in every case. Surgical histopathology showed evidence of subtle cortical dysplasia in 4 of 6 patients, with more neurons in the molecular layer of the cortex and white matter. CONCLUSIONS Cortical resection is unlikely to be beneficial in these children due to the genetic defect and the unexpected neuropathological finding of mild diffuse malformations of cortical development. Together, these findings suggest a diffuse pathophysiological mechanism of the patients’ epilepsy which will not respond to focal resective surgery.

scholarly journals An Interoperability Platform Enabling Reuse of Electronic Health Records for Signal Verification Studies

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Mustafa Yuksel ◽  
Suat Gonul ◽  
Gokce Banu Laleci Erturkmen ◽  
Ali Anil Sinaci ◽  
Paolo Invernizzi ◽  
...  
Keyword(s):  
Real Life ◽  
Case Series ◽  
Background Information ◽  
Data Sets ◽  
Local Data ◽  
Lombardy Region ◽  
Common Information ◽  
Spontaneous Reports ◽  
Wide Range ◽  
Common Information Model

Depending mostly on voluntarily sent spontaneous reports, pharmacovigilance studies are hampered by low quantity and quality of patient data. Our objective is to improve postmarket safety studies by enabling safety analysts to seamlessly access a wide range of EHR sources for collecting deidentified medical data sets of selected patient populations and tracing the reported incidents back to original EHRs. We have developed an ontological framework where EHR sources and target clinical research systems can continue using their own local data models, interfaces, and terminology systems, while structural interoperability and Semantic Interoperability are handled through rule-based reasoning on formal representations of different models and terminology systems maintained in the SALUS Semantic Resource Set. SALUS Common Information Model at the core of this set acts as the common mediator. We demonstrate the capabilities of our framework through one of the SALUS safety analysis tools, namely, the Case Series Characterization Tool, which have been deployed on top of regional EHR Data Warehouse of the Lombardy Region containing about 1 billion records from 16 million patients and validated by several pharmacovigilance researchers with real-life cases. The results confirm significant improvements in signal detection and evaluation compared to traditional methods with the missing background information.

scholarly journals Germline PRKACA amplification causes variable phenotypes that may depend on the extent of the genomic defect: molecular mechanisms and clinical presentations

2015 ◽  
Vol 172 (6) ◽  
pp. 803-811 ◽  
Author(s):  
Maya B Lodish ◽  
Bo Yuan ◽  
Isaac Levy ◽  
Glenn D Braunstein ◽  
Charalampos Lyssikatos ◽  
...  
Keyword(s):  
Copy Number ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Genetic Defect ◽  
Molecular Cytogenetics ◽  
Case Series ◽  
Sporadic Case ◽  
Genomic Rearrangements ◽  
Clinical Presentations ◽  
Depth Analysis

ObjectiveWe have recently reported five patients with bilateral adrenocortical hyperplasia (BAH) and Cushing's syndrome (CS) caused by constitutive activation of the catalytic subunit of protein kinase A (PRKACA). By doing new in-depth analysis of their cytogenetic abnormality, we attempted a better genotype–phenotype correlation of theirPRKACAamplification.DesignThis study is a case series.MethodsMolecular cytogenetic, genomic, clinical, and histopathological analyses were performed in five patients with CS.ResultsReinvestigation of the defects of previously described patients by state-of-the-art molecular cytogenetics showed complex genomic rearrangements in the chromosome 19p13.2p13.12 locus, resulting in copy number gains encompassing the entirePRKACAgene; three patients (one sporadic case and two related cases) were observed with gains consistent with duplications, while two sporadic patients were observed with gains consistent with triplications. Although all five patients presented with ACTH-independent CS, the three sporadic patients had micronodular BAH and underwent bilateral adrenalectomy in early childhood, whereas the two related patients, a mother and a son, presented with macronodular BAH as adults. In at least one patient,PRKACAtriplication was associated with a more severe phenotype.ConclusionsConstitutional chromosomalPRKACAgene amplification is a recently identified genetic defect associated with CS, a trait that may be inherited in an autosomal dominant manner or occurde novo. Genomic rearrangements can be complex and can result in different copy number states of dosage-sensitive genes, e.g., duplication and triplication.PRKACAamplification can lead to variable phenotypes clinically and pathologically, both micro- and macro-nodular BAH, the latter of which we speculate may depend on the extent of amplification.

Critical Values in Anatomic Pathology

2006 ◽  
Vol 130 (5) ◽  
pp. 638-640 ◽  
Author(s):  
Jan F. Silverman ◽  
Telma C. Pereira
Keyword(s):  
Patient Safety ◽  
Improve Patient Safety ◽  
Clinical Pathology ◽  
Critical Values ◽  
Surgical Pathology ◽  
Anatomic Pathology ◽  
Wide Range ◽  
Enhance Patient Safety ◽  
Pathology Reports ◽  
Improve Patient

Abstract Similar to critical values (CVs) in clinical pathology, occasional diagnoses in surgical pathology and cytology could require immediate notification of the physician to rapidly initiate treatment. However, there are no established CV guidelines in anatomic pathology. A retrospective review of surgical pathology reports was recently conducted to study the incidence of CVs in surgical pathology and to survey the perceptions of pathologists and clinicians about CVs in surgical pathology, with a similar analysis of CVs performed in cytology. The results indicated that CVs in surgical pathology and cytology are uncommon but not rare and that there is a wide range of opinion among pathologists and between pathologists and clinicians about the need for an immediate telephone call and about the degree of urgency. It was obvious from the study that there is a lack of consensus in identifying what constitutes surgical pathology and cytology CV cases. Since the Institute of Medicine's report on medical errors, there has been an increasing number of initiatives to improve patient safety. Having guidelines for anatomic pathology CVs could enhance patient safety, in contrast to the current practice in which CV cases are managed based on common sense and on personal experience. Therefore, a discussion involving the pathology community might prove useful in an attempt to establish anatomic pathology CV guidelines that could represent a practice improvement.

scholarly journals Tubularized proximally-incised plate in distal/midshaft hypospadias repair

2017 ◽  
Vol 39 (2) ◽  
Author(s):  
Antonio Marte ◽  
Lucia Pintozzi
Keyword(s):  
Perioperative Complications ◽  
Foley Catheter ◽  
Case Series ◽  
Functional Results ◽  
Inclusion Criteria ◽  
Urethral Plate ◽  
Age At Surgery ◽  
Long Term Follow Up

The aim of this study was to verify the validity, feasibility, and the functional results, by uroflowmetry, of Tubularized proximallyincised plate technique in selected case of distal/midshaft hypospadias. Out of 120 patients scheduled to undergo TIP (or Snodgrass) procedure, 23 were selected between January 2013 and January 2016 (19.1%). This case series comprised 16 patients with distal and 7 with midshaft hypospadias. Mean age at surgery was 2.9 years. The inclusion criteria were a deep and wide glandular groove and a proximal narrow urethral plate. The procedure was carried out as described by Snodgrass but the incision of the urethral plate, including the mucosal and submucosal tissue, was made only proximally, between the original meatus and the glandular groove in no case extending to the entire length of the plate. Postoperatively a foley catheter was left in place from 4 to 7 days. Uroflowmetry was performed when the patients age ranged from 2.5 to 5.7 years (mean age 3.11 years and mean follow-up 1.8 years, body surface 2). No patient presented fistulas nor perioperative complications. At uroflowmetry, eighteen patients presented values above the 25<sup>th</sup> percentile and 5 showed a borderline flow. All patients in this group remained stable without urinary symptoms. In selected cases, the tubularized proximally-incised plate yields satisfactory cosmetic and functional results for the treatment of midshaft proximal hypospadias. A long-term follow-up study is needed for further evaluation. Patient selection is crucial for the success of this technique.

scholarly journals Safety and efficacy of posterior iris claw intraocular lens fixation in aphakic patients

2018 ◽  
Vol 16 (2) ◽  
pp. 124-133
Author(s):  
Rosemary Tomy ◽  
Rajkumar Maheshwari ◽  
Ansa Parveen Kunhu Muhammed ◽  
Venkataramana Kalikivayi ◽  
Sajeev Cherian Jacob
Keyword(s):  
Intraocular Lens ◽  
Anterior Segment ◽  
Case Series ◽  
Visual Outcome ◽  
Applanation Tonometry ◽  
Long Term Results ◽  
Retrospective Case ◽  
Case Series Study ◽  
Wide Range

Purpose: To assess the indications and visual outcome of eyes undergoing posterior iris fixated intraocular lens (IFIOL) implantation for aphakia, to identify reasons for poor visual outcome, and report occurrence of complications. Methods: In this retrospective case series study, all cases of posterior IFIOL fixation performed over a 30-month period were identified retrospectively. Preoperative and postoperative evaluations comprised objective and subjective refraction, best corrected visual acuity (BCVA), slit lamp biomicroscopy, applanation tonometry, and dilated fundus examination. Results: Fifty-six eyes of 56 patients were analyzed. Mean age was 60.55 ± 17.2 years. The most common indication for IFIOL implantation was surgical aphakia following complicated cataract surgery (n = 33; 58.9%) followed by trauma (n = 10; 17.9%), dropped nucleus/IOL during primary surgery (n = 6; 10.7%), and subluxated/dislocated lens-induced glaucomas (n = 5; 8.9%). BCVA better than or equal to their preoperative BCVA was achieved in 96.43% patients. The surgical aphakia and paediatric/adolescent groups had the best visual results while the dropped nucleus/IOL group and subluxated lens-induced glaucoma groups fared poorly. On the long-term follow-up visit, the most common complication noted was pigment dusting on the corneal endothelium (65.7%). Conclusion: The long-term results suggest that posterior IFIOL implantation is a safe and effective method for correction of aphakia and can be used for a wide range of indications in eyes without adequate capsule support. It may be considered an easier and faster alternative with minimal manipulation to anterior segment structures in paediatric and post-traumatic aphakic eyes.

scholarly journals The use of the ketogenic diet in the treatment of epileptic encephalopathies

2018 ◽  
Author(s):  
Roberto Caraballo
Keyword(s):  
Ketogenic Diet ◽  
Case Reports ◽  
Case Series ◽  
Dravet Syndrome ◽  
Epilepsy Syndrome ◽  
Behavioral Disturbances ◽  
Paroxysmal Activity ◽  
Epileptic Encephalopathies ◽  
Progressive Encephalopathy ◽  
Epileptic Syndromes

Epileptic encephalopathies(EE) are severe conditions characterized by paroxysmal activity on the electroencephalogram (EEG) that is often aggressive, seizures that are commonly multi-form and intractable, and severe cognitive and behavioral disturbances that present or worsen after the onset of epilepsy. The ketogenic diet (KD) has been shown to be effective in the treatment of refractory epileptic encephalopathies, and has been suggested as an early treatment option in very young children. Although the experience is often anecdotal and mostly consists of case reports and case series, the aim of this study was to present our own experience and an overview of the current literature on the diet in patients with EE. Some encephalopathies, such as epilepsy with myoclonic and atonic seizures, West syndrome, Dravet syndrome, or Lennox-Gastaut syndrome, are well recognized and known to have a good response to the ketogenic diet, while others are more rare or only recently identified, such as epilepsy with focal migrating seizures in infancy, febrile infection-related epilepsy syndrome, or myclonic status in non-progressive encephalopathy, about which little is known and the KD is only tried in sporadic cases. EE are typically refractory to the antiepileptic drugs and the KD  should be considered earlier in the therapeutic scheme of these severe epileptic syndromes. The KD including the oral formula may be considered in all pediatric patients with EE even in infancy.

Pathologic Features of Dysplasia and Accompanying Alterations Observed in Surgical Specimens from Patients with Intractable Epilepsy

2004 ◽  
Vol 19 (3) ◽  
pp. 341-350 ◽  
Author(s):  
Akiyoshi Kakita ◽  
Shigeki Kameyama ◽  
Shintaro Hayashi ◽  
Hiroshi Masuda ◽  
Hitoshi Takahashi
Keyword(s):  
White Matter ◽  
Focal Cortical Dysplasia ◽  
Molecular Layer ◽  
Cortical Development ◽  
Neurofibrillary Tangle ◽  
Intractable Epilepsy ◽  
Clinical Findings ◽  
Cortical Layer ◽  
Pathologic Features ◽  
Cortical Dysplasias

Malformations caused by abnormalities of cortical development, or cortical dysplasias, were examined in surgical specimens from 108 patients with medically intractable epilepsy to determine the scope of histopathologic changes. The relevance of the clinical findings was also evaluated. Various types and degrees of dysplastic features were observed in various combinations, including architectural abnormalities, an increased number of neurons in the molecular layer and/or cortical layer II, neuronal clustering, an increased number of satellite oligodendrocytes, abnormal gyration, single and/or aggregates of heterotopic neurons in the white matter, and the appearance of cytologically abnormal cells, such as giant or dysmorphic neurons and balloon cells. In the temporal lobe specimens, microdysgenesis (corresponding to mild malformations caused by abnormalities of cortical development and type IA/B focal cortical dysplasias) was more frequently observed than Taylor-type focal cortical dysplasia (type IIA/B), whereas in the frontal lobe specimens, the frequency of occurrence of both types was even. The ages at seizure onset and surgery of patients with the latter type were significantly lower than those of patients with the former. On the other hand, prominent astrocytosis in the cortex and white matter was evident in all cases, and many corpora amylacea and neurofibrillary tangle—like inclusions were observed in a subset of cases. An ultrastructural investigation revealed dilatation of the postsynaptic dendritic spines and shafts in the cortex and features indicating the occurrence in the white matter of demyelination followed by remyelination. Thus, with regard to the epileptogenic lesions, although dysplastic changes constitute the pathogenetic basis, the overlapping subsequent degenerative processes involving synapses, dendrites, and axons might contribute to the development of epileptogenic processes. Astrocytes might also actively participate in the development of the pathogenesis of epilepsy. ( J Child Neurol 2005;20:341—350).

Case Series of Skull Base Meningioma Resection in the Octogenarian Population

2021 ◽  
Author(s):  
Dorian M. Kusyk ◽  
Gordon Mao ◽  
Rocco Dabecco ◽  
Alexander K. Yu
Keyword(s):  
Skull Base ◽  
Case Series ◽  
The Elderly ◽  
Outcome Data ◽  
Skull Base Tumor ◽  
Geriatric Population ◽  
Perioperative Morbidity ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Skull Base Meningiomas

Abstract Introduction The geriatric population is the fastest growing segment of the American population, and octogenarians are increasingly seen by neurosurgeons for relatively common lesions such as meningiomas. Unfortunately, providers do not have clear data to guide decision-making regarding these lesions, particularly if they involve the skull base. Current research in outcomes among the elderly looks at a wide range of ages, often anyone older than 65. Previous studies in octogenarians report a wide-range of mortality rates and do not focus on skull base lesions. This paper strives to clarify the experiences and outcomes of octogenarians. Patients and Methods This retrospective series reviews skull base tumor surgeries performed at a single academic institution over the past 15 years in octogenarian patients. Primary endpoint was 30-day mortality; however, potential risk factors, perioperative morbidity, postdischarge disposition, and longer term follow-up were also captured. Multivariate logistic regression was performed to identify relevant perioperative and medical characteristics that increases the risk of adverse events. Results Fourteen patients underwent craniotomies for skull base procedures with an average age of 84.5, with a 14% 30-day mortality rate. One patient required a tracheostomy on discharge and approximately half were able to either go home or rehabilitation after their procedure. On statistical analysis, there were no noted characteristics that predisposed any of the patients to a poorer outcome. Conclusion Octogenarian patients were able to tolerate surgery for skull base meningiomas resection. This outcome data may be used to inform surgical decision and guide conversation with patients and their families.

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