Epilepsy and Comorbidities: Towards unraveling the common underlying mechanisms

Epilepsy is a chronic neurological disorder characterized by the rapid occurrence of epileptic seizures affecting approximately 70 million people worldwide. The quality of life of people with epilepsy (PWE) is challenged by a series of comorbidities that might include neurologic and neuropsychiatric disorders (cognitive decline, depression, anxiety, schizophrenia, and autism) as well as metabolic, cardiovascular and respiratory diseases. Neurobehavioral and other comorbidities might share a reciprocal and complex relationship with epileptogenesis and ictogenesis thus biomarkers of the former might be useful for the prediction of the latter and vice versa. This bidirectional relationship between epilepsy and associated comorbidities has attracted significant attention in recent years as supported by data showing that one half of PWE demonstrate cognitive impairments, 30-50% depressive behavior, 10-25% anxiety disorders and 5-40% autism or autism spectrum disorder (ASD). In the past decades, epilepsy-related neurobehavioral comorbidities have been critically discussed, but the current need in unraveling the precise mechanism associated with epilepsy and these neurobehavioral comorbidities is unmet. The precise understanding of the mechanistic pathway underlying these epilepsy-associated comorbid conditions could be instrumental in developing therapeutic interventions that might modify seizure burden and accompanying comorbid conditions.

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Systematic Review - Time To Malignant Transformation In Low Grade Gliomas: Predicting A Catastrophic Event With Clinical, Neuroimaging And Molecular Markers

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab101 ◽

2021 ◽

Author(s):

Zabina Satar ◽

Gary Hotton ◽

George Samandouras

Keyword(s):

Malignant Transformation ◽

Epileptic Seizures ◽

Therapeutic Interventions ◽

Low Grade ◽

Invasive Treatment ◽

Who Grade ◽

Grade Ii ◽

Cortical Involvement ◽

Impaired Quality

Abstract Background Despite an initially indolent course, all WHO grade II, LGGs inevitably transform to malignant, WHO grades III and IV, without current curative options. Malignant transformation (MT) remains unpredictable with limited prognostic markers to steer timing of interventions. The aim of this study was to review and assign predictive value to specific clinical, molecular and radiological markers impacting MT, thereby justifying timely therapeutic interventions. Methods Searches of MEDLINE, Embase and Cochrane databases were conducted from inception to April 28, 2021 and outputs were analysed in accordance with PRISMA protocol. Results From an initial 5,032 articles, 31 articles were included, totalling 5,193 patients. Forty-three prognostic factors were registered to significantly impact MT. These were categorised as 7 clinical; 14 neuroimaging; 8 biological/molecular; 3 volumetric; 5 topological; 3 histological; and 3 treatment-related. Following analysis, 10 factors were highlighted: the pre-operative prognosticators were 1. presentation with epileptic seizures; 2. VDE >8mm/year; 3. VDE >4mm/year; 4. rCBV >1.75; 5. PTV ≥5 cm (65ml); 6. PTV ≥100 ml; and 7. cortical involvement. The post-operative prognosticators were 1.IDH-wt; 2. TP53 mutation; and 3. temozolomide monotherapy. Conclusions The management of LGGs remains controversial, as conservative and invasive treatment may be associated with MT and impaired quality of life, respectively. Our review indicates that MT can be predicted by specific metrics in VDE, PTV and rCBV, alongside cortical involvement. Additionally, patients with IDH-wt tumours TP53 mutations, or receiving TMZ monotherapy are more likely to undergo MT. Our data may form the basis of a predictive scoring system.

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Understanding the Link Between Allergy and Neurodevelopmental Disorders: A Current Review of Factors and Mechanisms

Frontiers in Neurology ◽

10.3389/fneur.2020.603571 ◽

2021 ◽

Vol 11 ◽

Author(s):

Regena Xin Yi Chua ◽

Michelle Jia Yu Tay ◽

Delicia Shu Qin Ooi ◽

Kewin Tien Ho Siah ◽

Elizabeth Huiwen Tham ◽

...

Keyword(s):

Neurodevelopmental Disorders ◽

Sleep Disturbances ◽

Environmental Pollutants ◽

Allergic Diseases ◽

Epidemiological Studies ◽

Autism Spectrum ◽

Convincing Evidence ◽

Hyperactivity Disorder ◽

Underlying Mechanisms

Both allergic diseases and neurodevelopmental disorders are non-communicable diseases (NCDs) that not only impact on the quality of life and but also result in substantial economic burden. Immune dysregulation and inflammation are typical hallmarks in both allergic and neurodevelopmental disorders, suggesting converging pathophysiology. Epidemiological studies provided convincing evidence for the link between allergy and neurodevelopmental diseases such as attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Possible factors influencing the development of these disorders include maternal depression and anxiety, gestational diabetes mellitus, maternal allergic status, diet, exposure to environmental pollutants, microbiome dysbiosis, and sleep disturbances that occur early in life. Moreover, apart from inflammation, epigenetics, gene expression, and mitochondrial dysfunction have emerged as possible underlying mechanisms in the pathogenesis of these conditions. The exploration and understanding of these shared factors and possible mechanisms may enable us to elucidate the link in the comorbidity.

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The Cross Talk between Underlying Mechanisms of Multiple Sclerosis and Epilepsy May Provide New Insights for More Efficient Therapies

Pharmaceuticals ◽

10.3390/ph14101031 ◽

2021 ◽

Vol 14 (10) ◽

pp. 1031

Author(s):

Atefeh Rayatpour ◽

Sahar Farhangi ◽

Ester Verdaguer ◽

Jordi Olloquequi ◽

Jesus Ureña ◽

...

Keyword(s):

Multiple Sclerosis ◽

General Population ◽

Neurodegenerative Diseases ◽

Cross Talk ◽

Huntington Disease ◽

Neurological Disorders ◽

Epileptic Seizures ◽

Bidirectional Association ◽

The Common ◽

Underlying Mechanisms

Despite the significant differences in pathological background of neurodegenerative diseases, epileptic seizures are a comorbidity in many disorders such as Huntington disease (HD), Alzheimer’s disease (AD), and multiple sclerosis (MS). Regarding the last one, specifically, it has been shown that the risk of developing epilepsy is three to six times higher in patients with MS compared to the general population. In this context, understanding the pathological processes underlying this connection will allow for the targeting of the common and shared pathological pathways involved in both conditions, which may provide a new avenue in the management of neurological disorders. This review provides an outlook of what is known so far about the bidirectional association between epilepsy and MS.

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Quality of Life and Depressive Symptomatology in Mothers of Individuals with Autism

Psico-USF ◽

10.1590/1413-82712015200312 ◽

2015 ◽

Vol 20 (3) ◽

pp. 505-515 ◽

Cited By ~ 1

Author(s):

Josieli Piovesan ◽

Silvana Alba Scortegagna ◽

Ana Carolina Bertoletti De Marchi

Keyword(s):

Quality Of Life ◽

Depressive Symptoms ◽

Low Income ◽

Depressive Symptomatology ◽

Depression Scale ◽

Autism Spectrum ◽

Therapeutic Interventions ◽

World Health ◽

World Health Organization Quality

Abstract This study aimed to investigate the Quality of Life (QOL) and the presence of the depressive symptoms in mothers of individuals with Autism Spectrum Disorder (ASD). Participants included 40 women, between 28 and 72 years old, married, with medium-low income and education levels, and with children between 10 and 40 years old. The instruments used were a social demographic and health characterization questionnaire, the World Health Organization Quality of Life (WHOQOL-Bref) questionnaire, the Beck Depression Inventory and Beck Hopelessness Scale (BDI-II and BHS), and the Baptista Depression Scale Adult Version (EBADEP A). The quality of life and the presence of depressive symptoms in mothers did not show significant correlation with the child's age. However, there was high and negative correlation between the quality of life and high levels of depressive symptoms and moderate correlation between environment and income. It concludes the necessity of preventive and therapeutic interventions for these mothers.

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Oral Submucous Fibrosis: A Review on Etiopathogenesis, Diagnosis, and Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms20122940 ◽

2019 ◽

Vol 20 (12) ◽

pp. 2940 ◽

Cited By ~ 15

Author(s):

Yin-Hwa Shih ◽

Tong-Hong Wang ◽

Tzong-Ming Shieh ◽

Yu-Hsin Tseng

Keyword(s):

Oral Submucous Fibrosis ◽

Mouth Opening ◽

Burning Sensation ◽

Therapeutic Interventions ◽

Future Research ◽

Oral Health Literacy ◽

Diagnostic Biomarkers ◽

Submucous Fibrosis ◽

Underlying Mechanisms

Oral submucous fibrosis (OSF) is characterized by abnormal collagen deposition. It is a precancerous disorder and transforms into a malignant tumor in 1.5–15% of all cases. Symptoms include submucous fibrosis, ulceration, xerostomia, a burning sensation, and restricted mouth opening. All of these greatly interfere with patient quality of life. The present review introduces OSF from a molecular perspective and summarizes what is known about its underlying mechanisms, diagnostic biomarkers, and therapeutic interventions. In addition to the aggressive treatment of OSF, its prevention is also important. Future research should, therefore, focus on improving the oral health literacy of the patients susceptible to OSF.

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A structured group intervention (TüTASS) with focus on self-perception and mindfulness for children with autism spectrum disorder, ASD. A pilot study

European Archives of Psychiatry and Clinical Neuroscience ◽

10.1007/s00406-021-01281-9 ◽

2021 ◽

Author(s):

Laura Drüsedau ◽

Anja Schoba ◽

Annette Conzelmann ◽

Alexander Sokolov ◽

Martin Hautzinger ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Pilot Study ◽

Externalizing Behavior ◽

Group Intervention ◽

Autism Spectrum ◽

Therapeutic Interventions ◽

Social Responsiveness ◽

Behavioral Disturbances ◽

Spectrum Disorders

AbstractAutism spectrum disorders (ASD) represent a set of long-lasting severe neurodevelopmental conditions and effective therapeutic interventions are needed. Recent research points to the importance of including mindfulness-based elements to improve emotion and body perception in the psychotherapy of patients with ASD. Therefore, we developed a structured group psychotherapy program The Tübinger Training for Autism Spectrum Disorders (Tübinger Training für Autismus-Spektrum-Störungen; TüTASS) which focuses on mindfulness-based training elements. This pilot study accompanying the TüTASS reports the first results on the feasibility of the program with a pre-post comparison of 25 treated children with ASD. The psychometric assessment comprised five standardized questionnaires/ scales evaluating on the basis of parents and patients self-reports the child’s social responsiveness, behavior, strengths and difficulties, quality of life, and depressive symptoms before and after training completion. The results indicated that upon training completion, symptoms with respect to emotional and social problems, externalizing behavior, and attentional and schizoid-compulsive behavior substantially declined. In a questionnaire assessing feasibility and quality of the group training, patients and parents found the therapy highly beneficial, especially as to the focus on emotions and body, and strengths and failures. This training program was developed to bridge the gap of lacking mindfulness-based interventions with the aim to optimize the course of ASD, especially with respect to behavioral disturbances and social-emotional problems.

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Co-occurrence of Autism Spectrum Disorder and Down Syndrome

The Oxford Handbook of Down Syndrome and Development ◽

10.1093/oxfordhb/9780190645441.013.23 ◽

2021 ◽

Author(s):

Cory Shulman

Keyword(s):

Autism Spectrum Disorder ◽

Down Syndrome ◽

Dual Diagnosis ◽

Combined Treatment ◽

Autism Spectrum ◽

Research Literature ◽

Spectrum Disorder ◽

Therapeutic Interventions ◽

Incidental Teaching ◽

Underlying Mechanisms

Autism spectrum disorder (ASD) refers to a heterogeneous condition characterized by deficits in social communication and the presence of restricted, repetitive, and stereotypic behaviors, interests, or activities. While some neurodevelopmental disorders have a well-established correlation with ASD, people continue to believe that because individuals with Down syndrome are characteristically perceived as affectionate and engaging, a diagnosis of ASD is contradictory. However, some people with Down syndrome indeed do meet diagnostic criteria for ASD and this chapter examines the research literature regarding Down syndrome and ASD, presenting information regarding the establishment of a diagnosis of ASD in individuals with Down syndrome and research techniques to understand the dual diagnosis of ASD and Down syndrome. Behavioral manifestations of ASD in Down syndrome are presented and research methodologies which address possible underlying mechanisms in Down syndrome and ASD are surveyed. Finally, the need for specification of behavioral profiles for individuals with a dual diagnosis of Down syndrome and ASD, in order to design and implement appropriate therapeutic interventions, is highlighted. Once a person with Down syndrome is diagnosed with ASD, he or she should automatically receive a combined treatment approach incorporating direct instruction, natural environment teaching, and incidental teaching. The manifestation of ASD in individuals with Down syndrome can shed light on our understanding of how ASD and intellectual disability are associated and what impact these diagnoses have on individuals and their families. This knowledge can help shape public policy and our research agenda in the areas of ASD, intellectual impairment, and Down syndrome.

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Malignant Gastrointestinal Obstruction: Options for Decompression and Nutrition

Digestive Disease Interventions ◽

10.1055/s-0040-1718390 ◽

2020 ◽

Vol 04 (03) ◽

pp. 311-322

Author(s):

Robert J. Litwin ◽

Johanna L. Chan ◽

Steven Y. Huang

Keyword(s):

Clinical Presentation ◽

Practice Patterns ◽

Patient Care Team ◽

Therapeutic Interventions ◽

Collaborative Approach ◽

Malignant Bowel Obstruction ◽

Advanced Malignancy ◽

Gastrointestinal Obstruction ◽

Malignant Gastrointestinal Obstruction

AbstractMalignant bowel obstruction (MBO) is a relatively common condition affecting patients with advanced malignancy. Therapeutic interventions should be aimed at maintaining quality of life. Given the lack of prospective controlled studies in this patient population, patient management is often based on local practice patterns and anecdotal experience. To foster a collaborative approach among the members of the patient care team involving internal medicine, oncology, palliative care, clinical nutrition, surgery, gastroenterology, and interventional radiology physicians, it is important to improve our understanding of MBO. The purpose of this article is to describe the clinical presentation, pathophysiology, as well as medical, surgical, and nonsurgical palliative options available to patients with MBO for purposes of decompression and nutrition.

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The concept of motivation for effective credit risk management

Finance and Credit ◽

10.24891/fc.26.11.2567 ◽

2020 ◽

Vol 26 (11) ◽

pp. 2567-2593

Author(s):

M.V. Pomazanov

Keyword(s):

Risk Management ◽

Economic Modeling ◽

Type I ◽

Credit Risk Management ◽

Curve Modeling ◽

Business Functions ◽

The Common ◽

Lending Decisions ◽

The One

Subject. The study addresses the improvement of risk management efficiency and the quality of lending decisions made by banks. Objectives. The aim is to present the bank management with a fair algorithm for risk management motivation on the one hand, and the credit management (business) on the other hand. Within the framework of the common goal to maximize risk-adjusted income from loans, this algorithm will provide guidelines for ‘risk management’ and ‘business’ functions on how to improve individual and overall efficiency. Methods. The study employs the discriminant analysis, type I and II errors, Lorentz curve modeling, statistical analysis, economic modeling. Results. The paper offers a mechanism for assessing the quality of risk management decisions as opposed to (or in support of) decisions of the lending business when approving transactions. The mechanism rests on the approach of stating type I and II errors and the corresponding classical metric of the Gini coefficient. On the ‘business’ side, the mechanism monitors the improvement or deterioration of the indicator of changes in losses in comparison with the market average. Conclusions. The study substantiates the stimulating ‘rules of the game’ between the ‘business’ and ‘risk management’ to improve the efficiency of the entire business, to optimize interactions within the framework of internal competition. It presents mathematical tools to calculate corresponding indicators of the efficiency of internally competing entities.

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Dysregulation of DNA methylation during development as a potential mechanisms contributing to obsessive compulsive disorders and autism

10.31234/osf.io/udfya ◽

2019 ◽

Author(s):

German I. Todorov ◽

Karthikeyan Mayilvahanan ◽

David Ashurov ◽

Catarina Cunha

Keyword(s):

Mouse Model ◽

Autism Spectrum ◽

Obsessive Compulsive ◽

Cancer Treatments ◽

Knock Out ◽

Treatment Priority ◽

Underlying Mechanisms ◽

Knock Out Mice ◽

Obsessive Compulsive Disorders ◽

Compulsive Disorders

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder, that is raising at a concerning rate. However, underlying mechanisms are still to be discovered. Obsessions and compulsions are the most debilitating aspect of these disorders (OCD), and they are the treatment priority for patients. SAPAP3 knock out mice present a reliable mouse model for repetitive compulsive behavior and are mechanistically closely related to the ASD mouse model Shank3 on a molecular level and AMPA receptor net effect. The phenotype of SAPAP3 knock out mice is obsessive grooming that leads to self-inflicted lesions by 4 months of age. Recent studies have accumulated evidence, that epigenetic mechanisms are important effectors in psychiatric conditions such as ASD and OCD. Methylation is the most studied mechanism, that recently lead to drug developments for more precise cancer treatments. We injected SAPAP3 mice with an epigenetic demethylation drug RG108 during pregnancy and delayed the onset of the phenotype in the offspring by 4 months. This result gives us clues about possible mechanism involved in OCD and ASD. Additionally, it shows that modulation of methylation mechanisms during development might be explored as a preventative treatment in the cases of high inherited risk of certain mental health conditions.

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