Extinguishing Febrile Infection-Related Epilepsy Syndrome: Pipe Dream or Reality?

2020 ◽  
Vol 40 (02) ◽  
pp. 263-272 ◽  
Author(s):  
Eric T. Payne ◽  
Sookyong Koh ◽  
Elaine C. Wirrell
Keyword(s):  
Interleukin 1 ◽  
Treatment Strategies ◽  
Febrile Illness ◽  
Epileptic Encephalopathy ◽  
Epilepsy Syndrome ◽  
Collaborative Studies ◽  
High Incidence ◽  
Neurocognitive Outcomes ◽  
Children And Young Adults ◽  
Pipe Dream

AbstractFebrile infection-related epilepsy syndrome (FIRES) is a rare and devastating epileptic encephalopathy with historically abysmal neurocognitive outcomes, including a high incidence of mortality. It tends to affect children and young adults and is characterized by superrefractory status epilepticus following a recent febrile illness. Growing evidence suggests a heterogeneous etiology resulting in fulminant nonantibody-mediated neuroinflammation. For some children with FIRES, this aberrant neuroinflammation appears secondary to a functional deficiency in the endogenous interleukin-1 receptor antagonist. A precise etiology has not been identified in all FIRES patients, and current treatments are not always successful. Limited treatment evidence exists to guide choice, dosing, and duration of therapies. However, the ketogenic diet and certain targeted immunomodulatory treatments, including anakinra, appear safe and have been associated with relatively excellent clinical outcomes in some FIRES patients. Future prospective multicenter collaborative studies are needed to further delineate the FIRES heterogeneous disease pathophysiology and to determine the safety and efficacy of treatment strategies through a robust measurement of neurocognitive outcomes.

scholarly journals Dramatic Course of Paediatric Cryptogenic Febrile Infection-Related Epilepsy Syndrome with Unusual Chronic Phase Presentation—A Case Report with Literature Study

2021 ◽  
Vol 11 (8) ◽  
pp. 1030
Author(s):  
Natalia Rachfalska ◽  
Jerzy Pietruszewski ◽  
Justyna Paprocka
Keyword(s):  
Acute Phase ◽  
Cognitive Deficit ◽  
Chronic Phase ◽  
Febrile Illness ◽  
Refractory Status Epilepticus ◽  
Epileptic Encephalopathy ◽  
Epilepsy Syndrome ◽  
Literature Study ◽  
School Aged Children ◽  
Refractory Status

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a catastrophic, extremely rare epileptic encephalopathy. It strikes previously healthy school-aged children and is usually cryptogenic. Its dramatic onset with refractory status epilepticus is always preceded by a nonspecific febrile illness. The seizure activity in FIRES may last for several weeks with little to no response to antiepileptic treatment, usually resulting in the usage of anaesthetics. This acute phase is followed by a chronic, refractory epilepsy and cognitive deficit, that persist for the rest of the patient’s life. Still to this day no definite cause has been described. In this study we review the current finding in FIRES and describe a case of a 4-year-old patient with a dramatic course of the acute phase in FIRES and unusual presentation of the chronic phase, which is dominated by extrapyramidal symptoms such as dystonia. This case highlights that the clinical presentation of FIRES may differ from those frequently described in literature.

Febrile Infection-Related Epilepsy Syndrome (FIRES) with Multifocal Subcortical Infarcts, A New Imaging Phenotype

2018 ◽  
Vol 49 (05) ◽  
pp. 347-352 ◽  
Author(s):  
Ai Tan
Keyword(s):  
Treatment Plan ◽  
Febrile Illness ◽  
Epileptic Encephalopathy ◽  
Unknown Etiology ◽  
Epilepsy Syndrome ◽  
Clinical Criteria ◽  
School Aged Children ◽  
Appropriate Treatment ◽  
Confirmatory Tests ◽  
Occipital Lobes

AbstractFebrile infection-related epilepsy syndrome (FIRES) is a catastrophic epileptic encephalopathy of unknown etiology which occurs predominantly in school-aged children, following a febrile illness. The term FIRES was first proposed in 2010 by van Baalen et al. The etiology of FIRES remains elusive, although most believed that it is likely related to inappropriate activation of the innate immune system. It is often a diagnosis of exclusion as it lacks specific clinical criteria and/or confirmatory tests. Familiarity with the range of imaging phenotypes associated with FIRES is crucial as this will assist timely recognition and institution of appropriate treatment plan. With this in mind, the author would like to present a rare case of FIRES with extensive subcortical infarcts, predominantly in the temporo-occipital lobes. This has never been reported before and may represent a new imaging phenotype of FIRES. A detailed literature review, focusing on the various pattern of imaging phenotypes, in relation to patients' age and clinical outcome, will also be included.

scholarly journals Towards a Treatment for Neuroinflammation in Epilepsy: Interleukin-1 Receptor Antagonist, Anakinra, as a Potential Treatment in Intractable Epilepsy

2021 ◽  
Vol 22 (12) ◽  
pp. 6282
Author(s):  
Gaku Yamanaka ◽  
Yu Ishida ◽  
Kanako Kanou ◽  
Shinji Suzuki ◽  
Yusuke Watanabe ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Small Sample Size ◽  
Interleukin 1 ◽  
Intractable Epilepsy ◽  
Evidence Base ◽  
Small Sample ◽  
Epilepsy Syndrome ◽  
Interleukin 1 Receptor Antagonist ◽  
Epileptic Syndromes ◽  
Systemic Symptoms

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a unique catastrophic epilepsy syndrome, and the development of drug-resistant epilepsy (DRE) is inevitable. Recently, anakinra, an interleukin-1 receptor antagonist (IL-1RA), has been increasingly used to treat DRE due to its potent anticonvulsant activity. We here summarized its effects in 38 patients (32 patients with FIRES and six with DRE). Of the 22 patients with FIRES, 16 (73%) had at least short-term seizure control 1 week after starting anakinra, while the remaining six suspected anakinra-refractory cases were male and had poor prognoses. Due to the small sample size, an explanation for anakinra refractoriness was not evident. In all DRE patients, seizures disappeared or improved, and cognitive function improved in five of the six patients following treatment. Patients showed no serious side effects, although drug reactions with eosinophilia and systemic symptoms, cytopenia, and infections were observed. Thus, anakinra has led to a marked improvement in some cases, and functional deficiency of IL-1RA was indicated, supporting a direct mechanism for its therapeutic effect. This review first discusses the effectiveness of anakinra for intractable epileptic syndromes. Anakinra could become a new tool for intractable epilepsy treatment. However, it does not currently have a solid evidence base.

CARCINOMA OF THE THYROID IN CHILDREN AND YOUNG ADULTS: IATROGENIC RELATION TO PREVIOUS IRRADIATION

PEDIATRICS ◽  
1966 ◽  
Vol 38 (1) ◽  
pp. 77-81 ◽  
Author(s):  
Sumner Hagler ◽  
Philip Rosenblum ◽  
Arthur Rosenblum
Keyword(s):  
Young Adults ◽  
Therapeutic Effect ◽  
Infants And Children ◽  
Thyroid Adenoma ◽  
Thyroid Neoplasia ◽  
High Incidence ◽  
Children And Young Adults ◽  
Previous Irradiation ◽  
Head Neck

Fifteen cases of carcinoma of the thyroid and four cases of thyroid adenoma in children and young adults are reported. In all, except one, irradiation had been given to the head, neck, or chest of these patients 5 to 17 years previously. These observations suggest that carcinoma of the thyroid in children is related to irradiation, often prescribed for uncertain therapeutic effect. Irradiation to the head, neck, or chest of infants and children should be avoided wherever possible. We believe these cases represent a remarkably high incidence of thyroid neoplasia to occur in a single practicing pediatric office. The practicing pediatrician who now follows his patients longitudinally from infancy through adolescence has a unique opportunity to observe the development of disease, even years later.

scholarly journals Targeting Cytokines as Evolving Treatment Strategies in Chronic Inflammatory Airway Diseases

2018 ◽  
Vol 19 (11) ◽  
pp. 3402 ◽  
Author(s):  
Jaleesa Garth ◽  
Jarrod Barnes ◽  
Stefanie Krick
Keyword(s):  
Clinical Trials ◽  
Allergic Asthma ◽  
Inflammatory Marker ◽  
Interleukin 1 ◽  
Treatment Strategies ◽  
Bronchial Epithelium ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Airway Diseases ◽  
Novel Treatment Strategies

Cytokines are key players in the initiation and propagation of inflammation in chronic inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD), bronchiectasis and allergic asthma. This makes them attractive targets for specific novel anti-inflammatory treatment strategies. Recently, both interleukin-1 (IL-1) and IL-6 have been associated with negative health outcomes, mortality and a pro-inflammatory phenotype in COPD. IL-6 in COPD was shown to correlate negatively with lung function, and IL-1beta was induced by cigarette smoke in the bronchial epithelium, causing airway inflammation. Furthermore, IL-8 has been shown to be a pro-inflammatory marker in bronchiectasis, COPD and allergic asthma. Clinical trials using specific cytokine blockade therapies are currently emerging and have contributed to reduce exacerbations and steroid use in COPD. Here, we present a review of the current understanding of the roles of cytokines in the pathophysiology of chronic inflammatory airway diseases. Furthermore, outcomes of clinical trials in cytokine blockade as novel treatment strategies for selected patient populations with those diseases will be discussed.

High Incidence of Early Cholelithiasis Detected by Ultrasonography in Children and Young Adults With Hereditary Spherocytosis

2003 ◽  
Vol 25 (12) ◽  
pp. 952-954 ◽  
Author(s):  
Hannah Tamary ◽  
Shraga Aviner ◽  
Enrique Freud ◽  
Hagit Miskin ◽  
Tatyana Krasnov ◽  
...  
Keyword(s):  
Young Adults ◽  
Hereditary Spherocytosis ◽  
High Incidence ◽  
Children And Young Adults

scholarly journals Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children’s Oncology Group

2017 ◽  
Vol 35 (23) ◽  
pp. 2700-2707 ◽  
Author(s):  
Kristina K. Hardy ◽  
Leanne Embry ◽  
John A. Kairalla ◽  
Shanjun Helian ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Treatment Strategies ◽  
Corticosteroid Treatment ◽  
Neurocognitive Functioning ◽  
Neurocognitive Outcomes ◽  
Leucovorin Rescue ◽  
B Lineage ◽  
The Impact

Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue. Patients were also randomly assigned to corticosteroid therapy that included either dexamethasone or prednisone. A neurocognitive evaluation of intellectual functioning (IQ), working memory, and processing speed (PS) was conducted 8 to 24 months after treatment completion (n = 192). Results The method of MTX delivery and corticosteroid assignment were unrelated to differences in neurocognitive outcomes after controlling for ethnicity, race, age, gender, insurance status, and time off treatment; however, survivors who were age < 10 years at diagnosis (n = 89) had significantly lower estimated IQ ( P < .001) and PS scores ( P = .02) compared with participants age ≥ 10 years. In addition, participants who were covered by US public health insurance had estimated IQs that were significantly lower ( P < .001) than those with US private or military insurance. Conclusion Children with high-risk B-lineage ALL who were age < 10 years at diagnosis are at risk for deficits in IQ and PS in the absence of cranial radiation, regardless of MTX delivery or corticosteroid type. These data may serve as a basis for developing screening protocols to identify children who are at high risk for deficits so that early intervention can be initiated to mitigate the impact of therapy on neurocognitive outcomes.

scholarly journals Corticosteroids versus clobazam in epileptic encephalopathy with ESES: a European multicentre randomised controlled clinical trial (RESCUE ESES*)

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Bart van den Munckhof ◽  
◽  
Alexis Arzimanoglou ◽  
Emilio Perucca ◽  
Heleen C. van Teeseling ◽  
...  
Keyword(s):  
Cognitive Functioning ◽  
Treatment Response ◽  
Controlled Trial ◽  
Epileptic Encephalopathy ◽  
Cognitive Outcome ◽  
Controlled Study ◽  
Controlled Clinical Trial ◽  
Epilepsy Syndrome ◽  
Eeg Abnormalities ◽  
Randomised Controlled

Abstract Background Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is an epilepsy syndrome occurring almost exclusively in children, usually at an age between 4 and 12 years. It is characterised by abundant sleep-induced epileptic activity in the electroencephalogram (EEG) and by acquired cognitive and behavioural deficits. The goal of treatment is to prevent further decline or even improve cognitive functioning. Based on mostly small and retrospective studies, corticosteroids and clobazam are regarded by many clinicians as the most effective pharmacological treatments. This European multicentre randomised controlled trial is designed to compare the effects of corticosteroids and clobazam on cognitive functioning after 6 months. Secondary outcomes include cognitive functioning after 18 months, EEG abnormalities in sleep, safety and tolerability, and seizure frequency. We also aimed at investigating whether treatment response in epileptic encephalopathy with ESES can be predicted by measurement of inflammatory mediators and autoantibodies in serum. Methods The pragmatic study will be performed in centres with expertise in the treatment of rare paediatric epilepsy syndromes across Europe. A total of 130 patients, 2 to 12 years of age, with epileptic encephalopathy with ESES will be enrolled and randomised in a 1:1 ratio to receive either corticosteroids (monthly intravenous methylprednisolone pulses or daily oral prednisolone) or oral clobazam for 6 months according to an open-label parallel-group design. Follow-up visits with clinical assessment, EEGs, and neuropsychological testing are scheduled for up to 18 months. Blood samples for cytokine and autoantibody testing are obtained before treatment and 8 months after treatment initiation. Discussion The treatment of epileptic encephalopathy with ESES aims at improving cognitive outcome. This randomised controlled study will compare the most frequently used treatments, i.e. corticosteroids and clobazam. If the study proves superiority of one treatment over the other or identifies biomarkers of treatment response, results will guide clinicians in the early treatment of this severe epilepsy syndrome. Trial registration ISRCTN, ISRCTN42686094. Registered on 24 May 2013.

Epileptic encephalopathy after HHV6 post-transplant acute limbic encephalitis in children: Confirmation of a new epilepsy syndrome

2013 ◽  
Vol 105 (3) ◽  
pp. 419-422 ◽  
Author(s):  
Miquel Raspall-Chaure ◽  
Thaís Armangué ◽  
Izaskun Elorza ◽  
Àngel Sanchez-Montanez ◽  
Mònica Vicente-Rasoamalala ◽  
...  
Keyword(s):  
Limbic Encephalitis ◽  
Epileptic Encephalopathy ◽  
Epilepsy Syndrome ◽  
Post Transplant

scholarly journals Anti-Inflammatory Cytokines: Important Immunoregulatory Factors Contributing to Chemotherapy-Induced Gastrointestinal Mucositis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Masooma Sultani ◽  
Andrea M. Stringer ◽  
Joanne M. Bowen ◽  
Rachel J. Gibson
Keyword(s):  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Financial Burden ◽  
Interleukin 1 ◽  
Treatment Strategies ◽  
Inflammatory Reactions ◽  
Anti Inflammatory

“Mucositis” is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). These proinflammatory cytokines are responsible for initiating inflammation in response to tissue injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also released to limit the sustained or excessive inflammatory reactions. In the past decade, intensive research has determined the role of proinflammatory cytokines in development of mucositis. However, a large gap remains in the knowledge of the role of anti-inflammatory cytokines in the setting of chemotherapy-induced mucositis. This critical paper will highlight current literature available relating to what is known regarding the development of mucositis, including the molecular mechanisms involved in inducing inflammation particularly with respect to the role of proinflammatory cytokines, as well as provide a detailed discussion of why it is essential to consider extensive research in the role of anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective targeted treatment strategies can be developed.

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