{'fraction_non_alphanumeric': 0.02250865717583686, 'fraction_numerical': 0.006733358984224702, 'mean_word_length': 5.867899603698811, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Workshop Report – Michael Foundation Forum 2012, Berlin, Germany

From October 4th to 6th, 2012, Berlin hosted the 11th edition of the Michael Forum. The special occasion of the 50th anniversary jubilee of the Michael Foundation brought together 24 Michael laureates to discuss the latest advancement in epilepsy research. The prestigious biannual Michael Prize, established in 1963 “to support scientific research on most effective treatment methods as well as the causes of illnesses associated with seizures, and to fight against individual and social consequences of epileptic diseases,” awards young investigators for their innovative contributions to clinical and experimental epilepsy research. Michael Forum 2012was sponsored by UCB. The first session of the Forum focused on epilepsy research in the developing, immature brain. Epileptogenesis and seizure recurrence in the immature brain is associated with significant comorbidity and mortality. Eli Mizrahi noted that current animal models of epilepsy may not reflect conditions in the human neonate in terms of patterns, generators, and burden of seizures. Although potential new therapies and understanding of epilepsy dynamics have been generated in the laboratory, the new clinical strategies they suggest may not directly translate to the human neonate. Solomon Mosh e presented a rat model of symptomatic infantile spasms (IS) induced by intracerebral administration of doxorubicin and lipopolysaccharide at postnatal (PN) day 3. Spasms appeared at PN4–13, followed at PN9 by other seizure types associated with neurodevelopmental and learning deficits. Spasms are adrenocorticotropic hormone (ACTH)-refractory, transiently sensitive to vigabatrin, and resistant to phenytoin. This model has been used to identify antiepileptic drugs (AEDs) that suppress human spasms acutely and modify the disease course (carisbamate, rapamycin), and it is well qualified for preclinical screening of disease-modifying and antiepileptogenic therapies and associated neurodevelopmental comorbidities. Progressive cognitive impairment due to underlying etiology, epileptiform discharges, and AEDs can be a devastating comorbidity of early life epilepsy. Gregory Holmes discussed how remedial training helps restoring memory function after early life seizures. Seizure-exposed rats showed initial difficulties in learning memory task, but performed similar to control rats when training was extended. During memory tasks, theta oscillatory activity increased in prefrontal cortex during early memory training and plateaued during extra training. CA1-prefrontal theta coherence was enhanced in correct (delayed) compared to incorrect (early) trials. The data support the idea that adapted involvement of hippocampal– prefrontal circuits following early life seizures may underpin cognitive rehabilitation following neurologic insults. Cardiac arrhythmia and respiratory deficiency have long been suspected to contribute to sudden unexpected death in epilepsy (SUDEP) following seizures both in pediatric and adult patients. Jeffrey Noebels reported that human mutations of KCNQ1, a gene that encodes for a potassium channel expressed in both heart (responsible for a lethal cardiac arrhythmia) and brain, produce a combined phenotype of epilepsy, cardiac long QT-interval syndrome (LQTS), and sudden death. LQT genes alter cardiorespiratory control centers that may impact SUDEP risk. Clinical and scientific research programs aimed at integrating a worldwide collection of SUDEP and near-SUDEP cases and their families have been planned to discover clinically useful genes. George Kostopoulos discussed the implication of thalamocortical circuits in altered cortical excitability in generalized spike and wave discharges (GSWDs), typical of childhood absence epilepsy and juvenile myoclonic epilepsy (JME). Bistability is evident in thalamus (tonic–phasic activity) and cortex (down–up states) in sleep–wake cycles/stages and during non–rapid eye movement (REM) cyclic alternating pattern (CAP). In patients, GSWDs appear mainly in cortical up-state of CAPs and show different topographic distribution compared to interictal and pregeneralization focal SWDs. During sleep transitions, corticothalamic responses become strong enough to generate autonomous GSWDs emerging from a preset system of bilaterally distributed cortical and subcortical networks. JME is a form of epilepsy easy to control with AEDs, but likely to relapses after stress and sleep deprivation. Dieter Janz reviewed the evidence that from four longitudinal studies, demonstrating a relatively low frequency of relapses after AED withdrawal and a corresponding high rate of cured patients, when long observation periods (20– 30 years) are evaluated, suggesting that long-term prognosis of JMEwithout AED treatment is better than previously assumed. Combination with absences and polytherapy were identified as significant predictors for a poor seizure outcome. During the second session of the Forum, the use of human biologic data/specimens to study epilepsy was discussed. The temporal cortex of patients with drug-resistant epilepsy undergoing epilepsy surgery treatment can be