Targeted Treatment in Childhood Epilepsy Syndromes

The mainstay of treatment of epilepsy has been antiepileptic drugs; however, despite the emergence of new agents, a consistent proportion remain drug-resistant. Newer AEDs show promise. However, as it becomes clear that the epilepsies are a group of diseases rather than a single disorder the prospect of targeted treatment in some may become a reality

A New Differential Positioning Method using Modulation Correlation of Signals of Opportunity

Global Navigation Satellite Systems (GNSS) have become the positioning systems of choice for many applications. However, GNSS signals are susceptible to obstruction, interference and jamming. Therefore, to maximize robustness and integrity, it is necessary to employ a dissimilar positioning technology that can operate independently and back-up GNSS. One such technology exploits 'signals of opportunity' - signals that are designed for purposes other than navigation.This paper presents a system that uses amplitude modulation (AM) radio broadcasts in the medium frequency (MF) band. At these frequencies, the predominant ground-wave propagation mode offers better coverage in remote areas and over sea than is achievable with higher frequency signals.The system is differential and operates by correlating modulation information between the reference and user receivers. A system of this form mitigates the deterioration in and around buildings encountered in prior systems and can provide absolute position using fewer signals than a system using only carrier phase.The system presented in this paper uses generalized cross correlation to obtain time difference of arrival measurements that are subsequently used for position determination. Preliminary results indicate the system provides a robust position solution. Moreover, the system offers the potential to be combined with carrier phase measurements to achieve enhanced performance, while the modulation correlation technique is readily extendable to other types of signal

Memory in paediatric temporal lobe epilepsy: effects of lesion type and side.

This study investigated the role of underlying pathology on memory function of children with temporal lobe epilepsy (TLE). Memory was assessed in 44 children with TLE resulting from hippocampal sclerosis (HS) or dysembryoplastic neuroepithelial tumours (DNT), and 22 control children. Delayed story and paired associate recall performance was significantly more impaired in children with HS compared to those with DNT, irrespective of the affected side. Semantic memory was impaired in both HS groups, and also in the left DNT group. These results suggest a role for type, and to a lesser extent, side of pathology in the memory profile of children with TLE

Guanidinoacetate methyltransferase (GAMT) deficiency: a rare but treatable epilepsy

Epilepsy commonly presents in childhood as part of a syndrome, and some such children may reach adult services without an underlying syndromic diagnosis. For adult neurologists taking over their care, it is often unclear how hard to search for an underlying diagnosis. The diagnostic yield may be small and such a diagnosis may not change management. Young adults with learning difficulties are also challenging to investigate, as they may not tolerate standard epilepsy tests.We present such a case in which simple tests identified a unifying diagnosis. With the new diagnosis came a new treatment that had a significant impact on seizures and quality of life

A Differential Positioning System Using Modulation Correlation of Signals of Opportunity

Global Navigation Satellite Systems (GNSS) have become the positioning systems of choice for many applications. However, GNSS signals are susceptible to obstruction, interference and jamming. Therefore, to maximize robustness and integrity, it is necessary to employ a dissimilar positioning technology that can operate independently and back-up GNSS. One such technology exploits ‘signals of opportunity’ – signals that are designed for purposes other than navigation. This paper presents a system that uses amplitude modulation (AM) radio broadcasts in the medium frequency (MF) band. At these frequencies, the predominant ground-wave propagation mode offers better coverage in remote areas and over sea than is achievable with higher frequency signals. The system is differential and operates by correlating modulation information between the reference and user receivers. A system of this form mitigates the deterioration in and around buildings encountered in prior systems and can provide absolute position using fewer signals than a system using only carrier phase. The system presented in this paper uses generalized cross correlation to obtain time difference of arrival measurements that are subsequently used for position determination. Preliminary results indicate the system provides a robust position solution. Moreover, the system offers the potential to be combined with carrier phase measurements to achieve enhanced performance, while the modulation correlation technique is readily extendable to other types of signal

Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy

OBJECTIVES: The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy. METHODS: The current study investigated the association of IEDs with intellectual functioning in 103 children with medication-resistant focal epilepsy. Hierarchical multiple regression analyses were used to determine the independent contribution of IED features on intellectual functioning, after controlling for effects of lesional pathology, epilepsy duration, and medication. Exploratory analyses were conducted for language and memory scores as well as academic skills available in a subset of participants. RESULTS: The results reveal that IEDs have a negative association with IQ with independent, additive effects documented for frequent and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left-lateralized IEDs had a prominent effect on verbal intelligence, in excess of the influence of left-sided brain pathology. These effects extended to other cognitive functions, most prominently for sleep-enhanced IEDs to be associated with deficits in expressive and receptive language, reading, spelling and numerical skills. SIGNIFICANCE: Overall, IED effects on cognition were of a magnitude similar to lesional influences or drug effects (topiramate use). This study demonstrates an association between IEDs and cognitive dysfunction, independent of the underlying focal brain pathology

Fenfluramine as antiseizure medication for epilepsy

Fenfluramine hydrochloride has classically been described as acting pharmacologically through a serotonergic mechanism. Therefore, it was initially used as an anorectic drug, given that impaired serotonin homeostasis may be associated with increased food intake. Although positive results were documented, cardiovascular concerns resulted in its temporary withdrawal. Nevertheless, a novel role in patients with epilepsy was later suggested by isolated clinical observations. The wide application of genetic testing allowed the classification (predominantly as Dravet syndrom) of patients in whom benefit was seen, while with the development of zebrafish models, its antiepileptic properties were confirmed at a molecular level. Data from randomized clinical trials have shown a beneficial effect of fenfluramine, as an adjunct therapy, on seizure control for children with Dravet syndrome, though there is still uncertainty about the impact on neurodevelopment in these patients. No signs of heart valve disease have been documented to date. Long-term and appropriately designed clinical studies will verify whether fenfluramine is a therapeutic agent of high importance, living up to the promise shown so far