Pre-surgical mapping of eloquent cortex for paediatric epilepsy surgery candidates: Evidence from a review of advanced functional neuroimaging.

PURPOSE: A review of all published evidence for mapping eloquent (motor, language and memory) cortex using advanced functional neuroimaging (functional magnetic resonance imaging [fMRI] and magnetoencephalography [MEG]) for paediatric epilepsy surgery candidates has not been conducted previously. Research in this area has predominantly been in adult populations and applicability of these techniques to paediatric populations is less established. METHODS: A review was performed using an advanced systematic search and retrieval of all published papers examining the use of functional neuroimaging for paediatric epilepsy surgery candidates. RESULTS: Of the 2724 papers retrieved, 34 met the inclusion criteria. Total paediatric participants identified were 353 with an age range of 5 months-19 years. Sample sizes and comparisons with alternative investigations to validate techniques are small and variable paradigms are used. Sensitivity 0.72 (95% CI 0.52-0.86) and specificity 0.60 (95% CI 0.35-0.92) values with a Positive Predictive Value of 74% (95% CI 61-87) and a Negative Predictive Value of 65% (95% CI 52-78) for fMRI language lateralisation with validation, were obtained. Retrieved studies indicate evidence that both fMRI and MEG are able to provide information lateralising and localising motor and language functions. CONCLUSIONS: A striking finding of the review is the paucity of studies (n=34) focusing on the paediatric epilepsy surgery population. For children, it remains unclear which language and memory paradigms produce optimal activation and how these should be quantified in a statistically robust manner. Consensus needs to be achieved for statistical analyses and the uniformity and yield of language, motor and memory paradigms. Larger scale studies are required to produce patient series data which clinicians may refer to interpret results objectively. If functional imaging techniques are to be the viable alternative for pre-surgical mapping of eloquent cortex for children, paradigms and analyses demonstrating concordance with independent measures must be developed.

Cogan's syndrome: a rare cause of meningoencephalitis.

We report a 14-year-old boy who presented with meningoencephalitis. Other features particularly auditory, vestibular, and ocular lead to the diagnosis of Cogan's syndrome. Treatment with prednisolone resulted in a rapid improvement and recovery of his hearing. Cogan's syndrome is a rare primary vasculitis, characterized by ocular, auditory, and vestibular symptoms, which can have significant morbidity and mortality. Presentation with a meningoencephalitic picture is unusual. Increased awareness of its clinical features among pediatricians and pediatric neurologists should lead to earlier diagnosis and increased recognition of the serious systemic manifestations. Early use of prednisolone can prevent hearing loss and can also be useful in treating the other vasculitic manifestations.

Treatment of Lennox-Gastaut Syndrome (LGS).

Lennox-Gastaut Syndrome (LGS) is a severe form of epilepsy that usually starts in early to mid childhood and is characterized by multiple seizure types, abnormal electroencephalogram with slow spike-and-wave discharges and cognitive problems. Numerous approaches are currently used to treat LGS, including use of conventional antiepileptic drugs (most commonly sodium valproate, lamotrigine and topiramate), other drug interventions (corticosteroids and intravenous immunoglobulin) and nonpharmacologic treatments (ketogenic diet, corpus callosotomy and vagus nerve stimulation). Rufinamide is the most recent antiepileptic drug to have shown efficacy in the treatment of LGS. Despite the variety of therapeutic options, there have been only five double-blind, placebo-controlled clinical trials of antiepileptic drugs in LGS and none of these were head-to-head comparison trials. The evidence supporting the use of available treatments for LGS is, therefore, not robust. Here, we review the evidence supporting the use of specific therapies in LGS and provide recommendations on how to set appropriate treatment goals, select treatments and minimize polypharmacy. A suggested treatment algorithm is presented and discussed. Sodium valproate is recommended for first-line therapy; if seizures persist, alternative interventions should be trialed on an individually tailored basis.

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.

Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified.