Peter Walsh

Respiratory pattern changes in sleep in children on vagal nerve stimulation for refractory epilepsy.

BACKGROUND An altered breathing pattern in sleep, over two to three weeks, reported by the parents of a child on Vagal Nerve Stimulation (VNS) therapy for refractory epilepsy, prompted a sleep study in him. His polysomnography (PSG) revealed respiratory irregularity concordant with VNS activation. Dyspnoea is a well recognised and reported side effect of the VNS. However there are only a few studies looking at respiration in sleep with VNS. We therefore undertook PSGs in seven other children on VNS. METHODS Sleep studies were undertaken, in accordance with standard clinical practice. Sleep and apnoeas and hypopneas were scored in accordance with conventional criteria. Respiratory pattern changes in sleep (RPCS) with VNS were looked for. RESULTS Respiratory pattern changes in sleep were seen during PSG in seven of eight children on VNS for refractory epilepsy. Decreased effort and tidal volume occurred in seven children, concordant with VNS activation. In one child, this was associated with a fall in respiratory rate, i the other six children with an increase. No study showed an apnoea/hypopnoea index in the abnormal range. The RPCS were not associated with significant hypoxia or hypercapnoea. CONCLUSION Our results suggest that RPCS occur in most children with VNS. This is not surprising in view of the significant influence vagal afferents have on respiratory control centres. The RPCS did not appear to have a clinical impact in our group. However further investigations are suggested to explore this phenomenon, especially in patients with sleep apnoea syndromes or compromised respiratory function.

VNS therapy in clinical practice in children with refractory epilepsy

Objectives– To study the efficacy, tolerability and safety of the vagus nerve stimulation (VNS) therapy in clinical practice, in 16 children and adolescents with refractory epilepsy. Methodology– We assessed the efficacy of VNS therapy, retrospectively by comparing seizure frequency, duration and severity at the time of most recent follow up (av: 24.9 months) to that in the 4 weeks prior to VNS surgery. Changes in quality of life, sleep and behaviour at last review was compared with that prior to VNS. Adverse effects elicited by specific questioning, spontaneous reporting and clinical examination are described. Results– Vagus nerve stimulation resulted in a >50% reduction in seizure frequency in 62.5% of children with 25% achieving a >90% reduction. Vagus nerve stimulation was well tolerated in all but one of our cohort, with no serious side‐effects. Conclusion– Our results support its role as one of the options in intractable childhood epilepsy.

Photoparoxysmal responses in children: their characteristics and clinical correlates

This study evaluates the characteristics of photoparoxysmal responses elicited with intermittent photic stimulation during a routine electroencephalogram in childhood and correlated this with the clinical profile of the child. Photoparoxysmal responses occurred in 8% (21/263) of children where activation was undertaken. Photoparoxysmal responses were often brief and had a variable onset latency. This study suggests increasing the duration of the stimulus train to 10 seconds or more will increase the diagnostic yield. Photoparoxysmal responses very rarely outlasted the stimulus, and self-limited photoparoxysmal responses probably have greater significance than previously attributed to them. They are highly correlated with epilepsy.

Severe γ-sarcoglycanopathy caused by a novel missense mutation and a large deletion

We report two siblings with a relatively severe limb-girdle muscular dystrophy. The elder sister presented at 8 years of age with inability to climb and abnormal gait. At 12 years she was barely ambulant. Her sister followed a similar course. Serum creatine kinase was 8500–10 000 IU (N 25–200) in the elder sister and 17 000–19 000 IU in the younger sister. Muscle biopsy of the elder sister at 8 years showed chronic myopathic changes with loss of muscle fibres, active necrosis and regeneration. Immunocytochemistry demonstrated normal spectrin and dystrophin, reduced α-sarcoglycan and absent γ-sarcoglycan – indicating a γ-sarcoglycanopathy. Haplotype analysis for the markers D13S115, D13S232, D13S292, D13S787, D13S1243 and D13S283 internal to and flanking the γ-sarcoglycan gene showed the affected sisters shared haplotypes, indicating it was possible they were suffering from a γ-sarcoglycanopathy. Non-inheritance of paternal alleles for D13S232, D13S292 and D13S1243 suggested the inheritance of a deletion, which was confirmed by FISH, using a genomic probe from the γ-sarcoglycan gene. The γ-sarcoglycan cDNA was amplified by reverse transcriptase PCR from the muscle biopsy of the elder sister and sequenced. A missense mutation changing codon 69 from GGC glycine to CGC arginine was identified. HhaI digestion of exon 3 genomic PCR products showed the two affected sisters were hemizygous for the mutation, while the mother and grandmother were heterozygotes. The mutation, identified by SSCP analysis, was not observed in 116 unrelated, unaffected individuals. Previously, only two other missense mutations, the Cys283Tyr missense mutation in Gypsies and the Leu193Ser mutation in a Dutch family, have been described in the γ-sarcoglycan gene. The fact that the affected individuals in the current and Gypsy families are γ-sarcoglycan negative may indicate that codons 69 and 283 are important in γ-sarcoglycan function.

Neuropathological homology in true Galloway-Mowat syndrome.

Galloway-Mowat syndrome is a rare condition that is likely hereditary though the underlying offending gene has not been identified, and is characterized by microcephaly and severe nephrotic syndrome culminating in childhood death. Some of the reported cases have abnormalities in neuronal migration and intractable seizures, but many of the described cases focus on the renal pathology and emphasize a diversity of clinical and pathological features. The case described herein includes a thorough neuropathological description, and when the neuroradiology and neuropathology of the previously published cases is scrutinized, a fairly consistent clinical and neuropathological phenotype emerges.

Balamuthia amebic meningoencephalitis and mycotic aneurysms in an infant

Balamuthia amebic encephalitis is rarely reported in infants. To the best of our knowledge, amebic encephalitis complicated by a mycotic aneurysm was only described once. We report on an 8-month-child with laboratory-confirmed Balamuthia mandrillaris meningoencephalitis, complicated by a mycotic aneurysm of the middle cerebral artery.

Lacosamide as adjunctive therapy in treatment‐resistant epilepsy in childhood

Lacosamide (LCM) is a novel anti‐epileptic drug (AED) that enhances the slow inactivation of voltage‐gated sodium channels. Its efficacy as adjunctive therapy for focal seizures is confirmed in adult placebo controlled trials with >50% reduction in seizure frequency in up to 50% patients. There is paucity of data on its efficacy and tolerance in treatment‐resistant epilepsy in childhood (TREC). This study aims to assess efficacy and tolerance of LCM as adjunct therapy in TREC.

Effective treatment of infant botulism on day 13 after symptom onset with human botulism antitoxin

Effective treatment of infant botulism on day 13 after symptom onset with human botulism antitoxin Anita J Campbell, Geoff Knight, Peter Walsh and Asha C Bowen Departments of Infectious Diseases, Paediatric Intensive Care, and Neurology, Princess Margaret Hospital, Pathwest Microbiology Department, QE11 Medical Centre, Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia and Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia

Seizure outcomes in children with epilepsy after resective brain surgery

PURPOSE To assess the role of resective brain surgery in childhood epilepsy. METHODOLOGY We retrospectively analysed the seizure outcomes in 55 children with epilepsy who had resective brain surgery between 1997 and 2012, at our centre. The children were 1.5-18 years at the time of surgery; their seizure onset was between 0.2 andto 15 years of age. 48 had refractory epilepsy. One child died of tumour progression. Follow-up duration in the survivors ranged from 2 to -16 years (mean: 9).Presurgical evaluation included clinical profiles, non-invasive V-EEG monitoring, neuroimaging with MRIs in all; SPECT and PET in selected patients. 54 had intraoperative ECoG. RESULTS An Engel Class 1 outcome was seen in 78% of the cohort, with 67% being off all AEDs at the most recent follow-up. Children with tumours constituted the majority (56%), with 87% of this group showing a Class 1 outcome and 84% being off AEDs. Children with cortical dysplasia had a Class 1 outcome in 56%. CONCLUSION Resective brain surgery is an efficacious option in some children with epilepsy. We found ECoG useful to tailor the cortical resection and in our opinion ECoG contributed to the good seizure outcomes.