Sixteen percent of ALL survivors had VIPN. VIPN should be increasingly recognised as a late effect of chemotherapy, as it significantly affects physical and social function quality of life.

We have recently shown that endogenous prostanoids are critical in bradykinin-stimulated interleukin (IL)-8 release from human airway smooth muscle (ASM) cells. In this study, we tested the ability of transforming growth factor (TGF)-beta1 to stimulate IL-8 release, cyclooxygenase (COX)-2 expression and PGE(2) generation in cultured human ASM cells and explored the role of COX products and COX-2 induction on IL-8 release. TGF-beta1 stimulated IL-8 release, COX-2 induction, and PGE(2) generation in a concentration- and time-dependent manner. Maximal IL-8 release was achieved with 10 ng/ml of TGF-beta1 after 16 h of incubation, which was inhibited by the transcription inhibitor actinomycin D and the corticosteroid dexamethasone but was not affected by the nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor NS-398 despite their inhibition on TGF-beta1-induced PGE(2) release. These results show for the first time that TGF-beta1 stimulates IL-8 release, COX-2 induction, and PGE(2) generation in human ASM cells and that PGE(2) generation is not critical for TGF-beta1-induced IL-8 release. These findings suggest that TGF-beta1 may play an important role in the pathophysiology of asthma.

This study evaluated prevalence and risk factors for vitamin D deficiency among children with epilepsy on long-term antiepileptic drugs treated in South Queensland, Australia. Children with epilepsy seen in a tertiary neurology clinic were contacted requesting bone health blood tests during winter of 2011. Vitamin D deficiency was defined as 25-hydroxy vitamin D levels <20 ng/mL, and insufficiency between 21 and 29 ng/mL. One hundred thirty letters were sent, with 111 (85%) subsequently having blood tests performed. Vitamin D deficiency was identified in 24 (22%) of 111 and an additional 45 (41%) of 111 had vitamin D insufficiency. Multiple logistic regression analysis identified children on >2 antiepileptic drugs or with underlying genetic etiologies were more likely to have vitamin D deficiency. High proportion of children on long-term antiepileptic drugs in Queensland risk vitamin D deficiency and insufficiency despite living in the subtropics. Vitamin D monitoring and supplementation is important in the management of children on long-term antiepileptic drugs requiring tertiary care in Queensland.

Despite living in the tropics, a high proportion of Malaysian children with epilepsy are at risk of vitamin D deficiency. Targeted strategies including vitamin D supplementation and lifestyle advice of healthy sunlight exposure behavior should be implemented among children with epilepsy, particularly for those at high risk of having vitamin D deficiency.

AIM We aimed to investigate the relationship between movement disorders, changes on brain magnetic resonance imaging (MRI), and vigabatrin therapy in children with infantile spasms. METHOD Retrospective review and brain MRI analysis of children enrolled in the InternationalCollaborative Infantile Spasms Study (ICISS) who developed a movement disorder on vigabatrin therapy. Comparisons were made with controls within ICISS who had no movement disorder. RESULTSTen of 124 infants had a movement disorder and in eight it had developed on vigabatrin therapy. Two had a movement disorder that resolved on dose-reduction of vigabatrin, one had improvement on withdrawing vigabatrin, two had resolution without any dose change, and in three it persisted despite vigabatrin withdrawal. The typical brain MRI changes associated with vigabatrin therapy were noted in two infants. Ten control infants were identified. Typical MRI changes noted with vigabatrin were noted in three controls.INTERPRETATION It is possible that in two out of eight cases, vigabatrin was associated with the development of a movement disorder. In six out of eight cases a causal relationship was less plausible. The majority of infants treated with vigabatrin did not develop a movement disorder. MRI changes associated with vigabatrin do not appear to be specifically related to the movement disorder.Infantile spasms are an age-related epileptic encephalopathy that occurs in children, usually between the ages of 3 months and 18 months. The seizures manifest typically as clusters of either flexor or extensor epileptic spasms, which are often coincident with an arrest or regression of neurodevelopment. The electroencephalograph characteristically, but not always, shows a chaotic high voltage interictal pattern known as hypsarrhythmia. Many underlying aetiologies, such as tuberous sclerosis complex, trisomy 21, neuronal migration disorders, and hypoxic-ischaemic encephalopathy, have been associated with infantile spasms but in a significant minority of cases no cause is found. There has been much debate about the most effective treatment modality for these patients but there appears to be a relatively wide consensus that the two most effective therapies are either the GABA-ergic anticonvulsant, vigabatrin, or hormonal therapies (prednisolone, adrenocorticotrophin hormone [ACTH], or synthetic ACTH). 1It has been known since the 1980s that vigabatrin usage in animals was associated with the development of intramyelinic oedema in the central nervous system, most notably in the cerebellum, reticular formation and optic tracts in rats, and columns of the fornix and the optic tracts in dogs. 2,3 Recently reports have surfaced in the literature linking vigabatrin usage in humans with characteristic magnetic resonance imaging (MRI) changes in the globus pallidus, thalamus, brain stem, and dentate nuclei of the cerebellum. 4,5 These changes appear to be dose-dependent

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p < 0.001). Absence seizures significantly predicted drug resistance in both males (OR = 3.0, p = 0.001) and females (OR = 3.0, p < 0.001) in univariate analysis. In multivariable analysis in females, catamenial seizures (OR = 14.7, p = 0.001), absence seizures (OR = 6.0, p < 0.001) and stress-precipitated seizures (OR = 5.3, p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation.

No abstract

ABBREVIATION IEDsInterictal epileptiform discharges AIM To evaluate the electroclinical features of epilepsy secondary to neonatal hypoglycaemia.METHOD This was a retrospective study of children who had seizures beyond infancy after neonatal hypoglycaemia treated at The Royal Children's Hospital, Melbourne between 1996 and 2012. Patients with perinatal asphyxia were excluded. Clinical details were obtained from medical records. Digital electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were reviewed. Eleven patients met the inclusion criteria (six males, five females; mean age 10y 5mo, range 4-18y at the time of review).RESULTS Age at seizure onset ranged from 4 months to 5 years. Seizures were focal occipital in nine and generalized tonic in two patients. MRI showed gliosis with or without cortical atrophy in the occipital lobe with or without parietal lobe in all. Predominant EEG findings were stereotyped occipital sharp-slow discharges in five, polymorphic occipital spike-wave or paroxysmal fast activity in three, and generalized slow spike-wave and fast activity in two. Seizures were infrequent or remitted in six of the nine children with focal occipital seizures, and frequent and refractory in both children with generalized seizures.INTERPRETATION Despite the common antecedent and bilateral occipital lobe injury, the seizure manifestations and course of epilepsy after neonatal hypoglycaemia were variable, with mild occipital, refractory occipital, and symptomatic generalized epilepsy recognized.