Journal of the International Child Neurology Association 2019-05-21T13:22:07+00:00 Professor Charles Newton Open Journal Systems <p>The Journal of the International Child Neurology Association (JICNA) is an Open Access Journal&nbsp;published by the International Child Neurology Association (ICNA), representing the Association’s official Journal. The journal aims to cover all sections of Child Neurology, Epilepsy, and Neuromuscular disorders, providing teaching, practical and professional support for clinicians dealing with neurological disorders in childhood. It publishes, after peer-review process papers concerning both clinical and basic research.</p> JICNA in 2018 2018-05-09T22:31:03+00:00 Charles Newton Biju A Hameed <p>2018 is the fourth year of the Journal of the International Child Neurology Association (JICNA), and continues to publish papers which are open access, without publication fees. JICNA was set up to: i) promote child neurology throughout the world, in particular encourage papers from low and middle income countries; ii) provide peer review scientifically sound papers on child neurology; iii) provide open access, so that papers can be accessed from anywhere free of charge in the world. In order to achieve these goals we ask members of ICNA contribute to making this a rigorous and vibrant journal, by submitting papers (particularly research papers), reviewing papers in a timely manner and if they have the time and energy put themselves forward as a section editor.</p> <p>There remain significant challenges in reviewing papers in timely manner and soliciting research based papers. Some reviewers are excellent, reviewing the papers quickly and thoroughly. In particular we would like to commend Professors Lieven Lagae and Jo Wilmshurst, who have reviewed more than four papers in a timely manner. We would also like to thank the following people who have reviewed papers since the start of the journal: Amina Abubakar, Banu Anlar, Harry Chugani, Paolo Curatolo, Russell Dale, Marilisa Guerreiro, Samson Gwer, Richard Idro, Symon Kariuki, Manju Kurian, Ming Lim, Lokesh Lingappa, Andrew Lux, Linda de Meirleir, Lakshmi Nagarajan, Robert Ouvrier, Raili Riikonen, Arushi Saini, Michael Shevell, Pratibha Singhi, Takao Takahashi, Ingrid Tein, Ruth Williams.</p> <p>We are still looking for section editors for the journal, who show commitment to the journal. We have suggested the following criteria: i) contribute at least two papers (one research and one review); ii) review at least two papers within 2 weeks; iii) be prepared to help people from low resource areas to analyse and write up their research; and iv) have acknowledged expertise in the area of section (reference from another person in the field). This does represent considerable commitment in terms of time and energy. Please contact us if you would like to be and can commit to be a section editor.</p> <p>Papers in JICNA can be accessed through the JICNA web site, and through CrossRef, Google Scholar and are distributed under the terms of the Creative Commons Attribution License. In 2018 we hope that JICNA will be recognised by other free search engines. &nbsp;&nbsp;</p> 2018-02-14T22:06:06+00:00 ##submission.copyrightStatement## The association between human herpes viruses and acute symptomatic seizures in Kenyan children 2019-02-18T10:08:10+00:00 Symon M Kariuki Christian Schubart Charles RJC Newton <p align="center"><strong>Background</strong></p><p>In malaria endemic areas, where up to 70% of children have peripheral parasitaemia, it is unclear why some children develop seizures. Human herpes viruses are common causes of febrile seizures. We investigated the hypothesis that seizures in children admitted to hospital are caused by concomitant human herpes virus infections.</p><p align="center"><strong>Methods</strong></p><p>We examined the presence of parasitaemia in plasma and viruses in cerebrospinal fluid (CSF) of 100 children with acute symptomatic seizures (84% with complex acute symptomatic seizures (focal, repetitive or prolonged)) and in 45 children without seizures using polymerase chain reaction. The analysis compared the distribution of human herpes virus between children with acute symptomatic seizures and those without these seizures by computing odds ratios using a logistic regression accounted for potential confounders.</p><p align="center"><strong>Results</strong></p><p>Human herpes viruses 6 &amp; 7 were found in the CSF of 22% of children with acute symptomatic seizures and in 24% of those without seizures, and overall, there was no association with acute symptomatic seizures ((adjusted odds ratio (OR)=1.48 (95%CI, 0.54-4.05), p=0.448) nor complex acute symptomatic seizures (OR=2.34 (95%CI, 0.92-5.97), p=0.075). Human herpes virus 7 was significantly associated with complex acute symptomatic seizures (OR=8.80 (95%CI, 1.20-64.84), p=0.033), while herpes virus 6 was not (OR=1.71 (95%CI, 0.55-5.30), p=0.351). The logistic regression model with significant association for human herpes virus 7 and complex acute symptomatic seizures accounted for falciparum malaria, malnutrition and CSF protein levels, whose inclusion effect modified the OR of a baseline model by 81%.</p><p align="center"><strong>Conclusions</strong></p><p>Human herpes virus 7 but not 6 is associated with common complex acute symptomatic seizures in a malaria endemic area in Kenya. Viruses should be screened in children admitted with acute symptomatic seizures.<strong></strong></p> 2019-02-18T10:08:10+00:00 ##submission.copyrightStatement## Hypochondroplasia and epilepsy: the neurological spectrum of FGFR3 mutations 2018-02-15T23:23:33+00:00 Emma A van der Poest Clement Edward Yang Ingrid Holm Jurriaan M Peters <p>Hypochondroplasia is a disorder caused by FGFR3 mutations, commonly featuring short limbs and stature. Thanatophoric dysplasia, achondroplasia and Muenke syndrome are genetically related conditions with skeletal dysplasia and temporal lobe dysgenesis. We present a 6-month old boy with hypochondroplasia and epilepsy. His brain MRI revealed bilateral temporal lobe dysplasia, with redundant sulci and a rotated hippocampus. The neuroimaging findings of our case provide direct insight in the pathogenesis of the cerebral dysgenesis in FGFR3-related disorders. In addition, through this case we review the neurological spectrum of FGFR3 mutations.</p> 2018-02-14T22:06:06+00:00 ##submission.copyrightStatement## Three Siblings with Progressive Encephalopathy and Destructive White Matter Lesions 2018-05-09T22:32:08+00:00 Helen Franckx Katriens Stouffs Tim Vanderhasselt Sara Seneca Alexander Gheldof Linda De Meirleir <p>Intellectual disability is an important health issue, with a prevalence estimated at 1%. Autosomal genes are increasingly identified as an important cause, although still few of them are known. Most cases are of recessive origin and are found in large consanguineous families in the Middle East.&nbsp; Mutations in the <em>TRAPPC9</em> gene have been reported in different families and are associated with a nonsyndromic form of intellectual disability, although phenotypic abnormalities such as a specific facial appearance, obesity, hypotonia and consistent brain abnormalities were linked to these mutations. Here, we describe three siblings of consanguineous Algerian parents with a homozygous c.1708C&gt;T, p. Arg570* mutation in the <em>TRAPPC9</em> gene. Initially a relatively normal development was seen until the age of 12-18 months, with from then on a progressive degradation of their mental and motor state and the presence of convulsions in two of them. This, in combination with progressive white matter lesions seen on repetitive magnetic resonance imaging, suggests that this <em>TRAPPC9</em> mutation should not only be considered as a form of intellectual disability, but also as a neurodegenerative disease.</p> 2018-02-14T22:06:06+00:00 ##submission.copyrightStatement## Status Epilepticus due to Baclofen Intoxication 2018-02-15T23:23:33+00:00 Maryam Bahreini <p><em>Background</em>. Baclofen is a muscle relaxant agent that in toxic doses exhibits symptoms such as depressed mental status, hypotonia, hyporeflexia, and respiratory depression. Seizure is a less common presentation of Baclofen toxicity, especially in pediatric patients. <br /> <em>Case</em> <em>Description</em>. The patient was a 4 year-old boy with no previous neurologic disorder who experienced status epilepticus after ingestion of high dose of Baclofen orally. He was treated conservatively and after 8 hours, he became awake in good condition without any abnormal finding in imaging or laboratory tests.<br /> <em>Discussion. </em>This case describes some rare clinical presentations of Baclofen toxicity that were seizure and bradycardia in an otherwise-normal pediatric patient which could be managed conservatively.</p> 2018-02-14T22:06:06+00:00 ##submission.copyrightStatement## Improvement of Symptomatic West Syndrome in a Child with Protein C Deficiency following Liver Transplantation 2018-05-11T20:09:47+00:00 Mariko Kasai Masatoshi Matsunami Hiroshi Terashima Akinari Fukuda Mureo Kasahara Masaya Kubota <p>In symptomatic West syndrome, multiple brain pathologies have been demonstrated as causal factors. Usually the epileptic spasms are intractable and the patients remain in a state of severe intellectual disability. Because adrenocorticotropic hormone (ACTH) is a standard and the most effective therapy for intractable spasms, neuro-immuno-modulatory aspects have been postulated to be involved in the pathogenesis, but details remain unclear. We here present the clinical course of a girl with West syndrome due to neonatal intracerebral hemorrhages secondary to protein C deficiency whose intractable spasms and electroencephalogram (EEG) abnormality improved dramatically after liver transplantation which included tacrolimus administration. Recently, many studies have shown that activation of calcineurin is involved in the enhancement of cortical excitability through the control of GABAergic inhibition. We speculate that tacrolimus, as a calcineurin inhibitor, may have played a role in the improvement of her spasms following liver transplantation by promoting GABAergic inhibition. This is the first report that West syndrome can be improved by tacrolimus.</p> 2018-05-11T19:57:05+00:00 ##submission.copyrightStatement## Lyme Disease or Multiple Sclerosis? Two cases with overlapping features. 2019-05-21T13:22:07+00:00 Katarzyna Kotulska-Jóźwiak Iliyana Pacheva Anna Patrova Elżbieta Jurkiewicz Jurkiewicz Ivan Ivanov Dariusz Kuczyński Ina Geneva <p><strong>Background</strong>, &nbsp;The etiology of multiple sclerosis is unclear and infectious agents have been considered. Borrelia infections can cause an intrathecal inflammatory response with accompanying cerebral and spinal imaging findings.</p> <p><strong>Cases. </strong>Two children with acute or subacute initial neurological presentation, subsequent relapsing&nbsp; course, and MR imaging features suggestive of multiple sclerosis are presented. A history of tick bite or dramatic response to antibiotic treatment supported Lyme disease in the beginning, but requirement of disaese-modifying treatment later in the course supported multiple sclerosis.</p> <p><strong>Results</strong>. These cases carrying features supportive of both multiple sclerosis and Lyme disease caused clinical dilemma and were treated for both disorders. Borrelia-specific IgG index testing before any treatment could have prevented the difficulty in differential diagnosis.</p> <p><strong>Conclusions</strong>. Clinical, imaging and CSF findings of multiple sclerosis and acute or chronic progressive borrelia encephalomyelitis may overlap and testing for Borrelia-specific intrathecal antibody synthesis should not be omitted in endemic areas.</p> 2019-02-18T09:55:18+00:00 ##submission.copyrightStatement## Valproate-induced reversible atrophy and cognitive decline: a case 2019-02-18T10:02:47+00:00 Emily Amy Innes Alexandra M Johnson <p>Background: Valproate (VPA) has been previously described to cause reversible cerebral atrophy and cognitive decline, but few cases are reported and neuropsychological data is lacking. We report a case of VPA induced encephalopathy in an 11-year-old girl with temporal lobe epilepsy, presenting with impaired cognition and sedation combined with cerebral atrophy.</p> <p>Methods: Cognitive capacity was assessed using Wechsler Intelligence Scales for Children IV (WISC), non-standardised word lists and visual reproduction. Brain magnetic resonance imaging (MRI) was performed prior to, during and post VPA therapy.</p> <p>Results: Our patient demonstrated average full-scale intelligence quotient, verbal comprehension, perceptual reasoning and working memory. There was a marked discrepancy in processing speed, which ranked low average (score – 80; 9<sup>th</sup> percentile). Difficulties with mental abstraction and manipulation were noted. Brain MRI (3T) demonstrated mild generalised parenchymal atrophy. Cessation of VPA resulted in dramatic improvement in clinical symptoms (1 month after cessation) and normalisation of brain MRI (11 months after cessation). Progress neuropsychological testing 13 months after cessation showed marked improvements in processing speed.&nbsp;</p> <p>Conclusion: This case provides an important reminder of this rare but importantly reversible syndrome with new information supporting the neuropsychological changes involved.</p> 2019-02-18T09:59:51+00:00 ##submission.copyrightStatement## Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in a child with ataxia and diplopia 2019-03-01T00:15:38+00:00 Erim van Os Malou Nijhuis Stephan Malm <p>We report the case of a 15-year-old boy with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). He presented with diplopia and ataxia and his cerebrospinal fluid showed mild pleocytosis and elevated protein. MRI demonstrated a reversible splenial lesion in the corpus callosum. He did not receive any treatment and recovered quickly within two weeks. Results of neurological examination after 3 months were completely normal. MERS is relatively unknown in Europe. The majority of patients are reported in East Asia. This post-infectious encephalitis/encephalopathy arises soon after the onset of symptoms. The prognosis is excellent and most patients recover completely without neurological sequelae. MRI typically shows a reversible splenial lesion with diffusion restriction and without contrast enhancement, sometimes with adjacent symmetrical lesions extending into the subcortical white matter. The pathogenesis is still unknown. Recognition of the condition and its clinic-radiological discrimination from acute disseminated encephalomyelitis may prevent unnecessary treatment.</p> 2019-03-01T00:00:21+00:00 ##submission.copyrightStatement## Diagnosing neurodegeneration with brain iron accumulation before iron starts to accumulate 2019-03-01T00:17:38+00:00 Ine Hoogwijs <p><span style="font-family: Calibri;">Introduction</span></p> <p><span style="font-family: Calibri;">Neurodegeneration with brain iron accumulation (NBIA) consists of a heterogeneous group of disorders with brain iron accumulation as common radiological endpoint. Mutations in multiple genes have been associated with NBIA. We present 2 cases with a different type of NBIA, in whom the diagnosis was confirmed before brain iron accumulation became evident on MRI.</span></p> <p><span style="font-family: Calibri;">&nbsp;</span><span style="font-family: Calibri;">Case description</span></p> <p><span style="font-family: Calibri;">The first patient was referred because of frequent falls at the age of 4 years. She had an ataxic gait and weak Achilles tendon reflexes. Two years later, pyramidal and more prominent cerebellar signs became evident. A skin and muscle biopsy revealed intra-axonal spheroids in the peri-and endomysial myelinated nerve bundles as well as in the motor endplates, which led to the diagnosis of PLA2G6-associated neurodegeneration (PLAN). Brain iron accumulation occurred at follow-up MRI at 9 years of age.</span></p> <p><span style="font-family: Calibri;">The second patient was referred because of developmental stagnation and detection of elevated liver enzymes at 3 months of age. Seizures started at 15 months of age, and were refractory to treatment with multiple anti-epileptic drugs. Molecular genetic testing using an epilepsy gene panel revealed a mutation in the <em>WDR45</em> gene, a known cause of beta-propeller protein-associated neurodegeneration (BPAN). Brain MRI at 14 months of age showed diffuse hypomyelination in the absence of BIA.</span></p> <p><span style="font-family: Calibri;">&nbsp;</span><span style="font-family: Calibri;">Discussion</span></p> <p><span style="font-family: Calibri;">This report highlights that NBIA can be suspected on a clinical basis and confirmed by genetic testing before iron accumulation becomes present on brain MRI. Early diagnosis will provide a longer timeframe for potential disease modulating treatments in the future.</span></p> 2019-03-01T00:17:38+00:00 ##submission.copyrightStatement## Febrile encephalopathy 2018-11-12T16:47:33+00:00 Pratibha Singhi Naveen Sankhyan <p>Febrile encephalopathy can be due to various causes that vary according to the local epidemiology and season. The critical window for diagnosis and effective intervention is often short. The basic principles of management include; the initial assessment and stabilization, focussed clinical evaluation and neurological assessment. Management include general and specific measures. Raised intracranial pressure, seizures and hemodynamic instability must be managed urgently and appropriately, since the diagnosis or specific etiology is not immediately apparent, empiric therapy based on local disease prevalence is initiated. A more specific management can be followed after a diagnosis is established or is reasonably certain.</p> 2018-11-12T16:47:33+00:00 ##submission.copyrightStatement## The use of the ketogenic diet in the treatment of epileptic encephalopathies 2018-11-12T16:55:08+00:00 Roberto Caraballo <p>Epileptic encephalopathies(EE) are severe conditions characterized by paroxysmal activity on the electroencephalogram (EEG) that is often aggressive, seizures that are commonly multi-form and intractable, and severe cognitive and behavioral disturbances that present or worsen after the onset of epilepsy. The ketogenic diet (KD) has been shown to be effective in the treatment of refractory epileptic encephalopathies, and has been suggested as an early treatment option in very young children.</p><p>Although the experience is often anecdotal and mostly consists of case reports and case series, the aim of this study was to present our own experience and an overview of the current literature on the diet in patients with EE.</p><p>Some encephalopathies, such as epilepsy with myoclonic and atonic seizures, West syndrome, Dravet syndrome, or Lennox-Gastaut syndrome, are well recognized and known to have a good response to the ketogenic diet, while others are more rare or only recently identified, such as epilepsy with focal migrating seizures in infancy, febrile infection-related epilepsy syndrome, or myclonic status in non-progressive encephalopathy, about which little is known and the KD is only tried in sporadic cases.</p><p>EE are typically refractory to the antiepileptic drugs and the KD  should be considered earlier in the therapeutic scheme of these severe epileptic syndromes. The KD including the oral formula may be considered in all pediatric patients with EE even in infancy.</p> 2018-11-12T16:55:05+00:00 ##submission.copyrightStatement##