Martin Kirkpatrick

Familial hemiplegic migraine is associated with febrile seizures in an FHM2 family with a novel de novo ATP1A2 mutation

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Risk and causes of death in children with a seizure disorder

Aim  To describe the frequency and causes of death in children with epilepsy, ascertain the contribution of seizure disorder to cause of death, and compare with rates of sudden unexplained death in children without epilepsy.

Adherence to antiepileptic drugs in children with epilepsy in a Scottish population cohort

To measure the adherence to antiepileptic drugs (AED) in a population cohort of children with epilepsy and to study the relationship between adherence and a series of clinical variables.

Growing up with spinal muscular atrophy with respiratory distress (SMARD1)

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an inherited neuromuscular condition resulting from recessive mutations in the immunoglobulin mu-binding protein (IGHMBP2) gene. Affected individuals characteristically present in infancy with progressive distal weakness and respiratory distress secondary to diaphragmatic weakness. Considerable clinical heterogeneity has been described both in its presentation and phenotype in childhood; however little data pertaining to phenotype in adulthood have been reported to date. This report describes a 21 year old woman with genetically confirmed SMARD1 who has stable muscle weakness, normal cognitive abilities and is able to lead a socially integrated lifestyle, using mechanical ventilation only overnight. This report adds new evidence for clinical variability throughout the course of SMARD1.

Developing clinical practice guidelines for epilepsy: A report from the ILAE Epilepsy Guidelines Working Group.

Clinical practice guidelines (CPGs) contain evidence‐based recommendations to guide clinical care, policy development, and quality of care improvement. A recent systematic review of epilepsy guidelines identified considerable variability in the quality of available guidelines. Although excellent frameworks for CPG development exist, processes are not followed uniformly internationally, and resources to develop CPGs may be limited in certain settings. An International League Against Epilepsy (ILAE) working group was charged with proposing methodology to guide the development of future epilepsy‐specific CPGs. A comprehensive literature search (1985–2014) identified articles related to CPG development and handbooks. Guideline handbooks were included if they were publicly available, and if their methodology had been used to develop CPGs. The working groups expertise also informed the creation of methodologies and processes to develop future CPGs for the ILAE. Five handbooks from North America (American Academy of Neurology), Europe (Scottish Intercollegiate Guidelines Network & National Institute for Health and Care Excellence), Australia (National Health and Medical Research Council), World Health Organization (WHO), and additional references were identified to produce evidence‐based, consensus‐driven methodology for development of epilepsy‐specific CPGs. Key components of CPG development include the following: identifying the topic and defining the scope; establishing a working group; identifying and evaluating the evidence; formulating recommendations and determining strength of recommendations; obtaining peer reviews; dissemination, implementation, and auditing; and updating and retiring the CPG. A practical handbook and toolkit was developed. The resulting CPG development toolkit should facilitate the development of high‐quality ILAE CPGs to improve the care of persons with epilepsy.

Aicardi syndrome in a 47 XXY male – A variable developmental phenotype?

BACKGROUND Aicardi syndrome (AS) is a rare neurodevelopmental disorder characterized by the triad of corpus callosum agenesis, chorioretinal lacunae, and infantile spasms. Most patients with AS also have intractable epilepsy, moderate to severe learning disability, and a reduced life expectancy. An X-linked dominant inheritance caused by de novo mutations pattern, lethal in males, is postulated, but the gene has not yet been isolated. There are three case reports of 47 XXY males with classic features of AS who all had severe developmental disability. CASE REPORT We report a case of a 3.5-year old 47 XXY male with the classic triad of Aicardi syndrome but with good seizure control and mild learning disability.

Acute motor neuropathy with pure distal involvement – A case report of multifocal motor neuropathy

Multifocal motor neuropathy is an acquired pure motor neuropathy seen principally in adults and usually responds to treatment with intravenous immunoglobulin. We report a 12 year old boy with marked distal weakness in both upper and lower limbs with no proximal involvement. These clinical features appear to be distinct from more common inflammatory childhood neuropathies and are in keeping with a diagnosis of Multifocal Motor Neuropathy. Confirming the diagnosis, serial nerve conduction studies showed a pattern of pure motor conduction block with normal sensory potentials. To our knowledge this is only the second case report of this condition occurring in childhood.

Guidelines, training, audit, and quality standards in children's epilepsy services: Closing the loop

There has been considerable evolution in epilepsy healthcare for children over the last decade in the United Kingdom. There has been no single explanation for this. The development of national clinical guidelines, locally delivered but nationally designed educational programmes, nation-wide clinical audit, clinical networks and development of designated services have all had complimentary roles in enabling the implementation of national recommendations for the development of epilepsy care. These models may be applicable to other healthcare settings outside the UK.

A novel mutation of NKX2-1 affecting 2 generations with hypothyroidism and choreoathetosis: part of the spectrum of brain-thyroid-lung syndrome.

The NKX2-1 (TTF-1 or TITF-1) gene on chromosome 14q13 codes for the thyroid transcription factor 1 (TTF-1). It is expressed in the developing brain, lung, and thyroid. Defects have been associated with chorea, hypothyroidism, and lung disease, comprising the “brain-thyroid-lung syndrome.” We describe here 3 cases of novel missense mutation (c.626G>C; p.Arg209Pro) in NKX2-1 in 2 generations of a nonconsanguinous family. Firstly 2 sons were affected by childhood-onset hypothyroidism and a movement disorder characterized by ataxia in the early years followed by the emergence of a superimposed chorea. The mutation was also found in the granddaughter, when she presented with the same clinical features. We hypothesize that the mutation arose as a result of gonadal mosaicism, as the mutation was not detected in leucocyte DNA from either grandparent. The features are consistent with a diagnosis of Brain-thyroid-lung syndrome, which previously could have been classified as benign hereditary chorea with hypothyroidism.

TBC1D24 Mutations in a Sibship with Multifocal Polymyoclonus

Background Advances in molecular genetic technologies have improved our understanding of genetic causes of rare neurological disorders with features of myoclonus. Case Report A family with two affected siblings, presenting with multifocal polymyoclonus and neurodevelopmental delay, was recruited for whole-exome sequencing following unyielding diagnostic neurometabolic investigations. Compound heterozygous mutations in TBC1D24, a gene previously associated with various epilepsy phenotypes and hearing loss, were identified in both siblings. The mutations included a missense change c.457G>A (p.Glu157Lys), and a novel frameshift mutation c.545del (p.Thr182Serfs*6). Discussion We propose that TBC1D24-related diseases should be in the differential diagnosis for children with polymyoclonus.