[«A most strange instance of illness in several siblings¼--first description of a rare neurological disease in 1830?]. / «Et høist mærkeligt Sygdomstilfælde hos flere Sødskende¼--en norsk førstegangsbeskrivelse fra 1830?

Was district medical officer Jensen the first doctor to describe patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN) in Volda in 1830? A case series of four siblings with the same disease written by district medical officer Peter Jensen (1799-1832) in Aalesund in 1830, was published in the Norwegian medical journal Eyr in 1832. The children, who were healthy almost up to school age, developed dystonic involuntary movements and deformities in all extremities, lost their ability to speak and were emaciated before they died at around the age of nine years. Further information about the family and a fifth affected child has been found in the parish records. The clinical picture is consistent with Pantothenate Kinase-Associated Neurodegeneration (PKAN), a rare condition with basal ganglia iron deposition, described in 1922 by the German neuropathologists Julius Hallervorden (1882-1965) and Hugo Spatz (1888-1969). The disease was formerly called Hallervorden-Spatz syndrome, but because of the medical activities undertaken by these two researchers before and during the Second World War, this eponym is no longer recommended.

Clinical and muscle biopsy findings in Norwegian paediatric patients with limb girdle muscular dystrophy 2I.

AIM: To describe patients diagnosed with limb girdle muscular dystrophy 2I (LGMD2I) in our paediatric departments between 2004 and 2012. METHODS: The hospital charts of 17 patients presenting for evaluation at a mean age of 7.8 years (range 1-13 years) were retrospectively reviewed. RESULTS: With one exception, all patients were homozygous for the common mutation c.826C>A in the FKRP gene. Three patients experienced transient pronounced weakness as toddlers. Fatigue and muscle pain were most prominent, weakness less so, in children presenting at an older age. The degree of severity varied substantially. In certain cases, increased creatine kinase was an incidental finding. All walked independently by 18 months. When last evaluated at a mean age of 14.3 years (range 3.5-18 years), five patients were part-time wheelchair users. One patient was then treated for a cardiomyopathy. Creatine kinase was consistently increased, except presymptomatic in one patient. Muscle biopsies showed focal acute and chronic myopathic changes and pathological expression of α-dystroglycan. No consistent relationship between clinical function and the degree of morphological pathology was found. CONCLUSION: LGMD2I is a relevant differential diagnosis when creatine kinase is increased in children presenting with fatigue, muscle pain and sometimes weakness.

[Assessment of ADHD with EEG]. / EEG-utredning ved AD/HD.

BACKGROUND: Many children with ADHD develop epilepsy, and approximately 20% of children with epilepsy also have ADHD. In this article we discuss the use of EEG in connection with ADHD in children, with emphasis on the diagnosis of comorbid epilepsy. METHOD: The article is based on a literature search in PubMed, personal literature archives and the authors' own experience with the use of EEG, treatment of epilepsy and the diagnosis and treatment of ADHD in children and adolescents. RESULTS: A moderately elevated prevalence of epileptiform EEG activity is described in children with ADHD without epilepsy compared with healthy children, during both wakefulness and sleep. Selected material and a lack of controlled blinded studies probably explain much of this difference. The significance of epileptiform EEG activity in children with ADHD without seizures is uncertain. Evaluating the extent to which EEG findings may explain the symptoms and whether anti-epileptic drugs should be tried is a specialist task. In many studies, spectral analysis of the frequency content of the EEG (QEEG) has shown higher slow theta activity and a higher theta/beta ratio in children with ADHD. INTERPRETATION: Seizure symptoms, disturbed sleep quality, significant changes in behaviour or regression of cognitive ability in children with ADHD should lead to paediatric neurological assessment with EEG and possibly a 24-hour EEG. In our view, the QEEG variables are artifact-prone and biologically unspecific. We therefore do not recommend the use of QEEG as a stand-alone diagnostic marker.

[Epilepsy in children in the Sunnmøre District]. / Epilepsi hos barn på Sunnmøre.

BACKGROUND: The intention of this retrospective study was to collect information on epilepsy in children in the catchment area of the Sunnmøre Hospital Trust, to compare the findings with other Norwegian and international studies and to assess the medical services for this patient group. MATERIAL AND METHODS: We studied hospital records for all children born in the period 1989-2003 (a population of 30,106), and estimated the point prevalence for the date 31.12.2003. Guidelines and proposals from the International League Against Epilepsy were followed. RESULTS: 141 children with epilepsy were identified (88 boys and 53 girls), the sex ratio was 1.66 and the total prevalence 4.7 (3.9-5.5) per 1000 children. At the prevalence date, 114 children had active epilepsy, giving a point prevalence of 3.8 (3.1-4.5) per 1000 children. For the year 2003, the incidence rate of new cases was 46.8 per 100,000. 52% of the seizures were classified as focal, 37% as generalized and 11% were unclassified. Of the epilepsies and epileptic syndromes, 50% were classified as focal, 40% as generalized and 10% were unclassified. A likely aetiology of the epilepsy was found in 41% of the cases. INTERPRETATION: The prevalence of epilepsy in children in the Sunnmøre District does not differ from that in other Nordic countries. Classification of seizures and the distribution of epilepsies and epileptic syndromes were similar to that in other studies. The incidence of epilepsy among children in Norway has remained quite stable the last 30-40 years. The study shows that patients were diagnosed and treated according to international guidelines and recommendations.

Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome.

BACKGROUND: The Björnstad syndrome, an autosomal recessive disorder associated with sensorineural hearing loss and pili torti, is caused by mutation of a previously unidentified gene on chromosome 2q34-36. METHODS: Refined genetic mapping and DNA sequencing of 44 genes between D2S2210 and D2S2244 revealed BCS1L mutations. Functional analyses elucidated how BCS1L mutations cause the Björnstad syndrome. RESULTS: BCS1L encodes a member of the AAA family of ATPases that is necessary for the assembly of complex III in the mitochondria. In addition to the Björnstad syndrome, BCS1L mutations cause complex III deficiency and the GRACILE syndrome, which in neonates are lethal conditions that have multisystem and neurologic manifestations typifying severe mitochondrial disorders. Patients with the Björnstad syndrome have mutations that alter residues involved in protein-protein interactions, whereas mutations in patients with complex III deficiency alter ATP-binding residues, as deduced from the crystal structure of a related AAA-family ATPase. Biochemical studies provided evidence to support this model: complex III deficiency mutations prevented ATP-dependent assembly of BCS1L-associated complexes. All mutant BCS1L proteins disrupted the assembly of complex III, reduced the activity of the mitochondrial electron-transport chain, and increased the production of reactive oxygen species. However, only mutations associated with complex III deficiency increased mitochondrial content, which further increased the production of reactive oxygen species. CONCLUSIONS: BCS1L mutations cause disease phenotypes ranging from highly restricted pili torti and sensorineural hearing loss (the Björnstad syndrome) to profound multisystem organ failure (complex III deficiency and the GRACILE syndrome). All BCS1L mutations disrupted the assembly of mitochondrial respirasomes (the basic unit for respiration in human mitochondria), but the clinical expression of the mutations was correlated with the production of reactive oxygen species. Mutations that cause the Björnstad syndrome illustrate the exquisite sensitivity of ear and hair tissues to mitochondrial function, particularly to the production of reactive oxygen species.