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Introduction Status epilepticus (SE) is a neurological emergency in which immediate intervention is required to prevent permanent brain damage and death. Intravenous (IV) valproic acid (VPA) is often used for the treatment of SE. However, IV VPA frequently increases the blood ammonia level. In this study, we explore the impact of IV VPA-induced hyperammonemia (HA) on treatment management of SE and discuss the challenges related to this particular condition. Methods We used data from medical records of 31 adult patients (≥ 18 years) treated with IV VPA for SE at Oslo University Hospital between January 2006 and October 2019. Clinical and blood sample data and information about the influence of HA on treatment were collected. Correlations between ammonia levels and other continuous or categorical variables were tested using the Pearson's correlation coefficient. The Kruskal–Wallis H-test was used to analyze associations between different variables and treatment decisions. Results Thirty of 31 patients had increased ammonia level during IV VPA treatment. In 16/30 patients, VPA was discontinued, and in 6/30 patients, the dose was reduced. We found a difference in the median peak ammonia level among the groups where VPA was discontinued (99 μmol/l), reduced (71 μmol/l), and continued (55.5 μmol/l) (P = 0.008). Also clinical status, measured by West Haven Criteria, varied among the groups where VPA was discontinued (3.5), reduced (2.5), and continued (2.0) (P = 0.01). Treatment decisions at peak ammonia were not associated with the level of liver enzymes and bilirubin. Conclusion Hyperammonemia had a substantial impact on further management. To date, no recommendations exist on how to manage VPA-induced HA in SE. We call for systematic prospective studies and evidence-based guidelines.

Objective: To investigate the presence of small nerve fiber dysfunction in subjects with X-linked adrenoleukodystrophy. Methods: Cross-sectional study in which 11 Norwegian subjects (3 males, 8 females) with X-linked adrenoleukodystrophy, phenotypes ranging from asymptomatic to wheelchair-bound with adrenomyeloneuropathy, were investigated with neurophysiologic studies including EMG, nerve conduction velocities, quantitative sensory testing, tests of autonomic function, and skin biopsy for intraepidermal nerve fiber density measurements. Results: We found small nerve fiber dysfunction in 10 of 11 subjects, increasing with age and more pronounced in males. Low intraepidermal nerve fiber densities were found in 5 of 11 subjects, indicating a loss of thin unmyelinated nerve fibers peripherally. Five of 11 subjects showed small nerve fiber dysfunction despite normal nerve fiber densities, suggesting possible involvement of the spinothalamic tracts. Two subjects showed moderate abnormalities in autonomic function tests. Conclusions: Evidence of small nerve fiber dysfunction was widespread in this cohort of subjects with X-linked adrenoleukodystrophy, with findings indicating loss of peripheral small nerve fibers and possibly also fibers of the spinothalamic tracts. The results support the theory of primary axonal degeneration in adrenomyeloneuropathy. Evidence of nervous system involvement was found in all heterozygotes, with severity increasing with age. Clinicians caring for these patients should be alert to signs of small nerve fiber involvement.

To investigate X-linked adrenoleukodystrophy in an unselected population, we performed a population based, cross-sectional prevalence study, supplemented by a retrospective study of deceased subjects. Sixty-three subjects (34 males, 29 females) belonging to 22 kindreds were included. Thirty-nine subjects (13 males, 26 females) were alive, and 24 (21 males, 3 females) were deceased on the prevalence day. The point prevalence of X-linked adrenoleukodystrophy in Norway on July 1, 2011, was 0.8 per 100,000 inhabitants. The incidence at birth in the period 1956-1995 was 1.6 per 100,000 inhabitants. An age-dependent penetrance was observed among males and females, with more severe phenotypes appearing with rising age. Only 5% of deceased males had not developed cerebral leukodystrophy. No female older than 50 years was neurologically intact. Sixteen mutations in the ABCD1 gene were identified. De novo mutations were found in 19% of probands. The frequency of X-linked adrenoleukodystrophy was lower in Norway than reported in the literature. A more severe natural course than previously reported was observed, indicating a need for better follow-up of both male and female patients. Given the high rate of de novo mutations, identification programs such as newborn screening may be required to offer timely treatment to all patients.

International audience; Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of rare diseases resulting from impaired neuromuscular transmission. Their clinical hallmark is fatigable muscle weakness associated with a decremental muscle response to repetitive nerve stimulation and frequently related to postsynaptic defects. Distal myopathies form another clinically and genetically heterogeneous group of primary muscle disorders where weakness and atrophy are restricted to distal muscles, at least initially. In both congenital myasthenic syndromes and distal myopathies, a significant number of patients remain genetically undiagnosed. Here, we report five patients from three unrelated families with a strikingly homogenous clinical entity combining congenital myasthenia with distal muscle weakness and atrophy reminiscent of a distal myopathy. MRI and neurophysiological studies were compatible with mild myopathy restricted to distal limb muscles, but decrement (up to 72%) in response to 3 Hz repetitive nerve stimulation pointed towards a neuromuscular transmission defect. Post-exercise increment (up to 285%) was observed in the distal limb muscles in all cases suggesting presynaptic congenital myasthenic syndrome. Immunofluorescence and ultrastructural analyses of muscle end-plate regions showed synaptic remodelling with denervation-reinnervation events. We performed whole-exome sequencing in two kinships and Sanger sequencing in one isolated case and identified five new recessive mutations in the gene encoding agrin. This synaptic proteoglycan with critical function at the neuromuscular junction was previously found mutated in more typical forms of congenital myasthenic syndrome. In our patients, we found two missense mutations residing in the N-terminal agrin domain, which reduced acetylcholine receptors clustering activity of agrin in vitro. Our findings expand the spectrum of congenital myasthenic syndromes due to agrin mutations and show an unexpected correlation between the mutated gene and the associated phenotype. This provides a good rationale for examining patients with apparent distal myopathy for a neuromuscular transmission disorder and agrin mutations.

Objectives X-linked adrenoleukodystrophy is an important cause of Addison's disease in boys, but less is known about its contribution to Addison's disease in adult men. After surveying all known cases of X-linked adrenoleukodystrophy in Norway in a separate study, we aimed to look for any missed cases among the population of adult men with nonautoimmune Addison's disease. Study design Among 153 adult men identified in a National Registry for Addison's Disease (75% of identified male cases of Addison's disease in Norway), those with negative indices for 21-hydroxylase autoantibodies were selected. Additionally, cases with low autoantibody indices (48-200) were selected. Sera from subjects included were analysed for levels of very long-chain fatty acids, which are diagnostic for X-linked adrenoleukodystrophy in men. Results Eighteen subjects had negative indices and 17 had low indices for 21-hydroxylase autoantibodies. None of those with low indices and only one of those with negative indices were found to have X-linked adrenoleukodystrophy; this subject had already been diagnosed because of the neurological symptoms. Cases of Addison's disease proved to be caused by X-linked adrenoleukodystrophy constitute 1·5% of all adult male cases in Norway; the proportion among nonautoimmune cases was 15%. Conclusions We found X-linked adrenoleukodystrophy to be an uncommon cause of Addison's disease in adult men. However, this aetiological diagnosis has far-reaching consequences both for the patient and for his extended family. We therefore recommend that all adult men with nonautoimmune Addison's disease be analysed for levels of very long-chain fatty acids.

Stiff person syndrome (SPS) is a rare neurological disorder characterized by simultaneous contraction of agonistic and antagonistic muscles. SPS can easily be confused with a psychogenic movement disorder, but the frequent finding of autoantibodies against glutamic acid decarboxylase (GAD65), positive response to immunomodulatory treatment and association with other autoimmune diseases strongly suggests an immununological pathogenesis.A 43-year-old man was admitted with a three-year history of stiffness and painful spasms in the left leg, causing walking problems and frequent falls. A clinical examination revealed a bizarre gait, pes equinovarus, and simultaneous contraction of agonistic and antagonistic muscles, but no other neurological deficits. Electromyography was normal except for simultaneous contraction of agonistic and antagonistic muscles. Magnetic resonance imaging of the neuraxis and routine examinations of blood and cerebrospinal fluid were normal. A diagnosis of conversion neurosis was considered, but was not supported by positive evidence. The symptoms gradually evolved to affect the back and both legs. Elevated levels of antibodies against GAD65 in serum and cerebrospinal fluid confirmed the diagnosis SPS three and a half years after symptom debut. Both stiffness and muscle cramps responded excellently to diazepam.This report calls attention to a rare neurological disease, in which absence of specific neurological deficits may lead to an erroneous diagnosis of a psychogenic disorder.

Osler's disease is an inherited disease of blood vessels that causes haemorrhage from the nasal mucosa, gastrointestinal tract, lungs or the urinary tract. Patients may also have abnormal intracerebral vessels.A patient with Osler's disease and recurrent epistaxis suffered a cerebellar infarction. He had no other risk factors for stroke. An arteriovenous fistula was demonstrated in the right lung. This fistula was the probable source or aberrant pathway of an embolus to the cerebellum. The patient was treated with endovascular occlusion of the fistula to prevent further emboli to the brain.Embolisation of thrombi from arteriovenous fistulae in the lungs is a rare cause of stroke, though important since secondary prophylaxis is very effective. Physicians should consider this possibility in the occasional patient with embolic stroke in whom no other risk factor is established.