Ivar Otto Gjerde

Leukoencephalopathy with brainstem and spinal cord involvement caused by a novel mutation in the DARS2 gene

Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) is a rare, autosomal recessive disorder caused by mutations in the gene encoding a mitochondrial aspartyl-tRNA synthetase, DARS2. The disease is characterized by progressive spastic ataxia and magnetic resonance imaging (MRI) shows a highly characteristic leukoencephalopathy with multiple long tract involvement. We describe the clinical and radiological features of two new cases of LBSL and report a novel pathogenic mutation in the DARS2 gene. Both patients had typical clinical and radiological findings, although no elevated lactate was found. The severity of MRI changes did not correlate with clinical course and severity suggesting that, although of highly specific diagnostic value, MRI does not necessarily reflect clinical activity and should not be used to assess disease severity or prognosis in LBSL.

Excellent response of intramedullary Erdheim-Chester disease to vemurafenib: a case report

BackgroundErdheim-Chester disease is a rare histiocytosis characterized by multi-systemic organ involvement. Immune-modulating agents such as interferon-alpha have limited success and the disorder is progressive and causes high morbidity and mortality. Treatment with the BRAF-inhibitor vemurafenib has recently produced substantial improvement in three patients with Erdheim-Chester disease expressing the p. V600E BRAF mutation. The disorder commonly affects the central nervous system and it is not yet known whether vemurafenib can reverse intra-axial infiltration and the resulting neurological impairment.Case presentationIn this work, we report for the first time an excellent clinical response to vemurafenib in a Norwegian patient with debilitating progressive spastic paraparesis due to intra-axial infiltration of the thoracic spinal cord. The patient had been unresponsive to interferon-alpha. Low dose vemurafenib (720xa0mg daily) for a period of three months resulted in significant tumor shrinkage by >60% and regression of contrast enhancement and fluorodeoxyglucose uptake on positron-emission tomography. The patient’s spastic paraparesis and gait function improved dramatically. She currently walks unaided and reports a substantially improved quality of life.ConclusionOur findings show that vemurafenib therapy, even at low doses, can be effective for the treatment of intra-axial central nervous system involvement in BRAF-positive Erdheim-Chester disease.

Progressive striatal necrosis associated with anti-NMDA receptor antibodies

BackgroundWe report a case of childhood onset, generalized dystonia due to slowly progressive bilateral striatal necrosis associated with anti-N-methyl-D-aspartate receptor (NMDAR) antibodies. This clinical phenotype has not been previously associated with NMDA receptor autoimmunity.Case presentationAn eighteen year old man presented with a history of childhood-onset, progressive generalized dystonia. Clinical examination revealed a pure generalized dystonia with no cognitive or other neurological findings. Magnetic resonance imaging showed bilateral high T2 signal striatal lesions, which were slowly progressive over a period of nine years. New parts of the lesion showed restricted water diffusion suggesting cytotoxic oedema. Positron emission tomography of the brain showed frontal hypermetabolism and cerebellar hypometabolism. Antibodies against the NR1 subunit of the NMDA receptor were detected in the patient’s serum and cerebrospinal fluid. There was no neoplasia or preceding infection or vaccination.ConclusionThis is the first report of chronic progressive bilateral striatal necrosis associated with anti-NMDAR antibodies. Our findings expand the clinical spectrum of disease associated with anti-NMDAR antibodies and suggest that these should be included in the work-up of dystonia with striatal necrosis.

Utredning ved mistenkt kronisk utmattelsessyndrom/myalgisk encefalopati

BACKGROUNDnChronic fatigue is a frequently occurring problem in both the primary and specialist health services. The Department of Neurology at Haukeland University Hospital has established a standard assessment for patients referred with suspected CFS/ME. This study reports diagnoses and findings upon assessment, and considers the benefit of supplementary examinations.nnnMATERIAL AND METHODnDiagnoses and findings from examinations of 365 patients assessed for suspected CFS/ME are retrospectively reported.nnnRESULTSnA total of 48 patients (13.2%) were diagnosed with CFS/ME, while a further 18 patients (4.9%) were diagnosed with post-infectious fatigue. Mental and behavioural disorders were diagnosed in 169 patients (46.3%), and these represented by far the largest group. Serious, but unrecognised somatic illness was discovered in two patients, while changes of uncertain significance were identified by MRI and lumbar puncture in a few patients.nnnINTERPRETATIONnFatigue is a frequently occurring symptom in the population. Thorough somatic and psychiatric investigation is necessary before referral to the specialist health services. Mental disorders and reactions to life crises are common and important differential diagnoses for CFS/ME. Long waiting times in the specialist health services may result in delayed diagnosis for these patients.

PNKP Mutations Identified by Whole-Exome Sequencing in a Norwegian Patient with Sporadic Ataxia and Edema.

We identified PNKP mutations in a Norwegian woman with AOA. This patient had the typical findings with cognitive dysfunction, peripheral neuropathy, cerebellar dysarthria, horizontal nystagmus, oculomotor apraxia, and severe truncal and appendicular ataxia. In addition, she had hypoalbuminemia and massive lower limb edema which showed some improvement with treatment. Exome sequencing identified two heterozygous mutations, one in exon 14 (c.1196T>C, p.Leu399Pro) and one in exon 16 (c.1393_1396del, p.Glu465*). This is the first non-Portuguese patient with AOA due to PNKP mutations and provides independent verification that PNKP mutations cause AOA.

Erdheim–Chester disease presenting with an intramedullary spinal cord lesion

Erdheim–Chester disease (ECD) is a rare form of nonLangerhans histiocytosis characterized by multi-systemic xanthogranulomatous infiltration. The disease commonly affects the skeleton, but may also involve the skin, viscera including the cardiovascular system and lungs, as well as the central nervous system [1–4]. Diagnosis is based on histopathology typically showing infiltration by histiocytes expressing CD68, but not CD1a [3]. In the nervous system, ECD commonly affects the neurohypophysis resulting in diabetes insipidus. Extrahypophyseal nervous system involvement is seen in about a third of ECD patients and includes intra-axial infiltrative lesions, meningioma-like masses, and periarterial infiltration [3, 5, 6]. Spinal cord involvement may occur due to extramedullary masses [3, 7, 8] but intra-axial cord lesions are rare and only a single patient has been described [9]. We report a case of ECD presenting with progressive spastic paraparesis caused by an intramedullary cord tumor. A 31-year-old female was referred to our clinic with a 10-year history of slowly progressive gait difficulties due to a spinal cord mass. She also complained of polydipsia, polyuria, and irregular menstruation. Clinical examination revealed spastic paraparesis with extensor plantar responses and normal sensory function. There was saccadic smooth pursuit in all directions and horizontal nystagmus on lateral gaze, but no other signs of cerebellar dysfunction. She had multiple periorbital xanthelasma-like lesions (Fig. 1). She did not complain of skeletal pain. MRI of the brain revealed symmetrical high T2 signal in the cerebellar white matter, sparing the dentate nuclei. There was calcification of the dentates and globus pallidus (Fig. 1). MRI of the spine showed diffuse, non-contrast enhancing, low T1 and T2 signal changes in multiple cervical and thoracic vertebrae. There was a fusiform masslesion of the thoracic cord showing inhomogeneously high T2 signal intensity and partial contrast enhancement (Fig. 2). Scintigraphy with technetium 99 and fluorodeoxyglucose positron-emission tomography (FDG-PET) showed pathological tracer uptake in the epiphyses of long bones, several cervical and thoracic vertebra (corresponding to signal changes on the MRI) and parts of the facial skeleton. Skeleton radiograms showed moderate hyperostosis of the skull and sclerotic changes in the epiphyses of the long bones (Fig. 1). A computed tomography (CT)-guided biopsy of the 9th thoracic vertebra was performed. Histology revealed a hypercellular bone marrow with focal fibrosis and infiltration C. Tzoulis (&) I. O. Gjerde Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway e-mail: chtzoulis@yahoo.com; charalampos.tzoulis@helsebergen.no

A man in his 50s with high ferritin levels and increasing cognitive impairment.

Laurence Albert Bindoff Department of Neurology Haukeland University Hospital and Department of Clinical Medicine University of Bergen A healthy man in his late 30s was found to have elevated ferritin levels, which raised suspicion of haemochromatosis. He was treated for many years with phlebotomy, but in his 50s developed progressive neuropsychiatric symptoms. A blood test finally provided a diagnosis – more than 20 years after the illness first appeared.

Spasms in legs--lesion in neck.

A woman in her 80s was found on the floor of her home. She was hypothermic, confused and had neck pain. The ambulance team observed spasms in her right leg. The patient experienced transient respiratory arrest with concomitant loss of consciousness and was admitted to hospital. A basic neurological examination on arrival was normal. She raised her arms and legs and walked with support. Functional assessment of the neck was not described in the medical records. ECG showed rapid atrial fibrillation. She was examined with CT of the head, blood tests, urine dipsticks, arterial blood gas, rhythm monitoring and EEG on suspicion of infection, arrhythmia or epileptic seizures. CT of the head showed recurrence of a previously operated right frontal meningioma and a new left parietal meningioma. EEG two days after admission showed no epileptiform activity. The neurologist who saw the spasms during EEG recording considered dystonia. However, the frequent right-sided movements had the same flexion pattern as the inverted plantar reflex, consistent with the Babinski sign (video). The spasms continued to occur spontaneously, sometimes also on the left side, and could be triggered by light touch. The neurologist therefore suspected myelopathy. A new neu-

Beta-propeller protein-associated neurodegeneration: a case report and review of the literature

Beta‐propeller protein‐associated neurodegeneration (BPAN) is a rare disorder, which is increasingly recognized thanks to next‐generation sequencing. Due to a highly variable phenotype, patients may present to pediatrics, neurology, psychiatry, or internal medicine. It is therefore essential that physicians of different specialties are familiar with this severe and debilitating condition.