Northern lights assay: a versatile method for comprehensive detection of DNA damage.

DNA damage assays have various limitations in types of lesions detected, sensitivity, specificity and samples that can be analyzed. The Northern Lights Assay (NLA) is based on 2D Strandness-Dependent Electrophoresis (2D-SDE), a technique that separates nucleic acids based on length, strandness, structure and conformation changes induced by damage. NLA is run on a microgel platform in 20-25 min. Each specimen is analyzed in pairs of non-digested DNA to detect single- and double-stranded breaks (DSBs) and Mbo I-digested DNA to detect other lesions. We used NLA to evaluate DNA in solution and isolated from human cells treated with various genotoxic agents. NLA detected and distinguished between single- and DSBs, interstrand and intrastrand DNA crosslinks, and denatured single-stranded DNA. NLA was sufficiently sensitive to detect biologically relevant amount of DNA damage. NLA is a versatile, sensitive and simple method for comprehensive and simultaneous analysis of multiple types of damage, both in purified DNA and in DNA isolated from cells and body fluids. NLA can be used to evaluate DNA quality in biosamples, monitor complex molecular procedures, assess genotoxicity, diagnose genome instability, facilitate cancer theranostics and in basic nucleic acids research.

[Occlusion of the vertebrobasilar artery. Case presentation and literature review]. / Lokun í botn- og hryggslagæð heila. Sjúkratilfelli og yfirlit

This paper is a case report of a 22 year old, previously healthy woman that presented comatose to the Emergency Room at Landspitali University Hospital Iceland. A CT image of the head on admission revealed a large right cerebellar infarct with oedema compressing the fourth ventricle. A CT angiogram on admission was suspicious for a dissection of the left vertebral artery (confirmed during endovascular treatment) and a total occlusion of the distal third of the basilar artery. Thrombolytic therapy with t-PA was initiated followed by thrombectomy with good recanalization. The following day the patient underwent suboccipital craniotomy for malignant cerebellar infarction. She made a good clinical recovery to a modified Ranking scale of 1 at 90 days after discharge from the hospital. Following the case is a literature review on the clinical aspects of occlusion of the vertebrobasilar system, use and utility of imaging and treatment with (anticoagulation, IV and IA thrombolysis) modalities that have been tried. Finally, the evidence regarding thrombectomy and the role of craniotomy for malignant stroke are reviewed.

A genetic risk factor for periodic limb movements in sleep.

BACKGROUND: The restless legs syndrome (RLS) is a common neurologic disorder characterized by an irresistible urge to move the legs. It is a major cause of sleep disruption. Periodic limb movements in sleep are detectable in most patients with RLS and represent an objective physiological metric. METHODS: To search for sequence variants contributing to RLS, we performed a genomewide association study and two replication studies. To minimize phenotypic heterogeneity, we focused on patients with RLS who had objectively documented periodic limb movements in sleep. We measured serum ferritin levels, since iron depletion has been associated with the pathogenesis of RLS. RESULTS: In an Icelandic discovery sample of patients with RLS and periodic limb movements in sleep, we observed a genomewide significant association with a common variant in an intron of BTBD9 on chromosome 6p21.2 (odds ratio, 1.8; P=2x10(-9)). This association was replicated in a second Icelandic sample (odds ratio, 1.8; P=4x10(-4)) and a U.S. sample (odds ratio, 1.5; P=4x10(-3)). With this variant, the population attributable risk of RLS with periodic limb movements was approximately 50%. An association between the variant and periodic limb movements in sleep without RLS (and the absence of such an association for RLS without periodic limb movements) suggests that we have identified a genetic determinant of periodic limb movements in sleep (odds ratio, 1.9; P=1x10(-17)). Serum ferritin levels were decreased by 13% per allele of the at-risk variant (95% confidence interval, 5 to 20; P=0.002). CONCLUSIONS: We have discovered a variant associated with susceptibility to periodic limb movements in sleep. The inverse correlation of the variant with iron stores is consistent with the suspected involvement of iron depletion in the pathogenesis of the disease.

Large genome-wide association study identifies three novel risk variants for restless legs syndrome.

Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10-18), rs10068599-T (OR = 1.09, P = 6.9 × 10-10) and rs10769894-A (OR = 0.90, P = 9.4 × 10-14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed.

[Role of Thrombectomy in Acute Ischemic Stroke].

This article discusses endovascular thrombectomy in acute ischemic stroke. This treatment is vascular medicine's most significant leap in years. This treatment is complicated, and various technical aspects are discussed. Close cooperation is required between different specialties since patient selection for treatment is complex. Interventionists need close collaboration with stroke neurologists. Government needs to be involved as this treatment mandates structural changes which will incur more manpower and financial resources. Telemedicine is also discussed as it has been shown to be advantageous for augmenting thrombolytic administration for acute ischemic stroke. Due to technical advances, it has been easier to provide such service, but hurdles need to be resolved so it can be fully implemented. It is likely that telemedi-cine will also play a role in thrombectomy. This article proposes how thrombectomy could be delivered in Iceland. It will prove difficult to provide such complex treatment in a scattered population of 343.000 people where expertise is limited to one or two sites. It is important to remember, that coronary intervention was a formidable challenge at one time, but it was accomplished. Can we learn from that experience?

[Restless legs syndrome - a review]. / Fótaóeird - yfirlitsgrein.

UNLABELLED: Restless legs syndrome (RLS) is a common disorder with a prevalence between 10-20% in Iceland. There are two forms of RLS, idiopathic and secondary. Symptom onset of RLS before the age of 45 suggests an idiopathic form with no known underlying cause but inheritance. Symptom onset after age of 45 indicates a secondary form with an underlying cause without inheritance. Causes for secondary forms are for example: iron depletion, uraemia and polyneuropathy. Symptoms of RLS are uncomfortable and unpleasant deep sensations in the legs that are felt at rest, accompanied by an urge to move the legs, typically just before sleep. Accompanying RLS is a sleep disturbance that can lead to daytime somnolence, decreased quality of life, poor concentration, memory problems, depression and decreased energy. Dopamine agonists are currently the first line treatment for RLS. KEYWORDS: restless legs, periodic limb movements, sleep disturbance, dopamine agonists.

[Tetanus: a case report and literature review]. / Stífkrampi - tilfelli og yfirlit

A 79 year old farmer was referred to the University Hospital with a three days history of difficulty in opening his mouth. On examination, both masseters were seen to be stiff, suggesting tetanus or jaw-subluxation. An attempt to reduce the joint was made, but failed. He subsequently developed progressive respiratory difficulties requiring intubation. The farmer had recently cut his finger on barbed wire. He had not received tetanus immunization for years and it was not clear whether primary immunization had been completed. Tetanus immunoglobulin and antibiotics were administered. He proceeded to develop autonomic instability and critical illness polyneuropathy requiring 45 days of ICU care. He was finally discharged eight months later. The farmer has gradually improved and is now living unaided at home. In this article we will review this case and the literature on tetanus.

Correlates of PLMs variability over multiple nights and impact upon RLS diagnosis.

OBJECTIVE: Night-to-night variability of periodic leg movements (PLMs) in restless legs syndrome (RLS) was examined to define the range of intra-subject values, impact upon diagnosing RLS, and clinical correlates. METHODS: Twenty RLS patients were monitored for 10-15 nights using a validated, tri-axial accelerometer worn on the ankle. RESULTS: The mean difference in PLMs index (PLMI) between the lowest and highest night was 25.1/h (range: 3.9-73.8). Inter-subject differences accounted for nearly five times the variance in PLMI relative to between nights within an individual. Based on a single night of recording, PLMI criterion thresholds of 5, 10, and 15/h were exceeded on approximately 70.1%, 51.9% and 34.1% of individual nights among these patients. Based on five randomly sampled nights of recordings, the likelihood that such thresholds were met on at least a single night increased to 91.2%, 80.8% and 62.7%, respectively. Women exhibited greater variability. CONCLUSIONS: Variability in PLMs within RLS subjects was substantial, yet individuals' characteristic PLM level represented a quantitative trait. Variability was unrelated to age or scores on scales of RLS severity, sleepiness, functional status, and mood. A larger number of recording nights increased the likelihood that any criterion was reached.

[Spontaneous intracranial hypotension--a case report and discussion]. / Sjálfsprottinn innankúpulágsrýstingur--sjúkratilfelli og umraeda.

Thirty-three year old woman came to the emergency room with 3 days' history of worsening headache which was relieved by lying down. Examination was normal. Magnetic Resonance Imaging (MRI) of the head showed an enhancement of the meninges. No pressure could be measured during lumbar puncture and cerebrospinal fluid (CSF) was obtained by elevating the patient's head. There was an elevation of protein in the CSF without signs of infection or inflammation. Computerised tomography (CT) myelogram showed a prominent leak from the 2nd right cervical nerve sheath. A blood patch was done at this level with some improvement of symptoms. The patient was readmitted four days later as the headache had worsened. A blood patch was repeated at the same level with limited results. Therefore a fibrinogen patch was done at the same level, of which the effect lasted only 24 hours. A repeated CT myelogram showed a leak from the left 8th cervical and 1st thoracic nerve sheets, but not from the 2nd right cervical nerve sheath. Blood and fibrinogen patches were done at these levels repeatedly with limited results. Therefore, a MRI of cervical-thoracic spine was done which showed signs of previous blood patch at the 1st left thoracic nerve sheath but no sign of a patch over the 8th left cervical nerve sheath. A fibrinogen patch was done at this level. The patient became symptom free and was finally discharged home. We present a case of complicated spontaneous intracranial hypotension and review of the literature.