Diagnosing dementia in the Arctic:translating tools and developing and validating an algorithm for assessment of impaired cognitive function in Greenland Inuit

Background: The ageing Arctic populations raise the need for work-up of cognitive function that reflects language and cultural understandings. Aim: To translate and evaluate tools for work-up of cognitive impairment in Greenland. Methods: Step A: An expert panel was established to select tools suitable for the work-up of cognitive impairment at three different settings in Greenland. Step B: Tools were translated in a multiple-step process of independent translations with back-translation and adaptations by two independent translators and two Greenlandic physicians. Step C: a testing and validation process of the tools at three locations: the national hospital in the capital city; regional hospital in a town; health care centre in a small town. Results: Tools selected were Mini-Cog and RUDAS. Participants for testing of tools were 43 of 61 invited, of which six had dementia. RUDAS and Mini-Cog scores were associated (p < 0.001). The smoothed AUC was 0.87 (95%-CI, 0.65–0.95) for Mini-Cog and 0.90 (95%-CI, 0.76–0.97) for RUDAS. The sensitivity of Mini-Cog with a cut-off at ≤3 was 83.3%, and specificity was 62.2%. For RUDAS with a cut-off at ≤23, these were 100% and 75.7%, respectively. Conclusion: Requested tools have been translated for assessing cognitive function in the native Arctic setting. Small town residents with a Mini-Cog score of 3 or lower should be referred to a regional hospital for RUDAS, and a score of 23 or less should cause referral to the national hospital for a full work-up of cognitive function

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Masteroppgave MBA Executive Master of Business administration ORG954 - Universitetet i Agder 2017Konfidensiell til / confidential until 01-07-202

Neurological signs in 23 dogs with suspected rostral cerebellar ischaemic stroke

Background: In dogs with ischaemic stroke, a very common site of infarction is the cerebellum. The aim of this study was to characterise neurological signs in relation to infarct topography in dogs with suspected cerebellar ischaemic stroke and to report short-term outcome confined to the hospitalisation period. A retrospective multicentre study of dogs with suspected cerebellar ischaemic stroke examined from 2010–2015 at five veterinary referral hospitals was performed. Findings from clinical, neurological, and paraclinical investigations including magnetic resonance imaging were assessed. Results: Twenty-three dogs, 13 females and 10 males with a median age of 8 years and 8 months, were included in the study. The Cavalier King Charles Spaniel (n = 9) was a commonly represented breed. All ischaemic strokes were located to the vascular territory of the rostral cerebellar artery including four extensive and 19 limited occlusions. The most prominent neurological deficits were gait abnormalities (ataxia with hypermetria n = 11, ataxia without hypermetria n = 4, non-ambulatory n = 6), head tilt (n = 13), nystagmus (n = 8), decreased menace response (n = 7), postural reaction deficits (n = 7), and proprioceptive deficits (n = 5). Neurological signs appeared irrespective of the infarct being classified as extensive or limited. All dogs survived and were discharged within 1–10 days of hospitalisation. Conclusions: Dogs affected by rostral cerebellar ischaemic stroke typically present with a collection of neurological deficits characterised by ataxia, head tilt, and nystagmus irrespective of the specific cerebellar infarct topography. In dogs with peracute to acute onset of these neurological deficits, cerebellar ischaemic stroke should be considered an important differential diagnosis, and neuroimaging investigations are indicated. Although dogs are often severely compromised at presentation, short-term prognosis is excellent and rapid clinical improvement may be observed within the first week following the ischaemic stroke

Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic lateral sclerosis (ALS)

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive lethal disorder of large motor neurons of the spinal cord and brain. In approximately 20% of the familial and 2% of sporadic cases the disease is due to a defect in the gene encoding the cytosolic antioxidant enzyme Cu, Zn-superoxide dismutase (SOD1). The underlying molecular defect is known only in a very small portion of the remaining cases and therefore involvement of other genes is likely. As SOD1 receives copper, essential for its normal function, by the copper chaperone, CCS (Copper Chaperone for SOD), we considered CCS as a potential candidate gene for ALS. RESULTS: We have characterized the genomic organization of CCS and determined exon-intron boundaries. The 823 bp coding region of the CCS is organized in 8 exons. We have evaluated involvement of the CCS in ALS by sequencing the entire coding region for mutations in 20 sporadic ALS patients. CONCLUSIONS: No causative mutations for the ALS have been detected in the CCS gene in 20 sporadic ALS patients analyzed, but an intragenic single nucleotide polymorphism has been identified

Spontaneous ischaemic stroke lesions in a dog brain: neuropathological characterisation and comparison to human ischaemic stroke

Abstract Background Dogs develop spontaneous ischaemic stroke with a clinical picture closely resembling human ischaemic stroke patients. Animal stroke models have been developed, but it has proved difficult to translate results obtained from such models into successful therapeutic strategies in human stroke patients. In order to face this apparent translational gap within stroke research, dogs with ischaemic stroke constitute an opportunity to study the neuropathology of ischaemic stroke in an animal species. Case presentation A 7\ua0years and 8\ua0months old female neutered Rottweiler dog suffered a middle cerebral artery infarct and was euthanized 3\ua0days after onset of neurological signs. The brain was subjected to histopathology and immunohistochemistry. Neuropathological changes were characterised by a pan-necrotic infarct surrounded by peri-infarct injured neurons and reactive microglia/macrophages and astrocytes. Conclusions The neuropathological changes reported in the present study were similar to findings in human patients with ischaemic stroke. The dog with spontaneous ischaemic stroke is of interest as a complementary spontaneous animal model for further neuropathological studies