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

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

Ataxin-2 intermediate-length polyglutamine expansions in European ALS patients

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease primarily affecting motor neurons. We recently identified intermediate-length polyglutamine (polyQ) expansions (27-33 Qs) in ataxin 2 as a genetic risk factor for sporadic ALS in North American ALS patients. To extend these findings, we assessed the ataxin 2 polyQ repeat length in 1294 European ALS patients and 679 matched healthy controls. We observed a significant association between polyQ expansions and ALS (>30 Qs; P= 6.2 × 10−3). Thus, intermediate-length ataxin 2 polyQ repeat expansions are associated with increased risk for ALS also in the European cohort. The specific polyQ length cutoff, however, appears to vary between different populations, with longer repeat lengths showing a clear association. Our findings support the hypothesis that ataxin 2 plays an important role in predisposing to ALS and that polyQ expansions in ataxin 2 are a significant risk factor for the diseas

Effects of Long-Term Treatment with T-PEMF on Forearm Muscle Activation and Motor Function in Parkinson’s Disease

Bipolar pulsed electromagnetic stimulation applied to the brain (T-PEMF) is a non-pharmacological treatment which has been shown to stimulate nerve growth, attenuate nerve abnormalities, and improve microcirculation. We report on a 62-year-old, medically well-treated man with idiopathic Parkinson’s disease. He was treated with T-PEMF, 30 min per day for three 8-week periods separated by two 1-week breaks. The disease made his handwriting impossible to read mainly due to small letters and lack of fluency. Forearm EMG measured during standardized conditions showed an involuntary spiky EMG pattern with regular burst activity (on his left side) at baseline. The intervention normalized the handwriting and forearm EMG. The UPDRS-motor score decreased from 25 to 17, and UPDRS-II-handwriting decreased from a pre-intervention value of 3 to 0 after the intervention. Finally, the patient reported improved fine motor function, less muscle stiffness, less muscle cramps and tingling, and less fatigue during the day in response to the T-PEMF treatment. The improved handwriting lasted for approximately 3 months after the treatment. Our results should be considered as preliminary, and large-scale, controlled studies are recommended to elucidate the therapeutic potential of long-term treatment with T-PEMF

Acute neurological signs as the predominant clinical manifestation in four dogs with Angiostrongylus vasorum infections in Denmark

Four dogs with acute neurological signs caused by haemorrhages in the central nervous system were diagnosed with Angiostrongylus vasorum infection as the underlying aetiology. Two dogs presented with brain lesions, one dog with spinal cord lesions and one with lesions in both the brain and spinal cord. Only one dog presented with concurrent signs of classical pulmonary angiostrongylosis (respiratory distress, cough), and only two dogs displayed overt clinical signs of haemorrhages. Results of coagulation assays were inconsistent. Neurological signs reflected the site of pathology and included seizures, various cranial nerve deficits, vestibular signs, proprioceptive deficits, ataxia and paraplegia. One dog died and three were euthanised due to lack of improvement despite medical treatment. This emphasises canine angiostrongylosis as a potential cause of fatal lesions of the central nervous system and the importance of including A. vasorum as a differential diagnosis in young dogs with acute neurological signs in Denmark

Study of Occupational Chromium, Iron, and Nickel Exposure and Amyotrophic Lateral Sclerosis in Denmark

Studies of occupational metal exposures and amyotrophic lateral sclerosis (ALS) have focused primarily on known neurotoxicants, including lead, mercury, selenium, and cadmium. However, these exposures are often co-occurring with other lesser studied metals. We conducted a population-based case-control study with the aim of assessing associations between occupational chromium, iron, and nickel exposures and risk of ALS. We identified ALS cases in Denmark from 1982 through 2013 from the Danish National Patient Registry and matched them to 100 controls based on birth year and sex. Cumulative metal exposures were estimated using job exposure matrices applied to occupational history from the Danish Pension Fund. Although mutually adjusted odds of ALS were higher in men with chromium exposures in the third quartile (aOR = 1.24; 95% CI 0.91, 1.69) and fourth quartile (aOR = 1.19; 95% CI: 0.80, 1.76) compared to those with no exposure, differences did not reach statistical significance. We also observed higher odds of ALS in women with nickel exposures in the third quartile (aOR = 2.21; 95% CI: 1.14, 4.28), but not for the fourth quartile (aOR = 0.61; 95% CI: 0.23, 1.64). Our findings do not suggest associations between occupational exposures to these metals and ALS. However, unavoidable non-differential misclassification from the use of JEMs may have masked truly increased risk

Spatial analyses of ALS incidence in Denmark over three decades

OBJECTIVE:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor neuron with very few known risk factors. We conducted a spatial epidemiologic analysis of ALS incidence in Denmark to assess the contribution of sociodemographic determinants to geographic variation. METHODS:We analyzed 4249 ALS cases (1982-2013), each with 100 controls matched on sex and birth year. Odds ratio and 95% confidence bands at birth and diagnosis/index locations were calculated using generalized additive models. We included a bivariate spatial smooth for location in our conditional logistic regression adjusted for socioeconomic status and marital status. We also conducted analyses adjusted for both birth and diagnosis addresses to separate location effects. RESULTS:We observed significantly elevated ALS odds near Copenhagen for both the birth and diagnosis period analyses. Sociodemographic factors did not explain the observed patterns. When we further adjusted our spatial analyses by including both birth and diagnosis addresses, the significant area of elevated male ALS odds by birth address shifted to northwest Denmark away from Copenhagen, and there was little evidence of variation among women. Geographic variation at diagnosis differed between male and females, suggesting that patterns are not just due to regional variation in case ascertainment. CONCLUSION:ALS incidence in Denmark is associated with both location at birth and diagnosis, suggesting that geographic variation may be due to exposures occurring at birth or closer to diagnosis, although the latter could relate to case ascertainment issues

Treatment of glioblastoma in Greenlandic patients

ABSTRACTGlioblastoma (GBM), WHO grade IV, is the most common primary malignant brain tumour among adults with a devastating overall survival of 14–22 months. Standard treatment of GBM includes maximum safe resection, radiotherapy plus concomitant and adjuvant temozolomide (TMZ), given over a period of approximately 9 months. Treatment and follow-up for Greenlandic patients with GBM are managed at Rigshospitalet (RH), Copenhagen. Greenlandic GBM patients, therefore, travel back and forth to RH, often unaccompanied, and challenged by cognitive failure or other symptoms from their disease and/or treatment. Few Greenlandic patients are diagnosed with GBM annually, but considering the poor prognosis and short remaining lifespan, it would be preferable to limit their travels. TMZ is administrated as capsules. Health personnel at Queen Ingrid’s Hospital (DIH), Nuuk, are trained in treating other oncological diseases and handling side effects. Hence, it could be investigated whether administration of adjuvant TMZ at DIH could be feasible after personnel education as well as economic consideration and compensation, in close collaboration with neuro oncologists at RH. In this article, we describe the Greenlandic cancer treatment, and the typical workflow from diagnosis of GBM to treatment to progression

The Hawthorne effect as a pre-placebo expectation in Parkinsons disease patients participating in a randomized placebo-controlled clinical study

Background: The Hawthorne effect on clinical studies in Parkinson’s disease has not been thoroughly investigated. Evidently the Hawthorne effect may have impact on study outcomes acting as a ‘pre-placebo’ effect in the recruitment phase, hence before inclusion. Aim: The aim of this study was to discuss the Hawthorne effect in relation to clinical and self-reported outcome measures in a randomized clinical study in the recruitment phase and during the study. Methods: Data from 97 participants with Parkinson’s disease treated with Transcranial Pulsed Electromagnetic Fields were applied, randomized to an active (n = 49) or a placebo treated group (n = 48). The participants received one home treatment session, for eight consecutive weeks. Outcome measures were the Unified Parkinson’s Disease Rating Scale, The 39-item Parkinson’s Disease Questionnaire and the WHO-5. Results: No difference in treatment effect between the two groups was found pertaining the Unified Parkinson’s Disease Rating Scale. No difference in treatment effect between the two groups was found pertaining the 39-item Parkinson’s Disease Questionnaire, apart from the dimension mobility. No difference in treatment effect between the two groups was found pertaining the WHO-5 scale. Conclusions: The Hawthorne effect may have caused a ‘pre-placebo’ effect on the outcome measures even before obtaining baseline outcomes measures. This study may have been particularly prone to a Hawthorne effect due to the intense contact with the participants before and during the study. Moreover, the Hawthorne effect should not be viewed upon as a single entity but rather as entities affecting outcome measures throughout the full study period.</p