Cognitive and behavioural deficits associated with the orbitomedial prefrontal cortex in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis, a progressive disease affecting motor neurons, may variably affect cognition and behaviour. We tested the hypothesis that functions associated with orbitomedial prefrontal cortex are affected by evaluating the behavioural and cognitive performance of 18 participants with amyotrophic lateral sclerosis without dementia and 18 healthy, matched controls. We measured Theory of Mind (Faux Pas Task), emotional prosody recognition (Aprosodia Battery), reversal of behaviour in response to changes in reward (Probabilistic Reversal Learning Task), decision making without risk (Holiday Apartment Task) and aberrant behaviour (Neuropsychiatric Inventory). We also assessed dorsolateral prefrontal function, using verbal and written fluency and planning (One-touch Stockings of Cambridge), to determine whether impairments in tasks sensitive to these two prefrontal regions co-occur. The patient group was significantly impaired at identifying social faux pas, recognizing emotions and decision-making, indicating mild, but consistent impairment on most measures sensitive to orbitomedial prefrontal cortex. Significant levels of aberrant behaviour were present in 50% of patients. Patients were also impaired on verbal fluency and planning. Individual subject analyses involved computing classical dissociations between tasks sensitive to different prefrontal regions. These revealed heterogeneous patterns of impaired and spared cognitive abilities: 33% of participants had classical dissociations involving orbitomedial prefrontal tasks, 17% had classical dissociations involving dorsolateral prefrontal tasks, 22% had classical dissociations between tasks of both regions, and 28% had no classical dissociations. These data indicate subtle changes in behaviour, emotional processing, decision-making and altered social awareness, associated with orbitomedial prefrontal cortex, may be present in a significant proportion of individuals with amyotrophic lateral sclerosis without dementia, some with no signs of dysfunction in tasks sensitive to other regions of prefrontal cortex. This demonstration of variability in cognitive integrity supports previous research indicating amyotrophic lateral sclerosis is a heterogeneous disease.

Motor neuron disease mortality rates in New Zealand 1992-2013.

BACKGROUND: We determined the mortality rates of motor neuron disease (MND) in New Zealand over 22 years from 1992 to 2013. Previous studies have found an unusually high and/or increasing incidence of MND in certain regions of New Zealand; however, no studies have examined MND rates nationwide to corroborate this. METHODS: Death certificate data coded G12.2 by International Classification of Diseases (ICD)-10 coding, or 335.2 by ICD-9 coding were obtained. These codes specify amyotrophic lateral sclerosis, progressive bulbar palsy, or other motor neuron diseases as the underlying cause of death. Mortality rates for MND deaths in New Zealand were age-standardized to the European Standard Population and compared with rates from international studies that also examined death certificate data and were age-standardized to the same standard population. RESULTS AND CONCLUSION: The age-standardized mortality from MND in New Zealand was 2.3 per 100,000 per year from 1992-2007 and 2.8 per 100,000 per year from 2008-2013. These rates were 3.3 and 4.0 per 100,000 per year, respectively, for the population 20 years and older. The increase in rate between these two time periods was likely due to changes in MND death coding from 2008. Contrary to a previous regional study of MND incidence, nationwide mortality rates did not increase steadily over this time period once aging was accounted for. However, New Zealand MND mortality rate was higher than comparable studies we examined internationally (mean 1.67 per 100,000 per year), suggesting that further analysis of MND burden in New Zealand is warranted.

C9ORF72 and UBQLN2 mutations are causes of amyotrophic lateral sclerosis in New Zealand: a genetic and pathologic study using banked human brain tissue.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, which causes progressive and eventually fatal loss of motor function. Here, we describe genetic and pathologic characterization of brain tissue banked from 19 ALS patients over nearly 20 years at the Department of Anatomy and the Centre for Brain Research, University of Auckland, New Zealand. We screened for mutations in SOD1, TARDBP, FUS, and C9ORF72 genes and for neuropathology caused by phosphorylated TDP-43, dipeptide repeats (DPRs), and ubiquilin. We identified 2 cases with C9ORF72 repeat expansions. Both harbored phosphorylated TDP-43 and DPR inclusions. We show that DPR inclusions can incorporate or occur independently of ubiquilin. We also identified 1 case with a UBQLN2 mutation, which showed phosphorylated TDP-43 and characteristic ubiquilin protein inclusions. This is the first study of ALS genetics in New Zealand, adding New Zealand to the growing list of countries in which C9ORF72 repeat expansion and UBQLN2 mutations are detected in ALS cases.

Not all patients with atrial fibrillation-associated ischemic stroke can be started on anticoagulant therapy.

BACKGROUND AND PURPOSE: Ischemic stroke patients in atrial fibrillation (AF) have a 10% to 20% risk of recurrent stroke. Warfarin reduces this risk by two thirds. However, warfarin is underutilized in this patient group. We performed a prospective study to determine the reasons why warfarin is not started in these patients. METHODS: All patients with AF-associated ischemic stroke over a 12-month period were identified. Demographic and other data, including whether warfarin was commenced or recommended at discharge, and if not why not, were recorded. RESULTS: Ninety-three of 412 (23%) ischemic stroke patients had paroxysmal or permanent AF. Of these patients, 17 (18%) died, 48 (52%) were discharged home, and 28 (30%) were discharged to institutional care. Only 13 of 64 (20%) patients with known AF were taking warfarin at stroke onset. Warfarin was started (or recommended) in 35 of 76 (46%) survivors. Of those not commenced on warfarin, 32 (78%) were dependent (P<0.001) and 23 (56%) were discharged to institutional care (P<0.001). Warfarin was not started because of severe disability and frailty in 13 (32%), risk of falls in 12 (30%), and limited life expectancy in 4 (10%). CONCLUSIONS: In this cohort of patients with AF, warfarin was primarily underutilized before stroke onset, and it was too late to use anticoagulation, in approximately half, once a stroke had occurred. The decision to start or continue anticoagulation requires clinical judgment and should be made on a case by case basis after a complete risk benefit assessment.

Changes in stroke care at Auckland Hospital between 1996 and 2001.

AIMS: In 1996, we performed a descriptive audit of stroke care in Auckland Hospital. Since then, a mobile stroke team has been established. We have repeated the 1996 audit to assess changes in stroke management. METHODS: From 1 June to 30 September 2001, information was prospectively recorded for all patients with stroke. RESULTS: There were 177 strokes in 175 patients (92 men, mean age 70.9, standard deviation [SD] 14.9 years). Ninety-seven percent of patients had cerebral imaging (median 4.5 hours; interquartile range [IQR] 2.7-11.6). Acute aspirin was given to 78% of patients in 2001 and 40% in 1996 (p <0.001). Twenty-four percent of patients were kept 'nil by mouth' for at least 24 hours (46% in 1996, p <0.001). At discharge, 73% of patients were taking antiplatelet or anticoagulant therapy (61% in 1996, p <0.001). Only 50% of the patients with elevated discharge blood pressures were taking antihypertensives. There had been a reduction in the mean length of hospital stay to 16 days (21 days in 1996) but no significant change in mortality (14% compared with 17% in 1996). CONCLUSION: A stroke service may increase the attention to the 'processes' of stroke care and use of therapies, which are shown to be of benefit in randomised controlled trials.