Richard A.L. Macdonell

Quality of Life After Stroke The North East Melbourne Stroke Incidence Study (NEMESIS)

Background and Purpose— Health-related quality of life (HRQoL) data are scarce from unselected populations. The aims were to assess HRQoL at 2 years poststroke, to identify determinants of HRQoL in stroke survivors, and to identify predictors at stroke onset of subsequent HRQoL. Methods— All first-ever cases of stroke in a population of 306 631 over a 1-year period were assessed. Stroke severity, comorbidity, and demographic information were recorded. Two-year poststroke HRQoL was assessed using the Assessment of Quality of Life (AQoL) instrument (deceased patients score=0). Handicap, disability, physical impairment, depression, anxiety, living arrangements, and recurrent stroke at 2 years were documented. If necessary, proxy assessments were obtained, except for mood. Linear regression analyses were performed to identify factors independently associated with HRQoL. Results— Of 266 incident cases alive at 2 years, 225 (85%) were assessed. The mean AQoL utility score for all survivors was 0.47 (95% CI, 0.42 to 0.52). Almost 25% of survivors had a score of ≤0.1. The independent determinants of HRQoL in survivors were handicap, physical impairment, anxiety and depression, disability, institutionalization, dementia, and age. The factors present at stroke onset that independently predicted HRQoL at 2 years poststroke were age, female sex, initial NIHSS score, neglect, and low socioeconomic status. Conclusions— A substantial proportion of stroke survivors have very poor HRQoL. Interventions targeting handicap and mood have the potential to improve HRQoL independently of physical impairment and disability.

Incidence of the Major Stroke Subtypes Initial Findings From the North East Melbourne Stroke Incidence Study (NEMESIS)

Background and Purpose— Population-based stroke incidence studies are the only accurate way to determine the number of strokes that occur in a given society. Because the major stroke subtypes have different patterns of incidence and outcome, information on the natural history of stroke subtypes is essential. The purpose of the present study was to determine the incidence and case-fatality rate of the major stroke subtypes in a geographically defined region of Melbourne, Australia. Methods— All suspected strokes that occurred among 133 816 residents of suburbs north and east of Melbourne, Australia, during a 12-month period of 1996 and 1997 were identified and assessed. Multiple overlapping sources were used to ascertain cases, and standard criteria for stroke and case-fatality were used. Stroke subtypes were defined by CT, MRI, and autopsy. Results— Three hundred eighty-one strokes occurred among 353 persons during the study period, with 276 (72%) being first-ever-in-a-lifetime strokes. Of these, 72.5% (95% CI 67.2% to 77.7%) were cerebral infarction, 14.5% (95% CI 10.3% to 18.6%) were intracerebral hemorrhage, 4.3% (95% CI 1.9% to 6.8%) were subarachnoid hemorrhage, and 8.7% (95% CI 5.4% to 12.0%) were stroke of undetermined type. The 28-day case-fatality rate was 12% (95% CI 7% to 16%) for cerebral infarction, 45% (95% CI 30% to 60%) for intracerebral hemorrhage, 50% (95% CI 22% to 78%) for subarachnoid hemorrhage, and 38% (95% CI 18% to 57%) for stroke of undetermined type. Conclusions— The overall distribution of stroke subtypes and 28-day case-fatality rates are not significantly different from those of most European countries or the United States. There may, however, be some differences in the incidence of subtypes within Australia.

Stroke Incidence on the East Coast of Australia: The North East Melbourne Stroke Incidence Study (NEMESIS)

Background and Purpose Community-based stroke incidence studies are the most accurate way of explaining mortality trends and developing public health policy. The purpose of this study was to determine the incidence of stroke in a geographically defined region of Melbourne, Australia. Methods All suspected strokes occurring in a population of 133 816 residents in suburbs north and east of Melbourne, Australia, during a 12-month period of 1996 and 1997 were found and assessed. Multiple overlapping sources were used to ascertain cases, and standard definitions and criteria for stroke and case fatality were used. Results A total of 381 strokes occurred among 353 people during the study period, 276 (72%) of which were first-ever-in-a-lifetime strokes. The crude annual incidence rate (first-ever strokes) was 206 (95% CI, 182 to 231) per 100 000 per year overall, 195 (95% CI, 161 to 229) for males, and 217 (95% CI, 182 to 252) for females. The corresponding rates adjusted to the “world” population were 100 (95% CI, 80 to 119) overall, 113 (95% CI, 92 to 134) for males, and 89 (95% CI, 70 to 107) for females. The 28-day case fatality rate for first-ever strokes was 20% (95% CI, 16% to 25%). Conclusions The incidence rate of stroke in our population-based study is similar to that of many European studies but is significantly higher than that observed on the west coast of Australia.

Array-Based Gene Discovery with Three Unrelated Subjects Shows SCARB2/LIMP-2 Deficiency Causes Myoclonus Epilepsy and Glomerulosclerosis

Action myoclonus-renal failure syndrome (AMRF) is an autosomal-recessive disorder with the remarkable combination of focal glomerulosclerosis, frequently with glomerular collapse, and progressive myoclonus epilepsy associated with storage material in the brain. Here, we employed a novel combination of molecular strategies to find the responsible gene and show its effects in an animal model. Utilizing only three unrelated affected individuals and their relatives, we used homozygosity mapping with single-nucleotide polymorphism chips to localize AMRF. We then used microarray-expression analysis to prioritize candidates prior to sequencing. The disorder was mapped to 4q13-21, and microarray-expression analysis identified SCARB2/Limp2, which encodes a lysosomal-membrane protein, as the likely candidate. Mutations in SCARB2/Limp2 were found in all three families used for mapping and subsequently confirmed in two other unrelated AMRF families. The mutations were associated with lack of SCARB2 protein. Reanalysis of an existing Limp2 knockout mouse showed intracellular inclusions in cerebral and cerebellar cortex, and the kidneys showed subtle glomerular changes. This study highlights that recessive genes can be identified with a very small number of subjects. The ancestral lysosomal-membrane protein SCARB2/LIMP-2 is responsible for AMRF. The heterogeneous pathology in the kidney and brain suggests that SCARB2/Limp2 has pleiotropic effects that may be relevant to understanding the pathogenesis of other forms of glomerulosclerosis or collapse and myoclonic epilepsies.

Informal Care for Stroke Survivors: Results From the North East Melbourne Stroke Incidence Study (NEMESIS)

Background and Purpose— Informal caregivers play an important role in the lives of stroke patients, but the cost of providing this care has not been estimated. The purpose of this study was to determine the nature and amount of informal care provided to stroke patients and to estimate the economic cost of that care. Methods— The primary caregivers of stroke patients registered in the North East Melbourne Stroke Incidence Study (NEMESIS) were interviewed at 3, 6, and 12 months after stroke, and the nature and amount of informal care provided were documented. The opportunity and replacement costs of informal care for all first-ever-in-a-lifetime strokes (excluding subarachnoid hemorrhages) that occurred in 1997 in Australia were estimated. Results— Among 3-month stroke survivors, 74% required assistance with activities of daily living and received informal care from family or friends. Two thirds of primary caregivers were women, and most primary caregivers (>90%) provided care during family or leisure time. Total first-year caregiver time costs for all first-ever-in-a-lifetime strokes were estimated to be A

Hemispheric threshold differences for motor evoked potentials produced by magnetic coil stimulation

21.7 million (opportunity cost approach) or A

Cerebellar infarction: natural history, prognosis, and pathology.

42.5 million (replacement cost approach), and the present values of lifetime caregiver time costs were estimated to be A

Long-Term Outcome in the North East Melbourne Stroke Incidence Study Predictors of Quality of Life at 5 Years After Stroke

171.4 million (opportunity cost approach) or A

Randomized trial of constraint-induced movement therapy and bimanual training on activity outcomes for children with congenital hemiplegia

331.8 million (replacement cost approach). Conclusions— Informal care for stroke survivors represents a significant hidden cost to Australian society. Because our community is rapidly aging, this informal care burden may increase significantly in the future.

Interrater Reliability of the National Institutes of Health Stroke Scale: Rating by Neurologistsand N urses in a Community-Based Stroke Incidence Study

A brief monophasic pulse through an electromagnetic coil preferentially activates motor pathways of each hemisphere, depending on the direction of coil current flow. Using the preferred direction for each hemisphere, the minimum stimulus intensity (threshold) that evoked compound muscle action potentials in the contralateral abductor digiti minimi (ADM) muscle was significantly less for the left hemisphere than the right. Threshold for biceps on each side was significantly higher than ADM, but there was no side-to-side difference. Assessing handedness using a standard handedness index, those who had less tendency to use the right hand for everyday tasks had greater differences between hemispheres for ADM thresholds. The lower threshold of the left-hemisphere projection to hand muscles is probably related to the asymmetry of corticomotoneuronal monosynaptic connections; a greater number project to the motor neuron pool of the right- than left-hand muscles.