Showing papers in "Journal of Neurology, Neurosurgery, and Psychiatry in 2006"
TL;DR: The lifetime prevalence of BPPV was 2.4%, the 1 year prevalence was 1.6% and the 1-year incidence was 0.6%, the median duration of an episode was 2 weeks.
Abstract: Objectives: To examine the prevalence and incidence, clinical presentation, societal impact and comorbid conditions of benign paroxysmal positional vertigo (BPPV) in the general population. Methods: Cross-sectional, nationally representative neurotological survey of the general adult population in Germany with a two stage sampling design: screening of 4869 participants from the German National Telephone Health Interview Survey 2003 (response rate 52%) for moderate or severe dizziness or vertigo, followed by validated neurotological interviews (n = 1003; response rate 87%). Diagnostic criteria for BPPV were at least five attacks of vestibular vertigo lasting Results: BPPV accounted for 8% of individuals with moderate or severe dizziness/vertigo. The lifetime prevalence of BPPV was 2.4%, the 1 year prevalence was 1.6% and the 1 year incidence was 0.6%. The median duration of an episode was 2 weeks. In 86% of affected individuals, BPPV led to medical consultation, interruption of daily activities or sick leave. In total, only 8% of affected participants received effective treatment. On multivariate analysis, age, migraine, hypertension, hyperlipidaemia and stroke were independently associated with BPPV. Conclusion: BPPV is a common vestibular disorder leading to significant morbidity, psychosocial impact and medical costs.
822 citations
TL;DR: Only 4.2% of live births to women with epilepsy had an MCM, and polytherapy exposure was greater than for monotherapy exposure, and carbamazepine was associated with the lowest risk of MCM.
Abstract: Objective: To assess the relative risk of major congenital malformation (MCM) from in utero exposure to antiepileptic drug (AEDs). Methods: Prospective data collected by the UK Epilepsy and Pregnancy Register were analysed. The presence of MCMs recorded within the first three months of life was the main outcome measure. Results: Full outcome data were collected on 3607 cases. The overall MCM rate for all AED exposed cases was 4.2% (95% confidence interval (CI), 3.6% to 5.0%). The MCM rate was higher for polytherapy (6.0%) (n = 770) than for monotherapy (3.7%) (n = 2598) (crude odds ratio (OR) = 1.63 (p = 0.010), adjusted OR = 1.83 (p = 0.002)). The MCM rate for women with epilepsy who had not taken AEDs during pregnancy (n = 239) was 3.5% (1.8% to 6.8%). The MCM rate was greater for pregnancies exposed only to valproate (6.2% (95% CI, 4.6% to 8.2%) than only to carbamazepine (2.2% (1.4% to 3.4%) (OR = 2.78 (p Conclusions: Only 4.2% of live births to women with epilepsy had an MCM. The MCM rate for polytherapy exposure was greater than for monotherapy exposure. Polytherapy regimens containing valproate had significantly more MCMs than those not containing valproate. For monotherapy exposures, carbamazepine was associated with the lowest risk of MCM.
752 citations
TL;DR: Identifying patients at a high risk for progression to dementia and establishing more specific and adapted therapeutic strategies at an early stage, together with more structured overall management, is made possible by the diagnostic procedure proposed.
Abstract: Mild cognitive impairment (MCI) was proposed as a nosological entity referring to elderly people with mild cognitive deficit but no dementia. MCI is a heterogeneous clinical entity with multiple sources of heterogeneity. The concept of MCI was reviewed and a diagnostic procedure with three different stages was proposed by the European Consortium on Alzheimer's Disease Working Group on MCI. Firstly, MCI should correspond to cognitive complaints coming from the patients or their families; the reporting of a relative decline in cognitive functioning during the past year by a patient or informant; cognitive disorders as evidenced by clinical evaluation; absence of major repercussions on daily life; and absence of dementia. These criteria, similar to those defined during an international workshop in Stockholm, make it possible to identify an MCI syndrome, which is the first stage of the diagnostic procedure. Secondly, subtypes of MCI had to be recognised. Finally, the aetiopathogenic subtype could be identified. Identifying patients at a high risk for progression to dementia and establishing more specific and adapted therapeutic strategies at an early stage, together with more structured overall management, is made possible by the diagnostic procedure proposed.
573 citations
TL;DR: Standard validity indices showed that the LARS is sensitive and capable of distinguishing between apathy and depression, and is able to support dichotomous judgements accurately and, when greater measurement sensitivity is required, determine the severity of apathy within a four category classification.
Abstract: Background: Apathy is usually defined as reduced interest and participation in various activities. It is a frequent consequence of neurological and psychiatric disorders. Although various scoring methods have been proposed, there is a lack of validated, standardised instruments for detecting apathy and assessing its severity. Objective: To develop an apathy rating scale using a structured standardised interview capable of distinguishing between the condition’s various features. Methods: The Lille Apathy Rating Scale (LARS) is based on a structured interview. It includes 33 items, divided into nine domains. Responses are scored on a dichotomous scale. The participants used to validate the scale consisted of 159 patients with probable Parkinson’s disease and 58 healthy control subjects. The Marin Apathy Scale, the Montgomery and Asberg Depression Rating Scale, and the Mattis Dementia Rating Scale were also administered. Results: Principal component analysis showed that the LARS probed a single construct which forms the root of an oblique factor structure reflecting four dimensions: intellectual curiosity, self awareness, emotion, and action initiation. The main psychometric properties of the LARS (internal consistency, inter-rater and test-retest reliability) were satisfactory. Concurrent validity was evaluated by reference to the Marin scale and to judgements provided by expert clinicians. Conclusions: Standard validity indices showed that the LARS is sensitive and capable of distinguishing between apathy and depression. As a screening tool, the scale is able to support dichotomous judgements accurately and, when greater measurement sensitivity is required, also determine the severity of apathy within a four category classification.
424 citations
TL;DR: A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD.
Abstract: Background: A previous cross sectional study found over-representation of a postural instability gait difficulty (PIGD) motor subtype in Parkinson’s disease patients with dementia (PDD) and dementia with Lewy bodies (DLB), compared with Parkinson’s disease (PD). Aims: (1) To examine rates of cognitive and motor decline over two years in PD (n = 40), PDD (n = 42) and DLB (n = 41) subjects, compared with age matched controls (n = 41), (2) to record whether motor phenotypes of PD, PDD, and DLB subjects changed during the study, (3) to find out if cognitive and motor decline in PD was associated with baseline motor subtype, and (4) to report the incidence of dementia in PD patients in relation to baseline motor subtype. Results: Most of PDD and DLB participants were PIGD subtype at baseline assessment. In the non-demented PD group, tremor dominant (TD) and PIGD subtypes were more evenly represented. Cognitive decline over two years was greater in PDD and DLB groups (mean decline in MMSE − 4.5 and − 3.9, respectively), compared with PD ( − 0.2) and controls (−0.3). There was an association between PIGD subtype and increased rate of cognitive decline within the PD group. Of 40 PD patients, 25% of the 16 PIGD subtype developed dementia over two years, compared with none of the 18 TD or six indeterminate phenotype cases (χ 2 = 6.7, Fisher’s exact test p Conclusion: A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD.
379 citations
TL;DR: Overall resource consumption, work capacity and quality of life of patients with multiple sclerosis in nine European countries was assessed, and Informal care use was highly correlated with disease severity, but was further influenced by healthcare systems and family structure.
Abstract: Objective: To assess overall resource consumption, work capacity and quality of life of patients with multiple sclerosis in nine European countries. Methods: Information on resource consumption related to multiple sclerosis, informal care by relatives, productivity losses and overall quality of life (utility) was collected with a standardised pre-tested questionnaire from 13 186 patients enrolled in national multiple sclerosis societies or followed up in neurology clinics. Information on disease included disease duration, self-assessed disease severity and relapses. Mean annual costs per patient (€, 2005) were estimated from the societal perspective. Results: The mean age ranged from 45.1 to 53.4 years, and all levels of disease severity were represented. Between 16% and 29% of patients reported experiencing a relapse in the 3 months preceding data collection. The proportion of patients in early retirement because of multiple sclerosis ranged from 33% to 45%. The use of direct medical resources (eg, hospitalisation, consultations and drugs) varied considerably across countries, whereas the use of non-medical resources (eg, walking sticks, wheel chairs, modifications to house and car) and services (eg, home care and transportation) was comparable. Informal care use was highly correlated with disease severity, but was further influenced by healthcare systems and family structure. All types of costs increased with worsening disease. The total mean annual costs per patient (adjusted for gross domestic product purchasing power) were estimated at €18 000 for mild disease (Expanded Disability Status Scale (EDSS) 7.0). Utility was similar across countries at around 0.70 for a patient with an EDSS of 2.0 and around 0.45 for a patient with an EDSS of 6.5. Intangible costs were estimated at around €13 000 per patient.
349 citations
TL;DR: There was a trend towards a reduction in fall events and injurious falls with a positive effect of exercises on near falls and quality of life.
Abstract: Objective: To evaluate the effectiveness of a personalised home programme of exercises and strategies for repeat fallers with Parkinson’s disease (PD). Method: Patients with a confirmed diagnosis of idiopathic PD, independently mobile, living at home in the community, experiencing more than one fall in the previous 12 months and with intact gross cognitive function were invited to participate in this randomised controlled trial. Usual care was compared with a personalised 6 week, home based exercise and strategy programme. The primary outcomes were rates of falling at 8 weeks and 6 months. Whether participants had repeat fallen, nearly fallen or experienced injurious falls were also examined. Functional Reach, the Berg Balance Test, PD Self-assessment Scale and the Euro Quol were rated by a blinded assessor. Results: Participants were randomised to the exercise (n = 70) and control (n = 72) groups. There was a consistent trend towards lower fall rates in the exercise group at both 8 weeks and 6 months and lower rates of injurious falls needing medical attention at 6 months. Lower rates of repeat near falling were evident for the exercise group at 8 weeks (p = 0.004) and 6 months (p = 0.007). There was a positive effect of exercises at 6 months on Functional Reach (p = 0.009) and quality of life (p = 0.033). No significant differences were found on other secondary outcomes measures. Conclusion: There was a trend towards a reduction in fall events and injurious falls with a positive effect of exercises on near falls and quality of life.
338 citations
TL;DR: The data suggest that fatigue in MS is at least partially mediated through activation of proinflammatory cytokines, and increased levels of inflammatory cytokines may be involved in MS fatigue.
Abstract: Background: Fatigue is a major complaint of multiple sclerosis (MS) patients. However, little is known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and studies on sickness behaviour suggest that immune and neuroendocrine factors may play a causative role in the development of fatigue. Methods: We compared whole blood stimulatory capacity for pro- (TNFα, IFNγ) and anti-inflammatory cytokines (IL-10) as well as hypothalamo-pituitary-adrenal (HPA) axis function in 15 MS patients with marked fatigue and 15 patients without fatigue as determined by the Fatigue Severity Scale (FSS). Results: Proinflammatory cytokines were significantly higher (TNFα: 478.9 v 228.2 pg/ml, p = 0.01; IFNγ: 57.6 v 27.8 pg/ml; p = 0.01) in MS patients with fatigue. Furthermore, TNFα values significantly correlated with daytime sleepiness as measured by the Epworth Sleepiness Scale (r = 0.64, p = 0.001). Controlling for disease activity (as measured by the Cambridge Multiple Sclerosis Basic Score), disease duration, Expanded Disability Status Scale, and depression further increased the correlation of cytokine production and fatigue. HPA axis activity was not related to fatigue but was modestly correlated with cognitive impairment. Conclusion: Our data suggest that fatigue in MS is at least partially mediated through activation of proinflammatory cytokines. In line with earlier findings, HPA axis dysfunction seems not to be relevant in MS fatigue pathogenesis but appears to be linked to cognitive impairment. Our findings suggest that increased levels of inflammatory cytokines may be involved in MS fatigue. Investigation of cytokine profiles may increase the understanding of fatigue pathogenesis in MS.
318 citations
TL;DR: New presentations of compressive neuropathies among patients registered with 253 general practices in the UK General Practice Research Database with 1.83 million patient years at risk in 2000 were analysed and revealed that in 2000 the annual age standardised rates per 100 000 of new presentations in primary care were carpal tunnel syndrome and Morton’s metatarsalgia.
Abstract: Apart from carpal tunnel syndrome, there are no population based studies of the epidemiology of compressive neuropathies. To provide this information, new presentations of compressive neuropathies among patients registered with 253 general practices in the UK General Practice Research Database with 1.83 million patient years at risk in 2000 were analysed. The study revealed that in 2000 the annual age standardised rates per 100 000 of new presentations in primary care were: carpal tunnel syndrome, men 87.8/women 192.8; Morton's metatarsalgia, men 50.2/women 87.5; ulnar neuropathy, men 25.2/women 18.9; meralgia paraesthetica, men 10.7/women 13.2; and radial neuropathy, men 2.97/women 1.42. New presentations were most frequent at ages 55-64 years except for carpal tunnel syndrome, which was most frequent in women aged 45-54 years, and radial nerve palsy, which was most frequent in men aged 75-84 years. In 2000, operative treatment was undertaken for 31% of new presentations of carpal tunnel syndrome, 3% of Morton's metatarsalgia, and 30% of ulnar neuropathy.
302 citations
TL;DR: Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.
Abstract: Background: Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer’s disease, and may both have a negative impact on the progression of the illness. Objectives: To examine the clinical correlates of apathy in Alzheimer’s disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline. Methods: Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation. Results: Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p Conclusions: Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.
301 citations
TL;DR: Disability is common 12–14 years after hospital admission with a HI and for some there is a dynamic process of change in disability over time that is associated with self-perceptions of control that could be a target for intervention based research.
Abstract: Background There is a need to establish how long term outcome evolves after head injury (HI) and factors related to this, to inform opportunities for intervention. Objective To determine late outcome in adults 12–14 years after hospital admission for HI and to examine relationships between injury, early and late factors, and disability. Methods A prospective cohort with HI, whose outcome was reported previously at 1 and 5–7 years after injury, were followed up after 12–14 years. Participants were assessed using structured and validated measures of disability (Glasgow Outcome Scale-Extended), psychological well being, alcohol use and health status. Results Of 219 survivors followed-up at 5–7 years, 34 (15.5%) had died by 12–14 years. Disability remained common in survivors at 12–14 years (51%), as found at 1 and 5–7 years (53%). For those disabled at 1 year, outcome was poor, with 80% dead or disabled at 12–14 years. Older age at injury, a premorbid history of brain illness or physical disability and post-injury low self-esteem and stress were associated with disability at 12–14 years. Disability changed between 5–7 and 12–14 years in 55% of survivors, improving in 23%. Late changes in disability between 5–7 and 12–14 years were associated with self-perceptions of locus of control as being ‘powerful others’ at 5–7 years. Conclusions Disability is common 12–14 years after hospital admission with a HI. For some there is a dynamic process of change in disability over time that is associated with self-perceptions of control that could be a target for intervention based research.
TL;DR: Surviving a first SE episode could lower the mortality and morbidity of subsequent episodes, suggesting that underlying aetiology, rather than SE per se, is the major determinant of outcome.
Abstract: Background: Identification of outcome-predictive factors could lower risk of under- or over-treatment in status epilepticus (SE). Older age and acute symptomatic aetiology have been shown to predict mortality, but other variables are controversial and level of consciousness has received relatively little attention. The objective of this study was to assess variables predictive of mortality, particularly those available at presentation. Methods: The discharge database (1997–2004) of two university hospitals was screened for adult patients with EEG confirmed SE, excluding cerebral anoxia. Outcome at discharge (mortality, return to baseline clinical conditions) was analysed in relation to demographics, clinical features, and aetiology. Aetiologies were also classified based on whether or not they were potentially fatal independently of SE. Results: Mortality was 15.6% among 96 patients with a first SE episode, 10 of whom also experienced recurrent SE during the study period. Eleven other patients had only recurrent SE. Mortality was 4.8% among these 21 patients with recurrent SE. Return to baseline condition was more frequent after recurrent than incident SE (p = 0.02). For the first SE episode, death was associated with potentially fatal aetiology (p = 0.01), age ⩾65 (p = 0.02), and stupor or coma at presentation (p = 0.04), but not with gender, history of epilepsy, SE type, or time to treatment ⩾1 h. Conclusions: At initial evaluation, older age and marked impairment of consciousness are predictive of death. Surviving a first SE episode could lower the mortality and morbidity of subsequent episodes, suggesting that underlying aetiology, rather than SE per se, is the major determinant of outcome.
TL;DR: In this article, a new peripheral neuropathy activities measure, the Overall Neuropathy Limitations Scale (ONLS), was derived by modifying the Overall Disability Sum Score (ODSS) slightly.
Abstract: A new peripheral neuropathy activities measure, the Overall Neuropathy Limitations Scale (ONLS), was derived by modifying the Overall Disability Sum Score (ODSS) slightly. Its inter-rater reliability was found to be high and its correlation with the ODSS (r = 0.97), 36-item Short Form Questionnaire Physical Component Summary Score, and participation and impairment measures was significant. Acceptable responsiveness (standardised response mean 0.76) was shown by the ONLS. The results obtained from the questionnaire agreed closely with those obtained from observation of the tasks on the ONLS, but were not equivalent. The simplicity of the ODSS is shared by the ONLS, but the ONLS has better content validity and less ceiling effect, which may make it more useful for clinical practice and research.
TL;DR: The data suggest that quality of life in dementia is complex, and that simple proxy substitutions of discrete measures such as cognition or function are likely to miss important factors.
Abstract: Objectives: To explore the extent to which commonly used measures of specific outcomes in dementia are an appropriate proxy for quality of life in dementia. Methods: This was a cross sectional study set in communities in London and Nottingham, comprising 101 people with dementia and their 99 main family caregivers. The main outcome measures were health related quality of life in dementia (measured by the DEMQOL-Proxy), cognition (Mini Mental State Examination), functional impairment (Barthel Index), behavioural and psychological symptoms in dementia (Neuropsychiatric Inventory; NPI), and carer mental health (General Health Questionnaire). Results: On univariate analysis, decreased quality of life was statistically significantly correlated with higher levels of behavioural and psychological disturbance (NPI total score and its agitation, depression, anxiety, disinhibition, and irritability subscales); younger age of the person with dementia; and poorer mental health of the carer. Quality of life was not statistically significantly associated with cognition or carer age. In a multivariate model, psychological and behavioural disturbance and patient age remained statistically significantly associated with quality of life. Carer mental health was no longer statistically significantly associated, and cognition and functional limitation remained statistically insignificant. Conclusions: These data suggest that quality of life in dementia is complex, and that simple proxy substitutions of discrete measures such as cognition or function are likely to miss important factors.
Journal Article•
TL;DR: A new peripheral neuropathy activities measure, the Overall Neuropathy Limitations Scale (ONLS), was derived by modifying the Overall Disability Sum Score (ODSS) slightly, and has better content validity and less ceiling effect, which may make it more useful for clinical practice and research.
Abstract: A new peripheral neuropathy activities measure, the Overall Neuropathy Limitations Scale (ONLS), was derived by modifying the Overall Disability Sum Score (ODSS) slightly. Its inter-rater reliability was found to be high and its correlation with the ODSS (r=0.97), 36-item Short Form Questionnaire Physical Component Summary Score, and participation and impairment measures was significant. Acceptable responsiveness (standardised response mean 0.76) was shown by the ONLS. The results obtained from the questionnaire agreed closely with those obtained from observation of the tasks on the ONLS, but were not equivalent. The simplicity of the ODSS is shared by the ONLS, but the ONLS has better content validity and less ceiling effect, which may make it more useful for clinical practice and research.
TL;DR: The findings show that dementia in Parkinson’s disease is associated with structural neocortical changes in the brain, and that cognitive impairment in patients with PDND may be associated withStructural changes inThe brain.
Abstract: Background: Dementia is common in Parkinson’s disease, but the underlying brain pathology is not yet fully understood. Aim: To examine the changes in the brain of patients with Parkinson’s disease with mild cognitive impairment (MCI) and dementia, using structural magnetic resonance imaging. Methods: Using voxel-based morphometry, the grey matter atrophy on brain images of patients with Parkinson’s disease and dementia (PDD; n = 16) and Parkinson’s disease without dementia (PDND; n = 20), and healthy elderly subjects (n = 20) was studied. In the PDND group, 12 subjects had normal cognitive status and 8 had MCI. Standardised rating scales for motor, cognitive and psychiatric symptoms were used. Results: Widespread areas of cortical atrophy were found in patients with PDD compared with normal controls (in both temporal and frontal lobes and in the left parietal lobe). Grey matter reductions were found in frontal, parietal, limbic and temporal lobes in patients with PDD compared with those with PDND. In patients with PDND with MCI, areas of reduced grey matter in the left frontal and both temporal lobes were found. Conclusion: These findings show that dementia in Parkinson’s disease is associated with structural neocortical changes in the brain, and that cognitive impairment in patients with PDND may be associated with structural changes in the brain. Further studies with larger groups of patients are needed to confirm these findings.
TL;DR: In this paper, the authors investigated the influence of deep white matter hyperintensities (DWMH) and periventricular WMH on progression of cognitive decline in non-demented elderly people and found that the volume of PVWMH at baseline was associated with reduced mental processing speed.
Abstract: Objective: To investigate the influence of deep white matter hyperintensities (DWMH) and periventricular white matter hyperintensities (PVWMH) on progression of cognitive decline in non-demented elderly people. Methods: All data come from the nested MRI sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We performed a 3 year follow up study on 554 subjects of the PROSPER study using both repeated magnetic resonance imaging and cognitive testing. Cognitive decline and its dependency on WMH severity was assessed using linear regression models adjusted for sex, age, education, treatment group, and test version when applicable. Results: We found that the volume of PVWMH at baseline was longitudinally associated with reduced mental processing speed (p = 0.0075). In addition, we found that the progression in PVWMH volume paralleled the decline in mental processing speed (p = 0.024). In contrast, neither presence nor progression of DWMH was associated with change in performance on any of the cognitive tests. Conclusion: PVWMH should not be considered benign but probably underlie impairment in cognitive processing speed.
TL;DR: Stereotactic implantation of electrodes for DBS, if performed with multiplanar three-dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity.
Abstract: Objective: To determine the surgery-related and hardware-related complications of deep-brain stimulation (DBS) at a single centre. Methods: 262 consecutive patients (472 electrodes) operated for DBS in our department from February 1996 to March 2003 were retrospectively analysed to document acute adverse events (30 days postoperatively). The data of 180 of these patients were additionally revised to assess long-term complications (352 electrodes, mean follow-up 36.3 (SD 20.8) months). Results: The frequency of minor intraoperative complications was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were registered as acute severe adverse events caused by surgery. Among minor acute complications were subcutaneous bleeding along the extension wire (1.2%) and haematoma at the pulse generator implantation site (1.2%). Skin infection caused by the implanted material was registered in 15 of 262 patients (5.7%). The infection rate during the first observation period was 1.5% (4/262 patients) and the late infection rate was 6.1% (11/180 patients). Partial or complete removal of the stimulation system was necessitated in 12 of 262 (4.6%) patients because of skin infection. During the long-term observation period, hardware-related problems were registered in 25 of 180 (13.9%) patients. Conclusions: Stereotactic implantation of electrodes for DBS, if performed with multiplanar three-dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity. The main causes for the patients’ prolonged hospital stay and repeated surgery were wound infections and hardware-related complications.
TL;DR: SVD has a different risk factor profile from the typical atherosclerotic profile found in LVD, with hypertension being important, and the association of ILI with hypercholesterolaemia, diabetes and myocardial infarction may be consistent with a more atheosclerotic aetiology.
Abstract: Background: The mechanisms of cerebral small vessel disease (SVD) are unclear. Both atherosclerosis and a non-atherosclerotic diffuse arteriopathy have been reported pathologically. Two pathological and radiological subtypes have been suggested: localised atherosclerotic disease in larger perforating arteries causing larger lacunar infarcts without leukoaraiosis, and diffuse disease in smaller arterioles causing multiple smaller lacunar infarcts with leukoaraiosis. If atherosclerosis were important in SVD as a whole or in one particular subtype, one would expect the risk factor profile to be similar to that of cerebral large vessel disease (LVD).
Methods: Risk factor profiles were compared in Caucasian stroke patients with SVD (n = 414), LVD (n = 471) and 734 stroke-free Caucasian population controls. Patients with SVD were subdivided according to the presence or absence of confluent leukoaraiosis, into isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA).
Results: Hypertension was commoner in SVD than LVD (odds ratio (OR) 3.43 (2.32 to 5.07); p<0.001) whereas hypercholesterolaemia (OR 0.34 (0.24 to 0.48); p<0.001), smoking (OR 0.63 (0.44 to 0.91); p = 0.012), myocardial infarction (OR 0.35 (0.20 to 0.59); p<0.001) and peripheral vascular disease (OR 0.32 (0.20 to 0.50); p<0.001) were commoner in LVD. Among SVD patients, age (OR 1.11 (1.09 to 1.14); p<0.001) and hypertension (OR 3.32 (1.56 to 7.07); p = 0.002) were associated with ILA and hypercholesterolaemia (OR 0.45 (0.28 to 0.74); p = 0.002), diabetes (OR 0.42 (0.21 to 0.84); p = 0.014) and myocardial infarction (OR 0.18 (0.06 to 0.52); p = 0.001) with ILI.
Conclusion: SVD has a different risk factor profile from the typical atherosclerotic profile found in LVD, with hypertension being important. There are differences in the risk factor profile between the SVD subtypes; the association of ILI with hypercholesterolaemia, diabetes and myocardial infarction may be consistent with a more atherosclerotic aetiology.
TL;DR: Although prevalence of pain after stroke decreased with time, after 16 months 21% had moderate to severe pain, and profoundly affected the patients’ wellbeing.
Abstract: Objective: To determine prevalence and intensity of pain after stroke, focusing on patients’ perspectives. Methods: During a one year period, 416 first-ever stroke patients were included in the population based Lund Stroke Register. After 4 and 16 months (median), 297 patients (98% of survivors) were followed up. Worst pain intensity during the previous 48 hours was assessed on a visual analogue scale (VAS), range 0 to 100: a score of 0 to 30 was defined as no or mild pain; 40 to 100 as moderate to severe pain. NIH stroke scale (NIHSS) score and HbA1c were assessed at baseline. At 16 months, screening for depression was done using the geriatric depression scale (GDS-20), and cognition with the mini-mental state examination (MMSE). Predictors of pain were determined by multivariate analyses. Results: Moderate to severe pain was reported by 96 patients (32%) after four months (VAS median = 60). Predictors of pain were younger age (p = 0.01), female sex (p = 0.006), higher NIHSS score (p Conclusions: Although prevalence of pain after stroke decreased with time, after 16 months 21% had moderate to severe pain. Late pain after stroke was on average more severe, and profoundly affected the patients’ wellbeing.
TL;DR: A patient with advanced Parkinson’s disease who developed pathological gambling within a month after successful bilateral subthalamic nucleus (STN) stimulation appears to be related to a combination of bilateral STN stimulation and treatment with dopamine agonists.
Abstract: We describe a patient with advanced Parkinson's disease who developed pathological gambling within a month after successful bilateral subthalamic nucleus (STN) stimulation. There was no history of gambling. On neuropsychological testing, slight cognitive decline was evident 1 year after surgery. Stimulation of the most dorsal contact with and without medication induced worse performances on decision making tests compared with the more ventral contact. Pathological gambling disappeared after discontinuation of pergolide and changing the stimulation parameters. Pathological gambling does not seem to be associated with decision making but appears to be related to a combination of bilateral STN stimulation and treatment with dopamine agonists.
TL;DR: DTI is sensitive enough to detect abnormal neural fibres related to cognitive dysfunction after nmTBI, and is seen to be coarser than in the controls in the individual magnetic resonance tractography of the corpus callosum and fornix.
Abstract: Background: Non-missile traumatic brain injury (nmTBI) without macroscopically detectable lesions often results in cognitive impairments that negatively affect daily life. Aim: To identify abnormal white matter projections in patients with nmTBI with cognitive impairments using diffusion tensor magnetic resonance imaging (DTI). Methods: DTI scans of healthy controls were compared with those of 23 patients with nmTBI who manifested cognitive impairments but no obvious neuroradiological lesions. DTI was comprised of fractional anisotropy analysis, which included voxel-based analysis and confirmatory study using regions of interest (ROI) techniques, and magnetic resonance tractography of the corpus callosum and fornix. Results: A decline in fractional anisotropy around the genu, stem and splenium of the corpus callosum was shown by voxel-based analysis. Fractional anisotropy values of the genu (0.47), stem (0.48), and splenium of the corpus callosum (0.52), and the column of the fornix (0.51) were lower in patients with nmTBI than in healthy controls (0.58, 0.61, 0.62 and 0.61, respectively) according to the confirmatory study of ROIs. The white matter architecture in the corpus callosum and fornix of patients with nmTBI were seen to be coarser than in the controls in the individual magnetic resonance tractography. Conclusions: Disruption of the corpus callosum and fornix in patients with nmTBI without macroscopically detectable lesions is shown. DTI is sensitive enough to detect abnormal neural fibres related to cognitive dysfunction after nmTBI.
TL;DR: This newly discovered serum autoantibody was markedly associated with longitudinally extensive spinal cord lesions and with complete blindness, suggesting severe optic–spinal disease.
Abstract: This study investigates the relation between the serological status of NMO (neuromyelitis optica)-IgG and the clinical and MRI features in Japanese patients with multiple sclerosis. Serum NMO-IgG was tested in 35 Japanese patients diagnosed with multiple sclerosis, including 19 with the optic–spinal form of multiple sclerosis (OSMS), three with the spinal form of multiple sclerosis (SMS), and 13 with the conventional form of multiple sclerosis (CMS), which affects the brain. NMO-IgG was detected in 14 patients, 12 with OSMS and 2 with CMS. In these patients, longitudinally extensive (>3 vertebral segments) spinal cord lesions (93% v 57%) and permanent, complete blindness (no perception of light) in at least one eye (50% v 0%) were the noticeable features as compared with NMO-IgG-negative OSMS. The two patients having CMS with NMO-IgG had unusual brain lesions, but in other respects had features suggesting OSMS. NMO-IgG was detected in more than half the number of patients with OSMS and in some patients with CMS. This newly discovered serum autoantibody was markedly associated with longitudinally extensive spinal cord lesions and with complete blindness, suggesting severe optic–spinal disease.
TL;DR: In this paper, the longitudinal relationship between CSF markers, Aβ42 and T-tau, measured in 1992, and change in Mini-Mental State Examination (ΔMMSE) score between 1992 and 2002 were investigated in 55 women (aged 70-84 years, mean (SD) MMSE score 28.3 (1.5)), who were participants in the Prospective Population Study of Women in Gothenburg, Sweden.
Abstract: Background: Low levels of cerebrospinal fluid (CSF) β-amyloid 1–42 (Aβ42) and high total tau (T-tau) are diagnostic for manifest Alzheimer’s disease. It is not known, however, whether these biomarkers may be risk indicators for cognitive decline in otherwise healthy older people. Methods: The longitudinal relationship between CSF markers, Aβ42 and T-tau, measured in 1992, and change in Mini-Mental State Examination (ΔMMSE) score between 1992 and 2002 were investigated in 55 women (aged 70–84 years, mean (SD) MMSE score = 28.3 (1.5)), who were participants in the Prospective Population Study of Women in Gothenburg, Sweden. These women did not have dementia when they experienced lumbar puncture in 1992–3. Results: Over the 8-year follow-up period, ΔMMSE (range = +3 to −21 points) was correlated with Aβ42 (Spearman’s r = 0.40, p = 0.002), such that lower levels of Aβ42 were related to greater decline. This was also observed after excluding 4 women who developed dementia between 1992 and 2002 (Spearman’s r = 0.34, p = 0.019). A multivariate logistic regression model predicting a decline of ⩾5 points on the MMSE (observed in six women), or a risk of developing dementia over the 8-year follow-up period (observed in four women), including age, education, Aβ42 and T-tau as covariates, showed that Aβ42 was the sole predictor of significant cognitive decline or dementia (OR per 100 pg/ml Aβ42 = 2.24, 95% CI 1.19 to 4.22, p = 0.013). Conclusions: Low levels of CSF Aβ42 may predict cognitive decline among older women without dementia.
TL;DR: Pain may be a representative feature of Parkinson’s disease frequently associated with motor complications and the association is independent of a number of potentially relevant demographic and clinical variables.
Abstract: Aims: To study the association of pain with motor complications in 117 patients with Parkinson’s disease. Methods: Patients were asked to refer any pain they experienced at the time of study and lasting since at least 2 months. Basic parkinsonian signs and motor complications (including motor fluctuations and dyskinesia) were assessed and Unified Parkinson’s Disease Rating Scale (UPDRS) motor score part III (during on) and part IV were calculated. Information on age, sex, duration of disease, use of dopamine agonists and levodopa, years of levodopa treatment and current levodopa dosage, medical conditions possibly associated with pain, and depression were collected. Single and multiple explanatory variable logistic regression models were used to check the association of pain with the investigated variables. Results: Pain was described by 47 patients (40%) and could be classified into dystonic (n.19) and non dystonic pain (n.16); in 12 patients both types coexisted. Multiple explanatory variable logistic regression models indicated a significant association of pain with motor complications (adjusted OR, 5.7; 95% CI, 2 to 16.5; p = 0.001). No association was found between pain, dystonic or non dystonic, and the other investigated variables including medical conditions known to be associated to pain in the general population. There was a significant correlation (r = 0.31, p Conclusions: Pain may be a representative feature of Parkinson’s disease frequently associated with motor complications. The association is independent of a number of potentially relevant demographic and clinical variables.
TL;DR: Although both the IPP and IMIS improved cognition in patients with Alzheimer’s disease, the IMIS program provided an improvement above and beyond that seen with IPP alone, which lasted for 24 weeks.
Abstract: Objective: To determine the usefulness of an interactive multimedia internet-based system (IMIS) for the cognitive stimulation of Alzheimer’s disease. Methods: This is a 24-week, single-blind, randomised pilot study conducted on 46 mildly impaired patients suspected of having Alzheimer’s disease receiving stable treatment with cholinesterase inhibitors (ChEIs). The patients were divided into three groups: (1) those who received 3 weekly, 20-min sessions of IMIS in addition to 8 h/day of an integrated psychostimulation program (IPP); (2) those who received only IPP sessions; and (3) those who received only ChEI treatment. The primary outcome measure was the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog). Secondary outcome measures were: Mini-Mental State Examination (MMSE), Syndrom Kurztest, Boston Naming Test, Verbal Fluency, and the Rivermead Behavioral Memory Test story recall subtest. Results: After 12 weeks, the patients treated with both IMIS and IPP had improved outcome scores on the ADAS-Cog and MMSE, which was maintained through 24 weeks of follow-up. The patients treated with IPP alone had better outcome than those treated with ChEIs alone, but the effects were attenuated after 24 weeks. All patients had improved scores in all of the IMIS individual tasks, attaining higher levels of difficulty in all cases. Conclusion: Although both the IPP and IMIS improved cognition in patients with Alzheimer’s disease, the IMIS program provided an improvement above and beyond that seen with IPP alone, which lasted for 24 weeks.
TL;DR: Anosognosia in those with Alzheimer’s disease is manifested as poor awareness of deficits in iADL and bADL, depressive changes and behavioural disinhibition, which may contribute to the early identification of this condition.
Abstract: Objective: To determine the earliest symptoms of anosognosia in people with Alzheimer’s disease and to validate a criteria-guided strategy to diagnose anosognosia in dementia. Methods: A consecutive series of 750 patients with very mild or probable Alzheimer’s disease attending a memory clinic, as well as their respective care givers, was assessed using a comprehensive psychiatric evaluation. Results: The factors of anosognosia for (1) basic activities of daily living (bADL), (2) instrumental activities of daily living (iADL), (3) depression and (4) disinhibition were produced by a principal component analysis on the differential scores (ie, caregiver score minus patient score) on the anosognosia questionnaire for dementia. A discrepancy of two or more points in the anosognosia-iADL factor was found to have a high sensitivity and specificity to identify clinically diagnosed anosognosia in people with Alzheimer’s disease. By logistic regression analysis, the severity of dementia and apathy were both shown to be noticeably associated with anosognosia in people with Alzheimer’s disease. Conclusion: Anosognosia in those with Alzheimer’s disease is manifested as poor awareness of deficits in iADL and bADL, depressive changes and behavioural disinhibition. The frequency of anosognosia is found to increase considerably with the severity of dementia. The validity of a specific set of criteria to diagnose anosognosia in people with Alzheimer’s disease was shown, which may contribute to the early identification of this condition.
TL;DR: Autonomic dysfunction occurs in all common dementias but is especially prominent in PDD with important treatment implications and the prevalence of orthostatic hypotension and autonomic neuropathies was higher in all dementias than in controls.
Abstract: Background: There are no studies of autonomic function comparing Alzheimer’s disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Aims: To assess cardiovascular autonomic function in 39 patients with AD, 30 with VAD, 30 with DLB, 40 with PDD and 38 elderly controls by Ewing’s battery of autonomic function tests and power spectral analysis of heart rate variability. To determine the prevalence of orthostatic hypotension and autonomic neuropathies by Ewing’s classification. Results: There were significant differences in severity of cardiovascular autonomic dysfunction between the four types of dementia. PDD and DLB had considerable dysfunction. VAD showed limited evidence of autonomic dysfunction and in AD, apart from orthostatic hypotension, autonomic functions were relatively unimpaired. PDD showed consistent impairment of both parasympathetic and sympathetic function tests in comparison with controls (all p Conclusion: Autonomic dysfunction occurs in all common dementias but is especially prominent in PDD with important treatment implications.
TL;DR: Improved survival was seen in patients with ALS attending tertiary ALS centres, independently from all other known prognostic factors, possibly through a better implementation of supportive treatments.
Abstract: Objective: To evaluate the effects of tertiary centres for amyotrophic lateral sclerosis (ALS) on ALS outcome and the use of hospital facilities. Methods: The study was based on the data of an epidemiological, prospective, population-based register on ALS (Piemonte and Valle d’Aosta Register for amyotrophic lateral sclerosis, PARALS). The 221 patients recruited between 1995 and 1996 were prospectively followed up for outcome and use of hospital-based services. Results: In all, 97 patients were followed up by tertiary ALS centres and 124 by general neurological clinics. Patients followed up by tertiary ALS centres were found to be 4 years younger and underwent percutaneous endoscopic gastronomy and non-invasive positive-pressure ventilation more often. Patients followed up by tertiary ALS centres were found to have a considerably longer median survival time (1080 v 775 days), even when stratifying by age, site of onset and respiratory function at diagnosis. In Cox multivariate analysis, attending a tertiary ALS centre was observed to be an independent positive prognostic factor. Moreover, patients attending a tertiary ALS centre were admitted to hospital less often (1.2 v 3.3) and were more frequently admitted for planned interventions. Conversely, patients followed up by general neurological clinics were more frequently admitted for acute events. Also, the hospital stay was considerably shorter for patients attending tertiary ALS centres (5.8 v 12.4 days). Conclusions: Improved survival was seen in patients with ALS attending tertiary ALS centres, independently from all other known prognostic factors, possibly through a better implementation of supportive treatments. Moreover, because of these centres, the hospitalisation rate was markedly reduced, thus offering a cost-effective service to patients with ALS and to the community as a whole.
TL;DR: The modified McDonald criteria for dissemination in space and time for assessing the development of clinically definite multiple sclerosis were more sensitive and more accurate than the original criteria.
Abstract: Background: The McDonald criteria include MRI evidence for dissemination in space and dissemination in time for the diagnosis of multiple sclerosis in young adult patients who present with clinically isolated syndromes (CIS) typical of the disease. Although a major advance, the criteria have limited sensitivity for making an early diagnosis. Objective: To compare the performance of McDonald criteria and modified McDonald criteria for dissemination in space and time for assessing the development of clinically definite multiple sclerosis. Methods: McDonald criteria were modified using the combination of a less stringent definition for dissemination in space and allowing a new T2 lesion per se after three months as evidence for dissemination in time. Modified and McDonald criteria were applied in 90 CIS patients at baseline and at three month follow up scans. Results: Both criteria were highly specific (>90%) but the modified criteria were more sensitive (77% v 46%) and more accurate (86% v 73%). Conclusions: These modified criteria should be evaluated in other CIS cohorts.