Showing papers in "Journal of Neurology, Neurosurgery, and Psychiatry in 2003"

Head injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication

Abstract: Objective: To determine, using a systematic review of case-control studies, whether head injury is a significant risk factor for Alzheimer’s disease. We sought to replicate the findings of the meta-analysis of Mortimer et al (1991). Methods: A predefined inclusion criterion specified case-control studies eligible for inclusion. A comprehensive and systematic search of various electronic databases, up to August 2001, was undertaken. Two independent reviewers screened studies for eligibility. Fifteen case-control studies were identified that met the inclusion criteria, of which seven postdated the study of Mortimer et al . Results: We partially replicated the results of Mortimer et al . The meta-analysis of the seven studies conducted since 1991 did not reach significance. However, analysis of all 15 case-control studies was significant (OR 1.58, 95% CI 1.21 to 2.06), indicating an excess history of head injury in those with Alzheimer’s disease. The finding of Mortimer et al that head injury is a risk factor for Alzheimer’s disease only in males was replicated. The excess risk of head injury in those with Alzheimer’s disease is only found in males (males: OR 2.29, 95% CI 1.47 to 2.06; females: OR 0.91, 95% CI 0.56 to 1.47). Conclusions: This study provides support for an association between a history of previous head injury and the risk of developing Alzheimer’s disease.

The prevalence and causes of dementia in people under the age of 65 years

Abstract: Objectives: To determine the prevalence of dementia in people under the age of 65 in a large catchment area, and use these figures to estimate the number of younger people affected by dementia in the UK. Design: Epidemiological catchment area prevalence survey. Setting: The London boroughs of Kensington and Chelsea, Westminster, and Hillingdon with a total population of 567 500 people. Participants: All residents of the catchment area with dementia, where the illness began before the age of 65 years. Participants were notified to the study by medical and care professionals. The diagnosis and age of onset was established from all available health and social care records. In total, 227 people were identified, of whom 185 fulfilled the inclusion criteria of having a dementia which started before their 65th birthday. Main outcome measures: Diagnosis of dementia and differential diagnosis of the cause of the dementia. Results: The prevalence of dementia in those aged 30–64 was 54.0 per 100 000 (95% CI 45.1 to 64.1 per 100 000). For those aged 45–64 years, the prevalence was 98.1 per 100 000 (95% CI 81.1 to 118.0 per 100 000). From the age of 35 onwards, the prevalence of dementia approximately doubled with each 5 year increase in age. Extrapolating these figures nationally suggests that there are 18 319 (15 296–21 758) people with dementia under the age of 65 in the UK. Conclusions: The study confirms previous “guestimates” of the number of younger people affected by dementia in UK. The prevalence figures generated are robust, and are supported by other smaller and targeted prevalence surveys. The prevalence figures provided by this study will allow health planners to accurately estimate need and plan services.

Outcome of contemporary surgery for chronic subdural haematoma: evidence based review

Abstract: Objective: To evaluate the results of surgical treatment options for chronic subdural haematoma in contemporary neurosurgery according to evidence based criteria. Methods: A review based on a Medline search from 1981 to October 2001 using the phrases “subdural haematoma” and “subdural haematoma AND chronic”. Articles selected for evaluation had at least 10 patients and less than 10% of patients were lost to follow up. The articles were classified by three classes of evidence according to criteria of the American Academy of Neurology. Strength of recommendation for different treatment options was derived from the resulting degrees of certainty. Results: 48 publications were reviewed. There was no article that provided class I evidence. Six articles met criteria for class II evidence and the remainder provided class III evidence. Evaluation of the results showed that twist drill and burr hole craniostomy are safer than craniotomy; burr hole craniostomy and craniotomy are the most effective procedures; and burr hole craniostomy has the best cure to complication ratio (type C recommendation). Irrigation lowers the risk of recurrence in twist drill craniostomy and does not increase the risk of infection (type C recommendation). Drainage reduces the risk of recurrence in burr hole craniostomy, and a frontal position of the drain reduces the risk of recurrence (type B recommendation). Drainage reduces the risk of recurrence in twist drill craniostomy, and the use of a drain does not increase the risk of infection (type C recommendation). Burr hole craniostomy appears to be more effective in treating recurrent haematomas than twist drill craniostomy, and craniotomy should be considered the treatment of last choice for recurrences (type C recommendation). Conclusions: The three principal techniques—twist drill craniostomy, burr hole craniostomy, and craniotomy—used in contemporary neurosurgery for chronic subdural haematoma have different profiles for morbidity, mortality, recurrence rate, and cure rate. Twist drill and burr hole craniostomy can be considered first tier treatment, while craniotomy may be used as second tier treatment. A cumulative summary of data shows that, overall, the postoperative outcome of chronic subdural haematoma has not improved substantially over the past 20 years.

Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996–2000

Abstract: Background: In recent years, there has been a paradigm shift in the method of healthcare delivery to amyotrophic lateral sclerosis (ALS) patients with the emergence of multidisciplinary ALS clinics that cater exclusively for patients with this condition. The impact of multidisciplinary management has not been previously evaluated. Methods: Using data from the Irish ALS Register, we conducted a prospective, population based study of all ALS cases diagnosed in Ireland over a five year period to evaluate the effectiveness of a multidisciplinary clinic on ALS survival. Results: Eighty two (24%) patients attended the multidisciplinary ALS clinic, with the remaining 262 (76%) cases followed in a general neurology clinic. The ALS clinic cohort was an average of five years younger (60.1 v 65.6 years) and were more likely to receive riluzole than the general neurology cohort (99% v 61%). The median survival of the ALS clinic cohort was 7.5 months longer than for patients in the general neurology cohort (logrank = 15.4, p < 0.0001). Overall, one year mortality was decreased by 29.7%. Prognosis of bulbar onset patients was extended by 9.6 months if they attended the ALS clinic. Using multivariate analysis, attendance at the ALS clinic was an independent covariate of survival (HR = 1.47, p = 0.02). Conclusions: ALS patients who received their care at a multidisciplinary clinic had a better prognosis than patients attending a general neurology clinic. The data suggest that active and aggressive management enhances survival, particularly among ALS patients with bulbar dysfunction. The effect of clinic type must be considered in future clinical trials design.

fMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease

Abstract: Objective: To examine alterations in patterns of brain activation seen in normal aging and in mild Alzheimer's disease by functional magnetic resonance imaging (fMRI) during an associative encoding task. Methods: 10 young controls, 10 elderly controls, and seven patients with mild Alzheimer's disease were studied using fMRI during a face–name association encoding task. The fMRI paradigm used a block design with three conditions: novel face–name pairs, repeated face–name pairs, and visual fixation. Results: The young and elderly controls differed primarily in the pattern of activation seen in prefrontal and parietal cortices: elderly controls showed significantly less activation in both superior and inferior prefrontal cortices but greater activation in parietal regions than younger controls during the encoding of novel face–name pairs. Compared with elderly controls, the Alzheimer patients showed significantly less activation in the hippocampal formation but greater activation in the medial parietal and posterior cingulate regions. Conclusions: The pattern of fMRI activation during the encoding of novel associations is differentially altered in the early stages of Alzheimer's disease compared with normal aging.

Intrathecal inflammation precedes development of Alzheimer’s disease

Abstract: Objectives: To analyse the cerebrospinal fluid (CSF) values of the proinflammatory cytokines, interleukin 1β (IL1β), tumour necrosis factor α (TNFα), GM-CSF, of the anti-inflammatory cytokine TGFβ, of tau protein, a marker for neurodegeneration, and of β amyloid (Aβ), a protein involved in the formation of senile plaques, in prospectively followed up patients with mild cognitive impairment (MCI). Methods: Analyses of CSF levels of TNFα, IL1β, GM-CSF, TGFβ, βa, and tau protein were performed using ELISA in 56 patients with MCI who were followed up prospectively and in 25 age matched, healthy controls. Results: Patients with MCI displayed significantly higher levels of TNFα and tau protein and significantly lower levels of TGFβ and Aβ compared with the healthy controls. After nine months of follow up, 25 patients still displayed MCI while the remaining 31 patients had progressed to Alzheimer’s disease (AD). Only MCI patients who progressed to AD at follow up, showed significantly higher CSF levels of TNFα than controls. In addition, reduced CSF-Aβ42 levels were only found in MCI patients that progressed to AD, further supporting the notion that disturbed metabolism of Aβ is an early finding in AD. Conclusions: These results demonstrate increased production of the proinflammatory cytokine, TNFα and decreased production of the anti-inflammatory cytokine TGFβ in patients with MCI at risk to develop AD, suggesting a propensity towards inflammation in this patient group and indicating that CNS inflammation is a early hallmark in the pathogenesis of AD.

Increased blood–brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging

Abstract: Objectives: Patients with type II diabetes are at increased risk of cognitive impairment. The retinal and renal complications of diabetes follow microvascular damage permitting small arterioles to leak, hence the cerebral damage might also follow loss of blood–brain barrier (BBB) integrity. Magnetic resonance (MR) brain imaging with intravenous gadolinium (Gd) diethylenetriamine pentaacetic acid (Gd-DTPA) was used to identify increased BBB permeability. Methods: Ten well controlled type II diabetic patients aged 65–70 years and 10 controls underwent MR brain imaging with fluid attenuated inversion recovery (FLAIR); T1 weighted (T1W) volumetric imaging before; and T1W volumetric imaging at 5, 15, 30, 45, 60, and 90 minutes after intravenous Gd-DTPA. The T1W image before Gd-DTPA was subtracted from the images at each time point after Gd-DTPA. Net signal intensity was plotted against time for different brain regions. White matter hyperintensities were scored from the FLAIR image. Results: The signal intensity/time curves showed that brain signal intensity increased more in the diabetic group than controls during the first 15 minutes after Gd-DTPA, particularly in the basal ganglia (p=0.018). Signal intensity in controls peaked at five minutes and diabetics at 15 minutes. Subjects with more white matter hyperintensities had greater signal increase after Gd-DTPA, whether diabetic or not (p=0.001). Conclusions: Increased BBB permeability with MR imaging was detected in patients with type II diabetes or white matter hyperintensities. Increased permeability of the BBB might account for some of the cerebral effects of type II diabetes, and so possibly also for the effect of other conditions that affect the microvasculature (like hypertension), on the brain.

Idiopathic intracranial hypertension: 12 cases treated by venous sinus stenting

Abstract: Background: The high pressures documented in the intracranial venous sinuses in idiopathic intracranial hypertension (IIH) could be the result of focal stenotic lesions in the lateral sinuses obstructing cranial venous outflow. Objective: To explore the relation between venous sinus disease and IIH. Methods: 12 patients with refractory IIH had dilatation and stenting of the venous sinuses after venography and manometry had shown intracranial venous hypertension proximal to stenoses in the lateral sinuses. Intrasinus pressures were recorded before and after the procedure and correlated with clinical outcome. Results: Intrasinus pressures were variably reduced by stenting. Five patients were rendered asymptomatic, two were improved, and five were unchanged. Conclusions: The importance of venous sinus disease in the aetiology of IIH is probably underestimated. Lateral sinus stenting shows promise as an alternative treatment to neurosurgical intervention in intractable cases.

Functional recovery after surgical resection of low grade gliomas in eloquent brain: hypothesis of brain compensation.

Abstract: Objectives: To describe functional recovery after surgical resection of low grade gliomas (LGG) in eloquent brain areas, and discuss the mechanisms of compensation. Methods: Seventy-seven right-handed patients without deficit were operated on for a LGG invading primary and/or secondary sensorimotor and/or language areas, as shown anatomically by pre-operative MRI and intraoperatively by electrical brain stimulation and cortico-subcortical mapping. Results: Tumours involved 31 supplementary motor areas, 28 insulas, 8 primary somatosensory areas, 4 primary motor areas, 4 Broca's areas, and 2 left temporal language areas. All patients had immediate post-operative deficits. Recovery occurred within 3 months in all except four cases (definitive morbidity: 5%). Ninety-two percent of the lesions were either totally or extensively resected on post-operative MRI. Conclusions: These findings suggest that spatio-temporal functional re-organisation is possible in peritumoural brain, and that the process is dynamic. The recruitment of compensatory areas with long term perilesional functional reshaping would explain why: before surgery, there is no clinical deficit despite the tumour growth in eloquent regions; immediately after surgery, the occurrence of a deficit, which could be due to the resection of invaded areas participating (but not essential) to the function; and why three months after surgery, almost complete recovery had occurred. This brain plasticity, which decreases the long term risk of surgical morbidity, may be used to extend the limits of surgery in eloquent areas.

CSF hypocretin-1 levels in narcolepsy, Kleine-Levin syndrome, and other hypersomnias and neurological conditions

Abstract: Objective: To determine the role of CSF hypocretin-1 in narcolepsy with and without cataplexy, Kleine-Levin syndrome (KLS), idiopathic and other hypersomnias, and several neurological conditions. Patients: 26 narcoleptic patients with cataplexy, 9 narcoleptic patients without cataplexy, 2 patients with abnormal REM-sleep-associated hypersomnia, 7 patients with idiopathic hypersomnia, 2 patients with post-traumatic hypersomnia, 4 patients with KLS, and 88 patients with other neurological disorders. Results: 23 patients with narcolepsy-cataplexy had low CSF hypocretin-1 levels, while one patient had a normal hypocretin level (HLA-DQB1*0602 negative) and the other two had intermediate levels (familial forms). One narcoleptic patient without cataplexy had a low hypocretin level. One patient affected with post-traumatic hypersomnia had intermediate hypocretin levels. The KLS patients had normal hypocretin levels while asymptomatic, but one KLS patient (also affected with Prader-Willi syndrome) showed a twofold decrease in hypocretin levels during a symptomatic episode. Among the patients without hypersomnia, two patients with normal pressure hydrocephalus and one with unclear central vertigo had intermediate levels. Conclusion: Low CSF hypocretin-1 is highly specific (99.1%) and sensitive (88.5%) for narcolepsy with cataplexy. Hypocretin ligand deficiency appears not to be the major cause for other hypersomnias, with a possible continuum in the pathophysiology of narcolepsy without cataplexy and idiopathic hypersomnia. However, partial hypocretin lesions without low CSF hypocretin-1 consequences cannot be definitely excluded in those disorders. The existence of normal hypocretin levels in narcoleptic patients and intermediate levels in other rare aetiologies needs further investigation, especially for KLS, to establish the functional significance of hypocretin neurotransmission alterations.

Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease.

Abstract: Activated microglia, the resident macrophages of the brain, are a feature of Alzheimer's disease. Animal models suggest that when activated microglia are further activated by a subsequent systemic infection this results in significantly raised levels of interleukin 1beta within the CNS, which may in turn potentiate neurodegeneration. This prospective pilot study in Alzheimer's disease subjects showed that cognitive function can be impaired for at least two months after the resolution of a systemic infection and that cognitive impairment is preceded by raised serum levels of interleukin 1beta. These relations were not confounded by the presence of any subsequent systemic infection or by baseline cognitive scores. Further research is needed to determine whether recurrent systemic infections drive cognitive decline in Alzheimer's disease subjects through a cytokine mediated pathway.

Treatment of IgM antibody associated polyneuropathies using rituximab

Abstract: Objectives: Polyneuropathies with associated serum IgM antibodies are often difficult to treat. Rituximab is a monoclonal antibody directed against the B cell surface membrane marker CD20. Rituximab eliminates B cells from the circulation, and, over time, could reduce cells producing autoantibodies. This study tested the ability of rituximab to produce changes in serum antibody titres, and improvement in strength, in patients with neuromuscular disorders and IgM autoantibodies. Methods: Over a period of two years, the authors evaluated changes in strength, measured by quantitative dynamometry, and concentrations of several types of serum antibodies in patients with polyneuropathies and serum IgM autoantibodies. Twenty one patients treated with rituximab were compared with 13 untreated controls. Results: Treatment with rituximab was followed by improved strength (an increase of mean (SEM) 23% (2%)of normal levels of strength), a reduction in serum IgM autoantibodies (to 43% (4%) of initial values), and a reduction in total levels of IgM (to 55% (4%) of initial values). There was no change in levels of serum IgG antibodies. There were no major side effects, even though B cells were virtually eliminated from the circulation for periods up to two years. Conclusions: In patients with IgM autoantibody associated peripheral neuropathies, rituximab treatment is followed by reduced serum concentrations of IgM, but not IgG, antibodies, and by improvement in strength. Additional studies, with placebo controls and blinded outcome measures, are warranted to further test the efficacy of rituximab treatment of IgM associated polyneuropathies.

Hans Berger (1873–1941), Richard Caton (1842–1926), and electroencephalography

Abstract: Hans Berger recorded the first human electroencephalograms (EEGs) in 1924. He obtained his medical degree from the University of Jena, Germany, in 1897 and then joined the university psychiatric clinic directed by Otto Binswanger. There he remained until retirement in 1938. Berger succeeded Binswanger as director of the clinic and became Professor of Neurology and Psychiatry at the University of Jena in 1919. In his early work Berger had hoped to discover the physiological basis of psychic phenomena. The results were disappointing and Berger turned to investigating electrical activity of the brain. He characterised the wave patterns including α and β waves and coined the term “electroencephalogram”. Berger’s paper Uber das Elektrenkephalogramm des Menschen (On the EEG in humans), published in 1929 in the Archive fur Psychiatre und Nervenkrankheiten , was the first …

Clinical surveillance of carpal tunnel syndrome in two areas of the United Kingdom, 1991-2001.

Abstract: Objective: To study the demographic characteristics of patients with carpal tunnel syndrome and changes in incidence over time. Methods: Prospective collection of neurophysiological and clinical data on all patients presenting to the subregional department of clinical neurophysiology in Canterbury, UK, from 1992 to 2001 and to the electromyography clinic in St Luke's Hospital, Huddersfield, UK, from 1991 to 1993. Results: 6245 new cases of neurophysiologically confirmed carpal tunnel syndrome were identified in Canterbury and 590 in Huddersfield. The average annual incidences (per 100 000) were 139.4 for women and 67.2 for men in East Kent, and 83.2 for women and 48.0 for men in Huddersfield. Corrected to the WHO European standard population these rates were 120.5 for women and 60.0 for men in East Kent, and 61.5 for women and 35.0 for men in Huddersfield. Between 1992 and 2001 there was an increase in the number of confirmed cases in East Kent but a decrease in their average severity. The age distributions were bimodal with a peak in the 50–54 age group and a second peak between 75 and 84 years. Over half the cases were bilateral. The disorder was consistently worse in the elderly, and more severe in men than in women in all age groups. Conclusions: The age distributions of unselected cases of carpal tunnel syndrome in both clinics differ markedly from that usually portrayed in surgical series. There was a significant increase in cases diagnosed between 1992 and 2001 in Canterbury, probably the result of increased ascertainment of milder cases. Median nerve impairment is more severe in the elderly and in men at all ages.

Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomised, placebo controlled trial

Abstract: Objective: To assess the efficacy and safety of Melissa officinalis extract using a fixed dose (60 drops/day) in patients with mild to moderate Alzheimer’s disease. Design: A four month, parallel group, placebo controlled trial undertaken in three centres in Tehran, Iran. Methods: Patients with mild to moderate Alzheimer’s disease aged between 65 and 80 years (n = 42; 18 women, 24 men) with a score of ≥ 12 on the cognitive subscale of Alzheimer’s disease assessment scale (ADAS-cog) and ≤ 2 on the clinical dementia rating (CDR) were randomised to placebo or fixed dose of Melissa officinalis extract. The main efficacy measures were the change in the ADAS-cog and CDR-SB scores compared with baseline. Side effects were systematically recorded. Results: At four months, Melissa officinalis extract produced a significantly better outcome on cognitive function than placebo (ADAS-cog: df = 1, F = 6.93, p = 0.01; CDR: df = 1, F = 16.87, p Conclusions: Melissa officinalis extract is of value in the management of mild to moderate Alzheimer’s disease and has a positive effect on agitation in such patients.

Incidence, risk, and case fatality of first ever stroke in the elderly population. The Rotterdam Study

Abstract: Objective: To estimate the incidence, survival, and lifetime risk of stroke in the elderly population. Methods: The authors conducted a study in 7721 participants from the population based Rotterdam Study who were free from stroke at baseline (1990–1993) and were followed up for stroke until 1 January 1999. Age and sex specific incidence, case fatality rates, and lifetime risks of stroke were calculated. Results: Mean follow up was 6.0 years and 432 strokes occurred. The incidence rate of stroke per 1000 person years increased with age and ranged from 1.7 (95% CI 0.4 to 6.6) in men aged 55 to 59 years to 69.8 (95% CI 22.5 to 216.6) in men aged 95 years or over. Corresponding figures for women were 1.2 (95% CI 0.3 to 4.7) and 33.1 (95% CI 17.8 to 61.6). Men and women had similar absolute lifetime risks of stroke (21% for those aged 55 years). The survival after stroke did not differ according to sex. Conclusions: Stroke incidence increases with age, also in the very old. Although the incidence rate is higher in men than in women over the entire age range, the lifetime risks were similar for both sexes.

Cognitive impairment in probable multiple sclerosis.

Abstract: Objectives: To evaluate and characterise cognitive impairment in the very early stage of multiple sclerosis (MS), in which patients are still diagnosed as suffering from probable MS. Methods: The Brief Repeatable Battery-Neuropsychological (BRB-N) that has been validated for MS patients was used. Abnormal performance was defined as one standard deviation below the mean reported for healthy age matched subjects. Neurological disability and brain magnetic resonance imaging (MRI) were performed for all patients. Correlation coefficients were calculated between disease burden variables and performance on the BRB-N. Results: Sixty seven patients with probable MS were evaluated within a mean of one month of the onset of new neurological symptoms. Evidence for the presence of cognitive impairment was shown in 53.7% of patients. Verbal abilities and attention span were most frequently affected. Impairment was not correlated with neurological disability or MRI disease burden. Conclusion: Prevalent cognitive impairment already exists at onset of MS.

Multicentre European study of thalamic stimulation in essential tremor: a six year follow up.

Abstract: Background: Thalamic stimulation is an efficient treatment for disabling essential tremor, as previously shown, but follow up has mostly been short term. Objectives: To see whether good results can be maintained in the longer term. Methods: 37 patients with essential tremor had implantation of a thalamic stimulator, either unilaterally or bilaterally. The results at one year have been reported earlier. After six years, 19 patients were available for follow up. The main instrument for evaluation was the essential tremor rating scale. The patients were examined with pulse generators turned on and off. Results: In the majority of patients, the very good results with stimulation seen at one year were maintained after a mean of 6.5 years. The reduction in tremor scores and improvement in activities of daily living were highly significant compared with baseline and with the stimulation turned off. There were few serious adverse events. Minor side effects related to stimulation were common. Few device related complications were observed and most could be resolved. Conclusions: Good reduction in tremor can be maintained for more than six years in the majority of these severely disabled patients. Thalamic stimulation can be recommended in essential tremor where there is insufficient response to drug treatment. Surgical procedures and follow up should be concentrated in relatively few centres, which will thereby acquire a high degree of expertise.

Performance on the dementia rating scale in Parkinson’s disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer’s disease

Abstract: Background: The relation between dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) is unknown. Objectives: To compare the cognitive profiles of patients with DLB and PDD, and compare those with the performance of patients with a subcortical dementia (progressive supranuclear palsy) and a cortical dementia (Alzheimer’s disease). Design: Survey of cognitive features. Setting: General community in Rogaland county, Norway, and a university dementia and movement disorder research centre in the USA. Patients: 60 patients with DLB, 35 with PDD, 49 with progressive supranuclear palsy, and 29 with Alzheimer’s disease, diagnosed by either standardised clinical procedures and criteria (all PDD and Alzheimer cases and 76% of cases of progressive supranuclear palsy), or necropsy (all DLB cases and 24% of cases of progressive supranuclear palsy). Level of dementia severity was matched using the total score on the dementia rating scale adjusted for age and education. Main outcome measures: Dementia rating scale subscores corrected for age. Results: No significant differences between the dementia rating scale subscores in the PDD and DLB groups were found in the severely demented patients; in patients with mild to moderate dementia the conceptualisation subscore was higher in PDD than in DLB (p = 0.03). Compared with Alzheimer’s disease, PDD and DLB had higher memory subscores (p < 0.001) but lower initiation and perseveration (p = 0.008 and p=0.021) and construction subscores (p = 0.009 and p = 0.001). DLB patients had a lower conceptualisation subscore (p = 0.004). Compared with progressive supranuclear palsy, PDD and DLB patients had lower memory subscores (p < 0.001). Conclusions: The cognitive profiles of patients with DLB and PDD were similar, but they differed from those of patients with Alzheimer’s disease and progressive supranuclear palsy. The cognitive pattern in DLB and PDD probably reflects the superimposition of subcortical deficits upon deficits typically associated with Alzheimer’s disease.

The topography of metabolic deficits in posterior cortical atrophy (the visual variant of Alzheimer’s disease) with FDG-PET

Abstract: Background:The term "posterior cortical atrophy" (PCA) refers to a clinical syndrome in which higher order visual processing is disrupted owing to a neurodegenerative disorder, the most commonly associated pathology being Alzheimer's disease. Objective:To map the topography of hypometabolic brain regions in a group of subjects with PCA who had undergone detailed neuropsychological characterisation. Methods:Resting cerebral metabolism was measured with (18F)fluorodeoxyglucose-positron emission tomography (FDG-PET) in patients with PCA (n = 6), typical Alzheimer's disease (n = 10), and healthy controls (n = 10). The data were analysed using statistical parametric mapping (SPM99) and region of interest techniques. Results:Clinically, the PCA subjects showed predominant visuospatial deficits (including features of Balint's syndrome) consistent with damage to the dorsal stream of visual processing. Compared with the controls, the PCA group showed marked glucose hypometabolism primarily affecting the posterior cerebral hemispheres (right worse than left). In addition, the PCA group showed two symmetrical areas of hypometabolism in the region of the frontal eye fields. Compared with typical Alzheimer's disease, the PCA group had selective hypometabolism in the occipito-parietal region (right much worse than left). Conclusions:The neuropsychological and PET findings are consistent with damage predominantly to the dorsal stream of visual processing. Frontal eye field hypometabolism secondary to loss of input from the occipito-parietal region may be the mechanism for the ocular apraxia seen in Balint's syndrome.

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: evaluation of active electrode contacts.

Abstract: Background: The subthalamic nucleus is the preferred target for deep brain stimulation in patients with advanced Parkinson’s disease. The site of permanent stimulation is the subject of ongoing debate, as stimulation both within and adjacent to the subthalamic nucleus may be effective. Objective: To assess the position of active electrode contacts in relation to the dorsal margin of the subthalamic nucleus as determined by intraoperative microrecordings and magnetic resonance imaging (MRI). Methods: In 25 patients suffering from severe levodopa sensitive parkinsonism, deep brain stimulating electrodes (n = 49) were implanted following mapping of the subthalamic nucleus by microrecording and microstimulation along five parallel tracks. Postoperative stereotactic radiography and fusion of pre- and postoperative MRI studies were used to determine the stereotactic position relative to the midcommissural point of the most effective electrode contacts selected for permanent stimulation (n = 49). Intraoperative microrecordings were analysed retrospectively to define the dorsal margin of the subthalamic nucleus. In cases where the dorsal margin could be defined in at least three microrecording tracks (n = 37) it was correlated with the position of the active contact using an algorithm developed for direct three dimensional comparisons. Results: Stimulation of the subthalamic nucleus resulted in marked improvement in levodopa sensitive parkinsonian symptoms and levodopa induced dyskinesias, with significant improvement in UPDRS III scores. In several instances, projection of the electrode artefacts onto the T2 weighted MRI visualised subthalamic nucleus of individual patients suggested that the electrodes had passed through the subthalamic nucleus. When the actual position of active electrode contacts (n = 35) was correlated with the dorsal margin of the subthalamic nucleus as defined neurophysiologically, most contacts were located either in proximity (± 1.0 mm) to the dorsal border of the subthalamic nucleus (32.4%) or further dorsal within the subthalamic region (37.8%). The other active contacts (29.7%) were detected within the dorsal (sensorimotor) subthalamic nucleus. The average position of all active contacts (n = 49) was 12.8 mm (± 1.0) lateral, 1.9 mm (± 1.4) posterior, and 1.6 mm (± 2.1) ventral to the midcommissural point. Conclusions: Subthalamic nucleus stimulation appears to be most effective in the border area between the upper subthalamic nucleus (sensorimotor part) and the subthalamic area containing the zona incerta, fields of Forel, and subthalamic nucleus projections.

Dementia with Lewy bodies according to the consensus criteria in a general population aged 75 years or older

Abstract: Objective: To estimate the prevalence of dementia with Lewy bodies (DLB) according to the consensus criteria in a general population aged 75 years or older. Methods: The “Kuopio 75+ study” is a population based health survey focused on the clinical epidemiology of dementia and functional capacity among elderly subjects aged 75 years or older. On 1 January 1998, a random sample of 700 subjects was drawn from a total population born before 1 January 1923, living in the city of Kuopio, northeast Finland (n = 4518). The study subjects underwent a structured interview and clinical examination. Results: 601 elderly subjects (86% of the random sample) were examined. A dementia disorder was diagnosed in 137—a prevalence of 22.8% (95% confidence interval 19.4% to 26.2%). The prevalence of DLB was 5.0% (3.2% to 6.7%), comprising 22% of all demented subjects. Probable DLB was diagnosed in 20 subjects (3.3% (1.9% to 4.8%)), and possible DLB in 10 (1.7% (0.6% to 2.7%)). The prevalence of Alzheimer’s disease was 10.6% (47% of all demented subjects), of vascular dementia, 5.3% (23%), and of other types of dementing disorders, 1.8% (8%). Conclusions: In a general population aged 75 years and older, the prevalence of a disorder fulfilling the diagnostic criteria of DLB is half that of Alzheimer’s disease and the same as for vascular dementia.

Brain white matter lesions detected by magnetic resosnance imaging are associated with balance and gait speed

Abstract: Objective: To investigate the relations between premorbid and current mental ability, mood, and white matter signal abnormalities detected by T2 weighted brain magnetic resonance imaging (MRI) and impairment of balance and mobility in older adults. Methods: 97 subjects from the Aberdeen 1921 birth cohort underwent brain MRI, evaluation of balance, and measurement of gait speed. White matter hyperintensities detected on T2 weighted MRI scans were rated by three independent raters on three variables: white matter lesions; periventricular lesions; and brain stem lesions. Results: Decreased gait speed was correlated with impaired visual acuity (p = 0.020), shorter stature (p = 0.008), a lower childhood IQ (p = 0.030), a lower current Raven’s progressive matrices score (Raven score) (p Conclusions: In this cohort, white matter lesions, periventricular lesions, and brain stem lesions were associated with impaired balance. Current mental ability was strongly related to gait speed. There appears to be a concordance between motor skills and intellect in old age, which is degraded by white matter disease.

Longitudinal study of cognitive dysfunction in multiple sclerosis: neuropsychological, neuroradiological, and neurophysiological findings

Abstract: Objective: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. Methods: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. Results: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. Conclusions: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.

Evidence of underdiagnosis of myasthenia gravis in older people.

Abstract: Background: Myasthenia gravis is a potentially serious but treatable muscle disease caused by autoantibodies directed at the acetylcholine receptor (AChR) on the postsynaptic membrane of the neuromuscular junction. There is anecdotal evidence that the diagnosis is sometimes missed in older patients. Objective: To examine the incidence and age distribution of positive AChR antibodies in samples referred to diagnostic laboratories in the UK, and the prevalence of positive AChR antibodies in samples from a cohort of older individuals. Methods: Positive AChR antibody tests were identified from all UK centres registered for the assay with the European quality assurance scheme (EQAS) during 1997–99, and the age and sex specific incidence was calculated, based on the UK population. The prevalence of AChR antibodies in sera from a sample of 2000 individuals aged > 60 years was determined. Results: 3183 individuals had positive AChR antibody tests on routine screening during the years 1997 to 1999 in the UK, giving an annual incidence of 1.8/100 000. In both sexes, the age specific incidence rose steeply between the ages of 45 and 74, reaching 9.9/100 000 in men, and then fell, with a sharp decline above the age of 80. In the prevalence study, whereas only one serum from individuals aged 60–74 years was positive for AChR antibodies (0.12%), sera from eight individuals aged > 75 years were positive (0.7%). Only one had a previous clinical diagnosis of myasthenia gravis but four others had histories of stroke or transient ischaemic attacks. Conclusions: The sharp fall in the incidence of clinically recognised myasthenia gravis in people over 80 years of age in our national AChR antibody incidence study, and the high prevalence of previously unrecognised positive AChR antibodies in those > 75 years old, suggest that myasthenia gravis may be substantially underdiagnosed in older people.

Dietary treatment of gluten ataxia

Abstract: Background: Gluten ataxia is an immune mediated disease, part of the spectrum of gluten sensitivity, and accounts for up to 40% of cases of idiopathic sporadic ataxia. No systematic study of the effect of gluten-free diet on gluten ataxia has ever been undertaken. Objective: To study the effect of gluten-free diet on patients presenting with ataxia caused by gluten sensitivity. Methods: 43 patients with gluten ataxia were studied. All were offered a gluten-free diet and monitored every six months. All patients underwent a battery of tests to assess their ataxia at baseline and after one year on diet. Twenty six patients (treatment group) adhered to the gluten-free diet and had evidence of elimination of antigliadin antibodies by one year. Fourteen patients refused the diet (control group). Three patients had persistently raised antigliadin antibodies despite adherence to the diet and were therefore excluded from the analysis. Results: After one year there was improvement in ataxia reflected in all of the ataxia tests in the treatment group. This was significant when compared with the control group. The diet associated improvement was apparent irrespective of the presence of an enteropathy. Conclusions: Gluten ataxia responds to a strict gluten-free diet even in the absence of an enteropathy. The diagnosis of gluten ataxia is vital as it is one of the very few treatable causes of sporadic ataxia.

The management of motor neurone disease

Abstract: The management of motor neurone disease (MND) has evolved rapidly over the last two decades. Although still incurable, MND is not untreatable. From an attitude of nihilism, treatments and interventions that prolong survival have been developed. These treatments do not, however, arrest progression or reverse weakness. They raise difficult practical and ethical questions about quality of life, choice, and end of life decisions. Coordinated multidisciplinary care is the cornerstone of management and evidence supporting this approach, and for symptomatic treatment, is growing.1–3 Hospital based, community rehabilitation teams and palliative care teams can work effectively together, shifting emphasis and changing roles as the needs of the individuals affected by MND evolve. In the UK, MND care centres and regional networks of multidisciplinary teams are being established. Similar networks of MND centres exist in many other European countries and in North America. Here, we review current practice in relation to diagnosis, genetic counselling, the relief of common symptoms, multidisciplinary care, the place of gastrostomy and assisted ventilation, the use of riluzole, and end of life issues. View this table: Table 1 Clinical syndromes of MND (ALS—amyotrophic lateral sclerosis) and related disorders (modified from Kato et al , 2003*, with permission) The average delay from onset of symptoms to diagnosis is about 14 months, about one third of expected survival. Occasionally, survival following diagnosis may be less than six months. The patient may already suspect the diagnosis …

Diffusion tensor imaging detects corticospinal tract involvement at multiple levels in amyotrophic lateral sclerosis

Abstract: Background: Histopathological studies of amyotrophic lateral sclerosis (ALS) are of end stage disease. Diffusion tensor imaging (DTI) provides the opportunity to investigate indirectly corticospinal tract pathology of ALS in vivo. Methods: DTI was used to study the water diffusion characteristics of the corticospinal tracts in 21 patients with ALS and 14 normal controls. The authors measured the fractional anisotropy (FA) and mean diffusivity (MD) along the pyramidal tracts from the internal capsules down to the pyramids. A mixed model regression analysis was used to compare FA and MD between the ALS and control groups. Results: FA showed a downward linear trend from the cerebral peduncles to the pyramids and was lower in the ALS group than controls at multiple levels of the corticospinal tract. At the internal capsules, FA was higher on the right. MD showed an upward trend, progressing caudally from the internal capsules to the pyramids. MD was higher at the level of the internal capsule in the ALS group, but caudally this difference was not maintained. No correlations were found between clinical markers of disability and water diffusion indices. Conclusions: These findings provide insights into the pathological processes of ALS. Differences in diffusion characteristics at different anatomical levels may relate to underlying tract architecture or the distribution of pathological damage in ALS. Further development may permit monitoring of progression and treatment of disease.

Cognitive and behavioural effects of chronic stimulation of the subthalamic nucleus in patients with Parkinson’s disease

Abstract: Objective: To investigate cognitive and behavioural effects of bilateral lead implants for high frequency stimulation (HFS) of the subthalamic nucleus in patients with Parkinson's disease; and to discriminate between HFS and the effects of surgical intervention on cognitive function by carrying out postoperative cognitive assessments with the stimulators turned on or off. Methods: Motor, cognitive, behavioural, and functional assessments were undertaken in 20 patients with Parkinson's disease before implantation and then at three, six, and 12 months afterwards. Nine patients were also examined 18 months after surgery. Postoperative cognitive assessments were carried out with stimulators turned off at three and 18 months, and turned on at six and 12 months. Results: Cognitive assessment showed a significant postoperative decline in performance on tasks of letter verbal fluency (across all postoperative assessments, but more pronounced at three months) and episodic verbal memory (only at three months, with stimulators off). At three, six, and 12 months after surgery, there was a significant improvement in the mini-mental state examination and in a task of executive function (modified Wisconsin card sorting test). On all postoperative assessments, there was an improvement in parkinsonian motor symptoms, quality of life, and activities of daily living while off antiparkinsonian drugs. A significant postoperative decrease in depressive and anxiety symptoms was observed across all assessments. Similar results were seen in the subgroup of nine patients with an 18 month follow up. Following implantation, three patients developed transient manic symptoms and one showed persistent psychic akinesia. Conclusions: Bilateral HFS of the subthalamic nucleus is a relatively safe procedure with respect to long term cognitive and behavioural morbidity, although individual variability in postoperative cognitive and behavioural outcome invites caution. Stimulation of the subthalamic nucleus does not per se appear to impair cognitive performance in patients with Parkinson's disease and may alleviate the postpoperative decline in verbal fluency.

Radiofrequency neurotomy for the treatment of third occipital headache

Abstract: Objective: To evaluate the efficacy of a revised technique of percutaneous radiofrequency neurotomy for third occipital headache. Methods: The revisions included using a large gauge electrode, ensuring minimum separation between the three electrode placements, and holding the electrode in place by hand. The revised technique was used to treat 51 nerves in 49 patients diagnosed as suffering from third occipital headache on the basis of controlled diagnostic blocks of the third occipital nerve. The criteria for successful outcome were complete relief of pain for at least 90 days associated with restoration of normal activities of daily living, and no use of drug treatment for the headache. Results: Of the 49 patients, 43 (88%) achieved a successful outcome. The median duration of relief in these patients was 297 days, with eight patients continuing to have ongoing relief. Fourteen patients underwent a repeat neurotomy to reinstate relief, with 12 (86%) achieving a successful outcome. The median duration of relief in these patients was 217 days, with six patients having ongoing relief. Side effects of the procedure were consistent with coagulation of the third occipital nerve and consisted of slight ataxia, numbness, and temporary dysaesthesia. No side effects required intervention, and they were tolerated by the patients in exchange for the relief of headache. Conclusions: Use of the revised procedure greatly improved the rather low success rate previously encountered with third occipital neurotomy. Although the relief of headache is limited in duration, it is profound and can be reinstated by repeat neurotomy. No other form of treatment has been validated for this common form of headache.