Showing papers in "Journal of Neurology, Neurosurgery, and Psychiatry in 2000"

What contributes to quality of life in patients with Parkinson's disease?

Abstract: Objective—To identify the factors that determine quality of life (QoL) in patients with idiopathic Parkinson’s disease in a population based sample. Quality of life (QoL) is increasingly recognised as a critical measure in health care as it incorporates the patients’ own perspective of their health. Methods—All patients with Parkinson’s disease seen in a population based study on the prevalence of parkinsonism were asked to complete a disease-specific QoL questionnaire (PDQ-39) and the Beck depression inventory. A structured questionnaire interview and a complete neurological examination, including the Hoehn and Yahr scale, the Schwab and England disability scale, the motor part of the unified Parkinson’s disease rating scale (UPDRS part III), and the mini mental state examination were performed by a neurologist on the same day. Results—The response rate was 78%. The factor most closely associated with QoL was the presence of depression, but disability, as measured by the Schwab and England scale, postural instability, and cognitive impairment additionally contributed to poor QoL. Although the UPDRS part III correlated significantly with QoL scores, it did not contribute substantially to predicting their variance once depression, disability, and postural instability had been taken into account. In addition, patients with akinetic rigid Parkinson’s disease had worse QoL scores than those with tremor dominant disease, mainly due to impairment of axial features. Conclusion—Depression, disability, postural instability, and cognitive impairment have the greatest influence on QoL in Parkinson’s disease. The improvement of these features should therefore become an important target in the treatment of the disease. (J Neurol Neurosurg Psychiatry 2000;69:308‐312)

Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer's disease?

Abstract: OBJECTIVES To investigate the prevalence of changes in mood, personality, and behaviour in frontotemporal dementia (FTD) and Alzheimer9s disease (AD) and hence, which features reliably distinguish between them. To establish whether the frontal and temporal variants of FTD are characterised by different behavioural changes. METHODS A questionnaire was designed to assess a wide range of neuropsychiatric changes; it incorporated features reported in previous studies of FTD and components of the neuropsychiatric inventory. 1 This was completed by 37 carers of patients with Alzheimer9s disease (AD) and 33 patients with frontotemporal dementia (FTD), comprising 20 with temporal variant FTD (tv FTD) or semantic dementia and 13 with frontal variant FTD (fv FTD). An exploratory principal components factor analysis and discriminant function analysis was applied. RESULTS Factor analysis showed four robust and meaningful symptom clusters: factor 1—stereotypic and eating behaviour; factor 2—executive dysfunction and self care; factor 3—mood changes; factor 4—loss of social awareness. Only stereotypic and altered eating behaviour and loss of social awareness reliably differentiated AD from FTD with no effect of disease severity. By contrast, executive dysfunction, poor self care, and restlessness showed a significant effect of disease severity only, with the more impaired patients scoring more highly. Changes in mood were found to be equally prevalent in the three patient groups. Analysis of individual symptoms showed increased rates of mental rigidity and depression in the patients with semantic dementia compared with those with fv FTD. Conversely, the latter group showed greater disinhibition. Discriminant function analysis correctly classified 71.4% overall and 86.5% of the patients with AD. CONCLUSIONS This questionnaire disclosed striking differences between patients with FTD and AD, but only stereotypic behaviour, changes in eating preference, disinhibition, and features of poor social awareness reliably separated the groups. The patients with fv FTD and semantic dementia were behaviourally very similar, reflecting the involvement of a common network, the ventral frontal lobe, temporal pole, and amygdala. Dysexecutive symptoms and poor self care were found to be affected by the severity of the disease, reflecting perhaps spread to dorsolateral prefrontal areas relatively late in the course of both FTD and AD. This questionnaire may be of value in the diagnosis and the monitoring of therapies.

Hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies

Abstract: Hedonistic homeostatic dysregulation is a neuropsychological behavioural disorder associated with substance misuse and addiction. The disorder has been recognised as a consequence of dopamine replacement therapy (DRT) in 15 patients with Parkinson's disease. The syndrome typically develops in male patients with early onset Parkinson's disease, and can occur with orally and subcutaneously administered DRT. These patients take increasing quantities of their DRT, despite increasingly severe drug induced dyskinesias, and may develop a cyclical mood disorder with hypomania or manic psychosis. There is impairment of social and occupational functioning. Tolerance develops to mood elevating effects of DRT and a negative affective withdrawal state occurs if the drugs are withdrawn or doses decreased. The clinical features and guidelines for managing this syndrome are discussed. A set of diagnostic criteria for further investigating this condition is proposed.

Homocysteine, folate, methylation, and monoamine metabolism in depression

Abstract: OBJECTIVES—Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, difficulties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression. METHODS—In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes. RESULTS—Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls. CONCLUSIONS—Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement.

Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging

Abstract: A novel MRI method-diffusion tensor imaging-was used to compare the integrity of several white matter fibre tracts in patients with probable Alzheimer's disease. Relative to normal controls, patients with probable Alzheimer's disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum. By contrast, pyramidal tract integrity seemed unchanged. This novel finding is consistent with the clinical presentation of probable Alzheimer's disease, in which global cognitive decline is a more prominent feature than motor disturbance.

NEUROLOGICAL ASPECTS OF TROPICAL DISEASE: Japanese encephalitis

Abstract: Although considered by many in the west to be a rare and exotic infection, Japanese encephalitis is numerically one of the most important causes of viral encephalitis worldwide, with an estimated 50 000 cases and 15 000 deaths annually. 2 About one third of patients die, and half of the survivors have severe neuropshychiatric sequelae. Most of China, Southeast Asia, and the Indian subcontinent are aVected by the virus, which is spreading at an alarming rate. In these areas, wards full of children and young adults aZicted by Japanese encephalitis attest to its importance.

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study

Abstract: OBJECTIVES To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism. METHODS A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment. RESULTS In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6 months). CONCLUSIONS Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

Diffusion tensor imaging can detect and quantify corticospinal tract degeneration after stroke

Abstract: Diffusion tensor imaging (DTI) fully characterises water molecule mobility in vivo, allowing an exploration of fibre tract integrity and orientation in the human brain. Using DTI this study demonstrates reduced fibre coherence (anisotropy) associated with cerebral infarction and in the corticospinal tract remote from the lesion, in five patients 2 to 6 months after ischaemic stroke. The study highlights the potential of DTI to detect and monitor the structural degeneration of fibre pathways, which may provide a better understanding of the pattern of clinical evolution after stroke.

Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, Anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone

Abstract: OBJECTIVES To evaluate the effect of a combination of immunoglobulins (IVIg), cyclophosphamide (CTX), and methylprednisolone (MP) on the clinical course of patients with paraneoplastic neurological syndrome (PNS) and antineuronal antibodies (Abs). METHODS Seventeen patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) with anti-Hu Abs (n=10) or cerebellar degeneration (PCD) with anti-Yo Abs (n=7) received one to nine cycles (mean 3.5) of a combination of IVIg (0.5 g/kg/day from days 1 to 5), CTX (600 mg/m2 at day 1) and MP (1g/day from day 1 to 3). The Rankin scale (RS) was used to evaluate the response. A positive response was considered as either improvement or stabilisation in patients who were still ambulatory (RS⩽3) at the onset of treatment, whereas only improvement, and not stabilisation, was considered a therapeutic benefit in bedridden patients (RS⩾4). RESULTS Tolerance was good and no patient experienced grade 3/4 toxicity (World Health Organisation). Sixteen patients were evaluable for response. Of the seven patients with RS⩾4, none improved. Of the nine patients with RS⩽3, none improved but three (two SN and one PCD) stabilised for 4, 35, and 16 months. CONCLUSIONS This study suggests that vigorous immunosuppressive treatment is not useful in severely disabled PNS patients with antineuronal Abs. In a minority of patients (mainly with SN) who are not severely disabled at the onset of treatment, a transient stabilisation is possible and deserves further evaluation.

Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study

Abstract: OBJECTIVES—Diffusion tensor imaging (DTI), a technique capable of examining water diffusion in different tissues and the organisation of white matter tracts, was used to investigate the neuropathology of the corpus callosum in vivo in patients with schizophrenia. METHODS—Diffusion tensor imaging was performed in 20 schizophrenic patients and 25 healthy controls. Two complementary measures, mean diffusivity and fractional anisotropy, which are considered to be sensitive indices of axonal integrity, were obtained from regions of interest in the genu (anterior) and splenium (posterior) of the corpus callosum. RESULTS—Mean diffusivity was significantly increased and fractional anisotropy significantly reduced in the splenium but not the genu of the corpus callosum in the schizophrenic group compared with controls. There were no significant sex differences in the DTI measures for either the schizophrenic or control group. Clinical variables such as age, duration of illness, dose of antipsychotic medication, and schizophrenic symptoms did not predict the DTI changes in the schizophrenic patients. CONCLUSIONS—The presence of DTI changes in the splenium but not the genu of the corpus callosum suggests that there may be a focal disruption of commisural connectivity in schizophrenia. However, these findings do not exclude the possibility of abnormalities in other areas of the corpus callosum or other regions of white matter and further research using different methods of analysis may enable us to clarify this. Diffusion tensor imaging is a valuable tool in investigating the structure of white matter in schizophrenia.

Impact of botulinum toxin type A on disability and carer burden due to arm spasticity after stroke: a randomised double blind placebo controlled trial

Abstract: OBJECTIVES—After stroke, abnormal arm posture due to spasticity in a functionally useless arm may interfere with self care tasks. In these patients botulinum toxin treatment presents an opportunity to reduce disability. The purpose was to investigate whether reduction in spasticity after botulinum toxin treatment translates into reduction in disability and carer burden. METHODS—Forty patients with stroke with spasticity in a functionally useless arm (median duration 3.1 years) were randomised to receive intramuscular botulinum toxin type A (BT-A; Dysport) (n=20) or placebo (n=20) in a total dose of 1000 MU divided between elbow, wrist, and finger flexors. Spasticity (using the modified Ashworth scale), muscle power, joint movement, and pain were assessed. Disability and carer burden were measured using an eight item and a four item scale respectively. Two baseline and three post-treatment assessments (weeks 2, 6, and 12) were made. Concurrent treatments as far as possible remained unchanged and not optimised. RESULTS—Disability improved at week 6 with BT-A compared with placebo. This effect, present at week 2, wore off by week 12. Reduction in carer burden was seen at week 6 with BT-A and continued for at least 12 weeks. Forearm flexor spasticity was reduced with BT-A up to 12 weeks after treatment. Although significant improvement in elbow flexor spasticity was seen at week 2 with BT-A compared with placebo, this effect was not evident at weeks 6 and 12. Arm pain was not improved after BT-A. Grip strength was reduced with BT-A. No serious BT-A related adverse effects were reported. CONCLUSION—BT-A is useful for treating patients with stroke who have self care difficulties due to arm spasticity. The decision to treat should also include relief of carer burden. As muscle weakness may occur, its potential impact on functional activities must be assessed before intervention.

The EQ-5D—a generic quality of life measure—is a useful instrument to measure quality of life in patients with Parkinson's disease

Abstract: Objective—To test the feasibility and validity of the EQ-5D (a widely used generic (disease non-specific) quality of life (QoL) instrument which allows comparisons between diVerent patient groups and the general population) to assess QoL in patients with Parkinson’s disease Methods—All 124 patients with Parkinson’s disease seen in a community based study on the prevalence of parkinsonism were asked to complete a QoL battery comprising the EQ-5D, the medical outcome study short form (SF-36), the PDQ39, a disease specific instrument to assess QoL in PD, and the Beck depression inventory A structured questionnaire interview and a complete neurological examination including the Hoehn and Yahr stage of illness scale, the Schwab and England disability scale, the motor section of the unified Parkinson’s disease rating scale (UPDRS), and the mini mental state examination (MMSE) were performed on the same day Results—The response rate was 78% and the completion rate of the EQ-5D among responders was 96% The EQ-5D summary index correlated strongly with the PDQ-39 (r=˛075, p<00001) as well as the physical score of the SF-36 (r=061, p<00001) There was a significant correlation of the EQ-5D summary index with disease severity, as measured by the Hoehn and Yahr stage of illness, the Schwab and England disability scale, the motor section of the UPDRS, and the depression score The EQ-5D summary index also distinguished between patients with and without depression, falls, postural instability, cognitive impairment hallucinations, and those with deterioration of health over the previous year Conclusion—The EQ-5D is a feasible and valid instrument to measure QoL in Parkinson’s disease and reflects the severity and complications of the disease (J Neurol Neurosurg Psychiatry 2000;69:67‐73)

Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART)

Abstract: OBJECTIVE To determine the change of incidence and prevalence of neurological disorders caused by the human immunodeficiency virus (HIV) and opportunistic infections in HIV positive patients under treatment since the introduction of highly active antiretroviral therapy (HAART). METHODS The data of all HIV infected patients were retrospectively analysed, who were examined in the HIV outpatients clinic of the neurological department of the University Clinic Essen between 1995 and 1998 (n=563, total number of visits=735). Data from identified patients were divided into two groups according to the time of examination from 1995 to 1996 (334 visits) and from 1997 to 1998 (401 visits). The incidence and prevalence of neurological disorders were statistically compared between both time intervals. RESULTS Significantly more patients received HAART in 1997–8 (p CONCLUSION The prevalence of the most frequent HIV associated neurological disorders and incidence of toxoplasma encephalitis decreased since the introduction of HAART. This may be due to the improvement of immunostatus by HAART as demonstrated by the higher CD4+ cell count in the later time interval. Direct antiretroviral effects within the nervous system may be considered causative as well. The prevalence and incidence of HIV associated neurological disorders and opportunistic CNS infections decreased after introduction of HAART.

Do medically unexplained symptoms matter? A prospective cohort study of 300 new referrals to neurology outpatient clinics

Abstract: OBJECTIVES—To determine (a) the proportion of patients referred to general neurology outpatient clinics whose symptoms are medically unexplained; (b) why they were referred; (c) health status and emotional disorder in this group compared with patients whose symptoms are explained by "organic" neurological disease. METHODS—The prospective cohort study with case note follow up at 6 months was carried out in the regional neurology service in Lothian, Scotland with 300 newly referred outpatients. Neurologists rated the degree to which patients' symptoms were explained by organic disease (organicity), GPs' reasons for referral, health status (SF-36), anxiety, and depressive disorders (PRIME-MD), RESULTS—Of 300 new patients 11% (95% confidence interval (95% CI) 7%-14%) had symptoms that were rated as "not at all explained" by organic disease, 19% (15% to 23%) "somewhat explained", 27% (22% to 32%) "largely explained", and 43% (37% to 49%) "completely explained" by organic disease. Reason for referral was not associated with "organicity". Comparison of these groups showed that although physical function was similar, the median number of physical symptoms and pain were greater in patients with lower organicity ratings (p<0.0005, p<0.0005). Depressive and anxiety disorders were more common in patients with symptoms of lower organicity (70% of patients in the not at all group had an anxiety or depressive disorder compared with 32% in the completely explained group (p<0.0005). CONCLUSION—One third of new referrals to general neurology clinics have symptoms that are poorly explained by identifiable organic disease. These patients were disabled and distressed. They deserve more attention.

Impaired cognitive performance in drug free users of recreational ecstasy (MDMA)

Abstract: Objectives—Ecstasy(3,4-methylenedioxymethamphetamine (MDMA) and related congerers: MDA, MDEA) is the name given to a group of popular recreational drugs. Animal data raise concern about neurotoxic eVects of high doses of ecstasy on central serotonergic systems. The threshold dose for neurotoxicity in humans is not clear and serotonin is involved in several functions including cognition. The purpose of this study was to investigate cognitive performance in a group of typical recreational ecstasy users. Methods—A comprehensive cognitive test battery was administered to 28 abstinent ecstasy users with concomitant use of cannabis only and to two equally sized matched groups of cannabis users and non-users. The sample consisted of ecstasy users with a typical recreational use pattern and did not include very heavy users. Results—Ecstasy users were unimpaired in simple tests of attention (alertness). However, they performed worse than one or both control groups in the more complex tests of attention, in memory and learning tasks, and in tasks reflecting aspects of general intelligence. Heavier ecstasy and heavier cannabis use were associated with poorer performance in the group of ecstasy users. By contrast, the cannabis users did not diVer significantly in their performance from the non-users. Conclusions—The present data raise concern that use of ecstasy possibly in conjunction with cannabis may lead to cognitive decline in otherwise healthy young people. Although the nature of the emerging cognitive disturbance is not yet clear, an impairment of working memory might be the common denominator underlying or contributing to declines of performance in various tasks. The cognitive disturbance is likely to be related to the well recognised neurotoxic potential of ecstasy. The data suggest that even typical recreational doses of ecstasy are suYcient to cause neurotoxicity in humans. (J Neurol Neurosurg Psychiatry 2000;68:719‐725)

Sudden unexpected death in epilepsy: a series of witnessed deaths

Abstract: OBJECTIVES Sudden unexpected death in epilepsy (SUDEP) represents a significant category of mortality in the population with chronic epilepsy. A consistent feature is that most of these deaths are unwitnessed. The aim was to identify witnessed deaths, examine the circumstances, and relate these findings to the proposed mechanisms for SUDEP. METHODS During the course of case ascertainment for a control study on SUDEP, witnessed deaths were identified and the circumstances examined in detail. Cases were notified by coroners, neurologists, and bereaved families. The findings were related to the proposed mechanisms for SUDEP which include central and obstructive apnoea and cardiac arrhythmia. RESULTS One hundred and thirty five SUDEP cases have been identified to date, of which 15 were witnessed deaths. Twelve deaths were associated with convulsive seizures, one collapse occurred 5 minutes after a generalised seizure, another collapse occurred after an aura and one patient died while in a probable post ictal state. Witnesses reported that 12 of the 15 cases experienced respiratory difficulty. CONCLUSIONS Most sudden epilepsy deaths are unwitnessed. Where witnessed most occur in association with a seizure and respiratory compromise is a prominent feature. Positioning or stimulation of respiration may be important in the prevention of these deaths.

Microvascular decompression for trigeminal neuralgia: comments on a series of 250 cases, including 10 patients with multiple sclerosis

Abstract: OBJECTIVE—To examine surgical findings and results of microvascular decompression (MVD) for trigeminal neuralgia (TN), including patients with multiple sclerosis, to bring new insight about the role of microvascular compression in the pathogenesis of the disorder and the role of MVD in its treatment. METHODS—Between 1990 and 1998, 250 patients affected by trigeminal neuralgia underwent MVD in the Department of Neurosurgery of the "Istituto Nazionale Neurologico C Besta" in Milan. Limiting the review to the period 1991-6, to exclude the "learning period" (the first 50 cases) and patients with less than 1 year follow up, surgical findings and results were critically analysed in 148 consecutive cases, including 10 patients with multiple sclerosis. RESULTS—Vascular compression of the trigeminal nerve was found in all cases. The recurrence rate was 15.3% (follow up 1-7 years, mean 38 months). In five of 10 patients with multiple sclerosis an excellent result was achieved (follow up 12-39 months, mean 24months). Patients with TN for more than 84 months did significantly worse than those with a shorter history (p<0.05). There was no mortality and most complications occurred in the learning period. Surgical complications were not related to age of the patients. CONCLUSIONS—Aetiopathogenesis of trigeminal neuralgia remains a mystery. These findings suggest a common neuromodulatory role of microvascular compression in both patients with or without multiple sclerosis rather than a direct causal role. MVD was found to be a safe and effective procedure to relieve typical TN in patients of all ages. It should be proposed as first choice surgery to all patients affected by TN, even in selected cases with multiple sclerosis, to give them the opportunity of pain relief without sensory deficits.

Health related quality of life in Parkinson's disease: a prospective longitudinal study

Abstract: OBJECTIVES—To examine the change over time in health related quality of life (HRQL) in a community based cohort of patients with Parkinson's disease. METHODS—One hundred and eleven patients were evaluated for HRQL in 1993 and then again in a follow up study 4 years later. The patients included in the study in 1993 were derived from a prevalence study of patients with Parkinson's disease in the county of Rogaland, Norway. The HRQL was measured by the Nottingham health profile (NHP). At both evaluations clinical and demographic variables were determined during semistructured interviews and by clinical examinations by a neurologist. RESULTS—During the 4 year follow up period there was a significant increase in NHP scores, reflecting a decreased HRQL, in the dimensions of physical mobility, emotional reactions, pain, and social isolation. In the same time period mean total NHP score increased from 120.0(SD 102.6) to 176.0 (SD 119.4) (p<0.01). There were no clinical or demographic factors found in 1993 that identified patients at higher risk for developing decreased HRQL. Increased UPDRS score (unified Parkinson's disease rating scale) and Hoehn and Yahr stage during the 4 year study period correlated with increased NHP scores. Even though there was no increase in depressive symptoms or self reported insomnia, these symptoms, together with lower Schwab and England score, were the most important factors for a poor HRQL in 1997. CONCLUSIONS—Parkinson's disease has a substantial impact on HRQL. Despite modern care, we found a significantly increased distress during the 4 year follow up period. Increased parkinsonism, measured by UPDRS and Hoehn and Yahr stage, correlated with increased stress, not only in the dimension of physical mobility, but also in the areas of pain, social isolation, and emotional reactions. In addition to the clinical examination, HRQL scoring provides valuable information on the total health burden of Parkinson's disease in both cross sectional and longitudinal evaluations, and contributes to a more comprehensive picture of the total disease impact.

Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in the Netherlands

Abstract: OBJECTIVE The aim of this study was to investigate prospectively in an unselected series of patients with an aneurysmal subarachnoid haemorrhage what at present the complications are, what the outcome is, how many of these patients have “modern treatment”—that is, early obliteration of the aneurysm and treatment with calcium antagonists—what factors cause a delay in surgical or endovascular treatment, and what the estimated effect on outcome will be of improved treatment. METHODS A prospective, observational cohort study of all patients with aneurysmal subarachnoid haemorrhage in the hospitals of a specified region in The Netherlands. The condition on admission, diagnostic procedures, and treatments were recorded. If a patient had a clinical deterioration, the change in Glasgow coma score (GCS), the presence of focal neurological signs, the results of additional investigations, and the final diagnosed cause of the deterioration were recorded. Clinical outcome was assessed with the Glasgow outcome scale (GOS) at 3 month follow up. In patients with poor outcome at follow up, the cause was diagnosed. RESULTS Of the 110 patients, 47 (43%) had a poor outcome. Cerebral ischaemia, 31 patients (28%), was the most often occurring complication. Major causes of poor outcome were the effects of the initial haemorrhage and rebleeding in 34% and 30% of the patients with poor outcome respectively. Of all patients 102 (93%) were treated with calcium antagonists and 45 (41%) patients had early treatment to obliterate the aneurysm. The major causes of delay of treatment were a poor condition on admission or deterioration shortly after admission, in 31% and 23% respectively. CONCLUSIONS In two thirds of the patients with poor outcome the causes of poor outcome are the effects of the initial bleeding and rebleeding. Improved treatment of delayed or postoperative ischaemia will have only minor effects on the outcome of patients with subarachnoid haemorrhage.

What contributes to quality of life in patients with Parkinson's disease?

Abstract: The question posed by Schrag et al 1(this issue, pp 308–312) is fundamental, but can it be answered? Quality of life belongs to a family of terms which has an improbably wide range of applications, from “quality” as an object of philosophical contemplation2 to “QoL” as an economic variable.3 It must be borne in mind that measures such as the PDQ-39 and the SF-36 differ considerably in content. More detail on the parallelism between the PDQ-39 and two other measures would be helpful but the data seem to support the assumption, which is gaining ground in the literature, that such measures reflect a single underlying dimension. Scales …

Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation

Abstract: OBJECTIVE To assess the effects of high frequency stimulation of the subthalamic nucleus (STN) on axial symptoms occurring in advanced stages of Parkinson9s disease (PD). METHODS The efficacy of STN stimulation on total motor disability score (unified Parkinson9s disease rating scale (UPDRS) part III) were evaluated in 10 patients with severe Parkinson9s disease. The subscores were then studied separately for limb akinesia, rigidity, and tremor, which are known to respond to levodopa, and axial signs, including speech, neck rigidity, rising from a chair, posture, gait, and postural stability, which are known to respond less well to levodopa. Patients were clinically assessed in the “off” and “on” drug condition during a levodopa challenge test performed before surgical implantation of stimulation electrodes and repeated 6 months after surgery under continuous STN stimulation. A complementary score for axial symptoms from the “activities of daily living” (ADL)—that is, speech, swallowing, turning in bed, falling, walking, and freezing—was obtained from each patient9s questionnaire (UPDRS, part II). RESULTS Improvements in total motor disability score (62%), limb signs (62%), and axial signs (72%) obtained with STN stimulation were statistically comparable with those obtained with levodopa during the preoperative challenge (68%, 69%, and 59%, respectively). When levodopa and STN stimulation were combined there was a further improvement in total motor disability (80%) compared with preoperative levodopa administration. This consisted largely of an additional improvement in axial signs (84%) mainly for posture and postural stability, no further improvement in levodopa responsive signs being found. Axial symptoms from the ADL showed similar additional improvement when levodopa and STN stimulation were combined. CONCLUSION These findings suggest that bilateral STN stimulation improves most axial features of Parkinson9s disease and that a synergistic effect can be obtained when stimulation is used in conjunction with levodopa treatment.

Alzheimer's disease comorbidity in normal pressure hydrocephalus: prevalence and shunt response

Abstract: The clinical impact of Alzheimer's disease pathology at biopsy was investigated in 56 cognitively impaired patients undergoing shunt surgery for idiopathic normal pressure hydrocephalus (NPH). Cognition was measured by means of the global deterioration scale (GDS), the mini mental status examination (MMSE) and a battery of six psychometric tests. Gait was assessed using objective measurements of velocity and the ambulatory index (AI). The prevalence of cases exhibiting neuritic plaques (positive biopsies) increased in parallel with dementia severity from 18% for patients with GDS 3 to 75% for patients with GDS scores⩾6. Patients with positive biopsies were more cognitively impaired (higher GDS and lower MMSE scores) as well as more gait impaired (higher AI scores and slower velocities) than patients with negative biopsies. After surgery, gait velocity and AI scores improved significantly and to a comparable degree for patients with and without positive biopsies. Similar proportions of positive and negative biopsy patients also had improved gait as assessed by means of subjective video tape comparisons. There were no significant differences between the biopsy groups in the magnitude of postoperative psychometric change or in the proportion of cases exhibiting improved urinary control. Alzheimer's disease pathology is a common source of comorbidity in older patients with idiopathic NPH where it contributes to the clinical impairment associated with this disorder. For patients accurately diagnosed with NPH, concomitant Alzheimer's disease pathology does not strongly influence the clinical response to shunt surgery.

Hereditary spastic paraparesis: a review of new developments

Abstract: Hereditary spastic paraparesis (HSP) or the Strumpell-Lorrain syndrome is the name given to a heterogeneous group of inherited disorders in which the main clinical feature is progressive lower limb spasticity. Before the advent of molecular genetic studies into these disorders, several classifications had been proposed, based on the mode of inheritance, the age of onset of symptoms, and the presence or otherwise of additional clinical features. Families with autosomal dominant, autosomal recessive, and X-linked inheritance have been described.

What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson's disease?

Abstract: OBJECTIVES—Few studies have attempted to identify what premortem features best differentiate multiple system atrophy (MSA) from Parkinson`s disease (PD). These studies are limited by small sample size, clinical heterogeneity, or lack of postmortem validation. We evaluated the sensitivity and specificity of different clinical features in distinguishing pathologically established MSA from PD. METHODS—One hundred consecutive cases of pathologically confirmed PD and 38 cases of pathologically confirmed MSA in one Parkinson's disease brain bank were included. All cases had their clinical notes reviewed by one observer (AH). Clinical features were divided into two groups: those occurring up to 5 years after onset of disease and those occurring up to death. Statistical analysis comprised multivariate logistic regression analysis to choose and weight key variables for the optimum predictive model. RESULTS—The selected early features and their weightings were: autonomic features (2), poor initial levodopa response (2), early motor fluctuations (2), and initial rigidity (2). A cut off of 4 or more on the ROC curve resulted in a sensitivity of 87.1% and specificity of 70.5%. A better predictive model occurred if the following features up to death were included: poor response to levodopa (2), autonomic features (2), speech or bulbar dysfunction (3), absence of dementia (2), absence of levodopa induced confusion (4), and falls (4). The resulting ROC curve based on individual scores showed a best cut off score of at least 11 of 17 (sensitivity 90.3%, specificity 92.6%). CONCLUSIONS—Predictive models may help differentiate MSA and PD premortem. Hitherto poorly recognised features, suggestive of MSA, included preserved cognitive function and absence of psychiatric effects from antiparkinsonian medication. Diagnostic accuracy was higher in those models taking into account all clinical features occurring up to death. Further studies need to be based on new incident cohorts of parkinsonian patients with subsequent neuropathological evaluation.

Botulinum toxin (Dysport®) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double blind, placebo controlled, dose ranging study

Abstract: OBJECTIVE—To define a safe and effective dose of Dysport for treating hip adductor spasticity. METHODS—Patients with definite or probable multiple sclerosis, and disabling spasticity affecting the hip adductor muscles of both legs, were randomised to one of four treatment groups. Dysport (500, 1000, or 1500 Units), or placebo was administered by intramuscular injection to these muscles. Patients were assessed at entry, and 2, 4 (primary analysis time-point), 8, and 12 weeks post-treatment. RESULTS—A total of 74 patients were recruited. Treatment groups were generally well matched at entry. The primary efficacy variables—passive hip abduction and distance between the knees—improved for all groups. The improvement in distance between the knees for the 1500 Unit group was significantly greater than placebo (p=0.02). Spasm frequency was reduced in all groups, but muscle tone was reduced in the Dysport groups only. Pain was reduced in all groups, but improvements in hygiene scores were evident only in the 1000Unit and 1500 Unit groups. Duration of benefit was significantly longer than placebo for all Dysport groups (p<0.05). Adverse events were reported by 32/58 (55%) Dysport patients, and by 10/16 (63%) placebo patients. Compared with the two lower dose groups, twice as many adverse events were reported by the 1500 Unit group (2.7/patient). The incidence of muscle weakness was higher for the 1500 Unit group (36%) than for placebo (6%). The response to treatment was considered positive by two thirds of the patients in the 500 Unit group, and by about half the patients in the other groups. CONCLUSION—Dysport reduced the degree of hip adductor spasticity associated with multiple sclerosis, and this benefit was evident despite the concomitant use of oral antispasticity medication and analgesics. Although evidence for a dose response effect was not statistically significant, there was a clear trend towards greater efficacy and duration of effect with higher doses of Dysport. Dysport treatment was well tolerated, with no major side effects seen at doses up to 1500 Units. The optimal dose for hip adductor spasticity seems to be 500-1000 Units, divided between both legs.

Visual rating and volumetry of the medial temporal lobe on magnetic resonance imaging in dementia: a comparative study.

Abstract: OBJECTIVES It has been shown that atrophy of medial temporal lobe structures such as the hippocampus and entorhinal cortex shown on MRI may distinguish patients with Alzheimer9s disease from healthy controls. However, the diagnostic value of visual inspection and volumetry of medial temporal lobe atrophy (MTA) on MRI in a clinical setting is insufficiently known. METHODS Medial temporal lobe atrophy in 143 patients was visually rated from hard copies, using a 0–4 rating scale and a comparison was made with the volumes (cm 3 ) of the medial temporal lobe as estimated with volumetry, using a stereological method. All patients were recruited in an unselected way in a clinical setting in the centre for memory impairments at the Huddinge University Hospital. Patients with Alzheimer9s disease (n=41), patients with other dementias (vascular dementia, frontotemporal dementia, and unspecified dementia; n=36) as well as non-demented subjects (n=66) were included. Medial temporal atrophy and volumetry were evaluated as a diagnostic tool by performing logistic regression analysis including age, sex, and mini mental state examination (MMSE) score and calculating the sensitivity and specificity and percentage correct classification. RESULTS Visual and volumetric analysis yielded statistically significant differences between patients with Alzheimer9s disease and non-demented subjects, as well as between those with other dementias and non-demented subjects. Combining MMSE scores and visually rated MTA ratings yielded a sensitivity of 95% for Alzheimer9s disease, 85% for other dementias. Non-demented subjects were identified with a specificity of 96%. Volumetry did not have an added value over the MMSE score alone. CONCLUSIONS Visual rating of MTA is a clinically useful method for differentiating Alzheimer9s disease from controls and is both quicker and more accurate than volumetry.

Effects of topiramate on cognitive function

Abstract: OBJECTIVE To explore the impact of topiramate on tests of intellect and other cognitive processes. METHODS This was a retrospective study. The neuropsychological test scores of 18 patients obtained before and after the introduction of treatment with topiramate (median dose 300 mg) were compared with changes in test performance of 18 patients who had undergone repeat neuropsychological assessments at the same time intervals. Complaints of cognitive decline precipitated referral for reassessment in five cases in the topiramate treated group. The groups were matched for age and intellectual level at the time of the first assessment. Patients were assessed using the WAIS-R, tests of verbal and non-verbal memory, language, and perceptual processing. A subgroup of patients underwent a brief reassessment after the withdrawal or substantial reduction of topiramate. RESULTS Repeat assessments in those taking topiramate were associated with a significant deterioration in many domains, which were not seen in the comparison group. The greatest changes were for verbal IQ, verbal fluency, and verbal learning (p CONCLUSIONS In our patient group topiramate had a negative impact on cognition which was consistent with subjective complaints of patients. Tests requiring verbal processing seemed especially sensitive to the drug. A decline in verbal intellect (VIQ), a measure which has been considered by some to be insensitive to antiepileptic drug effects, was particularly striking. Caution is warranted in the interpretation of the findings due to methodological limitations of the study design. Further investigation of mediating factors such as serum concentrations, comedication, and other potential risk factors, however, is needed to enable appropriate targeting of treatment with this effective antiepileptic agent.

Interference between gait and cognitive tasks in a rehabilitating neurological population

Abstract: Objectives—To quantify the extent of interference between gait and cognitive tasks after brain injury; to investigate whether such interference is common to various cognitive tasks, or confined to specific cognitive modules; to investigate whether such interference declines during recovery from brain injury. Method—Fifty participants were recruited from a neurological rehabilitation unit (33 people, 75% of sample); the stroke rehabilitation ward of an acute hospital (11 people, 20%); and a young disabled unit (six people, 5%). Measures of stride duration were taken in single task conditions, and in conjunction with each of four cognitive tasks. Outcome measures were dual task decrements in gait and in cognitive task performance. Results—Overall, a 7% decrement in stride duration was recorded under dual task conditions compared with single task, with stride duration being significantly longer during simultaneous performance of each cognitive task. There was a 4% decrement on average in cognitive task performance under dual task conditions, with significant decrements being recorded for word generation while walking and paired associate monitoring while walking. A significant correlation (r=0.45) was found between dual task decrements and scores on a standard measure of disability—the Barthel activities of daily living scale—but the correlation with 10 m walking time was not significant (r=0.18). Conclusion—Interference between cognitive tasks and motor control activities such as gait is a problem in neurological rehabilitation settings. Interference between cognition and locomotor tasks may be important in assessing neurological patients’ ability to function independently, and in designing therapies for both cognitive and motor rehabilitation. (J Neurol Neurosurg Psychiatry 2000;69:479‐486)

Phonological grouping is specifically affected in cerebellar patients: a verbal fluency study

Abstract: OBJECTIVES—Recent clinical and functional neuroimaging evidence points towards a cerebellar role in verbal production. At present it is not clear how the cerebellum participates in language production. The aim was to investigate the influence of cerebellar lesions on verbal fluency abilities with specific focus on the verbal searching strategies employed by patients with cerebellar damage. METHODS—Twenty five patients with focal or degenerative cerebellar disease and 14 control subjects were tested in a timed verbal fluency task requiring word production under forced (phonemic or semantic) conditions. To analyse the verbal searching strategy employed, semantic and phonemic cluster analyses were also performed. RESULTS—Performances of cerebellar patients were comparable with those of controls in the semantic task; conversely their performances were significantly impaired when tested in the letter task. Cluster analysis results showed that the verbal fluency impairment is linked to specific damage of phonemically related retrieval strategies. CONCLUSION—Cerebellar damage impairs verbal fluency by specifically affecting phonemic rule performances while sparing semantic rule ones. These findings underline the importance of the cerebellar computing properties in strategy development in the linguistic domain.

Psychiatric aspects of temporal lobe epilepsy before and after anterior temporal lobectomy

Abstract: OBJECTIVES—Psychopathology has been reported to be prevalent both before and after surgical treatment for medically intractable temporal lobe epilepsy. Individual patients were evaluated prospectively to assess the effect of anterior temporal lobectomy (ATL) on prevalence and severity of psychiatric disease. METHODS—Psychiatric status was assessed in a consecutive series of epilepsy patients before and 6 months after ATL using a structured psychiatric interview, psychiatric rating scales, and self report mood measures. RESULTS—A DSM-III-R axis I diagnosis was present in 65% of patients before and after surgery. The most common diagnoses were depression, anxiety, and organic mood/personality disorders. There was a trend for major psychiatric diagnoses to be more common in patients with right compared to left temporal lobe seizure focus, both before and after surgery. The apparent stability in the overall rate of psychiatric dysfunction concealed onset of new psychiatric problems in 31% of patients in the months shortly after surgery, and resolution of psychiatric diagnoses in 15% of patients. In the group as a whole, the severity of psychiatric symptoms was lower at 6 months postsurgery than before temporal lobectomy. CONCLUSIONS—The overall prevalence of psychiatric dysfunction was comparably high before and after ATL, but individual changes in psychiatric status and changes in severity of symptoms occurred in many patients in the 6 months after surgery.