Showing papers in "European Journal of Neurology in 2001"

Classification of gait patterns in spastic hemiplegia and spastic diplegia: a basis for a management algorithm

Abstract: Classifications of gait and postural patterns in spastic hemiplegia and spastic diplegiia are presented, based on the work of previous authors. The classifications are used as a biomechanical basis, linking spasticity, musculoskeletal pathology in the lower limbs, and the appropriate intervention strategies. The choice of target muscles for spasticity management, the muscle contractures requiring lengthening and the choice of orthotics are then linked to the underlying gait pattern.

Depression is an independent predictor of poor long-term functional outcome post-stroke.

Abstract: The influence of depression on the long-term outcome of stroke patients was examined among 390 of 486 consecutive patients aged 55-85 years. They completed, at 3 months after ischaemic stroke, a detailed medical, neurological, and radiological stroke evaluation, structured measures of emotion (Beck's Depression Inventory, BDI), handicap (Rankin scale, RS), and assessment of activities of daily living (Barthel Index, BI). Further RS and BI was evaluated at 15-month follow-up from these 390 patients and BDI in 276 patients. A group of 256 patients completed, in addition to the 15-month follow-up, a comprehensive psychiatric evaluation, including the Present State Examination 3 months after stroke. The DSM-III-R criteria were used for diagnosis of the depressive disorders. BDI identified depression (cut-off point > or = 10 for depression) in 171 (43.9%) of 390 and in 123 (44.6%) of 276 patients at 3- and 15-month follow-up. DSM-III-R major depression was diagnosed in 66 (25.8%), and minor depression in 32 (12.5%), of 256 patients 3 months after stroke. Patients with BDI > or = 10, or major, but not minor, depression more often had poor functional outcome (RS > II and BI or = 10) correlated with poor functional outcome at 15 months (RS > II) (OR 2.5, 95% CI 1.6-3.8). More careful examination and treatment of depression in stroke patients is emphasized.

Management of upper limb dysfunction in children with cerebral palsy: a systematic review.

Abstract: Effective use of the upper limb can impact on educational outcomes, participation in activities of daily living and vocational options for many children with cerebral palsy (CP). This article presents the results of a systematic review of the literature on the management of upper limb dysfunction in children with CP. The range of management options includes therapies such as physiotherapy, occupational therapy, neurodevelopmental therapy and conductive education; peripheral splinting and casting; focal or generalized pharmacotherapy; and surgery to improve upper limb function or correct deformity. A literature search identified 60 papers, of which four were randomized controlled trials and 44 were prospective studies with objective outcome measures. Principal studies undertaken for each type of treatment and the efficacy of the different types of treatment were critically evaluated. In addition, the current level of evidence for each study was evaluated according to Sackett’s (1989) model and ICIDH-2 classification. A close examination of two relatively new treatments for upper limb spasticity, constraint induced movement therapy and botulinum toxin type A (BTX-A) was conducted with reference to more extensive data on the efficacy of BTX-A in the lower limb.

Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions

Abstract: Botulinum toxin type A is an important therapeutic agent for the treatment of movement and other disorders. As the clinical uses of botulinum toxin type A expand, it is increasingly important to understand the biochemical and pharmacological actions of this toxin, as well as those of other botulinum toxin serotypes (B-G). Botulinum neurotoxin serotypes exhibit differences in neurotoxin complex protein size, percentage of neurotoxin in the activated or nicked form, intracellular protein target, and potency. These properties differ even between preparations that contain the same botulinum toxin serotype due to variations in product formulations. As demonstrated in preclinical and clinical studies, these differences result in a unique combination of efficacy, duration of action, safety, and antigenic potential for each botulinum neurotoxin preparation.

A randomized, double‐blind, placebo‐controlled study of the efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke

Abstract: Objective. To study the eAcacy and safety of botulinum toxin type A (BtxA) in the treatment of upper limb muscle spasticity, caused by stroke. Methods. This was a randomized, controlled trial. Patients received either placebo injections or a total of 1000 IU of BtxA (Dysport) into five muscles of the aAected arm. Muscle tone was assessed using the Modified Ashworth Scale (MAS). Other outcome measures were the change in the joint range of motion (ROM), the Barthel index, pain score, goal attainment and the subjective evaluation of benefit by patients and investigators. The patients were assessed blind to randomization at baseline and 4, 8, 12 and 16 weeks after treatment. Results. Fifty nine patients were recruited and received treatment. One patient was lost to follow-up before the last scheduled visit of the study. The group of patients who received BtxA had a significant reduction in the summed MAS score at week 4 compared with the placebo group (Pa 0.004). The magnitude of benefit over the 16 week follow-up period was significantly reduced for the BtxA group in the wrist (Pa 0.004) and the finger joints (Pa 0.001) when compared with the placebo. There was no statistically significant diAerence between the groups in the joint ROM, muscle pain, goal-attainment or the Barthel index scores at week 4 of the study. At week 16, the BtxA group showed significantly greater improvement in the passive ROM at the elbow (Pa 0.036). The patients’ global assessment of benefit at the end of the study showed that 16 (50%) patients in the placebo group had ‘much improved’ or had ‘some improvement’ compared with 24 (92.3%) patients in the BtxA group (Pa 0.007). The investigators’ rating for the same item was 16 (50%) and 23 (88.4%) patients, respectively (Pa 0.002). Sixteen and twenty patients in the BtxA and placebo groups, respectively, had an adverse event. The most frequently reported adverse events were accidental injury, respiratory and urinary tract infections and muscle pain. Conclusion. The findings of the present study suggest that treatment with BtxA in a dose of 1000 units reduces muscle tone in patients with post-stroke upper limb spasticity. This eAect is sustained for at least 16 weeks. BtxA is safe in the dose used in this study. Important note. The authors wish to emphasize that the botulinum toxin preparation used in this study was Dysport (Ipsen Ltd) which has a diAerent therapeutic equivalence from other commercially available product, Botox (Allergan Inc.).

Lateralization of motor circuits and handedness during finger movements.

Abstract: Although functional lateralization in the human brain has been studied intensively, there remains significant controversy over the brain mechanisms that instantiate it. The main objective of the present study is to characterize the regions associated with the generation of different movements by the fingers of both hands by right- and left-handed people. Thirteen right- and left-handers were studied using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) during performance of single and sequential finger movement tasks. We used single-shot whole-brain spiral fMRI to map the functional components of the motor system during these tasks. Regions of interest included the primary motor and sensory cortices, the pre-motor cortices and the cerebellum. Sequential movements were associated with intense brain activation in several bilateral regions, whereas single movements were associated with less activation in fewer regions, but with greater laterality. Right- and left-handers differed in their pattern of activation, sharing a pattern of activation on simple movements but responding differently to sequential movements. On simple movements, the brain activation patterns of left- and right-handers were similar in volume, number of areas and laterality. By contrast, on sequential movement, left-handers activated larger volumes and a larger number of brain areas than right-handers, and showed significantly less brain lateralization. These results highlight differences in the functional organization of motor areas in right- and left-handed people. The discrepancies that might reflect differences in the network features of motor systems in these two groups, could also determine differences in motor activity that occur during recovery from injury (e.g. after stroke).

Costs, quality of life and disease severity in multiple sclerosis: a cross-sectional study in Sweden

Abstract: This study assessed the cost to society of multiple sclerosis (MS) in Sweden in 1998. The cost-of-illness method, based on the human capital theory, was used as the theoretical framework. The study used a cross-sectional approach, in which resource utilization data and quality-of-life data (utilities) were collected at a single time point. The total cost of MS was estimated at 4868 MSEK, or 586 MEUR, giving an annual cost of 442 500 SEK, or 53 250 EUR, per patient (1USD = 9.73 SEK, 1 EUR = 8.31 SEK, as of 21 September 2000). Direct costs accounted for about 67% of total cost, and they were dominated by the cost of personal assistants and drugs. Indirect costs (loss of production) accounted for about 33% of total costs. To these economic costs, intangible costs of 2702 MSEK (325 MEUR) should be added as well. Direct, indirect and informal care costs all rose significantly with increased disability and were higher during a relapse. Quality of life declined substantially with increased disability and was lower during a relapse. Multiple sclerosis was found to be associated with much higher costs to society than has been ascertained by former studies. The study also revealed a strong correlation between severity of the disease and quality of life. These results are crucial for further studies on the cost-effectiveness of new treatments aimed at preventing relapses and reducing progression of the disease.

The measurement of health-related quality of life (HRQL) in children with cerebral palsy.

Abstract: The measurement of health-related quality of life (HRQL) in children with cerebral palsy is part of an emerging discipline. Theoretical models of disability and chronic illness developed by the World Health Organization, the National Center for Medical Rehabilitation Research and others are being adapted for children. Development of HRQL measures in paediatrics lags behind the work completed with adults due to challenges unique to children, such as what domains to measure, whose perspective to address and the developmental changes inherent to children. The descriptive HRQL studies of children with moderate to severe cerebral palsy and comparisons of children with quadriplegia vs. diplegia and hemiplegia are presented. Consistent with the functional measures, no significant difference in HRQL by treatment was documented in children with spastic diplegia participating in a randomized clinical trial of selective dorsal rhizotomy. HRQL measures that are specifically tailored to cerebral palsy need to be developed. Generic and individualized measures of HRQL are currently available and while limited, may be useful for evaluating the effect of different treatments for spasticity on the quality of life in children with cerebral palsy.

Dementia and cognitive impairment three months after stroke.

Abstract: To investigate the cognitive capacities of a cohort of ischaemic or haemorrhagic stroke survivors and to identify the clinical determinants of post-stroke cognitive impairment, we evaluated 237 patients admitted to a Stroke Unit (mean age 59; SD=12.7). Three months after stroke, patients were submitted to a neuropsychological evaluation that included the Mini-Mental State Examination (MMSE), a complementary battery to assess specific cognitive domains, the Hamilton Depression Rating Scale (HDRS) and the Blessed Dementia Scale (BDS). Disturbed performance on at least one domain was detected on 131 (55%) patients: 27% had cognitive deficits other than memory, 7% had focal memory deficit, 9% had memory and other cognitive deficits and 6% had dementia. Dementia was associated with female gender (P=0.01), older age (P=0.01) and lower education level (P=0.04). Patients with memory deficits were older (P=0.01) with lower educational level (P=0.08) and more left sided lesions (P=0.02) than patients without memory deficits. In this middle aged stroke survivors cognitive impairment was common 3 months after stroke, while dementia was infrequent.

Spasticity versus strength in cerebral palsy: relationships among involuntary resistance, voluntary torque, and motor function.

Abstract: Despite the lack of consensus of the role of spasticity in the observed motor disability in cerebral palsy (CP), alleviation of spasticity remains a primary focus in the clinical management of these patients. The purposes of this study were to: (1) quantify voluntary torque and passive resistance across speeds in the hamstrings and quadriceps muscle groups with respect to the presence of stretch responses and/or passive muscle stiffness in patients with CP compared to age-related children without disability, and (2) relate these parameters to each other and to functional performance, as measured by the Gross Motor Function Measure (GMFM), in CP. Included were 23 subjects with CP, sub-grouped by the presence or absence of stretch responses as determined by electromyography, and 9 subjects without CP. Results indicated that peak torque was considerably greater in the comparison group than for each of the CP groups and resistance was greater in the CP group with spasticity compared to the nonspastic CP group in both muscles at all speeds. Stiffness differed between the spastic CP group and the comparison group only for the quadriceps at the fastest speed. Higher passive resistance torque and stiffness were correlated with decreased voluntary torque, particularly for the antagonists, and with lower GMFM scores. In conclusion, strength and motor function are related to the magnitude of resistance torque and stiffness in CP, although the small amount of variance explained reinforces the multidimensional nature of this disorder, and the challenges inherent in managing it.

Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosis.

Abstract: Alcohol misusers frequently have difficulties in gait, and various muscle symptoms such as cramps, local pain and reduced muscle mass. These symptoms are common in alcoholic patients and have previously been ascribed as neuropathological in origin. However, biochemical lesions and/or the presence of a defined myopathy occur in alcoholics as a direct consequence of alcohol misuse. The myopathy occurs independently of peripheral neuropathy, malnutrition and overt liver disease. Chronic alcoholic myopathy is characterized by selective atrophy of Type II fibres and the entire muscle mass may be reduced by up to 30%. This myopathy is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere and occurs in approximately 50% of alcohol misusers. Alcohol and acetaldehyde are potent inhibitors of muscle protein synthesis, and both contractile and non-contractile proteins are affected by acute and chronic alcohol dosage. Muscle RNA is also reduced by mechanisms involving increased RNase activities. In general, muscle protease activities are either reduced or unaltered, although markers of muscle membrane damage are increased which may be related to injury by reactive oxygen species. This supposition is supported by the observation that in the UK, alpha-tocopherol status is poor in myopathic alcoholics. Reduced alpha-tocopherol may pre-dispose the muscle to metabolic injury. However, experimental alpha-tocopherol supplementation is ineffective in preventing ethanol-induced lesions in muscle as defined by reduced rates of protein synthesis and in Spanish alcoholics with myopathy, there is no evidence of impaired alpha-tocopherol status. In conclusion, by a complex series of mechanisms, alcohol adversely affects skeletal muscle. In addition to the mechanical changes to muscle, there are important metabolic consequences, by virtue of the fact that skeletal muscle is 40% of body mass and an important contributor to whole-body protein turnover.

A randomized study of combined botulinum toxin type A and casting in the ambulant child with cerebral palsy using objective outcome measures.

Abstract: It is recognized that objective gait analysis is of great value in planning a multilevel botulinum toxin type A (BTX-A) treatment. After BTX-A treatment, objective outcome measures can provide new and interesting information for each individual child with cerebral palsy (CP). Moreover, by studying group results, we may evaluate our treatment hypotheses. The present prospective study attempts to document the effect of integrated multilevel BTX-A treatment on objective gait parameters and to define the optimal strategy for the combined treatment of BTX-A with casting in children with cerebral palsy. Objective three-dimensional gait analysis (3DGA) data were collected pre- and 2 months post-treatment, in two randomized patient groups: a first group of 17 children treated with lower leg casting prior to BTX-A injections, and a second group of 17 patients who received casting immediately after injections. The present study demonstrates that improved gait can be achieved after a multilevel BTX-A treatment, combined with casting, using a set of 90 gait parameters. The most pronounced improvement was seen at the ankle joint. The results in the knee, hip and pelvis imply that multilevel treatment of the child with CP should start at an early age, in order to prevent development of muscle contractures. Slightly more pronounced benefits, mainly in the proximal joints, were seen for the children who were casted after injections as compared to the children who were casted before injections.

The effect of botulinum toxin type A on the functional ability of the child with spastic hemiplegia a randomized controlled trial

Abstract: It has been demonstrated that botulinum toxin type A (BTX-A) injections reduce spasticity and improve muscle growth in children with spasticity. It has been postulated that BTX-A allows the learning of more normal movement patterns. The aim of this study was to measure the effect of this treatment on functional ability, as measured by the Gross Motor Function Measure (GMFM), in children with spastic hemiplegic cerebral palsy. Children of 3--13 years and meeting the selection criteria were randomly allocated to the control or injection group using a matched pair design. A match constituted a child within 6 months of age with the same Modified Ashworth Score (MAS) for the gastroc-soleus and within 10% of the same goal scores on the Gross Motor Function Measure. Twelve matched pairs were enrolled. Outcomes were measured on enrolment and at 1, 3 and 6 months post injection. The time course of the response to BTX-A was assessed with measurements of the MAS, dynamic range of motion (R1) and static muscle length (R2). Motor function was assessed using the 88-item GMFM and parental satisfaction with a 10-point visual analogue scale. Within pair comparisons of the GMFM using the Wilcoxon signed rank test indicated that the treatment group made significantly greater gains than controls at 3 months (P=0.02) with even greater differences seen at 6 months (P=0.004). Using parametric statistics, the intrapair difference in proportional change of GMFM increased from 35% (4 to 65) at 3 months to 52% (17--87) at 6 months. Response to injection was confirmed by a decrease in MAS in the treatment group and very little change in controls. This difference was significant (P=0.002) at 3 months and was attenuated but still significant (P=0.016) at 6 months; the difference in proportional change decreased from 44% at 3 months to 22% at 6 months. Changes in R1 reflected those of MAS in the treatment group and deteriorated significantly over the study period in controls. Parents of children in the treatment group were more satisfied than controls, but satisfaction scores did not correlate with changes in function or technical outcomes suggesting that this may be a placebo effect. The changes in GMFM correlated with changes in technical outcomes at 3 months, suggesting a causal relationship. The intrapair differences in GMFM continued to increase even after the local response to injection had started to wane.

A review of the causes of central pontine myelinosis: yet another apoptotic illness?

Abstract: One of the well recognized stimuli for central pontine myelinosis (CPM) is the rapid correction of chronic hyponatraemia. Conventionally this has been perceived to lead to pontine glial cell swelling through osmosis and eventually to cell death. However, although a purely osmotic argument has been central to any patho-physiological understanding of CPM, there are deficiencies in this approach that do not account for why certain individuals develop CPM with relatively mild osmotic insults. Here we review the varying aetiologies of CPM and propose a novel hypothesis for CPM causation by suggesting that individuals predisposed to CPM have inadequate energy provision as well as other factors that result in a pro-apoptotic drive, which renders them susceptible to brain injury from diverse causes. In CPM, the precipitant of brain injury appears to be osmotic stress. Furthermore, this model suggests a number of therapeutic interventions that may prevent or at least mitigate the consequences of CPM.

Chronic polyneuropathies in Vest-Agder, Norway.

Abstract: Epidemiological data on chronic polyneuropathies, especially inflammatory types, is limited. The purpose of this study was to examine the spectrum of causes and estimated prevalence of various polyneuropathy types in Vest-Agder, and to examine the clinical features of the Vest-Agder population of chronic inflammatory demyelinating polyneuropathy (CIDP). In Vest-Agder county (population of 155 464), polyneuropathy patients are registered in a database and followed prospectively. We did a measure of the database on October 31 1999. A total of 192 patients were registered. The prevalence for chronic inflammatory demyelinating polyneuropathy (CIDP) was 7.7 per 100 000 population. The course was relapsing in five of fifteen patients, progressive in four patients and slowly progressive in six of fifteen patients. Two of the fifteen patients had pure sensory symptoms. The mean Rankin disability score was 3.4 at maximal deficit and 2.1 at last follow-up. The prevalence of paraproteinemic polyneuropathy was 5.1 per 100 000 population. None of the patients with paraproteinemic polyneuropathy were worse than slightly disabled (disability score < or = 2). The prevalences for other polyneuropathies were as follows: polyneuropathy and RA, 1.3; polyneuropathy and Sjogren's syndrome or sicca complex, 4.5 (polyneuropathy was the presenting symptom in five of seven patients); sarcoidosis 1.9; polyneuropathy and chronic Lyme, 0.6; paraneoplastic polyneuropathy, 1.9; diabetic polyneuropathy 23.2; vitamin deficiency, 5.1; alcoholic and toxic polyneuropathy, 19.9; hereditary polyneuropathy, 14.8. Cryptogenic polyneuropathies made up 26% of all polyneuropathies. The mean disability score was 2.0 (SD 1.1). In conclusion, prevalence of CIDP was significantly higher than previously reported, and the prognosis was good in the majority of patients. Patients with paraproteinemic polyneuropathy were not severely disabled. Polyneuropathy was the presenting symptom in the majority of patients with Sjogren's syndrome or sicca complex.

Botulinum A toxin improves life quality in severe primary focal hyperhidrosis.

Abstract: Focal hyperhidrosis is a condition that may disturb emotional, social and professional life. Treatment options for severe cases are surgical sympathectomy and local chemical sweat gland denervation by intradermal injections of botulinum toxin A (Btx A). The Dermatology Life Quality Index (DLQI) is a simple validated questionnaire designed to measure and compare disability in different skin diseases. The aim of this study was to assess quality of life with the DLQI before and after treatment with botulinum toxin injections in a group of patients with severe hyperhidrosis. DLQI was administered to 58 randomly chosen patients before and after treatment. All patients answered the DLQI questionnaire prior to treatment and 53/58 at mean 5.2 months after treatment. The mean DLQI score in the 58 patients before treatment was 10.3 (2-23). In the group of 16/53 patients who had a relapse of sweating when answering the DLQI a second time, no significant improvement was seen [score 10.6 before and 8.8 after treatment (P = 0.21)]. In patients without relapse, a 76% improvement was obtained (DLQI was reduced from 9.9 to 2.4; P < 0.0001). The study showed that focal hyperhidrosis may considerably reduce life quality and the disability experienced by the patients can be largely reversed by botulinum toxin injections.

Current evidence for the use of botulinum toxin type A in the management of children with cerebral palsy: a systematic review

Abstract: Management of children with cerebral palsy (CP) is the focus of considerable resources in many countries, so that evaluation of the efficacy for new and established treatments is imperative. Botulinum toxin type A (BTX-A) is a relatively new method of spasticity management in children with cerebral palsy. It has been the focus of extensive research since its application to cerebral palsy 10 years ago. In a systematic review relating to the management of the lower limb in cerebral palsy 156 papers were identified. These were categorized according to Sackett and the World Health Organisation International Classification of Impairments, Disabilities and Handicaps model. We identified 10 randomized trials evaluating the use of BTX-A in the lower limb in children with cerebral palsy in a systematic review. A meta-analysis showed the pooled risk difference between BTX-A and placebo in three trials was 0.25 (95% CI 0.13, 0.37) and 0.23 (95% CI −0.06, 0.53) for two trials of BTX-A and casting using the physicians rating scale. These represent moderate treatment effects that are dosage-dependent. Outcomes were also compared for function in five studies. The type of evidence for BTX-A was graded by each treatment indication and directions for future research were then drawn from the available evidence.

Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency

Abstract: Ataxia with vitamin E (Vit E) defciency (AVED) is an autosomal recessive disorder caused by mutations of the alpha tocopherol transfer protein gene. The Friedreich ataxia phenotype is the most frequent clinical presentation. In AVED patients, serum Vit E levels are very low in the absence of intestinal malabsorption. As Vit E is a major antioxidant agent, Vit E deficiency is supposed to be responsible for the pathological process. Twenty-four AVED patients were fully investigated (electromyography, nerve conduction velocity (NVC) studies, somatosensory evoked potentials, cerebral computed tomography scan, sural nerve biopsy, genetic studies) and supplemented with Vit E (800 mg daily) during a 1-year period. Clinical evaluation was mainly based on the Ataxia Rating Scale (ARS) for cerebellar ataxia assessment and serum Vit E levels were monitored. Serum Vit E levels normalized and ARS scores decreased moderately but significantly suggesting clinical improvement. Better results were noted with mean disease duration < or = 15 years. Reflexes remained abolished and posterior column disturbances unchanged. Vitamin E supplementation in AVED patients stabilizes the neurological signs and can lead to mild improvement of cerebellar ataxia, especially in early stages of the disease.

Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis

Abstract: Studies of chemokines in cerebrospinal fluid (CSF) of patients with active multiple sclerosis (MS) have indicated that specific chemokines may have important roles in disease pathogenesis. We previously reported that CSF concentrations of CXCL10 (previously known as IP-10) were elevated in MS patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials. Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls. The levels of CXCL10 were higher in the patient group than in controls but two outliers in the control group also had high CSF concentrations of CXCL10. The CSF concentrations of CXCL10 did not change over time or after treatment. The CSF concentration of CXCL10 was positively correlated with the CSF leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9 and IgG synthesis levels. CXCL10 may be involved in the maintenance of intrathecal inflammation whereas CCL2 correlates negatively with measures of inflammation, suggesting differential involvement of CXCL10 and CCL2 in CNS inflammation.

Review of the functional surgical treatment of dystonia

Abstract: A review of functional surgery for dystonia is presented. Recently renewed interest in stereotaxy for dystonia has followed the resurgence of pallidotomy and the introduction of deep brain stimulation (DBS) in Parkinson's disease (PD) in the early 1990s. However, even since the 1950s, small series of patients treated with ablative surgery have been carefully studied, providing useful information, notably regarding the tolerability of surgery. In the setting of dystonia, thalamotomy was first performed with substantial benefits, but some authors outlined the great variability in outcome, and the high incidence of operative side-effects. In the 'modern' era of functional surgery for movement disorders, the globus pallidus internus (GPi) has emerged to be currently the best target for dystonia, based on small series of patients published in the last few years. Both bilateral posteroventral pallidotomy (PVP) and bilateral pallidal stimulation, performed by several teams, have benefited a variety of patients with severe dystonia, the most dramatic improvements being seen in primary dystonia with a mutation in the DYT1 gene. Whereas patients with secondary dystonia have often shown a lesser degree of improvement, some publications have nevertheless reported major benefit. There is today a strong need for carefully controlled studies comparing secondary and primary dystonia, DYT1 and non-DYT1 dystonia, ablative surgery and DBS, with additional assessment of neuropsychological changes, especially in children treated with bilateral pallidal procedures.

T1 lesion load and cerebral atrophy as a marker for clinical progression in patients with multiple sclerosis. A prospective 18 months follow-up study.

Abstract: We investigated the relationship between local tissue destruction, diffuse cerebral atrophy and clinical progression in patients with established multiple sclerosis (MS). Twenty-nine patients with MS (13 patients with relapsing–remitting and 16 with secondary progressive disease) were included in a prospective serial study. Cerebral volumes, T1 hypointense lesion volumes, T2 hyperintense lesion volumes at baseline and at 18 months follow-up, and the volume of monthly enhancing lesions from month 0 to month 9 were assessed on magnetic resonance imaging (MRI) brain scans using highly reproducible semi-automated quantitative techniques. The main outcome measures were the MRI parameters and disability on Kurtzkes’ Expanded Disability Status Scale. There was a significant correlation between the change (increase) in T1 lesion volume and progressive cerebral atrophy, whereas no correlation between the T2 lesion volume and atrophy was seen over the same follow-up period. The change in T1 lesion volume correlated more strongly than did T2 lesion volume change with the change in disability. We conclude that hypointense abnormalities detected in T1-weighted brain scans and cerebral atrophy may be directly linked. Although one should bear in mind some potential for reversibility due to inflammatory, oedematous lesions, these MR measures are a useful marker of progressive tissue damage and clinical progression in established MS.

Multiple sclerosis in Oslo, Norway: prevalence on 1 January 1995 and incidence over a 25-year period.

Abstract: The Oslo Multiple Sclerosis (MS) Registry was established in 1990, and this is the first report on the prevalence and incidence of MS in the city of Oslo, Norway. The prevalence rate of definite MS on 1 January 1995 was 120.4/10(5). Inclusion of patients of native Norwegian ancestry only and exclusion of non-Norwegian immigrants yielded a prevalence rate of 136.0/10(5). A similar prevalence rate (136.5/10(5)) was found when patients and immigrants from the other Nordic countries (Finland, Sweden, Denmark) were included. Segregation of the native Norwegian patients according to the counties where they were born showed no significant differences except for a disproportionate increase of patients born in the inland county of Oppland. A total of 794 cases were resident in Oslo at the time of a diagnosis of definite MS in the period 1972-99. The crude average annual incidence rate for each 5-year period, between 1972 and 1996, increased significantly from 3.7/10(5) in the 1972-76 to 8.7/10(5) in the 1992-96 period. The increase was more marked in relapsing-remitting (RR) than in primary progressive disease and in female cases.

Ischemic stroke of unusual cause: clinical features, etiology and outcome

Abstract: The clinical features, etiology and neurological outcome of ischemic stroke of unusual cause (ISUC) have rarely been reported. We retrospective reviewed all patients with this stroke subtype entered in the Sagrat Cor Hospital of Barcelona Stroke Registry, which includes data from 2000 consecutive first-ever stroke patients admitted to the hospital between 1986 and 1995. Patients with previous ischemia and/or hemorrhagic stroke were excluded. Topographic, anamnestic, clinical and neuroimaging characteristics of ISUC were assessed. Predictors of this stroke subtype were determined by logistic regression analysis. Ischemic stroke of unusual etiology was diagnosed in 70 patients (32 men and 38 women), with a mean +/- SD age of 52 +/- 22.4 years. This stroke subtype accounted for 4.3% of all first-ever strokes and 6% of all first-ever brain infarcts. Etiologies included hematological disorders in 17 cases, infection in 11, migraine stroke in 10, cerebral infarction secondary to venous thrombosis in nine, primary inflammatory vascular conditions in six and miscellaneous causes in 17. In the multivariate analysis after excluding cerebral venous thrombosis (n = 9) and arterial dissection (n = 4), because of typical clinical and radiological features, independent predictors of ISUC included 45 years of age or less (odds ratio [OR] 14.8), seizures (OR 6.8), headache (OR 5.2), hemianopia (OR 2.6) and occipital lobe involvement (OR 3.0). Patients with ISUC presented a lower in-hospital mortality rate (7.1% vs. 14.4%; P < 0.05), were more frequently symptom free at discharge (35.7% vs. 25.80%; P < 0.05) and experienced a longer mean length of hospital stay (23.7 days vs. 18.2 days; P = 0.06) than non-ISUC patients. We conclude that ISUC is infrequent, etiologies are numerous and hematologic disorders are the most frequent cause. We emphasize the better prognosis and the need to distinguish it from other ischemic stroke subtypes which have a different treatment approach and outcome.

The effect of botulinum toxin type A and a variable hip abduction orthosis on gross motor function: a randomized controlled trial

Abstract: Hip displacement is the second most common deformity after equinus in children with cerebral palsy (CP), and may result in dislocation, pain, fixed deformity and loss of function. We studied the combined effects of intramuscular injections of botulinum toxin type A (BTX-A) to the adductors and hamstrings and a variable hip abduction orthosis (SWASH), on gross motor function, hip displacement and progression to surgery, in a randomized clinical trial. Thirty-nine children, with bilateral spastic cerebral palsy, and mean age 3 years + 2 months (range 1 year+7 months--4 years +10 months) entered the trial. Gross Motor Function Classification System (GMFCS) levels were as follows: one child was level II, 11 were level III, 13 were level IV and 14 were level V. After concealed randomization, 20 were allocated to the control group and 19 to the intervention group. Thirty-five children completed the follow up at 1 year. The novel intervention group received up to 4.0 U BOTOX/kg/muscle, 16 U/kg/body weight every 6 months plus the use of a SWASH brace. The control group received clinical best practice comprising physiotherapy but no hip abduction bracing. Both groups showed improvements in total Gross Motor Function Measure (GMFM) score [mean 6.0% BTX-A group; 6.1% Control; 95% CI -- 6.7, 6.5 (NS)], however, there was no additional treatment effect for the study group. There were similar improvements on GMFM goal scores and GMFM-66 scores, but again no additional treatment effect was observed. Multiple regression of change in total GMFM by GMFCS classification for each group showed greater improvement in the total scores from baseline in the BTX-A/SWASH treated group than the control group. In the first year, nine children (two in the intervention group and seven in the control group) required soft tissue surgery because of progressive hip migration in excess of 40%. A longer-term follow up of a larger cohort may be required to determine the effect of the combined treatment on hip displacement.

Rivastigmine in subcortical vascular dementia: a comparison trial on efficacy and tolerability for 12 months follow-up.

Abstract: Sir, In the Western world, vascular disease is thought to be the second most common cause of dementia, following Alzheimer's disease (Chui, 1989). It has long been known that cognitive de®cits may result from a stroke, yet only recently have reports demonstrated that dementia may occur in approximately one-fourth to onethird of stroke cases (Tatemichi et al., 1992). It is widely known that the prevalence of all forms of dementia increases with age; in Europe, the prevalence of vascular dementia (VaD) is estimated to be 1.5±4.8% for individuals between the ages of 70 and 80-year-old (Rocca et al., 1991). VaD has heterogeneous forms, amongst the more common are: subcortical VaD caused by small-vessel disease leading to lacunar infarcts and ischemic white matter changes; dementia caused by multiple cortical territorial or watershed infarcts; dementia as a result of single strategic infarcts seated in critical areas (particularly for cognition), such as hippocampus, thalamus and caudate nucleus and ®nally, dementia as a result of intracranial hematomas or mixed forms. Subcortical VaD incorporates the old entities, de®ned as `lacunar states' and is tightly related to small vessel disease and hypoperfusion, resulting in di€use ischemic white matter lesions and incomplete ischemic injury (Erkinjutti, 1987; Pantoni et al., 2000). We studied 16 patients, of both sexes (72.3 ‹ 4.67 years old) with a diagnosis of probable VaD in complete accordance with NINDS-AIREN criteria (Roman et al., 1993). Brain CT-scans were available for all the patients randomized and reassessed by two neurologist, independently. A patient was de®ned as a€ected by subcortical VaD when his/her CT scan showed moderate to severe degree of ischemic white matter changes (Erkinjutti, 1997) and one or more lacunar infarct in the absence of non-lacunar territorial infarct and radiological signs of normal pressure hydrocephalus. We decided to divide the patients into two groups: group A, receiving rivastigmine (3±6 mg daily) associated to previously assumed therapy (antihypertensive, antidyslpidemic, antidiabetic drugs) and group B, receiving only cardioaspirin associated to the previously assumed therapy. All the patients were followed for 12 months, with periodical neurological and neuropsychological examinations. Visits were programmed after the ®rst month therapy, after 3, 8 and 12 months from the beginning of the treatment. A complete neuropsychological examination was conducted at the ®rst and at the last visit, and results were compared; during all the visits, we tested selectively some part of cognitive performances, and collected caregiver impression, in order to have a more complete, although not parametric clinical impression of the situation. Our aim was to de®ne if there are modi®cation in cognition, in daily living performance, in behaviour and social conduct, and in relative's stress between the two groups, from baseline situation and after 1 year of therapy. There was no drop out, in both of the groups. Patients were tested with Mini Mental State ± MMSE (Folstein et al., 1975), Ten point clock Drawing test ± TPC (Manos, 1997), Word ̄uency (semantic and phonological) ± WFs and WFp (Wechsler, 1981), Relative Stress Scale (Greene et al., 1982), Instrumental Activity of Daily Living-IADL (Lawton and Brody, 1969), Neuropsychiatric Inventory (Cummings et al., 1994) and with particular attention to new prescription of neurolectics and/or benzodiazepines. At the beginning, there were no di€erence between the two groups in all the evaluation. After 1 year of therapy (and the results were also re ̄ected by the clinical impression obtained during the follow-up), group A remained stable in cognition, apart from a slight improvement in TPC test (P < 0.05), but there is an evident trend in reducing the caregiver's stress (RSS; P < 0.05) and a tendency to reduce behavioral discharge (P ˆ 0.09). None of the patient needs to assume benzodiazepine, hypnotics or neurolectic. On the contrary, group B demonstrate a trend in deteriorating all cognitive performances, although results were not statistical signi®cant, when compared with their baseline results. But, what strikes attention is that when the two groups are compared, group B TPC results were poorer than group A (P < 0.05), their caregivers resulted more stressed, as stated by RSS results (P < 0.05), their NPI score is higher (P < 0.01) and they have to use di€erent sedative or neurolectic (P < 0.05), for social and behavioural alteration. Therefore, in our groups there is a general stable performance in cognitive tasks, with a slight better performances in executive functions, and generally a better behavioural response in the group treated with rivastigmine. Results obtained could be considered limited, because of the few patients enrolled; however, considering that clinical trials performed in patients with VaD have so far achieved unsatisfactory results (Sachdev et al., 1999), and that many drugs have been investigated, but no drug can be positively recommended at present, our data may be stimulating to enrol amore exhaustivenumberofpatients, follow them and try to de®ne an eventual role, for cholinergic drugs in the treatment of vascular cognitive impairment.

Systematic review of proton magnetic resonance spectroscopy of the striatum in parkinsonian syndromes.

Abstract: It has been suggested that proton magnetic resonance spectroscopy (MRS) of the striatum can differentiate between parkinsonian syndromes. The present study aims to examine this claim by performing a systematic review of the existing literature. A MEDLINE search was performed between 1966 and October 1999, along with searches of conference abstracts and reference lists of papers identified. Eleven groups have used MRS to examine metabolite ratios in the striatum in Parkinsonian syndromes. A number of these have shown reduced N-acetylaspartate/choline (NAA/Cho) and/or N-acetylaspartate/creatine (NAA/Cr) ratios in either idiopathic Parkinson’s disease (IPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration. However, the heterogeneity in the results precludes the use of any of these findings in differential diagnosis at the present time. The only group to use absolute metabolite concentrations rather than ratios showed that the decreased NAA/Cho ratio in IPD was because of an increase in choline which is of uncertain biological significance. Further large multicentre trials are required using absolute quantitation of tissue metabolite concentrations and a standardized technique. The patients entering such studies must be rigorously assessed to establish the diagnosis of the type of parkinsonism as accurately as possible. Any discriminatory abnormality must be tested in a large prospective study of newly presenting parkinsonian patients with long-term clinical follow up and ultimate pathological confirmation of the diagnosis as far as possible.

Prevalence of Alzheimer's type dementia in an elderly Arab population.

Abstract: The aim of this study was to estimate the prevalence of dementia of the Alzheimer type (DAT) in an Arab Israeli community. Epidemiological studies of dementia have rarely been reported in Arab populations. The target population, aged 60 years or older, comprised 821 persons (362 males) who, on 1 October 1995, were residents of the rural area of Wadi Ara. These persons were examined for symptoms of dementia (DSM-IV criteria), using a semistructured questionnaire for collection of demographic and medical data. Age, gender, and education-specific prevalence rates were calculated for this population and compared to those obtained in other studies. DAT was diagnosed in 20.5% of this population. Its prevalence increased steeply with age, from 8% among those younger than 70 years to 33% among those aged 70-79 and 51% among those 80 years or older. Illiteracy was very common in this population, and strongly associated with higher prevalence of DAT (27% vs. 4%, P < 0.001). DAT was more prevalent among females than males (25% vs. 15%, P < 0.001). However, illiteracy was also significantly more frequent among women (96% vs. 42%, P < 0.001). After correction for illiteracy, the gender difference lost statistical significance. Few women smoked, but among men, the prevalence of DAT in those who smoked was lower as compared to non-smokers (14% vs. 23%, a non-significant difference). These results were confirmed by logistic regression wherein DAT was included as the dependent variable and age, illiteracy, gender and smoking as independent variables (OR=2.8, 2.8, 1.2 and 0.7, respectively; P < 0.005 for each, except for smoking). Our findings suggest that this population is unique because of extremely high rates of dementia. While the results support a protective effect of schooling against the development of dementia, other factors (e.g. genetic) must be sought to explain this high frequency.