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1.
Valsasina P Agosta F Benedetti B Caputo D Perini M Salvi F Prelle A Filippi M 《Journal of neurology, neurosurgery, and psychiatry》2007,78(5):480-484
Background
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with severe cervical cord damage due to degeneration of the corticospinal tracts and loss of lower motor neurones. Diffusion tensor magnetic resonance imaging (DT MRI) allows the measurement of quantities reflecting the size (such as mean diffusivity) and orientation (such as fractional anisotropy) of water‐filled spaces in biological tissues.Methods
Mean diffusivity and fractional anisotropy histograms from the cervical cord of patients with ALS were obtained to: (1) quantify the extent of tissue damage in this critical central nervous system region; and (2) investigate the magnitude of the correlation of cervical cord DT MRI metrics with patients'' disability and tissue damage along the brain portion of the corticospinal tracts. Cervical cord and brain DT MRI scans were obtained from 28 patients with ALS and 20 age‐matched and sex‐matched controls. Cord mean diffusivity and fractional anisotropy histograms were produced and the cord cross‐sectional area was measured. Average mean diffusivity and fractional anisotropy along the brain portion of the corticospinal tracts were also measured.Results
Compared with controls, patients with ALS had significantly lower mean fractional anisotropy (p = 0.002) and cord cross‐sectional area (p<0.001). Mean diffusivity histogram‐derived metrics did not differ between the two groups. A strong correlation was found between mean cord fractional anisotropy and the ALS Functional Rating Score (r = 0.74, p<0.001). Mean cord and brain fractional anisotropy values correlated moderately (r = 0.37, p = 0.05).Conclusions
Cervical cord DT MRI in patients with ALS allows the extent of cord damage to be graded. The conventional and DT MRI changes found are compatible with the presence of neuroaxonal loss and reactive gliosis, with a heterogeneous distribution of the pathological process between the brain and the cord. The correlation found between cord fractional anisotropy and disability suggests that DT MRI may be a useful adjunctive tool to monitor the evolution of ALS.Amyotrophic lateral sclerosis (ALS) is the most common adult‐onset motor neurone disease, characterised by a progressive and simultaneous degeneration of upper and lower motor neurones.1,2 In its typical form, the disease begins either in one limb or with a combination of bulbar and corticobulbar symptoms, and continues with progressive weakness of the bulbar, limb, thoracic and abdominal musculature.1,2 By using a variety of conventional magnetic resonance imaging (MRI) sequences, several studies3,4,5,6,7,8,9,10,11,12,13,14,15 have shown changes in signal intensity along the brain portion of the corticospinal tracts, particularly in the posterior limb of the internal capsule and cerebral peduncles, varying between 25% and 80%. Reduced magnetisation transfer ratios in the internal capsule8,11 and N‐acetylaspartate levels in the motor cortex13,16,17 of patients with ALS have also been observed. However, none of these studies has reported a correlation between such magnetic resonance abnormalities and the degree of disability.8,11,13,16,17Diffusion‐tensor magnetic resonance imaging (DT MRI) enables the random diffusional motion of water molecules to be measured and thus provides quantitative indices of the structural and orientational features of the central nervous system (CNS).18 DT MRI has been used to assess quantitatively the tissue damage of the brain portion of the corticospinal tracts in ALS,12,19,20,21,22,23 and all studies have shown increased mean diffusivity (indicating a loss of structural barriers limiting the motion of water molecules) and decreased fractional anisotropy (indicating a loss of tissue organisation). However, brain DT MRI studies also resulted in heterogeneous clinicopathological correlations, as some authors found a moderate correlation between brain DT MRI metrics and the severity of disability,12,21,23 but others did not.19 In the past few years, DT MRI has also been used successfully to grade the extent of cervical cord damage associated with demyelinating conditions.24,25,26Considering that the cervical cord in ALS is one of the most affected portions of the CNS (owing to the combined presence of neuronal loss in the anterior horns of the grey matter and degeneration of the corticospinal tracts), we obtained mean diffusivity and fractional anisotropy histograms of the cervical cord from patients with ALS with the following aims: (1) to quantify the extent of tissue damage in this critical CNS region; and (2) to investigate the magnitude of the correlation of cervical cord DT MRI metrics with patients'' disability and tissue damage along the brain portion of the corticospinal tracts. 相似文献2.
Pugdahl K Fuglsang-Frederiksen A de Carvalho M Johnsen B Fawcett PR Labarre-Vila A Liguori R Nix WA Schofield IS 《Journal of neurology, neurosurgery, and psychiatry》2007,78(7):746-749
Background
Amyotrophic lateral sclerosis (ALS) is defined as a disease of the motor neurones, although several studies indicate involvement of the sensory nervous system.Aim
To evaluate the sensory nerve conduction studies (NCS) in 88 patients with ALS as part of a European multicentre study.Methods
Seven European clinical neurophysiologists examined consecutive series of ALS patients. The examinations were peer reviewed, and the diagnosis of ALS was confirmed clinically.Results
20 (22.7%) patients with ALS had sensory NCS abnormalities in at least one nerve. Of those, 11 (12.5% of all patients) obtained an additional peer review diagnosis of electrophysiological polyneuropathy. There was no difference between the subgroups of patients with normal versus abnormal sensory NCS findings with respect to age, duration and region of onset.Conclusion
The findings support previous reports of sensory involvement in ALS, and raise the question of whether patients with ALS with sensory nerve abnormalities represent a variant of ALS. ALS associated with generalised sensory system abnormalities may be consistent with degeneration of motor neurones and dorsal root ganglion cells.Sporadic amyotrophic lateral sclerosis (ALS) is defined as a progressive degeneration of upper motor neurones (UMNs) and lower motor neurones (LMNs). Normal electrophysiological studies on sensory nerves are generally required for the diagnosis of ALS.1 Nevertheless, several neurological, clinical neurophysiological and neuropathological studies have suggested that ALS is a more generalised neurodegenerative disorder.2,3,4,5,6,7,8,9,10,11,12,13,14,15,16The aim of this study was to determine the incidence of patients with ALS with electrophysiological sensory nerve abnormalities and to examine the possible differences between patients with ALS with normal versus abnormal sensory nerve conduction studies (NCS). The study was carried out on the basis of electrodiagnostic examinations of 88 patients with ALS included in the European multicentre project ESTEEM (European Standardised Telematic tool to Evaluate Electrodiagnostic Methods).17 相似文献3.
Vucic S Krishnan AV Kiernan MC 《Journal of neurology, neurosurgery, and psychiatry》2007,78(11):1202-1208
Background
While patients with amyotrophic lateral sclerosis (ALS) may complain of fatigue, the underlying mechanisms appear complex, with dysfunction of central and peripheral nervous systems independently reported as contributing factors. The aim of the present study was to further delineate the mechanisms underlying increased fatigability in ALS by measuring activity dependent changes in axonal excitability following a maximum voluntary contraction (MVC).Methods
Nerve excitability changes were recorded before and after an MVC of the abductor pollicis brevis in 16 patients with ALS and 25 controls.Results
In patients with ALS, there was a greater increase in threshold (36.5 (5.9)%; controls 19.6 (3.5)%; p<0.05) as a result of MVC, with reduction in the amplitude of the compound muscle action potential generated by a submaximal stimulus (ALS 49 (7.6)%; controls 41.0 (5.4)%). These changes were associated with an increase in superexcitability (ALS 65.1 (25.4)%; controls 42.3 (5.7)%) and reduction in strength–duration time constant (ALS 20 (4.9)%; controls 10 (2.5)%; p<0.01), indicative of axonal hyperpolarisation. The increase in threshold was more pronounced in patients with ALS with predominantly lower motor neuronal involvement.Conclusions
Higher firing rates of surviving motor axons attempting to compensate for neurogenic weakness are likely to explain the greater activity dependent changes in ALS. As such, the present study suggests a further peripheral factor underlying the development of fatigue in ALS.Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects motor neurones in the spinal cord, brainstem and motor cortex.1,2 The consequences of this neurodegeneration are motor deficits in the limbs, bulbar and respiratory muscles.3 Although the mechanisms of neuronal dysfunction, and ultimately the development of symptoms in ALS, remain unknown, glutamate excitotoxicity,4,5,6 increased levels of inducible nitric oxide synthase levels4 and, in cases of inherited ALS, oxidative stress secondary to mutations in the superoxide dismutase‐1 gene, have been proposed.7,8,9,10Increased fatigability, defined as an inability to sustain a predictable maximal force during voluntary contraction, is a common symptom of ALS.11,12,13 The mechanisms underlying fatigue in ALS are complex, and contributions from both the central and peripheral nervous systems have been reported.11,12 Central fatigue refers to a reduced excitatory drive to motor neurones, secondary to central nervous system dysfunction, resulting in incomplete motor unit recruitment and submaximal motor unit discharge rates. In contrast, peripheral fatigue typically refers to impaired muscle activation, caused by dysfunction at or below the anterior horn cell.13,14 Perhaps somewhat counterintuitively, fatigue in ALS appears to be independent of muscle strength and disease severity.15,16 Regardless of the underlying mechanism, fatigue in ALS severely impacts on the patient''s quality of life.15,16The ability to sustain a motor output may be assessed by measuring changes in axonal membrane threshold following a voluntary contraction. Specifically, in peripheral nerves, voluntary contraction activates the axonal membrane Na+/K+ pump,17 which attempts to return the resting membrane potential to baseline after contraction has ceased,18,19,20,21 resulting in activity dependent hyperpolarisation. The magnitude of activity dependent hyperpolarisation is determined by the impulse load22 and, in neurological diseases where the safety margin for impulse conduction has been reduced as occurs for instance in demyelinating neuropathy, may be sufficient to induce conduction failure.23,24,25 In an attempt to further delineate the mechanisms underlying fatigability and weakness in ALS, the present study measured activity dependent changes in axonal excitability induced by voluntary contraction. 相似文献4.
Pasquini M Leys D Rousseaux M Pasquier F Hénon H 《Journal of neurology, neurosurgery, and psychiatry》2007,78(1):56-59
Background and purpose
Pre‐existing cognitive decline and new‐onset dementia are common in patients with stroke, but their influence on institutionalisation rates is unknown.Objective
To evaluate the influence of cognitive impairment on the institutionalisation rate 3 years after a stroke.Design
(1) The previous cognitive state of 192 consecutive patients with stroke living at home before the stroke (with the Informant Questionnaire on COgnitive Decline in the Elderly (IQCODE)), (2) new‐onset dementia occurring within 3 years and (3) institutionalisation rates within 3 years in the 165 patients who were discharged alive after the acute stage were prospectively evaluated.Results
Independent predictors of institutionalisation over a 3‐year period that were available at admission were age (adjusted odds ratio (adjOR) for 1‐year increase = 1.08; 95% confidence interval (CI) 1.03 to 1.15), severity of the neurological deficit (adjOR for 1‐point increase in Orgogozo score = 0.97; 95% CI 0.96 to 0.99) and severity of cognitive impairment (adjOR for 1‐point increase in IQCODE score = 1.03; 95% CI 1 to 1.06). Factors associated with institutionalisation at 3 years that were present at admission or occurred during the follow‐up were age (adjOR for 1‐year increase = 1.17; 95% CI 1.07 to 1.27) and any (pre‐existing or new) dementia (adjOR = 5.85; 95% CI 1.59 to 21.59), but not the severity of the deficit of the neurological deficit.Conclusion
Age and cognitive impairment are more important predictors of institutionalisation 3 years after a stroke than the severity of the physical disability.Institutionalisation after a stroke increases with the severity of the neurological deficit, increasing age, female gender, low socioeconomic level, marital status and poor social environment.1,2,3,4,5,6Dementia is common after a stroke,7 leading to autonomy loss.8 Pre‐existing dementia is present in up to 16% of patients with stroke,9,10,11,12 and post‐stroke de mentia (PSD) occurs in up to one third.7 Several studies have found a link between cognitive impairment and institutionalisation after a stroke,1,2,3,4,5 but they had several methodological limitations: (1) cross‐sectional studies were performed in long‐term stroke survivors and did not take into account patients who had been institutionalised but died before the study6; (2) there was no systematic cognitive assessment13 or only a Mini Mental State Examination,14 which is not appropriate for patients with stroke; and (3) most studies included only patients recruited in rehabilitation centres, leading to selection bias.1,2,3,4,5 To our knowledge, no study has prospectively evaluated the influence of pre‐existing cognitive impairment and PSD on the institutionalisation rate after a stroke.The aim of this study was to evaluate the influence of the previous cognitive state and new‐onset dementia on the institutionalisation rate 3 years after a stroke. 相似文献5.
Bugnicourt JM Roussel B Tramier B Lamy C Godefroy O 《Journal of neurology, neurosurgery, and psychiatry》2007,78(7):699-701
Background
High plasma concentrations of factor VIII (FVIII) and von Willebrand factor (VWF) have been recently associated with a moderately increased risk of venous thrombosis, but their roles in cerebral sinus and venous thrombosis (CSVT) have not been addressed. To determine whether elevation of FVIII and VWF is more frequent in CSVT, we analysed plasma levels of FVIII and VWF in a case control study.Methods
The study population consisted of 25 consecutive patients (of whom nine were excluded) admitted for CSVT to the Department of Neurology, Amiens University Hospital, France, from January 1997 to December 2002, for a general screening for thrombophilia. Sixty‐four healthy subjects matched for age and sex formed the group control.Results
Mean FVIII (CSVT: 167.3 (SD 48.8) IU/dl; control group: 117.9 (39.8) IU/dl; p = 0.001) and VWF levels (CSVT: 165.4 (76.5)%; control group: 108.5 (27.8)%; p = 0.01) were significantly higher in the CSVT group. Using the 95th percentile of the control group as the cut off value, elevated FVIII (>190 IU/dl) occurred in 25% (4/16) (p = 0.005) and elevated VWF (>168%) in 37.5% (6/16) of patients with CSVT (p<0.001). Using previously reported cut off values (>150 IU/dl or >150%) showed the same results (FVIII: p = 0.005; VWF: p = 0.009).Conclusion
Our study suggests that elevation of plasma factor VIII levels is the most common prothrombotic risk factor for CSVT. Elevation of VWF is also associated with an increased risk of CSVT but its effect seems to be partly mediated through FVIII.Cerebral sinus and vein thrombosis (CSVT) is a rare localisation of venous thromboembolic disease. It generally occurs in young or middle‐aged adults and accounts for approximately 1% of strokes.1 Many coagulation disorders have been associated with CSVT.2,3,4Several prospective studies showed that high concentrations of factor VIII (FVIII) are associated with a moderately increased risk of venous thromboembolism (VTE).5,6 The role of increased levels of von Willebrand Factor (VWF) in VTE remains unclear.5,7 Recent studies suggest that the effect of VWF is fully explained by FVIII concentrations.5 Indeed, the ABO blood group, which regulates plasma concentrations of both FVIII and VWF, may also play a role in susceptibility to thrombosis.8,9,10The increased risk of VTE with elevated levels of FVIII or VWF has been observed in previous studies.5,6,7,11 However, they did not specifically include patients with CSVT7,9 or they were incomplete.12The aim of our study was to assess plasma levels of FVIII, VWF and other thrombophilic factors in patients with CSVT in a case control study. 相似文献6.
Brekenfeld C Remonda L Nedeltchev K Arnold M Mattle HP Fischer U Kappeler L Schroth G 《Journal of neurology, neurosurgery, and psychiatry》2007,78(3):280-285
Background
The PROACT II trial showed that intra‐arterial thrombolysis (IAT) is effective for treatment of acute ischaemic stroke attributable to M1 and M2 segment occlusions. Incidence of symptomatic intracranial haemorrhage (sICH) was 10%.Objective
: To evaluate the risk and predictors of sICH after IAT by using urokinase in a large number of patients presenting with the whole spectrum of cerebral vessel occlusions.Methods
294 patients with stroke treated with intra‐arterial urokinase were retrospectively analysed. The risk of sICH as well as bleeding characteristics were assessed. Demographic and radiological data, time to treatment, urokinase dose, recanalisation rates, stroke aetiology and severity were analysed for predictors.Results
sICH occurred in 14 of 294 (4.8%) patients. The median National Institute of Health Stroke Scale score of all patients was 15. All but one sICH were located in the infarcted brain tissue, and no sICH occurred in patients with peripheral vessel occlusions (M3 or M4 segments of the middle cerebral artery). Poor collaterals (p = 0.001), early signs of ischaemia on computed tomography (p = 0.003), higher urokinase dose (p = 0.019), lower recanalisation rate (p = 0.02) and higher diastolic blood pressure on admission (p = 0.04) were found to be correlated with sICH on univariate analysis. On multivariate analysis, poor collaterals (p = 0.004), urokinase dose (p = 0.021) and early signs on computed tomography (p = 0.026) remained predictors of sICH.Conclusions
With regard to the whole spectrum of cerebral vessel occlusions, an incidence of <5% sICH after IAT is distinctly low. This result underlines the important role of IAT in the treatment of acute stroke.The aim of treatment in acute ischaemic stroke is revascularisation as fast as possible. For this purpose, both intravenous thrombolysis (IVT) and intra‐arterial thrombolysis (IAT) have proved to be effective.1,2,3,4,5 The most devastating complication of both treatments is intracranial haemorrhage (ICH). ICH is categorised into haemorrhagic transformation, which is usually petechial and asymptomatic, and parenchymal haematomas without deterioration and those with clinical deterioration. Those with clinical deterioration are referred to as symptomatic ICH (sICH), which is associated with an increased mortality and occurs spontaneously in 0.6–4% of patients with ischaemic strokes. Thrombolysis increases the risk of sICH. Current literature reports wide ranges of incidence—for example, 3.3–21.2% for IVT and 0–14.3% for IAT.1,3,6,7,8,9,10,11,12,13,14The largest IAT series was the PROACT II trial reporting on a defined subgroup of patients with stroke (n = 180) exclusively with M1 and M2 segment occlusions of the middle cerebral artery (MCA).3This study was conducted to evaluate the risk of sICH in the whole spectrum of patients with large cerebral artery occlusions treated with IAT. Characteristics of patients with sICH were assessed and predictors analysed. 相似文献7.
Mínguez-Castellanos A Escamilla-Sevilla F Hotton GR Toledo-Aral JJ Ortega-Moreno A Méndez-Ferrer S Martín-Linares JM Katati MJ Mir P Villadiego J Meersmans M Pérez-García M Brooks DJ Arjona V López-Barneo J 《Journal of neurology, neurosurgery, and psychiatry》2007,78(8):825-831
Background
Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal models of Parkinson disease (PD).Objective
We conducted a phase I–II clinical study to assess the feasibility, long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with PD.Methods
Thirteen patients with advanced PD underwent bilateral stereotactic implantation of CB cell aggregates into the striatum. They were assessed before surgery and up to 1–3 years after surgery according to CAPIT (Core Assessment Programme for Intracerebral Transplantation) and CAPSIT‐PD (Core Assessment Programme for Surgical Interventional Therapies in Parkinson''s Disease) protocols. The primary outcome measure was the change in video blinded Unified Parkinson''s Disease Rating Scale III score in the off‐medication state. Seven patients had 18F‐dopa positron emission tomography scans before and 1 year after transplantation.Results
Clinical amelioration in the primary outcome measure was observed in 10 of 12 blindly analysed patients, which was maximal at 6–12 months after transplantation (5–74%). Overall, mean improvement at 6 months was 23%. In the long term (3 years), 3 of 6 patients still maintained improvement (15–48%). None of the patients developed off‐period dyskinesias. The main predictive factors for motor improvement were the histological integrity of the CB and a milder disease severity. We observed a non‐significant 5% increase in mean putaminal 18F‐dopa uptake but there was an inverse relationship between clinical amelioration and annual decline in putaminal 18F‐dopa uptake (r = −0.829; p = 0.042).Conclusions
CB autotransplantation may induce clinical effects in patients with advanced PD which seem partly related to the biological properties of the implanted glomus cells.Parkinson disease (PD) is a progressive neurodegenerative disorder of unknown aetiology. Its main pathological hallmark is the degeneration of midbrain dopaminergic neurons projecting to the striatum, although other neuronal systems are also affected.1 Current pharmacological and surgical therapies are symptomatically effective but their long term utility is limited because of disease progression.2,3 Therefore, there is a need for neuroprotective and/or neurorestorative therapies capable of arresting or reversing the neurodegenerative process.Over the past two decades, cell replacement therapies have been tested in PD patients with the objective of restoring the striatal dopaminergic deficit.4 Transplantation of fetal mesencephalic neurons, the most frequently used technique, can increase the striatal dopamine storage, but does not always produce the expected clinical benefit and may induce disabling off‐medication dyskinesias.5,6 Thus it appears that the ectopic placement of dopamine secreting cells in the striatum is not the ideal approach to compensate for progressive nigrostriatal neuronal loss.7 Given this scenario, the clinical applicability of other transplantation procedures based on a similar rationale (eg, intrastriatal grafting of porcine mesencephalic neurons, retinal pigment epithelial cells or stem cell derived dopaminergic neurons) is, for the moment, uncertain.More recently, other strategies aiming to protect or restore the nigrostriatal pathway have emerged. Glial cell line derived neurotrophic factor (GDNF) has been shown to exert neuroprotective and neurorestorative actions in animal models of PD.8,9,10 The clinical efficacy of GDNF has been assayed in clinical trials, but the method of delivery is a critical issue. Whereas intraventricular administration failed to induce clinical benefit,11 intraputaminal infusion showed promising results,12,13 although a placebo controlled trial using this route has been halted because of lack of efficacy and safety concerns about recombinant human GDNF administration.14 Other alternative methods being tested experimentally in parkinsonian animals include in vivo gene therapy using GDNF encoding viral vectors15,16,17 and the intrastriatal grafting of recombinant GDNF producing cell lines.18,19,20,21 Carotid body (CB) glomus cells are neural crest derived dopaminergic cells that express high levels of GDNF. Glomus cell GDNF production is resistant to 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine administration, and maintained in aged rodents or after intrastriatal grafting.22,23 The survival rate of these cells after transplantation (>70%) is particularly high as hypoxia stimulates their growth and function. Moreover, CB grafts performed in young rats remain active for the entire animal lifespan.22,23 Transplantation of CB cell aggregates has been shown to induce a neurotrophic mediated recovery in animal models of PD22,23,24,25,26,27 and stroke.28,29We conducted a phase I–II video blinded clinical study to assess the long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with advanced PD. In a pilot report of our first six patients, we showed this procedure to be feasible.30 Here we report the clinical outcomes and prognostic factors in the whole study (n = 13), as well as 18F‐dopa positron emission tomography (PET) outcomes in a subgroup of patients (n = 7). 相似文献8.
Verheyden G Nieuwboer A De Wit L Feys H Schuback B Baert I Jenni W Schupp W Thijs V De Weerdt W 《Journal of neurology, neurosurgery, and psychiatry》2007,78(7):694-698
Background and aim
Trunk performance is an important predictor of functional outcome after stroke. However, the percentage of explained variance varies considerably between studies. This may be explained by the stroke population examined, the different scales used to assess trunk performance and the time points used to measure outcome. The aim of this multicentre study was to examine the predictive validity of the Trunk Impairment Scale (TIS) and its subscales when predicting the Barthel Index score at 6 months after stroke.Methods
A total of 102 subjects were recruited in three European rehabilitation centres. Participants were assessed on admission (median time since stroke onset 20 days) and 6 months after stroke. Correlation analysis and forward stepwise multiple regression analysis were used to model outcome.Results
The best predictors of the Barthel Index scores at 6 months after stroke were total TIS score (partial R2 = 0.52, p<.0001) and static sitting balance subscale score (partial R2 = 0.50, p<.0001) on admission. The TIS score on admission and its static sitting balance subscale were stronger predictors of the Barthel Index score at 6 months than the Barthel Index score itself on admission.Conclusions
This study emphasises the importance of trunk performance, especially static sitting balance, when predicting functional outcome after stroke. The TIS is recommended as a prediction instrument in the rehabilitation setting when considering the prognosis of stroke patients. Future studies should address the evolution of trunk performance over time and the evaluation of treatment interventions to improve trunk performance.Although the age specific incidence of major stroke has fallen over the past few years,1 it is still the main cause of long term disability in adults, with a growing number of survivors being dependent for activities of daily living (ADL).2,3 Frequently identified variables predicting ADL after stroke are age and initial severity of motor and functional deficits.4 Trunk performance has also been identified as an important independent predictor of ADL after stroke.5,6,7,8,9 However, based on multiple regression analyses, the reported variance of functional outcome after stroke explained by trunk performance ranges from 9% to 71%.5,6,7,8,9 Differences in reported variance could be explained by the stroke population included, the various scales used to measure trunk performance and the time points used to measure outcome.Previous studies evaluating the predictive validity of trunk performance after stroke were performed in a single rehabilitation setting, warranting caution when generalising results.5,6,7,8,9,10 Clinical tools used to assess trunk performance are the Trunk Control Test,5,6,10 trunk control items of the Postural Assessment Scale for Stroke patients7,8 and trunk assessment of Fujiwara et al.9 A limitation of the first two tests is that they both have a ceiling effect, which makes their use less suitable in long term outcome studies.5,11,12,13 Furthermore, the trunk control items of the Trunk Control Test and Postural Assessment Scale for Stroke patients are largely comparable with the items of the trunk measure of Fujiwara et al.9 All previously mentioned clinical tools include items in the supine position which involve rolling as well as only basic balance movements in sitting. Finally, with the exception of the trunk control items of the Postural Assessment Scale for Stroke patients,8 no study has evaluated the prognostic value of trunk performance when predicting functional outcome at 6 months after stroke.The Trunk Impairment Scale (TIS) for patients after stroke was designed to measure ADL related selective trunk movements rather than participation of the trunk in gross transfer movements.14 The TIS assesses static and dynamic sitting balance and trunk coordination. Reliability, validity, measurement error, internal consistency and discriminant ability of the TIS have been reported elsewhere.14,15 The TIS has no ceiling effect in subacute and chronic stroke patients and already appeared to be strongly related to measures of gait, balance and functional ability in a cross sectional study.12 To the best of our knowledge, the predictive value of the TIS and its subscales has not been evaluated. Including age and other measures of motor and functional performance could provide a useful combination of variables predicting outcome after stroke. The Barthel Index score is a widely accepted measure in stroke rehabilitation research and assesses functional milestones in stroke recovery. Predicting Barthel Index scores at 6 months after stroke based on measurements taken on admission to a rehabilitation centre would further establish the importance of trunk performance when predicting long term outcome after stroke. Experts in the field of neurological rehabilitation have addressed the trunk as the central key point of the body.16 Proximal stability of the trunk is a prerequisite for distal head and limb movement and therefore expected to be related to functional ADL.In summary, there is still a lack of clarity regarding the importance of trunk performance in functional outcome after stroke. Scales which have been used in previous studies have important statistical limitations and are likely to be a comprehensive measure of motor performance of the trunk. Therefore, the aim of this multicentre study was to examine the predictive validity of the TIS and its subcomponents, together with other known predictors, in predicting functional outcome measured as a Barthel Index score at 6 months after stroke. 相似文献9.
Bonan IV Hubeaux K Gellez-Leman MC Guichard JP Vicaut E Yelnik AP 《Journal of neurology, neurosurgery, and psychiatry》2007,78(1):49-55
Background
Subjective visual vertical (SVV) perception can be perturbed after stroke, but its effect on balance recovery is not yet known.Aim
To evaluate the influence of SVV perturbations on balance recovery after stroke.Methods
28 patients (14 with a right hemisphere lesion (RHL) and 14 with a left hemisphere lesion (LHL)) were included, 5 were lost to follow‐up. SVV perception was initially tested within 3 months after stroke, then at 6 months, using a luminous line, which the patients adjusted to the vertical position in a dark room. Mean deviation (V) and uncertainty (U), defined as the standard deviation of the SVV, were calculated for eight trials. Balance was initially assessed by the Postural Assessment Scale for Stroke (PASS), and at 6 months by the PASS (PASS6), a force platform (lateral and sagittal stability limits (LSL6 and SSL6)), the Rivermead Mobility Index (RMI6) and gait velocity (v6). Functional outcome was also assessed by the Functional Independence Measure at 6 months (FIM6).Results
The scores for balance and for FIM6 were related to the initial V value: PASS6 (p = 0.01, τ = −0.38); RMI6 (p = 0.002, τ = −0.48), LSL6 (p = 0.06, τ = −0.29), SSL6 (p = 0.004, τ = −0.43), v6 (p = 0.01, τ = −0.36) and FIM6 (p = 0.001, τ = −0.49), as well as to the initial U value: PASS6 (p = 0.03, τ = −0.32), RMI6 (p = 0.02, τ = −0.35), SSL6 (p = 0.005, τ = −0.43) and FIM6 (p = 0.01, τ = −0.38).Conclusions
Initial misperception of verticality was related to a poor score for balance after stroke. This relationship seems to be independent of motricity and neglect. Rehabilitation programmes should take into account verticality misperceptions, which could be an important factors influencing balance recovery after stroke.Balance recovery is crucial for the acquisition of autonomy in patients with hemiplegia after stroke. In addition to weakness, increase in stiffness or sensory disorders leading to lower limb instability, recent articles have emphasised the role of space exploration disturbance, such as hemineglect in imbalance after stroke. Balance difficulties are more frequent and recovery takes a longer time after a right than after a left stroke, especially in patients with visuospatial neglect.1,2 An additional argument supporting the crucial role of space exploration disturbance in patients with balance disorder after stroke is that sensory stimulations such as vestibular caloric stimulation1 or neck transcutaneous electric nerve stimulation3 reduce simultaneously space disturbance and postural imbalance. Further, space exploration and balance seem to be closely linked, as the ability to perform space exploration depends on trunk orientation and vice versa in normal people as well as in patients with stroke.4,5,6,7,8,9 The assumption for this predominance of imbalance in patients with hemineglect and more generally in patients with right stroke is that spatial cognition is processed in the right hemisphere.1,10Nethertheless, disorders of spatial cognition after stroke are not limited to space exploration. Spatial abilities such as the sense of straight ahead,11 central space representation12 or perception of verticality can be perturbed after stroke.13,14,15 Such abilities can be assumed to have a major role in maintaining balance. To our knowledge, no systematic study has been conducted to assess the role of these abilities on balance recovery. Regarding the perception of visual verticality, which is tested in a dark room asking patients to adjust a luminous line to a vertical position, two kinds of perturbations have been described after hemispheric stroke: a mean tilt, most of the time contralateral to the cerebral lesion,13,14,15 and an excessive range of uncertainty between the different adjustments.14,15 In this study, we aimed to determine whether initial SVV misperceptions (abnormal tilt or uncertainty) influence balance recovery after stroke. The results would give new insight into postural disturbance after stroke and may change clinical practice. Rehabilitation programmes of postural control for patients with hemiplegia after stroke should take into account the possible impairment of verticality perception. 相似文献10.
Beare NA Riva CE Taylor TE Molyneux ME Kayira K White VA Lewallen S Harding SP 《Journal of neurology, neurosurgery, and psychiatry》2006,77(11):1288-1290
Objective
To investigate capillary blood flow in the optic nerve head (ONH) of children with cerebral malaria.Methods
Malawian children with cerebral malaria admitted to a paediatric research ward were examined by direct and indirect ophthalmoscopy. ONH blood flow was measured using laser Doppler flowmetry (LDF) in suitable patients. Mean blood volume and velocity were obtained from 30 to 60 s recordings from the temporal ONH and used to calculate blood flow. These were compared with admission variables, funduscopic findings and disease outcomes.Results
45 children with cerebral malaria had LDF recordings; 6 subsequently died and 5 survivors had neurological sequelae. 12 (27%) had papilloedema. The mean microvascular blood volume was higher in patients with papilloedema (3.28 v 2.54 arbitrary units, p = 0.002). The blood velocity correlated directly with haematocrit (r = 0.46, p = 0.001) and inversely with blood glucose (r = −0.49, p = 0.001).Conclusion
The increase in ONH microvascular blood volume in papilloedema measured by LDF is consistent with current theories of pathogenesis of papilloedema. LDF has potential as a tool to distinguish papilloedema from pseudopapilloedematous disc swellings. The relationship between blood velocity and haematocrit may relate to levels of sequestration in cerebral malaria.Cerebral malaria, caused by Plasmodium falciparum, primarily affects children in sub‐Saharan Africa with mortality ranging from 15% to 50%. The characteristic histological feature of malaria caused by P falciparum is sequestration of parasitised erythrocytes within the microvasculature by cytoadherence. This occurs in the brain1,2,3 and other organs, including the retina.4 Sequestration in small vessels is implicated in the pathogenesis of coma in cerebral malaria, although the mechanism remains unclear.5Papilloedema occurs in 10–15% of patients with cerebral malaria, increasing the risk of death by 4.5‐fold.6,7 Other ocular fundus features associated with cerebral malaria are retinal whitening, orange or white vessels, and retinal haemorrhage.6,7,8,9 As in other neurological conditions, papilloedema is associated with raised intracranial pressure.5 The pathogenesis of papilloedema is associated with increased pressure within the optic nerve sheath, a compartment in contact with the subarachnoid space. This leads to interruption of axoplasmic flow in the optic nerve fibres, resulting in swelling of their prelaminar portion.10,11 The exact mechanism of this restriction and the importance of vascular changes remain unclear.12The optic nerve head (ONH) is an accessible element of the central nervous system (CNS), and measuring blood flow in the ONH could illuminate the pathogenic mechanisms in cerebral malaria. Laser Doppler flowmetry (LDF) is a non‐invasive method of measuring blood flow in the ONH using the Doppler shift in laser light scattered by moving erythrocytes. By directing the laser away from visible blood vessels the microcirculation can be sampled. The mean relative blood velocity and volume are computed from the spectrum of Doppler frequency shifts. The volume is derived from the width of the Doppler shift spectrum, and the velocity from the magnitude of Doppler shifts. LDF has proved useful in physiological studies of ONH blood flow13,14,15,16 and of glaucoma.17 A feasibility study of LDF in cerebral malaria produced promising results.18We report a study of ONH microcirculation in children with cerebral malaria in relation to clinical parameters, particularly papilloedema. 相似文献11.
Hoogman M van de Beek D Weisfelt M de Gans J Schmand B 《Journal of neurology, neurosurgery, and psychiatry》2007,78(10):1092-1096
Objective
To evaluate cognitive outcome in adult survivors of bacterial meningitis.Methods
Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls.Results
Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p<0.001) and tended to be cognitively slower than survivors of meningococcal meningitis (p = 0.08). We found a diffuse pattern of cognitive impairment in which cognitive speed played the most important role. Cognitive performance was not related to time since meningitis; however, there was a positive association between time since meningitis and self‐reported physical impairment (p<0.01). The frequency of cognitive impairment and the numbers of abnormal test results for patients with and without adjunctive dexamethasone were similar.Conclusions
Adult survivors of bacterial meningitis are at risk of cognitive impairment, which consists mainly of cognitive slowness. The loss of cognitive speed is stable over time after bacterial meningitis; however, there is a significant improvement in subjective physical impairment in the years after bacterial meningitis. The use of dexamethasone was not associated with cognitive impairment.The estimated annual incidence of bacterial meningitis is 4–6 per 100 000 adults and Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the causative bacteria in 80% of cases.1,2 Fatality rates in patients with pneumococcal meningitis (26%) and meningococcal meningitis (7%) are significant.1,2,3 Even in patients with apparent good recovery, cognitive impairment occurs frequently,4 especially after pneumococcal meningitis.4,5,6 The cognitive functions affected by bacterial meningitis differ between studies, most likely because of the limited numbers of patients examined, and the lack of uniformity across studies in assessment methods and in the definition of cognitive impairment.4,5,6,7,8,9,10 We therefore pooled data on cognitive outcome after bacterial meningitis from three of our previous studies to more clearly determine which cognitive functions are affected by bacterial meningitis and to identify which patients are at risk of developing cognitive impairment. 相似文献12.
Yelnik AP Colle FM Bonan IV Vicaut E 《Journal of neurology, neurosurgery, and psychiatry》2007,78(8):845-848
Objective
This randomised, double blind, placebo controlled, two parallel group study was conducted to assess the beneficial effect of injection of botulinum toxin A (Dysport) into the subscapularis muscle on shoulder pain in stroke patients with spastic hemiplegia.Methods
A single dose of botulinum toxin A (500 Speywood units) or placebo was injected into the subcapularis muscle. Pain was assessed using a 10 point verbal scale. Subscapularis spasticity was assessed by the change in passive shoulder lateral rotation and abduction. Upper limb spasticity was assessed using the Modified Ashworth Scale for shoulder medial rotators, and elbow, wrist and finger flexors. Assessments were carried out at baseline and at weeks 1, 2 and 4.Results
Twenty patients (10 patients per group), 11 with ischaemic stroke and 9 with haemorrhagic stroke, completed the study. Pain improvement with botulinum toxin A was observed from week 1; score difference from baseline at week 4 was 4 points versus 1 point with placebo (p = 0.025). Lateral rotation was also improved, with a statistically significant difference compared with placebo at week 2 (p = 0.05) and week 4 (p = 0.018). A general improvement in upper limb spasticity was observed; it was significant for finger flexors at week 4 (p = 0.025).Conclusions
Subscapularis injection of botulinum toxin A appears to be of value in the management of shoulder pain in spastic hemiplegic patients. The results confirm the role of spasticity in post‐stroke shoulder pain.Pain and spastic shoulder are frequent in hemiplegia following a stroke. Shoulder pain is a major problem for these patients, interfering with physiotherapy, sleep and daily activities. It is usually due to local causes: algoneurodystrophy (shoulder–hand syndrome), capsulitis, gleno‐humeral subluxation and also spasticity because of the prolonged muscular contracture and possible tendinopathies.1,2,3,4 These causes can be associated, especially spasticity and algoneurodystrophy in severe hemiplegia, and patients exhibit the typical arm posture: adduction and medial rotation of the shoulder, and flexion of the elbow, wrist and finger.Different approaches are used for treatment of pain in such patients, depending on the mechanism involved. Oral medications for pain, as those for spasticity, are usually ineffective or insufficient. Treatment of algoneurodystrophy and capsulitis mainly consists of corticosteroids, systemic treatment being more effective than local administration.3,5 To treat spasticity or its consequences, transection of the subscapularis tendon6,7 or subcapularis nerve block8,9 has been reported, but these treatments are not in common use. Botulinum toxin A has been shown to be effective in reducing spasticity and increasing the passive range of motion of the spastic upper limb in hemiplegic patients10,11,12,13,14 with a real functional benefit.15 The effect of botulinum toxin A on shoulder pain after a stroke has not been systematically studied. However, improvement of pain by the toxin has been reported in a placebo controlled study, although pain was not the main objective of the study.15 A beneficial effect has also been observed in an open study.16 Other controlled studies in which upper limb pain was assessed failed to show a significant reduction in pain.10,11,12No specific treatment of the spastic shoulder muscles has been studied. Suprasupinator and infrasupinator muscles are not involved in painful contracted shoulder,17 and among the muscles implicated in medial rotation, the subscapularis and pectoralis muscles undoubtedly play a major role,18 with apparent pre‐eminence of the subscapularis muscle.19 In a recent study of three cases, injection of botulinum toxin A into the subscapularis muscle was shown to reduce pain and improve the passive range of motion.18Based on these observations, we formed the hypothesis that shoulder pain occurring in patients with spastic hemiplegia, even with limited range of motion compatible with capsulitis, can be relieved by reducing the spasticity of the main medial rotator muscle (ie, the subscapularis muscle). Therefore, we conducted the present study to further assess the beneficial effect of injection of botulinum toxin A (Dysport) into the subscapularis muscle on shoulder pain. An improvement in the passive range of motion was expected as a parameter of the efficacy of botulinum toxin on spasticity and as a possible secondary benefit. 相似文献13.
Petzold A Keir G Kay A Kerr M Thompson EJ 《Journal of neurology, neurosurgery, and psychiatry》2006,77(6):753-759
Background
On the basis of preliminary evidence from patients with subarachnoid haemorrhage (SAH), axonal degeneration is thought to be an underestimated pathological feature.Methods
A longitudinal study in 17 patients with aneurysmal SAH. Ventricular CSF was collected daily for up to 14 days. The neurofilament heavy chainSMI35 (NfHSMI35, a biomarker for axonal damage) was quantified using a standard ELISA (upper limit of normal 0.73 ng/ml). The primary outcome measure was the Glasgow Outcome Score (GOS) at 3 months.Results
Of 148 samples from patients with SAH, pathologically high NfH levels in the CSF were found in 78 (52.7%) samples, compared with 20 (5%) of 416 samples from the reference population (p<0.0001). A pathological increase in NfH was observed in all patients with a bad outcome (GOS 1–3) compared with 8% of those with a good outcome (GOS 4–5, p<0.0001). This increase typically became significant 7 days after the haemorrhage (p<0.01). The result was confirmed by analysing the individual mean NfH concentrations in the CSF (3.45 v 0.37 ng/ml, p<0.01), and was reinforced by the inverse correlation of NfH in the CSF with the GOS (r = −0.65, p<0.01). Severity of injury was found to be correlated to NfHSMI35 levels in the CSF (World Federation of Neurological Surgeons, r = 0.63, p<0.01 and Glasgow Coma Score, r = −0.61, p<0.01).Conclusion
Patients with SAH thus have secondary axonal degeneration, which may adversely affect their outcome.The presence of axonal degeneration in patients with subarachnoid haemorrhage (SAH) has recently been suggested in a longitudinal study.1 One important finding was that damage to axons may continue after the primary injury and extend into the period of delayed cerebral ischaemia.1,2,3,4Presence of secondary axonal degeneration in patients with SAH may be relevant to the outcome because, despite the high mortality (32–67%) during the hyperacute phase,2,5 a considerable proportion of mostly young and otherwise healthy patients has the potential for good recovery from a limited degree of primary injury. In these patients, it is well known that secondary brain damage caused by delayed cerebral ischaemia adversely affects the potential for recovery.2,3,4 About 50% of patients who survive do not return to their previous level of employment.6,7,8In this longitudinal study, we monitored the development of axonal degeneration indirectly by measuring a biomarker for axonal degeneration (neurofilaments, reviewed by Petzold9). Firstly, we investigated whether neurofilaments would be increased early on (eg, a single peak, indicative of primary axonal injury) or rise late (eg, secondary peaks, suggestive of secondary axonal damage) in the disease course. Secondly, we tested whether the pattern of an anticipated1 increase in neurofilament levels over time would be related to the degree of recovery. 相似文献14.
Contarino MF Daniele A Sibilia AH Romito LM Bentivoglio AR Gainotti G Albanese A 《Journal of neurology, neurosurgery, and psychiatry》2007,78(3):248-252
Aim
To assess the long‐term cognitive and behavioural outcome after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients affected by Parkinson''s disease, with a 5‐year follow‐up after surgery.Methods
11 patients with Parkinson''s disease treated by bilateral DBS of STN underwent cognitive and behavioural assessments before implantation, and 1 and 5 years after surgery. Postoperative cognitive assessments were carried out with stimulators turned on.Results
A year after surgery, there was a marginally significant decline on a letter verbal fluency task (p = 0.045) and a significant improvement on Mini‐Mental State Examination (p = 0.009). 5 years after surgery, a significant decline was observed on a letter verbal fluency task (p = 0.007) and an abstract reasoning task (p = 0.009), namely Raven''s Progressive Matrices 1947. No significant postoperative change was observed on other cognitive variables. No patient developed dementia 5 years after surgery. A few days after the implantation, two patients developed transient manic symptoms with hypersexuality and one patient developed persistent apathy.Conclusion
The decline of verbal fluency observed 5 years after implantation for DBS in STN did not have a clinically meaningful effect on daily living activities in our patients with Parkinson''s disease. As no patient developed global cognitive deterioration in our sample, these findings suggest that DBS of STN is associated with a low cognitive and behavioural morbidity over a 5‐year follow‐up, when selection criteria for neurosurgery are strict.Chronic bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective neurosurgical procedure for treatment of motor symptoms in patients with advanced Parkinson''s disease, who cannot be satisfactorily treated with pharmacological treatments. The safety of this procedure has been investigated by several studies, which have assessed the effects of STN DBS on cognition and behaviour.1,2,3 Some investigations have also attempted to distinguish between the cognitive effects of surgical intervention and those of DBS of STN in itself.4,5,6,7All neuropsychological investigations in patients treated by STN DBS showed a postoperative decline of verbal fluency, whereas less consistent effects have been reported on other cognitive tasks in different studies. A postoperative decline of episodic verbal memory, which was detectable 3 months after surgery, has been reported in some investigations.6,8Different effects of STN DBS on various frontal cognitive functions have been described. STN stimulation may impair response‐inhibition performance on the interference task of the Stroop test, as compared with the off‐stimulation condition.5,7,9 A positron emission tomography study showed that such impaired performance on the Stroop test in the on‐stimulation condition is associated with decreased activation in both the right anterior cingulate cortex and the right ventral striatum.9 Conversely, short‐term STN stimulation may improve performance on cognitive flexibility tasks, including random number generation7 and the Modified Wisconsin Card Sorting Test (MWCST).5Various behavioural effects have been described in patients with Parkinson''s disease treated by STN DBS. Some studies reported cases of depression10 or increased apathy,11 whereas cases of mania were described in other studies12,13,14 and an improvement of depression1 or apathy15 was also found.The long‐term cognitive and behavioural effects of bilateral STN DBS were investigated in 70 patients with Parkinson''s disease followed up for 3 years.11 In this study, a decline of verbal fluency, an improvement of depression and an increased apathy were observed 3 years after surgery. Some patients showed behavioural changes (aggressive behaviour, hypomania, depression and psychosis), which were mostly transient. Recently, the long‐term outcome of bilateral DBS of STN was investigated in a multicentre study conducted in 49 patients with Parkinson''s disease followed up for 3 or 4 years.16 This study showed that stimulation of the STN induced a significant improvement in Parkinsonian motor symptoms and activities of daily living 3–4 years after surgery. Among the adverse events, the authors reported memory decline or psychiatric disturbances (including hallucinations, delirium, depression, apathy and anxiety), which occurred in about 30% of the patients.In two recent investigations, the long‐term outcome of bilateral DBS of STN was investigated in patients with a 5‐year follow‐up.17,18 In one study conducted on 49 patients with Parkinson''s disease,17 cognitive performance was assessed by means of the Mattis Dementia Rating Scale (MDRS)19 and a frontal‐lobe score.4 Five years after surgery, there was a marked improvement of both motor function, while off drugs, and activities of daily living, a statistical trend towards a decline on the MDRS (reflecting the appearance of progressive dementia in three patients between the third and the fifth postoperative years) and a significant decline in the average frontal‐lobe score. Another study carried out on 37 patients with Parkinson''s disease18 also assessed cognitive performance by means of MDRS19 and a frontal score.20 Five years after the implantation, there was an improvement in Parkinsonian motor symptoms and activities of daily living and a reduction of levodopa‐related motor complications and levodopa daily doses. However, a significant decline in cognitive performance was detected on the MDRS and the frontal score.To our knowledge, no extensive neuropsychological data have been reported so far in patients with a follow‐up >3 years. The aim of the present study was to assess the long‐term cognitive and behavioural outcome after bilateral DBS of the STN in a series of patients followed up for 5 years after surgery. 相似文献15.
Leocani L Rovaris M Boneschi FM Medaglini S Rossi P Martinelli V Amadio S Comi G 《Journal of neurology, neurosurgery, and psychiatry》2006,77(9):1030-1035
Background
Evoked potentials are used in the functional assessment of sensory and motor pathways. Their usefulness in monitoring the evolution of multiple sclerosis has not been fully clarified.Objective
The aim of this longitudinal study was to examine the usefulness of multimodal evoked potential in predicting paraclinical outcomes of disease severity and as a prognostic marker in multiple sclerosis.Methods
Eighty four patients with clinically definite multiple sclerosis underwent Expanded Disability Status Scale (EDSS) and functional system scoring at study entry and after a mean (standard deviation) follow‐up of 30.5 (11.7) months. Sensory and motor evoked potentials were obtained in all patients at study entry and at follow‐up in 64 of them, and quantified according to a conventional score.Results
Cross‐sectionally, the severity of each evoked potential score significantly correlated with the corresponding functional system (0.3216.
Kim SM Lee KM Hong YH Park KS Yang JH Nam HW Sung JJ Lee KW 《Journal of neurology, neurosurgery, and psychiatry》2007,78(12):1387-1389
Background
Many patients with amyotrophic lateral sclerosis (ALS) with cognitive impairment have fronto‐temporal dysfunction. Whereas in some patients with ALS the fronto‐temporal dysfunction is undoubtedly due to the degenerative process associated with the disease, in others dysfunction cannot be accounted for by an irreversible degenerative process alone, as it also appears to involve a reversible process. We hypothesised that reduced vital capacity can be a key contributor to the fronto‐temporal dysfunction observed in patients with ALS.Objective
To investigate the association between fronto‐temporal dysfunction and reduced vital capacity in ALS.Methods
16 consecutive patients who conformed to a diagnosis of definite or probable ALS (El escorial criteria) were grouped by vital capacity, and their clinical characteristics and cognitive functions, including disease duration, attention, executive function and memory, were measured.Results
Patients with a reduced vital capacity performed significantly poorer in memory retention (p = 0.028), retrieval efficacy (p = 0.003), spoken verbal fluency (p = 0.03) and spoken verbal fluency indexes (p = 0.016) than those with a normal vital capacity.Conclusion
The fronto‐temporal dysfunction in ALS might be attributable to potentially reversible secondary effects associated with reduced vital capacity, as well as to the primary degenerative process.Amyotrophic lateral sclerosis (ALS) is traditionally considered as a degenerative disease exclusively of the motor system, but recent studies revealed cognitive impairment in up to 50% of patients with ALS.1,2 Also, the most common pattern of cognitive impairment is fronto‐temporal dysfunction.1,2,3Whereas in some patients with ALS the fronto‐temporal dysfunction is undoubtedly due to the degenerative process associated with the disease, in others dysfunction cannot be accounted for by an irreversible degenerative process alone, as it also appears to involve a reversible process. The reasons for suspecting non‐degenerative reversible causes of cognitive dysfunction in ALS include: (1) improved cognitive function by non‐invasive positive pressure ventilation over 6 weeks in ALS,4 (2) significant difference in mean forced vital capacity (FVC) between patients with ALS with fronto‐temporal lobar dementia and those without (66% vs 95% predicted),1 (3) neuronal loss, gliosis, sponginess in the hippocampus and parahippocampal area which is vulnerable to hypoxia,5 according to the brain pathology of ALS patients with frontal lobe dysfunction6 and (4) cognitive impairment in patients with sleep disordered breathing, characterised as fronto‐temporal dysfunction.7 These findings appear to indicate that not only a degenerative process but also ventilatory status can be a key contributor to the cognitive dysfunction observed in patients with ALS, and that the reversible secondary fronto‐temporal dysfunction might be misinterpreted as irreversible symptoms of degenerative process. Thus, in this study, we measured cognitive function related to the frontal and temporal lobes and investigated their associations with the ventilatory status of the patient. 相似文献17.
Cronin S Greenway MJ Prehn JH Hardiman O 《Journal of neurology, neurosurgery, and psychiatry》2007,78(9):984-986
Background
The paraoxonases, PON1–3, play a major protective role both against environmental toxins and as part of the antioxidant defence system. Recently, non‐synonymous coding single nucleotide polymorphisms (SNPs), known to lower serum PON activity, have been associated with sporadic ALS (SALS) in a Polish population. A separate trio based study described a detrimental allele at the PON3 intronic variant INS2+3651 (rs10487132). Association between PON gene cluster variants and SALS requires external validation in an independent dataset.Aims
To examine the association of the promoter SNPs PON1−162G>A and PON1−108T>C; the non‐synonymous functional SNPs PON1Q192R and L55M and PON2C311S and A148G; and the intronic marker PON3INS2+3651A>G, with SALS in a genetically homogenous population.Methods
221 Irish patients with SALS and 202 unrelated control subjects were genotyped using KASPar chemistries. Statistical analyses and haplotype estimations were conducted using Haploview and Unphased software. Multiple permutation testing, as implemented in Unphased, was applied to haplotype p values to correct for multiple hypotheses.Results
Two of the seven SNPs were associated with SALS in the Irish population: PON155M (OR 1.52, p = 0.006) and PON3INS2+3651 G (OR 1.36, p = 0.03). Two locus haplotype analysis showed association only when both of these risk alleles were present (OR 1.7, p = 0.005), suggesting a potential effect modification. Low functioning promoter variants were observed to influence this effect when compared with wild‐type.Conclusions
These data provide additional evidence that genetic variation across the paroxanase loci may be common susceptibility factors for SALS.Epidemiological evidence suggests that environmental factors may contribute to the risk of sporadic amyotrophic lateral sclerosis (SALS). Such factors include insecticides, pesticides, arylesterases1,2 and oxidants in cigarette smoke.3 The incidence of SALS is increased in Gulf war veterans who may have been exposed to exogenous neurotoxins.4 These observations have led to the proposition that genetic determinants known to increase susceptibility to exogenous compounds may also increase the risk of SALS.5The human paraoxonase (PON) gene cluster is located on chromosome 7q21.3. The cluster comprises three genes ordered PON1, PON3 and PON2, with PON1 being the most centromeric.6 The PON1 enzyme acts as the major protective mechanism by which toxic exogenous compounds are hydrolysed in serum.7,8 PON1 has four common functional polymorphisms, two non‐synonymous coding single nucleotide polymorphisms (SNPs) (PON1Q192R and PON1L55M) which alter enzyme activity,9,10 and two promoter SNPs (PON1‐108T>C and PON1‐162G>A) which affect expression levels.11 PON2 and PON3 do not appear to have detoxifying activity, but along with PON1 have important roles in protecting against lipid peroxidation.13,14 Non‐synonymous coding polymorphisms associated with PON2 activity include PON2C311S and PON2A148G.15,16 The risk alleles, associated with lower PON activity, are PON1192R, 55M, −108T and −162G and PON2311C and 148G.9,10,11,12,13,14,15,16Two recent studies have reported associations between PON gene cluster polymorphisms and increased risk for SALS. The first reported an association of PON1192R and PON2311C with SALS in a Polish population.17 A separate haplotype study of trio pedigrees in the US observed an important intronic marker in PON3 (PON3INS2+3651A>G or rs10487132).18Reproduction of association in independent populations is of substantial importance to support the hypothesis that PON cluster polymorphisms modify the risk for SALS. Here we test for the association of PON cluster variants with SALS in an Irish population. We selected variants with previous association or an established biological role in PON kinetics, and explored the influence of PON promoter polymorphisms and the PON3 intronic variant. 相似文献18.
Logina I Krumina A Karelis G Elsone L Viksna L Rozentale B Donaghy M 《Journal of neurology, neurosurgery, and psychiatry》2006,77(12):1350-1353
Background
In Latvia and other endemic regions, a single tick bite has the potential to transmit both tick‐borne encephalitis (TBE) and Lyme borreliosis.Objective
To analyse both the clinical features and differential diagnosis of combined tick‐borne infection with TBE and Lyme borreliosis, in 51 patients with serological evidence, of whom 69% had tick bites.Results
Biphasic fever suggestive of TBE occurred in 55% of the patients. Meningitis occurred in 92%, with painful radicular symptoms in 39%. Muscle weakness occurred in 41%; in 29% the flaccid paralysis was compatible with TBE. Only two patients presented with the bulbar palsy typical of TBE. Typical Lyme borreliosis facial palsy occurred in three patients. Typical TBE oculomotor disturbances occurred in two. Other features typical of Lyme borreliosis detected in our patients were distal peripheral neuropathy (n = 4), arthralgia (n = 9), local erythema 1–12 days after tick bite (n = 7) and erythema chronicum migrans (n = 1). Echocardiogram abnormalities occurred in 15.Conclusions
Patients with double infection with TBE and Lyme borreliosis fell into three main clinical groups: febrile illness, 3 (6%); meningitis, 15 (30%); central or peripheral neurological deficit (meningoencephalitis, meningomyelitis, meningoradiculitis and polyradiculoneuritis), 33 (65%). Systemic features pointing to Lyme borreliosis were found in 25 patients (49%); immunoglobulin (Ig)M antibodies to borreliosis were present in 18 of them. The clinical occurrence of both Lyme borreliosis and TBE vary after exposure to tick bite, and the neurological manifestations of each disorder vary widely, with considerable overlap. This observational study provides no evidence that co‐infection produces unusual manifestations due to unpredicted interaction between the two diseases. Patients with tick exposure presenting with acute neurological symptoms in areas endemic for both Lyme borreliosis and TBE should be investigated for both conditions. The threshold for simultaneous treatment of both conditions should be low, given the possibility of co‐occurrence and the difficulty in ascribing individual neurological manifestations to one condition or the other.The Baltic region is an endemic focus for both tick‐borne encephalitis (TBE) and Lyme borreliosis transmitted by ticks.1,2,3,4 In Latvia, 7061 cases of TBE and 3566 cases of Lyme borreliosis were registered between 1994 and 2003, out of a population of 2.4 million. Both tick species present in Latvia, Ixodes ricinus and persulcatus, can transmit the encephalitis virus, the borreliosis spirochete and more rarely erlichiosis. A single tick bite has the potential to transmit both infections.5 Despite their different clinical courses, TBE and Lyme borreliosis have neurological features in common: lymphocytic meningitis, flaccid or spastic limb weakness and cranial nerve involvement. Thus, differentiating between these disorders is important, given different approaches to treatment.Of the two infections, only TBE runs a biphasic course with the initial prodomal period of influenza‐like symptoms usually developing 1–2 weeks after the tick bite. Hence, after an asymptomatic period lasting 2–10 days, about a third of infected patients enter a second phase with aseptic meningitis.2 Subsequently, 2–10% in Western TBE subtype or 10–25% in Eastern TBE subtype develop encephalitis, myelitis or meningoencephalomyelitis typically manifesting as combinations of flaccid paresis of the limbs, usually arms and neck, bulbar dysfunction, disorientation, aphasia and spastic paresis.1,2 A poliomyelitis‐like syndrome is described in central European TBE.6 Manifestations of TBE in the Baltic may be heterogeneous, given that infection with the Western, Far Eastern and Siberian subtypes all cause human infection in Latvia.7 Although severe manifestations usually subside after 3–6 weeks, the convalescence period of TBE may be very long, with nearly 40% having a postencephalitic syndrome at 4 years.8 The uptake of TBE vaccination is increasing in the Baltic region.Classical Lyme borreliosis differs considerably from TBE and produces local and generalised forms, systemic involvement, and development over several stages. Its acute and chronic courses pose problems of diagnosis and management.1,9 Diagnosis of neuroborreliosis requires a definite or possible tick bite, erythema migrans or seropositivity, and typical peripheral or central nervous system involvement.10 In early neuroborreliosis (2–10 weeks after tick bite) the most common neurological abnormalities are meningitis, meningoradiculoneuritis and cranial neuritis, particularly facial palsy.1,9,10,11 Progressive chronic encephalomyelitis, polyneuritis and cerebrovascular disorders are later manifestations of Lyme borreliosis, usually occurring months after the initial infection. Neurological features are noted in 10–12% of all patients with Lyme borreliosis in Europe1 and in 10–15% of patients in Northern America.11 Neurological manifestations in 330 European patients with Lyme borreliosis included radicular pain (70%), headache (18%), peripheral paresis (45%), central paresis (4%), sensory disturbances (44%) and facial palsy (39%).1 Borrelia infection takes a subclinical or minimally symptomatic course in up to 80% of the population after tick bites.12 Importantly, borreliosis is treatable with antibiotics.TBE infection can be proven by specific and sensitive ELISA detection of antibody in cerebrospinal fluid (CSF), or by detection of genome through polymerase chain reaction.13 Serum IgM antibodies can remain positive for ⩾10 months.2,14 By contrast, serological tests for Lyme borreliosis infection are less sensitive and specific to variable onset and occurrence of specific IgM and IgG antibodies, with recognised persistent seronegatives; direct detection of a pathogen is rarely possible, and reliance must be placed on interpreting the laboratory investigations in the light of the clinical picture.13,15,16 Demonstration of intrathecal antibody production provides a specific test,17 but is not sensitive in detecting all forms of neuroborreliosis.15 Despite their different clinical courses, TBE and Lyme borreliosis have neurological features in common: lymphocytic meningitis, flaccid or spastic limb weakness, and cranial nerve involvement. Pain, particularly in a radicular distribution, and sensory disturbance are regarded as features more typical of Lyme borreliosis than TBE.Only limited information on double infection with TBE and Lyme borreliosis is available. Single cases, small series or serologically defined series with limited clinical information are described from Germany, Slovenia, Central Russia and Finland.18,19,20,21,22,23,24 This retrospective clinical observational study analyses the clinical features and problems of differential diagnosis in patients with evidence of both TBE and Lyme borreliosis infection in Latvia. 相似文献19.
Lehmann DJ Refsum H Nurk E Warden DR Tell GS Vollset SE Engedal K Nygaard HA Smith AD 《Journal of neurology, neurosurgery, and psychiatry》2006,77(8):902-908
Background
Among elderly people without dementia, the apolipoprotein E ε4 allele (APOE4) has been associated with cognitive deficit, particularly in episodic memory, but few reports are available on whether this association differs by sex.Methods
In a community‐dwelling Norwegian cohort of 2181 elderly people (55% women), aged 70–74 years, episodic memory was examined in relation to sex and APOE4 zygosity, with the Kendrick Object Learning Test (KOLT).Results
Possession of at least one APOE4 allele had a modest, detrimental effect on episodic memory in women, whereas in men, heterozygotes were unaffected and homozygotes had markedly lower scores across the distribution of KOLT scores. This sex difference was found consistently in all analyses: on comparing means and medians, examining trends across quintiles, and studying the distribution of scores and the risk of cognitive impairment. Results were broadly similar when adjusted for known determinants of cognition and also when severely impaired participants were excluded. The adjusted odds ratio (OR) of cognitive impairment in women was shown to be 1.8 (95% confidence interval (CI): 1.1 to 2.8) for heterozygotes and 1.1 (0.3 to 3.7) for homozygotes; the adjusted OR in men was observed to be 1.1 (0.6 to 2.1) for heterozygotes and 10.7 (4.7 to 24) for homozygotes.Conclusions
Although the harmful effect of APOE4 on episodic memory was modest in women, the risk was found to occur in about 30%. APOE4 was observed to have a dramatic effect on episodic memory in men, but only in homozygotes, who comprised about 3% of men: the whole male homozygous group showed a marked shift to lower memory scores.Age and the apolipoprotein E ε4 allele (APOE4) are the most important known risk factors for sporadic Alzheimer''s disease. The disease is thought to have a long presymptomatic phase,1 which suggests that APOE4 starts exerting its detrimental effects in the preclinical phase. Most studies on elderly people without dementia have found that the APOE4 allele is associated with various cognitive deficits,2,3,4,5,6,7,8,9,10,11,12,13,14 particularly in memory.2,3,4,5,6,7 A recent meta‐analysis of more than 20 000 people concluded that this allele was associated with poorer performance on tests of global cognitive functioning, episodic memory and executive functioning.15The association of APOE4 with Alzheimer''s disease varies with sex.16,17,18,19,20 The meta‐analysis by Farrer et al20 found that APOE4 homozygosity affords a high risk of Alzheimer''s disease for both men and women, but that a single copy of the allele confers a greater risk on women than on men. A similar sex difference related to APOE4 has been found in the degree of hippocampal atrophy in a cohort with mild cognitive impairment.21 We may therefore expect to find an effect related to sex of the APOE4 allele in cognitive tests in elderly people without dementia. Two studies3,22 that have reported an influence of sex on this relationship found a stronger effect of APOE4 in women.3,22In this study, we investigated whether sex influences the relationship between APOE alleles and episodic memory in community‐dwelling elderly people. We selected episodic memory because memory deficit is a hallmark of Alzheimer''s disease. Tests of episodic memory have been found to be particularly effective in identifying people at risk.23,24 We compared the influence of sex in our cohort with that found on the risk of Alzheimer''s disease. We studied a relatively large group of 2181 people from western Norway. 相似文献20.
Pritchard AL Harris J Pritchard CW Coates J Haque S Holder R Bentham P Lendon CL 《Journal of neurology, neurosurgery, and psychiatry》2007,78(2):123-126