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Biomedical subjects

K Dujardin

Publications and source records attributed to K Dujardin.

At least 19 recordsLinked to original sources
PubMed2006

Improvement of gait by chronic, high doses of methylphenidate in patients with advanced Parkinson's disease.

BACKGROUND: Therapeutic management of gait disorders in patients with advanced Parkinson's disease (PD) can sometimes be disappointing, since dopaminergic drug treatments and subthalamic nucleus (STN) stimulation are more effective for limb-related parkinsonian signs than for gait disorders. Gait disorders could also be partly related to norepinephrine system impairment, and the pharmacological modulation of both dopamine and norepinephrine pathways could potentially improve the symptomatology. AIM: To assess the clinical value of chronic, high doses of methylphenidate (MPD) in patients with PD having gait disorders, despite their use of optimal dopaminergic doses and STN stimulation parameters. METHODS: Efficacy was blindly assessed on video for 17 patients in the absence of L-dopa and again after acute administration of the drug, both before and after a 3-month course of MPD, using a Stand-Walk-Sit (SWS) Test, the Tinetti Scale, the Unified Parkinson's Disease Rating Scale (UPDRS) part III score and the Dyskinesia Rating Scale. RESULTS: An improvement was observed in the number of steps and time in the SWS Test, the number of freezing episodes, the Tinetti Scale score and the UPDRS part III score in the absence of L-dopa after 3 months of taking MPD. The L-dopa-induced improvement in these various scores was also stronger after the 3-month course of MPD than before. The Epworth Sleepiness Scale score fell dramatically in all patients. No significant induction of adverse effects was found. INTERPRETATION: Chronic, high doses of MPD improved gait and motor symptoms in the absence of L-dopa and increased the intensity of response of these symptoms to L-dopa in a population with advanced PD.

Aged↗
PubMed2006

A biomechanical study of gait initiation in Huntington's disease.

BACKGROUND: Akinesia in basal ganglia disorders is essentially defined by delayed movement initiation; the reaction time increases and it becomes difficult (or even impossible) for the subject to initiate movement. A biomechanical study of gait initiation would help evaluate the role of akinesia in early stage Huntington's disease (HD) patients. METHODS: We recorded kinematic, spatiotemporal and angular parameters (using video motion analysis, a force platform and an optoelectronic system) for the first two steps taken by 15 HD patients and 15 gender- and age-matched controls. In order to evaluate the influence of an external cue on gait initiation parameters, we studied two movement paradigms: self-triggered initiation and initiation triggered (cued) by a "beep" sound. We analyzed kinematic, spatiotemporal (the speed, length and duration of the two first steps) and angular parameters (range of joint angles) as well as kinetic data (the trajectory of the centre of pressure (COP); the speed and trajectory of the centre of mass (COM)). RESULTS: HD patients presented akinesia in both externally triggered and self-triggered conditions. Patients had more difficulties with self-triggered gait than with triggered gait. In HD, anticipatory postural adjustments (APAs) were more impaired in self-triggered gait initiation than in cued initiation. Indeed, an alteration in the kinetic parameters revealed a reduction in first step speed in both conditions. Hypokinesia (as assessed by a reduction in the range of angle joints) played an important role in this reduction. CONCLUSION: Akinesia is a major feature of impaired gait initiation in HD. The deficiencies in self-triggered initiation in HD seen here fit with a hypothesis whereby deficient internal cueing can be replaced by an external trigger.

Biomechanical Phenomena↗
PubMed2006

Preservation of cognitive function in dystonia treated by pallidal stimulation.

OBJECTIVE: To assess the effects of bilateral pallidal deep brain stimulation (DBS) on mood and cognitive performance in patients with dystonia before surgery (at baseline, while patients received their usual treatment) and 12 months postoperatively (while patients received neurostimulation and their medications) in a multicenter prospective study. METHODS: Twenty-two patients with primary generalized dystonia were evaluated with tests focused on executive functions. The authors considered the patients' severe disability and selected the following tests: Raven Progressive Matrices 38, Similarities and Arithmetic subtests of the Wechsler Adult Intelligence Scale-R, Grober and Buschke, Wisconsin Card Sorting Test (WCST), verbal fluency, Trail Making Test, and the Beck Depression Inventory. Median age at surgery was 30 years (range = 14 to 54 years), median duration of disease was 18.5 years (range = 4 to 37 years). RESULTS: Before surgery, no patients showed cognitive decline or depression. The surgical procedure appeared to be benign cognitively. One year after surgery, free recall improved. There was a significant reduction in the number of errors in the WCST. No behavioral or mood changes were found. CONCLUSIONS: Bilateral pallidal stimulation has a good benefit-to-risk ratio as it did not negatively affect cognitive performance and mood in primary dystonia, while a significant motor improvement was obtained. Moreover, a significant mild improvement in executive functions was observed, which may have been related either to the surgical treatment or to the marked decrease in anticholinergic drugs.

Adolescent↗
PubMed2006

Stimulation of the subthalamic nucleus in Parkinson's disease: cognitive and affective changes are not linked to the motor outcome.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN0 DBS) is a widely performed surgical treatment in PD. However, the relationship between motor results and cognitive/behavioural modifications is unclear. OBJECTIVE: This study investigated the correlation patterns of the motor, cognitive and behavioural consequences of STN DBS with respect to positioning of the active contact. METHODS: Fifty-eight consecutive PD patients having undergone STN DBS were assessed pre-operatively and 12 months after surgery. RESULTS: Motor, cognitive and behavioural results were neither correlated to each other nor linked to the position of the active contact. Three patients with a history of pre-operative, dopaminergic psychosis or post-surgical confusion became demented. Age and a distant history of depression were associated with the occurrence of post-surgical depression. CONCLUSION: Correct screening of patients for STN DBS remains an important issue, since the current implantation procedure is not able to take account of potential functional heterogeneity within the target.

Affect↗
PubMed2006

Gait abnormalities induced by acquired bilateral pallidal lesions: a motion analysis study.

BACKGROUND: Bilateral pallidal lesions induce a range of cognitive and motor disorders, principally a parkinsonian syndrome in which severe disturbances of gait and gait initiation are frequently reported. However, the precise clinical features of these disorders (and the role of the pallidum therein) remain to be established. OBJECTIVES: The goal of this study was to characterise gait and gait initiation disorders within the context of a parkinsonian syndrome in patients with acquired, bilateral, pallidal lesions (PAL patients), to compare these disorders to those seen in Parkinson's disease (PD), and to assess the corresponding physiopathological implications. PATIENTS AND METHODS: By using a video motion analysis system (VICON), we studied gait kinematic parameters in two patients presenting with bilateral, pallidal lesions. Kinematic and kinetic parameters were also determined during gait initiation. The two patients were compared with a group of 17 PD patients and to 20 healthy controls. RESULTS: In both PAL and PD patients, kinematic parameters (gait and gait initiation) and kinetic parameters (gait initiation) were similarly impaired, evidenced by akinesia (difficulty in initiating gait characterized by impairment of anticipatory postural adjustments). Hypokinesia and bradykinesia (respectively reduced stride length and reduced speed during gait) were also noted. CONCLUSION: The gait and gait initiation disorders seen in cases of bilateral pallidal lesions (namely akinesia, hypokinesia and bradykinesia) are similar to those observed in PD. Subject to confirmation in more extensive studies, we hypothesize that bipallidal patients may present higher level gait disorders,with potential mediation by cognitive impairment.

Aged↗
PubMed2006

The Lille apathy rating scale (LARS), a new instrument for detecting and quantifying apathy: validation in Parkinson's disease.

BACKGROUND: Apathy is usually defined as reduced interest and participation in various activities. It is a frequent consequence of neurological and psychiatric disorders. Although various scoring methods have been proposed, there is a lack of validated, standardised instruments for detecting apathy and assessing its severity. OBJECTIVE: To develop an apathy rating scale using a structured standardised interview capable of distinguishing between the condition's various features. METHODS: The Lille Apathy Rating Scale (LARS) is based on a structured interview. It includes 33 items, divided into nine domains. Responses are scored on a dichotomous scale. The participants used to validate the scale consisted of 159 patients with probable Parkinson's disease and 58 healthy control subjects. The Marin Apathy Scale, the Montgomery and Asberg Depression Rating Scale, and the Mattis Dementia Rating Scale were also administered. RESULTS: Principal component analysis showed that the LARS probed a single construct which forms the root of an oblique factor structure reflecting four dimensions: intellectual curiosity, self awareness, emotion, and action initiation. The main psychometric properties of the LARS (internal consistency, inter-rater and test-retest reliability) were satisfactory. Concurrent validity was evaluated by reference to the Marin scale and to judgements provided by expert clinicians. CONCLUSIONS: Standard validity indices showed that the LARS is sensitive and capable of distinguishing between apathy and depression. As a screening tool, the scale is able to support dichotomous judgements accurately and, when greater measurement sensitivity is required, also determine the severity of apathy within a four category classification.

Aged↗
PubMed2005

Disturbance of sensory filtering in dementia with Lewy bodies: comparison with Parkinson's disease dementia and Alzheimer's disease.

INTRODUCTION: Prepulse inhibition (PPI) is considered to mirror an organism's ability to filter out irrelevant sensory or cognitive information. The disruption of PPI has never been studied in individuals suffering from dementia with Lewy bodies (DLB). As attention deficits largely contribute to cognitive impairment in DLB, an investigation with a PPI paradigm is useful for differential diagnosis of DLB versus Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). OBJECTIVE AND METHODS: PPI of the N1/P2 component of auditory evoked potentials was used to investigate the early stages of attention selectivity in 10 DLB, 10 AD, and 10 PDD patients, as well as in 10 healthy controls. The PPI paradigm consisted of the presentation of sound pulses (40 ms, 115 dB) preceded by a prepulse (40 ms, 80 dB). Sound stimuli were presented in a total of 80 trials in a pseudo-random order. RESULTS: Non-parametric analyses of variance revealed a significant group effect on the 120 ms lead interval. Retrospective analyses revealed that PPI was significantly reduced in DLB compared to healthy controls and AD. In the PDD group, the disturbance was of intermediate intensity. CONCLUSION: The present study revealed a severe disturbance of PPI in DLB patients. The DLB patients displayed a specific disruption profile in terms of magnitude as well as time course.

Acoustic Stimulation↗
PubMed2005

One-year cyclophosphamide treatment combined with methylprednisolone improves cognitive dysfunction in progressive forms of multiple sclerosis.

We conducted an evaluation of changes in cognition in progressive multiple sclerosis (MS) patients receiving monthly intravenously pulse of cyclophosphamide (700 mg/m2) with methylprednisolone (1g). Twenty-eight consecutive progressive MS patients (10 primary progressive, 18 secondary progressive MS) were evaluated before and after six and 12 months of treatment. The WAIS-R score, memory and executive functions were evaluated. Under treatment we found a significant improvement in global cognitive efficiency, encoding abilities, planning abilities and inhibition after six and 12 months. However, mechanisms of action of the positive effect of these anti-inflammatory and immunosuppressive treatments on cognition remain unclear.

Adult↗
PubMed2004

[BCcogSEP: a French test battery evaluating cognitive functions in multiple sclerosis].

In French language, there is no standardized procedure to assess cognitive function in patients with multiple sclerosis (MS). Such an assessment is however very useful to determine the consequences of the disease on cognitive function, to evaluate the disease progression and the consequences of usual treatments on cognition. This study aimed to develop and validate a French language battery based on "the Brief Repeatable Battery of Neuropsychological tests for Multiple Sclerosis" (BRB-N) often used in other countries. In an initial phase, the battery was composed of the French version of the 5 BRB-N tests to which were added 4 tests assessing immediate and working memory as well as executive function. 52 healthy control subjects (20-50 years) participated in the study. A principal component analysis (PCA) of their data examined the contribution of each test into the battery. 93 other healthy subjects participated in a second phase where analyses of variance were carried out to investigate the effect of the main demographical variables. Finally, the performance of two patient groups (20 with a EDSS score 3) was compared to the healthy controls in order to investigate the ability of our battery to detect cognitive impairment in MS patients. The PCA showed that each test, except one, had a specific contribution to the battery. The final battery (BCcogSEP) was thus comprised of 8 tests. MANOVA and ANOVA showed significant effects of age, sex and educational level on performance. In consequence, a procedure allowing to take into account these factors was developed. The battery was able to detect cognitive impairment in MS patients, even when the disease is not severe. In this case, deficits were observed in tests assessing executive function, information processing speed, immediate and working memory. This short battery with reliable psychometric qualities allows the interpretation of a MS patient's performance considering his/her demographical characteristics and is able to detect cognitive abnormalities even in case of mild physical handicap.

Cognition↗
PubMed2004

Subthalamic nucleus stimulation induces deficits in decoding emotional facial expressions in Parkinson's disease.

BACKGROUND: Bilateral subthalamic nucleus (STN) stimulation is recognised as a treatment for parkinsonian patients with severe levodopa related motor complications. Although adverse effects are infrequent, some behavioural disturbances have been reported. OBJECTIVE: To investigate the consequences of STN stimulation on emotional information processing in Parkinson's disease by assessing the performance of an emotional facial expression (EFE) decoding task in a group of patients before and after surgery. METHODS: 12 non-demented patients with Parkinson's disease were studied. They were assessed one month before surgery and three months after. Their ability to decode EFEs was assessed using a standardised quantitative task. Overall cognitive function, executive function, visuospatial perception, depression, and anxiety were also measured. Twelve healthy controls were matched for age, sex, and duration of education. RESULTS: Before surgery, the patients showed no impairment in EFE decoding compared with the controls. Their overall cognitive status was preserved but they had a moderate dysexecutive syndrome. Three months after surgery, they had significant impairment of EFE decoding. This was not related to their overall cognitive status or to depression/anxiety scores. Visuospatial perception was not impaired. There was no change in the extent of the dysexecutive syndrome except for a reduction in phonemic word fluency. CONCLUSIONS: Bilateral STN stimulation disturbs negative emotional information processing in Parkinson's disease. The impairment appears specific and unrelated to certain secondary variables. This behavioural complication of STN may have implications for the patient's social life.

Affect↗
PubMed2001

Neural and cognitive bases of upper limb apraxia in corticobasal degeneration.

OBJECTIVE: To investigate the neural and cognitive bases of upper limb apraxia in corticobasal degeneration (CBD). METHODS: Eighteen patients with CBD underwent a cognitive neuropsychological assessment of apraxia and resting [(18)F]-fluorodeoxyglucose PET scanning. Two complementary measures of apraxia were computed for each modality of gesture production. First, a performance score measured error frequency during gesture execution. Second, as a more stringent test of the integrity of the praxis system, the correction score measured the patient's ability to correct his or her errors on a second attempt. For each measure type, a cut-off score for the presence of apraxia was defined with regard to healthy controls. Using each cut-off score, the regional cerebral glucose metabolism of patients with CBD with apraxia (i.e., performing below cut-off score) was compared with that of patients with CBD without apraxia. RESULTS: Mean performance scores were below normal values in all modalities. Anterior cingulate hypometabolism predominated in patients with CBD who performed below the cut-off performance score. At variance, mean correction scores were below normal values for gesture imitation only. Hypometabolism in superior parietal lobule and supplementary motor area characterized patients with CBD who were unable to correct their errors at the same rate as control subjects did. CONCLUSIONS: Distinct neural networks underlie distinct aspects of the upper limb apraxic deficits in CBD. Extending previous findings of gesture production deficits in CBD, the use of complementary measures of apraxic behavior discloses a visuoimitative upper limb apraxia in CBD, underlain by a metabolic decrease in a parietofrontal neural network.

Aged↗
PubMed2001

Clinical features and genetic analysis of a new form of spinocerebellar ataxia.

BACKGROUND: The autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of disorders. The mutations for SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, and SCA-12 are identified and caused by an expansion of a CAG or a CTG repeat sequence of these genes. Six additional loci for SCA4, SCA5, SCA-10, SCA-11, SCA-13, and SCA-14 are mapped. The growing heterogeneity of the autosomal dominant forms of these diseases shows that the genetic etiologies of at least 20% of ADCA have yet to be elucidated. METHODS: The authors ascertained and clinically characterized a four-generation pedigree segregating an autosomal dominant phenotype for SCA. Direct mutation analysis, repeat expansion detection analysis, and linkage analysis for all known SCA loci were performed. RESULTS: Direct mutational analysis excluded SCA1, 2, 3, 6, 7, 8, and 12; genetic linkage analysis excluded SCA4, 5,10, 11, 13, and 14, giving significant negative lod scores. Examination of the family showed that all affected members had gait ataxia and akinesia with variable features of dysarthria, hyporeflexia, and mild intellectual impairment. Eye movements were normal. Head MRI showed atrophy of the cerebellum without involvement of the brainstem. In 10 parent-child pairs, median onset occurred 10.5 years earlier in offspring than in their parents, suggesting anticipation. CONCLUSION: This family is distinct from other families with SCA and is characterized by cerebellar ataxia and extrapyramidal signs.

Adult↗
PubMed2001

Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson's disease.

BACKGROUND: The clinical efficacy of chronic deep brain stimulation in the treatment of parkinsonian patients with severe levodopa-related motor adverse effects has been repeatedly shown. Bilateral subthalamic nucleus (STN) stimulation has been shown to present an advantage over pallidal stimulation as it induces a higher antiakinetic effect and has positive effects on all parkinsonian symptoms. The morbidity of such surgery is usually considered to be very low. However, few studies have extensively examined the effects of chronic STN stimulation on cognitive function. OBJECTIVE: The aim of the present study was to assess the effects of chronic bilateral STN stimulation on performance in an extensive battery of neuropsychological tests, three months and one year after surgery. METHODS: Nine patients with Parkinson's disease were selected for STN electrodes implantation. They underwent a neuropsychological evaluation at one month before and at three months after surgery. Six of them were examined again at one year after surgery. RESULTS: Before surgery, no patient showed cognitive decline. At three months after surgery, no modification was observed for most tasks. The information processing speed tended to improve. There was a significant reduction of the performance in a delayed free recall test and a trend toward a significant reduction of categorial word fluency. At one year after surgery, most task measures did not change. Slight impairment was observed for tasks evaluating executive function. Examination of individual results showed that some patients (30% at 3 months after surgery) showed an overall cognitive decline. Behavioural changes were also observed in 4 patients with overall cognitive decline in one of them. CONCLUSION: In general, STN deep brain stimulation can be considered as a significant contribution to the treatment of severe Parkinson's disease However, in some patients it can induce overall cognitive decline or behavioural changes.

Cognition Disorders↗
PubMed2001

Phase 2 prolongation, in the absence of instability and triangulation, antagonizes class III proarrhythmia.

OBJECTIVE: To evaluate whether prolongation of the plateau of the action potential duration, in the absence of instability and triangulation, can reverse the proarrhythmia elicited by a class III antiarrhythmic agent. METHODS: The effects of almokalant, erythromycin and their combination, on cardiac electrophysiological parameters (action potential duration (APD), instability, triangulation and ectopics) were evaluated in isolated hearts from female albino rabbits. In this study, proarrhythmia was estimated quantitatively by number of ectopic beats. RESULTS: Erythromycin lengthened the APD primarily by a prolongation of the plateau, while having only minor effects upon phase 3 repolarization. The prolongation did not induce much instability, triangulation or reverse use dependence and, as expected, erythromycin did not induce significant proarrhythmia. Almokalant also lengthened APD, but it did not lengthen the plateau; instead, it prolonged phase 3 repolarization. The prolongation markedly triangulated the action potential, elicited much instability and marked reverse use dependence. This combination of effects induced very marked proarrhythmia. When almokalant and erythromycin were combined, their effects upon APD appeared additive: both the plateau and the repolarization phase were prolonged. However, the larger prolongation of APD did not lead to more proarrhythmia; this suggests that a prolongation of APD is not proarrhythmic per se. On the contrary, proarrhythmia as a function of APD prolongation was reduced in the presence of erythromycin (P<0.05). CONCLUSION: Instability plus triangulation consistently lead to serious proarrhythmia especially when combined with reverse use dependence, but prolongation of APD in itself is not necessarily proarrhythmic. In fact, APD prolongation in the absence of instability and triangulation can be antiarrhythmic.

Action Potentials↗
PubMed2001

Memory and executive function in sporadic and familial Parkinson's disease.

Some studies have demonstrated that the motor symptomatology in sporadic and familial Parkinson's disease was identical. From a physiopathological point of view, and perhaps in the future from a therapeutic point of view, it seems important to determine whether sporadic and familial Parkinson's disease are also similar with regard to cognitive impairment. The aim of the present study was to assess cognitive functions in patients suffering from sporadic and familial Parkinson's disease. Executive functions and memory were investigated in particular. Two groups of 12 patients with Parkinson's disease (sporadic and familial) and 12 healthy controls performed a set of tasks known to evaluate different aspects of executive function and memory. One-way analysis of variance tested for significant group effects, and when justified, post hoc analysis was performed. Cognitive impairment was different in sporadic and familial forms of Parkinson's disease. Indeed, although executive function was impaired in both groups of patients, deficits in tests of explicit memory recall were only observed in patients with sporadic Parkinson's disease. Although the impairment observed in both groups of patients suggests a disruption of the striatoprefrontal circuits, this disruption seems to be quantitatively more important and more widespread in the sporadic patients than in the familial ones. In both patient groups, the deficits probably result from dopaminergic and nondopaminergic deprivation and a greater participation of nondopaminergic factors in patients with sporadic Parkinson's disease could be suggested. In this group, a xenobiotic could be responsible for an acquired metabolic defect involving more widespread structures of the striatoprefrontal circuits, leading to disruption of nondopaminergic loops. Cholinergic deprivation is considered in particular.

Adult↗
PubMed2000

A case of severe dysexecutive syndrome consecutive to chronic bilateral pallidal stimulation.

In treatment for severe Parkinson's disease (PD), a recent procedure was developed which consists of implanting electrodes in the internal Globus Pallidus (GPi) for chronic electrical stimulation. The consequences on cognitive function of such an intervention are quite variable. Although most group studies observed no significant post-operative change, individual cases of post-operative cognitive impairment were reported. The present study reports the case of a PD patient who underwent bilateral implantation of deep brain stimulation electrodes in the GPi and who, after surgery, suffered from a severe dysexecutive syndrome. An extensive neuropsychological examination showed a selective negative effect of pallidal stimulation on tests assessing executive function. When the stimulation was turned off, the impairment was partly reversible. This observation emphasizes the role of the GPi in executive function.

Attention↗