RFC1: Motifs and phenotypes.

Biallelic intronic expansions (AAGGG)exp in intron 2 of the RFC1 gene have been shown to be a common cause of late-onset ataxia. Since their first description, the phenotypes, neurological damage, and pathogenic variants associated with the RFC1 gene have been frequently updated. Here, we review the various motifs, genetic variants, and phenotypes associated with the RFC1 gene. We searched PubMed for scientific articles published between March 1st, 2019, and January 15th, 2024. The motifs and phenotypes associated with the RFC1 gene are highly heterogeneous, making molecular diagnosis and clinical screening and investigation challenging. In this review we will provide clues to give a better understanding of RFC1 disease. We briefly discuss new methods for molecular diagnosis, the origin of cough in RFC1 disease, and research perspectives.

Influence of continuous subcutaneous apomorphine infusion on cognition and behavior in Parkinson's disease: A systematic review.

INTRODUCTION: The efficacy of continuous subcutaneous apomorphine infusion (CSAI) for motor complications of Parkinson's disease (PD) is established. However, its effect on cognition and behavior remains controversial. The main objective of this systematic review was to describe the existing literature on the effects of CSAI on cognition and behavior and to determine the quality for each study. METHODS: PubMed/Medline, Embase, APA PsycInfo®, and Cochrane Library databases were searched, following PRISMA recommendations. Only longitudinal studies evaluating the effect of CSAI on cognition (global cognition, executive functions, visuospatial abilities, language, memory, attention, social cognition) and/or behavior (depression, anxiety, apathy, psychotic symptoms, impulse control disorders, neuropsychiatric fluctuations) in PD were included. The quality of the included studies was also assessed with a questionnaire. RESULTS: Twenty-three longitudinal studies evaluated the effect of CSAI on cognition and/or behavior. Overall, results were suggestive of positive effects, notably on executive functions and emotion recognition. However, there were some reports of cognitive slowing and long-term global cognitive deterioration. At the behavioral level, no study showed significant adverse effect of CSAI. Occasionally, a slight improvement of depression, anxiety, apathy, and neuropsychiatric fluctuations was reported. Nevertheless, only four studies met good quality criteria and controlled study regarding cognition were lacking. CONCLUSION: The results suggest that CSAI has no obvious negative effects on cognition and behavior in PD. This treatment even shows promise in reducing certain symptoms such as neuropsychiatric fluctuations. However, due to methodological limitations in many studies, no robust conclusions can be drawn. Further multicenter controlled trials are needed to confirm these results.

The neural correlates of the visual consciousness in schizophrenia: an fMRI study.

In the current literature, two distinct and opposite models are suggested to explain the consciousness disorders in schizophrenia. The first one suggests that consciousness disorders rely on a low-level processing deficit, when the second model suggests that consciousness disorders rely on disruption in the ability to consciously access information, with preserved unconscious processing. The current study aims to understand the mechanisms associated with visual consciousness disorder in order to pave the road that will settle the debate regarding these hypotheses. During a functional magnetic resonance imaging session, 19 healthy participants (HC) and 15 patients with schizophrenia (SCZ) performed a visual detection task to compare the neural substrates associated with the conscious access to the visual inputs. The visual detection threshold was significantly higher in SCZ than in HC [t(32) = 3.37, p = 0.002]. Whole-brain ANOVA demonstrated that around the visual detection threshold patients with SCZ failed to activate a large network of brain areas compared to HC. (1) During conscious vision, HC engaged more the left cuneus and the right occipital cortex than patients with SCZ, (2) during unconscious vision, HC engaged a large network that patients with SCZ failed to activate, and finally, (3) during the access to consciousness process, patients with SCZ failed to activate the anterior cingulate cortex. These results suggest that the consciousness disorders in schizophrenia rely on specific dysfunctions depending on the consciousness stage. The disorders of the conscious vision are associated with dysfunction of occipital areas while the ones associated with unconscious vision rely on a large widespread network. Finally, the conscious access to the visual inputs is impaired by a dysfunction of the anterior cingulate cortex. The current study suggests that none of the two suggested models can explain consciousness disorders in schizophrenia. We suggest that there is an alternative model supporting that the conscious access to visual inputs is due to a disengagement of the supragenual anterior cingulate during the unconscious processing of the visual inputs associated with a sensory deficit.

Factors that predict a change in quality of life among Parkinson's disease patients participating in a patient education program.

BACKGROUND: Patient education is essential in Parkinson's disease (PD). However, it is not known which aspects of patient education are associated with an improvement in quality of life (QoL). OBJECTIVE: To identify factors that predicted an improvement in QoL in PD patients that participate in an education program. METHODS: EduPark is a community-hospital patient education program. PD Patients that had participated in the program between September 2013 and March 2017 were retrospectively included. QoL was prospectively evaluated (using the PDQ-8 questionnaire) before and after the patient's participation. We used mixed linear models (adjusted for the initial value of the PDQ-8) to determine socio-demographic and clinical variables that predicted the change in the PDQ-8 score. RESULTS: A total of 181 patients were included (mean±standard deviation age: 62.9±8.2 years; disease duration: 9.1±5.3 years). 76.7% of the 103 patients having undergone a cognitive evaluation did not display cognitive impairment. We did not identify any factors that predicted the program's impact on the patient's QoL. Participation in the program was associated with a significant decrease (improvement) in the PDQ-8 score (39.4±17.81 before and 35.6±15.9 afterwards, P<0.001). CONCLUSION: We did not identify any factors that were predictive of the patient education program's impact on QoL in patients with PD. Participation in the program was associated with a significant improvement in QoL. Our results suggest that Patient Education Programs should be more widely prescribed and developed in the management of PD.

Validation in French of the Montreal Cognitive Assessment 5-Minute, a brief cognitive screening test for phone administration.

BACKGROUND: The prevalence of cognitive impairment and dementia is high and steadily increasing. Early detection of cognitive decline is crucial since some interventions can reduce the risk of progression to dementia. However, there is a lack of manageable scales for assessing cognitive functions outside specialized consultations. Recently, the MoCA-5min, a short version of the Montreal Cognitive assessment (MoCA), phone-administered, was validated for screening for vascular cognitive impairment. The aim of the present study was to validate the MoCA-5min in French in diverse clinical populations. METHODS: The Cantonese version of the MoCA-5min was adapted for French language. Healthy volunteers and patients with possible or established cognitive impairment (Alzheimer's disease or related disorders, Parkinson's disease, Huntington's disease, type-2 diabetes) participated in the study. The original MoCA and the MoCA-5min were administered, by phone, with a 30-day interval. Alternate forms were used to reduce learning effects. RESULTS: The scores of the original MoCA and MoCA-5min correlated significantly (Spearman rho=0.751, P<0.0001, 95% confidence interval 0.657 to 0.819). Internal consistency was good (Cronbach alpha=0.795). The area under the ROC curve was 0.870 and the optimal cut-off value for separating patients with and without cognitive impairment with the MoCA-5min was≤27 with 87.32% sensitivity and 76.09% specificity. Interrater and test-retest reliability were adequate. CONCLUSION: This study demonstrates that the French version of the MoCA-5min is a valid and reliable scale for detecting cognitive impairment in different clinical populations. It is administrable by phone and thus suitable for remote assessment as well as for large-scale screening and epidemiological studies.

Safety and effectiveness of levodopa-carbidopa intestinal gel for advanced Parkinson's disease: A large single-center study.

BACKGROUND: Treatment with levodopa-carbidopa intestinal gel (LCIG) can effectively relieve motor and non-motor symptoms in advanced Parkinson's disease (PD). However, adverse events (AEs) are frequent. OBJECTIVE: To describe AEs associated with LCIG treatment and the main reasons for treatment discontinuation. We also looked for factors that were potentially predictive of serious AEs and assessed the effectiveness of and satisfaction with LCIG. METHOD: We retrospectively analyzed data on AEs in patients treated with LCIG at a French university medical center. For patients still receiving treatment at last follow-up, effectiveness was assessed according to the Clinical Global Impression (CGI) scale and the Movement Disorders Society - Unified Parkinson's Disease Rating Scale motor score. RESULTS: Of the 63 patients treated with LCIG for a mean (range) of 19 months (8-47), 57 (90%) experienced at least one AE (340 AEs in total). Most of the AEs (in 69.8% of the patients) were related to percutaneous endoscopic gastrostomy with a jejunal tube (PEG-J) or affected the gastrointestinal tract (granuloma, leakage, or a local infection). Device-related AEs (such as PEG-J removal and device occlusion) were frequent (in 63.5% of patients). Forty-three patients (68%) required at least one additional endoscopic procedure. Dopatherapy-related AEs occurred in 30 patients (48%). Most of the AEs occurred long after treatment initiations, and only a small proportion led to discontinuation. On the CGI scale, 53 patients (84.4%) considered that their condition had improved during LCIG treatment. CONCLUSION: Despite the high frequency of AEs, patients with advanced PD gain clinical benefit from treatment with LCIG. This treatment requires a competent, multidisciplinary team on site.

French consensus procedure for assessing cognitive function in Parkinson's disease.

INTRODUCTION: One of the objectives of the French expert centers for Parkinson's disease (NS-Park) network was to determine a consensus procedure for assessing cognitive function in patients with Parkinson's. This article presents this procedure and briefly describes the selected tests. METHODS: A group of 13 experts used the Delphi method for consensus building to define the overall structure and components of the assessment procedure. For inclusion in the battery, tests had to be validated in the French language, require little motor participation, have normative data and be recognized by the international community. Experimental tasks and tests requiring specific devices were excluded. RESULTS: Two possibilities were identified, depending on whether an abbreviated or comprehensive assessment of cognitive function was necessary. For an abbreviated assessment, the experts recommended the Montreal Cognitive Assessment (MoCA) as a screening test for cognitive impairment or dementia. For a comprehensive neuropsychological assessment, the experts recommended assessing global efficiency plus the five main cognitive domains (attention and working memory, executive function, episodic memory, visuospatial function and language) that may be impaired in Parkinson's disease, using two tests for each domain. DISCUSSION AND CONCLUSION: A common procedure for assessing cognitive function is now available across the French network dedicated to Parkinson's disease, and is recommended for both research and clinical practice. It will also help to promote standardization of the neuropsychological assessment of Parkinson's disease.

[Continuous subcutaneous infusion of apomorphine in Parkinson's disease: retrospective analysis of a series of 81 patients]. / Le traitement par apomorphine en perfusion continue sous-cutanée dans la maladie de Parkinson : analyse rétrospective d'une série de 81 patients.

BACKGROUND: Continuous subcutaneous infusion of apomorphine (CAI) has shown efficacy in the treatment of motor fluctuations but its place in the therapeutic arsenal remains poorly defined in terms of indication, acceptability and long-term tolerance. Indeed, few studies have been carried out with a follow-up greater than 12 months. The main objective was to assess the quality of life of Parkinson's disease (PD) patients treated with CAI. We also evaluate the effectiveness on the motor fluctuations, the long-term tolerance of this treatment with its causes of discontinuation and the treatment regimens used. METHODS: We conducted a retrospective study of 81 PD patients treated with CAI between April 2003 and June 2012. Data were collected from medical records. A repeated measures analysis of variance by the linear mixed model was used (significance level: 5%). RESULTS: In August 2012, 27/81 patients were still treated with CAI with a mean duration of 28 months, 46/81 discontinued CAI (9 precociously), and 8 were lost to view. We didn't show improvement in the quality of life nor efficacy of CAI on the UPDRS IV score (P=0.54) and dyskinesia score (P=0.95). The CGI score patient also reflects this result with a majority response suggesting no significant change with CAI. We observed relative good cognitive and psychiatric tolerance. Adverse events were frequent but often benign. The average (±SD) rate of apomorphine was 3.15±1.71 mg/h and the oral dopaminergic treatment was decreased by 37.8%. DISCUSSION: The results are consistent with the literature except for the lack of efficiency on motor fluctuations which may be due to the use of too small doses of apomorphine. This seems to be a leading cause of discontinuation of CAI, especially when it is associated with side effects or important constraints. For better efficiency on motor fluctuations, we recommend the use of apomorphine at higher doses to obtain an optimal continuous dopaminergic stimulation.

Designing a new scale to measure anxiety symptoms in Parkinson's disease: item selection based on canonical correlation analysis.

BACKGROUND AND PURPOSE: The lack of appropriate measures has hindered the research on anxiety syndromes in Parkinson's disease (PD). The objective of the present cross-sectional, international study was to identify shared elements and grouping of components from anxiety scales as a basis for designing a new scale for use in PD. METHODS: For this purpose, 342 consecutive PD patients were assessed by means of the Mini International Neuropsychiatric Inventory (depression and anxiety sections), the Clinical Global Impression of severity of the anxiety symptoms, the Hamilton Anxiety Rating Scale (HARS), the Neuropsychiatric Inventory (section E), the Beck Anxiety Inventory (BAI) and the Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A). RESULTS: As the HADS-A showed a weak correlation with the HARS and BAI, it was not considered for more analyses. HARS and BAI exploratory factor analysis identified nine factors (62% of the variance), with only two of them combining items from both scales. Therefore, a canonical correlation model (a method to identify relations between components of two groups of variables) was built and it showed four factors grouping items from both scales: the first factor corresponded to 'generalized anxiety'; the second factor included muscular, sensory and autonomic 'non-specific somatic symptoms'; the third factor was dominated by 'respiratory symptoms'; and the fourth factor included 'cardiovascular symptoms'. CONCLUSIONS: BAI is heavily focused on panic symptoms, whilst HARS is more focused towards generalized anxiety symptoms. The new scale should include additional components in order to assess both episodic and persistent anxiety as well as items for evaluation of avoidance behaviour.

[Apathy in Parkinson's disease: clinical features, mechanisms and assessment]. / Apathie et maladie de Parkinson : aspects cliniques, physiopathologie et évaluation.

Apathy is a loss of motivation compared to the previous level of functioning of the subject. It affects the subject's behavior, cognition and emotional state. It is one of the main behavioral manifestations of Parkinson's disease. Although it may be a symptom of depression, it often exists as an isolated syndrome in Parkinson's disease patients. Apathy is usually not related to the severity of the motor symptoms, but frequently associated with the severity of cognitive impairment. Apathy is also a possible complication of treatment by stimulation of the subthalamic nucleus. Screening and assessment of apathy require the use of specific tools, some of which are validated in Parkinson's disease. From a pathophysiological point of view, apathy results from a dysfunction of the limbic circuit connecting the ventral striatum to orbitofrontal and anterior cingulate cortex. The dopaminergic denervation in these regions seems to play a key role, but other mechanisms are probably involved. Further studies are warranted to progress in the therapeutic management of this invalidating syndrome.

[Impulse control disorders in Parkinson's disease: A cohort of 35 patients]. / Troubles du contrôle des impulsions associés à la maladie de Parkinson : étude d'une cohorte de 35 patients.

INTRODUCTION: Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated with dopamine agonist treatment. Although discontinuation of dopamine agonist is recommended, ICD management has not been precisely stated. The aims of the study were to describe demographic and clinical characteristics in a group of PD patients with ICDs and to evaluate the management of dopamine agonist treatment proposed to the same patients in order to treat the ICDs. METHODS: Thirty-five PD patients with ICD and 607 PD patients without ICD were studied. In the ICD group, demographic and clinical data were collected prospectively (ICD characteristics, motor and cognitive evaluation); demographic and clinical data were obtained retrospectively in the group without ICD. RESULTS: In the ICD group, the sex ratio was 2.9 (versus 1.2 in the absence of ICD; p<0.05), the mean age was 57.5 years (versus 66.9 years; p<0.01) and the mean age at PD onset was 48.3 years (versus 55.5 years; p<0.01). All ICD patients were receiving a dopamine agonist when the ICD started (versus 50.9 % of patients receiving a dopamine agonist in the absence of ICD; p<10(-6)). In mean, ICDs started 2.8 years before they were diagnosed. No particular dopamine agonist was associated with ICDs more frequently than the others. Discontinuation of the dopamine agonist was the treatment the more frequently associated with the recovery of ICDs (93.3 %). Dose lowering and the change of dopamine agonist resulted in complete regression of ICDs respectively in 9.1% and 33.3% of patients. CONCLUSION: Young age, male gender and young age at PD onset are frequent in PD patients developing ICDs, as already described in American or Asian cohorts. We highlighted a long diagnosis delay and confirmed the strong efficacy of dopamine agonist withdrawal.

Diagnostic criteria for apathy in clinical practice.

BACKGROUND: Apathy is an important and distressing behavioural symptom in Alzheimer's disease and in various neuropsychiatric disorders. Recently, diagnostic criteria for apathy have been proposed. OBJECTIVES: In groups of patients suffering from different neuropsychiatric diseases, (i) to estimate the prevalence of patients meeting the proposed diagnostic criteria; (ii) to estimate the concurrent validity of the criteria with the neuropsychiatric inventory (NPI) apathy item; (iii) to identify the most frequently met criteria or sub-criteria in each specific neuropsychiatric disease and (iv) to estimate the inter-observer reliability of the diagnostic criteria for apathy. METHODS: This cross-sectional, multicentric, observational study was performed on 306 patients. Each of the participating centres had to check the presence of apathy according to the diagnostic criteria for apathy in consecutive patients belonging to the following diagnoses list: Alzheimer disease (AD), mixed dementia, mild cognitive impairment (MCI), Parkinson's disease (PD), Schizophrenia (DSM-IV) and major depressive episode. In addition to the clinical interview, the assessment included the Mini Mental Score Examination (MMSE) and the NPI. At the end of the visit, clinicians were required to check the diagnostic criteria for apathy. RESULTS: Using the diagnostic criteria for apathy, the frequency of apathy was of 53% in the whole population, 55% in AD, 70% in mixed dementia, 43% in MCI, 27% in PD, 53% in schizophrenia and 94% in major depressive episode. In AD, mixed dementia, MCI and PD, the NPI apathy score was significantly higher for patient fulfilling the apathy criteria. Goal-directed cognitive activity (criteria B2-Cognition) was the most frequently observed domain followed by goal-directed behaviour (criteria B1-Behaviour) and emotion (criteria B3), respectively. Inter-rater reliability was high for the overall diagnostic (κ coefficient = 0.93; p = 0.0001) and for each criteria. CONCLUSION: This study is the first one to test the diagnostic criteria for apathy in clinical practice. Results make the diagnostic criteria useful for clinical practice and research.

Looking back on 15 years of ultrasound-guided alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

Background: Septal reduction remains an important target of current therapeutic modalities in hypertrophic obstructive cardiomyopathy (HOCM). Surgical septal myectomy has long been considered the gold standard in pharmacotherapy-refractory severely symptomatic patients with marked left ventricular outflow tract (LVOT) obstruction. In recent years, percutaneous alcohol septal ablation (ASA) has matured into the preferred strategy for patients with favourable anatomy and no other coexisting surgically amenable disease.Methods: We discuss 26 HOCM patients with persistent dyspnoea, angina or syncope despite optimal medical treatment. Baseline septal wall thickness was 20 ± 3 mm, with peak resting/provoked LVOT gradients of 53 ± 35/112 ± 40 mmHg. Guided by echocardiography, alcohol injection could be restricted to the first septal coronary artery in 85% of patients, provoking basal septal infarction with average troponin rise of 3.0 ng/ml.Results: Eighty-six per cent of patients experienced sustained clinical improvement, associated with a reduction of septal wall thickness to 15 ± 3 mm and resting LVOT gradient to 21 ± 15 mmHg. One of the two non-responders underwent additional septal myectomy 11 years after ASA. Notable adverse events during the follow-up of 7.2 ± 4.7 years included: persistent conduction disturbances (65%) necessitating early postprocedural permanent pacemaker implantation (15%); atrial fibrillation (32%); ventricular tachycardia (4%) and aortic stenosis (14%). Six patients died, of which only 1 cardiac death.Conclusions: Our case series underscores the efficacy of ASA at relieving LVOT obstruction and improving symptoms in properly selected HOCM patients, with acceptably low procedural and long term mortality and morbidity.

Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders.

There is wide acknowledgement that apathy is an important behavioural syndrome in Alzheimer's disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy, and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and that will be easily applied in practice and research settings. Meeting these needs is the focus of the task force work reported here. The task force includes members of the Association Française de Psychiatrie Biologique, the European Psychiatric Association, the European Alzheimer's Disease Consortium and experts from Europe, Australia and North America. An advanced draft was discussed at the consensus meeting (during the EPA conference in April 7th 2008) and a final agreement reached concerning operational definitions and hierarchy of the criteria. Apathy is defined as a disorder of motivation that persists over time and should meet the following requirements. Firstly, the core feature of apathy, diminished motivation, must be present for at least four weeks; secondly two of the three dimensions of apathy (reduced goal-directed behaviour, goal-directed cognitive activity, and emotions) must also be present; thirdly there should be identifiable functional impairments attributable to the apathy. Finally, exclusion criteria are specified to exclude symptoms and states that mimic apathy.

[Continuous dopaminergic stimulation by Duodopa in advanced Parkinson's disease: Efficacy and safety]. / Intérêts de la stimulation dopaminergique continue par Duodopa((R)) dans la maladie de Parkinson évoluée : efficacité et tolérance.

INTRODUCTION: When advanced Parkinson's disease (PD) patients experience motor complications (fluctuations and dyskinesias) despite standard oral treatment, two treatment options are available: deep brain stimulation and subcutaneous apomorphine infusion with respects of indications for each strategy. Continuous intraduodenal infusion of levodopa (Duodopa) via a gastrojejunal tube may be proposed at this stage of the disease and the study of indications and clinical results with Duodopa may develop this new therapeutic alternative. PATIENTS AND METHODS: Seven patients with advanced PD (dementia for all and psychiatric disorders for some of them, axial signs) were treated with Duodopa. We evaluated neuropsychological functions, all UPDRS scales, gait and quality-of-life just before Duodopa onset and six months after treatment end. Moreover, we described all adverse events (early and late) and studied daily levodopa doses before and 6 months after treatment. RESULTS: We demonstrated an improvement in motor UPDRS (44%), in axial signs (40% for UPDRS part III axial subscore and 12% for gait) and a reduction of fluctuations (37.5%) and in UPDRS part IV dyskinesia (20%). These significant results are observed without any change in the quality-of-life. Adverse events were due to PEG positioning for four patients, the equipment (pump, connection, inner tube) for all patients and levodopa for four patients. Daily levodopa dose had to be increased 13.5%. CONCLUSION: Duodopa can be considered as a new treatment strategy providing significant improvements in motor fluctuations, dyskinesia and severe axial signs. These results were demonstrated in very advanced PD patients, who had been excluded from previous studies, with cognitive disorders and for some of them dopaminergic psychosis well controlled by medications.

[Classification of parkinsonian syndromes via factorial discriminant analysis of brain SPECT data]. / Intérêt de l'analyse factorielle discriminante pour classer les syndromes parkinsoniens à partir de la tomoscintigraphie d'émission monophotonique.

INTRODUCTION: The objective was to assess the value of single photon emission computerized tomography (SPECT) and factorial discriminant analysis (FDA) in the differential diagnosis of Parkinson's disease (PD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). PATIENTS AND METHODS: Sixty-two patients with clinical diagnoses of either CBD, PSP or PD were studied using brain HmPaO-SPECT. Thirteen pairs of regions of interest (ROIs) were drawn on the slices located 50mm and 90mm above the canthomeatal plane. Twenty-six uptake indices and 13 asymmetry indices were determined. FDA was performed in order to determine whether or not the patients could be classified into the correct clinical group on the basis of SPECT data alone. The most discriminant parameters were used to generate two predictive scores, which were tested in a second group of 15 patients. RESULTS: FDA of all 39 variables correctly classified all the patients. A subset of 10 variables was used to build predictive scores, which correctly classified 90% of PD patients, 100% of PSP patients and 86% of CBD patients. When tested in the validation group of 15 patients, these predictive scores correctly classified 87% of the individuals. The frontal medial, temporoparietal and parietal regions were the most discriminant. CONCLUSION: Using SPECT data alone, this study enabled us to distinguish between PD, PSP and CBD in patients with clear clinical presentations of the diseases in question. This novel, statistical approach provides reliable information. However, a prospective study dealing with de novo parkinsonian syndromes will be necessary.

Slowly progressive spinocerebellar ataxia with extrapyramidal signs and mild cognitive impairment (SCA21).

Spinocerebellar ataxia 21 is a slowly progressive and mild ataxia associated with extrapyramidal signs. Affected subjects exhibit a moderate gait and limb ataxia variably associated with akinesia, tremor, rigidity, hyporeflexia, and mild cognitive impairment. The responsible gene has been assigned to a 19 Mbases interval on chromosome 7p in a single French family. No evidence of significant linkage to this locus was found in 21 other families obtained from the EUROSCA consortium. The locus interval contains several candidate genes that could be responsible for the disease. Direct sequencing of NDUFA4, PHF14, KIAA0960, ARLA4, ETV1, DGKB, HDAC9, FERD3L, ITGB8, and SP4 genes were performed, but all the direct mutation analyses were negative excluding pathogenic mutations associated with the disease. Therefore, the gene responsible for SCA21 remains to be identified.

[About Huntington's disease: role of families and health professionals in information transmission]. / A propos de la maladie de Huntington : rôles respectifs de la famille et des professionnels de santé dans la transmission de l'information.

INTRODUCTION: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. However, little information is available concerning the way each patient learns about the existence of Huntington's disease in his family and the way he transmits the information to his descendants. This study aims to specify the role of families and healthcare professionals in delivering information about the disease and its hereditary risk. PATIENTS AND METHODS: Data from 105 consecutive patients were analyzed. The patients were categorized in four classes according to the way they received information about HD in their family: firstly, families where the disease was known; secondly, families where the HD was "poorly known"; thirdly, families where no antecedent could be found; fourthly, families where the disease was voluntarily hidden. The majority (52%) of the patients did not know the name of HD before being diagnosed. The patient choices for disclosure of hereditary risks to their relatives were influenced by the information they received about the disease in their own family. Patients from the second category (disease "poorly known") had the most difficulty in transmitting the information. DISCUSSION: Despite the high risk of transmission, information about the disease is poorly known and transmitted in families concerned by HD. Although healthcare professionals confronted with the question of information delivery to relatives must always respect patient confidentiality, our results underline the need to more fully inform patients about the disease and transmission patterns. More help from healthcare professionals is needed to accompany HD patients concerning the question of transmitting information. The efficacy of a specific educational program should be assessed.

[Cognitive impact of mitoxantrone and methylprednisolone in multiple sclerosis: an open label study]. / Impact cognitif d'un traitement associant mitoxantrone et méthylprednisolone dans la sclérose en plaques.

Interferons beta have shown some positive effects on cognitive function in multiple sclerosis (MS). The potential immunosuppressive impact of mitoxantrone on cognitive dysfunction in MS has never been evaluated. We assessed changes in cognitive dysfunction in patients with very active MS treated with mitoxantrone combined with methylprednisolone. We assessed a non randomized controlled trial including successively 15 consecutive MS patients. Very active MS was defined by a progression of at least two EDSS points or more than two relapses during the previous year and at least one enhanced lesion after gadolinium infusion on MRI. All patients received a monthly intravenous pulse of mitoxantrone (20mg) for six months with methylprednisolone (1g). Global cognitive efficiency, memory and executive function were assessed before treatment (M0) and after six months (M6) and 12 months (M12) of treatment. To evaluate the learning effect, 15 healthy subjects also participated. A significant improvement in global cognitive efficiency was observed at M6 and was sustained at M12, as a few parameters on memory and executive functions. We suggest that mitoxantrone combined with methylprednisolone has a potential positive effect on cognitive functions.