Première évaluation d’un programme de remédiation cognitive chez des patients atteints de sclérose en plaques : PROCOG-SEP

Background

Although cognitive disorders are well-known in multiple sclerosis (MS), even in earlier stages of the disease, their management may be overlooked. Our objective was to elaborate and evaluate the efficiency of a remedial program (PROCOG-SEP) designed for MS patients. The evidence-based program proposes exercises to both stimulate preserved functions and develop new abilities compensating for cognitive disabilities.

Design/Methods

Twenty-four patients with MS participated in 10/2-hour PROCOG-SEP sessions over a 6-month period. A neuropsychologist recorded BCcog-SEP performances before and after the PROCOG-SEP program. In addition, the same neuropsychologist conducted psychoclinical interviews to complete the before and after cognitive evaluations. The statistical analysis used the t-test performed with Excel.

Results

Compared with the initial levels, subtests of BCcog-SEP showing improvement after PROCOG-SEP were: verbal memory (SRT), visuospatial memory (10/36), verbal fluency (animal categories) and response to conflicting orders. Also, individual psychological interviews tended to be in favor of a general improvement in quality of life (more social interactions for instance).

Conclusions/Relevance

To our knowledge, the management program we have elaborated is the first designed to improve cognitive deficits in MS. These encouraging results suggest possibilities for improving cognition and thus quality-of-life in MS patients.     

Aspects cliniques, radiologiques, pronostiques et thérapeutiques des lésions démyélinisantes extensives

Background

Demyelinating diseases presenting with a tumefactive demyelinating lesion (TDL) raise questions about classification, diagnosis, prognosis, and treatment. Their long-term course is not well described in literature.

Patients/methods

In a retrospective study, we describe the main characteristics of 29 patients with TDLs. In a case control study, we compared two cohorts of multiple sclerosis (MS) patients: 24 MS patients with TDL versus a reference cohort of patients with relapsing remitting MS. We compared the extended disability status score (EDSS) concerning the first demyelinating event (DE) with TDL, EDSS score at the end of follow-up and treatment intake. The objective was to discuss the prognosis and the management of TDL.

Results

In our study, the prognosis was better for patients with non-prevalent TDL (first DE without TDL) compared with patients with prevalent TDL (first DE with TDL) and was not different compared with the MS reference cohort. At the end of follow-up, there was no significant difference between patients treated with immunosuppressors after a first DE with TDL and patients with classical MS. The EDSS at the end of follow-up was statistically more severe for untreated patients after a first DE with TDL than for classical MS patients (P = 0.0047).

Discussion

The prognosis of patients with TDL is difficult to assess because of its multifactorial nature (underlying disease and treatment impact). In our cohort, outcome of MS patients whose first severe DE involved a TDL was better when they received an early immunosuppressive treatment.     

Évènements psychotiques inauguraux de sclérose en plaques ?

Introduction

Psychotic symptoms are not readily recognized in multiple sclerosis, especially at the beginning of the disease.

Methods

We report the cases of four patients who developed psychotic symptoms that led to the diagnosis of multiple sclerosis. We describe the psychiatric and neurological features, MRI findings, clinical outcome and treatment.

Results

Two patients developed persecutory delusions, one presented a manic episode and the fourth melancholia with catatonia. Mean age was 39 years (range 20-49 years). Two patients had a personal history, but none a familial history of psychiatric disease. Examination of the cerebrospinal fluid revealed an oligoclonal pattern in all patients. All patients fulfilled Barkhof's MRI criteria. Three have had brain MRI with injection during psychotic symptoms. In these three cases, a frontal lesion appeared. The patient with catatonia also had a new lesion in the cerebellum and in the brainstem. All patients needed a “psychiatric” treatment, including antipsychotics. The psychiatric event lasted three months for two patients and the two others experienced relapse.

Conclusion

Acute psychiatric symptom may reveal multiple sclerosis at the beginning of the disease. Frontal lobe localization is suggested. We propose that a psychotic event may correspond to a multiple sclerosis event.     

Métamémoire, remémoration et familiarité dans la maladie d’Alzheimer

Introduction

The main objective of this review is to present a new approach to the memory deficit in Alzheimer's disease. Recent memory models suggest that information is recovered either on the basis of recollection or on the basis on familiarity. Recollection, unlike familiarity, requires the retrieval of contextual details related to the encoded information.

State of the art

This review suggests that recollection is particularly affected in Alzheimer's disease. In contrast, familiarity seems to be relatively preserved. A related deficit in metamemory is observed when recollection is required; a decrease in recollection in Alzheimer's disease could explain the pattern of metamemory problems. The deficit in recollection could be explained by a disconnection between medial temporal areas and frontal areas.

Perspectives

This novel approach to memory gives research perspectives concerning both early diagnosis and rehabilitation strategies of Alzheimer disease.

Conclusion

This overview showed deficits in conscious memory processes conceived of as recollection. These novel insights should provide new explanations for the deficits observed in Alzheimer's disease, particularly metamemory.     

Rétinopathie liée à l’interféron-ß 1a sous-cutané

Introduction

Interferon-α associated retinopathy is an ocular complication of hepatitis C treatment well established in the literature. But, there are far fewer reports on multiple sclerosis related interferon-ß retinopathy.

Case report

A 58-year-old male while receiving subcutaneous interferon-ß 1a 44 μg thrice a week since 2001 for multiple sclerosis developed blurred vision. Visual acuity remained stable throughout the course of surveillance. Cotton wool spots were found on fundus exam. The retinopathy disappeared without specific therapy 2 months after discontinuing interferon injections. The diagnosis of interferon-ß 1a retinopathy was retained due to the lack of any other etiology.

Conclusion

An ophthalmological examination including a fundus examination to search for a retinopathy should be undertaken when new ocular symptoms develop in a multiple sclerosis patient receiving interferon. An adverse event linked to interferon can be discussed and favored if the retinopathy resolves after interferon withdrawal.     

Stability of cognitive functions under mitoxantrone therapy in patients with progressive multiple sclerosis: a pilot analysis

Objective

Mitoxantrone (MX) is a potent immunosuppressant that is licensed as escalation therapy for the treatment of active multiple sclerosis (MS).

Methods

In an open-label, retrospective analysis, we investigated effects of MX therapy on parameters of cognitive functions in patients with progressive MS and significant disability. Twenty patients received a total of 42 mg/m² MX in 4 cycles. Six patients who fulfilled the criteria for MX therapy, yet did not receive this treatment, served as controls. Before initiation of therapy and after a mean observation period of 24 months, neurological examination and a neuropsychological test battery were performed. Neuropsychological analyses comprised tests for cognitive flexibility as a part of executive functioning, and verbal as well as non-verbal tests for memory and attention. Additionally, intelligence and symptoms of depression were investigated.

Results

While there was stability of EDSS over time, there were no differences in cognitive functions before and after MX treatment. In contrast, patients not receiving MX showed a worsening of verbal short term memory and cognitive flexibility over the same time period.

Conclusion

In conclusion, this preliminary observational study points at stability of cognitive functions under MX therapy in patients with progressive multiple sclerosis.     

Cognitive and behavioural correlates of different domains of psychological adjustment in early-stage multiple sclerosis

Objective

This study investigated a cognitive-behavioural model of adjustment to multiple sclerosis (MS). It aimed to determine the contribution of cognitions and behaviours to the explanation of two distinct adjustment outcomes above and beyond measures of MS severity. Illness-related functional impairment was anticipated to be most strongly related to unhelpful thoughts and behaviours that were specific for MS and the experience of symptoms. Psychological distress was hypothesised to be most strongly related to more general unhelpful cognitions about the self and emotions.

Methods

Ninety-four people with MS completed questionnaires. Correlations and hierarchical multiple regressions determined the relative contribution of illness severity, cognitions, and behaviours to the prediction of psychological distress and functional impairment.

Results

Illness-related functional impairment was related to disease severity, progressive versus relapsing-remitting disease, and unhelpful illness perceptions and cognitive and behavioural responses to symptoms. Illness severity factors accounted for a significant 23.7% of the variance in functional impairment (P<.001). Cognitive and behavioural variables explained a further 22.6% of the variance (P<.001), with behavioural responses to symptoms emerging as the strongest predictor. The correlates of distress were unhelpful beliefs about the self, unhelpful beliefs about emotions, acceptance, and unhelpful cognitive responses to symptoms and illness perceptions. Illness severity factors explained only 2.2% of the variance in distress (P>.05), while cognitive and behavioural variables accounted for 37.1% (P<.001). Unhelpful beliefs about the self were the strongest predictor.

Conclusion

Longitudinal and experimental research is required to investigate potential causal relationships. However, the cognitions and behaviours identified as important for adjustment are potentially modifiable and thus may be useful to address within interventions for adjustment to MS.     

Anévrismes intracrâniens et sclérose tubéreuse de Bourneville : une association rare

Introduction

Tuberous sclerosis is an autosomal dominant inherited phakomatosis. It is associated with a wide variety of central nervous system abnormalities, but intracranial aneurysms are rare.

Case report

We report a 34-year-old patient fulfilling the diagnostic criteria of tuberous sclerosis in association with intracranial aneurysm.

Discussion

This association has been reported in only 17 other cases of tuberous sclerosis. We discuss the etiopathogenic mechanisms, preferential localizations and the various therapeutic propositions.     

Le réseau cérébral par défaut : rôle cognitif et perturbations dans la pathologie

Introduction

A “resting state” or “default mode network” has been highlighted in functional neuroimaging studies as a set of brain regions showing synchronized activity at rest or in task-independent cognitive state.

State of the art

A considerable and increasing number of studies have been conducted over the last few years so as to unravel the cognitive function(s) of this brain network.

Perspectives

This review gives an overview of anatomical, physiological and phenomenological data regarding the default mode network. Different hypotheses have been proposed regarding the role of this network. Several studies have highlighted its involvement in autobiographical memory, prospection, self, attention, and theory of mind. The influence of the attention level and consciousness onto resting state brain network activity has also been discussed. Specific changes have been described in normal aging, Alzheimer's disease (AD) and multiple sclerosis (MS).

Conclusions

These studies altogether contribute to a better definition of the default mode network, in terms of implicated brain structures, subtending mechanisms, and potential cognitive roles. For instance, similarities and relationships were found between self-related brain activity and resting-state activity in regions belonging to this network, namely posterior cingulate and prefrontal areas that may reflect introspective activity experienced, more or less consciously, when the brain is not specifically engaged in a cognitive task. As a whole, the default mode network appears as a non human-specific intrinsic functional network, active all over the life from birth until aging where it is progressively modified, and sensitive to different pathologies including AD and MS. On the other hand, many points remain to be clarified concerning this network, such as the exact part of its activity dedicated to self-related cognitive processes (introspection, imaginary mental scenario based on past autobiographical experiences) and that involved in a sentinel-like attentional process designated to react to possible environmental events. Indeed, it seems that this network is functional even in case of low level of consciousness, i.e., during light sleep. Conversely, a loss of self and environment perception as in coma, deep sleep or anesthesia might modulate its connectivity along the anteroposterior axis, i.e., frontal activity disappearance associated with a parietal reinforcement of connectivity. Since studies aiming at highlighting these points are still uncommon to date, exhaustive and objective explorations are needed to better understand all these resting state processes.     

Apports des dispositifs robotisés à la rééducation du membre supérieur hémiplégique

Introduction

Poststroke rehabilitation care has evolved considerably over the last decade. The emergence of the concepts of brain plasticity and motor learning has led to the development of new therapeutic approaches. Most of the new strategies are based on movement therapy, which can have a real impact on neurological recovery, sometimes with significant functional benefit for the patient.

State of the Art

In this context of evolving practices, the hemiplegic arm is the subject of special attention. Considering the often unfavorable “natural” prognosis and the relatively limited impact of conventional therapies; researchers have focused work on new alternatives. Cooperation between developers of technological advances and the medical community has led to the development of innovative therapeutic options often based on the use of specific technological tools (functional electric stimulation, virtual reality, transcranial magnetic stimulation…) to solicit or facilitate movement.

Perspectives/conclusion

Robot-assisted rehabilitation lies within this scope. The positive results reported in the most recent publications and the growing interest for this type of therapy in the fields of medical and engineering research should open the way for extremely promising prospects. The technological performance of new robots has nevertheless raised a large number of unanswered questions, implying a significant amount of further research.     

Cerebral abscess due to an abnormal drainage of the superior vena cava

Introduction

Causes of brain abscesses are multiple and often unclear. We present the case of a pregnant woman who developed a temporal brain abscess revealed by an epileptic seizure.

Observation

Perfusion lung scan was performed because she had a mild hypoxemia: absence of contrast into the pulmonary arteries was suggestive of a massive intracardiac shunt or an anomalous drainage of the superior vena cava. Contrast-enhanced echography showed an abnormal drainage of the superior vena cava into the left atrium.

Conclusion

Although rare, this anomaly can exist in adults. This report emphazes the necessity of effective cardiologic investigations in case of unexplained brain abscess.     

Cognitive abilities and clinical variables in bipolar I depressed and euthymic patients and controls

Background

While studies demonstrated that bipolar patients (BP) display cognitive deficits during mood episodes and remission, little is known about the clinical influences underlying these deficits. The aim of this study was to compare the performance of euthymic and depressed BPs and non-affective/psychotic disorder controls at several cognitive tasks, exploring which clinical variables influenced the performance of these subtests. It is hypothesized that the cognitive deficits in rank order are: depressed BPs > euthymic BPs > controls.

Methods

Sixty-five bipolar-I outpatients and thirty-four controls were assessed by the Brazilian version of the Wechsler Adult Intelligence Scale, Third Edition (WAIS-III). BPs were divided into depressed and euthymics, and these two groups were then compared to non-affective/psychotic disorder controls.

Results

For 12 of 14 subtest scores, comparisons yielded statistically significant (p < 0.05) between-group differences, including three subtests of attention and working memory (Digit Span and its two subtests) with both depressed and euthymic BPs, compared to controls, displaying significantly worse performance, and six subtests of visual and working memory with depressed (but not euthymic) BPs performing worse than controls. For all subtests, comparisons of depressed and euthymic patients’ scores were non-significant. Performance on several subtests was negatively predicted by the severity of the disorder in both patient groups.

Limitations

The cross-sectional design of the study, as well as confounding effects of medications and co-morbidities.

Conclusions

The fact that the impairment of cognitive performance of both groups of patients is influenced by the severity of the illness is consistent with the literature.     

Maladie des grains argyrophiles : composante synergique de la démence ?

Introduction

Argyrophilic grain disease (AGD) is one cause of neurodegenerative dementia with a variable clinical spectrum. A neuropathology study is required for diagnosis.

Case report

We report the case of a 68-year-old patient presenting with cognitive decline associating with frontal dysfunction and parkinsonism. Death occurred two years after onset. The neuropathology study revealed a status criblosus in the basal ganglia, neurofibrillary tangles and AGD.

Discussion

We suggest that AGD could explain the atypical course of this dementia considering the fast cognitive decline, the clinical expression and the topography of the lesions.

Conclusion

This case illustrates the possible synergistic deleterious effect of this pathology on other causes of dementia.     

Étude longitudinale de la qualité de vie dans la sclérose en plaques : corrélation aux paramètres morphométriques de l’imagerie

Introduction

Health related quality of life (HRQOL) is often affected in multiple sclerosis (MS). Nevertheless, to our knowledge, there is no longitudinal study in the literature about the correlation between MRI parameters and HRQOL in MS patients.

Methods

We included 28 patients with clinically definite relapsing remitting MS. All patients initiated subcutaneous interferon beta-1a therapy. To assess HRQOL, we used the SEP-59 scale, the French validated translation of MSQOL-54, and the MusiQoL scale. Conventional MRI was performed every year. Lesion load (LL) and brain atrophy were automatically measured using SepINRIA, a free software developed by INRIA in Sophia Antipolis.

Results

The mean EDSS score was 1.7 and disease duration was 2.5 years. Our results revealed that HRQOL was significantly correlated to T1 and T2-LL with both SEP-59 and MusiQoL scales. T1-LL was better correlated with physical dimensions and T2-LL was better correlated with mental components. At 1-year follow-up, patients whose MRI showed either an increase of T1 LL or at least one gadolinium enhancing lesion had a worse HRQOL at the end of the study. Initial brain parenchymal fraction (BPF) measure was also correlated with the long-term follow-up HRQOL. EDSS scored at the end of the study had not significantly changed (1.3; P > 0.05).

Conclusion

Our study revealed pertinent clinicoradiological correlations between HRQOL and MRI parameters in our cohort.     

Bénéfice d’un programme cognitivo-comportemental et pluridisciplinaire de prise en charge de la maladie d’Alzheimer sur l’anxiété du conjoint : étude française ELMMA

Introduction

Over the last decade, several programs have been developed for caregivers of Alzheimer disease patients. In France however, studies exploring their effects are still scarce. We conducted a study to compare two different interventions: a structured multidisciplinary program versus a classical intervention designed for Alzheimer disease patients and their spouses.

Methods

Sixteen couples (Alzheimer's disease patient and spouse) residing in our administrative district participated in this monocentric study. For at least two years, these couples participated in a multidisciplinary program (n = 8 couples) or received usual care (n = 8 couples). The multidisciplinary program involved biannual consultations with a neurologist, a neuropsychologist and a psychologist, in addition to an annual meeting, stratified on the patient's MMSE score, for spouses). Usual care involved biannual consultations with the neurologist. The multidisciplinary program included a psychological intervention based on cognitive behavioral theories and centered on psycho-education, problem solving, adaptation strategies and on prevention of depression and anxiety. The spouses and the patients evaluated the 2-year follow-up during clinical interviews, completed by questionnaires. Sociodemographic data were noted for the patients and their spouses. Levels of depression and anxiety (Mini International Neuropsychiatric Inventory, Montgomery and Asberg Depression Scale, State-Trait Anxiety Inventory), perceived stress (Perceived Stress Scale) and care burden (Zarit Burden Inventory) were evaluated in spouses. Levels of cognitive impairment (Mini Mental State Examination), autonomy (Instrumental Activities of Daily Living), psychological state (Montgomery and Asberg Depression Scale, Covi Anxiety Scale), and behavioral symptoms frequency (Neuropsychiatric Inventory) were assessed in patients.

Results

The main significant result showed that the spouses’ state of anxiety was lower among participants in the multidisciplinary program, compared with the classical neurological intervention. It also was found that the spouses and the patients who participated in this multidisciplinary program were less depressed.

Conclusion

This study shows that a multidisciplinary structured intervention, with only two annual consultations and one annual meeting for spouses, can contribute to decrease significantly the spouses’ state of anxiety. Further studies including a larger number of subjects should be conducted to confirm these findings.     

Cardiac myxoma complicated with cerebral aneurysms and revealed by an ischemic stroke

Introduction

Myxoma is a rare benign primary cardiac tumor. It may cause vascular complications. Neurological symptoms may precede or accompany the diagnosis of myxoma with systemic embolization occurring most often in the cerebral circulation.

Observation

We report a case of cardiac myxoma complicated with cerebral aneurysms and revealed by an ischemic stroke in a 21-year-old patient. The cardiac myxoma was discovered during the transthoracic echocardiography performed as part of the etiological work-up. Because of the high risk of embolism, the mass was resected and mitral valve surgically repaired. The postoperative outcome was uneventful.

Conclusion

Although myxoma is a benign tumor histologically, it can lead to serious complications such as systemic embolism and sudden death.     

Subjective cognitive impairment: Functional MRI during a divided attention task

Background

Individuals with subjective cognitive impairment (SCI) have persistent memory complaints but normal neurocognitive performance. For some, this may represent a pre-mild cognitive impairment (MCI) stage of Alzheimer's disease (AD). Given that attentional deficits and associated brain activation changes are present early in the course of AD, we aimed to determine whether SCI is associated with brain activation changes during attentional processing.

Methods

Eleven SCI subjects and 10 controls completed a divided attention task during functional magnetic resonance imaging.

Results

SCI and control groups did not differ in sociodemographic, neurocognitive or behavioural measures. When group activation during the divided attention task was compared, the SCI group demonstrated increased activation in left medial temporal lobe, bilateral thalamus, posterior cingulate and caudate.

Conclusion

This pattern of increased activation is similar to the pattern of decreased activation reported during divided attention in AD and may indicate compensatory changes. These findings suggest the presence of early functional changes in SCI; longitudinal studies will help to further elucidate the relationship between SCI and AD.     

Strategy instruction in Parkinson's disease: Influence on cognitive performance

Objectives

Though strategic deficits are extensively investigated in Parkinson's disease (PD), little is known about the effects of instruction for PD patients. Thus, we compared the ability to internally generate a cognitive strategy with the ability to use a strategy after elaborate strategy instruction.

Methods

Patients with PD (n = 14) and matched healthy controls (n = 22) were administered a Numerosity Judgement task in which they had to determine different numerosities of blocks presented in a square grid. In more complex task configurations, healthy participants tend to use a subtraction strategy. Participants in our study were confronted with a counting condition (A), a strategy initiation condition without instruction (B), and a strategy elaboration and strategy training condition (C).

Results

Patients and controls were comparable with respect to basic cognitive measures. PD patients and controls performed equivalently within the counting condition (A), but patients needed significantly more trials to initiate the subtraction strategy. With the exception of 1 PD patient, all patients were able to internally initiate the strategy (condition B). In condition C, both groups increased reaction times, but patients were significantly slower than controls. Moreover, only patients significantly increased error rates after strategy instruction.

Conclusion

As long as sufficient time is provided for solving the task, results do not show a general deficit in the ability to internally generate a cognitive strategy in PD. Failures in strategy utilization strongly depend on cognitive load (working memory, executive functions). This bears important implications for the neuropsychological rehabilitation of PD patients.     

Reconnaissance visuelle des émotions faciales au cours d’un trouble dépressif majeur de type mélancolie délirante

Background

Abnormal recognition of facial expressions (ARFE) is associated with poor inter-relational difficulties. Among depressive patients, the difficulties in recognising facial expressions lead to errors in emotionally charged information.

Objectives

To evaluate ARFE following the Analysis method and the search for emotional integration (MARIE). This tool uses a continuation of fictive portraits created from two real portraits and in varying proportions (Professor Eckman's portraits with his agreement). This is an emotional series, which can be either unipolar or bipolar (neutral/emotion, emotion/emotion). The subject has to choose between two possibilities for each portrait. The programme comprises nine series of 19 pictures of three different faces (a fair-haired woman, a dark-haired woman and a man).

Statistical analysis

An average between the two evaluations (X² test) can be compared according to the patient's answers. Comparison of results between patient's answers before and after the treatment and results before and after of a standard reference, which is, by definition, 100%. Comparing the averages of time answering between the two evaluations (Student test) by logarithms.

Results

The joy would be the emotion most sensitive to improve the mood and thus therapy. Conversely, recognition of fear and surprise would be the less sensitive. There would be a gradient answer of qualitative (type of emotion) and quantitative (intensity score) over treatment. The patient hardly recognizes the sadness at the opposite of the anger. There would be a hypo-sensibility to sadness or hypersensitivity to anger in a major depression. However, the disorder varies according to the face presented.

Discussion

We report the results of a unique case and we must remain critical. However, the results are in the line with most writers. It credits the interest of the measurement tool. The graduation in the intensity of the scores does not suggest a single system but seven emotional subsystems separated which intensity of the response is proportional to the mood disorder. This work should be extended to a homogeneous population of patients with more tests faces to avoid the idiosyncrasie and to better study the interactions between emotions and mood.