[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.

Vigilance and effects of fatigability, practice and motivation on simple reaction time tests in patients with lesion of the frontal lobe.

Despite the wide use of RT tests in brain-damaged patients assessment, effects of the level of vigilance, fatigability, practice and motivation on RT have been poorly investigated. We assessed vigilance and effects of fatigability, practice and motivation on brain-damaged patients suffering from lesion of the prefrontal cortex prominent in basofrontal areas and controls using simple RT tests. Our study showed fatigability and practice effects which did not affect RT differences between groups, whereas motivation effect was not significant. Finally, patients did not suffer from a deficit of vigilance. These results suggest that the attentional disorders demonstrated in the same patient group were related neither to a higher sensitivity to fatigability nor to an insufficient practice.

Cognitive and psychiatric impairment in herpes simplex virus encephalitis suggest involvement of the amygdalo-frontal pathways.

The long-term neuropsychological and psychiatric sequelae of herpes simplex virus encephalitis (HSVE) and their relationship to the volume of temporal lesions and to amygdala and hippocampus damage remain undefined. We have conducted a prospective study of long-term sequelae in 11 patients with clinically presumed HSVE and detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction. Six months after encephalitis, patients underwent neuropsychological and language assessment. At the same stage, single photon emission computed tomography (SPECT) evaluated the occurrence of hypoperfusion with an index of asymmetry. MRI was used for the measurement of amygdala, hippocampus and cerebral lesions by two blind neurologists. The volume of the amygdala and hippocampus was compared with those of five controls, matched for age and level of education. Long-term memory disorders were seen in 6 patients, associated with the larger lesions and damage of at least two structures. Long-term behavioural changes with emotionalism, irritability, anxiety or depression were prominent in 7. Left prefrontal hypoperfusion appeared in 8 patients, associated with psychiatric disorders in 7 and left amygdala damage in 6. The reduction of amygdala and hippocampus volume was correlated with the overall volume of lesions. Different patterns of mesial temporal lobe damage occurred, involving either amygdala alone, or amygdala and hippocampus, but never hippocampus alone. MRI volumetric measurements in HSVE could be a good indicator of long-term prognosis. Persistant behavioural changes could be related to an amygdala and frontal dysfunction.

[Post-traumatic retrograde amnesia]. / Amnesie retrograde post traumatique.

A case of post traumatic retrograde amnesia is described. The patient presented after an initial coma a global amnesia, but the fixation deficit rapidly disappeared, and a severe retrograde amnesia dating back to childhood experience and learning remained the main symptom. Amnesia for remote events was associated with didactic memory deficit and, at a lesser degree, with a verbal memory deficit. Recovery of fixation allowed a progressive relearning. This pattern of impairment was recently related to mesencephalic lesions, but we think that the role of temporal lobe involvement cannot be neglected.

[Evaluation of the amnesia caused by restricted thalamic infarcts--6 cases]. / Bilan de l'amnesie des infarctus thalamiques restreints--6 cas.

The amnesic syndrome is analysed in 6 infarctions restricted to the thalamic area. Bilateral lesions were linked to more definite deficits; the anterograde forgetting was unequivocal at the initial stage and affected both verbal and visual memory. In unilateral lesions, deficits were far more discrete and there was no evidence enough for assuming a strict hemispheric specialisation, left for verbal memory, and right for visual memory. These cases and others from the literature suggested that amnesia is more important and pure in infarctions of the anterior part of the thalamus.

Control functions of the frontal lobes. Modularity of the central-supervisory system?

Lesions of the prefrontal cortex result in a wide variety of neuropsychological disorders. Despite recent advances, the executive processes and their functional architecture remain poorly specified. This study assessed control processes operating in novel, conflicting and combined tasks in patients with lesion of the prefrontal or posterior cortices. Experiments used two-choice reaction time tests with similar perceptuo-motor and decision processes. It mainly showed (1) impaired short term memory in posterior patients, and (2) impairment of response inhibition and tasks combination in some frontal patients. Selective deficits with double dissociations were evidenced on novel, conflicting and combined tasks. This study provides additional evidence for the prominent role of the frontal lobes in control processes. The demonstration of selective deficits of specific control processes suggests that executive functions depend on multiple separable control processes, and that their operations can be specified in cognitive terms.

[Acute amnesia caused by a hematoma of the 3d ventricle and the fornix]. / Amnésie aiguë par hématome du troisième ventricule et du fornix.

An acute amnesic syndrome accompanied the development of a hematoma of the upper part of the third ventricle affecting the fornix. The initial deficit was substantial with corresponding forgetfulness, but there was no false recognition nor fabulation. Recollection of past events was fairly well conserved, subject to difficulties with the temporal structuring of memories. Secondarily. psychometric tests showed preferential impairment of spontaneous recollection and logical learning. The role of lesions of the upper fornix projecting onto the dorsomedian nuclei of the thalamus is discussed.

[Learning disorders after ruptured aneurysms of the anterior communicating artery]. / Les déficits d'apprentissage après rupture des anévrysmes de l'artère communicante antérieure.

The aim of this study was to reevaluate short term and long term memory disorders after anterior communicating artery rupture, then to more specifically assess the importance and the role of forgetting, proactive and retroactive interferences, impaired memory for temporal order, attention disorders and dysexecutive syndrome, and finally MRI-defined brain lesions. Twenty one patients presenting with selective anterior brain injury, were assessed at the secondary and late post stroke phases. The short term memory analysis showed the digit span was reduced at the secondary stage, but that mean performances were preserved in the Peterson and Sternberg paradigms. Verbal and visuospatial learning in long term memory showed a severe deficit in free recall, chiefly serial, and associative recall. Recognition was mildly impaired at the secondary phase, and later normalized. A definite and lasting increase of proactive and retroactive interferences and an impairment in discriminating the temporal order of word presentations were observed. Amnesic impairment was relatively well correlated with forgetting, severity of interferences and temporal order amnesia, so as with disorders of attention and executive functions (Wisconsin Card Sorting Test). However, intrusions in free recall and false recognitions were not clearly related with the dysexecutive syndrome. The severity of amnesia was associated with lesions of the left anterior cingulate cortex, and of the corpus callosum. These results suggest that these patients mainly had a deficit in information retrieval, mostly compromising long term memory, but also to a lesser degree short term memory. Forgetting, interferences and the dysexecutive syndrome probably play an important role in the decline of mnemonic performance, but do not clearly explain intrusions in recall and errors in recognition.

[Deficit of verbal recall caused by left dorso-lateral thalamic infarction]. / Déficit du rappel verbal par infarctus thalamique dorso-latéral gauche.

A case of amnesia with preferential disorder of verbal recall, associated to a limited infarct of the left superior, external and anterior thalamus, is reported. This lesion involved the anterior and middle dorso-lateral nuclei and the centrolateral nucleus, sparing most of the structures classically incriminated in diencephalic amnesia. At the initial stage, the patient presented discrete language impairment and severe deficit of semantic processing, which later recovered. At the late stage, the anterograde and retrograde amnesia principally concerned the recall of verbal information used in daily life, verbal learning using short-term and long-term recall, questionnaires evaluating retrograde memory and requiring the evocation of proper names. Verbal priming was also affected. Verbal recognition was preserved. Evocation of the most recent events of the personal life was also impaired. Confrontation of this case with others previously reported suggests that various thalamic amnesias may be described, associated to different cognitive deficits, in relation with the preferential situation of lesions.

[Dysexecutive syndrome and disorders of motor control in prefrontal mediobasal and cingulate lesions]. / Syndrome dysexécutif et troubles du contrôle moteur dans les lésions préfrontales médio-basales et cigulaires.

Disorders of executive function and motor control are considered to be classical consequences of prefrontal lesions. The aim of this study was to investigate these disorders and their evolution in a series of patients presenting with prefrontal and cingulate lesion following rupture of an anterior communicating artery aneurysm. Twenty one subjects were included, and assessed in the secondary and late post stroke phases. We have used the following tests to assess planning and/or execution time and performance: Trail Making test, Wisconsin Card Sorting Test, London Tower Test, Shopping Test of Martin, sequential gestual test and contradictory responses test from Luria. Correlations between these parameters were used to evaluate subjects strategy. In evaluation of execution time, patients were slower than controls, and the difference was more marked using the Trail Making Test (p < 0.01) and the London Tower Test (p < 0.01). Furthermore, the initiation time was increased in the London Tower Test (p < 0.01), this suggesting that they were slower than impulsive. Groups analysis showed that their performance level was most often similar to that of of controls, even in the secondary phase, with the exception of the number of problems solved whatever number of moves in the London Tower test (p < 0.01) and of the percentage of errors in the sequential motor task (p < 0.03). Similar results were observed in the evaluation of single cases. Correlations between execution time and performance were most often significant and negative, in patients and controls. These results suggest that the management of the speed-accuracy compromise was relatively similar, and that impulsivity, which associates reduction of time to poor performance, was absent or mild. Cingulate, and caudate lesions were identified as the source of most cognitive disorders.

[Neuropsychological correlates of cerebral blood flow anomalies and MRI lesions after rupture of anterior communicating artery aneurysms]. / Corrélations neuropsychologiques des anomalies du débit sanguin cérébral et des lésions IRM après rupture des anévrysmes de l'artère communicante antérieure.

The aim of this study was to investigate relations between neuropsychological disorders resulting from rupture of aneurysms of the anterior communicating artery, regional cerebral blood flow anomalies and brain lesions revealed on MRI. Blood flow was analyzed in 22 consecutive patients at least 3 weeks after surgery using single photon emission computed tomography. Flow values were calculated in 10 regions of interest on each side of the brain. Attention, motor control, executive functions, short-term and long-term learning (verbal, visuo-spatial), categorical evocation, general intellectual performances were investigated. Flow drop was observed over frontal areas, which predominated on the right side. The correlation analyses showed that

[Amnesic syndrome caused by limited infarction in the right anterior thalamus]. / Syndrome amnésique par infarctus restreint du thalamus antérieur droit.

A case of global and persistent amnesia due to a right polar and anterior thalamic infarction is reported. There was a moderate impairment of attention and categorization ability. The amnesia was primarily anterograde, with partial disturbance of short-term memory and severe deficit of long-term memory for verbal and visuo-spatial materials. A severe increase of pro-active interference was present. Retrograde memory was mildly affected. Two years later, a second infarction in the right thalamo-sub-thalamic territory occurred, increasing the deficits of attention, short-term memory and recall.

[BCcogSEP: a French test battery evaluating cognitive functions in multiple sclerosis]. / La BCcogSEP: une batterie courte d'évaluation des fonctions cognitives destinées aux patients souffrant de sclérose en plaques.

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 score3) 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.

[Residual deficit of verbal recall after a left internal cerebral vein infarct]. / Déficit résiduel du rappel verbal après un infarctus de la veine cérébrale interne gauche.

A case of unilateral infarct in the territory of the left internal cerebral vein, severely disturbing cognitive processes, and more especially recall in verbal memory, is reported. This 22-year-old patient survived a left thalamic and striato-capsular infarct related to a straight sinus and left internal cerebral vein thrombosis. Motor and functional recovery was fair, despite late dystonia. At the secondary phase post-stroke, cognitive disorders were severe, including increased short-term forgetting and episodic (anterograde and retrograde) and semantic amnesia. One year later, a residual deficit of verbal recall was observed, which participated in the anterograde and retrograde amnesia. Recognition was well preserved. This case showed that: (1) internal cerebral vein thrombosis can have severe consequences on cognition and memory, and that late prognosis is not as fair as has been previously reported in selected patients, and (2) left diencephalic structures are specifically associated with recollection of verbal information from long-term memory.

[Retrograde memory after rupture of aneurysms of the anterior communicating artery]. / La mémoire rétrograde après rupture des anévrysmes de l'artère communicante antérieure.

The aim of this study was to investigate deficits of retrograde memory, semantic, autobiographical, and for famous events, associated with prefrontal, cingulate and subcortical lesions resulting from anterior communicating artery rupture. Analyses were performed during the secondary phase post-stroke in 16 patients, and performances were compared to those of an equivalent number of matched control subjects. Semantic investigations revealed a significant deficit in each task using evocation, more especially categorical and literal evocations, and the verbal subtests of the WAIS-R: vocabulary, information, comprehension, and similarities. Furthermore, the capacity to categories was preserved. The Crovitz paradigm, which evaluated the autobiographical memory showed a severe deficit in the evocation of events associated with a precise context in place and moreover in time, with a clear tendency to produce semantic responses, but without significant increase in confabulations. The questionnaire on famous events (1936-1985) did not document deficit in recognition and recall. Furthermore, the patients disorder was more severe in learning new information. Memory disorders were best explained by the severity of lesions in the medio-basal frontal and cingulate cortices, but also by the subcortical injury. Significant correlations were observed between the retrograde memory performance and "frontal" tasks, more especially the WCST; however, similar relations were also documented between learning new information and "frontal" performance. These data suggest that retrograde amnesia results from a selective impairment in accessing old memory representations, and that cognitive processes more specifically altered have tight relations with the capacity to organize the search and to shift.

[Analysis and course of cognitive deficits after rupture of aneurysms of the anterior communicating artery]. / Analyse et évolution des déficits cognitifs après rupture des anévrysmes de l'artère communicante antérieure.

The aim of this study is to investigate general intellectual and memory performances at the secondary (3 weeks to 4.5 months) and late (10 to 16 months) stages following rupture of anterior communicating artery aneurysms (AACA). Twenty one patients presenting with selective lesion within frontal, or cingulate, callosal, caudate, basal forebrain areas were evaluated. At the secondary stage, the analysis of the general intellectual capacities revealed a drop of performance, prominent on performance IQ, which was more severe than the learning deficit. Specific cognitive evaluations revealed increase of the execution time, but performance was relatively preserved: in the Stroop test, focused attention disorder was moderate: the modified Wisconsin Card Sorting test was correctly performed in most cases; significant deficits of verbal short-term memory, long-term verbal and visuo-spatial learning, and access to semantic memory were observed. At the late stage, general intellectual performance improved, but did not reached the estimated prelesional level in most cases; specific cognitive disorders had most often disappeared. Most performances were best explained by the severity of lesions in the left cingulate cortex and corpus callosum area. These results show that the cognitive profile of AACA patients is different from classical descriptions of the "amnesic syndrome", and is also different at the secondary and late stages; this evolution has to be taken into account in studies describing cognitive deficits of such patients, or comparing them with others presenting with "annesic syndrome".

[Correlation of thalamic aphasia and cerebral blood flow]. / Corrélations de l'asphasie thalamique avec le débit sanguin cérébral.

Relations between linguistic deficits and cerebral blood flow (CBF) were studied in 20 cases of thalamic aphasia due to hemorrhage. Language analysis was based on BDAE, verbal intelligence quotient and verbal subtest of the memory quotient (Wechsler). CBF analysis (and of asymmetry index: AI) was done with 133 Xenon by SPECT technique in tomographic slices and in 15 areas of interest, i.e. cortical and deep areas. Relationships were analyzed by multiple correlations procedure and stepwise regression. Significant correlations were observed between linguistic results and AI of cortical but also deep areas (lenticular). Dynamic anomalies (fluency) were correlated with the IA and/or CBF of the frontal cortex. Verbal comprehension, naming and paraphasia were related to the AI of deep structures (insula and lenticular nucleus) and the AI of posterior cortex (temporo-occipital). Several correlations were found significant between results on verbal IQ of the WAIS and IA of the insula and lenticular nucleus.

[Psychometric study in Huntington disease]. / Etude psychométrique de la maladie de Huntington.

Thirty-two patients suffering from Huntington's disease (HD) were tested with a short neuropsychological tests battery in order to make a global evaluation of their cognitive functions, and to ascertain whether the tests would be sensitive enough, even in the first stages of the disease, and whatever the individual neuropsychological profile, to be, possibly, an assessment tool for treatment efficacy. Nineteen HD presented with a "mild" form of the disease [stage I and II of Shoulson and Fahn (1979)], 7 men and 12 women, with a duration of illness of nearly 5 years and 13 HD presented with a "moderate" form (stage III and IV), 5 men and 8 women, with a duration of illness of nearly 8 years. These 2 groups had a comparable age at the assessment time (nearly 47) and did not differ, significantly, for the age at onset (39 and 43 respectively), duration of illness or psychiatric disorders. Each test result was reduced to its number of standard-deviations apart the normal mean-value for the same sex, age and study level group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Amnesia in thalamic infarction]. / L'amnésie des infarctus thalamiques.

Restricted thalamic infarctions are in man a useful model for investigating the consequences of limited diencephalic lesions on memory and verbal or visual learning. Two new cases of amnesia with thalamo-sub-thalamic infarctions are presented, with a general review of the problem. The gathering of the different cases according to the vascular thalamic territories and, as a consequence, to nuclear or associative structures concerned, allows a better approach of the relations between amnesia and infarctions. Uni or bilateral anterior lesions are the cause of more important and pure memory deficits, posterior infarctions are more often associated to language involvement or spatial cognitive problems which interfere with memorizing.