[Study of episodic memory in multiple sclerosis using the California Verbal Learning Test: the data favour altered encoding]. / Etude de la mémoire épisodique dans la sclérose en plaques grâce au California Verbal Learning Test: données en faveur d'une altération de l'encodage.

INTRODUCTION: Alteration of episodic memory is one of the main cognitive deficits observed in MS patients. PATIENTS AND METHODS: We studied episodic memory in a group of 71 MS patients (37 RR, 34 SP) with the California Verbal Learning test (CVLT). Direct scores and calculated indices from CVLT performances were analyzed in comparison with controls. RESULTS: We observed a deficit of episodic memory in 69 p.cent of patients. This deficit was related to an alteration of encoding and retrieval processes. Despite SP-MS patients performances were constantly lower than those of RR-MS patients no significant difference was observed between the two groups. Significant correlation between the disease duration and CVLT performances were observed for the whole group but not for RR- or SP-MS groups separately, indicating that duration is more important than the phase of the disease in the worsening of memory deficit.

[Quantitative relationships between ADC and perfusion changes in acute ischemic stroke using combined diffusion-weighted imaging and perfusion MR (DWI/PMR)]. / Relation quantitative des modifications de la diffusion et de la perfusion au sein du parenchyme cerebral au cours de l'accident ischémique aigu.

UNLABELLED: MR-based diffusion- and perfusion-weighted imaging (DWI/PWI) has become the standard imaging technique to assess the individual brain pathophysiological status in acute ischemic stroke. The finding of a "mismatch" with larger PWI than DWI abnormality is thought to reflect the presence of tissue at-risk of infarction, i.e., penumbra. However, there has been no detailed study of the quantitative relationships between perfusion and diffusion changes in stroke patients. According to the experimental concept of penumbra, the ADC would be expected to remain unchanged despite decreasing perfusion until a critical threshold is reached. We have tested this hypothesis directly in man. METHODS: DWI/PWI was performed in 7 patients with MCA territory stroke within 4-10 hrs from onset. Mismatch was defined on diffusion and rMTT maps, and circular ROIs were positioned within the ADC lesion (D), the mismatch area (M), and the normal appearing cortex (N); mirror ROIs were also obtained, and affected/unaffected ratios for ADC and rCBF were computed for each ROI. RESULTS: The mean (+/-1 SD) ADC ratios were 0.60 +/- 0.09, 0.95 +/- 0.10 and 1.02 +/- 0.04 in L, M and N, respectively; the corresponding rCBF ratios were 0.32 +/- 0.12, 0.75 +/- 0.14 and 0.97 +/- 0.09, respectively. The relationship was non-linear, with the rCBF but not the ADC ratio for M being significantly lower (p < 0.01) than that for N. A threshold for decline in ADC was apparent around 0.50 rCBF ratio. COMMENT: These results directly document in man that the ADC declines only after hypoperfusion has reached a certain degree (about 50%), consistent with the concept of the ischaemic penumbra.

Nitrous oxide anesthesia-associated myelopathy.

BACKGROUND: The role of nitrous oxide exposure in neurologic complications of subclinical cobalamin deficiency has been reported, but few cases are well documented. OBSERVATION: Two weeks after surgery for prosthetic adenoma, a 69-year-old man developed ascending paresthesia of the limbs, severe ataxia of gait, tactile sensory loss on the 4 limbs and trunk, and absent tendon reflexes. After a second surgical intervention, the patient became confused. Four months after onset, the patient had paraplegia, severe weakness of the upper limbs, cutaneous anesthesia sparing the head, and confusion. Moderate macrocytosis, low serum B12 levels, and a positive Schilling test result led to the diagnosis of pernicious anemia. Results of electrophysiologic examinations showed a diffuse demyelinating neuropathy. Magnetic resonance imaging of the spinal cord disclosed hyperintensities of the dorsal columns on T2-weighted images. CONCLUSIONS: Pernicious anemia can result in severe neurologic symptoms with only mild hematologic changes. The role of nitrous oxide anesthesia in revealing subclinical B12 deficiency must be emphazised. Magnetic resonance imaging of the spinal cord might be helpful in making the diagnosis.

Sequential activation brain mapping after subcortical stroke: changes in hemispheric balance and recovery.

We prospectively studied 5 patients while they were recovering from left-sided subcortical stroke affecting the cortico-spinal tract, and examined them twice with H(2)(15)O-PET over several months while performing an identical task with the affected hand. Concomitant motor recovery was assessed by measuring the number of thumb-to-index tappings performed in 15 s at each PET session. Across patients, the hemispheric activation balance tended to shift over time toward the unaffected hemisphere, but the magnitude of this shift was highly variable from patient to patient and significantly correlated with recovery. Thus, in subcortical stroke, a shift of activation balance towards the unaffected hemisphere appears associated with lesser initial recovery and, conversely, the more this physiological balance is maintained over time the better the recovery.

Relationships between striatal dopamine denervation and frontal executive tests in Parkinson's disease.

Indirect evidence from human and monkey investigations supports the idea that impaired frontal tasks in Parkinson's disease (PD) may result from striato-frontal disruption caused by dopamine (DA) denervation of the caudate nucleus. To directly investigate this hypothesis, we used PET with 11C-S-Nomifensine (11C-S-NMF), a sensitive marker of striatal DA denervation, in 10 non-demented PD patients in whom two frontal executive tests, the object alternation (OA) and the conditional associative learning (CAL) tasks, thought to reflect mainly set-shifting/inhibition and planning, respectively, were given. In addition, the central executive function of verbal working memory was assessed with the Brown Peterson paradigm (BPP). We found a highly significant correlation between right caudate 11C-S-NMF specific binding and OA performance, less significant and reverse-direction correlations between CAL performance and putamen 11C-S-NMF binding, and no significant correlation with BPP performance. Thus, caudate DA denervation may subtend poor set-shifting/inhibition process in PD. Our results also point to distinct and complex relationships between striatal DA and specific frontal tasks.

Cognitive patterns in subtypes of schizophrenia.

AIM: Because of the heterogeneity of schizophrenia, this study researched different cognitive patterns in distinct subtypes of schizophrenic patients. METHODS: Thirty-five Diagnostic and Statistical Manual IV (DSM IV) schizophrenic patients and 35 healthy controls were included. Patients were categorized into deficit, disorganized and positive subtypes with the schedule for the deficit syndrome (SDS) and the positive and negative syndrome scale (PANSS). Executive/attentional functions were assessed with the modified card sorting test (MCST), a test of verbal fluency, the trail making test (TMT) and the Stroop color-word test (Stroop test). Episodic memory was explored through the California verbal learning test (CVLT). RESULTS: The positive subtype had some executive/attentional (fluency and Stroop tests) and mnesic performances in the normal range, suggesting the preservation of good cognitive skills. In contrast, the deficit and disorganized subtypes had major mnesic and executive/attentional dysfunctions compared to healthy subjects. The deficit subtype compared to the control group performed predominantly worse on the MCST and fluency, whereas the disorganized subtype had the lowest scores on the TMT and the Stroop test. CONCLUSION: This study showed distinct cognitive patterns in deficit, disorganized and positive patients in comparison with the controls, suggesting a heterogeneous cognitive dysfunction in schizophrenia.

[Memory and executive functions in multiple sclerosis: preliminary findings with a cognitive battery]. / Mémoire et fonctions exécutives dans la sclérose en plaques: proposition d'une batterie adaptée.

Twenty one MS patients suffering from a relapsing-remitting (four patients), a secondary progressive (12 patients) or a primary progressive form of the disease (five patients) were assessed using a cognitive battery specifically devoted to executive and memory processes. Results showed that, patients without significant depressive state evaluated by the MADR scale, exhibited significant impairments in executive processes, working, episodic and procedural memories whereas short term memory, language and global intellectual efficiency were normal. The preliminary data suggest an impairment of encoding, a process previously underestimated in this disease. In addition, the battery was easily administered to the patients and relevant for the cognitive assessment of MS.

[Familial idiopathic striato-pallido-dentate calcifications: clinical and brain imaging study in a family]. / Calcifications striato-pallido-dentelées idiopathiques familiales. Etude clinique et en imagerie d'une famille et revue de la littérature.

Familial idiopathic basal ganglia calcification (FIBGC) is a rare condition and its pathophysiology has not so far been elucidated. We report the results of a clinical study in two patients of a family affected with FIBGC. Brain imaging with 18-FDG-PET was performed in one. Psychiatric and cognitive troubles were the main clinical symptoms. Basal ganglia calcifications were associated with white matter lesions. The PET study performed in one patient revealed a striatal and a posterior cingulate hypometabolism. Posterior cingulate gyrus is involved in episodic memory processing, and could be involved in episodic memory deficit observed in this patient. These results suggest that a cortical dysfunction could be associated to the disease. The underlying mechanism, that could be a neuronal loss, a cortical deafferentation or an alteration of synaptic transmission, remains to be elucidated.

[Clinical and cognitive study of apraxia in cortico-basal atrophy. A selective disorder of the production system]. / Etude clinique et cognitive de l'apraxie dans l'atrophie cortico-basale. Un trouble sélectif du système de production.

The aim of this study was to characterize the different processes underlying apraxic disorders in cortico-basal degeneration. Three patients were submitted to a prospective paradigm elaborated in the theoretical framework proposed by Roy and Square (1985). This cognitive model postulates a two-steps system in the control mechanisms in limb praxis: the conceptual system and the production system. Our results, strictly similar for the three patients, showed a sparing of the conceptual system and an impairment of the production system with a dramatic lack in the control of the temporal and spatial aspects of the gestures. These results suggest a dysfunction of the premotor cortex including the supplementary motor area.

[Ataxic hemiparesis with cerebellar dysarthria due to an opercular lesion]. / Hémiparésie ataxique avec dysarthrie cérébelleuse par lésion operculaire.

A 63 year-old-man, with an opercular infarct had a motor deficit with ataxic hemiparesis and cerebellar dysarthria. The motor deficit disappeared, but the cerebellar signs remained after three months. A voice instrumental analysis confirmed the cerebellar pattern of the dysarthria. CT and MRI showed the opercular lesion and the normality of the cerebellum and the pons. A volumic MRI analysis precised the localisation and the volume of the lesion. The oxygen consumption (CMRO2) was measured with PET and showed no cerebellar diaschisis. We propose that, in this case, the cerebellar dysarthria is the orofacial ataxic component of the hemiparesis. We suggest that it is related to disruption of the cortico-cerebellar tract, connecting the right orofacial frontal area of the primary motor cortex with the paravermal segment of the left cerebellar hemisphere.

The metabolic substrates of bradykinesia and tremor in uncomplicated Parkinson's disease.

The pathophysiological mechanisms of bradykinesia and resting tremor, i.e., two major features of Parkinson's disease (PD), remain incompletely understood despite extensive studies, including functional imaging investigations. Using high-resolution positron emission tomography (PET) and [(18)F]fluoro-2-deoxyglucose (FDG) in 17 nondemented patients with uncomplicated PD on a stable therapeutic regimen, we measured the resting-state cerebral metabolic rate of glucose (CMRGlc), a validated marker of synaptic density/activity. Following formulation of distinct a priori hypotheses about potentially involved brain regions based on previous experimental and clinical literature, correlations between CMRGlc and objective scores of bradykinesia and tremor were searched in a voxel-based fashion using SPM99. Bradykinesia scores were significantly positively correlated with bilateral putamen and globus pallidum CMRGlc, while tremor scores were negatively correlated with bilateral putamen and cerebellar vermis CMRGlc. There was a large overlap of putamenal voxels significantly but inversely correlated with both extrapyramidal features. For both bradykinesia and tremor, the observed patterns of subcortical correlations largely concurred with our a priori hypotheses, and point to the major role of disruption of the striatofrontal and corticocerebellar pathways in the genesis of these extrapyramidal features. The direction of these correlations was not entirely expected, however, which may be due to the patients' being studied on medication, contrary to most studies performed to date. The observation that overlapping portions of the putamen inversely correlated with bradykinesia and tremor was a novel and striking finding which points to the complexity of the underlying pathophysiology of PD. Because it allows greater control of the neurological status, studying patients on medication may partly explain our findings. Voxel-based analysis of resting FDG-PET holds considerable potential for assessing the neural substrates of motor impairment in PD.

PET imaging of neocortical monoaminergic terminals in Parkinson's disease.

Post-mortem neurochemical studies in Parkinson's disease (PD) have shown that, in addition to the typical nigro-striatal dopamine denervation, there exists a concomitant neocortical monoamine fibre deafferentation (of variable severity) whose role in motor, and especially in associated cognitive and affective impairment, remains elusive. We have extensively examined whether PET imaging with 11C-S-Nomifensine (11C-NMF), a radioligand of the dopamine and norepinephrine presynaptic reuptake sites which has been used so far to investigate the striatum, could provide a method for assessing in vivo the neocortical monoamine terminal loss in PD; previously, this has been a little addressed and controversial issue. To this end, we prospectively selected a highly homogeneous sample of nine non-demented, non-depressed idiopathic PD patients with mild to marked side-to-side asymmetry in motor impairment. In addition to recovering the previously-reported correlations with putaminal 11C-NMF specific uptake asymmetries, the clinical motor asymmetries also significantly correlated in the clinically expected direction to neocortical (especially frontal) 11C-NMF asymmetries, suggesting the monoamine neocortical denervation might play a direct role in motor impairment in PD. These results demonstrate that it is possible to assess in vivo the neocortical monoamine terminal loss, and to elucidate its potential role in the complex cognitive and affective impairment, in both PD and atypical degenerative parkinsonism.

Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD).

In 1992 the Core Assessment Program for Intracerebral Transplantations (CAPIT) was published providing the minimal requirements for a common patient evaluation protocol. Despite the intent, the program was thought to be too laborious to carry out in large scale trials, and it also lacked evaluations of cognitive functions and quality of life. Moreover, the CAPIT was designed for neural transplantation only and has not been revised since. Since then, pallidotomy and deep brain stimulation have emerged as additional treatment modalities but there exists no common tool for evaluation of, and between, the techniques. In 1996, within the framework of NECTAR (Network for European CNS Transplantation and Restoration), a dedicated program entitled "Neurosurgical Interventions in Parkinson's Disease" (NIPD) was funded by the European Union Biomed 2 program to develop a new Core Assessment Program for Surgical Interventional Therapies in PD (CAPSIT-PD) and to establish an European registry for patients with PD subjected to functional neurosurgery. This article presents the recommendations of this new program.

Clues about the functional neuroanatomy of verbal working memory: a study of resting brain glucose metabolism in Parkinson's disease.

In addition to motor impairment, non-demented patients with Parkinson's disease (PD) exhibit a variable degree of cognitive impairment which could indicate dysfunction in the central executive of working memory. In this study, we have employed positron emission tomography measurements of resting brain glucose metabolism (CMRglc) to investigate the neural substrates underlying this dysfunction, taking PD as a model disease to assess, within the framework of Alexander's striato-pallido-thalamo-cortical cognitive circuits the functional neuroanatomy of the central executive. We studied central executive performance in 17 non-demented, highly selected PD patients, by means of the Brown-Peterson paradigm (BPP), and correlated the BPP performance according to various response delays (from 0 to 18 s) with local cerebral metabolic rates of glucose. We document for the first time that the BPP performance in PD is heterogeneous not only across delays (with PD patients selectively impaired for the 0 and 3 s delays, compatible with impaired attention and central executive, respectively), but also from subject to subject; a multiple correspondence analysis was able to distinguish two patient subgroups according to short delay BPP performance. The correlational analysis with PET data evidenced a limited number of significant correlations, most of which were consistent with our working hypothesis. Notably, a positive correlation between lateral frontal relative metabolism and BPP performance for short delays, and a negative one between these scores and mediodorsal (MD) thalamic nucleus metabolism, would fit the way in which caudate dopamine denervation would alter in opposite directions frontal cortex and MD nucleus synaptic activity and in turn affect central executive function. The results from this study lend further support to the role of altered thalamo-prefrontal interplay as the basis for central executive dysfunction in PD.

Cognitive processes involved in delayed non-matching-to-sample performance in Parkinson's disease.

Visual recognition memory was assessed in terms of delay duration, memory load and amount of interference(s) in non-demented patients with Parkinson's disease (PD) using an automated delayed non-matching-to-sample (DNMS) task with trial-unique stimuli. Special attention was focused on the different cognitive functions engaged by these patients in solving this recognition memory task. Thirteen patients with PD, carefully selected according to their stable regimen and anticholinergic medication, were compared to 12 controls matched by age and educational level. Besides the DNMS task, a neuropsychological battery that included tasks carefully selected according to processes potentially required to perform the DNMS task (e.g. attention, executive functions, visual discrimination and motor speed) was administered to the subjects. As compared with controls, patients with PD showed a deficit on most DNMS subscores, except those requiring the least cognitive load. The correlative analysis between the DNMS and other neuropsychological tasks suggests involvement of long-term memory mainly in the DNMS performance for the control group, contrasting with a major involvement of executive functions for the patients with PD. These data indicate that visual recognition memory impairment in non-demented patients with PD is largely due to an executive dysfunction, notably in working memory. Several hypotheses are proposed concerning the neuronal substrates underlying the impairment on the visual DNMS task in PD.