Stability of face recognition abilities after left or right anterior temporal lobectomy.

Patients with anterior temporal lobe (ATL) resection due to mesial temporal lobe epilepsy (MTLE) have difficulties at identifying familiar faces and explicitly remembering newly learned faces but their ability to individuate unfamiliar faces remains largely unknown. Moreover, the extent to which their difficulties with familiar face identity recognition and learning is truly due to the ATL resection remains unknown. Here, we report a study of 24 MTLE patients and matched healthy controls tested with an extensive set of seven face and visual object recognition tasks (including three tasks evaluating unfamiliar face individuation) before and about 6 months after unilateral (nine left, 15 right) ATL resection. We found that ATL resection has little or no effect on the patients' preserved pre-surgical ability to perform unfamiliar face individuation, both at the group and individual levels. More surprisingly, ATL resection also has little effect on the patients' performance at recognizing and naming famous faces as well as at learning new faces. A substantial proportion of right MTLE patients (33%) even improved their response times on several tasks, which may indicate a functional release of visuo-spatial processing after resection in the right ATL. Altogether this study shows that face recognition abilities are mainly unaffected by ATL resection in MTLE, either because the critical regions for face recognition are spared or because performance at some tasks is already lower than normal preoperatively. Overall, these findings urge caution when interpreting the causal effect of brain lesions on face recognition ability in patients with ATL resection due to MTLE. They also illustrate the complexity of predicting cognitive outcomes after epilepsy surgery because of the influence of many different intertwined factors.

Naming impairments evoked by focal cortical electrical stimulation in the ventral temporal cortex correlate with increased functional connectivity.

BACKGROUND: High-frequency cortical electrical stimulations (HF-CES) are the gold standard for presurgical functional mapping. In the dominant ventral temporal cortex (VTC) HF-CES can elicit transient naming impairment (eloquent sites), defining a basal temporal language area (BTLA). OBJECTIVE: Whether naming impairments induced by HF-CES within the VTC are related to a specific pattern of connectivity of the BTLA within the temporal lobe remains unknown. We addressed this issue by comparing the connectivity of eloquent and non-eloquent sites from the VTC using cortico-cortical evoked potentials (CCEP). METHODS: Low frequency cortical electrical stimulations (LF-CES) were used to evoke CCEP in nine individual brains explored with Stereo-Electroencephalography. We compared the connectivity of eloquent versus non eloquent sites within the VTC using Pearson's correlation matrix. RESULTS: Overall, within the VTC, eloquent sites were associated with increased functional connectivity compared to non-eloquent sites. Among the VTC structures, this pattern holds true for the inferior temporal gyrus and the parahippocampal gyrus while the fusiform gyrus specifically showed a high connectivity in both non eloquent and eloquent sites. CONCLUSIONS: Our findings suggest that the cognitive effects of focal HF-CES are related to the functional connectivity properties of the stimulated sites, and therefore to the disturbance of a wide cortical network. They further suggest that functional specialization of a cortical region emerges from its specific pattern of functional connectivity. Cortical electrical stimulation functional mapping protocols including LF coupled to HF-CES could provide valuable data characterizing both local and distant functional architecture.

Preserved time but altered numerosity processing in epileptic patients with postoperative lesion in the inferior frontal gyrus.

Previous researches have shown that the inferior frontal gyrus (IFG) is involved in time and numerosity processing. This study aimed at examining (i) interval timing and (ii) interaction between duration and numerosity processing in four drug-resistant epileptic patients with postoperative lesions in the IFG in comparison with thirteen healthy controls. The duration reproduction and discrimination tasks performed in the sub- and supra-second ranges did not reveal any significant differences between patients and controls. The duration discrimination task of stimuli varying in numerosity (DurN) and the numerosity discrimination task of stimuli varying in duration (NumD) revealed that only numerosity judgment was altered in IFG patients. A time-order effect was notably observed in the NumD task but in opposite directions for the two groups: The second patch was perceived as more numerous than the first patch in controls and conversely as less numerous in patients. Finally in the DurN task, we observed a congruency effect which was dependent on numerical distance in patients but not in controls. These converging results suggest that the IFG would be more specifically involved in numerosity than in duration processing, possibly playing a role in numerical decision.

Anxiety and Depression in Newly Diagnosed Epilepsy: A Matter of Psychological History?

Purpose: Anxiety and depression are highly prevalent in patients with epilepsy (PWE), and these symptoms can even precede the onset of the pathology. We aimed to define the prevalence of anxiety and depressive symptoms at the time of the epilepsy diagnosis and the factors related to their presence in newly diagnosed adult patients. Methods: One hundred and twelve newly diagnosed patients were assessed, usually in the week after diagnosis. Patients were untreated at this time. We used the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E, cut-off ≥15) and the Generalized Anxiety Disorder 7-Item scale (GAD-7, cut-off >7). A semi-structured interview was conducted to collect sociodemographic and epilepsy data and patients' psychiatric history. We first compared patients with and without anxiety symptoms, then patients with and without depressive symptoms. Results: According to the GAD-7 scale, the prevalence of anxiety symptoms at the time of diagnosis was 35%. Patients with anxiety symptoms had significantly more psychiatric history (26%, p = 0.001) and more history of psychological trauma (51%, p = 0.003) than patients with no anxiety symptoms. According to the NDDI-E scores, the prevalence of depressive symptoms at the time of the diagnosis was 11%. Patients with depressive symptoms had significantly more psychiatric history (43%, p < 0.001) and more history of psychological trauma (65%, p = 0.007) than patients with no depressive symptoms. No difference between groups was found for other sociodemographic variables (age and gender), epilepsy characteristics (number of seizures prior to diagnosis, time from first seizure to diagnosis, type of epilepsy, and localization in focal epilepsy), or neurological comorbidities. Conclusions: Anxiety symptoms are common whereas depressive symptoms are less prevalent at the time of diagnosis. It appears essential to be aware of anxiety and depression in newly diagnosed epileptic patients. They should be screened and routinely monitored, especially those patients with a history of psychological trauma and/or psychiatric disorders. Longitudinal follow-up is required to identify whether these factors and anxiety and depression themselves have an impact on the future course of care.

Stereoelectroencephalographic language mapping of the basal temporal cortex predicts postoperative naming outcome.

OBJECTIVE: In drug-resistant temporal lobe epilepsy (TLE) patients, the authors evaluated early and late outcomes for decline in visual object naming after dominant temporal lobe resection (TLR) according to the resection status of the basal temporal language area (BTLA) identified by cortical stimulation during stereoelectroencephalography (SEEG). METHODS: Twenty patients who underwent SEEG for drug-resistant TLE met the inclusion criteria. During language mapping, a site was considered positive when stimulation of two contiguous contacts elicited at least one naming impairment during two remote sessions. After TLR ipsilateral to their BTLA, patients were classified as BTLA+ when at least one positive language site was resected and as BTLA- when all positive language sites were preserved. Outcomes in naming and verbal fluency tests were assessed using pre- and postoperative (means of 7 and 25 months after surgery) scores at the group level and reliable change indices (RCIs) for clinically meaningful changes at the individual level. RESULTS: BTLA+ patients (n = 7) had significantly worse naming scores than BTLA- patients (n = 13) within 1 year after surgery but not at the long-term evaluation. No difference in verbal fluency tests was observed. When RCIs were used, 5 of 18 patients (28%) had naming decline within 1 year postoperatively (corresponding to 57% of BTLA+ and 9% of BTLA- patients). A significant correlation was found between BTLA resection and naming decline. CONCLUSIONS: BTLA resection is associated with a specific and early naming decline. Even if this decline is transient, naming scores in BTLA+ patients tend to remain lower compared to their baseline. SEEG mapping helps to predict postoperative language outcome after dominant TLR.

Typical visual unfamiliar face individuation in left and right mesial temporal epilepsy.

Patients with chronic mesial temporal lobe epilepsy have difficulties at identifying familiar faces as well as at explicit old/new face recognition tasks. However, the extent to which these difficulties can be attributed to visual individuation of faces, independently of general explicit learning and semantic memory processes, is unknown. We tested 42 mesial temporal lobe epilepsy patients divided into two groups according to the side of epilepsy (left and right) and 42 matched controls on an extensive series of individuation tasks of unfamiliar faces and control visual stimuli, as well as on face detection, famous face recognition and naming, and face and non-face learning. Overall, both patient groups had difficulties at identifying and naming famous faces, and at explicitly learning face and non-face images. However, there was no group difference in accuracy between patients and controls at the two most widely used neuropsychological tests assessing visual individuation of unfamiliar faces (Benton Facial Recognition Test and Cambridge Face Memory Test). While patients with right mesial temporal lobe epilepsy were slowed down at all tasks, this effect was not specific to faces or even high-level stimuli. Importantly, both groups showed the same profile of response as typical participants across various stimulus manipulations, showing no evidence of qualitative processing impairments. Overall, these results point to largely preserved visual face individuation processes in patients with mesial temporal lobe epilepsy, with semantic and episodic memory difficulties being consistent with the localization of the neural structures involved in their epilepsy (anterior temporal cortex and hippocampus). These observations have implications for the prediction of neuropsychological outcomes in the case of surgery and support the validity of intracranial electroencephalographic recordings performed in this population to understand neural mechanisms of human face individuation, notably through intracranial electrophysiological recordings and stimulations.

The neural basis of rapid unfamiliar face individuation with human intracerebral recordings.

Rapid individuation of conspecifics' faces is ecologically important in the human species, whether the face belongs to a familiar or unfamiliar individual. Here we tested a large group (N = 69) of epileptic patients implanted with intracerebral electrodes throughout the ventral occipito-temporal cortex (VOTC). We used a frequency-tagging visual stimulation paradigm optimized to objectively measure face individuation with direct neural recordings. This enabled providing an extensive map of the significantly larger neural responses to upright than to inverted unfamiliar faces, i.e. reflecting visual face individuation processes that go beyond physical image differences. These high-level face individuation responses are both distributed and anatomically confined to a strip of cortex running from the inferior occipital gyrus all along the lateral fusiform gyrus, with a large right hemispheric dominance. Importantly, face individuation responses are limited anteriorly to the bilateral anterior fusiform gyrus and surrounding sulci, with a near absence of significant responses in the extensively sampled temporal pole. This large-scale mapping provides original evidence that face individuation is supported by a distributed yet anatomically constrained population of neurons in the human VOTC, and highlights the importance of probing this function with face stimuli devoid of associated semantic, verbal and affective information.

Memory improvement in multiple sclerosis after an extensive cognitive rehabilitation program in groups with a multicenter double-blind randomized trial.

OBJECTIVE: The aim of this study is to determine the effectiveness of an extended cognitive rehabilitation program in group's sessions in multiple sclerosis. DESIGN: Double-blind multicenter randomized trial. PARTICIPANTS: People with multiple sclerosis of 18 to 60 years, Expanded Disability Status Scale ⩽6.0, mild to moderate cognitive impairment. INTERVENTIONS: They were randomized into cognitive rehabilitation program (ProCog-SEP) or in a placebo program. ProCog-SEP comprises 13 group's sessions over 6 months and includes psychoeducational advices and cognitive exercises. Placebo program included non-cognitive exercises. No strategy and no cognitive advice were provided. MAIN MEASURES: The primary endpoint was the percentage of verbal memory learning measured by the Selective Reminding Test. A comprehensive neuropsychological assessment is carried out before and after interventions by a neuropsychologist blinded to intervention. Effectiveness of the ProCog-SEP versus Placebo has been verified using linear regression models. RESULTS: In total, 128 participants were randomized and 110 were included in the study after planning session in groups; 101 completed this trial (77.2% females); mean age: 46.1 years (±9.6); disease duration: 11.8 years (±7.5). ProCog-SEP was more effective in increasing in learning index (9.21 (95% confidence interval (CI): 1.43, 16.99); p = 0.02) and in working memory on manipulation (0.63 (95% CI: 0.17, 1.09); p = 0.01), and updating capacities (-1.1 (95% CI: -2.13, -0.06); p = 0.04). No difference was observed for other neuropsychological outcomes. Regarding quality of life outcomes, no change was observed between the two groups. CONCLUSION: These findings suggest that ProCog-SEP could improve verbal learning abilities and working memory in people with multiple sclerosis. These improvements were observed with 13 group sessions over 6 months.

Role of the supplementary motor area during reproduction of supra-second time intervals: An intracerebral EEG study.

The supplementary motor area (SMA) has been shown to be involved in interval timing but its precise role remains a matter of debate. The present study was aimed at examining, by means of intracerebral EEG recordings, the time course of the activity in this structure, as well as in other functionally connected cortical (frontal, cingulate, insular and temporal) areas, during a visual time reproduction task. Four patients undergoing stereo-electroencephalography (SEEG) for presurgical investigation of refractory focal epilepsy were enrolled. They were selected on the presence of depth electrodes implanted within the SMA. They were instructed to encode, keep in memory and then reproduce the duration (3, 5 and 7 s) of emotionally-neutral or negative pictures. Emotional stimuli were used with the aim of examining neural correlates of temporal distortions induced by emotion. Event-related potentials (ERPs) were analyzed during three periods: During and at the extinction of the target interval (TI) and at the beginning of the reproduction interval (RI). Electrophysiological data revealed an ERP time-locked to TI-offset whose amplitude varied monotonically with TI-duration. This effect was observed in three out of the four patients, especially within the SMA and the insula. It also involved the middle and anterior cingulate cortex, the superior, middle and inferior frontal gyri and the paracentral lobule. These effects were modulated by the prior TI-duration and predicted variations in temporal reproduction accuracy. In contrast, modulations of ERPs with TI-duration, emotion or temporal performance during the target or the reproduction interval were modest and less consistent across patients. These results demonstrate that, during reproduction of supra-second time intervals, the SMA, in concert with a fronto-insular network, is involved at the end of the target interval, and suggest a role in the duration categorization and decision making operations or alternatively in the preparedness of the timing of the future movement that will be executed during the reproduction phase.

A face identity hallucination (palinopsia) generated by intracerebral stimulation of the face-selective right lateral fusiform cortex.

We report the case of a patient (MB, young female human subject) who systematically experienced confusion between perceived facial identities specifically when electrically stimulated inside the lateral section of the right fusiform gyrus. In the presence of a face stimulus (an experimenter or a photograph), intracerebral electrical stimulation in this region generated a perceptual hallucination of an individual facial part integrated within the whole perceived face, i.e., facial palinopsia. In the presence of a distracting stimulus (visual scene or object picture), the patient also experienced an individual face percept superimposed on the non-face stimulus. The stimulation site evoking this category-selective transient palinopsia was localized in a region showing highly selective responses to faces both with functional magnetic resonance imaging ("Fusiform Face Area", "FFA") and intracerebral electrophysiological recordings during fast periodic visual stimulation (FPVS). Importantly, the largest electrophysiological response to fast periodic changes of facial identity was also found at this location. Altogether, these observations suggest that the face-selective right lateral fusiform gyrus plays a role in generating vivid percepts of individual faces, supporting the active role of this region in individual face representation.

Intracerebral stimulation of left and right ventral temporal cortex during object naming.

While object naming is traditionally considered asa left hemisphere function, neuroimaging studies have reported activations related to naming in the ventral temporal cortex (VTC) bilaterally. Our aim was to use intracerebral electrical stimulation to specifically compare left and right VTC in naming. In twenty-three epileptic patients tested for visual object naming during stimulation, the proportion of naming impairments was significantly higher in the left than in the right VTC (31.3% vs 13.6%). The highest proportions of positive naming sites were found in the left fusiform gyrus and occipito-temporal sulcus (47.5% and 31.8%). For 17 positive left naming sites, an additional semantic picture matching was carried out, always successfully performed. Our results showed the enhanced role of the left compared to the right VTC in naming and suggest that it may be involved in lexical retrieval rather than in semantic processing.

The Face-Processing Network Is Resilient to Focal Resection of Human Visual Cortex.

UNLABELLED: Human face perception requires a network of brain regions distributed throughout the occipital and temporal lobes with a right hemisphere advantage. Present theories consider this network as either a processing hierarchy beginning with the inferior occipital gyrus (occipital face area; IOG-faces/OFA) or a multiple-route network with nonhierarchical components. The former predicts that removing IOG-faces/OFA will detrimentally affect downstream stages, whereas the latter does not. We tested this prediction in a human patient (Patient S.P.) requiring removal of the right inferior occipital cortex, including IOG-faces/OFA. We acquired multiple fMRI measurements in Patient S.P. before and after a preplanned surgery and multiple measurements in typical controls, enabling both within-subject/across-session comparisons (Patient S.P. before resection vs Patient S.P. after resection) and between-subject/across-session comparisons (Patient S.P. vs controls). We found that the spatial topology and selectivity of downstream ipsilateral face-selective regions were stable 1 and 8 month(s) after surgery. Additionally, the reliability of distributed patterns of face selectivity in Patient S.P. before versus after resection was not different from across-session reliability in controls. Nevertheless, postoperatively, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1 of the resected hemisphere. Diffusion weighted imaging in Patient S.P. and controls identifies white matter tracts connecting retinotopic areas to downstream face-selective regions, which may contribute to the stable and plastic features of the face network in Patient S.P. after surgery. Together, our results support a multiple-route network of face processing with nonhierarchical components and shed light on stable and plastic features of high-level visual cortex following focal brain damage. SIGNIFICANCE STATEMENT: Brain networks consist of interconnected functional regions commonly organized in processing hierarchies. Prevailing theories predict that damage to the input of the hierarchy will detrimentally affect later stages. We tested this prediction with multiple brain measurements in a rare human patient requiring surgical removal of the putative input to a network processing faces. Surprisingly, the spatial topology and selectivity of downstream face-selective regions are stable after surgery. Nevertheless, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1. White matter connections from outside the face network may support these stable and plastic features. As processing hierarchies are ubiquitous in biological and nonbiological systems, our results have pervasive implications for understanding the construction of resilient networks.

A face-selective ventral occipito-temporal map of the human brain with intracerebral potentials.

Human neuroimaging studies have identified a network of distinct face-selective regions in the ventral occipito-temporal cortex (VOTC), with a right hemispheric dominance. To date, there is no evidence for this hemispheric and regional specialization with direct measures of brain activity. To address this gap in knowledge, we recorded local neurophysiological activity from 1,678 contact electrodes implanted in the VOTC of a large group of epileptic patients (n = 28). They were presented with natural images of objects at a rapid fixed rate (six images per second: 6 Hz), with faces interleaved as every fifth stimulus (i.e., 1.2 Hz). High signal-to-noise ratio face-selective responses were objectively (i.e., exactly at the face stimulation frequency) identified and quantified throughout the whole VOTC. Face-selective responses were widely distributed across the whole VOTC, but also spatially clustered in specific regions. Among these regions, the lateral section of the right middle fusiform gyrus showed the largest face-selective response by far, offering, to our knowledge, the first supporting evidence of two decades of neuroimaging observations with direct neural measures. In addition, three distinct regions with a high proportion of face-selective responses were disclosed in the right ventral anterior temporal lobe, a region that is undersampled in neuroimaging because of magnetic susceptibility artifacts. A high proportion of contacts responding only to faces (i.e., "face-exclusive" responses) were found in these regions, suggesting that they contain populations of neurons involved in dedicated face-processing functions. Overall, these observations provide a comprehensive mapping of visual category selectivity in the whole human VOTC with direct neural measures.

Beyond the core face-processing network: Intracerebral stimulation of a face-selective area in the right anterior fusiform gyrus elicits transient prosopagnosia.

According to neuropsychological evidence, a distributed network of regions of the ventral visual pathway - from the lateral occipital cortex to the temporal pole - supports face recognition. However, functional magnetic resonance imaging (fMRI) studies have generally confined ventral face-selective areas to the posterior section of the occipito-temporal cortex, i.e., the inferior occipital gyrus occipital face area (OFA) and the posterior and middle fusiform gyrus fusiform face area (FFA). There is recent evidence that intracranial electrical stimulation of these areas in the right hemisphere elicits face matching and recognition impairments (i.e., prosopagnosia) as well as perceptual face distortions. Here we report a case of transient inability to recognize faces following electrical stimulation of the right anterior fusiform gyrus, in a region located anteriorly to the FFA. There was no perceptual face distortion reported during stimulation. Although no fMRI face-selective responses were found in this region due to a severe signal drop-out as in previous studies, intracerebral face-selective event-related potentials and gamma range electrophysiological responses were found at the critical site of stimulation. These results point to a causal role in face recognition of the right anterior fusiform gyrus and more generally of face-selective areas located beyond the "core" face-processing network in the right ventral temporal cortex. It also illustrates the diagnostic value of intracerebral electrophysiological recordings and stimulation in understanding the neural basis of face recognition and visual recognition in general.

Distortion of time interval reproduction in an epileptic patient with a focal lesion in the right anterior insular/inferior frontal cortices.

This case report on an epileptic patient suffering from a focal lesion at the junction of the right anterior insular cortex (AIC) and the adjacent inferior frontal cortex (IFC) provides the first evidence that damage to this brain region impairs temporal performance in a visual time reproduction task in which participants had to reproduce the presentation duration (3, 5 and 7s) of emotionally-neutral and -negative pictures. Strikingly, as compared to a group of healthy subjects, the AIC/IFC case considerably overestimated reproduction times despite normal variability. The effect was obtained in all duration and emotion conditions. Such a distortion in time reproduction was not observed in four other epileptic patients without insular or inferior frontal damage. Importantly, the absolute extent of temporal over-reproduction increased in proportion to the magnitude of the target durations, which concurs with the scalar property of interval timing, and points to an impairment of time-specific rather than of non temporal (such as motor) mechanisms. Our data suggest that the disability in temporal reproduction of the AIC/IFC case would result from a distorted memory representation of the encoded duration, occurring during the process of storage and/or of recovery from memory and leading to a deviation of the temporal judgment during the reproduction task. These findings support the recent proposal that the anterior insular/inferior frontal cortices would be involved in time interval representation.

Intracerebral electrical stimulation of a face-selective area in the right inferior occipital cortex impairs individual face discrimination.

During intracerebral stimulation of the right inferior occipital cortex, a patient with refractory epilepsy was transiently impaired at discriminating two simultaneously presented photographs of unfamiliar faces. The critical electrode contact was located in the most posterior face-selective brain area of the human brain (right "occipital face area", rOFA) as shown both by low- (ERP) and high-frequency (gamma) electrophysiological responses as well as a face localizer in fMRI. At this electrode contact, periodic visual presentation of 6 different faces by second evoked a larger electrophysiological periodic response at 6 Hz than when the same face identity was repeated at the same rate. This intracerebral EEG repetition suppression effect was markedly reduced when face stimuli were presented upside-down, a manipulation that impairs individual face discrimination. These findings provide original evidence for a causal relationship between the face-selective right inferior occipital cortex and individual face discrimination, independently of long-term memory representations. More generally, they support the functional value of electrophysiological repetition suppression effects, indicating that these effects can be used as an index of a necessary neural representation of the changing stimulus property.

Cognitive impairment among different clinical courses of multiple sclerosis.

BACKGROUND: As of yet, no consensus has been reached regarding cognitive impairment profiles in multiple sclerosis (MS) patients based on the MS type and disease duration. The main objective of this study was to describe cognitive impairment at the early stages of MS. The secondary objective was to compare cognitive performances in patients with relapsing remitting multiple sclerosis (RRMS), secondary progressive (SP) MS and primary progressive (PP) MS. METHODS: The study included 128 MS patients and 63 healthy controls (HC). The study constituted five groups: early RR (ERR) (<3 years); late RR (LRR) (>10 years), SP, PP, and healthy Controls (HC). A neuropsychological assessment was performed including information processing speed (IPS), working memory, verbal episodic memory and executive functions. RESULTS: Compared to HC, only impairment in phonemic fluency was observed in ERR. Slowing IPS, impairment in working memory and phonemic fluency were shown in LRR. In progressive forms, deficits were observed in verbal episodic memory, in working memory, in flexibility, in semantic and phonemic fluencies, with a slowing IPS. CONCLUSION: Verbal fluency is impaired at early stage of RRMS, in this form of MS, impairment increased with MS duration, and distinct cognitive profiles were observed between chronic and progressive forms.

Integration of cognitive impairment in the expanded disability status scale of 215 patients with multiple sclerosis.

BACKGROUND: Estimates of the prevalence of cognitive impairment among patients with multiple sclerosis (MS) range between 40 and 70%. The current cerebral functional system (CFS) of the Expanded Disability Status Scale (EDSS) is subjective. AIM: To define a new cerebral functional system (NCFS) based on neuropsychological evaluation (NE). METHODS: We prospectively included 215 MS patients. NE evaluated cognitive functions. Fatigue was assessed with the Fatigue Impact Scale. The NCFS was devised with grades from 0 to 5, excluding depression but including fatigue. Grade 1 of the NCFS was integrated in the EDSS as other functional scores. The NCFS and new EDSS including the NCFS were compared with the current CFS and EDSS. RESULTS: 215 patients (69% women, 67% with relapsing-remitting MS, median EDSS 3.0) were assessed. 98% of these patients presented fatigue and/or cognitive impairment with the NCFS compared to 62% with the CFS. The NCFS was higher than the CFS, and the EDSS had changed in 31% of the 113 patients with an EDSS <3.5. Change in functional score was not correlated to current age or age at onset of MS. CONCLUSIONS: We propose a new CFS grading based on NE, including fatigue, and integrating grade 1 at EDSS.

Physical dimension of fatigue correlated with disability change over time in patients with multiple sclerosis.

To determine the value of fatigue in predicting the change in disability status in patients with multiple sclerosis (MS), we realized a prospective population-based cohort study of 196 patients with clinically definite MS. In 2002, baseline data were collected on fatigue (Modified Fatigue Impact Scale), health-related quality of life (SF-36), and disability status (EDSS score). The EDSS scores were determined again at least three years later. Univariate and multivariate analysis were performed to determine the predictive value of different dimensions of fatigue and other variables (depression and SF- 36) on the change in disability status. Of the 196 patients, 106 (54%) patients had an unchanged status or improvement and 90 (46%) showed a worsening of disability. After three years, with control for gender, age, and baseline disability status, a high baseline level of physical fatigue was associated with a worsening of disability status, whereas a low baseline level of physical fatigue was associated with the absence of worsening of the EDSS score. Other dimensions of fatigue, depression and SF-36 were not associated with a worsening of disability.A patient's perceived fatigue may be not only a clinically and psychosocially meaningful outcome but also a predictor of objective outcomes such as changes in disability status at three years.