A Reliable and Rapid Language Tool for the Diagnosis, Classification, and Follow-Up of Primary Progressive Aphasia Variants.

Background: Primary progressive aphasias (PPA) have been investigated by clinical, therapeutic, and fundamental research but examiner-consistent language tests for reliable reproducible diagnosis and follow-up are lacking. Methods: We developed and evaluated a rapid language test for PPA ("PARIS") assessing its inter-examiner consistency, its power to detect and classify PPA, and its capacity to identify language decline after a follow-up of 9 months. To explore the reliability and specificity/sensitivity of the test it was applied to PPA patients (N = 36), typical amnesic Alzheimer's disease (AD) patients (N = 24) and healthy controls (N = 35), while comparing it to two rapid examiner-consistent language tests used in stroke-induced aphasia ("LAST", "ART"). Results: The application duration of the "PARIS" was ~10 min and its inter-rater consistency was of 88%. The three tests distinguished healthy controls from AD and PPA patients but only the "PARIS" reliably separated PPA from AD and allowed for classifying the two most frequent PPA variants: semantic and logopenic PPA. Compared to the "LAST" and "ART," the "PARIS" also had the highest sensitivity for detecting language decline. Conclusions: The "PARIS" is an efficient, rapid, and highly examiner-consistent language test for the diagnosis, classification, and follow-up of frequent PPA variants. It might also be a valuable tool for providing end-points in future therapeutic trials on PPA and other neurodegenerative diseases affecting language processing.

Aphasia outcome: the interactions between initial severity, lesion size and location.

OBJECTIVES: The outcome of aphasia at 3 months is variable in patients with moderate/severe stroke. The aim was to predict 3-month aphasia outcome using prediction models including initial severity in addition to the interaction between lesion size and location at the acute phase. METHODS: Patients with post-stroke aphasia (assessed by the Aphasia Rapid Test at day 7-ART D7) and MRI performed at day 1 were enrolled (n = 73). Good outcome at 3-months was defined by an Aphasia Handicap Score of 0-2. Each infarct lesion was overlapped with an area of interest in the left temporo-parietal region to compute an intersection index (proportion of the critical region damaged by the infarct). We tested ART D7, age, lesion volume, and intersection index as well as a combined variable lesion volume*intersection in a univariate analysis. Then, we performed a multivariate analysis to investigate which variables were independent predictors of good outcome. RESULTS: ART at D7, infarct volume, and the intersection index were univariate predictors of good outcome. In the multivariate analysis, ART D7 and "volume ≥ 50 ml or intersection index ≥ 20%" correctly classified 89% of the patients (p < 0.0001). When added to the model, the interaction between both variables was significant indicating that the impact of the size or site variable depends on the initial severity of aphasia. CONCLUSION: In patients with initially severe aphasia, large infarct size or critical damage in left temporoparietal junction is associated with poor language outcome at 3 months.

Critical brain regions related to post-stroke aphasia severity identified by early diffusion imaging are not the same when predicting short- and long-term outcome.

OBJECTIVES: To identify the critical brain regions associated with 7-days, 3 and 6-months aphasia severity using diffusion-weighted imaging (DWI) in acute post-stroke patients. MATERIALS AND METHODS: We performed a voxel-based ADC (Apparent Diffusion Coefficient) analysis to identify the critical brain areas correlated with aphasia at the acute (7-days outcome) and chronic stages (3 and 6-months). The location of these areas was compared with the trajectory of the dorsal (the arcuate fasciculus) and the ventral language pathways (the inferior fronto-occipital and the uncinate fasciculi). RESULTS: Disconnections of the language fasciculi, which were correlated with aphasia outcome, were not the same for the 7-days outcome (disconnection of the ventral stream) and the chronic outcome (3 and 6 months) (disconnection of the dorsal and ventral streams). CONCLUSION: Routine clinical images can be merged with atlases of anatomical connectivity to provide new insights about the relationship between the lesion location and aphasia severity.

Repetitive sessions of tDCS to improve naming in post-stroke aphasia: Insights from an individual patient data (IPD) meta-analysis.

OBJECTIVES: Small clinical trials reported that repetitive sessions of tDCS could improve naming abilities in post-stroke aphasia. However, systematic meta-analyses found no effect, but all of these analyses pooled data from both single and repetitive sessions at the group level. The aim of this paper was to perform a meta-analysis based on individual patient data to explore the effects of repetitive tDCS sessions on naming in post-stroke aphasia and in prespecified subgroups. METHODS: We searched for published sham-controlled trials using the keywords "aphasia OR language" AND "transcranial direct current stimulation OR tDCS" AND "stroke". We computed an active and sham improvement ratio by dividing the difference between naming scores after and before the active or sham sessions, respectively, by the total number of picture items. Because of heterogeneity (I2 = 66%, p: 0.002), we used random-effects models to estimate the standardized mean difference (SMD) for the naming outcome. We then analyzed subgroups according to number of sessions, polarity, side/location of the active electrode, post-stroke delay, aphasia severity and comprehension disorders. RESULTS: Seven eligible studies were identified, including 68 chronic stroke patients. tDCS was beneficial on naming ability (35% ±34% in the active vs. 25% ±37% in the sham condition). An SMD of 0.8 (95% CI: 0.27-1.33) was found for the naming outcome. Additionally, there was a dose-dependent effect (5 vs. >5 sessions). We also demonstrated a prevalence of anodal vs. cathodal condition and left vs. right targeting electrode. Finally, repetitive sessions were beneficial regardless of the severity of aphasia, comprehension disorders or post-stroke delay. CONCLUSION: Repetitive sessions of tDCS are likely to be valuable in enhancing naming accuracy in post-stroke aphasia.

Aphasia severity in chronic stroke patients: a combined disconnection in the dorsal and ventral language pathways.

BACKGROUND: The contribution of lesion size and location in poststroke aphasia is debated, especially the extent to which aphasia severity is affected by damage to specific white matter areas. OBJECTIVE: To identify specific white matter areas critical for poststroke aphasia global severity and to determine whether injury to these areas had more impact on aphasia severity than the infarct volume. METHODS: Twenty-three chronic poststroke aphasic patients were assessed with the Aphasia Rapid Test (ART) and the Boston Diagnosis Aphasia Examination (BDAE) global severity scales and underwent diffusion tensor and structural imaging. Voxel-based diffusion tensor imaging regression analysis was used to determine in which areas fractional anisotropy (FA) abnormalities were correlated with ART and BDAE severity scales. The relationships between aphasia severity, FA values, and infarct volumes were investigated using global and partial correlations. RESULTS: We found a critical area associated with aphasia severity overlapping with the arcuate and the inferior fronto-occipital fasciculi, resulting in a combined disconnection of the dorsal and ventral pathways. ART scores were inversely correlated with FA values in this region, with greater severity present with lower FA values (correlation coefficient = -0.833, P < .0001). The proportion of variance explained by the FA value was higher than the proportion of variance explained by the infarct volume (R (2) = 68% vs 27%, P = .01). The impact of infarct volume on aphasia severity disappeared when damage to this critical white matter area was taken into account (P = .38). CONCLUSION: The assessment of the integrity of this region may potentially have a clinical impact in neurorehabilitation and acute decision making.

Damage to the medial motor system in stroke patients with motor neglect.

BACKGROUND AND OBJECTIVES: Motor neglect (MN) is a clinically important condition whereby patients with unilateral brain lesions fail to move their contralateral limbs, despite normal muscle strength, reflexes, and sensation. MN has been associated with various lesion sites, including the parietal and frontal cortex, the internal capsule, the lenticulostriate nuclei, and the thalamus. In the present study, we explored the hypothesis that MN depends on a dysfunction of the medial motor system by performing a detailed anatomical analysis in four patients with MN. METHODS: Ten patients participated in the study: four with MN, four with left visual neglect but without MN, and three patients with left hemiplegia without MN. We used specific scales for clinical and neuropsychological assessment. We drew the lesion borders directly onto the original brain images of each patient, and plotted the lesions on anatomical atlases for gray and white matter. RESULTS: Lesion locations were highly heterogeneous in our MN patients, and included frontal and parietal sites, basal ganglia, and white matter. The only consistently damaged structure across all MN patients was the cingulum bundle, a major pathway of the medial motor system important for motor initiative, and a key connection with limbic structures crucial for motivational aspects of actions. Three MN patients with additional damage to lateral fronto-parietal networks had also signs of contralesional visual neglect. The cingulum bundle was intact in all the control patients with visual neglect or hemiplegia. CONCLUSIONS: Cingulum damage may induce MN through unilateral dysfunction of the medial motor system. Additional lateral fronto-parietal dysfunction can result in the association with visual neglect.