Sensitivity and Specificity of Qualitative Visual Field Tests for Screening Visual Hemifield Deficits in Right-Brain-Damaged Stroke Patients.

A timely detection of visual hemifield deficits (VHFDs; hemianopias or quadrantanopias) is critical for both the diagnosis and treatment of stroke patients. The present study determined the sensitivity and specificity of four qualitative visual field tests, including face description, confrontation tests (finger wiggle), and kinetic boundary perimetry, to screen large and dense VHFDs in right-brain-damaged (RBD) stroke patients. Previously, the accuracy of qualitative visual field tests was examined in unselected samples of patients with heterogeneous aetiology, in which stroke patients represented a very small fraction. Building upon existing tests, we introduced some procedural ameliorations (incl. a novel procedure for kinetic boundary perimetry) and provided a scoresheet to facilitate the grading. The qualitative visual field tests' outcome of 67 consecutive RBD stroke patients was compared with the standard automated perimetry (SAP; i.e., reference standard) outcome to calculate sensitivity and specificity, as well as positive and negative predictive values (PPV and NPV), both for each individual test and their combinations. The face description test scored the lowest sensitivity and NPV, while the kinetic boundary perimetry scored the highest. No test returned false positives. Combining the monocular static finger wiggle test (by quadrants) and the kinetic boundary perimetry returned the highest sensitivity and specificity, in line with previous studies, but with higher accuracy (100% sensitivity and specificity). These findings indicate that the combination of these two tests is a valid approach with RBD stroke patients, prompting referral for a formal visual field examination, and representing a quick, easy-to-perform, and inexpensive tool for improving their care and prognosis.

Immersive Virtual Reality for Treatment of Unilateral Spatial Neglect via Eye-Tracking Biofeedback: RCT Protocol and Usability Testing.

About one-third of stroke survivors present unilateral spatial neglect (USN) that negatively impacts the rehabilitation outcome. We reported the study protocol and usability results of an eye-tracking (ET) biofeedback immersive virtual reality (iVR) protocol. Healthy controls and stroke patients with and without USN underwent a single session of the three iVR tasks. The system usability scale (SUS), adverse events (AEs), and ET data were collected and analyzed via parametric analysis. Twelve healthy controls (six young adults and six older adults) and seven patients with a diagnosis of single ischemic stroke (four without USN and three with confirmed diagnosis of USN) completed the usability investigation. SUS results showed good acceptability of the system for healthy controls and stroke patients without USN. ET results showed a lower performance for patients with USN concerning healthy controls and stroke patients without USN, in particular in the exploration of the left visual field. The results showed that the proposed iVR-ET biofeedback protocol is a safe and well-tolerated technique in patients with USN. The real-time feedback can induce a performance response supporting its investigation such as a treatment approach.

Sensitivity and Specificity of the Brentano Illusion Test in the Detection of Visual Hemi-Field Deficits in Patients with Unilateral Spatial Neglect.

Stroke survivors with right-brain damage (RBD) often present with attentional deficits such as left unilateral spatial neglect. Some patients also present with contralesional visual hemi-field deficits. A late detection of visual hemi-field deficits (VHFD) contributes to hampering neurorehabilitation and functional outcome of patients with neglect. The Brentano Illusion Test (BRIT) may be used for an early detection of VHFD during the neuropsychological assessment. In the present study, we determined the sensitivity and specificity of the BRIT for screening VHFD in patients with neglect. Sixty-four consecutive RBD patients were examined. Forty-five presented with neglect. Of these, 23 presented with VHFD (hemianopia or quadrantanopia) as detected by the Humphrey automated static visual field testing (reference standard). Consecutive patients also included 19 participants without neglect, who did not have any VHFD. The sensitivity and specificity of the BRIT for neglect patients were 78.3% (95% CI: 61.4-95.1) and 90.9 (95% CI: 78.9-100.0), respectively. Positive predictive value (PPV) was 89.6% (95% CI: 76.4-100.0); negative predictive value (NPV) 80.7% (95% CI: 65.2-96.2). No false positives in the group without neglect were identified. We conclude that the BRIT is an effective tool for clinical neuropsychologists to screen for possible VHFD in neglect patients during the neuropsychological assessment, allowing the refinement of the clinical picture in the neuropsychological report. An early detection of VHFD also allows referring the patient to standard diagnostics for a formal visual field examination, right from the first neuropsychological assessment.

The impact of cognitive function deficits and their recovery on functional outcome in subjects affected by ischemic subacute stroke: results from the Italian multicenter longitudinal study CogniReMo.

BACKGROUND: The recovery of independence in activities of daily living is a fundamental goal of rehabilitation programs in subjects affected by subacute stroke. Rehabilitation is focused both on motor and cognitive aspects, and some evidence has reported cognitive deficits as prognostic factors of motor recovery. However, rehabilitation is a dynamic process during which executive functions and motor functions should be improved. AIM: The aim of the study is to evaluate the relationships between impairments in cognitive functions and recovery of functional independence in stroke patients during the subacute phase. DESIGN: Multicenter observational study. SETTING: Intensive rehabilitation units. POPULATION: A sample of 319 stroke patients in subacute phase (70.6±11.6 years, 40.4% females), consecutively admitted from November 2019 to July 2021 at sixteen rehabilitation centers were enrolled in this observational, prospective and multicentric study with longitudinal assessments. METHODS: Cognitive and functional assessments were performed at hospital admission and discharge, including Oxford Cognitive Screen, modified Barthel Index, Functional Independent Measure, Fugl-Meyer assessment scale and National Institutes of Health Stroke Scale. RESULTS: A regression analysis identified five predictors (out of about 200 tested variables) of functional recovery related to four aspects assessed at admission: functional status (P<0.001), lower limb functioning (P=0.002), attention (P=0.011), and executive functions (P=0.017). Furthermore, patients who recovered deficits in executive functions had the same recovery of those without deficits, whereas those who maintained deficits had a smaller recovery (P=0.019). CONCLUSIONS: The relationship between cognitive and motor deficits is increasingly highlighted and the recovery of executive functions deficits seems to contribute to motor recovery. CLINICAL REHABILITATION IMPACT: Our results suggest that the recovery of executive functions may promote the recovery of the functional outcome of the patient with subacute stroke. Future treatment protocols may benefit from paying more attention to the recovery of executive functions.

Left egocentric neglect in early subacute right-stroke patients is related to damage of the superior longitudinal fasciculus.

A typical consequence of stroke in the right hemisphere is unilateral spatial neglect. Distinct forms of neglect have been described, such as space-based (egocentric) and object-based (allocentric) neglect. However, the relationship between these two forms of neglect is still far from being understood, as well as their neural substrates. Here, we further explore this issue by using voxel lesion symptoms mapping (VLSM) analyses on a large sample of early subacute right-stroke patients assessed with the Apples Cancellation Test. This is a sensitive test that simultaneously measures both egocentric and allocentric neglect. Behaviourally, we found no correlation between egocentric and allocentric performance, indicating independent mechanisms supporting the two forms of neglect. This was confirmed by the VLSM analysis that pointed out a link between a damage in the superior longitudinal fasciculus and left egocentric neglect. By contrast, no association was found between brain damage and left allocentric neglect. These results indicate a higher probability to observe egocentric neglect as a consequence of white matter damages in the superior longitudinal fasciculus, while allocentric neglect appears more "globally" related to the whole lesion map. Overall, these findings on early subacute right-stroke patients highlight the role played by white matter integrity in sustaining attention-related operations within an egocentric frame of reference.

Topological and hodological aspects of body representation in right brain damaged patients.

The triadic taxonomy posits that three distinct types of body representations do exist, namely the body schema (BS), which corresponds to the representation derived from multiple sensory and motor inputs, the body structural representation (BSR), which corresponds to the structural description of spatial relations among the body parts, and the body semantics (SEM), which corresponds to the lexical-semantic representation of the body. Although several studies have assessed neural correlates of these representations, no study has compared them in brain-damaged patients, controlling for deficits in other cognitive domains. Also, little is known about the contribution of the right hemisphere to different body representations. Here we used a computerized battery to test these three body representations in twenty-six right brain damaged patients, controlling for other cognitive deficits by means of tests tapping similar spatial and lexical processes on non-body related stimuli. Residual scores corresponding to the BS, the BSR and the SEM were used to test neural correlates, which were assessed by integrating topological and hodological approaches to lesion-deficit analyses. We found that the BSR was associated with lesion of the superior temporal gyrus, the insula, the supramarginal gyrus and the temporo-parietal junction, extending also to the Rolandic operculum and the inferior frontal gyrus. Also, it was associated with the disconnection probability of the posterior arcuate segment. The BS was associated with a small cluster of voxels in the precentral and postcentral gyri, whereas the SEM was associated with white matter lesion at the boundary between the parietal and temporal lobes. Overall, these results provide strong support to the regional and connectional contribution of the right hemisphere to body representation, and more specifically to the BSR.

Duration reproduction in regular and irregular contexts after unilateral brain damage: Evidence from voxel-based lesion-symptom mapping and atlas-based hodological analysis.

It has been proposed that not completely overlapping brain networks support interval timing depending on whether or not an external, predictable temporal cue is provided during the task, aiding time estimation. Here we tested this hypothesis in a neuropsychological study, using both a topological approach - through voxel-based lesion-symptom mapping (VLSM), that assesses the relation between continuous behavioral scores and lesion information on a voxel-by-voxel basis - and a hodological approach, using an atlas-based tractography. A group of patients with unilateral focal brain lesions and their matched controls performed a duration reproduction task assessing time processing in two conditions, namely with regularly spaced stimuli during encoding and reproduction (Regular condition), and with irregularly spaced stimuli during the same task (Irregular condition). VLSM analyses showed that scores in the two conditions were associated with lesions involving partly separable clusters of voxels, with lower performance only in the Irregular condition being related to lesions involving the right insular cortex. Performance in both conditions correlated with the probability of disconnection of the right frontal superior longitudinal tract, and of the superior and middle branches of the right superior longitudinal fasciculus. These findings suggest that the dissociation between timing in regular and irregular contexts is not complete, since performance in both conditions relies on the integrity of a common suprasecond timing network. Furthermore, they are consistent with the hypothesis that tracking time without the aid of external cues selectively relies on the integration of psychophysiological changes in the right insula.

Using the Oxford Cognitive Screen to Detect Cognitive Impairment in Stroke Patients: A Comparison with the Mini-Mental State Examination.

BACKGROUND: The Oxford Cognitive Screen (OCS) was recently developed with the aim of describing the cognitive deficits after stroke. The scale consists of 10 tasks encompassing five cognitive domains: attention and executive function, language, memory, number processing, and praxis. OCS was devised to be inclusive and un-confounded by aphasia and neglect. As such, it may have a greater potential to be informative on stroke cognitive deficits of widely used instruments, such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment, which were originally devised for demented patients. OBJECTIVE: The present study compared the OCS with the MMSE with regards to their ability to detect cognitive impairments post-stroke. We further aimed to examine performance on the OCS as a function of subtypes of cerebral infarction and clinical severity. METHODS: 325 first stroke patients were consecutively enrolled in the study over a 9-month period. The OCS and MMSE, as well as the Bamford classification and NIHSS, were given according to standard procedures. RESULTS: About a third of patients (35.3%) had a performance lower than the cutoff (<22) on the MMSE, whereas 91.6% were impaired in at least one OCS domain, indicating higher incidences of impairment for the OCS. More than 80% of patients showed an impairment in two or more cognitive domains of the OCS. Using the MMSE as a standard of clinical practice, the comparative sensitivity of OCS was 100%. Out of the 208 patients with normal MMSE performance 180 showed impaired performance in at least one domain of the OCS. The discrepancy between OCS and MMSE was particularly strong for patients with milder strokes. As for subtypes of cerebral infarction, fewer patients demonstrated widespread impairments in the OCS in the Posterior Circulation Infarcts category than in the other categories. CONCLUSION: Overall, the results showed a much higher incidence of cognitive impairment with the OCS than with the MMSE and demonstrated no false negatives for OCS vs MMSE. It is concluded that OCS is a sensitive screen tool for cognitive deficits after stroke. In particular, the OCS detects high incidences of stroke-specific cognitive impairments, not detected by the MMSE, demonstrating the importance of cognitive profiling.

A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors.

Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off). Dose escalation was guided by a Bayesian logistic regression model with overdose control and real-time PK.Results: Thirty-two patients (median age, 5.5 years) received ribociclib 280, 350, or 470 mg/m2 Three patients had dose-limiting toxicities of grade 3 fatigue (280 mg/m2; n = 1) or grade 4 thrombocytopenia (470 mg/m2; n = 2). Most common treatment-related adverse events (AE) were hematologic: neutropenia (72% all-grade/63% grade 3/4), leukopenia (63%/38%), anemia (44%/3%), thrombocytopenia (44%/28%), and lymphopenia (38%/19%), followed by vomiting (38%/0%), fatigue (25%/3%), nausea (25%/0%), and QTc prolongation (22%/0%). Ribociclib exposure was dose-dependent at 350 and 470 mg/m2 [equivalent to 600 (RP2D)-900 mg in adults], with high interpatient variability. Best overall response was stable disease (SD) in nine patients (seven with neuroblastoma, two with primary CNS MRT); five patients achieved SD for more than 6, 6, 8, 12, and 13 cycles, respectively.Conclusions: Ribociclib demonstrated acceptable safety and PK in pediatric patients. MTD (470 mg/m2) and RP2D (350 mg/m2) were equivalent to those in adults. Observations of prolonged SD support further investigation of ribociclib combined with other agents in neuroblastoma and MRT. Clin Cancer Res; 23(10); 2433-41. ©2017 AACR.

A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) in Patients with Advanced Solid Tumors and Lymphomas.

PURPOSE: Ribociclib (an oral, highly specific cyclin-dependent kinase 4/6 inhibitor) inhibits tumor growth in preclinical models with intact retinoblastoma protein (Rb+). This first-in-human study investigated the MTD, recommended dose for expansion (RDE), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of ribociclib in patients with Rb+ advanced solid tumors or lymphomas. EXPERIMENTAL DESIGN: Patients received escalating doses of ribociclib (3-weeks-on/1-week-off or continuous). Dose escalation was guided by a Bayesian Logistic Regression Model with overdose control principle. RESULTS: Among 132 patients, 125 received ribociclib 3-weeks-on/1-week-off and 7 were dosed continuously. Nine dose-limiting toxicities were observed among 70 MTD/RDE evaluable patients during cycle 1, most commonly neutropenia (n = 3) and thrombocytopenia (n = 2). The MTD and RDE were established as 900 and 600 mg/day 3-weeks-on/1-week-off, respectively. Common treatment-related adverse events were (all-grade; grade 3/4) neutropenia (46%; 27%), leukopenia (43%; 17%), fatigue (45%; 2%), and nausea (42%; 2%). Asymptomatic Fridericia's corrected QT prolongation was specific to doses ≥600 mg/day (9% of patients at 600 mg/day; 33% at doses >600 mg/day). Plasma exposure increases were slightly higher than dose proportional; mean half-life at the RDE was 32.6 hours. Reduced Ki67 was observed in paired skin and tumor biopsies, consistent with ribociclib-mediated antiproliferative activity. There were 3 partial responses and 43 patients achieved a best response of stable disease; 8 patients were progression-free for >6 months. CONCLUSIONS: Ribociclib demonstrated an acceptable safety profile, dose-dependent plasma exposure, and preliminary signs of clinical activity. Phase I-III studies of ribociclib are under way in various indications. Clin Cancer Res; 22(23); 5696-705. ©2016 AACR.

Persistence of Gender Related-Effects on Visuo-Spatial and Verbal Working Memory in Right Brain-Damaged Patients.

The aim of the present study was to verify if gender differences in verbal and visuo-spatial working memory would persist following right cerebral lesions. To pursue our aim we investigated a large sample (n. 346) of right brain-damaged patients and healthy participants (n. 272) for the presence of gender effects in performing Corsi and Digit Test. We also assessed a subgroup of patients (n. 109) for the nature (active vs. passive) of working memory tasks. We tested working memory (WM) administering the Corsi Test (CBT) and the Digit Span (DS) using two different versions: forward (fCBT and fDS), subjects were required to repeat stimuli in the same order that they were presented; and backward (bCBT and bDS), subjects were required to repeat stimuli in the opposite order of presentation. In this way, passive storage and active processing of working memory were assessed. Our results showed the persistence of gender-related effects in spite of the presence of right brain lesions. We found that men outperformed women both in CBT and DS, regardless of active and passive processing of verbal and visuo-spatial stimuli. The presence of visuo-spatial disorders (i.e., hemineglect) can affect the performance on Corsi Test. In our sample, men and women were equally affected by hemineglect, therefore it did not mask the gender effect. Generally speaking, the persistence of the men's superiority in visuo-spatial tasks may be interpreted as a protective factor, at least for men, within other life factors such as level of education or kind of profession before retirement.

Recovery of personal neglect.

BACKGROUND: Extrapersonal unilateral spatial neglect after stroke is associated to a poor rehabilitation outcome. Minor attention has been paid to the recovery of personal neglect, to its relationship with the recovery of extrapersonal neglect and of independency in activities of daily living. AIM: The present study aims at evaluating whether there is an association between recovery of extrapersonal and personal neglect. The secondary aim was to investigate if personal neglect may affect the effectiveness of neurorehabilitation in patients with subacute stroke. DESIGN: Observational study. SETTING: Neurorehabilitation Hospital in Rome, Italy, inpatients. POPULATION: A sample of 49 patients with unilateral spatial neglect resulting from right ischemic cerebral infarction was enrolled in this study, divided into three subgroups according to the presence and the degree of personal neglect, and evaluated pre and postneurorehabilitation. METHODS: Personal neglect was evaluated using Zoccolotti and Judica's Scale, extrapersonal neglect using Letter Cancellation Test, Barrage Test, Sentence Reading Test and Wundt-Jastrow Area Illusion Test. Barthel Index (BI), Rivermead Mobility Index, and Canadian Neurological Scale were also administered. RESULTS: Results showed the following: 1) recovery of personal neglect was not significantly correlated with that of extrapersonal neglect, despite both the disorders were ameliorated after a "non-specific" rehabilitation treatment; 2) personal neglect per se was not an additional negative prognostic factor in the rehabilitation findings. CONCLUSIONS: Our results suggested that the recoveries of the two types of neglect are independent from each other, and that the presence of personal neglect does not imply significant additional problems to the functional outcomes. CLINICAL REHABILITATION IMPACT: Our study highlighted the need of novel tools to assess the presence and to improve the recovery of personal neglect.

Bisecting or not bisecting: this is the neglect question. Line bisection performance in the diagnosis of neglect in right brain-damaged patients.

In the present study we analysed the bisecting behaviour of 287 chronic right brain-damaged patients by taking into account the presence and severity of extrapersonal and/or personal neglect diagnosed with the hemineglect battery. We also analysed right brain-damaged patients who had (or did not have) neglect according to their line bisection performance. Our results showed that performance of the line bisection task correlates with performance of cancellation tasks, reading and perceptual tasks, but not with the presence of personal neglect. Personal neglect seems to be unrelated to line bisection behaviour. Indeed, patients affected by extrapersonal and personal neglect do not show more severe neglect in line bisection than patients with only extrapersonal neglect. Furthermore, we observed that 20.56% of the patients were considered affected or not by neglect on the line bisection task compared with the other spatial tasks of the hemineglect battery. We conclude that using a battery with multiple tests is the only way to guarantee a reliable diagnosis and effectively plan for rehabilitative training.

Hemispheric differences in VEPs to lateralised stimuli are a marker of recovery from neglect.

Visual-evoked potentials (VEPs) were recorded in seventeen patients with unilateral lesions of the right hemisphere (RH) and visuospatial neglect. Hemispheric differences were detected for VEP components in the time window from 130 to 280 msec; this result replicates data from a previous study using a larger group of patients (Di Russo et al., 2008). Three patients were tested twice; their hemispheric differences, i.e., the differences in latency and amplitude of VEPs to ipsilesional and contralesional stimuli, were evaluated at the beginning and end of visuospatial rehabilitation training for neglect. The hemispheric differences were limited to components anterior N1 (N1a), posterior N1 (N1p) and P2 (not C1 and P1) and showed a significant decrease after training; amelioration at the behavioural level was also observed. Fourteen patients were tested only once, at different steps of their training. For the overall group, we determined the correlation between VEP hemispheric differences and the number of sessions attended by the patients at the time of VEP recording. The correlation was negative, the higher the number of sessions, the lower the hemispheric asymmetry, and high, ranging from .45 to .64, for both the latency and amplitude of the N1p and P2 components, and for the amplitude of the N1a component. The correlation between VEP hemispheric differences and time from onset (TFO) of the pathological event was not significant. Overall, the hemispheric differences between specific components of the VEP responses to lateralised stimuli appear to be a good marker of recovery from neglect.

An open-label pilot study of the use of rivastigmine to promote functional recovery in patients with unilateral spatial neglect due to first ischemic stroke.

The aim of this study was to evaluate the efficacy and safety of rivastigmine as add-on treatment to specific cognitive rehabilitation for unilateral spatial neglect (USN). Twenty patients were randomly assigned either to rehabilitation treatment only (No-RIV) or to rivastigmine (3 mg twice a day, for 8 weeks) add-on treatment (RIV+,). USN and functional status were evaluated by means of specific and validated instruments at baseline, at discharge and at one-month follow up. Compared with the untreated patients, the RIV+ subjects, at discharge, recorded significantly better discharge scores and higher effectiveness on two of the scales. However, subsequent further improvement of the No-RIV patients meant that at follow up there was no significant difference between the two groups. No other statistically significant difference was found. Rivastigmine as add-on treatment to specific cognitive training for USN may improve and accelerate recovery on some specific impairment tests as compared with cognitive training alone.

Hemispheric contribution to categorical and coordinate representational processes: a study on brain-damaged patients.

According to Kosslyn, two types of spatial relations can be used to arrange parts in mental imagery, i.e., categorical spatial relations and coordinate spatial relations, which are processed respectively by the left and right hemispheres. To investigate this possible hemispheric specialization in the imagery domain, we tested 34 left or right brain-damaged patients using both a categorical and a coordinate mental imagery task. The results show that left brain-damaged patients were selectively impaired on processing categorical representations, while right brain-damaged patients were more impaired on the processing the coordinate ones, regardless of the presence of visuo-spatial neglect. The present study partly support Kosslyn's theory and, despite data reported in previous studies of brain-damaged patients, it also supports the hypothesis of a possible bilateral neural representation of mental imagery, with the two hemispheres taking part in this process in different ways.

Efficacy of visuo-spatial training in right-brain damaged patients with spatial hemineglect and attention disorders.

Several rehabilitative approaches have been used to reduce neglect disorders. Some studies tried to demonstrate that hemineglect can be ameliorated by using tasks promoting attentional activation towards the neglected hemispace (Robertson et al., 1995, 2001). As a consequence, a functional link between level of attention and disorders of space exploration has been proposed. For this reason we tried to explore the possible role of attentional deficits on the efficacy of a standard neglect treatment based on visuo spatial rehabilitation. In this study we then examined the performances of a selected group of seven right brain damaged patients, suffering from both severe hemineglect and attentional deficits (of both phasic and tonic components of attention), to several tasks before and after a visuo-spatial training (VST) whose efficacy has been already demonstrated (Pizzamiglio et al., 1992). Results showed that VST induces a significant remission of hemineglect symptoms independently from disorders of attention. Moreover, after visuo-spatial rehabilitation, no improvement of attentional deficits is detectable.

Rehabilitation of left brain-damaged ischemic stroke patients: the role of comprehension language deficits. A matched comparison.

BACKGROUND: Aphasia is considered a risk factor for disability after stroke. The aim of this study was to assess the specific influence of aphasia on rehabilitation results. METHOD: A case-control study in consecutive left brain-damaged stroke inpatients, enrolled in three homogeneous subgroups [nonaphasic (NA) patients, aphasic with comprehension deficit (CD), and without comprehension deficit (NCD)] matched for age and onset-admission interval. Rehabilitation results (gain, efficiency, effectiveness of treatment, percentage and odds ratio of dropouts and of each degree of therapeutic response, assessed by Barthel Index and Rivermead Mobility Index) were compared among the subgroups. RESULTS: Two hundred and forty patients with sequelae of a first stroke were enrolled. CD patients, as compared with NCD and NA ones, had a significantly more severe basal neurological and functional status at admission, minor effectiveness on ADL and mobility, a higher percentage of low responders on ADL and urinary incontinence at discharge, and a risk of low therapeutic response on ADL nearly 4 times higher than the other patients (OR = 4.22, 95% CI = 1.90-9.38). The rehabilitative behavior between NCD and NA was similar. However, all subgroups (NA, CD and NCD) showed a significant improvement (p < 0.001) between their basal and discharge score, both on BI and RMI. CONCLUSIONS: Comprehension language deficit was confirmed to be a strong negative rehabilitation prognostic factor despite the speech therapy done by all CD patients.