Computer-assisted training of executive functions in adult patients with non-progressive acquired brain damage - a pilot study on efficacy of a new therapeutic application.

Executive dysfunction is most often caused by post-traumatic or post-stroke damage to the prefrontal regions of the brain. The aim of this study was to compare the efficacy of two computer-assisted therapy programs for executive dysfunctions in patients with acquired brain injury. Patients were trained using either a newly developed application ExeSystem (designed to help improve the ability to manage and control one's own behavior by performing tasks imitating natural, everyday situations) or a combination of two commercial applications RehaCom and CogniPlus. Data collected after a three-week period of therapy conducted in two 15-person groups of participants indicated comparable efficacy of both therapy programs in improving quality of daily functioning, executive attention, as well as planning and problem-solving but not memory. The improvement in social competence (p = .028) was the only advantage of therapy with the ExeSystem. Therapeutic interactions using computer programs were shown to be positively evaluated by patients (p < .01). This study confirmed at least equal efficacy of computer-based executive function therapy using ExeSystem compared to RehaCom and CogniPlus. However, despite the implementation of a more ecological and comprehensive approach to the content of a new application, the benefits of this approach were limited.

Clinical significance of self-descriptive apathy assessment in patients with neurological form of Wilson's disease.

BACKGROUND AND AIM: Apathy is one of the neuropsychiatric symptoms of Wilson's disease (WD) which typically affects the brain's fronto-basal circuits. Lack of agreed diagnostic criteria and common use of self-description assessment tools lead to underestimation of this clinical phenomenon. The aim of this study was to investigate whether subjective and informant-based clinical features of apathy in patients with WD enable clinicians to make a valid diagnosis. METHODS: Multiple aspects of goal-oriented behavior were assessed in 30 patients with the neurological form of WD and 30 age-matched healthy participants using two questionnaires, the Lille Apathy Rating Scale (LARS) and the Dysexecutive Questionnaire (DEX). Both included a self-descriptive and a caregiver/proxy version. Cognitive functioning was estimated with the use of Addenbrooke's Cognitive Examination-Revised. RESULTS: Patients obtained significantly worse scores on all clinical scales when more objective measures were considered. Features of apathy and executive dysfunction were revealed in patients' caregiver versions of LARS and DEX, which may indicate poor self-awareness of patients with WD. Roughly 30% of participants were likely to present with clinically meaningful symptoms, independent of cognitive dysfunction. CONCLUSIONS: Methods relying on self-description appear inferior to informant-based scales when diagnosing apathy. More objective criteria and measurement tools are needed to better understand this clinical syndrome.

Neuronavigated 1 Hz rTMS of the left angular gyrus combined with visuospatial therapy in post-stroke neglect.

BACKGROUND: Visuospatial neglect (VSN) may be caused by an inter-hemispheric imbalance of neural activity after brain injury. Repetitive transcranial magnetic stimulation (rTMS) allows rebalancing restoration to a certain degree, relieving neglect symptoms. OBJECTIVE: This study investigates the therapeutic effect of 1 Hz rTMS applied over the left angular gyrus combined with visual scanning training in patients with left VSN in the subacute stroke phase. METHODS: Twenty-eight patients with VSN were randomly assigned to either experimental (fifteen sessions of rTMS consisted of 1800 magnetic pulses delivered to the left angular gyrus with a neuronavigation control), or control group (fifteen sessions of sham stimulation), followed by visual scanning training. VSN severity was assessed both before and after treatment with a 3-month follow up employing the Behavioural Inattention Test and functional measures. RESULTS: No statistically significant differences were detected in outcome measures between the rTMS and sham groups after completion of 3-week therapy and at 3-month follow up. The magnitude of stimulation effects was not associated either with lesion volume, its location, or baseline motor threshold. CONCLUSIONS: Our study did not confirm efficacy of 1 Hz rTMS over the angular gyrus as an adjuvant method to visual scanning training in patients with VSN in the subacute stroke.

Comprehensive cognitive training improves attention and memory in patients with severe or moderate traumatic brain injury.

Traumatic brain injury (TBI) leads to cognitive disorders, the most frequently affected functions being attention and memory. The present study aimed to investigate the effects of a cognitive rehabilitation program, consisting of individual and group interventions, on attention and memory in patients with TBI. Fifteen patients-in the postacute phase of recovery from moderate-to-severe TBI and subsequent cognitive disorders-were enrolled on a three-week waiting list and then underwent a three-week cognitive rehabilitation program. The patients were assessed using a set of five neuropsychological attention and memory tests. The patients and their caregivers were questioned to assess subjective changes in the everyday functioning of the former. The introduction of cognitive training was associated with improvement in one memory test and in two measures of attention. Mean effect size across all tests was higher over the period with treatment compared to the period without (d = 0.36 vs. 0.03). Both patients and caregivers reported significant improvements in everyday functioning (p < .05). There were no further improvements at the four-month follow-up assessment. A comprehensive program of cognitive rehabilitation may improve attention and memory, as well as everyday cognitive functioning, in patients with severe or moderate TBI.

Effects of group versus individual therapy for patients with memory disorder after an acquired brain injury: A randomized, controlled study.

INTRODUCTION: This randomized, controlled, single-blind study compared the efficacy of group versus individual memory rehabilitation therapy for patients with acquired brain injury (ABI). Subjects (N = 65) were assigned to individual (IT), group (GT), or no (NT) therapy during the three-week rehabilitation program. A neuropsychological assessment was conducted before treatment, immediately after completing treatment, and 4 months after completing treatment. Three levels of functioning were assessed: participation, disability, and impairment. The primary outcome measure was the Rivermead Behavioural Memory Test (RBMT). The results of the cognitive measures in the three groups at subsequent assessments were compared, and the effect sizes were calculated to investigate the magnitude of improvement. RESULTS: There were no significant changes in self-reported patient memory problems for the participation-level measures. However, relatives of participants in the GT group reported a decreased frequency of memory failures (p = .026). According to the ability-level measure (RBMT), both therapeutic groups had similar significant improvements (p < .001), and the effect sizes were large in both groups. Although the NT group also improved (p = .015), the effect size was small. The differences between the three groups were not significant according to analysis of variance (ANOVA). However, after therapy was completed, only the GT group continued to improve (p = .013). For the impairment-level measures, the IT group showed significant improvement post treatment in three out of four measures (p < .05). This group had medium effect sizes, while the other groups showed a small or marginal effect. CONCLUSIONS: Cognitive rehabilitation - either in a group or individually - led to equally enhanced memory functioning in ABI patients, but the effects were not significantly different from those for patients in the NT group. GT and IT had specific effects on different levels of functioning.

Adding transcutaneous electrical nerve stimulation to visual scanning training does not enhance treatment effect on hemispatial neglect: a randomized, controlled, double-blind study.

BACKGROUND: Left-sided transcutaneous electrical nerve stimulation (TENS) increases right hemispheric activity, which may improve the rehabilitative outcome of hemispatial neglect. OBJECTIVE: To examine the behavioral effect of electrical stimulation of the nerve afferents of the left hand during early neuropsychological rehabilitation of post-stroke patients with hemispatial neglect. METHODS: This randomized, controlled, double-blind study included 29 patients (enrolled in the experimental or control group) with left hemispatial neglect after right hemispheric stroke. For 3 weeks, patients received 15 therapeutic sessions involving TENS (active or sham) with a mesh glove applied on the entire left hand during the first 30 minutes of a 45-minute conventional visual scanning training (VST). Signs of hemispatial neglect were assessed using a psychometric test before and after treatment. RESULTS: Univariate analysis of covariance revealed that differences between the control and experimental groups were not significant after treatment (F(1, 22) = 0.294, P = 0.593) when adjusted for pre-treatment scores and time since stroke onset. This suggested that electrical stimulation failed to mitigate the severity of hemispatial neglect symptoms. CONCLUSION: Our study did not provide evidence of the effectiveness of TENS when added to VST during early rehabilitation for patients with post-stroke hemispatial neglect. Other techniques (applied alone or together) should be sought to improve recovery in this population.

Diverse attention deficits in patients with neurologically symptomatic and asymptomatic Wilson's disease.

OBJECTIVE: Cognitive deficits in patients with Wilson's disease (WD) have been reported in several studies, but there was no detailed analysis of the various components of attention, one of the most significant factors of the executive system. Our study determined the pattern of deficits in attention subsystems in WD patients, including selective attention, divided attention, attention switching, and sustained attention. METHOD: We examined 67 WD patients using the Test of Everyday Attention (TEA)-33 participants with neurological symptoms and 34 who were neurologically asymptomatic, but most with mild hepatic dysfunctions. The results were compared with 43 matched healthy controls. RESULTS: The group of WD patients with neurological symptoms performed significantly worse (p < .05) in all components of attention: sustained attention, selective attention, divided attention, and attentional switching. WD patients without neurological symptoms exhibited significantly lower results in one component-sustained attention (p < .05). None of the TEA subtests scores were associated significantly with Unified Wilson's Disease Rating Scale scores, which may reflect that the cognitive and neurological consequences of WD are relatively independent. CONCLUSIONS: We found a deficiency in all components of attention in neurological WD patients. The most frequently disturbed function was attention switching. Relatively milder deficits concerned divided, selective, and sustained attention. These are all abilities creating the core of the executive system and are regulated by subcortical prefrontal circuits, which are usually dysfunctional in WD patients. In neurologically asymptomatic patients, an isolated deficit of sustained attention occurs; this may be a sign of mild hepatic encephalopathy.

Pure alexia after damage to the right fusiform gyrus in a right-handed male.

Pure alexia refers to a rare acquired reading disorder commonly associated with damage to the posterior part of the left medial occipito-temporal (fusiform) gyrus, which is known as the visual word-form area (VWFA) and thought to be the neural basis for visual processing of letters and words. Right-sided lesions very rarely lead to pure alexia in right-handed individuals. We report a case of a 33-year-old right-handed man with isolated pure alexia resulting from a hemorrhagic lesion to the right fusiform gyrus. A limited recovery of reading skills was observed within six weeks post onset. During this period, the patient spontaneously developed a letter-by-letter reading strategy. Functional magnetic resonance imaging revealed right-hemisphere dominance for language as well as bilateral reading-related activity in the fusiform gyri. Our case indicates that pure alexia may arise as a consequence of damage to the right fusiform gyrus even in right-handed patients (who still may have right hemisphere dominance for language and reading skills), and may lead to a severe reading disorder, as in individuals with left-hemisphere dominance for language.

Effects of repeated anodal tDCS coupled with cognitive training for patients with severe traumatic brain injury: a pilot randomized controlled trial.

OBJECTIVE: To determine whether cumulative anodal transcranial direct current stimulation (A-tDCS) of the left dorsolateral prefrontal cortex (DLPFC) could enhance rehabilitation of memory and attention in patients with traumatic brain injury (TBI). SETTING: Inpatient and outpatient neurorehabilitation unit. PARTICIPANTS: Twenty-three adult patients, 4- to 92- months post severe TBI. DESIGN: Participants were randomly allocated to 2 groups. The experimental group received A-tDCS (10 minutes; 1 mA; in the DLPFC), followed by rehabilitative cognitive training, daily for 15 days. Controls received A-tDCS for 25 seconds (sham condition) with the same rehabilitation. MAIN MEASURES: Battery of memory and attention tests, which included visual and auditory modalities. Participants were tested twice before beginning rehabilitation (to control for spontaneous recovery), after rehabilitation completion, and 4 months later. RESULTS: Tests scores in both groups were similar at 3 weeks before and immediately before treatment. After treatment, the experimental group exhibited larger effect sizes in 6 of 8 cognitive outcome measures, but they were not significantly different from controls. At follow-up, differences remained insignificant. CONCLUSION: In contrast to previous studies, our study did not provide sufficient evidence to support the efficacy of repeated A-tDCS for enhancing rehabilitation of memory and attention in patients after severe TBI.

Anodal transcranial direct current stimulation in early rehabilitation of patients with post-stroke non-fluent aphasia: a randomized, double-blind, sham-controlled pilot study.

PURPOSE: Recent research in patients with chronic aphasia shows an association between excitatory anodal transcranial direct current stimulation (A-tDCS) of the stroke-affected left hemisphere coupled with speech and language therapy (SLT) and better language performance. The present study aimed to investigate this association during the early post-stroke rehabilitation period, when adaptive changes are most possible on neurophysiological and behavioral levels. METHODS: We randomized 24 patients with non-fluent aphasia to receive 15 consecutive sessions (5 days/week for 3 weeks) of A-tDCS (1 mA, 10 min; n = 14) or sham tDCS (S-tDCS: 1 mA, 25 sec; n = 10) over Broca's area followed by 45-min SLT. Naming ability was assessed before the rehabilitation, after its completion, and three months later. RESULTS: Both groups significantly improved after the therapy. There were no statistically significant between-group differences in the short-term or long-term tDCS effects on naming accuracy and naming time. The A-tDCS group obtained higher effect sizes in naming time, both post-treatment and at the 3-month follow-up, suggesting potential benefits of the stimulation. CONCLUSIONS: The findings provide only weak evidence for A-tDCS-related language gains during early neurorehabilitation of post-stroke aphasia. Further research is needed to explore the effectiveness of this kind of neuromodulation.

Transcranial magnetic stimulation combined with speech and language training in early aphasia rehabilitation: a randomized double-blind controlled pilot study.

BACKGROUND: Functional neuroimaging studies with poststroke aphasia patients have shown increased activation of the unaffected hemisphere, which hypothetically reflects a maladaptive strategy of brain reorganization. OBJECTIVE: We investigated whether repetitive transcranial magnetic stimulation (rTMS) inhibiting the right-hemisphere homologue of Broca's area improves language restitution if combined with speech/language therapy. METHODS: Forty aphasic patients during the subacute phase of ischemic stroke were randomized to a 3-week aphasia rehabilitation protocol in combination with real or sham rTMS. Naming, repetition, and comprehension were assessed using the Boston Diagnostic Aphasia Examination at baseline, immediately after therapy, and 15 weeks after completing treatment. RESULTS: Although language functions improved in both experimental and control groups after 3 weeks, only slight group differences in degree of recovery were revealed between patients receiving rTMS and control participants. Follow-up revealed that severely aphasic rTMS patients demonstrated significantly greater improvement than patients receiving sham stimulation in repetition. CONCLUSIONS: Inhibitory rTMS applied to the right frontal language homologue is not effective for all poststroke aphasia patients, although it might benefit selected patients.

Association between BDNF-196 G>A and BDNF-270 C>T polymorphisms, BDNF concentration, and rTMS-supported long-term rehabilitation outcome after ischemic stroke.

BACKGROUND: The efficacy of rehabilitation in ischemic stroke patients likely varies because of brain plasticity. One of the main neurotrophins in the central nervous system is brain-derived neurotrophic factor (BDNF). OBJECTIVES: This study aimed to determine allelic and genotypic distribution of BDNF-196 G>A and -270 C>T polymorphisms, and to assess the impact of repetitive transcranial magnetic stimulation (rTMS) on serum BDNF concentrations measured before rehabilitation, after the first 6 h of rehabilitation, and after 3 weeks of rehabilitation. METHODS: Twenty-six patients with hand paresis and 20 with aphasia were randomly assigned to treatment with rTMS or sham stimulation (placebo group). RESULTS: In men with aphasia, after the first 6 h of rTMS-supported rehabilitation, BDNF concentration was lower among rTMS-treated patients than placebo-treated patients. A similar difference was observed in women with aphasia after 3 weeks of rTMS-supported rehabilitation. No significant differences in serum BDNF concentration were observed in patients with different BDNF-196 G>A or -270 C>T genotypes. During the observation period, BDNF concentration did not differ significantly between patients who improved and those who did not. DISCUSSION: One possible explanation for the observed difference between rTMS-stimulated and sham-stimulated patients is the suppression of BDNF production by rTMS in the healthy brain hemisphere.

Effect of low-frequency repetitive transcranial magnetic stimulation on naming abilities in early-stroke aphasic patients: a prospective, randomized, double-blind sham-controlled study.

BACKGROUND AND PURPOSE: Functional brain imaging studies with aphasia patients have shown increased cortical activation in the right hemisphere language homologues, which hypothetically may represent a maladaptive strategy that interferes with aphasia recovery. The aim of this study was to investigate whether low-frequency repetitive transcranial magnetic stimulation (rTMS) over the Broca's homologues in combination with speech/language therapy improves naming in early-stroke aphasia patients. METHODS: 26 right-handed aphasic patients in the early stage (up to 12 weeks) of a first-ever left hemisphere ischemic stroke were randomized to receive speech and language therapy combined with real or sham rTMS. Prior to each 45-minute therapeutic session (15 sessions, 5 days a week), 30 minutes of 1-Hz rTMS was applied. Outcome measures were obtained at baseline, immediately after 3 weeks of experimental treatment and 15 weeks; posttreatment using the Computerized Picture Naming Test. RESULTS: Although both groups significantly improved their naming abilities after treatment, no significant differences were noted between the rTMS and sham stimulation groups. The additional analyses have revealed that the rTMS subgroup with a lesion including the anterior part of language area showed greater improvement primarily in naming reaction time 15 weeks after completion of the therapeutic treatment. Improvement was also demonstrated in functional communication abilities. CONCLUSIONS: Inhibitory rTMS of the unaffected right inferior frontal gyrus area in combination with speech and language therapy cannot be assumed as an effective method for all poststroke aphasia patients. The treatment seems to be beneficial for patients with frontal language area damage, mostly in the distant time after finishing rTMS procedure.

Transcranial magnetic stimulation combined with physiotherapy in rehabilitation of poststroke hemiparesis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralesional primary motor cortex (M1) may improve recovery in patients with hemiparetic stroke. OBJECTIVE: To evaluate the effectiveness of applying 1 Hz rTMS to the contralesional M1 in addition to physiotherapy during early rehabilitation for stroke patients with hand hemiparesis in a randomized, sham-controlled, double-blind study. METHODS: Forty patients with moderate upper extremity hemiparesis were randomized to receive 3 weeks of motor training (45 minutes daily) preceded by 30 minutes of 1 Hz rTMS applied to the contralesional M1 or 30 minutes of sham rTMS. Functional assessment of the paretic hand using the Wolf Motor Function Test was performed before, immediately after, and 3 months after completing treatment. RESULTS: No statistically significant differences were found between the experimental and the control group for hand function (Wolf Motor Function Test; P = .92) or the level of neurological deficit (National Institutes of Health Stroke Scale [NIHSS]; P = .82) after treatment. Effect sizes for the experimental (d = 0.5) and the control group (d = 0.47) were small. Similar results were observed at the 3-month follow-up. CONCLUSIONS: The findings did not suggest that rTMS suppression of the contralesional motor cortex augments the effect of early neurorehabilitation for upper limb hemiparesis. Larger trials that stratify subjects based on residual motor function or physiological measures of excitation and inhibition may identify responders in the future.

Validation of uv derivative spectrophotometric method for determination of benazepril hydrochloride in tablets and evaluation of its stability.

The absorbance and first-, second- and third-order derivative UV spectroscopic methods were applied for the determination of benazepril hydrochloride (BEN) in model solutions and tablets, as well as the estimation of its stability in solid phase. Derivative UV spectroscopy and HPLC methods were tested for: precision, linearity, accuracy and repeatability. HPLC was used as a reference method. The study presents that derivative UV spectroscopy (the first and second derivative only) and HPLC can be successfully applied for the quantitative analysis of benazepril hydrochloride both pure and in pharmaceutical formulations. Although, the first and second derivative spectrophotometric methods are fast, precise and accurate, but they cannot be used for evaluation of purity and stability of BEN in pharmaceutical formulations (due to a lack of selectivity).

Pharmacotherapy in stroke rehabilitation.

BACKGROUND: Pharmacotherapy is commonly given to patients recovering from a stroke to prevent further complications (e.g. recurrent stroke, seizures) or enhance recovery. However, some drugs may have a negative impact on neuroplasticity. OBJECTIVES: This review examines currently used drugs that are believed to promote recovery from motor and cognitive disturbances associated with stroke. METHODS: Literature regarding the properties, efficacy, safety, and dosing of drugs used to promote recovery after stroke was reviewed. RESULTS: The data on pharmacotherapy are insufficient to support a claim of significantly improved rehabilitation outcomes. Moreover, a growing body of evidence indicates that some agents can impair functional reorganization and slow the recovery process. However, a few chemicals are reported to be beneficial for stroke rehabilitation. The most promising are noradrenergic and dopaminergic agents, as well as several growth factors; these should be the future focus of extensive randomized clinical trials. CONCLUSIONS: Currently there is no drug with proven efficacy in enhancing poststroke recovery.

Are cognitive and behavioural deficits a part of the clinical picture in Kennedy's disease? A case study.

Two years prior to diagnosis of Kennedy's disease (KD), a 53-year-old man began experiencing neurological symptoms, including nasal speech, postural tremor, tremor in the upper extremities, and muscle weakness. Genetic analysis revealed 46 CAG repeats in the androgen receptor gene. The patient's altered social conduct and complaints of forgetfulness led to a neuropsychological assessment. A mild impairment in visuospatial and visuoconstructive abilities, visual short-term memory, and a personality disorder were detected. Although cognition and behaviour in KD are typically normal, our findings suggest that the disease may cause mild cognitive and behavioural changes as part of the disease's clinical manifestation.

The relationship between non-linguistic cognitive deficits and language recovery in patients with aphasia.

BACKGROUND AND PURPOSE: Non-linguistic cognitive impairments may limit rehabilitation efficacy in patients with aphasia. The aim of this study was to determine whether post-stroke aphasia was associated with impairments of visuo-spatial working memory and abstract thinking and whether these deficits adversely affected language recovery. METHODS: Baseline visuo-spatial memory and abstract thinking abilities were assessed in 78 patients with post-stroke aphasia and 38 healthy controls. Then, 47 of the 78 patients with aphasia completed three weeks of speech and language training. Therapy outcome was assessed by comparing pre- and post-treatment scores on the Boston Diagnostic Aphasia Examination. RESULTS: Even though the patients' non-linguistic cognitive abilities were impaired in general, the patients were heterogeneous with regard to their deficits. Linguistic and non-linguistic deficits appeared to be distinct, although they could be concurrent. Visuo-spatial working memory was associated with the degree of improvement in two functions crucial to language communication: naming and comprehension. No relationship was found between language therapy outcome and abstract thinking ability.

Left-hand somatosensory stimulation combined with visual scanning training in rehabilitation for post-stroke hemineglect: a randomised, double-blind study.

The aim of this randomised, double-blind study was to investigate the therapeutic effectiveness of left-hand electrical stimulation for patients with post-stroke left visuo-spatial neglect. This approach was hypothesised to enhance activation of the right hemisphere attention system and to improve visual exploration of extrapersonal space. Participants (n = 40) in the study were in a relatively early stage of recovery from their first right hemisphere stroke, and were randomly assigned to the experimental (E) or control (C) group. Group E received conventional visual scanning training combined with electrostimulation of the left hand, while Group C received scanning training with sham stimulation. Their visuo-spatial neglect was assessed twice, prior to the rehabilitation programme and on its completion, using cancellation tests and a letter-reading task. The effect of electrostimulation on hemineglect was assessed following a single administration and after a month-long rehabilitation programme. Although the immediate effect of stimulation was poor, after a month-long rehabilitation period we found significantly greater improvement in Group E patients than in Group C patients. Interestingly, the presence of hemisensory loss did not weaken the observed effect. Therefore, we claim that contralesional hand stimulation combined with visual scanning was a more effective treatment for hemineglect rehabilitation than scanning training alone.

Frequency and prognostic value of cognitive disorders in stroke patients.

BACKGROUND: Stroke is one of the most common diseases to cause cognitive disorders in adults. AIMS: To assess the frequency of cognitive deficits in stroke patients and to evaluate the prognostic value of cognitive syndromes for functional recovery. METHODS: 200 consecutive patients were examined using a clinical screening battery for cognitive assessment in the second week after their first-ever stroke. 80 were re-examined after a 1-year follow-up. RESULTS: In the post-acute stage, 78% patients were impaired in one or more cognitive domains. The most frequently affected cognitive abilities were attention (48.5%), language (27%), short-term memory (24.5%) and executive functions (18.5%). At the 1-year follow-up, attention deficits were still the most frequent symptom. In contrast, executive dysfunction, aphasia, and long-term memory disorder were significantly less frequent than in the post-acute period. Logistic regression analysis showed that older age, lower score on the Barthel Index, and the presence of executive dysfunction on initial examination were significant predictors of a poor functional outcome at the 1-year follow-up examination. CONCLUSIONS: Cognitive-behavioral syndromes are frequent and often chronic consequences of stroke. Executive deficits proved to be the most robust cognitive predictor of poor functional recovery after stroke.