Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

BACKGROUND AND OBJECTIVES: The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. PROTOCOL DESIGN: The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125 mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8 mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. OUTCOMES: Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. SAMPLE SIZE CALCULATION: It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.

Type 2 diabetes; elderly; cognitive deficit; cognitive flexibility; executive functions Resumen

Through meditation, people become aware of what happens in the body and mind, accepting the present experiences as they are and getting a better understanding of the true nature of things. Meditation practices and its inclusion as an intervention technique, have generated great interest in identifying the brain mechanisms through which these practices operate. Different studies suggest that the practice of meditation is associated with the use of different neural networks as well as changes in brain structure and function, represented in higher concentration of gray matter structures at the hippocampus, the right anterior insula, orbital frontal cortex (OFC) and greater involvement of the anterior cingulate cortex (ACC). These and other unrelated studies, shows the multiple implications of the regular practice of mindfulness in the structures and functions of the brain and its relation to certain observable and subjective states in people who practice it. Such evidence enabling the inclusion of mindfulness in psychological therapy where multiple applications have been developed to prove its effectiveness in treating affective and emotional problems, crisis management, social skills, verbal creativity, addiction and craving management, family and caregivers stress of dementia patients and others. However, neuropsychological rehabilitation has no formal proposals for intervention from these findings. The aim of this paper is to propose use of Mindfulness in neuropsychological rehabilitation process, taking the positions and theory of A.R. Luria.

Can we harness computerised cognitive bias modification to treat anxiety in schizophrenia? A first step highlighting the role of mental imagery

A new wave of computerised therapy is under development which, rather than simulating talking therapies, uses bias modification techniques to target the core psychological process underlying anxiety. Such interventions are aimed at anxiety disorders, and are yet to be adapted for co-morbid anxiety in psychosis. The cognitive bias modification (CBM) paradigm delivers repeated exposure to stimuli in order to train individuals to resolve ambiguous information in a positive, rather than anxiety provoking, manner. The current study is the first to report data from a modified form of CBM which targets co-morbid anxiety within individuals diagnosed with schizophrenia. Our version of CBM involved exposure to one hundred vignettes presented over headphones. Participants were instructed to actively simulate the described scenarios via visual imagery. Twenty-one participants completed both a single session of CBM and a single control condition session in counter-balanced order. Within the whole sample, there was no significant improvement on interpretation bias of CBM or state anxiety, relative to the control condition. However, in line with previous research, those participants who engage in higher levels of visual imagery exhibited larger changes in interpretation bias. We discuss the implications for harnessing computerised CBM therapy developments for co-morbid anxiety in schizophrenia.

Can social interaction skills be taught by a social agent? The role of a robotic mediator in autism therapy

Increasingly socially intelligent agents (software or robotic) are used in education, rehabilitation and therapy. This paper discusses the role of interactive, mobile robots as social mediators in the particular domain of autism therapy. This research is part of the project AURORA that studies how mobile robots can be used to teach children with autism basic interaction skills that are important in social interactions among humans. Results from a particular series of trials involving pairs of two children and a mobile robot are described. The results show that the scenario with pairs of children and a robot creates a very interesting social context which gives rise to a variety of different social and non-social interaction patterns, demonstrating the specific problems but also abilities of children with autism in social interactions. Future work will include a closer analysis of interactional structure in human-human and robot-human interaction. We outline a particular framework that we are investigating.

Clinical implications of cognitive bias modification for interpretative biases in social anxiety: an integrative literature review

Cognitive theories of social anxiety indicate that negative cognitive biases play a key role in causing and maintaining social anxiety. On the basis of these cognitive theories, laboratory-based research has shown that individuals with social anxiety exhibit negative interpretation biases of ambiguous social situations. Cognitive Bias Modification for interpretative biases (CBM-I) has emerged from this basic science research to modify negative interpretative biases in social anxiety and reduce emotional vulnerability and social anxiety symptoms. However, it is not yet clear if modifying interpretation biases via CBM will have any enduring effect on social anxiety symptoms or improve social functioning. The aim of this paper is to review the relevant literature on interpretation biases in social anxiety and discuss important implications of CBM-I method for clinical practice and research.

Can therapy dogs evoke awareness of one's past and present life in persons with Alzheimer's disease?

BACKGROUND: Persons with Alzheimer's disease (AD) sometimes express themselves through behaviours that are difficult to manage for themselves and their caregivers, and to minimise these symptoms alternative methods are recommended. For some time now, animals have been introduced in different ways into the environment of persons with dementia. Animal-Assisted Therapy (AAT) includes prescribed therapy dogs visiting the person with dementia for a specific purpose. AIM: This study aims to illuminate the meaning of the lived experience of encounters with a therapy dog for persons with Alzheimer's disease. METHOD: Video recorded sessions were conducted for each visit of the dog and its handler to a person with AD (10 times/person). The observations have a life-world approach and were transcribed and analysed using a phenomenological hermeneutical approach. RESULTS: The result shows a main theme 'Being aware of one's past and present existence', meaning to connect with one's senses and memories and to reflect upon these with the dog. The time spent with the dog shows the person recounting memories and feelings, and enables an opportunity to reach the person on a cognitive level. CONCLUSIONS: The present study may contribute to health care research and provide knowledge about the use of trained therapy dogs in the care of older persons with AD in a way that might increase quality of life and well-being in persons with dementia. IMPLICATIONS FOR PRACTICE: The study might be useful for caregivers and dog handlers in the care of older persons with dementia.

Phonological remediation program in students with developmental dyslexia

Background: program for phonological remediation in developmental dyslexia. Aim: to verify the efficacy of a program for phonological remediation in students with developmental dyslexia. Specific goals of this study involved the comparison of the linguistic-cognitive performance of students with developmental dyslexia with that of students considered good readers; to compare the results obtained in pre and post-testing situations of students with dyslexia who were and were not submitted to the program; and to compare the results obtained with the phonological remediation program in students with developmental dyslexia to those obtained in good readers. Method: participants of this study were 24 students who were divided as follows: Group I (GI) was divided in two other groups - Gle with 6 students with developmental dyslexia who were submitted to the program; and Glc with 6 students with developmental dyslexia who were not submitted to the program; Group II (GII) was also divided in two other groups - GIIe with 6 good readers who were submitted to the program, and GIIc with 6 good readers who were not submitted to the program. The phonological remediation program (Gonzalez & Rosquete, 2002) was developed in three stages: pre-testing, training and post-testing. Results: results indicate that GI presented a lower performance in phonological skills, reading and writing when compared to GII in the pre-testing situation. However, GIe presented a similar performance to that of GII in the post-testing situation, indicating the effectiveness of the phonological remediation program in students with developmental dyslexia. Conclusion: this study made evident the effectiveness of the phonological remediation program in students with developmental dyslexia.

Multimodal exercise intervention improves frontal cognitive functions and gait in Alzheimer's disease: A controlled trial

Aim: The objective of the present study was to investigate the effect of a multimodal exercise intervention on frontal cognitive functions and kinematic gait parameters in patients with Alzheimer's disease. Methods: A sample of elderly patients with Alzheimer's disease (n=27) were assigned to a training group (n=14; aged 78.0±7.3years) and a control group (n=13; aged 77.1±7.4years). Multimodal exercise intervention includes motor activities and cognitive tasks simultaneously. The participants attended a 1-h session three times a week for 16weeks, and the control participants maintained their regular daily activities during the same period. The frontal cognitive functions were evaluated using the Frontal Assessment Battery, the Clock Drawing Test and the Symbol Search Subtest. The kinematic parameters of gait-cadence, stride length and stride speed were analyzed under two conditions: (i) free gait (single task); and (ii) gait with frontal cognitive task (walking and counting down from 20 - dual task). Results and discussion: The patients in the intervention group significantly increased the scores in frontal cognitive variables, Frontal Assessment Battery (P<0.001) and Symbol Search Subtest (P<0.001) after the 16-week period. The control group decreased the scores in the Clock Drawing Test (P=0.001) and increased the number of counting errors during the dual task (P=0.008) after the same period. Conclusion: The multimodal exercise intervention improved the frontal cognitive functions in patients with Alzheimer's disease. © 2012 Japan Geriatrics Society.

Trajectory and outcomes of speech language therapy in the Prader-Willi syndrome (PWS): case report

The aim of this study was to describe the trajectory and the outcomes of speech-language therapy in Prader-Willi syndrome through a longitudinal study of the case of an 8 year-old boy, along four years of speech-language therapy follow-up. The therapy sessions were filmed and documental analysis of information from the child's records regarding anamnesis, evaluation and speech-language therapy reports and multidisciplinary evaluations were carried out. The child presented typical characteristics of Prader-Willi syndrome, such as obesity, hyperfagia, anxiety, behavioral problems and self aggression episodes. Speech-language pathology evaluation showed orofacial hypotony, sialorrhea, hypernasal voice, cognitive deficits, oral comprehension difficulties, communication using gestures and unintelligible isolated words. Initially, speech-language therapy had the aim to promote the language development emphasizing social interaction through recreational activities. With the evolution of the case, the main focus became the development of conversation and narrative abilities. It were observed improvements in attention, symbolic play, social contact and behavior. Moreover, there was an increase in vocabulary, and evolution in oral comprehension and the development of narrative abilities. Hence, speech-language pathology intervention in the case described was effective in different linguistic levels, regarding phonological, syntactic, lexical and pragmatic abilities.

Effect of Nintendo Wii (TM)-based motor and cognitive training on activities of daily living in patients with Parkinson's disease: A randomised clinical trial

Objectives To investigate the effect of Nintendo Wii (TM)-based motor cognitive training versus balance exercise therapy on activities of daily living in patients with Parkinson's disease. Design Parallel, prospective, single-blind, randomised clinical trial. Setting Brazilian Parkinson Association. Participants Thirty-two patients with Parkinson's disease (Hoehn and Yahr stages 1 and 2). Interventions Fourteen training sessions consisting of 30 minutes of stretching, strengthening and axial mobility exercises, plus 30 minutes of balance training. The control group performed balance exercises without feedback or cognitive stimulation, and the experimental group performed 10 Wii Fit (TM) games. Main outcome measure Section II of the Unified Parkinson's Disease Rating Scale (UPDRS-II). Randomisation Participants were randomised into a control group (n = 16) and an experimental group (n = 16) through blinded drawing of names. Statistical analysis Repeated-measures analysis of variance (RM-ANOVA). Results Both groups showed improvement in the UPDRS-II with assessment effect (RM-ANOVA P < 0.001, observed power = 0.999). There was no difference between the control group and the experimental group before training {8.9 [standard deviation (SD) 2.9] vs 10.1 (SD 3.8)}, after training [7.6 (SD 2.9) vs 8.1 (SD 3.5)] or 60 days after training [8.1 (SD 3.2) vs 8.3 (SD 3.6)]. The mean difference of the whole group between before training and after training was -0.9 (SD 2.3, 95% confidence interval -1.7 to -0.6). Conclusion Patients with Parkinson's disease showed improved performance in activities of daily living after 14 sessions of balance training, with no additional advantages associated with the Wii-based motor and cognitive training. Registered on http://www.clinicaltrials.gov (identifier: NCT01580787). (C) 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Spectrum of cognitive impairment in neurocysticercosis Differences according to disease phase

Objectives: Cognitive decline related to neurocysticercosis (NC) remains poorly characterized and underdiagnosed. In a cross-sectional study with a prospective phase, we evaluated cognitive decline in patients with strictly calcified form (C-NC), the epidemiologically largest subgroup of NC, and investigated whether there is a spectrum of cognitive abnormalities in the disease. Methods: Forty treatment-naive patients with C-NC aged 37.6 +/- 11.3 years and fulfilling criteria for definitive C-NC were submitted to a comprehensive cognitive and functional evaluation and were compared with 40 patients with active NC (A-NC) and 40 healthy controls (HC) matched for age and education. Patients with dementia were reassessed after 24 months. Results: Patients with C-NC presented 9.4 +/- 3.1 altered test scores out of the 30 from the cognitive battery when compared to HC. No patient with C-NC had dementia and 10 patients (25%) presented cognitive impairment-no dementia (CIND). The A-NC group had 5 patients (12.5%) with dementia and 11 patients (27.5%) with CIND. On follow-up, 3 out of 5 patients with A-NC with dementia previously still presented cystic lesions with scolex on MRI and still had dementia. One patient died and the remaining patient no longer fulfilled criteria for either dementia or CIND, presenting exclusively calcified lesions on neuroimaging. Conclusions: Independently of its phase, NC leads to a spectrum of cognitive abnormalities, ranging from impairment in a single domain, to CIND and, occasionally, to dementia. These findings are more conspicuous during active vesicular phase and less prominent in calcified stages. Neurology (R) 2012; 78: 861-866

Gene therapy for a novel mouse model of Canavan disease

Canavan disease (CD) is a rare leukodystrophy caused by loss-of-function mutations in the gene encoding aspartoacylase (ASPA), an oligodendrocyte-enriched enzyme. It is characterised by the accumulation of the ASPA substrate N-acetylaspartate (NAA) in brain, blood and urine, leading to a spongiform vacuolisation of the brain, severe motoric and cognitive impairments and premature death. To date, no therapy is available due to the lack of a gene-transfer system allowing transgene expression in oligodendrocytes (OLs) and the restoration of the missing enzyme. Hence, the aim of this study was to establish a novel gene-transfer system and its preclinical evaluation in a CD animal model.rnIn the first part of this thesis, a novel ASPA mouse mutant was generated. A βgeo cassette (including the genes encoding β-galactosidase and neomycin) flanked by frt sites was inserted into intron 1 of the intact aspa gene. Additionally, exon 2 was flanked by loxP sites for optional conditional deletion of the targeted locus. The resulting ASPA-deficient aspalacZ/lacZ-mouse was found to be an accurate model of CD and an important tool to identify novel aspects of its complex pathology. Homozygous mutants showed a CD-like histopathology, neurological impairment, behavioural deficits as well as a reduced body weight. Additionally, MRI data revealed changes in brain metabolite composition. rnRecombinant adeno-associated viral (rAAV) vectors have become a versatile tool for gene transfer to the central nervous system because they are efficient, non-toxic and replication-deficient. Based on the natural neurotropism of AAV vectors, AAV-based gene delivery has entered the clinics for the treatment of neurodegenerative diseases. However, the lack of AAV vectors with oligodendroglial tropism has precluded gene therapy for leukodystrophies. In the second part of this work, it was shown that the transduction profile of established AAV serotypes can be targeted towards OLs in a transcriptional approach, using the oligodendrocyte-specific myelin basic protein (MBP) promoter to drive transgene expression in OLs.rnIn the last part of this work, the therapeutic efficacy of AAV-mediated aspa gene transfer to OLs of juvenile aspalacZ/lacZ mice was evaluated. AAV-aspa injections into multiple sites of the brain parenchyma resulted in transduction of OLs in the grey and white matter throughout the brain. Histological abnormalities in the brain of ASPA-deficient mice were ameliorated and accompanied by a reduction of NAA levels. Furthermore, the treatment resulted in normalisation of body weight, motor function and nest-building behaviour. These data provide a proof-of-concept for a successful gene therapy of Canavan disease. This might pave the way towards translation into clinical application and serve as the basis for the genetic treatment of other leukodystrophies.

Intensity modulated radiation therapy or stereotactic fractionated radiotherapy for infratentorial ependymoma in children: a multicentric study

This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8-60). The median follow-up for surviving patients was 4.8 years (range, 1.3-8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques.