Effect of NAC treatment and physical activity on neuroinflammation in subchronic Parkinsonism; is physical activity essential?

BACKGROUND: Neuroprotective strategies are becoming relevant to slow down dopaminergic cell death and inflammatory processes related to the progressive neurodegeneration in Parkinson's disease (PD). Interestingly, among others, physical activity (PA) or anti-oxidant agents (such as N-acetyl-L-cysteine, NAC) are common therapeutic strategies. Therefore, this study aims to analyze if there is a synergistic effect of physical activity along with NAC treatment on dopaminergic degeneration and neuroinflammatory response in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism model after subchronic intoxication. METHODS: To ascertain this possibility, 48 8-week-old male mice (C57BL/6 strain) were used. Twenty four of them were placed individually in cages where voluntary physical activity was automatically monitored during 30 days and were divided into groups: (i) control; (ii) NAC; (iii) MPTP, and (iv) MPTP+NAC. The other 24 mice were divided into the same four groups but without physical activity. RESULTS: The data collected during the treatment period showed that there was an overall increase in the total running distance in all groups under physical activity, including Parkinsonian animals. However, the monitoring data per day showed that the activity routine by MPTP and MPTP+NAC groups was disrupted by alterations in the circardian rhythm because of MPTP intoxication. Results from post-mortem studies in the substantia nigra pars compacta (SNpc) showed significant decrease in the number of TH+ cells in all MPTP groups. Moreover, TH+ expression in the striatum was significantly decreased in all MPTP groups. Thus, PA + NAC treatment do not protect dopaminergic neurons against a subchronic intoxication of MPTP. Regarding glial response, the results obtained from microglial analysis do not show significant increase in the number of Iba-1+ cell in MPTP+NAC and MPTP+PA + NAC. In the striatum, a significant decrease is observed only in the MPTP+NAC group compared with that of the MPTP group. The microglial results are reinforced by those obtained from the analysis of astroglial response, in which a decrease in the expression of GFAP+ cells are observed in MPTP+NAC and MPTP+PA + NAC compared with MPTP groups both in the SNpc and in the striatum. Finally, from the study of the astroglial response by the co-localization of GFAP/S100b, we described some expression patterns observed based on the severity of the damage produced by the MPTP intoxication in the different treated groups. CONCLUSIONS: These results suggest that the combination of physical activity with an anti-oxidant agent does not have a synergistic neuroprotective effect in the nigrostriatal pathway. Our results show a potential positive effect, only due to NAC treatment, on the neuroinflammatory response after subchronic MPTP intoxication. Thus, physical activity is not essential, under these conditions. However, we believe that physical activity, used for therapeutic purposes, has a beneficial long-term effect. In this line, these results open the door to design longer studies to demonstrate its promising effect as neuroprotective strategy.

[Meta-Cognitive Ability and Brain Damage in Autoimmune Encephalitis: A Case Report]. / Otoimmün Ensefalitte Beyin Hasari ve Üst Bilissel Beceri: Bir Olgu Sunumu.

Autoimmune encephalitis is an important contributor to rapidly progressive cognitive and behavioral decline. The purpose of this work was to evaluate the effects of cognitive rehabilitation in a patient with autoimmune encephalitis. We also wanted to evaluate the effectiveness of rehabilitative treatment by monitoring the cognitive and metacognitive outcomes over a time interval. We reported a case of 22 year-old female patient with autoimmune encephalitis, cognitive behavioral impairments, and severe reduction in metarepresentational capacity. We performed an assessment of personality, neuropsychological, and meta-cognitive functions at the beginning of the rehabilitative training. The last evaluation was performed six months after the discharge from the rehabilitation unit. We applied a combination of remediation, psycho-educational treatment, and psychotherapy to improve the knowledge and the empathy of the patient, to promote the selfcontrol strategies, and to prompt better behavioral management. Our findings revealed an improvement in the performance of the individual tests after rehabilitative training.

[The interdisciplinary approach to the rehabilitation of the patients presenting with congenital atresia of the external auditory canal and the concomitant microtia]. / Mezhdistsiplinarnyi podkhod k reabilitatsii patsientov s vrozhdennoi atreziei naruzhnogo slukhovogo prokhoda i mikrotiei.

The objective of the present study was to develop and introduce into the clinical practice the method for the combined aesthetic and functional rehabilitation of the patients presenting with congenital atresia of the external auditory canal (CAEAC) and the concomitant microtia. A total of 8 patients at the age from 6 to 21 years with unilateral CAEAC and microtia were given the surgical treatment. During the intervention, atresia was resolved using the trans-mastoid approach, tympanoplasty of autofasciae and ossiculoplasty making use of the partial titanium prosthesis and the placement of cranial osteointegratable titanium implants. At the second stage of the surgical intervention the 3D silicone prosthesis of the auricle shaped on an individual basis were used. The long-term follow-up observations have demonstrated the stable formation of the tube of the external auditory canal, with the bone-air interval amounting to 15-20 dB. The auricular prosthesis was the mirror image of the natural ear and completely concealed the congenital defect.

Elaborative encoding through self-generation enhances outcomes with errorless learning: Findings from the Skypekids memory study.

Errorless learning has demonstrated efficacy in the treatment of memory impairment in adults and older adults with acquired brain injury. In the same population, use of elaborative encoding through supported self-generation in errorless paradigms has been shown to further enhance memory performance. However, the evidence base relevant to application of both standard and self-generation forms of errorless learning in children is far weaker. We address this limitation in the present study to examine recall performance in children with brain injury (n = 16) who were taught novel age-appropriate science and social science facts through the medium of Skype. All participants were taught these facts under conditions of standard errorless learning, errorless learning with self-generation, and trial-and-error learning after which memory was tested at 5-minute, 30-minute, 1-hour and 24-hour delays. Analysis revealed no main effect of time, with participants retaining most information acquired over the 24-hour testing period, but a significant effect of condition. Notably, self-generation proved more effective than both standard errorless and trial-and-error learning. Further analysis of the data revealed that severity of attentional impairment was less detrimental to recall performance under errorless conditions. This study extends the literature to provide further evidence of the value of errorless learning methods in children with ABI and the first demonstration of the effectiveness of self-generation when delivered via the Internet.

Gastric perforation and critical illness polyneuropathy after steroid treatment in a patient with encephalitis/encephalopathy with transient splenial lesion.

The outcome of mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is favorable whether or not specific treatment is performed. We report a patient with MERS treated with methylprednisolone, complicated by gastric perforation followed by critical illness polyneuropathy. The patient was a 14-year-old male with mildly impaired consciousness and hyponatremia who was treated with methylprednisolone pulse therapy. High fever appeared after methylprednisolone pulse therapy and free air was recognized on an abdomen roentgenogram. Gastric perforation was recognized on emergent endoscopic surgery and omental implantation repair was performed. His consciousness was fully recovered after surgery, whereas he was noted to have motor and sensory impairment of the lower extremities and vesico-rectal disturbance. Nerve conduction studies revealed decreased compound muscle action potentials with preserved motor conduction velocity and decreased sensory nerve action potentials. He was diagnosed as having critical illness polyneuropathy, and bedside physical rehabilitation was initiated. His neurological symptoms resolved within 6months. Our patient highlighted possible serious adverse events associated with steroid treatment for children with MERS.

Effects of exercise on adolescent and adult hypothalamic and hippocampal neuroinflammation.

Adolescence is a period of significant brain plasticity that can be affected by environmental factors, including the degree of physical activity. Here we hypothesized that adolescent rats would be more sensitive to the beneficial metabolic and anti-inflammatory effects of voluntary exercise than adult rats, whose more mature brains have less capacity for plasticity. We tested this by giving adolescent and adult Wistar rats four weeks' voluntary access to running wheels. At the end of this period we assessed metabolic effects, including weight and circulating leptin and ghrelin, as well as performance in a novel object recognition test of memory and central changes in neuronal proliferation, survival, synaptic density, and inflammatory markers in hippocampus. We found exercise reduced fat mass and circulating leptin levels in both adults and adolescents but suppressed total weight gain and lean mass in adults only. Exercise stimulated neuronal proliferation in the suprapyramidal blade of the dentate gyrus in both adults and adolescents without altering the number of mature neurons during this time frame. Exercise also increased dentate microglial numbers in adolescents alone and microglial numbers in this region were inversely correlated with performance in the novel object recognition test. Together these data suggest that adolescent hippocampal microglia are more sensitive to the effects of exercise than those of adults, but this leads to no apparent improvement in recognition memory. © 2016 Wiley Periodicals, Inc.

Physical activity and exercise attenuate neuroinflammation in neurological diseases.

Major depressive disorder (MDD), schizophrenia (SCH), Alzheimer's disease (AD), and Parkinson's disease (PD) are devastating neurological disorders, which increasingly contribute to global morbidity and mortality. Although the pathogenic mechanisms of these conditions are quite diverse, chronic neuroinflammation is one underlying feature shared by all these diseases. Even though the specific root causes of these diseases remain to be identified, evidence indicates that the observed neuroinflammation is initiated by unique pathological features associated with each specific disease. If the initial acute inflammation is not resolved, a chronic neuroinflammatory state develops and ultimately contributes to disease progression. Chronic neuroinflammation is characterized by adverse and non-specific activation of glial cells, which can lead to collateral damage of nearby neurons and other glia. This misdirected neuroinflammatory response is hypothesized to contribute to neuropathology in MDD, SCH, AD, and PD. Physical activity (PA), which is critical for maintenance of whole body and brain health, may also beneficially modify neuroimmune responses. Since PA has neuroimmune-modifying properties, and the common underlying feature of MDD, SCH, AD, and PD is chronic neuroinflammation, we hypothesize that PA could minimize brain diseases by modifying glia-mediated neuroinflammation. This review highlights current evidence supporting the disease-altering potential of PA and exercise through modifications of neuroimmune responses, specifically in MDD, SCH, AD and PD.

Computerised cognitive training in acquired brain injury: A systematic review of outcomes using the International Classification of Functioning (ICF).

Computerised cognitive training (CCT) is an increasingly popular intervention for people experiencing cognitive symptoms. This systematic review evaluated the evidence for CCT in adults with acquired brain injury (ABI), focusing on how outcome measures used reflect efficacy across components of the International Classification of Functioning, Disability and Health. Database searches were conducted of studies investigating CCT to treat cognitive symptoms in adult ABI. Scientific quality was rated using the PEDro-P and RoBiNT Scales. Ninety-six studies met the criteria. Most studies examined outcomes using measures of mental functions (93/96, 97%); fewer studies included measures of activities/participation (41/96, 43%) or body structures (8/96, 8%). Only 14 studies (15%) provided Level 1 evidence (randomised controlled trials with a PEDro-P score ≥ 6/10), with these studies suggesting strong evidence for CCT improving processing speed in multiple sclerosis (MS) and moderate evidence for improving memory in MS and brain tumour populations. There is a large body of research examining the efficacy of CCT, but relatively few Level 1 studies and evidence is largely limited to body function outcomes. The routine use of outcome measures of activities/participation would provide more meaningful evidence for the efficacy of CCT. The use of body structure outcome measures (e.g., neuroimaging) is a newly emerging area, with potential to increase understanding of mechanisms of action for CCT.

Effect of Amplification on Speech and Language in Children With Aural Atresia.

PURPOSE: There currently is no guideline regarding amplification or verification for children with aural atresia. This population, with the absence of the ear canal, has obvious congenital hearing loss. Research suggests that delayed treatment for hearing loss can result in speech and language impairments, including poor performance in school. In this study we examined the relationship between amplification and emerging speech and language development in children with aural atresia. METHOD: Subjects included children, 3 to 6 years of age, with conductive hearing loss due to atresia. Clinical evaluations were used to determine relationships between amplification and speech and language development. Subjects underwent an audiology exam, including pure-tone or warble-tone air and bone conduction using play audiometry techniques, and a speech and language evaluation assessing language and vocabulary skills. RESULTS: Subjects who were fitted before 1 year of age showed better compliance with aid use and exhibited fewer delays in speech and language development. Children with right-sided atresia had significantly greater speech and language delays when compared with age norms from standardized tests. CONCLUSION: Our findings highlight a relationship between side of atresia, time of first amplification, compliance in aid use, and speech and language abilities.

Functional status of children with encephalitis in an inpatient rehabilitation setting: a case series.

INTRODUCTION: Patterns and predictors of recovery from encephalitis are poorly understood. METHODS: This study examined functional status and reviewed charts of all children who presented to a pediatric inpatient rehabilitation facility with encephalitis between 1996 and 2010. Functional status at admission and discharge from inpatient rehabilitation was evaluated using the Functional Independence Measure for Children (WeeFIM) Self-care, Mobility, Cognitive, and Total Developmental Functional Quotient scores (DFQ, % of age-appropriate function). Charts were reviewed to characterize key clinical features and findings. RESULTS: Of the 13 children identified, the mean age was 9 years (range 5-16) with 54% males. Mean WeeFIM Total DFQ at admission was 37 (range: 15-90) and at discharge was 64 (range: 16-96). Average change in WeeFIM Total DFQ from admission to discharge was 26.7 (range 0-55, p < 0.001). WeeFIM domain scores improved between admission and discharge (Self-Care: p < 0.001, Cognition: p < 0.01, Mobility: p < 0.001). Eleven children displayed significant impairments in functional skills, defined as DFQ of < or =85, at discharge. Key clinical features and findings were diverse and not related to functional outcome. CONCLUSIONS: Results suggest that significant functional improvement in children with encephalitis occurs during inpatient rehabilitation. Further research is necessary to identify predictors of outcome in children with encephalitis.

Evolución posquirúrgica en pacientes con encefalitis de Rasmussen operados por hemisferotomía / Post-operative progress of patients with Rasmussen’s encephalitis who have undergone hemispherotomy surgery

Introducción. La encefalitis de Rasmussen (ER) es una afección cerebral progresiva que provoca una atrofia hemisférica unilateral, disfunción neurológica y epilepsia refractaria. La hemisferotomía se considera actualmente el tratamiento más efectivo, pero algunos casos presentan particularidades que dificultan la decisión de realizarla. Objetivo. Evaluar la evolución posquirúrgica de niños con ER operados por hemisferotomía, que en la evaluación prequirúrgica presentaron algunas características que dificultaron la decisión quirúrgica. Pacientes y métodos. Se seleccionaron los casos con ER, atendidos en el Hospital São Paulo entre 2003 y 2012, que en la evaluación prequirúrgica presentaran evidencias clínicas, electroencefalográficas o en la neuroimagen de participación de ambos hemisferios cerebrales, afectación del hemisferio cerebral dominante, ausencia de déficit neurológico grave y ausencia de criterios de epilepsia refractaria y crisis atípicas. Para la evaluación posquirúrgica de las crisis epilépticas se utilizó la escala de Engel; para analizar la función motora, las escalas Gross Motor Function Classification System y Manual Ability Classification System, y el lenguaje se evaluó clínicamente. Resultados. Se seleccionaron seis casos (cuatro niñas), con edad media de inicio clínico de 3,3 ± 1,2 años (rango: 2-7 años) y edad media de hemisferotomía de 6,7 años (rango: 2,3-16,5 años). El tiempo medio de seguimiento posquirúrgico fue de tres años (rango: 0,5-7,2 años). En la evaluación posquirúrgica de las crisis epilépticas, cuatro casos se clasificaron como Engel clase I (66%); hubo mejoría en la función motora en cinco, y mejoría en el lenguaje, en todos. Conclusión. La hemisferotomía debe considerarse una opción eficiente de tratamiento en niños con ER (AU)

Introduction. Rasmussen’s encephalitis (RE) is a progressive pathology affecting the brain that causes unilateral hemispheric atrophy, neurological dysfunction and refractory epilepsy. Hemispherotomy is considered the most effective treatment today, but some cases present certain peculiarities that can seriously affect the decision to go ahead with this procedure. Aims. To evaluate the post-operative progress made by children with RE who have undergone hemispherotomy surgery, and who, in the pre-operative assessment, presented certain characteristics that complicated the decision to perform surgery. Patients and methods. The sample selected for study consisted of the cases of RE attended in the Hospital São Paulo between 2003 and 2012 who, in the pre-surgery evaluation, presented clinical, electroencephalographic or neuroimaging evidence of involvement of both brain hemispheres, compromise of the dominant brain hemisphere, absence of severe neurological deficit and absence of criteria for refractory epilepsy and atypical crises. The post-operative assessment of the epileptic seizures was evaluated using the Engel scale; motor function was analysed with the Gross Motor Function Classification System and Manual Ability Classification System scales, and language was evaluated clinically. Results. Six cases were selected (four girls), with a mean age at clinical onset of 3.3 ± 1.2 years (range: 2-7 years) and a mean age at hemispherotomy of 6.7 years (range: 2.3-16.5 years). The mean post-surgery follow-up time was three years (range: 0.5-7.2 years). In the post-surgery evaluation of the epileptic seizures, four cases were classified as Engel class I (66%); there was some improvement in motor functioning in five of them, and language improved in all cases. Conclusions. Hemispherotomy must be considered an efficient option for treatment in children with RE (AU)

A case of anti-NMDAR (N-methyl-D-aspartate receptor) encephalitis: a rehabilitation perspective.

Anti-NMDAR (N-Methyl-D-Aspartate Receptor) Encephalitis is a rare occurring autoimmune disease that is mediated by antibodies against the NR1 subunit of the NMDA receptor. While this condition has a known predilection for young females with ovarian tumors, heightened awareness has led to increasing recognition of this condition in other population groups as well. Afflicted patients typically evolve through a multi-staged course of neurological, behavioral, cognitive and physical deficits. The diverse nature of this condition often necessitates a multi-disciplinary team for management. As the recovery of patients with anti-NMDAR encephalitis is often protracted, the role of the rehabilitation is important particularly beyond its acute stages. We describe a case of anti-NMDAR encephalitis in a 17-year-old girl who presented to our rehabilitation centre for management in the gradual recovery phase of her condition. This case illustrates the multiple challenges faced in the rehabilitation of such a patient.

[Three children with Rasmussen encephalitis showing marked improvement in daily life activity following the functional hemispherectomy].

We investigated seizure, intelligence quotient (IQ), and neurological outcomes including the process of motor function recovery after functional right hemispherectomy in 3 children with Rasmussen's encephalitis (RE). Before the procedure, they were unable to walk, nor sit without support due to progressive worsening of left hemiplegia and relentless epilepsia partialis continua (EPC) of the left extremities, which were refractory to antiepileptic drug and immunological treatment. After functional right hemispherectomy, EPC completely disappeared, although complete left hemiplegia was sustained. However, they recovered up to being able to walk independently with assistance devices, and to have an ordinary life with family support within 1.5 to 5 months through rehabilitation. At the same time, the interictal EEG improved on the unaffected side of hemisphere, exhibiting a posterior alpha rhythm. Their IQ also improved, and they were able to attend school. Early functional hemispherectomy should be considered before patients with RE are left in a serious condition due to progressive worsening of hemiplegia and seizures refractory to the available treatment.

Efficacy of alertness training in a case of brainstem encephalitis: clinical and theoretical implications.

Although attention functions are often impaired after stroke, traumatic brain injury or inflammatory diseases, little is known about the time course and the long-term efficacy of training-induced improvement. The present single case study evaluates the time course and longitudinal stability of attention improvement after alertness training by repeatedly testing the subject between individual training sessions as well as one and seven months after the end of the training. The outpatient (M.P.) trained developed severe alertness deficits following brainstem encephalitis in 2003 without signs of cortical damage, and since then had not achieved full recovery. In 2008, M.P. participated in 15 treatment sessions on 15 separate working days over a period of three weeks. In each session a 45-minute alertness training task was administered, using the CogniPlus ALERT computer training program. Attention performance was assessed by neuropsychological tests four years, one year, and immediately before the therapy after every third training session and three times after the termination of therapy. Furthermore, a self-report questionnaire measured subjective experience of attention in everyday life situations. In order to compare the performance between training sessions, a procedure specialised for psychometric single-case diagnosis was used to analyse the data. Surprisingly, even after three consecutive training sessions, M.P. showed immense improvement in alertness. Furthermore, after two weeks she felt more energetic and more able to concentrate. Six months after the end of the training the improvement remained stable. The unexpectedly fast time course of recovery induced by the training, as well as the stable long-term effects, probably depend on intact cortical structures. In M.P. it appeared that top-down control of the alertness network on impaired brainstem arousal structures had been re-activated by the training procedure and had remained stable across a long time period.

Using a paging system in the rehabilitation of encephalitic patients.

Memory and executive problems following encephalitis are common yet there are few published papers on the successful rehabilitation of such patients. We recently demonstrated (Wilson, Emslie, Quirk, & Evans, 2001; Wilson, Emslie, Quirk, Evans, & Watson, 2005) that a paging system could reduce the everyday memory and planning problems for people with non-progressive brain injury. Among the 143 patients who participated in the 2001 study were four people who had survived encephalitis. Their results are reported here. During a 2-week baseline, the successful task achievement of our four clients ranged from 2-81%. They then received a pager for 7 weeks and task achievement was documented in weeks 6 and 7. All were significantly more successful with the pager than they had been at baseline with success rates ranging from 45-96%. Five weeks after returning their pagers they were monitored once more. One of the encephalitic patients failed to achieve any of his target tasks, returning to baseline level, the other three dropped back a little but were still significantly more successful than at baseline. It is concluded that the paging system can reduce everyday memory and planning problems of patients with encephalitis.

Rehabilitation of West Nile Fever (WNF) encephalitis in elderly.

In the summer of 2000, an outbreak of WNF affected Israel. Thirty-two elderly patients were admitted to Meir Hospital. WNF encephalitis may result in residual functional damage. However, little information is available regarding the rehabilitation of these patients. Five elderly subjects with residual functional damage were referred to geriatric rehabilitation. Patients were treated with the routine program for neurological rehabilitation after stroke, including daily physiotherapy and occupational therapy. All five were over 77 years and independent before admission. The mean FIM score on admission was 71 (S.D. = +/-8.5) and increased to 102 (S.D. = +/-14) on discharge. MMSE on admission was 60% (S.D. = +/-7.5%), and increased to over 90% on discharge in all of the patients. Clock Completion Test was normal in four on admission, and improved to normal in the fifth patient on discharge. WNF encephalitis may present with functional and intellectual impairment in the elderly. Routine geriatric neurological rehabilitation may benefit those with prolonged functional decline.

Transient and long-term feeding by means of percutaneous endoscopic gastrostomy in neurological rehabilitation.

In 28 patients of a neurological rehabilitation unit of a hospital the use of enteral nutrition via percutaneous endoscopic gastrostomy (PEG) tubes was reviewed. During a total observation period of 5,172 days no life-threatening complications occurred. Minor complications were observed in 12 patients (43%) in the first 2 weeks after the insertion and in 5 patients (18%) afterwards. The nutritional status stabilized in all subjects. Transient PEG feeding was performed in 11 patients (39%) with a mean duration of 150 days. We conclude that hesitation in the application of PEG feeding in neurological rehabilitation should be abandoned. The timing and monitoring of PEG feeding in patients undergoing neurological rehabilitation for acute remitting neurological disorders is discussed.