Chronic Neurological Illness Research Articles

Repetitive mild traumatic brain injury with impact acceleration in the mouse: Multifocal axonopathy, neuroinflammation, and neurodegeneration in the visual system

Repetitive mild traumatic brain injury (mTBI) is implicated in chronic neurological illness. The development of animal models of repetitive mTBI in mice is essential for exploring mechanisms of these chronic diseases, including genetic vulnerability by using transgenic backgrounds. In this study, the rat model of impact acceleration (IA) was redesigned for the mouse cranium and used in two clinically relevant repetitive mTBI paradigms. We first determined, by using increments of weight dropped from 1m that the 40g weight was most representative of mTBI and was not associated with fractures, brain contusions, anoxic–ischemic injury, mortality, or significant neurological impairments. Quantitative evaluation of traumatic axonal injury (TAI) in the optic nerve/tract, cerebellum and corpus callosum confirmed that weight increase produced a graded injury. We next evaluated two novel repetitive mTBI paradigms (1 time per day or 3 times per day at days 0, 1, 3, and 7) and compared the resulting TAI, neuronal cell death, and neuroinflammation to single hit mTBI at sub-acute (7days) and chronic time points (10weeks) post-injury. Both single and repetitive mTBI caused TAI in the optic nerve/tract, cerebellum, corticospinal tract, lateral lemniscus and corpus callosum. Reactive microglia with phagocytic phenotypes were present at injury sites. Severity of axonal injury corresponded to impact load and frequency in the optic nerve/tract and cerebellum. Both single and repeat injury protocols were associated with retinal ganglion cell loss and optic nerve degeneration; these outcomes correlated with impact load and number/frequency. No phosphorylated tau immunoreactivity was detected in the brains of animals subjected to repetitive mTBI. Our findings establish a new model of repetitive mTBI model featured by TAI in discrete CNS tracts, especially the visual system and cerebellum. Injury in retina and optic nerve provides a sensitive measure of severity of mTBI, thus enabling further studies on mechanisms and experimental therapeutics. Our model can also be useful in exploring mechanisms of chronic neurological disease caused by repetitive mTBI in wild-type and transgenic mice.

Risk of venous thromboembolism in people with epilepsy.

Risk of venous thromboembolism (VTE) among people with epilepsy (PWEs) has not been previously reported. Standard VTE prevention methods may increase the risk of complications in this population. This statewide study assessed the risk of VTE in PWEs. Main risk categories were grouped into definite epilepsy (DE), probable epilepsy (PE), and migraine, a comparable neurologic condition. All inpatient, emergency department, and hospital-based outpatient encounters in South Carolina from January 1, 2000 through December 31, 2011, were evaluated for the primary outcome variable of VTE, defined as having a diagnosis of VTE at or after the diagnosis of epilepsy or migraine. Coagulopathies and common comorbidities of epilepsy were enumerated. Differences in VTE proportions were assessed using 95% confidence intervals (CIs). Association of VTE with epilepsy and migraine was evaluated with Cox proportional hazard modeling. A total of 138,497 people with migraine (PWMs) and 67,900 PWEs (32,186 DE, 35,714 PE) were included. VTE occurred in 2.7% of PWEs (4.2% among DE), and 0.6% of PWMs. The hazard ratio for VTE in DE compared with PWMs was 3.08 (95% CI 2.76-3.42), adjusted for all covariables. Higher numbers of comorbidities were strongly associated with VTE. PWE had higher numbers of comorbidities (52% with 2+ comorbidities versus 23% of PWM), but the impact of comorbidities on VTE risk was larger in PWM. Higher VTE risk in PWE than PWM suggests risk factors associated with epilepsy, independent of chronic neurologic illness. VTE occurrence in PWE is comparable to published rates among people with cancer.

An evaluation of serum paraoxonase together with arylesterase activities and oxidative stress in children with intractable epilepsy: A cross-sectional study

Epilepsy is the most common chronic neurological illness in childhood and adolescence. The aim of this study was to investigate paraoxonase and arylesterase activities along with oxidative status parameters in children with intractable epilepsy. The study comprised 42 subjects with intractable epilepsy and a control group of 35 healthy subjects. Serum paraoxonase and arylesterase activities, and lipid hydroperoxide levels were determined. All paraoxonase and arylesterase activities were significantly lower in the intractable epilepsy subjects than in the controls (P<0.001), whereas lipid hydroperoxide levels were significantly higher (P<0.05). In conclusion, paraoxonase and arylesterase activities were decreased and the lipid hydroperoxide level was increased in patients with intractable epilepsy. These results showed that intractable epilepsy subjects may be more prone to the development of atherosclerosis.

Transitions between SNF and home-based care in patients with multiple sclerosis

To assess patient characteristics and risk factors associated with care transitions between skilled nursing facility (SNF) and home care for patients with multiple sclerosis (MS) in an effort to improve outcomes and optimize patient care pathways. MS is a chronic neurologic illness of younger adults that is associated with physical disability, cognitive impairment and a high need for supportive services. The study was based on the 2005 Nursing Home Minimum Data Set and the Outcome and Assessment Information Set data (n = 10,064). We performed multivariate evaluation of patient risk factors for skilled nursing facility (SNF) admission and disposition while controlling for potential patient self-selection and other characteristics that affect care utilization. MS patients with recent history of home care use were less likely to be admitted to an acute care hospital and had higher physical disability at SNF admission than SNF patients who did not use home care. Insurance type (Medicaid) and availability of informal caregivers were associated with the use of homecare services after a SNF stay, while patient demographic and clinical characteristics did not explain SNF disposition. Future studies should explore the association between the local availability and affordability of home-based services and physician attitude about community-based care management of disabled patients.

Investigating the bundle compliance of IVIG delivery in the Greater Manchester Neuroscience centre.

Salford Royal Hospital is one of the largest users of IVIG for chronic neurological illnesses within the UK. The majority of patients are being treated for chronic inflammatory polyneuropathy and multifocal motor neuropathy. We hypothesised that the components of care being delivered to these patients differed to our stated standard of care (IVIG care bundle). We performed a service review exercise to identify shortcomings and improve quality of patient care. The aim was to measure overall bundle compliance being delivered to 75 patients with a view to improving the overall quality of care being delivered in the future. A retrospective case note study was carried out to measure compliance with the 17 areas of care, which constituted the IVIG bundle. Nine areas of care were being delivered to all 75 patients. This meant that all patients were receiving three monthly bloods, a documented cannula pathway, a filed prescription, a medical assessment, and the correct follow-up. Not all patients had a filed consent form, ECG or HAT assessment and an even smaller number of patients had a documented calculation for the amount of IVIG that needed to be given and few had a serum save. No patient in the group was receiving the intended complete bundle of care.The results led to the development of an electronic treatment dashboard for the delivery of chronic IVIG therapy to this group. A re-audit has shown that rates of individual areas of care being delivered has increased markedly but overall compliance has only increased a slightly due to a lack of serum saves for patients.

Multiple Sclerosis and Pregnancy

Multiple sclerosis (MS) is a chronic neurological illness affecting adults at the time when they are most likely to consider starting a family. It is known that the risk of MS relapse declines during pregnancy but increases in the first 3 to 6 months postpartum. It is also known that this risk is not affected by delivery method, anesthesia type, or parity. Unanswered questions remain, including long-term pregnancy effects on MS outcomes, effects of lactation on postpartum relapses, or the best management strategies of MS patients through reproductive cycle. This review provides information and guidelines for counseling patients with MS desiring motherhood.

Hemichorea-hemiballismus as the presenting manifestation of nonketotic hyperglycemia in an adolescent with undiagnosed type 2 diabetes mellitus

Hemichorea-hemiballismus as the presenting manifestation of nonketotic hyperglycemia in an adolescent with undiagnosed type 2 diabetes mellitus

Why are some people with neurological illness more resilient than others?

The current qualitative study was designed to evaluate the coping strategies of people living with a chronic progressive neurological illness and their carers. The neurological illnesses were Huntington's disease, motor neurone disease, multiple sclerosis and Parkinson's disease. Participants included 15 people who showed high levels of adjustment and 15 who showed low levels of adjustment. Participants were selected from an earlier study, to ensure that they satisfied the inclusion criteria for the current study. Interviews were completed to determine the strategies used to cope with the demands of the illness. Participants who demonstrated good adjustment were more likely to draw on social support to provide them with the resources to deal with the illness. In contrast, those who evidenced poor adjustment were more likely to draw on external supports to complete tasks for them. The implications of these findings for people with chronic neurological illnesses and their families are discussed.

Disability in elderly patients with chronic neurological illness: Stroke, multiple sclerosis and epilepsy

The aim of the study was to evaluate disability in patients with elderly stroke, multiple sclerosis (MS) and epilepsy, and to analyze its relationship with demographic characteristics. We conducted a cross-sectional study involving 113 patients with neurological diseases. The data were collected with a Personal Information Form, the Rivermead Mobility Index (RMI), and the Brief Disability Questionnaire (BDQ) were used. The data were evaluated using percentage, variance analysis, the Kruskal–Wallis test and the Pearson correlation analysis. The study results demonstrate that among three disorders, the severity of disability increased in patients with stroke, epilepsy and MS, respectively. It was also found that in patients with stroke, MS and epilepsy experiencing disability in mobility, 32.7% had experienced moderate physical–social disability, and 63.3% had experienced severe physical–social disability, and that there was a significantly high relationship between mobility disability and physical–social disability. The severity of disability was found to be higher for older age, low level education, self-employed and widows. Especially in stroke patients, disability is a common problem in patients with epilepsy and MS. Detecting the level of disability is very important for decreasing the limitation in elderly patients with neurological illness.

Predictors of quality of life in carers for people with a progressive neurological illness: a longitudinal study

The aim of the present research was to determine the predictors of quality of life (QOL) among carers for people living with a chronic degenerative neurological illness, with comparisons of the differences in significant predictors of QOL between illness groups. Psychosocial and economic variables were examined among 192 carers for people living at home with motor neurone disease, Huntington's disease, multiple sclerosis, and Parkinson's, over a twelve-month period, to determine their contribution to the prediction of carer QOL. Mood was the only consistent predictor of carer QOL across groups; however, marital relationship satisfaction, social support satisfaction, income, and economic pressure significantly predicted carer QOL for at least one of the illness groups, in addition to mood. The findings highlight the importance of recognising the varying roles that psychosocial and economic variables play on the prediction of carer QOL within each of these illness groups.

Introduction

Introduction

A Highly Toxic Cellular Prion Protein Induces a Novel, Nonapoptotic Form of Neuronal Death

Several different deletions within the N-terminal tail of the prion protein (PrP) induce massive neuronal death when expressed in transgenic mice. This toxicity is dose-dependently suppressed by coexpression of full-length PrP, suggesting that it results from subversion of a normal physiological activity of cellular PrP. We performed a combined biochemical and morphological analysis of Tg(DeltaCR) mice, which express PrP carrying a 21-aa deletion (residues 105-125) within a highly conserved region of the protein. Death of cerebellar granule neurons in Tg(DeltaCR) mice is not accompanied by activation of either caspase-3 or caspase-8 or by increased levels of the autophagy marker, LC3-II. In electron micrographs, degenerating granule neurons displayed a unique morphology characterized by heterogeneous condensation of the nuclear matrix without formation of discrete chromatin masses typical of neuronal apoptosis. Our data demonstrate that perturbations in PrP functional activity induce a novel, nonapoptotic, nonautophagic form of neuronal death whose morphological features are reminiscent of those associated with excitotoxic stress.

OC-066 A preliminary study of neurostimulation based interventions in the treatment of chronic dysphagia post-stroke

<h3>Introduction</h3> Oropharyngeal dysphagia after stroke has an incidence up to 45% and when chronic, leads to increased risk of institutionalisation and death in the long term. Pharyngeal electrical stimulation (PES),1 repetitive transcranial magnetic stimulation (rTMS)2 and paired associative stimulation (PAS)3 are three neurostimulation techniques developed to increase cortical excitability of pharyngeal motor cortex, with therapeutic potential. However the effects of these techniques on chronic but stable swallowing problems in stroke patients remain unknown. We therefore investigated the effects of these interventions in stroke patients with dysphagia persisting for &gt;6 weeks. <h3>Methods</h3> In 12 dysphagic stroke patients (69±9 years (mean±SD), 79±25 weeks post-stroke (mean±SD), 6 left, 5 right hemispheric, 1 undetermined) pharyngeal electromyographic responses were recorded using an intraluminal catheter after the application of single TMS pulses over pharyngeal motor cortex, in order to measure cortico-bulbar excitability before, immediately and 30 minutes after real and sham applications of either: a) PES (10 mins of 5 Hz), b) rTMS (250 repeated TMS pulses at 5 Hz), or c) PAS (10 mins of repeated pairs of pharyngeal and TMS pulse every 20 s). In nine subjects, swallowing performance and safety (aspiration-penetration scores, APs) were assessed with videofluoroscopy before and after both real and sham neurostimulation techniques. <h3>Results</h3> Compared to sham, the application of all neurostimulation interventions showed a significant increase in cortical excitability in the unaffected hemisphere by 54%±17% (mean±SEM) immediately post (repeated measures ANOVA p&lt;0.001, Time*Intervention p=0.005), not observed in the affected hemisphere (p=0.12). In addition, after active neurostimulation, APs were reduced by −14%±6% (mean±SEM) compared to sham (Wilcoxon9s test, p=0.05). Moreover, the delay between the oral and pharyngeal phases of swallowing, important for swallowing safety, was shortened by −56%±13% (mean±SEM) after real neurostimulation (Wilcoxon9s test, p=0.01) compared to sham. There was no consistent difference in cortical or swallowing response between the interventions. <h3>Conclusion</h3> These preliminary results show that neurostimulation interventions have beneficial neurophysiological and behavioural effects in chronic stroke patients with dysphagia, increasing cortical excitability and improving swallowing safety. These findings provide support for neurostimulation being a useful adjunct in swallowing rehabilitation, even in chronic neurologic illness, and lay the foundation for further clinical trials of these forms of intervention.

Hyperbaric oxygen therapy for multiple sclerosis.

Multiple sclerosis (MS) is a chronic, inflammatory, and degenerative neurological illness with no cure. It has been suggested that Hyperbaric Oxygen Therapy (HBO(2)T) may slow or reverse the progress of the disease. This article summarizes the clinical evidence for the use of HBO(2)T in the treatment of MS. We conducted a literature review focused on the interaction of hyperbaric oxygenation and MS. In particular, we appraised the clinical data regarding treatment and performed a meta-analysis of the randomized evidence using the methodology of the Cochrane Collaboration. We found 12 randomized studies in the area, all of which were performed between 1983 and 1987. A meta-analysis of this evidence suggests there is no clinically significant benefit from the administration of HBO(2)T. The great majority of randomized trials investigated a course of 20 treatments at pressures between 1.75ATA and 2.5ATA daily for 60-120 min over 4 weeks against a placebo regimen. None have tested the efficacy of HBO(2)T against alternative current best practice. No plausible benefit of HBO(2)T on the clinical course of MS was identified in this review. It remains possible that HBO(2)T is effective in a subgroup of individuals not clearly identified in the trials to date, but any benefit is unlikely to be of great clinical significance. There is some case for further human trials in selected subgroups and for prolonged courses of HBO(2)T at modest pressures, but the case is not strong. At this time, the routine treatment of MS with HBO(2)T is not recommended.

Welche Rolle spielt das Kohärenzgefühl in der Krankheitsverarbeitung bei Morbus Parkinson?

In this study the relevance of sense of coherence (SOC) for coping with an illness was examined in subjects with Parkinson's disease. According to Antonovsky's model (1997) the sense of coherence is an important resource when it comes to dealing with stressors. To take into consideration the integrated view of Parkinson patients, severity of the illness (UPDRS) was determined by the neurologist and tendency toward depression was recorded. 51 patients with PD (mean age: 67.7; 43.1% female; 56.9% male) and 59 volunteers without any neurological illness (mean age: 65.7; 54.2% female; 45.8% male) took part in this study. The sample was recruited from the Neurological Department of the Medical University of Vienna. This quasi-experimental sample was assessed with standardized self-assessment questionnaires: FKV-LIS-SE, SOC-Scale and GDS. Correlations, t-tests, U-tests, multivariate analyses of variance and linear regressions were used for calculation. Persons with PD were characterized by lower SOC (p<.01) and higher scores on depression (p<.01), compared to persons of the control group. Parkinson patients tend to use depressive and minimizing coping strategies (p<.01). In addition the study indicates an influence of SOC and tendency toward depression on coping (R(2)=0.43). Sense of coherence and coping strategies are independent of severity of illness, but there is a significant association between the duration of illness and active-problem focused coping. In general, sense of coherence correlates only with psychological variables, and not with physical variables. Results indicate the importance of SOC on effective coping. Therefore strengthening of SOC is important, especially in context with chronic neurological illness. Individual orientated analysis of resources should be implemented in every counselling interview, so that possibilities for activities of daily living and leisure can be developed.

Psychopathology and psychological adjustment in children and adolescents with epilepsy

Epilepsy is the most common chronic neurological illness in childhood and adolescence, and this condition may increase the risk of psychopathology at these ages. A literature review, including MEDLINE and PsychLIT database, was made covering the period of 1966-2007. Research studies were included if they were concerned with children suffering from epilepsy and measures of psychopathology. Studies found a more elevated rate of psychological and psychiatric disorders, both behavioral and emotional, in these samples compared to general population or children with other chronic conditions. The problems presented in children and adolescents with epilepsy are quite similar to those in general population with a slight increase of hyperkinetic and attention problems likely related to both direct brain damage and anticonvulsant treatment. There is no evidence of psychotic disorders and/or specific personality traits associated with epilepsy at these ages. Family factors, specially those related to psychopathology in other family members and parent-child relationships, appear to have stronger influence on children psychopathology than illness factors themselves. Some guidelines are provided in order to improve future research.

Personality Development in the Context of Intractable Epilepsy

To investigate the developmental time frame of epilepsy onset on adult personality traits of neuroticism and extraversion and to consider their role in adjustment to intractable epilepsy. Prospective, preoperative and postoperative survey of the psychological and psychosocial effects of intractable epilepsy and its surgical treatment. Data from the preoperative phase are reported. Comprehensive Epilepsy Program (CEP), Austin Health. Sixty adult patients with focal epilepsy undergoing inpatient monitoring. Groups of patients with epilepsy onset in different developmental periods were empirically derived and compared with each other and with normative personality data from 1571 cases. Scores on the Eysenck Personality Questionnaire Revised-Short Form; the Beck Depression Inventory-II; the State-Trait Anxiety Inventory (state form); and the Austin CEP Interview, a semistructured interview providing in-depth psychosocial assessment. Patients with onset of epilepsy during the self-defining period of adolescence had higher neuroticism scores relative to normative data (95% confidence interval, 0.16 to 3.57) and other patients (-0.46 to -5.63). High neuroticism, particularly when accompanied by lower extraversion, predisposed to poor adjustment to intractable epilepsy as reflected by impaired mood (P < .01) and difficulties with family functioning (48% of patients). These data provide initial evidence that onset of chronic neurologic illness in adolescence influences the development of adult personality traits. We also found a relationship between personality and adjustment to chronic epilepsy. The findings are relevant to the provision of psychologically informed neurologic care.

Initial Perspectives from Midwestern Neurologists: Epilepsy Patients' Barriers and Motivators for Seeking Treatment

Epilepsy is a chronic neurological illness that affects 2.7 million people in the United States, but remains poorly understood. Care providers may not recognize their patients' need for epilepsy information, contributing to treatment barriers, such as stigmatization and poor patient-provider communication. The current study piloted a survey of epilepsy-related attitudes and perceptions of 33 Midwestern neurologists. The survey included questions about perceived barriers to and motivators for treatment, thoughts on misperceptions of epilepsy in the community and in the patient population, and potential interventions to address misperceptions. Respondents perceived misinformation and lack of knowledge in patients and the general public that could be contributing to the barriers that exist to treat patients adequately. Respondents suggested potential methods for addressing misperceptions effectively. This study of neurologists' perceptions about epilepsy barriers and needs provides an important perspective for the development of interventions to address misperceptions and barriers among patients and the public.

Long-term neurological illness in parents has a substantial impact on the lives of children

A chronic illness, such as Parkinson's disease, affects the daily life of the patient and that of the family. While the effects of Parkinson's on the psychosocial functioning and quality of life of the patients and the spouse/carer have been investigated, there is limited information about the impact of parental Parkinson's on children. No instruments were available for quantitative assessment of the impact of chronic parental illness on children. As a first step towards investigating the psychosocial effects of parental Parkinson's on children, the Parental Illness Impact (PII) Scale was developed by our group at the Institute of Neurology. Studies of its psychometric properties have established that the PII Scale is a reliable and valid measure. Using this scale, we found that the greatest effect of parental Parkinson's was in terms of family functioning, burden of daily help, communication and understanding, and impact on personal future. In contrast, for the sample as a whole, the domains of social development, independence and responsibility, and friends' reactions were less severely affected. Compared to other chronic disorders, parental Parkinson's had the least negative impact (and parental multiple sclerosis and stroke the greatest impact) on children. Medical professionals need to be aware of the implications of chronic neurological illness for the family. Medical management of long-term neurological disorders should extend to the impact of these disorders on families.

Psychosocial adjustment following relief of chronic narcolepsy

Background and purpose No previous research has examined the psychosocial adjustment of chronic narcolepsy patients following efficacious pharmacotherapy. In contrast, considerable research has examined the process of psychosocial adjustment following surgical relief of chronic epilepsy. This process can manifest as a clinical syndrome, the ‘burden of normality’, comprising psychological, behavioural, affective and sociological features. The aim of the present study was to characterise the process of psychosocial adjustment of patients with successfully treated narcolepsy and to explore the applicability of the burden of normality. Patients and methods Thirty-three narcolepsy patients and 31 epilepsy surgery patients were recruited through routine outpatient follow-up at the Austin Hospital in Melbourne. All patients underwent in-depth, qualitative psychosocial assessment using a well-validated semi-structured interview, the Austin CEP Interview. They were also administered quantitative measures of anxiety ( State Trait Anxiety Inventory) and depression ( Beck Depression Inventory-II). Results Narcolepsy patients spontaneously reported similar themes of post-treatment adjustment to successfully treated epilepsy patients, including symptoms of the burden of normality. Chi-squared analyses revealed that the two groups differed only on disease-specific factors, reflecting the later diagnosis and treatment of narcolepsy ( P < 0.05). Conclusion The results support a general model of adjustment following successful treatment of chronic neurological illness, as the patient discards perceptions of illness and behaviours associated with being ‘sick’ and learns to become ‘well’. Recognition of the burden of normality has important clinical implications for maximising the post-treatment care and outcome of narcolepsy patients.