Elevated Levels of Methylmalonate and Homocysteine in Parkinson's Disease, Progressive Supranuclear Palsy and Amyotrophic Lateral Sclerosis

Background/Aims: Increasing evidence suggests that elevated levels of homocysteine (Hcy) and methylmalonate (MMA) may be involved in the pathogenesis of neurodegenerative diseases. Methods: The urine levels of MMA and serum levels of Hcy as well as folic acid and vitamin B 12 were measured in patients suffering from the distinct neurodegenerative diseases progressive supranuclear palsy (PSP), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), and compared to age-and gender-matched control subjects. Results: We found significantly elevated concentrations of Hcy (PD 15.1, PSP 15.8, ALS 13.9, control 11.2 mu mol/l) and MMA (PD 3.7, PSP 3.1, ALS 3.7, control 1.8 mg/g) in all patient groups in comparison with controls. Levels of Hcy and MMA did not differ significantly between the neurodegenerative diseases. Conclusion: Our findings might imply that Hcy and MMA are released as a consequence of neurodegeneration regardless of the underlying cause and serve as surrogate markers of neurodegeneration. Alternatively they might be directly implicated in the pathogenesis of these diseases. Since elevated levels of both Hcy and MMA are neurotoxic, further studies might investigate the effect of vitamin therapy on disease progression. Copyright (C) 2010 S. Karger AG, Base

High Burden and Depression Among Late-Stage Idiopathic Parkinson Disease and Progressive Supranuclear Palsy Caregivers

Objectives: Caregivers of patients with late-stage idiopathic Parkinson disease (IPD) and late-stage progressive supranuclear palsy (PSP) often suffer from severe psychological strain themselves. This study investigates the influence of the different kind of symptoms in IPD and PSP on the psychological burden of the caregivers. Methods: Twenty patients with late-stage IPD and 20 patients with late-stage PSP and their caregivers were investigated. To measure the degree of motor, cognitive, and affective impairment of the patients, the instruments Subscale III of the Unified Rating Scale for Parkinsonism(UPDRS-III), a shortened 24-item version of the Mini-Mental State Examination, and the Geriatric Depression Scale (GDS-30) were used. Psychological burden of the caregivers was determined by using the Beck Depression Inventory (BDI-II) and the Zarit Caregiver Burden Inventory (ZBI). Results: Patients with IPD suffered from a higher level of depression (GDS-30: 15.9 vs 10.2, P=.020), whereas patients with PSP showed greater motor impairment (UPDRS-III: 38.3 vs 29.9, P=.002). Caregivers of both groups reported high psychological burden (ZBI: 36.5 in IPD vs 42.8 in PSP) and symptoms of a depression (BDI-II: 12.5 in IPD vs 15.1 in PSP). No significant influence of motor impairment, cognitive dysfunction, and depressive symptoms of the patient on the burden of the caregiver could be found. Conclusions: Psychological strain and depression among caregivers seem to become even more relevant in the late stages of IPD and PSP. Further studies will be necessary to investigate the specific determining factors in late-stage parkinsonian syndromes

Telemedicine in Palliative Care: Implementation of New Technologies to Overcome Structural Challenges in the Care of Neurological Patients

Telemedicine provides a possibility to deal with the scarcity of resources and money in the health care system. Palliative care has been suggested to be appropriate for an increasing number of patients with neurodegenerative disorders, but these patients often lack care from either palliative care or neurology. Since palliative care means a multidisciplinary approach it is meaningful to use palliative care structures as a basis. There exists no systematic access to neurological expertise in an outpatient setting. A successful link of two existing resources is shown in this project connecting the Department of Neurology of an University Hospital with specialized outpatient palliative care (SPC) teams. A videocounselling system is used to provide expert care for neurological outpatients in a palliative setting.Methods: A prospective explorative single arm pilot trial was implemented to provide a mobile telesystem for 5 SPC teams. The opportunity was given to consult an expert in neuropalliative care at the specialized center in the hospital (24/7). Semistructured interviews were conducted with the physicians of the SPC teams after a trial duration of 9 months.Results: Our data provides strong evidence that the technical structure applied in this project allows a reasonable neurological examination at distance. Qualitative interviews indicate a major impact on the quality of work for the SPC teams and on the quality of care for neurological patients.Conclusion: The system proves to be useful and is well accepted by the SPC teams. It supplies a structure that can be transported to other disciplines

Managing Advanced Progressive Supranuclear Palsy and Corticobasal Degeneration in a Palliative Care Unit: Admission Triggers and Outcomes

Background: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are characterized by rapid deterioration and a fatal outcome. Objectives: Admission triggers, treatment efficacy, and care patterns. Methods: Retrospective analysis of patients with PSP/CBD admitted to an inpatient specialized palliative care service. Results: In 38 patients, there were 63 admissions for swallowing difficulties, falls, pain, impaired communication, cognitive/mood disturbances, respiratory symptoms, and infection. Mean length of stay was 11.6 days. Treatment response was variable. In 68%, of admission episodes there was stabilization or improvement, 75% were discharged home. In case of readmission, the mean interval has been 9.7 months. Time since diagnosis and admission triggers were not associated with outcome or death. Conclusion: Patients showed high symptom load contrasting with discharge rates and subsequent health care utilization. Brief multidisciplinary interventions might be helpful to preserve autonomy

Needs Assessment of Safe Medicines Management for Older People With Cognitive Disorders in Home Care: An Integrative Systematic Review

Background and Objectives: The global trend of healthcare is to improve the quality and safety of care for older people with cognitive disorders in their own home. There is a need to identify how medicines management for these older people who are cared by their family caregivers can be safeguarded. This integrative systematic review aimed to perform the needs assessment of medicines management for older people with cognitive disorders who receive care from their family caregivers in their own home.Methods: An integrative systematic review of the international literature was conducted to retrieve all original qualitative and quantitative studies that involved the family caregivers of older people with cognitive disorders in medicines management in their own home. MeSH terms and relevant keywords were used to search four online databases of PubMed (including Medline), Scopus, CINAHL, and Web of Science and to retrieve studies published up to March 2021. Data were extracted by two independent researchers, and the review process was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Given that selected studies were heterogeneous in terms of the methodological structure and research outcomes, a meta-analysis could not be performed. Therefore, narrative data analysis and knowledge synthesis were performed to report the review results.Results: The search process led to retrieving 1,241 studies, of which 12 studies were selected for data analysis and knowledge synthesis. They involved 3,890 older people with cognitive disorders and 3,465 family caregivers. Their methodologies varied and included cohort, randomised controlled trial, cross-sectional studies, grounded theory, qualitative framework analysis, and thematic analysis. The pillars that supported safe medicines management with the participation of family caregivers in home care consisted of the interconnection between older people's needs, family caregivers' role, and collaboration of multidisciplinary healthcare professionals.Conclusion: Medicines management for older people with cognitive disorders is complex and multidimensional. This systematic review provides a comprehensive image of the interconnection between factors influencing the safety of medicines management in home care. Considering that home-based medicines management is accompanied with stress and burden in family caregivers, multidisciplinary collaboration between healthcare professionals is essential along with the empowerment of family caregivers through education and support

Telemedicine in Palliative Care: Implementation of New Technologies to Overcome Structural Challenges in the Care of Neurological Patients

Telemedicine provides a possibility to deal with the scarcity of resources and money in the health care system. Palliative care has been suggested to be appropriate for an increasing number of patients with neurodegenerative disorders, but these patients often lack care from either palliative care or neurology. Since palliative care means a multidisciplinary approach it is meaningful to use palliative care structures as a basis. There exists no systematic access to neurological expertise in an outpatient setting. A successful link of two existing resources is shown in this project connecting the Department of Neurology of an University Hospital with specialized outpatient palliative care (SPC) teams. A videocounselling system is used to provide expert care for neurological outpatients in a palliative setting. Methods: A prospective explorative single arm pilot trial was implemented to provide a mobile telesystem for 5 SPC teams. The opportunity was given to consult an expert in neuropalliative care at the specialized center in the hospital (24/7). Semistructured interviews were conducted with the physicians of the SPC teams after a trial duration of 9 months. Results: Our data provides strong evidence that the technical structure applied in this project allows a reasonable neurological examination at distance. Qualitative interviews indicate a major impact on the quality of work for the SPC teams and on the quality of care for neurological patients. Conclusion: The system proves to be useful and is well accepted by the SPC teams. It supplies a structure that can be transported to other disciplines

CCAAT/enhancer binding protein β expression is increased in the brain during HIV-1-infection and contributes to regulation of astrocyte tissue inhibitor of metalloproteinase-1

Human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND) associated with infection and activation of mononuclear phagocytes (MP) in the brain, occur late in disease. Infected/activated MP initiate neuroinflammation activating glial cells and ultimately disrupting neuronal function. Astrocytes secrete tissue inhibitor of metalloproteinase (TIMP)-1 in response to neural injury. Altered TIMP-1 levels are implicated in several CNS diseases. CCAAT enhancer-binding protein ß (C/EBPß), a transcription factor, is expressed in rodent brains in response to neuroinflammation, implicating it in Alzheimer’s, Parkinson’s, and HAND. Here, we report that C/EBPß mRNA levels are elevated and its isoforms differentially expressed in total brain tissue lysates of HIV-1-infected and HIV-1 encephalitis patients. In vitro, HAND-relevant stimuli additively induce C/EBPß nuclear expression in human astrocytes through 7 days of treatment. Over-expression of C/EBPß increases TIMP-1 promoter activity, mRNA, and protein levels in human astrocytes activated with interleukin-1ß. Knockdown of C/EBPß with siRNA decreases TIMP-1 mRNA and protein levels. These data suggest that C/EBPß isoforms are involved in complex regulation of astrocyte TIMP-1 production during HIV-1 infection; however, further studies are required to completely understand their role during disease progression

A Pilgrim's Journey—When Parkinson's Disease Comes to an End in Nursing Homes

Our interdisciplinary mixed-methods exploratory study was aimed at gaining empirical data on the medical and nursing demands of residents who are in a late stage of Parkinson Disease (PD) and are cared for in residential homes in Salzburg (Austria). In earlier studies it has been concluded that symptom burden of late stage PD patients is similar to or even higher compared with oncological patients. However, although all nine residents who took part in our study had severe limitations in performing their daily activities and experienced enormous restrictions in their mobility, they were quite content with their present living situations and did not show significant symptom burden. From the ethnographic family interviews that we conducted the following features emerged: a strong closeness in the family, an improved quality of life when the patients lived in the nursing home and fears about the future. Therefore, we concluded that living in a nursing home that provides for the needs of these patients is the best option for PD patients in the final stages of their disease as well as for their relatives

Assisted Suicide in Parkinsonian Disorders

Background: Due to the high prevalence of suicidal ideation in Parkinson's Disease (PD) and exploratory data indicating a similar prevalence in atypical Parkinsonian disorders (APD), we sought to determine the frequency of assisted suicide (AS) as well as factors driving these decisions in PD and APD. Methods: Retrospective chart analysis (2006-2012) at a Swiss Right-to-Die organization. Patients with PD and APD who completed AS were analyzed concerning disease state, symptom burden, medication, and social factors. Results: We identified 72 patients (PD = 34, PSP = 17, MSA = 17, CBS = 4; 7.2% of all AS cases), originating mainly from Germany (41.7%), Great Britain (29.2%), and the US (8.3%). Predominant symptoms at the time of application were immobility (PD/APD: 91%/97%), helplessness (63%/70%), pain (69%/19%), dysarthria (25%/32%), and dysphagia (19%/59%). APD patients generally showed a higher symptom burden and a higher frequency of diagnosed depression (8.8%/28.9%). While most patients with diagnosed depression received antidepressants (80%), other symptoms such as pain (59%) were treated less consistently. Of note, time from diagnosis to application differed greatly between PD (8.5 ± 6.8 years) and APD (1.5 ± 1.3 years, p < 0.0001). Conclusions: In our analysis, Parkinsonian disorders appeared to be overrepresented as a cause of AS considering the prevalence of these diseases. The observation that assisted suicide is sought early after initial diagnosis in APD implies the need for early comprehensive psychological support of these patients and their relatives