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The determinants of ALS caregiver burden and the feeling of the patients as being a burden were assessed using the Caregiver Burden Inventory and the Self-Perceived Burden Scale in 60 caregiver-patient couples. Caregiver burden was correlated to their level of depression and quality of life and, differently from other chronic disorders, increased with the worsening of patients' disability. ALS patients have a good objective perception of their impact on caregivers.
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PMID:Caregiver burden and patients' perception of being a burden in ALS. 1591 11

Considering the few studies published on the psychopathology of ALS patients, we carried out a preliminary study evaluating depression, anxiety, emotional reactions and coping strategies in such patients. Twenty-seven ALS patients were included and evaluated using a semi-structured interview, after which they were asked to complete a questionnaire. The rater asessed the DSM-IV criteria for a major depressive episode, dysthymia and generalized anxiety, using the MADRS scale for depression, the Covi anxiety scale and the Depressive Mood scale. Subsequently, patients completed the Ways of Coping checklist. Patients were neither anxious nor depressed. Patients whose diagnosis was recent (less than six months) presented greater emotional deficit. Patients younger than 50 years of age used problem focused strategies more frequently. Those having received the diagnosis in the preceeding six months used emotion focused strategies significantly more often.The absence of characterized depression and anxiety confirmed results of the literature. The significance of this study is found in the observation of specific emotional reactions present in the first six months following diagnosis disclosure. The results show that it is useful to continue the affective evaluation of these patients and to undertake longitudinal studies starting at the time of diagnosis disclosure.
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PMID:Psychopathology in amyotrophic lateral sclerosis: a preliminary study with 27 ALS patients. 1631 25

We sought to characterize ALS patients who opt for tracheostomy and long-term mechanical ventilation (LTMV) and compare them with respect to medical, psychiatric, and psychosocial measures to patients who declined tracheostomy and died. We studied 72 ALS patients who were identified as hospice-eligible. They were assessed monthly until the endpoint of death or tracheostomy. LTMV patients continued to be followed for up to 55 months. The spouse or other caregiver was similarly interviewed and followed. Medical and psychiatric evaluations were conducted, in addition to self-reported depressive symptoms, future orientation, attitudes about hastened death, religious beliefs, and quality of life. Global cognitive capacity was assessed by caregivers. Fourteen patients chose LTMV; 58 died without LTMV. At study entry, those who later chose LTMV were younger, more had young children, had more education, and higher household incomes on average. Although their physical conditions were similar, they reported higher levels of optimism including belief in imminent cure, and more positive appraisals of their ability to function in daily life, their physical health and overall life satisfaction. At study entry, none who later chose LTMV were clinically depressed, compared to 26% of those who later refused LTMV, and their mean scores on the Beck Depression Inventory were in the "not depressed" range while the mean for patients who later died was in the "probable depression" range. Fourteen percent of patients who later chose LTMV were reported by caregivers to have had at least mild cognitive problems, compared to 49% of those who later died. After an average of 33 months on LTMV, only about half retained high levels of optimism and enjoyment of daily life, independent of residence (home vs. facility). Two patients expressed interest in hastening death but none had asked to terminate ventilation despite disease progression. However, half identified future circumstances that would render life intolerable. At last contact with caregivers, only one LTMV patient was reported to have major cognitive impairment. While reporting substantial emotional burden after LTMV, most but not all spousal caregivers continued to express satisfaction with care-giving. Our findings suggest that the choice of LTMV was not about desperation (although it may involve unrealistic expectations of cure by some), ignorance, or inability to make wishes clear during a chaotic dying period. Rather, LTMV choice was consistent with a sustained sense that life was worth living in any way possible, at least for some time and within certain boundaries. ALS clinicians will need to recognize this motivation and provide appropriate clinical education to both patient and family.
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PMID:Predictors and course of elective long-term mechanical ventilation: A prospective study of ALS patients. 1675 72

During the past decade, numerous molecular mediators of neurodegenerative diseases and neurological disorders have been identified and validated, yet few novel therapies have emerged and the unmet medical needs remain high. These molecular mediators belong to target classes such as ion channels, neurotransmitters and neurotransmitter receptors, cytokines, growth factors, enzymes and other proteins. In some cases, substantial pre-clinical validation exists, but the molecular target has not been readily druggable with small molecules, proteins or antibodies. RNA interference represents a therapeutic approach applicable to such non-druggable targets. Both non-viral and viral delivery strategies are being undertaken for in vivo silencing of molecular targets by RNA interference, which has resulted in robust efficacy in animal models of Alzheimer's disease, ALS, Huntington's disease, spinocerebellar ataxia, anxiety, depression, neuropathic pain, encephalitis and glioblastoma. These proof-of-concept data in animal models, together with the commencement of clinical trials using RNA interference for macular degeneration and respiratory syncytial virus infection, point to the potential of direct RNA interference for neurological disorders and neurodegenerative diseases.
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PMID:Therapeutic potential of RNA interference for neurological disorders. 1681 77

In the literature, few studies refer specifically to the psychological and psychopathological aspects of the ALS. However most of these studies mention the psychological specificities observed in ALS patients. In fact, they are not depressed, nor anxious, and they seem to accept surprisingly well the threathening diagnosis. Some authors have mentionned the presence of denial as an adaptive mechanism. It remains very difficult to compare the various studies. First, the stage of the evolution of the disease and the physical abilities of the patients differ greatly; in fact it has been demonstrated that at each stages the patient present specific psychological concerns. Second, the psychological concepts refer to different level of understanding. Some authors study depression or anxiety, others focus on the global psychological status and others focus on a psychological mechanism, such as denial for example. Third, the scales used to assess these psychological or psychopathological aspects are, on one hand, never specific to ALS and, on the other hand, are sometimes filled by the clinicien or sometimes self reports filled by the patient, his caregiver or even by the medical staff. Thus, many studies have created their own scales or interview, which are not validated. So, it appears necessary, in order to be able to compare the different results, to use validated scales which are recognized by the scientific community, while waiting for specific tools created and validated in populations of ALS patients.
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PMID:[Psychological and psychopathological evaluation in amyotrophic lateral sclerosis]. 1712 5

Amyotrophic lateral sclerosis is a devastating disorder for which the psychological consequences of both the diagnosis announcement and the evolution of paralysis not only concern the patient but also his family. The role of the psychologist is to develop an individualized follow up considering the patient in his globality. The first consultation is, ideally, initiated after a medical consultation explaining the importance of the psychological area in ALS patient care. The psychological follow up will consist in an empathic listening of history and problems. Information will also be given to the patient by the psychologist who's role should not be only passive. When talking about "globality" of the psychological intervention for a given patient, his family takes a determinant place. The psychologist should be able to establish a contact with the family members concerned by the daily support to the patient. The psychological processes through which a patient will evolve should be explained to the family. Depression frequently affects family members, and a specific follow up in those cases has to be undertaken as soon as possible. Such a depressive reaction may also take place after death and a psychological follow up do not end after the death of a patient. The role of a psychologist in ALS care ideally takes places in the context of a multidisciplinary team such as a motoneuron clinic now largely available in our country. The burden of care is frequently heavy both for the family and the team of professional carers into and outside the hospital. The psychologist has a role of mediation between those persons, facilitating verbal exchanges, paying attention to specific difficulties and maintaining a fruitful exchange between the carers, the patient and his family. More prospectively, the psychologist also has a pedagogic role for the carers explaining psychological processes and giving clues for a constructive relationship between the patient and his family and also between this patient and his carers.
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PMID:[Psychological treatment for the patient and caregivers during the course of amyotrophic lateral sclerosis]. 1712 29

We aimed to establish age-related reference values for Erythropoietin (EPO) in cerebrospinal fluid (CSF) and to evaluate concentrations in neurological diseases. CSF and serum EPO was measured in controls with tension-type headache (CTTH), in patients with ALS, dementia and depression using ELISA technique. Stability experiments showed CSF EPO to be stable for two and a half months and over two thaw/freeze cycles. A positive correlation of CSF EPO with age was found (P<0.01). We found a CSF/serum EPO concentration ratio of 0.126, pointing towards an intrathecal synthesis of EPO. The ALS group showed significantly lowered CSF EPO compared to age-matched CTTH (P<0.012), whereas the dementia and depression group showed no significant differences compared to CTTH.The establishment of age-related reference values in a large cohort of controls will improve the interpretation of future CSF EPO evaluations in neurological diseases.
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PMID:Erythropoietin in cerebrospinal fluid: age-related reference values and relevance in neurological disease. 1740 63

We wished to determine whether a screening test battery for cognitive impairment can be given practicably in a busy multidisciplinary ALS clinic, and to assess initial test performance in a sequentially drawn ALS population. We administered a word generation task (letter fluency), the Frontal Behavioral Inventory (FBI), and the Beck Depression Inventory (BDI) to 49 ALS patients and their caregivers during a visit to our ALS clinic. We also computed Clinical Dementia Rating (CDR) scale and ALS Functional Rating Scale (ALSFRS-R) scores for patients. Pearson correlation coefficients and regression analyses assessed associations between outcome measures. The test battery took 30 min to administer. Word generation was associated with the FBI score (r = -0.36, p = 0.01), and time to ALS diagnosis (p = 0.01). Caregiver depressive symptoms (BDI) correlated with the FBI (r = 0.40, p = 0.005) and motor severity (r = -0.47, p<0.01) in patients. CDR scores were associated with behavioral abnormalities and lower ALSFRS-R scores. We concluded that a screen of cognition could be administered during multidisciplinary ALS clinics. Frontostriatal cognitive impairment may be associated with behavioral syndromes and more rapid forms of ALS. Behavioral and motor impairment is associated with depressive symptoms in caregivers. Studies with formal neuropsychological tests are needed to determine the sensitivity and specificity of the screen in ALS.
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PMID:A screening assessment of cognitive impairment in patients with ALS. 1785 14

Marked reduction of RNA editing at the glutamine (Q)/arginine (R) site of the glutamate receptor subunit type 2 (GluR2) in motor neurons may be a contributory cause of neuronal death specifically in sporadic ALS. It has been shown that deregulation of RNA editing of several mRNAs plays a causative role in diseases of the central nervous system such as depression. We analyzed the effects of eight antidepressants on GluR2 Q/R site-RNA editing in a modified HeLa cell line that stably expresses half-edited GluR2 pre-mRNA. We also measured changes in RNA expression levels of adenosine deaminase acting on RNA type 2 (ADAR2), the specific RNA editing enzyme of the GluR2 Q/R site, and GluR2, in order to assess the molecular mechanism causing alteration of this site-editing. The editing efficiency at the GluR2 Q/R site was significantly increased after treatment with seven out of eight antidepressants at a concentration of no more than 10 microM for 24h. The relative abundance of ADAR2 mRNA to GluR2 pre-mRNA or to beta-actin mRNA was increased after treatment with six of the effective antidepressants, whereas it was unchanged after treatment with milnacipran. Our results suggest that antidepressants have the potency to enhance GluR2 Q/R site-editing by either upregulating the ADAR2 mRNA expression level or other unidentified mechanisms. It may be worth investigating the in vivo efficacy of antidepressants with a specific therapeutic strategy for sporadic ALS in view.
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PMID:Effects of antidepressants on GluR2 Q/R site-RNA editing in modified HeLa cell line. 1944 93

This article provides a theoretical basis and experimental evidence for the following rules: (1) All mental activities involving some level of intelligence ultimately follow the laws of operant conditioning and can exert a long-term control of behaviour only if they regularly provide the midbrain centres with the minimal set of neural rewards that these centres expect (2) Mental activity is always accompanied by a proportional amount of efferent-controlled physiological activity, which may be, for example, voluntary muscular work, but also internal, possibly surreptitious phenomena like inflammation, immune reactions, blood pressure increase, etc. These rules provide an explanation for most 'civilization' diseases whose ultimate causes are currently unknown or uncontrollable, e.g. cardiovascular troubles, cancer, allergies, auto-immune disorders, non-congenital degenerative diseases, neural dysfunctions including Alzheimer and Parkinson diseases, ALS or multiple sclerosis, emotional troubles including depression, cyclothymic/bipolar disorders, uncontrollable compulsions, etc. Potentially, this explanation also provides a cure for all these diseases as long as there is no accumulation of many of them because, for example, of very advanced age, and only if we are ready to adopt a philosophy of happiness based on moderation and appreciation of the value of life, dignity and empathy, instead of attempting an unlimited accumulation of pleasure, which does not seem neurologically viable.
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PMID:The probable cause of civilization diseases and the structural limits of pleasure. 1952 23


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