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Neurologia Mar 2024To identify the neurological diseases for which euthanasia and assisted suicide are most frequently requested in the countries where these medical procedures are legal... (Review)
Review
OBJECTIVE
To identify the neurological diseases for which euthanasia and assisted suicide are most frequently requested in the countries where these medical procedures are legal and the specific characteristics of euthanasia in some of these diseases, and to show the evolution of euthanasia figures.
METHODS
We conducted a systematic literature review.
RESULTS
Dementia, motor neuron disease, multiple sclerosis, and Parkinson's disease are the neurological diseases that most frequently motivate requests for euthanasia or assisted suicide. Requests related to dementia constitute the largest group, are growing, and raise additional ethical and legal issues due to these patients' diminished decision-making capacity. In some countries, the ratios of euthanasia requests to all cases of multiple sclerosis, motor neuron disease, or Huntington disease are higher than for any other disease.
CONCLUSIONS
After cancer, neurological diseases are the most frequent reason for requesting euthanasia or assisted suicide.
Topics: Humans; Suicide, Assisted; Euthanasia; Nervous System Diseases; Huntington Disease; Multiple Sclerosis; Motor Neuron Disease
PubMed: 38272260
DOI: 10.1016/j.nrleng.2024.01.007 -
Frontiers in Aging Neuroscience 2023Parkinson's disease (PD) is a progressive and debilitating neurological disorder. While dopaminergic medication improves PD symptoms, continued management is complicated...
INTRODUCTION
Parkinson's disease (PD) is a progressive and debilitating neurological disorder. While dopaminergic medication improves PD symptoms, continued management is complicated by continued symptom progression, increasing medication fluctuations, and medication-related dyskinesia. Deep brain stimulation (DBS) surgery is a well-accepted and widespread treatment often utilized to address these symptoms in advanced PD. However, DBS may also lead to complications requiring hospitalization. In addition, patients with PD and DBS may have specialized care needs during hospitalization.
METHODS
This systematic review seeks to characterize the complications and risk of hospitalization following DBS surgery. Patient risk factors and modifications to DBS surgical techniques that may affect surgical risk are also discussed.
RESULTS
It is found that, when candidates are carefully screened, DBS is a relatively low-risk procedure, but rate of hospitalization is somewhat increased for DBS patients.
DISCUSSION
More research is needed to determine the relative influence of more advanced disease vs. DBS itself in increased rate of hospitalization, but education about DBS and PD is important to insure effective patient care within the hospital.
PubMed: 38046469
DOI: 10.3389/fnagi.2023.1258190 -
The Cochrane Database of Systematic... Dec 2023This is an updated version of a Cochrane Review last updated in 2020. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. In nearly 30%... (Review)
Review
BACKGROUND
This is an updated version of a Cochrane Review last updated in 2020. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. In nearly 30% of cases, epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is a second-generation antiseizure medication. When used as an add-on (in combination with other antiseizure medications), lamotrigine can reduce seizures, but with some adverse effects.
OBJECTIVES
To evaluate the benefits and harms of add-on lamotrigine, compared with add-on placebo or no add-on treatment in people with drug-resistant focal epilepsy.
SEARCH METHODS
For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 3 October 2022 with no language restrictions. CRS Web includes randomised and quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups, including Epilepsy.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that investigated add-on lamotrigine versus add-on placebo or no add-on treatment in people of any age with drug-resistant focal epilepsy. We used data from the first period of eligible cross-over trials.
DATA COLLECTION AND ANALYSIS
For this update, two review authors independently selected trials and extracted data. Our primary outcome was 50% or greater reduction in seizure frequency. Our secondary outcomes were treatment withdrawal, adverse effects, cognitive effects, and quality of life. Primary analyses were by intention-to-treat. We performed sensitivity best- and worse-case analyses to account for missing outcome data. We calculated pooled risk ratios (RRs) with 95% confidence intervals (95% Cls) for dichotomous outcomes.
MAIN RESULTS
We identified no new studies for this update, so the results and conclusions of the review are unchanged. We included five parallel-group studies in adults or children, eight cross-over studies in adults or children, and one parallel study with a responder-enriched design in infants. In total, these 14 studies enroled 1806 eligible participants (38 infants, 199 children, 1569 adults). Baseline phases ranged from four to 12 weeks and treatment phases ranged from eight to 36 weeks. We rated 11 studies (1243 participants) at low overall risk of bias and three (697 participants) at unclear overall risk of bias due to lack of information on study design. Four studies (563 participants) reported effective blinding. Lamotrigine compared with placebo probably increases the likelihood of achieving 50% or greater reduction in seizure frequency (RR 1.80, 95% CI 1.45 to 2.23; 12 trials, 1322 participants (adults and children); moderate-certainty evidence). There is probably little or no difference in risk of treatment withdrawal for any reason among people treated with lamotrigine versus people treated with placebo (RR 1.11, 95% CI 0.91 to 1.37; 14 trials; 1806 participants; moderate-certainty evidence). Lamotrigine compared with placebo is probably associated with a greater risk of ataxia (RR 3.34, 99% Cl 2.01 to 5.55; 12 trials; 1525 participants; moderate-certainty evidence), dizziness (RR 1.76, 99% Cl 1.28 to 2.43; 13 trials; 1768 participants; moderate-certainty evidence), nausea (RR 1.81, 99% CI 1.22 to 2.68; 12 studies, 1486 participants; moderate-certainty evidence), and diplopia (RR 3.79, 99% Cl 2.15 to 6.68; 3 trials, 944 participants; moderate-certainty evidence). There is probably little or no difference in the risk of fatigue between lamotrigine and placebo (RR 0.82, 99% CI 0.55 to 1.22; 12 studies, 1552 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Lamotrigine as an add-on treatment for drug-resistant focal seizures is probably effective for reducing seizure frequency. Certain adverse effects (ataxia, dizziness, diplopia, and nausea) are probably more likely to occur with lamotrigine compared with placebo. There is probably little or no difference in the number of people who withdraw from treatment with lamotrigine versus placebo. The trials were of relatively short duration and provided no long-term evidence. In addition, some trials had few participants. Further trials are needed to assess the long-term effects of lamotrigine and to compare lamotrigine with other add-on drugs.
Topics: Adult; Child; Humans; Lamotrigine; Diplopia; Dizziness; Drug Therapy, Combination; Anticonvulsants; Seizures; Drug Resistant Epilepsy; Ataxia; Drug-Related Side Effects and Adverse Reactions; Nausea; Epilepsies, Partial
PubMed: 38078494
DOI: 10.1002/14651858.CD001909.pub4 -
Journal of Neurology Oct 2023With the development of noninvasive brain stimulation (NIBS) techniques, many researchers have turned their attention to NIBS as a promising treatment for cerebellar... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the development of noninvasive brain stimulation (NIBS) techniques, many researchers have turned their attention to NIBS as a promising treatment for cerebellar ataxia. Therefore, we conducted a systematic review and meta-analysis to investigate the efficacy and safety of NIBS in treating patients with cerebellar ataxia.
METHODS
Databases, including PubMed, Embase, Web of Science, Medline, and Cochrane Library, were retrieved for relevant randomized controlled trials (RCTs). Two researchers conducted literature screening, data extraction, literature quality assessment, and heterogeneity analysis between RCTs. According to the magnitude of heterogeneity I, an appropriate data analysis model was selected for meta-analysis.
RESULTS
A total of 14 RCTs including 406 patients with cerebellar ataxia met the inclusion criteria. The included RCTs had an overall low-risk bias and an intermediate level of evidence recommendation for key outcome indicators, such as the scale for the assessment and rating of ataxia (SARA) and international cooperative ataxia rating scale (ICARS). The results of meta-analysis showed that cerebellar NIBS, including transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), was effective in reducing the SARA scores (MD = - 3.45, 95%CI = [- 4.85, - 2.50], P < 0.05) and ICARS scores (MD = - 10.87, 95%CI = [- 14.46, - 7.28], P < 0.05) in patients with cerebellar ataxia compared to controls. Subgroup analysis showed that the efficacy of tDCS and rTMS was statistically different in patients with cerebellar ataxia as assessed by the SARA scores, but not by the ICARS scores. There was statistically significant difference in the efficacy of NIBS for the treatment of cerebellar ataxia caused by different etiologies. As for safety, 8 of 14 included studies documented the adverse effects of NIBS, and only two studies reported the mild adverse events of NIBS.
CONCLUSIONS
Cerebellar NIBS was safe and effective in improving the motor coordination of patients with cerebellar ataxia, and tDCS was better than rTMS in the treatment of cerebellar ataxia. In addition, the efficacy of NIBS was different in the treatment of different types of cerebellar ataxia.
Topics: Humans; Cerebellar Ataxia; Randomized Controlled Trials as Topic; Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation; Cerebellum
PubMed: 37460852
DOI: 10.1007/s00415-023-11799-8 -
European Journal of Neurology Dec 2023The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European... (Review)
Review
BACKGROUND
The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European Reference Network of Rare Neurological Disorders funded by the European Commission conducted a systematic review to assess drug treatment of chorea in NKX2-1-RD, aiming to provide clinical recommendations for its management.
METHODS
A systematic pairwise review using various databases, including MEDLINE, Embase, Cochrane, CINAHL, and PsycInfo, was conducted. The review included patients diagnosed with chorea and NKX2-1-RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events. The methodological quality of the studies was assessed, and the study protocol was registered in PROSPERO.
RESULTS
Of the 1417 studies examined, 28 studies met the selection criteria, consisting of 68 patients. The studies reported 22 different treatments for chorea, including carbidopa/levodopa, tetrabenazine, clonazepam, methylphenidate, carbamazepine, topiramate, trihexyphenidyl, haloperidol, propranolol, risperidone, and valproate. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported. However, most patients treated with methylphenidate experienced improvements in chorea and reported only a few negative effects. The quality of evidence was determined to be low.
CONCLUSIONS
The management of chorea in individuals with NKX2-1-RD presents significant heterogeneity and lack of clarity. While the available evidence suggests that methylphenidate may be effective in improving chorea symptoms, the findings should be interpreted with caution due to the limitations of the studies reviewed. Nonetheless, more rigorous and comprehensive studies are necessary to provide sufficient evidence for clinical recommendations.
Topics: Humans; Chorea; Tetrabenazine; Levodopa; Carbidopa; Clonazepam; Methylphenidate
PubMed: 37694681
DOI: 10.1111/ene.16038 -
Reviews in Medical Virology May 2024Cytomegalovirus (CMV) belongs to the Herpesviridae family and is also known as human herpesvirus type 5. It is a common virus that usually doesn't cause any symptoms in... (Meta-Analysis)
Meta-Analysis Review
Cytomegalovirus (CMV) belongs to the Herpesviridae family and is also known as human herpesvirus type 5. It is a common virus that usually doesn't cause any symptoms in healthy individuals. However, once infected, the virus remains in the host's body for life and can reactivate when the host's immune system weakens. This virus has been linked to several neurological disorders, including Alzheimer's disease, Parkinson's disease, Autism spectrum disorder, Huntington's disease (HD), ataxia, Bell's palsy (BP), and brain tumours, which can cause a wide range of symptoms and challenges for those affected. CMV may influence inflammation, contribute to brain tissue damage, and elevate the risk of moderate-to-severe dementia. Multiple studies suggest a potential association between CMV and ataxia in various conditions, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, acute cerebellitis, etc. On the other hand, the evidence regarding CMV involvement in BP is conflicting, and also early indications of a link between CMV and HD were challenged by subsequent research disproving CMV's presence. This systematic review aims to comprehensively investigate any link between the pathogenesis of CMV and its potential role in neurological disorders and follows the preferred reporting items for systematic review and meta-analysis checklist. Despite significant research into the potential links between CMV infection and various neurological disorders, the direct cause-effect relationship is not fully understood and several gaps in knowledge persist. Therefore, continued research is necessary to gain a better understanding of the role of CMV in neurological disorders and potential treatment avenues.
Topics: Humans; Autism Spectrum Disorder; Cytomegalovirus Infections; Cytomegalovirus; Nervous System Diseases; Ataxia
PubMed: 38549138
DOI: 10.1002/rmv.2532 -
International Journal of Molecular... Aug 2023This review explores the emerging role of hydrogen sulfide (HS) in modulating epigenetic mechanisms involved in neurodegenerative diseases. Accumulating evidence has... (Review)
Review
This review explores the emerging role of hydrogen sulfide (HS) in modulating epigenetic mechanisms involved in neurodegenerative diseases. Accumulating evidence has begun to elucidate the multifaceted ways in which HS influences the epigenetic landscape and, subsequently, the progression of various neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's disease. HS can modulate key components of the epigenetic machinery, such as DNA methylation, histone modifications, and non-coding RNAs, impacting gene expression and cellular functions relevant to neuronal survival, inflammation, and synaptic plasticity. We synthesize recent research that positions HS as an essential player within this intricate network, with the potential to open new therapeutic avenues for these currently incurable conditions. Despite significant progress, there remains a considerable gap in our understanding of the precise molecular mechanisms and the potential therapeutic implications of modulating HS levels or its downstream targets. We conclude by identifying future directions for research aimed at exploiting the therapeutic potential of HS in neurodegenerative diseases.
Topics: Humans; Hydrogen Sulfide; Epigenesis, Genetic; Neurodegenerative Diseases; Huntington Disease; Cell Survival
PubMed: 37628735
DOI: 10.3390/ijms241612555 -
Tremor and Other Hyperkinetic Movements... 2023Movement disorders, particularly chorea, are uncommon in inborn errors of metabolism, but their identification is essential for improved clinical outcomes. In this... (Review)
Review
BACKGROUND
Movement disorders, particularly chorea, are uncommon in inborn errors of metabolism, but their identification is essential for improved clinical outcomes. In this context, comprehensive descriptions of movement disorders are limited and primarily derived from single cases or small patient series, highlighting the need for increased awareness and additional research in this field.
METHODS
A systematic review was conducted using the MEDLINE database and GeneReviews. The search included studies on inborn errors of metabolism associated with chorea, athetosis, or ballismus. The review adhered to PRISMA guidelines.
RESULTS
The systematic review analyzed 76 studies out of 2350 records, encompassing the period from 1964 to 2022. Chorea was observed in 90.1% of the 173 patients, followed by athetosis in 5.7%. Various inborn errors of metabolism showed an association with chorea, with trace elements and metals being the most frequent. Cognitive and developmental abnormalities were common in the cohort. Frequent neurological features included seizures, dysarthria, and optic atrophy, whereas non-neurological features included, among others, facial dysmorphia and failure to thrive. Neuroimaging and biochemical testing played crucial roles in aiding diagnosis, revealing abnormal findings in 34.1% and 47.9% of patients, respectively. However, symptomatic treatment efficacy for movement disorders was limited.
DISCUSSION
This study emphasizes the complexities of chorea in inborn errors of metabolism. A systematic approach with red flags, biochemical testing, and neuroimaging is required for diagnosis. Collaboration between neurologists, geneticists, and metabolic specialists is crucial for improving early detection and individualized treatment. Utilizing genetic testing technologies and potential therapeutic avenues can aid in the improvement of patient outcomes.
Topics: Humans; Chorea; Athetosis; Metabolism, Inborn Errors; Movement Disorders; Dyskinesias
PubMed: 37810989
DOI: 10.5334/tohm.801 -
Clinical Neurology and Neurosurgery Apr 2024Levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced parkinson's... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced parkinson's disease (PD). However, the optimal strategy, including the type and dose of COMT inhibitors remains unknown. This systematic review and network meta-analysis aimed to assess the efficacy and safety of different COMT inhibitors and for treating PD patients.
METHODS
PubMed, Embase, Cochrane Library and Web of Science were screened up to November 20, 2022. Randomized controlled trials (RCTs) of COMT inhibitors (entacapone, opicapone, tolcapone) for PD patients were included. Eligible outcomes were total ON-time, rate of ON-time >1 h, total daily dose of levodopa therapy, mean change from baseline to final follow up in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, adverse events and dyskinesia. Network meta-analyses integrated direct and indirect evidence with placebo as a common comparator.
RESULTS
We identified 18 studies with 7564 patients. Opicapone, entacapone, and tolcapone could increase total ON-time when compared with placebo. However, opicapone (25 mg, MD 4.0, 95%CrI: 1.1-7.5) and opicapone (50 mg, MD 5.1, 95%CrI: 2.2-8.7) statistically significant increase the total ON-time. opicapone and entacapone could increase the rate of ON-time >1 h when compared with placebo. Only opicapone (5 mg) showed no statistically significant with placebo (OR 1.4, 95%CrI: 0.74-2.4). We found that opicapone (50 mg, SURCA, 0.796) is the best option compared with other treatments. TOL (200 mg) was ranked highest in the rank probability test for total daily dose of levodopa therapy, followed by OPI (50 mg), TOL (400 mg) and TOL (100 mg) in order. SUCRA rankings identified TOL (200 mg) as the most likely therapy for increasing adverse events (SUCRA 27.19%), followed by TOL (400 mg, SUCRA 27.20%) and OPI (5 mg, SUCRA 30.81%). The SUCRA probabilities were 91.6%, 75.2%, 67.9%, 59.3%, 45.6%, 41.1%, 35.1%, 24.6% and 9.4% for PLA, TOL (400 mg), ENT (100 mg), ENT (200 mg), OPI (5 mg), TOL (100 mg), OPI (25 mg), OPI (50 mg), and TOL (200 mg) respectively.
CONCLUSION
In conclusion, opicapone (50 mg) may be a better choice for treatment PD when compared with other COMT inhibitors.
Topics: Humans; Parkinson Disease; Levodopa; Antiparkinson Agents; Tolcapone; Network Meta-Analysis; Catechol O-Methyltransferase Inhibitors; Catechols; Transferases; Randomized Controlled Trials as Topic; Nitriles
PubMed: 38437773
DOI: 10.1016/j.clineuro.2024.108189 -
Social Neuroscience Dec 2023Numerous lines of research indicate that our social brain involves a network of cortical and subcortical brain regions that are responsible for sensing and controlling... (Review)
Review
Numerous lines of research indicate that our social brain involves a network of cortical and subcortical brain regions that are responsible for sensing and controlling body movements. However, it remains unclear whether movement disorders have a systematic impact on social cognition. To address this question, we conducted a systematic review examining the influence of hyperkinetic movement disorders (including Huntington disease, Tourette syndrome, dystonia, and essential tremor) on social cognition. Following the PRISMA guidelines and registering the protocol in the PROSPERO database (CRD42022327459), we analyzed 50 published studies focusing on theory of mind (ToM), social perception, and empathy. The results from these studies provide evidence of impairments in ToM and social perception in all hyperkinetic movement disorders, particularly during the recognition of negative emotions. Additionally, individuals with Huntington's Disease and Tourette syndrome exhibit empathy disorders. These findings support the functional role of subcortical structures (such as the basal ganglia and cerebellum), which are primarily responsible for movement disorders, in deficits related to social cognition.
Topics: Humans; Social Cognition; Hyperkinesis; Tourette Syndrome; Social Perception; Movement Disorders; Theory of Mind; Cognition; Emotions
PubMed: 37580305
DOI: 10.1080/17470919.2023.2248687