Lancet neurology
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Epileptic activity is frequently associated with Alzheimer's disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer's disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer's disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment. ⋯ Moreover, studies in mouse models of Alzheimer's disease suggest that certain classes of AEDs that reduce network hyperexcitability have disease-modifying properties. These AEDs target mechanisms of epileptogenesis involving amyloid β and tau. Clinical trials targeting network hyperexcitability in patients with Alzheimer's disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline.
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The neuropathology of different neurodegenerative diseases begins in different brain regions, and involves distinct brain networks. Evidence indicates that transcellular propagation of protein aggregation, which is the basis of prion disease, might underlie the progression of pathology in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. ⋯ Indeed, evidence indicates that self-propagating aggregate conformers, or so-called strains, are associated with distinct neuropathological syndromes. The extension of this hypothesis to our understanding of common neurodegenerative disorders can suggest new therapeutic approaches, such as immunotherapy and small molecules, to block transcellular propagation, and new diagnostic tools to detect early evidence of disease.
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Review
Mobile stroke units for prehospital thrombolysis, triage, and beyond: benefits and challenges.
In acute stroke management, time is brain. Bringing swift treatment to the patient, instead of the conventional approach of awaiting the patient's arrival at the hospital for treatment, is a potential strategy to improve clinical outcomes after stroke. This strategy is based on the use of an ambulance (mobile stroke unit) equipped with an imaging system, a point-of-care laboratory, a telemedicine connection to the hospital, and appropriate medication. ⋯ Moreover, novel medical options for the treatment of stroke patients are also under investigation, such as prehospital differential blood pressure management, reversal of warfarin effects in haemorrhagic stroke, and management of cerebral emergencies other than stroke. However, crucial concerns regarding safety, clinical efficacy, best setting, and cost-effectiveness remain to be addressed in further studies. In the future, mobile stroke units might allow the investigation of novel diagnostic (eg, biomarkers and automated imaging evaluation) and therapeutic (eg, neuroprotective drugs and treatments for haemorrhagic stroke) options in the prehospital setting, thus functioning as a tool for research on prehospital stroke management.
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Review
Impulse control disorders and levodopa-induced dyskinesias in Parkinson's disease: an update.
Dopaminergic medications used in the treatment of patients with Parkinson's disease are associated with motor and non-motor behavioural side-effects, such as dyskinesias and impulse control disorders also known as behavioural addictions. Levodopa-induced dyskinesias occur in up to 80% of patients with Parkinson's after a few years of chronic treatment. Impulse control disorders, including gambling disorder, binge eating disorder, compulsive sexual behaviour, and compulsive shopping occur in about 17% of patients with Parkinson's disease on dopamine agonists. ⋯ Therapeutic interventions to treat patients with Parkinson's disease and impulse control disorders have shown efficacy in randomised controlled trials. Large-scale studies are warranted to identify individual risk factors and novel therapeutic targets for these diseases. Mechanisms underlying impulse control disorders and dyskinesias could provide crucial insights into other behavioural symptoms in Parkinson's disease and addictions in the general population.
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Pain is a largely neglected symptom in patients with amyotrophic lateral sclerosis (ALS) although it is reported by most of these patients. It occurs at all stages of the disease and can be an onset symptom preceding motor dysfunction. Pain is correlated with a deterioration in patients' quality of life and increased prevalence of depression. ⋯ The site of pain depends on the pain type or underlying mechanism (eg, painful cramps, nociceptive pain, or neuropathic pain). Given the multifactorial nature of pain in patients with ALS, different treatments have been suggested, ranging from non-steroidal anti-inflammatory drugs, drugs for neuropathic pain, opioids, and cannabinoids, to physical therapy strategies and preventive assistive devices. Further understanding of the pathophysiology is crucial to drive assessment in clinical trials of therapeutic strategies targeted at specific mechanisms and studies of individualised therapies.