Lancet neurology
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Disease-modifying therapies that slow or halt the progression of Parkinson's disease are an unmet clinical need. Many hypotheses have been put forward to explain the pathogenesis of the disease, but none has led to the development of disease-modifying drugs. ⋯ Genetic discoveries and mechanistic investigations have highlighted early alterations to synaptic function, endosomal maturation, and protein sorting that might lead to an intracellular proteinopathy. We propose that these cellular processes constitute one pathway to pathogenesis and suggest that neuroprotection, as an adjunct to current symptomatic treatments, need not remain an elusive goal.
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Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. ⋯ Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis.
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The management of patients with migraine is often unsatisfactory because available acute and preventive therapies are either ineffective or poorly tolerated. The acute treatment of migraine attacks has been limited to the use of analgesics, combinations of analgesics with caffeine, ergotamines, and the triptans. ⋯ In migraine prevention, the most promising new approaches are humanised antibodies against CGRP or the CGRP receptor. Non-invasive and invasive neuromodulation approaches also show promise as both acute and preventive therapies, although further studies are needed to define appropriate candidates for these therapies and optimum protocols for their use.
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Alzheimer's disease is a progressive neurodegenerative disease that typically manifests clinically as an isolated amnestic deficit that progresses to a characteristic dementia syndrome. Advances in neuroimaging research have enabled mapping of diverse molecular, functional, and structural aspects of Alzheimer's disease pathology in ever increasing temporal and regional detail. ⋯ These findings have fuelled clinical interest in the use of specific imaging markers for Alzheimer's disease to predict future development of dementia in patients who are at risk. The potential clinical usefulness of single or multimodal imaging markers is being investigated in selected patient samples from clinical expert centres, but additional research is needed before these promising imaging markers can be successfully translated from research into clinical practice in routine care.