Current Neurology and Neuroscience Reports最新文献

Purpose of review: Headache is one of the most frequent symptoms of the acute and post-acute phase of COVID-19. Specific epidemiology, clinical features, risk factors, pathophysiology, and treatment have been reported in these two scenarios. With this narrative review of the literature, we aim to provide updated knowledge on headache in the COVID-19 setting and give clinicians a practical approach on this topic to guide them in their clinical practice.

Recent findings: Headache mechanisms in COVID-19 are still poorly understood. Strong evidence is also lacking on how to best treat and manage these patients, especially those with persistent and disabling headache after COVID-19. Data are also scarce on the characteristics of headache in COVID-19 caused by the new SARS-CoV-2 (Omicron) variants and how these may influence the acute and persistent symptoms of COVID-19. Patients with pre-existing primary headache disorders remain a particularly concerning population due to their biological predisposition in suffering from headaches and the potential risk of worsening in the setting of SARS-CoV-2 infection. Although there is an exponential growth of scientific evidence, studies are often controversial and focused on the first wave of the pandemic, making COVID-19 headache still a challenging matter for clinicians. New research is therefore needed.

Purpose of review: Molecular profiling enables the evaluation of genetic alterations for the diagnosis and classification of gliomas and the selection of appropriate therapies. This review summarizes the current role of molecular profiling and targeted therapies for gliomas.

Recent findings: Molecular profiling is an integral part of the 2021 WHO classification of gliomas. Progress in the development of targeted therapies remains limited due to many factors including the presence of the blood-brain barrier and issues of tumor heterogeneity. Nonetheless, advances have been made with the IDH1/2 inhibitor vorasidenib for IDH-mutant grade 2 gliomas, the combination of dabrafenib and trametinib for BRAFV600E mutated gliomas, and the therapies for subsets of patients with fusions and H3K27M-altered diffuse midline gliomas. While there has been progress in the use of molecular profiling for the classification and treatment of gliomas, much work remains for targeted therapies to realize their potential.

Purpose of review: Lewy body dementia (LBD) encompasses dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). This article will emphasize potential disease-modifying therapies as well as investigative symptomatic treatments for non-motor symptoms including cognitive impairment and psychosis that can present a tremendous burden to patients with LBD and their caregivers.

Recent findings: We review 11 prospective disease-modifying therapies (DMT) including four with phase 2 data (neflamapimod, nilotinib, bosutinib, and E2027); four with some limited data in symptomatic populations including phase 1, open-label, registry, or cohort data (vodabatinib, ambroxol, clenbuterol, and terazosin); and three with phase 1 data in healthy populations (Anle138b, fosgonimeton, and CT1812). We also appraise four symptomatic therapies for cognitive impairment, but due to safety and efficacy concerns, only NYX-458 remains under active investigation. Of symptomatic therapies for psychosis recently investigated, pimavanserin shows promise in LBD, but studies of nelotanserin have been suspended. Although the discovery of novel symptomatic and disease-modifying therapeutics remains a significant challenge, recently published and upcoming trials signify promising strides toward that aim.

Purpose of review: To summarize the current evidence on the associations between autoimmune neurological diseases (e.g., multiple sclerosis, myasthenia gravis) and sleep disturbances (e.g., insomnia, parasomnias), as well as to review the main characteristics of sleep disorders with an immune-related pathophysiology (e.g., narcolepsy, anti-IgLON5 disease).

Recent findings: An immune-mediated damage of the areas in the central nervous system that control sleep and wake functions (e.g., hypothalamus, brainstem) can lead to sleep disorders and sleep symptoms. Sleep disturbances are the reason to seek for medical attention in certain neuroimmunological conditions (e.g., narcolepsy, anti-IgLON5 disease) where sleep-related alterations are the main clinical feature. The assessment of sleep-related symptomatology and disorders should be included in the routine evaluation of patients with autoimmune neurological diseases. Clinicians should be aware of the typical clinical presentation of certain neuroimmunological disorders mainly affecting sleep.

Purpose of review: To critically review recent research in the development of non-pharmacological interventions to improve cognitive functioning in individuals with Alzheimer's disease (AD) or Parkinson's disease (PD).

Recent findings: Cognitive interventions can be grouped into three categories: cognitive stimulation (CS), cognitive training (CT), and cognitive rehabilitation (CR). CS confers temporary, nonspecific benefits and might slightly reduce dementia risk for neurologically healthy individuals. CT can improve discrete cognitive functions, but durability is limited and real-world utility is unclear. CR treatments are holistic and flexible and, therefore, most promising but are difficult to simulate and study under rigorous experimental conditions. Optimally effective CR is unlikely to be found in a single approach or treatment paradigm. Clinicians must be competent in a variety of interventions and select those interventions best tolerated by the patient and most relevant to their needs and goals. The progressive nature of neurodegenerative disease necessitates that treatment be consistent, open-ended in duration, and sufficiently dynamic to meet the patient's changing needs as their disease progresses.

Purpose of review: To summarize the available literature as well as the authors' experience on trigeminal autonomic cephalalgias (TACs) and cranial neuralgias in children and adolescents.

Recent findings: While TACs and cranial neuralgias are rare in children, several recent case series have been published. TACs in children share most of the clinical features of TACs in adults. However, there are many reported cases with clinical features which overlap more than one diagnosis, suggesting that TACs may be less differentiated in youth. Indomethacin-responsive cases of cluster headache and SUNCT/SUNA have been reported in children, whereas in adults indomethacin is usually reserved for paroxysmal hemicrania and hemicrania continua. Neuralgias appear to be rare in children. Clinical features are often similar to adult cases, though clinicians should maintain a high index of suspicion for underlying causes.

Purpose of review: Neuromyelitis optica spectrum disorder (NMOSD) is a rare but highly disabling disease of the central nervous system. Unlike multiple sclerosis, disability in NMOSD occurs secondary to relapses that, not uncommonly, lead to blindness, paralysis, and death. Recently, newer, targeted immunotherapies have been trialed and are now in the treatment arsenal. We have endeavoured to evaluate the current state of NMOSD therapeutics.

Recent findings: This review provides a pragmatic evaluation of recent clinical trials and post-marketing data for rituximab, inebilizumab, satralizumab, eculizumab, and ravalizumab, contrasted to older agents. We also review contemporary issues such as treatment in the context of SARS-CoV2 infection and pregnancy. There has been a dramatic shift in NMOSD morbidity and mortality with earlier and improved disease recognition, diagnostic accuracy, and the advent of more effective, targeted therapies. Choosing a maintenance therapy remains nuanced depending on patient factors and accessibility. With over 100 putative agents in trials, disease-free survival is now a realistic goal for NMOSD patients.

Purpose of review: Since the beginning of the coronavirus disease 2019 pandemic, many lasting neurological sequelae including cognitive impairment have been recognized as part of the so-called long COVID syndrome. This narrative review summarizes the cognitive aspects of COVID-19.

Recent findings: Studies have consistently identified attention, memory, and executive functions as the cognitive domains most often affected by COVID-19 infection. Many studies have also reported neuroimaging, biofluid, and neurophysiological abnormalities that could potentially reflect the pathophysiological aspects of post-COVID cognitive impairment. While patients suffering from dementia have an elevated risk of COVID-19 infection, increasing evidence has also indicated that COVID-19 infection may increase the risks of Alzheimer's disease, suggesting bidirectional relationships. Post-COVID cognitive dysfunction is a pervasive and multifaceted problem and we are surely in our infancy of understanding. Future elucidation into the long-term effects, mechanisms, and therapies will depend on a concerted effort from clinicians, researchers, patients, and policy-makers alike.

Purpose of review: Multiple sclerosis is characterized by a diverse and complex pathology. Clinical relapses, the hallmark of the disease, are accompanied by focal white matter lesions with intense inflammatory and demyelinating activity. Prevention of these relapses has been the major focus of pharmaceutical development, and it is now possible to dramatically reduce this inflammatory activity. Unfortunately, disability accumulation persists for many people living with multiple sclerosis owing to ongoing damage within existing lesions, pathology outside of discrete lesions, and other yet unknown factors. Understanding this complex pathological cascade will be critical to stopping progressive multiple sclerosis. Positron emission tomography uses biochemically specific radioligands to quantitatively measure pathological processes with molecular specificity. This review examines recent advances in the understanding of multiple sclerosis facilitated by positron emission tomography and identifies future avenues to expand understanding and treatment options.

Recent findings: An increasing number of radiotracers allow for the quantitative measurement of inflammatory abnormalities, de- and re-myelination, and metabolic disruption associated with multiple sclerosis. The studies have identified contributions of ongoing, smoldering inflammation to accumulating tissue injury and clinical worsening. Myelin studies have quantified the dynamics of myelin loss and recovery. Lastly, metabolic changes have been found to contribute to symptom worsening. The molecular specificity facilitated by positron emission tomography in people living with multiple sclerosis will critically inform efforts to modulate the pathology leading to progressive disability accumulation. Existing studies show the power of this approach applied to multiple sclerosis. This armamentarium of radioligands allows for new understanding of how the brain and spinal cord of people is impacted by multiple sclerosis.