NEURO

Purpose of review We reviewed present topics on neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD). Recent findings The number of NMOSD-related publications have increased year by year after the discovery of aquaporin 4 (AQP4)-antibody, and those on MOGAD started to surge since 2012–2013. Recent clinic-epidemiological surveys in NMOSD suggest that some racial differences in the prevalence and the clinical course. At present, experts feel the 2015 diagnostic criteria of AQP4-antibody-seronegative NMOSD should be revised. Randomized controlled trials of monoclonal antibodies in NMOSD have demonstrated a significant risk reduction of relapse, especially in AQP4-antibody-positive cases. Meanwhile, the efficacy in seronegative NMOSD was unclear. MOGAD can show NMO and other clinical phenotypes, but the clinical manifestations and frequencies are different in children and adults. One pathological study has suggest...

Purpose of review Migraine is the second leading cause of years lived with disability after back pain. Poor tolerability, contraindications, drug–drug interactions and efficacy limited to a subpopulation make new approaches necessary for the acute and preventive treatment of migraine. The study of the calcitonin-gene-related peptide (CGRP) pathway over the last decades is a good example of translational medicine leading to directed therapies for patients. Recent findings After some of the first-generation CGRP receptor antagonists, gepants, were not fully developed because of hepatotoxicity, the second generation of gepants have shown efficacy, safety and tolerability in recent clinical trials. Summary Both rimegepant and ubrogepant have published positive randomized placebo-controlled clinical trials data. Vazegepant is the first intranasal gepant for the acute treatment of migraine and has announced a positive phase II/III study. Daily rimegepant use has preliminary data to suggest e...

Purpose of review Posttraumatic headache (PTH) attributed to mild traumatic brain injury is common and debilitating. In up to one-half of those with acute PTH, the PTH becomes persistent (PTH), enduring for longer than 3 months. The high incidence and persistence of PTH necessitate research into PTH pathophysiology and treatment. In this review, recent developments regarding the diagnostic criteria for PTH, the pathophysiology of PTH, and PTH treatment are discussed. Recent findings International Classification of Headache Disorders 3 diagnostic criteria for PTH attributed to head trauma require that ‘a headache of any type’ starts within 7 days of a head injury. PTH is considered ‘persistent’ when it endures for more than 3 months. Preclinical and human PTH research suggest multiple pathophysiologic mechanisms including genetic influences, neuroinflammation, increased release and inadequate clearance of neuropeptides and neurotransmitters, mast cell degranulation, and brain structural...

Purpose of review Cluster headache is a neurological disorder that patients consider the most severe pain they experience. Recognizing new treatments provides opportunities to advance current management. Recent findings In contrast to the classic treatments, new options narrow in on the therapeutic target and are better tolerated. Calcitonin gene-related peptide (CGRP) pathway blockade with monoclonal antibodies (MABs), specifically the CGRP MAB galcanezumab, represents an important advance for episodic cluster headache, reducing the number of attacks during a bout. Neuromodulation strategies aimed at anatomical structures involved in the pathophysiology of cluster headache, such as the sphenopalatine ganglion and the vagus nerve, have proved effective in reducing the pain intensity and the number of attacks, and also to be safe and well tolerated. Summary Our understanding of the pathophysiology of cluster headache and its management continues to grow. Novel treatments have appeared f...

Purpose of review Neuromodulatory approaches add to our armamentarium of therapeutic tools for the treatment of primary headaches. This review provides a comprehensive overview of current controlled studies on the different neuromodulation techniques and recommendations for clinical practice. Recent findings Evidence for efficacy of transcutaneous vagal nerve stimulation (tVNS) is limited to acute use in migraine with ambiguous results and episodic cluster headache as well as chronic cluster headache if applied in addition to conventional treatment. Transcutaneous stimulation of the supraorbital and supratrochlear nerve was effective in both acute and preventive stimulation (the latter with ambiguous results) in episodic migraines. Thus, invasive procedures should be reserved for severe and refractory cases only. Occipital nerve stimulation for chronic refractory cluster headache is the only available invasive approach with a Conformité Européenne mark. Summary Neuromodulation can comp...

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Purpose of review Apart from mental, motor and sensory functions, the human central nervous system (CNS) regulates a plethora of homeostatic (autonomic and hormonal) bodily functions. These functions are dependent on specialized neuronal networks. To ensure connectivity of these networks, they are continuously refined and supported by glial cells that outnumber neurons by, according to some accounts, an order of magnitude. Among glial cells, microglia – the brain resident macrophages – plays a crucial role in maintaining neuronal networks. However, in their concomitant role as brain immune cells microglia also engage in inflammatory signaling that may disrupt neuronal networks. Here, we review novel insights for molecular pathways involved in the protective functions of microglia and other immune cells in response to systemic signals and stimuli. Recent findings Recent evidence suggests that aging and systemic disease push individual microglia toward proinflammatory phenotypes compromi...

Purpose of review Recently, experiments show that the autoantibodies with direct access to neurons following blood brain barrier (BBB) disruption destroy neurons and lead to remodeling in damaged neurons. These are critical steps in autoantibody-mediated central nervous system disorder called neuropsychiatric syndromes in systemic lupus erythematosus (NPSLE). The purpose of this review is to examine therapeutic opportunities to repress neuronal remodeling by microglia after acute neuronal injury by autoantibodies. Recent findings Recent studies have demonstrated that BBB disruption is a critical step for developing NPSLE, and serum anti-Sm antibodies have been significantly associated with BBB breakdown. In addition, it has been reported that antiglucose regulated protein-78 in patients with SLE also disrupt the BBB. Experiments with anti-N-methyl-D-aspartate antibodies show that HMGB1 and C1q were essential to activate microglia which, in turn, remodel damaged neurons in vivo. Interes...

Purpose of review Neuropsychiatric lupus (NPSLE) comprises a disparate collection of syndromes affecting the central and peripheral nervous systems. Progress in the attribution of neuropsychiatric syndromes to SLE-related mechanisms and development of targeted treatment strategies has been impeded by a lack of objective imaging biomarkers that reflect specific neuropsychiatric syndromes and/or pathologic mechanisms. The present review addresses recent publications of neuroimaging techniques in NPSLE. Recent findings Imaging studies grouping all NPSLE syndromes together are unable to differentiate between NPSLE and non-NPSLE. In contrast, diffusion tensor imaging, FDG-PET, resting, and functional MRI techniques in patients with stable non-NPSLE demonstrate abnormal network structural and functional connectivity and regional brain activity in multiple cortical areas involving the limbic system, hippocampus, frontal, parietal, and temporal lobes. Some of these changes associate with impai...

Purpose of review This review summarizes recent insights into the pathogenesis and therapeutic options for patients with MOG- or AQP4-antibodies. Recent findings Although AQP4-IgG are linked to NMOSD, MOG-IgG-associated diseases (MOGAD) include a broader clinical spectrum of autoimmune diseases of the central nervous system (CNS). Details of membrane assembly of AQP4-IgG required for complement activation have been uncovered. Affinity-purified MOG-IgG from patients were shown to be pathogenic by induction of demyelination when the blood--brain barrier (BBB) was breached and by enhancement of activation of cognate T cells. A high-affinity AQP4-IgG, given peripherally, could induce NMOSD-like lesions in rats in the absence of BBB breach. Circulating AQP4-specific and MOG-specific B cells were identified and suggest differences in origin of MOG-antibodies or AQP4-antibodies. Patients with MOG-IgG show a dichotomy concerning circulating MOG-specific B cells; whether this is related to diff...

Purpose of review To systematically review the clinical features, diagnosis, and management of anti-gamma-aminobutyric acid receptor Type A (GABAA) autoimmune encephalitis with a focus on recent data. Recent findings In a review of published reports, we identified 50 cases of anti-GABAA receptor encephalitis with clinical features reported. The median age at presentation was 47 years old (range, 2.5 months–88 years old), 64% were adults, 36% were children and it occurred in both males and females. Eight-two percent (41/50) presented with seizures, 72% (36/50) with encephalopathy, and 58% (29/50) with both. Of those presenting with seizures, 42% developed status epilepticus during their disease course. Ninety-six percent (48/50) had MRI results reported, with 83% of these cases having abnormal findings, most commonly multifocal/diffuse cortical and subcortical T2/FLAIR hyperintense lesions without associated gadolinium enhancement. Almost one-third, 28% (14/50), had an associated malign...

Purpose of review Galectin interactions with glycoproteins and glycolipids modulate a variety of cellular responses that are now increasingly explored to better understand neuroinflammation processes and eventually find new therapeutic opportunities for neurological diseases. Recent findings Gal-1 confirmed its indirect neuroprotective roles through anti-inflammatory properties whereas Gal-3 remains elusive, showing anti-inflammatory or pro-inflammatory roles depending on damaging conditions and genetic background of mice models. Interestingly, microglial intracellular rather than extracellular overexpression of Gal-3 arose as contributing to the pathogenesis of Huntington disease, involving NLRP3 inflammasome activation and inhibition of autophagic removal of damaged endolysosomes. Decreasing Gal-3 expression had favorable effects upon disease symptoms. Gal-3 expanded its role in this endolysosomal surveillance system originally involving Gal-8 and Gal-9, which protect cells against n...

Purpose of review Chronic fatigue is common in cancer, neurodegenerative, and chronic inflammatory diseases and is regarded by many patients as their absolutely worst problem. Lately, fatigue is increasingly understood to have a genetic and molecular basis. Recent findings Biologically, fatigue occurs as part of the sickness behavior response, a complex and automated behavior triggered by the activation of innate immunity and neuroinflammation. IL-1β causes neuronal activation in the brain and subsequent fatigue. In addition to proinflammatory molecules, potential partners in the complex brain signaling of fatigue include downregulatory mechanisms for inflammation and cellular stress responses and the neuropeptide hypocretin-1. These mechanisms all become constantly activated in chronic conditions. Genetic studies indicate that fatigue may have evolved to enhance survival during infection and injury. Summary Fatigue is a major clinical problem. Finding the right treatment is challengin...

Purpose of review Chronic inflammation is a major component of HIV infection, the effects of which can be devastating in the central nervous system (CNS). Protecting the brain is, therefore, critical as efforts proceed to cure HIV infection by reactivating latent viral reservoirs and driving immune responses. We review the clinical presentation and pathology findings of inflammatory processes in the CNS in patients managed with ART and the drivers of these processes. Recent findings Chronic inflammation is associated with increased mortality and morbidity and HIV infection increases the risk for chronic diseases, especially cognitive impairment. Latent viral reservoirs, including microglia and tissue macrophages, contribute to inflammation in the CNS. Inflammation is generated and maintained through residual viral replication, dysregulation of infected cells, continuously produced viral proteins and positive feedback loops of chronic inflammation. Novel therapeutics and lifestyle chang...

Purpose of review The present review will outline neuroprotective and neurotoxic effects of central nervous system (CNS) infiltrating T cells during viral infections. Evidence demonstrating differential roles for antiviral effector and resident memory T-cell subsets in virologic control and immunopathology in the CNS will be discussed. Potential therapeutic targets emanating from a growing understanding of T-cell-initiated neuropathology that impacts learning and memory will also be delineated. Recent findings The critical role for T cells in preventing and clearing CNS infections became incontrovertible during the era of acquired immunodeficiency syndrome. Recent studies have further defined differential roles of T-cell subsets, including resident memory T cells (Trm), in antiviral immunity and, unexpectedly, in postinfectious cognitive dysfunction. Mechanisms of T-cell-mediated effects include differential innate immune signaling within neural cells that are virus-specific. Summary T...

Purpose of review The retina is growingly recognized as a window into cerebrovascular and systemic vascular conditions. The utility of noninvasive retinal vessel biomarkers in cerebrovascular risk assessment has expanded due to advances in retinal imaging techniques and machine learning-based digital analysis. The purpose of this review is to underscore the latest evidence linking retinal vascular abnormalities with stroke and vascular-related cognitive disorders; to highlight modern developments in retinal vascular imaging modalities and software-based vasculopathy quantification. Recent findings Longitudinal studies undertaken for extended periods indicate that retinal vascular changes can predict cerebrovascular disorders (CVD). Cerebrovascular ties to dementia provoked recent explorations of retinal vessel imaging tools for conceivable early cognitive decline detection. Innovative biomedical engineering technologies and advanced dynamic and functional retinal vascular imaging metho...

Purpose of review Optic neuropathies refer to a collection of diseases in which retinal ganglion cells (RGCs), the specialized neuron of the retina whose axons make up the optic nerve, are selectively damaged. Blindness secondary to optic neuropathies is irreversible as RGCs do not have the capacity for self-renewal and have a limited capacity for self-repair. Numerous strategies are being developed to either prevent further RGC degeneration or replace the cells that have degenerated. In this review, we aim to discuss known limitations to regeneration in central nervous system (CNS), followed by a discussion of previous, current, and future strategies for optic nerve neuroprotection as well as approaches for neuro-regeneration, with an emphasis on developments in the past two years. Recent findings Neuro-regeneration in the CNS is limited by both intrinsic and extrinsic factors. Environmental barriers to axon regeneration can be divided into two major categories: failure to clear myeli...

Purpose of review The aim of this review is to highlight novel artificial intelligence-based methods for the detection of optic disc abnormalities, with particular focus on neurology and neuro-ophthalmology. Recent findings Methods for detection of optic disc abnormalities on retinal fundus images have evolved considerably over the last few years, from classical ophthalmoscopy to artificial intelligence-based identification methods being applied to retinal imaging with the aim of predicting sight and life-threatening complications of underlying brain or optic nerve conditions. Summary Artificial intelligence and in particular newly developed deep-learning systems are playing an increasingly important role for the detection and classification of acquired neuro-ophthalmic optic disc abnormalities on ocular fundus images. The implementation of automatic deep-learning methods for detection of abnormal optic discs, coupled with innovative hardware solutions for fundus imaging, could revolut...

Purpose of review In the last three decades, the use of eye movements and vestibular testing in many neurological disorders has accelerated, primarily because of practical technologic developments. Although the acute vestibular syndrome is a prime example of this progress, more chronic neurologic and systemic disorders have received less attention. We focus here on recent contributions relating vestibular and ocular motor abnormalities in inflammatory, demyelinating, metabolic, and peripheral nervous system disorders Recent findings Vestibular abnormalities have been identified in acute demyelinating neuropathies (AIDP), in novel genetic mutations responsible for CANVAS (cerebellar ataxia, neuropathy vestibular areflexia syndrome), and in other inherited neuropathies (variants of Charcot-Marie-Tooth disease). In addition, there are differentiating characteristics between the most common CNS demyelinating disorders: multiple sclerosis and neuromyelitis optica (NMO). We summarize new inf...

Purpose of review To provide an update on diagnostic algorithms for differential diagnosis of acute vertigo and dizziness and swift identification of potentially harmful causes. Recent findings About 25% of patients with acute vertigo and dizziness have a potentially life-threatening diagnosis, including stroke in 4–15%. Diagnostic work-up relies on the combination of symptom features (triggers, duration, history of vertigo/dizziness, accompanying symptoms) and a comprehensive vestibular, ocular motor, and balance exam. The latter includes head impulse, head-shaking nystagmus, positional nystagmus, gaze-holding, smooth pursuit, skew deviation, and Romberg's test. Recent standardized diagnostic algorithms (e.g., HINTS, TriAGe+) suggest the combination of several elements to achieve a good diagnostic accuracy in differentiation of central and peripheral vestibular causes. Neuroimaging with MRI must be applied and interpreted with caution, as small strokes are frequently overlooked, e...