Current Neurology and Neuroscience Reports

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Online ISSN: 1534-6293
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Purpose of the Review The purpose of this article is to help clinicians understand how underlying pathophysiologies and medical comorbidities associated with acute traumatic brain injury (TBI) can impact assessment of cognition during the initial stages of recovery. Clinicians can use information from this article to develop assessment plans rooted in patient-centered care. Recent Findings The authors conducted a review of the literature related to the assessment of cognition in acute TBI, focusing on pathophysiology, medical comorbidities, and assessment approaches. Summary Results indicated that TBI pathophysiologies associated with white and gray matter changes make many patients vulnerable to cognitive deficits. Acute comorbidities such as psychological and pain status influence cognitive abilities as well. The current approaches to cognitive assessment can be limited in many ways, though by using the patient’s neuropathological profile, noted comorbidities, and other patient specific factors, clinicians can potentially improve the effectiveness of assessment.
 
The interplay of synchronous and asynchronous telehealth with incorporation of artificial intelligence. Synchronous telehealth is live/interactive telehealth that can be either clinic or home based. It includes video or phone visits. Asynchronous telehealth is a “store-and-forward” approach where testing/information is obtained and then shared through a portal for a physician to review later. Hybrid telehealth incorporates both synchronous and asynchronous modalities including capturing a visual field or fundus photograph asynchronously for the neuro-ophthalmologist to review at a later time point. A video visit is then scheduled for the neuro-ophthalmologist to synchronously review with the patient the testing results and care management plan. An example of a potential artificial intelligence (AI)-driven future state of neuro-ophthalmology is where asynchronous data is obtained via augmented reality (AR) home monitoring of a visual field defect. Deep learning (DL) algorithms then interpret the change in the visual field defect from previously obtained visual fields of the patient. If there are significant changes, DL can then pivot to either alert scheduling of an urgent synchronous video visit or a routine video visit with the patient
Artificial intelligence, machine learning, and deep learning defined. AI is the broad umbrella concept under which machine and deep learning reside. AI is defined as any technique that is used to mimic sentient behavior. Machine learning (ML) is a form of AI focused on data analysis by the construction and study of algorithms that process data to develop prediction or decision models. Deep learning (DL) is a form of machine learning that mimics human learning by layering multiple automated learning algorithms over the data in an iterative process to achieve the desired level of accuracy
Purpose of the Review Neuro-ophthalmologists rapidly adopted telehealth during the COVID-19 pandemic to minimize disruption to patient care. This article reviews recent research on tele-neuro-ophthalmology adoption, current limitations, and potential use beyond the pandemic. The review considers how digital transformation, including machine learning and augmented reality, may be applied to future iterations of tele-neuro-ophthalmology. Recent Findings Telehealth utilization has been sustained among neuro-ophthalmologists throughout the pandemic. Adoption of tele-neuro-ophthalmology may provide solutions to subspecialty workforce shortage, patient access, physician wellness, and trainee educational needs within the field of neuro-ophthalmology. Digital transformation technologies have the potential to augment tele-neuro-ophthalmology care delivery by providing automated workflow solutions, home-based visual testing and therapies, and trainee education via simulators. Summary Tele-neuro-ophthalmology use has and will continue beyond the COVID-19 pandemic. Digital transformation technologies, when applied to telehealth, will drive and revolutionize the next phase of tele-neuro-ophthalmology adoption and use in the years to come.
 
COVID 19 vaccine related neurological adverse events
A, B MR venography in a 60-year-old lady with prior history of migraine, presenting with a three week history of increasing headaches starting about a fortnight after her second dose of AstraZeneca (COVISHIELD vaccine), showing segmental partial occlusion of both transverse sinuses. She did not have any thrombocytopenia or raised D-dimer but had a low protein S level suggesting a pre-existing prothrombotic state. She was started on apixaban 2.5 mg twice daily. Her headaches were relieved. Repeat venography done over 6 months later revealed recanalization of the thrombosed segments (C). Her protein S level was persistently low. She was advised to continue apixaban indefinitely. She had no problem after her third booster dose of the same vaccine (adapted from [39•], with permission)
Purpose of Review A variety of neurological complications have been reported following the widespread use of the COVID-19 vaccines which may lead to vaccine hesitancy and serve as a major barrier to the public health aim of achieving protective herd immunity by vaccination. In this article, we review the available evidence regarding these neurological adverse events reported, to provide clarity regarding the same so that unfounded fears maybe put to rest. Recent Findings There is a greater than expected occurrence of severe neurological adverse events such as cortical sinus venous thrombosis, Bell’s palsy, transverse myelitis, and Guillain–Barré syndromes along with other common effects such as headaches following different kinds of COVID-19 vaccination. Precipitation of new onset demyelinating brain lesions with or without detection of specific antibodies and worsening of pre-existing neurological disorders (like epilepsy, multiple sclerosis) are also a matter of great concern though no conclusive evidence implicating the vaccines is available as of now. Summary The COVID-19 pandemic is far from being over. Till such time that a truly effective anti-viral drug is discovered, or an appropriate therapeutic strategy is developed, COVID-appropriate behavior and highly effective mass vaccination remain the only weapons in our armamentarium to fight this deadly disease. As often occurs with most therapeutic means for the treatment and prevention of any disease, vaccination against COVID-19 has its hazards. These range from the most trivial ones like fever, local pain and myalgias to several potentially serious cardiac and neurological complications. The latter group includes conditions like cerebral venous thrombosis (curiously often with thrombocytopenia), transverse myelitis and acute inflammatory demyelinating polyneuropathy amongst others. Fortunately, the number of reported patients with any of these serious complications is far too low for the total number of people vaccinated. Hence, the current evidence suggests that the benefits of vaccination far outweigh the risk of these events in majority of the patients. As of now, available evidence also does not recommend withholding vaccination in patients with pre-existing neurological disorders like epilepsy and MS, though adenoviral vaccines should be avoided in those with history of thrombotic events.
 
Purpose of Review To critically appraise the literature on the application, methods, and advances in emergency electroencephalography (EEG). Recent Findings The development of rapid EEG (rEEG) technologies and other reduced montage approaches, along with advances in machine learning over the past decade, has increased the rate and access to EEG acquisition. These achievements have made EEG in the emergency setting a practical diagnostic technique for detecting seizures, suspected nonconvulsive status epilepticus (NCSE), altered mental status, stroke, and in the setting of sedation. Summary Growing evidence supports using EEG to expedite medical decision-making in the setting of suspected acute neurological injury. This review covers approaches to acquiring EEG in the emergency setting in the adult and pediatric populations. We also cover the clinical impact of this data, the time associated with emergency EEG, and the costs of acquiring EEG in these settings. Finally, we discuss the advances in artificial intelligence for rapid electrophysiological interpretation.
 
Therapeutic development pipeline for Leber hereditary optic neuropathy (LHON) AAV, adeno-associated virus; BDNF/TrkB, brain-derived neurotrophic factor/tropomycin receptor kinase B; DdCBE, DddA-derived cytosine base editors; EAP, expanded access program; OXPHOS, oxidative phosphorylation; PAROS, post-authorisation observational study; RGC, retinal ganglion cell; ROS, reactive oxygen species; ZFD, zinc finger deaminases
Purposeof Review To outline the current landscape of treatments for Leber hereditary optic neuropathy (LHON) along the therapeutic delivery pipeline, exploring the mechanisms of action and evidence for these therapeutic approaches. Recent Findings Treatments for LHON can be broadly classified as either mutation-specific or mutation-independent. Mutation-specific therapies aim to correct the underlying mutation through the use of a gene-editing platform or replace the faulty mitochondrial DNA-encoded protein by delivering the wild-type gene using a suitable vector. Recent gene therapy clinical trials assessing the efficacy of allotopically expressed MT-ND4 for the treatment of LHON due to the m.11778G > A mutation in MT-ND4 have shown positive results when treated within 12 months of symptom onset. Mutation-independent therapies can have various downstream targets that aim to improve mitochondrial respiration, reduce mitochondrial stress, inhibit or delay retinal ganglion cell apoptosis, and/or promote retinal ganglion cell survival. Idebenone, a synthetic hydrosoluble analogue of co-enzyme Q10 (ubiquinone), is the only approved treatment for LHON. Mutation-independent approaches to gene therapy under pre-clinical investigation for other neurodegenerative disorders may have the potential to benefit patients with LHON. Summary Although approved treatments are presently limited, innovations in gene therapy and editing are driving the expansion of the therapeutic delivery pipeline for LHON.
 
The role of GABAergic projection neurons in the basal ganglia. Striatal medium spiny neurons (B1, B2) and globus pallidal projection neurons (C1, C2) are GABAergic (marked by red areas). All blue neurons fire transiently upon excitation, while all orange neurons are tonically active. 1 In the direct pathway, transient active medium spiny neurons in putamen and caudate (B1) will inhibit the tonically active neurons of globus pallidus internal segment (C1), thereby decreasing the inhibitory outflow of the basal ganglia. The dopaminergic neurons of pars compacta substantia nigra (D1) excite striatal neurons (B1) by D1 receptors and increase the outcome of the direct pathway. 2 In the indirect pathway, transient active inhibitory, striatal neurons (B2) that project to the tonically active neurons in globus pallidus external segment (C2) have D2-dopaminergic receptors and the dopaminergic modulation from substantia nigra (D2) is therefore inhibitory. Globus pallidus external neurons (C2) project to the subthalamic nucleus and the internal segment of globus pallidus, thereby modulating the effect of the direct pathway and increasing the overall inhibitory output of the basal ganglia [2, 3] (created with Biorender.com)
Purpose of Review During recent years, there has been a growing interest in GABAergic alterations in parkinsonian disorders. This paper aims to review the latest literature published, focusing on in vivo neuroimaging, and to suggest potential future avenues of research in the field. Recent Findings A growing number of neuroimaging studies have focused on the association with different symptoms of Parkinson’s disease, thereby suggesting a GABAergic role in motor symptoms, gait disturbances, frontal cognition, somatic symptom disorder, and hallucinations. However, there are a number of conflicting results, and further investigations in larger, clinically well-defined cohorts are needed to elucidate possible correlations. In progressive supranuclear palsy, recent evidence suggests a decrease of GABA in the frontal lobe. Summary In this narrative review, we discuss the possible GABAergic role in the symptoms of PD and atypical parkinsonisms and outline possible research strategies for future neuroimaging of GABAergic changes in parkinsonian disorders.
 
Overview of different language domains predominantly affected or preserved in thalamic aphasia as suggested by the current literature. While lexical-semantic deficits are described after lesions to almost all areas to the thalamus, some symptoms seem to be more common after lesions to specific thalamic nuclei, although more thorough analyses are needed. For example, lesions to the pulvinar are more often associated with fluent aphasia including naming deficits and semantic paraphasias, while lesions to the anterior nuclei can lead to reduced word fluency and show an overall higher severity. However, many phenotypical variations beyond this classification exist
Purpose of Review Thalamic aphasia is a rare language disorder resulting from lesions to the thalamus. While most patients exhibit mild symptoms with a predominance of lexical-semantic difficulties, variations in phenotype have been described. Overall, the exact mechanisms of thalamic aphasia await empirical research. The article reviews recent findings regarding phenotypes and possible underlying mechanisms of thalamic aphasia. Recent Findings Variations in phenotype of thalamic aphasia may be related to different lesion locations. Overall, the thalamus’ role in language is thought to be due to its involvement in cortico-thalamic language networks with lesioning of certain nuclei resulting in the diachisis of otherwise interconnected areas. Its possible monitoring function in such a network might be due to its different cellular firing modes. However, no specific evidence has been collected to date. Summary While recent findings show a more distinct understanding of thalamic aphasia phenotypes and possible underlying mechanisms, further research is needed. Additionally, as standard language testing might oftentimes not pick up on its subtle symptoms, thalamic aphasia might be underdiagnosed.
 
Management of cardiovascular autonomic neuropathy
Illustrative example: autonomic reflex screen of a patient with diabetic autonomic neuropathy
Purpose of Review Autonomic neuropathies are a complex group of disorders and result in diverse clinical manifestations that affect the cardiovascular, gastrointestinal, urogenital, and sudomotor systems. We focus this review on the diagnosis and treatment of peripheral autonomic neuropathies. We summarize the diagnostic tools and current treatment options that will help the clinician care for individuals with peripheral autonomic neuropathies. Recent Findings Autonomic neuropathies occur often in conjunction with somatic neuropathies but they can also occur in isolation. The autonomic reflex screen is a validated tool to assess sympathetic postganglionic sudomotor, cardiovascular sympathetic noradrenergic, and cardiac parasympathetic (i.e., cardiovagal) function. Initial laboratory evaluation for autonomic neuropathies includes fasting glucose or oral glucose tolerance test, thyroid function tests, kidney function tests, vitamin-B12, serum, and urine protein electrophoresis with immunofixation. Other laboratory tests should be guided by the clinical context. Reduced intraepidermal nerve density on skin biopsy is a finding, not a diagnosis. Skin biopsy can be helpful in selected individuals for the diagnosis of disorders affecting small nerve fibers; however, we strongly discourage the use of skin biopsy without clinical–physiological correlation. Ambulatory blood pressure monitoring may lead to early identification of patients with cardiovascular autonomic neuropathy in the primary care setting. Disease-modifying therapies should be used when available in combination with nonpharmacological management and symptomatic pharmacologic therapies. Autonomic function testing can guide the therapeutic decisions and document improvement with treatment. Summary A systematic approach guided by the autonomic history and standardized autonomic function testing may help clinicians when identifying and/or counseling patients with autonomic neuropathies. Treatment should be individualized and disease-modifying therapies should be used when available.
 
Purposeof Review Migraine is a chronic and disabling disease affecting a significant proportion of the world’s population. There is evidence that gastroparesis, a gastrointestinal (GI) dysmotility disorder in which transit of gastric contents is delayed, can occur in the setting of migraine. This article aims to review recent literature on overlap in the pathophysiology and clinical manifestations of migraine and gastroparesis and highlight management considerations when these disorders coexist. Recent Findings There has been increasing recognition of the importance of the connection between the GI tract and the brain, and mounting evidence for the overlap in the pathophysiology of migraine and gastroparesis specifically. There exists a complex interplay between the central, autonomic, and enteric nervous systems. Studies show that gastroparesis may be present during and between acute migraine attacks necessitating modification of management to optimize outcomes. Summary Gastric dysmotility in the setting of migraine can impact absorption of oral migraine medications and alternate formulations should be considered for some patients. Noninvasive vagus nerve stimulation has been FDA cleared for migraine treatment and is also being studied in gastroparesis. Dysfunction of the autonomic nervous system is a significant feature in the pathophysiology of gut motility and migraine, making treatments that modulate the vagus nerve attractive for future research.
 
Path model (reproduced from Richards et al. BMJ Open 2019;9:e024404)
Purpose of Review Birth cohorts are studies of people the same time; some of which have continuously followed participants across the life course. These are powerful designs for studying predictors of age-related outcomes, especially when information on predictors is collected before these outcomes are known. This article reviews recent findings from these cohorts for the outcomes of cognitive function, cognitive impairment, and risk of dementia, in relation to prior cognitive function, and social and biological predictors. Recent Findings Cognitive function and impairment are predicted by a wide range of factors, including childhood cognition, education, occupational status and complexity, and biological factors, including genetic and epigenetic. The particular importance of high and rising blood pressure in midlife is highlighted, with some insight into brain mechanisms involved. Some limitations are noted, including sources of bias in the data. Summary Despite these limitations, birth cohorts have provided valuable insights into factors across the life course associated with cognitive impairment.
 
BTK inhibition can affect cells of the adaptive and innate immune system outside and within the CNS. Abbreviations: Bruton’s Tyrosine Kinase (BTK), B cell receptor (BCR), Fc-gamma receptor (FcyR), multiple sclerosis (MS). Created with BioRender.com
Purpose of Review Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) with a chronic and often progressive disease course. The current disease-modifying treatments (DMTs) limit disease progression primarily by dampening immune cell activity in the peripheral blood or hindering their migration from the periphery into the CNS. New therapies are needed to target CNS immunopathology, which is a key driver of disability progression in MS. This article reviews Bruton’s Tyrosine Kinase Inhibitors (BTKIs), a new class of experimental therapy that is being intensely evaluated in MS. We focus on the potential peripheral and central mechanisms of action of BTKIs and their use in recent clinical trials in MS. Recent Findings There is evidence that some BTKIs cross the blood–brain barrier and may be superior to currently available DMTs at dampening the chronic neuroinflammatory processes compartmentalized within the CNS that contribute to progressive worsening in people withMS (pwMS). Recently, evobrutinib and tolebrutinib have shown efficacy in phase II clinical trials, and there are numerous ongoing phase III clinical trials of various BTKIs in relapsing and progressive forms of MS. Results from these clinical trials will be essential to understand the efficacy and safety of BTKIs across the spectrum of MS and keydifferences between specific BTKIs when treating pwMS. Summary Inhibition of BTK has emerged as an attractive strategy to target cells of the adaptive and innate immune system outside and within the CNS. BTKIs carry great therapeutic potential across the MS spectrum, where key pathobiology aspects seem confined to the CNS compartment.
 
Anti-Aβ antibodies tested for immunotherapy efficacy targeting various residues of the Aβ peptide. Figure created in BioRender.com
Active vs. passive immunization. Figure created in BioRender.com
IgG isotypes, isomers, and FcγR affinities. A Four structures of IgG antibody subtypes characterized by variations in hinge disulfide bonds between the two heavy chains. (A’) Three of the IgG2 isomers characterized by the variations in heavy and light chain disulfide bonds. (A’’) Highlight of the regions where isotypes and hinges vary. B IgG isotypes identified by Fcγ receptor affinity. Figure created in BioRender.com
Three mechanisms of Aβ clearance. Figure created in BioRender.com
Reported ARIA incidence for bapineuzumab, aducanumab, donanemab, and lecanemab in APOEε4 carriers and non-carriers. ARIA incidences above 10% in the patient population are highlighted in red
Purpose of Review Amyloid beta (Aβ) plaque accumulation is a hallmark pathology contributing to Alzheimer’s disease (AD) and is widely hypothesized to lead to cognitive decline. Decades of research into anti-Aβ immunotherapies provide evidence for increased Aβ clearance from the brain; however, this is frequently accompanied by complicated vascular deficits. This article reviews the history of anti-Aβ immunotherapies and clinical findings and provides recommendations moving forward. Recent Findings In 20 years of both animal and human studies, anti-Aβ immunotherapies have been a prevalent avenue of reducing hallmark Aβ plaques. In both models and with different anti-Aβ antibody designs, amyloid-related imaging abnormalities (ARIA) indicating severe cerebrovascular compromise have been common and concerning occurrence. Summary ARIA caused by anti-Aβ immunotherapy has been noted since the early 2000s, and the mechanisms driving it are still unknown. Recent approval of aducanumab comes with renewed urgency to consider vascular deficits caused by anti-Aβ immunotherapy.
 
Purpose For many patients, the multiple sclerosis (MS) diagnostic process can be lengthy, costly, and fraught with error. Recent research aims to address the unmet need for an accurate and simple diagnostic process through discovery of novel diagnostic biomarkers. This review summarizes recent studies on MS diagnostic fluid biomarkers, with a focus on blood biomarkers, and includes discussion of technical limitations and practical applicability. Recent Findings This line of research is in its early days. Accurate and easily obtainable biomarkers for MS have not yet been identified and validated, but several approaches to uncover them are underway. Summary Continue efforts to define laboratory diagnostic biomarkers are likely to play an increasingly important role in defining MS at the earliest stages, leading to better long-term clinical outcomes.
 
Study identification flow diagram
Purpose of review: To provide perspectives on the importance of understanding longitudinal profiles of posterior cortical atrophy (PCA) and report results of a scoping review to identify data and knowledge gaps related to PCA survival and longitudinal clinical and biomarker outcomes. Recent findings: Thirteen longitudinal studies were identified; all but two had fewer than 30 participants with PCA. Relatively few longitudinal data exist, particularly for survival. In PCA, posterior cortical dysfunction and atrophy progress at faster rates compared to non-posterior regions, potentially up to a decade after symptom onset. Unlike typical AD, PCA phenotype-defined cognitive dysfunction and atrophy remain relatively more severe compared to other regions throughout the PCA course. Select cognitive tests hold promise as PCA outcome measures and for staging. Further longitudinal investigations are critically needed to enable PCA inclusion in treatment trials and to provide appropriate care to patients and enhance our understanding of the pathophysiology of dementing diseases.
 
Purpose of Review The benefit of using antiplatelet monotherapy in acute ischemic stroke and secondary stroke prevention is well established. In the last few years, several large randomized trials showed that the use of short-term dual antiplatelet therapy in particular stroke subtypes may reduce the risk of recurrent ischemic events. The aim of this article is to provide a critical analysis of the current evidence and recommendations for the use of antiplatelet agents for stroke prevention. Recent Findings Long-term therapy with aspirin, clopidogrel, or aspirin plus extended-release dipyridamole is recommended for secondary stroke prevention in patients with noncardioembolic ischemic stroke. Short-term dual antiplatelet therapy with aspirin and clopidogrel is superior to antiplatelet monotherapy in secondary stroke prevention when used in patients with mild noncardioembolic stroke or high-risk transient ischemic attack. Dual therapy, however, is associated with an increased risk of major bleeding, particularly when the treatment is extended for greater than 30 days. Similarly, aspirin plus ticagrelor is superior to aspirin monotherapy for the prevention of recurrent ischemic stroke, although this combination is associated with a higher risk of hemorrhagic complications when compared to other dual antiplatelet regimens. Among patients who carry CYP2C19 genetic polymorphisms associated with a slow bioactivation of clopidogrel, short-term treatment with aspirin plus ticagrelor is superior to aspirin plus clopidogrel for the reduction of recurrent stroke; however, the use of ticagrelor is associated with a higher risk of any bleeding. In patients with symptomatic intracranial stenosis, aggressive medical management in addition to dual antiplatelet therapy up to 90 days is recommended. Summary Antiplatelet therapy has an essential role in the management of ischemic stroke. The specific antiplatelet regimen should be individualized based on the stroke characteristics, time from symptom onset, and patient-specific predisposition to develop hemorrhagic complications.
 
SHINE trial primary efficacy outcome according to subgroups. This figure was generated and provided by the SHINE trial Data Coordination Unit at the Medical University of South Carolina RD - risk difference
Purposeof Review Diabetes mellitus (DM) causes systemic vascular complications. Chronic hyperglycemia is a hallmark of DM and appears to be at least partially responsible for the vascular complications. In addition, hyperglycemia during acute tissue injury has been postulated to augment the injury. This review addresses the potential therapeutic benefits related to ischemic stroke from lowering hyperglycemia in two settings, in chronic hyperglycemia and during acute ischemic stroke. Recent Findings A recent efficacy trial to lower hyperglycemia during acute ischemic stroke showed no significant benefit overall as well as in patient subgroups. This finding helps to establish good clinical practice protocols for patients with acute ischemic stroke and hyperglycemia. Summary Hyperglycemia appears to be a key mediator of the systemic vascular complications of DM. Despite current lack of evidence that lowering hyperglycemia during acute ischemic stroke improves functional outcome, unanswered questions remain in specific acute ischemic stroke settings that warrant additional research.
 
A Number of publications relating to the investigation of non-motor symptoms in dystonia per annum over the past 10 years (2011–2021). B Total number of publications examining each non-motor symptom type (psychiatric symptoms, cognition, sleep, pain, and quality of life (QoL)) over the past 10 year. C Schematic representation of key brain regions involved in the network-based model of dystonia and how the non-motor symptoms observed may map onto these anatomical regions
Purpose of Review To review recent literature evaluating psychiatric and cognitive symptoms in dystonia, the two non-motor symptom groups most frequently evaluated in dystonia research and recognised in clinical practice. Recent Findings Recent work has embedded clinical recognition of psychiatric symptoms in dystonia, with depressive and anxiety-related symptoms routinely observed to be the most common. Less explored symptoms, such as self-harm, suicidal ideation, and substance abuse, represent newer areas of investigation, with initial work suggesting higher rates than the background population. Investigation of cognitive function has provided less consistent results, both within individual dystonia subtypes and across the spectrum of dystonias, partly reflecting the heterogeneity in approaches to assessment. However, recent work indicates impairments of higher cognitive function, e.g. social cognition, and disrupted visual and auditory sensory processing. Summary Dystonia demonstrates psychiatric and cognitive symptom heterogeneity, with further work needed to recognise endophenotypes and improve diagnostic accuracy, symptom recognition, and management.
 
Sleep and its disorders strictly interconnected with stroke
The role of sleep disorders in pre-stroke, acute stroke and chronic stroke phases
Purpose of Review To elucidate the interconnection between sleep and stroke. Recent Findings Growing data support a bidirectional relationship between stroke and sleep. In particular, there is strong evidence that sleep-disordered breathing plays a pivotal role as risk factor and concur to worsening functional outcome. Conversely, for others sleep disorders (e.g., insomnia, restless legs syndrome, periodic limb movements of sleep, REM sleep behavior disorder), the evidence is weak. Moreover, sleep disturbances are highly prevalent also in chronic stroke and concur to worsening quality of life of patients. Promising novel technologies will probably allow, in a near future, to guarantee a screening of commonest sleep disturbances in a larger proportion of patients with stroke. Summary Sleep assessment and management should enter in the routinary evaluation of stroke patients, of both acute and chronic phase. Future research should focus on the efficacy of specific sleep intervention as a therapeutic option for stroke patients.
 
Example clinical vignette of a patient with LATE. A 78-year-old woman presents with several years of subjective memory loss and was clinically diagnosed with AD. A At baseline, T1-weighted coronal MRI (top) shows some volume loss in the bilateral hippocampi and medial temporal lobes, with axial FLAIR sequence scan depicting periventricular white matter hyperintensities corresponding to small vessel ischemia. B Ten years after baseline scan, coronal (top) computed tomography (CT) shows mild interval change of limbic structures, with some ventricular dilatation and widening of the lateral fissures compared to prior studies. Small vessel disease is redemonstrated as periventricular hypodensities on axial CT (bottom). C Psychometric testing over about nine years shows slow, minimal decline in Mini-Mental Status Examination (MMSE), Animal fluency, Word List (WL) delayed recall, and Trails B time (natural log-transformed). D At autopsy, immunohistochemistry of the hippocampus with TDP-43 antibody (1D3, images at × 20 and × 50) reveals TDP-43 cytoplasmic inclusions, consistent with a primary neuropathological diagnosis of LATE-NC. Additional staining showed diagnostic evidence of primary age-related tauopathy and Lewy body disease (amygdala-predominant) and did not reflect AD neuropathologic change
Limbic PET imaging patterns in susceptible and resilient patients with similar ¹⁸F-FDG standardized uptake value ratio (SUVR 0.87 to 0.89) but different tau load (SUVR 1.41 to 1.75) in the inferior temporal gyrus (ITG). ¹⁸F-Florbetaben (amyloid), ¹⁸F-Flortaucipir (tau), and.¹⁸F-FDG PET scans are shown for a A cognitively impaired 84-year-old male with amyloid + /tau + status and AD Assessment Scale-Cognitive (ADAS-Cog) score of 37.0 (higher is worse) and a B cognitively impaired 62-year-old female with A + /T + status and ADAS-Cog of 14.7. The patient in A demonstrates an imaging marker related to LATE seen as the relative sparing of the inferior temporal gyrus (I) relative to medial temporal lobe (MTL) and frontal supraorbital gyrus (FSO), measured by higher I/MTL/FSO than the patient in B. Hence, the patient in A has evidence concerning for both AD and non-AD (TDP-43) pathology potentially contributing to neurodegeneration not accounted for by tau pathology alone (as in “limbic susceptibility”)
Purpose of Review Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently defined neurodegenerative disease characterized by amnestic phenotype and pathological inclusions of TAR DNA-binding protein 43 (TDP-43). LATE is distinct from rarer forms of TDP-43 diseases such as frontotemporal lobar degeneration with TDP-43 but is also a common copathology with Alzheimer’s disease (AD) and cerebrovascular disease and accelerates cognitive decline. LATE contributes to clinicopathologic heterogeneity in neurodegenerative diseases, so it is imperative to distinguish LATE from other etiologies. Recent Findings Novel biomarkers for LATE are being developed with magnetic resonance imaging (MRI) and positron emission tomography (PET). When cooccurring with AD, LATE exhibits identifiable patterns of limbic-predominant atrophy on MRI and hypometabolism on ¹⁸F-fluorodeoxyglucose PET that are greater than expected relative to levels of local AD pathology. Efforts are being made to develop TDP-43-specific radiotracers, molecularly specific biofluid measures, and genomic predictors of TDP-43. LATE is a highly prevalent neurodegenerative disease distinct from previously characterized cognitive disorders.
 
Purpose of Review Stroke is a common cause of disability in aging adults. A given individual’s needs after stroke vary as a function of the stroke extent and location. The purpose of this review was to discuss recent clinical investigations addressing rehabilitation of an array of overlapping functional domains. Recent Findings Research is ongoing in the domains of movement, cognition, attention, speech, language, swallowing, and mental health. To best assist patients’ recovery, innovative research has sought to develop and evaluate behavioral approaches, identify and refine synergistic approaches that augment the response to behavioral therapy, and integrate technology where appropriate, particularly to introduce and titrate real-world complexity and improve the overall experience of therapy. Summary Recent and ongoing trials have increasingly adopted a multidisciplinary nature — augmenting refined behavioral therapy approaches with methods for increasing their potency, such as pharmaceutical or electrical interventions. The integration of virtual reality, robotics, and other technological advancements has generated immense excitement, but has not resulted in consistent improvements over more universally accessible, lower technology therapy.
 
Renin–angiotensin–aldosterone pathway with therapeutic targets for personalized hypertension treatment
Changes in systolic blood pressure (A) and diastolic blood pressure (B) over 12 months among Ghanaian ischemic stroke survivors according to renin-aldosterone status
Purpose of Review Worldwide, compared to other racial/ethnic groups, individuals of African ancestry have an excessively higher burden of hypertension-related morbidities, especially stroke. Identifying modifiable biological targets that contribute to these disparities could improve global stroke outcomes. In this scoping review, we discuss how pathological perturbations in the renin–angiotensin–aldosterone pathways could be harnessed via physiological profiling for the purposes of improving blood pressure control for stroke prevention among people of African ancestry. Recent Findings Transcontinental comparative data from the USA and Ghana show that the prevalence of treatment-resistant hypertension among stroke survivors is 42.7% among indigenous Africans, 16.1% among African Americans, and 6.9% among non-Hispanic Whites, p < 0.0001. A multicenter clinical trial of patients without stroke in 3 African countries (Nigeria, Kenya, and South Africa) demonstrated that physiological profiling using plasma renin activity and aldosterone to individualize selection of antihypertensive medications compared with usual care resulted in better blood pressure control with fewer medications over 12 months. Among Ghanaian ischemic stroke survivors treated without renin-aldosterone profiling data, an analysis revealed that those with low renin phenotypes did not achieve any meaningful reduction in blood pressure over 12 months on 3–4 antihypertensive medications despite excellent adherence. Summary For a polygenic condition such as hypertension, individualized therapy based on plasma renin-aldosterone-guided selection of therapy for uncontrolled BP following precision medicine principles may be a viable strategy for primary and secondary stroke prevention with the potential to reduce disparities in the poor outcomes of stroke disproportionately shared by individuals of African ancestry. A dedicated clinical trial to test this hypothesis is warranted.
 
Kidney function declines linearly with age. At age 80 and above, the mean eGFR is approximately 60 mL/min/1.73m². Data are from 3985 patients (1959 women, 2026 men) attending the Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Canada
Carotid total plaque area by quartile of eGFR (CKD-EPI). Carotid plaque burden increases markedly with impaired kidney function. With an eGFR below 80 mL/min per 1.73 m², the mean TPA was above 119 mm², the lower threshold for the top quartile of TPA among vascular prevention patients, with a 5-year risk of stroke/myocardial infarction/vascular death of 20%. Data are from 3985 patients (1959 women, 2026 men) attending the Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Canada
Resistant atherosclerosis by quartile of serum creatinine. Among patients with a serum LDL-C < 1 mmol/L (38 mg/dL), patients with higher serum creatinine levels were more likely to have “Resistant Atherosclerosis,” i.e., plaque progression despite such a low level of LDL-C. The reason for this is probably that the patients with plaque progression were being treated more and more intensively to achieve plaque regression, in a process called “Treating Arteries” instead of merely treating risk factors to consensus targets. (A similar figure stratified by LDL-C < 1.8 was published in: Spence JD, Solo K. Resistant Atherosclerosis: The Need for Monitoring of Plaque Burden. Stroke. 2017;48(6):1624–9)
Effect of renal function on plasma levels of toxic intestinal metabolites. Even a modest reduction of renal function to an eGFR < 66 mL/min per 1.73 m.² was associated with significantly higher plasma levels of all the intestinal metabolites (analysis of variance p < 0.0001 for all except 0.01 for p-cresyl glucuronide and 0.006 for phenyl sulfate). Levels of P-cresyl sulfate were also increased significantly (p < 0.0001), but the levels were much higher (increasing from 30 μmol/L in the highest quartile of eGFR to 70 μmol/L in the lowest quartile), so they are omitted from this graph because of scale. eGFR indicates estimated glomerular function; and TMAO, trimethylamine n-oxide. (Reprinted by permission of Wolters Kluwer Health, from: Spence JD, Azarpazhooh MR, Larsson SC, Bogiatzi C, Hankey GJ. Stroke prevention in older adults: recent advances. Stroke. 2020;51:3770–3777)
Purpose of Review We reviewed reasons for the high cardiovascular risk (CVD) of patients with chronic kidney disease (CKD), and explored alternatives to treatment of traditional risk factors to reduce CVD in CKD. Recent Findings Besides traditional risk factors, patients with CKD are exposed to uremic toxins of two kinds: systemically derived toxins include asymmetric dimethylarginine (ADMA), total homocysteine (tHcy), thiocyanate, tumor necrosis factor alpha, and interleukin 6. Gut-derived uremic toxins (GDUT), products of the intestinal microbiome, include hippuric acid, indoxyl sulfate, p-cresyl sulfate, p-cresyl glucuronide, phenylacetylglutamine, and trimethylamine N-oxide (TMAO). Cyanocobalamin is toxic in patients with CKD. Approaches to reducing plasma levels of these uremic toxins would include diet to reduce GDUT, kidney transplantation, more intensive dialysis, and vitamin therapy to lower tHcy with methylcobalamin rather than cyanocobalamin. Summary The high CVD risk in CKD requires consideration of therapies beyond treatment of traditional risk factors.
 
Neuroanatomy of wake promoting nuclei (A) and REM controlling nuclei (B). Sleep promoting nuclei are not shown here; for a review of neurobiology controlling sleep and wake states, see [137]. A: Several monoaminergic nuclei from the pons and midbrain (green) are involved in arousal including the locus coeruleus (LC), parabrachial nucleus (PB), precoeruleus area (PC), dorsal raphe nuclei (DR), ventral periaqueductal gray matter (vPAG), and tuberomammillary nucleus (TMN). In addition, cholinergic nuclei (light blue), particularly from the lateral dorsal tegmentum (LDT) and pedunculopontine tegmentum (PPT), contribute to the alerting signal. This system is further augmented by cholinergic signal from the basal forebrain (BF), and orexinergic neurons from the lateral hypothalamus (dark blue) stabilize wakefulness and inhibit REM sleep. Brainstem pathology affecting wake promoting nuclei within the midbrain or pons can lead to sleep–wake disruption such as hypersomnia and insomnia. B: REM-generator neurons in the pons and midbrain (red) include the sublaterodorsal nucleus (SLD) and precoeruleus region (PC). These regions have ascending projections to the basal forebrain (BF) that promote a dreaming state and descending projections to the medulla and spine that promote muscle atonia. Disruption of these areas, particularly involving descending projections, may cause REM sleep without atonia and REM sleep behavior disorder. Figure modified with permission from Saper CB et al., Neuron, 2010 [138]
A simplified model linking sleep, circadian rhythms, and neurodegeneration
Purpose of Review To comprehensively summarize the sleep pathologies associated with movement disorders, focusing on neurodegenerative diseases. Recent Findings Mounting evidence has further implicated both sleep and circadian disruption in the pathophysiology of many movement disorders. In particular, recent data illuminate the mechanisms by which poor sleep quality and circadian dysfunction can exacerbate neurodegeneration. In addition, anti-IgLON5 disease is a recently described autoimmune disease with various symptoms that can feature prominent sleep disruption and parasomnia. Summary Many movement disorders are associated with sleep and circadian rhythm disruption. Motor symptoms can cause sleep fragmentation, resulting in insomnia and excessive daytime sleepiness. Many neurodegenerative movement disorders involve brainstem pathology in regions close to or affecting nuclei that regulate sleep and wake. Further, commonly used movement medications may exacerbate sleep concerns. Providers should screen for and address these sleep symptoms to improve function and quality of life for patients and caregivers.
 
Purpose of review: Deep brain stimulation (DBS) is an established treatment in several movement disorders, including Parkinson's disease, dystonia, tremor, and Tourette syndrome. In this review, we will review and discuss the most recent findings including but not limited to clinical evidence. Recent findings: New DBS technologies include novel hardware design (electrodes, cables, implanted pulse generators) enabling new stimulation patterns and adaptive DBS which delivers potential stimulation tailored to moment-to-moment changes in the patient's condition. Better understanding of movement disorders pathophysiology and functional anatomy has been pivotal for studying the effects of DBS on the mesencephalic locomotor region, the nucleus basalis of Meynert, the substantia nigra, and the spinal cord. Eventually, neurosurgical practice has improved with more accurate target visualization or combined targeting. A rising research domain emphasizes bridging neuromodulation and neuroprotection. Recent advances in DBS therapy bring more possibilities to effectively treat people with movement disorders. Future research would focus on improving adaptive DBS, leading more clinical trials on novel targets, and exploring neuromodulation effects on neuroprotection.
 
Purpose of Review To explore recent developments in vestibular migraine (VM). Recent Findings This review discusses the current diagnostic criteria for VM in the adult and pediatric populations, as proposed by the International Headache Society and Bárány Society. Recent VM studies confirm the prior findings and reveal new insights, including the wide range of vestibular symptoms, symptoms in the attack-free period, and triggers. Many patients experience persistent vestibular symptoms, even in the absence of acute attacks, which often significantly impact patients’ quality of life. The syndrome of benign recurrent vertigo and its relationship to migraine, VM, and Meniere’s disease is also discussed. There is a dearth of randomized controlled trials in VM treatment. Prospective and retrospective studies support the benefit of many migraine treatments are effective in VM, including neuromodulation, and calcitonin gene-related peptide monoclonal antibodies. Summary VM affects almost 3% of the population, but remains under-diagnosed. Recent diagnostic criteria can help clinicians diagnose VM in adults and children.
 
Neuroimaging features of catastrophic antiphospholipid syndrome (CAPS). MRI brain showing multifocal areas of restricted diffusion (arrows) on axial DWI sequences highlighting multifocal acute ischemic strokes (A1, A2, A3); non-specific, predominantly subcortical white-matter T2-hyperintensities (arrows) on axial T2 FLAIR sequences (B1, B2); and profound cortical atrophy (arrows) on axial T2 FLAIR sequences (C1, C2) in a 44-year-old woman with CAPS and triple antiphospholipid antibody positivity
Purpose of Review Understanding of antiphospholipid antibody syndrome (APS), associated neurological manifestations, and disease-directed treatment has grown considerably over the last decade. Herein, we critically review the current and high-yield literature related to the pathophysiology, neurological presentations, and management of APS with particular emphasis on the rare and more fatal subset of APS, catastrophic antiphospholipid syndrome (CAPS). Recent Findings APS may manifest with a variety of neurologic syndromes, with cerebrovascular disease representing the most commonly encountered presentation. Diagnostic evaluation and treatment are often tailored to the specific presentation, with suspicion and testing for antiphospholipid antibodies recommended when neurologic presentations occur atypically or in younger individuals. In CAPS, which is more rapidly progressive with multiorgan involvement, potential alternative microangiopathic syndromes should be carefully considered in the differential diagnosis. To date, anticoagulation with vitamin K antagonists remains the mainstay of therapy in APS while triple therapy with anticoagulation, corticosteroids, and plasma exchange is standard of care in CAPS. Immunotherapy has shown early promise in refractory cases. Summary APS is an autoimmune clinical syndrome with neurologic presentations classically characterized by vascular thrombosis, though recent understandings suggest additional direct immune-mediated phenomena. Our understanding of the underlying pathogenic mechanisms of APS continues to grow and will continue to influence our therapeutic approaches.
 
European Headache Federation consensus criteria for resistant and refractory migraine
Purpose of Review Migraine is one of the top reasons for consulting a pediatric neurologist. Although the majority of children and adolescents who receive evidence-based first-line interventions for migraine will improve substantially, a subset of patients develop resistant or refractory migraine. Recent Findings In this review, we summarize the level of evidence for a variety of acute and preventive treatment options to consider in children and adolescents with resistant or refractory migraine. We describe the level of evidence for interventional procedures (onabotulinumtoxinA injections, greater occipital and other nerve blocks), neuromodulation (single-pulse transcranial magnetic stimulation, external trigeminal nerve stimulation, remote electrical neuromodulation, and non-invasive vagal nerve stimulation), calcitonin gene-related peptide (CGRP) pathway antagonists (anti-CGRP monoclonal antibodies and gepants), psychological therapies, and manual therapies (acupuncture, craniosacral therapy, massage and physical therapy, and spinal manipulation).
 
Purpose of Review Sleep disorders are among the most common non-motor symptoms in Parkinson’s disease (PD). Recent longitudinal studies of sleep in PD have utilized validated sleep questionnaires and video-polysomnography performed over multiple time points. This review summarizes existing longitudinal studies focusing on the prevalence, associations, and changes of sleep disorders in PD over time, as well as the methodologies used in these studies. Recent Findings Fifty-three longitudinal studies of sleep in PD were identified: excessive daytime sleepiness, insomnia, obstructive sleep apnea, rapid eye movement sleep behavior disorder (RBD), restless legs syndrome, and shift work disorder were studied in addition to other studies that had focused on either multiple sleep disorders or broadly on sleep disorders as a whole. The prevalence of sleep disorders increases over time and are associated particularly with non-motor features of disease. RBD is now considered an established prodromal feature of PD, but other sleep disorders do not clearly increase risk of subsequent PD. Further work is necessary to determine if treatment of sleep disorders in PD alters disease symptom and their progression or reduces PD risk. Summary Longitudinal studies of sleep in PD have demonstrated a high prevalence of sleep disorders that are associated with non-motor features of PD which can increase over time. More work is necessary to determine if treatment of sleep disorders can alter the course of PD.
 
Purpose of Review We explore the anatomy of the central and peripheral autonomic pathways involved in primary headache as well as the mechanisms for secondary headache associated with disorders of the autonomic nervous system. The prevalence and clinical presentation of cranial and systemic autonomic symptoms in these conditions will be discussed, with a focus on recent studies.Recent FindingsSeveral small studies have utilized the relationship between headache and the autonomic nervous system to identify potential biomarkers to aid in diagnosis of migraine and cluster headache. Headache in postural orthostatic tachycardia syndrome (POTS) has also been further characterized, particularly in its association with orthostatic headache and spontaneous intracranial hypotension (SIH).SummaryThis review examines the pathophysiology of primary and secondary headache disorders in the context of the autonomic nervous system. Mechanisms of headache associated with systemic autonomic disorders are also reviewed.
 
The video-polysomnography. A polysomnograpic 18-s epoch with 2 electro-oculography (EOG) channels (LSO-A2 and RIO-A2), 4 electroencephalography (EEG) channels, an elecrocardiography (ECG) channel, a chin electromyography (EMG) channel, and a leg EMG channel (covering both tibialis anterior muscles). A NREM sleep stage 2 with sleep spindles, K complexes and periodic limb movement. B NREM sleep stage 3 with slow wave sleep. C Rapid-eye-movement (REM) sleep with REM sleep without atonia (RSWA). D A 3-min epoch with respiratory-related variables: a snoring detector channel, a pulse transit time channel, a peripheral pulse oximetry channel, nasal airflow channels, and 2 respiratory effort channels on thorax and abdomen. Several obstructive hypopneas are shown. Blue arrows: periodic limb movements. Green arrows: sleep spindles. Red arrow: rapid-eye-movements on the ocular channels. Yellow arrow: RSWA on the chin EMG channel. Grey arrow: obstructive hypopnea
The PRISMA flowchart. The results of the search strategy are summarized in the PRISMA flow diagram
Purpose of Review Sleep disturbances are an important nonmotor feature of Parkinson’s disease (PD) that can cause polysomnographic (PSG) alterations. These alterations are already present in early PD and may be associated with a specific disease course. This systematic review describes the role of PSG variables as predictors of sleep dysfunction, motor and cognitive dysfunction progression in PD. Recent Findings Nineteen longitudinal cohort studies were included. Their main findings were that (1) REM sleep behavioral events, REM sleep without atonia (RSWA), and electroencephalography (EEG) changes (mainly microsleep instability) are predictors of the development of REM sleep behavior disorder (RBD); (2) RBD, RSWA, and lower slow-wave sleep energy predict motor progression; (3) RBD, EEG slowing, and sleep spindles changes are predictors of cognitive deterioration; and (4) OSA is associated with severe motor and cognitive symptoms at baseline, with inconsistent findings on the effect of continuous positive airway pressure (CPAP) therapy for these symptoms. Summary The results of our systematic review support a role of the video-PSG in disease progression prediction in PD and its usefulness as a biomarker. However, future studies are needed to investigate whether treatment of these PSG abnormalities and sleep disturbances may have a neuroprotective effect on disease progression.
 
Paraganglionic tissue locations in the head and neck. Sara Yang, MD (original illustration by Batsakis JG [2])
Radiologic options in the evaluation of paragangliomas of the head and neck. A Axial contrast-enhanced MRI showing a right glomus jugulare tumor (arrow). B Axial MRI displaying bilateral glomus vagale tumors (arrows). C Cervicocerebral angiogram showing bowing of the external carotid artery (ECA) and internal carotid artery (ICA) by a large carotid body tumor ( ) which also encased the common carotid artery (CCA). D Intraoperative view of a carotid body tumor (CBT) with bowing of the external carotid artery (ECA) and the internal carotid artery (ICA). Vagal nerve (X) and internal jugular vein (IJV)
Purpose of Review This paper will outline the clinical neurologic presentation and diagnostic evaluation of patients with paragangliomas of the head and neck. Contemporary management options will be outlined for these rare and complex tumors. Recent Findings The majority of recent publications and research on these tumors are dedicated to traditional and robotic image-guided radiosurgery in the treatment of head and neck paragangliomas. Summary Paragangliomas are rare, slow-growing tumors of the head and neck which usually cause silent cranial nerve deficits or compensated mild speech or swallowing symptoms. While radiologic surveillance is often the best treatment option, subtotal resection with case-specific radiosurgery is commonly used in patients with large tumors.
 
Non-contrast head CT of a 22-year-old man with DENV encephalitis shows hypodensities in both thalami and brain stem (reprinted from the literature [3••]; case 1.2.1with permission of publishers)
(A) Brain MRI (T2 sequence) of a 16-year-old adolescent girl with dengue fever who presented with seizures, right hemiplegia, and altered sensorium, showing a large left parietal intracerebral hemorrhage. She also complained of visual blurring of the right eye and ophthalmoscopy demonstrated macular edema with star formation (B) (reprinted from the literature [3••]; case 1.2.7 with permission of publishers)
Brain MRI (FLAIR sequence) of a 68-year-old woman with dengue fever presented with generalized seizures and altered sensorium. (a) On admission, brain MRI showed symmetrical hyperintensities in both occipital regions suggestive of PRES. (b) Two weeks after recovery, there was complete resolution of the previously observed signal changes (reprinted from the literature [78••] with permission of publishers)
Purpose of Review To discuss the neurological complications of dengue virus (DENV) infection and their pathogenesis. Recent Findings Include recognition of the four different serotypes of DENV and their epidemiology as well as recognition of the expanded dengue syndrome encompassing multisystem involvement in the severe form of the disease including involvement of the central nervous system (CNS). DENV is a neurotropic virus with the ability to infect the supporting cells of the CNS. Neural injury during the acute stage of the infection results from direct neuro-invasion and/or the phenomenon of antibody-dependent enhancement, resulting in plasma leakage and coagulopathy. Immune mechanisms have been implicated in the development of the delayed neurological sequelae through molecular mimicry. A myriad of neurological syndromes has been described as a result of the involvement of the CNS, the peripheral nervous system (PNS), or both. Summary Neurological manifestations in DENV infection are increasingly being recognized, some of which are potentially fatal if not treated promptly. DENV encephalopathy and encephalitis should be considered in the differential diagnosis of other acute febrile encephalopathies, autoimmune encephalitides, and in cases of encephalopathy/encephalitis related to SARS-CoV2 infection, especially in dengue-endemic areas. Acute disseminated encephalomyelitis (ADEM) may be occasionally encountered. Clinicians should be knowledgeable of the expanded dengue syndrome characterized by the concurrent compromise of cardiac, neurological, gastrointestinal, renal, and hematopopoietic systems. Isolated cranial nerve palsies occur rather uncommonly and are often steroid responsive. These neuropathies may result from the direct involvement of cranial nerve nuclei or nerve involvement or may be immune-mediated. Even if the diagnosis of dengue is confirmed, it is absolutely imperative to exclude other well-known causes of isolated cranial nerve palsies. Ischemic and hemorrhagic strokes may occur following dengue fever. The pathogenesis may be beyond the commonly observed thrombocytopenia and include cerebral vasculitis. Involvement of ocular blood vessels may cause maculopathy or retinal hemorrhages. Posterior reversible encephalopathy syndrome (PRES) is uncommon and possibly related to dysregulated cytokine release phenomena. Lastly, any patient developing acute neuromuscular weakness during the course or within a fortnight of remission from dengue fever must be screened for acute inflammatory demyelinating polyneuropathy (AIDP), hypokalemic paralysis, or acute myositis. Rarely, a Miller–Fisher-like syndrome with negative anti-GQ1b antibody may develop.
 
Eschar in a patient with Scrub typhus
MRI of the brain (FLAIR image) of a 20-year-old woman presenting with fever, headache, diplopia, gaze-evoked nystagmus, and areflexia (clinically suggestive of overlap of Bickerstaff rhombencephalitis and Miller Fisher syndrome) showing a hyperintense lesion involving the pons extending up to the right half of the midbrain along with similar involvement of the right caudate nucleus. Serum IgM for Scrub typhus was positive. The patient recovered fully after treatment with doxycycline (reprinted from [27•]; case 1.5.1 with permission from publishers)
Purpose of Review The occurrence of cases of scrub typhus is on the rise in South Asian and Southeast Asian countries. The present review discusses neurological complications following scrub typhus to appraise clinicians practicing in endemic regions about considering this treatable disease in the differential diagnosis of acute febrile illnesses, especially when accompanied with clinical neurological features. Recent Findings While the association of aseptic meningitis, encephalitis, and meningoencephalitis with scrub typhus is well known, more recently described neurological syndromes associated with scrub typhus include acute disseminated encephalomyelitis, various cranial nerve palsies, cerebellitis, cerebrovascular diseases including cerebral venous sinus thrombosis, transverse myelitis, longitudinally extensive transverse myelitis, Guillain-Barré syndrome, opsoclonus-myoclonus syndrome, parkinsonism, and many more. Early diagnosis is key to successful treatment. While diagnostic confirmation is generally made by the detection of IgM antibody by either ELISA or indirect fluorescent antibody tests, conventional PCR using 56 kDa gene (cPCR) and loop-mediated isothermal amplification assay (LAMP assay), as well as a newly introduced metagenomic next-generation sequencing (mNGS), are currently available for detection of Orientia tsutsugamushi infection in clinically suspected cases. Summary Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. The cutaneous hallmark of the disease is the “eschar.” Scrub typhus results in multisystem involvement. Neurological compromise is present in about 20% of scrub typhus patients and affects both the central nervous system and the peripheral nervous system. The postulated underlying mechanisms include direct invasion of the organism, a vasculitis-like process, or an immune-mediated injury. Diagnosis of scrub typhus is confirmed by detection of O. tsutsugamushi IgM antibody in serum. Awareness among clinicians regarding the varied presentations of this disease is very important in order to reduce morbidity and mortality. Co-infection with dengue and/or chickungunya viruses may occur in endemic regions. The history of an acute febrile illness preceding the neurological illness is crucial. A very careful search for the eschar is essential; however, the absence of the skin lesion cannot exclude the diagnosis of scrub typhus. Neurological manifestations mostly respond to doxycycline therapy.
 
Treatment algorithm for generalized epilepsy
Purpose of Review To summarize current evidence and recent developments in the surgical treatment of drug-resistant generalized epilepsy. Recent Findings Current surgical treatments of drug-resistant generalized epilepsy include vagus nerve stimulation (VNS), deep brain stimulation (DBS) and corpus callosotomy (CC). Neurostimulation with VNS and/or DBS has been shown to be effective in reducing seizure frequency in patients with generalized epilepsy. DBS for generalized epilepsy is primarily consisted of open-loop stimulation directed at the centromedian (CM) nucleus in the thalamus, though closed-loop stimulation and additional targets are being explored. CC can be effective in treating some seizure types and can be performed using traditional surgical techniques or with the less invasive methods of laser ablation and radiosurgery. Summary This current literature supports the use of VNS, DBS and CC, alone or in combination, as palliative treatments of drug-resistant generalized epilepsy.
 
Purpose of Review Epilepsy has a bidirectional association with suicidality, and epilepsy patients are at much higher risk for suicide than the general population. This article reviews the recent literature on suicide risk factors, assessments, and management as they pertain specifically to suicidality in people with epilepsy, a population that requires unique considerations. Recent Findings Risk factors for suicidality include younger age (independent of comorbid psychiatric disorders), poor social support, psychiatric comorbidity (depression, anxiety, obsessive-compulsive symptoms, and alcohol use), and epilepsy-related factors (more frequent seizures, temporal lobe epilepsy, and drug-resistant epilepsy). Most clinicians agree with the need for addressing suicidality; however, there is inconsistency in the approach to caring for these patients. An example neurology clinic-based approach is outlined. Summary Although PWE are at risk for suicide and risk factors have been characterized, care gaps remain. Screening strategies may help close these gaps.
 
Purpose of Review This overview of the history of diagnosis and treatment of multiple sclerosis serves as an introduction to the rich history of multiple sclerosis, and shows we are on a continuum of incremental advances that date back centuries. Recent Findings The current understanding of MS demonstrates a dramatic series of advances and this brief historical overview will provide some context for these discoveries. Summary Although cases we would now recognize as multiple sclerosis can be found in older literature and diaries, the contribution of Jean-Martin Charcot at the Salpêtrière in Paris in 1868 was to frame the clinical and pathological features of a disorder he called la sclérose en plaque disséminées. Soon after, reports came from many countries. Over the next half-century, the diagnosis was a clinical conclusion with no confirmatory tests. Some CSF and evoked potential tests later helped but it remained for the MRI imaging and oligoclonal banding to substantially aid the clinical diagnosis. It is tempting to think that therapy is new in MS, but in previous centuries, hundreds of drugs, procedures, and surgeries were applied to patients with MS, many more than we use today. It remained for the development of the randomized clinical trial to show which therapies were beneficial and safe. Everything changed in 1993 when the first of a long list of new therapies was approved, therapies that were shown to alter the activity and outcome of the disease.
 
Purpose of Review To discuss the neurological complications and pathophysiology of organ damage following malaria infection. Recent Findings The principal advancement made in malaria research has been a better understanding of the pathogenesis of cerebral malaria (CM), the most dreaded neurological complication generally caused by Plasmodium falciparum infection. However, no definitive treatment has yet been evolved other than the use of antimalarial drugs and supportive care. The development of severe cerebral edema in CM results from two distinct pathophysiologic mechanisms. First, the development of “sticky” red blood cells (RBCs) leads to cytoadherence, where red blood cells (RBCs) get stuck to the endothelial walls and between themselves, resulting in clogging of the brain microvasculature with resultant hypoxemia and cerebral edema. In addition, the P. falciparum-infected erythrocyte membrane protein 1 (PfEMP1) molecules protrude from the raised knob structures on the RBCs walls and are in themselves made of a combination of human and parasite proteins in a tight complex. Antibodies to surfins, rifins, and stevors from the parasite are also located in the RBC membrane. On the human microvascular side, a range of molecules involved in host–parasite interactions, including CD36 and intracellular adhesion molecule 1, is activated during interaction with other molecules such as endothelial protein C receptor and thrombospondin. As a result, an inflammatory response occurs with the dysregulated release of cytokines (TNF, interleukins 1 and 10) which damage the blood–brain barrier (BBB), causing plasma leakage and brain edema. This second mechanism of CNS injury often involves multiple organs in adult patients in endemic areas but remains localized only to the central nervous system (CNS) among African children. Summary Neurological sequelae may follow both P. falciparum and P. vivax infections. The major brain pathology of CM is brain edema with diffuse brain swelling resulting from the combined effects of reduced perfusion and hypoxemia of cerebral neurons due to blockage of the microvasculature by parasitized RBCs as well as the neurotoxic effect of released cytokines from a hyper-acute immune host reaction. A plethora of additional neurological manifestations have been associated with malaria, including posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), malarial retinopathy, post-malarial neurological syndrome (PMNS), acute disseminated encephalomyelitis (ADEM), Guillain-Barré syndrome (GBS), and cerebellar ataxia. Lastly, the impact of the COVID-19 pandemic on worldwide malaria control programs and the possible threat from co-infections is briefly discussed.
 
Purpose of Review COVID-19 has posed a continuously evolving challenge for providers caring for patients with multiple sclerosis (MS). While guidelines from national and international organizations came quickly, these have required constant reassessment and modification as the pandemic has progressed. This review aims to assess the first 2 years of literature on COVID-19 relevant to the clinical management of patients with MS. In particular, we will review how MS impacts the risk of COVID-19 infection, how disease-modifying therapies may alter this risk, and explore considerations regarding disease-modifying therapy (DMT) and vaccination for COVID-19. We will also explore potential ways in which a COVID-19 infection may impact multiple sclerosis. Our goal is to provide an overarching review of the major findings at this stage of the pandemic relevant to those that care for patients with MS. Recent Findings Over the course of the COVID-19 pandemic, providers have had to re-evaluate the priorities in the management of MS. A growing number of studies have evaluated the relevant risk factors and considerations regarding MS and particular disease-modifying therapies. Summary The long-term impacts of the pandemic on the health of those with MS will continue to be revealed. In general, most patients with MS do not need major revisions to their treatment plan due to COVID-19 risk. However, individuals who are older, more disabled, and on more potent therapies may need to consider strategies for decreasing their overall risk. Regardless, continued improvement in our understanding of interactions between infections, disease-modifying therapy, and MS are paramount to optimizing the care of those with MS going forward.
 
Purpose of Review Pica is defined by the American Psychiatric Association’s Diagnostic and Statistical Manual, 5th edition (DSM 5) as the ongoing ingestion of materials with no nutritive or food value. More specifically such ingestions must be unremitting for at least 1 month and occur at a developmentally inconsistent age for such behavior. This article reviews the association of pica with pregnancy, micronutrient deficiencies, psychiatric disorders, dementia, and developmental disorders with emphasis on autism spectrum disorders (ASD). Recent Findings Some variants of non-nutritive consumption are prevalent behavioral norms in non-western cultures, so not all picas should be considered pathological. However, the strong association of pica with iron deficiency anemia (IDA) lends credence to the hypothesis that dopamine transmission may be disrupted in this disorder. Picas associated with ASD are resistant to medications but can be treated with applied behavioral analysis therapy (ABA). Summary Etiological hypotheses for pica are explored with a focus on neurobiological, neuroimaging, and psychiatric correlations. Pharmacological management and behavior modification strategies are also discussed. The possibility that pica is a form of addiction analogous to food cravings is introduced and suggested as an area for further research pursuits.
 
Purpose of Review Psychogenic nonepileptic seizures (PNES) are the most common Functional Neurological Disorder/Conversion Disorder subtype. Significant advances have been made related to diagnosis, neurobiology, and treatment. In this review, we summarize updates in diagnosis and management over the past 3 years. Recent Findings Although evidence is mixed for the treatment of PNES, psychotherapeutic modalities remain a powerful instrument to empower patients and reduce seizures. A multidisciplinary, holistic approach is beneficial. While seizure freedom in all patients may not be the achieved endpoint in this chronic, paroxysmal disorder, quality of life can be improved with treatment. Additional treatment modalities and further research are needed for patients who are refractory to current treatment. Summary Evidence-based therapies exist for PNES, and recent findings represent an increased understanding of the clinical and neurophysiologic aspects of PNES.
 
Gender affirming hormone therapy and anti-seizure medications [2••, 3••, 4, 11, 14, 16–18, 20, 21•, 23]
Purpose of Review The goal of this review is to outline the main considerations when treating transgender patients with epilepsy. Points to be addressed include the gender affirming hormone therapy regimens and how they interact with anti-seizure medications and seizure control, as well as common co-morbidities in the transgender epilepsy population. Recent Findings Gender affirming hormone therapy (GAHT) may affect seizure control directly, due to proconvulsant or anticonvulsant properties. GAHT may interact with anti-seizure medications; most notably, estrogen will decrease serum concentration of lamotrigine. Enzyme-inducing anti-seizure medications may decrease hormone levels, potentially interfering with goals of GAHT. Transgender epilepsy patients are at risk for co-morbidities such as decreased bone mineral density and depression. Summary There are minimal direct studies on treatment or outcomes in the transgender epilepsy population. Providers must be knowledgeable about the bi-directional interactions between gender affirming hormone therapy and anti-seizure medications, as well as direct hormonal influences on seizure control. Future research should directly evaluate outcomes in transgender epilepsy patients with regard to seizure control, success of hormone therapy, and management of co-morbidities, to further educate providers and patients how to best manage their healthcare.
 
Cyclical patterns in epilepsy. A Ultradian cycles occur during sleep. Seizures tend to occur during stage 1 and stage 2 of sleep and increased interictal epileptiform activity is most frequently seen in stage 3 (slow wave sleep). NREM parasomnias (e.g., night terrors) occur in the first cycle of stage 3 of sleep at night and REM parasomnias (e.g., nightmares) tend to occur during cycle 4. Cycle 5 is often a state of awakening. B Circadian seizure patterns. Seizures can demonstrate circadian patterns, based on their location, as seen with frontal seizures (12–6 AM) in sleep, generalized seizures (6–9 AM) in wakefulness, temporal lobe seizures (6–9 AM and 9–12 AM) in wakefulness, parietal lobe seizures (6–9 AM), and occipital lobe seizures (9–12 PM and 3–6 PM) [130]. C Seizures and interictal epileptiform activity exhibits multidien cycle patterns, with an average cycling time of 20–35 days seen in patients undergoing long-term monitoring with RNS [138••]. D Circannual cycles of seizures have been reported in 12% of focal epilepsy patients implanted with RNS [125••]. This figure demonstrates a seasonal tendency for seizures to occur during the winter months and cloudy days in a hypothetical patient
Purpose of Review To review the mutual interactions between sleep and epilepsy, including mechanisms of epileptogenesis, the relationship between sleep apnea and epilepsy, and potential strategies to treat seizures. Recent Findings Recent studies have highlighted the role of functional network systems underlying epileptiform activation in sleep in several epilepsy syndromes, including absence epilepsy, benign focal childhood epilepsy, and epileptic encephalopathy with spike-wave activation in sleep. Sleep disorders are common in epilepsy, and early recognition and treatment can improve seizure frequency and potentially reduce SUDEP risk. Additionally, epilepsy is associated with cyclical patterns, which has led to new treatment approaches including chronotherapy, seizure monitoring devices, and seizure forecasting. Adenosine kinase and orexin receptor antagonists are also promising new potential drug targets that could be used to treat seizures. Summary Sleep and epilepsy have a bidirectional relationship that intersects with many aspects of clinical management. In this article, we identify new areas of research involving future therapeutic opportunities in the field of epilepsy.
 
Example of large muscle group movements during polysomnographic recording in a child with RSD. The movements interrupt a period of stable non-REM sleep stage N2 with regular breathing, are associated to increased heart rate, and are followed by unstable non-REM sleep
Purpose of Review Restless sleep disorder (RSD) is a recently identified pediatric sleep disorder characterized by frequent movements during sleep associated with daytime symptoms. In this review we summarize the expanding evidence of the clinical presentation of RSD, potential pathophysiology, associated comorbidities, and current treatment options that will help the pediatrician identify children with RSD in a timely manner. Recent Findings RSD is diagnosed in 7.7% of children referred evaluated in a pediatric sleep center. Children with RSD present with frequent nightly movements during sleep for at least 3 months, and have daytime symptoms related to poor sleep quality including excessive sleepiness, hyperactivity, irritability among other symptoms. Current evidence shows an increased sympathetic predominance, increased NREM sleep instability, and iron deficiency, as well as increased prevalence in parasomnias and attention deficit hyperactivity disorder. Summary Consensus diagnostic criteria were recently published to diagnose RSD and emergent evidence suggests that iron supplementation improves its nighttime and daytime symptoms.
 
Heme biosynthetic pathway. The porphyrias in red are characterized by neurologic dysfunction as opposed to those in green which have cutaneous manifestations represented, most commonly, by skin photosensitivity. ALA synthase 1 is the rate-limiting enzyme in the production of heme in the liver. The activity of this enzyme is controlled via negative-feedback regulation by the intracellular heme pool. ALA, δ-aminolevulinic acid; Gly, glycine
Purpose of Review Porphyrias constitute a group of rare metabolic disorders that result in a deficiency of the heme biosynthetic pathway and lead to the accumulation of metabolic intermediaries. Patients with porphyria can experience recurrent neurovisceral attacks which are characterized by neuropathic abdominal pain and acute gastrointestinal symptoms, including nausea, vomiting, and constipation. Depending on the type of porphyria, patients can present with cutaneous manifestations, such as severe skin photosensitivity, chronic hemolysis, or evidence of neurologic dysfunction, including alterations in consciousness, neurovascular involvement, seizures, transient sensor-motor symptoms, polyneuropathy, and behavioral abnormalities. Recent Findings More recently, cases of posterior reversible encephalopathy syndrome, cerebral vasoconstriction, and acute flaccid paralysis have also been described. While the exact pathogenic mechanisms linking the accumulation of abnormal heme biosynthetic intermediaries to neurologic manifestations have not been completely elucidated, it has been proposed that these manifestations are more common than previously thought and can result in permanent neurologic injury. Summary This article reviews the basic principles of heme synthesis as well as the pathogenic mechanism of disease, presentation, and treatment of acute hepatic porphyrias with emphasis on those with neurologic manifestations.
 
Emerging mechanism of enteroendocrine regulation in Parkinson’s disease (PD). Short-chain fatty acids (SCFA) produced by intestinal microbiota stimulate secretion of glucagon-like peptide 1 (GLP-1) by L-cells via transmembrane free fatty acid receptors (FFAR2). GLP-1 receptors (GLP-1R) on microglia and dopaminergic neurons can influence neuroinflammation, brain pathology, and motor dysfunction. PD stool is characterized by low SCFA content, which likely explains low postprandial systemic GLP-1 found in PD patients. Approaches to increase SCFA with prebiotics or dietary changes may offer neuroprotection as has been shown with GLP-1 agonists such as exendin-4
Purpose of Review Defective gut-brain communication has recently been proposed as a promoter of neurodegeneration, but mechanisms mediating communication remain elusive. In particular, the Parkinson’s disease (PD) phenotype has been associated with both dysbiosis of intestinal microbiota and neuroinflammation. Here, we review recent advances in the PD field that connect these two concepts, providing an explanation based on enteroendocrine signaling from the gut to the brain. Recent Findings There have been several recent accounts highlighting the importance of the microbiota-gut-brain axis in PD. The objective of this review is to discuss the role of the neuroendocrine system in gut-brain communication as it relates to PD pathogenesis, as this system has not been comprehensively considered in prior reviews. The incretin hormone glucagon-like peptide 1 (GLP-1) is secreted by enteroendocrine cells of the intestinal epithelium, and there is evidence that it is neuroprotective in animal models and human subjects with PD. Agonists of GLP-1 receptors used in diabetes appear to be useful for preventing neurodegeneration. New tools and models have enabled us to study regulation of GLP-1 secretion by intestinal microbiota, to understand how this process may be defective in PD, and to develop methods for therapeutically modifying disease development or progression using the enteroendocrine system. Summary GLP-1 secretion by enteroendocrine cells may be a key mediator of neuroprotection in PD, and new findings in this field may offer unique insights into PD pathogenesis and therapeutic strategies.
 
Schema showing current and future tools for diagnosing leptomeningeal disease. Current approaches rely on neuroimaging, CSF cytology, and clinical exam. In future, the detection of circulating tumor cells and cancer-specific nucleic acids from CSF and blood will likely assist in the diagnosis. CTC, circulating tumor cell; cfDNA, cell-free DNA; ctDNA, circulating tumor DNA; miRNA, microRNA
Purpose of Review Leptomeningeal disease (LMD) is a rare, late complication of systemic cancer and is associated with significant neurological morbidity and high mortality. Here we provide an overview of this condition, summarizing key recent research findings and clinical practice trends in its diagnosis and treatment. We also review current clinical trials for LMD. Recent Findings Improved molecular diagnostic tools are in development to enable more sensitive detection of LMD, including circulating tumor cells and circulating tumor DNA. The use of targeted and CNS-penetrant therapeutics has shown survival improvements with tyrosine kinase inhibitors, antibody–drug conjugates, and select chemotherapy. However, these studies have primarily been phase I/II and retrospective analyses. There remains a dearth of clinical trials that include LMD patients. Summary The combination of patient-specific molecular information and novel therapeutic approaches holds significant promise for improving outcomes in patients with LMD.
 
Metabolism of bilirubin. Bilirubin originates primarily from the senescence of circulating red blood cells. Heme, a protoporphyrin ring that functions as a prosthetic group in hemoglobin (Hb), is sequentially metabolized to biliverdin and bilirubin. In physiologic conditions, more than 99% of the unconjugated bilirubin in the circulation is bound to albumin and only a small portion remains as free bilirubin which is liposoluble and can cross the blood–brain barrier. In the liver, bilirubin is conjugated with glucuronic acid which is water soluble and excreted into the biliary track and the intestine. Hyperbilirubinemia in the neonate can result from overproduction of bilirubin (hemolytic anemia), low availability of albumin, reduced UDP-glucuronyltransferase activity, or impaired excretion
Purpose of Review Hyperbilirubinemia is commonly seen in neonates. Though hyperbilirubinemia is typically asymptomatic, severe elevation of bilirubin levels can lead to acute bilirubin encephalopathy and progress to kernicterus spectrum disorder, a chronic condition characterized by hearing loss, extrapyramidal dysfunction, ophthalmoplegia, and enamel hypoplasia. Epidemiological data show that the implementation of universal pre-discharge bilirubin screening programs has reduced the rates of hyperbilirubinemia-associated complications. However, acute bilirubin encephalopathy and kernicterus spectrum disorder are still particularly common in low- and middle-income countries. Recent Findings The understanding of the genetic and biochemical processes that increase the susceptibility of defined anatomical areas of the central nervous system to the deleterious effects of bilirubin may facilitate the development of effective treatments for acute bilirubin encephalopathy and kernicterus spectrum disorder. Scoring systems are available for the diagnosis and severity grading of these conditions. The treatment of hyperbilirubinemia in newborns relies on the use of phototherapy and exchange transfusion. However, novel therapeutic options including deep brain stimulation, brain-computer interface, and stem cell transplantation may alleviate the heavy disease burden associated with kernicterus spectrum disorder. Summary Despite improved screening and treatment options, the prevalence of acute bilirubin encephalopathy and kernicterus spectrum disorder remains elevated in low- and middle-income countries. The continued presence and associated long-term disability of these conditions warrant further research to improve their prevention and management.
 
Purpose of Review The present review discusses the neurological complications associated with myocarditis of different etiologies. Recent Findings Myocarditis can be idiopathic or caused by different conditions, including toxins, infections, or inflammatory diseases. Clinical findings are variable and range from mild self-limited shortness of breath or chest pain to hemodynamic instability which may result in cardiogenic shock and death. Several neurologic manifestations can be seen in association with myocarditis. Tissue remodeling, fibrosis, and myocyte dysfunction can result in heart failure and arrhythmias leading to intracardiac thrombus formation and cardioembolism. In addition, peripheral neuropathies, status epilepticus, or myasthenia gravis have been reported in association with specific types of myocarditis. Summary Multiple studies suggest the increasing risk of neurologic complications in patients with myocarditis. Neurologists should maintain a high suspicion of myocarditis in cases presenting with both cardiovascular and neurological dysfunction without a clear etiology.
 
Polysomnography in central sleep apnea. a The above tracing shows central sleep apnea with ataxic breathing pattern. Note the absence of airflow without respiratory effort characteristic of central apnea. The oximetry shows associated desaturations. b The tracing shows the EEG (C3M2), Cflow (airflow), thoracic (THO), and abdominal (ABD) belts to assess respiratory effort and the IPAP (inspiratory positive airway pressure) and EPAP (expiratory positive airway pressure) being provided via machine. Note again the absence of airflow without respiratory effort defining central apnea
Purpose The purpose of this article is to review the recent literature on central apnea. Sleep disordered breathing (SDB) is characterized by apneas (cessation in breathing), and hypopneas (reductions in breathing), that occur during sleep. Central sleep apnea (CSA) is sleep disordered breathing in which there is an absence or diminution of respiratory effort during breathing disturbances while asleep. In obstructive sleep apnea (OSA), on the other hand, there is an absence of flow despite ongoing ventilatory effort. Recent Findings Central sleep apnea is a heterogeneous disease with multiple clinical manifestations. Summary OSA is by far the more common condition; however, CSA is highly prevalent among certain patient groups. Complex sleep apnea (CompSA) is defined as the occurrence/emergence of CSA upon treatment of OSA. Similarly, there is considerable overlap between CSA and OSA in pathogenesis as well as impacts. Thus, understanding sleep disordered breathing is important for many practicing clinicians.
 
Purpose of Review We reviewed lipid-modifying therapies and the risk of stroke and other cerebrovascular outcomes, with a focus on newer therapies. Recent Findings Statins and ezetimibe reduce ischemic stroke risk without increasing hemorrhagic stroke risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors similarly reduce ischemic stroke risk in statin-treated patients with atherosclerosis without increasing hemorrhagic stroke, even with very low achieved low-density lipoprotein cholesterol levels. Icosapent ethyl reduces the risk of total and first ischemic stroke in patients with established cardiovascular disease or diabetes mellitus. Clinical outcome trials are underway for newer lipid-modifying agents, including inclisiran, bempedoic acid, and pemafibrate. New biologic agents including evinacumab, pelacarsen, olpasiran, and SLN360 are also discussed. Summary In addition to statins and ezetimibe, PCSK9 inhibitors and icosapent ethyl reduce the risk of ischemic stroke without increasing the risk of hemorrhagic stroke. These therapies dramatically expand options for reducing stroke in high-risk settings.
 
Top-cited authors
Michelle H Cameron
  • Oregon Health and Science University
Sheri Holmen
  • University of Utah
Martha Nance
  • Park Nicollet Health Services
Eamonn M M Quigley
  • Houston Methodist Hospital
Alexander Rotenberg
  • Harvard Medical School