A 14-year-old girl presented to the epilepsy monitoring unit for diagnostic evaluation of recurrent episodic abdominal pain. During the admission, multiple typical episodes lacked ictal correlate, and she was diagnosed with nonepileptic events. However, her long-term EEG recording revealed several transient findings in wakefulness and sleep exemplifying normal developmental variants in the awake (Figure

Previous reports of variants associated with the MAP1B gene in patients with periventricular nodular heterotopia (PVNH) have described frontally predominant PVNH and perisylvian polymicrogyria, with clinical manifestations of seizures and cognitive impairment.1

Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS occurring in immunocompromised individuals in which large demyelinating lesions are induced by polyomavirus JC (JCV). In the absence of effective antiviral treatment, control of the infection relies on restoring anti-JCV immunity. Thus, particularly in long-standing immunocompromising conditions such as organ transplantation

Objectives To determine the timing and predictors of T2-lesion resolution in myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). Methods This retrospective observational study using standard-of-care data had inclusion criteria of MOGAD diagnosis, ≥2 MRIs 12 months apart, and ≥1 brain/spinal cord T2-lesion. The median (interquartile range [IQR]) number of MRIs (82% at disease onset)

Objectives To identify the type, frequency, and consequences of seizures while driving (SzWD) in people with epilepsy before diagnosis. Methods We performed a retrospective cohort study using the Human Epilepsy Project (HEP) to identify prediagnostic SzWD. Clinical descriptions from seizure diaries and medical records were used to classify seizure types and frequencies, time to diagnosis, and SzWD

Objectives The etiology of central retinal artery occlusion (CRAO) is unclear in approximately 50% of patients, suggesting pathomechanical heterogeneity; moreover, little is known about outcomes according to etiology. This study investigated whether the presence of an embolic source affects outcome in CRAO. Methods CRAO patients within 7 days of symptom onset were retrospectively enrolled. Clinical

Objectives The purpose of this report was to study the incidence of sudden unexpected death in epilepsy (SUDEP) after laser interstitial thermal therapy (LITT) for drug-resistant epilepsy (DRE). Methods A prospective observational study of consecutive patients treated with LITT between 2013 and 2021 was conducted. The primary outcome was the occurrence of SUDEP during postoperative follow-up. Surgical

Background and Objectives Chronic axonal polyneuropathy is a common disease of the peripheral nervous system with increasing prevalence with age. Typical neurologic signs are present in patients with polyneuropathy but may also occur in individuals without disease. Owing to limited knowledge on normal aging of the peripheral nervous system, it can be difficult to distinguish peripheral nerve dysfunction

Background and Objectives The APOE 4 allele confers susceptibility to faster decline in odor identification and subsequently to Alzheimer disease (AD). Odor identification requires recognizing and naming odors and detecting them (odor sensitivity). Whether APOE 4 is associated with decline of odor sensitivity and whether such decline serves as a harbinger of cognitive decline and AD remains unclear

Background and Objectives Research on olfaction and brain neuropathology may help understand brain regions associated with normal olfaction and dementia pathophysiology. To identify early regional brain structures affected in poor olfaction, we examined cross-sectional associations of microstructural integrity of the brain with olfaction in the Atherosclerosis Risk in Communities Neurocognitive Study

Background and Objectives The objective of this study was to determine the relationship between plasma β-amyloid (Aβ), specifically the ratio of 2 Aβ peptides (the Aβ42/Aβ40 ratio, which correlates with increased accumulation of Aβ in the CNS), and late-onset epilepsy (LOE). Methods We used Medicare fee-for-service claims codes from 1991 to 2018 to identify cases of LOE among 1,424 Black and White

Background and Objectives For children with cerebral malaria, mortality is high, and in survivors, long-term neurologic and cognitive dysfunctions are common. While specific clinical factors are associated with death or long-term neurocognitive morbidity in cerebral malaria, the association of EEG features with these outcomes, particularly neurocognitive outcomes, is less well characterized. Methods

Background and Objectives Surgery is an effective treatment for drug-resistant epilepsy, which modifies the brain's structure and networks to regulate seizure activity. Our objective was to examine the relationship between brain structure and function to determine the extent to which this relationship affects the success of the surgery in controlling seizures. We hypothesized that a stronger association

Background and Objectives Early treatment is associated with better long-term outcomes in patients with a first demyelinating event and early multiple sclerosis (MS). However, magnetic resonance (MR) findings are not usually integrated to construct propensity scores (PSs) when evaluating outcomes. We assessed the association of receiving very early treatment with the risk of long-term disability including

Many adult patients with a history of seizures and global developmental delay do not have an identified etiology for their epilepsy. Rapid whole-genome sequencing (rWGS) can be used to identify a genetic etiology in critically ill patients to provide actionable interventions. In this case, a 27-year-old patient with a history of epilepsy, global developmental delay, and intellectual disability presented

A 59-year-old man had severe and constant oral, facial, lingual dyskinesias and memory loss after metoclopramide and prochlorperazine treatment for approximately 3 months. Brain MRI and reversible causes of memory loss (vitamin B12, folate, and thyroid-stimulating hormone) were normal. PET CT scan (Figure 1) showed significant hypometabolism of bilateral frontal, temporal lobes and caudate nuclei.

Fifty years have passed since the 1973 publication of Awakenings, a remarkable book by a remarkable author, Oliver Sacks.1 At the time he wrote it, Sacks was a newly minted neurologist and, approaching age 40 years, struggling to find his place in the world. By chance, he sought work at a hospital in New York that housed patients who, decades earlier, contracted encephalitis lethargica. First encountered

Our fate and the world's hinges on our brains. As the mediator of all our experiences and motor of all our actions, the brain's state and performance become paramount in an increasingly complex world. This is reflected in the expanding interest in "brain health." However, "brain health" is defined in many ways or not at all but used with profligate ease. We need to anchor the multiple definitions to

Brain health is crucial to optimizing both the function and well-being of every person at each stage of life and is key to both individual and social progress. As a concept, brain health is complex and requires a multidisciplinary collaborative approach between many professional and public organizations to bring into effect meaningful change. Neurologists are uniquely positioned to serve as specialists

We are saddened by the passing in June 2023 of Dr. Martin A. Samuels at age 77 years. Marty made an indelible mark on Neurology through contributions to the field and, because of his personal and professional range, was perhaps the most recognizable neurologist in America. He was a remarkable man in many respects, but none so much as a friend who would extend himself for everyone in his orbit.

Late-onset epilepsy, or epilepsy that begins in late adulthood, now accounts for approximately 50% of all new cases of epilepsy and is a growing public health concern. Older adults are not only the fastest growing demographic worldwide, but the proportion of older adults developing epilepsy has more than quadrupled over the past 50 years.1 In up to half of all patients with late-onset epilepsy, the

Over the past decades, clinical trial successes have led to a profusion of treatment options for multiple sclerosis (MS), while evolving consensus definitions of disease have allowed for earlier diagnosis. Best practices for using these treatment options have yet to be fully defined and adopted. Particularly, the timing of when disease-modifying therapies (DMTs) should be initiated and the sequencing

A 54-year-old man from rural China presented with a 4-month history of proximally progressive weakness in the left upper limb, where diminished strength and hyperreflexia were noted. Head MRI showed a 5.5 x 4.8 x 4.6-cm right frontoparietal septate cyst with an enhancing mural nodule (Figure 1, A–C). CT revealed foci of calcification (Figure 1D). Diagnosis of neurocysticercosis was suspected, given

A 51-year-old man developed sudden-onset anterograde amnesia several hours after a typical migraine attack. He had no medical history or vascular risk factors other than a migraine disorder since early adulthood. There were no deficits in other cognitive domains and no loss of personal identity. Symptoms resolved within 24 hours. CT brain and angiogram during the episode were normal; however, CT perfusion

The primary function of the cerebellum is the coordination and regulation of movement; therefore, cerebellar tumors usually present with ataxia, dysarthria, and vertigo. Large tumors also cause elevated intracranial pressure that may lead to a disturbance of consciousness. Furthermore, it has become increasingly evident that the cerebellum plays a substantial role in cognitive and affective processing

Background and Objectives Medulloblastomas are embryonal tumors predominantly affecting children. Recognition of molecularly defined subgroups has advanced management. Factors influencing the management and prognosis of adult patients with medulloblastoma remains poorly understood. Methods We examined the management, prognostic factors, and, when possible, molecular subgroup differences (subset) in

Background and Objectives IV thrombolysis (IVT) for suspected ischemic stroke in patients with intracranial neoplasms is off-label. However, data on risks of intracranial hemorrhage (ICH) are scarce. Methods In a multicenter registry-based analysis within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration, we assessed frequencies of symptomatic and fatal ICH after IVT for suspected

Background and Objectives Growing evidence links air pollution with dementia risk, but the biological mechanisms are largely unknown. We investigated the role played by homocysteine (tHcy) and methionine in this association and explored whether this could be explained by cardiovascular diseases (CVDs). Methods Data were extracted from the ongoing Swedish National study on Aging and Care in Kungsholmen

Background and Objectives Choroid plexus (ChP) is emerging as a key brain structure in the pathophysiology of neurodegenerative disorders. In this observational study, we investigated ChP volume in a large cohort of patients with frontotemporal lobar degeneration (FTLD) spectrum to explore a possible link between ChP volume and other disease-specific biomarkers. Methods Participants included patients

Background and Objectives The predictable Braak staging scheme suggests that cortical tau progression may be related to synaptically connected neurons. Animal and human neuroimaging studies demonstrated that changes in neuronal activity contribute to tau spreading. Whether similar mechanisms explain tau progression from the locus coeruleus (LC), a tiny noradrenergic brainstem nucleus involved in novelty

Background and Objectives Progressive nigrostriatal pathway degeneration occurs in individuals with dementia with Lewy bodies (LB). Our objective was to investigate whether repeat 123[I]-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) single photon emission computed tomography (SPECT) can identify progressive dopaminergic loss in mild cognitive impairment (MCI) with Lewy

Background and Objectives Neuropsychiatric symptoms (NPS) are closely associated with cognitive decline in patients with Parkinson disease (PD). We investigated which profiles of NPS are associated with the risk of dementia in PD with mild cognitive impairment (PD-MCI). Methods We retrospectively assessed 338 patients with PD-MCI from a single tertiary hospital, who underwent neuropsychological tests

In the Contemporary Issues in Practice, Education, & Research article "Flowchart for Implementing Advanced Imaging and Electrophysiology in Patients With Disorders of Consciousness: To fMRI or Not to fMRI?" by Monti and Schnakers,1 first published online January 20, 2022, pervasive errors were introduced into Figure 1 during the figure editing process. The corrected Figure 1 has been resupplied online

We thank Drs. Shah, Carhuapoma, Hanley, and Ziai for their comments. Our study is an analysis of intracerebral hemorrhage (ICH) outcomes in a real-world setting.1 We agree that it should inform, not determine current practice, much as did the original ICH score study.2

Abulhasan et al.1 reported unfavorable outcomes in patients with intracerebral hemorrhage (ICH) despite "aggressive" treatment and concluded that poor outcomes in ICH are related to the primary insult, not a consequence of premature termination of medical care. The conclusion is concerning because it suggests that aggressive treatment of ICH may not improve outcome.

In "Functional Outcomes and Mortality in Patients With Intracerebral Hemorrhage After Intensive Medical and Surgical Support," Abulhasan et al. reported outcome data for 319 patients with spontaneous intracerebral hemorrhage (ICH) treated with at least 3 days of aggressive medical management consistent with the 2015 Canadian stroke guidelines. They found that (1) 3-month mortality was 22%; (2) 3-month

It is late in the evening, yet the dawn of my night shift. The nurse pages me with concern, taking me away from all the admissions, discharges, family updates, pages, and orders that routinely fill the night of a postgraduate year (PGY)–2 neurology resident. I enter the patient's dark, quiet room. She has progressive neuromuscular respiratory failure and her wishes had been clear: Do Not Intubate.

Rho-associated coiled-coil containing kinases (ROCK), including ROCK1 and ROCK2, are the primary effectors of the Rho family of small guanosine triphosphatases (GTPases)1 (Figure). The Rho/ROCK signaling pathway has a critical role in regulating the cytoskeleton dynamics responsible for cell adhesion, proliferation, motility, and contraction.2,3 In the nervous system, ROCK proteins phosphorylate a

In this review, we describe the pathophysiology, diagnosis, and treatment of spinal dorsal intradural arteriovenous fistulas (DI-AVFs), focusing on novel research areas. DI-AVFs compose the most common subgroup of spinal arteriovenous lesions and most commonly involve the thoracic spine, followed by lumbar and sacral segments. The pathogenesis underlying DI-AVFs is an area of emerging understanding

In this issue of Neurology®, Inoue et al.1 describe a patient with a small cerebellar hemangioblastoma who presented for evaluation of depression, emotional blunting, and concentration difficulties developing over a period of 1 month. Examination revealed depression, anxiety, errors on the Mini-Mental State Examination, and impairments in attention, executive function, and processing speed. She demonstrated

Several neurodegenerative diseases affect the midbrain dopaminergic system. A key component of disease pathogenesis is dysfunction of presynaptic dopamine neurotransmission by the dopamine transporter (DAT). The DAT is a sodium/chloride–dependent transporter responsible for dopamine release and reuptake, thereby maintaining dopaminergic homeostasis in the extracellular environment, which plays a key

Neuropsychiatric symptoms (NPS) include apathy, emotional dysregulation, impulse control disorders, social inappropriateness, and abnormal perception or thought content.1 Such symptoms are common and affect quality of life and caregiver burden in people living with Parkinson disease (PD).2 In this issue of Neurology®, Lee et al.3 publish a study in which they examined which profile of NPS is associated

A 23-year-old woman presented with constant pendular vertical oscillations in primary gaze along with bilateral horizontal gaze palsy (Video 1) within 3 days of acute pontine hemorrhage (Figure). There was no palatal tremor. Gaze palsy was likely due to involvement of the paramedian pontine reticular formation. Pendular vertical oscillations (PVOs) after pontine stroke are a unique clinical finding

A 53-year-old man with a history of left parietal astrocytoma treated with radiation at age 14 years, epilepsy, diabetes mellitus, hyperlipidemia, prior tobacco use, chronic lacunar infarcts, and left basal ganglia infarct 1 month prior with petechial hemorrhage continued on 81 mg of aspirin daily presented with acute-onset lethargy. Neurologic examination showed acute-on-chronic right hemiparesis

CSF1R-related leukoencephalopathy is an autosomal dominant neurologic disorder causing microglial dysfunction with a wide range of neurologic complications, including motor dysfunction, dementia, and seizures. This case report highlights an unusual presentation of CSF1R-related leukoencephalopathy with radiographic spinal cord involvement initially diagnosed as multiple sclerosis. This case highlights

Background and Objectives The objective of this study was to determine the external validity of the Axon Registry by comparing the 2019 calendar year data with 2 nationally representative, publicly available data sources, specifically the National Ambulatory Medical Care Survey (NAMCS) and the Medical Expenditure Panel Survey (MEPS). The Axon Registry is the American Academy of Neurology's neurology-focused

Background and Objectives Inclusion body myositis (IBM) is a progressive autoimmune skeletal muscle disease in which cytotoxic CD8+ T cells infiltrate muscle and destroy myofibers. IBM has required a muscle biopsy for diagnosis. Here, we administered to patients with IBM a novel investigational PET tracer 89Zr-Df-crefmirlimab for in vivo imaging of whole body skeletal muscle CD8 T cells. This technology

Background and Objectives It is unclear whether blood pressure variability's (BPV) association with worse outcomes is unique to patients with stroke or a risk factor among all critically ill patients. We (1) determined whether BPV differed between patients with stroke and nonstroke patients, (2) examined BPV's associations with in-hospital death and favorable discharge destination in patients with

Background and Objectives Apraxia is commonly attributed to left hemisphere (LH) lesions of the cortical fronto-temporo-parietal praxis networks or white matter lesions causing disconnections between cortical nodes. By contrast, the contribution of lesions to the subcortical gray matter, that is, basal ganglia or thalamus, to apraxic deficits remains controversial. Here, we investigate whether damage

Background and Objectives Prevention strategies for Alzheimer disease and Alzheimer disease–related dementias (AD/ADRDs) are urgently needed. Lipid variability, or fluctuations in blood lipid levels at different points in time, has not been examined extensively and may contribute to the risk of AD/ADRD. Lipid panels are a part of routine screening in clinical practice and routinely available in electronic

Background and Objectives Due to current limitations in diagnosing chronic traumatic encephalopathy (CTE) clinically, traumatic encephalopathy syndrome (TES) has been proposed as the clinical presentation of suspected CTE. This study aimed to determine whether there was an association between a clinical diagnosis of TES and subsequent temporal decline in cognitive or MRI volumetric measures. Methods

Background and Objectives Epidemiologic evidence has shown that social isolation, a low frequency of social contact with others, is associated with the risk of dementia and late-life depressive symptoms. Therefore, we hypothesized that low frequency of social contact may be involved in brain atrophy, and depressive symptoms may play some role in this relationship. We aimed to evaluate the association

We thank Stenzel et al. for their comment on our article1 and agree that muscle biopsy analysis should ideally use more "modern" pathologic analysis to help distinguish polymyositis (PM) from inclusion body myositis (IBM). We have recently shown that transcriptomics2,3 or reverse transcription PCR detection of mis-splicing events from muscle biopsies because of TAR DNA-binding protein 43 loss of function

We read with interest the article by Michelle et al.1 about clinical subgroups and factors associated with progression in patients with inclusion body myositis (IBM). The authors used Griggs criteria,2 European Neuromuscular Centre 2011 criteria, and Lloyd Greenberg data-derived criteria,3 including endomysial inflammation, invasion of non-necrotic fibers, and rimmed vacuoles.

Dr. Michelle and investigators from the Johns Hopkins Myositis Center retrospectively analyzed clinical and pathologic data from 335 patients with inclusion body myositis (IBM) to identify unique phenotypes of the condition. The distinct clinical and pathologic characteristics of each demographic subgroup may be useful in clinical trial design and prognostication. Among the key findings, patients meeting

A 46-year-old man experienced a complete C6 spinal cord injury with minimal recovery. Two years later, he underwent olfactory stem cell injection into the cervical posttraumatic syrinx but developed progressive weakness. A C5 syringo-subarachnoid shunt was placed, but his strength declined further, so he underwent syrinx evacuation. On dural opening, white gelatinous material exuded under pressure

A 49-year-old man presented with low-grade fever for 4 weeks, headache and vomiting for 2 weeks, and altered sensorium for 1 day. He was drowsy, was obeying intermittently, and had terminal neck stiffness, but no localizing/lateralizing neurologic signs. Brain MRI showed right occipital lobe lesion (Figure 1), and CT chest showed features of pneumonitis (Figure 2, C and D). Differential diagnosis included

Objectives This study investigated video eye tracking (VET) in comatose patients with traumatic brain injury (TBI). Methods We recruited healthy participants and unresponsive patients with TBI. We surveyed the patients' clinicians on whether the patient was tracking and performed the Coma Recovery Scale–Revised (CRS-R). We recorded eye movements in response to motion of a finger, a face, a mirror,

Objectives To assess the frequency and characteristics of late responders (>12 weeks) to monoclonal antibodies (mAbs) targeting the calcitonin gene–related peptide (CGRP). Methods This is a multicenter (n = 16) prospective real-life study considering all consecutive adults with high-frequency or chronic migraine treated with anti-CGRP mAbs for ≥24 weeks. We defined responder patients with a ≥50% reduction

Juhn A. Wada, MD