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Altered mental status is a nonspecific diagnosis that encompasses a wide spectrum of disease and is frequently cited as a reason for both hospital admission and inpatient neurologic consultation. There are numerous etiologies of altered mental status, and so although many are facile with the workup of this potentially life-threatening entity, it can nevertheless be overwhelming. Our goal was to provide a practical framework embedded in a current, comprehensive review of the epidemiology, clinical evaluation, and management of undifferentiated altered mental status. We pay particular attention to the management of a critical yet underdiagnosed subtype of altered mental status: delirium.

ImportanceDespite discrete etiologies leading to delirium, it is treated as a common end point in hospital and in clinical trials, and delirium research may be hampered by the attempt to treat all instances of delirium similarly, leaving delirium management as an unmet need. An individualized approach based on unique patterns of delirium pathophysiology, as reflected in predisposing factors and precipitants, may be necessary, but there exists no accepted method of grouping delirium into distinct etiologic subgroups.ObjectiveTo conduct a systematic review to identify potential predisposing and precipitating factors associated with delirium in adult patients agnostic to setting.Evidence ReviewA literature search was performed of PubMed, Embase, Web of Science, and PsycINFO from database inception to December 2021 using search Medical Subject Headings (MeSH) terms consciousness disorders, confusion, causality, and disease susceptibility, with constraints of cohort or case-control studies. Two reviewers selected studies that met the following criteria for inclusion: published in English, prospective cohort or case-control study, at least 50 participants, delirium assessment in person by a physician or trained research personnel using a reference standard, and results including a multivariable model to identify independent factors associated with delirium.FindingsA total of 315 studies were included with a mean (SD) Newcastle-Ottawa Scale score of 8.3 (0.8) out of 9. Across 101 144 patients (50 006 [50.0%] male and 49 766 [49.1%] female patients) represented (24 015 with delirium), studies reported 33 predisposing and 112 precipitating factors associated with delirium. There was a diversity of factors associated with delirium, with substantial physiological heterogeneity.Conclusions and RelevanceIn this systematic review, a comprehensive list of potential predisposing and precipitating factors associated with delirium was found across all clinical settings. These findings may be used to inform more precise study of delirium’s heterogeneous pathophysiology and treatment.

Even low-acuity patients suffer from disrupted sleep in the hospital in part due to routine overnight vital sign (VS) checks. When invasive monitoring is not needed, vital sign monitoring devices (VSMDs) similar to consumer-grade health monitors may play a role in promoting sleep, which can aid healing and recovery.We provided one VSMD to neuroscience ward patients during their hospital stays and used surveys to assess patient and nurse attitudes toward the device and the impact of the device on patient comfort. We also compared VSMD-streamed vS data to nurse-recorded vS data in the chart to evaluate the consistency of data streaming and data concordance between the device and nurse-collected vital sign values.21 patients and 15 nurses enrolled. Overall, patients and nurses responded positively to the device and patients preferred wearing the device to receiving manual vital checks overnight. The most common device-related cause of sleep disruption per patients was device weight (29%). Device vS were concordant with nurse vS on average but there was significant variance in agreement between nurse and device values.Patients and nurses feel positively about the use of VSMDs and their use in the hospital. The device we tested may be limited in its sleep promotion by its weight and patient comfort assessment. Further research is needed to assess the precision of the device in measuring vital signs when used in a clinical setting. Future studies should compare VSMD models and assess their impacts on patient sleep in the absence of manual vS checks overnight.Funding provided by the SaraEvan Williams Foundation Endowed Neurohospitalist Chair at UCSF.

Women's Neurology is an emerging subspecialty that focuses on neurologic disorders across a woman's lifetime. This new domain recognizes that both health and disease are directly affected by hormonal and reproductive changes throughout the life span. This field includes neurologic diseases with a higher prevalence in women and diseases that require specialized management during pregnancy, postpartum period, lactation, and menopause. A survey was sent to US neurology residency program directors to understand the state of training in the area. Their responses highlighted an urgent need for additional education in this field for neurology residents. In this study, we discuss the educational gaps in this area, the clinical benefits of a women's neurology discipline, and the instructional gaps in this area and provide practical recommendations for training programs in women's neurology using 2 innovative fellowship programs.

Background and ObjectivesDiagnosis and treatment of CNS nocardiosis is challenging and often delayed, which increases morbidity and mortality. The primary objective was to compare the clinical and radiographic characteristics of patients with CNS nocardiosis with non-Nocardiabacterial brain abscesses.MethodsWe performed a case-control study of patients with brain abscesses diagnosed between 1998 and 2018 at a tertiary academic center. We identified 56 patients with brain MRI demonstrating brain abscess from the institutional imaging database: 14 with culture-confirmed nocardiosis and 42 randomly selected prevalent controls with culture-confirmed non-Nocardiabacterial infection. The primary outcomes were the diagnosis of concomitant lung infection and history of immunosuppression. Secondary outcomes included abscess radiographic characteristics: multifocality, occipital lobe and/or infratentorial location, and bilobed morphology.ResultsCompared with patients with non-Nocardiabrain abscesses, patients with CNS nocardiosis were older (median 61 years [IQR 59–69] vs 48 years [IQR 34–61];p= 0.03), more likely to be immunosuppressed [71% (10) vs 19% (8);p< 0.001), have diabetes (36% (5) vs 10% [4];p= 0.03), or a concomitant lung infection (86% [12] vs 2% [1];p< 0.001). Radiographically, more cases of CNS nocardiosis exhibited multifocal abscesses (29% [4] vs 2% [1];p= 0.01), which were located in the infratentorial (43% [6] vs 10% (4);p= 0.01) or occipital (36% [5] vs 5% [2];p= 0.008) regions and had a bilobed (as opposed to unilobed) morphology (79% [11] vs 19% [8];p< 0.001). Blood and CSF cultures were negative in most of the cases and controls, whereas neurosurgical specimen culture yielded a diagnosis in 100% of specimens.DiscussionPatients with CNS nocardiosis were more likely to be older, have a history of diabetes or immunosuppression, or have a concomitant lung infection compared with those with non-Nocardiabrain abscesses. Abscesses because of CNS nocardiosis were more likely to be multifocal, affect the infratentorial region or occipital lobe, or have a bilobed appearance. Neurosurgical specimen culture was most likely to yield a diagnosis for bothNocardiaand non-Nocardiaabscesses. The combination of clinical and imaging findings may suggest CNS nocardiosis and inform early initiation of targeted empiric treatment.

Author(s): LaHue, Sara C; Albers, Kathleen; Goldman, Samuel; Lo, Raymond Y; Gu, Zhuqin; Leimpeter, Amethyst; Fross, Robin; Comyns, Kathleen; Marras, Connie; de Kleijn, Annelie; Smit, Robin; Katz, Maya; Ozelius, Laurie J; Bressman, Susan; Saunders-Pullman, Rachel; Comella, Cynthia; Klingman, Jeffrey; Nelson, Lorene M; Van Den Eeden, Stephen K; Tanner, Caroline M | Abstract: BackgroundCurrent cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized.ObjectivesTo determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization.MethodsWe identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration.ResultsCD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68).ConclusionsCD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society.

Many neurologic diseases disproportionately affect women, particularly during their reproductive years. For many of these diseases, monoclonal antibodies (mAbs) are becoming widely available as a treatment option, for example, in migraine, multiple sclerosis, and myasthenia gravis. Yet, despite how common pregnancy is (latest estimates suggest that 86% of US women ages 40–44 have given birth), there is a paucity of research on the safety of prescription medications, including mAbs, during the peripartum period. In this article, we focus on the safety of mAbs during breastfeeding. We summarize how pregnancy affects the trajectory of these diseases and explore the benefit derived from mAb therapies. We posit that as neurologists, we are uniquely poised to lead the study of peripartum safety for the mAbs now on the market and provide a framework for their future study.

OBJECTIVES To describe the clinical characteristics and risk factors of male-to-female transgender (transwomen) patients with acute stroke. METHODS The study population included all patients admitted for stroke at San Francisco General Hospital from October 1, 2010 through August 31, 2017 who self-identified as transwomen. Patient charts were reviewed by the study coauthors for demographics, stroke risk factors, stroke characteristics, and clinical outcomes. Means, percentiles, and ranges were calculated. RESULTS Eight transwomen (average age, 50±9 y; range, 38 to 61 y) were admitted for stroke (average NIHSS, 8; range, 0 to 27). The majority of patients presented subacutely. The most common type of stroke was ischemic stroke (4, 50%), followed by intracerebral hemorrhage (2, 22%), transient ischemic attack (1, 13%), and concurrent ischemic stroke with subarachnoid hemorrhage (1, 13%). While traditional stroke risk factors were present, these patients also disproportionally had alternative risk factors: stimulant use (5, 63%), tobacco use (5, 63%), hepatitis C (5, 63%), human immunodeficiency virus (3, 38%), and prior stroke or transient ischemic attack (2, 25%). Six patients (75%) used estradiol (oral or injection) or conjugated estrogen as part of gender-affirming treatment at the time of stroke; one patient used estrogen remotely. Only 2 patients (33%) were prescribed their hormone therapy on discharge. CONCLUSIONS Understanding unique vulnerabilities of the transgender community for cerebrovascular events is essential to provide culturally appropriate counseling for harm reduction.

Jugular foramen syndrome (JFS) is a lower cranial neuropathy syndrome characterized by dysphonia and dysphagia. The syndrome is caused by dysfunction of the glossopharyngeal, vagus, and spinal accessory nerves at the level of the pars nervosa and pars vascularis within the jugular foramen. There are numerous etiologies for JFS, including malignancy, trauma, vascular, and infection. Here, we present the case of a healthy adult man who developed JFS secondary to an atypical presentation of Varicella Zoster meningitis, and was promptly diagnosed and treated with rapid symptom resolution. We diagnosed the patient using specialized skull-based imaging which detailed the jugular foramen, as well as CSF analysis. This case highlights the clinical value of detailed structural evaluation, consideration for infection in the absence of systemic symptoms, and favorable outcomes following early identification and treatment.

BACKGROUND: Delirium is associated with poor clinical outcomes that could be improved with targeted interventions. OBJECTIVE: To determine whether a multicomponent delirium care pathway implemented across seven specialty nonintensive care units is associated with reduced hospital length of stay (LOS). Secondary objectives were reductions in total direct cost, odds of 30-day hospital readmission, and rates of safety attendant and restraint use. METHODS: This retrospective cohort study included 22,708 hospitalized patients (11,018 preintervention) aged ≥50 years encompassing seven nonintensive care units: neurosciences, medicine, cardiology, general and specialty surgery, hematology-oncology, and transplant. The multicomponent delirium care pathway included a nurse-administered delirium risk assessment at admission, nurse-administered delirium screening scale every shift, and a multicomponent delirium intervention. The primary study outcome was LOS for all units combined and the medicine unit separately. Secondary outcomes included total direct cost, odds of 30-day hospital readmission, and rates of safety attendant and restraint use. RESULTS: Adjusted mean LOS for all units combined decreased by 2% post intervention (proportional change, 0.98; 95% CI, 0.96-0.99; P = .0087). Medicine unit adjusted LOS decreased by 9% (proportional change, 0.91; 95% CI, 0.83-0.99; P = .028). For all units combined, adjusted odds of 30-day readmission decreased by 14% (odds ratio [OR], 0.86; 95% CI, 0.80-0.93; P = .0002). Medicine unit adjusted cost decreased by 7% (proportional change, 0.93; 95% CI, 0.89-0.96; P = .0002). CONCLUSION: This multicomponent hospital-wide delirium care pathway intervention is associated with reduced hospital LOS, especially for patients on the medicine unit. Odds of 30-day readmission decreased throughout the entire cohort.

Background Despite recognition of the neurologic and psychiatric complications associated with SARS-CoV-2 infection, the relationship between coronavirus disease 19 (COVID-19) severity on hospital admission and delirium in hospitalized patients is poorly understood. This study sought to measure the association between COVID-19 severity and presence of delirium in both intensive care unit (ICU) and acute care patients by leveraging an existing hospital-wide systematic delirium screening protocol. The secondary analyses included measuring the association between age and presence of delirium, as well as the association between delirium and safety attendant use, restraint use, discharge home, and length of stay. Methods In this single center retrospective cohort study, we obtained electronic medical record (EMR) data using the institutional Epic Clarity database to identify all adults diagnosed with COVID-19 and hospitalized for at least 48-h from February 1-July 15, 2020. COVID-19 severity was classified into four groups. These EMR data include twice-daily delirium screenings of all patients using the Nursing Delirium Screening Scale (non-ICU) or CAM-ICU (ICU) per existing hospital-wide protocols. Results A total of 99 patients were diagnosed with COVID-19, of whom 44 patients required ICU care and 17 met criteria for severe disease within 24-h of admission. Forty-three patients (43%) met criteria for delirium at any point in their hospitalization. Of patients with delirium, 24 (56%) were 65 years old or younger. After adjustment, patients meeting criteria for the two highest COVID-19 severity groups within 24-h of admission had 7.2 times the odds of having delirium compared to those in the lowest category [adjusted odds ratio (aOR) 7.2; 95% confidence interval (CI) 1.9, 27.4; P = 0.003]. Patients > 65 years old had increased odds of delirium compared to those P = 0.003). Delirium was associated with increased odds of safety attendant use (aOR 4.5; 95% CI 1.0, 20.7; P = 0.050), decreased odds of discharge home (aOR 0.2; 95% CI 0.06, 0.6; P = 0.005), and increased length of stay (aOR 7.5; 95% CI 2.0, 13; P = 0.008). Conclusions While delirium is common in hospitalized patients of all ages with COVID-19, it is especially common in those with severe disease on hospital admission and those who are older. Patients with COVID-19 and delirium, compared to COVID-19 without delirium, are more likely to require safety attendants during hospitalization, less likely to be discharged home, and have a longer length of stay. Individuals with COVID-19, including younger patients, represent an important population to target for delirium screening and management as delirium is associated with important differences in both clinical care and disposition.

The epidemic of concussion is particularly poignant as it relates to children and adolescents. There is much yet to learn about the mechanisms and consequences of traumatic brain injury (TBI), but this case discussion attempts to codify a useful clinical approach.

Most migraine auras are brief and in some ways provide an early warning for the migraine attack, but when the aura persists it should prompt attention.

Delirium is becoming increasingly recognized as a symptom of serious illness as well as a risk factor for poor clinical outcomes in its own right. This case provides a framework for these often nebulous presentations.

Vertigo is one of the most disturbing symptoms patients can experience and while generally a symptoms of vestibular dysfunction, cerebrovascular and other etiologies may be at play.

Stroke is an important cause of morbidity and mortality in the young, with key considerations that differ from adults.

Myopathy is an underrecognized cause of weakness with a growing number of differential diagnoses. Expanded testing and treatment options make this disorder a don’t-miss diagnosis.

Subtle or severe, generalized weakness should come to attention promptly and has a wide range of potential causes.

Immune checkpoint inhibitors are a revolutionary new category of medication for many people with cancer, but they carry with them unique side effects that are reviewed in this case.

Transplant patients are at increased risk for many medical hurdles, including posterior reversible encephalopathy syndrome (PRES). This case reviews the diagnosis, workup, and management of PRES as well as recommendations for anticipating secondary complications.

This classic presentation suggests intracranial hemorrhage but a number of other conditions have been shown to cause sudden severe headache.

The first seizure is a perennial enigma. This case discussion should provide a paradigm for evaluation and treatment.

The longer seizure activity continues, the higher the chance of irreversible brain injury, so time is of the essence. An update of generalized convulsive status epilepticus management is discussed.

The differential diagnosis for acute ataxia is reviewed, including the most common explanation, a benign, self-limited postinfectious acute cerebellar ataxia.

The classic conversion disorder is difficult to diagnose with certainty. This chapter attempts to provide a way to sort out this presentation.

Myelopathy is an important localization with a broad differential. This case walks through an approach to compressive and noncompressive causes of myelopathy.

This case outlines the dramatic shift in the treatment of acute ischemic stroke and the updated time window for endovascular therapy.

A review of transient ischemic attack, prediction of future stroke, and methods to reduce that risk, including carotid endarterectomy and stenting.

The pregnant migraineur is often frustrated by the lack of safe therapies. Fortunately there are actually a number of good management options.

Identification of atrial fibrillation can provide the explanation for a stroke, but it is not always clear when to start anticoagulation in order to prevent another stroke. This chapter breaks down stroke risk and anticoagulation timing in patients with atrial fibrillation as a cause for stroke.

Targeted temperature management is increasingly used for neuroprotection in patients who remain unresponsive after a cardiac arrest. The indications for this therapy and tools for prognostication are discussed.

Key historical details and exam findings help point to cauda equina syndrome, which requires urgent attention. A review of the various causes and management are reviewed.

Discovering the cause of syncope, whether cardiovascular, pulmonary, metabolic, or neurological, can be life-saving.

There are several misconceptions about nonepileptic spells, which this case discussion attempts to clarify.

Acute respiratory failure can be due to a variety of causes, and neuromuscular weakness is an important consideration. Myasthenic crisis identification and management is reviewed.

Meningitis can be a life-threatening emergency that requires rapid identification and management. This case summarizes the workup for meningitis, including the appropriate timing of imaging studies and lumbar puncture.

While carotid endarterectomy can be enormously effective in preventing recurrent stroke, this chapter illustrates the potential adverse effects of the procedure.