What's new in neurology

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

CEREBROVASCULAR DISEASE

Reversal strategy for intracerebral hemorrhage associated with direct factor Xa inhibitors (May 2024)

The optimal reversal strategy for direct factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) in acute intracerebral hemorrhage (ICH) is uncertain. In the ANNEXA-I trial, which randomly assigned 530 patients with factor Xa inhibitor-associated ICH to andexanet alfa or standard care (typically including a prothrombin complex concentrate [PCC]), patients assigned to andexanet had higher rates of hemostasis than those assigned to standard therapy (67 versus 53 percent) [1]. However, thrombotic events, including ischemic stroke and myocardial infarction, were more common with andexanet (10.3 versus 5.6 percent). Mortality and functional outcomes at 30 days were similar. Based on these results, we individualize selection of andexanet alfa or PCC for direct factor Xa inhibitor reversal in acute ICH and other life-threatening bleeding; previously, we favored andexanet in most cases. Andexanet may restore hemostasis more effectively than PCC but is associated with higher thrombotic risk. (See "Reversal of anticoagulation in intracranial hemorrhage", section on 'Reversal agent options'.)

Minimally invasive surgery for acute hemispheric intracerebral hemorrhage (May 2024)

Surgical evacuation is used for select patients with large hemispheric intracerebral hemorrhage (ICH) to reduce risk of mortality, but the effect on functional outcomes is less certain. In a clinical trial of 300 patients with acute ICH, functional outcome at 180 days was better in patients assigned to minimally invasive surgery than those assigned to guideline-based medical therapy [2]. The 30-day death rate was also lower in the surgery group (9 versus 18 percent). These results support the role of minimally invasive surgery to improve functional outcomes and reduce mortality risk for properly selected patients with acute ICH. (See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis", section on 'Supratentorial hemorrhage'.)

Mechanical thrombectomy for extremely large core infarcts (March 2024)

Randomized controlled trials have shown that mechanical thrombectomy (MT) improves outcomes for patients with acute anterior circulation ischemic stroke due to large vessel occlusion who have a large ischemic core, as defined by an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 3 to 5 or by a core volume ≥50 mL. Emerging evidence now suggests that even patients with extremely large core infarcts (ie, a baseline ASPECTS of 0 to 2) may benefit from MT [3,4]. These data also support studies suggesting that the clinical and imaging parameters (eg, APSECTS, CT perfusion) used to differentiate irreversible core infarction from the salvageable ischemic penumbra are imperfect. However, further trials are needed to confirm the benefit of MT for patients with extremely large core infarcts. (See "Mechanical thrombectomy for acute ischemic stroke", section on 'Benefit for large core infarcts'.)

Cerebral amyloid angiopathy as a risk for isolated subdural hematoma (February 2024)

Cerebral amyloid angiopathy (CAA) commonly presents with acute intracerebral hemorrhage that may extend into the subarachnoid or subdural spaces in some instances, but the risk of isolated spontaneous subdural hematoma (SDH) from CAA is uncertain. In a retrospective study of data from two large population-based cohorts, CAA was associated with an elevated risk of SDH after adjustment for patient demographics, cardiovascular risks, and antithrombotic medication use [5]. Leptomeningeal amyloid deposition may predispose such patients to spontaneous SDH. These results expand our understanding of the varied hemorrhagic presentations associated with CAA. (See "Cerebral amyloid angiopathy", section on 'Imaging features'.)

Time window to start dual antiplatelet therapy for high-risk TIA or minor ischemic stroke (January 2024)

There is evidence from several randomized trials that early initiation of short-term dual antiplatelet therapy (DAPT) for select patients with high-risk transient ischemic attack (TIA) or minor ischemic stroke reduces the risk of recurrent ischemic stroke. The evidence comes from trials that started DAPT within 12 to 24 hours of symptom onset. Results from the recent INSPIRES trial suggest that DAPT is still beneficial when started up to 72 hours after symptom onset [6]. Although the time window is extended by the results from INSPIRES, we start DAPT as soon as possible for patients with high-risk TIA or minor ischemic stroke. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'High-risk TIA and minor ischemic stroke'.)

Management of CADASIL (November 2023)

A recent American Heart Association (AHA) scientific statement reviews various clinical aspects of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) [7]. The AHA statement notes that safety and efficacy of thrombolysis are unknown for patients with CADASIL presenting with small vessel stroke, while mechanical thrombectomy without thrombolysis may be preferred for patients presenting with large vessel stroke unrelated to CADASIL. The AHA also suggests specific perioperative measures to avoid cerebral ischemia during anesthesia and surgery, and recommends avoidance of catheter angiography except for patients with acute ischemic stroke due to large vessel occlusion. (See "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)", section on 'Management'.)

DEMENTIA

Adult-onset ADHD and dementia (December 2023)

Individuals with adult-onset attention deficit hyperactivity disorder (ADHD) may have difficulties compensating for deficits from neurodegenerative or cerebrovascular processes, but any association with dementia has been inconsistent. In a prospective study including over 100,000 adults without ADHD or dementia at baseline, those who were subsequently diagnosed with adult-onset ADHD were more likely to receive a diagnosis of dementia (adjusted relative risk 2.8) [8]. Whether symptoms that resulted in the ADHD diagnosis were early or prodromal dementia symptoms is uncertain; nevertheless, these findings suggest that caregivers be alert for signs of dementia in individuals with adult-onset ADHD. (See "Attention deficit hyperactivity disorder in adults: Epidemiology, clinical features, assessment, and diagnosis", section on 'Comorbidity'.)

DEMYELINATING DISEASE

Cerebral cortical encephalitis as a manifestation of MOGAD (November 2023)

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) was originally described as a demyelinating disease often presenting as acute disseminated encephalomyelitis. Over time, additional MOGAD phenotypes have emerged, including a novel syndrome termed cerebral cortical encephalitis. Clinical manifestations include seizures, aphasia, stroke-like episodes, headache, and fever [9]. Most episodes are unilateral with ipsilateral symptoms and cortical swelling, T2 hyperintensity, and leptomeningeal enhancement on magnetic resonance imaging. A recent report describes children with bilateral cerebral cortical encephalitis and more fulminant disease, including critical illness, severe encephalopathy, seizures, and worse outcomes [10]. Thus, the clinical spectrum of MOGAD continues to expand. (See "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Clinical features and diagnosis", section on 'Cerebral cortical encephalitis'.)

EPILEPSY

Risk of epilepsy after aneurysmal subarachnoid hemorrhage (May 2024)

Epilepsy is a known sequelae of aneurysmal subarachnoid hemorrhage (SAH), but risk factors are poorly understood. In a retrospective analysis of 419 patients with SAH who were followed for a median of 4.2 years, epilepsy was diagnosed in 12 percent at a median of seven months after SAH [11]. Incidence was modified by several variables: premorbid functional impairment, SAH-associated cerebral ischemia, surgical treatment of the aneurysm, and early-onset seizures. A predictive model for the risk of epilepsy was developed using these data, with predicted risk ranging from 3 to 76 percent depending on the score. These results may provide insight into the individual risk of epilepsy after SAH. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Epilepsy'.)

Acute encephalopathy with biphasic seizures and late reduced diffusion (November 2023)

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a parainfectious syndrome characterized by presentation with febrile status epilepticus (FSE) followed by a brief seizure-free period before recurrence of seizures in clusters. In a retrospective study from Japan of 55 patients presenting with FSE, the development of AESD in 11 patients was associated with longer time from seizure onset to hospital arrival, presence of hypoxia, and later treatment with antiseizure medications [12]. These findings suggest that shortening the seizure duration by early effective treatment and preventing hypoxia during ambulance transportation might reduce the risk of AESD. (See "Clinical features and evaluation of febrile seizures", section on 'Acute encephalopathy with biphasic seizures and late reduced diffusion'.)

Expert panel on epilepsy with eyelid myoclonia (November 2023)

Epilepsy with eyelid myoclonia (EEM; Jeavons syndrome) is a female-predominant generalized epilepsy syndrome with onset from 3 to 12 years of age characterized by eyelid myoclonia, photosensitivity, and eye closure-induced seizures or paroxysms on electroencephalography (EEG). Recently, an international expert panel found a strong consensus that EEM is often underdiagnosed, that a correct diagnosis can only be made with EEG including photic stimulation, and that an earlier age at onset is associated with an increased risk of intellectual disability and drug-resistant epilepsy [13]. Management generally involves reducing exposure to provoking factors (eg, visual stimuli, various sources of natural and artificial light) and use of antiseizure medication such as levetiracetam or valproate [14]. (See "Photosensitive epilepsies", section on 'Epilepsy with eyelid myoclonia (Jeavons syndrome)'.)

HEADACHE

Calcitonin gene-related peptide antagonists as a first-line preventive therapy for migraine (April 2024)

Several calcitonin gene-related peptide (CGRP) antagonists available for migraine prevention have frequently been reserved for patients with an inadequate response to initial therapy. However, in a position statement by the American Headache Society, CGRP antagonists are now considered among first-line therapies for migraine prevention, based on cumulative evidence of efficacy, safety, and tolerability from several clinical trials, meta-analyses, and postapproval open-label cohort studies [15]. They may be effective for patients with severe symptoms or frequent migraines and may provide earlier benefit than other preventive agents, and the formulations given by injection may also be helpful for those who have difficulty with daily dosing. However, cost or insurance approval may limit access to these agents as first-line therapy for some patients. (See "Preventive treatment of episodic migraine in adults", section on 'Choosing pharmacologic therapy'.)

Early use of ubrogepant to abort migraine headache (November 2023)

Acute migraine treatments, including calcitonin gene-related peptide (CGRP) antagonists, are typically given at headache onset, but the benefit of earlier dosing is uncertain. In a trial of 477 patients with migraine who were treated at the onset of prodromal symptoms (prior to headache), ubrongepant improved the proportion of patients who remained free of moderate to severe headache at 24 hours compared with placebo (46 versus 29 percent) [16]. Enrolled patients had migraines that consisted of prodromal symptoms (eg, photophobia, fatigue, neck pain) occurring one to six hours before headache onset in at least 75 percent of attacks. These results support our practice to administer acute migraine treatments, such as ubrogepant, early in the course of migraine symptoms. (See "Acute treatment of migraine in adults", section on 'CGRP antagonists'.)

MOVEMENT DISORDERS

Glucagon-like peptide-1 receptor agonists in Parkinson disease (April 2024)

Glucagon-like peptide-1 (GLP-1) receptor agonists have been proposed as neuroprotective agents in Parkinson disease (PD) based on observations that treatment may be associated with lower risk of PD in patients with diabetes. Two recent trials in nondiabetic patients with PD have shown mixed results:

●In a randomized phase II trial of daily subcutaneous lixisenatide versus placebo injections in 156 patients with early PD, the lixisenatide group exhibited stable motor disability scores over 12 months, compared with a 3-point decline (on a 132-point scale) in the placebo group [17]. Nausea was dose limiting in some patients.

●A slightly larger phase III trial of an investigational, pegylated formulation of exenatide failed to show a difference in motor disability progression between groups at 36 weeks [18].

Larger studies with longer follow-up are needed to determine whether this class of agents has meaningful neuroprotective effects in PD. (See "Epidemiology, pathogenesis, and genetics of Parkinson disease", section on 'Protective factors'.)

Suicidality in Parkinson disease (February 2024)

Patients with Parkinson disease (PD) are at risk for suicidality, but the magnitude of risk has been uncertain. In a meta-analysis that included 28 observational studies and more than 500,000 patients with PD, the pooled prevalence of suicidal ideation was 22 percent [19]. The risk of suicidal behavior was low (1.25 percent) but nonetheless elevated relative to the general population or patients with nonneurologic diseases (hazard ratio 1.7). Other studies indicate that risk is primarily mediated by depression; whether treatments for PD, including dopaminergic agents and deep brain stimulation, contribute to excess risk remains uncertain. Depression screening and treatment are important components of longitudinal care in all patients with PD. (See "Clinical manifestations of Parkinson disease", section on 'Depression' and "Management of nonmotor symptoms in Parkinson disease", section on 'Depression'.)

Botulinum toxin injections for essential head tremor (November 2023)

Botulinum toxin (BoNT) injections have been used for refractory head tremor in patients with essential tremor (ET) based on limited data. In a randomized trial of 117 patients with essential or isolated head tremor, BoNT type A injections into each splenius capitis muscle improved subjective and objective head tremor severity measurements compared with placebo injections, with expected waning of response by 12 weeks after each injection [20]. Adverse effects were more frequent with BoNT (47 versus 16 percent), most commonly headache or neck pain, dysphagia, and posterior neck weakness. BoNT type A injections are an option for patients with bothersome head tremor due to ET who do not tolerate oral medications or whose tremor does not respond, but side effects are common and may outweigh potential benefits in some patients. (See "Essential tremor: Treatment and prognosis", section on 'Administration and efficacy'.)

NEUROMUSCULAR DISEASE

Givinostat for Duchenne muscular dystrophy (April 2024)

The histone deacetylase inhibitor givinostat was recently approved by the US Food and Drug Administration for the treatment of Duchenne muscular dystrophy (DMD) in patients six years of age and older. Approval was based on results from a small randomized trial, which suggest that givinostat may slow DMD progression [21]. Benefit was found on only one outcome (the four-stair climb test), as shown by a smaller performance decline from baseline to 72 weeks for the givinostat group compared with placebo (1.25 versus 3.03 seconds); statistical significance was marginal. Adverse effects of givinostat include gastrointestinal disturbances, thrombocytopenia, elevated triglycerides, fever, and potential QTc interval prolongation. While givinostat may be used in combination with glucocorticoid therapy and genetic therapies, its role in the treatment of DMD remains to be defined, and further data are needed to confirm benefit. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Givinostat'.)

Sodium phenylbutyrate-taurursodiol withdrawn from market (April 2024)

Sodium phenylbutyrate-taurursodiol (PB-TURSO) was approved by the US Food and Drug Administration for patients with amyotrophic lateral sclerosis (ALS) in September 2022 after an initial placebo-controlled trial of 137 participants showed a slowing in clinical deterioration at 24-week follow-up. However, the company has indicated that a confirmatory trial involving 664 participants with ALS failed to confirm the efficacy of PB-TURSO at 48 weeks (unpublished data) [22]. In response, in April 2024, the medication was withdrawn from the market by the manufacturer in Canada and the United States [23]. PB-TURSO may continue to be available for some patients already on therapy and trial participants. (See "Disease-modifying treatment of amyotrophic lateral sclerosis", section on 'Sodium phenylbutyrate-taurursodiol'.)

Vamorolone for Duchenne muscular dystrophy (December 2023)

Glucocorticoid treatment with prednisone or deflazacort for Duchenne muscular dystrophy (DMD) is associated with improved motor function, but adverse effects include weight gain, slowing of growth, and bone loss. Vamorolone, a novel steroid, was designed to reduce adverse effects of glucocorticoid therapy for DMD. In the VISION-DMD trial, vamorolone treatment led to improvement on several motor outcomes compared with placebo, while efficacy was similar compared with prednisone [24]. Prednisone treatment (but not vamorolone) led to growth deceleration and bone biomarker abnormalities. Based on these findings, the US Food and Drug Administration approved vamorolone for children age ≥2 years with DMD [25]. We suggest glucocorticoid treatment for children with DMD and anticipate using vamorolone as an alternative to prednisone and deflazacort. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Benefits of glucocorticoid therapy'.)

NEUROONCOLOGY

Tovorafenib in BRAF-altered pediatric low-grade gliomas (May 2024)

Tovorafenib is a first-in-class oral type II RAF inhibitor recently approved by the US Food and Drug Administration for treatment of relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF V600E mutation or BRAF fusion or rearrangement [26]. In a phase II trial among 69 such patients (50 percent with optic pathway glioma), response rates ranged from 51 to 67 percent depending on response criteria, with a median duration of response of 14 to 17 months [27]. Tovorafenib is now one of several targeted therapy options for children with recurrent/progressive BRAF-altered LGG; ongoing phase III trials are investigating these agents in the upfront setting versus chemotherapy. (See "Optic pathway glioma", section on 'Role of MAPK pathway inhibition'.)

ONC201 in H3 H27M-mutant diffuse midline glioma (May 2024)

Diffuse midline gliomas (DMGs) are highly aggressive tumors with a poor prognosis despite radiation therapy, and no standard systemic therapies exist. Among DMGs with a histone 3 (H3) K27M mutation, the investigational therapy ONC201 (dordaviprone) has shown promising activity. In a summary of 50 patients with recurrent H3 K27M-mutant DMG treated with ONC201 on one of four clinical trials (46 adults, 4 children), the overall response rate was 20 percent with a median duration of response of 11.2 months [28]. The drug was well tolerated. Based on these results, an international, randomized, placebo-controlled phase III trial is underway in patients with newly diagnosed H3 K27M-mutant diffuse gliomas (excluding pontine and spinal tumors) [29]. (See "Diffuse intrinsic pontine glioma", section on 'Investigational therapies'.)

Intraoperative techniques for glioblastoma resection (December 2023, Modified April 2024)

Two recent trials in patients with glioma illustrate the utility of intraoperative neurosurgical techniques to improve extent of resection while minimizing damage to normal brain.

●In a multicenter parallel-group trial that included 314 patients undergoing resection of a newly diagnosed glioblastoma, rates of complete resection were comparable with use of either intraoperative magnetic resonance imaging (iMRI) or 5-aminolevulinic acid (ALA; 81 and 78 percent, respectively) [30]. In both groups, absence of any enhancing tumor postoperatively was associated with improved progression-free and overall survival.

●In a randomized trial of iMRI versus conventional neuronavigation in 321 patients with new low- or high-grade glioma, iMRI improved progression-free survival, and there was a nonsignificant trend towards improved overall survival in patients with high-grade glioma [31].

These results further support use of adjunctive tools like iMRI and ALA to facilitate maximal safe resection; selection of a specific operative plan is individualized based on neurosurgeon preference, tumor location, and availability of various technologies. (See "Clinical presentation, diagnosis, and initial surgical management of high-grade gliomas", section on 'Intraoperative techniques'.)

Chimeric antigen receptor T cell therapies in glioblastoma (March 2024)

Genetically manipulated immunologic therapies are under investigation in patients with recurrent glioblastoma. Several groups have demonstrated that chimeric antigen receptor T (CAR-T) cells targeted against glioblastoma surface antigens can be delivered systemically or intraventricularly to achieve on-target T cell trafficking and radiographic tumor responses [32-34]. In the largest study in 65 patients with recurrent high-grade glioma, CAR-T cells targeting interleukin-13 receptor alpha 2 were delivered intratumorally and/or intraventricularly at escalating doses; administration was safe, and several partial or complete responses were observed [33]. Tumor responses generally have not been durable, however, and clinical trials are ongoing. (See "Management of recurrent high-grade gliomas", section on 'Immunotherapy'.)

Osimertinib and chemotherapy in EGFR-mutated NSCLC with brain metastases (March 2024)

Trials are investigating systemic treatment options for those with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with central nervous system (CNS) disease. In a randomized trial, among the 222 patients with baseline CNS disease from EGFR-mutated NSCLC, osimertinib plus chemotherapy resulted in a 24-month CNS progression-free survival of 74 percent versus 54 percent with chemotherapy alone, but the difference was not statistically significant (hazard ratio 0.58, 95% CI 0.33-1.01) [35]. Results in the overall study population (with and without CNS disease) also favored combination therapy, with a trend towards improved overall survival [36]. For patients with EGFR-mutated NSCLC and brain metastases, we now suggest osimertinib and chemotherapy, but consider osimertinib alone a reasonable alternative. (See "Brain metastases in non-small cell lung cancer", section on 'Osimertinib with chemotherapy'.)

No role for central nervous system prophylaxis with high-dose methotrexate in diffuse large B cell lymphoma (February 2024)

Patients with diffuse large B cell lymphoma (DLBCL) are at substantial risk for central nervous system (CNS) relapse, but there is controversy about whether adding high-dose methotrexate (HD-MTX) prophylaxis to CD20-based induction chemoimmunotherapy can reduce this risk. In a recent observational study that included 2418 patients, administration of HD-MTX prophylaxis (at the discretion of the treating physician) was not associated with a clinically meaningful reduction in two-year risk of CNS relapse [37]. Toxicity with HD-MTX includes encephalopathy, hepatotoxicity, and kidney toxicity. Based on this and other studies, we do not routinely add HD-MTX prophylaxis to induction chemoimmunotherapy for DLBCL. (See "Initial treatment of advanced stage diffuse large B cell lymphoma", section on 'CNS management'.)

PEDIATRIC NEUROLOGY

Intrathecal gene therapy for giant axonal neuropathy (April 2024)

Giant axonal neuropathy (GAN) is a severe, hereditary neurodegenerative disorder of childhood characterized by a motor and sensory polyneuropathy with ataxia. In a small dose-escalation study in 14 children with GAN, intrathecal administration of an adeno-associated virus-based gigaxonin-containing transgene was associated with slowing of functional decline at 6 to 24 months compared with the pretreatment baseline, and electrodiagnostic studies improved in some patients [38]. Cerebrospinal fluid pleocytosis was observed in nearly all patients within six months after gene transfer but was asymptomatic and self-limited with immunosuppression; two deaths at 8 and 60 months after treatment were deemed possibly related to disease progression and unlikely related to the transgene. These promising results support the possibility of future disease-modifying therapy for GAN, pending further safety and efficacy assessments. (See "Overview of hereditary neuropathies", section on 'Giant axonal neuropathy'.)

Concussion and mental health disorders in children and adolescents (March 2024)

Ongoing research continues to examine the complex relationship between concussion and mental health disorders. In a recent case-control study of over 18,000 children (≤17 years old) with concussion and over 37,000 matched controls, concussion was associated with an increased risk for a new diagnosis of a behavior disorder at two and four years after injury [39]. For most diagnoses, the absolute numbers were low. Confidence in a causal relationship is limited by risk of confounding and reliance on an electronic medical record for establishing lack of baseline behavioral problems prior to injury. Whether pediatric concussion is an independent risk factor for new behavioral problems after recovery remains unclear. (See "Concussion in children and adolescents: Management", section on 'Mental health disorders'.)

N-acetyl-l-leucine (NALL) for Niemann-Pick disease type C (February 2024)

Niemann-Pick disease type C (NPD-C) is a rare lysosomal disease with a wide phenotypic spectrum; most patients have onset in childhood with cerebellar ataxia and slowly progressive neurologic deterioration. Investigational therapies include N-acetyl-l-leucine (NALL), a putative neuroprotective agent that improves cellular energy production and reduces neuroinflammation. In a recent placebo-controlled, 12-week crossover trial of 60 patients (age ≥4 years) with NPD-C, treatment with NALL was well tolerated and led to improved neurologic status on a scale that measures ataxia and other neurologic signs and symptoms [40]. While these results are promising, longer-term trials are needed to determine if NALL is beneficial for patients with NPD-C. (See "Overview of Niemann-Pick disease", section on 'Experimental therapies'.)

Benign acute childhood myositis (January 2024)

Benign acute childhood myositis (BACM) is a self-limited syndrome associated with calf pain and creatinine kinase elevation, often following infection with influenza. In a retrospective study of 65 patients with BACM, the median age was 6.6 years and 66 percent of patients were male [41]. The most common symptoms were bilateral calf pain, refusal to walk, and diffuse weakness. The median creatinine kinase was 1827 U/L, which normalized after an average of seven days. Early recognition of this syndrome allows the clinician to avoid an unnecessary evaluation for other muscle diseases. (See "Overview of viral myositis", section on 'Benign acute childhood myositis'.)

OTHER NEUROLOGY

Updated guideline on postoperative delirium in adults (February 2024)

The European Society of Anaesthesiology and Intensive Care Medicine has published an updated guideline on postoperative delirium (POD) [42]. Recommendations include preoperatively screening older adults for risk factors for POD and multicomponent nonpharmacological interventions for all patients with risk factors. In addition, review of recent evidence showed that perioperative use of dexmedetomidine was associated with a lower incidence of POD, particularly when administered postoperatively in the intensive care unit. We agree with the recommendations and often use dexmedetomidine in the perioperative period to reduce the incidence of POD in high-risk patients. (See "Perioperative neurocognitive disorders in adults: Risk factors and mitigation strategies", section on 'Intravenous agents associated with lower risk'.)

Fusarium meningitis associated with epidural anesthesia (February 2024)

In early 2023, there was an outbreak of Fusarium spp meningitis in 33 immunocompetent patients who received epidural anesthesia at two clinics in Mexico. In a review of 13 cases, hospital admission was delayed by a median of 39 days after symptom onset [43]. Severe neurovascular complications, such as aneurysm, intracranial hemorrhage, stroke, and hydrocephalus, occurred despite initial improvement on antifungal therapy. Susceptibility testing was performed on one isolate and revealed resistance to all antifungals approved in the United States; however, it was susceptible to fosmanogepix, an investigational agent. Nine patients (69 percent) died from the infection; of the four survivors, three received compassionate-use fosmanogepix. Understanding the clinical features and management challenges of Fusarium meningitis are important to providing effective care should future outbreaks occur. (See "Clinical manifestations and diagnosis of Fusarium infection", section on 'Outbreaks of meningitis'.)