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

Mechanical thrombectomy for large ischemic core infarcts (February 2023)

Mechanical thrombectomy (MT) for acute ischemic stroke due to a large artery occlusion in the anterior circulation has been limited to patients with a small- to moderate-sized core infarct at baseline. The exclusion of patients with large core infarcts was first challenged in 2022 by results from the RESCUE-Japan LIMIT. The recent SELECT2 and ANGEL-ASPECT trials now confirm that MT compared with medical treatment alone improves outcomes for patients with a large ischemic core infarct (defined by an Alberta Stroke Program Early CT Score [ASPECTS] <6 or a core volume ≥50 ml) [1,2]. As an example, the SELECT2 trial showed that functional independence for patients with large infarcts was more likely with MT than with medical care alone (20 versus 7 percent) [1]. Based on these results, in addition to previously defined eligible groups, we now recommend MT for patients who have a large ischemic core infarct as defined in these trials and can start treatment within 24 hours of the time last known to be well. (See "Mechanical thrombectomy for acute ischemic stroke", section on 'Benefit for large core infarcts'.)

Timing of surgery after ischemic stroke (December 2022)

The risk of perioperative stroke is increased in patients with a prior ischemic stroke, though optimal timing of surgery after stroke is unclear. In a database study including nearly six million patients, the risk of postoperative ischemic stroke was increased eightfold in patients who had a stroke within 30 days before surgery, compared with those who never had a stroke [3]. The risk of recurrent stroke decreased and leveled off for surgery between 60 and 90 days after stroke, but remained elevated. The timing of surgery in patients with prior ischemic stroke should consider the risk of recurrent stroke and the risk of delaying surgery. We suggest delaying elective surgery for at least three months, and if possible up to nine months, after a stroke to reduce the risk of recurrence. (See "Perioperative stroke following noncardiac, noncarotid, and nonneurologic surgery", section on 'Timing of surgery after ischemic stroke'.)

Mechanical thrombectomy for acute stroke due to basilar artery occlusion (October 2022)

Mechanical thrombectomy (MT) is well established for treating acute ischemic stroke caused by a large artery occlusion in the anterior circulation, but the benefit for posterior circulation stroke is uncertain. The recent ATTENTION and BAOCHE randomized trials from China provide moderate-quality evidence that MT plus medical therapy, compared with medical therapy alone, is beneficial for selected patients with moderate to severe stroke caused by a basilar artery occlusion who can be treated within 24 hours of onset [4,5]. However, the results are not generalizable to all patients with basilar artery stroke, since the Chinese population has higher rates of large artery intracranial atherosclerotic disease relative to other populations. Larger randomized controlled trials in more diverse populations are needed to assess the efficacy of MT for basilar artery occlusion. (See "Mechanical thrombectomy for acute ischemic stroke", section on 'Basilar artery occlusion'.)

IVIG for vaccine-induced immune thrombotic thrombocytopenia (October 2022)

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenoviral-vectored COVID-19 vaccines that presents with thrombocytopenia and thrombosis. Emerging evidence on management continues to support a role for intravenous immune globulin (IVIG) as a component of therapy, along with anticoagulation. In a new nonrandomized study involving 99 individuals with VITT presenting with cerebral venous thrombosis, receipt of IVIG was associated with lower mortality (29 versus 70 percent) [6]. In contrast, the choice of anticoagulant (heparin versus a nonheparin agent) and receipt of a platelet transfusion were not associated with statistically different mortality rates. We continue to suggest IVIG plus a nonheparin agent, especially if there is concern for possible heparin-induced thrombocytopenia (HIT; including delayed or spontaneous HIT). (See "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)", section on 'IVIG'.)

Delayed functional improvement after intracerebral hemorrhage (September 2022)

Functional improvement after intracerebral hemorrhage (ICH) can be slow and the temporal trajectory is often uncertain. In an analysis of individual patient data from two clinical trials in nearly 1000 patients with intracerebral or intraventricular hemorrhage, 72 percent of patients had a poor functional outcome at 30 days [7]. By one year, 46 percent had recovered further and achieved a good functional outcome, including 211 (30 percent) who were functionally independent. Acute ICH complications such as sepsis, new ischemic stroke, prolonged mechanical ventilation, hydrocephalus, and the need for a gastrostomy feeding tube were predictors of poor outcome at one year. These results support the practice of providing aggressive acute treatment of patients with ICH and sustained rehabilitation to help avoid premature withdrawal of support and improve long-term outcomes. (See "Spontaneous intracerebral hemorrhage: Secondary prevention and long-term prognosis", section on 'Functional recovery'.)

DEMENTIA

Risk of progression to dementia in Down syndrome (October 2022)

Down syndrome (DS) is now considered a genetically determined form of Alzheimer disease (AD), with an estimated age of onset (53.8 years) and age of death (58.4 years) similar to that seen in autosomal dominant AD [8]. In one series of 632 adults with DS and varying levels of cognitive disability (436 asymptomatic, 69 with prodromal AD, and 127 with AD dementia) followed for five years, progression to AD dementia was seen in 17.1 percent of asymptomatic patients and was age dependent (0.6 percent for age <40 years, 21.1 percent for 40 to 44 years, 41.4 for 45 to 49 years, and 57.5 for ≥50 years) [9]. Patients with DS should be monitored closely for cognitive decline, particularly after age 40 years. (See "Down syndrome: Management", section on 'Alzheimer disease'.)

DEMYELINATING DISEASE

Diagnostic criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (March 2023)

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory disorder of the central nervous system characterized by attacks of immune-mediated demyelination predominantly targeting the optic nerves, brain, and spinal cord. New diagnostic criteria for MOGAD proposed by an expert international consensus panel require the following [10]:

●One of six core clinical demyelinating events (ie, optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, cerebral monofocal or polyfocal deficits, brainstem or cerebellar deficits, or cerebral cortical encephalitis)

●A positive MOG-immunoglobulin G (IgG) antibody test

●The exclusion of a better diagnosis

The new MOGAD criteria include supportive features that argue for the diagnosis if the MOG-IgG titer is not clearly positive and red flag features that argue against the diagnosis. These criteria are intended to improve the identification of people with MOGAD and distinguish it from other disorders with overlapping clinical features, including multiple sclerosis and aquaporin 4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder. (See "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Clinical features and diagnosis", section on 'Diagnostic criteria'.)

Ublituximab in patients with multiple sclerosis (January 2023)

Ublituximab, a recombinant monoclonal antibody that targets B cells, was approved by the US Food and Drug Administration in December 2022 for the treatment of adults with relapsing forms of multiple sclerosis (MS). Its efficacy was established in two identical randomized trials comparing intravenous ublituximab with oral teriflunomide [11]. At 95 weeks in both trials, the annualized relapse rate and the mean number of gadolinium-enhancing brain lesions on MRI were lower with ublituximab. Common adverse effects of ublituximab include infusion reactions and upper respiratory tract infections; as with other B cell depleting therapies, there is also a risk of life-threatening infections. Although its role in clinical practice is not yet defined, ublituximab will likely be used in a similar manner to other high-efficacy disease-modifying therapies for relapsing forms of MS. (See "Disease-modifying therapies for multiple sclerosis: Pharmacology, administration, and adverse effects", section on 'Ublituximab'.)

Mechanisms causing disability accrual in multiple sclerosis (October 2022)

An analysis of the large Novartis-Oxford multiple sclerosis data set evaluated the two main mechanisms leading to accrual of disability in multiple sclerosis (MS), which are relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) [12]. The study found that RAW contributed to disability progression primarily in the early stages of MS. PIRA was also present early in the course of all MS phenotypes (relapsing and progressive) and became the main driver of disability in the later stages. Early use of disease-modifying therapy (DMT) delayed disability progression by several years. These findings help to clarify the relative contributions of RAW and PIRA to disability accrual in MS and support the importance of starting DMT early in the course of MS. (See "Clinical presentation, course, and prognosis of multiple sclerosis in adults", section on 'Relapsing versus progressive disease'.)

EPILEPSY

Surgical evaluation for drug-resistant epilepsy (October 2022)

Surgery is the treatment of choice for patients with drug-resistant epilepsy (DRE). Recent expert consensus recommendations from the International League Against Epilepsy (ILAE) support early referral for epilepsy surgery for patients with DRE (if adherent to management) up to 70 years of age, as soon as drug resistance is ascertained and regardless of epilepsy duration, seizure type, epilepsy type, localization, or comorbidities [13]. We recommend referring patients with DRE for epilepsy surgery evaluation as early as the failure of the first antiseizure medication. (See "Evaluation and management of drug-resistant epilepsy", section on 'Epilepsy surgery'.)

HEADACHE

Zavegepant for acute treatment of migraine in adults (March 2023)

Several calcitonin gene-related peptide (CGRP) receptor antagonists are available by oral formulation for acute migraine treatment. Zavegepant is the first CGRP-receptor antagonist to be approved for intranasal administration [14]. In a trial of 1405 adult patients with migraine, those assigned to zavegepant 10 mg were more likely to be pain free at two hours than patients assigned to placebo (24 versus 15 percent); resolution of the most bothersome acute symptom (eg, photophobia, nausea) was also more common with zavegepant (40 versus 31 percent) [15]. Nasal administration of a CGRP-receptor antagonist provides rapid absorption and may be preferred for patients with nausea/vomiting who are unable to tolerate oral options. (See "Acute treatment of migraine in adults", section on 'CGRP antagonists'.)

Occipital nerve blocks for chronic migraine (March 2023)

Occipital nerve block (ONB) is used for cranial pain and some headache syndromes, but the utility for chronic migraine is uncertain. In a trial of 44 patients with chronic migraine who received bilateral greater occipital nerve injections every 4 weeks for 12 weeks, those who received lidocaine 40 mg had a greater mean reduction in the number of migraine days at weeks 9 to 12 than patients who received placebo (least squares mean reduction -4.7 days) [16]. In addition, patients who received lidocaine injection were more likely to report ≥50 percent reduction in headache days (41 versus 9 percent). These results support the use of ONB as an effective treatment option for patients with chronic migraine. (See "Chronic migraine", section on 'Occipital nerve block'.)

Elevated risk of superficial siderosis associated with spontaneous intracranial hypotension (March 2023)

Persistent cerebrospinal fluid (CSF) leak may be associated with morbidity, including a long-term risk of superficial siderosis. In a single-center registry of nearly 1600 patients with spontaneous intracranial hypotension (SIH), superficial siderosis was identified in 3.6 percent [17]. The prevalence was higher among patients with ventral spinal CSF leaks (10.3 percent) compared with those with other spinal leaks, including dural ectasia (3.9 percent), CSF-venous fistulas (2.6 percent), or meningeal diverticula (0.9 percent). The median interval from onset of SIH to the development of superficial siderosis was approximately 10 years. Timely identification of sources of SIH are warranted to treat symptoms and to reduce risk of long-term complications such as superficial siderosis. (See "Spontaneous intracranial hypotension: Treatment and prognosis", section on 'Prognosis'.)

MOVEMENT DISORDERS

Omaveloxolone for patients with Friedreich ataxia (March 2023)

Omaveloxolone is a novel activator of the transcription factor Nrf2, which is involved in cellular response to oxidative injury. It was approved by the US Food and Drug Administration in February 2023 as the first therapy for Friedreich ataxia (FA) in patients ≥16 years of age [18]. In a multicenter randomized trial in 103 patients with FA aged 16 to 40 years, 48 weeks of omaveloxolone improved modified FA rating scale (mFARS) scores by 2.4 points compared with placebo, and open-label follow-up suggested sustained effect and safety with up to 144 weeks of therapy [19]. The most common adverse effects were elevated liver transaminases, headache, nausea, and diarrhea. Although benefits appear to be modest, we intend to offer omaveloxolone to patients with FA who are ≥16 years old, based on the progressive nature of the disease and lack of other therapies. (See "Friedreich ataxia", section on 'Omaveloxolone'.)

Investigational oral agent for Parkinson disease-related constipation (January 2023)

Constipation is very common in patients with Parkinson disease (PD), and current management is symptomatic. ENT-01 (squalamine phosphate) is an investigational steroid-polyamine conjugate that displaces alpha-synuclein from enteric nerve cell membranes and improves gut motility in preclinical PD models. In a randomized phase 2 trial in 150 patients with PD and constipation, escalating daily doses of oral ENT-01 for 25 days improved the number of weekly bowel movements, stool consistency, and laxative use compared with placebo [20]. Selected neurologic outcomes also improved, and there were no serious adverse effects. A larger phase 3 trial with a longer treatment period is needed. (See "Management of nonmotor symptoms in Parkinson disease", section on 'Constipation'.)

Natural history of Friedreich ataxia based on age of onset (January 2023)

Early age of onset is an important predictor of overall disease severity and speed of progression in patients with Friedreich ataxia, which is due to guanine-adenine-adenine (GAA) triplet repeat expansion of the frataxin (FTX) gene on chromosome 9. Based on review of more than 1100 patients with Friedreich ataxia, four age-of-onset categories have been proposed: early onset (0 to 7 years), typical onset (8 to 14 years), intermediate onset (15 to 25 years), and late onset (≥25 years) [21]. Among these groups, the rate of disease progression varies inversely with the age of onset. Age of onset also correlates with the number of GAA repeats; for every 100 repeats, disease onset occurs approximately 2.5 years earlier. These groups will help in patient counseling and in the design of clinical trials for new therapies. (See "Friedreich ataxia", section on 'Age of onset'.)

Novel cause of late-onset ataxia due to intronic GAA repeat expansion (December 2022)

Genetic causes of late-onset ataxia syndromes continue to be discovered. As an example, pathogenic guanine-adenine-adenine (GAA) repeat expansion of the first intron of the fibroblast growth factor 14 (FGF14) gene has been identified as a cause of familial and sporadic late-onset ataxia in four independent cohorts of patients and families from Quebec, Germany, Western Australia, and southern India [22]. Among 122 patients, the median age of onset was 55 years, and approximately half of patients had episodic ataxia and/or downbeat nystagmus as early symptoms. This syndrome is distinct from spinocerebellar ataxia type 27 (SCA27), which generally presents earlier and is caused by pathogenic variants in the coding region of FGF14. (See "Autosomal dominant spinocerebellar ataxias", section on 'SCA types 21 to 48'.)

Deferiprone does not slow progression in Parkinson disease (December 2022)

Iron content is elevated in the substantia nigra of patients with Parkinson disease (PD), and brain-permeable iron chelators prevent experimentally induced degeneration of dopamine neurons in mouse models. However, in a randomized trial of 372 patients with newly diagnosed PD, deferiprone (an iron chelator) resulted in worsened functional scores and earlier need for dopaminergic therapy compared with placebo, despite decreasing nigrostriatal iron content by imaging [23]. Further studies are needed to better understand the role of iron metabolism in PD. (See "Epidemiology, pathogenesis, and genetics of Parkinson disease", section on 'Iron metabolism'.)

Mucuna pruriens as source of levodopa in dietary supplements (December 2022)

Levodopa is an active ingredient in the Mucuna pruriens bean, which is available as a dietary supplement and may be contained in other substances marketed for cognitive enhancement or brain health [24]. Data in patients with Parkinson disease (PD) indicate that use of Mucuna and other supplements is common and often not reported to clinicians. Patients with PD should be asked about use of supplements, particularly when side effects arise on relatively low doses of prescribed levodopa or in patients with signs of dopamine dysregulation syndrome. (See "Initial pharmacologic treatment of Parkinson disease", section on 'General principles'.)

Association of premenopausal oophorectomy with parkinsonism (November 2022)

Bilateral oophorectomy in premenopausal patients is associated with increased risk of serious long-term health consequences, including all-cause mortality, cardiovascular disease, and cognitive impairment; its association with parkinsonism is less clear. In a cohort study of almost 5500 age-matched premenopausal patients, those with a history of oophorectomy compared with no oophorectomy had increased rates of examination or medical record-confirmed parkinsonism (hazard ratio [HR] 1.59) [25]. While rates of Parkinson disease were similar between groups overall, risk was elevated in those with oophorectomy prior to age 43 years (HR 5). Despite its limitations, this study further supports our practice to suggest ovarian conservation to premenopausal patients undergoing hysterectomy for benign indications. (See "Elective oophorectomy or ovarian conservation at the time of hysterectomy", section on 'Cognitive function and neurologic disease'.)

NEUROMUSCULAR DISEASE

Sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis (October 2022)

Sodium phenylbutyrate-taurursodiol (PB-TURSO) is a combination of two orally available drugs that each reduce neuronal cell death in preclinical models of amyotrophic lateral sclerosis (ALS). In a randomized trial of 137 patients with ALS (75 percent also taking riluzole and/or edaravone) who were within 18 months of symptom onset, patients assigned to PB-TURSO showed a slower median rate of monthly functional decline than those assigned to placebo by 24-week follow-up [26]. There were nonsignificant trends toward slower decline in both vital capacity and muscle strength with treatment. In a subsequent analysis of patients who continued open-label treatment (up to 35 months), those originally randomized to PB-TURSO had a longer median time to tracheostomy (26 versus 19 months) and a longer median time to first hospitalization [27]. Based on these results, the combination product received regulatory approval in the United States and Canada [28,29]. We now suggest use of PB-TURSO for all patients with ALS, along with riluzole (prioritized as initial therapy) and edaravone. (See "Disease-modifying treatment of amyotrophic lateral sclerosis", section on 'Efficacy'.)

Transaxillary decompression for neurogenic thoracic outlet syndrome (September 2022)

Surgical decompression can improve symptoms of neurogenic thoracic outlet syndrome (nTOS) refractory to conservative management, but may not be durable. In the STOPNTOS trial, decompression in patients refractory to conservative management resulted in significantly improved DASH (Disability of the Arm, Shoulder, and Hand) scores at three months compared with continued conservative treatment, and all conservatively treated patients subsequently elected to undergo surgery [30]. Postoperatively, transient neurologic complications occurred in 7 of 46 patients, and 9 patients had persistent or recurrent nTOS after one year. These outcomes are consistent with prior observational studies and support our generally conservative approach. Additional larger trials with longer follow-up are needed to better compare surgery for refractory symptoms with ongoing conservative treatment. (See "Overview of thoracic outlet syndromes", section on 'nTOS'.)

NEUROONCOLOGY

Natural history of internal tumors in adults with neurofibromatosis type 1 (March 2023)

Peripheral neurofibromas in patients with neurofibromatosis type 1 (NF1) often grow in size and number during childhood and adolescence, but less is known about the growth trajectory in adulthood. In a prospective cohort study that included 47 adults with NF1 (median age 42 years at baseline) who were followed with serial whole-body magnetic resonance imaging for a median of 10.4 years, 63 percent of internal tumors shrank volumetrically by ≥20 percent without treatment, and only 17 percent enlarged [31]. Growth patterns were not uniform among tumors within the same patient, and no strong predictors of growth were identified. These data may aid in counseling adults with NF1 about the natural history of internal tumors. (See "Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis", section on 'Peripheral neurofibromas'.)

Reirradiation in patients with recurrent glioblastoma (March 2023)

Small studies in patients with recurrent high-grade gliomas have suggested that repeat radiation using modern high-precision techniques is feasible in selected patients, but its effect on survival has been unclear. In a phase II multicenter randomized trial of bevacizumab with or without repeat radiation (35 Gy in 10 fractions) in 182 patients with recurrent glioblastoma, bevacizumab plus reirradiation improved median progression-free survival compared with bevacizumab alone (7.1 versus 3.8 months), but median overall survival was similar between groups (10.1 versus 9.7 months) [32]. The trial population was heterogeneous, and quality-of-life outcomes were not available. Further studies are needed to determine which patients with recurrent glioblastoma are most likely to benefit from reirradiation. (See "Management of recurrent high-grade gliomas", section on 'External beam delivery techniques'.)

Tucatinib in advanced HER2-positive breast cancer with brain metastases (March 2023)

Newer anti-HER2-directed tyrosine kinase inhibitors such as tucatinib are being used for patients with advanced, HER2-positive breast cancer, but data in those with brain metastases are emerging. In an updated analysis of the HER2CLIMB trial, which included patients with heavily pretreated HER2-positive metastatic breast cancer, the addition of tucatinib to capecitabine and trastuzumab improved median overall survival among patients with brain metastases (22 versus 13 months), including in the subset with active brain metastases (21 versus 12 months) [33]. For patients with advanced HER2-positive breast cancer, we consider the tucatinib, capecitabine, and trastuzumab combination to be an effective subsequent-line systemic treatment option, including for those with brain metastases. (See "Brain metastases in breast cancer", section on 'Tucatinib, capecitabine, and trastuzumab'.)

Direct oral anticoagulants for treatment of venous thromboembolism in patients with brain tumors (January 2023)

Accumulating evidence in patients with brain tumors suggests that direct oral anticoagulants (DOACs) are associated with a lower risk of intracranial hemorrhage (ICH) than other forms of anticoagulation. In a recent observational study of 121 patients with glioblastoma and venous thromboembolism (VTE) who were treated with a DOAC or low molecular weight (LMW) heparin, the six-month incidence of clinically relevant ICH was lower with DOACs than LMW heparin (0 versus 24 percent), while rates of recurrent VTE were similar (0 versus 4 percent) [34]. Based on these and other data, we favor DOACs as a safer and more convenient option in patients with primary and metastatic brain tumors who are selected to receive anticoagulation for VTE. We generally avoid anticoagulation in patients with intratumoral hemorrhage within the past four weeks or a remote history of a clinically significant ICH. (See "Treatment and prevention of venous thromboembolism in patients with brain tumors", section on 'Direct oral anticoagulants'.)

Fam-trastuzumab deruxtecan in breast cancer brain metastases (January 2023)

Treatment for patients with breast cancer brain metastases (BMs) typically includes a local approach (ie, surgery or radiation), and few data exist regarding systemic therapy alone. In a study including 13 patients with advanced HER2-positive breast cancer and either asymptomatic untreated BMs or progressive BMs after local therapy, the antibody-drug conjugate fam-trastuzumab deruxtecan was associated with an intracranial response rate of 46 percent [35]. Data on durability of response were not yet mature for this subgroup. Although limited, these data add to accumulating evidence supporting fam-trastuzumab deruxtecan in patients whose BMs have progressed despite prior local therapy; however, the number of patients with newly diagnosed BMs treated with fam-trastuzumab deruxtecan in lieu of radiotherapy is very small, and further data are required before this strategy is employed in routine clinical practice. (See "Brain metastases in breast cancer", section on 'Fam-trastuzumab deruxtecan'.)

Role of pneumocystis pneumonia prophylaxis with temozolomide (December 2022)

Patients with glioblastoma treated with daily temozolomide can develop pneumocystis pneumonia as a result of selective lymphopenia, but rates are not well characterized and use of antimicrobial prophylaxis in the neuro-oncology community is variable.

●In a population-based study that included more than 5000 Canadian patients with gliomas treated with temozolomide chemoradiotherapy, the incidence of pneumocystis pneumonia within one year of treatment was low (0.74 percent) and there were few infection-related deaths [36].

●In a related case-control study, the absolute risk reduction associated with prophylaxis was low (estimated number needed to treat to prevent one infection = 288), while the risk of grade 3/4 neutropenia was elevated (number needed to harm = 34) [37].

We suggest pneumocystis prophylaxis during chemoradiation in patients with glioblastoma who have additional risk factors for opportunistic infection (eg, glucocorticoid use, lymphopenia); in others, risks of prophylaxis may outweigh benefits. (See "Initial treatment and prognosis of IDH-wildtype glioblastoma in adults", section on 'Pneumocystis prophylaxis'.)

Guideline on circumscribed astrocytic gliomas, glioneuronal, and neuronal tumors (October 2022)

A new multinational guideline is available on the diagnosis and treatment of rare glial and neuronal tumors in children and adults [38]. Over 20 tumors are included in the guideline, corresponding to the 2021 update of the World Health Organization classification of central nervous system tumors. Surgery is the cornerstone of management for nearly all of these tumors, and radiation therapy is used selectively in the adjuvant and recurrent/refractory setting. Relevant molecular markers and targeted therapies are also reviewed. (See "Uncommon brain tumors", section on 'Circumscribed astrocytic gliomas'.)

Proton craniospinal irradiation in patients with solid tumor leptomeningeal disease (October 2022)

For patients with leptomeningeal disease (LMD) from solid tumors, craniospinal irradiation (CSI) with photons is typically not appropriate due to high risk of toxicity and low likelihood of meaningful benefit. However, proton CSI has an improved toxicity profile compared with photon CSI, and there has been renewed interest in its role. In a randomized phase II trial of proton CSI versus involved field radiation in 63 patients with LMD from either breast cancer or non-small cell lung cancer, proton CSI improved both median central nervous system progression-free survival (7.5 versus 2.3 months) and overall survival (9.9 versus 7.5 months) compared with involved field radiation, with no difference in the rate of serious adverse effects [39]. Although more data are needed, where available, proton CSI is an option in selected patients with LMD who have adequate functional status and controlled systemic disease. (See "Treatment of leptomeningeal disease from solid tumors", section on 'Proton craniospinal radiation'.)

PEDIATRIC NEUROLOGY

Cerebral palsy and maternal injury during pregnancy (January 2023)

The underlying causes of cerebral palsy (CP) are often unknown, though several perinatal risk factors have been identified (eg, prematurity, hypoxic-ischemic injury, intrauterine infections). In a large cohort study that included over 2 million children, those with in utero exposure to accidental maternal injury requiring emergency department or inpatient care had a higher prevalence of CP compared with unexposed children (3.6 versus 2.5 per 1000 children, respectively) [40]. CP risk correlated with severity of maternal injury. These findings highlight the importance of prevention efforts to reduce the risk of severe injury during pregnancy (correct use of seat belts and airbags). (See "Cerebral palsy: Epidemiology, etiology, and prevention", section on 'Antenatal infection or injury'.)

Gene therapy for early childhood cerebral adrenoleukodystrophy (November 2022)

Standard treatment for the early childhood cerebral form of adrenoleukodystrophy (ALD), caused by pathogenic variants in the ABCD1 gene, is allogenic hematopoietic cell transplantation (HCT), if the child has a human leukocyte antigen (HLA)-matched donor. Recently, the US Food and Drug Administration (FDA) approved elivaldogene autotemcel, a novel ex vivo lentiviral gene therapy consisting of autologous HCT using stem cells transfected with manufactured ABCD1 complementary DNA [41]. The approval was based upon published and unpublished data showing that survival at nine months following treatment appeared to be better in patients treated with either HLA-matched allogenic HCT or elivaldogene autotemcel compared with HLA-mismatched allogenic HCT [42]. No patient treated with elivaldogene autotemcel developed graft-versus-host disease, which can complicate allogenic HCT. These results suggest that elivaldogene autotemcel may have comparable efficacy for early cerebral ALD compared with allogeneic HCT and may be safer, particularly when compared with HLA-mismatched allogenic HCT. However, given the relatively short follow-up, the results should be regarded as preliminary. The FDA label carries a boxed warning about the risk of hematologic malignancy and life-threatening myelodysplastic syndrome. (See "X-linked adrenoleukodystrophy and adrenomyeloneuropathy", section on 'Autologous HCT with ex vivo gene therapy'.)

OTHER NEUROLOGY

Diagnosis and misdiagnosis of autoimmune encephalitis in adults (January 2023)

Autoimmune encephalitis (AE) is a rare but treatable disorder that shares select features with other disorders, making correct diagnosis challenging. In a recent study of over 100 adults referred to tertiary care centers with a diagnosis of AE who were ultimately diagnosed with an alternative disorder, the most common correct diagnoses were functional neurologic symptom disorder, neurodegenerative disease, primary psychiatric disease, cognitive deficits from comorbidities, and cerebral neoplasm [43]. In retrospect, approximately half of the misdiagnoses of AE were caused by overinterpretation of nonspecific positive serum antibody testing. Clinicians should use clinical judgement and adhere to diagnostic criteria (table 1) when considering the diagnosis of AE, particularly when cerebrospinal fluid is not investigated for antibodies. (See "Paraneoplastic and autoimmune encephalitis", section on 'Differential diagnosis'.)

CDC updates opioid prescribing guidelines (November 2022)

The United States Centers for Disease Control and Prevention (CDC) has published a new guideline for prescribing opioids for acute, subacute, and chronic pain, updating their 2016 guideline (table 2). The guideline is intended for clinicians who prescribe opioids to outpatients ≥18 years of age and does not apply to pain related to sickle cell disease, cancer, palliative care, or end of life care [44]. (See "Use of opioids in the management of chronic non-cancer pain", section on 'Opioid therapy in the context of the opioid epidemic'.)