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

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 [1]. 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) [2]. 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'.)

Risk of intracerebral hemorrhage in transfusion recipients (September 2023)

In an explorative study using a database of blood donors and >100,000 individuals who received a transfusion, the risk of spontaneous intracerebral hemorrhage (ICH) was slightly more than twofold greater in transfusion recipients whose donors later developed two or more episodes of ICH [3]. ICH is the most common manifestation of cerebral amyloid angiopathy, which is seen in Alzheimer disease, and the study also found an increased risk of ICH in patients who received a transfusion from a donor with a single previous episode of ICH plus dementia. These findings do not demonstrate causality, and a plausible mechanism for transmission of ICH has not been identified. Further study is needed to confirm or refute this finding. (See "Blood donor screening: Medical history", section on 'Neurodegenerative and other neurologic disorders'.)

Using head CT alone to exclude aneurysmal subarachnoid hemorrhage (July 2023)

Diagnosing aneurysmal subarachnoid hemorrhage (SAH) can be challenging in patients with isolated headache whose initial bleeding is minor because head computed tomography (CT) can miss small bleeds. Morbidity and mortality risk associated with misdiagnosis causes many centers to perform a follow-up lumbar puncture to assess for blood in the cerebrospinal fluid in patients with no evidence of bleeding on CT. However, the sensitivity of high-quality head CT ranges from 95.5 to 100 percent among patients with isolated headache when performed within six hours of the onset of symptoms, potentially rendering a follow-up lumbar puncture unnecessary. Updated guidelines from the American Heart Association now endorse use of head CT to exclude SAH for selected patients when imaging performed within six hours of symptom onset is normal [4]. For properly selected patients (table 1), we agree with using head CT alone when performed within six hours of headache onset to exclude SAH. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Need for lumbar puncture when early CT is negative'.)

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) [5]. 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 [6]. 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 [7]. 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

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 [8]. 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 [9]. 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 [10]. (See "Photosensitive epilepsies", section on 'Epilepsy with eyelid myoclonia (Jeavons syndrome)'.)

New guidelines for the treatment of neonatal seizures (October 2023)

New guidelines from the International League Against Epilepsy (ILAE) recommend phenobarbital as first-line antiseizure medication (ASM) therapy for treating most etiologies of neonatal seizures [11]. The one exception is that sodium channel blockers (phenytoin/fosphenytoin or carbamazepine) are considered a first-line therapy for neonates with a channelopathy. Phenytoin, levetiracetam, midazolam, and lidocaine are considered second-line ASMs for infants who continue to have seizures despite first-line therapy. Our approach is in accordance with the ILAE guidelines. (See "Treatment of neonatal seizures", section on 'Phenobarbital for most etiologies'.)

HEADACHE

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) [12]. 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'.)

Low-dose dexamethasone for severe migraine in adults (October 2023)

Parenteral dexamethasone is used along with short-acting abortive therapies to reduce migraine recurrence for patients with severe symptoms, but optimal dosing is uncertain. Prior trials have reported benefit at doses ranging from 8 to 24 mg. In a recent trial of 209 adults with moderate to severe migraine presenting to the emergency department treated with metoclopramide and intravenous (IV) dexamethasone, rates of sustained relief at 48 hours were similar between groups randomly assigned to 4 versus 16 mg of dexamethasone [13]. Rates of immediate headache relief and medication use in the week following discharge were also similar. These results support our preference for adjunctive dexamethasone at a dose of 4 mg IV to reduce migraine recurrence. (See "Acute treatment of migraine in adults", section on 'Abortive therapy plus parenteral dexamethasone'.)

MOVEMENT DISORDERS

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 [14]. 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'.)

Neurostimulation device for restless legs syndrome (November 2023)

Noninvasive neuromodulation techniques are of interest for treatment of restless legs syndrome (RLS). One new device, tonic motor activation (TOMAC), delivers peroneal nerve stimulation via bilateral therapy units worn externally just below the knee, over the head of the fibula. In a randomized sham-controlled trial of TOMAC in 133 adults with medication-refractory RLS, TOMAC improved clinician-rated responses and RLS severity scores at 4 weeks [15], and the device was well tolerated for up to 24 weeks [16]. TOMAC received marketing approval in the United States in 2023 [17], and availability is anticipated in 2024. (See "Management of restless legs syndrome and periodic limb movement disorder in adults", section on 'Neurostimulation'.)

Valbenazine in patients with Huntington disease chorea (August 2023)

Vesicular monoamine transporter type 2 (VMAT2) inhibitors such as valbenazine are showing utility for chorea in patients with Huntington disease (HD). In a 12-week randomized trial in 128 patients with HD, valbenazine improved chorea severity compared with placebo and was well tolerated [18], leading to its approval by the US Food and Drug Administration for patients with HD and chorea [19]. For most HD patients with chorea that interferes with function, we suggest a VMAT2 inhibitor (valbenazine, deutetrabenazine, or tetrabenazine) as first-line therapy (algorithm 1). Where available, valbenazine or deutetrabenazine may be preferred over tetrabenazine due to their longer half-lives and more convenient dosing. A major exception is patients with depression, in whom VMAT2 inhibitors should be avoided due to risk of worsening depression and suicidality. (See "Huntington disease: Management", section on 'Valbenazine'.)

DaxibotulinumtoxinA for treatment of cervical dystonia (August 2023)

A new formulation of botulinum toxin A, daxibotulinumtoxinA, has received regulatory approval in the United States for treatment of cervical dystonia; it has been approved for cosmetic use since 2022 [20]. In an earlier open-label, phase 2 study in 37 patients with cervical dystonia, the proportion of responding patients was 94 percent at week 6 and 68 percent at week 24, and the median time until retreatment or loss of effect was 25 weeks. These data suggest that daxibotulinumtoxinA may have a longer duration of effect than other formulations used to treat cervical dystonia, but comparative studies and clinical experience will be needed to confirm. (See "Cervical dystonia: Treatment and prognosis", section on 'Efficacy'.)

NEUROMUSCULAR DISEASE

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 [21]. 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 [22]. 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'.)

Eplontersen for polyneuropathy related to hereditary transthyretin amyloidosis (November 2023)

Hereditary transthyretin amyloidosis (ATTR) is a rare but serious form of amyloidosis that can cause a rapidly progressive, sensory-motor and autonomic polyneuropathy. The efficacy of eplontersen, an antisense oligonucleotide that inhibits hepatic production of transthyretin (TTR), was evaluated in an open-label trial in nearly 170 patients with ATTR amyloidosis and polyneuropathy who received this agent for up to 66 weeks [23]. Patients treated with eplontersen had greater reductions in serum TTR concentrations, less neuropathy-related impairment, and better quality of life compared with historical controls receiving placebo. This trial contributed to US Food and Drug Administration approval of eplontersen in December 2023 for treatment of polyneuropathy of ATTR in adults [24]. (See "Overview of amyloidosis", section on 'Therapies for individual amyloid types'.)

New biologic agents for treatment of myasthenia gravis (July 2023, Modified October 2023)

Treatment options for acute and chronic immunosuppression in patients with myasthenia gravis (MG) continue to expand.

●Rozanolixizumab is a monoclonal antibody that binds to the Fc receptor to promote lysosomal degradation of IgG autoantibodies. In a randomized trial of 200 patients with acetylcholine receptor-positive or muscle-specific tyrosine kinase-positive MG, improvement in baseline symptoms by day 43 was greater among those assigned to rozanolixizumab (six-week course of weekly infusions at 7 or 10 mg/kg) than placebo [25]. These results led to approval by the US Food and Drug Administration (FDA) in June 2023 [26].

●Zilucoplan is a novel complement C5 inhibitor designed to prevent the autoimmune destruction of the postsynaptic membrane. In a randomized trial of 174 patients with generalized MG, patients assigned to zilucoplan (once daily subcutaneous self-injection of 0.3 mg/kg) had greater improvement in baseline symptoms at 12 weeks than those assigned to placebo [27]. These results led to FDA approval in October 2023 [28].

As with other antibody-based biologic agents, both agents may be considered early in the course of disease instead of glucocorticoids, as a bridge therapy to slower-acting agents, or as chronic maintenance therapy. (See "Chronic immunotherapy for myasthenia gravis", section on 'Rozanolixizumab' and "Chronic immunotherapy for myasthenia gravis", section on 'Zilucoplan'.)

Fatal immune reaction after gene therapy for Duchenne muscular dystrophy (September 2023)

Recombinant adeno-associated virus (rAAV) vectors used to deliver gene therapy can be associated with a risk of severe immune reactions. This was illustrated by a report of a 27-year-old patient with advanced Duchenne muscular dystrophy (DMD) and impaired cardiopulmonary function who was treated with a high dose of rAAV containing a CRISPR-based transgene designed to upregulate dystrophin [29]. After treatment, he developed worsening cardiac dysfunction, acute respiratory distress syndrome, and fatal cardiac arrest. Laboratory and postmortem studies suggested his death was due to an innate immune reaction. Further research to develop safer approaches and identify high-risk patients may help to mitigate the acute toxic effects of rAAV gene therapy. (See "Overview of gene therapy, gene editing, and gene silencing", section on 'Potential concerns with gene therapy' and "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Risk of immune reactions with AAV vectors'.)

NEUROONCOLOGY

Intraoperative techniques for glioblastoma resection (December 2023)

Several intraoperative neurosurgical techniques are available to improve the extent of glioblastoma resection while minimizing damage to normal brain, but little comparative data exist. In a multicenter parallel-group trial that included over 300 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. 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'.)

Systemic therapy for brain metastases from NSCLC (October 2023)

Trials are evaluating systemic therapy as an initial treatment option for subsets of patients with non-small cell lung cancer (NSCLC) with brain metastases:

●In a single-arm trial of single-agent targeted therapy in 19 patients with KRAS G12C-mutated NSCLC and untreated measurable intracranial disease, adagrasib was associated with an intracranial objective response rate of 42 percent and progression-free survival (PFS) of 5.4 months [31].

●In a single-arm trial of chemoimmunotherapy in 40 patients with advanced nonsquamous NSCLC with asymptomatic brain metastases, atezolizumab plus carboplatin and pemetrexed was associated with an intracranial median PFS of 6.9 months and response rate of 43 percent [32].

We consider either of these options to be reasonable initial systemic strategies in the patient populations in the respective trials; nevertheless, radiation is appropriate in such patients with untreated brain metastases, pending further comparative data between radiation and systemic therapy as an initial treatment strategy. (See "Brain metastases in non-small cell lung cancer", section on 'KRAS G12C'.)

BRAF/MEK targeted therapy in pediatric low-grade glioma (September 2023)

Targeted therapy is preferred for many children with BRAF V600E-mutant low-grade gliomas who require treatment beyond surgery. In a randomized, open-label, phase 2 trial in 110 such children requiring treatment after surgery for either symptoms or progression, first-line targeted BRAF/MEK inhibition (dabrafenib plus trametinib) improved overall response rate compared with carboplatin plus vincristine chemotherapy (47 versus 11 percent); it also improved median progression-free survival (20.1 versus 7.4 months) and was better tolerated [33]. Overall survival data are not yet mature. Although not compared with radiation therapy, targeted therapy has the advantage of avoiding or at least delaying the long-term neurologic and cognitive consequences of radiation, which are of particular concern in younger patients. (See "Uncommon brain tumors", section on 'Ganglioglioma and gangliocytoma'.)

Prevalence of Lynch syndrome in younger adults with glioblastoma (August 2023)

Mismatch repair (MMR) deficiency and Lynch syndrome are rare among patients with glioma as a whole, but certain patients are at increased risk. In a study that included 1225 adult glioma samples referred to a single neuropathology department, nine gliomas were MMR deficient (0.73 percent), including eight isocitrate dehydrogenase (IDH)-wildtype glioblastomas [34]. In a complementary analysis that included >250 additional IDH-wildtype glioblastomas enriched for young-onset cases, the rate of MMR deficiency was as high as 12.5 percent in patients between 18 and 39 years of age. Based on these data, we suggest tumor testing for MMR deficiency in IDH-wildtype glioblastomas in patients younger than 50 years at diagnosis; all patients with MMR deficiency on somatic (tumor) testing should be offered genetic counseling and germline testing for Lynch syndrome. (See "Risk factors for brain tumors", section on 'Mismatch repair deficiency'.)

Resection versus biopsy of glioblastoma in older adults (August 2023)

The role of surgical resection in older adults with glioblastoma is controversial. In the first completed trial, 101 older adults (≥70 years) with a suspected operable glioblastoma were randomly assigned to either resection or biopsy, followed by radiation therapy (in all patients) and temozolomide (in later years of the trial) [35]. Although overall survival was similar between groups (9.4 versus 9.0 months), progression-free survival and quality-of-life outcomes favored resection. The trial was limited by slow enrollment, and confidence intervals for survival were wide. We continue to suggest maximal safe resection for most older adults with operable tumors who are good surgical candidates. (See "Management of glioblastoma in older adults", section on 'Role of surgery'.)

BRAF/MEK targeted therapy in papillary craniopharyngioma (July 2023)

Nearly all papillary craniopharyngiomas harbor a BRAF V600E mutation, and new data confirm that these tumors are exquisitely sensitive to combined BRAF/MEK inhibition. In a multicenter, single-arm, phase 2 study in 16 patients with biopsy-confirmed BRAF V600E-mutant papillary craniopharyngioma and no prior therapy, treatment with vemurafenib plus cobimetinib led to a partial or complete response in 15 of 16 patients (94 percent) [36]. Among responders, median volumetric tumor reduction from baseline was 91 percent. For most patients with newly diagnosed BRAF-mutant papillary craniopharyngioma, we suggest a trial of BRAF/MEK inhibition before proceeding with definitive radiation therapy or an attempt at maximal resection; treatment decisions after four to six cycles of therapy should be individualized based on tumor response, patient age, comorbidities, and risks of radiation and surgery. (See "Craniopharyngioma", section on 'Targeted therapy for BRAF-mutant tumors'.)

PEDIATRIC NEUROLOGY

Intrapartum magnesium sulfate before preterm birth and cerebral palsy (October 2023)

Magnesium sulfate is typically administered to pregnant women with impending preterm birth <32 weeks of gestation to decrease the incidence and severity of cerebral palsy in offspring. However, the recent MAGENTA trial comparing the effects of magnesium sulfate versus placebo administered before impending preterm birth between 30 and 34 weeks of gestation found that it did not prevent cerebral palsy among surviving infants [37]. These findings do not change our current practice because the trial used a single 4 g bolus of magnesium sulfate alone, whereas we also provide an ongoing 1 g/hour infusion until delivery and do not use the medication after 32 weeks; the trial was likely underpowered to find a significant difference. (See "Neuroprotective effects of in utero exposure to magnesium sulfate", section on 'Lower and upper gestational age'.)

Management of spinal deformities in children with NF1 (September 2023)

New consensus-based guidelines on the management of spinal deformities, including scoliosis in children with neurofibromatosis type 1 (NF1), have been published [38]. The guidelines recommend screening for spine deformity by physical examination at diagnosis and yearly thereafter. To limit radiation exposure in the pediatric population, diagnostic spine imaging is suggested only if clinical suspicion for a spinal abnormality arises from patient history or physical examination. Spinal tumor burden must be assessed preoperatively in any patient with NF1 undergoing surgery for scoliosis because instrumentation that impedes visualization of spinal tumors by magnetic resonance imaging is not recommended when spinal tumor burden is high. (See "Neurofibromatosis type 1 (NF1): Management and prognosis", section on 'Scoliosis'.)

Gene therapy for Duchenne muscular dystrophy (August 2023)

Delandistrogene moxeparvovec is a microdystrophin transgene delivered by an adeno-associated virus vector. The drug received accelerated approval from the US Food and Drug Administration (FDA) for the treatment of ambulatory males, ages four through five years, with Duchenne muscular dystrophy (DMD) who have a pathogenic variant in the DMD gene [39]. FDA approval was based upon the surrogate outcome of increased dystrophin production, as shown in a placebo-controlled trial of 41 patients with DMD [40]. There was no improvement in functional outcome with delandistrogene moxeparvovec treatment compared with placebo, but a subgroup analysis suggested possible improvement with active treatment for the four- to five-year age group. Despite lack of proven benefit, we anticipate that most eligible patients and their families will request treatment. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Delandistrogene moxeparvovec'.)

OTHER NEUROLOGY

6th International Conference on Concussion in Sport (August 2023)

Recently, a consensus statement and multiple systematic reviews and other studies were published based on work completed at the 6^th International Conference on Concussion in Sport held in Amsterdam in late 2022 [41]. Highlights from the conference include evidence summaries emphasizing the effectiveness of policies to reduce the risk for sports-related concussion (SRC), including mouthguard use in ice hockey and limiting contact drills in American football, and updated clinical assessment tools. These tools include the sixth edition of the Sport Concussion Assessment Tool for adults and children (SCAT6 and Child SCAT6), designed for acute evaluations, and the new Sports Concussion Office Assessment Tool 6 for adults and children (SCOAT6 and Child SCOAT6). The conference affirmed the importance of physical activity and aerobic exercise that does not exacerbate symptoms as an early intervention. The conference consensus statement is consistent with our approach to the assessment and management of SRC. (See "Clinic-based evaluation of sports-related concussion in adolescents and adults", section on 'Introduction'.)