Safety and Efficacy of Adjunct Dexamethasone in Adults with Herpes Simplex Virus Encephalitis in The UK - Part 2

In this lab update, Dr. Stacey Clardy discusses the latest information on chronic wasting disease. 

In part two of this series, Dr. Aaron Zelikovich discusses the clinical implications for patients with HSV encephalitis.  Show citation:  Solomon T, Hooper C, Easton A, et al. Safety and efficacy of adjunct dexamethasone in adults with herpes simplex virus encephalitis in the UK (DexEnceph): a multicentre, observer-blind, randomised, phase 3, controlled trial. Lancet Neurol. 2026;25(2):136-146. doi:10.1016/S1474-4422(25)00454-5 

Dr. Greg Cooper and Dr. Kerry Sheets discuss how hearing aid use affects cognition and the risk of dementia in older adults with hearing impairment.  Show citations: Cribb L, Moreno-Betancur M, Pase MP, et al. Treating Hearing Loss With Hearing Aids for the Prevention of Cognitive Decline and Dementia. Neurology. 2026;106(3):e214572. doi:10.1212/WNL.0000000000214572  Show transcript: Dr. Greg Cooper: Hi, this is Greg Cooper. I just finished interviewing Kerry Sheets for this week's Neurology Podcast. For today's Neurology Minute, I'm hoping you can tell us the main points of your paper. Dr. Kerry Sheets: The central message of our paper is that hearing aid use in adults aged 70 years or older with hearing impairment may reduce dementia risk over 7 years. Results for the impact of hearing aid use on cognitive decline were less. Dr. Greg Cooper: Well, thank you for that summary and for all of your work on this topic. Please check out this week's podcast to hear the full interview and read the full article published in Neurology: Treating Hearing Loss with Hearing Aids for the Prevention of Cognitive Decline and Dementia. 

Dr. Jessica Ailani and Dr. Richard Lipton discuss future advancements in headache medicine.  Show transcript:  Dr. Jessica Ailani:  Hello and welcome to the Neurology Minute. I'm Jessica Ilani from Georgetown Headache Center in Washington, DC. In the neurology podcast with Richard Lipton from the Montefiore Headache Center, we'll be discussing the latest clinical trials in headache medicine, where our field is going, where it's been, and you'll get lots of great advice on thinking through a clinical trial, what the advances have been, where their pitfalls have been, and really how to think of both positive and negative trials. So Richard, what are you most looking forward to when it comes to new treatment targets within headache? Dr. Richard Lipton:  First, let me say that I'm sure most know about the eight CGRP targeted treatments have been approved for migraine, both as acute and preventive treatments. And it's very clear that those treatments have had incredible benefits for our patients and have really improved headache practice. There's another neuropeptide target also targeted by monoclonal antibodies called PACAP or pituitary adenolyte cyclase activating polypeptide. This peptide is also a potent vasodilator involved in pain signaling like CGRP. While CGRP is primarily linked to sensory pathways, PACAP is found in parasympathetic ganglia. And for that reason, it may have a special role in headaches associated with cranial autonomic symptoms. And that includes both migraine, which commonly has cranial autonomic symptoms and also cluster headache. There's a recent randomized trial published in New England Journal showing that a monoclonal antibody targeting PACAP reduced monthly migraine day frequency and was beneficial in people who failed to respond to CGRP inhibitors. So that's at least one area that I'm hopeful about. Dr. Jessica Ailani:  So Richard, thank you so much. I hope you have a few moments and listen to our full podcast that'll tell you a lot more about the future of headache medicine. 

In part one of this series, Dr. Aaron Zelikovich discusses the trial design and primary results.  Show citation:  Solomon T, Hooper C, Easton A, et al. Safety and efficacy of adjunct dexamethasone in adults with herpes simplex virus encephalitis in the UK (DexEnceph): a multicentre, observer-blind, randomised, phase 3, controlled trial. Lancet Neurol. 2026;25(2):136-146. doi:10.1016/S1474-4422(25)00454-5  Show transcript:  Dr. Aaron Zelikovich:  Welcome to today's Neurology Minute. My name is Aaron Zelikovich. I'm a neuromuscular specialist at Lenox Hill Hospital in New York City. Today, we'll discuss part one of a three-part series reviewing a recent article titled Safety and Efficacy of Adjunct Dexamethasone in Adults with Herpes Simplex Virus Encephalitis in the United Kingdom (DexEnceph) Study, a multicenter observer-blind randomized phase three control trial published in Lancet Neurology. In the first episode, we'll focus on the trial design and primary results. In part two, we'll discuss the clinical implications for patients with HSV encephalitis, and in part three, discuss the outcomes seen across the trial during and after an acute infection. Overall, the study found that adjunct dexamethasone did not improve outcomes in patients with CSF-confirmed HSV encephalitis. But importantly, it also did not worsen outcomes. Prior research that was non-randomized and retrospective of 45 patients with HSV encephalitis found that patients did not receive corticosteroids had worse outcomes. A different randomized trial looking at dexamethasone and HSV encephalitis was only able to recruit 41 patients and was stopped prematurely due to the lack of recruitment. Prior to the study, there was no clear evidence that adjunct steroids with acyclovir improved outcomes in HSV encephalitis. The Dex and phase three randomized clinical trial performed in the United Kingdom at 53 hospitals recruited patients from 2016 to 2022. They screened over 1,400 patients of which only 94, or 6%, were enrolled. Patients were randomized to either acyclovir only or acyclovir and intravenous dexamethasone. In order to be randomized, patients had to have a febrile illness with new onset seizure or new focal neurological sign or altered mental status as well as a positive HSV type one or two PCR from the CSF. The primary outcome for this study was the Wechsler Memory Scale Type Four Auditory Memory Index Score which was collected at 26 weeks. It had a range of 40, which is the worst outcome, to a range of 160 which was considered normal. 81 patients were included in the modified intention-to-treat analysis. Of the 13 patients, six were lost to follow-up, and seven withdrew consent. There were 39 patients in the dexamethasone group and 42 in the acyclovir-only group in the final analysis. The primary outcome of the Wechsler Memory Scale had similar scores in both groups. 71 in the dexamethasone group and 69 in the control group with a P value of 0.76. The safety profile was similar in both groups, and there were no additional safety signals found in the dexamethasone-treated group. At 26 weeks, there were 12 deaths from HSV encephalitis, six from each group, as well as a similar time to discharge between both cohorts. The DexEnceph clinical trial did not show any clear clinical benefit for dexamethasone with regards to clinical outcomes but also didn't show any increased safety concerns compared to only acyclovir. In part two, we will discuss the implications of this trial in patients with undifferentiated encephalitis and the role that steroids play in patients that HSV encephalitis is suspected. Thank you so much, and have a wonderful day.   

In the second part of this series, Dr. Tesha Monteith and Dr. Jennifer Robblee discuss updates to the emergency room recommendations for the acute treatment of migraines.  Show citations:  Robblee J, Minen MT, Friedman BW, Cortel-LeBlanc MA, Cortel-LeBlanc A, Orr SL. 2025 Guideline Update to Acute Treatment of Migraine for Adults in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. Headache. 2026;66(1):53-76. doi:10.1111/head.70016 Robblee J, Khan FA, Marmura MJ, et al. Reaching International Consensus on the Definition of Refractory Migraine Using the Delphi Method. Cephalalgia. 2025;45(9):3331024251367767. doi:10.1177/03331024251367767 Show transcript:  Dr. Tesha Monteith:   Hi, this is Tesha Monteith with the Neurology Minute. I've just been speaking with Jennifer Robblee about her exciting work, defining refractory migraine with an international consensus, as well as her work with the American Headache Society on a guideline update for parental pharmacotherapies for migraine in the emergency department. So Jennifer, we've just been chatting on the podcast about all the great work out of the American Headache Society, updating the emergency room recommendations for acute treatment of migraine. Can you give a summary of those findings? Dr. Jennifer Robblee:  We looked at all of the new data for randomized control trials in the emergency room. We found 26 new trials, and several of those were actually a class one study that we felt had a low risk of bias. And from that, we applied the grading. So we actually have two grade A medications where it is that you must offer, of course, to the appropriate patient. And that's prochlorperazine IV, and greater occipital nerve blocks. Now, there's also a grade A must not offer, and that's IV hydromorphone. Then we have some grade B, which is should offer, and that's dexketoprofen, ketorolac, metaclopramide, sumatriptan subcutaneous, and supraorbital nerve blocks. So really exciting that we have lots of things that we can now say we have pretty good evidence or very good evidence to offer them to our patients. Dr. Tesha Monteith:  Great. It's always nice to see this update based on evidence. Dr. Jennifer Robblee:  Yes, I think it's so important, because right now when we see patients, and I'm sure you get this all the time, they come back, say they were in the emergency room for a severe headache and they got a migraine cocktail. And you're like, "Do you know what you were given?" And they say, "I don't know. I was just told it's a migraine cocktail." And as you know, that mean many, many different things. And when you are able to pull the records, it is many, many different things that a migraine cocktail can mean. So I'm hoping that this can start to standardize what we're actually giving our patients as we await more trials in the future that might start to tell us what that combo of treatments really should be. For right now, these at least tell us what individual treatments have the best evidence. Dr. Tesha Monteith:  Thanks so much, Jennifer.  

In this episode, Dr. Jason Crowell reviews the March 9th Capitol Hill Report discussing the AAN's advocacy priorities for 2026. Stay updated with what's happening on the hill by visiting aan.com/chr.  Learn how you can get involved with AAN advocacy.  Show transcript:  Dr. Jason Crowell: Hey, this is Jason Crowell. Thanks for listening to today's Neurology Minute. Today, we have an advocacy update from the AAN's Capitol Hill Report. The AAN has come out with its top advocacy priorities for 2026, and the first is access to care which includes affordable prescription drug prices, telehealth, and adequate coverage policies. Neurological conditions can require expensive specialty drugs as we know, so the AAN supports policies that ensure prescription medications are accessible to patients. Related to this priority, the Center for Medicare and Medicaid Innovation recently announced the GLOBE and GUARD models, two proposed mandatory drug pricing models that would make manufacturers pay rebates if their drug prices exceed global benchmarks. The AAN has responded to these proposals with recommendations to avoid unintended access issues. It's also important to make telehealth flexibilities permanent for Medicare beneficiaries, and the AAN has been lobbying for the CONNECT for Healthcare Act to do that. The second top priority is reducing regulatory and administrative burdens, like prior authorization and step therapy which we're familiar with. This is a longtime problem for physicians who spend a lot of time each week. We deal with these processes and we'd rather be treating patients, as you know. A new Medicare initiative called the WISeR Model establishes new prior authorization requirements for some medical services, and while it doesn't directly affect neurology, the AAN and other organizations are pushing back and closely monitoring for future similar models. Next is the neurology workforce. This includes making sure Medicare reimbursement for neurological services is enough to maintain a practice, as well as supporting wellness and immigration policy to allow international medical graduates to practice in the US. Related to this priority, the AAN has been pushing for a permanent inflationary update to the Medicare Physician Fee Schedule and to end the schedule's outdated budget neutrality requirement that ends up causing cuts to reimbursement each year. The final priority is neuroscience research and brain health. There have been a lot of threats to research funding recently, and the AAN has been lobbying for NIH and NINDS funding that includes the BRAIN Initiative, an important program that's led to neurology breakthroughs. It's set to lose a big part of this funding at the end of the year when funding from the 21st Century Cures Act expires. So the AAN has been asking Congress to help make up the gap through appropriation spending. There's much more in this week's Capitol Hill Report, and this is available on aan.com/chr, and for our US members, you can also find this Capitol Hill Report in your inbox. So check it out to learn more. 

Dr. Halley Alexander and Dr. Abel Sandmann discuss seizure rates and risk factors in patients with cerebral cavernous malformations (CCMs) during long-term follow-up without CCM intervention.  Show citation:  Sandmann ACA, Vandertop WP, White PM, Verbaan D, Coutinho JM, Al-Shahi Salman R. Seizures and Epilepsy in Patients With Untreated Cerebral Cavernous Malformations: A Prospective, Population-Based Cohort Study. Neurology. 2025;105(11):e214387. doi:10.1212/WNL.0000000000214387  Show transcript:  Dr. Halley Alexander: Hi, this is Halley Alexander with today's Neurology Minute. I'm here with Abel Sandmann from Amsterdam University Medical Center, and we just finished recording a full-length podcast about some exciting findings related to cerebral cavernous malformations and the risk of seizures and epilepsy. Abel, can you give our listeners a rundown of the most exciting findings and how it can change practice? Dr. Abel Sandmann:  In our paper, we show that patients with a cerebral cavernous malformation who have a first unprovoked seizure should be diagnosed with epilepsy and considered for anti-seizure medication, as most of them achieve long-term seizure freedom with medical therapy alone. These findings are based on a prospective population-based cohort study in which we analyze long-term follow-up and assess the rates and risk factors for: one, a first-ever epileptic seizure; two, seizure recurrence to evaluate the updated ILAE definition of epilepsy; and three, seizure freedom over two years and five years among patients with epilepsy. We found that among patients who had never experienced a seizure before, the 10-year risk of a first-ever seizure was only 6%. This supports current recommendations against prophylactic anti-seizure medication in patients who are incidentally diagnosed with a cerebral cavernous malformation. However, following a first unprovoked seizure, the 10-year risk of recurrence was 80%, which exceeds the 60% threshold defined by the ILAE. This justifies diagnosing epilepsy after the first and provoked seizure in this population. Given that the risk of recurrence was lower in patients treated with anti-seizure medication after the first seizure, this supports early initiation of therapy, although these treatment analyses were non-randomized and should be interpreted cautiously. Most patients who met the definition of epilepsy became two year and five years seizure-free with medical management alone. But some patients with cerebral cavernous malformations develop medically intractable seizures and might benefit from surgical treatments. Dr. Halley Alexander: Excellent. Thank you so much, Abel. You can find the full-length podcast, which is available now on the Neurology Podcast, or you can also find the full article in Neurology at neurology.org, or in the December 2025 print issue. As always, thanks for tuning in for today's Neurology Minute.   

In part one of this series, Dr. Tesha Monteith and Dr. Jennifer Robblee discuss an international consensus definition for refractory migraine and why clearer criteria are needed.  Show citations: Robblee J, Minen MT, Friedman BW, Cortel-LeBlanc MA, Cortel-LeBlanc A, Orr SL. 2025 Guideline Update to Acute Treatment of Migraine for Adults in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. Headache. 2026;66(1):53-76. doi:10.1111/head.70016 Robblee J, Khan FA, Marmura MJ, et al. Reaching International Consensus on the Definition of Refractory Migraine Using the Delphi Method. Cephalalgia. 2025;45(9):3331024251367767. doi:10.1177/03331024251367767 Show transcript:  Dr. Tesha Monteith: Hi, this is Tesha Monteith with the Neurology Minute. I've just been speaking with Jennifer Robblee about her exciting work defining refractory migraine with an international consensus, as well as her work with the American Headache Society on a guideline update for parental pharmacotherapies for migraine in the emergency department. Hi, Jennifer. Thanks again for coming on our Neurology Minute. Dr. Jennifer Robblee: Thank you so much for having me. I'm delighted to be here. Dr. Tesha Monteith: You've done a lot of work in the area of refractory migraine. Why don't you tell us why you felt there need to be clarification on the definition? Dr. Jennifer Robblee: Well, this is a patient population that I'm really passionate about. There's not enough research out there. We don't really know who these patients are, why they're not responding to treatment, and we don't know how to help them because we have no guidelines, obviously, since they're refractory to what we use for treating. So I thought it was really good to get an international group to standardize our definition and hopefully help move the research forward. Dr. Tesha Monteith: Why don't you tell us a little bit about the consensus definition Dr. Jennifer Robblee: So we came up with an international consensus definition for refractory migraine that was laid out the same way that migraine is, say, laid out in the ICHD-3 diagnostic manual, if you want to call it that. So we have different criteria on. So criterion A basically allowed for it to be episodic or chronic migraine. Criterion B had three subcriteria, so you needed to have at least two out of three of severe to very severe disability and/or a constant background headache and/or at least eight monthly migraine days. Criterion C was about the lack of response to treatment. And basically it says that you needed to have failure of all medication categories, and there is an extra one for an other in case any new treatments emerge before the diagnostic criteria get updated. And what we considered a, quote, unquote, failure was that you did not have a 50% improvement in monthly migraine days, or you had intolerable side effects, or you had an absolute contraindication. There is a caveat that you need to have at least four true lack of efficacies. And then the CGRP monoclonal antibody or gepant category and the onabotulinumtoxin toxin category both had to be a true lack of response. And of course, there's a criterion B to say that this should not be from another diagnosis. Dr. Tesha Monteith: Thanks so much, Jennifer.

Dr. Stacey Clardy reviews biotin deficiency and biotin-related lab interference. Show transcript:  Dr. Stacey Clardy: Hi, this is Stacey Clardy from the Salt Lake City VA and the University of Utah, and I'm back with you for another lab minute. Today, let's talk about Biotin or vitamin B7, because the Biotin story in neurology has two very different aspects. The first is a real deficiency, which is uncommon, but clinically really important. And the second is the modern problem of biotin supplementation that's quietly wrecking our lab interpretation. So first, true biotin deficiency in adults is less common, but it can look like a multi-system neurologic syndrome. The classic teaching is dermatitis and alopecia, so keep those in your mind. But neurologists end up seeing the downstream features. So lethargy, depression, paresthesias and sometimes ataxia. Now, in infants and children, the bigger higher stakes entity is biotinidase deficiency, which is fortunately screened in many newborn programs in the US. Untreated, it can produce seizures, developmental delay, optic atrophy, and hearing loss. And the key point is that these neurologic injuries can be prevented if biotin is started early enough. Also, remember, there are numerous reports now in the literature of it mimicking the clinical and radiological features of neuromyelitis optica spectrum disorder or multiple sclerosis. So if you have one of those diagnoses and you're not quite sure that it's right, keep biotinidase deficiency in the back of your mind. Now, what most of us clinicians are living with is the biotin supplement era. So high dose biotin, taken by a lot of people, either knowingly or unknowingly, can interfere with biotin streptavidin immunoassay platforms. And the direction of error depends on the assay design, but the practical pitfalls are simple. You can be handed a lab pattern that screams something like hyperthyroidism or other endocrine pathology, and it can actually be purely analytical artifact. Thyroid testing is the most common example, and troponin and other assays can also be affected depending on the assay platform. So a common clinical misstep is to treat the lab burnout rather than the patient. So if your patient symptoms don't match this new endocrine emergency that the lab appears to be showing, ask, are they taking biotin? This is commonly in hair and nail supplements or buried in the myriad ingredients of another fix all supplement. So you need to find out if it's in any of those. The easiest thing is to say, tell me all of the supplements and the brands you're taking. And then I usually do a quick internet search right there to find out if biotin's in there. And so the lowest friction fix is generally to repeat the test after holding biotin for an appropriate interval. At least a week is usually a safe time to guess about. The key is coordination with the laboratory. Not every lab behaves the same and some systems now actually have evolved mitigations, which is quite helpful. So that's the biotin update. So remember, biotin deficiency is treatable and sometimes urgent. And also, biotin supplementation is now a common lab confounder that can trigger avoidable diagnostic and therapeutic errors. Thanks for spending a few minutes with me. This is Stacey Clardy, and that's your lab minute.