First-of-its-kind therapeutic for dangerous neurodegenerative symptom, common neuro condition causes memory loss, and a new way to improve drug adherence

It’s not often that the worlds of neurology, pulmonology, and oncology come together all at once, but this week, we’re bringing you a story that makes it happen, with an interesting set of benefits for all three specialties. That’s not all, though—we’ve got brand new bona fides for one of the most-prescribed migraine drugs, new long-term concerns for migraine sufferers, new ways to predict post-op delirium, and much, much more.

Neuro Flashback

Since the 1300s, scientific texts have made allusions to multiple sclerosis-like progressive illnesses, but the disease didn’t become an official diagnosis until the famous French neurologist Jean-Martin Charcot lectured on the features of MS and gave it its name back in 1868. Because of his contributions (he defined and treated many other neurological disorders, too), some point to Charcot as the founder of modern neurology. At the very least, we ought to point to him as being extremely humble, because, unlike Alois Alzheimer, Guillaume Benjamin Amand Duchenne, James Parkinson, and Pierre Paul Broca, Charcot selflessly refrained from stamping his name on all of his discoveries.

Throughout the 1800s and 1900s, scientists and physicians like Charcot tried hundreds of therapies for MS, including (get ready to cringe) arsenic, mercury, and deadly nightshade—a plant with poisonous fruit. Today, more than 20 medications are approved for relapsing forms of MS. Our newest therapies aren’t perfect, but there’s no doubt that we’ve come a long way.

In the News

Don’t forget the migraine. Recent research is beginning to uncover a link between migraines and memory that’s deeply concerning. We hate to continue to break the bad news, but new evidence suggests having a personal or family history of migraine increases the risk of recurrent transient global amnesia (TGA). Currently, common practice is for physicians to reassure patients that TGA is benign and has a low risk for recurrence. The results of this study could change that practice.

Researchers reviewed the medical records of 1,044 patients diagnosed with TGA from 1992 to 2018, of which 86% had a single TGA episode and 14% had recurrent episodes. There was a personal history of migraines in 20% of individuals with a single episode of TGA and 36% of those with recurrent episodes. This study, combined with other evidence, indicates that TGA recurrence is not as rare as we thought—rates of between 10% to 15% within 5 years are common—and that patients with a personal or family history of migraine have a significantly higher likelihood of TGA recurrence.

Multiple sclerosis and migraine. Have a patient with multiple sclerosis? Odds are about 31% that they have migraine, too, according to a new systematic review and meta-analysis published in the Journal of Clinical Neuroscience.

To explore the links between migraine and multiple sclerosis, researchers led by Omid Mirmosayyeb, MD, from Isfahan University in Iran, pulled data from 11 articles and 12 abstract conference papers. The pooled studies included more than 11,000 cases of patients with multiple sclerosis, in which researchers found that the prevalence of migraine ranged from 2% to 67%, with a pooled prevalence of 31%. This pooled prevalence varied widely by geographic region: 24% in Asian countries, 43% in the Americas, 25% in European countries, and 43% in African countries. Next up: more research to find out whether there is genetic involvement in the development of both diseases, and if so, how that could impact diagnosis and treatment.

From AHA: New details on stroke reduction. The American Heart Association (AHA) has published new strategies aimed at helping clinicians reduce their patients’ risk of stroke during and after heart surgery. Here are the big ideas: Intraoperative neuromonitoring based on local availability and expertise is suggested for stroke prevention, and the use of epiaortic scanning is recommended. A mean arterial pressure of between 60 to 65 mm Hg should be maintained during cardiopulmonary bypass. Active perfusion techniques should be employed in aortic cases with an expected long circulatory rest time. Surgical thrombectomy or delay of surgery and anticoagulation should be considered in the presence of intracardiac thrombus.

Here’s what is perhaps the most relevant for neurologists: A complete postoperative neurologic exam should be performed as soon as the clinical situation allows. A fast-track anesthesia protocol should be considered for those at high risk for stroke. A “stroke team” should be in place, and the team should be alerted immediately in the case of clinical suspicion of stroke. In the case of perioperative stroke, the patient should be transferred to the intensive care setting. Cerebral oxygenation and perfusion should be optimized, and thrombolysis and thrombectomy should be considered.

Neurologic telehealth getting the go-ahead. We’re learning a lot from the COVID-19 pandemic, and we hope you are too. Investigators at the Children’s Hospital of Philadelphia (CHOP) are now learning that most children’s neurology care can be accomplished via telemedicine. That’s the takeaway from new research published in Neurology, which analyzed 2,589 child neurology telehealth encounters necessitated by the pandemic.

Results showed that clinicians considered telemedicine satisfactory in 93% of encounters and suggested telemedicine as a component for follow-up care in 89% of encounters. On the flip side, technical challenges were reported in 40% of encounters, and in-person assessment was warranted in 5% of cases. Both patients and caregivers said they’d be interested in telemedicine for future care in 86% of encounters. The findings suggest that telemedicine is feasible and effective for most child neurology care, authors noted, but additional studies will need to ensure that it can be used equitably.

Neuro Trivia

What is the average lifespan of a neuron?

About the same as your lifespan. According to Dr Randall Platt, “the neurons you’re born with are mostly the neurons you have when you die, so these cells live with you your entire life.” 

Novel Diagnostics

Predicting postoperative delirium. Physicians have previously used the modified frailty index (mFI), which reflects the status of a patient’s physiologic decline, to successfully predict adverse outcomes in several surgical patient cohorts. Now, they’re adding a new ability to the list: predicting postoperative delirium (POD) and delayed neurocognitive recovery after total joint arthroplasty (TJA). 

In a new study published in the New England Journal of Medicine, researchers monitored 383 participants admitted for primary elective TJA under general anesthesia combined with inhalation agents from January 2018 to December 2019. POD and delayed neurocognitive recovery were assessed for each patient. Investigators found that the total incidence of POD was 17.2% and the total incidence of delayed neurocognitive recovery was 24.8%. Higher age (≥ 72 years) and higher mFI level (≥ 0.18) were both independent risk factors for POD and delayed neurocognitive recovery. The big takeaway? Preoperative mFI evaluation can be used for risk stratification, offering significant potential for clinical applications, according to the authors.

More disconcerting data for depression and dementia. What’s the best way to beat dementia? Get way ahead of it. That’s why researchers have put so much energy into identifying risk factors for the condition—especially modifiable ones, like depression. Now, new research further bolsters the connection between depression and dementia. In a study at two nursing homes in Spain, investigators have found that depressive symptomology is associated with cognitive deterioration in geriatric patients.

Using the Cambridge Cognitive Test (CAMCOG) and the Geriatric Depression Scale (GDS), researchers analyzed 70 dependent and 70 nondependent adults, and found that depression was correlated with cognitive level in the nondependent older adult sample. Age was inversely associated with score obtained in CAMCOG, and the functional capacity in several activities of daily living was correlated with the score obtained in the CAMCOG in each of the two groups. Depression was more prevalent in the dependent than in the nondependent older adults. Combined with other data, it appears convincing that depression is a risk factor for dementia. Depression is highly prevalent in nursing homes—nearly 50%, according to one estimate from the CDC.

TBI overstays its welcome. Traumatic brain injury (TBI) is bad enough as it is, but new research published in Neurology suggests it brings long-lasting chemical effects, which can be detected decades after the initial injury. Investigators set out to determine whether blood-based biomarkers could differentiate older veterans with and without TBI and cognitive impairment (CogI), so they enrolled 155 veterans from 2 veterans’ retirement homes (90 without TBI and 65 with TBI history). They further stratified these patients into CogI groups: 60 controls with no CogI, 30 patients with TBI who didn’t have CogI, and 35 with CogI and TBI.

In adjusted analyses, the TBI and CogI groups differed on CNS-enriched exosome concentration of p-tau, NfL, IL-6, TNF-α, and GFAP, but not on Aβ42 or other markers. Adjusted area under the curve analyses found that all significantly associated biomarkers combined separated TBI with/without CogI (AUC 0.85) and CogI with/without TBI (AUC 0.88). In veterans with TBI, increased levels of blood-based, CNS-enriched exosome concentration of p-tau, NfL, IL-6, and TNF-α are associated with CogI.

DNA content gives clues for cardiometabolic strokes. According to a new study published in Stroke, thrombus DNA content may provide an accurate biomarker for the identification of cardioembolic thrombi in patients with acute ischemic stroke (AIS) and stroke of undetermined source. How’d we get here? Identifying the cause of AIS is crucial for determining which secondary intervention is best, but previous studies have given the scientific community inconsistent results regarding possible correlations between AIS cause and thrombus composition.

In this study, researchers studied the homogenates of 250 patients with AIS thrombi, which were prepared by mechanical grinding. Platelet, red blood cell, and leukocyte content of the AIS thrombi were estimated by quantification of glycoprotein VI, heme, and DNA thrombus in homogenates, and AIS cause was defined as cardiometabolic, noncardioembolic, or embolic stroke of undetermined source. Researchers found that cardioembolic thrombi were richer in DNA and poorer in glycoprotein VI than noncardioembolic ones, suggesting that thrombus DNA content may provide an accurate biomarker in patients with AIS.

Novel Treatments

Going beyond dementia for Alzheimer’s. Dementia and memory problems are front and center in Alzheimer’s. But behind those serious problems there’s a world of lesser-known behavioral and psychological symptoms, like psychosis, agitation, and aggression. In fact, Alzheimer’s disease psychosis (ADP) is its own unique diagnosis—one with no approved treatments. That could change, thanks to a new study published in Geriatric Psychiatry, which suggests that patients with ADP who show improvement in psychotic symptoms after taking pimavanserin also experience improvements in concomitant agitation and aggression.

Specifically, patients treated with pimavanserin with ≥ 50% response in psychotic symptoms showed a greater improvement in agitation and aggression symptoms at week six as measured by an approximately 4-point change from baseline on the Neuropsychiatric Inventory-Nursing Home Version-Psychosis Score (NPI-NH-PS). Collectively, these results suggest that the improvement in hallucinations and delusions after pimavanserin treatment are related to improvements observed in agitation and aggression. The mechanisms that drive that relation are still unclear, but what’s most important is the fact that safe and effective treatments to address symptoms of ASD, as well as concomitant agitation and aggression, are a critical unmet need.

Improving AED adherence. Between 20% and 30% of epilepsy patients have poor seizure control. It’s not always because they’re resistant to antiepileptic drugs (AEDs)—they may just be non-adherent to their treatments. That doesn’t just make seizures worse, it also increases costs, morbidity, and even mortality. So how can we increase antiepileptic drug adherence? An app? A phone call reminder? Some fancy technology?

None of the above. In a new study, South Korean researchers found that simply switching AEDs to a once-daily dosing regimen was an effective therapeutic option in patients with poor seizure control because of non-adherence. Among 401 patients with drug-resistant epilepsy, 88 patients with AED non-adherence were switched to once-daily dosing regimens. In those patients, 52.3% experienced successful seizure control following the switch. Successful switches were more likely in patients without MRI abnormality and those who were switched to extended-release formulations or AEDs with longer half-lives. The bottom line? A simpler approach is warranted, and clinicians should consider prescribing extended-release formulations and drugs with longer half-lives.

Duchenne’s drug speeding through the pipeline. The FDA has accepted a new drug application (NDA) from Sarepta Therapeutics, Inc, for SRP-4045 for the treatment of patients with Duchenne’s muscular dystrophy who have genetic mutations that are amenable to skipping exon 45 of the dystrophin gene. The agency also announced it has granted priority review status to SRP-4045, because the drug would likely represent a significant improvement in safety and efficacy compared to standard applications if approved.

SRP-4045’s application was accepted and prioritized based on evidence from an interim analysis of the ESSENCE study, a double-blind, placebo-controlled, multi-center phase 3 study evaluating the drug’s safety and efficacy alongside another drug, SRP-4053. The interim analysis found that patients who took SRP-4045 demonstrated a statistically significant increase in dystrophin production compared to baseline and placebo. In the ongoing study, eligible patients with out-of-frame deletion mutations amenable to exon 45 or 53 skipping are randomized to receive once weekly intravenous infusions of SRP-4045 of SRP-4053, respectively, or placebo for up to 96 weeks. This is followed by an open-label extension period, during which all patients will receive active treatment for an additional 48 weeks. For a full decision, check back in on the FDA’s regulatory action date: February 25, 2021.

Sodium valproate lukewarm for migraine. Sodium valproate is often used to treat epilepsy and bipolar disorder, but it’s only occasionally used to treat migraines intravenously. Why? Because its role in acute migraine attack hasn’t been completely established. That’s where a new meta-analysis published in Acta Neurologica Scandinavica comes into play. Investigators pooled and analyzed data from seven double-blind, randomized controlled trials involving 682 patients, and they found some pretty underwhelming results.

In relation to active comparators, patients receiving sodium valproate had less improvement of headache intensity and lower rate of headache relief. Intravenous sodium valproate also increased the odds that a patient would need rescue therapy compared to other drugs (OR: 3.76). Researchers found no significant difference in headache intensity improvement when intravenous sodium valproate was compared with active comparators. In the end, sodium valproate may be a reasonable alternative or salvage therapy, authors noted, particularly for migraine with aura, but certainly not a first choice.

New in Patient Management

Unexpected side effects of epilepsy medication. Enzyme-inducing anti-seizure drugs (ASDs) may help detoxify tobacco-specific lung toxins, leading to a reduced risk of lung cancer and chronic obstructive pulmonary disease (COPD) in patients who smoke, according to a new study published in the British Journal of Pharmacology. To arrive at these results, researchers monitored cases of COPD and lung cancer (with matched controls) from a population of smokers with ≥ 1 prescription for any type of ASD.

Out of 5,952 incident COPD and 1,373 incident lung cancer cases (plus 59,328 and 13,681 controls, respectively), investigators found that, compared with those who never used ASDs, the use of ≥ 1 ASD was associated with about a 15% decreased risk estimate of COPD and an 18% decreased risk estimate of lung cancer. The association remained significant for light or moderate smokers and short-term users of enzyme-inducing ASDs, but not for medium- and long-term users of enzyme-inducing ASDs who were heavy smokers. 

Heated debate over fluids cools down. One of the most important parts of treating traumatic brain injury (TBI) is preventing secondary brain injury in the process—that means taking concerted steps to avoid hypotension, which, in turn, means using fluid resuscitation to get the job done. The choice of fluid has been the subject of an on-going debate between clinicians. Fortunately, we’re here to tell you which fluid won: none of them!

According to a new systematic review and meta-analysis published in the International Journal of the Care of the Injured, qualitative analysis did not demonstrate a survival or neurological benefit associated with any one fluid type. There were no better survival rates seen in patients treated with hypertonic saline compared with normotonic crystalloids. The bottom line? Take your pick. Current data simply don’t allow for a recommendation on which type of fluid should be preferred.

Setting realistic expectations with erenumab for migraines. Tons of physicians are already prescribing erenumab for migraines. If you’re one of them, a new study published in Headache might help you and your patients set clearer expectations for how the drug could impact their monthly migraine days response thresholds. The good news is that erenumab continues to show efficacy as a preventive treatment for episodic migraine. The previous STRIVE study showed that 43.3% of patients on erenumab 70 mg and 50% of patients on erenumab 140 mg achieved a ≥ 50% reduction in monthly migraine days (MMD), compared with just 26.6% in the placebo group.

In the new study, erenumab showed efficacy across a variety of response thresholds, from the standard ≥ 50% threshold to the stricter ≥ 75% threshold and 100% thresholds. At months 4 through 6, 20.8% and 22% of those on erenumab 70 mg and erenumab 140 mg, respectively, achieved ≥ 75% reductions, vs just 7.9% of those on placebo. A reduction of 100% response was achieved by 3.2% of those on erenumab 70 mg and 5% for erenumab 140 mg, vs 2.8% for placebo. That’s kind of a big deal, according to the authors. “It’s worth noting that achievement of a 100% reduction in MMD over months 4 through 6 is an extremely strict endpoint, as it means that a patient must not have had a single migraine day during a 3-month period,” they noted.

Frontal lobe epilepsy and the heart. All day, all year, and hopefully all life long, our hearts beat away in our chests without complaining much. But for those with frontal lobe epilepsy (FLE), that’s not something to take for granted. A new study suggests that FLE may impair autonomic heart rate modulation, leading to decreased heart rate variability (HRV), which may increase the risk for sudden death.

In the study, 10 patients with FLE and 15 healthy controls underwent 24-hour Holter monitoring and had their SUDEP-7 scores calculated. All 24-hour time-domain parameters were associated inversely and significantly with SUDEP-7, especially one known to deteriorate with diminished physical activity and that is decreased in patients with more generalized seizures. Wakefulness parameters didn’t correlate with SUDEP-7, while correlations to sleep parameters were very strong. The bottom line? Be on the lookout for FLE—HRV is impaired in patients who have it, and low HRV scores are associated with increased risk for SUDEP.

Latest in Journal Summaries

Early predictive factors for upper and lower extremity motor recovering following ischemic stroke.

Results of continuous EEGs in patients with COVID-19.

Endoscopic vascular decompression for trigeminal neuralgia.

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Upcoming Medical Meetings

The following meeting is entirely virtual:

145th Annual Meeting of the American Neurological Association (ANA 2020). October 4-9, 2020.

The following meeting has been cancelled:

Neuroscience 2020: The Society for Neuroscience (SfN) 50th Annual Meeting, Washington DC, October 24-28.

The following meeting has been rescheduled:

20201 Congress of Neurological Surgeons (CNS) Annual Meeting, to be held in Miami, FL, has been rescheduled for October 16-20, 2021, in Austin, TX.

 

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