This week’s updates in epilepsy, neurogenetics, and… sports injuries?

A lot is going on in neurology. From a battle of the sexes in Alzheimer research, to scientists finally giving young football players the ‘okay’ to bang their heads a few times, you won’t want to miss this week’s Neuro Brief.

Neuro Flashback

What’s the most common disease that’s also the most undiagnosed, as it doesn’t usually cause any “serious” health issues? If you guessed herpes simplex virus 1 (HSV1), you’re right. But what if it’s not as harmless as once thought? Around this time last year, researchers found strong evidence that HSV1 actually accounts for more than half of Alzheimer cases. If that won’t help you forget about the cold sores, we don’t know what will.

Novel Diagnostics


Battle of the sexes? Women have a knack for remembering most details, but how do they fare against men in terms of Alzheimer prevalence? In a study in nearly 1,000 participants, researchers found that when verbal memory test cut-offs were tailored according to patient sex, 10% more female patients and fewer male patients were diagnosed with amnestic mild cognitive impairment (aMCI)—often a precursor to Alzheimer disease. Researchers conducted this study based on previous findings that women typically score higher than men on tests of verbal memory, and therefore, may not receive a diagnosis of mild cognitive impairment as early as men do—even when they have the same levels of Alzheimer disease-related brain changes. Their results may change the way clinicians diagnose aMCI, and perhaps even enable earlier detection.


Suspect epilepsy? Look at the genes, and we’re not talking the kind you wear one too many times before you finally throw them in the wash (it’s ok we do it too). Researchers from the Cleveland Clinic’s Genomic Medicine Institute have developed a new genetic-based epilepsy risk score that may pave the wave for a more personalized approach to both the diagnosis and treatment of epilepsy. These new polygenic risk scores can accurately distinguish healthy patients from those with epilepsy, even generalized epilepsy. This is important because after a first seizure, it can be difficult, if not impossible, to predict which patients will go on to develop epilepsy. The hope is that this new genetic risk score will help clinicians with this and enable them to intervene and treat patients who develop epilepsy earlier. Dennis Lal, PhD, and colleagues conducted this analysis—the largest study of epilepsy genetics to date, and the largest study of epilepsy using human samples. Their findings highlight the promise of genetic testing for epilepsy, and are considered landmark results that will take epilepsy research in new directions.


Speaking of genes, in another study, researchers found new molecular clues about which tumors are most likely to be aggressive in patients with the genetic syndrome neurofibromatosis type 1 (NF1). Although NF1 is rare, it is one of the most common genetic syndromes. Tumor formation is common, particularly in the brain and peripheral nerves. Most tumors are low-grade, but some can be malignant. Researchers found that malignant tumors in those with NF1 were more likely to lack ATRX, a protein associated with alternative lengthening of telomeres (ALT)—a specific biological process associated specifically with cancer. Although testing for ALT is not yet possible, its identification as a molecular marker in patients with NF1 is important, and may be used to evaluate and better predict treatment outcomes, as can surrogate markers like loss of ATRX. Their results are published online in Acta Neuropathologica Communications.


It’s not just in your head, it’s also in your walk. Earlier measurement of gait speed (at age 45) is a useful indicator of brain health. Researchers found that gait speed—a well-known indicator of the risks of functional decline and mortality in older adults—can be measured earlier and give a good indication of midlife aging and lifelong brain functionality. Of the 904 participants in whom they measured gait speed at 45 years, those with slower gait speed had smaller brain volume (P < 0.001), more cortical thinning (P = 0.01), smaller cortical surface area (P = 0.003), and more white matter hyperintensities (P = 0.01).

Novel Treatments


It’s like enzymes on steroids – which we don’t actually recommend. Amplifying healthy enzymes rather than stabilizing unhealthy ones may one day help alleviate the symptoms of Parkinson disease (PD). In patients with PD, mutations in the GBA1 gene can produce misshapen GCase enzymes, which facilitate the buildup of toxic proteins in the neurons that produce dopamine. This results in symptoms such as tremors and slowness of movement. Researchers have now developed chemical activators—small molecules—that bind to normal GCase enzymes, stabilizing and amplifying them for improved PD-related cellular dysfunction. This approach was successful in a wide range of patients with PD, and represents a new therapeutic approach to this common neurological condition.


Because neurologists are the backbone of medicine. In a systematic review and meta-analysis of preclinical and clinical data, researchers found significant overall improvement in the rate of bone fusion after a course of electrical stimulation. This is good news for the approximately 400,000 people who undergo spinal fusion surgery annually for spinal instability, pain, or loss of function. For many, surgery alone cannot achieve complete spinal fusion, and adjuvant therapies are needed to help with bone healing. Electrical stimulation is one such therapy. Encouragingly, these researchers found that augmenting spinal fusion with electrical stimulation resulted in a greater than twofold increase in the odds of successful bone fusion.


Endovascular recanalization in kids? Previously, there have been no large trials of the safety and efficacy of endovascular recanalization in children. Researchers of the Save ChildS study, who published their results in JAMA Neurology, changed this. They found that endovascular recanalization is feasible, and provides beneficial neurological outcomes in children suffering stroke. In their retrospective, multicenter study, they found good angiographic outcomes in 87% of the 71 children, and poor results in only 9%. Most patients demonstrated improvements in neurologic deficits, which was similar to those seen in adults. No periprocedural complication occurred except for transient vasospasm in four children. Their results suggest that the safety of thrombectomy for childhood stroke is similar to that in adults, and brought about largely favorable neurologic outcomes.


A Trojan horse for Duchenne muscular dystrophy, but without the Greek soldiers. In preclinical trials, a modified gene therapy has shown promise in safely mitigating the severe muscle deterioration associated with Duchenne muscular dystrophy (DMD). Results are published online in Nature Medicine. Researchers engineered adeno-associated virus vectors that could deliver a substitute protein in place of dystrophin, a muscle-building protein that patients with DMD have very little of. This substitute protein was based on utrophin, a naturally occurring protein. In both mice and dogs with naturally occurring DMD-like mutations, the substitute protein safely and effectively protected muscle. Researchers are hopeful that their findings could lead to a utrophin-based gene therapy that may be a potential cure for DMD.

New in Patient Management


Side effects of checkpoint inhibitor immunotherapy? In patients with cancer treated with checkpoint inhibitor immunotherapy (CII), researchers found an association with a wide range of neurologic toxicities. Cranial neuropathies with and without meningitis and non-length-dependent polyradiculoneuropathies with and without cranial nerve involvement were the most common, according to a retrospective series of 19 patients, published in Neurology. With the increasingly common use of CII for melanoma, non-small cell lung, and other cancers, clinicians should be aware of the possibility of these complications, as well as of the efficacy of glucocorticoids and CII discontinuation in resolving them.


You may want to skip the antipsychotics in patients with Alzheimer disease. Researchers found that over the course of 2 years, people with Alzheimer disease who used antipsychotic drugs were in the hospital for 11 more days/year than those who did not use antipsychotics. These hospital days were due to dementia, mental and behavioral disorders, respiratory and genitourinary diseases, cardiovascular disorders, and various symptoms. Caregiver days off also played a role.


Tell all the young sports enthusiasts: Football is fair game! CU Boulder researchers have found no association between contact sports—like football—and cognitive or mental health problems. They published their results in the Orthopaedic Journal of Sports Medicine. In more good news, they also found that those who play sports in early adulthood are less likely to suffer from mental health issues by their late 20s to early 30s. It’s important to know this because there is a perception that youth contact sports, head injuries, impaired cognitive ability, and mental health are directly linked. In fact, researchers even found that football players had a lower incidence of depression in early adulthood compared with others. Furthermore, in youth in the National Longitudinal Study of Adolescent to Adult Health (Add Health), those who reported that they didn’t want to participate in sports at ages 8 and 14 years were 22% more likely to suffer depression in their late 20s and 30s.


What affects outcomes after traumatic spinal cord injury? Acute adverse events occur often in patients with traumatic spinal cord injury and—even worse—are associated with worse long-term outcomes, according to this analysis of data from 11 university-affiliated medical centers in the North American Clinical Trials Network. This study is one of the few to assess the spectrum of adverse events in this patient population, as well as their association with long-term clinical outcomes. Among 502 patients who had traumatic spinal cord injury, 2,303 adverse events occurred—an alarming incidence of 63%. Those who had adverse events achieved less neurologic recovery and were more likely to require assisted breathing, have dependent ambulation, and have impaired bladder or bowel function. Clinicians should be aware of the association and monitor these patients for worse outcomes.

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Upcoming Medical Meetings:

Brain Summit 2019: Current Trends in Neurology & Stroke CME in Dallas, TX, November 1-2, 2019

13th Annual Meeting of the American Society of Functional Neuroradiology CME in San Francisco, CA, November 3-5, 2019

Headache Symposium 2019: The Art of Headache Medicine in Cleveland, OH, November 9, 2019

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