Researchers identify new genetic brain disease; a genetic mutation that may protect against Alzheimer’s; and more

With the holidays quickly approaching, your time will become even more of a precious commodity.

To that end, MDLinx is bringing you the skinny on the latest neuro happenings, from the discovery of a new genetic brain disease, to a genetic mutation that offers seemingly long-term protection against Alzheimer disease, and much more.

Read on for the latest news in neurology.

Neuro Flashback

Seventy years ago, Portuguese neurologist António Egas Moniz—regarded as one of the founders of modern psychosurgery—shared the Nobel Prize for Physiology or Medicine with Walter Rudolf Hess for his “discovery of the therapeutic value of leucotomy in certain psychoses.” What’s leucotomy you ask? It’s more widely known as… lobotomy. Show of hands, who else cringes at that word? Share your thoughts below.

In the News

New genetic brain disease? As if there weren’t enough brain diseases to go around, now researchers have identified a new genetic brain disease that may cause paraplegia and epilepsy. Mutations in the PCYT2 gene—which cause the gene to be less active—have been identified as a new cause of hereditary spastic paraplegias (HSPs), a group of genetic disorders that cause weakness and stiffness in the muscles of the legs. PCYT2 encodes an enzyme that produces a lipid used in building cellular membranes in every cell in the body, and this lipid is markedly abundant in brain cell membranes. In a zebrafish model, absence of PCYT2 activity caused worse survival rates. In humans, researchers identified abnormal biochemical cellular signatures in serum samples. But at least there’s a silver lining. Their hope is that further study of PCYT2 will aid in the understanding of HSP and other neurodegenerative disorders.

Why have one tumor when you can have two? Researchers from Tufts and colleagues have developed 3-dimensional human tissue culture models of pediatric and adult brain cancers in a brain-mimicking environment. Included in the models is the brain-derived extracellular matrix (ECM). Alterations in ECM are associated with the progression of brain tumors. Specifically, ECM protein composition can either prevent or enable diffusion of tumor cells in the brain. So, what does this mean? These 3-dimensional in vitro systems will allow researchers to study various components of ECM and any role they may play in tumor development. Using these models will also allow them to study the effects of various drugs on tumor growth in patient-derived cells.

Weekly Trivia

Who began the practice of trepanning? Evidence of trepanation was found as early as prehistoric times among the people of the Cuzco region of Peru. This ancient Andean practice—usually prompted by cranial trauma—involved circular cutting and scraping, and seemed to be highly successful, with an overall 83% survival rate and few complications. Those were some pretty good odds for the science of that time.

Novel Diagnostics

Speaking of Veteran’s Day. Brain imaging studies show that Gulf War Illness (GWI) and chronic fatigue syndrome (CFS) are two distinct disorders that have different effects on the brain. These findings came from two studies presented at the annual meeting of the Society for Neurology. GWI occurs in veterans of the 1990-1991 Persian Gulf War exposed to nerve agents, pesticides, and other neurotoxins. CFS is idiopathic, and affects up to 2.5 million Americans. The two conditions share some symptoms, such as disabling fatigue, pain, systemic hyperalgesia, negative emotions, and sleep and cognitive dysfunctions, which occur primarily after physical exercise.

Sound about right? Well, because of this overlap, it was thought that they perhaps shared common mechanisms of disease. Results from these two studies, however, revealed unique physical and chemical changes in the brains of patients with GWI. Researchers used functional MRI on patients who performed a cognitive task 1 day before and 1 day after bicycle exercise stress tests. Before exercise, brain activation was similar in all groups, but after exercise, those in the CFS group had significantly increased midbrain activation compared with those in the GWI group, who had decreased activation. Those in the CFS group also demonstrated increased activation in the insula, while the GWI group had decreased cerebellar activation. Thus, researchers found that specific brain regions in both conditions acted in opposite ways, recording a distinct neurological difference between GWI and CFS.

Predictive powers of MRI after spinal cord injury. The value of MRI in predicting neurological outcomes in patients suffering thoracolumbar (TL) spinal cord injury was validated in a study published in the European Spine Journal. Upon univariate analysis of data from 76 patients undergoing surgical management for acute TL spinal injuries, researchers found an association between spinal cord compression, length of cord swelling, and length of edema and complete neurological deficit at presentation. Interesting stuff, right? Well, they found that the only association that remained significant upon multivariate analysis was length of edema at admission and follow-up. Plus, they found that greater rostrocaudal length of edema was linked to worse neurology upon presentation and related to poor neurological recovery upon follow-up.

Got memory loss? Take an MRI, it lasts longer. As if MRIs weren’t awesome enough, other researchers found that they can distinguish between memory loss caused by traumatic brain injury (TBI) and Alzheimer disease (AD), according to their results published the Journal of Alzheimer’s Disease. MRI is valuable because it can reveal subtle abnormalities in patients with neurological disorders like AD. As many as 21% of older adults with dementia may be misdiagnosed with AD and fail to receive appropriate treatment. When MRI scans from 40 patients who suffered TBI and later developed memory problems were analyzed, researchers found that TBI was most damaging to the ventral diencephalon, and caused the least atrophy in the hippocampus. In AD, the hippocampus is the most impacted. Their results demonstrate that TBI damage is distinct. Researchers concluded that not all memory loss is caused by AD, and stressed the importance of differentiating between TBI damage and other dementias and neurodegenerative disorders.

A blood test for glioblastoma? In more good news for diagnosticians, researchers have found that a simple blood test that measures the amount of cell-free DNA (cfDNA) can predict progression in patients with glioblastoma, the deadliest and most common primary brain tumor in adults. Those with higher cfDNA concentrations had shorter progression-free survival compared with those with less cfDNA. Further, they found that at the time of disease progression, or just before, cfDNA seemed to spike in patients with glioblastoma. Finally, after comparing genetic sequences from solid tissue biopsies with liquid biopsies, they found that none of the mutations detected by either test overlapped. Thus, liquid biopsy could provide further and complementary genetic information about tumors.

Novel Treatments

Don’t underestimate the value of a case study. A woman who carried the gene mutation known to cause early-onset Alzheimer disease (AD) did not develop signs of the disease until her 70s. Sound like a case for Sherlock Holmes? Like her family, she had the gene mutation for early-onset AD (PSEN1 E28A), but also had two copies of the APOE3 Christchurch (APOE3ch) gene variant, which no other family member carried. Other family members developed AD in their 40s, but this woman was free of disease until her 70s, when she demonstrated only minor neurodegeneration. Imaging reveled large amounts of amyloid protein deposits, a hallmark of AD, but a low number of tau tangles—also a hallmark of AD. Hang on to your socks, Watson, because here comes the good part: Researchers found that the APOE3ch variant could reduce the ability of APOE to bind to heparan sulphate proteoglycans, a possible factor in the buildup of amyloid and tau protein deposits in the brain. Their findings point to the utility of a drug or gene therapy that may reduce this binding, and its potential as a treatment or even preventive measure against AD.

Outsmarting post-stroke pain. Perispinal administration of tumor necrosis factor (TNF)-blocking agents may help relieve central post-stroke pain, which can occur after stroke, and can be chronic, disabling, and treatment-resistant. Researchers presented results from two studies. In the first, researchers used perispinal administration of an antibody blocking TNF in a preclinical model. They found that this treatment selectively blocked brain TNF to reduce pain. Previously, delivery of such agents to the brain were thought to require either brain surgery or a spinal tap. In the second study, investigators demonstrated immediate resolution of post-stroke pain after only one perispinal injection of another TNF blocker, etanercept.

New in Patient Management

Get the lead out or say bye to the ZZZZZs. One of the adverse consequences of lead exposure in children may be lower quality sleep. Researchers found associations of higher cumulative exposure to lead during early childhood with shorter sleep durations in adolescence. In fact, kids with the highest blood lead levels slept, on average, 23 minutes less than those with the lowest levels. Think that’s no big deal? Well, they also found that higher lead exposure during childhood was associated with high sleep fragmentation and movement index in kids under 14 years old. Their results open the door to further investigation into the link between lead, sleep, and cognition in children.

Evacuate immediately! Surgical evacuation for cerebellar hemorrhages greater than 3 cm in diameter is recommended by current guidelines, and was bolstered by results from a meta-analysis of four observational studies involving 304 patients equally divided between surgical hematoma evacuation and conservative treatment. Anyone else humming “Get Out” by JoJo in their head right now? Oh, just us then?

Well, good news is, researchers found that surgical hematoma evacuation was associated with an improved survival at 3 months compared with conservative treatment (78.3% vs 61.2%, respectively), but had a similar rate of favorable functional outcomes. In patients with a hematoma of 15 cm3 or greater (comparable to more than 3 cm in diameter), favorable functional outcomes were more likely with surgical hematoma evacuation.

A mixed bag of results. Findings vary greatly when trying to determine which is the best anesthetic strategy for mechanical thrombectomy for acute stroke. There are retrospective studies that support procedural sedation, as well as randomized trials that show no differences or only slightly improved early outcomes with general anesthesia. So, what’s a doc to do? Researchers recently conducted a meta-analysis of three randomized trials, and found that disability scores at 3 months were lower with general anesthesia compared with procedural sedation (2.8 vs 3.2, respectively). They recommended general anesthesia for patients in whom either strategy is appropriate.

Early to bed, early to rise. Some people need their coffee, some need their sleep. In patients with Parkinson disease (PD), improved sleep quality may equate to shorter times of reduced mobility in the early morning. The number of patients with PD who report sleep problems is high (60%), and even in those with early stage disease, early morning akinesia is common. Using actigraphy, researchers studied the association between sleep and morning mobility in 157 patients with PD. They measured sleep efficiency, wake after sleep onset, total sleep time, and fragmentation index. When sleep efficiency, wake after sleep onset, and fragmentation index were better, times of low mobility within 2 hours of rising were better. Researchers concluded that even a 13.6% increase in sleep efficiency brought about a 5.7-minute decrease (10.2%) in low morning mobility time. If you need us, we’ll be celebrating with a nap.

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Upcoming Medical Meetings

Chronic Traumatic Encephalopathy (CTE): 4th Annual Conference CME in Boston, MA, November 14-15, 2019

International Society for Traumatic Stress Studies (ISTSS) 35th Annual Meeting in Boston, MA, November 14-16, 2019

2019 New Frontiers in the Diagnosis and Management of Movement Disorders CME in Chicago, IL,

November 16, 2019

10th Biennial Conference on Pediatric Sleep Medicine CME,  in Naples, FL, November 14-17, 2019

View more upcoming Neuro meetings

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