Latest in autism spectrum disorders, stroke in cancer patients, and… cognitive function in people with half a brain?
It’s almost the end of the year, which means holidays and festivities. But, it’s also the end of the decade, which means it’s time to reflect on the past 10 years in medicine: from life-changing drug approvals, to novel medical devices that promise to change the medical landscape, there’s no denying that medicine is one of the most dynamic fields, especially that of neurology.
But with all these changes, it might be hard to keep up. We know your time (and perhaps even patience) may be particularly scarce, so MDLinx has gathered the newest, freshest neuro happenings for you, so you can catch up in one sitting— from the discovery of a genetic mutation that might explain autism and schizophrenia to monumental drug approvals for migraine, seizures, and pediatric diffuse midline gliomas, to a new study that measured cognitive function in patients with only half a brain. Be sure to read on for what’s new and exciting.
At this time in 2017, the Allen Institute for Brain Science released the free “Brain Atlas” database in hopes of helping neuroscientists interpret human nerve cell data. The database contains electrophysiologic, morphologic, and transcriptomic data from select areas of the cerebral cortex and thalamic neurons, all derived from single cell data from both humans and mice. Talk about a lot of info in one place!
In the News
Autistic mice? Researchers from Case Western Reserve University School of Medicine have identified a gene that may contribute to the development of autism spectrum disorders and schizophrenia. The protein cullin 3 plays a vital role in clearing out any unnecessary proteins in the brain. Mutations in its gene, CUL3, have been associated with autism and schizophrenia, but researchers have only now found that CUL3 has an important role in brain development and cellular communications within the brain. In murine models, alterations in the CUL3 gene caused social problems in mice that were similar to those in people with autism spectrum disorders and schizophrenia. Specifically, CUL3-mutated mice could not differentiate between inanimate objects and one of their compadres—a live mouse. Mutated mice were also more anxious than normal mice, and had problems with social memory—they couldn’t remember mice they had previously “met.” Must’ve been some hurt feelings in that cage!
A … what? The basic sampling unit of a functional MRI (fMRI) study is a “voxel”. Hard to remember? Think of it this way: a voxel is to fMRIs as a pixel is to pictures. Just think of a voxel as a combination of “volume” and “pixel.” They are small rectangular prisms that are the basic sampling units in fMRIs, and represent a value on a regular grid in three-dimensional space. Voxels are the scanners’ units of measurement for capturing image data in measuring brain activity using the ratio of oxygenated blood to deoxygenated blood in a given area.
Look into my … MRI? In a study published online in Stroke, researchers showed that MRI scans may help predict future decline in both cognition and function in those with cerebral small vessel disease. They used an MRI segmentation tool to assess 560 older adults with cerebral small vessel disease from the Leukoaraiosis and Disability Study. They sought to quantity different brain changes related to small vessel disease, and see whether they could predict future cognition and function in these patients.
For 3 years, patients returned for annual neuropsychological exams, and for 7 years, were evaluated in how well they performed instrumental activities of daily living. Well, imagine the results: Researchers found that a combine measure of total volumes of white matter hyperintensities, gray matter, and hippocampi were the strongest predictors of cognitive performance and functional outcomes over time. So, in the future, you may be able to assess vascular cognitive impairment by reviewing these combined measures. Pretty handy!
Better bang for your buck? What’s the best way to image patients with idiopathic normal pressure hydrocephalus (iNPH)? Linear measurement of vertical or horizontal frontal horn diameters, according to one study. Researchers compared 3T brain MRI studies from 35 patients with iNPH with those from 45 matched healthy controls. After comparing 15 cross-sectional imaging biomarkers of iNPH, they discovered that linear measurements of caudocranial alterations of the ventricular geometry provided the best diagnostic performance. Thus, they concluded that simple linear measurement of vertical or horizontal frontal horn diameters worked just as well as calculated, time-consuming z-Evans or Evans indexes.
New options abound for seizure patients. Cenobamate (XCOPRI) was just approved by the FDA for the treatment of partial-onset seizures in adults. Approval was based on results from two randomized, double-blind, placebo-controlled trials that included 655 adults. Cenobamate in doses of 100, 200, and 400 mg/d reduced the percentage of seizures per 28 days significantly better than placebo. A maintenance dose of 200 mg/d is recommended after titration, but some patients could need up to 400 mg/d, which is the maximum recommended dose. The risk of multiorgan hypersensitivity exists, as do risks for suicidal thought or behavior. Luckily, neurologists now have another option in treating these patients.
Making new connections. A new cell therapy that could improve memory and prevent seizures after traumatic brain injury (TBI) has just been developed by researchers from the University of California, Irvine. In their research, funded by the NIH, they transplanted embryonic progenitor cells into the hippocampi of mice with TBI. You won’t believe it—the transplanted neurons not only migrated to the injury, but also formed new connections with injured brain cells and thrived over time. Within 1 month of the transplant, the mice exhibited memory improvements. Compared with non-injured mice, treated mice were also able to differentiate between boxes where unpleasant experiences befell them from boxes where they did not. What’s more, when researchers silenced the transplanted neurons, mouse memories were again impaired, validating that the new neurons specifically improved memory.
Stopping migraines cold. When it comes to halting migraines already in progress, a new investigational agent may be just what the doctor ordered. Researchers have seen promising results with ubrogepant, which belongs to a new class of agents known as calcitonin gene-related peptide (CGRP) inhibitors. During migraine attacks, CGRP—a protein—is released by the trigeminal nerve, and plays a vital role in symptomatology. There are currently three injectable CGRP inhibitors that are approved for regular use for the prevention of migraine, but ubrogepant is different because it is a tablet taken after the migraine has started.
In a study involving nearly 1,700 patients, ubrogepant was more effective at stopping migraines in progress than placebo, easing symptoms such as nausea, pain, and light/sound sensitivities. Researchers caution, however, that this study was done after only a single dose of ubrogepant, and its long-term safety and side-effect profile are as yet unknown. So, let’s not break out the champagne just yet. Stay tuned: More research on ubrogepant is underway.
Hard-to-treat tumors meet their match? A new drug combo could be the future for treatment of childhood diffuse midline gliomas (DMG). In preclinical studies, a combo of panobinostat and marizomib was more effective than either agent alone in killing DMG patient cells grown in the laboratory and in animal models. The combo approach also helped to counter the effects of a genetic mutation that causes these diseases, which include diffuse intrinsic pontine glioma (DIPG), thalamic glioma, and spinal cord glioma. Their results were published in Science Translational Medicine.
DMGs are aggressive, hard-to-treat tumors mostly caused by a specific mutation in histone genes. They are the leading cause of brain cancer-related deaths in US children, and while they affect only a few hundred children ages 4-12 years annually, most die within a year of diagnosis. In other words, DMGs = very bad.
Panobinostat is a histone deacetylase inhibitor, and marizomib, a proteasome inhibitor. Their combination was highly toxic to DIPG cells and seems to shut down the production of ATP by tumor cells. More study is needed, but researchers are happily making progress. This calls for a round of applause!
New in Patient Management
Flu shots, anyone? Flu shots seem to be safe in patients with autoimmune neuromuscular disorders. Researchers did a web-based survey of US neurologists to find out whether and how they recommend flu shots for patients with myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), or Guillain-Barré syndrome (GBS). They published their results in Muscle & Nerve, and also presented their findings at the 2019 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, held in Austin, TX, in October.
Included in the study were 6,448 patients with MG, 2,310 with CIDP, and 1,907 with GBS. Overall, neurologists recommended flu shots for all or more than 50% in 95% of patients with MG, 84% of patients with CIDP, and 67% of patients with GBS. In those who got the flu shot, temporal association of disease relapse happened in 1.6%, 4%, and 9%, respectively. And among the 30 patients with MG, 25 patients with CIDP, and 35 patients with GBS who got additional flu shots, recurrent relapse happened in 87%, 92%, and 74%, respectively.
These numbers led researchers to conclude that “influenza vaccination was perceived to be safe in the majority of patients with autoimmune neuromuscular disorders.”
They added: “Neurologists appeared to be more conservative in recommending immunization for patients with a history of GBS. Temporally associated disease relapses appeared to be a risk factor for relapse with subsequent immunization.” So, take care in recommending subsequent flu shots in some of these patients.
“If you have half a brain…” Actually, if you had half a brain, you might still be fine. Six adults in their 20s and 30s who underwent hemispherectomy as kids were found to function at remarkably high levels, and had intact language skills, according to a new study published in Cell Reports. But still, we recommend you don’t try this at home.
These adults had hemispherectomy for intractable epilepsy, and had suffered terrible epileptic seizures from a very early age. The youngest was only 3 months old at the time of surgery, and the oldest, 11 years. Four had the right side of their brains excised, and two, the left.
For this study, they underwent functional MRI in an awake state, and their brain activities were tracked in the areas that regulate vision, movement, emotion, and thought processes. Compared with six healthy adults, as well as data from nearly 1,500 healthy people (mean age: 22 years), the patients showed incredible reorganization and compensation in building communications between the different regulatory networks of the brain—and these skills were actually stronger than those in the normal adults. Food for thought?
What’s remarkable, according to the researchers, is how well these six functioned with only half their brains, while patients who have small brain lesions—like those that can be caused by tumors, strokes, and even traumatic brain injury—often suffer devastating effects. Researchers are excited about further study of the compensatory workings in these six patients, which—if harnessed—could help treat all sorts of different conditions. Just imagine!
A deadly pairing. A deadly disease just got deadlier. Researchers found that—compared with the general population—people who have or have had cancer have a two-fold increase in their risk of stroke and associated mortality. Even more bad news: Breast, prostate, and colorectal cancers were the most often associated with fatal strokes. And those who had cancer at a younger age had a higher chance of fatal stroke. In their study published in Nature Communications, researchers used SEER data from over 7.2 million patients with diagnoses of invasive cancers between 1992 and 2015. Among these patients, 80,513 died of a stroke. In those who received diagnoses before age 40, the most strokes occurred in those treated for brain tumors and lymphomas. Among those who received diagnoses after age 40, stroke was most common in those with breast, prostate, and colorectal cancers. Two possible causes for the increased risk: People with cancer may be in a prothrombotic state, and cancer treatments such as chemo or radiation therapy may affect the vasculature. Researchers are working to establish the relation between cancer and stroke.
This might shake you to your core. Good news for those with hand, head, or voice tremors who don’t improve with medication: ultrasound may be the answer. Researchers studied the use of focused ultrasound thalamotomy in 76 people (mean age: 71 years) with essential tremor for an average of 17 years. Participants were followed for 3 years, and—on average—showed improvements of 50% in hand tremors, 56% in disability, and 42% in quality of life. Side effects were mild to moderate in severity, and included numbness, tingling, and balance problems. Although improvements were most significant at 6 months after treatment, they were only a little worse at the 3-year mark.
Latest in Peer-Reviewed Studies
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Upcoming Medical Meetings
2019 Advances in the Management of Epilepsy, in New Orleans, LA, December 6, 2019
31st Annual Pan Philadelphia Neurosurgery Conference, in Philadelphia, PA, December 6, 2019
American Epilepsy Society (AES) 2019 Annual Meeting, Baltimore, MD, December 6-10, 2019