Neurology News
Follow our Neurology News blog for the latest news on neurologic diseases and research.

Thursday, August 17, 2017

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BY SARAH OWENS

More than 200 cases of Zika virus infection in pregnant women were reported in Texas between January 2016 and July 2017, including one case of local mosquito-borne Zika virus transmission late last year, and these infections were associated with microcephaly and other birth defects among infants or fetuses who were tested, according to a new report published by the Centers for Disease Control and Prevention (CDC) in the August 11 online edition of the Morbidity and Mortality Weekly Report.

Following an initial global outbreak of Zika virus infection and reports of associated birth defects early in 2016, the first cases of local transmission in Florida were reported in June of that year. [Neurology Today reported on the CDC's response to those reports in Florida.] Most cases of Zika virus infection in the United States are related to travel outside the country, but reports of local mosquito-borne transmission in US territories and states have raised concerns about the potential for widespread infection, especially as the range of birth defects associated with birth defects continues to grow.

"The occurrence of travel-related Zika virus infections, combined with the threat of local transmission in Texas, indicates a need for continued surveillance for birth defects associated with Zika virus infection," wrote the authors of the report, led by Noemi Borsay Hall, PhD, epidemic intelligence service officer at the CDC.

Between January and July of 2017, the researchers reported, 219 pregnant women in Texas had laboratory evidence of possible Zika virus transmission; of these, 185 reported birth outcomes, including 182 live births and three pregnancy losses. Strikingly, Zika virus testing was only completed for 80 of these infants or fetuses (43 percent). For most of the remaining 104 infants or fetuses, no reason was given for lack of testing; ten infants or fetuses had a placental or cord blood specimen available for testing, but the researchers noted this is insufficient to determine infection status.

Birth defects were identified in 15 of the infants or fetuses tested for Zika (8 percent). These included microcephaly in ten infants, five of whom had additional birth defects, including holoprosencephaly, hydranencephaly, craniosynostosis, and clubfeet. The remaining infants had other Zika virus-associated birth defects, including holoprosencephaly, cataracts, and ventral pons hypoplasia.

Health care professionals should continue to be vigilant about possible Zika cases, and should report  those cases to health care officials at state departments of health, the authors of the report wrote. In addition, they wrote, the findings support the need for increased collection and testing of specimens from infants born to mothers with laboratory evidence of possible recent Zika virus infection.

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For more information on the Zika virus, its associated neurologic defects, and efforts to develop a vaccine for the virus, read our collection of reports at bit.ly/NT-ZikaCollection.


Wednesday, August 16, 2017

BY SARAH OWENS

Patients with Huntington's disease (HD)-associated chorea who converted overnight from tetrabenazine to a comparable dose of deutetrabenazine maintained effective control of their symptoms and had improved safety measures over eight weeks, according to a single-arm study published online on July 10 in JAMA Neurology.

While tetrabenazine is an effective treatment for controlling chorea, some patients have had difficulty tolerating the medication. Deutetrabenazine, approved earlier this year for chorea, has been shown to significantly improve chorea and motor scores while maintaining a relatively effective safety profile.

The current findings suggest that patients "can achieve treatment goals with fewer doses given across the day, a lower total daily dose, and equivalent or potentially improved tolerance, all important considerations in populations with neurodegenerative disease," the study authors, led by Samuel Frank, MD, director of the Huntington's Disease Society of America Center of Excellence at Beth Israel Deaconess Medical Center, wrote.

The Huntington Study Group, comprising more than 400 active investigators at more than 100 research sites, enrolled 37 patients with chorea at 13 sites in the United States and Australia beginning on December 21, 2013. All patients were taking stable doses of tetrabenazine that provided a therapeutic benefit.

All patients were switched overnight to a dosage of deutetrabenazine calculated to provide a comparable systemic active metabolite exposure to the prior regimen of tetrabenazine. Among all patients, the initial mean deutetrabenazine dosage was about half the prior tetrabenazine dosage and increased slightly until week eight. The investigators assessed the patients at one week, four weeks, and eight weeks after conversion for safety measures. They also monitored patients for adverse events, and conducted clinical laboratory tests, vital signs, electrocardiograms, and validated scales. Finally, they looked for maintenance of symptoms, measured by changes in the Unified Huntington's Disease Rating Scale total maximal chorea score and total motor score.

They found that deutetrabenazine was generally well tolerated with low rates of adverse events, including mild depression and somnolence. On laboratory tests, conversion to deutetrabenazine did not result in subclinical toxicity.

Deutetrabenazine was also effective for maintaining chorea control; the patients' total maximal chorea scores were maintained at 1 week and significantly improved at 8 weeks (mean [SD] change from baseline, 2.1 [3.2]; p<0.001).

The study authors concluded that overnight treatment conversion can safely maintain chorea control in patients with HD.  However, they cautioned, the small, single-arm, open-label trial design, using unmasked investigators, so the findings may be subject to bias and "should be considered to be exploratory."

The researchers also noted that although all patients who enrolled had been stable on tetrabenazine, some may have previously found higher doses of the drug intolerable or had an incomplete response, which may have led to an ascertainment bias.

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Tuesday, August 15, 2017

BY SARAH OWENS

No common etiology or source of exposure was found to be responsible for ten cases of acute flaccid myelitis (AFM) reported in Washington State between September and November of 2016, but with treatment most children recovered with no or mild residual deficits, according to a new report published by the Centers for Disease Control and Prevention (CDC) in the August 11 online edition of the Morbidity and Mortality Weekly Report.

The cluster coincides with a modest increase in cases of AFM, a rare condition caused by sudden-onset weakness in the arms or legs, in the United States and a dramatic increase in Europe in 2016. [Neurology Today reported on the rise earlier this year.] All of the European cases were linked to infection with enterovirus D68 (EV-D68), which was also detected in two out of 10 patients in the Washington State cluster, but a definitive etiology has not yet been established.

The cases among patients admitted to Seattle Children's Hospital were first reported by the hospital to the CDC and Washington State Department of Health in October 2016. The patients averaged six years in age, and seven were male. Most had gastrointestinal symptoms, respiratory symptoms, or both, and most developed a fever in the four weeks before symptom onset. All patients underwent MRI imaging that revealed distinctive spine lesions characteristic of AFM.

Researchers conducted interviews and tested specimens from the patients' upper respiratory tract, stool, rectum, serum, cheek, and cerebrospinal fluid. They detected EV-D68 in the nasopharyngeal swabs of two patients, one of whom also tested positive for adenovirus. They detected enterovirus A71 (EV-A71) in a third patient's stool. Two patients had elevated mycoplasma spp. immunoglobulin M, but their upper respiratory swabs tested negative for mycoplasma spp.

Four patients received intravenous immunoglobulin, eight received intravenous steroids, and seven underwent rehabilitation. Most patients recovered with no, mild or moderate symptoms 1.5 to 3 months after discharge. Of all patients, five had no or mild residual deficits, three had moderate improvement with residual limb weakness, and one still needed help walking.

The researchers noted that although EV-D68 or EV-A71 were detected in three patients, the association between these viruses and AFM remains hypothetical, since "as in previously reported clusters of AFM, no pathogen was consistently isolated from all specimens tested." However, they added, the fact that some patients had gastrointestinal symptoms or a fever "suggests that the etiology of these AFM cases is infectious" or "postinfectious."

In the meantime, they concluded, "Clinicians, specifically pediatric neurologists, should maintain vigilance for AFM." The researchers encouraged doctors "to report cases as soon as possible to state or local health departments to add to information regarding clinical signs, severity, and illness prognosis."

The researchers noted several important limitations to their report. Because reporting of AFM is voluntary, the actual incidence of AFM in the United States is unknown; and because symptoms of AFM are similar to other neurologic conditions like Guillain-Barré syndrome, there may have been misdiagnoses.

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Thursday, August 10, 2017

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BY SUSAN FITZGERALD

Doctors often must tell parents of children with early-life epilepsy that they don't know why their child has seizures, but a new study suggests that they would have more answers if genetic testing was routinely done as part of the diagnostic workup.

The study, which tracked more than 700 infants and young children with epilepsy, found that 40 percent of those who underwent genetic testing for epilepsy had one of the genetic variants known to be associated with the disease.

In a July 31 online report in JAMA Pediatrics, the authors concluded that genetic testing, particularly gene sequencing, should be incorporated into the initial evaluation of young children with epilepsy so that an optimal treatment plan can be devised. Often genetic testing for epilepsy is not conducted until doctors exhaust traditional means of evaluation, such as neuroimaging and metabolic testing, the study authors said.

"Genetic testing can end the diagnostic odyssey and that is a huge thing," said lead author Anne T. Berg, PhD, research professor of pediatrics at Ann & Robert H. Lurie Children's Hospital of Chicago and the Northwestern University Feinberg School of Medicine. She said the sooner a precise diagnosis can be made, the sooner a child can be started on the most appropriate therapy, which can help protect against seizures during a critical time of development and perhaps save on medical expenses.

The study involved a prospective review of medical charts and diagnostic evaluations (neuroimaging, metabolic, genetic) for 775 children under age 3 who were seen between 2012 and 2015 for newly diagnosed epilepsy at 17 US pediatric epilepsy centers.  Ninety-five of the children had an acquired brain injury and were excluded from the analysis.

Of the remaining 680 children, 327 (48 percent) underwent genetic testing, whether karyotyping, microarrays, epilepsy panels, whole exome sequencing, mitochondrial function gene panels and other targeted genetic investigations. Genetic testing identified pathogenic variants in 40 percent of the children who were tested.

"Aside from dysmorphic syndromes, pathogenic yields were highest for children with tuberous sclerosis complex (9/11, 82 percent), metabolic diseases (11/14, 79 percent) and brain malformations (20/61, 33 percent)," the researchers reported.  Genetic testing yielded a specific diagnosis in 25 percent of children for whom the cause of epilepsy would have been otherwise impossible to pinpoint.

The researchers found that in children with initially unexplained etiology, the diagnostic yield was substantially less for chromosome microarray, which is currently more commonly used, than it was for sequencing methods, including epilepsy panels and whole exome sequencing.

They noted that like magnetic resonance imaging, genetic tests "have substantial diagnostic yields regardless of clinical features, certainly higher than the many metabolic tests that are frequently ordered."

They concluded that "genetic investigation emphasizing sequencing tests should be incorporated into the initial evaluations of early-presenting ELE [early-life epilepsies] and not just reserved for those with severe presentations and poor outcomes."

The researchers acknowledged that genetic testing technology continues to evolve. The meanings of many of the genetic variants associated with epilepsy are not fully understood.

"Previously, most ELEs were relegated to the undifferentiated category pf symptomatic (sometimes 'secondary' or 'catastrophic) generalized epilepsy with a few electroclinical syndromes (for example, West syndrome or infantile spasms) specifically recognized. Causes in half or more remain unknown."

The study noted that while neuroimaging is standard in the evaluation of ELE, genetic testing has never been recommended for the initial diagnostic work-up.

"This is despite a growing literature directed at gene discovery for ELE, which has utilized individual techniques such as whole exome sequencing, chromosome microarray, epilepsy panels, and single-gene testing in selected patients," the paper said.

The researchers also noted limitations of their study. It was not a population-based study and involved only children evaluated at hospital-based epilepsy centers. It is not known whether the same trends for genetic testing would emerge for children at community practices.

Another downside is that genetic testing can cost thousands of dollars, and even with genetic testing, the cause of a child's seizures may not be found.

Still, Dr. Berg said genetic testing could result "in a huge cost savings" if it allows for better tailoring of treatment and keeps kids out of the hospital.

"We are just on the cusp of precision medicine in epilepsy, being able to select therapies that target the underlying physiology rather than just suppressing the symptoms," Dr. Berg said. She said precision medicine begins with a precise diagnosis, and she said she hoped the paper's findings would influence insurance coverage policies.

Look for expanded coverage of the study, including expert commentary, in an upcoming issue of ​Neurology Today.


Wednesday, August 9, 2017

BY SARAH OWENS

The re-emergence of post-stroke symptoms and deficits after they have initially resolved is more common than previously thought and associated with a number of identifiable triggers and risk factors, according to a new study published online on August 7 in JAMA Neurology.

Risk factors for post-stroke recrudescence (PSR), defined as the transient worsening or reemergence of neurologic deficits after a stroke — including changes in consciousness levels, vision, language skills, or weakness in the face, limbs, and muscles — have not yet been well characterized. But understanding them is crucial for treating physicians, since PSR can often be confused for other conditions, such transient ischemic attack, stroke mimics, and seizure – all of which require different management.

Findings from the present study "should enable prompt diagnosis and help [physicians] distinguish poststroke recrudescence from mimics," the study authors, led by Mehmet A. Topcuoglu, MD, of the neurology department at Hacettepe University Hospitals in Ankara, Turkey, wrote.

For their study, researchers at Hacettepe University Hospitals, Massachusetts General Hospital and Harvard Medical School retrospectively reviewed the records of 1,700 patients who'd had an ischemic or hemorrhagic stroke and who experienced PSR. The researchers used preliminary diagnostic criteria for PSR – including the presence of chronic stroke on brain imaging, no acute lesions on diffusion weighted imaging, unlikely cerebral ischemia, and no evidence of seizure at the time of the event – to identify a total of 164 who were included in the final analysis.

The mean age of patients with PSR was 67, and 60 percent were women. The average time from index stroke to PSR was 3.9 years; PSR occurred after both ischemic and hemorrhagic stroke, but was far more common after ischemic stroke. The mean duration of the deficits, documented in 131 episodes, was 18.4; of these episodes, 91 (69.5 percent) resolved on day 1, 23 (17.5 percent) resolved on day 2, 8 (6.1 percent) resolved on day 3, and 9 (6.9 percent) resolved on day 4 or beyond.

Among the triggers and risk factors for PSR they identified were infections, hypotension, and hyponatremia, and to a lesser extent insomnia or stress, benzodiazepine use, and fever. The resolution of PSR symptoms was correlated with treatment or removal of the presumed trigger. Risk factors included female gender, being African American or self-identified "other" race, diabetes, dyslipidemia, smoking, and having more severe neurologic deficits at the time of the stroke.

The findings, the study authors concluded, suggest that PSR "appears to be relatively frequent, [but] recognition of PSR remains sporadic." They hope their results will "stimulate larger validation studies and ultimately enable prompt diagnosis and distinction from mimics in medical centers across the world."

The researchers noted several limitations to their study. Among them were its retrospective design, which meant they had to rely on medical records to determine the severity and evolution of stroke; the unblinded review of medical records may have contributed to bias; and the list of possible triggers was predefined. They noted that there may be as yet unknown factors contributing to PSR, as well.

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