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

Tuesday, July 11, 2017

Non-Convulsive Status Epilepticus Frequently Missed by EMS, Study Finds

BY SARAH OWENS

Convulsive status epilepticus was almost always recognized, but non-convulsive status epilepticus (NCSE) was frequently missed by emergency medical services (EMS) in out-of-hospital cases, according to findings from a 10-year observational cohort study published online on June 28 in Neurology.

In addition, missed NCSE was associated with lack of treatment and slower recovery to functional baseline in surviving patients, the study authors found.

Status epilepticus (SE), though relatively rare, has a high mortality rate and can lead to serious complications, including brain atrophy. Until now, a dearth of research examining the accuracy of EMS response to has made establishing levels of evidence for prehospital guidelines difficult, the study authors wrote.

The findings "call for heightened awareness for NCSE…as missed NCSE is independently associated with lack of treatment and increased odds for no recovery to functional baseline in survivors," the study authors, led by Saskia Semmlack, MD, of the department of neurology at the University Hospital Basel (UHB) in Basel, Switzerland, wrote.

For their study, researchers at UHB assessed pre-hospital and in-hospital data on patients who were admitted to UHB and diagnosed with out-of-hospital SE between 2005 and 2014. They prospectively assessed a variety of measures, including time of alarm of the EMS, time of hospital admission, prehospital Glasgow Coma Scale (GCS) scores, medication administered by the EMS and in hospital, presumed initial diagnoses by the EMS, and SE severity, duration, and cessation.

They identified a total of 213 patients with status epilepticus; of these, 150 were admitted via EMS. Overall, status epilepticus was missed by EMS in 55.3 percent of cases; it was missed more frequently in patients with NCSE (63.7 percent) compared to patients with convulsive status epilepticus (four patients; 15.4 percent). NCSE was more likely to be missed if the patient was older (odds ratio [OR] per year, 1.06; 95% confidence interval [CI] 1.02–1.10, p=0.003) and no seizure history (OR 6.64, 95% CI 2.43–18.1, p<0.001).

In addition, among surviving patients, the researchers found that missed NCSE was associated with an increased risk of not returning to functional baseline (OR 3.83, 95% CI 1.22–11.98, p=0.021). Patients with missed NCSE were also less frequently treated with benzodiazepines, the first-line drug for seizures, in the prehospital setting (20.3 percent) compared to patients whose NCSE was identified pre-hospital (51.1 percent) or who had CSE (86.4 percent).

The results, the study authors concluded, "add credence to the limited body of evidence that recognition and adequate response of the EMS to SE in adult patients is an important and yet underestimated factor determining functional outcome."

The researchers noted several limitations to their analysis. Among them were its observational, single-center design; their inability to determine causality; and that patients who were diagnosed with status epilepticus after the initial neurologic workup were excluded, which may have resulted in an under-reporting of patients with missed epileptic events.

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Thursday, June 29, 2017

Adverse Events Reported to Be Higher for Neurological In-Patients in Canadian Study

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BY KURT SAMSON

Nearly 50 percent of adverse events that occur in hospitals are preventable, experts in patient safety told Neurology Today, which is why new data from a Canadian study showing that patients with neurological conditions had significantly more complications that those in the general hospital population are disturbing. The report, they said, speaks to the need for evidence-based best practices that better promote hospital safety.

Published in the June 14 online edition of Neurology, the retrospective, population-based study looked at discharge data for 177,612 pediatric and adult patients with neurological conditions from 115 Alberta health care facilities from 2009 to 2015. The report found 11 adverse events (AEs) occurred for every 100 admissions for neurological conditions — this, compared with an earlier (2004) Canadian Adverse Events Study that found 7.5 AEs per 100 patients admitted for any condition at a representative sample of Canadian hospitals.

In the new study, AEs occurred most often in patients with spinal cord injury, stroke, Alzheimer disease and related dementia (ADRD), and traumatic brain injury (TBI). Infections and respiratory complications were the most common AEs except in brain tumor and spinal cord injury patients. Patients with spinal cord injury had 5.4 times greater odds of an AE compared to those with other neurological conditions. Adverse events were also more common in older patients and in those with higher comorbidity scores.

"Neurological patients with AEs had 2.4 times the odds of dying compared to those without AEs," said lead author Nathalie Jetté, MD, professor of neurology and community health sciences at the University of Calgary Cumming School of Medicine and Canada Research Chair in Neurological Health Services Research at the Hotchkiss Brain Institute & O'Brien Institute for Public Health.

"Our findings support previous reports that hospitalized patients are at great risk for AEs, with higher estimates reported in this neurological population compared to the prior Canadian study in the general hospital population." She noted that a number other international studies have reported that around 37 percent to 51 percent of AEs in hospital patients are preventable.

There are several of steps that can be taken to minimize the risk of AEs in neurological patients such as determining fall risk on admission, avoiding sedating medications, assessing swallowing function early, implementing deep venous thrombosis prophylaxis when necessary and doing careful medication reconciliation so patients do not miss any critical drugs on admission, noted Dr. Jetté.

"The time is right to carefully explore the reasons for these AEs and to develop and implement standardized clinical care pathways to reduce the rates of AEs for hospitalized neurological patients," she said.

The study authors assessed adverse events from discharge data for patients with one of nine neurological conditions: ADRD, brain tumor, epilepsy, motor neuron disease, multiple sclerosis, parkinsonism/Parkinson disease, spinal cord injury, traumatic brain injury, and stroke.

The researchers included 15 AEs in 18 categories: infections; ulcers; endocrinological AEs; venous thromboembolic; cardiac; respiratory; hemorrhagic; drug-related; fluid-related; obstetrical; fetal; surgical; traumatic; anesthetic; delirium-related; other CNS issues; gastrointestinal; and falls.

Among spinal cord patients, AEs occurred in 39.4 out of every 100 admissions, and among these patients, surgery-related AEs accounted for the highest proportion of AEs followed by infections and respiratory-related AEs (24.4 percent, 23.9 percent, and 16.7 percent, respectively).

The reason for the high proportion of AEs in those with a spinal cord injury is likely multifactorial, Dr. Jetté told Neurology Today. Spinal cord patients were more likely to have a surgical AE, she noted, adding that these patients have more procedures and interventions in the hospital.

Look for expanded coverage of this study in the July 6 issue of Neurology Today.


Friday, June 16, 2017

Children with Acute Flaccid Myelitis Have Long-Term Functional Deficits, Study Shows

​BY SARAH OWENS

Eight children in Colorado who had been diagnosed with acute flaccid myelitis (AFM) in 2014 had lingering motor and functional deficits one year later, despite functional improvements in some areas, according to a new study published online on June 14 in Neurology.

Nationwide cases of AFM, a neurologic condition associated with enterovirus infections that causes weakness and loss of muscle tone and reflexes, rose to 120 in 34 states in 2014, correlating with an outbreak of severe respiratory illness. [Earlier this year, Neurology Today reported on another widespread outbreak in the US and Europe in 2016.] Because the disease's clinical course and long-term outcomes remain unknown, researchers enrolled a small cluster of children with the aim of characterizing short- and long-term outcomes using clinical, neuroimaging and electrophysiological assessments.

The findings suggest that functional deficits due to AFM are "severe and are likely permanent," the study authors, led by Jan A. Martin, MD, assistant professor of pediatric neurology at the University of Colorado School of Medicine, wrote. "Future studies should investigate tools to accurately predict the course of this disease and identify effective treatments to prevent the severe long-term outcomes observed in this cohort."

For the study, researchers enrolled 12 children in Colorado who had been diagnosed with acute flaccid myelitis between August and October of 2014. Every three months for one year or until the clinical resolution of symptoms, children were given a neurologic examination, magnetic resonance imaging (MRI) scans, electromyography (EMG)/nerve conduction studies (NCS), tests of functional measures, and questionnaires of patient-reported outcomes.

Eight of the 12 children completed the year-long study; of these, six children had persistent motor deficits at the study's endpoint on clinical assessments, while two demonstrated a full recovery. The patients' proximal muscles were the weakest, demonstrating significant atrophy and minimal to no movement at the end of the study period, while distal muscles showed some functional improvement.

On MRI scans, seven children showed hyperintensities on initial T2-weighted imaging; these had resolved in six of eight children by the final scan. On NCS, three of eight children showed ongoing nerve deterioration and chronic reinnervation. Overall, changes on EMG tests correlated with functional deficits better than neuroimaging, the researchers noted.

Among notable patient-reported outcomes were symptoms of fatigue in one patient and depressive symptoms in three of eight patients; the children also reported anxiety and depression and behavioral outbursts.

The findings demonstrate that AFM has "substantial long-term functional effects on affected children," the study authors concluded. In addition, the occurrence of depression in over a third of the patients suggests that AFM can have "a substantial psychosocial effect."

Also, they wrote, the finding that EMG/NCS tests correlated better than MRI with functional assessments "provides important insights into the ability of diagnostic tools to evaluate recovery in AFM… EMG/NCS [rather than imaging] may be a useful tool to evaluate recovery of affected muscles and warrants further evaluation as a diagnostic tool in late presentations of illness."

The researchers noted several limitations to their study. Among them were the small cohort size, the lack of follow-up among four of the 12 original patients, and the fact that the functional testing measures used have not been validated for AFM.

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Thursday, June 15, 2017

Amandatine Extended-Release Capsules Reduce Levodopa-Induced Dyskinesia in Patients with Parkinson’s Disease

BY SARAH OWENS

Taking once-daily extended-release capsules of ADS-5012 (amantadine) at bedtime was safe and effective for reducing levodopa-induced dyskinesia (LID) and helped reduce off-times in patients with Parkinson's disease, according to the results of a randomized, double-blind, placebo-controlled clinical trial published online on June 12 in JAMA Neurology.

LID is common among patients with PD who take levodopa, but there are no approved Food and Drug Administration (FDA) treatments to treat it. Small, preliminary studies have suggested that amantadine-immediate release (IR) can have an antidyskinetic effect, but those findings have not yet been studied in well-controlled clinical trials. And at higher doses, amantadine IR has been associated with increased adverse events.

The study authors wanted to see if the extended-release capsules of ADS-5012 was safe and effective for LID. They concluded that based on the data on efficacy and safety, "these data support the use of ADS-5102 for patients with PD with LID, irrespective of its severity and duration, as well as off time. ADS-5012, 274 mg once daily at bedtime, should therefore be considered for the primary treatment of LID in patients with LID," wrote the study authors, led by Rajesh Pahwa, MD, FAAN, professor of neurology at the University of Kansas Medical Center.

For the study, researchers enrolled 126 patients with PD who were taking levodopa and had drug-associated dyskinesia at 44 sites in North America; 121 patients were included in the modified intent-to-treat population. They randomly assigned the patients to take 274 mg of extended-release amantadine  at bedtime (n=63) or placebo (n=58) for up to 25 weeks. Their primary efficacy endpoint was the change from baseline to week 12 in the Unified Dyskinesia Rating Scale, which assesses involuntary movements associated with Parkinson's disease, with higher scores indicating greater involuntary movement.

They found that extended-release amantadine significantly reduced the duration, severity, and impact of levodopa-induced dyskinea compared with placebo. At the end of the 12-week study period, the least-squares mean (SE) change (the group change after adjusting for covariables) in the Unified Dyskinesia Rating Scale score was –15.9 (1.6) in the amantadine group and –8.0 (1.6) in the placebo group (treatment difference, –7.9; 95%CI, –12.5 to –3.3; p<0.001). The study was stopped early, at week 12, by the sponsor to accelerate the availability of primary efficacy data. However, the benefit of the treatment was sustained in a subgroup of patients (n=39 for ADS-5102 n=45 for placebo) who continued treatment until 24 weeks (least-squares mean treatment difference, –9.3; 95% CI, –14.7 to –4.0; p<0.001).

Additionally, extended-release amantadine was effective at reducing off-times associated with levodopa; off-time decreased by a mean (SE) of 0.6 (0.3) hours in the amantadine group, while it increased by 0.3 (0.3) hours in the placebo group (treatment difference, –0.9 hours; 95%CI, –1.6 to –0.2; p=0.02).

The most common adverse events associated with ADS-5102 vs placebo included visual hallucinations (15 [23.8 percent] vs 1 [1.7 percent]), peripheral edema (15 [23.8 percent] vs 0), and dizziness (14 [22.2 percent] vs 0). Thirteen patients receiving extended-release amantadine (20.6 percent) discontinued treatment, compared to four patients receiving placebo (6.9 percent).

The researchers noted several limitations to their study. Among them, the study was stopped early, which decreased the number of patients contributing to the secondary endpoint assessments; and conclusions about the safety and efficacy of extended release amantadine relative to amantadine-IR require comparison in a randomized clinical trial.

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Monday, June 12, 2017

Tenecteplase Led to Better Rates of Recanalization, Early Clinical Improvement vs. Alteplase for Patients with Ischemic Stroke

BY SARAH OWENS

Patients with ischemic stroke and a complete vessel occlusion who were treated with the next-generation thrombolytic tenecteplase had greater complete recanalization rates and better early clinical improvement at 24 hours, according to a new study published online on June 2 in Neurology.

Those on tenecteplase also had a higher chance of a favorable outcome at 90 days, compared to patients treated with the standard-of-care alteplase, the study authors found.

Though the present findings on the superiority of tenecteplase remain preliminary, if confirmed in larger, blinded trials, they have "major potential relevance given the limited access to endovascular therapy in much of the world," the study authors, led by Andrew Bivard, PhD, of the School of Medicine and Public Health at the University of Newcastle in Australia, wrote.

For their study, researchers at several institutions in Australia pooled clinical and imaging data from two randomized, prospective, open-label phase 2 trials comparing tenecteplase with alteplase for the treatment of ischemic stroke – the Australian-TNK and ATTEST trials. In both trials, patients presenting with a large vessel occlusion on CT angiography scans were randomized to receive 0.25 mg/kg of tenecteplase or 0.9 mg/kg of alteplase. A total of 146 patients were included in the pooled analysis; of these, 69 had a total vessel occlusion at baseline.

They found that patients who had a complete vessel occlusion and were treated with tenecteplase had superior recanalization rates (71 percent for tenecteplase vs. 43 percent for alteplase, p<0.001). In fact, the study authors noted, the recanalization rates in patients treated with tenecteplase "were approaching rates seen in the recent endovascular trials."

Additionally, among patients with a complete occlusion at baseline, those treated with tenecteplase had better early neurologic recovery (median NIHSS change with tenecteplase = 9, interquartile range [IQR] 6, alteplase 1, IQR 1, p=0.001) as well as higher rates of a favorable 90-day functional outcome (mRS 0–1 of tenecteplase compared with alteplase, odds ratio [OR] 4.82, 95% confidence interval 1.02–7.84, p=0.05). They also had a better rate of hemorrhage transformation (3 percent for tenecteplase vs. 7 percent for alteplase, p=0.002) and reduced symptomatic intracranial hemorrhage (0 percent for tenecteplase vs 3 percent for alteplase, p=0.04).

However, the researchers noted, there was no significant difference between treatment groups in patients with a partial occlusion on rates of recanalization and 90-day outcomes.

The findings, the study authors concluded, "indicate that tenecteplase produces significantly higher rates of recanalization of occluded vessels." While tenecteplase was superior only for patients with a complete occlusion, they added, "this does not mean that there is no treatment benefit [for patients with a partial occlusion] as our study may lack power to measure the treatment effect in this group."

The researchers noted several limitations to their study. Among them were the small size of the datasets and that the data were from 2 small, open-label trials, which could have included biases in decision-making, clinical assessments, and patient motivation and compliance.

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