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Objective

To test whether targeting hippocampal-cortical brain networks with high-frequency transcranial magnetic stimulation in older adults influences behavioral and neural measures characteristic of age-related memory impairment.

Methods

Fifteen adults aged 64 to 80 years (mean = 72 years) completed a single-blind, sham-controlled experiment. Stimulation targets in parietal cortex were determined based on fMRI connectivity with the hippocampus. Recollection and recognition memory were assessed after 5 consecutive daily sessions of full-intensity stimulation vs low-intensity sham stimulation using a within-subjects crossover design. Neural correlates of recollection and recognition memory formation were obtained via fMRI, measured within the targeted hippocampal-cortical network vs a control frontal-parietal network. These outcomes were measured approximately 24 hours after the final stimulation session.

Results

Recollection was specifically impaired in older adults compared to a young-adult control sample at baseline. Relative to sham, stimulation improved recollection to a greater extent than recognition. Stimulation increased recollection fMRI signals throughout the hippocampal-cortical network, including at the targeted location of the hippocampus. Effects of stimulation on fMRI recollection signals were greater than those for recognition and were greater in the targeted network compared to the control network.

Conclusions

Age-related recollection impairments were causally related to hippocampal-cortical network function in older adults. Stimulation selectively modified neural and behavioral hallmarks of age-related memory impairment, indicating effective engagement of memory intervention targets in older adults.

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Monitoring of chronic degenerative diseases, such as multiple sclerosis (MS), in individual patients represents one of the most important challenges for clinicians. MS evolves over decades, but therapeutic decisions are based on short-term, risk-benefit analyses. In addition, in all areas of medicine, therapeutics often develop in conjunction with the means for measuring their efficacy. As an example, highly active antiretroviral therapies were able to be developed for the treatment of the human immunodeficiency virus because of the development of CD4 count and viral load as outcomes that could be targeted for treatment. Although T2 lesion load and new gadolinium-enhancing lesions are very useful metrics for measuring inflammatory activity in MS, they only have a modest correspondence with disability. For these reasons, developing biomarkers that reflect the degree of neurologic injury and predict the future course of the disease is a high priority for personalizing health care for people with MS.1 Internuclear ophthalmoplegia (INO) is commonly found in patients with MS due to plaques in the medial longitudinal fasciculus and imposes substantial disability.2,3 A previous study using MRI and the new technology of infrared oculography found a well-defined mapping between damage of the medial longitudinal fasciculus in the brainstem and INO.4

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Objective

To determine the effect of erenumab, a human anti-calcitonin gene-related peptide receptor monoclonal antibody, in patients with chronic migraine and medication overuse.

Methods

In this double-blind, placebo-controlled study, 667 adults with chronic migraine were randomized (3:2:2) to placebo or erenumab (70 or 140 mg), stratified by region and medication overuse status. Data from patients with baseline medication overuse at baseline were used to assess changes in monthly migraine days, acute migraine-specific medication treatment days, and proportion of patients achieving ≥50% reduction from baseline in monthly migraine days.

Results

Of 667 patients randomized, 41% (n = 274) met medication overuse criteria. In the medication overuse subgroup, erenumab 70 or 140 mg groups had greater reductions than the placebo group at month 3 in monthly migraine days (mean [95% confidence interval] –6.6 [–8.0 to –5.3] and –6.6 [–8.0 to –5.3] vs –3.5 [–4.6 to –2.4]) and acute migraine-specific medication treatment days (–5.4 [–6.5 to –4.4] and –4.9 [–6.0 to –3.8] vs –2.1 [–3.0 to –1.2]). In the placebo and 70 and 140 mg groups, ≥50% reductions in monthly migraine days were achieved by 18%, 36% (odds ratio [95% confidence interval] 2.67 [1.36–5.22]) and 35% (odds ratio 2.51 [1.28–4.94]). These clinical responses paralleled improvements in patient-reported outcomes with a consistent benefit of erenumab across multiple measures of impact, disability, and health-related quality of life. The observed treatment effects were similar in the non–medication overuse subgroup.

Conclusions

Erenumab reduced migraine frequency and acute migraine-specific medication treatment days in patients with chronic migraine and medication overuse, improving disability and quality of life.

Clinicaltrials.gov identifier

NCT02066415.

Classification of evidence

This study provides Class II evidence that erenumab reduces monthly migraine days at 3 months in patients with chronic migraine and medication overuse.

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Of neurologic emergencies, status epilepticus (SE) is one of the most common with an incidence of approximately 10–20/100,000/y. In addition, it carries a high mortality between 3% and 40% depending on age, etiology, and other factors. Not unexpectedly, SE is also costly with an estimated annual burden of $4 billion in the United States.1 To put this in perspective, the annual direct costs of epilepsy care are approximately $9 to $12 billion.2 Now imagine that the care of patients with this common emergency was guided by low-level evidence. Furthermore, imagine that it was becoming clear that early treatment of SE is substantially more effective and prevents the need for additional aggressive, invasive, and costly treatments. This is the current state of the treatment of SE.

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Objective

To define the in-hospital course, complications, short- and long-term functional outcomes of patients with angiographically negative subarachnoid hemorrhage (anSAH), particularly those with aneurysmal-pattern anSAH (aanSAH).

Methods

Retrospective cohort study of patients with aneurysmal subarachnoid hemorrhage (aSAH), aanSAH, and perimesencephalic-pattern anSAH (panSAH) treated at a single tertiary referral center between January 2006 and April 2018. Ninety-nine patients with anSAH (33 aanSAH and 66 panSAH) and 464 patients with aSAH were included in this study. Outcomes included symptomatic hydrocephalus requiring CSF drainage, need for ventriculoperitoneal shunt, radiographic vasospasm, delayed cerebral ischemia (DCI), radiographic infarction, disability level within 1 year of ictus, and at last clinical follow-up as defined by the modified Rankin Scale.

Results

Patients with aanSAH and panSAH had similar rates of DCI and radiologic infarction, and patients with aanSAH had significantly lower rates compared to aSAH (p ≤ 0.018). Patients with aanSAH were more likely than those with panSAH to require temporary CSF diversion and ventriculoperitoneal shunt (p ≤ 0.03), with similar rates to those seen in aSAH. Only one patient with anSAH died in the hospital. Compared to those with aSAH, patients with aanSAH were significantly less likely to have a poor functional outcome within 1 year of ictus (odds ratio 0.26, 95% confidence interval 0.090–0.75) and at last follow-up (hazard ratio 0.30, 95% confidence interval 0.19–0.49, p = 0.002).

Conclusions

DCI is very uncommon in anSAH, but patients with aanSAH have a similar need for short- and long-term CSF diversion to patients with aSAH. Nevertheless, patients with aanSAH have significantly better short- and long-term outcomes.

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Normal-pressure hydrocephalus (NPH) is a poorly defined clinical syndrome, classically characterized by the phenotypic triad of gait instability, cognitive impairment, and urinary incontinence, accompanied by neuroimaging evidence of ventriculomegaly and disproportionally enlarged subarachnoid space hydrocephalus and normal intracranial pressure.1,2 The diagnosis of this syndrome is complex since the characterizing symptoms are highly nonspecific and occur together in fewer than two thirds of NPH patients. In addition, a growing body of evidence supports the observation that NPH patients often have a coexistent neurodegenerative disorder that may be a concurrent or sole cause of both clinical symptoms and ventriculomegaly. This may be the main cause for the short-lived benefits secondary to an NPH-targeted therapeutic intervention, such as the placement of a ventriculoperitoneal shunt.2

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We thank Prof. Sidiropoulos for commenting on our article.1 Indeed, other studies targeted the posterior subthalamic area (PSA) more ventrally, and there might exist a certain degree of current spread from the ventral intermediate nucleus of the thalamus (VIM) into the PSA and vice versa, especially at higher amplitudes. However, we2 and others3 implanted contacts at similar z coordinates before.

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Articles appearing in the October 2018 issue

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Objective

To determine whether quantitative EEG (QEEG) features predict neurologic outcomes in children after cardiac arrest.

Methods

We performed a single-center prospective observational study of 87 consecutive children resuscitated and admitted to the pediatric intensive care unit after cardiac arrest. Full-array conventional EEG data were obtained as part of clinical management. We computed 8 QEEG features from 5-minute epochs every hour after return of circulation. We developed predictive models utilizing random forest classifiers trained on patient age and 8 QEEG features to predict outcome. The features included SD of each EEG channel, normalized band power in alpha, beta, theta, delta, and gamma wave frequencies, line length, and regularity function scores. We measured outcomes using Pediatric Cerebral Performance Category (PCPC) scores. We evaluated the models using 5-fold cross-validation and 1,000 bootstrap samples.

Results

The best performing model had a 5-fold cross-validation accuracy of 0.8 (0.88 area under the receiver operating characteristic curve). It had a positive predictive value of 0.79 and a sensitivity of 0.84 in predicting patients with favorable outcomes (PCPC score of 1–3). It had a negative predictive value of 0.8 and a specificity of 0.75 in predicting patients with unfavorable outcomes (PCPC score of 4–6). The model also identified the relative importance of each feature. Analyses using only frontal electrodes did not differ in prediction performance compared to analyses using all electrodes.

Conclusions

QEEG features can standardize EEG interpretation and predict neurologic outcomes in children after cardiac arrest.

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