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Tuesday, August 23, 2016

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​Credit: foto74​

BY SARAH OWENS

Calcium supplementation was associated with an increased risk of developing dementia in elderly women with cerebrovascular disease, according to the results of a five-year observational study published online on August 17 ahead of the print edition of Neurology. The risk was mainly confined to women who had a history of stroke or who had white matter lesions on brain imaging, the study authors said.

Some studies have associated increased intake of supplemental calcium, taken to prevent osteoporosis, with an elevated risk of vascular events, which also has been associated with the risk of Alzheimer's disease and dementia, the the study authors noted.

Researchers at the University of Gothenburg in Mölndal, Sweden followed 700 older women between the ages of 70 and 92 who did not have dementia at the beginning of the study. The study sample was derived from the Prospective Population Study of Women and the H70 Birth Cohort Study. Among all study participants, 108 women had a history of stroke, and 316 of the 447 participants who had computed tomography (CT)  scans had white matter lesions, a marker of cerebrovascular disease.

Ninety-eight of the women were treated with calcium supplements over the five-year follow-up period, while 602 women were not given calcium supplements. At the end of the follow-up period, geriatric psychiatrists evaluated the study participants using psychiatric examinations and interviews. They diagnosed dementia according to DSM-III-R criteria and Alzheimer's disease, as well as criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association.

The researchers found that calcium supplementation was associated with the development of dementia in women with a history of stroke (p=0.020), but not in women without a history of stroke (p=0.381). Additionally, calcium supplementation was associated with dementia in women who had white matter lesions on CT scans (p=0.011); there was no association found in women taking calcium supplements who did not have white matter lesions (p=0.351).

"This association was mainly confined to individuals with cerebrovascular disease at baseline," the study authors, led by Jürgen Kern, MD, PhD, neurologist at the Institute of Neuroscience and Physiology at the Sahlgrenska Academy at the University of Gothenburg.

The study authors hypothesized that calcium supplements "may potentiate changes in the vessel walls in individuals with vascular disease, leading to ischemia and hypoperfusio" or that calcium supplements may stimulate vascular calcification by abnormal extraosseous deposition in atherosclerotic plaques. They noted that that study participants' levels of serum calcium – a measure of calcium in the blood – increased sharply after they took the supplements, which may have altered blood flow in the brain, in turn increasing dementia risk.

Dietary calcium is not associated with the same vascular risks as calcium supplementation, the study authors noted. They hypothesized the difference in risk effect between the two may be attributable to corresponding changes in serum calcium levels, since "dietary intake does not increase the serum calcium levels to the same extent as supplements."

The researchers noted that among several limitations, the study was small and observational; they had no information on dietary calcium intake; the participants' levels of serum calcium, or whether their use of calcium was casual or persistent.

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Thursday, August 18, 2016

BY SARAH OWENS

A history of stroke was associated with a two-fold increased risk for both familial and sporadic forms of late-onset Alzheimer's disease (LOAD), according to an analysis of data from two longitudinal studies that was published online August 15 in JAMA Neurology. But hypertension was associated with decreased disease risk, and there was no association found between type 2 diabetes and LOAD.

Previous studies have found an association between cerebrovascular and cardiovascular risk factors — such as type 2 diabetes, hypertension, smoking, lipid disorders — and LOAD, but little was known about causal associations and the timing of cardiovascular and cerebrovascular disease and LOAD, the authors noted.

The researchers, led by Giuseppe Tosto, MD, PhD, assistant professor of neurology at Columbia University Medical Center, wanted to parse out the contribution of cardiovascular risk factors and stroke to the risk for LOAD.

They analyzed clinical outcomes from a total of 6,553 adults — participants in National Institute on Aging Late-Onset Disease/National Cell Repository for Alzheimer Disease family study and the multiethnic community-based Washington Heights-Inwood Columbia Aging Project — who met several criteria for familial AD.

To explain the finding of an inverse association between hypertension and LOAD risk, the authors hypothesized that "high blood pressure in late life may protect against LOAD" and antihypertensive treatments – including diuretics, beta-blockers, calcium channel blockers, and others — may confer a "protective effect."

The findings reflect what the researchers referred to as a phenomenon of "inconsistent mediation," in which a direct pathway — hypertension decreases stroke risk — and an indirect pathway —hypertension leads to stroke, which leads to increased stroke risk — operate simultaneously.

The results suggest the importance of interventions targeting modifiable risk factors in LOAD and the complex relationships between hypertension and LOAD, the study authors wrote, adding that more longitudinal studies and a larger set of variables – different classes of treatments — need to be studied.

The study authors noted a number of limitations: the absence of confounders – including smoking, physical activity level, and body mass index – in analyses; the fact that several predictors were self-reported, including heart disease and medications, which may have contributed to a bias; and that history of stroke did not account for multiple stroke events.

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Wednesday, August 17, 2016

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BY SARAH OWENS

People who have a stroke at a young age may have a higher risk of developing cerebral small vessel disease. Moreover, cerebral aging may be accelerated by 10 to 20 years in these patients, suggesting an increased vulnerability to vascular risk factors, according to a study published online on August 12 ahead of the print edition of Neurology.

"The suggested increased vulnerability supports the need for accurate identification of vascular risk factors at presentation and immediate treatment accordingly, even in these often young patients," the study authors, led by Renate M. Arntz, MD, PhD, professor of neurology at Radmoud University Medical Center in Nijmegen, the Netherlands, wrote.

Researchers in the Netherlands evaluated 337 people between the ages of 18 and 50 who had had an ischemic stroke or a transient ischemic attack (TIA), as well as 90 controls who had identical vascular risk factors as the stroke group but no history of stroke. All were participating in the Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) study, a prospective cohort study designed to investigate the causes and consequences of young stroke. The researchers used MRI scans at follow-up to assess the presence of vascular risk factors, including lacunes, microbleeds, and white matter hyperintensity (WMH) volume.

After a mean follow-up of 9.9 years, they found that 81 patients who had had a stroke at a young age (24 percent) had at least one lacune on MRI, compared with 4 controls (4.5 percent, p<0.001). They found no difference in microbleeds between patients who had had a stroke and controls. However, the stroke cohort had an average of 1.5 mL more WMH volume compared to controls (p<0.001).

The stroke cohort had an elevated risk of lacunes and higher WMH than controls even after adjusting for confounders, including age, sex, smoking, diabetes, and hypertension, the researchers noted. Additionally, the stroke group already had the same volume of WMHs on average 10 to 20 years earlier in life than controls with identical vascular risk factors, suggesting that cerebral aging may be accelerated in young stroke patients.

The findings have "prognostic implications," the study's authors suggested. Cerebral small vessel disease has been linked with other diseases independent of stroke, including depression and cognitive impairments, they noted. Long-term follow-up of young patients who have a stroke is therefore "of utmost importance," they concluded.

The study's authors noted several study limitations, including possible underestimation of WMH volume in the young stroke group due to incomplete follow-up by smokers in that group; their inability to determine incident small vessel disease, which made the study cross-sectional; and the possible influence of confounders, although the researchers attempted to adjust their analyses to eliminate the most important confounders for small vessel disease.

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Monday, August 15, 2016

BY SARAH OWENS

Most people who had a mild traumatic brain injury (TBI) regained the ability to make reasoned medical decisions twelve months later, but many who had a moderate/severe TBI had lingering deficits that inhibited medical decision-making at one year, according to a new study published online on August 10, 2016 ahead of the print edition of Neurology.

People who sustain a TBI have a number of treatment decisions to face during their stay in the hospital, during rehabilitation, and during long-term recovery, including managing medications, following advance directives, or treating orthopedic injuries and secondary complications, the study's authors noted. The researchers had previously studied and found impairments at the time of injury in MDC in complicated mild and moderate/severe TBI groups, but they had not assessed their longer-term recovery.

"Clinically, the current findings underscore the importance of evaluating MDC soon after injury and over time in all individuals with TBI," the study authors, led by Kayla A. Steward, BS, of the University of Alabama at Birmingham, wrote.

Researchers recruited 111 people who were being treated for TBI at an inpatient/outpatient rehabilitation unit and at an outpatient neurology department and 66 healthy controls for the study. They divided participants in the TBI group into several subgroups based on severity of injury: those with mild TBI (n=28), complicated mild TBI (n=23), and moderate/severe TBI (n=60).

They assessed the study participants' ability to make medical decisions at one month, six months, and 12 months post-injury using the Capacity to Consent to Treatment Instrument (CCTI), a psychometric instrument that presents hypothetical medical problems with symptoms and asks patients to select a treatment option. The instrument measures five standards of consent: expressing a treatment choice (expressing choice); appreciating the personal consequences of a choice (appreciation); providing rational reasons for a choice (reasoning); understanding the treatment choices and respective risks/benefits (understanding); and ability to make a reasonable treatment choice (reasonable choice).

They found that compared with controls, no TBI group showed impaired MDC expressing choice or reasonable choice at any timepoint. However, they observed notable differences among the three TBI groups in certain aspects of decision-making over the first year.

Participants with mild TBI recovered MDC relatively quickly, and most regained full MDC after six months. Participants with complicated mild TBI showed more initial MDC impairment and slower recovery than those with mild TBI, but approached full recovery at 12 months. However, for participants with moderate/severe TBI, all three complex consent standards — appreciation, reasoning, and understanding — remained "below the level of control performance" at one year.

Among findings, less than 20 percent of participants with mild TBI continued to have impaired appreciation and understanding, and no more than 14 percent of participants with complicated mild TBI continued to have impaired appreciation, reasoning, or understanding one year post-injury. By contrast, a "large proportion" of participants with moderate/severe TBI remained impaired on all three consent standards one year after injury: 17 percent had impaired appreciation, 25 percent had impaired reasoning, and 50 percent had impaired understanding.

The study's authors added that in all groups, most recovery took place during the first six months after the injury, and recovery stabilized after six months with limited MDC improvement between six and 12 months.

The results, the study's authors wrote, support the "need for continual monitoring of MDC in those with more severe head injuries for at least a year post-injury."

The study's authors noted several trial limitations, including their inability to compare outcomes between moderate and severe TBI (due to a lack of participants with moderate injuries); the relatively short duration of the study; and the fact that a quarter of the study participants did not complete all three visits.

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Thursday, August 11, 2016

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​Credit: Walsh & Hoyt's Clinical Neuro-Ophthalmology: The Essentials

BY SARAH OWENS

Thymectomy combined with prednisone improved clinical outcomes in patients with nonthymomatous myasthenia gravis over a three-year period compared to prednisone alone, according to a new study published August 11 in the New England Journal of Medicine.

The randomized, controlled, multicenter trial is the first of its kind to assess the benefit of thymectomy versus medical treatment alone for myasthenia gravis, an autoimmune neuromuscular disease that can cause muscle weakness, vision problems, and other symptoms.

Thymectomy has been used to treat nonthymomatous myasthenia gravis — a form of the disease that does not include a thymoma, or chest tumor — for 75 years, the study's authors noted, but observational and retrospective studies were limited and have not shown a clinical benefit to surgery versus medical therapy alone. Because the neurologic disease is so rare, it was challenging to enroll enough patients to conduct a randomized, controlled study to ascertain the benefit of the surgery and identify "the clinical characteristics of the patients who should be offered the procedure," the study's authors added.

Previous nonrandomized studies had bias problems, said Gil I. Wolfe, MD, FAAN, Irvin and Rosemary Smith chair of the department of neurology at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo of the State University of New York and chief study author, in a press release accompanying the study. The new findings confirm that thymectomy is beneficial, the authors noted.

The researchers enrolled 126 patients who had myasthenia gravis for less than three years in the MGXT trial. The participants were randomized to receive alternate-day prednisone alone (n=60) or thymectomy plus alternate-day prednisone (n=66). The primary outcomes were a reduction in the Quantitative Myasthenia Gravis score – a 13-item, 39-point scale of muscle weakness, with higher scores indicating more severe weakness, and a reduction of 2.3 points signifying improved clinical status – and a significant reduction in prednisone dosage.

They found that patients in the thymectomy group had "significantly lower" Quantitative Myasthenia Gravis scores compared to patients in the prednisone group (a difference of 2.85 points, p<0.001) over the three-year study period. They also found that patients in the thymectomy group had lower prescribed dosages of prednisone (44 mg versus 60 mg in the prednisone-only group, p<0.001).

In addition, patients in the thymectomy group had fewer hospitalizations for exacerbations of myasthenia gravis (9 percent) than those in the prednisone-only group (37 percent, p<0.001). Among patients who were hospitalized, those in the thymectomy group had fewer cumulative days in the hospital (8.4±8.6 days) compared to those in the prednisone-only group (19.2±24.5 days; p=0.09). Compared to the prednisone-only group, patients in the thymectomy group had better scores on the Myasthenia Gravis Activities of Daily Living scale, an eight-question survey that assesses interference of myasthenia gravis symptoms with daily life.

The results, the study's authors wrote, provide evidence "supporting the use of thymectomy for improving clinical outcomes and reducing the need for immunosuppressive therapy" for patients with myasthenia gravis.

The study's authors noted several limitations, including the single-blind nature of the study and the pill-count method used to assess medical outcomes, which was "not a precise measure of actual intake."

In an accompanying editorial, Allan H. Ropper, MD, professor and executive vice chair of neurology at Harvard Medical School, noted that the results of the trial "reflect the difficulty in capturing these fluctuating and fatigable myasthenic symptoms."  The clinical outcomes were better in the thymectomy group, he said, but the "absolute differences were moderate," and the main results were supported by secondary outcomes, showing that more patients in the thymectomy group had "minimal manifestations" by three years and a lower rate of need for immunosuppression with azathioprine.

While the findings "will be useful in counseling patients," he cautioned that they "offer no further clarity" for the selection of patients receiving thymectomy because secondary analyses did not show relative benefits based on gender or age. "Nevertheless, the appeal of a virtual cure by means of thymectomy is likely to persist because of the unappealing alternative of a long-term commitment to the use of glucocorticoids and immunosuppression," he said.

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