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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
Patent foramen ovale (PFO) device closure for prevention of recurrent ischemic stroke (October 2017)
Treatment for patients with a cryptogenic stroke who have a patent foramen ovale (PFO) has been controversial. In earlier randomized controlled trials, point estimates suggested that percutaneous device closure of a PFO in patients ≤60 years of age was more effective than antiplatelet therapy for reducing recurrent stroke, but the findings did not reach statistical significance. However, the results of three recent randomized trials, RESPECT extended follow-up , REDUCE , and CLOSE , provide stronger evidence that device closure of a PFO plus antiplatelet therapy is more effective than antiplatelet therapy alone for preventing recurrent ischemic stroke in such patients, with absolute risk reductions ranging from 2.2 to 6 percent. Based upon these results, we now suggest percutaneous PFO closure in addition to antiplatelet therapy for patients who meet all of the following criteria: age ≤60 years, embolic-appearing cryptogenic ischemic stroke (ie, no evident source of stroke despite a comprehensive evaluation), and a PFO with a right-to-left interatrial shunt detected by bubble study. (See "Treatment of atrial septal abnormalities (PFO, ASD, and ASA) for prevention of stroke in adults", section on 'Percutaneous closure of PFO'.)
Head position in acute stroke (July 2017)
A supine position with the head flat has been preferred for patients with acute ischemic stroke because it maximizes cerebral perfusion. However, the benefit of maintaining the head flat in this setting remains unproven. In the HeadPoST controlled trial of over 11,000 subjects with acute stroke (85 percent ischemic) who were randomly assigned to either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, there was no difference between treatment groups in disability outcomes, mortality, or serious adverse events . For most patients with acute ischemic stroke, we suggest keeping the head of the bed in the position that is most comfortable for the patient. Exceptions include those at risk for elevated intracranial pressure, aspiration, cardiopulmonary decompensation, or oxygen desaturation, where we recommend elevating the head of the bed to 30 degrees. (See "Initial assessment and management of acute stroke", section on 'Head and body position'.)
Risk of cognitive impairment in adults with sleep-disordered breathing (November 2017)
Obstructive sleep apnea (OSA) and other causes of sleep-disordered breathing are increasingly recognized as a risk factor for cognitive impairment and dementia, possibly through deleterious effects of hypoxemia or shared vascular risk factors. In a pooled analysis of prospective studies in over 200,000 adults, those with sleep-disordered breathing were 26 percent more likely to develop clinically relevant cognitive decline or dementia . Further studies are needed to determine whether effective treatment of OSA can reduce the risk of dementia. (See "Risk factors for cognitive decline and dementia", section on 'Obstructive sleep apnea'.)
Long-term cognitive outcomes in American high school football players (October 2017)
Based on increasing concerns about risk of chronic traumatic encephalopathy (CTE) in professional American football players and other athletes, there is a need for studies to determine whether less intensive exposure to high-risk sports poses risk. In a case-control study of nearly 3000 men whose cognitive function was assessed at age 65 years, past participation in high school American football was not associated with worse cognition, mood, or other emotional symptoms compared with non-participation . Although somewhat reassuring, these data have significant limitations, and more longitudinal studies are needed to determine modifiable risk factors for CTE and other forms of dementia. (See "Risk factors for cognitive decline and dementia", section on 'Head trauma'.)
Methylphenidate for apathy in patients with Alzheimer disease (October 2017)
Apathy is a common and understudied symptom of dementia that can emerge early in the disease course and contribute to functional impairment and caregiver burden. In a randomized trial of 77 patients with mild Alzheimer disease (AD), methylphenidate improved apathy scores compared with placebo over a 12-week treatment period . Adverse effects were similar between groups. These results add support to low-dose methylphenidate as an option in patients with persistent and distressing apathy despite a cholinesterase inhibitor and treatment of depression. (See "Management of neuropsychiatric symptoms of dementia", section on 'Apathy'.)
Dementia risk factors and prevention (September 2017)
Two major reports released by a Lancet Commission in the United Kingdom and the Agency for Healthcare Research and Quality in the United States review the literature on risk factors for dementia and the impact of risk factor modification on dementia incidence [8,9]. The Lancet Commission estimates that approximately one-third of dementia cases are attributable to a combination of nine potentially modifiable risk factors: low educational attainment, midlife hypertension, midlife obesity, hearing loss, late-life depression, diabetes, physical inactivity, smoking, and social isolation . While the overall evidence is generally of low quality and does not support any single intervention, there is optimism that intensive risk factor modification, especially during midlife, has the potential to delay or prevent dementia. (See "Risk factors for cognitive decline and dementia" and "Prevention of dementia".)
Revised diagnostic criteria for dementia with Lewy bodies (July 2017)
Revised consensus criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) have been published . The updated criteria now recognize rapid eye movement (REM) sleep behavior disorder as a core clinical feature of DLB, along with three previously recognized features: cognitive fluctuations, visual hallucinations, and parkinsonism (table 1). In patients with dementia, probable DLB can be diagnosed in the presence of two or more core clinical features or at least one core feature plus an indicative biomarker (reduced dopamine transporter [DAT] uptake in basal ganglia, abnormal 123-iodine-metaiodobenzylguanidine [MIBG] myocardial scintigraphy, or REM sleep without atonia on polysomnography). (See "Clinical features and diagnosis of dementia with Lewy bodies", section on 'Clinical features'.)
Minocycline for clinically isolated syndrome suggestive of multiple sclerosis (June 2017)
In a recent trial, 142 subjects with a first central nervous system demyelinating event (ie, a clinically isolated syndrome or CIS) were randomly assigned to minocycline or placebo . At six months, the difference in the risk of conversion to multiple sclerosis was lower for minocycline compared with placebo, and MRI outcomes also favored minocycline. However, at 24 months, there was no difference between groups for any of these outcomes. Thus, more data are needed from larger trials to determine if minocycline has any benefit for patients with CIS or early multiple sclerosis. (See "Clinically isolated syndromes suggestive of multiple sclerosis", section on 'Minocycline'.)
Epilepsy surgery in children with drug-resistant epilepsy (October 2017)
In the only randomized trial of epilepsy surgery to date in children with drug-resistant epilepsy, surgery plus medical therapy was superior to medical therapy alone on multiple one-year outcomes, including rate of seizure freedom at one year (77 versus 7 percent), seizure severity, quality of life, social maturity, and child behavior . Rates of seizure freedom ranged from 100 percent in 14 children who underwent temporal lobectomy to 0 percent in 10 children who underwent corpus callosotomy. Postoperative hemiparesis occurred exclusively among children who underwent hemispherectomy, all of whom had baseline deficits; all but two recovered to antigravity strength or better by one year. These results support the role of surgery as a treatment option for selected children with refractory epilepsy following a comprehensive and individualized epilepsy evaluation. (See "Seizures and epilepsy in children: Refractory seizures and prognosis", section on 'Specific procedures'.)
Cannabidiol in patients with Dravet syndrome and refractory epilepsy (May 2017)
Although cannabidiol (CBD), a component of cannabis, has received interest in the epilepsy community, particularly in children with Dravet syndrome (DS), controlled trials have not been available. In the first multicenter trial comparing oral CBD solution with placebo (in addition to standard antiseizure treatment) in 120 children and young adults with DS, seizure frequency was decreased at 14 weeks in the CBD group . Common side effects of CBD were diarrhea, sedation, and fatigue. Further study of CBD in patients with refractory epilepsy is indicated. In the absence of an available regulated preparation of CBD, we do not advocate use of cannabis or its derivatives outside of the context of a clinical trial. (See "Dravet syndrome: Management and prognosis", section on 'Cannabinoids'.)
Exenatide for Parkinson disease (August 2017)
Exenatide, a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist, has shown neuroprotective effects in animal models of Parkinson disease (PD). In a 60-week randomized trial of 60 patients with PD, the group assigned to subcutaneous exenatide 2 mg weekly showed a small improvement in motor scores, while the placebo group exhibited a slight worsening . However, there were no differences between the groups on any of the secondary clinical outcome measures. Given the small size of the trial and other limitations, more data are needed to confirm whether exenatide is beneficial in patients with PD. (See "Potential disease-modifying therapies for Parkinson disease", section on 'Exenatide'.)
Association between Parkinson disease and melanoma (August 2017)
Several studies have suggested an association between Parkinson disease (PD) and melanoma. A retrospective study using medical records from 1976 to 2013 found that, compared with controls, PD patients had nearly a four-fold increased likelihood of having a history of melanoma; likewise, patients with melanoma had approximately a four-fold risk of developing PD after the diagnosis of melanoma . Although the underlying cause of this reciprocal association remains unclear, these findings suggest that PD and melanoma may share genetic risk factors. (See "Etiology and pathogenesis of Parkinson disease", section on 'Risk factors' and "Risk factors for the development of melanoma", section on 'Other proposed risk factors'.)
Duration of postradiation temozolomide in glioblastoma (July 2017)
Postradiation monthly temozolomide is a standard component of initial therapy for glioblastoma, but the number of cycles has been subject to variation, with some centers treating beyond six cycles for patients with stable disease. In a retrospective study of over 600 patients with glioblastoma enrolled in four randomized trials who were free of progression after six cycles of adjuvant temozolomide, receipt of more than six cycles was associated with a slight improvement in progression-free survival but no difference in overall survival . Since extended adjuvant therapy exposes patients to ongoing treatment-related toxicities, these results support our practice of stopping adjuvant therapy after six cycles of monthly temozolomide. (See "Initial postoperative therapy for glioblastoma and anaplastic astrocytoma", section on 'Treatment duration'.)
Postoperative stereotactic radiosurgery for resected brain metastases (July 2017)
Two randomized trials lend further support to the use of postoperative stereotactic radiosurgery (SRS) rather than whole brain radiation therapy (WBRT) or observation after resection of a single brain metastasis. In one trial, patients treated with single-fraction SRS to the surgical cavity had improved neurocognitive function and similar overall survival compared with those treated with WBRT . In the second trial, single-fraction SRS decreased rates of local recurrence compared with observation, especially for tumors smaller than 2.5 cm preoperatively . Larger tumors may be better suited for multiple-fraction SRS, which allows for a higher dose of radiation to be delivered to the surgical cavity. (See "Overview of the treatment of brain metastases", section on 'Postoperative radiation'.)
Hematopoietic stem cell gene therapy for adrenoleukodystrophy (October 2017)
Childhood cerebral adrenoleukodystrophy (ALD) is a severe neurologic disease that rapidly progresses to total disability and death unless treated with allogeneic hematopoietic cell transplantation (HCT), which has considerable morbidity and mortality. Gene therapy with autologous hematopoietic stem cells is emerging as a possible alternative treatment. A study of 17 boys with early-stage cerebral ALD enrolled to undergo transplantation with autologous CD34+ cells transfected with Lenti-D (a lentiviral vector containing manufactured ABCD1 complementary DNA) reported 88 percent were alive with no major functional disabilities at 24 months posttransplantation . One boy died from disease progression that began during pretransplantation conditioning, and one was withdrawn from the study and died from complications of subsequent allogeneic HCT. None of the survivors had evidence of graft failure or graft-versus-host disease. These results suggest that autologous hematopoietic stem cell gene therapy may be as effective as, and safer than, HCT for treatment of early cerebral ALD. The treatment has not received regulatory approval. The clinical trial is ongoing and important uncertainties remain. (See "Adrenoleukodystrophy", section on 'Gene therapy'.)
Complex motor behaviors during REM sleep in children with narcolepsy type 1 (September 2017)
Complex motor behaviors during rapid eye movement (REM) sleep are well described in adults with narcolepsy, but their prevalence in children has not been well documented. In a series of 40 children with narcolepsy type 1 who underwent video polysomnography, nearly one-third of patients exhibited motor behaviors during REM sleep ranging from classic dream enactment (eg, vigorous reaching or throwing movements) to more calm, slow pantomime-like events . Events were more common among children with impaired nighttime sleep, worse daytime sleepiness, and severe cataplexy. (See "Narcolepsy in children", section on 'Other sleep disturbances'.)
Genetic testing in neonates with epileptic encephalopathy (August 2017)
The role of genetic testing in the clinical care of neonates with epilepsy is evolving as the number of monogenetic causes of early epileptic encephalopathy increases and specific treatments become available for some syndromes. In a prospective cohort study of over 600 consecutive newborns with seizures, 13 percent had an epilepsy syndrome, including 35 infants (6 percent) with epileptic encephalopathy . Among these, the large majority had a genetic etiology identified by genetic testing, most commonly KCNQ2 encephalopathy, for which sodium channel blocking antiseizure drugs are a preferred therapy. We pursue genetic testing in neonates with epilepsy who do not have an acute symptomatic cause identified on initial history, examination, and neuroimaging. (See "Clinical features, evaluation, and diagnosis of neonatal seizures", section on 'Genetic testing'.)
Low yield of lumbar puncture after complex febrile seizure (July 2017)
After a febrile seizure, lumbar puncture to assess for infection can be avoided in most well-appearing children who have returned to their baseline, even when the febrile seizure has complex features (ie, focal onset, >15 minutes in duration, or recurrent within 24 hours). In a multicenter cohort study of more than 800 children age six months to five years presenting to a pediatric emergency department with a complex febrile seizure, rates of bacterial meningitis and herpes simplex encephalitis were 0.7 and 0 percent, respectively . All five cases of infection occurred in children with a clinical examination suggestive of meningitis. (See "Clinical features and evaluation of febrile seizures", section on 'Lumbar puncture'.)
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