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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.
Anesthesia for patients with acute ischemic stroke undergoing mechanical thrombectomy (January 2017)
The type of anesthesia used for patients with acute ischemic stroke undergoing mechanical thrombectomy may affect outcomes, but data are limited and inconsistent. In a randomized trial testing general anesthesia versus conscious sedation in this setting, there was no significant difference between the two groups for the outcome of early neurologic improvement . Subjects assigned to general anesthesia were more likely to achieve functional independence at three months, but small patient numbers lower the confidence in this result. The findings of this trial conflict with earlier reports that general anesthesia was associated with worse outcomes. (See "Reperfusion therapy for acute ischemic stroke", section on 'Mechanical thrombectomy'.)
Antipsychotic drugs and risk of falls and fracture (March 2017)
In a large, population-based sample of Finnish people with Alzheimer disease, new users of antipsychotic medication had an increased risk of hip fractures from the first days of use . Subsequent to multiple similar reports in patients with varied disorders, the US Food and Drug Administration (FDA) issued a warning that antipsychotic drugs may cause falls and fractures as a result of somnolence, postural hypotension, and/or motor and sensory instability, and recommended that a fall risk assessment be completed when initiating antipsychotic treatment and recurrently for patients continuing on long-term antipsychotics. (See "Second-generation antipsychotic medications: Pharmacology, administration, and side effects", section on 'Falls'.)
Air pollution and the risk of dementia (February 2017)
Two recent studies highlight the potential role of air pollution as a contributor to cognitive decline and dementia. In a population-based study of older adults in Ontario, Canada, residing in close proximity to a major traffic road was associated with a 7 percent increase in the relative risk of incident dementia after adjusting for multiple potential confounders . In another cohort study, the adjusted relative risk of all-cause dementia was nearly twofold higher among older women living in areas with high concentrations of fine particulate matter compared with those living in areas with low concentrations . In a subgroup analysis, the effect size was largest in women with genetic susceptibility to Alzheimer disease, and in mouse models, fine particulate exposure promoted amyloid deposition and caused selective hippocampal atrophy. (See "Risk factors for cognitive decline and dementia", section on 'Toxins and air pollution'.)
High-risk drug prescribing in adults with dementia (February 2017)
Older adults with dementia are at heightened risk for adverse drug effects from anticholinergic drugs, benzodiazepines, and opioids, among many others. Despite these risks, polypharmacy remains common in this population. In a study that included over 75,000 adults with dementia, 44 percent of patients were prescribed at least one potentially unsafe medication (mostly drugs with high anticholinergic activity), and rates were consistently higher in patients receiving care from multiple providers . These results highlight the need for careful monitoring of drug therapy in patients with dementia and the importance of communication among providers before starting new therapies. (See "Safety and societal issues related to dementia", section on 'Polypharmacy'.)
Decision aids for advance care planning in dementia (February 2017)
Structured interventions to improve advance care planning among families of patients with advanced dementia have not been well studied. In a cluster randomized trial, use of a video decision aid and structured family meeting resulted in better communication about end of life care, greater use of medical orders defining scope of treatment, and fewer hospital transfers compared with a control intervention (informational video and usual care plan meeting) . Audiovisual decision aids and structured meetings may thus be effective components of multidimensional decision-making support for families of patients with advanced dementia. (See "Palliative care of patients with advanced dementia", section on 'Advance care planning'.)
Ocrelizumab for relapsing multiple sclerosis (January 2017)
Two randomized, controlled trials in patients with relapsing-remitting multiple sclerosis (RRMS) have found that ocrelizumab, a recombinant anti-CD20 monoclonal antibody, is more effective than interferon beta-1a for reducing relapses and may also slow disability progression . In both trials, ocrelizumab significantly reduced the relapse rate and the mean number of gadolinium-enhancing brain lesions on MRI scan. In a pooled analysis, ocrelizumab also reduced the proportion of subjects with confirmed disability progression at 24 weeks. Infusion reactions were the most common adverse effect of ocrelizumab, and there were more neoplasms with ocrelizumab than with interferon beta-1a (0.5 versus 0.2 percent). The role of this agent in the early treatment of RRMS remains to be clarified, pending drug approval and further safety data on rates of infection and neoplasm. (See "Disease-modifying treatment of relapsing-remitting multiple sclerosis in adults", section on 'Ocrelizumab'.)
Ocrelizumab for primary progressive multiple sclerosis (January 2017)
Ocrelizumab is the first drug to reduce the risk of disability progression among patients with primary progressive multiple sclerosis (PPMS), as shown by the double-blind, multicenter ORATORIO trial . Compared with placebo, ocrelizumab modestly reduced 24-week confirmed disability progression (30 versus 36 percent, absolute risk reduction 6 percent). In addition, ocrelizumab slowed deterioration from baseline to week 120 on the timed 25-foot walk and led to improvements on other endpoints. The role of this agent in treatment of PPMS remains to be clarified, pending drug approval and further safety data on rates of infection and neoplasm. (See "Treatment of progressive multiple sclerosis in adults", section on 'Ocrelizumab'.)
Thrombotic microangiopathy from interferon (October 2016)
Drug-induced thrombotic microangiopathy (DITMA) has been described with a number of chemotherapeutic, immunosuppressive, and other drugs. Unlike thrombotic thrombocytopenic purpura (TTP), DITMA is not associated with severely reduced ADAMTS13 activity, and the principal treatment is drug discontinuation rather than plasma exchange. A new report has provided strong evidence for interferon as a cause of TMA . Patients receiving interferon who develop signs of a TMA should have the drug discontinued promptly before organ failure develops. (See "Drug-induced thrombotic microangiopathy", section on 'Immunosuppressive agents'.)
Premature mortality in people with epilepsy (February 2017)
People with epilepsy are at increased risk for premature mortality compared with the general population. In systematic reviews commissioned by the International League Against Epilepsy (ILAE), standardized mortality ratios (SMRs) across all age groups indicate that the observed number of deaths in people with epilepsy is two- to threefold higher than in reference populations without epilepsy [10,11]. SMRs are substantially higher in children compared with adults and among those with structural/metabolic etiologies, medically-refractory epilepsy, and convulsive seizures. Causes of death attributable to epilepsy include convulsive status epilepticus, unintentional injuries, suicide, and sudden unexpected death in epilepsy (SUDEP). (See "Seizures and epilepsy in children: Refractory seizures and prognosis", section on 'Mortality' and "Overview of the management of epilepsy in adults", section on 'Mortality'.)
No benefit of hypothermia in convulsive status epilepticus (January 2017)
Convulsive status epilepticus is prolonged and refractory to standard first-line medications in approximately one-third of patients, and outcomes associated with refractory status epilepticus are often poor. Induced hypothermia has been proposed as a potential neuroprotective strategy. However, in a randomized trial of 250 critically ill adults with convulsive status epilepticus, induced hypothermia did not improve 90-day mortality, functional outcomes, or rate of progression to refractory status epilepticus when added to standard first-line therapies . (See "Convulsive status epilepticus in adults: Treatment and prognosis", section on 'Others'.)
Intravenous carbamazepine approved for use in adults (November 2016)
An intravenous (IV) preparation of carbamazepine has been approved by the US Food and Drug Administration for use as short-term replacement therapy in adult patients on stable doses of oral carbamazepine who are transiently unable to ingest oral preparations . The recommended IV conversion dose is 70 percent of the total daily oral dose, divided into four equal doses and given every six hours. (See "Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects", section on 'Carbamazepine'.)
Everolimus for refractory epilepsy associated with tuberous sclerosis (September 2016)
Tuberous sclerosis complex (TSC) is characterized by the development of benign tumors in multiple organs, including the brain, and medically intractable epilepsy is a major cause of morbidity. The mammalian target of rapamycin (mTOR) pathway is over-activated in TSC, and mTOR inhibitors such as everolimus are known to have antitumor efficacy. Data on antiseizure effects have been limited, however. In the recent 18-week EXIST-3 trial, which enrolled over 360 subjects with TSC and treatment-resistant epilepsy, the proportion of subjects achieving a ≥50 percent reduction in seizure frequency was significantly greater for the low- and high-exposure everolimus groups compared with placebo (28, 40, and 15 percent, respectively) . The most common adverse events associated with everolimus were stomatitis, diarrhea, and pyrexia. While longer-term data are needed, these results suggest that everolimus is an effective and safe treatment option for patients with TSC and treatment-resistant epilepsy. (See "Tuberous sclerosis complex: Management", section on 'Refractory epilepsy'.)
Amitriptyline and topiramate for prevention of pediatric migraine (November 2016)
Amitriptyline and topiramate are commonly used as prophylactic agents for pediatric migraine, and two previous randomized trials found that topiramate was effective for this indication. However, neither amitriptyline nor topiramate was better than placebo for headache prevention in the 24-week CHAMP trial of children and adolescents (8 to 17 years of age) with episodic or chronic migraine . Adverse events were more common in the amitriptyline and topiramate groups. There is no single best preventive treatment for migraine in children, and choice of therapy should be individualized based on comorbidities and patient preferences. (See "Preventive treatment of migraine in children", section on 'Amitriptyline'.)
Nusinersen for spinal muscular atrophy (January 2017)
Nusinersen, an antisense oligonucleotide, is the first drug approved to treat spinal muscular atrophy (SMA) by the US Food and Drug Administration (FDA). In an interim analysis of the double-blind ENDEAR trial, which enrolled 82 infants with SMA, improvement in motor milestones was observed in 40 percent of patients treated with intrathecal nusinersen, versus none for those who received the sham procedure . The FDA based its approval upon data from this trial and open-label studies in older patients with SMA [17,18]. We recommend nusinersen for most infants with SMA and select children ages 2 to 12 years with SMA. (See "Spinal muscular atrophy", section on 'Nusinersen'.)
Diaphragmatic pacing harmful in patients with amyotrophic lateral sclerosis (January 2017)
Pacing the diaphragm in patients with amyotrophic lateral sclerosis (ALS) is controversial. A recent randomized trial of patients with early respiratory impairment from ALS reported that, compared with sham pacing, diaphragmatic pacing resulted in increased mortality and did not delay time to noninvasive ventilation . We continue to prefer to avoid diaphragmatic pacing in this population until future trials demonstrate a clear benefit. (See "Pacing the diaphragm: Patient selection, evaluation, implantation, and complications", section on 'Amyotrophic lateral sclerosis'.)
Revised clinical criteria for neurofibromatosis type 2 (March 2017)
Clinical criteria for neurofibromatosis type 2 (NF2), caused by mutations in the NF2 gene, have been modified to include requirement for negative LZTR1 genetic testing in patients with a unilateral vestibular schwannoma and two or more non-intradermal schwannomas . Previously, these patients would have met clinical criteria for NF2. The change was prompted by recognition that the phenotypic spectrum of both NF2 and LZTR1-related schwannomatosis includes unilateral vestibular schwannoma in selected patients. (See "Neurofibromatosis type 2", section on 'Clinical criteria'.)
Potential interaction between high-dose methotrexate and levetiracetam (November 2016)
Levetiracetam is sometimes used for prophylaxis and treatment of seizures in patients undergoing high-dose methotrexate (MTX) treatment for brain or other central nervous system (CNS) cancers, including lymphomas. Health Canada has issued a safety review describing a potential interaction between the two drugs, noting 13 reports received by the levetiracetam manufacturer and concluding that concurrent use can lead to significantly elevated levels of MTX and increased risk of toxicity . The labeling is being revised to recommend careful MTX blood level monitoring. Additional details are available from Lexi-Interact, the drug interactions tool included within UpToDate. (See "Therapeutic use and toxicity of high-dose methotrexate", section on 'Coadministered drugs that may interfere with excretion'.)
Eteplirsen for Duchenne muscular dystrophy (September 2016)
Small studies of eteplirsen, an exon 51 skipping drug, suggest that it can increase dystrophin production in skeletal muscle without drug-related adverse effects in patients with Duchenne muscular dystrophy (DMD) with an amenable dystrophin gene mutation. Based upon this finding, the US Food and Drug Administration granted accelerated approval of eteplirsen in September 2016 for the treatment patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping . The mutation is present in approximately 13 percent of patients with DMD. (See "Treatment of Duchenne and Becker muscular dystrophy", section on 'Eteplirsen'.)
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- Koponen M, Taipale H, Lavikainen P, et al. Antipsychotic Use and the Risk of Hip Fracture Among Community-Dwelling Persons With Alzheimer's Disease. J Clin Psychiatry 2017.
- Chen H, Kwong JC, Copes R, et al. Living near major roads and the incidence of dementia, Parkinson's disease, and multiple sclerosis: a population-based cohort study. Lancet 2017; 389:718.
- Cacciottolo M, Wang X, Driscoll I, et al. Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models. Transl Psychiatry 2017; 7:e1022.
- Thorpe JM, Thorpe CT, Gellad WF, et al. Dual Health Care System Use and High-Risk Prescribing in Patients With Dementia: A National Cohort Study. Ann Intern Med 2017; 166:157.
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- Powers SW, Coffey CS, Chamberlin LA, et al. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine. N Engl J Med 2017; 376:115.
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- Gonzalez-Bermejo J, Morélot-Panzini C, Tanguy ML, et al. Early diaphragm pacing in patients with amyotrophic lateral sclerosis (RespiStimALS): a randomised controlled triple-blind trial. Lancet Neurol 2016; 15:1217.
- Smith MJ, Bowers NL, Bulman M, et al. Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1-related schwannomatosis. Neurology 2017; 88:87.
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- FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. U.S. Food & Drug Administration. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm (Accessed on September 22, 2016).