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What's new in neurology
Official reprint from UpToDate® ©2017 UpToDate®
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What's new in neurology
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2017. | This topic last updated: Aug 14, 2017.

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.


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 [1]. 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'.)


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 [2]. 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 [3]. 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 [4]. 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 [5]. 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) [6]. 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'.)


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 [7]. 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'.)


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 [8]. 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'.)

Revised ILAE classification of seizures and epilepsy (March 2017)

The International League Against Epilepsy (ILAE) has revised its working classification of seizures and epilepsy [9-11]. This is the first major update since 2010. The current framework allows for diagnosis at four levels, according to seizure type (level 1) (table 1), epilepsy type (level 2), epilepsy syndrome (level 3) (table 2), and epilepsy with etiology (level 4). The proposal recognizes six etiologic categories of epilepsy: genetic, structural, metabolic, immune, infectious, and unknown (figure 1). (See "ILAE classification of seizures and epilepsy", section on 'Introduction'.)

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 [12,13]. 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'.)


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 [14]. 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'.)

Valbenazine for tardive dyskinesia (May 2017)

Tetrabenazine and valbenazine are vesicular monoamine transporter 2 inhibitors that deplete presynaptic dopamine and may be useful therapeutic agents for tardive dyskinesia (TD). Data from old, small studies supported the utility of tetrabenazine for this indication. Now there is evidence from the placebo-controlled KINECT 3 trial that valbenazine 40 mg once daily reduces dyskinesia in patients with TD [15]. For patients who have disturbing and intrusive tardive dyskinesia or tardive dystonia not amenable to treatment with botulinum toxin, we suggest treatment with tetrabenazine or valbenazine. (See "Tardive dyskinesia: Prevention and treatment", section on 'Valbenazine'.)


Edaravone for amyotrophic lateral sclerosis (May 2017)

Edaravone is a free radical scavenger that is thought to reduce oxidative stress, which has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Edaravone may slow functional deterioration in some patients with ALS. An earlier trial found no benefit for edaravone compared with placebo, but a post-hoc analysis showed a possible treatment effect in a subgroup of individuals with early-stage ALS. A subsequent trial enrolled 137 Japanese patients within two years of ALS diagnosis who were living independently and had a forced vital capacity (FVC) of ≥80 percent [16]. Compared with placebo, functional decline at 24 weeks was smaller in the edaravone group, and the difference was considered clinically meaningful. Edaravone was approved in 2015 for the treatment of ALS in Japan and Korea and has now received regulatory approval to treat patients with ALS in the United States [17]. We now suggest edaravone for patients with early-stage disease as well as for those with more advanced disease, although the data are less compelling for the latter group. (See "Disease modifying treatment of amyotrophic lateral sclerosis", section on 'Edaravone'.)


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 [18]. 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 [19]. In the second trial, single-fraction SRS decreased rates of local recurrence compared with observation, especially for tumors smaller than 2.5 cm preoperatively [20]. 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'.)

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 [21]. 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'.)


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 [22]. 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 [23]. 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'.)

Consensus panel guidelines on Dravet syndrome in children and adults (April 2017)

A North American consensus panel has published guidelines on the diagnosis and management of Dravet syndrome (DS), an early-onset epileptic encephalopathy most often due to de novo mutations in the voltage-gated sodium channel, alpha-1 subunit (SCN1A) gene [24]. The document includes a description of the typical clinical presentation of DS; guidance on genetic testing and family counseling; and recommendations for first-line treatment with clobazam and/or valproic acid, avoidance of sodium channel blocking drugs, and provision of home rescue medications and an emergency seizure protocol. DS should be suspected in previously healthy infants presenting with recurrent tonic-clonic seizures, often in the setting of fever, beginning before one year of age and associated with neurodevelopmental regression after the onset of seizures. (See "Dravet syndrome: Genetics, clinical features, and diagnosis" and "Dravet syndrome: Management and prognosis".)

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  2. 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; 78:e257.
  3. 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.
  4. 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.
  5. 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.
  6. Hanson LC, Zimmerman S, Song MK, et al. Effect of the Goals of Care Intervention for Advanced Dementia: A Randomized Clinical Trial. JAMA Intern Med 2017; 177:24.
  7. Metz LM, Li DKB, Traboulsee AL, et al. Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis. N Engl J Med 2017; 376:2122.
  8. Devinsky O, Cross JH, Laux L, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med 2017; 376:2011.
  9. Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58:522.
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  16. Writing Group, Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2017; 16:505.
  17. FDA approves drug to treat ALS. (Accessed on May 09, 2017).
  18. Blumenthal DT, Gorlia T, Gilbert MR, et al. Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG. Neuro Oncol 2017.
  19. Brown PD, Ballman KV, Cerhan JH, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 2017; 18:1049.
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