Carl A. Gold

An evaluation of recollection and familiarity in Alzheimer’s disease and mild cognitive impairment using receiver operating characteristics

There is a need to investigate exactly how memory breaks down in the course of Alzheimers disease (AD). Examining what aspects of memorial processing remain relatively intact early in the disease process will allow us to develop behavioral interventions and possible drug therapies focused on these intact processes. Several recent studies have worked to understand the processes of recollection and familiarity in patients with mild cognitive impairment (MCI) and very mild AD. Although there is general agreement that these patient groups are relatively unable to use recollection to support veridical recognition decisions, there has been some question as to how well these patients can use familiarity. The current study used receiver operating characteristic (ROC) curves and a depth of processing manipulation to understand the effect of MCI and AD on the estimates of recollection and familiarity. Results showed that patients with MCI and AD were impaired in both recollection and familiarity, regardless of the depth of encoding. These results are discussed in relation to disease pathology and in the context of recent conflicting evidence as to whether familiarity remains intact in patients with MCI. The authors highlight differences in stimuli type and task difficulty as possibly modulating the ability of these patients to successfully use familiarity in support of memorial decisions.

The picture superiority effect in patients with Alzheimer’s disease and mild cognitive impairment

The fact that pictures are better remembered than words has been reported in the literature for over 30 years. While this picture superiority effect has been consistently found in healthy young and older adults, no study has directly evaluated the presence of the effect in patients with Alzheimers disease (AD) or mild cognitive impairment (MCI). Clinical observations have indicated that pictures enhance memory in these patients, suggesting that the picture superiority effect may be intact. However, several studies have reported visual processing impairments in AD and MCI patients which might diminish the picture superiority effect. Using a recognition memory paradigm, we tested memory for pictures versus words in these patients. The results showed that the picture superiority effect is intact, and that these patients showed a similar benefit to healthy controls from studying pictures compared to words. The findings are discussed in terms of visual processing and possible clinical importance.

Memory loss in Alzheimer’s disease: implications for development of therapeutics

Alzheimer’s disease (AD) is a progressive neurodegenerative disease marked by a constellation of cognitive disturbances, the earliest and most prominent being impaired episodic memory. Episodic memory refers to the memory system that allows an individual to consciously retrieve a previously experienced item or episode of life. Many recent studies have focused on characterizing how AD pathology impacts particular aspects of episodic memory and underlying mental and neural processes. This review summarizes the findings of those studies and discusses the effects of current and promising treatments for AD on episodic memory. The goal of this review is to raise awareness of the strides that cognitive neuroscientists have made in understanding intact and dysfunctional memory. Knowledge of the specific memorial processes that are impaired in AD may be of great value to basic scientists developing novel therapies and to clinical researchers assessing the efficacy of those therapies.

Anticipating the Challenges of Zika Virus and the Incidence of Guillain-Barré Syndrome

Guillain-Barré syndrome (GBS) most commonly presents with acute progressive paralysis with absent deep tendon reflexes.1 Bacterial and viral infections can precede the onset of this neurological emergency. In recent years, cases of GBS have been associated with arboviral infections including dengue and chikungunya. As of February 2016, 6 countries affected by outbreaks of Zika virus infection have reported an increased incidence of GBS.2 While some have postulated that concurrent circulation of dengue or other factors could contribute, a case-control study of patients who developed GBS during a Zika outbreak in French Polynesia provides evidence that Zika infection is the culprit.3 In response, the World Health Organization recently released a statement on GBS aimed at health care professionals and policy makers in countries affected by Zika.2 There is concern that the Zika outbreak may soon affect the United States. Aedes aegypti and Aedes albopictus, mosquito vectors of Zika virus, are present in much of the country during the warmer months. Neighboring nations, including Mexico, currently report transmission of Zika. One recent study estimated that 60% of Americans live in regions at risk for the spread of Zika.4 In the French Polynesia outbreak, 66% of the population was infected with Zika and the incidence of GBS was estimated at 0.24 cases per 1000 infections.3 Numerous factors will influence the number of cases of GBS in the United States. However, if conditions were to mimic the French Polynesian outbreak, then as many as 30 000 cases of Zikaassociated GBS might be expected (population 318 million; 60% of the population at risk for infection; 66% infection rate in those at risk; 0.24 cases/1000 Zika infections), representing a roughly 10-fold increase from the baseline incidence of GBS nationally. As neurohospitalists who frequently care for patients with neuromuscular emergencies, we seek to anticipate challenges that could face our health care system if the incidence of GBS were to sharply rise with the arrival of Zika.

Mitochondrial myopathy with dystrophic features due to a novel mutation in the MTTM gene

Introduction: A 61‐year‐old woman with a 5‐year history of progressive muscle weakness and atrophy had a muscle biopsy characterized by a combination of dystrophic features (necrotic fibers and endomysial fibrosis) and mitochondrial alterations [ragged‐red, cytochrome c oxidase (COX)‐negative fibers]. Methods: Sequencing of the whole mtDNA, assessment of the mutation load in muscle and accessible nonmuscle tissues, and single fiber polymerase chain reaction. Results: Muscle mitochondrial DNA (mtDNA) sequencing revealed a novel heteroplasmic mutation (m.4403G>A) in the gene (MTTM) that encodes tRNAMet. The mutation was not present in accessible nonmuscle tissues from the patient or 2 asymptomatic sisters. Conclusions: The clinical features and muscle morphology in this patient are very similar to those described in a previous patient with a different mutation, also in MTTM, which suggests that mutations in this gene confer a distinctive “dystrophic” quality. This may be a diagnostic clue in patients with isolated mitochondrial myopathy. Muscle Nerve 50:292–295, 2014

Electrographic Correlates of Plateau Waves in Patients With Leptomeningeal Metastases

We describe video electroencephalography (video-EEG) correlates of transient neurological attacks due to plateau waves—paroxysmal elevations in intracranial pressure—in patients with leptomeningeal metastases. We identified 3 patients with leptomeningeal metastases, intracranial hypertension, and transient neurological attacks captured on video-EEG without evidence of seizures or epileptiform activity. We identified all clinical events on video and reviewed the corresponding EEG data for evidence of abnormalities. All 3 patients had mild to moderate slowing and 2 had frontal intermittent rhythmic delta activity during background EEG recording. There were 33 clinical events recorded and stereotyped for each patient. All 33 events were associated with an increase in delta range slowing of ≥30% compared to the background. This abnormality started ≤2 minutes before the onset of clinical symptoms and persisted for minutes after clinical resolution. This study is the first to carefully describe the electrographic correlates of transient neurological attacks due to plateau waves in patients with leptomeningeal metastasis. Clinical attacks were consistently associated with a possible EEG signature of diffuse delta range slowing. Future studies can validate the sensitivity and specificity of these EEG changes as a prognostic and/or response biomarker in patients with leptomeningeal metastases with or without intracranial hypertension.

Driving after a stroke

2011;76;e35 Neurology Steven Karceski and Carl A. Gold Driving after a stroke February 22, 2011 This information is current as of http://www.neurology.org/content/76/8/e35.full.html located on the World Wide Web at: The online version of this article, along with updated information and services, is rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X. All since 1951, it is now a weekly with 48 issues per year. Copyright

Coexistence of Neuromyelitis Optica and Amyotrophic Lateral Sclerosis: A Case Report:

The occurrence of amyotrophic lateral sclerosis (ALS) and neuromyelitis optica (NMO) in a single patient is exceedingly rare. We report a case of a 54-year-old woman of East Asian descent with a prior diagnosis of ALS who developed an episode of unexplained hiccups and nausea and vomiting consistent with area postrema syndrome 3 months prior to the onset of acute transverse myelitis. Magnetic resonance imaging revealed abnormal T2 hyperintensity and gadolinium enhancement at the cervicomedullary junction with extension to C3. Imaging was also notable for nonenhancing central cord T2 hyperintensity from T6 to T8 suggesting previous demyelination. The patient’s cerebrospinal fluid analysis was mildly inflammatory. She was found to have a positive NMO/aquaporin-4 immunoglobulin G titer (cell-based assay) greater than 1:100 000, consistent with a diagnosis of NMO. The unusual coexistence of ALS and NMO prompts consideration of potential common pathological neuroinflammatory processes.

Video NeuroImages: Paraneoplastic spinal myoclonus associated with Caspr2 antibodies

A 42-year-old man with thymoma-associated myasthenia gravis presented with 6 weeks of abnormal leg movements. Examination revealed myoclonus in the legs bilaterally (video, links.lww.com/WNL/A322). Chest CT showed recurrence of metastatic thymoma. MRI spine revealed nonspecific hemosiderin deposition at the T9 level without metastases or vascular malformation. EMG demonstrated right leg and rectus abdominus myoclonus up to T6, most prominently at T9-L1 (figure). Serum anti-contactin-associated protein-like 2 (Caspr2) antibodies were positive. Chemotherapy led to resolution of the myoclonus. Caspr2 antibodies have been associated with limbic encephalitis and neuromyotonia,1,2 but our patient showed unusual Caspr2-associated spinal myoclonus.

Expanding Access to Magnetic Resonance Imaging for Patients With Cardiac Rhythm Devices

Magnetic resonance imaging (MRI) of the brain and spine is an essential tool for confirming and tracking a wide variety of neurological conditions. The impact of MRI is reflected in studies of clinical use. For example, the use of MRI of the brain in a national sample of patients experiencing acute stroke rose from 28% of patients in 1999 to 66% in 2008.1 With advancing technology and decreasing cost, the number of MRI scanners per million people in the United States nearly doubled between 2003 and 2016.2 Despite this, certain patient populations have historically been denied access to MRI because of safety concerns. One sizable group is composed of patients with cardiovascular implantable electronic devices (CIEDs), such as pacemakers, implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy devices. In 2013, there were approximately 1 million Americans living with a pacemaker and 400 000 living with an ICD or cardiac resynchronization therapy–defibrillator.3 While certain devices with programmable safety modes have been granted conditional status for MRI access (termedMR-conditionalstatus)fromtheUSFoodandDrug Administration, most devices do not meet these criteria. The 2017 performance reports of 2 large manufacturers of CIEDs, Medtronic and Abbott (formerly known as St. Jude Medical), show that 73% to 81% of active devices in the United States are MR-nonconditional devices (which are also termed legacy devices).4,5 As the population ages, it has been suggested that 50% to 75% of patients with CIEDs will have a clinical indication for MRI examination in their lifetimes.6 Most of these patients will have legacy devices. Historically, CIEDs were deemed incompatible with the MRI environment because of concerns over device malfunction and local tissue injury from migration and heating. Prior to implementation of standardized intrascan monitoring, significant device failures and even death had been reported.6 However, 2 recent large studies have demonstrated the apparent safety of MRI in patients with legacy devices. In the MagnaSafe Registry, 1500 patients with legacy CIEDs (of which 1000 were pacemakers and 500 ICDs) underwent nonthoracic 1.5-T MRI at 19 centers in the United States.7 Notably, 75% of the MRI examinations were performed on the brain or spine.7 Excluding 1 improperly programmed device, there were no major adverse effects.7 Observed changes in device parameters, such as lead impedance, pacing thresholds, and battery settings, were not clinically significant through the 6-month follow-up period.7 A single-center study confirmed these results in 2103 thoracic and nonthoracic MRI scans performed in 1509 patients (of which 880 were pacemakers and 629 ICDs).8 The proximity of the scan location to the device, the number of scans, and the timing of the scan after lead placement were not associated with increased risk of harm.8 In response to these data, the Heart Rhythm Society (HRS) released a guideline statement in 2017 with moderate strength (Class IIa) recommendations supporting the use of MRI in patients with legacy devices, assuming that certain parameters are met.9 These parameters include a strong clinical indication for the MRI examination and documented integrity of device leads.9 Most importantly, the recommendations call for thorough institutional policies that ensure appropriate supervision.9 While many facilities have been performing MRI in patients with conditional devices for years, only those few who participate in the trials described7,8 have large-scale experience in monitoring legacy devices. Establishing or broadening policies to include legacy devices will likely be the most considerable barrier faced by imaging centers nationwide. The HRS guideline provides a basic outline for this process.9 Safe monitoring starts with prescan evaluation by radiology personnel to confirm the necessity of the examination, choose imaging sequences, and schedule the examination. Then cardiology specialists will evaluate the CIED type, ensure lead integrity, and determine the correct programming strategy. On the day of the scan, the device is programmed into a safety mode by a technician, and vital sign monitoring is performed. Upon scan completion, the device is checked and reprogrammed to prescan settings if necessary. Outpatient follow-up evaluation by cardiology specialists may be indicated if considerable changes in device parameters were observed. The institution must have emergency procedures for device failure, including the ability to quickly reprogram or even replace devices and perform advanced cardiac life support, including involvement of on-call physicians and rapid response teams. Though general principles would remain the same, some differences in protocol details are expected between the outpatient and inpatient settings. Translating this framework into practice poses more nuanced challenges. In addition to device programming, performing MRI scans safely in these patients requires customized sequence protocols with limitation of the specific absorption rate. Until such protocols are included by vendors as a push-button feature, involving a medical physicist in sequence generation may be necessary. Another difficulty will be the task of defining when MRI should be pursued for an individual patient, given the added cost and minor risks. Ordering clinicians and radiologists will need to critically weigh whether the additional information provided by an MRI examination (compared with other imaging modaliVIEWPOINT