Nicholas A. Morris

An fMRI study of working memory in first-degree unaffected relatives of schizophrenia patients

Identifying intermediate phenotypes of genetically complex psychiatric illnesses such as schizophrenia is important. First-degree relatives of persons with schizophrenia have increased genetic risk for the disorder and tend to show deficits on working memory (WM) tasks. An open question is the relationship between such behavioral endophenotypes and the corresponding brain activation patterns revealed during functional imaging. We measured task performance during a Sternberg WM task and used functional magnetic resonance imaging (fMRI) to assess whether 23 non-affected first-degree relatives showed altered performance and functional activation compared to 43 matched healthy controls. We predicted that a significant proportion of unaffected first-degree relatives would show either aberrant task performance and/or abnormal related fMRI blood oxygen level dependent (BOLD) patterns. While task performance in the relatives was not different than that of controls they were significantly slower in responding to probes., Schizophrenia relatives displayed reduced activation, most markedly in bilateral dorsolateral/ventrolateral (DLPFC/VLPFC) prefrontal and posterior parietal cortex when encoding stimuli and in bilateral DLPFC and parietal areas during response selection. Additionally, fMRI differences in both conditions were modulated by load, with a parametric increase in between-group differences with load in several key regions during encoding and an opposite effect during response selection.

Neurologic complications in infective endocarditis: identification, management, and impact on cardiac surgery.

Neurologic complications of infective endocarditis (IE) are common and frequently life threatening. Neurologic events are not always obvious. The prediction and management of neurologic complications of IE are not easily approached algorithmically, and the impact they have on timing and ability to surgically repair or replace the affected valve often requires a painstaking evaluation and joint effort across multiple medical disciplines in order to achieve the best possible outcome. Although specific recommendations are always tailored to the individual patient, there are some guiding principles that can be used to help direct the decision-making process. Herein, we review the pathophysiology, epidemiology, manifestations, and diagnosis of neurological complications of IE and further consider the impact they have on clinical decision making.

Severe motor neuropathy or neuronopathy due to nitrous oxide toxicity after correction of vitamin B12 deficiency.

Introduction: Nitrous oxide (N2O) toxicity can cause a sensory predominant myeloneuropathy identical to subacute combined degeneration caused by vitamin B12 deficiency. We describe a patient with a typical vitamin B12 deficiency syndrome after N2O abuse who recovered and then developed a severe lower motor neuron syndrome following vitamin B12 correction. This suggests N2O toxicity independent of functional vitamin B12 deficiency. Methods: Electrophysiological, serological, and clinical evaluations were undertaken in the evaluation of this patient. Results: A 22‐year‐old man abused N2O and presented with a dorsal column syndrome with low vitamin B12 and high homocysteine serum levels. He recovered with treatment but presented later with profound motor axonal degeneration and normal vitamin B12, homocysteine, and methlymalonic acid levels. Conclusions: This case illustrates that N2O‐associated severe motor neuropathy or neuronopathy can develop separately from typical vitamin B12 deficiency dorsal column myelopathy. This syndrome can present when functional measures of vitamin B12 deficiency have normalized. Muscle Nerve 51: 614–616, 2015

Timing of Incident Stroke Risk After Cervical Artery Dissection Presenting Without Ischemia

Background and Purpose— Cervical artery dissection is a common cause of stroke in young people. The temporal profile of stroke risk after cervical artery dissection presenting without ischemia remains uncertain. Methods— We performed a crossover cohort study using administrative claims data on all emergency department visits and acute care hospitalizations from 2005 to 2011 in CA, 2006 to 2013 in NY, and 2005 to 2013 in FL. Using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification codes, we identified patients with a cervical artery dissection and no previous or concurrent stroke or transient ischemic attack diagnosis. We compared the risk of stroke in successive 2-week periods during the 12 weeks after dissection versus the corresponding 2-week period 1 year later. Absolute risk increases were calculated using McNemar test for matched data. In a sensitivity analysis, we limited our population to patients presenting with typical symptoms of cervical artery dissection. Results— We identified 2791 patients with dissection without ischemia. The absolute increase in stroke risk was 1.25% (95% confidence interval, 0.84–1.67%) in the first 2 weeks after dissection compared with the same time period 1 year later. The absolute risk increase was 0.18% (95% confidence interval, 0.02–0.34%) during weeks 3 to 4 and was no longer significant during the remainder of the 12-week postdissection period. Our findings were similar in a sensitivity analysis identifying patients who presented with typical symptoms of acute dissection. Conclusions— The risk of stroke after cervical artery dissection unaccompanied by ischemia at time of diagnosis seems to be limited to the first 2 weeks.

Neurological complications after tuberculous meningitis in a multi-state cohort in the United States

BACKGROUND AND PURPOSE To assess the rate of neurological complications and mortality after tuberculous meningitis in the United States. METHODS The authors performed a retrospective cohort study of all patients 18years or older hospitalized for tuberculous meningitis in California between 2005 and 2010, New York between 2006 and 2012, and Florida between 2005 and 2012. Outcomes of interest were mortality and the following neurological complications: stroke, seizure, hydrocephalus requiring a ventriculoperitoneal shunt, vision impairment, and hearing impairment. Kaplan-Meier survival statistics were used to assess the cumulative rate of neurological complications and death. Cox proportional hazards regression was used to compare rates of complications in patients with and without human immunodeficiency virus (HIV) after adjustment for comorbidities. RESULTS 806 patients with tuberculous meningitis were identified, among whom the cumulative rate of any complication or death was 55.4% (95% CI, 51.5-59.3%). More than two-thirds of complications occurred during the initial hospitalization for tuberculous meningitis. Individual neurological complications were not uncommon: the cumulative rate of stroke was 16.8% (95% CI, 14.0-20.0%), the rate of seizure was 18.8% (95% CI, 15.4-22.8%), and the rate of ventriculoperitoneal shunting was 8.4% (95% CI, 6.4-10.9%). Vision impairment occurred in 21.6% (95% CI, 18.5-25.1%) of patients and hearing impairment occurred in 6.8% (95% CI, 4.9-9.4%). The mortality rate was 21.5% (95% CI, 18.4-24.9%). Patients with HIV infection were not at increased risk of complications compared to patients without HIV (hazard ratio, 1.2; 95% CI, 0.9-1.6). CONCLUSIONS Tuberculous meningitis is associated with significant risk of neurological complications and death in the United States.

Intracranial Multimodality Monitoring for Delayed Cerebral Ischemia.

Summary: Management of patients with aneurysmal subarachnoid hemorrhage focuses on prevention of rebleeding by early treatment of the aneurysm, as well as detection and management of neurologic and medical complications. Early detection of delayed cerebral ischemia and management of modifiable contributing causes such as vasospasm take a central role, with the goal of preventing irreversible cerebral injury. In efforts to prevent delayed cerebral ischemia, multimodality monitoring has emerged as a promising tool in detecting subclinical physiologic changes before infarction occurs. However, there has been much variability in the utilization of this technology. Recent consensus guidelines discuss the role of multimodality monitoring in acute brain injury. In this review, we evaluate these guidelines and the utility of each modality of multimodality monitoring in aneurysmal subarachnoid hemorrhage.

Specialty Classifications of Physicians Who Provide Neurocritical Care in the United States.

BackgroundWe sought to characterize the specialty classification of US physicians who provide critical care for neurological/neurosurgical disease.MethodsUsing inpatient claims between 2009 and 2015 from a nationally representative 5% sample of Medicare beneficiaries, we selected hospitalizations for neurological/neurosurgical diseases with potential to result in life-threatening manifestations requiring critical care. Using Current Procedural Terminology® codes, we determined the medical specialty of providers submitting critical care claims, and, using National Provider Identifier numbers, we merged in data from the United Council for Neurologic Subspecialties (UCNS) to determine whether the provider was a UCNS diplomate in neurocritical care. We defined providers with a clinical neuroscience background as neurologists, neurosurgeons, and/or UCNS diplomates in neurocritical care. We defined neurocritical care service as a critical care claim with a qualifying neurological/neurosurgical diagnosis in patients with a relevant primary hospital discharge diagnosis and ≥ 3 total critical care claims, excluding claims from the first day of hospitalization since these were mostly emergency-department claims. Our findings were reported using descriptive statistics with exact confidence intervals (CI).ResultsAmong 1,952,305 Medicare beneficiaries, we identified 99,937 hospitalizations with at least one claim for neurocritical care. In our primary analysis, neurologists accounted for 28.0% (95% CI, 27.5–28.5%) of claims, neurosurgeons for 3.7% (95% CI, 3.5–3.9%), UCNS-certified neurointensivists for 25.8% (95% CI, 25.3–26.3%), and providers with any clinical neuroscience background for 42.8% (95% CI, 42.2–43.3%). The likelihood of management by physicians with a clinical neuroscience background increased proportionally with patients’ county-level socioeconomic status and such providers were 3 times more likely to be based at an academic medical center than other physicians who billed for critical care in our sample (odds ratio, 2.9; 95% CI, 1.1–8.1).ConclusionsPhysicians with a dedicated clinical neuroscience background accounted for less than half of neurocritical care service in US Medicare beneficiaries.

The Risk of Takotsubo Cardiomyopathy in Acute Neurological Disease

Background Case series have reported reversible left ventricular dysfunction, also known as stress cardiomyopathy or Takotsubo cardiomyopathy (TCM), in the setting of acute neurological diseases such as subarachnoid hemorrhage. The relative associations between various neurological diseases and Takotsubo remain incompletely understood.MethodsWe performed a cross-sectional study of all adults in the National Inpatient Sample, a nationally representative sample of US hospitalizations, from 2006 to 2014. Our exposures of interest were primary diagnoses of acute neurological disease, defined by ICD-9-CM diagnosis codes. Our outcome was a diagnosis of TCM. Binary logistic regression models were used to examine the associations between our pre-specified neurological diagnoses and TCM after adjustment for demographics.ResultsAmong acute neurological diagnoses, the strongest associations were seen with subarachnoid hemorrhage (odds ratio [OR] 11.7; 95% confidence interval [CI] 10.2–13.4), status epilepticus (OR 4.9; 95% CI 3.7–6.3), and seizures (OR 1.3; 95% CI 1.1–1.5). In a sensitivity analysis including secondary diagnoses of acute neurological diagnoses, associations were also seen with transient global amnesia (OR 2.3; 95% CI 1.5–3.6), meningoencephalitis (OR 2.1; 95% CI 1.7–2.5), migraine (OR 1.7; 95% CI 1.5–1.8), intracerebral hemorrhage (OR 1.3; 95% CI 1.1–1.5), and ischemic stroke (OR 1.2; 95% CI 1.1–1.3). In addition, female sex was strongly associated with Takotsubo (OR 5.1; 95% CI 4.9–5.4).ConclusionTCM appears to be associated with varying degrees with several acute neurological diseases besides subarachnoid hemorrhage.

Medical Specialties of Clinicians Providing Mechanical Thrombectomy to Patients With Acute Ischemic Stroke in the United States

This cross-sectional analysis of Medicare data determined the specialty of physicians providing mechanical thrombectomy to patients with ischemic stroke.

Subarachnoid Hemorrhage and Long-Term Stroke Risk After Traumatic Brain Injury

Background: Recent studies suggest that traumatic brain injury (TBI) is a risk factor for subsequent ischemic stroke, even years after the initial insult. The mechanisms of the association remain unclear. The presence of traumatic subarachnoid hemorrhage (tSAH) may mediate the effect of TBI on long-term stroke risk, as it has previously been linked to short-term vasospasm and delayed cerebral ischemia. Methods: Using administrative claims data, we conducted a retrospective cohort study of acute care hospitalizations. Patients discharged with a first-recorded diagnosis of tSAH were followed for a primary diagnosis of stroke. They were matched to patients with TBI but not tSAH. Cox proportional hazards modeling was used to assess the association between tSAH and stroke while adjusting for covariates. Results: We identified 40 908 patients with TBI (20 454 patients with tSAH) who were followed for a mean of 4.3 + 1.8 years. A total of 531 had an ischemic stroke after discharge. There was no significant difference in stroke risk between those with tSAH (1.79%; 95% confidence interval [CI] 1.54%-2.08%) versus without tSAH (2.12%; 95% CI 1.83%-2.44%). The same pattern was found in adjusted analyses even when the group was stratified by age-group or by proxies of TBI severity. Conclusions: Our findings do not support a role of tSAH in mediating the association between TBI and protracted stroke risk. Further study is required to elucidate the mechanisms of long-term increased stroke risk after TBI.