Network Localization of Spontaneous Confabulation.

OBJECTIVE: Spontaneous confabulation is a symptom in which false memories are conveyed by the patient as true. The purpose of the study was to identify the neuroanatomical substrate of this complex symptom and evaluate the relationship to related symptoms, such as delusions and amnesia. METHODS: Twenty-five lesion locations associated with spontaneous confabulation were identified in a systematic literature search. The network of brain regions functionally connected to each lesion location was identified with a large connectome database (N=1,000) and compared with networks derived from lesions associated with nonspecific (i.e., variable) symptoms (N=135), delusions (N=32), or amnesia (N=53). RESULTS: Lesions associated with spontaneous confabulation occurred in multiple brain locations, but they were all part of a single functionally connected brain network. Specifically, 100% of lesions were connected to the mammillary bodies (familywise error rate [FWE]-corrected p<0.05). This connectivity was specific for lesions associated with confabulation compared with lesions associated with nonspecific symptoms or delusions (FWE-corrected p<0.05). Lesions associated with confabulation were more connected to the orbitofrontal cortex than those associated with amnesia (FWE-corrected p<0.05). CONCLUSIONS: Spontaneous confabulation maps to a common functionally connected brain network that partially overlaps, but is distinct from, networks associated with delusions or amnesia. These findings lend new insight into the neuroanatomical bases of spontaneous confabulation.

Cannabis Use in a Cohort of Healthcare-Seeking United States Military Veterans With Persisting Symptoms After Mild Traumatic Brain Injury: Preliminary Observations.

INTRODUCTION: Cannabis products, including cannabidiol (CBD) and tetrahydrocannabinol (THC), are increasingly easy to procure and use across the United States. The 2018 National Survey on Drug Use and Health (NSDUH) reported a past-month cannabis use rate of 8.6% among adults 26 years of age or older in the U.S. general population. Cannabis use is commonly reported by U.S. Military Veterans with histories of mild traumatic brain injury (mTBI) receiving services at the Marcus Institute for Brain Health (MIBH), a specialty interdisciplinary clinic serving this population. The aims of this study are to describe the frequency and characteristics of cannabis product use among Veterans evaluated at MIBH and to compare the rate of cannabis use in this group to that in the general and Veteran populations reported in the 2018 NSDUH. MATERIALS AND METHODS: Study data were collected as part of MIBH clinical assessments between January 2018 and December 2019, which included the evaluation of the current use of cannabis products. Affirmative cannabis use responses were clarified with inquiries about the frequency of use, method of administration, product ingredients (i.e., THC and/or CBD), and reason(s) for use. RESULTS: Among 163 MIBH patients (92.6% male), 72 (44.2%) endorsed cannabis product use during the month preceding the clinical assessment. Cannabis users were significantly younger than nonusers. The frequency of past-month cannabis use was significantly greater than that reported in the comparably aged NSDUH survey general and Veteran populations (44.2% vs. 8.6% and 44.2% vs. 7.7%, respectively, both P < .00001). Among the 72 MIBH patients reporting cannabis use, 62 (86.1%) reported THC or combination product use, and 10 (13.9%) reported CBD product use. Concurrent medication use, including psychotropic medications use, did not differ significantly between cannabis users and nonusers. CONCLUSIONS: Self-reported cannabis use is significantly higher in the MIBH population than in similarly aged individuals in the general population and significantly more frequent among younger than older members of this cohort. Self-reported reasons for cannabis use in this cohort included mTBI-associated neuropsychiatric symptoms, sleep disturbances, and pain for which standard treatments (both pharmacologic and nonpharmacologic) provided insufficient relief and/or produced treatment-limiting adverse events. However, cannabis use did not provide sufficient improvement in those symptoms to obviate the need for further evaluation and treatment of those problems at MIBH or to replace, in part or in whole, standard medications and other treatments for those problems. Further study of cannabis use, including standardized individual cannabinoid (i.e., THC and CBD) and whole-plant cannabis preparations, in this and similar cohorts is needed to more fully understand the drivers, benefits, risks, and safety of cannabis use in this and in similar Veteran populations, as well as the potential pharmacological and/or nonpharmacological therapeutic alternatives to cannabis use.

Implementation issues relevant to outpatient neurology palliative care.

BACKGROUND: There is growing interest in the application of palliative care principles to improve care for patients and families affected by neurologic diseases. We developed an interdisciplinary outpatient clinic for patients and families affected by neurologic disorders to better address the problems faced by our highest need patients. We have developed and improved this program over the past three years and share several of our most important lessons as well as ongoing challenges and areas where we see our clinic evolving in the future. METHODS: We provide a description of our clinic logistics, including key steps in the initiation of the clinic, and provide descriptions from similar clinics at other institutions to demonstrate some of the variability in this growing field. We also provide results from a formal one-year quality improvement project and a one-year retrospective study of patients attending this clinic. RESULTS: Our clinic has grown steadily since its inception and maintains high satisfaction ratings from patients, caregivers, and referring providers. To maintain standardized and efficient care we have developed materials for patients and referring physicians as well as checklists and other processes used by our interdisciplinary team. Feedback from our quality improvement project helped define optimal visit duration and refine communication among team members and with patients and families. Results from our chart review suggest our clinic influences advance care planning and place of death. Common referral reasons include psychosocial support, complex symptom management, and advance care planning. Current challenges for our clinic include developing a strategy for continued growth, creating a sustainable financial model for interdisciplinary care, integrating our services with disease-specific sections, improving primary palliative care knowledge and skills within our referral base, and building effective alliances with community neurologists, geriatrics, primary care, nursing homes, and hospices. CONCLUSIONS: Specialized outpatient palliative care for neurologic disorders fills several important gaps in care for this patient population, provides important educational opportunities for trainees, and creates opportunities for patient and caregiver-centered research. Educational initiatives are needed to train general neurologists in primary palliative care, to train neurologists in specialist palliative care, and to train palliative medicine specialists in neurology. Research is needed to build an evidence base to identify patient and caregiver needs, support specific interventions, and to build more efficient models of care in both academic and community settings.

The Expanding Prominence of Toxic Leukoencephalopathy.

Toxic leukoencephalopathy (TL) is a disorder of brain white matter caused by exposure to leukotoxic agents. Magnetic resonance imaging (MRI) can readily identify this syndrome, and, together with diffusion tensor imaging, MRI continues to offer important insights into its nature. Since the first formal description of TL in 2001, many new leukotoxic disorders have been recognized, and the range of leukotoxins has expanded to include more therapeutic drugs, drugs of abuse, and environmental insults. While the understanding of pathophysiology remains incomplete, TL is increasingly common in clinical practice, and the potential long-term cognitive sequelae of toxic white matter injury merit attention.

Effects of pioglitazone or exercise in older adults with mild cognitive impairment and insulin resistance: a pilot study.

AIMS: To examine the effects of pioglitazone or endurance exercise training on cognitive function in older adults with mild cognitive impairment (MCI) and insulin resistance. METHODS: Seventy-eight adults (mean age ± SD: 65 ± 7 years) with central obesity and MCI were randomized to 6 months of endurance exercise, pioglitazone or control. RESULTS: Sixty-six participants completed the study. Exercise training did not significantly increase peak oxygen uptake compared to control (p = 0.12). Compared to control, insulin resistance improved in the pioglitazone group (p = 0.002) but not in the exercise group (p = 0.25). There was no measureable effect of pioglitazone or exercise on cognitive performance compared to control. CONCLUSION: In this pilot study, pioglitazone improved insulin resistance but not cognitive performance in older adults with MCI and insulin resistance.

Diffusion tensor imaging in mild traumatic brain injury litigation.

A growing body of literature addresses the application of diffusion tensor imaging (DTI) to traumatic brain injury (TBI). Most TBIs are of mild severity, and their diagnosis and prognosis are often challenging. These challenges may be exacerbated in medicolegal contexts, where plaintiffs seek to present objective evidence that supports a clinical diagnosis of mild (m)TBI. Because DTI permits quantification of white matter integrity and because TBI frequently involves white matter injury, DTI represents a conceptually appealing method of demonstrating white matter pathology attributable to mTBI. However, alterations in white matter integrity are not specific to TBI, and their presence does not necessarily confirm a diagnosis of mTBI. Guided by rules of evidence shaped by Daubert v. Merrell Dow Pharmaceuticals, Inc., we reviewed and analyzed the literature describing DTI findings in mTBI and related neuropsychiatric disorders. Based on this review, we suggest that expert testimony regarding DTI findings will seldom be appropriate in legal proceedings focused on mTBI.

Screening for cognitive decline following single known stroke using the Mini-Mental State Examination.

BACKGROUND: Progressive cognitive decline develops in a nontrivial minority of stroke survivors. Although commonly used to identify cognitive decline in older stroke survivors, the usefulness of the Mini-Mental State Examination (MMSE) as a screening tool for post-stroke cognitive decline across a wider range of ages is not well established. This study therefore investigated the usefulness of the MMSE for this purpose. METHODS: Twenty-seven subjects, aged 18-82 years, with a single known remote stroke were assessed using the MMSE. The frequency of cognitive impairment was determined by comparison of MMSE scores with population-based norms. Relationships between cognitive performance, motor impairments, age, gender, handedness, stroke laterality, and time since stroke also were explored. RESULTS: Age-adjusted MMSE scores identified mild cognitive impairment in 22.2% and moderate-to-severe cognitive impairment in 7.4% of subjects. Raw and age-adjusted MMSE scores were inversely correlated with time since stroke, but not with other patient or stroke characteristics. CONCLUSION: A relationship between time since single known stroke and MMSE performance was observed in this study. The proportion of subjects identified as cognitively impaired in this group by Z-transformation of MMSE scores using previously published normative data for this measure comports well with the rates of late post-stroke cognitive impairment reported by other investigators. These findings suggest that the MMSE, when normatively interpreted, may identify cognitive decline in the late period following single known stroke. Additionally, the lack of a relationship between MMSE and Fugl-Meyer scores suggests that the severity of post-stroke motor impairments is unlikely to serve as a clinically useful indicator of the need for cognitive assessment. A larger study of stroke survivors is needed to inform more fully on the usefulness of normatively interpreted MMSE scores as a method of screening for post-stroke cognitive decline.

Clock-drawing performance predicts inpatient rehabilitation outcomes after traumatic brain injury.

The authors used clock-drawing performance to assess cognition and predict inpatient rehabilitation outcomes among persons with traumatic brain injury. Clock-drawing performance, as assessed with the Clock Drawing Interpretation Scale, predicts rehabilitation length of stay as well as Functional Independence Measure scores at the time of neurobehavioral assessment and rehabilitation discharge.

Functional imaging of hippocampal dysfunction among persons with Alzheimer's disease: a proof-of-concept study.

Cholinergic deficits are an early and functionally significant manifestation of Alzheimer's disease (AD). These deficits contribute to impairment of hippocampally mediated information processing, including declarative memory impairments and abnormal auditory sensory gating. A functional imaging technique that facilitates identification of changes in cholinergically dependent hippocampal information processing would be of considerable use in the study and clinical evaluation of persons with this condition. Techniques that interrogate hippocampal function passively, ie, in a manner requiring no cognitive effort or novel task learning during the neuroimaging procedure, would also be especially useful in this cognitively impaired population. The functional magnetic resonance imaging sensory gating paradigm developed at the University of Colorado, CO, USA, is a functional neuroimaging technique that possesses both of these characteristics. We developed a demonstration project using this paradigm in which we passively interrogated hippocampal function in two subjects with probable AD of mild severity. Imaging data were quick and easy in these subjects and served usefully as an initial demonstration of the feasibility of using this neuroimaging method in this population. Preliminary analyses of the data obtained from these subjects identified abnormal blood oxygen level-dependent responses when compared with four healthy comparators, and the pattern of these responses was consistent with impaired function of the auditory sensory gating network. The strengths and limitations of this neuroimaging paradigm and the additional issues that require investigation in order to continue its development into a research and clinical technique for use in this population are discussed.

Cognitive sequelae of hypoxic-ischemic brain injury: a review.

Despite improvements in the pre-hospital and critical care management of persons with hypoxic-ischemic brain injury (HI-BI) and the conditions with which it is associated, acute and chronic cognitive impairments remain problems for many survivors of such injuries. Disorders of consciousness, attention, speed of processing, and memory impairments, and executive dysfunction are among the most prominent and common disturbances of cognition after HI-BI. Acute interventions, including therapeutic hypothermia, may improve global outcomes after HI-BI, but their specific effects on post-hypoxic cognitive impairments remain uncertain. Additionally, treatments for cognitive impairments after HI-BI are underdeveloped and are generally arrived at by analogy to the treatment of such problems arising from other neurological conditions, especially traumatic brain injury. In the service of offering a practical approach to the evaluation and care of persons with cognitive impairments after HI-BI, the most common types of post-hypoxic cognitive impairments are reviewed. Cognitive outcomes after HI-BI are discussed and suggestions for the nonpharmacologic and pharmacologic neurorehabilitation of these problems are offered.