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Cognitive impairment is common in veterans with histories of traumatic brain injury (TBI). Cholinergic deficits have been hypothesized as contributors to this impairment. We report the effects of cholinesterase inhibitor rivastigmine transdermal patch treatment in veterans with TBI and post-traumatic memory impairment. Our objective was to evaluate the efficacy and safety of a 9.5 mg/24 h (10 cm

Objective: As part of an initiative led by the Brain Injury Special Interest Group Mild Traumatic Brain Injury (TBI) Task Force of the American Congress of Rehabilitation Medicine (ACRM) to update the 1993 ACRM definition of mild TBI, the present study aimed to characterize current expert opinion on diagnostic considerations. Design: Cross-sectional web-based survey. Setting: Not applicable. Participants: An international, interdisciplinary group of clinician-scientists (N=31) with expertise in mild TBI completed the survey by invitation between May and July 2019 (100% completion rate). Interventions: Not applicable. Main Outcome Measures: Ratings of agreement with statements related to the diagnosis of mild TBI and ratings of the importance of various clinical signs, symptoms, test findings, and contextual factors for increasing the likelihood that the individual sustained a mild TBI, on a scale ranging from 1 (“not at all important”) to 10 (“extremely important”). Results: Men (n=25; 81%) and Americans (n=21; 68%) were over-represented in the sample. The survey revealed areas of expert agreement (eg, acute symptoms are diagnostically useful) and disagreement (eg, whether mild TBI with abnormal structural neuroimaging should be considered the same diagnostic entity as “concussion”). Observable signs were generally rated as more diagnostically important than subjective symptoms (Wilcoxon signed ranks test, Z=3.77; P

Psychological distress is common in persons with traumatic brain injury (TBI) but treatments remain underdeveloped. This randomized controlled trial of Acceptance and Commitment Therapy (ACT) was designed to address this gap. Ninety-three persons with medically-documented complicated mild to severe TBI, normal-to-mildly impaired memory, and clinically significant psychological distress in the chronic phase of recovery were randomized to receive eight weeks of ACT (manualized with adaptations to address TBI-related cognitive impairments) or a single session of needs assessment, brief counseling/education, and referral. The ACT group showed significantly greater reduction of psychological distress (Brief Symptom Inventory 18) and demonstrated improvements in psychological flexibility and commitment to action (Acceptance and Action Questionnaire-II (AAQ-II) scores). The number of treatment responders (post-treatment BSI 18 GSI T scores

Aims: The overarching goal of this project was to establish a group comprised of a variety of TBI stakeholders for the purpose of: (1) determining facilitators and barriers in management of neuropsychiatric symptoms after TBI; (2) identifying strategies for maintaining a TBI PCOR network; (3) enumerating research topics related to TBI neuropsychiatry; and (4) highlighting policy changes related to TBI neuropsychiatry.Methods: Twenty-nine TBI stakeholders participated in focus group discussions. Qualitative analyses were conducted both manually and using Dedoose software.Results: Participant-identified barriers included stigma associated with experiencing neuropsychiatric symptoms and poor insurance coverage. Facilitators included treatment focused on education of neuropsychiatric symptoms after TBI and having a comprehensive caregiver plan. Best strategies for maintaining TBI PCOR network included having a well-defined project, continued regular meetings, and on-going education of network members. Pertinent research topics included TBI and aging, factors influencing outcomes after TBI, substance use disorders related to TBI, and effectiveness of telemental health services. Needed policy changes included making TBI neuropsychiatry education accessible to stakeholders and improving accessibility of TBI neuropsychiatric care.Conclusion: TBI stakeholders identified several facilitators of care for neuropsychiatric symptoms after TBI and suggested research topics and best practices for conducting PCOR in this area.

Background Prior studies on the effects of lithium on limbic and subcortical gray matter volumes are mixed. It is possible that discrepant findings may be explained by the duration of lithium exposure. We investigated this issue in individuals with type I bipolar disorder (BP-I). Methods Limbic and subcortical gray matter volume was measured using FreeSurfer in 60 subjects: 15 with BP-I without prior lithium exposure [no-exposure group (NE)]; 15 with BP-I and lithium exposure 24 months [long-exposure group (LE)]; and 15 healthy controls (HC). Results No differences in limbic and subcortical gray matter volumes were found between LE and HC. Hippocampal and amygdalar volumes were larger bilaterally in both LE and HC when compared to NE. Amygdalar volumes were larger bilaterally in SE when compared to NE but did not differ from LE. Hippocampal volumes were smaller bilaterally in SE when compared to LE and HC but did not differ from NE. No between-group differences on subcortical gray matter or other limbic structure volumes were observed. Limitations Cross-sectional design and concurrent treatment with other medications limit attribution of between-group differences to lithium exposure alone. Conclusions The effect of lithium exposure on limbic and subcortical gray matter volumes appears to be time-dependent and relatively specific to the hippocampus and the amygdala, with short-term effects on the amygdala and long-term effects on both structures. These results support the clinical importance of long-term lithium treatment in BP-I.

To study the predictive relationship among persons with traumatic brain injury (TBI) between an objective indicator of injury severity (the adapted Marshall computed tomography [CT] classification scheme) and clinical indicators of injury severity in the acute phase, functional outcomes at inpatient rehabilitation discharge, and functional and participation outcomes at 1 year after injury, including death.The sample involved 4895 individuals who received inpatient rehabilitation following acute hospitalization for TBI and were enrolled in the Traumatic Brain Injury Model Systems National Database between 1989 and 2014.Head CT variables for each person were fit into adapted Marshall CT classification categories I through IV.Prediction models were developed to determine the amount of variability explained by the CT classification categories compared with commonly used predictors, including a clinical indicator of injury severity.The adapted Marshall classification categories aided only in the prediction of craniotomy or craniectomy during acute hospitalization, otherwise making no meaningful contribution to variance in the multivariable models predicting outcomes at any time point after injury.Results suggest that head CT findings classified in this manner do not inform clinical discussions related to functional prognosis or rehabilitation planning after TBI.CT: computed tomography; DRS: disability rating scale; EGOS: extended Glasgow outcome scale; FIM: functional independence measure; NDB: National Data Base; PTA: posttraumatic amnesia; RLOS: rehabilitation length of stay; SPOS: semipartial omega squared statistic; TBI: traumatic brain injury; TBIMS: Traumatic Brain Injury Model Systems.

Background Alterations in hippocampal structure and function are present in bipolar disorder (BD). Childhood trauma is associated with risk for BD, and the several subfields of the hippocampus are differentially sensitive to the effects of stressors of the sort associated with risk for BD. The current study therefore sought to test the hypothesis that childhood trauma may be differentially associated with abnormal hippocampal subfield volumes in BD. Methods 104 participants with BD type I (BD-I, n = 56) or BD type II (BD-II, n = 48) and 81 healthy controls (HC) underwent high-resolution structural magnetic resonance neuroimaging. Hippocampal subfield volumes were determined using FreeSurfer. Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ). Results There were significant effects of diagnosis on intracranial volume corrected hippocampal subfield volumes bilaterally as well as a significant interaction between diagnosis and childhood trauma. Hippocampal volumes did not differ between the BD-I and BD-II subgroups but hippocampal volumes were smaller in both groups when compared to HC. There was a significant effect of childhood trauma on bilateral presubiculum volume as well as significant interactions between diagnosis and childhood trauma on bilateral CA1, presubiculum and subiculum volumes, the direction of which differed between individuals with BD (larger) and HC (smaller). Limitations Recall bias may influence the reliability of the retrospective assessment of childhood trauma experiences. Conclusions Childhood trauma demonstrates differential effects on hippocampal subfield volumes of BD and HC, particularly in hippocampal subfields involved in emotion regulation.

Few studies have assessed the long-term functional outcomes of patients with a disorder of consciousness due to traumatic brain injury (TBI). This study examined functional status during the first 10 years after TBI among a cohort with disorders of consciousness (i.e., coma, vegetative state, minimally conscious state). The study sample included 110 individuals with TBI who were unable to follow commands prior to inpatient rehabilitation and for whom follow-up data were available at 1, 2, 5, and 10 years post-injury. The sample was subdivided into those who demonstrated command-following early (before 28 days post-injury) versus late (≥ 28 days post-injury or never). Functional Independence Measure (FIM) at 1, 2, 5, and 10 years following TBI was used to measure functional outcomes. Measureable functional recovery occurred throughout the 10-year period, with more than two thirds of the sample achieving independence in mobility and self-care, and about one quarter achieving independent cognitive function by 10 years. Following commands prior to 28 days was associated with greater functional independence at all outcome time-points. Multi-trajectory modeling of recovery of three FIM subscales (self-care, mobility, cognition) revealed four distinct prognostic groups with different temporal patterns of change on these subscales. More than half the sample achieved near-maximal recovery by 1 year post-injury, while the later command-following subgroups recovered over longer periods of time. Significant late functional decline was not observed in this cohort. Among a cohort of patients unable to follow commands at the time of inpatient rehabilitation, a substantial proportion achieved functional independence in self-care, mobility, and cognition. The proportion of participants achieving functional independence increased between 5 and 10 years post-injury. These findings suggest that individuals with disorders of consciousness may benefit from ongoing functional monitoring and updated care plans for at least the first decade after TBI.

Repeated traumatic brain injuries (rmTBI) are frequently associated with debilitating neuropsychiatric conditions such as cognitive impairment, mood disorders, and post-traumatic stress disorder. We tested the hypothesis that repeated mild traumatic brain injury impairs spatial memory and enhances anxiety-like behaviour.We used a between groups design using single (smTBI) or repeated (rmTBI) controlled cranial closed skull impacts to mice, compared to a control group.We assessed the effects of smTBI and rmTBI using measures of motor performance (Rotarod Test [RT]), anxiety-like behaviour (Elevated Plus Maze [EPM] and Open Field [OF] tests), and spatial memory (Morris Water Maze [MWM]) within 12 days of the final injury. In separate groups of mice, astrocytosis and microglial activation were assessed 24 hours after the final injury using GFAP and IBA-1 immunohistochemistry.RmTBI impaired spatial memory in the MWM and increased anxiety-like behaviour in the EPM and OFT. In addition, rmTBI elevated GFAP and IBA-1 immunohistochemistry throughout the mouse brain. RmTBI produced astrocytosis and microglial activation, and elicited impaired spatial memory and anxiety-like behaviour.rmTBI produces acute cognitive and anxiety-like disturbances associated with inflammatory changes in brain regions involved in spatial memory and anxiety.

Recent scientific reports and popular press describing chronic traumatic encephalopathy (CTE) collectively link this condition to a broad array of neuropsychiatric symptoms, including extremely rare and multi-determined behaviors such as murder-suicide. These reports are difficult to reconcile with several decades of research on the science of traumatic brain injury (TBI) and its consequences, especially the natural history and prognosis of mild TBI. This article attempts to reconcile these sources by reviewing the state of the science on CTE, with particular attention to case definitions and neuropathological criteria for this diagnosis. The evidence for links between TBI, CTE, and catastrophic clinical events is explored, and the complexity of attributing rare frequency behavioral events to CTE is highlighted. The clinical and medicolegal implications of the best available evidence are discussed, concluding with a cautionary note against prematurely generalizing current findings on CTE to entire populations of persons with, or at risk for, concussion exposures.

The incidence of traumatic brain injury (TBI) in the United States was 3.5 million cases in 2009, according to the Centers for Disease Control and Prevention. It is a contributing factor in 30.5% of injury-related deaths among civilians. Additionally, since 2000, more than 260,000 service members were diagnosed with TBI, with the vast majority classified as mild or concussive (76%). The objective assessment of TBI via imaging is a critical research gap, both in the military and civilian communities. In 2011, the Department of Defense (DoD) prepared a congressional report summarizing the effectiveness of seven neuroimaging modalities (computed tomography [CT], magnetic resonance imaging [MRI], transcranial Doppler [TCD], positron emission tomography, single photon emission computed tomography, electrophysiologic techniques [magnetoencephalography and electroencephalography], and functional near-infrared spectroscopy) to assess the spectrum of TBI from concussion to coma. For this report, neuroimaging experts identified the most relevant peer-reviewed publications and assessed the quality of the literature for each of these imaging technique in the clinical and research settings. Although CT, MRI, and TCD were determined to be the most useful modalities in the clinical setting, no single imaging modality proved sufficient for all patients due to the heterogeneity of TBI. All imaging modalities reviewed demonstrated the potential to emerge as part of future clinical care. This paper describes and updates the results of the DoD report and also expands on the use of angiography in patients with TBI.

Psychiatrists are increasingly called upon to care for individuals with cognitive, emotional, and behavioral disturbances after TBI, especially in settings serving military service personnel and Veterans. In both the early and late post-injury periods, cognitive impairments contribute to disability among persons with TBI and are potentially substantial sources of suffering for persons with TBI and their families. In this article, the differential diagnosis, evaluation, and management of posttraumatic cognitive complaints is reviewed. The importance of pre-treatment evaluation as well as consideration of non-cognitive contributors to cognitive problems and functional limitations is emphasized first. The course of recovery after TBI, framed as a progression through posttraumatic encephalopathy, is reviewed next and used to anchor the evaluation and treatment of posttraumatic cognitive impairments in relation to injury severity as well as time post-injury. Finally, pharmacologic and rehabilitative interventions that may facilitate cognitive and functional recovery at each stage of posttraumatic encephalopathy are presented.

At some point in their careers, most neurologists encounter patients who they find difficult to help.1,2 This experience may arise as a natural reaction to the challenging diagnostic and therapeutic work that so often is a part of work in the clinical neurosciences. Reports of the physician's reactions to difficult patient encounters appear infrequently in the neurology literature but, when offered, are informative and useful.3 Their publication cuts through the sense of being the only one to face such difficult experiences and provides an opportunity to learn from them both personally and in discussion with colleagues. Other patients are experienced as difficult because the neuropsychiatric sequelae of their neurologic conditions, comorbid psychiatric problems, and/or other challenging behaviors provoke strong reactions in the neurologist and his or her staff. Physician reactions in these encounters run the gamut of emotions, but frequently include aversion, anxiety, hopelessness, and anger, and may sometimes even include feelings of malice.4 These kinds of reactions to patients, and sometimes to their caregivers, complicate and can compromise one's ability to provide neurologic care.1,2,5 In the midst of a strong negative reaction to a difficult encounter with a patient or caregiver, one may be tempted to consider dismissing that patient from one's practice. There are circumstances in which such dismissals of patients from neurologic practices are necessary.1 However, patient dismissals are logistically complicated, stress and strain an already damaged physician–patient relationship, and may result in legal and regulatory penalties for the physician if done improperly. Most importantly, the dismissal itself is rarely in the patient's best interest: it fails to address the cause of the patient's behaviors, results in the transfer of a highly upset patient to an entirely unsuspecting or unprepared colleague, and almost ensures that the …

David B Arciniegas1,2, Jason R Tregellas1,3, Donald C Rojas1, Burlleen Hewitt1, C Alan Anderson1,2,41Neurobehavioral Disorders Program, Department of Psychiatry, 2Behavioral Neurology Section, University of Colorado Denver, Aurora, CO, USA; 3Research Service, 4Neurology Service, Denver Veterans Affairs Medical Denver, Denver, CO, USAAbstract: 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.Keywords: Alzheimer’s disease, hippocampus, acetylcholine, functional magnetic resonance imaging

Purpose Approximately 14–54% of patients with systemic lupus erythematosus without a history of major neuropsychiatric syndromes (nonNPSLE) have cognitive deficits. Elevated N-methyl-D-aspartate (NMDA) receptor antibodies (anti-NR2) have been reported in 35% of patients with SLE, but few studies have utilized controls or a composite memory index. We hypothesized that serum anti-NR2 would be elevated in nonNPSLE compared to healthy controls, and that elevated anti-NR2 would be associated with memory dysfunction and depression. Methods Subjects included 43 nonNPSLE patients with a mean age of 36.5 (SD = 9.0) and mean education level of 14.7 years (SD = 2.5). Twenty-seven healthy control subjects with similar demographic characteristics were also enrolled in this study. A global Cognitive Impairment Index (CII) and a Memory Impairment Index (MII) were calculated using impaired test scores from the ACR–SLE neuropsychological battery. Serum samples were analyzed using a standard ELISA for anti-NR2. Results Elevations of serum anti-NR2 were found in 14.0% of the nonNPSLE and 7.4% of the controls (p = 0.47). There was no relationship between elevated anti-NR2 status and higher CII or performance on the MII. No relationship between levels of depressive symptoms and anti-NR2 was found. Conclusions The frequency of elevated anti-NR2 was low (14.0%) in this sample of SLE patients and not significantly different from controls. A relationship was not found between the presence of anti-NR2 in serum and global cognitive or memory indices, or with depression. Results suggest that serum anti-NR2 is not likely related to mild cognitive dysfunction in SLE patients without a prior history of NPSLE.

Objective We examined clinical features, referral patterns, and diagnostic outcome of patients receiving cognitive evaluation in a behavioral neurology clinic who had no neurologic disorder. Background Cognitive complaints may indicate Alzheimer Disease (AD) or many other conditions. Accurate early evaluation of these complaints is critical, and appropriate subspecialty clinic referral has public health policy implications. Method This retrospective medical records review included 342 consecutive patients seen at the Neurobehavior Clinic of the University of Colorado Hospital from July 2006 through June 2008. All patients received an initial diagnosis by a clinic attending and subsequent consensus diagnosis by 3 subspecialists board certified in Behavioral Neurology & Neuropsychiatry. Results Among the 342 patients, 68% had a neurologic disorder, the most common of which was probable AD (17%). The remainder had nonneurologic diagnoses: 20% had a psychiatric diagnosis, 7% had no neuropsychiatric disorder, and 5% had a medical diagnosis. Of those with nonneurologic diagnoses, 65% were referred by primary care providers, and the most common symptom was memory loss (72%). In the psychiatric subgroup, depression was the most frequent diagnosis (56%). All normal individuals had concern about cognitive decline. In the medical subgroup, medication effect was the most frequent diagnosis (50%). Conclusions Probable AD was the most common neurologic diagnosis, but 32% of the referred patients had no neurologic disorder, and most of these individuals had a psychiatric cause for cognitive complaints. These results highlight the need for policies promoting more effective use of subspecialty clinics dedicated to neurologic disorders of cognition.

Traumatic brain injury (TBI) results in approximately 230,000 hospitalizations annually in the United States. Advances in the acute management of TBI have improved survival after TBI. Many TBI survivors develop neurobehavioral disturbances in the acute post-injury period. Neurobehavioral sequelae present clinical management challenges for critical care professionals. This article defines and describes TBI and reviews its common neuroanatomic and neurobehavioral consequences. These disturbances are organized under the framework of posttraumatic encephalopathy, and the characteristic forms and stages of recovery of this condition are discussed. Recommendations regarding evaluation and management of posttraumatic neurobehavioral problems in the critical care setting are offered.

Daniel J Abrams1, Donald C Rojas1, David B Arciniegas1,21Department of Psychiatry; 2Neurobehavioral Disorders Program, Departments of Psychiatry and Neurology, University of Colorado School of Medicine, Denver, CO, USAAbstract: Considerable debate surrounds the inclusion of schizoaffective disorder in psychiatric nosology. Schizoaffective disorder may be a variant of schizophrenia in which mood symptoms are unusually prominent but not unusual in type. This condition may instead reflect a severe form of either major depressive or bipolar disorder in which episode-related psychotic symptoms fail to remit completely between mood episodes. Alternatively, schizoaffective disorder may reflectthe co-occurrence of two relatively common psychiatric illnesses, schizophrenia and a mood disorder (major depressive or bipolar disorder). Each of these formulations of schizoaffective disorder presents nosological challenges because the signs and symptoms of this condition cross conventional categorical diagnostic boundaries between psychotic disorders and mood disorders. The study, evaluation, and treatment of persons presently diagnosed with schizoaffective may be more usefully informed by a dimensional approach. It is in this context that this article reviews and contrasts the categorical and dimensional approaches to its description, neurobiology, and treatment. Based on this review, an argument for the study and treatment of this condition using a dimensional approach is offered.Keywords: schizoaffective disorder, schizophrenia, bipolar disorder, manic-depressive disorder

Pathologic laughing and crying (PLC) denotes paroxysms of involuntary and uncontrollable crying and/or laughing resulting from neurologic illnesses. These paroxysms of affect are often provoked by nonsentimental stimuli; even when the inciting stimulus is sentimentally meaningful, the intensity of the affective response is excessive. The crying and/or laughing of PLC are variably accompanied by episode-congruent subjective emotional feelings. In unusual cases, episode-related feelings are of a valence contradictory to the expressed affect (ie, feeling happy while crying, or vice versa). PLC does not bear a predictable relationship to the prevailing mood of the patient, and the occurrence of such episodes does not produce a sustained mood disturbance. Therefore, patients with PLC must not be misunderstood as "depressed" or "manic" solely on the basis of their frequent episodic crying or laughing. In rare circumstances, PLC or PLC-like symptoms may be the presenting symptom of a neurologic illness. In such circumstances, a prompt and thorough diagnostic evaluation for that neurologic illness should be undertaken before initiating treatment for PLC. Selective serotonin reuptake inhibitors (SSRIs) are efficacious, safe, and well-tolerated treatments for PLC and are recommended as first-line treatments for this condition. Tricyclic antidepressants, dextromethorphan/quinidine, or dopaminergic agents may be useful alternative treatments in patients in whom SSRIs are ineffective or poorly tolerated. Education and supportive therapy may help patients and families mitigate the social isolation and embarrassment that PLC episodes frequently produce.

Extensive clinical experience and research suggest that a cortico-limbic-subcortico-thalamic-ponto-cerebellar network plays a significant role in the expression of human emotions. This network includes specific cerebral, cerebellar, and brainstem areas and their multiple projections/pathways, with activity modulated through serotonergic, dopaminergic, glutamatergic, and possibly sigma receptor neurotransmitter systems. Disruptions of regulatory and inhibitory mechanisms in the structure and function of this network likely constitute a pathophysiological basis for the crying and laughing episodes characteristic of involuntary emotional expression disorder. Pharmacologic interventions targeting the neurochemical modulators of the emotional expression systems may afford opportunities for symptom control among persons affected by this disorder.

The Journal of Neuropsychiatry and Clinical Neurosciences is in its 27th year of publication. Through its nearly three decades of operation, it has become a premier venue for publishing articles on the psychiatric aspects of neurological conditions and the neurology of psychiatric disorders. Our latest impact factor is 2.77, our 5-year impact factor is 3.14, our current H-index is 85, and the articles in our journal have been collectivelycitedmorethan41,000times.Ourreadershipbasehas expanded to more than 1,500 subscribers, including nearly 600 individual subscribers, more than 500 institutional subscribers, and more than 400 institutional subscribers with access to Journal of Neuropsychiatry and Clinical Neurosciences through the PsychiatryOnline program. The journal is home to many of the most highly cited articles in the field of neuropsychiatry, and our websiteis accessedmorethan 650,000 times annually.Wealso are honored to continue our more than 25 years of service as the official journal of the American Neuropsychiatric Association. While our successes are substantial, progress requires continued growth and periodic redevelopment. Toward that end, American Psychiatric Publishing (APP) began this publishing year with a new cover design and article layout aligned with others in its catalog. The table of contents of each issue now includes brief abstracts describing each article and highlights articles that address one or more of the Accreditation Council for Graduate Medical Education core competencies. Our peer review process has been expanded and expedited by shared use of ScholarOne with our sister journals in the APP catalog, enabling us to reduce the time from submission to first editorial decision to 20.5 days. During the last year, APP also instituted JNP in Advance, which makes articles available to subscribers and indexes them in PubMed within 12 weeks of their acceptance for publication. The creation of the Online Exclusives section of the journal enabled rapid movement of articles through our publication queue. Together, these maneuvers have positioned theJournal of Neuropsychiatry and Clinical Neurosciences to expeditiously publish cutting-edge neuropsychiatric research, scholarly reviews, and instructive cases. With regard to the cases in our Letters to the Editor section, this issue also marks the transition to a refined focus for these reports:novelclinicalobservationsthatinformusefullyonthe neuropsychiatric manifestations of neurological conditions and/or the neurology of psychiatric disorders. This issue also marks a time of renewal for the journal’s Editorial Board. With deep gratitude and great respect, we thank our outgoing Editorial Board members for their many years of volunteer service to the journal: Consulting Editors Floyd

Depression is a common consequence of traumatic brain injury (TBI), and is a source of substantial distress and disability for persons with TBI and their families. This article offers a practical approach to the evaluation and treatment of this condition. Diagnostic and etiologic considerations relevant to this issue are reviewed first. Next, somatic therapies for posttraumatic depression, including antidepressant medications and electroconvulsive therapy, are discussed. Use of these therapies is also considered in the context of the common medical and neurological comorbidities among persons with TBI. Finally, psychosocial interventions relevant to the care of persons with posttraumatic depression are presented.

Psychiatric symptoms in Guillain-Barré syndrome (GBS) can include anxiety and affective lability, which require treatment to improve functional outcomes. Three cases in which modest doses of selective serotonin reuptake inhibitors (SSRIs), alone or in combination with anticonvulsants, reduced symptoms of anxiety and affective lability during acute rehabilitation of GBS are presented. These agents were both more effective and better tolerated than benzodiazepines and appeared to facilitate engagement in rehabilitation therapies, including psychotherapy. Further investigation of the pharmacotherapy of neuropsychiatric disturbances in this population using prospective, blinded, placebo-controlled methods is recommended.

Delayed post-hypoxic encephalopathy is an uncommon but potentially debilitating consequence of hypoxic-ischemic brain injury. This condition is characterized by delayed neurological deterioration days-to-weeks after an initial partial or complete recovery from hypoxic-ischemic brain injury. The course of recovery from this condition is highly variable, ranging from rapid and fatal progression over several weeks to delayed but occasionally complete recovery. There are no reports describing neurorehabilitative, including neuropharmacologic, interventions for persons with persistent neurological and/or neurobehavioural deficits following delayed post-hypoxic encephalopathy. This study describes the case of a 24-year old male who developed delayed post-hypoxic encephalopathy following an unintentional methadone and diazepam overdose and who demonstrated cognitive and neurobehavioural improvements during treatment with amantadine HCl hydrochloride in a single-case, open-label design. A brief review of the literature regarding this condition, its treatment and suggestions for further study are presented.

Viral encephalitis, a condition in which a virus infects the brain and produces an inflammatory response, affects approximately 20,000 individuals per year in the United States. The viral encephalidities include sporadic and epidemic acute viral encephalidities and subacute and chronic/progressive viral encephalitis or encephalomyelitis. In people who survive these conditions, postencephalitic impairments of elemental neurologic, cognitive, emotional, and behavioral function are common. This article will provide a brief overview of the diagnosis and acute management of acute viral infections of the central nervous system. The neurologic and neuropsychiatric features, neuropathologies, and treatments of two of the more common types of acute viral encephalitis in North America--herpes simplex encephalitis and West Nile encephalitis--will be reviewed. The current and future role of psychiatrists and neuropsychiatrists in the care and study of individuals with these conditions will be discussed.

This article reviews the applications of the P50 evoked response to paired auditory stimuli (P50 ERP) in the study and evaluation of cognitive impairments after traumatic brain injury (TBI). The cholinergic hypothesis of cognitive impairment after TBI and the relationship of impaired auditory sensory gating to that hypothesis are presented. The neurobiology of impaired sensory gating, the relationship of that neurobiology to the P50 ERP, and the principles of P50 ERP recording are discussed. Studies of the P50 ERP among patients with persistent cognitive complaints after TBI are reviewed. Finally, possible clinical applications and limitations of the P50 ERP in the study, evaluation, and treatment of patients with cognitive impairments after TBI are offered.

The risk of attempted or completed suicide is increased in patients with migraine with aura, epilepsy, stroke, multiple sclerosis, traumatic brain injury, and Huntington's disease. Contrary to the general perception that the risk of suicide among patients with Alzheimer's disease and other dementing conditions is low, several reports suggest that the risk of suicide in these patients increases relative to the general population. Some patients at risk for neurologic disorders are also at increased risk for suicide; in particular, the risk of suicide is increased among persons at risk for Huntington's disease, independent of the presence or absence of the Huntington's gene mutation. The risk of attempted or completed suicide in neurologic illness is strongly associated with depression, feelings of hopelessness or helplessness, and social isolation. Additional suicide risk factors in persons with neurologic illness include cognitive impairment, relatively younger age (under 60 years), moderate physical disability, recent onset or change in illness, a lack of future plans or perceived meaning in life, recent losses (personal, occupational, or financial), and prior history of psychiatric illness or suicidal behavior. Substance dependence, psychotic disorders, anxiety disorders, and some personality disorders (eg, borderline personality disorder) may also contribute to increased risk of suicide among persons with neurologic illnesses. Identification and aggressive treatment of psychiatric problems, especially depression, as well as reduction of modifiable suicide risk factors among patients with neurologic illness is needed to reduce the risk of attempted and completed suicide in this population.

The diagnosis and treatment of individuals with problems involving both psychiatry and neurology have become more sophisticated in recent years, but these advances may be difficult to implement in the modern health care environment. For 16 years, an inpatient Geriatric Treatment Center within a state mental hospital has been used to diagnose and treat older persons with complex neuropsychiatric disorders. Eight illustrative cases are presented of patients with major behavioral dysfunction that could not be managed effectively in other health care facilities. After neuropsychiatric evaluation and behavioral neurology consultation, all had neurologic diagnoses established as the cause of their presentation. Seven improved with appropriate treatment, of whom one could return to independent living, and the eighth died and had an autopsy diagnosis of his disease at a nearby academic medical center. This series highlights the value of collaboration between psychiatry and neurology for evaluation and treatment of older patients with neuropsychiatric problems not easily accommodated by many existing health care settings.

Traumatic brain injury (TBI) can produce persistent attention and memory impairment that may in part be produced by impaired auditory sensory gating. The P50 evoked waveform response to paired auditory stimuli appears to be a useful measure of auditory gating. The first controlled measurement of the P50 ratio in TBI patients is described: when 20 patients with persistently symptomatic TBI were compared with 20 control subjects, the P50 ratio was significantly greater in the TBI group. The potential neurophysiologic and therapeutic implications of this finding in TBI patients who report symptoms consistent with impaired auditory gating are discussed.

• Cognitive impairment is a common consequence of traumatic brain injury (TBI) and a substantial source of disability. Across all levels of TBI severity, attention, processing speed, episodic memory, and executive function are most commonly affected.• The differential diagnosis for post-traumatic cognitive impairments is broad, and includes emotional, behavioral, and physical problems as well as substance use disorders, medical conditions, prescribed and self-administered medications, and symptom elaboration. Thorough neuropsychiatric assessment for such problems is a prerequisite to treatments specifically targeting cognitive impairments.• First-line treatments for post-traumatic cognitive impairments are nonpharmacologic, including education, realistic expectation setting, environmental and lifestyle modifications, and cognitive rehabilitation.• Pharmacotherapies for post-traumatic cognitive impairments include uncompetitive N-methyl-D-aspartate receptor (NMDA) antagonists, medications that directly or indirectly augment cerebral catecholaminergic or acetylcholinergic function, or agents with combinations of these properties.• In the immediate post-injury period, treatment with uncompetitive NMDA receptor antagonists reduces duration of unconsciousness. The mechanism for this effect may involve attenuation of neurotrauma-induced glutamate-mediated excitotoxicity and/or stabilization of glutamate signaling in the injured brain.• During the subacute or late post-injury periods, medications that augment cerebral acetylcholinergic function may improve declarative memory. Among responders to this treatment, secondary benefits on attention, processing speed, and executive function impairments as well as neuropsychiatric disturbances may be observed. During these post-injury periods, medications that augment cerebral catecholaminergic function may improve hypoarousal, processing speed, attention, and/or executive function as well as comorbid depression or apathy.• When medications are used, a "start-low, go-slow, but go" approach is encouraged, coupled with frequent reassessment of benefits and side effects as well as monitoring for drug-drug interactions. Titration to either beneficial effect or medication intolerance should be completed before discontinuing a treatment or augmenting partial responses with additional medications.

Objective: This study examined the relationship between immune, cognitive and neuroimaging assessments in subjects with systemic lupus erythematosus (SLE) without histories of overt neuropsychiatric (NP) disorders. Methods: In total, 84 subjects with nonNPSLE and 37 healthy controls completed neuropsychological testing from the American College of Rheumatology SLE battery. Serum autoantibody and cytokine measures, volumetric magnetic resonance imaging, and magnetic resonance spectroscopy data were collected on a subset of subjects. Results: NonNPSLE subjects had lower scores on measures of visual/complex attention, visuomotor speed and verbal memory compared with controls. No clinically significant differences between nonNPSLE patients and controls were found on serum measures of lupus anticoagulant, anticardiolipin antibodies, beta 2-glycoproteins, or pro-inflammatory cytokines (interleukin (IL)-1, IL-6, interferon alpha (IFN-alpha), and interferon gamma (IFN-gamma)). Higher scores on a global cognitive impairment index and a memory impairment index were correlated with lower IFN-alpha. Few associations between immune functions and neuroimaging parameters were found. Conclusions: Results indicated that nonNPSLE patients demonstrated cognitive impairment but not immune differences compared with controls. In these subjects, who were relatively young and with mild disease, no relationship between cognitive dysfunction, immune parameters, or previously documented neuroimaging abnormalities were noted. Immune measures acquired from cerebrospinal fluid instead of serum may yield stronger associations.

David B Arciniegas1,2,3, Gregory F Kellermeyer1,2, Nancy M Bonifer1, Kristin M Anderson-Salvi1, C Alan Anderson2,3,41Brain Injury Rehabilitation Unit, HealthONE Spalding Rehabilitation Hospital, Aurora, CO, USA; 2Neuropsychiatry Service, Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO, USA; 3Behavioral Neurology Section, Department of Neurology, University of Colorado Health Sciences Center, Denver, CO, USA; 4Neurology Service, Denver Veterans Affairs Medical Center, Denver, CO, USABackground: 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.Keywords: stroke, Mini-Mental State Examination, cognitive decline, Fugl-Meyer evaluation, motor impairment&nbsp