Concussion and its neurobehavioural sequelae.

A concussion results from a force to the brain that results in a transient loss of connectivity within the brain. Sport psychiatrists are increasingly called to be part of the concussion team and need to be prepared to manage issues related to concussion and its behavioural sequelae. Objectively, the best evidence available suggests that deficits in attention and/or in balance are the most reliable objective findings that a concussion has occurred. Prognosis after a concussion is generally very good, although a sub-set of patients that are yet well defined seem pre-disposed to delayed recovery. Neither head CT nor MRI are sufficiently sensitive to diagnose the type of injuries that pre-dispose patients to the neurobehavioural sequelae that have been associated with a concussion; confounding this is the finding that many of these signs and symptoms associated with concussion occur in other types of non-head injuries. Brain biomarkers and functional MRI (fMRI) hold promise in both diagnosis and prognosis of concussion, but are still research tools without validated clinical utility at this time. Finally, neurocognitive testing holds promise as a diagnostic criterion to demonstrate injury but, unfortunately, these tests are also limited in their prognostic utility and are of limited value.

Neurobehavior and Mild Traumatic Brain Injury.

Neurobehavioral sequelae after mild traumatic brain injury are multifactorial, often necessitating a multidisciplinary approach. Neurobehavioral sequelae generally resolve within 3 months; when more persistent, a search for contributing factors beyond a brain injury should be done. To accomplish this, a systematic and comprehensive evaluation is recommended to place the complaint in context of the patient's premorbid state. The treatment of neurobehavioral sequelae cannot be accomplished without a clear understanding of the underlying cause, and the treatment must be placed within a patient's social and functional framework. Normalizing the experience through education of patients and their families facilitates recovery.

Clinical policy: neuroimaging and decisionmaking in adult mild traumatic brain injury in the acute setting.

This clinical policy provides evidence-based recommendations on select issues in the management of adult patients with mild traumatic brain injury (TBI) in the acute setting. It is the result of joint efforts between the American College of Emergency Physicians and the Centers for Disease Control and Prevention and was developed by a multidisciplinary panel. The critical questions addressed in this clinical policy are: (1) Which patients with mild TBI should have a noncontrast head computed tomography (CT) scan in the emergency department (ED)? (2) Is there a role for head magnetic resonance imaging over noncontrast CT in the ED evaluation of a patient with acute mild TBI? (3) In patients with mild TBI, are brain specific serum biomarkers predictive of an acute traumatic intracranial injury? (4) Can a patient with an isolated mild TBI and a normal neurologic evaluation result be safely discharged from the ED if a noncontrast head CT scan shows no evidence of intracranial injury? Inclusion criteria for application of this clinical policy's recommendations are nonpenetrating trauma to the head, presentation to the ED within 24 hours of injury, a Glasgow Coma Scale score of 14 or 15 on initial evaluation in the ED, and aged 16 years or greater. The primary outcome measure for questions 1, 2, and 3 is the presence of an acute intracranial injury on noncontrast head CT scan; the primary outcome measure for question 4 is the occurrence of neurologic deterioration.

Extrapyramidal side-effects of antipsychotics in a randomised trial.

BACKGROUND: There are claims that second-generation antipsychotics produce fewer extrapyramidal side-effects (EPS) compared with first-generation drugs. AIMS: To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and perphenazine in people with schizophrenia. METHOD: Incidence analyses integrated data from standardised rating scales and documented use of concomitant medication or treatment discontinuation for EPS events. Mixed model analyses of change in rating scales from baseline were also conducted. RESULTS: There were no significant differences in incidence or change in rating scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second-generation antipsychotics with perphenazine or comparing between second-generation antipsychotics. Secondary analyses revealed greater rates of concomitant antiparkinsonism medication among individuals on risperidone and lower rates among individuals on quetiapine, and lower rates of discontinuation because of parkinsonism among people on quetiapine and ziprasidone. There was a trend for a greater likelihood of concomitant medication for akathisia among individuals on risperidone and perphenazine. CONCLUSIONS: The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and perphenazine or between second-generation antipsychotics in people with schizophrenia.

Clinical policy: neuroimaging and decisionmaking in adult mild traumatic brain injury in the acute setting.

This clinical policy provides evidence-based recommendations on select issues in the management of adult patients with mild traumatic brain injury (TBI) in the acute setting. It is the result of joint efforts between the American College of Emergency Physicians and the Centers for Disease Control and Prevention and was developed by a multidisciplinary panel. The critical questions addressed in this clinical policy are: (1) Which patients with mild TBI should have a noncontrast head computed tomography (CT) scan in the emergency department (ED)? (2) Is there a role for head magnetic resonance imaging over noncontrast CT in the ED evaluation of a patient with acute mild TBI? (3) In patients with mild TBI, are brain specific serum biomarkers predictive of an acute traumatic intracranial injury? (4) Can a patient with an isolated mild TBI and a normal neurologic evaluation result be safely discharged from the ED if a noncontrast head CT scan shows no evidence of intracranial injury? Inclusion criteria for application of this clinical policy's recommendations are nonpenetrating trauma to the head, presentation to the ED within 24 hours of injury, a Glasgow Coma Scale score of 14 or 15 on initial evaluation in the ED, and aged 16 years or greater. The primary outcome measure for questions 1, 2, and 3 is the presence of an acute intracranial injury on noncontrast head CT scan; the primary outcome measure for question 4 is the occurrence of neurologic deterioration.

Insulin receptor deficits in schizophrenia and in cellular and animal models of insulin receptor dysfunction.

Schizophrenia is associated with abnormalities in glucose metabolism that may lead to insulin resistance and a 3 fold higher incidence of type II diabetes mellitus. The goal of the present studies was to assess the role of insulin-dependent Akt signaling in schizophrenia and in animal and cellular models of insulin resistance. Our studies revealed a functional decrease in insulin receptor (IR)-mediated signal transduction in the dorsolateral prefrontal cortex (BA46) of medicated schizophrenics relative to control patients using post-mortem brain material. We found approximately 50% decreases in the content and autophosphorylation levels of IRbeta and approximately 76-78% decreases in Akt content and activity (pSer(473)-Akt). The inhibition of IRbeta signaling was accompanied by an elevated content of glycogen synthase kinase (GSK)-3 alpha and GSK-3beta without significant changes in phospho-Ser(21/9) GSK-3 alpha/beta levels. A cellular model of insulin resistance was induced by IRbeta knockdown (siRNA). As in schizophrenia, the IRbeta knockdown cells demonstrated a reduction in the Akt content and activity. Total GSK-3 alpha/beta content remained unaltered, but phospho-Ser(21/9) GSK-3 alpha/beta levels were reduced indicating a net increase in the overall enzyme activity similar to that in schizophrenia. Insulin resistance phenotype was induced in mice by treatment with antipsychotic drug, clozapine. Behavioral testing showed decreases in startle response magnitude in animals treated with clozapine for 68 days. The treatment resulted in a functional inhibition of IRbeta but the Akt activation status remained unaltered. Changes in GSK-3 alpha/beta were consistent with a net decrease in the enzyme activity, as opposed to that in schizophrenia. The results suggest that alterations in insulin-dependent Akt signaling in schizophrenia are similar to those observed in our cellular but not animal models of insulin resistance. In animal model, clozapine ameliorates IRbeta deficits at the GSK-3 alpha/beta level, which may justify its role in treatment of schizophrenia. Our studies suggest that aberrant IR function may be important in the pathophysiology of schizophrenia.

Psychiatric manifestations of nonconvulsive status epilepticus.

Nonconvulsive status epilepticus (NCSE) is clinically characterized by altered mental status and the diagnosis is confirmed by electroencephalography. Absence status (AS) and complex partial status (CPS) are the two primary types of NCSE. Patients in NCSE may exhibit a wide range of clinical presentations including subtle memory deficits, bizarre behavior, psychosis, or coma. While prognosis is dependent on the underlying etiology and possibly related to duration of the event, there is limited research in this area. Treatment focuses on correcting underlying pathologic abnormalities such as hyponatremia or drug toxicity, and initiating pharmacologic therapy. The benzodiazepines are considered the first line treatment for both AS and CPS.

Neurocognition, symptomatology, and functional skills in older alcohol-abusing schizophrenia patients.

Deficits in neurocognitive functioning are common to both schizophrenia and alcoholism. Recent studies suggest that neurocognitive functioning is the most significant predictor of social-adaptive functioning in schizophrenia. Cognitive impairment induced by alcoholism may result in more impaired functional outcome for comorbid patients. Past research examining alcohol-abusing schizophrenia patients has not examined correlates with functional outcome and has generally been limited to relatively younger patients. This study examined neurocognitive functioning and its correlates in alcohol-abusing schizophrenia patients between the ages of 40 and 80. Outpatients with schizophrenia (SZ; n = 17) or both schizophrenia and alcohol abuse or dependence (SZ + ETOH; n = 18) were tested on a neurocognitive battery, rated for symptomatology, and assessed for functional abilities. The results suggest that alcohol abuse in schizophrenia is associated with more impaired functioning across many domains, including memory impairment, negative and general psychopathology symptoms, and adaptive functions. The only significant predictor of impaired functional status in the overall sample and the SZ + ETOH group was neurocognitive functioning.

Nonconvulsive status epilepticus: clinical features and diagnostic challenges.

NCSE, once thought to be a rare disorder, should be considered in any patient presenting with an alteration in mental status of indeterminate cause. The psychiatrist needs to be aware of the different clinical characteristics of this disorder as well as similarities and differences from psychiatric disorders. A history of seizure is not necessary for the diagnosis, nor is motor activity necessarily associated with NCSE. An EEG is required to confirm the diagnosis and should be performed when possible, because early recognition and treatment may improve outcome. There is usually a good response to an intravenous benzodiazepine; when response has been delayed, other anticonvulsants have been used as adjuncts. The EEG is necessary to distinguish AS from CPS so that, when indicated, the proper long-term antiepileptic drug therapy can be started. Although NCSE has been described in the literature for many years, there is still a great need for carefully designed prospective studies to help define clear guidelines to assist in clinical and management decision making and, ultimately, to improve outcomes.

Concussion guidelines step 1: systematic review of prevalent indicators.

BACKGROUND: Currently, there is no evidence-based definition for concussion that is being uniformly applied in clinical and research settings. OBJECTIVE: To conduct a systematic review of the highest-quality literature about concussion and to assemble evidence about the prevalence and associations of key indicators of concussion. The goal was to establish an evidence-based foundation from which to derive, in future work, a definition, diagnostic criteria, and prognostic indicators for concussion. METHODS: Key questions were developed, and an electronic literature search from 1980 to 2012 was conducted to acquire evidence about the prevalence of and associations among signs, symptoms, and neurologic and cognitive deficits in samples of individuals exposed to potential concussive events. Included studies were assessed for potential for bias and confound and rated as high, medium, or low potential for bias and confound. Those rated as high were excluded from the analysis. Studies were further triaged on the basis of whether the definition of a case of concussion was exclusive or inclusive; only those with wide, inclusive case definitions were used in the analysis. Finally, only studies reporting data collected at fixed time points were used. For a study to be included in the conclusions, it was required that the presence of any particular sign, symptom, or deficit be reported in at least 2 independent samples. RESULTS: From 5437 abstracts, 1362 full-text publications were reviewed, of which 231 studies were included in the final library. Twenty-six met all criteria required to be used in the analysis, and of those, 11 independent samples from 8 publications directly contributed data to conclusions. Prevalent and consistent indicators of concussion are (1) observed and documented disorientation or confusion immediately after the event, (2) impaired balance within 1 day after injury, (3) slower reaction time within 2 days after injury, and/or (4) impaired verbal learning and memory within 2 days after injury. CONCLUSION: The results of this systematic review identify the consistent and prevalent indicators of concussion and their associations, derived from the strongest evidence in the published literature. The product is an evidence-based foundation from which to develop diagnostic criteria and prognostic indicators.

Traumatic brain injury and its neurobehavioral sequelae.

The neurobehavioral sequelae of TBI consist of a spectrum of somatic, neurologic, and psychiatric symptoms. The challenge for clinicians lies in understanding the interface of the various symptoms and how they interrelate with other entities. Specifically, the challenge is differentiating post-TBI-related symptoms from preexisting or de novo psychiatric, neurologic, and/or systemic disorders. A comprehensive evaluation and a multidisciplinary approach to evaluating patients are essential to be able to develop the differential diagnosis needed to design a management plan that maximizes recovery.

Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia.

OBJECTIVE: We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. METHOD: This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2) tests. Data were collected from January 2001 to December 2004. RESULTS: Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score. CONCLUSIONS: Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00014001.

Traumatic brain injury and its neurobehavioral sequelae.

The neurobehavioral sequelae (NBS) of traumatic brain injury (TBI) consist of a spectrum of somatic, neurological, and psychiatric symptoms. The challenge for clinicians lies in understanding the interface of the various symptoms and how they interrelate with other entities. Specifically, the challenge is differentiating post-TBI-related symptoms from pre-existing or de novo psychiatric, neurological, and/or systemic disorders. A comprehensive evaluation and a multidisciplinary approach to evaluating patients are essential to be able to develop the differential diagnosis needed to design a management plan that maximizes recovery.

Neurobehavioral sequelae of traumatic brain injury.

The neurobehavioral sequelae of traumatic brain injury consist of a spectrum of somatic and neuropsychiatric symptoms. The neuropsychiatric symptoms are divided into cognitive and behavioral presentations. In the literature, these neurobehavioral sequelae have been called postconcussive symptoms, postconcussive syndrome, and postconcussive disorder; however, the authors of this review do not use this terminology because the symptoms are not restricted to patients with concussion but instead can be found in all traumatic brain injury patients of all injury severities. The development of neurobehavioral sequelae after traumatic brain injury is a multifactorial process. The patient evaluation requires a multidisciplinary approach in order to delineate physiologic dysfunction and place deficits in the context of the patient's preinjury and postinjury psychiatric status. Consequently, the evaluation of the posttraumatic brain injury patient with neurobehavioral sequelae requires a carefully structured history and physical examination with an emphasis on neurological and psychiatric function. Adjunctive evaluations must be tailored to the patient with neuroimaging, neurophysiological, and neuropsychiatric testing. Maximized outcomes may be achieved by the performance of a careful and detailed assessment that places complaints within the context of the individual.