Cost-Effectiveness of Routine Screening for Autoimmune Encephalitis in Patients With First-Episode Psychosis in the United States.

OBJECTIVE: Autoimmune encephalitis (AE) is a highly treatable neurologic condition that can cause psychosis. Screening for AE is not currently recommended in routine workup for first-episode psychosis (FEP), owing partly to the high cost of testing for AE-associated neuronal autoantibodies. METHODS: This study used a decision-analytic model to estimate the cost-effectiveness of routine serum screening for AE compared with clinically targeted screening in patients with FEP. Model parameters drawn from prior published literature included the prevalence of neuronal autoantibodies in FEP (4.5%), serum autoantibody panel cost (US $291), remission probability with antipsychotics (0.58), and remission probability with immunotherapy for patients diagnosed with AE (0.85). Outcomes included quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs), assessed over a 5-year horizon from the US health care sector and societal perspectives. ICER thresholds of $50,000/QALY to $150,000/QALY were used to define cost-effectiveness. The analysis was conducted between June 2018 and January 2020. RESULTS: Routine screening led to mean QALY gains of 0.008 among all patients and 0.174 among the subgroup of patients with neuronal autoantibodies. Mean costs increased by $780 from a societal perspective and $1,150 from a health care sector perspective, resulting in ICERs of $99,330/QALY and $147,460/QALY, respectively. Incorporating joint input data uncertainty, the likelihood routine screening has an ICER ≤ $150,000/QALY was 55% from a societal perspective and 37% from a health care sector perspective. The model parameter with the greatest contribution to overall uncertainty was the effectiveness of immunotherapy relative to antipsychotics. CONCLUSIONS: Routine screening for AE in patients with FEP may be cost-effective in the United States. As further immunotherapy effectiveness data become available, a more definitive recommendation to perform routine screening could be warranted.

Telemedicine assessment of long-term cognitive and functional status in anti-leucine-rich, glioma-inactivated 1 encephalitis.

OBJECTIVE: To assess the feasibility of a structured telephone interview examining the long-term cognitive and functional status in anti-leucine-rich, glioma-inactivated 1 (LGI1) encephalitis. METHODS: Telephone interviews were conducted with 37 patients after a median follow-up of 87 months from disease onset and 23 healthy controls matched for age and sex. Cognitive status was assessed with the telephone Mini-Mental State Examination (t-MMSE) and 3 tests exploring verbal memory, fluency, and executive function. Functional status was evaluated with the Functional Activities Questionnaire and the modified Rankin Scale (mRS). Patients were classified as normal, with mild cognitive impairment (MCI), or with dementia based on cognitive and functional status. Assessment of the cognitive reserve was performed with a structured questionnaire. Logistic regression analysis was applied to identify predictors of cognitive impairment. RESULTS: Telephone interviews were successful in 36/37 (97%) patients. Cognitive impairment was detected in 27 (75%) including 17 with MCI and 10 with dementia. Eight (29%) patients would have been misclassified using only the t-MMSE. Twenty-six (72%) patients were functionally independent according to the mRS, but only 9 (35%) were cognitively normal. Independent predictors for long-term cognitive impairment were a low cognitive reserve (OR = 1.36, 95% CI: 1.05-1.76; p = 0.02) and bilateral hippocampal hyperintensity at initial MRI (OR = 27.03, 95% CI: 1.87-390; p = 0.02). CONCLUSIONS: Telemedicine is a feasible tool to assess the cognitive and functional outcome in patients with anti-LGI1 encephalitis. Cognitive impairment is often missed if only functional scales are used. Premorbid cognitive reserve and MRI with bilateral hippocampal hyperintensity were predictors for long-term cognitive impairment.

Development of the clinical assessment scale in autoimmune encephalitis.

OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92). INTERPRETATION: CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352-358.

[ZONISAMIDE: FIRST CHOICE AMONG THE FIRST-LINE ANTIEPILEPTIC DRUGS IN FOCAL EPILEPSY]. / ZONISAMID: AZ ELSOKÉNT VÁLASZTANDÓ ANTIEPILEPTIKUMOK KÖZÖTT FOKÁLIS EPILEPSZIÁBAN.

Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term 'epilepsy' which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level "A") as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient's compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.

Antineuronal antibodies and infectious pathogens in severe acute pediatric encephalitis.

The pathogenesis of acute encephalitis is divided into either direct infection or by immune-mediated inflammation, but the cause is still unknown. This retrospective study aimed to screen antineuronal antibodies in children with severe acute encephalitis. Thirty-four children (22 boys and 12 girls) underwent assessments such as antineuronal antibodies survey for autoimmune encephalitis and polymerase chain reaction/viral culture and antibody assays for all commonly recognized causes of infectious encephalitis. Sixteen (47.1%) were positive for autoantibodies, including antiglutamic acid decarboxylase antibodies in 16 and voltage-gated potassium channel complex antibodies in 1. Sixteen patients (47.1%) had presumed infectious etiologies, including 6 with influenza, 6 with Mycoplasma pneumoniae, 3 with enterovirus, and 1 with herpes simplex virus. In this study, influenza and Mycoplasma pneumoniae infection are the main presumed causes of severe acute encephalitis in children, although an immune-mediated mechanism may also play a role.

The functional, social and economic impact of acute encephalitis syndrome in Nepal--a longitudinal follow-up study.

BACKGROUND: Over 133,000 children present to hospitals with Acute Encephalitis Syndrome (AES) annually in Asia. Japanese encephalitis (JE) accounts for approximately one-quarter of cases; in most cases no pathogen is identified and management is supportive. Although JE is known to result in neurological impairment, few studies have examined the wider impact of JE and AES on patients and their families. METHODOLOGY/PRINCIPAL FINDINGS: Children (aged 1 month-14 years) with AES were assessed 5-12 months after discharge from two Nepali hospitals. Assessment included clinical examination, the Liverpool Outcome Score (LOS) - a validated assessment of function following encephalitis, questionnaires about the child's social participation since discharge, and out-of-pocket costs to the family. Children were classified as JE or 'other AES' based on anti-JE virus antibody titres during acute illness. Contact was made with the families of 76% (73/96) of AES children. Six children had died and one declined participation. 48% (32/66) reported functional impairment at follow-up, most frequently affecting behaviour, language or limb use. Impairment was more frequent in JE compared to 'other AES' cases (68% [13/19] versus 40% [19/47]; p = 0.06). 49% (26/53) had improvement in LOS between discharge and follow-up. The median out-of-pocket cost to families, including medical bills, medication and lost earnings was US$ 1151 (10 times their median monthly income) for children with severe/moderate impairment and $524 (4.6 times their income) for those with mild/no impairment (P = 0.007). Acute admission accounted for 74% of costs. Social participation was limited in 21% of children (n = 14). CONCLUSIONS/SIGNIFICANCE: Prolonged functional impairment was common following AES. Economic impact to families was substantial. Encouragingly, almost half the children improved after discharge and most reported sustained social participation. This study highlights a need for long-term medical support following AES. Rationalisation of initial expensive hospital treatments may be warranted, especially since only supportive treatment is available.

Forecasting burden of long-term disability from neonatal conditions: results from the Projahnmo I trial, Sylhet, Bangladesh.

INTRODUCTION: The burden of disease resulting from neonatal conditions is substantial in developing countries. From 2003 to 2005, the Projahnmo I programme delivered community-based interventions for maternal and newborn health in Sylhet, Bangladesh. This analysis quantifies burden of disability and incorporates non-fatal outcomes into cost-effectiveness analysis of interventions delivered in the Projahnmo I programme. METHODS: A decision tree model was created to predict disability resulting from preterm birth, neonatal meningitis and intrapartum-related hypoxia ('birth asphyxia'). Outcomes were defined as the years lost to disability (YLD) component of disability-adjusted life years (DALYs). Calculations were based on data from the Projahnmo I trial, supplemented with values from published literature and expert opinion where data were absent. RESULTS: 195 YLD per 1000 neonates [95% confidence interval (CI): 157-241] were predicted in the main calculation, sensitive to different DALY assumptions, disability weights and alternative model structures. The Projahnmo I home care intervention may have averted 2.0 (1.3-2.8) YLD per 1000 neonates. Compared with calculations based on reductions in mortality alone, the cost-effectiveness ratio decreased by only 0.6% from $105.23 to $104.62 ($65.15-$266.60) when YLD were included, with 0.6% more DALYs averted [total 338/1000 (95% CI: 131-542)]. DISCUSSION: A significant burden of disability results from neonatal conditions in Sylhet, Bangladesh. Adding YLD has very little impact on recommendations based on cost-effectiveness, even at the margin of programme adoption. This model provides guidance for collecting data on disabilities in new settings.

[Diagnostic medical error as an overinterpretation of toxicology screening combined with inadequate clinical assessment]. / Blad diagnostyczny jako nadinterpretacja przesiewowego badania toksykologicznego przy niedostatecznej ocenie klinicznej.

Problems of patient safety within the system of health care are defined by prescriptive and ethical regulations; a breach of such regulations is associated with entering a complex category of situations covered by the term "medical error" or "appropriateness of medical management". In order to minimize the sources of diagnostic errors, with the knowledge on such errors largely originating from medico-legal practice, numerous initiatives emerge, according to which monitoring of adverse events and subjecting such events to a profound discussion is the most important element of prevention. The problem discussed in the paper is illustrated by the case of a 13-year old boy, in whom opioid poisoning was mistakenly diagnosed instead of a neurological condition in consequence of the physician disregarding significant symptoms of the disease and accepting his subjective suspicion of poisoning. The erroneous diagnosis was further compounded by lack of verification of the preliminary diagnosis and failure to perform further laboratory diagnostic management addressing the neurological status of the patient. The presented case supports data from publications found in the literature on the subject that describe a high risk of diagnostics errors in neurological conditions; such errors are often committed by emergency physicians other than neurologists.

The health care matrix formulation: a tool for competency assessment in psychiatry residency training.

OBJECTIVE: To assert the importance of the use of the healthcare matrix formulation for competency assessment in psychiatry residency training. METHODS: We present a case from our inpatient psychiatric facility and format it in the form of the healthcare matrix, which was developed at Vanderbilt University incorporating the Institute of Medicine 'aims' and the Accreditation Council for Graduate Medical Education 'core competencies'. We also analyze the healthcare matrix and elucidate its use in clinical practice. RESULTS: The healthcare matrix provides us with a practical tool to analyze any complex episode of patient care, like the one in our psychiatric setting, and allows us to learn from the shortcomings in order to improve. CONCLUSION: The optimal utilization of this tool in the competency assessment of psychiatry residents has an enormous practical implication by transforming the case and morbidity and mortality conferences into a well-structured learning and improvement format.

Childhood convulsive status epilepticus: epidemiology, management and outcome.

Convulsive status epilepticus (CSE) in childhood is a medical emergency and its aetiology and outcome mean that it should be studied separately from adult CSE. The incidence in developed countries is between 17 and 23/100,000 with a higher incidence in younger children. Febrile CSE is the commonest single group with a good prognosis in sharp distinction to CSE related to central nervous system infections which have a high mortality. The aim of treatment is to intervene at 5 min and studies indicate that intravenous (i.v.) lorazepam may be a better first-line treatment than rectal diazepam and i.v. phenytoin a better second-line treatment than rectal paraldehyde. An epidemiological study strongly supports the development of prehospital treatment with buccal midazolam becoming a widely used but unlicensed option in the community. More than two doses of benzodiazepines increase the rate of respiratory depression without obvious benefit. The 1 year recurrence rate is 17% and the hospital mortality is about 3%.

The assessment and management of the dizzy patient.

A significant number of individuals are affected by symptoms of dizziness. It is the most common complaint among patients over 75 years of age. A large number of these patients seek counsel from their physicians. It is imperative for the evaluating physician to obtain a thorough history and perform a complete physical exam. The proper diagnostic studies must also be obtained to confirm or rule out particular diagnoses. The physician should never assume that the dizziness is the result of normal aging prior to ruling out pathologic conditions.

Experimenting on the past: the enigma of von Economo's encephalitis lethargica.

Encephalitis lethargica (EL) was a complex and mysterious disease that appeared around the same time as the great influenza pandemic of 1918. The contemporaneous relationship of the 2 diseases led to speculation that they were causally related. Contemporary and subsequent observers conjectured that the influenza virus, directly responsible for the deaths of more than 20 million people, might also have been the cause of EL. A review of the extensive literature by observers of the EL epidemic suggests that most contemporary clinicians, epidemiologists, and pathologists rejected the theory that the 1918 influenza virus was directly responsible for EL. Disappearance of the acute form of EL during the 1920s has precluded direct study of this entity. However, modern molecular biology techniques have made it possible to examine archival tissue samples from victims of the 1918 pandemic in order to detect and study the genetic structure of the killer virus. Similarly, tissue samples from EL victims can now be examined for evidence of infection by the 1918 influenza virus.

Why would you remove half a brain? The outcome of 58 children after hemispherectomy-the Johns Hopkins experience: 1968 to 1996.

PURPOSE: To report the outcomes of the 58 hemispherectomies performed at Johns Hopkins between 1968 and January 1996. METHODS: Charts were reviewed of the 58 hemispherectomies performed at Johns Hopkins Medical Institutions by the Pediatric Epilepsy Group during the years 1968 to 1996. Twenty-seven operations were done for Rasmussen's syndrome, 24 operations for cortical dysplasias/hemimegalencephalies, and 7 for Sturge-Weber syndrome or other congenital vascular problems. Seizure control alone did not seem to adequately describe the outcomes of the procedure. Therefore, a score was constructed that included seizure frequency, motor disability, and intellectual handicap. This burden of illness score better described the child's handicap before and after surgery. RESULTS: Perioperative death occurred in 4 out of 58 children. Of the 54 surviving children, 54% (29/54) are seizure-free, 24% (13/54) have nonhandicapping seizures, and 23% (12/54) have residual seizures that interfere to some extent with function. Reduction in seizures was related to the etiology of the unilateral epilepsy. Eighty-nine percent of children with Rasmussen's, 67% of those with dysplasias, and 67% of the vascular group are seizure-free, or have occasional, nonhandicapping seizures. All operations were considered by the parents and the physicians to have been successful in decreasing the burden of illness. In 44 the procedure was very successful, in 7 it was moderately successful, and in 3 it was minimally successful. Success was related to the etiology, and early surgery was preferable. CONCLUSION: Hemispherectomy can be a valuable procedure for relieving the burden of seizures, the burden of medication, and the general dysfunction in children with severe or progressive unilateral cortical disease. Early hemispherectomy, although increasing the hemiparesis in children with Rasmussen's syndrome, relieves the burden of constant seizures and allows the child to return to a more normal life. In children with dysplasias, early surgery can allow the resumption of more normal development.

A neuropathologic study of long-term, Economo-type postencephalitic parkinsonism with a prolonged clinical course.

In this report, the neuropathologic features of five autopsied cases of postencephalitic parkinsonism of the Economo-type (PEPE) with a mean age of 66.6 years and a mean duration of the illness of 53.6 years are described. All five patients had presented with personality changes and severe parkinsonism. In addition, four patients had also had ocular symptoms. A pronounced chronic progression of the symptoms characterized all five cases. Active degenerating lesions were found in the substantia nigra (patients 3, 4 and 5) and the oculomotor nucleus (patient 5) which might explain the clinical observation of chronic active disease in these patients. We found that the intraneuronal neurofibrillary tangles (NFT) were immunoreactive to paired helical filaments (PHF), tau and ubiquitin; but ghost tangles demonstrated immunoreactivity only to glial fibrillary acid protein (GFAP). The ghost tangles consisted of dispersed bundles of abnormal tubules, and electron-dense glial filaments would surround and occasionally invade the ghost tangles. The present study suggests that NFT in PEPE are similar in their immunohistochemistry and ultrastructure to those observed in the case of Alzheimer-type dementia.

Childhood coma in Ibadan. Relationship to socio-economic factors.

According to the literature, socio-economic factors may contribute more to geographic variations in the aetiology and prognosis of childhood coma than has previously been recognised. This prospective study involving 118 children with strictly defined coma demonstrated that the commonest causes of coma in Ibadan were cerebral malaria (55%), meningitis (13%) and encephalitis (10%). The prognosis was poor. Forty-three (36%) of 118 cases died and 75 (64%) survived, including 23 who showed neurologic deficits. Noteworthy prognostic indices of coma were the aetiology of the condition, the presence of severe anaemia, hypoglycaemia and pneumonia. The findings are discussed in the context of the socio-economic background of children in the tropics.

A comparative study of postnatally-acquired cerebral palsy in Cape Town.

The importance of socio-economic conditions in the causation of postnatally-acquired cerebral palsy has not been stressed in previous studies. A comparative survey was undertaken in Cape Town, South Africa. Three ethnic groups were compared--white, coloured (mixed ancestry) and black. The percentage of postnatally-acquired cerebral palsy in these groups was 13.2, 24.0 and 36.1 per cent, respectively. These figures can be explained by the differing socio-economic conditions of each group, the white group belonging to the highest socio-economic stratum and the black group to the lowest. The main causes of postnatally-acquired cerebral palsy were cerebral infections (particularly meningitis), cerebral trauma and cerebrovascular accidents. The proportion in each group, the main causal factors, age at onset, types of cerebral palsy and intellectual status are similar to those of most previous studies.