Decrease in mortality of adult epilepsy patients since 1980: lessons learned from a hospital-based cohort.

BACKGROUND AND PURPOSE: Data on mortality in patients with epilepsy have been available since the 1800s. They consistently show a 2-3-fold increase compared to the general population. Despite major advances in diagnostic tools and treatment options, there is no evidence for a decrease in premature deaths. The temporal trend of mortality in a hospital-based epilepsy cohort over three decades was assessed. METHODS: A hospital-based incidence cohort was recruited from a specialized epilepsy outpatient clinic at Innsbruck Medical University between 1980 and 2007, divided by decade into three cohorts and followed for 5 years after initial epilepsy diagnosis. Deaths and their primary causes were determined using probabilistic record linkage with the Austrian death registry. Age-, sex- and period-adjusted standardized mortality rates (SMRs) were computed in relation to the general population of the same area and grouped according to time of diagnosis. RESULTS: In all, 122 deaths in 4549.9 person-years (1954.5 women, 2595.2 men) were identified. The overall SMR was 2.2 [95% confidence interval (CI) 1.8-2.6] and decreased from 3.0 (95% CI 2.1-4.3) in 1980-1989, to 2.7 (95% CI 2.0-3.5) in 1990-1999 and to 1.4 (95% CI 1.0-2.0) in 2000-2007. CONCLUSIONS: This study indicates a decrease in mortality in newly diagnosed epilepsy patients over the last three decades. This may be due to advances in diagnosis and treatment over the past three decades, including early identification of drug resistance, introduction of new anti-epileptic drugs and establishment of a comprehensive epilepsy surgery programme in this region.

Overnight switching from oxcarbazepine to eslicarbazepine acetate: an observational study.

OBJECTIVES: There are clinical situations where it might be appropriate to switch patients from immediate-release oxcarbazepine (OXC) to eslicarbazepine acetate (ESL). We investigated the effects of transitioning patients overnight from OXC to ESL. MATERIALS AND METHODS: A retrospective, single-center study was conducted in which patients with drug-resistant focal epilepsy on a stable dose of immediate-release OXC for at least 4 weeks were switched overnight to ESL. Patients were switched because they experienced persistent seizures with OXC but were unable to tolerate increased OXC dosing due to adverse events. Tolerability was assessed using the Adverse Events Profile (AEP), quality of life was assessed using the Quality of Life in Epilepsy Inventory 10 (QOLIE-10), and alertness was assessed as reaction time using a subtest of the Test Battery for Attention Performance version 2.3. Assessments were performed immediately prior to and 5 days after switching from OXC to ESL (days 0 and 5, respectively). RESULTS: The analysis included 21 patients (12 women, 9 men; mean age 36 years). After switching from OXC to ESL, there were significant improvements in mean scores for AEP (P<.001), QOLIE-10 (P=.001), and alertness (P<.05). Adverse Events Profile total scores improved for 21/21 (100.0%) patients, QOLIE-10 total scores improved for 17/21 (81.0%) patients, and alertness scores improved for 16/21 (76.2%) patients. CONCLUSIONS: In this short-term, single-center study, an overnight switch from twice-daily OXC to once-daily ESL in patients with drug-resistant focal epilepsies resulted in improvements in side effects, quality of life, and alertness.

Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibodies have been recently described in children with acute disseminating encephalomyelitis (ADEM), but the clinical and neuroradiological characterisation of this subgroup is lacking. OBJECTIVE: To compare the clinical and neuroradiological features of paediatric ADEM with and without MOG antibodies. METHODS: Clinical course, cerebrospinal fluid (CSF)-, MRI studies, outcome and MOG status of 33 paediatric ADEM prospectively studied were reviewed. RESULTS: MOG antibodies (median 1:2560; range 1:160-1:20 480) were detected in 19 children with ADEM. The majority of children showed a decline of serum MOG-IgG titres over time. Children with MOG antibodies did not differ in their age at presentation, sex ratio, the presence of oligoclonal bands, clinical symptoms or initial severity, apart from a higher CSF cell count (p=0.038), compared with children without MOG antibodies. In addition, further relapsing demyelinating episodes associated with MOG antibodies were observed only in children with MOG antibodies. All 19 children with MOG antibodies had a uniform MRI pattern, characterised by large, hazy and bilateral lesions and the absence of atypical MRI features (eg, mainly small lesions, well-defined lesions), which was significantly different compared to that of children without MOG antibodies (p=0.003; and p=0.032, respectively). In addition, children with MOG antibodies had involvement of more anatomical areas (p=0.035) including the myelon characterised by a longitudinally extensive transverse myelitis (p=0.003), more often a complete resolution of lesions (p=0.036) and a better outcome (p=0.038). CONCLUSIONS: Patients with ADEM with MOG antibodies in our cohort had a uniform MRI characterised by large, bilateral and widespread lesions with an increased frequency of longitudinal extensive transverse myelitis and a favourable clinical outcome in contrast to children lacking MOG antibodies.

Predicting outcome of status epilepticus.

BACKGROUND: Status epilepticus (SE) is a frequent neurological emergency complicated by high mortality and often poor functional outcome in survivors. The aim of this study was to review available clinical scores to predict outcome. METHODS: Literature review. PubMed Search terms were "score", "outcome", and "status epilepticus" (April 9th 2015). Publications with abstracts available in English, no other language restrictions, or any restrictions concerning investigated patients were included. RESULTS: Two scores were identified: "Status Epilepticus Severity Score--STESS" and "Epidemiology based Mortality score in SE--EMSE". A comprehensive comparison of test parameters concerning performance, options, and limitations was performed. Epidemiology based Mortality score in SE allows detailed individualization of risk factors and is significantly superior to STESS in a retrospective explorative study. In particular, EMSE is very good at detection of good and bad outcome, whereas STESS detecting bad outcome is limited by a ceiling effect and uncertainty of correct cutoff value. Epidemiology based Mortality score in SE can be adapted to different regions in the world and to advances in medicine, as new data emerge. In addition, we designed a reporting standard for status epilepticus to enhance acquisition and communication of outcome relevant data. A data acquisition sheet used from patient admission in emergency room, from the EEG lab to intensive care unit, is provided for optimized data collection. CONCLUSION: Status Epilepticus Severity Score is easy to perform and predicts bad outcome, but has a low predictive value for good outcomes. Epidemiology based Mortality score in SE is superior to STESS in predicting good or bad outcome but needs marginally more time to perform. Epidemiology based Mortality score in SE may prove very useful for risk stratification in interventional studies and is recommended for individual outcome prediction. Prospective validation in different cohorts is needed for EMSE, whereas STESS needs further validation in cohorts with a wider range of etiologies. This article is part of a Special Issue entitled "Status Epilepticus".

Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit.

INTRODUCTION: In refractory status epilepticus (SE), because of subcellular maladaptive changes, GABAergic drugs are no longer effective, and the excitatory neurotransmitter glutamate (Glu) plays a major role in seizure perpetuation. Perampanel (PER, licensed since 09/2012) is the first orally active noncompetitive AMPA receptor antagonist for adjunctive treatment of refractory focal epilepsy. METHODS: We analyzed treatment response, seizure outcome, and adverse effects of add-on treatment with perampanel in patients with refractory status epilepticus in the Neurological Intensive Care Unit (NICU), Salzburg, Austria between 09/2012 and 11/2014 by retrospective chart review. RESULTS: Twelve patients (75% women) with refractory status epilepticus were treated with PER administered per nasogastric tube between 09/2012 and 11/2014. Median age was 75 years [range: 60-91]. The most frequent SE type was nonconvulsive SE (NCSE) with (5/12, 42%) and without coma (6/12, 50%). In seven patients (58%), SE arose de novo, with an acute symptomatic cause in five patients (42%). Cerebrovascular diseases (4/12, 33%) and cerebral tumors (4/12, 33%) were the most common etiologies. Perampanel was given after a median number of four antiepileptic drugs [range: 2-7] and a median time of 1.5 days [range: 0.8-18.3]. In one patient (8%), clinical improvement was observed within 24h and EEG improvement within 60 h after administration of PER, while in another patient (8%), clinical and EEG improvement was observed more than 48 h after administration. Median initial dose was 4 mg [range: 2-12; SD: 4.11], titrated up to a median of 12 mg [range: 4-12] in steps of 2 to 4 mg per day. No adverse effects were reported regarding cardiorespiratory changes or laboratory parameters. Outcomes after SE were moderate disability in five patients (42%), death in three patients (25%), and persistent vegetative state in two patients (17%). CONCLUSION: Though glutamate plays a major role in seizure perpetuation, the noncompetitive AMPA receptor antagonist PER could only ameliorate seizure activity in a few patients with refractory SE. The long duration of SE before the administration of PER via nasogastric tube, as well as relatively low doses of PER, might be responsible for the modest result. Perampanel was well tolerated, and no adverse events were reported. This article is part of a Special Issue entitled Status Epilepticus.

Salzburg Consensus Criteria for Non-Convulsive Status Epilepticus--approach to clinical application.

BACKGROUND: Salzburg Consensus Criteria for diagnosis of Non-Convulsive Status Epilepticus (SCNC) were proposed at the 4th London-Innsbruck Colloquium on status epilepticus in Salzburg (2013). METHODS: We retrospectively analyzed the EEGs of 50 consecutive nonhypoxic patients with diagnoses of nonconvulsive status epilepticus (NCSE) at discharge and 50 consecutive controls with abnormal EEGs in a large university hospital in Austria. We implemented the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology, 2012 version (ACNS criteria) to increase the test performance of SCNC. In patients without preexisting epileptic encephalopathy, the following criteria were applied: (1) more than 25 epileptiform discharges (ED) per 10-second epoch, i.e., >2.5/s and (2) patients with EDs ≤ 2.5/s or rhythmic delta/theta activity (RDT) exceeding 0.5/s AND at least one of the additional criteria: (2a) clinical and EEG improvements from antiepileptic drugs (AEDs), (2b) subtle clinical phenomena, or (2c) typical spatiotemporal evolution. In case of fluctuation without evolution or EEG improvement without clinical improvement, "possible NCSE" was diagnosed. For identification of RDT, the following criteria were compared: (test condition A) continuous delta-theta activity without further rules, (B) ACNS criterion for rhythmic delta activity (RDA), and (C) ACNS criteria for RDA and fluctuation. RESULTS: False positive rate in controls dropped from 28% (condition A) to 2% (B) (p = 0.00039) and finally to 0% (C) (p = 0.000042). Application of test condition C in the group with NCSE gives one false negative (2%). Various EEG patterns were found in patients with NCSE: (1) 8.2%, (2a) 2%, (2b) 12.2%, and (2c) 32.7%. Possible NCSE was diagnosed based on fluctuations in 57.1% and EEG improvement without clinical improvement in 14.2%. CONCLUSION: The modified SCNC with refined definitions including the ACNS terminology leads to clinically relevant and statistically significant reduction of false positive diagnoses of NCSE and to minimal loss in sensitivity. This article is part of a Special Issue entitled "Status Epilepticus".

Epidemiology-based mortality score in status epilepticus (EMSE).

BACKGROUND: Status epilepticus (SE) is a neurological emergency with high mortality and often a poor functional outcome amongst survivors. So far, only status epilepticus severity score (STESS) is available to predict individual outcomes. STESS is based on weighted sum scores of age, type of seizure, level of consciousness and history of previous seizures. Weighting factors were based on a priori assumptions. METHODS: We tested in an explorative, hypothesis generating approach, whether epidemiological data (i.e. mortality rates) can be combined to form a score (Epidemiology-based Mortality score in SE-EMSE), and further, which combination of aetiology, age, comorbidity, EEG, duration and level of consciousness yields highest test performance. Positive and negative predictive value, and correctly classified were compared to STESS (with different cut-off levels: STESS-3, STESS-4). Score points for each parameter, e.g. age, were derived from previously published specific mortality rates. For each combination of parameters, the lowest sum-score of deceased individuals was taken as cut-off. Ninety-two consecutive non-hypoxic patients (age range 20-90 years), with various forms of SE admitted to a tertiary care neurological intensive care unit were investigated retrospectively. RESULTS: EMSE using a combination of aetiology, age, comorbidity and EEG (NPV = 100 %, PPV = 68.8 %, correctly classified 89.1 %) was superior to STESS-3 and STESS-4 (p = 0.0022 or lower). CONCLUSION: EMSE explained individual mortality in almost 90 % of cases, and performed significantly better than previous scores. This explorative study needs external prospective corroboration. EMSE may be a valuable tool for risk stratification in interventional studies in the future.

Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica.

BACKGROUND: Recently we showed that antibodies to myelin oligodendrocyte glycoprotein (MOG) can be found in aquaporin-4 (AQP4)-immunoglobulin (IgG) seronegative pediatric and adult patients with definite and high-risk neuromyelitis optica (NMO). OBJECTIVE: The purpose of this study was to describe the clinical characteristics and temporal dynamics of MOG-IgG in AQP4-IgG seronegative pediatric patients presenting with definite NMO. METHODS: Children with definite NMO who were referred for further testing of serum antibodies for AQP4 and MOG with a cell-based assay were included in this study. Clinical disease course, cerebrospinal fluid and magnetic resonance imaging (MRI) studies of these patients were reviewed. RESULTS: Between 2008 and 2012 eight children who fulfilled the diagnostic criteria of definite NMO were recruited. Two children with definite NMO tested positive for AQP4-IgG but were negative for MOG-IgG antibodies. Three children had an absence of AQP4-IgG and MOG-IgG antibodies. Three children with definite NMO had high titers of serum MOG-IgG antibodies (≥1: 160), but no AQP4-directed humoral immune response. Longitudinal analysis of serum samples of the latter three children showed persisting high MOG-IgG titers over time. CONCLUSION: Pediatric patients presenting with clinical symptoms and MRI findings highly suggestive of NMO but with high and persisting MOG-IgG antibody titers are most likely to represent a distinct subgroup of acute demyelinating diseases with important clinical and therapeutic implications.

Prevalence of restless legs syndrome in a Georgian primary healthcare setting: a pilot study.

BACKGROUND: The prevalence of restless legs syndrome (RLS) is approximately 10% in Western Europe, but unknown in Georgia. This pilot study aimed to assess RLS prevalence in a focused Georgian population. METHODS: An RLS epidemiological questionnaire [Allen et al.: Sleep Med 2003;4:101-119] was filled out by patients in five primary healthcare centers in two Georgian cities between March and September 2006. Additionally, questions related to RLS symptom onset, family history, treatment, sleep disturbance and history of iron deficiency were included. RLS diagnosis was based on an expert interview and an epidemiological questionnaire for RLS. RESULTS: The total number of respondents was 115 (75% women/25% men); mean age was 47 years (range 18-85). Thirteen subjects (11.3%) reported RLS symptoms (9 women/4 men); mean age was 52 years (range 32-83). Eleven (85%) had a positive family history of RLS. All subjects had sleep disturbance and none had a history of known iron deficiency. CONCLUSION: The prevalence of RLS in a focused Georgian population is in line with other RLS epidemiologic studies performed in clinical settings. However, the prevalence rate of RLS in a studied group might not be representative for the general Georgian population. Further population-based epidemiological studies are required.

Low BMI increases all-cause mortality rates in patients with drug-resistant TB.

BACKGROUND: Loss to follow-up (LTFU) is common among patients with drug-resistant TB (DR-TB) receiving second-line TB treatment; however, little is known about outcomes after LTFU, including mortality.OBJECTIVE: To determine rates of and factors associated with all-cause mortality among patients with DR-TB who were LTFU.METHODS: Retrospective cohort study of adult patients with DR-TB in Georgia who initiated second-line TB treatment during 2011-2014 and were LTFU. Survival analyses were used to estimate all-cause mortality rates and adjusted hazard ratios (aHR).RESULTS: During 2011-2014, 2,437 second-line treatment episodes occurred and 695 patients were LTFU. Among 695 LTFU patients, 143 (21%) died during 2,686 person-years (PY) post-LTFU (all-cause mortality rate 5.1%, 95% CI 4.3-6.0 per 100 PY). In multivariable analysis, low weight (BMI < 18.5 kg/m²) at treatment initiation (aHR 3.2, 95% CI 2.2-4.7), return to treatment after LTFU (aHR 3.1, 95% CI 2.2-4.4), <12 months of treatment (aHR 2.4, 95% CI 1.4-4.1) and a pre-LTFU positive culture (aHR 3.3, 95% CI 2.2-4.9) were associated with all-cause mortality.CONCLUSION: High all-cause mortality occurred among patients with DR-TB after LTFU despite a low HIV prevalence. Providing additional assistance for patients during DR-TB treatment to prevent LTFU and use of new and shorter treatment regimens may reduce mortality among LTFU.

Prevalence of comorbidities, and affective disorders in epilepsy: A latent class analysis approach.

OBJECTIVE: Epilepsies are severe chronic neurological diseases that impair several domains in life and are often accompanied by various somatic and psychiatric comorbidities. Associations between epilepsy and its comorbidities remain poorly understood. As epidemiological research mainly relies on cross-sectional designs and descriptive results, homogeneities regarding comorbidities in individuals suffering from epilepsy remain uncovered. Therefore, we aimed to identify clusters of individuals based on selected seizure-related variables and somatic comorbidities, and their respective risk of experiencing affective disorders, using a Latent Class Analysis (LCA). METHODS: Latent class analysis, is a model-driven statistical approach, which aims at latent, unobservable clusters on selected disease features. LCA has therefore the potential for uncovering previously unobservable groups or classes with similar comorbidity patterns. It allows for comparisons between those classes regarding risk or promotive factors - such as affective disorders. Our data derives from the Austrian cohort of the European Study on Burden and Care of Epilepsy (ESBACE; http://www.esbace.eu/). In ESBACE, multiple factors were collected to get a detailed picture on prevalence, epilepsy-related variables and comorbidities in a population-based cohort from the region of Salzburg, Austria. We used LCA to identify epilepsy-somatic-comorbidity-clusters and further, compared them to the observed the risk of suffering from affective disorders. RESULTS: The prevalence of epilepsy in the study region was 9.14/1000 inhabitants. LCA unveiled a three-cluster solution, of which one cluster, mainly consisting of individuals with mixed seizure types, higher age, and discrete somatic comorbidities (stroke, cardiovascular - and respiratory/pulmonary diseases) had a higher risk of experiencing affective disorders. SIGNIFICANCE: To our knowledge, this is the first large scale study that uses LCA to identify epilepsy-related comorbidity phenotypes, and therefore it might open a new way for epidemiological research.

New anti-seizure medication for elderly epilepsy patients - a critical narrative review.

Introduction: The number of elderly patients with epilepsy is growing in resource rich countries due to demographic changes and increased longevity. Management in these patients is challenging as underlying etiology, co-morbidities, polypharmacy, age-related pharmacokinetic and pharmacodynamic changes need to be considered.Areas covered: Lacosamide, eslicarbazepine acetate, brivaracetam, and perampanel have been approved in the USA and Europe for monotherapy and/or adjunctive treatment of seizures in the last few years. The authors review the pharmacological properties and safety profile of these drugs and provide recommendations for their use in in the elderly.Expert opinion: There are only limited data available on more recent antiseizure medications (ASMs). Drugs with a low risk of interaction (lacosamide, brivaracetam) are preferred choices. Once daily formulations (perampanel and eslicarbazepine acetate) have the advantage of increased compliance. Intravenous formulations (brivaracetam and lacosamide) are useful in emergency situations and in patients who have difficulties to swallow. Dose adjustments are necessary for all ASMs used in the elderly with slow titration and lower target doses than in the regulatory trials. The adverse event profile does not significantly differ from that found in the general adult population.

Idiopathic generalised epilepsy of late onset: a separate nosological entity?

AIM: Seizure onset in idiopathic generalised epilepsies (IGE) is considered to be rare after the second decade of life. The authors aimed to explore age of seizure onset in patients with IGE and compare 'classical' onset to late onset cases. METHODS: Patients with IGE, treated at the outpatient epilepsy clinic (Medical University of Innsbruck, Austria, 1985-2006, n=798) were retrospectively screened. The inclusion criteria were: diagnosis of IGE, more than two follow-up (FU) visits, duration of FU more than 1 year and normal brain imaging. The authors analysed demographic data, age of seizure onset, seizure types, syndromes, neuroimaging and EEG findings, seizure triggers and seizure freedom for 1 and 5 years at last FU. RESULTS: A total of 492 patients (mean age at seizure onset 14.6 years, range 0.1-55, SD 7.9) with IGE were identified: childhood absence epilepsy (n=113, range 1-55, SD 6.5), juvenile absence epilepsy (n=75, range 4-39, SD 5.1), juvenile myoclonic epilepsy (n=112, range 2-39, SD 5.7), and epilepsy with grand mal seizures on awakening (n=192 range 1-52, SD 17.3). Population was stratified into three groups: 28 patients with seizure onset at >30 years, 180 patients between 15 and 30 years and 284 patients <15 years. The distribution of seizure types and epilepsy syndromes differed significantly in a group comparison (p<0.001); seizure outcome and other clinical variables did not differ throughout the groups. CONCLUSION: Apart from age-related onset of seizure types and syndromes with a loose upper limit of onset age, patients with a late onset did not differ from their younger counterparts. These data do not support the view of IGE of late onset as a separate syndrome.

Tuberous sclerosis complex with unilateral perisylvian polymicrogyria and contralateral hippocampal sclerosis - a case report.

Malformations of cortical development (MCD) encompass a wide spectrum of brain disorders. Although rare, the combination of certain MCD may occur. We report a rare case of combination of three distinct cerebral pathologies: tuberous sclerosis, polymicrogyria and hippocampal sclerosis in a patient with intractable epilepsy. Ictal EEG and ictal SPECT suggested right perisylvian area as a seizure onset zone. However, on MRI multiple potentially epileptogenic lesions were identified. The neurobiological background of the coexistence of different types of malformations of cortical development remains enigmatic.

Electroclinical and imaging findings in ulegyria and epilepsy: a study on 25 patients.

PURPOSE: Ulegyria refers to cerebral cortex scarring, which results from a perinatal ischaemic brain injury. It presents with a characteristic gyral pattern: small circumvolutions with atrophy at sulci bottom and spared apex. Ulegyria is frequently associated with epilepsy, cerebral palsy and mental disability. We analysed electroclinical and MRI features in patients with ulegyria and epilepsy. PATIENTS AND METHODS: We reviewed 25 patients (14 males/11 females) with ulegyria and epilepsy from the database (about 5000 patients with epilepsy) of our unit. Patients were examined clinically, underwent high resolution MRI, EEG recordings, positron emission tomography, single photon emission computed tomography and neuropsychological testing. Two patients with refractory seizures underwent epilepsy surgery. RESULTS: Mean age of patients was 34 years (5-66) at the reassessment time. The majority (16/25, 64%) had a history of perinatal asphyxia. 15 patients had delayed developmental milestones; 20 had learning disabilities and five patients were severely disabled. Mean age at seizure onset was 4.2 years (1-18). 17 patients (68%) had medically intractable epilepsy. 11 patients (44%) had occipital lobe seizures. The majority (n = 24, 96%) had parieto-occipital lesions on MRI. In 13 patients (52%), ulegyria was bilateral. 12 patients (48%) had hippocampal sclerosis. Two patients underwent epilepsy surgery with an excellent postoperative outcome (Engel class IA and IC). CONCLUSION: Patients with ulegyria often have a history of perinatal asphyxia and present with pharmacoresistant seizures. Their presurgical assessment is complicated because of frequent dual pathology (hippocampal sclerosis) and bilateral lesions.

A population-based tuberculosis contact investigation in the country of Georgia.

Setting: Identification and screening of contacts of patients with active tuberculosis (TB) is infrequent in low- and middle-income countries. Objective: To estimate the incidence, prevalence and risk factors of latent tuberculous infection (LTBI) and active TB among contacts of newly reported smear-positive TB patients. Design: A population-based contact investigation of sputum smear-positive pulmonary TB (PTB) cases diagnosed between April and December 2012 in Georgia was conducted. LTBI was assessed using the tuberculin skin test (TST). Contacts with active TB were identified from the National TB Program surveillance database. Results: Among 896 index patients with active TB, 3133 contacts were identified and 1157 (37%) underwent a TST, 34% of whom were positive. Most contacts were household contacts (86%) and female (58%). Among contacts, the 1-year period prevalence of active TB was 3.3% (95%CI 2.70-3.98); the incidence rate was 1101 per 100 000 person-years (95%CI 822-1443). In multivariable analysis, household contacts were more likely to have LTBI (adjusted OR [aOR] 2.28, 95%CI 1.49-3.49) than close contacts. Conclusions: A high prevalence of both LTBI and active TB was identified among contacts of PTB cases. Efforts aimed at active case finding among TB contacts should improve early case detection and enhance TB control efforts.

Contexte : Identifier et dépister les contacts des patients atteints de tuberculose (TB) active n'est pas souvent réalisé dans les pays à revenu faible et moyen.Objectif : Estimer l'incidence, la prévalence et les facteurs de risque d'infection tuberculeuse latente (LTBI) et de TB active parmi les contacts de patients TB nouveaux à frottis positif.Schéma : Une investigation en population a été réalisée à la recherche des contacts de cas de TB pulmonaire à frottis positif diagnostiqués entre avril et décembre 2012 en Géorgie ; la LTBI a été évaluée grâce à un test cutané à la tuberculine (TST). Les contacts atteints de TB active ont été identifiés à partir de la base de données de surveillance du Programme National TB.Résultats : Parmi 896 patients index atteints de TB active, 3133 contacts ont été identifiés et 1157 (37%) ont eu un TST, dont 34% ont été positifs. La majorité des contacts ont été des contacts domiciliaires (86%) et des femmes (58%). Parmi les contacts, la prévalence sur un an de la TB active a été de 3,3% (IC95% 2,70­3,98) tandis que le taux d'incidence a été de 1101 par 100 000 années-personne (IC95% 822­1443). En analyse multivariée, les contacts domiciliaires ont été plus susceptibles d'avoir une LTBI (OR ajusté [ORa] 2,28 ; IC95% 1,49­3,49) comparés aux contacts étroits.Conclusion : Une prévalence élevée à la fois de LTBI et de TB active a été identifiée parmi les contacts des cas de TB pulmonaire. Les efforts visant à une recherche active de cas parmi les contacts de TB devraient améliorer une détection précoce des cas et renforcer les efforts de lutte contre la TB.

Marco de referencia: La localización y la investigación de contactos de pacientes con tuberculosis (TB) activa rara vez se siguen en los países con ingresos bajos y medianos.Objetivo: Estimar la incidencia, la prevalencia y los factores de riesgo de contraer la infección tuberculosa latente (LTBI) y la TB activa en los contactos de los casos nuevos de TB con baciloscopia positiva notificados.Método: Se llevó a cabo una investigación de base poblacional de los contactos de casos de TB pulmonar con baciloscopia positiva diagnosticados de abril a diciembre del 2012 en Georgia; se investigó la LTBI mediante la prueba cutánea de la tuberculina (TST). Los contactos con TB activa se localizaron en la base de datos de vigilancia del Programa Nacional contra la Tuberculosis.Resultados: Se reconocieron 3133 contactos de los 896 casos iniciales con TB activa y se practicó la TST en 1157 (37%), de los cuales el 34% obtuvo un resultado positivo. La mayoría de los contactos fueron contactos domiciliarios (86%) y de sexo femenino (58%). En los contactos, la prevalencia a un año de TB activa fue 3,3% (IC95% 2,70­3,98) y la tasa de incidencia fue 1101 por 100 000 años-persona (IC95% 822­1443). El análisis multivariante reveló que la probabilidad de padecer la ITL era mayor en los contactos domiciliarios (cociente de posibilidades ajustado 2,28; IC95% 1,49­3,49) que los contactos directos (no domiciliarios).Conclusiones: Se encontró una alta prevalencia de LTBI y de TB activa en los contactos de los casos de TB pulmonar. Las iniciativas de búsqueda activa de casos en los contactos de los pacientes con TB deberían mejorar la detección temprana y reforzar los esfuerzos de control de la TB.

Unilateral polymicrogyria with ipsilateral cerebral hemiatrophy: a distinct syndrome?

INTRODUCTION: There are sporadic reports of unilateral polymicrogyria with ipsilateral hemiatrophic cerebri associated with epilepsy, focal neurological deficit and mental retardation. The mechanisms which cause this condition are not well understood. The aim of our study was to delineate further, clinical and neuroimaging features of this malformation of cortical development and to explore its possible etiological background. PATIENTS AND METHODS: Four patients (two males and two females), aged from 23 to 31 years (mean age range 27.5 years) were evaluated. Subjects underwent clinical, electrophysiological, neuropsychological and high resolution magnetic resonance imaging assessment. RESULTS: No significant perinatal event or exposure to intrauterine infection was noted. None suffered from birth asphyxia or ischemic injury. The parents of two patients were first cousins. Every subject had delayed developmental milestones, mental disability and congenital, non-progressive, spastic hemiparesis. They had epilepsy with seizure-onset ranging from three months to 17 years (mean 6.8 years); two had intractable seizures. In all patients, unilateral, right-sided polymicrogyria was associated with ipsilateral cerebral hemiatrophy. Polymicrogyria involved mainly anterior perisylvian areas; occipital regions were relatively spared. CONCLUSION: The evaluated patients showed homogenous clinical and neuroimaging characteristics. We support the idea that the disorder could constitute a clinical entity with an underlying genetic cause.

Risk factors associated with loss to follow-up among multidrug-resistant tuberculosis patients in Georgia.

SETTING: Georgia, a country with a high-burden of multi-drug-resistant tuberculosis (MDR-TB). OBJECTIVE: To determine the proportion of loss to follow-up (LFU) among MDR-TB patients treated nationwide from 2009 to 2011, and associated risk factors. DESIGN: Retrospective cohort study involving a review of the National Tuberculosis Programme electronic surveillance database. A Cox proportional hazards model was used to assess risk factors for time to LFU. RESULTS: Among 1593 patients, 458 (29%) were lost to follow-up. A total of 1240 MDR-TB patients were included in the final analysis (845 treatment success, 395 LFU). Over 40% of LFU occurred during the first 8 months of MDR-TB treatment; 40% of patients had not achieved culture conversion at the time of LFU. In multivariate analysis, the factors associated with LFU included male sex, illicit drug use, tobacco use, history of previous anti-tuberculosis treatment, site of TB disease, and place and year of initiating treatment. CONCLUSION: LFU was high among MDR-TB patients in Georgia and posed a significant public health risk, as many were culture-positive at the time of LFU. A multi-pronged approach is needed to address the various patient- and treatment-related characteristics associated with LFU.

Prescribed and self-medication use increase delays in diagnosis of tuberculosis in the country of Georgia.

SETTING: Georgia has a high burden of tuberculosis (TB), including multidrug-resistant TB. Enhancing early diagnosis of TB is a priority to reduce transmission. OBJECTIVE: To quantify delays in TB diagnosis and identify risk factors for delay in the country of Georgia. DESIGN: In a cross-sectional study, persons with newly diagnosed, culture-confirmed pulmonary TB were interviewed within 2 months of diagnosis and medical and laboratory records were abstracted. RESULTS: Among 247 persons enrolled, the mean and median total TB diagnostic delay was respectively 89.9 and 59.5 days. The mean and median patient delay was 56.2 and 23.5 days, while health care system delay was 33.7 and 14.0 days. In multivariable analysis, receipt of a medication prior to TB diagnosis was associated with increased overall diagnostic delay (adjusted odds ratio [aOR] 2.28, 95%CI 1.09-4.79); antibiotic use prior to diagnosis increased the risk of prolonged health care delay (aOR 4.16, 95%CI 1.97-8.79). TB cases who had increased patient-related diagnostic delay were less likely to have prolonged health care diagnostic delay (aOR 0.38, 95%CI 0.19-0.74). CONCLUSION: Prolonged delays in detecting TB are common in Georgia. Interventions addressing the misuse of antibiotics and targeting groups at risk for prolonged delay are warranted to reduce diagnostic delays and enhance TB control.