Long-Term Outcome After Decompressive Craniectomy in a Developing Country.

BACKGROUND: Decompressive craniectomy (DC) may reduce mortality but might increase the number of survivors in a vegetative state. In this study, we assessed the long-term functional outcome of patients undergoing DC in a middle-income country. METHODS: This was a prospective observational study of patients undergoing DC at a single tertiary hospital in southern Brazil between January 2015 and December 2018. RESULTS: Of the 125 patients who were included in this study, 57.6% (72/125) had a traumatic brain injury (TBI), 21.6% (27/125) had a stroke, 19.2% (24/125) had a cerebral hemorrhage (intracerebral or subarachnoid hemorrhage), and 0.8% (1/125) had a cerebral abscess. The mean age was 45.18 ± 19.6 years, and 71% of the patients were men. The mean initial Glasgow Coma Scale (GCS) score was 7.8 ± 3.6. The in-hospital mortality rate was 44.8% (56/125). Of the survivors, 50.7% (35/69) had a favorable outcome 6 months after DC. After multivariate analysis, a lower initial GCS score (7.5 ± 3.6 versus 8.8 ± 3.5, P = 0.007) and older age (49.7 ± 18.9 versus 33.3 ± 16.2 years, P = 0.0001) were associated with an unfavorable outcome. CONCLUSION: Six months after DC, almost half of the patients who survive have a favorable outcome.

Effects of Cranioplasty After Decompressive Craniectomy on Neurological Function and Cerebral Hemodynamics in Traumatic Versus Nontraumatic Brain Injury.

After decompressive craniectomy (DC), cranioplasty (CP) can help to normalize vascular and cerebrospinal fluid circulation besides improving the patient's neurological status. The aim of this study was to investigate the effects of CP on cerebral hemodynamics and on cognitive and functional outcomes in patients with and without a traumatic brain injury (TBI). Over a period of 3 years, 51 patients were included in the study: 37 TBI patients and 14 non-TBI patients. The TBI group was younger (28.86 ± 9.71 versus 45.64 ± 9.55 years, P = 0.0001), with a greater proportion of men than the non-TBI group (31 versus 6, P = 0.011). Both groups had improved cognitive outcomes (as assessed by the Mini-Mental State Examination) and functional outcomes (as assessed by the Barthel Index and Modified Rankin Scale) 90 days after CP. In the TBI group, the mean velocity of blood flow in the middle cerebral artery ipsilateral to the cranial defect increased between the time point before CP and 90 days after CP (34.24 ± 11.02 versus 42.14 ± 10.19 cm/s, P = 0.0001). In conclusion, CP improved the neurological status in TBI and non-TBI patients, but an increment in cerebral blood flow velocity after CP occurred only in TBI patients.

A Comparative Study of the Effects of Early Versus Late Cranioplasty on Cognitive Function.

Cranioplasty (CP) after decompressive craniectomy (DC) is associated with neurological improvement. We evaluated neurological recovery in patients who underwent late CP (more than 6 months after DC) in comparison with early CP. This prospective study of 51 patients investigated neurological function using the Addenbrooke's Cognitive Examination Revised (ACE-R), Mini-Mental State Examination (MMSE), Barthel Index (BI), and Modified Rankin Scale (mRS) prior to and after CP. Most patients with traumatic brain injury (74%) were young (mean age 33.4 ± 12.2 years) and male (33/51; 66%). There were general improvements in the patients' cognition and functional status, especially in the late-CP group. The ACE-R score increased from the time point before CP to 3 days after CP (51 ± 28.94 versus 53.1 ± 30.39, P = 0.016) and 90 days after CP (51 ± 28.94 versus 58.10 ± 30.43, P = 0.0001). In the late-CP group, increments also occurred from the time point before CP to 90 days after CP in terms of the MMSE score (18.54 ± 1.51 versus 20.34 ± 1.50, P = 0.003), BI score (79.84 ± 4.66 versus 85.62 ± 4.10, P = 0.028), and mRS score (2.07 ± 0.22 versus 1.74 ± 0.20, P = 0.015). CP is able to improve neurological outcomes even more than 6 months after DC.

Early Transcranial Doppler Evaluation of Cerebral Autoregulation Independently Predicts Functional Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Cerebral autoregulation (CA) impairment after aneurysmal subarachnoid hemorrhage (SAH) has been associated with delayed cerebral ischemia and an unfavorable outcome. We investigated whether the early transient hyperemic response test (THRT), a transcranial Doppler (TCD)-based CA evaluation method, can predict functional outcome 6 months after aneurysmal SAH. METHODS: This is a prospective observational study of all aneurysmal SAH patients consecutively admitted to a single center between January 2016 and February 2017. CA was evaluated within 72 h of hemorrhage by THRT, which describes the changes in cerebral blood flow velocity after a brief compression of the ipsilateral common carotid artery. CA was considered to be preserved when an increase ≥ 9% of baseline systolic velocity was present. According to the modified Rankin Scale (mRS: 4-6), the primary outcome was unfavorable 6 months after hemorrhage. Secondary outcomes included cerebral infarction, vasospasm on TCD, and an unfavorable outcome at hospital discharge. RESULTS: Forty patients were included (mean age = 54 ± 12 years, 70% females). CA was impaired in 19 patients (47.5%) and preserved in 21 (52.5%). Impaired CA patients were older (59 ± 13 vs. 50 ± 9, p = 0.012), showed worse neurological conditions (Hunt&Hess 4 or 5-47.4% vs. 9.5%, p = 0.012), and clinical initial condition (APACHE II physiological score-12 [5.57-13] vs. 3.5 [3-5], p = 0.001). Fourteen patients in the impaired CA group and one patient in the preserved CA group progressed to an unfavorable outcome (73.7% vs. 4.7%, p = 0.0001). The impaired CA group more frequently developed cerebral infarction than the preserved CA group (36.8% vs. 0%, p = 0.003, respectively). After multivariate analysis, impaired CA (OR 5.15 95% CI 1.43-51.99, p = 0.033) and the APACHE II physiological score (OR 1.67, 95% CI 1.01-2.76, p = 0.046) were independently associated with an unfavorable outcome. CONCLUSIONS: Early CA impairment detected by TCD and admission APACHE II physiological score independently predicted an unfavorable outcome after SAH.

Understanding the association of neurocysticercosis and mesial temporal lobe epilepsy and its impact on the surgical treatment of patients with drug-resistant epilepsy.

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is one of the most common types of focal epilepsies. This is an epileptic syndrome commonly associated with treatment-resistant seizures, being also the most prevalent form of drug-resistant epilepsy which is treated surgically in most epilepsy surgery centers. Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system, and one of the most common etiological agents of focal epilepsy, affecting millions of patients worldwide. Recently, researchers reported a curious association between MTLE-HS with NCC, but this association remains poorly understood. Some argue that calcified NCC lesions in MTLE-HS patients is only a coincidental finding, since both disorders are prevalent worldwide. However, others suppose there might exist a pathogenic relationship between both disorders and some even suspect that NCC, by acting as an initial precipitating injury (IPI), might cause hippocampal damage and, eventually, MTLE-HS. In this review, we discuss the various reports that examine this association, and suggest possible explanations for why calcified NCC lesions are also observed in patients with MTLE-HS. We also propose mechanisms by which NCC could lead to MTLE-HS. Finally, we discuss the implications of NCC for the treatment of pharmacologically-resistant focal epilepsies in patients with calcified NCC or in patients with MTLE-HS and calcified NCC lesions. We believe that investigations in the relationship between NCC and MTLE-HS might offer further insights into how NCC may trigger epilepsy, and into how MTLE-HS originates. Moreover, observations in patients with drug-resistant epilepsy with both NCC and hippocampal sclerosis may not only aid in the understanding and treatment of patients with MTLE-HS, but also of patients with other forms of dual pathologies aside from NCC. This article is part of a Special Issue titled Neurocysticercosis and Epilepsy.

Tyrosine receptor kinase B gene variants (NTRK2 variants) are associated with depressive disorders in temporal lobe epilepsy.

RATIONALE: Psychiatric comorbidities are highly prevalent in epilepsy, adding an important burden to the disease and profoundly affecting the quality of life of these individuals. Patients with temporal lobe epilepsy (TLE) are especially at risk to develop depression and several lines of evidence suggest that the association of depression with epilepsy might be related to common biological substrates. In this study, we test whether NTRK2 allele variants are associated with mood disorders or depressive disorders in patients with TLE. METHODS: An association study of 163 patients with TLE. The NTRK2 variants studied were rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. All patients were submitted to the Structured Clinical Interview for DSM-IV (SCID) and epilepsy patients with mood disorders or depressive disorders were compared to epilepsy patients without mood disorders or depressive disorders. RESULTS: In our TLE cohort, 76 patients (46.6%) showed mood disorders. After logistic regression, independent risk factors for mood disorders in TLE were female sex, presence of concomitant anxiety disorders, and genetic variations in rs1867283 and rs10868235 NTRK2 variants. Depressive disorders accounted for this results and independent variables associated with depressive disorders in TLE were female sex (OR=2.59; 95%CI=1.15-5.82; p=0.021), presence of concomitant anxiety disorders (OR=3.72; 95%CI=1.71-8.06; p=0.001) or psychotic disorders (OR=3.86; 95%CI=1.12-13.25; p=0.032), A/A genotype in the rs1867283 NTRK2 gene (OR=3.06; 95%CI=1.25-7.50; p=0.015) and C/C genotype in the rs10868235 NTRK2 gene (OR=3.54; 1.55-8.08; p=0.003). Similarly, these genotypes also remained independently and significantly associated with depressive disorders when patients with depressive disorders were compared to TLE patients without any psychiatric comorbidity. CONCLUSION: In the present study, female sex, presence of concomitant anxiety or psychotic disorders, and specific allelic variations in the NTRK2 gene were independently associated with mood disorders or depressive disorders in TLE. If our results were confirmed, variants in the NTRK2 gene could be considered as risk factors or biomarkers for depressive disorders in patients with TLE.

Tryptophan hydroxylase 2 (TPH2) gene polymorphisms and psychiatric comorbidities in temporal lobe epilepsy.

Psychiatric comorbidities are frequent in temporal lobe epilepsy (TLE). It is plausible that variance in serotonin-related genes is involved in the susceptibility of these associations. We report here the results on the association of tryptophan hydroxylase 2 (TPH2) gene polymorphisms with psychiatric comorbidities in TLE. A cohort study was conducted on 163 patients with TLE. We assessed the influence of the rs4570625 and rs17110747 polymorphisms in the TPH2 gene on psychiatric comorbidities in TLE. In patients with TLE, the presence of the T allele in the rs4570625 polymorphism was associated with psychotic disorders (OR=6.28; 95% CI=1.27-17.54; p=0.02), while the presence of the A allele in the rs17110747 polymorphism was associated with alcohol abuse (OR=20.33; 95% CI=1.60-258.46; p=0.02). Moreover, we identified male gender (OR=11.24; 95% CI=1.68-76.92; p=0.01) and family history of psychiatric disorder (OR=15.87; 95% CI=2.46-100; p=0.004) as factors also associated with alcohol abuse in TLE. Conversely, a family history of epilepsy was inversely associated with alcohol abuse (OR=0.03; 95% CI=0.001-0.60; p=0.02). Tryptophan hydroxylase 2 gene allele variants might be risk factors for psychiatric conditions in TLE. More specifically, we observed that the T allele in the rs4570625 polymorphism was associated with psychotic disorders, and the A allele in the rs17110747 TPH2 polymorphism was associated with alcohol abuse in patients with TLE. We believe that this study may open new research venues on the influence of the serotonergic system associated with psychiatric comorbidities in epilepsy.

Autoimmune encephalitis in a resource-limited public health setting: a case series analysis.

BACKGROUND: Autoimmune encephalitis (AE) consists of a group of acquired diseases that affect the central nervous system. A myriad of phenotypes may be present at the onset. Due to the heterogeneity of clinical presentations, it is difficult to achieve uniformity for the diagnostic and therapeutic processes and follow-up strategies. OBJECTIVE: To describe a series of patients diagnosed with AE in a resource-limited public hospital in southern Brazil and to analyze therapeutics and outcomes. METHODS: We retrospectively reviewed the electronic medical records of patients diagnosed with AE at the Hospital de Clínicas de Porto Alegre from 2014 to 2022. Data collected included clinical presentation, neuroimaging, cerebrospinal fluid testings, electroencephalogram, autoantibodies, treatments, outcomes, follow-up time, degree of neurological impairment, and mortality. RESULTS: Data from 17 patients were retrieved. Eleven cases were classified as definite AE and 6 as possible AE. Autoantibodies were identified in 9 patients. Timing for diagnosis was impacted by the high costs associated with autoantibody testing. Most patients became functionally dependent (82.4%) and most survivors remained with autoimmune-associated epilepsy (75%). Five patients died during hospitalization, and one after a 26-month of follow-up. CONCLUSION: In this resource-limited hospital, patients with AE had a worse clinical outcome than that previously described in the literature. Development of epilepsy during follow-up and mortality were greater, whilst functional outcome was inferior. Autoantibody testing was initially denied in most patients, which impacted the definitive diagnosis and the use of second-line therapies.

ANTECEDENTES: A encefalite autoimune (EA) consiste em um grupo de doenças adquiridas que afetam o sistema nervoso central. OBJETIVO: Descrever uma série de pacientes diagnosticados com EA em um contexto de atenção terciária à saúde com recursos limitados e analisar a terapêutica e os resultados. MéTODOS: Revisamos retrospectivamente os prontuários eletrônicos de pacientes diagnosticados com EA no Hospital de Clínicas de Porto Alegre de 2014 a 2022. Os dados coletados incluíram apresentação clínica, neuroimagem, exames de líquido cefalorraquidiano, eletroencefalograma, autoanticorpos, tratamentos, resultados, tempo de acompanhamento, grau de comprometimento neurológico e mortalidade. RESULTADOS: Dados de 17 pacientes foram coletados. Onze casos foram classificados como EA definitivo e seis como EA possível. Autoanticorpos foram identificados em nove pacientes. O tempo para o diagnóstico foi afetado pelos altos custos associados ao teste de autoanticorpos. A maioria dos pacientes tornou-se funcionalmente dependente (82,4%), e a maioria dos sobreviventes permaneceu com epilepsia autoimune associada (75%). Cinco pacientes faleceram durante a internação, e um após 26 meses de seguimento. CONCLUSãO: No hospital em questão, os pacientes com EA tiveram um desfecho clínico pior do que o previamente descrito na literatura. O desenvolvimento de epilepsia durante o acompanhamento e a mortalidade foram maiores, enquanto o desfecho funcional foi inferior. Os testes de autoanticorpos foram inicialmente negados para a maioria dos pacientes, o que impactou o diagnóstico definitivo e o uso de terapias de segunda linha.

Measuring quality and safety of epilepsy monitoring units in Brazil: Adoption of quality indicators.

PURPOSE: Drug-resistant epilepsy affects a substantial proportion (30-40 %) of patients with epilepsy, often necessitating video-electroencephalography (video-EEG) monitoring. In 2016, Sauro et al. introduced a set of measures aimed at improving the quality and safety indicators reported in video-EEG evaluations. This study aims to report our experience with the implementation of these measures. METHODS: We analyzed video-EEG data regarding quality and safty from a period spanning January 2016 to January 2018, involving a total of 101 patients monitored in our video-EEG unit. RESULTS: Among the patients included in the study, a definitive diagnosis was attainable for 92.1 %, with 36.6 % experiencing a change in diagnosis and 65.3 % undergoing a change in treatment as a result of the video-EEG evaluation. Additionally, the referral question was fully addressed in 60.4 % of admissions, and video-EEG was considered to be very useful or extremely useful in 66.4 % of cases. Adverse events were observed in 26.7 % of patients, with the most common being the progression of focal seizures to bilateral tonic-clonic seizures (11.9 %) and the occurrence of seizure clusters (5.9 %). CONCLUSION: Our findings support the implementation of Sauro et al.'s set of measures, as they provide valuable criteria for improving the reporting of video-EEG quality and safety indicators. However, challenges may arise due to variations in terminology across studies and the lack of standardized criteria for defining essential questions in video-EEG evaluations. Further research utilizing these measures is necessary to enhance their effectiveness and encourage consistent reporting of results from epilepsy monitoring units.

Morphological variations of hippocampal formation in epilepsy: image, clinical and electrophysiological data.

Morphological variations of hippocampal formation (MVHF) are observed in patients with epilepsy but also in asymptomatic individuals. The precise role of these findings in epilepsy is not yet fully understood. This study analyzes the hippocampal formation (HF) morphology of asymptomatic individuals (n = 30) and of patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) (n = 68), patients with malformations of cortical development (MCD) (n = 34), or patients with pure morphological variations of hippocampal formation (pure MVHF) (n = 12). Main clinical and electrophysiological data of patients with MVHF were also analyzed. Morphological variations of hippocampal formation are more frequently observed in patients with MCD than in patients with MTLE-HS or in asymptomatic individuals. Patients with pure morphological variations of hippocampal formation showed higher incidence of extratemporal seizure onset. Refractoriness seems to be more associated with other abnormalities, like HS or MCD, than with the HF variation itself. Thus, although morphological HF abnormalities might play a role in epileptogenicity, they seem to contribute less to refractoriness.

Impact of the chronic use of benzodiazepines prescribed for seizure control on the anxiety levels of patients with epilepsy.

In a cross-sectional study, we evaluated the impact of the chronic use of benzodiazepines (BDZ) prescribed for seizure control on the anxiety levels of patients with temporal lobe epilepsy. We assessed the anxiety level of 99 patients with temporal lobe epilepsy with (n=15) or without (n=84) BDZ for seizure control, using the Beck Anxiety Inventory (BAI) or the Hamilton Anxiety Scale (HAMA). Independent risk factors for high anxiety levels were being a female patient (O.R.=2.93; 95% C.I.=1.05-8.16; p=0.039), having uncontrolled seizures (O.R.=4.49; 95% C.I.=1.66-12.11; p=0.003) and having a history of a psychiatric disorder (O.R.=4.46; 95% C.I.=1.63-12.21; p=0.004). However, there were no statistically significant differences in anxiety levels between patients utilizing or not utilizing BDZ prescribed exclusively for seizure control. We concluded that in our study, patients with chronic use of BDZ prescribed exclusively for seizure control showed similar anxiety levels than patients who were not using this class of drug. Additional studies are needed to define better strategies for the treatment of anxiety disorders in epilepsy.

Primary Microglia Dysfunction or Microgliopathy: A Cause of Dementias and Other Neurological or Psychiatric Disorders.

Microglia are unique cells in the central nervous system (CNS), being considered a sub-type of CNS macrophage. These cells monitor nearby micro-regions, having roles that far exceed immunological and scavengering functions, being fundamental for developing, protecting and maintaining the integrity of grey and white matter. Microglia might become dysfunctional, causing abnormal CNS functioning early or late in the life of patients, leading to neurologic or psychiatric disorders and premature death in some patients. Observations that the impairment of normal microglia function per se could lead to neurological or psychiatric diseases have been mainly obtained from genetic and molecular studies of Nasu-Hakola disease, caused by TYROBP or TREM2 mutations, and from studies of adult-onset leukoencephalopathy with axonal spheroids (ALSP), caused by CSF1R mutations. These classical microgliopathies are being named here Microgliopathy Type I. Recently, mutations in TREM2 have also been associated with Alzheimer Disease. However, in Alzheimer Disease TREM2 allele variants lead to an impaired, but functional TREM2 protein, so that patients do not develop Nasu-Hakola disease but are at increased risk to develop other neurodegenerative diseases. Alzheimer Disease is the prototype of the neurodegenerative disorders associated with these TREM2 variants, named here the Microgliopathies Type II. Here, we review clinical, pathological and some molecular aspects of human diseases associated with primary microglia dysfunctions and briefly comment some possible therapeutic approaches to theses microgliopathies. We hope that our review might update the interesting discussion about the impact of intrinsic microglia dysfunctions in the genesis of some pathologic processes of the CNS.

Device size selection can enhance Y-stentrieving efficacy and safety as a rescue strategy in stroke thrombectomy.

BACKGROUND: Despite advancements in stroke treatment, refractory clots are relatively common, prompting the exploration of alternative techniques. Bifurcation occlusions pose specific intraprocedural challenges, occasionally dealt with by two stentrievers deployed in Y-configuration. Previous studies have portrayed this strategy as feasible, yet little is known about its safety and efficacy, and how to best select retrievers. OBJECTIVE: To determine whether device selection influences the efficacy and safety of Y-stentrieving. METHODS: We performed a multicentric, retrospective analysis of patients undergoing Y-stentrieving rescue for bifurcation occlusions. Demographics, devices, procedural metrics, neurological severity, reperfusion, disability, and safety were assessed. RESULTS: Y-configuration stents were used as a rescue maneuver after 2.16±1.5 failed attempts with other techniques in 20 patients. Successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3) was achieved in 70% of patients after the first Y-stentrieving attempt. The first stentriever more often had a larger diameter (5.15±0.92 vs 3.67±0.57 mm, p=0.017) and longer length (33.12±5.78 vs 20.67±1.15 mm, p=0.002) in successfully reperfused cases. Also, the diameter of the first device was associated with both any parenchymal (6.0 vs 4.71±0.99 mm, p=0.045) and symptomatic (6.0 vs 4.86±1.02 mm, p<0.001) hemorrhages. Exact logistic regression demonstrated that a longer length first stentriever independently predicted better angiographic outcomes (OR=1.26, p=0.036), and a 6 mm diameter first stentriever independently predicted more intracranial hemorrhages (OR=15.28, p=0.044). No periprocedural mortality was recorded. CONCLUSION: Y-stentrieving is an effective and safe bail-out strategy for refractory bifurcation clots. Longer stents may promote better angiographic outcomes, whereas avoidance of disproportionately large retrievers may mitigate intracranial hemorrhage. Future studies should account for these factors when evaluating alternative stentriever techniques.

Biomarkers in the prognostic evaluation of ischemic stroke: Is there benefit in the measurements of TREM-1 and TREM-2 in the acute phase?

BACKGROUND AND PURPOSE: Triggering receptors expressed on myeloid cells 1 and 2 (TREM-1 and TREM-2) are cell surface receptors important for modulation of microglia immune response. In this study, we evaluate serum levels of TREM-1 and TREM-2 as potential biomarkers in acute ischemic stroke (AIS). MATERIAL AND METHODS: Prospective cohort study of 50 patients with AIS admitted at our hospital. Serum TREM-1 and TREM-2 was evaluated within 24 h of the acute event and on the third and fifth days after the stroke. Neurological stroke severity and global disability were determined with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at the same three times and at the time of hospital discharge. RESULTS: TREM-1 and TREM-2 levels were elevated in stroke. TREM-1, but not TREM-2, exhibited correlations with NIHSS and mRS within 24 h (NIHSS and TREM-1: rS = 0.31, p = 0.029; mRS and TREM-1: rS = 0.32, p = 0.023). The serum level of TREM-1 within 24 h correlated with the neurological outcomes at hospital discharge (NIHSS and TREM-1: p = 0.021; mRS and TREM-1: p = 0.049). The serum concentrations of TREM-1 protein within 24 h after stroke was significantly higher in patients with poor outcome (mRS > 2) at hospital discharge (p = 0.021). After Exact Logistic Regression, large segmental stroke (O.R. = 4.14; 95CI = 1.07-16.09; p = 0.040) and initial sTREM levels (O.R. = 1.02; 95CI 1.00-1.04; p = 0.045) remained independent prognostic factors for AIS poor outcome (mRS > 2). CONCLUSION: In our study, TREM-1 and TREM-2 were significantly increased in AIS. Early elevation of TREM-1 correlated with stroke severity and it was an independent prognostic factor for stroke outcome.

IL-23 and IL-17 in acute ischemic stroke: Correlation with stroke scales and prognostic value.

BACKGROUND AND PURPOSE: Inflammation plays a crucial role in brain damage following stroke. Here, we evaluate interleukin 23 (IL-23) and interleukin 17 (IL-17) in the inflammatory process and its relations with neurological findings of patients with acute ischemic stroke (AIS). MATERIAL AND METHODS: Fifty consecutive patients with AIS admitted to our hospital within 24 h of stroke onset were enrolled in a prospective cohort study. Serum IL-23 and IL-17 were measured in the first, third and fifth day after the stroke. Neurological stroke severity were determined with the National Institutes of Health Stroke Scale (NIHSS) and with the modified Rankin Scale (mRS) within 24 h of the acute event, on the third and fifth day after the stroke, and at the time of hospital discharge. RESULTS: Both neurological scores for stroke outcome at hospital discharge were related to IL-23 protein within 24 h and on the fifth day, but with low stroke outcome predictive values. The other measurements did not show predictive capacity for stroke outcome. There was a significant increase in median serum concentrations of IL-23 on the fifth day (p < 0.001) and in IL-17 median levels on the third day compared to the first 24 h after the acute injury (p < 0.001). However, there was no correlation between IL-23 and IL-17 levels with neurological outcomes at hospital discharge or after four years. CONCLUSION: IL-23 and IL-17 increase after stroke, but had no sufficient discriminative capacity to be of clinical use as outcome stroke predictors.

Evaluating the Association of Calcified Neurocysticercosis and Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis in a Large Cohort of Patients With Epilepsy.

BACKGROUND: Neurocysticercosis (NCC) is a parasitic infection of the central nervous system that has been associated with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). However, this association has not been completely established. OBJECTIVE: To evaluate the prevalence of calcified NCC (cNCC), its characteristics and a possible association between cNCC and MTLE-HS in a cohort of 731 patients with epilepsy. METHODS: We review clinical, EEG and neuroimaging findings of 731 patients with epilepsy. From these, 659 had CT-scans and 441 patients had complete neuroimaging with CT-scans and MRI. In these patients, we review the prevalence and characteristic of epilepsy in cNCC and in MTLE-HS patients. RESULTS: Forty-two (6.4%) of the 659 patients studied with CT-scans had cNCC. cNCC lesions were more frequent in women than in men (n = 33-78.6% vs. n = 09-21.4%, respectively; OR = 3.64;(95%CI = 1.71-7.69); p < 0.001). cNCC was more often in patients who developed epilepsy later in life, in older patients, in patients who had a longer history of epilepsy, and in those with a lower educational level. MTLE-HS was observed in 93 (21.1%) of 441 patients that had complete neuroimaging, and 25 (26.9%) of these 93 patients also had cNCC. Calcified NCC was observed in only 17 (4.9%) of the remaining 348 patients that had other types of epilepsy rather than MTLE-HS. Thus, in our cohort, cNCC was more frequently associated with MTLE-HS than with other forms of epilepsy, O.R. = 11.90;(95%CI = 6.10-23.26); p < 0.0001). CONCLUSIONS: As expected, in some patients the epilepsy was directly related to cNCC lesional zone, although this was observed in a surprisingly lower number of patients. Also, cNCC lesions were observed in other forms of epilepsy, a finding that could occur only by chance, with epilepsy probably being not related to cNCC at all. In this cohort, cNCC was very commonly associated with MTLE-HS, an observation in agreement with the hypothesis that NCC can contribute to or directly cause MTLE-HS in many patients. Given the broad world prevalence of NCC and the relatively few studies in this field, our findings add more data suggesting a possible and intriguing frequent interplay between NCC and MTLE-HS, two of the most common causes of focal epilepsy worldwide.

Methylation of BDNF and SLC6A4 Gene Promoters in Brazilian Patients With Temporal Lobe Epilepsy Presenting or Not Psychiatric Comorbidities.

The relationship between epilepsy and psychiatric comorbidities has been recognized for centuries, but its pathophysiological mechanisms are still misunderstood. It is biologically plausible that genetic or epigenetic variations in genes that codify important neurotransmitters involved in epilepsy as well as in psychiatric disorders may influence the development of the latter in patients with epilepsy. However, this possibility remains poorly investigated. The aim of this study was to evaluate the methylation profile of the BDNF and SLC6A4, two genes importantly involved in neuroplasticity, in patients with temporal lobe epilepsy (TLE) regarding the development or not of psychiatric comorbidities. One hundred and thirty-nine patients with TLE, 90 females and 45 males, were included in the study. The mean age of patients was 44.0 (+12.0) years, and mean duration of epilepsy was 25.7 (+13.3) years. The Structured Clinical Interview for DSM-IV shows that 83 patients (59.7%) had neuropsychiatric disorders and 56 (40.3%) showed no psychiatric comorbidity. Mood disorders were the most common psychiatric disorder observed, being present in 64 (46.0%) of all 139 patients. Thirty-three (23.7%) patients showed anxiety disorders, 10 (7.2%) patients showed history of psychosis and 8 (5.8%) patients showed history of alcohol//drug abuse. Considering all 139 patients, 18 (12.9%) demonstrated methylation of the promoter region of both BDNF and SLC6A4 genes. A significant decreased methylation profile was observed only in TLE patients with mood disorders when compared with TLE patients without a history of mood disorders (O.R. = 3.45; 95% C.I. = 1.08-11.11; p = 0.04). A sub-analysis showed that TLE patients with major depressive disorder mostly account for this result (O.R. = 7.20; 95% C.I. = 1.01-56.16; p = 0.042). A logistic regression analysis showed that the independent factors associated with a history of depression in our TLE patients was female sex (O.R. = 2.30; 95% C.I. = 1.02-5.18; p = 0.044), not controlled seizures (O.R. = 2.51; 95% C.I. = 1.16-5.41; p = 0.019) and decreased methylation in BDNF and SLC6A4 genes (O.R. = 5.32; 95% C.I. = 1.14-25.00; p = 0.033). Our results suggest that BDNF or SLC6A4 genes profile methylation is independently associated with depressive disorders in patients with epilepsy. Further studies are necessary to clarify these matters.

Home-Based Transcranial Direct Current Stimulation for the Treatment of Symptoms of Depression and Anxiety in Temporal Lobe Epilepsy: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

We conducted a double-blind randomized clinical trial in order to examine the effects and the safety of home-based transcranial direct current stimulation (tDCS) on depressive and anxious symptoms of patients with temporal lobe epilepsy (TLE). We evaluated 26 adults with TLE and depressive symptoms randomized into two different groups: active tDCS (tDCSa) and Sham (tDCSs). The patients were first submitted to 20 sessions of tDCS for 20 min daily, 5 days a week for 4 weeks and then received a maintenance tDCS application in the research laboratory once a week for 3 weeks. The intensity of the current was 2 mA, applied bilaterally over the dorsolateral prefrontal cortex, with the anode positioned on the left side and the cathode on the right side. Participants were evaluated on days 1, 15, 30, and 60 of the study using the Beck Depression Inventory II (BDI). A follow-up evaluation was performed 1 year after the end of treatment. They were also evaluated for quality of life and for anxious symptoms as secondary outcomes. The groups did not differ in clinical, socioeconomic or psychometric characteristics at the initial assessment. There was no statistically significant difference between groups regarding reported adverse effects, seizure frequency or dropouts. On average, between the 1st and 60th day, the BDI score decreased by 43.93% in the active group and by 44.67% in the Sham group (ΔBDIfinal - initial = -12.54 vs. -12.20, p = 0.68). The similar improvement in depressive symptoms observed in both groups was attributed to placebo effect and interaction between participants and research group and not to tDCS intervention per se. In our study, tDCS was safe and well tolerated, but it was not effective in reducing depressive or anxiety symptoms in patients with temporal lobe epilepsy. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03871842].

Migraine and epilepsy: a focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects.

The association of epilepsy and migraine has been long recognized. Migraine and epilepsy are both chronic disorders with episodic attacks. Furthermore, headache may be a premonitory or postdromic symptom of seizures, and migraine headaches may cause seizures per se (migralepsy). Migraine and epilepsy are comorbid, sharing pathophysiological mechanisms and common clinical features. Several recent studies identified common genetic and molecular substrates for migraine and epilepsy, including phenotypic-genotypic correlations with mutations in the CACNA1A, ATP1A2, and SCN1A genes, as well as in syndromes due to mutations in the SLC1A3, POLG, and C10orF2 genes. Herein, we review the relationship between migraine and epilepsy, focusing on clinical aspects and some recent pathophysiological and molecular studies.

Prevalence of psychiatric comorbidities in temporal lobe epilepsy: the value of structured psychiatric interviews.

BACKGROUND: Although many studies have demonstrated a high prevalence of psychiatric disorders in epileptic patients, most have used unstructured psychiatric interviews for diagnosis, which may lead to significant differences in results. Here we present a study evaluating the prevalence of major psychiatric comorbidities in a cohort of South Brazilian patients with temporal lobe epilepsy using a structured clinical interview. METHODS: Neuropsychiatric symptoms were analyzed in 98 patients (39 men and 59 women) with temporal lobe epilepsy. Patient mean age was 43 years old, and mean duration of epilepsy was 25 years. Patients were diagnosed according to the ILAE Classification of Epileptic Syndromes using clinical, EEG, and neuroimaging criteria. All patients participated in the Structured Clinical Interview for DSM-IV (SCID). RESULTS: Fifty-three patients (54.1%) presented major psychiatric comorbidities. Mood disorders were observed in 42 patients (42.9%), the most common being neuropsychiatric disorders. Anxiety disorders were the second most frequent disorders, observed in 18 patients (18.4%). Psychotic disorders and substance abuse were each observed in six patients (6.1%). There were no clinical variables regarding epilepsy characteristics (age of onset, duration, response to antiepileptic drugs) and no MRI features associated with psychiatric disorders. A seven-fold increased risk of mood disorders was identified in patients with inter-ictal EEG abnormalities associated with the left hemisphere. CONCLUSION: Relative to previous reports, we identify a high prevalence of psychiatric disorders in TLE patients, although our data is similar to that observed in other studies which have used similar structured interviews in populations of epileptic patients attending tertiary centres. The wide variation in percentages is probably attributable to the different patient groups investigated and to the even greater variety of diagnostic methods. Structured psychiatric interviews may contribute to a better evaluation of the true prevalence of psychiatric comorbidities in temporal lobe epilepsy.