The Emerging Role of Combined Brain/Heart Magnetic Resonance Imaging for the Evaluation of Brain/Heart Interaction in Heart Failure.

Heart failure (HF) patients frequently develop brain deficits that lead to cognitive dysfunction (CD), which may ultimately also affect survival. There is an important interaction between brain and heart that becomes crucial for survival in patients with HF. Our aim was to review the brain/heart interactions in HF and discuss the emerging role of combined brain/heart magnetic resonance imaging (MRI) evaluation. A scoping review of published literature was conducted in the PubMed EMBASE (OVID), Web of Science, Scopus and PsycInfo databases. Keywords for searches included heart failure, brain lesion, brain, cognitive, cognitive dysfunction, magnetic resonance imaging cardiovascular magnetic resonance imaging electroencephalogram, positron emission tomography and echocardiography. CD testing, the most commonly used diagnostic approach, can identify neither subclinical cases nor the pathophysiologic background of CD. A combined brain/heart MRI has the capability of diagnosing brain/heart lesions at an early stage and potentially facilitates treatment. Additionally, valuable information about edema, fibrosis and cardiac remodeling, provided with the use of cardiovascular magnetic resonance, can improve HF risk stratification and treatment modification. However, availability, familiarity with this modality and cost should be taken under consideration before final conclusions can be drawn. Abnormal CD testing in HF patients is a strong motivating factor for applying a combined brain/heart MRI to identify early brain/heart lesions and modify risk stratification accordingly.

Neuro-inflammatory Sequelae of Minimal Trauma in the Non-traumatized Human Brain: A Microdialysis Study.

Cytokine measurement directly from the brain parenchyma by means of microdialysis has documented the activation of certain procedures in vivo, after brain trauma in humans. However, the intercalation of the micro-catheter insertion with the phenomena triggered by the head trauma renders the assessment of the findings problematic. The present study attempts to elucidate the pure effect of minimal trauma, represented by the insertion of the micro-catheter, on the non-traumatized human brain. Microdialysis catheters were implanted in 12 patients with drug-resistant epilepsy, and subjected to invasive electroencephalography with intracranial electrodes. Samples were collected during the first 5 days of monitoring. The dialysate was analyzed using bead flow cytometry, and the concentrations of interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α (TNF-α) were measured. The levels of IL-1 and IL-8 were found to be raised until 48 h post-implantation, and thereafter they reached a plateau of presumably baseline values. The temporal profile of the IL-6 variation was different, with the increase being much more prolonged, as its concentration had not returned to baseline levels at the fifth day post-insertion. TNF-α was found to be significantly raised only 2 h after implantation. IL-10 and IL-12 did not have any significant response to micro-trauma. These findings imply that the reaction of the neuro-inflammatory mechanisms of the brain exist even after minimal trauma, and is unexpectedly intense for IL-6. Questions may arise regarding the objectivity of findings attributed by some studies to inflammatory perturbation after head injury.

Telemetric intracranial pressure monitoring: our experience with 22 patients investigated for intracranial hypertension.

INTRODUCTION: We present the application of the Raumedic® P-tel telemetric device that monitors Intracranial Pressure (ICP) over long periods, in 22 patients, with suspected intracranial hypertension. METHODS: A telemetric device (Raumedic®, Neurovent® P-tel) was surgically implanted in 22 patients aged between 21 and 65 years. Among the patients, the inconclusive diagnosis of benign intracranial hypertension was set in 10, the possible diagnosis of postoperative hydrocephalus in 3, and the possible diagnosis of aqueduct stenosis in 2. Additionally, shunt malfunction and Normal Pressure Hydrocephalus (NPH) were investigated in 1 and 3 patients, respectively. Finally, 3 patients presented ventricular dilatation of unknown origin. All the individuals underwent a 3-day ICP recording within the nursing unit. Three more recordings were obtained over a period of 2-6 months at the outpatient base. RESULTS: Analysis of the data excluded the diagnosis of intracranial hypertension in 12 patients. Elevated ICP values were confirmed in 10 patients. Subsequently, 7 of them underwent shunts' implantation, while 2 refused further neurosurgical treatment and 1 was treated with acetazolamide. Additionally, 1 patient who demonstrated normal ICP values, thus confirmed with NPH, underwent VP shunt implantation, while another 2 with similar characteristics refused further surgery. In our series the overall clinical complication rate after P-tel implantation was insignificant. CONCLUSIONS: The telemetric device is safely implanted via a rather simple procedure. In selected patients, it could provide long-term ICP recordings, which are necessary to confirm diagnosis and guide to the appropriate treatment.

Effect of constant-current pallidal deep brain stimulation for primary dystonia on cognition, mood and quality of life: Results from a prospective pilot trial.

OBJECTIVE: Knowledge on the effects of DBS on cognitive functions is limited and no data exists on the effects of constant-current DBS (CC-GPi-DBS), which appears to prevail over constant-voltage stimulation. Our aim was to prospectively assess the effect of Constant-Current-GPi-DBS, using an 8-contact lead, on cognition, mood and quality of life. PATIENTS AND METHODS: Ten patients aged 27-49 underwent prospective neuropsychological assessment using dedicated tests. Various cognitive domains (intelligence, executive functions, memory, attention, visuo-spatial perception, verbal intelligence) as well as emotional state and quality of life were examined preoperatively and 1, 6 and 12 months after continuous constant-current DBS. RESULTS: Patients performed preoperatively below average on information processing speed, phonemic verbal fluency and working memory. At 6-months there was an improvement in phonemic verbal fluency (p < .05), which was retained at 12-months postoperatively (p = .05). Results also showed marginal improvement in the Trail Making-A test (p = .051) and the Stroop colour-word test (p < .05). Despite improvement in Quality of Life (Physical and Mental Component improved by 32.42% and 29.46% respectively), patients showed no discernible change in anxiety and depression status. CONCLUSIONS: CC-GPi-DBS for primary dystonia has no discernible negative impact on cognition and mood. If anything, we noted an improvement of certain cognitive functions.

Verbal and Figural Fluency in Temporal Lobe Epilepsy: Does Hippocampal Sclerosis Affect Performance?

BACKGROUND AND OBJECTIVES: Clinicians commonly use verbal and nonverbal measures to test fluency in patients with epilepsy, either during routine cognitive assessment or as part of pre- and postsurgical evaluation. We hypothesized that patients with mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis would perform worse than patients with lateral TLE in both verbal and design fluency. METHODS: We assessed semantic, phonemic, and nonverbal fluency in 49 patients with TLE: 31 with lateral TLE and 18 with mesial TLE plus hippocampal sclerosis. We also gave non-fluency cognitive measures: psychomotor speed, attentional set shifting, selective attention, abstract reasoning, verbal and visual episodic memory, and incidental memory. RESULTS: Patients with mesial TLE performed significantly worse on figural fluency than patients with lateral TLE. Even though group differences on verbal fluency measures were not significant, the patients with mesial TLE had a pattern of poorer performance. The patients with mesial TLE scored significantly worse on measures of selective attention, verbal episodic memory, and incidental memory. CONCLUSIONS: Our study underlines differences in cognitive function between patients with mesial and lateral TLE, particularly in figural fluency. Although we cannot directly assess the role of the hippocampus in cognitive aspects of creative and divergent thinking related to figural fluency, the cognitive discrepancies between these two TLE groups could be ascribed to the mesial TLE hippocampal pathology shown in our study and addressed in the literature on hippocampal involvement in divergent thinking. Our findings could benefit cognitive rehabilitation programs tailored to the needs of patients with TLE.

Constant-Current Deep Brain Stimulation of the Globus Pallidus Internus in the Treatment of Primary Dystonia by a Novel 8-Contact (Octrode) Lead.

OBJECTIVE: To evaluate bilateral constant-current globus pallidus internus (GPi) deep brain stimulation using an 8-contact lead. METHODS: This prospective, open-label, single-center pilot study of 10 patients assessed the feasibility of delivering bilaterally constant-current GPi deep brain stimulation with a novel 8-channel lead to treat primary dystonia using standard scales as outcome measures. RESULTS: Patients included 4 men and 6 women with a mean age of 35.8 years ± 9.2 (range, 27-49 years). Mean age of onset was 18.5 years ± 9.1 (range, 8-35 years), and mean disease duration was 17.3 years (range, 7-27 years). All had primary dystonia (8 generalized dystonia, 1 segmental dystonia, 1 focal dystonia). The primary variable was determined as 50% reduction in dystonia symptoms from baseline to the 6-month follow-up, as defined by the Burke-Fahn-Marsden Dystonia Rating Scale. Six patients (60.0%) achieved >50% reduction in Burke-Fahn-Marsden Dystonia Rating Scale score and were classified as responders at the 6-month follow-up. Five of these 6 responders (83.3%) sustained that response through the assessment at the end of the first year. Constant-current stimulation was associated with significant improvement in pain and quality of life in all patients. Nearly 84% of the overall improvement occurred by the end of first month after stimulation onset, documenting an early response to treatment. Axial symptoms responded the best. CONCLUSIONS: Constant-current GPi deep brain stimulation proved safe and efficacious for treatment of primary dystonia. Motor scores improved by 54%, mostly within the first month. No phenotype-specific stimulation could be achieved, despite the capability of the new lead to stimulate specific loci within the GPi.

Preliminary evidence for gender effects of levetiracetam monotherapy duration on bone health of patients with epilepsy.

Enzyme-inducing antiepileptic drugs AEDs have adverse effects on bone mineral density (BMD), whereas studies on levetiracetam (LEV), a nonenzyme-inducing agent, have showed conflicting results. The aim of this study was to further elucidate the role of LEV in bone health. A sample of forty-six patients with epilepsy (mean age: 35.7 years, range: 20.2-64.2 years, 39.1% males) on LEV monotherapy for at least one year (range: 1.5-14.5 years, median 5.5 years) underwent femoral neck (FN) and lumbar spine (LS) BMD measurements. The T- and Z-scores were calculated. Results showed that 15.2% of the patients were identified with osteopenia and none with osteoporosis. Pearson's correlations revealed a negative but not significant association of LEV duration with bone-related measurements (range of rhos: from -0.004 to -0.23), except for LS T-scores. In terms of FN BMD measurements, Z-scores, and T-scores, longer LEV therapy duration had adverse but not significant effects on bone health after adjusting for age and gender. With regard to LS BMD measurements, Z-scores, and T-scores, men taking LEV for at least 5.5 years had better, although not significant, bone health compared with men with shorter LEV exposure, after adjusting for age. The opposite was found in women, although differences did not reach significance. These preliminary results are indicative of a differential effect of LEV therapy duration in men and women, which could presumably account for the incongruity of the already published studies. Also, LS assessments were more sensitive to these gender differences. Future larger studies should validate these results.

Juvenile myoclonic epilepsy is not associated with the DRPLA gene in a European population.

BACKGROUND: Juvenile myoclonic epilepsy (JME), is an early-onset inherited generalized epilepsy which displays genetic heterogeneity, with at least 10 known loci. Another neurogenetic disease, dentato-rubro-pallido-luysian atrophy (DRPLA) presents three clinical phenotypes, one of which in Japanese displays many similarities to JME. AIM: The purpose of this study was to investigate whether the DRPLA gene is associated with JME in Caucasians. PATIENTS AND METHODS: The CAG repeat polymorphism in the DRPLA gene, which is expanded in patients with DRPLA, was examined with polymerase chain reaction amplification in 107 individuals of Greek origin, including 24 patients with sporadic and 8 with familial JME, 25 healthy relatives and 50 healthy controls. RESULTS: The repeat sizes of all studied individuals were within the normal range. DISCUSSION: These results seem to exclude the DRPLA gene as a major candidate gene for JME in this European population.

Auditory event-related potentials (P300) and mesial temporal sclerosis in temporal lobe epilepsy patients.

AIMS: To investigate the role of centrally recorded P300 in patients suffering from mesial temporal sclerosis-temporal lobe epilepsy (MTS-TLE). METHODS: Sixteen patients (3 men and 13 women; median age: 32.5 years old) suffering from TLE with MTS and 43 healthy controls (12 men and 31 women; median age: 35 years old) participated in the study. P300 was elicited using an auditory two-stimulus oddball paradigm. In order to address the aim of the study, we adopted two statistical approaches; hierarchical linear regression analyses and ROC curves. RESULTS: After adjusting for age, MTS patients had a mean reduction of P300 amplitude by 6.93 µV and a mean increase of P300 latency by 38.78 ms, compared to controls. Age and MTS-TLE status accounted for 32 and 16% of the variance of latency and amplitude, respectively. Diagnostic analyses to detect MTS-TLE status revealed a sensitivity and specificity of 88 and 65% for amplitude and 81 and 70% for latency, respectively. No association between duration of disease and P300 characteristics were found. CONCLUSIONS: This study, along with other studies, contributes to our understanding and clinical significance of centrally recorded P300s in MTS-TLE patients. Future studies should focus on the association of these P300s with cognition in such patients.

Patterns of depressive symptoms in epilepsy.

OBJECTIVE: The purpose of this study was to determine the nature and extent of depressive symptoms among patients with epilepsy. METHODS: Ninety patients were investigated over a three-month period: 42 were suffering from generalized epilepsy, 29 from focal epilepsy and 19 from undetermined epilepsy. All completed the Zung self-rating scale for assessment of the depressive symptoms. RESULTS: Sixty-seven patients felt stigmatized because of epilepsy (67%): 73.6% in the undetermined epilepsy group, 55.1% in the focal epilepsy group and 88% in the generalized epilepsy group. Moreover, among the 90 epileptic patients studied, symptoms of irritability, indecisiveness, personal devaluation and emptiness showed a constant increasing trend for their presence from the undetermined epilepsy group through the generalized epilepsy group to the focal epilepsy group. CONCLUSIONS: These findings indicate that although the focal epilepsy patients felt less stigmatized, they did not differ greatly in terms of depressive symptoms, in relation to the undetermined epilepsy and generalized epilepsy patients.

Patterns of depressive symptoms in epilepsy / Perfis de sintomas depressivos na epilepsia

Objective: The purpose of this study was to determine the nature and extent of depressive symptoms among patients with epilepsy. Methods: Ninety patients were investigated over a three-month period: 42 were suffering from generalized epilepsy, 29 from focal epilepsy and 19 from undetermined epilepsy. All completed the Zung self-rating scale for assessment of the depressive symptoms. Results: Sixty-seven patients felt stigmatized because of epilepsy (67%): 73.6% in the undetermined epilepsy group, 55.1% in the focal epilepsy group and 88% in the generalized epilepsy group. Moreover, among the 90 epileptic patients studied, symptoms of irritability, indecisiveness, personal devaluation and emptiness showed a constant increasing trend for their presence from the undetermined epilepsy group through the generalized epilepsy group to the focal epilepsy group. Conclusions: These findings indicate that although the focal epilepsy patients felt less stigmatized, they did not differ greatly in terms of depressive symptoms, in relation to the undetermined epilepsy and generalized epilepsy patients. .

Objetivo: O objetivo deste estudo foi determinar a natureza e extensão dos sintomas depressivos entre pacientes com epilepsia. Métodos: Noventa pacientes foram avaliados durante o período de três meses: 42 apresentando epilepsia generalizada, 29 com epilepsia focal e 19 com epilepsia indeterminada. Todos completaram a auto-escala de Zung para avaliação de sintomas depressivos. Resultados: Sessenta e sete pacientes se sentiam estigmatizados por causa da epilepsia (67%), sendo 73,6% do grupo epilepsia indeterminada, 55,1% do grupo epilepsia focal e 88% do grupo epilepsia generalizada. Além disto, entre os 90 pacientes epilépticos estudados, os sintomas de irritabilidade, dificuldade para tomar decisões, baixa estima pessoal e sensação de vazio mostraram-se presentes de forma crescente entre os grupos de epilepsia indeterminada, epilepsia generalizada e epilepsia focal. Conclusões: Estes achados indicam que embora os pacientes com epilepsia focal se sintam menos estigmatizados, eles não diferiram de maneira considerável daqueles com epilepsia indeterminada e epilepsia generalizada em termos de sintomas depressivos. .

Vitamin D receptor Bsm1 polymorphism, calcium metabolism and bone mineral density in patients with multiple sclerosis: a pilot study.

Vitamin D receptor's (VDR) genotypes have been associated both with the development of bone disease and the pathogenesis of multiple sclerosis (MS). We aimed to evaluate the association between the presence of Bsm1 restriction fragment length polymorphism of VDR and bone loss in ambulatory patients with MS. This cross-sectional study included 82 adult patients with relapsing-remitting MS. Fasting blood samples were obtained for biochemical-hormonal assessment and genotyping. Bone mineral density (BMD) was assessed at the lumbar spine (LS) and the femoral neck (FN), using dual energy X-ray absorptiometry. Possible associations between VDR's genotypes and BMD levels as well as biochemical and hormonal indices were evaluated. Among premenopausal women and men, carriers of the B allele exhibited higher BMD and Z score at the FN and a trend toward higher BMD at the LS, compared to patients with the bb genotype, after adjusting for age, BMI, sex, EDSS scoring, interferon administration, duration of MS and total steroids intake. Among postmenopausal women, the presence of the B allele was not associated with BMD or T score at any site, whereas carriers of the B allele exhibited higher levels of calcium (p value 0.008, univariate). No other significant differences were exhibited between levels of electrolytes, parathormone, 25-hydroxyvitamin D3 and the genotype of VDR, in any of the groups. VDR's Bsm1 polymorphism is associated with a mild effect on BMD in younger patients with MS. Larger studies are necessary to corroborate these findings.

Depression and anxiety in epilepsy: the association with demographic and seizure-related variables.

BACKGROUND: Depression and anxiety are common psychiatric symptoms in patients with epilepsy, exerting a profound negative effect on health-related quality of life. Several issues, however, pertaining to their association with psychosocial, seizure-related and medication factors, remain controversial. Accordingly, the present study was designed to investigate the association of interictal mood disorders with various demographic and seizure-related variables in patients with newly-diagnosed and chronic epilepsy. METHODS: We investigated 201 patients with epilepsy (51.2% males, mean age 33.2 +/- 10.0 years, range 16-60) with a mean disease duration of 13.9 +/- 9.5 years. Depression and anxiety were assessed in the interictal state with the Beck Depression Inventory, 21-item version (BDI-21) and the state and trait subscales of the State-Trait Anxiety Inventory (STAI-S and STAI-T), respectively. The association of mood disorders with various variables was investigated with simple and multiple linear regression analyses. RESULTS: High seizure frequency and symptomatic focal epilepsy (SFE) were independent determinants of depression, together accounting for 12.4% of the variation of the BDI-21. The STAI-S index was significantly associated with the type of epilepsy syndrome (SFE). Finally, high seizure frequency, SFE and female gender were independent determinants of trait anxiety accounting for 14.7% of the variation of the STAI-T. CONCLUSION: Our results confirm the prevailing view that depression and anxiety are common psychological disorders in epileptics. It is additionally concluded that female gender, high seizure frequency and a symptomatic epilepsy syndrome are independent risk factors for the development of anxiety and/or depression.