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Ioannis Siasios, Eftychia Z. Kapsalaki, Kostas N. Fountas, Aggeliki Fotiadou, Alexander Dorsch, Kunal Vakharia, John Pollina and Vassilios Dimopoulos

OBJECTIVE

Diffusion tensor imaging (DTI) for the assessment of fractional anisotropy (FA) and involving measurements of mean diffusivity (MD) and apparent diffusion coefficient (ADC) represents a novel, MRI-based, noninvasive technique that may delineate microstructural changes in cerebral white matter (WM). For example, DTI may be used for the diagnosis and differentiation of idiopathic normal pressure hydrocephalus (iNPH) from other neurodegenerative diseases with similar imaging findings and clinical symptoms and signs. The goal of the current study was to identify and analyze recently published series on the use of DTI as a diagnostic tool. Moreover, the authors also explored the utility of DTI in identifying patients with iNPH who could be managed by surgical intervention.

METHODS

The authors performed a literature search of the PubMed database by using any possible combinations of the following terms: “Alzheimer's disease,” “brain,” “cerebrospinal fluid,” “CSF,” “diffusion tensor imaging,” “DTI,” “hydrocephalus,” “idiopathic,” “magnetic resonance imaging,” “normal pressure,” “Parkinson's disease,” and “shunting.” Moreover, all reference lists from the retrieved articles were reviewed to identify any additional pertinent articles.

RESULTS

The literature search retrieved 19 studies in which DTI was used for the identification and differentiation of iNPH from other neurodegenerative diseases. The DTI protocols involved different approaches, such as region of interest (ROI) methods, tract-based spatial statistics, voxel-based analysis, and delta-ADC analysis. The most studied anatomical regions were the periventricular WM areas, such as the internal capsule (IC), the corticospinal tract (CST), and the corpus callosum (CC). Patients with iNPH had significantly higher MD in the periventricular WM areas of the CST and the CC than had healthy controls. In addition, FA and ADCs were significantly higher in the CST of iNPH patients than in any other patients with other neurodegenerative diseases. Gait abnormalities of iNPH patients were statistically significantly and negatively correlated with FA in the CST and the minor forceps. Fractional anisotropy had a sensitivity of 94% and a specificity of 80% for diagnosing iNPH. Furthermore, FA and MD values in the CST, the IC, the anterior thalamic region, the fornix, and the hippocampus regions could help differentiate iNPH from Alzheimer or Parkinson disease. Interestingly, CSF drainage or ventriculoperitoneal shunting significantly modified FA and ADCs in iNPH patients whose condition clinically responded to these maneuvers.

CONCLUSIONS

Measurements of FA and MD significantly contribute to the detection of axonal loss and gliosis in the periventricular WM areas in patients with iNPH. Diffusion tensor imaging may also represent a valuable noninvasive method for differentiating iNPH from other neurodegenerative diseases. Moreover, DTI can detect dynamic changes in the WM tracts after lumbar drainage or shunting procedures and could help identify iNPH patients who may benefit from surgical intervention.

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Kostas N. Fountas, Ioannis Tsougos, Efstathios D. Gotsis, Stylianos Giannakodimos, Joseph R. Smith and Eftychia Z. Kapsalaki

Object

The purpose of this prospective study was to compare the results of proton MR spectroscopy (MRS) in temporal poles in patients with unilateral mesial temporal sclerosis (MTS) with the histopathological findings of the resected temporal poles.

Methods

A total of 23 patients (14 male and 9 female) with a mean age of 25.2 years (range 17–45 years) were included in this study, which was conducted over a 4-year period. All patients suffered medically refractory epilepsy due to unilateral, MRI-proven MTS, with no other imaging abnormalities. All participants underwent preoperative single-voxel proton MRS using a 3-T MRI unit. The hippocampi and temporal poles were examined bilaterally. The concentrations of N-acetyl-aspartate (NAA), choline (Cho), and creatine (Cr) were measured, and the NAA/Cho, NAA/Cr, and NAA/Cho+Cr ratios were calculated. All patients underwent anterior temporal lobectomy and ipsilateral amygdalohippocampectomy, and surgical specimens from the temporal poles were sent for histopathological examination. Comparisons of the spectroscopic and histopathological results of the resected temporal poles were performed. The modified Engel classification system was used for evaluating seizure outcome in the cohort.

Results

The preoperative spectroscopic profiles of the sclerotic hippocampi were abnormal in all patients, and the contralateral hippocampus showed altered spectroscopic findings in 12 patients (52.2%). Spectroscopy of the temporal poles demonstrated severely decreased concentrations of NAA, markedly increased concentrations of Cho, and increased concentrations of Cr in the temporal pole ipsilateral to the MTS in 15 patients (65.2%). Similarly, the NAA/Cho, NAA/Cr, and NAA/Cho+Cr ratios were severely decreased in the temporal pole ipsilateral to the MTS in 16 patients (69.6%). Histopathological examination of the resected temporal poles demonstrated ischemic changes in 5 patients (21.7%), gliotic changes in 4 (17.4%), demyelinating changes in 3 (13.0%), and microdysplastic changes in 1 patient (4.3%). Comparisons of the spectroscopic and histopathological findings showed that the sensitivity of proton MRS was 100%, its specificity was 80%, its positive predictive value was 87%, and its negative predictive value was 100%. The mean follow-up time in this study was 3.4 years. At the end of the 2nd postoperative year, 17 patients (73.9%) were in Engel Class I, 5 (21.7%) were in Class II, and 1 (4.3%) was in Class III.

Conclusions

Proton MRS detected altered ipsilateral temporal pole metabolism in patients with unilateral MTS. These metabolic changes were associated with permanent histological abnormalities of the temporal pole. This finding demonstrates that MTS may be a more diffuse histological process, and exact preoperative knowledge of its temporal extent becomes of paramount importance in the selection of the best surgical approach in these patients. Further validation of the observations is necessary for defining the role of temporal pole proton MRS in cases of temporal lobe epilepsy.

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Aristotelis S. Filippidis, Dimitrios C. Papadopoulos, Eftychia Z. Kapsalaki and Kostas N. Fountas

Object

The aim of this study was to provide a systematic update of the current literature regarding the clinical role of the S100B serum biomarker in the initial evaluation of children who have sustained a mild traumatic brain injury (TBI).

Methods

Searches in MEDLINE were defined with the keywords “mild TBI children S100,” “mild TBI pediatric S100,” and “children S100 brain injury.” From the pool of obtained studies, those that had the inclusion criteria of mild TBI only or mixed types of TBI but including detailed information about groups of children with mild TBI were used.

Results

Few studies were identified and fewer included more than 100 cases. The prospective studies showed that the S100B biomarker levels could be influenced by patient age and the time frame between head injury and blood sampling. Moreover, extracranial sources of S100B or additional injuries could influence the measured levels of this biomarker. A normal value of S100B in children with mild TBI could rule out injury-associated abnormalities on CT scans in the majority of reported cases.

Conclusions

The vulnerability of S100B serum levels to the influences of patient age, blood sampling time, and extracranial S100B release limits the biomarker's role in the initial evaluation of children with mild TBI. The application of S100B in pediatric mild TBI cases has an elusive role, although it could help in selected cases to avoid unnecessary head CT scans.

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Kostas N. Fountas, Eftychia Kapsalaki and Georgios Hadjigeorgiou

Object

The wide application of deep brain stimulation in the management of movement as well as other degenerative neurological and psychiatric disorders has renewed the interest in using deep brain stimulation in the management of medically intractable epilepsy. Various stimulation targets have been used with significantly varying results in aborting seizure activity. Electrical cerebellar stimulation (CS) has been used for more than 50 years in the management of epilepsy, with conflicting results. In the current study, the authors review the pertinent literature to outline the role of CS in the management of medically refractory epilepsy.

Methods

The PubMed medical database was systematically searched for the following terms: “cerebellar,” “epilepsy,” “stimulation,” and “treatment,” and all their combinations. Case reports were excluded from this study.

Results

The pertinent articles were categorized into 2 large groups: animal experimental and human clinical studies. Particular emphasis on the following aspects was given when reviewing the human clinical studies: their methodological characteristics, the number of participants, their seizure types, the implantation technique and its associated complications, the exact stimulation target, the stimulation technique, the seizure outcome, and the patients' psychological and social poststimulation status. Three clinical double-blind studies were found, with similar implantation surgical technique, stimulation target, and stimulation parameters, but quite contradictory results. Two of these studies failed to demonstrate any significant seizure reduction, whereas the third one showed a significant poststimulation decrease in seizure frequency. All possible factors responsible for these differences in the findings are analyzed in the present study.

Conclusions

Cerebellar stimulation seems to remain a stimulation target worth exploring for defining its potential in the treatment of medically intractable epilepsy, although the data from the double-blind clinical studies that were performed failed to establish a clear benefit in regard to seizure frequency. A large-scale, double-blind clinical study is required for accurately defining the efficacy of CS in epilepsy treatment.

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Efthimios Dardiotis, Kostas N. Fountas, Maria Dardioti, Georgia Xiromerisiou, Eftychia Kapsalaki, Anastasia Tasiou and Georgios M. Hadjigeorgiou

Traumatic brain injury (TBI) constitutes a major cause of mortality and disability worldwide, especially among young individuals. It is estimated that despite all the recent advances in the management of TBI, approximately half of the patients suffering head injuries still have unfavorable outcomes, which represents a substantial health care, social, and economic burden to societies.

Considerable variability exists in the clinical outcome after TBI, which is only partially explained by known factors. Accumulating evidence has implicated various genetic elements in the pathophysiology of brain trauma. The extent of brain injury after TBI seems to be modulated to some degree by genetic variants.

The authors' current review focuses on the up-to-date state of knowledge regarding genetic association studies in patients sustaining TBI, with particular emphasis on the mechanisms underlying the implication of genes in the pathophysiology of TBI.

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Georgia Xiromerisiou, Efthimios Dardiotis, Vaïa Tsimourtou, Persa Maria Kountra, Konstantinos N. Paterakis, Eftychia Z. Kapsalaki, Kostas N. Fountas and Georgios M. Hadjigeorgiou

Over the past few years, considerable progress has been made in understanding the molecular mechanisms of Parkinson disease (PD). Mutations in certain genes are found to cause monogenic forms of the disorder, with autosomal dominant or autosomal recessive inheritance. These genes include alpha-synuclein, parkin, PINK1, DJ-1, LRRK2, and ATP13A2. The monogenic variants are important tools in identifying cellular pathways that shed light on the pathogenesis of this disease. Certain common genetic variants are also likely to modulate the risk of PD. International collaborative studies and meta-analyses have identified common variants as genetic susceptibility risk/protective factors for sporadic PD.

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Aristotelis S. Filippidis and Kostas N. Fountas

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Aristotelis Filippidis, Eftychia Kapsalaki, Gianna Patramani and Kostas N. Fountas

Cerebral venous sinus thrombosis (CVST) is a rare clinicopathological entity. The incidence of CVST in children and neonates has been reported to be as high as 7 cases per million people, whereas in adults the incidence is 3–4 cases per million. The predisposing factors to this condition are mainly genetic and acquired prothrombotic states and infection. The clinical picture of CVST is nonspecific, highly variable, and can mimic several other clinical conditions. Diagnosis of CVST is established with the implementation of neuroimaging studies, especially MR imaging and venography. Identification and elimination of the underlying cause, anticoagulation, proper management of intracranial hypertension, and anticonvulsant prophylaxis constitute cornerstones of CVST treatment. Newer treatment strategies such as endovascular thrombolysis and decompressive craniectomy have been recently used in the treatment of patients with CVST with variable success rates. Further clinical research must be performed to delineate the exact role of these newer treatments in the management of severe cases of CVST. The recent advances in the diagnosis and treatment of patients with CVST have significantly lowered the associated mortality and morbidity and have improved the outcome of these patients.

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Kostas N. Fountas, Anastasia Tasiou, Eftychia Z. Kapsalaki, Konstantinos N. Paterakis, Arthur A. Grigorian, Gregory P. Lee and Joe Sam Robinson Jr.

Object

Cerebral vasospasm is a common and potentially devastating complication of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes seem to play a major role in the pathogenesis of vasospasm. The Creactive protein (CRP) constitutes a highly sensitive inflammatory marker. The association of elevated systemic CRP and coronary vasospasm has been well established. Additionally, elevation of the serum CRP levels has been demonstrated in patients with aSAH. The purpose of the current study was to evaluate the possible relationship between elevated CRP levels in the serum and CSF and the development of vasospasm in patients with aSAH.

Methods

. A total of 41 adult patients in whom aSAH was diagnosed were included in the study. Their demographics, the admitting Glasgow Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography studies, and daily neurological examinations were recorded. Serial serum and CSF CRP measurements were obtained on Days 0, 1, 2, 3, 5, 7, and 9. All patients underwent either surgical or endovascular treatment within 48 hours of their admission. The outcome was evaluated using the Glasgow Outcome Scale and the modified Rankin Scale.

Results

The CRP levels in serum and CSF peaked on the 3rd postadmission day, and the CRP levels in CSF were always higher than the serum levels. Patients with lower admission GCS scores and higher Hunt and Hess and Fisher grades had statistically significantly higher levels of CRP in serum and CSF. Patients with angiographic vasospasm had higher CRP measurements in serum and CSF, in a statistically significant fashion (p < 0.0001). Additionally, patients with higher CRP levels in serum and CSF had less favorable outcome in this cohort.

Conclusions

Patients with aSAH who had high Hunt and Hess and Fisher grades and low GCS scores showed elevated CRP levels in their CSF and serum. Furthermore, patients developing angiographically proven vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and increased CRP measurements were strongly associated with poor clinical outcome in this cohort.

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Kostas N. Fountas, Eftychia Z. Kapsalaki, Gregory P. Lee, Theofilos G. Machinis, Arthur A. Grigorian, Joe S. Robinson Jr., Ioannis Vergados and Panagiotis G. Theodosiadis

Object

The association of vitreous and/or subhyaloid hemorrhage with aneurysmal subarachnoid hemorrhage (SAH) has been frequently identified since the original description by Terson in 1900. In this prospective clinical study the authors examined the actual incidence of Terson hemorrhage in patients suffering aneurysmal SAH, they attempted to identify those parameters that could predispose its development, and they evaluated its prognostic significance in the overall patients' outcome.

Methods

A total of 174 patients suffering aneurysmal SAH were included in this study. The admitting Glasgow Coma Scale scores (GCS), World Federation of Neurological Societies (WFNS) scale scores, Hunt and Hess grades, and Fisher grades were recorded. A careful ophthalmological evaluation was performed in all participants. The exact anatomical locations and the largest diameter of the dome of the ruptured aneurysms were also recorded. Surgical clipping or endovascular coiling was used in 165 patients. Clinical outcome was evaluated at discharge from the hospital by using the Glasgow Outcome Scale and the modified Rankin Scale. Periodic ophthalmological evaluations were performed for 2 years.

Results

In this series, the observed incidence of Terson hemorrhage was 12.1%. Statistical analysis of our data demonstrated that patients with low GCS scores and high WFNS scores, Hunt and Hess grades, and Fisher grades had an increased incidence of Terson hemorrhage. The mortality rate for patients with Terson hemorrhage was 28.6%, whereas that for patients without Terson hemorrhage was 2.0%. Moreover, patients with Terson hemorrhage who survived had significantly worse outcomes than those in patients without Terson hemorrhage.

Conclusions

Terson hemorrhage constitutes a common SAH-associated complication. Its incidence is increased in patients with low GCS and high WFNS scores, and high Hunt and Hess and Fisher grades. Its presence is associated with increased mortality and morbidity rates.