Foteini Christidi

Diffusion Tensor Imaging of the Perforant Pathway Zone and Its Relation to Memory Function in Patients with Severe Traumatic Brain Injury

Based on the importance of the perforant pathway (PP) for normal hippocampal function, the vulnerability of temporal structures, and significant memory impairment in patients with traumatic brain injury (TBI), we investigated in vivo changes in the PP zone, hippocampus, and temporal lobe white and gray matter using diffusion tensor imaging (DTI) and volumetric analysis, and any specific relations with memory performance (Verbal Selective Reminding Test, Rey-Osterrieth Complex Figure Test), in 14 patients with severe TBI. Compared to a demographically-similar control group, our patients had significantly decreased fractional anisotropy (FA) and higher apparent diffusion coefficient (ADC) for the PP zone bilaterally, and higher ADC bilaterally in the hippocampus. Volumetric analysis revealed significantly decreased volumes in both hippocampi and temporal gray matter bilaterally. Consistent long-term retrieval (CLTR) and delayed recall were significantly related to (1) right and left PP zone ADC, (2) left hippocampus ADC, and (3) left hippocampal volume. Nonverbal memory (immediate and delayed recall) was significantly associated with (1) right and left PP zone ADC, (2) left hippocampal volume, and (3) gray (immediate recall) and white (immediate recall, bilaterally; delayed recall, left) matter temporal volumes. Advanced neuroimaging analysis can detect in vivo changes in the PP zone and temporal structures in patients with severe TBI, with these changes being highly associated with memory impairment.

Fiber tracking: A qualitative and quantitative comparison between four different software tools on the reconstruction of major white matter tracts

Purpose Diffusion tensor imaging (DTI) enables in vivo reconstruction of white matter (WM) pathways. Considering the emergence of numerous models and fiber tracking techniques, we herein aimed to compare, both quantitatively and qualitatively, the fiber tracking results of four DTI software (Brainance, Philips FiberTrak, DSI Studio, NordicICE) on the reconstruction of representative WM tracts. Materials and methods Ten healthy participants underwent 30-directional diffusion tensor imaging on a 3T-Philips Achieva TX MR-scanner. All data were analyzed by two independent sites of experienced raters with the aforementioned software and the following WM tracts were reconstructed: corticospinal tract (CST); forceps major (Fmajor); forceps minor (Fminor); cingulum bundle (CB); superior longitudinal fasciculus (SLF); inferior fronto-occipital fasciculus (IFOF). Visual inspection of the resulted tracts and statistical analysis (inter-rater and betweensoftware agreement; paired t-test) on fractional anisotropy (FA), axial and radial diffusivity (Daxial, Dradial) were applied for qualitative and quantitative evaluation of DTI software results. Results Qualitative evaluation of the extracted tracts confirmed anatomical landmarks at least for the core part of each tract, even though differences in the number of fibers extracted and the whole tract were evident, especially for the CST, Fmajor, Fminor and SLF. Descriptive values did not deviate from the expected range of values for healthy adult population. Substantial inter-rater agreement (intraclass correlation coefficient [ICC], Bland-Altman analysis) was found for all tracts (ICC; FA: 0.839–0.989, Daxial: 0.704–0.991, Dradial: 0.972–0.993). Low agreement for FA, Daxial and Dradial (ICC; Bland-Altman analysis) and significant paired t-test differences (p < 0.05) were detected regarding between-software agreement. Conclusions Qualitative comparison of four different DTI software in addition to substantial inter-rater but poor between-software agreement highlight the differences on existing fiber tracking methodologies and several particularities of each WM tract, further supporting the need for further study in both clinical and research settings.

Uncinate fasciculus microstructure and verbal episodic memory in amyotrophic lateral sclerosis: a diffusion tensor imaging and neuropsychological study

The present study evaluates the integrity of uncinate fasciculus (UF) and the association between UF microstructure and verbal episodic memory (as one of the cognitive functions linked to UF) in non-demented patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). We studied 21 patients with ALS and 11 healthy, demographically-comparable volunteers. Fractional anisotropy, apparent diffusion coefficient, axial and radial diffusivity were the DTI metrics examined. Episodic memory was evaluated with Babcock Story Recall Test and Rey Auditory Verbal Learning Test (RAVLT) for patients; measures of immediate and delayed recall and retention for both tests and sum of words recalled through five learning trials for RAVLT were considered. Patients with ALS showed significant bilateral reduction of axial diffusivity in the UF as compared to controls. Furthermore, there were several significant relations between various DTI metrics (mostly in left hemisphere) and memory measures (specifically for the RAVLT). UF microstructural changes may contribute to ALS-related memory impairment, with word-list learning performance relying more upon the integrity of frontal and temporal connections than memory components associated with story recall.

Derived Trail Making Test indices: demographics and cognitive background variables across the adult life span

We examined the contribution of demographics and cognitive background variables (processing speed, visuospatial skill, working memory, and interference control) on derived Trail Making Test (TMT) scores in a large sample of Greek healthy participants. We included 775 participants and administered the TMT (TMT-A and TMT-B) and the Wechsler Intelligence Adult Scale (WAIS). Direct (TMT-A & TMT-B time-to-completion) and derived [difference TMT-(B − A) & ratio TMT-(B/A)] scores were calculated. Demographics (age, age2, education, and gender) and WAIS Full Intelligence Quotient significantly predicted the direct TMT-A (R2 = 0.426) and TMT-B (R2 = 0.593) scores and to a lesser extent, the derived TMT-(B − A) (R2 = 0.343) and TMT-(B/A) (R2 = 0.088) scores. In a subsample of 537 healthy participants who also completed the Stroop Neuropsychological Screening Test (SNST), demographics (age and education), WAIS Digit Symbol, Block Design, Arithmetic, and SNST accounted for 44.8% and 59.7% of the variance on TMT-A and TMT-B, and 32.5% and 9.6% of the variance on TMT-(B − A) and TMT-(B/A), respectively. We found minimal influence of Block Design and Arithmetic on TMT-(B − A) and an absence of significant influence of any cognitive variable on TMT-(B/A) score. Concluding, derived TMT scores are suggested as indices to detect impairment in cognitive flexibility across the adult life span, since they minimize the effect of demographics and other cognitive background variables.

Can Executive Cognitive Measures Differentiate Between Patients with Spinal- and Bulbar-Onset Amyotrophic Lateral Sclerosis?

Although executive functions in sporadic non-demented amyotrophic lateral sclerosis (ALS) patients are mostly affected, it remains unclear whether executive measures can differentiate between patients with bulbar and spinal ALS forms. Thirty spinal and 18 bulbar-onset ALS patients (ALS-s and ALS-b, respectively) as well as 47 demographically related healthy controls were examined in executive processes (Trail Making Test-part B [TMT-(B-A)]; Stroop Neuropsychological Screening Test [SNST]; Similarities subtest of the Wechsler Adult Intelligence Scale [WAIS Similarities]; Wisconsin Card Sorting Test [WCST]). ALS subgroups were similar with regard to demographic characteristics and disease duration; yet, ALS-b showed greater disease severity compared with ALS-s patients (p = .006). Both ALS-s and ALS-b patients were significantly inferior to healthy controls on TMT-(B-A) (p < .001), SNST (p = .009 and p = .02, respectively) and WAIS Similarities (p = .031 and p = .021, respectively), whereas ALS-s performed significantly worse than controls on the WCST perseverative responses (p = .005). However, neuropsychological measures did not significantly differ between ALS subgroups (p > .05). Despite the fact that ALS-b patients may present greater disease severity, specific executive impairments that are present early in the course of ALS seems to be independent of the site of onset.

Investigating the neuroanatomical substrate of pathological laughing and crying in amyotrophic lateral sclerosis with multimodal neuroimaging techniques

Abstract Objective: Pathological laughing and crying (PLC) is common in several neurological and psychiatric diseases and is associated with a distributed network involving the frontal cortex, the brainstem and cortico-pontine-cerebellar circuits. By applying multimodal neuroimaging approach, we examined the neuroanatomical substrate of PLC in a sample of patients with amyotrophic lateral sclerosis (ALS). Methods: We studied 56 non-demented ALS patients and 25 healthy controls (HC). PLC was measured in ALS using the Center of Neurologic Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based morphometry and tract-based spatial-statistics analysis was used to examine gray matter (GM) and white matter (WM) differences between ALS patients with and without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted to regions with detected differences between ALS and HC, controlling for age, gender, total intracranial volume and depressive symptoms. Results: In regions with significant differences between ALS and HC, ALS-PLC patients showed decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased fractional anisotropy in left cingulum bundle and posterior corona radiata. WM abnormalities were additionally detected in WM associative and ponto-cerebellar tracts (using a more liberal threshold). Conclusions: PLC in ALS is driven by both GM and WM abnormalities which highlight the role of circuits rather than isolated centers in the emergence of this condition. ALS is suggested as a useful natural experimental model to study PLC.

The Clinical and Radiological Spectrum of Hippocampal Pathology in Amyotrophic Lateral Sclerosis

Hippocampal pathology in Amyotrophic Lateral Sclerosis (ALS) remains surprisingly under recognized despite compelling evidence from neuropsychology, neuroimaging and neuropathology studies. Hippocampal dysfunction contributes significantly to the clinical heterogeneity of ALS and requires structure-specific cognitive and neuroimaging tools for accurate in vivo evaluation. Recent imaging studies have generated unprecedented insights into the presymptomatic and longitudinal processes affecting this structure and have contributed to the characterisation of both focal and network-level changes. Emerging neuropsychology data suggest that memory deficits in ALS may be independent from executive dysfunction. In the era of precision medicine, where the development of individualized care strategies and patient stratification for clinical trials are key priorities, the comprehensive review of hippocampal dysfunction in ALS is particularly timely.

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.

Central Nervous System Involvement as Relapse in Undiagnosed Whipple’s Disease with Atypical Symptoms at Onset

Whipple’s disease (WD) is a rare systemic disease caused by the gram-positive bacillus Tropheryma Whipplei and mostly characterized by arthralgias, chronic diarrhea, weight loss, fever and abdominal pain. Central Nervous System involvement is not uncommon and it may precede other disease manifestations, appear after treatment and improvement of gastrointestinal signs or rarely be the only WD symptom. We report a case in a middle-aged male with unexplained neurological signs and symptoms which were presented as relapse of previously undiagnosed WD with atypical symptoms at onset. After diagnosis confirmation, the patient was appropriately treated which resulted in improvement of major symptoms.

Ipsilateral and contralateral cerebro-cerebellar white matter connections: A diffusion tensor imaging study in healthy adults

BACKGROUND AND PURPOSE The cerebellum has a pivotal role in regulating human behavior; yet whether this function is mediated only through contralateral cerebro-cerebellar pathways is under-investigated. Thus, we examined feed-backward and feed-forward ipsilateral and contralateral cerebro-cerebellar connections using a detereministic diffusion tensor imaging (DTI) algorithm, the robustness of which was also estimated using phantom DTI data. MATERIALS AND METHODS Fifty-one healthy controls (22-60 years old; 15 males/36 females) were scanned in a 3T MRI scanner with a 30-direction DTI sequence. Multiple region-of-interest (ROI) method was applied for the reconstruction of the ipsilateral and contralateral (based on cerebellar seed ROI) fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC), occipito-ponto-cerebellar (OPC) and dentate-rubro-thalamo-cortical (DRTC) tract bilaterally using the Brainance DTI Suite. A realistic diffusion MR phantom was used to evaluate the fiber tracking methodology for 16 fibers containing crossing, kissing, splitting and bending configurations. RESULTS Both contralateral and ipsilateral FPC, PPC, OPC and ipsilateral DRTC tracts were successfully reconstructed; the contralateral DRTC tract was not reconstructed in all subjects. Also, the TPC tract was not reproduced in several subjects mostly regarding the contralateral connection. Descriptive DTI measures (number of fibers, fractional anisotropy, radial and axial diffusivity) are presented for each tract. Regarding phantom data, Brainance DTI Suite returned a dataset of 16 fibers that almost perfectly matched the 16 ground truth fibers. CONCLUSIONS We identified ipsilateral and contralateral connections using a clinically applicable DTI sequence, a robust deterministic algorithm and an unbiased methodology, which can be applied in daily practice in different brain pathologies.