Objective
To identify early structural alterations preceding the development of drug‐resistance in mild mesial temporal lobe epilepsy (mMTLE), a drug‐responsive syndrome ideal for investigating ...epilepsy pathophysiology and potential prognostic markers of long‐term clinical outcome, using magnetic resonance imaging (MRI) at baseline and after 12‐year follow‐up.
Methods
Since 2002, a total of 55 participants with a baseline diagnosis of mMTLE underwent three‐dimensional (3D) T1 1.5T MRI. Based on long‐term outcome (follow‐up 12 ± 3 years), we identified 39 patients with stable mMTLE (smMTLE) and 16 patients who had developed drug‐resistance overtime (refractory MTLE rMTLE). At follow‐up, 21 smMTLE and 13 rMTLE patients underwent 3T‐MRI including diffusion‐weighted scans. Structural images were processed using longitudinal voxel‐based morphometry and standard Freesurfer analysis. Statistical analyses were carried out accounting for age, age at onset, gender, hippocampal volume, and hippocampal sclerosis (Hs).
Results
Patients presented similar demographic, clinical, and Hs features. White matter volume of the arcuate fasciculi, corticospinal tracts, left retrosplenial cingulum, and left inferior longitudinal fasciculus was reduced only in rMTLE patients before the development of drug‐resistance. At follow‐up, rMTLE showed decreased fractional anisotropy in the corpus callosum, superior longitudinal fasciculi, and major bundles of the right hemisphere.
Significance
White matter temporal and extratemporal abnormalities are preexisting in patients with mild MTLE who will develop drug‐resistance, independently from the presence of Hs. Thus, these changes might be due to an inherited genetic alteration rather than a subordinate worsening after repeated seizures, multiple antiepileptic drugs, or initial precipitating factors.
Objective
To evaluate the frequency of qualitative features for hippocampal developmental abnormalities (HiDeA) definition on magnetic resonance imaging (MRI) in mesial temporal lobe epilepsy (MTLE) ...patients and healthy controls, highlighting which were more sensitive and specific to the epileptic syndrome.
Methods
We enrolled 93 healthy controls and 187 MTLE patients. Among patients, 133 were MRI‐negative and 54 had hippocampal sclerosis (HS). Two blinded, trained investigators defined HiDeA if three signs were present, including at least one of the following: (1) globular hippocampal shape (HCS), (2) verticalized collateral sulcus, and (3) medial positioning of hippocampus (HCP). After evaluating the prevalence of HiDeA in MTLE and controls, we assessed the frequency of each sign. Then, we classified differences in type or number of HiDeA diagnostic features, calculating their sensitivity and specificity. Fisher exact test was used to assess statistical significance.
Results
HiDeA was detected in 36 of 187 MTLE cases (19.25%) and in eight of 93 (8.6%) controls. In particular, HiDeA was present in 25 of 133 (18.8%) patients with MRI‐negative MTLE. Among all visual criteria here considered, HCS showed higher sensitivity both in the MRI‐negative MTLE group (88%) and in the HS‐MTLE group (91%). HCP, thickened subiculum, and reduction of the upper horizontal portion of the parahippocampal gyrus (HCTH) signs demonstrated a 100% specificity in both groups. In healthy controls, HCS was confirmed to have the highest sensitivity (100%), whereas HCP showed the highest specificity (98.8%). All these criteria were statistically associated with HiDeA. Electroencephalographic focus was concordant with the HiDeA side in 52.2% of MTLE patients. An association was not found among signs of HiDeA and treatment responsiveness.
Significance
We identified characteristic signs of HiDeA, such as HCTH or HCP, differentiating HiDeA features between MTLE and healthy controls. The identification of sensitive and, more importantly, specific criteria of HiDeA could be helpful to make a more confident visual diagnosis.
Abstract
Mutations of the voltage-gated sodium channel SCN1A gene (MIM#182389) are among the most clinically relevant epilepsy-related genetic mutations and present variable phenotypes, from the ...milder genetic epilepsy with febrile seizures plus to Dravet syndrome, a severe developmental and epileptic encephalopathy. Qualitative neuroimaging studies have identified malformations of cortical development in some patients and mild atrophic changes, partially confirmed by quantitative studies. Precise correlations between MRI findings and clinical variables have not been addressed. We used morphometric methods and network-based models to detect abnormal brain structural patterns in 34 patients with SCN1A-related epilepsy, including 22 with Dravet syndrome. By measuring the morphometric characteristics of the cortical mantle and volume of subcortical structures, we found bilateral atrophic changes in the hippocampus, amygdala, and the temporo-limbic cortex (P-value < 0.05). By correlating atrophic patterns with brain connectivity profiles, we found the region of the hippocampal formation as the epicenter of the structural changes. We also observed that Dravet syndrome was associated with more severe atrophy patterns with respect to the genetic epilepsy with febrile seizures plus phenotype (r = −0.0613, P-value = 0.03), thus suggesting that both the underlying mutation and seizure severity contribute to determine atrophic changes.
Background
Idiopathic normal pressure hydrocephalus (iNPH) shares clinical and radiological features with progressive supranuclear palsy (PSP) and Alzheimer’s disease (AD). Corpus callosum (CC) ...involvement in these disorders is well established on structural MRI and diffusion tensor imaging (DTI), but alterations overlap and lack specificity to underlying tissue changes.
Objective
We propose a semi-automated approach to assess CC integrity in iNPH based on the spatial distribution of DTI-derived principal diffusion direction orientation (V1).
Methods
We processed DTI data from 121 subjects (Site1: iNPH = 23, PSP = 27, controls = 14; ADNI: AD = 35, controls = 22) to obtain V1, fractional anisotropy (FA) and mean diffusivity (MD) maps. To increase the estimation accuracy of DTI metrics, analyses were restricted to the midsagittal CC portion (± 6 slices from midsagittal plane). Group-wise comparison of normalized altered voxel count in midsagittal CC was performed using Kruskal–Wallis tests, followed by post hoc comparisons (Bonferroni-corrected
p
< 0.05). ROC analysis was used to evaluate the diagnostic power of DTI alterations compared to callosal volume.
Results
We found specific changes of V1 distribution in CC splenium of iNPH compared to AD and PSP, while MD and FA showed patterns of alterations common to all disorders. ROC curves showed that, compared to splenial volume, V1 represented the most accurate marker of iNPH diagnosis versus AD and PSP.
Conclusions
Our results provide evidence that V1 is a powerful biomarker for distinguishing patients with iNPH from patients with AD or PSP. Indeed, our findings also provide more specific insight into the pathophysiological mechanisms that underlie tissue damage across iNPH and its mimics.
To compare quantitative spectral parameters of visually-normal EEG between Mesial Temporal Lobe Epilepsy (MTLE) patients and healthy controls (HC).
We enrolled 26 MTLE patients and 26 HC. From each ...recording we calculated total power of all frequency bands and determined alpha-theta (ATR) and alpha-delta (ADR) power ratios in different brain regions. Group-wise differences between spectral parameters were investigated (p < 0.05). To test for associations between spectral-power and cognitive status, we evaluated correlations between neuropsychological tests and quantitative EEG (qEEG) metrics.
In all comparisons, ATR and ADR were significantly decreased in MTLE patients compared to HC, particularly over the hemisphere ipsilateral to epileptic activity. A positive correlation was seen in MTLE patients between ATR in ipsilateral temporal lobe, and results of neuropsychological tests of auditory verbal learning (RAVLT and RAVLT-D), short term verbal memory (Digit span backwards), and executive function (Weigl's sorting test). ADR values in the contralateral posterior region correlated positively with RAVLT-D and Digit span backwards tests.
Results confirmed that the power spectrum of qEEG is shifted towards lower frequencies in MTLE patients compared to HC.
Of note, our results were found in visually-normal recordings, providing further evidence of the value of qEEG for longitudinal monitoring of MTLE patients over time. Exploratory analysis of associations between qEEG and neuropsychological data suggest this could be useful for investigating effects of antiseizure medications on cognitive integrity in patients.
MicroRNAs (miRNAs) are small noncoding RNAs that have emerged as new potential epigenetic biomarkers. Here, we evaluate the efficacy of six circulating miRNA previously described in the literature as ...biomarkers for the diagnosis of temporal lobe epilepsy (TLE) and/or as predictive biomarkers to antiepileptic drug response. We measured the differences in serum miRNA levels by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays in a cohort of 27 patients (14 women and 13 men; mean ± SD age: 43.65 ± 17.07) with TLE compared to 20 healthy controls (HC) matched for sex, age and ethnicity (11 women and 9 men; mean ± SD age: 47.5 ± 9.1). Additionally, patients were classified according to whether they had drug-responsive (
= 17) or drug-resistant (
= 10) TLE. We have investigated any correlations between miRNAs and several electroclinical parameters. Three miRNAs (miR-142, miR-146a, miR-223) were significantly upregulated in patients (expressed as average expression ± SD). In detail, miR-142 expression was 0.40 ± 0.29 versus 0.16 ± 0.10 in TLE patients compared to HC (
-test,
< 0.01), miR-146a expression was 0.15 ± 0.11 versus 0.07 ± 0.04 (
-test,
< 0.05), and miR-223 expression was 6.21 ± 3.65 versus 1.23 ± 0.84 (
-test,
< 0.001). Moreover, results obtained from a logistic regression model showed the good performance of miR-142 and miR-223 in distinguishing drug-sensitive vs. drug-resistant TLE. The results of this pilot study give evidence that miRNAs are suitable targets in TLE and offer the rationale for further confirmation studies in larger epilepsy cohorts.
In this work, we investigated motor network structure in patients affected by essential tremor (ET) with or without resting tremor, using probabilistic tractography of the cerebello–thalamo–basal ...ganglia–cortical loop. Twenty-five patients with ET, twenty-two patients with ET associated with resting tremor (rET), and twenty-five age- and sex-matched healthy controls were included in the study. All participants underwent whole-brain 3D T1-weighted and diffusion-weighted MRI, and DAT–SPECT. Probabilistic tractography was performed on diffusion data in network mode, reconstructing connections between the different structures of the cerebello–thalamo–basal ganglia–cortical loop. All patients with ET, regardless of the presence of resting tremor, had normal DAT–SPECT, but showed significantly decreased connectivity in the cerebello–thalamo–precentral cortex network bilaterally, compared to healthy controls. In addition, patients with rET showed reduced connectivity in a pathway connecting globus pallidus, caudate, and supplementary motor area, compared to ET and controls. This latter circuit was significantly damaged in the hemisphere contralateral to the side clinically most affected by resting tremor. These findings provide insights upon structural changes underlying the different clinical presentations of ET. Our study demonstrates that ET and rET share common alterations in the cerebello–thalamo–precentral cortex circuit, while rET patients are characterized by specific damage to additional structures of motor network, such as globus pallidus, caudate nucleus, and supplementary motor area. Our findings suggest that ET and rET are different subtypes of the same neurodegenerative disorder.
Introduction
There is some debate on the relationship between essential tremor with rest tremor (rET) and the classic ET syndrome, and only few MRI studies compared ET and rET patients. This study ...aimed to explore structural cortical differences between ET and rET, to improve the knowledge of these tremor syndromes.
Methods
Thirty-three ET patients, 30 rET patients and 45 control subjects (HC) were enrolled. Several MR morphometric variables (thickness, surface area, volume, roughness, mean curvature) of brain cortical regions were extracted using Freesurfer on T1-weighted images and compared among groups. The performance of a machine learning approach (XGBoost) using the extracted morphometric features was tested in discriminating between ET and rET patients.
Results
rET patients showed increased roughness and mean curvature in some fronto-temporal areas compared with HC and ET, and these metrics significantly correlated with cognitive scores. Cortical volume in the left pars opercularis was also lower in rET than in ET patients. No differences were found between ET and HC. XGBoost discriminated between rET and ET with mean AUC of 0.86 ± 0.11 in cross-validation analysis, using a model based on cortical volume. Cortical volume in the left pars opercularis was the most informative feature for classification between the two ET groups.
Conclusion
Our study demonstrated higher cortical involvement in fronto-temporal areas in rET than in ET patients, which may be linked to the cognitive status. A machine learning approach based on MR volumetric data demonstrated that these two ET subtypes can be distinguished using structural cortical features.
•In MTLE, one year of COVID-19 pandemic had a substantial neuropsychological impact.•Compared to the year before, patients showed a worsening in depression and anxiety.•Sleep quality, psychological ...distress, and anhedonia were variously pathological.•Concomitantly, patients with MTLE revealed a worsening in life quality and somatization.•Pandemic distress levels correlated with anxiety, somatization, and depression.
We assessed levels of depression, anxiety, stress, anhedonia, somatization, psychological distress, sleep, and life quality in patients with mesial temporal lobe epilepsy (MTLE) after one year of containment measures started in Italy to stem the COVID-19 pandemic.
We consecutively enrolled 51 patients with MTLE, administering an online survey that compared the year before and after the COVID-19 propagation. We analyzed clinical data (e.g., seizure frequency, life quality) and neuropsychological assessment through Somatic Symptom Scale–8 (SSS-8), Beck Depression Inventory (BDI-2), State-Trait Anxiety Inventory (STAI-Y), Depression, Anxiety and Stress Scale (DASS-21), Pittsburgh Sleep Quality Index (PSQI), Snaith-Hamilton Pleasure Scale (SHAPS), Impact of Event Scale-Revised (IES-R). The BDI-2 and STAI-Y scores were compared to those acquired in the same patients before the COVID-19 outbreak.
Comparing our population with MTLE before and after COVID-19 outbreak, we found a significant worsening in life quality (p = 0.03), SSS-8 (p = 0.001), BDI-2 (p = 0.032), and STAI-Y scores (p < 0.001). After one year of pandemic, 88.2% of patients obtained pathological scores at PSQI, 19.6% at SHAPS, 29.4% at IES-R. Reduction of life quality correlated with anxiety, depression, stress, and somatization. Higher levels of anhedonia correlated with stress, depression, and anxiety. Somatization correlated with depression, anxiety, and sleep quality. Distress levels correlated with anxiety, somatization, and depression.
We demonstrated a significant worsening of depression, anxiety, life quality, and somatization in patients with MTLE after one year of COVID-19 beginning. Concomitantly, results suggest that the pandemic had a negative impact on sleep quality, psychological distress, and anhedonia, but not on epilepsy itself.
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