Carlos M. Quesada

Volume determination of amygdala and hippocampus at 1.5 and 3.0T MRI in temporal lobe epilepsy.

Since magnetic resonance imaging (MRI) technique is constantly evolving with higher field strength scanners, the question arises whether images from different field strength scanners can be used interchangeably for scientific and clinical purposes. We address this issue in a study group of patients with temporal lobe epilepsy (TLE). Two different quantification methods for analysing structural (MRI) were used. Conventional volumetry was performed by manually tracing amygdala and hippocampus volumes on both 1.5 and 3T scans of 10 TLE patients. Additionally a voxel-based morphometry (VBM)-based extraction of those structures was conducted. As an answer to the main question, it was determined that the volumetrically derived volumes of amygdala and hippocampus from 1.5 and 3.0T images did not differ. Our findings concerning the volumetry are consistent with findings in healthy controls, thus offering the possibility to use volumetry of the different scanners interchangeably. The results of the VBM-analyses show satisfying inter-scanner volume quantification but not consistent enough to be deemed interchangeable. Further investigations analysing the outcomes of conventional VBM of different field strength scanners are necessary.

Cerebellar contributions to episodic memory encoding as revealed by fMRI

Event-related functional Magnetic Resonance Imaging (fMRI) allows for the comparison of hemodynamic responses evoked by items that are remembered in a subsequent memory task vs. items that are forgotten. In this way, brain regions that assumingly contribute to successful memory encoding have been identified, including the left inferior prefrontal cortex (LIPC) and the medial temporal lobe. Although a cerebellar involvement in verbal working memory is well-established, a contribution of the cerebellum to episodic long-term encoding has only sporadically been described, and mechanisms underlying cerebellar memory effects are unclear. We conducted a typical incidental verbal memory fMRI experiment with three different encoding tasks varying the depth of semantic processing. Slice positioning allowed for the coverage of the entire cerebellum. We observed a significant subsequent memory effect within the superior and posterior right cerebellar hemisphere that was task independent. Additionally, we found a different area within the superior right cerebellum displaying a memory effect specifically for semantically processed words and a bilateral cerebellar activation specifically associated with encoding success only for a non-semantic task. Our results suggest that besides its known role in verbal working memory, the cerebellum contributes to episodic long-term encoding and should therefore be considered in future fMRI studies dealing with episodic memory.

Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe

In 2014 the European Union–funded E‐PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers.

Neurodevelopmental disruption in early-onset temporal lobe epilepsy: Evidence from a voxel-based morphometry study

Childhood onset of epilepsy has long been associated with an adverse impact on brain development and cognition. In this study it is proposed that earlier (vs later) onset of temporal lobe epilepsy (TLE) has a negative developmental impact on distant brain structures. One hundred ten patients with TLE were assigned to early (≤14 years, N=58) and late (>15 years, N=52) age at onset of epilepsy groups. Voxel-based morphometry revealed onset-dependent abnormalities (in terms of a gray matter excess in the early-onset group), which were found mainly in frontal regions. An excess of gray matter is not a usual finding in TLE. However, within a neurodevelopmental framework, retained gray matter is discussed as reflecting neurodevelopmental disruption. The findings indicate the importance of quantitative MRI for the detection of subtle secondary abnormalities in focal TLE and once more underline the importance of early seizure management in children with intractable TLE.

Neurons in the human amygdala encode face identity, but not gaze direction

The amygdala is important for face processing, and direction of eye gaze is one of the most socially salient facial signals. Recording from over 200 neurons in the amygdala of neurosurgical patients, we found robust encoding of the identity of neutral-expression faces, but not of their direction of gaze. Processing of gaze direction may rely on a predominantly cortical network rather than the amygdala.

Volumetric hemispheric ratio as a useful tool in personality psychology.

The present study investigates the link between volumetric hemispheric ratios (VHRs) and personality measures in N=267 healthy participants using Eysencks Personality Inventory-Revised (EPQ-R) and the BIS/BAS scales. A robust association between extraversion and VHRs was observed for gray matter in males but not females. Higher gray matter volume in the left than in the right hemisphere was associated with higher extraversion in males. The results are discussed in the context of positive emotionality and laterality of the human brain.

An interaction of a NR3C1 polymorphism and antenatal solar activity impacts both hippocampus volume and neuroticism in adulthood

The investigation of the interaction of genes and environment in the context of mental health and personality yields important new insights for a better understanding of human nature. Both antenatal and postnatal environmental factors have been considered as potential modulators of genetic activity. Antenatally, especially smoking or alcohol drinking habits of the mother dramatically influence the health of the child during pregnancy and even later on in life. In the present study we would like to introduce a more “distant” factor that is not under the control of the becoming mother but that nevertheless plays a potential role for the health of the unborn child later on in adulthood. Here, we retrospectively investigate the influence of solar activity (while the child is still in the uterus of the becoming mother) on brain structure (with a focus on hippocampus and amygdala volume) and personality in adulthood. We observe an interaction of a genetic variant (rs41423247) of the glucocorticoid receptor gene (NR3C1) and solar activity in the first trimester after conception on both hippocampal volume and the personality trait neuroticism in adulthood in N = 254 participants. The NR3C1 gene is the focus of interest, because of its influence on the hypothalamic-pituitary-adrenal (HPA) axis and negative emotionality. Carriers of the CC variant of rs41423247 grown in the womb under the influence of high sun radiation (high solar activity) show both the highest hippocampal volume in the left hemisphere and lowest neuroticism scores. The present findings should encourage researchers in psychology and psychiatry to include also environmental influences such as solar activity besides genetics to better understand the etiogenesis of psychiatric disorders.

Rasmussen encephalitis with ipsilateral brain stem involvement in an adult patient

Rasmussen encephalitis is a rare unihemispheric inflammatory disease of the brain that leads to intractable seizures, cognitive decline and progressive neurological deficits associated with the affected hemisphere. It predominantly affects children, with the onset in adults having a milder course. Immunotherapy has been suggested to improve the outcome of Rasmussen encephalitis.1,2nnIn November 2000, a left-handed 37-year-old woman experienced a head trauma with brief loss of consciousness. Shortly after, she had mild clumsiness of her right leg, which went on for the next 2 years. No magnetic resonance imaging (MRI) study was performed at that time. Her family also noticed a change in her character (all of which was retrospectively interpreted as the “prodromal stage” of Rasmussen encephalitis2).nnIn February 2002, the patient started having epilepsia partialis continua (EPC) of her right hand (later on interpreted as an onset of the “acute stage” of Rasmussen encephalitis2). Apart from EPC and impaired motor function of her right leg and hand (due to the EPC), the neurological examination and electroencephalogram were normal at this time. Cerebrospinal fluid contained 10 cells/μl, had a normal protein level and showed oligoclonal bands. Microbiological studies showed no sign of an infectious agent. MRI of the brain showed a mild left temporal atrophy. …

Low-dose radiosurgery or hypofractionated stereotactic radiotherapy as treatment option in refractory epilepsy due to epileptogenic lesions in eloquent areas – Preliminary report of feasibility and safety

PURPOSEnThe eradication of epileptogenic lesions (e.g. focal cortical dysplasia) can be used for treatment of drug-resistant focal epilepsy, but in highly eloquent cortex areas it can also lead to a permanent neurological deficit. In such cases the neuromodulation effect of low-dose high-precision irradiation of circumscribed lesions may represent an alternative therapy.nnnMETHODnA total of 10 patients with eloquent localized lesions causing pharmacoresistant focal epilepsy were prospectively identified. After informed consent, six patients agreed and were treated with risk adapted low-dose radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (hfSRT). Comprehensive data concerning treatment modalities and outcome after short-term follow up (mean=16.3 months) were prospectively collected and evaluated.nnnRESULTSnFrom the six patients, two patients were treated with hfSRT (marginal dose 36 Gy) and four with SRS (marginal dose 13 Gy). Clinical target volume (CTV) ranged from 0.70 ccm to 4.32 ccm. The short-term follow-up ranged from 6 to 27 months. There were no side effects or neurological deficits after treatment. At last available follow-up two patients were seizure-free, one of them being off antiepileptic drugs. The seizure frequency improved in one and remained unchanged in three patients.nnnCONCLUSIONnTreatment of eloquent localized epileptogenic lesions by SRS and hfSRT showed no adverse events and an acceptable seizure outcome in this small prospective patient series. The relatively short-term follow-up comprises one of the studys drawbacks and therefore a longer follow-up should be awaited in order to evaluate the neuromodulation effect of the treatment. These preliminary results may however justify the initiation of a larger prospective trial investigating whether focused low-dose stereotactic irradiation could be an option for lesions in eloquent brain areas.

Treating a GAD65 Antibody-Associated Limbic Encephalitis with Basiliximab: A Case Study.

Background Antibodies (ABs) against the 65-kDa isoform of the intracellular enzyme glutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) and other neurological conditions. The direct significance of anti-GAD65-ABs for epilepsy is unclear. However, in histological preparations from biopsies of resective epilepsy surgeries, predominantly cytotoxic T-lymphocytes were detected making close contacts to neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeutic interleukin-2 receptor Abs, such as basiliximab. Case presentation We report of a 25-year-old male patient with epilepsy since the age of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebrospinal fluid (CSF) and serum. Monthly, repetitive, intravenous cortisone pulse therapies that were initially administered for 6u2009months failed to improve his condition. Subsequent flow-cytometry analysis of CSF showed especially an increased fraction of activated HLA-DR+ CD8+ T-lymphocytes (fCD8+TL) when compared to controls. Thus, a second, intravenous cortisone pulse therapy with an additional basiliximab dose of 20u2009mg/month was started. After 3u2009months, the fCD8+TL in the CSF normalized; after 6u2009months, the psychological impulse-control deficits normalized; and after 11u2009months the patient was seizure free. However, 7u2009weeks later, seizures and, later on, psychological deficits recurred and fCD8+TL was once again present in the CSF. Flumazenil PET, magnetic resonance imaging-volumetry, and neuropsychological changes during therapy are described. Conclusion The correlation of the fCD8+TL in the CSF with clinical and paraclinical measures of disease activity combined with the unambiguous response to basiliximab strongly argues in favor of the putative pathogenic role fCD8+TL in anti-GAD65 LE. The clinical relapse at the end of the observation period might be due to the formation of human anti-drug ABs, a well-known complication of therapy with chimeric ABs.