MRI Atrophy Research Articles

A family with atypical CADASIL

Dear Sirs, Patients with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) typically manifest migraine with aura, subcortical ischemic events, mood disturbances, apathy and cognitive impairment [1–3]. We report three of four siblings with atypical CADASIL manifestations, namely progressive ataxia and spastic paraparesis. Patient 1 (female b. 1953) complained of tension type headache, reduced concentration and memory, and fatigue after a moderate whiplash injury in 1998. Neurological examination at that time was normal, but Wechsler memory scale test showed reduced visuospatial memory. CSF and evoked potentials were normal, but MRI showed hyperintense white matter lesions. When re-examined in 2009 (Fig. 1a, b) her cognitive complaints were unchanged and neurological examination remained normal. MRI showed minor progression of the white matter disease. Fig. 1 All four patients had characteristic MRI findings of CADASIL. Coronar (FLAIR) and axial (T2) MRIs of patients 1 (a, b), 2 (c, d), 3 (e, f) and 4 (g, h) show hyperintense signals of white matter. Figure e and f also shows subcortical lacunar infarcts Patient 2 (male b. 1940) was diagnosed as having possible multiple sclerosis in 1993 because of spastic paraparesis and internuclear ophthalmoplegia. CSF and evoked potentials at that time were normal, but MRI showed hyperintense signals in white matter (examination no longer available). Re-examination in 2001 and 2009 still showed a spastic paraparesis, but also the presence of a truncal ataxia. MRI in 2009 showed hyperintense white matter lesions (Fig. 1c, d). Patient 3 (male b.1943) complained of slowly progressive unsteadiness from 1998. Neurological examination in 2001 and 2008 showed bilateral dysdiadochokinesis, truncal ataxia and mild spasticity in the lower limbs with hypereflexia. MRI in 2008 showed hyperintense white matter signals and subcortical infarcts in both hemispheres and basal ganglia (Fig. 1e, f). Patient 4 (male b. 1937) complained of unsteadiness from 2008. Neurological examination in 2009 showed pathological ocular smooth pursuit and bilateral dysdiadochokinesis. MRI in 2009 showed similar hyperintense white matter lesions as seen in the other siblings (Fig. 1e, f). Molecular genetic testing showed that all four siblings had the NOTCH3 gene mutation c.3065G>T that changes a cysteine to phenylalanine at position 1022. Three of our patients had features of slowly progressive cerebellar disease combined in two with pyramidal tract signs. No MRI lesions or atrophy involving the cerebellum were seen in our patients, but subcortical lacunar infarcts were present in patient 3. Patient 2, who was initially diagnosed with possible multiple sclerosis, had a transient diplopia and the finding of an internuclear ophthalmoplegia, was probably caused by a brain stem infarction. Ischemic episodes or transient ischemic attacks occur in 60–85% of the patients with CADASIL, and most of these are subcortical ischemic events [1–3]. Our patients had slowly progressive cognitive, cerebellar and/or pyramidal signs most likely due to the cerebral arteriopathy NOTCH3 mutations, which affects vascular smooth muscle cells [4]. The main mechanism of the progressive symptoms in our patients is probably chronic hypoperfusion due to the arteriopathy which is characterised by a failure of arteries to dilate properly [4]. We have no information on the siblings' children and only little information concerning their parents who are both dead. The father was apparently healthy, but the mother had progressive visual impairment said to be due to retinitis pigmentosa. Of her six siblings, one also had progressive blindness and two had cerebrovascular attacks. We have no MRI or biological material available for genetic testing from any of these individuals. Retinal abnormalities with axonal loss have been described in CADASIL while no visual symptoms were present in these patients [5, 6]. It therefore remains possible that the mother of our patients was a carrier of the NOTCH3 mutation. We present a family with CADASIL in which cerebellar disease including ataxia was a major feature in three of four siblings and two of these also had pyramidal tract signs. Only one of the siblings presented with a feature typical for CADASIL, namely cognitive impairment. This family confirms the intrafamilial variation in CADASIL and demonstrates that ataxia and spastic paraparesis can be presenting features.

Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with considerable evidence suggesting an initiation of disease in the entorhinal cortex and hippocampus and spreading thereafter to the rest of the brain. In this study, we combine genetics and imaging data obtained from the Alzheimer's Disease Neuroimaging Initiative and the AddNeuroMed study. To identify genetic susceptibility loci for AD, we conducted a genome-wide study of atrophy in regions associated with neurodegeneration in this condition. We identified one single-nucleotide polymorphism (SNP) with a disease-specific effect associated with entorhinal cortical volume in an intron of the ZNF292 gene (rs1925690; P-value=2.6 × 10(-8); corrected P-value for equivalent number of independent quantitative traits=7.7 × 10(-8)) and an intergenic SNP, flanking the ARPP-21 gene, with an overall effect on entorhinal cortical thickness (rs11129640; P-value=5.6 × 10(-8); corrected P-value=1.7 × 10(-7)). Gene-wide scoring also highlighted PICALM as the most significant gene associated with entorhinal cortical thickness (P-value=6.7 × 10(-6)).

Functional expressions of the aging brain

In the conventional view, aging of the brain is associated with atrophy vascular abnormalities and loss of volume in hippocampus and amygdala. Cognitively, aging is associated with slowing of processing and memory loss. However, many studies of aging do not examine the cases to exclude demented people. The nutrition and memory in the homebound elderly study (NAME) excluded cases clinically diagnosed as having dementia. Cortical atrophy based on MRI ratings was significantly correlated with vascular disease, white matter hyperintensities, processing speed, and memory but not hippocampus and amygdala volume. Renal function and homocysteine were also associated with cortical atrophy but not with the cognitive variables. In conclusion, brain atrophy of aging in the absence of dementia is related to vascular disease but not hippocampal atrophy. Studies of nutritional interventions should consider using MRI atrophy rather than cognition as outcome.

Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia.

Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) are hypothesized to cause clinically distinct forms of primary progressive aphasia (PPA) that predominantly affect expressive speech. AD is thought to cause logopenic progressive aphasia (LPA), and FTLD may cause progressive nonfluent aphasia (PNFA). We sought to determine the value of clinical characterization, neuropsychological analysis, and MRI atrophy in predicting pathology of LPA and PNFA. Patients with LPA (n = 19) and patients with PNFA (n = 19) were evaluated with neuropsychological assessments, structural MRI, CSF analysis, and neuropathologic examination. Twelve of 19 patients with LPA (63%) and 6 of 19 patients with PNFA (32%) had neuropathologic findings or CSF biomarkers consistent with AD. Neuropsychological testing showed that naming was more impaired in patients with AD, and letter-guided fluency was more affected in patients with a non-AD disorder. Voxel-based morphometry analysis revealed that in patients with AD, patients with LPA and PNFA had significant posterior-superior temporal atrophy; in patients with non-AD, patients with LPA had peri-Sylvian atrophy and patients with PNFA had dorsolateral prefrontal and insular atrophy. Receiver operator characteristic curve analysis showed that combining neuropsychological testing with MRI atrophy pattern had 90% specificity for pathology or CSF biomarkers consistent with AD, and combining clinical features with neuropsychological analysis had 100% sensitivity for pathology or CSF biomarkers consistent with AD. Neither PPA phenotyping nor imaging alone is a reliable predictor of pathology. Multimodal predictors, such as combining neuropsychological testing with MRI analysis, can improve noninvasive prediction of underlying pathology in nonfluent forms of PPA.

Correlation between brain atrophy in MRI and CSF markers in Alzheimer's disease (AD)

Correlation between brain atrophy in MRI and CSF markers in Alzheimer's disease (AD)

Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease

To study the effect of apolipoprotein E epsilon4 status on biomarkers of neurodegeneration (atrophy on magnetic resonance imaging [MRI]), neuronal injury (cerebrospinal fluid [CSF] t-tau), and brain Abeta amyloid load (CSF Abeta(1-42)) in cognitively normal subjects (CN), amnestic subjects with mild cognitive impairment (aMCI), and patients with Alzheimer disease (AD). We included all 399 subjects (109 CN, 192 aMCI, 98 AD) from the Alzheimer's Disease Neuroimaging Initiative study with baseline CSF and MRI scans. Structural Abnormality Index (STAND) scores, which reflect the degree of AD-like anatomic features on MRI, were computed for each subject. A clear epsilon4 allele dose effect was seen on CSF Abeta(1-42) levels within each clinical group. In addition, the proportion of the variability in Abeta(1-42) levels explained by APOE epsilon4 dose was significantly greater than the proportion of the variability explained by clinical diagnosis. On the other hand, the proportion of the variability in CSF t-tau and MRI atrophy explained by clinical diagnosis was greater than the proportion of the variability explained by APOE epsilon4 dose; however, this effect was only significant for STAND scores. Low CSF Abeta(1-42) (surrogate for Abeta amyloid load) is more closely linked to the presence of APOE epsilon4 than to clinical status. In contrast, MRI atrophy (surrogate for neurodegeneration) is closely linked with cognitive impairment, whereas its association with APOE epsilon4 is weaker. The data in this paper support a model of AD in which CSF Abeta(1-42) is the earliest of the 3 biomarkers examined to become abnormal in both APOE carriers and noncarriers.

Measuring disease progression in frontotemporal lobar degeneration

There is currently much interest in biomarkers of disease activity in frontotemporal lobar degeneration (FTLD). We assessed MRI and behavioral measures of progression in a longitudinal FTLD cohort. Thirty-two patients with FTLD (11 behavioral variant frontotemporal dementia [bvFTD], 11 semantic dementia [SemD], 10 progressive nonfluent aphasia [PNFA]) and 24 age-matched healthy controls were assessed using volumetric brain MRI and standard behavioral measures (Mini-Mental State Examination, Frontal Assessment Battery, Clinical Dementia Rating Scale, Neuropsychiatric Inventory with Caregiver Distress scale) at baseline and 1 year later. A semi-automated image registration protocol was used to calculate annualized rates of brain atrophy (brain boundary shift integral [BBSI]) and ventricular expansion (ventricular boundary shift integral [VBSI]). Associations between these rates and changes in behavioral indices were investigated. Rates of whole brain atrophy were greater in the entire FTLD cohort and in each subgroup compared with controls (all p < or = 0.004). Rates of ventricular expansion were greater in the entire cohort (p < 0.001) and the SemD (p = 0.002) and PNFA (p = 0.05) subgroups compared with controls. Changes in Mini-Mental State Examination, Frontal Assessment Battery, and Clinical Dementia Rating Scale scores were associated with MRI measures of progression, though not uniformly across FTLD subgroups. Both BBSI and VBSI yielded feasible sample size estimates for detecting meaningful treatment effects in SemD and PNFA language subgroups. Sample sizes were substantially larger using MRI biomarkers for the bvFTD subgroup, and using behavioral biomarkers in general. Semi-automated MRI atrophy measures are potentially useful objective biomarkers of progression in frontotemporal lobar degeneration (FTLD); however, careful stratification of FTLD subtypes will be important in future clinical trials of disease-modifying therapies.

PW01-90 - Influence of apolipoprotein e genotype on cognitive function in patients with mild Alzheimer dementia

BackgroundApolipoprotein E allele ɛ4 is a well established risk factor for Alzheimer dementia (AD). Its presence modifies also the influence of other risk factors as well as the conversion rate of mild cognitive impairment (MCI) to overt dementia. In how far it also influences the clinical presentation of AD, is not known yet.MethodPatients of the memory clinic Göttingen were approached if they fulfilled the inclusion criteria: very mild or mild AD according to NINCDS-ADRDA criteria, MMSE 20-30, and at least two of three typical instrumental findings (hippocampal atrophy in MRI, bilateral temporo-parietal hypoperfusion in Neurolite-SPET, low Aβ1-42and increased tau in CSF). They underwent an extensive neuropsychological investigation. A follow-up took place within one year.ResultsN=74 patients (38M, 36F; mean age 68.1y; MMSE 25.9 ± 2.8) and N=28 age- and sex- and education-matched controls could be recruited. N=36 patients had one (N=20) or two (N=16) APOE -ɛ4-alleles. 53 of 57 CSF analyses revealed AD-typical findings, 64 of 74 cranial MRT revealed bilateral hippocampal or global atrophy and 42 of 64 Neurolite-SPETs showed typical findings. Results of non-memory tests - language, visuospatial ability, attention - did not reveal any difference with regard to APOE genotype. Two memory tests and a memory composite score were significantly worse in the APOE -ɛ4-positive group and even worse in the homozygote group.ConclusionAPOE -ɛ4 influences in a dose dependent manner the neuropsychological functioning in mild AD.

CHARACTERIZING RADIOLOGY REPORTS IN PATIENTS WITH FRONTOTEMPORAL DEMENTIA

Frontotemporal lobar degeneration (FTLD) is a common early onset dementing condition.1 The subtypes of FTLD, behavioral variant frontotemporal dementia (bvFTD), and semantic dementia (SemD) have distinctive imaging patterns that separate them from healthy aging, Alzheimer disease (AD), and from each other.2–4 The bvFTD causes frontotemporal tissue loss while SemD displays selective atrophy of the anterior temporal lobes. We performed a retrospective analysis of MRI atrophy patterns in 40 patients with bvFTD.5 ### Methods. #### Participants. All patients evaluated between 1999 and 2006 at the UCSF Memory and Aging Center who consented to research, met the Neary research criteria for FTD,5 and had an MRI scan within 1 year of presentation were included (figure e-1 on the Neurology ® Web site at www.neurology.org). The referring diagnosis in patients’ records and the radiologist’s findings and impression on the first scan were recorded. Thirty-four scans were performed in academic settings and 6 in private centers. #### Standard protocol approvals, registrations, and patient consents. We received ethics approval from the UCSF Research ethical standards committee on human experimentation and informed consent was obtained from all participants. #### Test methods. Nine categories were identified based on the radiologist’s reports of the 40 patients: 1) bvFTD, 2) white matter/ischemic disease, 3) AD, 4) normal pressure hydrocephalus (NPH)/hydrocephalus, 5) mitochondrial/metabolic, 6) encephalomalacia, …

Correlation between medial temporal lobe atrophy in MRI and CSF markers in Alzheimer's disease (AD)

Correlation between medial temporal lobe atrophy in MRI and CSF markers in Alzheimer's disease (AD)

Differentiation of PA from early PSP with different patterns of symptoms and CBF reduction

Objective: To clarify the features of pure akinesia (PA) and progressive supranuclear palsy (PSP) in the early stage of disease.Methods: We investigated 15 PA and 41 PSP patients' clinical and radiologic features including head MRI, ethyl cysteinate dimmer-single photon emission-computed tomography (ECD-SPECT) and iodine-123 meta-iodobenzyl guanidine (123I-MIBG) myocardial scintigraphy. In ECD-SPECT study, cerebral blood flow (CBF) reduction was quantitatively expressed as Z-score, and that in the frontal lobe was evaluated.Results: Many PSP patients claimed falls as the initial symptom but no PA patients did. Eye movement, as well as optokinetic nystagmus elicitation, was more frequently disturbed in PSP. Dementia, dysarthria and rigidity were also more frequent in PSP than in PA. Midbrain tegmentum atrophy in head MRI was more frequently observed in PSP. CBF in the frontal lobe, especially in the frontal eye field, was significantly lower in PSP than in PA. MIBG myocardial scintigraphy showed no difference between two groups.Discussion: PA and PSP show distinct symptoms from the early stage, indicating that they are distinct disorders. The occurrence of falls and eye movement disturbance, as well as CBF reduction at the frontal eye field, is very important for distinguishing these disorders.

Episodic ataxia type 2 showing ictal hyperhidrosis with hypothermia and interictal chronic diarrhea due to a novel CACNA1A mutation

Autosomal dominant episodic ataxia type 2 (EA2) results from mutations of the CACNA1A gene. We describe EA2 with unusual features in a father and daughter with a novel CACNA1A mutation coding for Y248C. Both patients showed severe cerebellar atrophy in MRI and clinical signs of progressive spinocerebellar atrophy type 6. Most disabling were the very frequent episodes of ataxia with migraine (with aura in the father and without aura in the daughter) and nystagmus in our patients. Additionally, they suffered from ictal hyperhidrosis with acute hypothermia of the extremities. Lastly, the father presented with interictal chronic diarrhea not associated to a known primary gastrointestinal disorder. Both ictal hyperhidrosis and interictal diarrhea ameliorated upon acetazolamide intake, the typical treatment for EA2. The significance of these findings is discussed and the phenotype correlated to previously reported cases.

Poster Abstract #14: Magnetic Resonance Disease Severity Scale (MRDSS) Predicts Clinical Progression in Multiple Sclerosis

Objective Combine MRI measures of disease severity into a composite score in patients with multiple sclerosis (MS). Background Brain MRI lesion and atrophy measures assessed individually have fairly weak ability to predict clinical progression in MS. Methods In the Comprehensive Longitudinal Investigation of MS at Brigham, we studied 103 patients [age (mean ± SD) 42.7 ± 9.1 years, disease duration 14.1 ± 9.2 years, Expanded Disability Status Scale (EDSS) score 3.3 ± 2.2, 60% (n = 62) relapsing–remitting (RR), 32% (n = 33) secondary progressive (SP), and 8% (n = 8) primary progressive]. Brain MRI measures included baseline T2 hyperintense (T2LV) and T1 hypointense (T1LV) lesion volume, and brain parenchymal fraction (BPF), a marker of global atrophy. The ratio of T1LV to T2LV assessed lesion severity. A Magnetic Resonance Disease Severity Scale (MRDSS) score, on a continuous scale from 0 to 10, was derived for each patient using T2LV, BPF, and T1/T2 ratio. Results MRDSS score averaged 5.1 ± 2.6. Baseline MRI and EDSS correlations were moderate for BPF, T1/T2, and MRDSS and weak for T2LV. MRDSS showed a larger effect size than any of the individual MRI components in distinguishing RR from SP patients. Models containing either T2LV or MRDSS were significantly associated with EDSS disability progression during the 3.2 ± 0.3 year observation period, when adjusting for baseline EDSS score. Conclusions These results show that combining brain MRI lesion and atrophy measures can predict clinical progression in patients with MS and provide the basis to develop an MRI-based continuous scale as a marker of MS disease severity.

Distinct MRI atrophy patterns in autopsy-proven Alzheimer's disease and frontotemporal lobar degeneration.

To better define the anatomic distinctions between Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), we retrospectively applied voxel-based morphometry to the earliest magnetic resonance imaging scans of autopsy-proven AD (N = 11), FTLD (N = 18), and controls (N = 40). Compared with controls, AD patients showed gray matter reductions in posterior temporoparietal and occipital cortex; FTLD patients showed atrophy in medial prefrontal and medial temporal cortex, insula, hippocampus, and amygdala; and patients with both disorders showed atrophy in dorsolateral and orbital prefrontal cortex and lateral temporal cortex (P(FWE-corr) < .05). Compared with FTLD, AD patients had decreased gray matter in posterior parietal and occipital cortex, whereas FTLD patients had selective atrophy in anterior cingulate, frontal insula, subcallosal gyrus, and striatum (P < .001, uncorrected). These findings suggest that AD and FTLD are anatomically distinct, with degeneration of a posterior parietal network in AD and degeneration of a paralimbic fronto-insular-striatal network in FTLD.

Longitudinal CSF isoprostane and MRI atrophy in the progression to AD

Very little data exist to evaluate the value of longitudinal CSF biological markers for Alzheimer's disease (AD). Most studies indicate that tau and amyloid beta markers do not reflect disease progression. We now report on a longitudinal, three-time point, CSF Isoprostane (IsoP) and quantitative MRI study that examined 11 normal elderly (NL) volunteers and 6 Mild Cognitive Impairment (MCI) patients. After 4 years, all 6 MCI patients declined to AD and 2 of the NL subjects declined to MCI. At baseline and longitudinally, the MCI patients showed reduced delayed memory, increased IsoP levels, and reduced medial temporal lobe gray matter concentrations as compared to NL. A group comprised of all decliners to AD or to MCI (n = 8) was distinguished at baseline from the stable NL controls (n = 9) by IsoP with 100% accuracy.Moreover, both at baseline and longitudinally, the IsoP measures significantly improved the diagnostic and predictive outcomes of conventional memory testing and quantitative MRI measurements. These data indicate that IsoP is potentially useful for both the early detection of AD-related pathology and for monitoring the course of AD.

Patterns of MRI atrophy in tau positive and ubiquitin positive frontotemporal lobar degeneration

We applied optimised voxel based morphometry (VBM) to brain MRIs from autopsy proven cases of tau positive frontotemporal lobar degeneration (FTLD-T, n = 6), ubiquitin and TDP-43 positive/tau negative FTLD...

P-025: MRI atrophy in mci is specific, not sensitive, for progression to Alzheimer disease

P-025: MRI atrophy in mci is specific, not sensitive, for progression to Alzheimer disease

Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI

The vitamin E and donepezil trial for the treatment of amnestic mild cognitive impairment (MCI) was conducted at 69 centers in North America; 24 centers participated in an MRI sub study. The objective of this study was to evaluate the effect of treatment on MRI atrophy rates; and validate rate measures from serial MRI as indicators of disease progression in multi center therapeutic trials for MCI. Annual percent change (APC) from baseline to follow-up was measured for hippocampus, entorhinal cortex, whole brain, and ventricle in the 131 subjects who remained in the treatment study and completed technically satisfactory baseline and follow-up scans.Although a non-significant trend toward slowing of hippocampal atrophy rates was seen in APOE ∈4 carriers treated with donepezil; no treatment effect was confirmed for any MRI measure in either treatment group. For each of the four brain atrophy rate measures, APCs were greater in subjects who converted to AD than non-converters, and were greater in APOE ∈4 carriers than non-carriers. MRI APCs and changes in cognitive test performance were uniformly correlated in the expected direction (all p<0.000). Results of this study support the feasibility of using MRI as an outcome measure of disease progression in multi center therapeutic trials for MCI.

Use of the Putamen/Caudate Volume Ratio for Early Differentiation between Parkinsonian Variant of Multiple System Atrophy and Parkinson Disease

Background and purposeNeuropathological studies have demonstrated that multiple system atrophy (MSA) produces selective atrophy of the putamen with sparing of the caudate nucleus, while both structures are spared in idiopathic Parkinson's disease (PD). In this study we evaluated the clinical efficacy of using putaminal atrophy in brain MRI to differentiate MSA and PD.MethodsWe measured the putamen/caudate volume ratio on brain MRI in 24 patients with MSA and 21 patients with PD. Two clinicians who were blinded to the patients' diagnoses and to each other's assessments measured the volume ratio using a computer program.ResultsThe measured volume ratios of the two investigators were highly correlated (r=0.72, p<0.0001). The volume ratio was significantly lower in MSA (1.29±0.28) than PD (1.91±0.29, p<0.0001). Setting an arbitrary cutoff ratio of 1.6 resulted in about 90% of patients with MSA falling into the group with a lower ratio, whereas more than 80% of patients with PD belonged to the other group.ConclusionsThe present results demonstrate that putaminal atrophy in MSA as measured on brain MRI represents an effective tool for differentiating MSA from PD.

Voltage sources in mesial temporal lobe epilepsy recorded with foramen ovale electrodes

Objective We introduce a monopole model to examine the sources of ictal and interictal activity in mesial temporal lobe epilepsy (MTLE) recorded using foramen ovale electrodes (FOE). Methods Classical electrostatic theory was applied to derive mathematical expressions. Interictal and ictal activity was acquired using FOE and scalp video-electroencephalography (v-EEG) during awake and sleep states. A total of 2057 interictal spikes and 712 ictal spikes were analyzed. Thirty-five seizures from several consecutive episodes were examined. MRI and clinical data were correlated with voltage source localization. Results Patients (20) were grouped according to the spatial distribution of voltage sources of interictal activity. Voltage sources were located over 3.4 and 21.6 mm in the anterior-to-posterior axis of mesiotemporal structures and separated no more than 7 mm from this axis. In most patients (16), sources were restricted to 11.1 ± 1.5 mm, whereas other patients (4) exhibited a wider distribution (29.6–43.5 mm). Sources of ictal and interictal activity partially overlapped, with ictal sources exhibiting a posterior localization at 20–40 mm. Both interictal and ictal sources were anterior to MRI atrophy. No difference between awake and sleep states were found, neither correlation between source scattering and history of epilepsy. Conclusions Voltage source analysis applied to FOE suggests that, in most MTLE patients, interictal activity emerges from very restricted areas. Some patients, however, exhibited sources which are distributed all along the mesiotemporal structures. Our data suggest an anterior-to-posterior alignment of the irritative, ictal and atrophic zones. Significance The voltage source model applied to FOE can help to map the extension of the irritative and ictal areas in mesiotemporal structures.