Differential influence of hippocampal subfields to memory formation: insights from patients with temporal lobe epilepsy.

To clarify the anatomical organization of human memory remains a major challenge in clinical neuroscience. Experimental data suggest dentate gyrus granule cells play a major role in memory acquisition, i.e. pattern separation and rapid pattern completion, whereas hippocampal CA1 neurons are implicated in place memory and autobiographical memory retrieval. Patients with temporal lobe epilepsy present with a broad spectrum of memory impairment, which can be assessed during clinical examination. Although long seizure histories may contribute to a pathophysiological reorganization of functional connectivity, surgical resection of the epileptic hippocampus offers a unique possibility to anatomically study the differential contribution of hippocampal subfields to compromised learning and memory in humans. Herein, we tested the hypothesis of hippocampal subfield specialization in a series of 100 consecutive patients with temporal lobe epilepsy submitted to epilepsy surgery. Memory profiles were obtained from intracarotid amobarbital testing and non-invasive verbal memory assessment before surgery, and correlated with histopathologically quantified cell loss pattern in hippocampal subfields obtained from the same patients using the new international consensus classification for hippocampal sclerosis proposed by the International League against Epilepsy (HS ILAE). Interestingly, patients with CA1 predominant cell loss (HS ILAE Type 2; n = 13) did not show declarative memory impairment and were indistinguishable from patients without any hippocampal cell loss (n = 19). In contrast, 63 patients with neuronal loss affecting all hippocampal subfields including CA1, CA4 and dentate gyrus (HS ILAE Type 1), or predominant cell loss in CA4 and partially affecting also CA3 and dentate gyrus (HS ILAE Type 3, n = 5) showed significantly reduced declarative memory capacities (intracarotid amobarbital testing: P < 0.001; verbal memory: P < 0.05). Our results suggested an alternative model of how memory processing can be organized amongst hippocampal subfields, and that CA1 pyramidal cells are less critically involved in declarative human memory acquisition compared to dentate gyrus granule cells or CA4/CA3 pyramidal cells.

Risk reduction in dominant temporal lobe epilepsy surgery combining fMRI/DTI maps, neuronavigation and intraoperative 1.5-Tesla MRI.

BACKGROUND: In dominant temporal lobe epilepsy surgery, speech, memory and visual systems are at risk. OBJECTIVE: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging combined with intraoperative neuronavigation and MRI were investigated retrospectively regarding risk reductions for favorable neurological and seizure outcome. METHODS: Functional imaging risk maps were generated for 14 patients suffering from dominant temporal lobe epilepsy [7 with hippocampal sclerosis (HS), 7 with various lesions] and used for neuronavigation-guided tailored resection. Postoperative neurological and seizure outcome and complications were evaluated. RESULTS: None of the patients had postoperative speech dysfunction despite 2.3/3.6-cm mean hippocampal/neocortical resection. Verbal memory decline was found in 2 of the 14 (14.3%) patients, correlating with surgical lesions in fMRI memory-activated functional areas in the dominant posterior parahippocampal gyrus. Verbal memory scores did not statistically differ between the HS and the lesional group, neither pre- nor postoperatively. A contralateral visual field defect occurred in 1 patient (7.1%). An Engel class I seizure outcome was found in 12 patients (85.7%), and 11 were completely seizure free (78.6%) at a mean follow-up of 19.5 months. CONCLUSION: This retrospectively investigated protocol led to an excellent neurological and seizure outcome and a low complication rate in dominant temporal lobe epilepsy surgery.

Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia.

Periventricular nodular heterotopia (PNH) is a developmental disorder of the central nervous system, characterized by heterotopic nodules of gray matter resulting from disturbed neuronal migration. The most common form of bilateral PNH is X-linked dominant inherited, caused by mutations in the Filamin A gene (FLNA) and associated with a wide variety of other clinical findings including congenital heart disease. The typical patient with FLNA-associated PNH is female and presents with difficult to treat seizures. In contrast, hemizygous FLNA loss of function mutations in males are reported to be perinatally lethal. In X-linked dominant traits like FLNA-associated PNH the causal mutation is commonly inherited from the mother. Here, we present an exceptional family with paternal transmission of classic bilateral FLNA-associated PNH from a mildly affected father with somatic and germline mosaicism for a c.5686G>A FLNA splice mutation to both daughters with strikingly variable clinical manifestation and PNH extent in cerebral MR imaging. Our observations emphasize the importance to consider in genetic counseling and risk assessment the rare genetic constellation of paternal transmission for families with X-linked dominant inherited FLNA-associated PNH.

Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: a proof of concept trial.

To elucidate, in a pilot-study, whether noninvasive transcutaneous vagus nerve stimulation (t-VNS) is a safe and tolerable alternative treatment option in pharmacoresistant epilepsy. t-VNS was applied to 10 patients with pharmacoresistant epilepsies. Stimulation via the auricular branch of the vagus nerve of the left tragus was delivered three times per day for 9 months. Subjective documentation of stimulation effects was obtained from patients' seizure diaries. For a more reliable assessment of seizure frequency, we carried out prolonged outpatient video-electroencephalography (EEG) monitoring. In addition, computerized testing of cognitive, affective, and emotional functions was performed. Three patients aborted the study. Of the remaining seven patients, an overall reduction of seizure frequency was observed in five patients after 9 months of t-VNS. The noninvasive t-VNS stimulation is a safe and well-tolerated method for relatively long periods, and might be an alternative treatment option for patients with epilepsy.

Localization of beta power decrease as measure for lateralization in pre-surgical language mapping with magnetoencephalography, compared with functional magnetic resonance imaging and validated by Wada test.

Objective: Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task. Methods: Twenty-five patients with pharmaco-resistant epilepsy, including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects. Results: Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and parietal language areas (Cohen's Kappa = 1, p < 0.001). fMRI agreed with Wada test in 12 out of 14 cases (85.7%) for Broca's area (Cohen's Kappa = 0.71, p = 0.024), while the agreement for temporal and temporo-parietal language areas were non-significant. Concordance between MEG and fMRI laterality indices was highest within the inferior frontal gyrus, with an agreement in 19/24 cases (79.2%), and non-significant for Wernicke's area. Spatial agreement between fMRI and MEG varied considerably between subjects and brain regions with the lowest Euclidean distances within the inferior frontal region of interest. Conclusion: Localizing the desynchronization of MEG beta power using a verb generation task is a promising tool for the identification of language dominance in the pre-surgical evaluation of epilepsy patients. The overall agreement between MEG and fMRI was lower than expected and might be attributed to differences within the baseline condition. A larger sample size and an adjustment of the experimental designs are needed to draw further conclusions.

High NIHSS values predict impairment of cardiovascular autonomic control.

BACKGROUND AND PURPOSE: Stroke is frequently associated with autonomic dysfunction, which causes secondary cardiovascular complications. Early diagnosis of autonomic imbalance prevents complications, but it is only available at specialized centers. Widely available surrogate markers are needed. This study tested whether stroke severity, as assessed by National Institutes of Health Stroke Scale (NIHSS) scores, correlates with autonomic dysfunction and thus predicts risk of autonomic complications. METHODS: In 50 ischemic stroke patients, we assessed NIHSS scores and parameters of autonomic cardiovascular modulation within 24 hours after stroke onset and compared data with that of 32 healthy controls. We correlated NIHSS scores with parameters of total autonomic modulation (total powers of R-R interval [RRI] modulation; RRI standard deviation [RRI-SD], RRI coefficient of variation), parasympathetic modulation (square root of the mean squared differences of successive RRIs, RRI-high-frequency-powers), sympathetic modulation (normalized RRI-low-frequency-powers, blood pressure-low-frequency-powers), the index of sympatho-vagal balance (RRI-LF/HF-ratios), and baroreflex sensitivity. RESULTS: Patients had significantly higher blood pressure and respiration, but lower RRIs, RRI-SDs, RRI coefficient of variation, square root of the mean squared differences of successive RRIs, RRI-low-frequency-powers, RRI-high-frequency-powers, RRI-total powers, and baroreflex sensitivity than did controls. NIHSS scores correlated significantly with normalized RRI-low-frequency-powers and RRI-LF/HF-ratios, and indirectly with RRIs, RRI-SDs, square root of the mean squared differences of successive RRIs, RRI-high-frequency-powers, normalized RRI-high-frequency-powers, RRI-total-powers, and baroreflex sensitivity. Spearman-Rho values ranged from 0.29 to 0.47. CONCLUSIONS: Increasing stroke severity was associated with progressive loss of overall autonomic modulation, decline in parasympathetic tone, and baroreflex sensitivity, as well as progressive shift toward sympathetic dominance. All autonomic changes put patients with more severe stroke at increasing risk of cardiovascular complications and poor outcome. NIHSS scores are suited to predict risk of autonomic dysregulation and can be used as premonitory signs of autonomic failure.

18Fluoroethyl-L-tyrosine-PET in long-term epilepsy associated glioneuronal tumors.

PURPOSE: Long-term epilepsy associated tumors (LEATs) are a frequent cause of drug-resistant partial epilepsy. A reliable tumor diagnosis has an important impact on therapeutic strategies and prognosis in patients with epilepsy, but often is difficult by magnetic resonance imaging (MRI) only. Herein we analyzed a large LEAT cohort investigated by 18fluoroethyl-L-tyrosine-positron emission tomography (FET-PET). METHODS: Thirty-six patients with chronic partial epilepsy and a LEAT-suspect MRI lesion were analyzed by FET-PET using visual inspection and quantitative analysis of standard uptake values (SUV). PET results were correlated with clinical and histopathologic data. RESULTS: FET-PET study was positive in 22 of 36 analyzed lesions and in 14 of 22 histologically verified LEAT lesions. The precise World Health Organization (WHO) tumoral entity was not predicted by FET-PET. Notably, FET uptake correlated strikingly with age at epilepsy onset (p = 0.001). Further correlations were seen for age at surgery (p = 0.007) and gadolinium-contrast enhancement on MRI (p < 0.05). DISCUSSION: FET-PET is a helpful tool for LEAT diagnosis, particularly when MRI readings are ambiguous. FET uptake, which is likely mediated by the l-amino acid transporter (LAT) family, might indicate a principally important biologic property of certain LEATs, since LAT molecules also are involved in cell growth regulation.

Standardized antipyretic treatment in stroke: a pilot study.

BACKGROUND: Fever after acute cerebral injury is associated with unfavorable functional outcome and increased mortality, but there is controversy about the optimal antipyretic treatment. This study investigated an institutional standard operating procedure (SOP) for fever treatment in stroke patients including a sequence of pharmacologic and physical interventions. METHODS: A 4-step antipyretic SOP was established for patients with acute cerebral ischemia or hemorrhage and a body temperature ≥37.5°C within the first 6 days after admission. Data on the course of body temperature, duration of fever and achievement of normothermia were recorded. Results were compared to a historic control group that underwent conventional treatment. RESULTS: A total of 77 patients (mean age 70.4 ± 14.2 years) received 331 antipyretic interventions. Sequential administration of paracetamol (n = 219), metamizole (n = 71) and calf packing (n = 24) resulted in a significant drop in body temperature after 60 min in each instance. In 5 of 9 cases which were refractory to previous attempts, normothermia followed the infusion of ice-cooled saline. In more than 90% of cases treated per protocol, normothermia was achieved within 120 min. Compared to conventional treatment, fever burden was significantly lower within the first 4 days after admission (p < 0.001). CONCLUSION: This SOP may help to optimize antipyretic treatment for stroke patients.

Low proliferation and differentiation capacities of adult hippocampal stem cells correlate with memory dysfunction in humans.

The hippocampal dentate gyrus maintains its capacity to generate new neurons throughout life. In animal models, hippocampal neurogenesis is increased by cognitive tasks, and experimental ablation of neurogenesis disrupts specific modalities of learning and memory. In humans, the impact of neurogenesis on cognition remains unclear. Here, we assessed the neurogenic potential in the human hippocampal dentate gyrus by isolating adult human neural stem cells from 23 surgical en bloc hippocampus resections. After proliferation of the progenitor cell pool in vitro we identified two distinct patterns. Adult human neural stem cells with a high proliferation capacity were obtained in 11 patients. Most of the cells in the high proliferation capacity cultures were capable of neuronal differentiation (53 ± 13% of in vitro cell population). A low proliferation capacity was observed in 12 specimens, and only few cells differentiated into neurons (4 ± 2%). This was reflected by reduced numbers of proliferating cells in vivo as well as granule cells immunoreactive for doublecortin, brain-derived neurotrophic factor and cyclin-dependent kinase 5 in the low proliferation capacity group. High and low proliferation capacity groups differed dramatically in declarative memory tasks. Patients with high proliferation capacity stem cells had a normal memory performance prior to epilepsy surgery, while patients with low proliferation capacity stem cells showed severe learning and memory impairment. Histopathological examination revealed a highly significant correlation between granule cell loss in the dentate gyrus and the same patient's regenerative capacity in vitro (r = 0.813; P < 0.001; linear regression: R²(adjusted) = 0.635), as well as the same patient's ability to store and recall new memories (r = 0.966; P = 0.001; linear regression: R²(adjusted) = 0.9). Our results suggest that encoding new memories is related to the regenerative capacity of the hippocampus in the human brain.

Autobiographical memory in temporal lobe epilepsy: role of hippocampal and temporal lateral structures.

The present study was aimed at investigating the impact of hippocampal and temporal cortical lesions on remote autobiographical memories in temporal lobe epilepsy (TLE). Episodic specificity, episodic richness, and personal semantic memory from different life periods were assessed using a modified version of the Autobiographical Memory Interview (AMI) (M.D. Kopelman, A.E. Wilson, A. Baddeley, The autobiographical memory interview. Bury St. Edmunds: Thames Valley Test Co.; 1990) in 47 patients with unilateral mesial or lateral TLE and 38 healthy controls. Patients with TLE performed significantly more poorly than controls. Patients with left and right mTLE were equally moderately impaired, but patients with left lateral TLE had the most severe episodic memory deficits, particularly for childhood memories. With respect to personal semantic memory, patients with left TLE were significantly more impaired than those with right TLE, most pronounced for childhood memories. Both autobiographical memory aspects, episodic and personal semantic memory, were significantly intercorrelated, but both did not correlate with anterograde memory, indicating a structural dissociation between both functions.

A distinct variant of focal cortical dysplasia type I characterised by magnetic resonance imaging and neuropathological examination in children with severe epilepsies.

Focal Cortical Dysplasias (FCDs) present with a large clinicopathological spectrum. FCDs are believed to relate directly to an epileptogenic condition, although seizure control by surgical resection is variable. This applies in particular to young children with multilobar FCDs, suffering from severe epilepsies and psychomotor retardation. Herein, we performed a comparative analysis of presurgically available data and microscopic inspection of resected cortical specimens to further characterise the pathomorphological spectrum of FCD. Multilobar resection procedures were performed in a consecutive series of 18 young children (mean 7.6 years) with severe pharmaco-resistant epilepsies following extensive presurgical surface-/invasive video-EEG monitoring intraoperative electro-corticography (iECoG), as well as high resolution MRI. In all cases, systematic neuropathological examination of surgical specimens was performed with respect to architectural abnormalities and cell density measurements. These histomorphological data were compared with volumetric MRI analysis. Histopathological examination revealed increased neuronal densities correlating with decreased cortical thickness and abundance of neuronal microcolumns in all cases. Intriguingly, the affected cerebral hemisphere was significantly smaller, relative to the non-epileptogenic contralateral side, in 16 children of our patient series. In conclusion, hypoplastic neocortex and columnar architectural disorganisation point to compromised cortical development, and appear as distinct FCD I subtype in children suffering from severe epilepsies and psychomotor retardation.

Increased reelin promoter methylation is associated with granule cell dispersion in human temporal lobe epilepsy.

Mesial temporal sclerosis (MTS) is the most common lesion in chronic, intractable temporal lobe epilepsies (TLE) and characterized by segmental neuronal cell loss in major hippocampal segments. Another histopathological hallmark includes granule cell dispersion (GCD), an architectural disturbance of the dentate gyrus encountered in approximately 50% of patients with mesial temporal sclerosis. Reelin, which plays a key role during hippocampal development and maintenance of laminar organization, is synthesized and released by Cajal-Retzius cells of the dentate molecular layer, and previous studies have shown that Reelin transcript levels are downregulated in human temporal lobe epilepsies specimens. To investigate whether epigenetic silencing by Reelin promoter methylation may be an underlying pathogenetic mechanism of GCD, DNA was harvested from 3 microdissected hippocampal subregions (i.e. molecular and granule cell layers of the dentate gyrus and presubiculum) from 8 MTS specimens with GCD, 5 TLE samples without GCD, and 3 autopsy controls. Promoter methylation was analyzed after bisulfite treatment, cloning, and direct sequencing; immunohistochemistry was performed to identify Cajal-Retzius cells. Reelin promoter methylation was found to be greater in TLE specimens than in controls; promoter methylation correlated with GCD among TLE specimens (p < 0.0002). No other clinical or histopathological parameter (i.e. sex, age, seizure duration, medication or extent, of MTS) correlated with promoter methylation. These data support a compromised Reelin-signaling pathway and identify promoter methylation as an epigenetic mechanism in the pathogenesis of TLE.

Towards a clinico-pathological classification of granule cell dispersion in human mesial temporal lobe epilepsies.

The dentate gyrus (DG) plays a pivotal role in the functional and anatomical organization of the hippocampus and is involved in learning and memory formation. However, the impact of structural DG abnormalities, i.e., granule cell dispersion (GCD), for hippocampal seizure susceptibility and its association with distinct lesion patterns in epileptic disorders, such as mesial temporal sclerosis (MTS) remains enigmatic and a large spectrum of pathological changes has been recognized. Here, we propose a clinico-pathological classification of DG pathology based on the examination of 96 surgically resected hippocampal specimens obtained from patients with chronic temporal lobe epilepsy (TLE). We observed three different histological patterns. (1) A normal granule cell layer was identified in 11 patients (no-GCP; 18.7%). (2) Substantial granule cell loss was evident in 36 patients (referred to as granule cell pathology (GCP) Type 1; 37.5%). (3) Architectural abnormalities were observed in 49 specimens, including one or more of the following features: granule cell dispersion, ectopic neurons or clusters of neurons in the molecular layer, or bi-lamination (GCP Type 2; 51%). Cell loss was always encountered in this latter cohort. Seventy-eight patients of our present series suffered from MTS (81.3%). Intriguingly, all MTS patients displayed a compromised DG, 31 (40%) with significant cell loss (Type 1) and 47 (60%) with GCD (Type 2). In 18 patients without MTS (18.7%), seven displayed focally restricted DG abnormalities, either cell loss (n = 5) or GCD (n = 2). Clinical histories revealed a significant association between DG pathology patterns and higher age at epilepsy surgery (p = 0.008), longer epilepsy duration (p = 0.004), but also with learning dysfunction (p < 0.05). There was no correlation with the extent of pyramidal cell loss in adjacent hippocampal segments nor with postsurgical seizure relief. The association with long-term seizure histories and cognitive dysfunction is remarkable and may point to a compromised regenerative capacity of the DG in this cohort of TLE patients.

Different presurgical characteristics and seizure outcomes in children with focal cortical dysplasia type I or II.

PURPOSE: Cortical dysplasia (FCD) is a frequent cause of epilepsy in childhood. Two major pathological variants are distinguished, FCD type I and II. The aim of the study was to characterize differences between FCD type I and II with respect to imaging and EEG findings, clinical and neuropsychological presentations, and surgical outcome. METHODS: Forty children with refractory epilepsy and histopathologically confirmed FCD were retrospectively analyzed. FCD type I was identified in 24 and FCD type II in 16 patients. RESULTS: Characteristic MRI abnormalities in FCD type I included subtle white matter signal changes and regional reduction of the white matter volume. Typical MRI findings in FCD type II were increased cortical thickness, transmantle sign, gray-white matter junction blurring, fluid-attenuated inversion recovery (FLAIR) and proton density (PD) gray matter signal changes as well as T1w, and PD white matter signal changes. Continuous EEG slowing was significantly more common in patients with FCD type I. Children with FCD type I presented with lower levels of intelligence and were suffering more often from maladaptive behavior and behavioral disorders. Surgical outcome was significantly worse in the FCD type I group (seizure freedom was achieved in 21% FCD type I patients and in 75% FCD type II subjects, p < 0.001). CONCLUSIONS: Clinically important differences were found in children with distinct histopathological subtypes of FCD. Due to prominent neuropsychological deficits and worse seizure outcome, treatment strategies in FCD type I are more challenging than previously reported and these children should be recognized and specifically addressed within the incoherent group of patients with malformative brain disorders.

Postoperative speech processing in temporal lobe epilepsy: functional relationship between object naming, semantics and phonology.

Deficits in confrontation naming ability can occur after epilepsy surgery in the left temporal lobe. This study addresses the functional relationship between postoperative object naming and semantic and phonological speech processing in patients with epilepsy. Fifty-eight consecutive patients with temporal lobe epilepsy from our epilepsy surgery program (24 patients with left temporal lobe epilepsy, 34 patients with right temporal lobe epilepsy) were investigated using the Boston Naming Test and comprehensive semantic and phonological speech testing. Language dominance was evaluated in all patients with the preoperative intracarotid sodium amytal test. Naming decline was observed exclusively in patients with left temporal lobe epilepsy. Regression analysis with semantic processing and phonological input/output processing as independent variables, and naming change in the Boston Naming Test (preoperative-postoperative score) as a dependent variable, revealed a significant association between postoperative naming decline and impaired semantic functions. Accordingly, patients exhibited deficits in the category-related differentiation of objects. It is hypothesized that naming deficits arise from the functional specialization of the left temporal lobe for semantic interpretation of visual input.

Drug withdrawal after successful epilepsy surgery: how safe is it?

Discontinuation of antiepileptic drugs (AEDs) is one reason patients undergo epilepsy surgery, but little is known about the risk of seizure recurrence. We describe a prospective pilot study of withdrawal performed at our epilepsy center. Sixty completely seizure-free patients were included between 1997 and 2003. AED withdrawal was proposed 1 year after surgery after a detailed discussion of the risks and benefits. On the basis of their decision on withdrawal, patients were stratified into two cohorts (withdrawal group, N=34; control group, N=26). Discontinuation was carried out in small tapering steps over 1 year with yearly follow-up visits. Withdrawal was stopped when seizures recurred or the patients objected to further discontinuation. Twenty-six of 34 (76.5%) persons in the withdrawal group and 16 of 26 (61.5%) persons in the control group were seizure free 5 years after surgery. In this study, AED discontinuation 1 year after successful epilepsy surgery was not associated with a risk of seizure recurrence higher than that of controls.

Magnetic resonance imaging and neuropsychological testing after middle fossa vestibular schwannoma surgery.

OBJECTIVE: To analyze temporal lobe gliosis and temporal lobe dysfunction after middle fossa vestibular schwannoma surgery. STUDY DESIGN: Temporal lobe analysis of a series of cases. SETTING: Tertiary referral center. PATIENTS: Thirty-two patients after enlarged middle fossa surgery (EMFS) and 20 subjects for control (preferably husbands/wives). INTERVENTIONS: Magnetic resonance evaluation of the temporal lobe and neuropsychological testing. MAIN OUTCOME MEASURES: Magnetic resonance imaging of the temporal lobe 1 year after treatment and neuropsychological testing (Berliner Amnesia Test [BAT], Boston Naming Test [BT], Token Test, Beck Depression Inventory, Freiburger Personality Inventory). RESULTS: Temporal lobe gliosis after EMFS was observed in 22 of 32 analyzed patients (degree of gliosis: 11, slight; 9, moderate; 2, severe). Neuropsychological testing of 23 of the 32 previously analyzed patients after EMFS compared with control subjects (n=20) found only in few subdomains (figural score, personality test) statistically significant worse test results, but no major disturbances of the temporal lobe function compared with the control group. Only one patient with a finding of severe temporal lobe gliosis was proven in the BAT and BT to have a temporal lobe deficit. CONCLUSION: In a significant number of patients, temporal lobe gliosis has to be expected after EMFS; however, the gliosis is only slight or moderate in most of the patients and not associated with essential functional deficits of the temporal lobe. Nevertheless, the possibility of a severe temporal lobe gliosis with functional deficits in the BAT and BT has to be taken into consideration.

Investigations in subjects with cough following upper respiratory tract infection.

The study aimed to investigate subjects with cough following acute upper respiratory tract infection (URTI), and to compare those subjects unable to suppress cough ("non-suppressors") with those who were able to suppress cough ("suppressors"). Forty-three URTI subjects participated, 31 with cough associated with acute URTI and 12 healthy controls; 21 of the coughing subjects were "suppressors", 10 were "non-suppressors". We obtained responses to chemical and mechanical stimulation of the nasal cavity or the pharynx using both psychophysical measures and event-related potentials. The study provided the following results: (1) "non-suppressors" did not exhibit significantly different intensity ratings or event-related potentials in comparison to "suppressors" in terms of responses to intranasal irritant, mechanical, or olfactory stimuli; (2) when pharyngeal mechanical stimuli were investigated "suppressors" rated the stimuli as more intense than "non-suppressors" and controls; (3) latencies of event-related potentials to pharyngeal stimuli were longest in "non-suppressors". Keeping in mind the relatively small sample size, it appears possible to differentiate certain types of cough during uncomplicated URTI. This may help to explain interindividual differences in responsiveness to cough medication.

Activation of the RAGE pathway: a general mechanism in the pathogenesis of polyneuropathies?

OBJECTIVES: Binding of ligands to the receptor for advanced glycation end products (RAGE) results in activation of the transcription factor NF-kappaB and subsequent expression of NF-kappaB regulated cytokines and is a possible pathomechanism in diabetic and in vasculitic polyneuropathies (PNP). We wanted to investigate whether the newly discovered RAGE pathway also contributes to the pathogenesis of various other PNP. METHODS: The presence of the RAGE ligand Nepsilon-Carboxymethyllysine (CML), the receptor itself and NF-kappaBp65 was studied in sural nerve biopsies of patients with alcohol-associated PNP (n=5), PNP owing to vitamin B12 deficiency (n=5), chronic inflammatory demyelinating PNP (CIDP, n=10), Charcot-Marie-Tooth disease (CMT) I or II (n= 10), PNP caused by monoclonal gammopathy of unknown significance (MGUS) (n=5), idiopathic PNP (n=10) and five normal controls by immunohistochemistry. Biopsies of either ten patients with diabetic and vasculitic PNP served as positive controls. RESULTS: CML, RAGE and NF-kappaBp65 were found in co-localization in epineurial vessels in PNP owing to vitamin B12 deficiency, diabetes and vasculitis and in the perineurium in diabetic PNP, vasculitic PNP and in some cases in CIDP and vitamin B12 deficiency. Only diabetic subjects demonstrated co-expression of the three antigens in endoneurial vessels. Increased CML, RAGE and NF-kappaBp65 expression was detected in endoneurial and epineurial mononuclear cells in CIDP and in vasculitic PNP. Additionally, RAGE expression in Schwann cells was significantly increased in diabetic PNP. DISCUSSION: These data suggest that activation of the RAGE pathway might contribute to the pathogenesis of CIDP, PNP owing to vitamin B12 deficiency, diabetes and vasculitis, whereas it does not seem to be involved in the pathogenesis of PNP owing to alcohol, MGUS, CMT I or II and idiopathic PNP.