Bernd Pohlmann-Eden

Functional MRI Predicts Memory Performance after Right Mesiotemporal Epilepsy Surgery

Summary:  Purpose: Anterior temporal lobe resection (ATR) is a treatment option in drug‐resistant epilepsy. An important risk of ATR is loss of memory because mesiotemporal structures contribute substantially to memory function. We investigated whether memory‐activated functional MRI (fMRI) can predict postoperative memory loss after anterior temporal lobectomy in right‐sided medial temporal lobe epilepsy (MTLE).

Comparison of Brain Extracellular Fluid, Brain Tissue, Cerebrospinal Fluid, and Serum Concentrations of Antiepileptic Drugs Measured Intraoperatively in Patients with Intractable Epilepsy

Summary:  Purpose: The mechanisms of drug resistance in epilepsy are only incompletely understood. According to a current concept, overexpression of drug efflux transporters at the blood–brain barrier may reduce levels of antiepileptic drugs (AEDs) in epileptogenic brain tissue. Increased expression of drug efflux transporters such as P‐glycoprotein has been found in brain tissue surgically resected from patients with medically intractable epilepsy, but it is not known whether this leads to decreased extracellular (interstitial) AED concentrations in affected brain regions. This prompted us to measure concentrations of AEDs in the extracellular space of human neocortical tissue by using intraoperative microdialysis (IOMD) in those parts of the brain that had to be removed for therapeutic reasons. For comparison, AED levels were determined in brain tissue, subarachnoid CSF, and serum.

Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal approach combining neurobiochemical and electrophysiological investigations may provide high prognostic certainty in patients after cardiac arrest.

A reliable and reproducible method for precisely predicting the neurological outcome of patients with hypoxic-ischemic encephalopathy after cardiac arrest is urgently needed in neurological intensive care units. We prospectively investigated the predictive power of serum concentrations of neuron-specific enolase (NSE) and protein S-100B (S-100B) measured on days 1, 2, 3 and 7 as well as somatosensory-evoked potentials (SEPs) recorded within 48 h and on day 7 after cardiopulmonary resuscitation (CPR) in 27 patients (14 females, 13 males; mean age 61.3 ± 17.3 years) with hypoxic-ischemic encephalopathy. During the first 7 days after CPR, median values of NSE and S-100B were increased in patients who remained unconscious after CPR compared to those patients who regained consciousness (significance up to ≤0.001). The best predictor of negative outcome was an NSE cutoff point ≧43 µg/l on day 2; this had a sensitivity of 90.9% and a specificity of 100%. Additional use of S-100B on day 2 did not increase sensitivity, but this could be markedly increased by combining NSE and S-100B on days 1, 3 and 7. SEPs showing bilateral loss of cortical responses identified patients who did not regain consciousness with a specificity of 100%.

Transient lesion in the splenium of the corpus callosum and antiepileptic drug withdrawal

Objective: To test pathophysiologic hypotheses regarding the occurrence of a splenial lesion in patients with epilepsy. Methods: The authors studied 16 patients with a splenial lesion and 32 control patients, all of whom had MRI examination immediately after presurgical EEG long-term monitoring (LTM). The authors compared the number of generalized tonic-clonic and partial seizures during LTM, antiepileptic drug (AED) withdrawal, and laboratory results. Results: All of the patients with a splenial lesion had their AEDs stopped completely, vs 47% of the controls (p = 0.001). Patients with SCC lesion had a longer duration of complete withdrawal (median 3.5 vs 2 days, p = 0.03). There was no correlation with seizure frequency or the introduction of new AEDs. Conclusion: A lesion of the splenium of the corpus callosum in patients with epilepsy is not associated with toxic drug effects or high seizure frequency, but might be induced by a rapid and relatively long-lasting reduction of antiepileptic drugs. Its frequency might be underestimated as MRI after long-term monitoring is rarely done.

Neural correlates of decision making with explicit information about probabilities and incentives in elderly healthy subjects

Recent functional neuroimaging and lesion studies demonstrate the involvement of the orbitofrontal/ventromedial prefrontal cortex as a key structure in decision making processes. This region seems to be particularly crucial when contingencies between options and consequences are unknown but have to be learned by the use of feedback following previous decisions (decision making under ambiguity). However, little is known about the neural correlates of decision making under risk conditions in which information about probabilities and potential outcomes is given. In the present study, we used functional magnetic resonance imaging to measure blood-oxygenation-level-dependent (BOLD) responses in 12 subjects during a decision making task. This task provided explicit information about probabilities and associated potential incentives. The responses were compared to BOLD signals in a control condition without information about incentives. In contrast to previous decision making studies, we completely removed the outcome phase following a decision to exclude the potential influence of feedback previously received on current decisions. The results indicate that the integration of information about probabilities and incentives leads to activations within the dorsolateral prefrontal cortex, the posterior parietal lobe, the anterior cingulate and the right lingual gyrus. We assume that this pattern of activation is due to the involvement of executive functions, conflict detection mechanisms and arithmetic operations during the deliberation phase of decisional processes that are based on explicit information.

First seizure: EEG and neuroimaging following an epileptic seizure

An early EEG (within 48 h) and high‐resolution magnetic resonance imaging (hr_MRI) are the methods of choice for an accurate diagnosis after a first seizure presentation. Together with a careful history and examination, they will allow definition of the epilepsy syndrome in two‐thirds of patients and help assess the individual risk for seizure recurrence, which is determined by the specific syndrome and is highest with focal epileptiform activity on EEG. Despite the heterogeneity of first seizure studies, EEG and etiology are consistently found to be the best predictors for seizure recurrence and prognosis. The additional yield of sleep‐deprived EEG and sleep EEG is uncertain; yet MRI is essential for detecting brain tumors and other structural bases for new epilepsy. The rate occurrence of remote symptomatic seizures increases significantly with age and the most common etiology in the elderly with a first seizure is stroke; however, its exact relevance to epileptogenicity is yet to be defined. There is a striking lack of systematic studies using early EEG and hr_MRI in order to better characterize epileptogenic areas and elucidate the mechanisms of seizure provocation.

Epileptic activity influences the lateralization of mesiotemporal fMRI activity

Objective: To identify clinical factors contributing to the lateralization of mesiotemporal memory functions in epilepsy by using memory-activated fMRI. Methods: Sixty patients aged 16 to 63 years with mesial temporal lobe epilepsy (MTLE) and 20 patients aged 16 to 60 years with extratemporal epilepsy (ETE) due to circumscribed epileptogenic lesions who consecutively underwent presurgical evaluation including continuous video-EEG monitoring and structural MRI examinations were examined. During memory fMRI, the activation condition consisted of retrieval from long-term memory induced by self-paced performance of an imaginative walk through the patient’s hometown. On the basis of a previous study, memory lateralization was defined as typical if larger fMRI activation was in the mesiotemporal structures contralateral to the epileptic focus. Results: There were 45 patients with MTLE who had typical memory lateralization (75%), whereas only 9 patients (45%) with ETE exhibited typical memory lateralization (p = 0.013). In MTLE patients, bilateral independent epileptiform discharges occurred more often in the atypical group than in patients with typical memory lateralization (p = 0.015). Conclusions: The fMRI lateralization of mesiotemporal visuospatial memory functions in patients with mesiotemporal lobe epilepsy (MTLE) is asymmetric: The larger activation usually appears contralateral to the side of the epileptogenic region. These findings occur more often in MTLE; in patients with extratemporal epilepsy, such type of asymmetry is not characteristic. In MTLE patients with bilateral independent epileptiform discharges, this type of asymmetry is also less frequent.

Development of psychosis in patients with epilepsy treated with lamotrigine: Report of six cases and review of the literature

Lamotrigine (LTG) is a generally well-tolerated antiepileptic drug (AED) with broad-spectrum efficacy in several forms of partial and generalized epilepsy and is also licensed for use in bipolar disorder in several countries. We describe six patients who developed a psychotic disorder--in most, but not all, cases schizophrenia-like in character--under treatment with LTG, within a group of about 1400 patients treated with this drug in our center. This indicates that psychosis is a rare adverse event under LTG treatment. On the background of available drug serum levels, we suggest, in particular, an intrinsic or toxic psychotogenic effect of LTG. Possible risk factors seem to be psychiatric comorbidity and temporal lobe pathology. The described phenomenon is discussed within the context of possible psychotogenic effects of other AEDs.

Issues when treating epilepsy in the elderly

Single seizures and epilepsy are one of the most commonly encountered neurologic disorders in elderly individuals, arising as a result of complex and often multiple acquired underlying pathologies. Ischemia is by far the most frequent etiology, and is found in up to one‐third of these patients, followed by tumors, which are diagnosed in approximately 10% of affected individuals. Thus, a multidisciplinary approach to its diagnosis and management is required. Antiepileptic drug (AED) therapy is the mainstay of treatment for epilepsy in the elderly, but age‐specific changes in drug metabolism, increased sensitivity to side effects, and the risk of drug interactions must be considered. Some newer AEDs seem to offer advantages over the older agents in terms of their reduced drug interaction potential (due to lack of enzyme induction), and improved tolerability profiles, which is supported by few recent clinical trials. In order to achieve seizure freedom without causing intolerable side effects, treatment should be initiated with monotherapy at low doses and titrated slowly to within the recommended dose range.

Interaktionen zwischen Antiepileptika und Psychopharmaka

Co-morbidity leads to an increasing number of drug prescriptions in the individual patient. Co-morbidity of epilepsy and psychiatric diseases is common. Therefore, possible interactions between antiepileptic drugs and those used in psychiatric diseases have to be considered. Pharmacokinetic interactions are common among drugs that are metabolized by cytochrome-P450 isoenzymes. It is crucial to know about possible drug interactions as they may lead both to impaired effectiveness and to uncontrolled toxicity of specific drugs.ZusammenfassungBegleiterkrankungen führen zur vermehrten Verordnung von Medikamentenkombinationen und damit zur Möglichkeit von Wechselwirkungen. Aufgrund einer hohen Komorbidität der Epilepsien mit psychischen Störungen kommt möglichen Interaktionen zwischen Antiepileptika und Psychopharmaka eine besondere Bedeutung zu. Die Möglichkeit pharmakokinetischer Interaktionen wird im Wesentlichen vom Stoffwechselweg der beteiligten Medikamente bestimmt. Dabei spielen die Isoenzyme des Cytochrom- P450 eine besonders große Rolle. Die Verordnung von Medikamenten, die nicht auf diesem Weg metabolisiert werden, kann das Risiko von Interaktionen verringern. Die Kenntnis möglicher Interaktionen ist unabdingbar, da diese einerseits über eine Beschleunigung des Abbaus zur verminderten Wirksamkeit eines Medikamentes, andererseits über eine Inhibition zu einem Anstieg des Serumspiegels und zu Intoxikationen führen können.