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Biomedical subjects

C Helmstaedter

Publications and source records attributed to C Helmstaedter.

At least 37 records · Page 2Linked to original sources
PubMed2002

Evidence of brain abnormality in patients with psychogenic nonepileptic seizures.

Markers of brain abnormalities in patients with psychogenic nonepileptic seizures (PNES) were studied to explore whether physical brain disorder is associated with an increased risk of PNES. Evidence of epileptiform EEG changes, MRI abnormalities, and neuropsychological (NPS) deficits was obtained from the records of 329 consecutive patients in whom the diagnosis of PNES was established at our center between 1991 and 2001. Two hundred six patients had PNES alone, and 123 PNES and epilepsy (PNES+E). In the PNES-only group, at least one marker of brain disorder was detected in 22.3% of patients (epileptiform potentials in 8.7%, MRI changes in 9.7%, NPS deficits in 9.7%). The actual prevalence of abnormalities is likely to be higher because 54.9% of the patients with only psychogenic seizures did not undergo MRI or neuropsychological testing. Evidence of brain abnormality was found more frequently in the PNES+E group (epileptiform potentials in 70.7%, MRI changes in 60.2%, NPS deficits in 52.8%). Although markers of brain abnormality were detected much less commonly in the PNES than in the PNES+E group, they were still found in a substantial proportion of patients with PNES alone. This suggests that physical brain disease plays a role in the development of PNES. Markers of physical abnormality were not more common in the right hemisphere.

Journal Article↗
PubMed2002

The localizing value of ictal consciousness and its constituent functions: a video-EEG study in patients with focal epilepsy.

Using ictal neuropsychological testing in pre-surgical patients with focal epilepsies, we examined the localizing value of the constituent functions of consciousness as opposed to 'conscious behaviour' as a unitary variable. 'Conscious behaviour' was defined in terms of awareness and responsiveness. The constituent functions of consciousness examined included the orientation to the examiner, intentional behaviour demonstrated by expressive or receptive speech, and postictal memory. Frequency and patterns of impairment of constituent functions and 'conscious behaviour' were assessed. To achieve this, pre-surgical video-EEG (n = 40) or video-electrocorticography recordings (n = 76) of ictal neuropsychological assessments were reviewed retrospectively. Patients were divided into groups with frontal (n = 29), right temporal (n = 21), left temporal (n = 38) and bitemporal (n = 28) seizure activity. Consciousness was most commonly impaired in patients with bitemporal and left temporal seizure activity. There were different patterns of impairment of the assessed constituent functions in the four groups: patients with frontal seizure activity showed loss of orientation behaviour and expressive speech whereas patients with left temporal seizure activity had impairments of memory, expressive and receptive speech. Patients with seizure activity limited to the right temporal lobe rarely exhibited ictal impairment of any of the assessed functions. In contrast, patients with bitemporal seizure activity showed impairment of all examined functions. Hence, normal functioning of the left temporal lobe or both temporal lobes is necessary for the preservation of all constituent aspects of consciousness. The localizing value of patterns of impairment of constituent functions is superior to that of 'consciousness' as a whole.

Adolescent↗
PubMed2001

Self-Reported Mood Changes following 6 Months of Vagus Nerve Stimulation in Epilepsy Patients.

Vagus nerve stimulation (VNS) for treatment of drug-resistant epileptic seizures has been reported to have additional positive mood effects as obtained by psychiatric ratings. To avoid rater bias effects, this study used self-report questionnaires and examined changes in self-reported mood and health-related quality of life following 6 months of VNS treatment. From 40 adult patients treated with VNS since the beginning of the study, 28 patients (mean age: 35.4 years) with unchanged medication were included. Repeated-measures MANOVA revealed a significant general mood improvement. Post hoc univariate tests obtained improvements of tenseness and dysphoria but not of depression, level of activity, or health-related quality of life. Mood and seizure outcome were correlated. VNS may improve unspecific states of indisposition and dysphoria. Absolute seizure reduction contributes to this antidysphoric effect. Since baseline depression scores were low, findings do not contradict but complement earlier reports of an antidepressive effect of VNS.

Journal Article↗
PubMed2001

No evidence for cognitive side effects after 6 months of vagus nerve stimulation in epilepsy patients.

Vagus nerve stimulation (VNS) can reduce seizure frequency in epilepsy patients and may affect central mechanisms of brain functioning. Experimental studies have provided evidence of cognitive alterations during VNS on phases. This single-arm follow-up study evaluates the potential of VNS to affect cognitive performance following long-term treatment. Thirty-six adult patients with medication-resistant epilepsies enrolled. Cognition was assessed before and at least 6 months after implantation of the stimulation device by a comprehensive neuropsychological assessment battery comprising tests on attention, motor functioning, short-term memory, learning and memory, and executive functions. Neither multiple testing of single score changes nor multivariate testing of cognitive domains revealed significant pre-post changes. Improvements in attentional performance were completely explained by practice effects as is usually expected. In particular, no negative side effects were revealed. These findings are in line with the clinical impression that VNS does not affect cognitive performance.

Journal Article↗
PubMed2001

Memory alterations during acute high-intensity vagus nerve stimulation.

Left cervical vagus nerve stimulation (VNS) is an accepted add-on treatment for pharmacoresistant epilepsy. However, it also allows the investigation of the effects of peripheral nerve stimulation on central nervous functions. The impact of 4.5 min high intensity VNS (>1 mA) on material-specific memory and decision times was evaluated in an experimental 'box car' design in 11 patients with pharmacoresistant epilepsy. Results indicate reversible deterioration of figural but not verbal memory and a trend of accelerated decision times during VNS. Thus, further support of cognitive effects of VNS is provided. There are indications of a major projection of VNS to activating brain structures of and the right hemisphere. Significant cognitive side effects in clinical application are unlikely because of the reversibility of the effect and differences between experimental and therapeutic stimulation conditions. However, since the effectors and the direction of the cognitive effects of VNS seem to depend strongly on stimulation conditions, we recommend future experimental research covering a larger range of stimulation conditions.

Adolescent↗
PubMed2001

Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study.

PURPOSE: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Comparison of seizure outcome and AED us in operated-on TLE patients (n=148) and nonsurgically treated TLE patients (n=94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. RESULTS: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure- free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. CONCLUSIONS: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup.

Adult↗
PubMed2001

Memory and epilepsy: characteristics, course, and influence of drugs and surgery.

Memory processing in humans is essential for consciousness, cognitive-behavioral development and individual biography. In epilepsy, declarative memory functions show characteristic patterns of impairment when mesiotemporal and associated neocortical structures are affected by lesions, ongoing epileptic activity, or the undesired effects of conservative or operative treatment. Major issues are thus the etiology, onset and course of memory impairment, as well as the prevention of further memory decline during treatment. New input in the field has resulted from improved imaging techniques, sophisticated experimental study designs, more selective surgical approaches, and new antiepileptic drugs.

Animals↗
PubMed2001

Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study.

The objective was to evaluate response rate, response duration, and toxicity after systemic and intraventricular chemotherapy in primary CNS lymphoma (PCNSL). From September 1995 to September 1998, 20 consecutive patients with PCNSL (median age 64, range 27 to 71 years) were enrolled in a pilot study evaluating chemotherapy without radiotherapy. A high dose methotrexate (MTX) (cycles 1, 2, 4, 5) and cytarabine (ara-C) (cycles 3, 6) based systemic therapy (including dexamethasone, vinca alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ara-C. Complete response was achieved in 11 and partial remission in two patients; in one response could not be determined. Four patients showed progressive disease and two (70, 71 years) died from treatment related complications. Observation time was 2 to 59 months (median 31.5 months). Kaplan-Meier estimate for median time to treatment failure (TTF) was 20.5 months, and for median survival 54 months. Systemic toxicity was mainly hematological. Ommaya reservoir infection occurred in four patients and acute transient MTX induced encephalopathy in two (subacute in another). Cognitive dysfunction possibly due to treatment was seen in only one patient after relapse and after a total of 12 cycles (six at relapse). In conclusion, primary chemotherapy based on high dose MTX and ara-C is highly efficient in PCNSL. Toxicity is manageable in patients younger than 70 years.

Adult↗
PubMed2000

Limbic encephalitis not associated with neoplasm as a cause of temporal lobe epilepsy.

OBJECTIVE: To describe four patients with temporal lobe epilepsy with limbic encephalitis unrelated to neoplasm. METHODS: The authors performed a retrospective evaluation of patient data obtained during presurgical evaluation, with additional CSF analyses, serum analyses, and histopathologic investigations. RESULTS: The patients shared the following clinical features: onset of the disease in young adulthood with subacute onset or exacerbation of frequent intractable temporal lobe seizures, verbal and visual memory deficits, and affective abnormalities. MRI showed variably extended areas of increased T2 signal in limbic structures and adjacent areas. In the histopathologic investigation, chronic inflammation was observed without evidence of a viral origin. There was no evidence of an underlying malignancy. CONCLUSIONS: Nonparaneoplastic limbic encephalitis should be included in the differential diagnosis of adult patients with temporal lobe epilepsy.

Adult↗
PubMed2000

Synaptic plasticity in the human dentate gyrus.

Activity-dependent plasticity is a fundamental feature of most CNS synapses and is thought to be a synaptic correlate of memory in rodents. In humans, NMDA receptors have been linked to verbal memory processes, but it is unclear whether NMDA receptor-dependent synaptic plasticity can be recruited for information storage in the human CNS. Here we have for the first time analyzed different forms of synaptic plasticity in human hippocampus. In human subjects who show a morphologically intact hippocampus that is not the primary seizure focus, NMDA receptor-dependent long-term potentiation (LTP) and forskolin-induced long-lasting potentiation are readily induced at the perforant path-dentate gyrus synapse. In this group, long-term potentiation could be partially depotentiated by low-frequency stimulation. Because patients with a hippocampal seizure focus showed a marked reduction in verbal memory performance in previous studies, we asked whether synaptic plasticity is similarly affected by the presence of a hippocampal primary seizure focus. We found that the amount of potentiation induced by high-frequency stimulation or perfusion of forskolin is dramatically reduced in this patient group. In addition, low-frequency stimulation is not effective in inducing synaptic depression. In summary, we show that activity-dependent synaptic plasticity with properties similar to the rodent is available for information storage in the human hippocampus. Because both verbal memory processes and synaptic plasticity are impaired by a hippocampal seizure focus, we suggest that impaired synaptic plasticity may contribute to deficient declarative memory in human temporal lobe epilepsy.

1-Methyl-3-isobutylxanthine↗
PubMed2000

[Temporal lobe epilepsy: longitudinal clinical, neuropsychological and psychosocial follow-up of surgically and conservatively managed patients].

Little is known about the differential long-term outcome from surgical and nonsurgical therapy in patients with chronic epilepsy. In the present study, 161 surgically or nonsurgically treated patients with drug-resistant temporal lobe epilepsy (TLE) were re-evaluated according to a detailed clinical, neuropsychological, and psychosocial protocol with a mean follow-up interval of 58 months. Freedom from seizures was achieved in 64% of the surgical group; yet 23% of the nonsurgical patients became seizure-free as a result of modifications in drug therapy. Generally, socioeconomic development was poorer in nonsurgical than in surgical patients. Freedom from seizures, employment, and the absence of depression were significant determinants of better quality of life. As for neuropsychological outcome, verbal memory impairment was common after left-sided temporal resection; however, there was no evidence of a marked progression of cognitive impairment after the first postoperative year. In nonsurgical patients, too, cognitive capacities were surprisingly stable over time, although persisting seizures and good baseline performance predicted a poorer neuropsychological outcome.

Adult↗
PubMed2000

Behavioral markers for self- and other-attribution of memory: a study in patients with temporal lobe epilepsy and healthy volunteers.

OBJECTIVES: The correlation between clinical measures of memory and subjectively reported memory is often poor. Regarding this we investigated in patients with temporal lobe epilepsy (TLE) whether there is evidence that persons mistake other cognitive performances for memory due to subjective memory theories. METHODS: a neuropsychological test battery comprising measures of attention, verbal/figural memory and other visual or language related functions was applied in patients with left (L-TLE, n=24) or right temporal lobe epilepsy (R-TLE, n=21) and healthy volunteers (n=20). In addition, subjective self- and other-reported memories were assessed by the subjective memory questionnaire (SMQ). RESULTS: subjective measures as well as objective measures indicate significant cognitive impairment in TLE and in L-TLE in particular. Self-reports and other-reports are interrelated but only self-reported memory correlates significantly with objective memory performance. Regression analysis indicates that self-reported memory is best predicted by word fluency followed by verbal memory and vocabulary, and other-reported memory is best predicted by word fluency, vocabulary, confrontation naming, and verbal recognition memory. DISCUSSION: The results suggest that attribution of memory refers to a subjective view of memory which is wider than its neuropsychological definition. It furthermore differs dependent on the observer's point of view. Memory is preferentially concluded from verbal behaviors. These reflect language skills and access to vocabulary rather than declarative memory. Consideration of subjective memory theories and associated attribution processes can significantly contribute to our understanding of the often-poor relationship between objective test results and subjective impairment in TLE.

Adolescent↗
PubMed2000

Depression in patients with temporal lobe epilepsy is related to mesial temporal sclerosis.

Depression is a frequent psychiatric symptom in epilepsy and has been related to epilepsy of temporal origin, especially of left-sided foci. No study differentiated the precise localization of the epileptogenic lesion within the temporal lobe. Regarding this issue, we evaluated depression assessed by the Beck Depression Inventory in 60 patients with temporal lobe epilepsy, with particular consideration of morphological abnormalities within the temporal lobe (mesial temporal sclerosis (MTS) versus neocortical lesions) and lateralization of the lesion. Multivariate analyses indicated significant higher depression scores in MTS independent of the lateralization of the lesion. Depression was a good indicator for MTS but not vice versa. Hence, MTS can be discussed as a predisposing factor for the development of mood disorders in focal epilepsy.

Adult↗
PubMed2000

Behavioural disorders in children with epilepsy: early improvement after surgery.

OBJECTIVES: Epilepsy surgery has proved to be a successful intervention method to achieve freedom from seizures or seizure relief in children with pharmacoresistant epilepsy. Long term studies on operated children suggest that behavioural disorders, which are often seen before surgery, improve after surgery. However, the early postoperative development of behavioural problems has not been systematically evaluated. METHODS: Parents of 28 children with pharmacoresistant focal epilepsies completed the child behaviour checklist (CBCL) preoperatively and 3 months after surgery. Surgeries comprised 24 focal resections (13 temporal, 11 extratemporal), two hemispherectomies, and two callosotomies. Twenty eight conservatively treated children with comparable CBCL scores served as a control group. A repeated measurement multivariate analysis of variance (MANOVA) and a regression analysis were computed to compare the development of behaviour between both groups and to identify predictors of postoperative changes in behaviour. RESULTS: Preoperatively 39% of the children exhibited significant behavioural problems, a further 11% were within the borderline range. The MANOVA disclosed a significant interaction between time of examination and group (F=2.23, p<0.05). The surgery group showed significant improvements on the scales "internalising problems", "externalising problems", "attention problems", and "thought problems". Behavioural problems in the control group, however, remained unchanged. No changes were seen in social problems in both groups. The significant predictor of total behavioural improvement was a good seizure outcome (R(2)=0.11, p<0.05). Age, sex, onset, and duration of epilepsy, the site of the focus, and changes in antiepileptic drug regimen did not influence changes in behaviour. CONCLUSIONS: The data demonstrate an early improvement of behavioural problems after epilepsy surgery in children. The behavioural improvements can be assumed to result directly from the removal of the epileptic focus. They are not predictable on the basis of information available preoperatively, but depend on the seizure outcome.

Adolescent↗
PubMed2000

Neuropsychology of childhood epilepsy: pre- and postsurgical assessment.

Childhood epilepsy is one of the most prevalent forms of chronic and disabling childhood disorders. Because it disrupts brain maturation, it has long been thought to produce non-specific consequences such as mental deficiency and behavioral problems. However, advances in medical knowledge have shown that childhood epilepsy should not be considered as a single disorder, and it is now becoming apparent that various clinical entities have different cognitive expressions that yet need to be specified. The purpose of this paper is to provide an up-to-date analysis of this multi-faceted pathology. The first section is devoted to the characterization of the neuropsychological profile that accompanies focal epilepsies, as defined by the site of the epileptic process. We report the first group study of children with frontal lobe epilepsy. The results indicate that frontal lobe epilepsy produces symptoms (deficits of planning, attention and motor dexterity) that are akin to those found in frontal-lesioned adults. Similarly, like in adults, temporal lobe epilepsy produces memory impairment in children as well as behavioral and academic disturbances. Occipito-parietal lobe epilepsy is rare in children and its effects still need to be specified. The second section deals with the neuropsychological techniques used in presurgical evaluation. Finally, the various neurosurgical procedures that are increasingly being used as part of the arsenal of epilepsy treatment are described along with the neuropsychological findings that are associated with these interventions. It can be concluded that the beneficial effects of epilepsy surgery (callosotomy, hemispherectomy, temporal and extra-temporal resections) by far outweigh the few cognitive deficits that are occasionally reported following these interventions.

Adult↗
PubMed1999

Sex differences in material-specific cognitive functions related to language dominance: an intracarotid amobarbital study in left temporal lobe epilepsy.

Population-based studies of material-specific cognitive functions yield evidence of sex differences: women are superior on verbal tasks whereas men are superior on figural and visuo-spatial tasks. Although there is still no direct evidence, these sex differences have been assumed to be related to a different cerebral organisation of language and nonlanguage functions, i.e. language in women is suggested to be more bilaterally organised than in men. We investigated this issue with respect to verbal/nonverbal memory functions in 42 men and 43 women with left temporal lobe epilepsies who all underwent intracarotid amobarbital testing for language dominance. The results indicate that atypical language dominance is not significantly more frequent in women than in men (44% vs 33%). Atypical dominance was related to an onset of epilepsy before puberty and appeared to be a consequence of the left hemisphere pathology rather than being naturally predisposed. Furthermore, women indeed showed the expected advantage with respect to verbal memory, and men showed an advantage in figural memory. With consideration of language dominance, however, the sex difference in verbal memory was observed particularly with atypical dominance, whereas the sex difference in figural memory was observed with left dominance.

Journal Article↗
PubMed1999

Pre- and postoperative neuropsychological profiles in children and adolescents with temporal lobe epilepsy.

PURPOSE: To evaluate the neuropsychological performance of children before and after temporal lobe resection (TLR). METHODS: Memory, attention, language, and visuoconstructive abilities were examined in 20 children (age 10-16 years) before, and 3 and 12 months after TLR (right, n = 10; left, n = 10; two-thirds anterior resection, n = 16; amygdalohippocampectomy, n = 4). Preoperative performance was compared with data of 30 age-matched healthy children; changes in performance after surgery were determined by repeated-measurement multivariate analysis of variance (MANOVA) and by use of reliable change indices (RCI). RESULTS: Preoperatively, no differences were observed between patients and controls in verbal and figural memory performance. Children with temporal lobe epilepsy (TLE), however, and particularly those with a left temporal focus, showed significantly reduced language performance. Repeated-measurement statistics indicated that memory performance did not change after surgery, whereas language performance and attention significantly improved 3 months and 1 year after surgery, respectively. Individual evaluations of memory showed gains in five children and deterioration in four children. Poor seizure control appeared the decisive variable characterizing children with losses in memory. CONCLUSIONS: Compared with adults, pre- and postoperative memory data suggest less pronounced hemispheric differences in school-age children with TLE. The results raise the possibility that children have a lower risk of memory deterioration after TLR, which may be due to their larger potential for cerebral plasticity.

Adolescent↗