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Biomedical subjects

H Holthausen

Publications and source records attributed to H Holthausen.

At least 37 records · Page 2Linked to original sources

Ictal motor signs and interictal regional cerebral hypometabolism.

Early motor manifestations are the main components of focal seizures involving the frontal lobe. We examined the relationship between the initial ictal motor manifestations and interictal abnormalities of cerebral glucose consumption (rCMRGlc) as assessed by PET in 48 consecutive patients with focal seizures of neocortical origin. Group data analysis revealed that patients with predominantly unilateral clonic seizures had a significant contralateral perirolandic hypometabolism and to a lesser degree a contralateral frontomesial hypometabolism. Patients with predominantly focal tonic manifestations showed a hypometabolism within the frontomesial and perirolandic regions that was unilateral in all patients with lateralized tonic seizures. Patients with versive seizures had mainly contralateral metabolic depressions without a consistent regional pattern. Patients with hypermotor seizures had metabolic depressions involving frontomesial, anterior cingulate, perirolandic, and anterior insular/frontal operculum areas. In all patient groups, bilateral and symmetric hypometabolism of the thalamus and cerebellum was observed. We propose that this pattern of distinctly abnormal metabolic brain regions demonstrates not only possible epileptogenic zones but also symptomatogenic brain regions as shown by the associations between clinical manifestations and sets of abnormal brain regions, particularly if epileptogenic zones are in a clinically silent neocortical brain region. The detection and possible differentiation of symptomatogenic and epileptogenic zones might improve the effectiveness of presurgical noninvasive studies.

Adult↗

Individual prediction of change in delayed recall of prose passages after left-sided anterior temporal lobectomy.

Prognostic variables for individual memory outcome after left anterior temporal lobectomy (ATL) were studied in 27 patients with refractory temporal lobe epilepsy. The difference between pre- and postoperative performance in the delayed recall of two prose passages (Story A and B) from the Wechsler Memory Scale served as measure of postoperative memory change. Fifteen independent clinical, neuropsychological, and electrophysiological variables were submitted to a multiple linear regression analysis. Preoperative immediate and delayed recall of story content and right hemisphere Wada memory performance for pictorial and verbal items explained very well postoperative memory changes in recall of Story B. Delayed recall of Story B, but not of Story A, had high concurrent validity to other measures of memory. Patients who became seizure-free did not differ in memory change from patients who continued to have seizures after ATL. The variables age at epilepsy onset and probable age at temporal lobe damage provided complementary information for individual prediction but with less effectiveness than Wada test data. Our model confirmed that good preoperative memory functioning and impaired right hemispheric Wada memory performance for pictorial items predict a high risk of memory loss after left ATL. The analyses demonstrate that the combination of independent measures delivers more information than Wada test performance or any other variable alone. The suggested function can be used routinely to estimate the individual severity of verbal episodic memory impairment that might occur after left-sided ATL and offers a rational basis for the counseling of patients.

Adolescent↗

Epileptic negative myoclonus. Subdural EEG recordings indicate a postcentral generator.

We report a patient with epileptic negative myoclonus (ENM) presenting as status epilepticus of the right arm. The etiology was a cortical malformation in the contralateral postcentral gyrus. Electrical stimulation of the right median nerve revealed giant surface somatosensory evoked potentials. Subdural recordings, performed to plan epilepsy surgery, demonstrated that the epileptogenic zone was in the left postcentral gyrus. Repetitive left postcentral spikes were consistently followed by an EMG silent period in the right arm with a latency of about 20 to 30 msec. The silent period in the EMG reflected the negative myoclonus and lasted 30 to 340 msec, mostly between 100 and 200 msec. Spikes in other regions of the cortex did not elicit ENM. The amplitude and duration of the spikes correlated with the EMG silent period: the more cortex involved in the spike generation, the longer the duration of the silent period. This suggests that epileptic activation of postcentral cortex leads to an inhibition of tonic activity of motor neurons. Focal ENM may be related to a hyperexcitability of the postcentral cortex.

Adult↗

Reorganization of memory functions after human temporal lobe damage.

Hemispheric (re-)organization of episodic memory functions after temporal lobe damage (TLD) was investigated by the intracarotid amobarbital procedure in patients suffering temporal lobe epilepsy. Memory of the speech-dominant left hemisphere was intact after right-sided TLD independent of the age at manifestation. In contrast, the right hemisphere mediated memory well only after early left-sided TLD. These findings suggest a predisposition of the speech-dominant left hemisphere for the encoding of episodic memory, and indicate that for left-sided TLD the right hemisphere may compensate memory encoding sufficiently only if the damage occurred within a critical period in childhood.

Brain Damage, Chronic↗

Cerebellar hypometabolism in focal epilepsy is related to age of onset and drug intoxication.

PURPOSE: We wished to investigate the cerebellar depression of regional cerebral glucose metabolism (rCMRGlu) in patients with focal epilepsy. METHOD: In 170 consecutive patients with medically refractory, focal epilepsy the rCMRGlu was measured in cerebellum and brain. RESULTS: rCMRGlu was markedly decreased in both cerebellar hemispheres and slightly in brain. The cerebellum to brain rCMRGlu ratio was significantly decreased in patients with seizure manifestation in infancy, but was normal due to a progressive decrease in brain rCMRGlu in later age. A subgroup of patients with focal epilepsy involving the frontal lobe had a reduced cerebellum/brain rCMRGlu ratio, whereas in patients with mesiotemporal lobe epilepsy (MTLE), the rCMRGlu was decreased to the same degree in cerebellum and brain. The difference in the cerebellum/brain rCMRGlu ratio between the two groups was accounted for by the younger age of the patients with focal epilepsy involving the frontal lobe, however. In another subgroup of patients with a documented history of critical drug intoxications, the cerebellar rCMRGlu was severely decreased, resulting in a significantly reduced cerebellum/brain rCMRGlu ratio. CONCLUSION: Our retrospective study suggests that the cerebellum is particularly vulnerable in infancy to ongoing epileptic activity and high dosage of antiepileptic drugs (AEDs).

Adult↗

Systematic testing of medical intractability for carbamazepine, phenytoin, and phenobarbital or primidone in monotherapy for patients considered for epilepsy surgery.

PURPOSE: To assess medical intractability in patients considered for restrictive epilepsy surgery. METHODS: Seventy-four patients received single drug treatment with carbamazepine (CBZ), phenytoin (PHT), and either phenobarbital (PB) or primidone (PRM). Medical intractability was established if seizure control was not obtained despite maximum tolerable doses of the drug. In all, 120 single drug treatments were administered with the drugs that has not been administered at maximal doses in monotherapy before the study. RESULTS: Complete seizure control was not achieved in any patient. However, 7 patients (9.5%) had significant seizure reduction of at least 80%. In 4 patients, only the third antiepileptic drug (AED) proved effective. CONCLUSION: The poor result of AED monotherapy in our patients may be attributed to the patients' long-standing chronic epilepsies and high seizure frequencies. Our findings suggest that despite the failure of one or two major AEDs in controlling seizures completely, further single drug treatment may still improve the quality of life in some patients who are candidates for epilepsy surgery.

Adolescent↗

Epileptic seizures triggered directly by focal transcranial magnetic stimulation.

Focal, secondarily generalizing, epileptic seizures were released by magnetic stimulation in a patient with focal epilepsy. The stimulation induced seizures had a similar clinical appearance to the patient's spontaneous seizures. They were released exclusively by an angulated "figure-of-8" coil which stimulates the brain more focally as compared to the commonly used flat round coil. The epileptic focus could be located in the left frontal cortex by electroencephalographic recordings, by magnetic resonance and by positron emission tomography imaging. Functional assessment of the motor system by transcranial magnetic stimulation (TMS) disclosed markedly prolonged electrical silence of contralesional electromyographic activity following the early excitation. This is the first EMG-documented demonstration of a focal motor seizure directly triggered by magnetic brain stimulation.

Adolescent↗

Supplementary sensorimotor area seizures in children and adolescents.

RATIONALE: Some types of seizures in children may be difficult to recognize; the diagnosis of seizures arising near the mesial posterior frontal supplementary sensorimotor area (SSMA) may be especially challenging. Such seizures have been well described in adults, but few pediatric cases have been reported even though onset is typically in childhood. METHODS: We studied 11 children and adolescents with SSMA seizures diagnosed by prolonged video electroencephalography (EEG). RESULTS: Mean age at onset was 5.8 years, and diagnosis by video EEG was made at a mean age of 12 years. Children had at least borderline intelligence and few abnormal findings on neurologic examination. Seizures were typically brief, frequent, and predominantly nocturnal, with bilateral tonic posturing, gross proximal limb movements, and preserved consciousness. Magnetic resonance imaging showed normal findings or a superior or mesial posterior frontal tumor or cortical dysplasia. Routine EEG findings were usually normal, but prolonged EEG showed epileptiform discharges over the vertex. Seizure onset in the region of the SSMA was confirmed by subdural EEG in six patients who were studied for epilepsy surgery. Five patients had seizure-free outcome or worthwhile improvement after operation. Two nonoperated patients are seizure-free on antiepileptic medication, and three are undergoing surgical evaluation. CONCLUSIONS: Diagnosis of SSMA seizures in children may be challenging because of unusual symptoms (bilateral tonic limb involvement with preserved consciousness) and frequently normal routine EEG findings. Video EEG may be necessary for diagnosis, and magnetic resonance imaging may reveal a focal lesion. Increased recognition of this seizure type in pediatric patients should lead to earlier diagnosis for optimal medical or surgical treatment.

Adolescent↗

Amnesia of the epileptic aura.

In a prospective study lasting 6 months, we recorded on video 108 seizures with aura of 23 patients in an attempt to evaluate the mechanisms involved in the encoding of memories. In 88 of those seizures, we also recorded an EEG. The percentage of auras remembered decreased significantly with increasing severity of the seizures. The recollection of auras was also significantly dependent on the ictal EEG changes during the aura. Ninety-seven percent of the auras without EEG changes, 94% of the auras with unilateral EEG changes, and 73% of the auras with bilateral EEG changes during the aura were remembered. The spread of the ictal EEG pattern during the aura also showed a significant correlation with the severity of the ensuing seizure. Three patients with bitemporal epilepsy made up a considerable proportion of those who never remembered their aura before secondary generalized tonic-clonic seizures (2 of 3) and of those who had a transient postictal amnesia of their aura (2 of 3). The only patient who failed to remember a previously documented isolated aura also suffered from bitemporal epilepsy. During the second part of the study, we questioned whether information provided during the history could be helpful in defining the type of epilepsy syndrome or localizing the EEG seizure pattern of the 80 patients who had been admitted for presurgical epilepsy diagnosis. Localized (regional, unilateral, and independent left and right lateral) EEG seizure patterns occurred in 82% of the 51 patients with auras in their history as compared with 24% of the 17 patients who did not have auras in their history (p < 0.01).

Amnesia↗

[Analysis of postoperative seizure recurrence after 65 temporal lobe partial resections].

Sixty-five patients (aged between 3 years 5 months and 60 years) suffering from medically resistant temporal lobe epilepsy (TLE) were operated on over a period of 33 months in Bethel Epilepsy Center. Thirty-three patients had mesial TLE and 32 patients had TLE of different etiology. The postoperative follow-up lasted 2 years in 30 patients and was on average 13.2 months or at least 8 months in the 35 patients who did not have their last examination 2 years after surgery. Many of the patients (70.9%) were seizure-free; 92.3% achieved a rewarding improvement in seizure frequency and quality of life. Reduction of medication was the cause for relapse in 10 patients, in 6 patients incomplete resection, and in 5 patients the prognosis was not good even before surgery. The cause remained unclear in 4 patients. Freedom from seizures was achieved again by renewed medication or by repeated operation in 10 of 25 patients.

Adolescent↗

[Hemimegalencephaly. Therapy with hemispherectomy].

Hemimegalencephaly is associated with a poor clinical course characterized by intractable seizures and severe encephalopathy. We present a case report of a girl with hemimegalencephaly. At the age of 9 month hemispherectomy was undertaken to preserve function of the other hemisphere. MRI and histologic examinations showed characteristic dysplastic malformations. Follow-up and the complications are described.

Cerebral Angiography↗

Lyme-borreliosis and possible association with HLA-antigens.

The frequencies of HLA A, B, C and DR antigens were evaluated in 220 persons from West Germany with inapparent and manifest Borrelia burgdorferi infections. Thirty-seven forest workers showing elevated antibody titres against Borrelia burgdorferi had asymptomatic infection, and are described as stage 0. One hundred and eighty-three patients presented with the clinical stages 1-3 of the infection. Control persons (n = 655) were typed in the same time period and by identical staff. HLA CW3 was present in 36.3% of patients as compared to 23.2% of the controls (RR = 1.88, pcorr = 0.03) and was significantly associated with manifest infection. In addition, the antigen A2 was found slightly but not significantly more frequent in the patients (55.2% vs 44%; pcorr = 0.41). The phenotype combination HLA A2 and Cw3, however, was significantly elevated in patients (24.6% vs 10.8%; pcorr = 0.0005). In contrast to these class 1 antigens, HLA DR3 showed a tendency of negative association with manifest infection. But this finding was not yet found to be significant (15.3% vs 25.3%; RR = 0.53, pcorr = 0.26). The frequency of HLA DR2 showed a constant decrease from stage 0 to stage 3 (inapparent infection to late complications). Using the rank correlation coefficient of Spearman, this association was found to be significant (-1.00, p less than or equal to 0.05). All other tested HLA antigens and antigen combinations showed no significant differences. The data suggest that HLA CW3 may be associated with Borrelia burgdorferi infection, whereas HLA DR2 and DR3 may be associated with less incidence of severe courses and less complications in this disorder.

Borrelia Infections↗

Etomidate: a selective adrenocortical 11 beta-hydroxylase inhibitor.

To investigate the adrenocortical suppression caused by the anesthetic etomidate, plasma levels of progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycorticosterone (DOC), corticosterone (B), aldosterone (Aldo), 11-deoxycortisol (S), cortisol (F), and cortisone (E) were measured simultaneously before and after a short-term ACTH stimulation test in a 6.5-year-old boy whose convulsions could be kept under control only with constant etomidate infusions. During etomidate therapy, plasma levels of DOC and S were extremely elevated, the progestins P and 17-OHP were slightly elevated, whereas B and Aldo were in the lower normal range, and F and E were markedly decreased. A short-term ACTH stimulation test during etomidate infusion gave a blunted response of B, Aldo, F and E, whereas the level of DOC remained high and S even further increased. P and 17-OHP showed a positive response to ACTH. The ratios of B/DOC and F/S, which reflect adrenocortical 11 beta-hydroxylase activity, were extremely decreased during etomidate and did not change after ACTH stimulation. In contrast, the ratios of DOC/P and S/17-OHP, which reflect 21-hydroxylase activity, were elevated and remained elevated after ACTH stimulation. After discontinuation of etomidate therapy, all the baseline steroid levels were somewhat elevated, but responded normally to ACTH. These results demonstrate that etomidate causes a specific and reversible blockade of the 11 beta-hydroxylation of adrenal steroid synthesis.

17-alpha-Hydroxyprogesterone↗