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H Holthausen

Publications and source records attributed to H Holthausen.

At least 19 recordsLinked to original sources
PubMed2005

SCN1A mutation analysis in myoclonic astatic epilepsy and severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures.

Severe myoclonic epilepsy in infancy (SMEI), severe idiopathic generalized epilepsy of infancy (SIGEI) with generalized tonic clonic seizures (GTCS), and myoclonic astatic epilepsy (MAE) may show semiological overlaps. In GEFS+ families, all three phenotypes were found associated with mutations in the SCN1A gene. We analyzed the SCN1A gene in 20 patients with non-familial myoclonic astatic epilepsy -- including 12 probands of the original cohort used by Doose et al. in 1970 to delineate MAE. In addition, 18 patients with sporadic SIGEI -- mostly without myoclonic-astatic seizures -- were analyzed. Novel SCN1A mutations were found in 3 individuals. A frame shift resulting in an early premature stop codon in a now 35-year-old woman with a borderline phenotype of MAE and SIGEI (L433fsX449) was identified. A splice site variant (IVS18 + 5 G --> C) and a missense mutation in the conserved pore region (40736 C --> A; R946 S) were detected each in a child with SIGEI. We conclude that, independent of precise syndromic delineation, myoclonic-astatic seizures are not predictive of SCN1A mutations in sporadic myoclonic epilepsies of infancy and early childhood.

Child↗
PubMed2004

Fatal propofol infusion syndrome in association with ketogenic diet.

Propofol is used for the treatment of refractory status epilepticus. When given as a long-term infusion propofol may cause a rare but frequently fatal complication, the propofol infusion syndrome. The hallmarks are metabolic acidosis, lipemia, rhabdomyolysis and myocardial failure. Propofol infusion syndrome is caused by impaired fatty acid oxidation. Beside anticonvulsants the ketogenic diet, a high-fat, low-carbohydrate, adequate-protein diet, is an effective treatment for difficult-to-control seizures. We report a 10-year-old boy with catastrophic epilepsy, who developed fatal propofol infusion syndrome when a ketogenic diet was initiated. Substances like propofol which impair fatty acid oxidation may pose an increased risk if combined with ketogenic diet.

Acidosis↗
PubMed2003

Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders.

X-linked isolated lissencephaly sequence (XLIS) and subcortical band heterotopia (SBH) are allelic disorders caused by mutations in the doublecortin (DCX) gene. This genetic analysis of seven families revealed four novel mutations in the DCX gene. The authors detected a high rate of somatic mosaicism in male and female patients with variable penetrance of bilateral SBH including nonpenetrance in a heterozygous woman. In addition, the authors implemented prenatal diagnosis in a family with SBH/XLIS.

Adult↗
PubMed2002

Epilepsy surgery in children with focal cortical dysplasia (FCD): results of long-term seizure outcome.

The purpose of this study was to assess the effect of epilepsy surgery on seizure outcome in children and adolescents under 18 years with intractable epilepsy due to focal cortical dysplasia. We analysed clinical data, such as age at seizure onset, epilepsy course, localisation of focus from presurgical evaluation, MRI, tissue pathology and seizure outcome in 68 patients 6 months to 9 years after epilepsy surgery. Seizure outcome was classified according to the Engel classification. Mean age at seizure onset was 7 months, ranging from the first days of life to 7 years. All patients had medically intractable epilepsy. Localisation of the lesion was predominantly extratemporal: posterior (uni- or multilobar) 43 %, frontal without central region 26 %, multilobar involving central area 19 % and temporal in 12 %. MRI signs typically seen in cortical dysplasia (FCD) such as localised blurring of gray-white matter junction was found in 68 %, dysgyria in 62 %, thickening of the cortical ribbon in 46 % and T2 signal elongation of the subcortical white matter in 40 % of the patients' MRI. Age at surgery ranged from 5 months to 16 years; 14 patients were under 2 years when operated on. In 34 patients (6 patients under 3 years) subdural grid electrode evaluation was performed prior to surgery. Pathology revealed focal cortical dysplasia without balloon cells (type I) in 60 %, FCD of the balloon cell subtype (type II) in 40 % of the specimens. Postoperative complications were subdural hygroma in 5 and an increased motor deficit in 2 patients. Up to two years after epilepsy surgery 50 % of the children were seizure free (Engel class I), 10 % Engel class II, 33 % Engel class III and 7 % unchanged (Engel class IV). Long-term seizure outcome (> 3 years post surgery) in 32 patients showed similar results (class I 50 %, class II 19 %, class III 28 %, class IV 3 %). Complete resection of the dysplastic lesion was significantly correlated with favorable seizure outcome, whereas seizure outcome was not significantly different in patients with mild (type I) or balloon cell (type II) FCD. Children operated after 6 years of age had no better outcome than children operated in infancy or at preschool age. Epilepsy surgery resulted in good (class I and II) seizure control in 60 % of children with intractable epilepsy due to focal cortical dysplasia.

Adolescent↗
PubMed2001

The long-term use of vigabatrin and lamotrigine in patients with severe childhood onset epilepsy.

Our purpose was to compare the initial efficacy and retention at 5 years of lamotrigine (LTG) and vigabatrin (VGB) in patients with severe childhood-onset epilepsies, especially with regard to loss of efficacy. Add-on therapy in 95 young patients with severe epilepsies in a neuropaediatric department was prospectively followed in open label studies for up to 5 years. VGB group: 56 patients (mean age: 11.1 years). LTG group: 39 patients (mean age: 13.6 years). Definition of initial responders: more than 50% reduction in seizure-frequency after 6 weeks of VGB treatment or after 4 months of LTG treatment. Definition of retention at 5 years: percentage of patients still taking LTG or VGB after 5 years. Definition of loss of efficacy: return to the baseline seizure frequency. The results were: VGB group: after 6 weeks 18 of 56 patients (32%) were initial responders. The retention at 5 years was five of 56 patients (8.9%). One patient (1.8%) was still seizure free. A loss of efficacy occurred in 10 of the 18 initial responders, usually within the first 9 months after the initial response. In the LTG group, after 4 months, 11 of 39 patients (28%) were initial responders. The retention at 5 years was 10 of 39 patients (25.6%). Five patients (12.8%) were still seizure free. The rate of adverse events was equal in both groups (41%). All but one occurred within the first 6 months of treatment. Our study in patients with difficult to treat childhood epilepsies suggests that in clinical practice patients were less likely to be discontinued from LTG than from VGB within 5 years, after similiar initial efficacy. This was mainly due to a loss of efficacy in VGB treatment early after initial response.

Adolescent↗
PubMed2001

Functional MRI in a 6-year-old boy with unilateral cortical malformation: concordant representation of both hands in the unaffected hemisphere.

Functional magnetic resonance imaging (fMRI) was performed in a 6-year-old boy with a complex malformation of the right hemisphere who suffered from pharmaco-refractory epilepsy. Clinical examination revealed left-sided hemiparesis and marked mirror movements of the opposite hand both during paretic and non-paretic hand movements. Functional MRI of repetitive unimanual grasping demonstrated that the two hands share a common cortical representation located in the central motor region of the unaffected left hemisphere. The affected right hemisphere did not show any activation during either task. This case study demonstrates the feasibility and usefulness of motor fMRI in young children before they undergo epilepsy surgery.

Brain Mapping↗
PubMed2000

Temporal lobe epilepsy with sensory aura: interictal glucose hypometabolism.

Patients with mesial temporal lobe epilepsy (mTLE) exhibit marked depressions of the regional cerebral glucose metabolism (rCMRGlu) in the mesiotemporal region. We hypothesised that patients with temporal lobe epilepsy (TLE) who have a bilateral somatosensory or acoustic ( = temporolateral/SII-) aura can be differentiated from mTLE by rCMRGlu depressions primarily involving temporo-perisylvian locations. We therefore used this ictal semiology as a clinical criterion to define a subgroup of such patients and measured the rCMRGlu in 16 patients with TLE as evident from interictal and ictal EEG-video monitoring. Clinically, they presented with medically refractory complex partial seizures and were subjected to presurgical evaluation. The pattern of the interictal rCMRGlu in the TLE patients was different from that observed in patients with mTLE and showed significant depressions ipsilateral to the epileptic focus in mesial temporal and lateral temporal regions but spared the thalamus. The neocortical metabolic depressions were spatially more extended in right than in left TLE patients. Magnetic resonance images (MRI) were either normal (n = 5) or revealed unilateral or bilateral hippocampal atrophy/sclerosis (n = 7), or temporal or extratemporal focal cortical dysplasia (n = 4). The selected TLE patients presented here comprise a heterogeneous group showing most pronounced metabolic depressions in the lateral temporal cortex. Thus, our data suggest that non-invasive metabolic imaging can assist in identifying the neocortical symptomatogenic zone in putative temporo-perisylvian lobe epilepsy.

Abdomen↗
PubMed2000

Heterotopic ossification in childhood and adolescence.

Heterotopic ossification, or myositis ossificans, denotes true bone in an abnormal place. The pathogenic mechanism is still unclear. A total of 643 patients (mean age, 9.1 years) admitted for neuropediatric rehabilitation were analyzed retrospectively with respect to the existence of neurogenic heterotopic ossification. The purpose of this study was to obtain information about incidence, etiology, clinical aspect, and consequences for diagnosis and therapy of this condition in childhood and adolescence. Heterotopic ossification was diagnosed in 32 patients (mean age, 14.8 years) with average time of onset of 4 months after traumatic brain injury, near drowning, strangulation, cerebral hemorrhage, hydrocephalus, or spinal cord injury. The sex ratio was not significant. In contrast to what has been found in adult studies, serum alkaline phosphatase was not elevated during heterotopic ossification formation. A persistent vegetative state for longer than 30 days proved to be a significant risk factor for heterotopic ossification. The incidence of neurogenic heterotopic ossification in children seems to be lower than in adults. A genetic predisposition to heterotopic ossification is suspected but not proven. As a prophylactic regimen against heterotopic ossification we use salicylates for those patients in a coma or persistent vegetative state with warm and painful swelling of a joint and consider continuous intrathecal baclofen infusion and botulinum toxin injection for those patients with severe spasticity. We prefer to wait at least 1 year after trauma before excision of heterotopic ossification.

Adult↗
PubMed1999

Benign epileptic discharges in patients with lesional partial epilepsies.

Case reports of four patients with therapy-resistant lesional partial epilepsies and additional foci of benign epileptic discharges of childhood, in addition to the usual electroencephalogram (EEG) changes, are presented. A family history of epileptic or febrile seizures in childhood was reported in all four patients. A distant relative of one patient, not manifesting seizures, demonstrated rolandic spikes on EEG. An abnormal pregnancy (polyhydramnion, premature pains, induced labor because of an abnormal CTG , placenta insufficiency) was reported in one patient, risk factors during birth (birth 14 days after term, placenta insufficiency) were reported in one, and bacterial meningitis at 4 weeks of age was reported in one. All patients manifested a retarded, partly severe, unfavorable infantile psychomotor development. An early seizure onset was observed in all patients (in three patients during the first year of life and in one patient during the second year). A hemifacial seizure symptomatology was seen, in addition to other symptoms, in two patients, possibly indicating the seizure pattern indicative of benign partial seizures; seizures occurred exclusively in sleep in one patient. The benign focus was never located in the lesional area. It was recorded over the same hemisphere in two patients and over the other hemisphere in the other two.

Cerebral Cortex↗
PubMed1999

A new epileptic seizure classification based exclusively on ictal semiology.

Historically, seizure semiology was the main feature in the differential diagnosis of epileptic syndromes. With the development of clinical EEG, the definition of electroclinical complexes became an essential tool to define epileptic syndromes, particularly focal epileptic syndromes. Modern advances in diagnostic technology, particularly in neuroimaging and molecular biology, now permit better definitions of epileptic syndromes. At the same time detailed studies showed that there does not necessarily exist a one-to-one relationship between epileptic seizures or electroclinical complexes and epileptic syndromes. These developments call for the reintroduction of an epileptic seizure classification based exclusively on clinical semiology, similar to the seizure classifications which were used by neurologists before the introduction of the modern diagnostic methods. This classification of epileptic seizures should always be complemented by an epileptic syndrome classification based on all the available clinical information (clinical history, neurological exam, ictal semiology, EEG, anatomical and functional neuroimaging, etc.). Such an approach is more consistent with mainstream clinical neurology and would avoid the current confusion between the classification of epileptic seizures (which in the International Seizure Classification is actually a classification of electroclinical complexes) and the classification of epileptic syndromes.

Electroencephalography↗
PubMed1999

Evaluation with subdural plates in children and adolescents.

Noninvasive EEG examination is not always adequate for the determination of the epileptogenic area. In such cases invasive methods are required. The authors report on their experience with the implantation of subdural plates for the precise ictal and inter-ictal determination of the epileptogenic areal and the stimulation of the eloquent cortex. From December 1992 to December 1997, 97 patients were evaluated in the Bethel epilepsy center using subdural plates. Of these patients, 44 were children or adolescents, who underwent 45 resections. In order to be able to draw differentiated conclusions on the use of subdural plates in children and adolescents, these patients were divided into three age groups: Group 1, 0-5 years (n = 12); Group 2, 6-11 years (n = 13 + 1 repeat evaluation and resection); Group 3, 12-18 years (n = 19). In the groups of children and adolescents examined there were no complications or progress impediments which might give reason to assume that the application of these techniques involves risks or hazards. This has been verified by the results, in which 75% of age Groups 1 and 3 were categorized as 1 a/b or 2d according to the Engel classification.

Adolescent↗
PubMed1998

[Semiologic classification of epileptic seizures].

Recent advances in epileptology and epilepsy surgery require revision of the currently used International Classification of Epileptic Seizures, which was published 1981. We present a classification of epileptic seizures which is based purely on the clinical seizure semiology. The advantages of a semiological seizure classification are stressed.

Brain Mapping↗
PubMed1998

Semiological seizure classification.

We propose an epileptic seizure classification based exclusively on ictal semiology. In this semiological seizure classification (SSC), seizures are classified as follows: a. Auras are ictal manifestations having sensory, psychosensory, and experiential symptoms. b. Autonomic seizures are seizures in which the main ictal manifestations are objectively documented autonomic alterations. c. "Dialeptic" seizures have as their main ictal manifestations an alteration of consciousness that is independent of ictal EEG manifestations. The new term "dialeptic" seizure has been coined to differentiate this concept from absence seizures (dialeptic seizures with a generalized ictal EEG) and complex partial seizures (dialeptic seizures with a focal ictal EEG). d. Motor seizures are characterized mainly by motor symptoms and are subclassified as simple or complex. Simple motor seizures are characterized by simple, unnatural movements that can be elicited by electrical stimulation of the primary and supplementary motor area (myoclonic, tonic, clonic and tonic-clonic, versive). Complex motor seizures are characterized by complex motor movements that resemble natural movements but that occur in an inappropriate setting ("automatisms"). e. Special seizures include seizures characterized by "negative" features (atonic, astatic, hypomotor, akinetic, and aphasic seizures). The SSC identifies in detail the somatotopic distribution of the ictal semiology as well as the seizure evolution. The advantages of a pure SSC, as opposed to the current classification of the International League Against Epilepsy (ILAE), which is actually a classification of electroclinical syndromes, are discussed.

Electroencephalography↗
PubMed1997

The genetics of localization-related symptomatic epilepsy: risk of a family history with seizures in patients who have undergone surgery.

A family history of epileptic seizures including febrile convulsions was found in 15 of 103 patients (15%) with localization related epilepsy with partial seizures with and without secondary generalization, who were operated on because of drug resistance. This rate was significantly higher than that of the cumulative incidence in the general population (4%). The localization of the brain damage did not play a role (temporal lobe resection left: 15%, right: 17%, extra-temporal lesion excision: 20%, hemispherectomy: 11%). Various family members were involved. Some patients had more than one relative with seizures. Thus, 21 relatives suffered from seizures. Eleven of them had generalized tonic-clonic seizures (one grand mal on awakening), 7 had febrile convulsions (4 complicated), and in 1 patient the grand mal seizures on awakening were preceded by absences; 1 had generalized tonic-clonic and complex partial seizures; 1 after complicated febrile seizures likewise had complex partial seizures; another mentally retarded patient suffered from generalized tonic-clonic, axial tonic and myoclonic-astatic seizures. The seizure type of 3 remote relatives was not known. The first seizure occurred in 16 family members during childhood, in 3 in adolescence and in only 1 in adulthood (1 unknown). Eight showed mental retardation of slight degree in most. It is interesting that only one-third of the patients with a family history with seizures were seizure-free after the operation; 5 still had seizures, mostly reduced in frequency, 3 had seizures and isolated auras and 2 had only isolated auras. On comparing the findings in patients with and without a family history with seizures, those with family members with epileptic seizures showed a lower rate of an intellectual deficit (7 vs 47%) and brain tumours (13 vs 44%). Our earlier findings with a different group of patients are thus confirmed: that genetics play a role in symptomatic epilepsies.

Adolescent↗
PubMed1997

Localization of epileptic auras induced on stimulation by subdural electrodes.

PURPOSE: This study evaluates the localization of stimulation-induced auras (SIA) and tries to determine whether the SIA can help to define the boundaries of resection in epilepsy surgery. METHODS: Using subdural grid electrodes, 31 patients with drug resistant focal epilepsy were examined in a retrospective and prospective study lasting 2 years. RESULTS: On stimulation by subdural electrodes, we elicited habitual auras in 16 patients (52%). The zone of SIA overlapped the epileptogenic lesion in 12 patients (75%), the EEG seizure onset zone in 12 patients (75%), and the irritative zone of interictal spikes in eight patients (50%). Postoperative results showed a significant correlation with the complete removal of the epileptogenic lesion (p < 0.001). Because the number of patients in the study was small, we could not find a significant correlation with the complete removal of the SIA zone, EEG seizure onset zone, and irritative zone. CONCLUSIONS: Our study confirms previous analyses which indicate that complete resection of the epileptogenic lesion is essential to achieve a good outcome. Frequent overlap of the SIA zone with the epileptogenic lesion and the EEG seizure onset zone indicates proximity of the SIA with the epileptogenic zone. Nevertheless, this study does not support the concept that the SIA zone and the EEG seizure onset zone have additional value in defining the boundaries of resection in epilepsy surgery. Three case presentations suggest that SIA result from facilitated pathways between the stimulated cortex, the epileptogenic zone around the lesion, and the symptomatogenic zone. Functional reorganization in the vicinity of the cortical lesion cannot be ruled out but was not seen in our patients. Thus, SIA often do not reflect the normal function of the stimulated underlying cortex.

Adolescent↗