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A Hufnagel

Publications and source records attributed to A Hufnagel.

At least 19 recordsLinked to original sources
PubMed2006

Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study.

Nicotinic acetylcholine receptors (nAChRs) are involved in a familial form of frontal lobe epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In several ADNFLE families, mutations were identified in the nAChR alpha4 or beta2 subunit, which together compose the main cerebral nAChR. Electrophysiological assessment using in vitro expression systems indicated a gain of function of the mutant receptors. However the precise mechanisms by which they contribute to the pathogenesis of a focal epilepsy remain obscure, especially since alpha4beta2 nAChRs are known to be widely distributed within the entire brain. PET study using [18F]-F-A-85380, a high affinity agonist at the alpha4beta2 nAChRs, allows the determination of the regional distribution and density of the nAChRs in healthy volunteers and in ADNFLE patients, thus offering a unique opportunity to investigate some in vivo consequences of the molecular defect. We have assessed nAChR distribution in eight non-smoking ADNFLE patients (from five families) bearing an identified mutation in nAChRs and in seven age-matched non-smoking healthy volunteers using PET and [(18)F]-F-A-85380. Parametric images of volume of distribution (Vd) were generated as the ratio of tissue to plasma radioactivities. The images showed a clear difference in the pattern of the nAChR density in the brains of the patients compared to the healthy volunteers. Vd values revealed a significant increase (between 12 and 21%, P < 0.05) in the ADNFLE patients in the mesencephalon, the pons and the cerebellum when compared to control subjects. Statistical parametric mapping (SPM) was then used to better analyse subtle regional differences. This analysis confirmed clear regional differences between patients and controls: patients had increased nAChR density in the epithalamus, ventral mesencephalon and cerebellum, but decreased nAChR density in the right dorsolateral prefrontal region. In five patients who underwent an additional [(18)F]-fluorodeoxyglucose (FDG) PET experiment, hypometabolism was observed in the neighbouring area of the right orbitofrontal cortex. The demonstration of a regional nAChR density decrease in the prefrontal cortex, despite the known distribution of these receptors throughout the cerebral cortex, is consistent with a focal epilepsy involving the frontal lobe. We also propose that the nAChR density increase in mesencephalon is involved in the pathophysiology of ADNFLE through the role of brainstem ascending cholinergic systems in arousal.

Adult↗
PubMed2005

MRI changes associated with partial status epilepticus.

Neurological disorders of different etiology may cause identical clinical symptoms requiring additional diagnostic procedures for a precise differential diagnosis. Focal epileptic seizures have been shown to cause increased signal intensities in T2 and diffusion-weighted magnetic resonance images (MRI), mimicking other neurological disorders or diseases such as viral encephalitis. In some cases even the combination of neuroimaging and cerebrospinal fluid (CSF) analysis is not sufficient to obtain the final diagnosis, since epileptic seizures may cause pleocytosis as well. Some epilepsy centers presented cases of focal status epilepticus with severe but reversible MRI changes. These cases indicate that MRI-changes following focal seizures are reversible over a different time window compared to MRI changes associated with other etiologies, such as viral infection. This data further suggest that in cases where focal seizures can not be ruled out, a follow-up MRI scan within a few days following the onset of symptoms significantly improves the precision of the differential diagnosis. Recently new scientific data were reported in this review.

Animals↗
PubMed2003

[Altered cerebral excitability and spreading depression. Causes for the comorbidity of epilepsy and migraine?].

Increased co-occurrence and common clinical aspects of epilepsy and migraine lead to the question of a common pathophysiological model of the diseases. Shared genetic risk factors as an explanation for comorbidity could not be proven. Clinical studies underline the unspecific association of migraine and epilepsy. Comorbidity is based on spreading depression as an expression of altered brain state with neuronal hyperexcitability. In comorbid conditions, therapy with valproate, gabapentin, or topiramate may be effective.

Anticonvulsants↗
PubMed2001

Cortical activation in patients with functional hemispherectomy.

Functional hemispherectomy, a safe and effective therapeutical procedure in medically intractable epilepsy, offers the chance to investigate a strictly unilateral cortical activation in ipsilateral limb movement. We assessed the pattern of cortical activation in a group of patients following functional hemispherectomy. We measured regional cerebral blood flow (rCBF) in 6 patients postoperatively and 6 normal subjects with positron emission tomography using 15[O]H2O as a tracer. Brain activation was achieved by passive elbow movements of the affected arm. Analysis of group results and between-group comparisons were performed with statistical parametric mapping, (SPM96). In normal subjects brain activation was found contralaterally in the cranial sensorimotor cortex and the supplementary motor area and ipsilaterally in the inferior parietal cortex. In patients significant rCBF increases were found in the inferior parietal cortex, caudal sensorimotor cortex and the supplementary motor area ipsilaterally. The activation was weaker than in normal subjects. Compared with normal subjects patients showed additional activation in the premotor cortex, caudal sensorimotor cortex and the inferior parietal cortex of the remaining hemisphere. Less activation compared with normal subjects was found in the cranial sensorimotor cortex and the supplementary motor area. A functional network connecting the inferior parietal cortex, premotor cortex and the supplementary motor area as well as the existence of ipsilateral projections originating from these regions may explain why these areas are predominantly involved in reorganization confined to a single hemisphere.

Adult↗
PubMed2001

Seizure-associated headache in epilepsy.

PURPOSE: Headache is often ignored as a symptom of epileptic seizures. The purpose of this prospective study was to analyze frequency, classification, and characteristics of seizure-associated headache (SH) according to the criteria of the International Headache Society. METHODS: Over a period of 15 months, 341 patients with epilepsy, consecutively evaluated at our outpatient clinic for SH, completed a standardized questionnaire. RESULTS: Of the 341 epilepsy patients, 115 (34%) experienced SH with a pain intensity of 6.1 +/- 1.6 (SD) on the visual analogue scale and a duration of 12.8 +/- 15.7 (SD) h. Seizures were always accompanied by headache in 69 (60%) of these 115 patients. SH occurred in four (3%) of 115 patients only preictally, in 31 (27%) of 115 patients periictally, and in 80 (70%) of 115 patients only postictally. In the majority of the 115 patients (55.7%), SH could be classified as migraine headache, whereas in 36.5%, as tension-type headache. The type of SH was not correlated with sex, an epilepsy syndrome, or a seizure type. Migraine-like SH was significantly associated with a history of migraine (p < 0.001). In 20 (77%) of the 26 patients experiencing migraine-like SH with a history of migraine, the phenomenology of migraine-like SH and migraine attacks was identical. CONCLUSIONS: SH is a frequent, long-lasting, and severe symptom of epileptic seizures, causing major impairment of daily living. A history of migraine significantly increases the risk for developing migraine-like SH.

Adult↗
PubMed2000

Cortical reorganization following multiple subpial transection in human brain - a study with positron emission tomography.

We investigated the cortical activation pattern in a 30-year-old woman 4 years after multiple subpial transection (MST) of the right fronto-parietal cortex and six healthy controls using positron emission tomography. Sequential finger-to-thumb opposition at the frequency of 1.5 Hertz contralateral to the operated hemisphere was used as the activation paradigm. We found preserved cortical activation in the transected fronto-parietal cortex and additional activation of the prefrontal cortex bilaterally and the inferior parietal cortex contralaterally when compared with the control group. This activation pattern indicates that MST induces a rather selective lesion leaving the cortical structures functionally intact. However, it necessitates the recruitment of additional motor areas.

Adult↗
PubMed2000

Cortical motor reorganization following early brain damage and hemispherectomy demonstrated by transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) was utilized to study 7 patients who had undergone hemispherectomy for control of longstanding intractable epilepsy to assess cortical motor reorganization and MEP (motor evoked potentials) ipsilateral to the remaining hemisphere. Five patients were seizure-free post-operatively. All patients displayed a spastic hemiparesis, were able to walk, raise and bend the paretic arm and use the paretic hand to different degrees. METHODS: We examined MEP threshold, site of maximal response to TMS, and latency to the biceps brachii, abductor pollicis brevis and the anterior tibial muscles using a 7 and 12 cm diameter round coil. RESULTS: The following results were obtained: (1) No MEP could be induced to either side by use of the small coil. (2) When using the large coil MEP-threshold was elevated also when stimulating the non-affected hemisphere in comparison to normal controls. (3) Ipsilateral MEP were found to: be non-inducible in two patients, demonstrate largely increased latencies in 3 and be identical to contralateral MEP in two patients. (4) Ipsilateral MEP could be evoked more often in distal than proximal muscles. (5) The site of maximal ipsilateral MEP response was found approximately 2 cm anteriorly to that of the contralateral MEP to the non-affected side of the body (6) No correlation was found between the degree of hemiparesis and inducability of MEP. CONCLUSIONS: The pattern of reorganization of ipsilateral motor control following early brain damage and hemispherectomy appears to be extremely diverse and does not correlate with the degree of neurological impairment.

Adult↗
PubMed2000

Different effects of GABAergic anticonvulsants on 4-aminopyridine-induced spontaneous GABAergic hyperpolarizations of hippocampal pyramidal cells--implication for their potency in migraine therapy.

Clinical studies indicate anti-migrane efficacy of the probably GABAergic anticonvulsants valproate and gabapentin. For the GABAergic anticonvulsants vigabatrin and tiagabine, studies about antimigrane efficacy are missing. The aim of this study was to test the GABAergic potency of these drugs in vitro before further clinical studies. Intracellular recordings were obtained from hippocampal pyramidal cells. Spontaneous GABAergic hyperpolarizations (SGH) elicited by 75 microM 4-aminopyridine were used to test the effect of these drugs on GABA-dependent potentials. Tiagabine (0.1 mM) prolonged the duration of SGH. Furthermore, monophasic SGH turned over into triphasic typical GABAergic membrane potential fluctuations within 20 min. In contrast, valproate, gabapentin, and vigabatrin failed to affect SGH up to 60 min of application. The reason for the fast action of tiagabine on SGH may be caused by a faster increase of synaptic GABA levels compared with other drugs. As migraine therapy benefits from an augmentation of GABA activity, we recommend clinical studies of tiagabine as a fast-acting agent in migraine attacks.

4-Aminopyridine↗
PubMed2000

Clinical relevance of quantified intracranial interictal spike activity in presurgical evaluation of epilepsy.

PURPOSE: Electrocorticograms of 32 patients with medically intractable seizures, recorded through intracranial electrodes, were retrospectively analyzed. The objective was to assess whether quantitative analysis of interictal spikes may be used for delineation of the epileptogenic zone. METHODS: We used a newly developed computer program for automatic detection of interictal spikes and averaging procedures. This allowed determination of the earliest spike of each spike cluster, the maximal averaged spike amplitude, the highest spike frequency, and the shortest averaged spike duration at each recording site. RESULTS: The following results were obtained: (a) Within a zone </=2 cm from the site of seizure origin, we localized the averaged earliest spike of a spike cluster in 27 (84%) of 32 patients, the highest averaged spike amplitude in 24 (75%) of 32, the shortest averaged spike duration in 22 (69%) of 32, and the maximal spike frequency in 17 (53%) of 32; (b) No correlation was found between spike occurrence and histopathology; (c) No evidence was found for decreased postoperative seizure control in patients with several multilobar or bihemispheric occurrence of spike clusters. CONCLUSIONS: The zones of the earliest spike and seizure origin demonstrate a high correlation that favors a common epileptic generator. Removal of all brain areas demonstrating spike clusters is unnecessary to achieve seizure control. Quantification of interictal spike activity is a valuable tool for localization of the seizure generator.

Adolescent↗
PubMed2000

Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART).

OBJECTIVE: To determine the change of incidence and prevalence of neurological disorders caused by the human immunodeficiency virus (HIV) and opportunistic infections in HIV positive patients under treatment since the introduction of highly active antiretroviral therapy (HAART). METHODS: The data of all HIV infected patients were retrospectively analysed, who were examined in the HIV outpatients clinic of the neurological department of the University Clinic Essen between 1995 and 1998 (n=563, total number of visits=735). Data from identified patients were divided into two groups according to the time of examination from 1995 to 1996 (334 visits) and from 1997 to 1998 (401 visits). The incidence and prevalence of neurological disorders were statistically compared between both time intervals. RESULTS: Significantly more patients received HAART in 1997-8 (p<0. 001) and mean CD4+ cell count was significantly higher in 1997-8 (p<0.001). The prevalence of HIV associated dementia and HIV associated polyneuropathy were significantly lower in 1997-8 (both: p=0.02) and the incidence of toxoplasma encephalitis decreased from 5.7% in 1995-6 to 2.2% in 1997-8 (p=0.015). Based on the small number of patients significant changes in HIV associated myopathy, progressive multifocal leukoencephalopathy, cryptoccocal meningitis, and cytomegalovirus-encephalitis could not be detected. CONCLUSION: The prevalence of the most frequent HIV associated neurological disorders and incidence of toxoplasma encephalitis decreased since the introduction of HAART. This may be due to the improvement of immunostatus by HAART as demonstrated by the higher CD4+ cell count in the later time interval. Direct antiretroviral effects within the nervous system may be considered causative as well. The prevalence and incidence of HIV associated neurological disorders and opportunistic CNS infections decreased after introduction of HAART.

Adult↗
PubMed1999

Stroke following chiropractic manipulation of the cervical spine.

We analyzed the clinical course and neuroradiological findings of ten patients aged 27-46 years, with ischemic stroke secondary to vertebral artery dissection (VAD; n = 8) or internal carotid artery dissection (CAD; n = 2), all following chiropractic manipulation of the cervical spine. The following observations were made: (a) All patients had uneventful medical histories, no or only mild vascular risk factors, and no predisposing vascular lesions. (b) VAD was unilateral in five patients and bilateral in three. VAD was located close to the atlantoaxial joint in all eight patients and showed additional involvement of lower sections in six, as well as temporary occlusion of one vertebral artery in three. (c) Nine of ten patients had brain infarction documented by magnetic resonance imaging or computed tomography. (d) Onset of symptoms was immediately after the manipulation (n = 5) or within 2 days (n = 5). (e) Progression of neurological deficits occurred within the following hours to a maximum of 3 weeks. (f) Maximum neurological deficits were severe in nine of ten patients. (g) Outcome after 4 weeks-3 years included no or mild neurological deficits in five patients, marked deficits in three, persistent locked-in syndrome in one, and persistent vegetative state in one. (h) Informed consent was obtained in only one of ten patients. Thus, patients at risk for stroke after chiropractic manipulation may not be identified a priori. Neurological deficits may be severely disabling and are potentially life threatening.

Adult↗
PubMed1998

Properties of advanced headmodelling and source reconstruction for the localization of epileptiform activity.

During the last decade multiple work has been done to determine the sources of epileptiform activity by means of dipole source localization based on recordings of the magnetoencephalogram (MEG) or the electroencephalogram (EEG). The actual available advanced volume conductor models and the multiple source reconstruction by regularization may give new impulse to EEG based source analyses in epilepsy patients. This study demonstrates the principal properties of these techniques. We applied two different EEG source reconstruction techniques within different volume conductor models to localize induced spike activity in a selected patient suffering from medically intractable temporal lobe epilepsy: 1) single moving dipole solution in a 3-shell spherical model versus individual head models (boundary-element-model, BEM, and finite-element-model, FEM); 2) a regularization technique for current density reconstructions using both BEM and FEM. When compared to findings of invasive recordings no adequate source locations were derived from the moving dipole solution in both the 3-shell head model and BEM. In contrast, a high congruence of source reconstruction and invasive determination of the focus was obtained using the regularization techniques in both BEM and FEM, indicating the high spatial accuracy of this technique in individual head models.

Adult↗
PubMed1997

[The Churg-Strauss syndrome with cerebral seizures and terminal kidney failure].

HISTORY AND CLINICAL FINDINGS: A 67-year-old man with known bronchial asthma was admitted to hospital because of deteriorating general state of health, fever, progressive renal failure and confusional states. INVESTIGATIONS: Erythrocyte sedimentation rate was 70/95 mm and the concentration of C-reactive protein raised to 30 mg/dl. WBC count was 19,000/microliter with 39% eosinophilia. Anticytoplasmatic antibodies (cANCA) had a high titre (1:160). On admission the creatinine level was 5.6 mg/dl. Renal biopsy indicated marked glomerular and tubulo-interstitial scarring. Chest radiograms showed transient pulmonary infiltrates. Churg-Strauss syndrome (CSS) was diagnosed on the basis of the clinical and biochemical findings. TREATMENT AND COURSE: Haemodialysis was instituted to counteract the renal failure with water retention. Inflammatory parameters and clinical symptoms rapidly responded to administration of corticosteroids (prednisolone, initially 250 mg/d for 3 days, then 150 mg/d for 5 days followed by slowly decreasing doses). Two weeks after starting prednisolone he had secondary generalised seizures. Magnetic resonance imaging (MRI) of the skull demonstrated marked hyperintense focal changes which in their pattern were characteristic of cerebral vasculitis. As a steroid-refractory condition had to be assumed, cyclophosphamide was also given (100 mg/d). Within 6 weeks the clinical symptoms gradually regressed and the MRI changes became practically normal. CONCLUSION: Early combined immunotherapy should be given if CSS runs a complicated course, rather than the usually recommended corticosteroid monotherapy.

Aged↗
PubMed1997

Effect of partial volume correction on muscarinic cholinergic receptor imaging with single-photon emission tomography in patients with temporal lobe epilepsy.

Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [123I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration.

Adult↗
PubMed1997

Surgical treatment of neoplasms associated with medically intractable epilepsy.

OBJECTIVE: Surgical treatment in patients with brain tumors and medically intractable epilepsy is aimed at the removal of the neoplasm and complete seizure control. However, an adequate surgical approach is still controversial. This study was designed to analyze the factors for the optimum surgical treatment of these patients. METHODS: The clinical, electrophysiological, operative, and histopathological data of 146 consecutive patients who underwent surgery between November 1987 and May 1995 for intrinsic brain tumors and pharmacoresistant epilepsy were evaluated. RESULTS: The majority of the tumors were located in the temporal lobe (n = 116) and involved the cortical gray matter. The most frequent tumors were gangliogliomas (n = 65), pilocytic astrocytomas (n = 21), and dysembryoplastic neuroepithelial tumors (n = 19). All but three tumors (98%) were of low histopathological grade (World Health Organization Grades I or II). The biological behavior of the tumors was strikingly indolent, as indicated by a long preoperative history of chronic seizures (mean, 14 yr). In all cases, complete resection of the tumor, including the epileptogenic area (as determined by noninvasive and/or invasive recordings of the zone of seizure onset and persistent interictal activity), was intended. Complications were encountered in 11 cases (8%). However, no patient died and there was no permanent morbidity. Of the 124 patients who had postoperative follow-up examinations more than 6 months after resection, 71% were seizure-free, 11% had no more than two seizures per year, 13% showed a reduction of seizure frequency of at least 75%, and 5% had no appreciable reduction in seizure frequency. CONCLUSION: The data indicate that neoplasms associated with medically intractable epilepsy constitute a distinct clinicopathological group of tumors that arise in young hosts, involve the cortex, and exhibit indolent biological behavior for many years. Complete surgical removal of these tumors, including the epileptogenic area, can achieve excellent seizure control.

Adolescent↗
PubMed1997

Multiple subpial transection for control of epileptic seizures: effectiveness and safety.

PURPOSE: To assess the efficacy and safety of multiple subpial transection (MST), a new technique in epilepsy surgery, alone and in combination with resection. METHODS: MST was performed in 22 patients with intractable epilepsy, 10 of whom were treated with a combination of a resection and MST in functionally important cortex, 6 of whom were treated with a combination of a resection and MST performed outside functionally important cortex, and 6 of whom were treated with MST alone. RESULTS: Of the 6 patients who received MST alone, none became seizure free and 4 showed > 50% reduction of all seizure types. In 2 patients, including 1 with Rasmussen's encephalitis, no change in seizure frequency or intensity occurred. Of the 16 patients in whom MST was combined with a resection, 9 (56%) became seizure free. Six of the remaining 7 patients showed > 95% reduction of all seizure types. Disappearance of epileptiform potentials in the postoperative EEG correlated significantly with complete relief from seizures. Subtle, permanent neurological deficits remained in 5 of 14 patients who received MST in functionally important brain areas. CONCLUSIONS: Reduction of the seizure frequency was substantial in 4 of 6 patients who received MST alone, but complete seizure control was not observed. MST surrounding a lesionectomy may be a new surgical approach which would minimize the excised volume and improve seizure control.

Adolescent↗