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1.
HNO ; 67(3): 184-189, 2019 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-30689007

RESUMEN

BACKGROUND: Recent advances in DNA sequencing technology have enabled researchers to identify the genetic background underlying human illness. In addition, the latest genome editing technology, CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9), provides great potential to edit genomic DNA sequences precisely with high efficiency. This technology has been evaluated for treatment of genetic diseases in recently published preclinical studies. Since many such genetic disorders can affect functional structures in the head and neck area, the technology bears high therapeutic potential in otorhinolaryngology. OBJECTIVE: In this article, we summarize the concept of CRISPR-Cas9-based therapies, recent achievements in preclinical applications, and future challenges for the implementation of this technology in otolaryngology. MATERIALS AND METHODS: Genetic targeting strategies were analyzed or established using genome sequencing data derived from online databases and literature. RESULTS: Recent research on animal models has shown that genome editing can be used to treat genetic diseases by specifically targeting mutant genomic loci. For example, one preclinical study in the field of otolaryngology has demonstrated that inherited autosomal dominant deafness in mice can be treated using CRISPR-Cas9. Moreover, the same strategies can be used to establish applications for the treatment of head and neck cancer. The greatest challenge appears to be establishment of a system for the safe and efficient delivery of therapeutic nucleotides in clinics. CONCLUSIONS: In theory, genome editing could be used in otolaryngology to target disease-causing genomic loci specifically. However, various challenges have to be overcome until applications can be used clinically.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Otolaringología , Animales , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Marcación de Gen , Humanos , Ratones
2.
J Neurol Neurosurg Psychiatry ; 80(7): 773-80, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19324869

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the short- and long-term seizure outcome and to find predictors of outcome after epilepsy surgery in lesional posterior cortical epilepsies (PCEs). METHODS: The operative outcome in 80 consecutive adult patients with lesional PCEs who underwent resective surgery for intractable partial epilepsy between 1991 and 2006 was retrospectively studied. RESULTS: The probability of remaining in Engel Class I was 66.3% (95% CI 60 to 72) at 6 months, 52.5% (95% CI 47 to 57) at 2 years, 52.9% (CI 45 to 59) at 5 years and 47.1% (CI 42 to 52) at 10 years. Factors predicting poor outcome were the presence of a somatosensory aura, extraregional spikes, incomplete resection, interictal epileptiform discharge (IED) in EEG 6 months and 2 years postsurgery, history of generalised tonic-clonic seizure (GT-CS) and the presence of focal cortical dysplasia in the resected specimen. Factors predicting good outcome were childhood onset of epilepsy, short epilepsy duration, ipsilateral spikes, visual aura, presence of well-circumscribed lesion in preoperative MRI and a pathologically defined tumour. In the multivariate analysis, predictors were different in the long and short term as follows: incomplete resection as proven by postoperative MRI (hazard ratio (HR) 2.059 (CI 1.19 to 3.67)) predicts seizure relapse in short-term follow-up. The presence of IED in the EEG performed 6 months after surgery (HR 2.3 (CI 1.128 to 4.734)) predicts seizure relapse in the long-term fellow-up. However, the absence of a history of GT-CS independently predicts seizure remission in short- and long-term follow-up. CONCLUSIONS: Surgery in PCEs proved to be effective in short- and long-term follow-up. Lesional posterior cortical epilepsy may be a progressive process in a substantial number of cases.


Asunto(s)
Corteza Cerebral/fisiopatología , Corteza Cerebral/cirugía , Epilepsias Parciales/fisiopatología , Epilepsias Parciales/cirugía , Neurocirugia/métodos , Adulto , Edad de Inicio , Corteza Cerebral/patología , Electroencefalografía , Epilepsias Parciales/patología , Epilepsia Parcial Sensorial/fisiopatología , Epilepsia Parcial Sensorial/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud , Periodo Posoperatorio , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Convulsiones/fisiopatología , Convulsiones/cirugía , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
3.
Zentralbl Neurochir ; 66(4): 213-6, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16317604

RESUMEN

A case is presented with secondary trigeminal neuralgia (TN) caused by an arteriovenous malformation (AVM) of the cerebellopontine cistern, which was detected by radiological work-up for planned microvascular decompression. An AVM surrounding the trigeminal nerve was demonstrated on thin-slice heavily T (2)-weighted 3D-sequence on magnetic resonance imaging (MRI) and confirmed by angiography. The first therapeutic step was endovascular embolization with complete obliteration of the AVM and cessation of pain. Nevertheless surgical excision was performed in order to remove compressive vessels and to prevent a recurrence of pain.


Asunto(s)
Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/cirugía , Malformaciones Arteriovenosas Intracraneales/terapia , Procedimientos Neuroquirúrgicos , Neuralgia del Trigémino/etiología , Neuralgia del Trigémino/cirugía , Procedimientos Quirúrgicos Vasculares , Angiografía Cerebral , Embolización Terapéutica , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad
4.
Zentralbl Neurochir ; 64(1): 12-8, 2003.
Artículo en Alemán | MEDLINE | ID: mdl-12582941

RESUMEN

Seven patients presented with intracranial hemorrhage due to arteriovenous dural fistula. Six patients showed intracerebral hemorrhage combined with subdural hematoma and intraventricular hemorrhage in one case respectively, and one patient had infratentorial subarachnoid hemorrhage. Location of the fistulae was frontobasal (n=2), tentorium (n=2), transverse sinus (n=2), and superior sagittal sinus (n=1). Angiography revealed reflux into cortical veins in all cases. Therapy was surgery in both cases with fistula of the anterior cranial fossa with good results. An endovascular intraarterial therapy was performed in a case with circumscribed fistula of the superior sagittal sinus, this patient developed a second dural fistula during follow-up. Two patients with tentorial fistulae had primary endovascular treatment complicated by infarction of both thalami in one case and a recurrence of the fistula in the other. In the last case the fistula was closed by surgery. Out of two patients with widespread fistulae of the transverse sinus one made a good clinical recovery and the other remained unchanged. In the first case definite closure of a remnant of the fistula was refused, in the second no further therapy was recommended.


Asunto(s)
Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/cirugía , Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/cirugía , Anciano , Fístula Arteriovenosa/complicaciones , Angiografía Cerebral , Femenino , Hematoma Subdural/complicaciones , Humanos , Hemorragias Intracraneales/etiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia , Hemorragia Subaracnoidea/complicaciones , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares
5.
Brain Res ; 906(1-2): 74-83, 2001 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-11430863

RESUMEN

Cortical spreading depression (CSD) occurrence has been suggested to be associated with seizures, migraine aura, head injury and brain ischemia-infarction. Only few studies identified CSD in human neocortical slices and no comprehensive study so far evaluated this phenomenon in human. Using the neocortical tissue excised for treatment of intractable epilepsy, we aimed to investigate CSD in human. CSD was induced by KCl injection and by modulating T-type Ca(2+) currents in incubated human neocortical tissues in an interphase mode. The DC-fluctuations were recorded by inserting microelectrodes into different cortical layers. Local injection of KCl triggered single CSD that propagated at 3.1+/-0.1 mm/min. Repetitive CSD also occurred spontaneously during long lasting application (5 h) of the T-type Ca(2+) channel blockers amiloride (50 microM) or NiCl(2) (10 microM) which was concomitant with a reversible extracellular potassium increase up to 50 mM. CSD could be blocked by the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid in all cases. The results demonstrate that modulation of the Ca(2+) dynamics conditioned human neocortical slices and increased their susceptibility to generate CSD. Furthermore, these data indicate that glutamatergic pathway plays a role in CSD phenomenon in human.


Asunto(s)
Depresión de Propagación Cortical/fisiología , Epilepsia/metabolismo , Neocórtex/metabolismo , Neuronas/metabolismo , Adolescente , Adulto , Amilorida/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/efectos de los fármacos , Canales de Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/fisiología , Niño , Depresión de Propagación Cortical/efectos de los fármacos , Diuréticos/farmacología , Epilepsia/inducido químicamente , Epilepsia/fisiopatología , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Ácido Glutámico/metabolismo , Humanos , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Persona de Mediana Edad , Neocórtex/efectos de los fármacos , Neocórtex/fisiopatología , Neuronas/efectos de los fármacos , Níquel/farmacología , Potasio/metabolismo , Cloruro de Potasio/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo
6.
Neuroscience ; 100(3): 445-52, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11098107

RESUMEN

The antiepileptic effect of the dihydropyridine calcium channel blocker nifedipine was tested in neocortical slice preparations (n=27) from patients ranging in age from four to 46 years (mean=25) who underwent surgery for the treatment of intractable epilepsy. Epileptiform events consisted of spontaneously occurring rhythmic sharp waves as well as of untriggered epileptiform field potentials induced by omission of Mg(2+) from the superfusate, or epileptiform field potentials elicited by application of bicuculline and triggered by single electrical stimuli. (1) Spontaneous rhythmic sharp waves (n=6): with nifedipine (40micromol/l), the repetition rate was decreased down to 30% of initial value, whereas the area under the field potential remained nearly unchanged. (2) Untriggered low Mg(2+) epileptiform field potentials (n=6): with nifedipine (40micromol/l) the area under the field potentials was reduced while the action on the repetition rate was ambiguous. (3) Triggered bicuculline epileptiform field potentials (n=15): with nifedipine (40micromol/l; n=4), no antiepileptic effect was found. There was, however, a marked increase in the area under the epileptiform field potentials. The area under the field potentials was reduced only at a dosage of 60micromol/l (n=11). This effect was stronger when nifedipine was applied with a K(+) concentration raised from 4 to 8mmol/l. The results show that the calcium channel blocker nifedipine is able to reduce differential epileptiform discharges in human neocortical tissue. These observations are in line with previous findings, suggesting that calcium flux into neurons is involved in epileptogenesis. The present results therefore support the idea that some organic calcium antagonists may be useful in human epilepsy therapy, although the etiology of epileptic seizures seems to be a critical factor for the efficacy of the drug.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Neocórtex/fisiología , Nifedipino/farmacología , Periodicidad , Adolescente , Bicuculina , Niño , Preescolar , Convulsivantes , Relación Dosis-Respuesta a Droga , Electrofisiología , Epilepsia/inducido químicamente , Epilepsia/fisiopatología , Humanos , Técnicas In Vitro , Lactante , Recién Nacido , Magnesio/administración & dosificación
7.
Eur J Pharmacol ; 401(2): 167-72, 2000 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-10924922

RESUMEN

Human neocortical temporal lobe tissue resected for treatment of pharmacoresistant epilepsy was investigated. In slices prepared from this tissue, epileptiform field potentials (EFP) were induced by omission of magnesium from the artificial cerebrospinal fluid (ACSF). The effects of the gamma-aminobutyric acid transaminase inhibitor vigabatrin on EFP were tested. Vigabatrin exerted a dose-dependent reduction of the repetition rate of EFP: after 3 h of administration of vigabatrin in concentrations of 100 and 200 micromol/l, the repetition rate of EFP was reduced to 35% and 18% of the initial values, respectively. This effect was not reversible. In control experiments with neocortical slices from rats, vigabatrin reduced EFP in a comparable range. The results demonstrate a strong antiepileptic effect of vigabatrin on EFP in tissues from pharmacoresistant epilepsy patients.


Asunto(s)
Anticonvulsivantes/farmacología , Encéfalo/efectos de los fármacos , Epilepsia/prevención & control , Vigabatrin/farmacología , Adolescente , Adulto , Animales , Encéfalo/fisiopatología , Relación Dosis-Respuesta a Droga , Resistencia a Medicamentos , Electrofisiología , Epilepsia/fisiopatología , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/prevención & control , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Neostriado/efectos de los fármacos , Neostriado/fisiopatología , Ratas
8.
Neurol Res ; 21(5): 463-74, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10439427

RESUMEN

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.


Asunto(s)
Electrodos Implantados , Electroencefalografía/instrumentación , Epilepsias Parciales/diagnóstico , Adolescente , Factores de Edad , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirugía , Niño , Preescolar , Craneotomía , Epilepsias Parciales/etiología , Epilepsias Parciales/fisiopatología , Epilepsias Parciales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Espacio Subdural
9.
Neurol Res ; 21(1): 51-9, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10048056

RESUMEN

The authors report on their experience of lesionectomies close to or in the thalamus, basal ganglia, third ventricle and in the temporal lobe. The resection itself is performed stereotactically, MRI or CT guided, either microscopically or endoscopically through a sleeve designed by one of the authors and named PAN working sleeve. Over the last four years this new minimally invasive technique has been successfully applied in 39 cases. Eighteen patients with 11 astrocytoma (6AA, 5All), 5 cavernoma and 2 metastases (melanoma, adenocarcinoma) of the basal ganglion-thalamus area and the trigonum were resected by means of a frontal or an occipital burr-hole, whereby in some cases there were subtotal resections. With four of these patients an existing hemiparesis increased by one degree (according to the proposal of the British Medical Research Council I-V). Seventeen patients with lesions in the foramen Monroi and in the third ventricle also underwent operation by means of frontal access, and in each case there was a total resection. Two of the patients required a shunt due to a persistent hydrocephalus internus. In one of these cases there was intraventricular bleeding which necessitated an intra-operative craniotomy. Four patients with intractable epilepsy were operated through a burr-hole in the anterior area of the os zygomaticum. Three patients were submitted to a selective resection of mesial structures and one to an anterior temporal lobe resection. To date the four patients have had no further seizures and no deficits have been observed.


Asunto(s)
Procedimientos Quirúrgicos Mínimamente Invasivos , Neurocirugia/métodos , Técnicas Estereotáxicas , Adolescente , Adulto , Anciano , Ganglios Basales/cirugía , Ventrículos Cerebrales/cirugía , Niño , Preescolar , Diseño de Equipo , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neurocirugia/instrumentación , Estudios Retrospectivos , Lóbulo Temporal/cirugía , Tálamo/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
10.
Schmerz ; 13(2): 113-20, 1999 Apr 14.
Artículo en Alemán | MEDLINE | ID: mdl-12799940

RESUMEN

OBJECTIVES: We performed 52 peripheral nerve stimulation procedures since 1991. In addition to 48 patients with CRPS II, 4 patients with phantom-limb pain were treated. Incomplete or complete lesion of the stimulated peripheral nerves was determined in all patients. Surgically treatment failed in all cases. All patients had been given extensive conservative pain therapy. MATERIAL AND METHOD: The aim was to define a standardised method, which would be as objective as possible, to verify the success of treatment, by measuring the pain-related disability assessment, the subjective intensity of pain and the subjective perception of pain. Long-term follow-up was arranged in addition to determine social and occupational re-integration. The implantation of the stimulating electrode, proximal to the lesion, was performed after microsurgical neurolysis of the peripheral nerves. The patient carried out a stimulation trial after the operation. At the conclusion of the trial stimulation phase, a stimulator unit was permanently implanted in 47 cases, with a marked reduction in pain. Only in 5 cases, the success of the trial stimulation was unsatisfactory. RESULTS: After implanting the stimulator unit an average pain-related disability of 10% was achieved by the 47 patients fitted with a permanent implant. 43 patients have used the permanent stimulator implants with lasting, excellent to good success. The stimulator system was removed in only 4 cases, due to the need for stimulation having passed, or due to a lack of lasting success with stimulation. CONCLUSION: Neurostimulation of peripheral nerves should be considered as an established concept to treat surgically failed peripheral nerve lesions.

11.
Epilepsy Res ; 32(1-2): 224-32, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9761323

RESUMEN

The spatio-temporal distribution of epileptiform activity was investigated in slices from human temporal neocortex resected during epilepsy surgery. Activity was recorded by use of a voltage-sensitive dye and an optical recording system. Epileptiform activity was induced with 10 microM bicuculline and electrical stimulation of layer I. In 10 slices from six patients investigated, epileptiform activity spread across most of the slice. Largest amplitudes were located in layer II/III. Epileptiform activity was characterized by long-lasting potentials with slow rising phases and a low velocity of spread in the horizontal direction (0.044 m/s). This spatio-temporal pattern of epileptiform activity in human slices was similar to that found previously in neocortical slices from guinea pigs with bicuculline. In four of nine human slices investigated under control bath conditions (in non-epileptogenic medium), the spatio-temporal activity patterns were similar to those of guinea pigs in non-epileptogenic medium. In the remaining five human slices, however, the spread in the horizontal direction was significantly larger (4188 microm) in non-epileptogenic medium than that found in slices from guinea pigs (2171 microm). Activity in human slices showing such 'wide spread' in control bath conditions occasionally had characteristic features of epileptiform activity. Further work will have to clarify whether these epileptiform features reflect intrinsic epileptiform properties in human tissue slices.


Asunto(s)
Mapeo Encefálico , Epilepsia del Lóbulo Temporal/fisiopatología , Potenciales Evocados/fisiología , Neocórtex/fisiopatología , Neuronas/fisiología , Animales , Bicuculina/farmacología , Colorantes , Estimulación Eléctrica , Epilepsia del Lóbulo Temporal/cirugía , Potenciales Evocados/efectos de los fármacos , Cobayas , Humanos , Técnicas In Vitro , Neocórtex/efectos de los fármacos , Neocórtex/fisiología , Neuronas/efectos de los fármacos
12.
Brain ; 121 ( Pt 6): 1073-87, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9648543

RESUMEN

Human neocortical temporal lobe tissue resected for treatment of pharmacoresistant epilepsy was investigated. In slices prepared from this tissue, field potentials sometimes superimposed by population spikes were found to appear spontaneously. In individual slices, they were generalized or highly localized to a field of approximately 200 microns in diameter. Synchronous with these potentials, hyperpolarizing and depolarizing postsynaptic potentials were recorded from neurons in the vicinity of the field potential electrode. Hyperpolarizing postsynaptic potentials appeared to be mainly chloride mediated. All potentials, i.e. sharp field potentials as well as postsynaptic potentials, were reversibly suppressed by blockade of the non-NMDA (non-N-methyl-D-aspartate) glutamate-subreceptor and of the GABAA (gamma-aminobutyric acid) receptor, and by application of the organic calcium channel blocker verapamil. By contrast, all potentials remained unaffected by blockade of the NMDA glutamate-subreceptor and the GABAB receptor. The antiepileptic drugs carbamazepine and phenytoin failed to suppress the spontaneous potentials at therapeutic concentrations. Washout of Mg2+ from the superfusate left the spontaneous potentials unchanged or converted them to ictal-type discharges. This epileptiform activity was not suppressed, but augmented by blockade of the GABAA receptor. As a whole, the spontaneously appearing field potentials may be assumed to reflect a state of increased neuronal synchronization.


Asunto(s)
Epilepsia/fisiopatología , Lóbulo Temporal/fisiopatología , Potenciales de Acción/fisiología , Adolescente , Adulto , Anticonvulsivantes/farmacología , Canales de Calcio/fisiología , Niño , Estimulación Eléctrica , Electrofisiología , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Receptores de GABA/fisiología , Receptores de Glutamato/fisiología , Transmisión Sináptica/fisiología , Lóbulo Temporal/efectos de los fármacos
13.
Brain Res ; 794(1): 28-34, 1998 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-9630491

RESUMEN

The so-called terminal negativity (TN) of the DC-potential is a characteristic reaction of neuronal tissue to hypoxia or ischemia. In a previous study on human neocortical slices, two types of TN with flat and steep slopes of rise (< or >10 mV/min) were found with hypoxia. The aim of the present study was to further investigate causes underlying the occurrence of flat and steep TN. Experiments were performed on 23 human neocortical slices (500 micron) resected from 13 patients (epilepsy and tumour surgery). DC-potential and evoked potentials (white matter stimulation) were recorded in layer III. The extracellular potassium concentration ([K+]o) was measured by K+-sensitive microelectrodes. In an interface type chamber, ischemic episodes were induced by oxygen and glucose deprivation. They were terminated when TN had peaked. Both flat and steep TN also existed with ischemic conditions. There was a linear correlation between the slope of rise of TN and the associated slope of rise in [K+]o, respectively, but none regarding latencies of TN or recovery of evoked potentials. Peak levels in [K+]o were 13.9+/-0.9 mmol/l. Compared to control, the slope of rise and latency of TN were clearly increased by addition of dimethyl sulfoxide (DMSO, 0.4%) to the bath solution, whereas nimodipine (40 micromol/l) in 0.4% DMSO had neither an effect on slope of rise of TN nor on latency of TN. As a whole, our observations suggest, that the actual metabolic state determines the occurrence of flat or steep TN.


Asunto(s)
Isquemia Encefálica/fisiopatología , Glucosa/deficiencia , Hipoxia Encefálica/fisiopatología , Neocórtex/fisiología , Terminales Presinápticos/fisiología , Isquemia Encefálica/metabolismo , Estimulación Eléctrica , Potenciales Evocados/fisiología , Humanos , Hipoxia Encefálica/metabolismo , Técnicas In Vitro , Modelos Lineales , Neocórtex/irrigación sanguínea , Neocórtex/metabolismo , Fármacos Neuroprotectores/farmacología , Potasio/farmacología , Tiempo de Reacción/efectos de los fármacos
14.
Brain Res ; 741(1-2): 174-9, 1996 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-9001720

RESUMEN

In animal models, the hallmark of a hypoxic condition is a strong negative shift of the DC potential (anoxic terminal negativity, ATN). This DC-shift is interpreted to be primarily due to a breakdown of the membrane potential of neurons. Such massive neuronal depolarizations have not been reported for all human neocortical neurons in vitro even during prolonged hypoxic periods. This poses the question whether ATN develop also in human neocortical slices made hypoxic. ATN could be observed when human brain slice preparations (n = 15, 13 patients) were subjected to periods of hypoxia (10 to 120 min). These ATN were usually monophasic and appeared with a latency of 16 +/- 4 min (mean +/- S.E.M.). Separating the ATN according to their slopes of rise, steep (> 10 mV/min) and flat (< 10 mV/min) ATN could be distinguished. Steep and flat ATN may be regarded as two different entities of reactions since steep ATN had also greater amplitudes and slopes of decay as compared a flat ATN. With repetitive hypoxias, the latency of both the steep and flat ATN was reduced for the following hypoxic episodes. During hypoxic DC-shifts, evoked potentials were suppressed. With the 1st through 4th hypoxia, they recovered fully within 30 min after reoxygenation when hypoxia was terminated at the plateau of ATN; with extension of hypoxia, recovery was only partial. From the 5th hypoxia onwards, recovery usually did not take place or was not complete.


Asunto(s)
Corteza Cerebral/fisiopatología , Hipoxia Encefálica/fisiopatología , Terminales Presinápticos/fisiología , Adolescente , Adulto , Niño , Preescolar , Epilepsia/fisiopatología , Epilepsia/cirugía , Potenciales Evocados/fisiología , Femenino , Humanos , Técnicas In Vitro , Lactante , Masculino
15.
Brain Res ; 733(2): 307-11, 1996 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-8891316

RESUMEN

In human neocortical slices the specific L-type calcium channel blocker verapamil had been shown to be antiepileptic in the low Mg(2+)-model of epilepsy. The present investigation demonstrated: (1) verapamil exerted also an antiepileptic effect on epileptiform field potentials (EFP) induced by the GABAA-antagonist bicuculline. (2) The unspecific calcium channel modulator flunarizine, which in contrast to verapamil penetrates the blood-brain barrier, depressed EFP in the low Mg(2+)-model and in the bicuculline model. (3) There was no significant difference in the antiepileptic efficacy of verapamil and flunarizine in epileptic (epilepsy surgery) and primary non-epileptic (tumor surgery) neocortical slices.


Asunto(s)
Bicuculina/farmacología , Corteza Cerebral/fisiopatología , Epilepsia del Lóbulo Frontal/metabolismo , Epilepsia del Lóbulo Temporal/fisiopatología , Flunarizina/farmacología , Magnesio/farmacología , Verapamilo/farmacología , Astrocitoma/metabolismo , Astrocitoma/cirugía , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/fisiopatología , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/cirugía , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Ependimoma/metabolismo , Ependimoma/fisiopatología , Epilepsia del Lóbulo Frontal/fisiopatología , Epilepsia del Lóbulo Temporal/metabolismo , Epilepsia del Lóbulo Temporal/cirugía , Potenciales Evocados/efectos de los fármacos , Femenino , Humanos , Técnicas In Vitro , Masculino , Oligodendroglioma/metabolismo , Oligodendroglioma/fisiopatología
16.
Nervenarzt ; 66(12): 901-6, 1995 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-8584074

RESUMEN

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.


Asunto(s)
Epilepsia del Lóbulo Temporal/cirugía , Complicaciones Posoperatorias/etiología , Psicocirugía , Lóbulo Temporal/cirugía , Adolescente , Adulto , Niño , Preescolar , Epilepsia del Lóbulo Temporal/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Calidad de Vida , Recurrencia , Resultado del Tratamiento
17.
Nervenarzt ; 64(7): 468-73, 1993 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-8366972

RESUMEN

The therapeutic concept of local administration of opioids into the perimedullar and cerebrospinal fluid is the result of fundamental studies concerning the discovery and localization of specific binding sites. These studies provoked considerable clinical interest, because they suggested a non-destructive and fully reversible method. In our department we have been gathering experience with an implantable pump system for various indications of chronic pain on a sample of 25 patients. The first implantation was performed in February 1987 and the latest included in this study in February 1991. The sample of patients consisted of two groups: (A) Chronic non-malignant pain (13 cases), (B) Chronic pain due to cancer (12 cases). We used two different pump devices: the gas-filled continuous infusion pump (Infusaid, Mod. 400) in 10 cases and the manually tractable micro pump (Cordis) in 15 cases. In 23 cases we decided in favour of an intraventricular drug administration, mainly because of the site of the pain; in each of these a ventricular catheter was placed in the frontal horn of the lateral ventricle. In the remaining two cases, the catheter was placed intraspinally, the catheter tip terminating at thoracic segments. Nine of the patients with cancer-related pain experienced from excellent to acceptable pain relief, as did also 10 patients with chronic non-malignant pain. Side effects were rare. Our findings also indicate that, in carefully selected patients, both malignant and non-malignant pain may be managed satisfactorily with this technique.


Asunto(s)
Bombas de Infusión Implantables , Inyecciones Espinales/instrumentación , Morfina/administración & dosificación , Neoplasias/fisiopatología , Dolor/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Inyecciones Intraventriculares/instrumentación , Masculino , Persona de Mediana Edad , Morfina/efectos adversos , Umbral del Dolor/efectos de los fármacos
18.
Neurochirurgia (Stuttg) ; 36(4): 131-4, 1993 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-8350975

RESUMEN

A 75-year old patient was admitted to hospital in June 1989. She was suffering from headache since three months. In the neurological examination a mild hemiparesis on the left side, personal changes and apractic disturbances could be found. 10 years before a granulosa-cell tumour of the left ovary was extirpated, postoperatively the patient received radiation and polychemotherapy. CT-scan and MRI of the head showed a tumour parieto-occipital on the right hemisphere with multiple cystic and solid areas. The tumour was extirpated in toto. The postoperative course was uneventful. Primary tumour of the left ovary and intracranial metastasis showed the same histological findings.


Asunto(s)
Neoplasias Encefálicas/secundario , Tumor de Células de la Granulosa/secundario , Lóbulo Occipital , Neoplasias Ováricas/cirugía , Lóbulo Parietal , Anciano , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Femenino , Estudios de Seguimiento , Tumor de Células de la Granulosa/patología , Tumor de Células de la Granulosa/cirugía , Humanos , Imagen por Resonancia Magnética , Lóbulo Occipital/patología , Lóbulo Occipital/cirugía , Neoplasias Ováricas/patología , Ovario/patología , Lóbulo Parietal/patología , Lóbulo Parietal/cirugía , Tomografía Computarizada por Rayos X
19.
Clin Neuropathol ; 11(1): 16-9, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1312401

RESUMEN

Dermoids are rare tumors of the central nervous system. So far, no electron microscopic studies of these tumors have been available. We describe the histology and ultrastructure of a dermoid cyst in a patient with situs inversus and discuss the relationship of keratin and aseptic meningitis, a well-known complication. Histological examination showed an epidermal matrix with 2-4 layers, a cyst containing keratin and debris, some hairs and sebaceous glands. In some areas, chronic inflammation had destroyed the matrix of the cyst wall. Gliosis of the adjacent brain parenchyma was evident, as were eosinophilic rod-shaped crystals. Electron microscopy revealed gliosis with Rosenthal fibers in brain parenchyma adjacent to the tumor capsule. Intracellular osmiophilic, crystalline inclusions were prominent within this area. Glial cells and neuropil were spared. No gross intracellular pathology was seen.


Asunto(s)
Neoplasias Encefálicas/patología , Corteza Cerebral/patología , Colesterol/metabolismo , Quiste Dermoide/patología , Cuerpos de Inclusión/ultraestructura , Cristalización , Femenino , Humanos , Microscopía Electrónica , Persona de Mediana Edad
20.
Brain Inj ; 6(1): 45-52, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1739852

RESUMEN

The quality of outcome after severe closed head injury has become of increasing concern to neurosurgeons. The assessment of residual deficits in patients who have recovered from closed head injury can be very difficult. Many patients are classified as having a good recovery according to the Glasgow Outcome Scale (GOS), but this may be insufficiently focused or sensitive to demonstrate mental deficits objectively. We investigated 33 patients with severe closed head injury who subsequently were diagnosed as having made a good recovery according to the GOS. The severity of the injury was determined by the Glasgow Coma Scale (GCS) and by the presence of a midline shift in the preoperative CT scans. There was a minimal interval of 15 months (means = 1080.5 days, SD = 491 days) between injury and time of neuropsychological testing. Their performance was compared with that of 15 orthopaedic cases. Residual neuropsychological deficits can be demonstrated on the majority of measures in a group of patients who have achieved good recovery on the GOS. Midline shift in preoperative CT scans is not of prognostic value for long-lasting neuropsychological deficits.


Asunto(s)
Daño Encefálico Crónico/diagnóstico , Traumatismos Cerrados de la Cabeza/complicaciones , Pruebas Neuropsicológicas , Actividades Cotidianas , Adulto , Conmoción Encefálica/complicaciones , Edema Encefálico/complicaciones , Enfermedad Crónica , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Escala de Coma de Glasgow , Hematoma Subdural/complicaciones , Humanos , Masculino , Persona de Mediana Edad
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