Martin Ortler

Neuropeptide Y biosynthesis is markedly induced in mossy fibers during temporal lobe epilepsy of the rat

Neuropeptide Y (NPY) immunoreactivity and gene expression was investigated in the hippocampus after kainic acid-induced seizures and pentylenetetrazol kindling in the rat. Pronounced increases of NPY immunoreactivity were found in the terminal field of mossy fibers in both animal models. In kainic acid-treated rats the peptide progressively accumulated in the hilus and the stratum lucidum of CA3, 5-60 days after injection of the toxin and, at the later intervals, extended to the supragranular molecular layer of the dentate gyrus indicating sprouting of these neurons. Unilateral injection of colchicine into the hilus abolished NPY staining of the mossy fibers. Using in situ hybridization, in both animal models markedly enhanced expression of prepro-NPY mRNA was observed in the granular layer, containing the perikarya of the mossy fibers. It is suggested that sustained expression of the neuromodulatory neuropeptide NPY, in addition to the observed plastic changes, may contribute to altered excitability of hippocampal mossy fibers in epilepsy. Neither somatostatin immunoreactivity nor gene expression were enhanced in granule cells/mossy fibers.

Successful surgical treatment of insular epilepsy with nocturnal hypermotor seizures

Nocturnal hypermotor seizures (NHSs) suggest seizure onset in the frontal lobe. We present a patient with NHSs and insular seizure onset who underwent successful surgical treatment.

Management of spontaneous extramedullary spinal haematomas: results in eight patients after MRI diagnosis and surgical decompression.

Spinal cord compression due to extradural and subdural haemorrhage is a neurosurgical emergency. Differences in clinical presentation in relation to localisation of the haematoma, value of MRI as a diagnostic tool, surgical treatment, and prognosis were investigated in a retrospective case series of eight patients with extradural (n = four) and subdural (n = four) haematomas. Results of MRI were compared with operative findings and proved to be of high sensitivity in defining the type of bleeding and delineating craniocaudal extension and ventrodorsal location. Surgical treatment by decompressive laminectomy, haematoma evacuation, and postoperative high dose corticosteroids resulted in resolution of symptoms in five patients and improvement in the clinical situation in two patients. One patient with a chronic subdural haematoma had a second operation because of arachnoidal adhesions. One patient presented with a complete cord transection syndrome due to an acute subdural haematoma and remained paraplegic. It is concluded that prompt, reliable, and non-invasive diagnosis by MRI leads to efficient surgical treatment and a favourable outcome in this rare condition.

Limbic seizures cause pronounced changes in the expression of neurokinin B in the hippocampus of the rat

Immunohistological and in situ hybridization techniques were used to study the influence of kainic acid-induced seizures and of pentylenetetrazol kindling on neurokinin B immunoreactivity and neurokinin B mRNA in the rat hippocampus. Pronounced increases in neurokinin B immunoreactivity were observed in the terminal field of mossy fibres 10-60 days after intraperitoneal injection of kainic acid. These slow but persistent increases in immunoreactivity were accompanied by markedly enhanced expression of neurokinin B mRNA in the granule cells and in hilar interneurons adjacent to the granule cell layer. These changes were preceded by transient increases in neurokinin B mRNA and immunoreactivity in CA1 pyramidal cell layer two and 10 days after kainic acid, which, however, subsided later on. Pentylenetetrazol kindling caused similar increases in neurokinin B mRNA expression in granule cells and in CA1 pyramidal cells, but not in hilar interneurons. In CA1, increased neurokinin B message was present two days after termination of the kindling procedure but not after 10 days. Sixty days after kainic acid injection, neurokinin B immunoreactivity extended to the inner-third of the molecular layer of the dentate gyrus. After pentylenetetrazol kindling, a neurokinin B-immunoreactive band was observed in the infrapyramidal region of CA3. Lesions of the dentate granule cells by local injection of colchicine in kainic acid-treated rats abolished the supragranular neurokinin B-positive staining, whereas it was almost unchanged after transection of the ventral hippocampal commissure. These observations suggest that neurokinin B immunoreactivity may be located in ipsilateral mossy fibres undergoing collateral sprouting to the inner molecular layer or to the infrapyramidal region in CA3, respectively. Preprotachykinin A mRNA, which encodes for neurokinin A and substance P, and substance P immunoreactivity were not changed in the hippocampus of epileptic rats compared with untreated animals. The observed changes in neurokinin B immunoreactivity and mRNA indicate that specific functional and morphological changes may be induced in hippocampal neurons by recurrent limbic seizures.

Genital Automatisms: A Video‐EEG Study in Patients with Medically Refractory Seizures

Summary:  Purpose: Genital automatisms (GAs) are rare clinical phenomena during or after epileptic seizures. They are defined as repeated fondling, grabbing, or scratching of the genitals. The anatomic correlates of GAs have been discussed controversially. The aim of this investigation was to assess the localizing and lateralizing value of GAs.

Quadriplegia after lumbar disc surgery : A case report

Study Design Case report. Objective To report a case of quadriplegia after surgery in the prone position for a herniated lumbar disc. Summary of Background Data Ischemia in the vascular territories of the vertebral arteries after back surgery in the prone position is rare. Degenerative changes of the cervical spine or decreased blood flow to the head with mechanical vessel obstruction during extreme neck movements, systemic hypotension, and thromboembolism have mostly been implicated in the pathogenesis. Methods The case of a 33‐year‐old man undergoing surgery for an unilateral single level disc herniation at L4‐L5 is presented. Within a few hours after surgery he developed quadriplegia and signs of occipital lobe dysfunction. He underwent magnetic resonance imaging investigation. Therapy included arterial blood pressure control, low molecular dextran, dexamethasone, bladder catheterization, and physiotherapy. Results Magnetic resonance imaging demonstrated intramedullary ischemic changes in the cervical spinal cord and at the borderline between anterior and posterior circulation. Outcome after 2 years is fair regarding the severe initial deficit‐the patient walks alone with a cane and bladder function is under control. He is employed in a sedentary job. Conclusions The authors believe that a temporary mechanical occlusion of a vertebral artery led to stasis, formation of thrombi, and subsequent embolism in the vertebrobasilar vascular territory. Extreme head rotation and neck extension is to be avoided in the prone position.

Deep Wound Infection After Vagus Nerve Stimulator Implantation: Treatment Without Removal of the Device

Summary: Effective treatment of deep wound infection without removal of a previously implanted foreign body is difficult. The Neurocybernetic Prosthesis (NCP) System (Cyberonics Inc., Webster, TX, U.S.A.), implanted for vagus nerve stimulation in patients with medically refractory epilepsy, uses coil‐like electrodes placed around the left vagus nerve after exposure of the nerve in the carotid sheath. Infection within this compartment endangers the contained structures and makes removal of the system hazardous. We report the case of one patient implanted with the NCP who underwent successful open wound treatment without removal of the system. A 35‐year‐old man had local signs of wound infection 5 weeks after implantation of a vagus nerve stimulator. Systemic signs of infection were absent. C‐reactive protein was slightly elevated, but all other laboratory values were normal. After open wound debridement and thorough rinsing with bacitracin‐containing solution, the wound was packed with 3% iodoformized gauze. The NCP was left in place. Systemic antibiotic therapy with fosfomycin and cefmenoxim was started. Cultures confirmed an infection with Staphylococcus aureus. The wound was rinsed daily with 3% hydrogen peroxide solution and 5% saline until cultures were sterile and granulation tissue started to fill the wound. Delayed primary closure was performed 2 weeks later. Wound healing was accomplished without removal of the device. No signs of recurrent infection were observed during a follow‐up of 1 year. Open wound treatment without removal of the implanted vagus nerve stimulator is feasible in cases of deep cervical wound infection and can be an alternative if removal of the device appears hazardous.

Glutamate Decarboxylase67 is Expressed in Hippocampal Mossy Fibers of Temporal Lobe Epilepsy Patients

Recently, expression of glutamate decarboxylase‐67 (GAD67), a key enzyme of GABA synthesis, was detected in the otherwise glutamatergic mossy fibers of the rat hippocampus. Synthesis of the enzyme was markedly enhanced after experimentally induced status epilepticus. Here, we investigated the expression of GAD67 protein and mRNA in 44 hippocampal specimens from patients with mesial temporal lobe epilepsy (TLE) using double immunofluorescence histochemistry, immunoblotting, and in situ hybridization. Both in specimens with (n = 37) and without (n = 7) hippocampal sclerosis, GAD67 was highly coexpressed with dynorphin in terminal areas of mossy fibers, including the dentate hilus and the stratum lucidum of sector CA3. In the cases with Ammons horn sclerosis, also the inner molecular layer of the dentate gyrus contained strong staining for GAD67 immunoreactivity, indicating labeling of mossy fiber terminals that specifically sprout into this area. Double immunofluorescence revealed the colocalization of GAD67 immunoreactivity with the mossy fiber marker dynorphin. The extent of colabeling correlated with the number of seizures experienced by the patients. Furthermore, GAD67 mRNA was found in granule cells of the dentate gyrus. Levels, both of GAD67 mRNA and of GAD67 immunoreactivity were similar in sclerotic and nonsclerotic specimens and appeared to be increased compared to post mortem controls. Provided that the strong expression of GAD67 results in synthesis of GABA in hippocampal mossy fibers this may represent a self‐protecting mechanism in TLE. In addition GAD67 expression also may result in conversion of excessive intracellular glutamate to nontoxic GABA within mossy fiber terminals.

Functional imaging of semantic memory predicts postoperative episodic memory functions in chronic temporal lobe epilepsy

Medial temporal (MTL) structures have crucial functions in episodic (EM), but also in semantic memory (SM) processing. Preoperative functional magnetic resonance imaging (fMRI) activity within the MTL is increasingly used to predict post-surgical memory capacities. Based on the hypothesis that EM and SM memory functions are both hosted by the MTL the present study wanted to explore the relationship between SM related activations in the MTL as assessed before and the capacity of EM functions after surgery. Patients with chronic unilateral left (n=14) and right (n=12) temporal lobe epilepsy (TLE) performed a standard word list learning test pre- and postoperatively, and a fMRI procedure before the operation using a semantic decision task. SM processing caused significant bilateral MTL activations in both patient groups. While right TLE patients showed asymmetry of fMRI activation with more activation in the left MTL, left TLE patients had almost equal activation in both MTL regions. Contrasting left TLE versus right TLE patients revealed greater activity within the right MTL, whereas no significant difference was observed for the reverse contrast. Greater effect size in the MTL region ipsilateral to the seizure focus was significantly and positively correlated with preoperative EM abilities. Greater effect size in the contralateral MTL was correlated with better postoperative verbal EM, especially in left TLE patients. These results suggest that functional imaging of SM tasks may be useful to predict postoperative verbal memory in TLE. They also advocate a common neuroanatomical basis for SM and EM processes in the MTL.

Complete removal of vagus nerve stimulator generator and electrodes

Vagus nerve stimulation has become widely used in the palliative treatment of refractory epilepsy. Removal of a vagus nerve stimulator may be desirable or even necessary due to lack of efficacy, intolerable side effects, signs of infection, or failure of the device. Unless the lead or the helical electrodes are defective, only the generator is explanted and the electrodes are usually left behind for fear of damaging nerve or surrounding structures. The authors review their experience with complete removal of the stimulating electrodes and pacemaker-like generator device in 9 consecutive patients, 3 of whom were children. Using microsurgical techniques, the authors were able to completely remove the stimulator, including electrodes in all patients. All nerves remained morphologically intact. One case of temporary and one of permanent clinically silent ipsilateral vocal cord paresis were observed.