Clinical Neuroscience


VUTSKITS László1,2, GASCON Eduardo2,3, KISS Zoltán József2

MARCH 20, 2007

Clinical Neuroscience - 2007;60(03-04)

[Ketamine is a widely used drug in pediatric anesthesia practice, acting primarily through the blockade of the Nmethyl- D-aspartate (NMDA) type of glutamate receptors. A growing body of laboratory evidence, accumulated during the past few years, suggests that this drug could have potential adverse effects on the developing central nervous system. The goal of this short review is to give a brief synopsis of experimental work indicating ketamine-induced developmental neurotoxicity as well as to discuss potential limitations concerning extrapolation of these studies to clinical practice.]


  1. Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, Geneva
  2. Department of Neuroscience, University of Geneva Medical School, Geneva
  3. Institut de Biologie du Développement de Marseille-Luminy, Marseille



Further articles in this publication

Clinical Neuroscience


FODOR Mariann, PALKOVITS Miklós, GALLATZ Katalin

[The area subpostrema (ASP) is a V-shaped area, ventral and ventrolateral to the area postrema. It constitutes the upper border zone of the commissural portion of the nucleus of the solitary tract. The ASP is considered as a morphological and functional key area for the medullary autonomic center. The capillaries here, in contrast to the capillaries of the area postrema are not fenestrated but establish a specific staining for acetylcholinaestherase (AChE). The ASP contains a high density of fibers and terminals of several neuropeptides which are known to affect on NTS activity. Receptors of different neuropeptids and cathecholamines and a dense network of GFAP positive glial processes are found also here. The neurons and the glial cells of the ASP are connected with the AP and a bidirectional connection exists between the ASP and NTS.]

Clinical Neuroscience


MOLNÁR Tünde, FEKETE Kútiné Erzsébet, KARDOS Julianna, PALKOVITS Miklós

[A synaptic receptor for gamma-hydroxybutyric acid (GHB) - a naturally occuring metabolite of succinic acid1 - interacting succinate has been disclosed in rat and human nucleus accumbens (NA) subcellular fractions2, but the molecular properties of this recognition site were not characterised. To address the presumed recognition site for succinate, the pharmacological profile of [3H]succinate binding to synaptic membranes prepared from rat forebrain and human NA samples has been investigated. Specific [3H]succinate binding sites in the human NA synaptic membrane fraction showed a strong pH-dependence and were characterized by binding of succinate (IC50,SUCC=2.9±0.6 µM), GHB (IC50,GHB=2.1±1.3 µM) and gap junction blocker carbenoxolone (IC50,CBX=7.1±5.8 µM). A similar [3H]succinate binding profile was found in rat forebrain synaptic membrane fractions. We conclude the existence of a pHo-dependent synaptic membrane binding site for the intermediary metabolite succinate. The pharmacological properties of this recognition site may possibly suggest the existence of a hemichannel-like target protein for succinate.]

Clinical Neuroscience



[Bone marrow derived stem cells (BMDSCs) have been reported to form neurons and supportive cells in the brain. We describe a technique that combines the simplicity of in vitro studies with many of the advantages of in vivo experiments. We cultured mouse brain slices, deposited GFPtagged BMDSCs evenly distributed on their surfaces, and then added test factors to the culture medium. Addition of both SDF-1 and EGF resulted in morphological changes of BMDSC and in the induction of islet-1, a marker of neuroepithelial progenitors. We conclude that organotypic tissue culture (OTC) may allow us to detect the effects of exogenous factors on the differentiation of BMDSCs (or any other type of stem cells) in an environment that may resemble the CNS after brain injury. Once such factors have been identified they could be evaluated for tissue regeneration in more complex, whole animal models.]

Clinical Neuroscience



[Background and purpose - Previous studies using the viral transneuronal tracing technique demonstrated that central autonomic circuits are involved in the innervation of the adrenal gland. Since increasing number of data indicate laterality in the neuroendocrine system, we aimed to investigate whether the supraspinal innervation of the adrenal gland exhibits asymmetry or not. Methods - The central circuitry involved in the innervation of the left and the right adrenal gland was studied in individual rats by dual transneuronal tracing using isogenic recombinant strains (BDG and BDL) of Bartha strain of pseudorabies virus. Results - Viral infection of brain nuclei (dorsal vagal nucleus, nucleus of the solitary tract, caudal raphe nuclei, A5 cell group, hypothalamic paraventricular nucleus) from the left adrenal was more severe than that from the right organ. Dual-infected neurons from the two adrenals were also detected both in the brain stem and in the hypothalamus. Conclusion - The results indicate a predominance in the supraspinal innervation of the left adrenal gland. Data further suggest that each adrenal gland is innervated both by side-specific neurons and by neurons which project to both organs.]

Clinical Neuroscience


SIMON László, GARAB Sándor, NOSZEK Annamária, ELIZABETH Römmer, ZÁBORSZKY László

[3D reconstruction from electronmicroscopic (EM) serial sections substantially differs from modeling body parts by linking convoluted planes delivered by CT and NMR. Namely, variations both in relative X-Y position and rotation of the target elements between the adjacent images and also additional problems caused by deformed, deteriorated or missing sections can only be overruled by an aligning paradigm, which exploits all the pixel-level information, and results in an optimal fitting with selected precision. This paper presents a complex computer program called Optimal Alignment®, which performs the precise elaboration of X-Y shift and relative rotation of two consecutive images. The required searching process will be customized by setting four independent parameters which relate the span and density of the pixel-scanning basic process. Optimalization of fitting accuracy versus running time can be achieved by a rather short training period. The potential precision of Optimal Alignment based on complex algorythms is far superior to manual aligning of EM photographs with the eye-wrist-mouse facility. The resulted database of alignment orientation parameters can serve as an advanced source for the 3D reconstructing programs. Optimal Alignment® software tool (supported by Hungarian Space Office grant TP 138) will be demonstrated on a basal forebrain NPY+ axonal reconstruction, performed in L. Záborszky’s laboratory (supported by NIH grant NSO23945).]

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Clinical Neuroscience

A case with reversible neurotoxicity induced by metronidazole

EREN Fulya, ALDAN Ali Mehmet, DOGAN Burcu Vasfiye, GUL Gunay, SELCUK Hatem Hakan, SOYSAL Aysun

Background - Metronidazole is a synthetic antibiotic, which has been commonly used for protozoal and anaerobic infections. It rarely causes dose - and duration - unrelated reversible neurotoxicity. It can induce hyperintense T2/FLAIR MRI lesions in several areas of the brain. Although the clinical status is catastrophic, it is completely reversible after discontinuation of the medicine. Case report - 36-year-old female patient who had recent brain abscess history was under treatment of metronidazole for 40 days. She admitted to Emergency Department with newly onset myalgia, nausea, vomiting, blurred vision and cerebellar signs. She had nystagmus in all directions of gaze, ataxia and incompetence in tandem walk. Bilateral hyperintense lesions in splenium of corpus callosum, mesencephalon and dentate nuclei were detected in T2/FLAIR MRI. Although lumbar puncture analysis was normal, her lesions were thought to be related to activation of the brain abscess and metronidazole was started to be given by intravenous way instead of oral. As lesions got bigger and clinical status got worse, metronidazole was stopped. After discontinuation of metronidazole, we detected a dramatic improvement in patient’s clinical status and MRI lesions reduced. Conclusion - Although metronidazole induced neurotoxicity is a very rare complication of the treatment, clinicians should be aware of this entity because its adverse effects are completely reversible after discontinuation of the treatment.

Lege Artis Medicinae

[Central nervous system hemorrhage in Wegener’s granulomatosis]

SZABOLCSI Orsolya, SZÁNTÓ Antónia, ZEHER Margit

[In our case a 41-year-old man with following symptoms: non-productive coughing, fever, difficulty in breathing and weight loss was examined in February 2007, and on the basis of chest X-ray, CT and bronchoscopy, the possibility of neoplasm or tuberculosis cropped up. After the applied therapy (steroid, antibiotics, tuberculostatic drugs) the symptoms became more severe, i.e. hematuria and epistaxis were manifested. A tissue biopsy was carried out during bronchoscopy and the histological examination revealed granulomatous reaction. Meanwhile, the presence of c-ANCA was proved, and Wegener’s granulomatosis (WG) was diagnosed. In March 2007, sudden somnolence and left side hemiplegia developed, and a large haemorrhage was recognised on CT scan in the right fronto-temporal region, with regard to the haemorrhage, the patient had to undergo a neurosurgical operation. We started to treat him in April 2007 by intravenous steroid and 600 mg of cyclophosphamide (Cyc), and he regained the ability to walk again. In October 2007, the Cyc treatment was terminated, and we administered a maintenance therapy with methotrexat. During the regular medical check-up, a chest X-ray indicated a second attack in March 2008, which was confirmed by the chest CT, the clinical symptoms, increased anti-PR3 levels and c-ANCA positivity as well. The flair of the disease was established. Consequently, in April 2008 we decided on plasmapheresis therapy synchronised with Cyc. After that, we started an azathioprine maintenance therapy and he got rid of all the activation symptoms. We can say that with the adequate therapy started in good time and with the regular medical check up of the patient a good result can be achieved. It is true even in the case of WG disease associated by severe complication, for example central nervous hemorrhage.]

Clinical Neuroscience

[Thallium poisoning induced polyneuropathy - clinical and electrophysiological data]


[Introduction - The aim of the study was the electrophysiological investigation of thallium induced polyneuropathy. Beyond the rarity of the illness, the motivation of this work was the possibility of following up the pattern of neuronal damage. Thallium is one of the most toxic heavy metal and its wide use increases the chance of chronic or accidental acute poisoning. The entero-hepatic circulation makes the accumulation of this toxic agent in tissues possible, mostly in neurons, in the epithelial cells of the digestive tract, in the germinative cells of the skin and testicles. In addition to alopecia and digestive complaints, the clinical picture of thallium poisoning is dominated by neurological signs. Severe axonal polyneuropathy develops in almost all cases, with further damage to the retina and impairment of cognitive functions being not unusual. The diagnosis is confirmed by finding high levels of thallium in body fluids, especially in saliva and urine. Case report - Electrophysiological examination of our accidentally poisoned patient revealed severe, sensory-motor, predominant motor axonal polyneuropathy and pointed out some aspects of the pattern of neurotoxic process: the initially distal lesion, the dying-back course and the capacity for regeneration. Conclusion - Because thallium has the same molecular targets as potassium ion thus impairing the energetical supply of the nerve cell, the most effective treatment is carefully loading with potassium. If recognized and treated early, thallium poisoning has a favourable prognosis.]

Lege Artis Medicinae

[Tuberculous meningoencephalitis in a toddler child]

REISZ Zita, GÁL Péter, TAJTI Zsanett, TERHES Gabriella, URBÁN Edit, KISS Ildikó, BARZÓ Pál, KIS Dávid, SENONER Zsuzsanna, SZABÓ Nóra, SZAPPANOS Norbert, TISZLAVICZ László

[INTRODUCTION - Central nervous system complications occur in 1% of patients with Mycobacterium tuberculosis infection, but the mortality is very high, about 50 percent. CASE REPORT - A 1-year-old child in tenebrous condition was admitted to the hospital with suspicion of meningitis. MRI detected disseminated encephalitis and dilated ventricles. Examination of the serum and cerebrospinal fluid didn’t bring any results. The microscopic examination of the brain biopsy raised the possibility of tuberculous meningoencephalitis, and the culture and PCR from the brain tissue revealed meningoencephalitis caused by Mycobacterium tuberculosis Beijing. DISCUSSION - Tuberculous meningitis is a very rare, but severe consequence of extrapulmonary tuberculosis. Due to the high mortality, early diagnosis and whenever suspected, the use of empiric antituberculotic therapy are the only chances of recovery.]

Clinical Neuroscience

Electrophysiological alterations and general toxic signs obtained by subacute administration of titanium dioxide nanoparticles to the airways of rats

HORVÁTH Tamara, PAPP András, KOVÁCS Dávid, KÁLOMISTA Ildikó, KOZMA Gábor, VEZÉR Tünde

Introduction and aims - Particles of titanium dioxide (TiO2) with typical size below 100 nm have gained a broad range of application by now, partly involving direct human exposure. Their known properties - high specific surface, mobility within the organism, induction of oxidative stress, release of inflammation mediators etc. - raise the possibility of nervous system damage but the available data regarding this are scarce and contradictory. Based on that, and the experiences with other metal oxide nanoparticles, the aim of the present study was to investigate certain general end nervous system toxic effects of TiO2 nanoparticles applied in the airways of rats. Materials and methods - Young adult Wistar rats (5 groups of 10 rats each) received, daily for 28 days, intratracheal instillations of titanium dioxide nanoparticles of ca. 10 nm diameter, suspended in 1% hydroxyethyl cellulose dissolved in phosphate-buffered saline, in the doses of 1, 3, and 10 mg/kg b. w. Vehicle controls received the suspension medium and there was also an untreated control group. During treatment, the rats’ body weight was measured, and their clinical state observed, daily. After the 28 days, spontaneous cortical activity, sensory evoked potentials and tail nerve action potential was recorded in urethane anesthesia, then the rats were dissected and tissue samples were taken for Ti level determination and biochemical measurements of some oxidative stress indicators. Results - The two higher doses reduced the rate of body weight gain significantly. Sensory evoked potentials and tail nerve action potential were significantly slowed, but the change in the spectrum of spontaneous cortical activity was not significant. Correlation of moderate strength was found between certain evoked potential parameters and brain Ti level and oxidative stress data. Conclusion - Our results underlined the possible neurotoxicity of TiO2 NPs but also the need for further investigations.