Slit Ventricle as a Neurosurgical Emergency: Case Report and Review of Literature.

BACKGROUND: Symptomatic slit ventricle is one of the most challenging complications of shunt surgery in children. Clinical signs and symptoms may appear with a wide range of intracranial pressure (ICP) values. We report the case of a 10-year-old girl, who did not present the classic clinical features of extremely elevated ICP, which was proven by multiple invasive ICP recordings, performed during shunt revisions. CASE DESCRIPTION: At the age of 6 months, the patient presented squeal for many hours, accompanied with sunset eyes, bulging anterior fontanel, and dilated ventricles of all 4 ventricles on computed tomography scan. Acute ventriculoperitoneal shunt insertion was performed with adjustable valve. During the following 9 years, she was regularly seen and medically treated for intermittent headache, with nausea and vomiting. From 9 years of age, she was hospitalized for severe (10/10 on the visual analog scale), unbearable headache, agitation, and screaming on multiple occasions. Altogether, we had to revise the shunt system 5 times throughout 1 year. Radiologic imaging always showed narrow ventricles. Ophthalmologic examination of the fundus never revealed signs of raised ICP. Perioperative monitoring of the ICP with intraparenchymal sensor showed unexpected high values of 40-45 mm Hg. However, repetitive shunt revisions were successful only temporarily because the symptoms always returned. Only bilateral shunting of the ventricular system was able to eliminate the symptoms permanently. CONCLUSIONS: Images of slit ventricle can be associated either with low or extremely high ICP needing urgent surgical consideration, including ICP monitoring. Bilateral shunt insertion can be effective treatment for slit ventricle syndrome.

Immunohistochemistry of cerebellar seizures: mossy fiber afferents play an important role in seizure spread and initiation in the rat.

Clinical reports suggest the participation of the cerebellum in epilepsy. Mossy fibers are the main excitatory afferents of the cerebellar cortex; most of them use glutamate and strongly excite granule cells through NMDA and AMPA receptors. The role of the ponto-cerebellar mossy fibers in cerebellar neuronal hyperactivity was investigated in the present study in experimental adult Wistar rats. We detected neuronal hyperactivity through the expression of the glutamate-induced c-fos protein, by means of immunohistochemistry and immunoblotting in the vermis and in the hemispheres. Generalized seizures were induced by means of intraperitoneal 4-aminopyridine injections. Following the 4-aminopyridine seizures, the c-fos expression of cerebellar granule cells was significantly elevated at 1.5h in every lobule. Maximum c-fos expression was seen at 3h. The role of the ponto-cerebellar mossy fiber afferents in the induction of c-fos expression was examined after the transection of the middle cerebellar peduncle on the left side. Immunohistochemical analysis 14 days after the surgery revealed that the synapsin I immunoreactivity was significantly reduced in the cerebellar cortex on the operated side, compared to the sham-operated controls and to the non-operated cerebellar hemisphere of the operated animals, indicating the degeneration of mossy fiber terminals. Transection of the middle cerebellar peduncle suppressed cerebellar c-fos expression in the vermis and in the hemispheres significantly. These findings suggest the strong involvement of the middle cerebellar peduncle and the ponto-cerebellar mossy fibers in the pathophysiology of cerebellar epilepsy.

Target identification for stereotactic thalamotomy using diffusion tractography.

BACKGROUND: Stereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography. METHODOLOGY AND PRINCIPAL FINDINGS: Here we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop) and the ventral intermedius (Vim) nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively. CONCLUSIONS: Our data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery.

Alterations of behavior and spatial learning after unilateral entorhinal ablation of rats.

The entorhinal cortex (EC) is the key input and output structure of the hippocampus. It plays a crucial role in sensory processing, memory and learning, as well as in mechanisms of epileptic seizures. Our previous studies on the 4-aminopyridin induced epilepsy model of rats showed that ablation of unilateral EC prompted weakening of limbic seizure manifestation, thus the possibility of therapeutical benefit of this kind of surgery can be risen. Open field, elevated plus-maze and Morris water-maze test were performed to analyze changes of the basal activity level, exploratory behavior, and spatial memory capacity, respectively, of adult Wistar rats having undergone left EC excision. Compared with the sham-operated control group, rats with lesions of the EC showed enhanced locomotor activity in the open-field test. The elevated plus-maze test revealed higher frequency of entries and more time spent in the open arms. Morris water-maze test suggested impairment of the spatial learning capacity following left lateral EC lesion. Therefore, our data showed that EC lesions induced hyperactivity, increased exploratory behavior, and impaired spatial learning. Entorhinal cortex ablation, as a potential method for controlling epileptic seizures has multiple effects on animals' behavior and spatial learning. To determine the cost-benefit ratio of a potential surgical intervention needs further experimental and human investigations.

Lateral entorhinal cortex lesions rearrange afferents, glutamate receptors, increase seizure latency and suppress seizure-induced c-fos expression in the hippocampus of adult rat.

The entorhinal cortex (EC) provides the predominant excitatory drive to the hippocampal CA1 and subicular neurones in chronic epilepsy. Here we analysed the effects of one-sided lateral EC (LEC) and temporoammonic (alvear) path lesion on the development and properties of 4-aminopyridine-induced seizures. Electroencephalography (EEG) analysis of freely moving rats identified that the lesion increased the latency of the hippocampal seizure significantly and decreased the number of brief convulsions. Seizure-induced neuronal c-fos expression was reduced in every hippocampal area following LEC lesion. Immunocytochemical analysis 40 days after the ablation of the LEC identified sprouting of cholinergic and calretinin-containing axons into the dentate molecular layer. Region and subunit specific changes in the expression of ionotropic glutamate receptors (iGluRs) were identified. Although the total amount of AMPA receptor subunits remained unchanged, GluR1(flop) displayed a significant decrease in the CA1 region. An increase in NR1 and NR2B N-methyl-d-aspartate (NMDA) receptor subunits and KA-2 kainate receptor subunit was identified in the deafferented layers of the hippocampus. These results further emphasize the importance of the lateral entorhinal area in the spread and regulation of hippocampal seizures and highlight the potential role of the rewiring of afferents and rearrangement of iGluRs in the dentate gyrus in hippocampal convulsive activity.

Neocortical c-fos mRNA transcription in repeated, brief, acute seizures: is c-fos a coincidence detector?

The effect of acute brief seizures on neocortical c-fos expression was investigated in rats injected with 5 mg/kg 4-aminopyridine. Electroencephalography in freely moving animals with implanted neocortical electrodes detected an average of 2.67 tonic-clonic convulsions within 1 h following the 4-AP treatment. Tissue samples of the somatosensory neocortex were collected at 30 min, 1 h, 3 h, 5 h and 8 h following the treatment for PCR and immunohistochemistry. The c-fos mRNA displayed the first significant rise at 1 h, and remained significantly higher through 3 h. The number of c-fos protein immunoreactive cells was significantly elevated already at 30 min, peaked at 1 h, and declined by 5 h. We conclude that in repetitive, brief seizures, the first convulsion does not increase c-fos RNA transcription, whilst the second causes a long-lasting gene expression and a large increase of c-fos protein synthesis. The phenomenon may have implications in the pathogenesis of human and animal epilepsies.