Combined therapy (Rho-A-kinase inhibitor and chitosan/collagen porous scaffold) provides a supportive environment for endogenous regenerative processes after spinal cord trauma.

Due to the complexity of pathological processes in spinal cord injury (SCI), it is increasingly recognized that combined strategies are more effective than single treatments. The aim of the present study was to enhance neural tissue regeneration and axon regrowth using Rho-A-kinase inhibitor (Y-27632) in a rat SCI model (Th9 compression) and to bridge the lesion with a chitosan/collagen porous scaffold (ChC-PS) applied two weeks after SCI. In addition, to see the synergic effect of Y-27632 and ChC-PS, we combined these single therapeutic strategies to enhance the regenerative capacity of injured spinal cord tissue. The animals survived eight weeks. Application of Y-27632 modulated the inhibitory milieu by specifically targeting gray and white matter integrity, glial fibrillary acidic protein (GFAP)-immunoreactivity, and the outgrowth of neurofilaments and growth-associated protein-43 (GAP-43) immunoreactive axons across the lesion sites, leading to significant positive functional outcome from day 20 to 56. Compared to single treatments, combined Y-27632/ChC-PS therapy was more effective in neurofilaments and GAP-43 expression and GFAP immunoreactivity in the perilesional area of dorsal, lateral and ventral columns, and in enhancing the gray and white matter integrity throughout the cranio-caudal extent. The findings indicate that combined therapy provides a supportive environment for endogenous regenerative processes.

Post-traumatic frontal and parieto-occipital extradural haematomas: a retrospective analysis of 41 patients and review of the literature.

BACKGROUND: The purpose of this study was to analyse the differences between patients with frontal (FEDH) or parieto-occipital (POEDH) epidural haematomas and evaluate possible statistically significant prognostic factors. MATERIAL AND METHODS: In this retrospective study of a group of 41 patients with a FEDH (17) or POEDH (24 individuals), the authors analysed the influence of gender, age, type of injury, clinical presentation, Glasgow coma scale (GCS) score on admission, radiological findings, and time interval from trauma to surgery on outcomes. A good recovery and moderate disability were considered a "good" or "favourable outcome", whereas severe disability, a vegetative state or death was a "poor outcome". RESULTS: In the POEDH subgroup, a higher GCS score on admission and a younger age were statistically significant prognostic factors for a better outcome (p=0.006, rs=0.702). In the subgroup of patients with FEDHs, the results were not significant. However, patients with FEDHs more frequently had "good outcomes" than members of the POEDH subgroup (88.2 vs. 70.9%). Children (≤ 18 years old) constituted a smaller portion of the POEDH subgroup (12.5%) than those in the FEDH subgroup (41.2%). The evaluation of time intervals between the accident and surgery (≤ 24 h vs. > 24 h) showed no significant influence on outcomes in any of the studied subgroups. However, patients undergoing surgery within 24 h of their injury had a less favourable GCS score on admission than those operated on more than 24 h after their injury. Subacute and chronic clinical courses predominated in patients with a FEDH (10/17 FEDH vs. 11/22 POEDH). Different accompanying intradural lesions occurred in 12 patients of the POEDH subgroup, but only in 2 of the FEDH subgroup (50 vs. 11.8%). However, the presence of such lesions did not significantly deteriorate surgical outcomes in either of the subgroups.

[Syndroma caudae equinae of rare etiology]. / Syndroma caudae equinae zriedkavej etiológie.

The results of treatment patients suffering from syndroma caudae equinae (SCE) are not generally satisfactory. The authors decided to evaluate occurrence according to etiology and permanent consequences after treatment in patients that were treated at the Department of Neurosurgery P. J. Safarik University Hospital in Kosice during 12 years (1996-2007). 95 patients from the 101 members file had SCE caused by disc herniation or spinal stenosis. Rare etiology of SCE was found in the six cases: three had traumatic origin, one spinal epidural abscess, one tumor. SCE developed after surgery of intervetebral disc herniation in one patient. Patients underwent control examination or answered by a questionnaire one year from the beginning of SCE or later. Three patients with traumatic SCE had the moderate residual problems. One patient suffered from intermittent pain, perianogenital hypesthesia had two patients, light motor deficit another one. One patient needs to use increased abdominal pressure for urination. Nobody from this subgroup had sexual difficulties or problems with anal spincters' control. The result of treatment patient with SCE caused by spinal epidural abscess was unfavourable. Permanent pain, perianogenital hypesthesia, hard motor deficit and loss of sexual functions persisted. Patient with oncological SCE had deficit in every traced signs. Similar clinical picture was in a patient with postoperative SCE, but residual deficit was moderate.

Posterior fossa extradural haematomas.

BACKGROUND: Posttraumatic epidural haematoma (EDH) of the temporal region is the most common site of supratentorial extradural bleeding; other locations are considered atypical. We reviewed 24 patients with EDH located in the posterior cranial fossa (PFEDH) treated at two neurosurgical centres between January 2000 and November 2006. MATERIAL AND METHODS: In the retrospective study we analysed gender and age distribution, type of injury, clinical presentation, Glasgow Coma Scale (GCS) score on admission, radiological images, interval between trauma and surgery, and outcome. RESULTS: 24 patients with PFEDH constituted 11.5% of 209 surgically treated individuals with EDH. The best outcomes were obtained by patients with GCS scores of 15-14 on admission. Patients in the fourth to seventh decade of life had less favourable outcomes than younger ones. More than half of the patients with PFEDH had associated intradural lesions. Only patients with concomitant brain contusion had a more favourable recovery. The 3 worst levels on the Glasgow Outcome Scale (GOS) were observed in patients suffering from subdural or intracerebral haematoma, or both, associated with the PFEDHs. The majority of patients with concurrent lesions and supratentorial extension of the haemorrhage were in the subgroup undergoing craniotomy between 24 and 72 h after injury. Patients treated in this time interval also had the most unfavourable outcomes. A classical lucid interval was observed only in one patient. The mortality rate in the series was 4.2%. CONCLUSION: The most significant factors influencing outcome in our patients were GCS on admission, age, and associated intradural lesions.

[Post-radiation dedifferentiation of meningioma into chondroblastic osteosarcoma]. / Postradiacná dediferenciácia meningeómu do chondroblastického osteosarkómu.

We report a case of post-radiation dedifferentiation of meningothelial meningioma into chondroblastic osteosarcoma. The tumor developed in a 61-year-old man, seven years after adjuvant stereotactical radiotherapy of recurring meningioma. Histologically, there was a continuous transition from atypical meningioma into chondroblastic osteosarcoma. The patient died three weeks after the surgery, without additional oncological treatment. To our knowledge, this case represents only the second reported case of post-radiation dedifferentiation of meningioma into osteosarcoma.

Meningioma 40 years after radiation therapy for retinoblastoma: genetic and phenotypic analysis, and minireview of literature.

The authors present a case of 44-year-old Caucasian female diagnosed with meningothelial meningioma 40 years after radiotherapy for sporadic unilateral retinoblastoma. The genetic analysis of DNA from the meningioma revealed no oncogenic mutation in the RB1 gene. The analysis of meningioma cells by flow cytometry revealed the following immunophenotype: vimentin++ CD56+ GFAP- EGFR-. Intermediate intensities of Her-2/neu and Pgp expression were detected in a small percentage of tumour cells. Data suggest that the tumour was most likely induced by radiotherapy and did not arise as a second tumour as there was no hereditary predisposition to retinoblastoma.

Nosocomial meningitis caused by Staphylococcus other than S. aureus in children: multicentre study.

Analysing 101 cases of nosocomial meningitis due to staphylococci other than S. aureus within last 15 years, coagulase negative staphylococci represented the commonest pathogen. Major risk factor for staphylococcal meningitis was prior neurosurgery, mainly ventriculoperitoneal shunt insertion. Ten of 101 cases were caused by glycopeptide intermediate resistant strains in patients pretreated with multiple combination of antibiotics including vancomycin and shunt exchanges: 76% of strains were also oxacillin resistant.

Vertex extradural haematoma with associated lesions--improving clinical course with sudden death. Conservative versus surgical treatment.

Although precise criteria have not been assessed yet, small haematomas and clinical improvement claim only close observation according to literature. However a question can arise how to advance in patient with vertex epidural haematoma (VEPH) thinner than 10 mm associated with intradural lesions, when his neurological state is improving. The authors present a case of a man who was conservatively treated due to an epidural clot at the vertex associated with intracerebral haematomas, subarachnoid haemorrhage and haemocephalus diagnosed by computed tomography (CT). Despite his neurologically stable condition with slow, but continuous improvement, after few days the patient suddenly died. Authors analyze advantages and disadvantages of conservative vs. surgical treatment of this pathological condition (Fig. 8, Ref. 31). Full Text (Free, PDF) www.bmj.sk.

Diazepam enhances hypericin-induced photocytotoxicity and apoptosis in human glioblastoma cells.

Glioblastoma multiforme (GBM) is neoplasm which is resistant to all currently used treatment modalities including surgery, radiation therapy and chemotherapy. Photodynamic therapy (PDT) has been suggested as a novel therapeutical approach to the treatment of malignant gliomas. Here, we attempted to enhance hypericin-induced photocytotoxicity and apoptosis by diazepam, a non-selective ligand of peripheral benzodiazepine receptors (PBR) which seem to play an important role in apoptosis regulation. For the study, we used U-87 MG and U373 MG glioma cell lines and primary cultures of GBM cells prepared from peroperatively obtained tumor specimens. The patients included 7 histologically confirmed GBMs. Colorimetric MTT assay was employed to study the photocytotoxic effects of hypericin and diazepam. Flow cytometry was used to detect apoptosis and assess the proapoptotic effects of diazepam. We found that hypericin upon photoactivation exerts strong cytotoxic effects against U-87 MG and U373 MG cells as well as primary GBM cell cultures. No cytotoxic effect of hypericin was observed under dark conditions. Diazepam inhibited cell growth in U-87 MG cells and primary cultures whereas proliferation of U373 MG cells remained unaffected. When hypericin was combined with diazepam, photocytotoxicity was increased in U-87 MG cells and primary cultures unlike U373 MG cells. Flow cytometric analysis revealed photoactivated hypericin-induced apoptosis in both cell lines. Apoptosis was significantly enhanced by diazepam in U-87 MG cells. However, no such effect was observed in U373 MG cells. In the present study, we showed that photocytotoxic effect of hypericin in glioma cells can be potentiated by diazepam. This effect is underlied by the ability of diazepam to facilitate hypericin-induced apoptosis. This work provides support to performe clinical studies involving diazepam in the antiglioma treatment regimens as an apoptosis-modulating agent.

[Ischemic-reperfusion paraplegia in the dog and its light microscopy imaging]. / Ischemicko-reperfúzna paraplégia u psa a jej svetelnomikroskopický obraz.

Paraplegia, which develops after operation on aorta, represents a real catastrophe for the patient and for the surgeon. The aim of the present work was to investigate the light microscopy picture of this complication and consequently better understand related processes. Twenty one adult dogs, cross breeds of both sexes, weight 18-25 kg, were divided into four groups: 1. Controls (n = 3); 2.30-min ischemia induced by occlusion of thoracic aorta by a tourniquet, followed for 30 min survival (n = 6); 3.30-min ischemia and 72 h of survival (n = 6); 4) 30-min ischemia and 6 days of survival (n = 6). All these manipulations were made in sterile conditions under general anesthesia. As soon as the planned time of survival passed, the animals were flushed out, in deep pentobarbital anesthesia, with 3,000 ml of sodium chloride and fixed with 3,000 ml of 10% neutral formaldehyde. Sections, 30 microns thick, from L3-S1 medulla segments were processed in the laboratory of Neurobiological Institute by the method of Nauta for light microscopy examination. Neurohistological picture was characterized by a marked damage of the medulla neurons. The changes proved to be irreversible and resulted, in the course of six days of survival, to death of the cells, characterized by their disintegration. The results indicate that the only rational procedure in conditions of threatening ischemic-reperfusion injury of medulla is to prevent it.

Allelic and haplotype frequencies of the p53 polymorphisms in brain tumor patients.

The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in intron 6 (p53 MspI) have been suggested to be associated with the genetically determined susceptibility in diverse types of human cancer. In our hospital-based case-control study, we examined the allele and genotype incidence of these polymorphisms as well as their haplotype combinations in 60 brain tumor patients (27 males and 33 females) and 183 controls without malignancies. The genotype characteristics were determined by the PCR-based RFLP method using DNA extracted from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI polymorphisms are not associated with increased risk of brain tumors. Thus, we conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor suppressor gene p53 do not represent genetic determinants of susceptibility to brain tumors.

[Surgical treatment of discogenic compression of the spinal cord in the thoracic region]. / Chirurgická liecba diskogénnej kompresie miechy v hrudníkovej oblasti.

The objective of the submitted work was to draw attention to some problems associated with the diagnosis and treatment of prolapse of sequestra of thoracic intervertebral discs. The investigated group comprised 9 subjects (4 women, 5 men) aged 33 to 67 years operated upon at the Neurosurgical Clinic in Kosice between Jan. 1 1982 and June 30 2001 on account of compression of nervous structures in the thoracic portion of the spine by sequestra of intervertebral discs. This was manifested by back pain, a sensation of stiffening of the muscles of the lower extremities, altered sensitivity and in all by impaired gait. Only one female patient developed urinary retention, another one painless paraparesis of the lower extremities, therefore the condition was evaluated as a demyelinisation process. In three patients as the only imaging examination method perimyelography was used, in another two it was supplemented by CT. Four patients were examined by MRI. This graphic method proved to be the most suitable. In all subjects of the investigated group the clinical picture and examination methods indicated a unilateral predominance of the affection. In five subjects it proved possible to remove the sequestream of the intervertebral disc via laminectomy, in another four a transpedicular approach into the spinal canal was used successfully. In all patients the condition improved after surgery.

Diazepam enhances etoposide-induced cytotoxicity in U-87 MG human glioma cell line.

Various approaches might be employed in an effort to increase efficacy of the chemotherapeutic treatment of cancer. Recently, various modulators of anticancer therapy effectiveness have been studied. Antiproliferative effects of peripheral benzodiazepine receptor (PBR) ligands might be exploited to enhance cytotoxic effect of a chemotherapeutic drug towards cancer cells. In this work, we sought to enhance cytotoxic effect of etoposide (VP-16) by a PBR ligand, diazepam (DZ) in U-87 MG human glioma cells. Cytotoxicity of VP-16, DZ and their combinations was assessed by using the microculture MTT assay. Cell survival, effective concentrations (EC) and the onset of cytotoxic effect were determined. After 72 h of cultivation, survival of U-87 MG cells was reduced to 57 +/- 7% in the presence of VP-16 at 12.5 microg/mL alone, whereas DZ at 10-4 mol/L alone caused 28 +/- 6% reduction in cell survival. Coincubation of VP-16 at 12.5 microg/mL with DZ at 10-4 mol/L led to a further decrease in cell survival to 45 +/- 6%. Furthermore, DZ at 10-4 mol/L significantly decreased effective concentrations, EC10, EC30 and EC50, of VP-16 and the dose-response curves were shifted to the left. Addition of DZ at 10-4 mol/L to VP-16 also facilitated the onset of its cytotoxic effect. The same decrease in survival was thus achieved approximately 30 h earlier in comparison with VP-16 alone. However, DZ at 10-9 mol/L failed both to exert any effect on glioma cells survival and enhance cytotoxic effect of VP-16. DZ at 10-4 mol/L was capable of both reducing U-87 MG glioma cells survival when applied alone and also enhancing the cytotoxic effect of VP-16. No such observation was made for the lower concentrations of DZ. Potential implementation of diazepam in the antiglioma/anticancer armamentarium awaits further experimentation but phase I and phase II clinical trials could be suggested.

[A patient with spontaneous healing of traumatic spondylolisthesis of the cervical vertebrae]. / Pozorovanie pacienta so spontánne zahojenou traumatickou spondyloptózou krcného stavca.

The authors submit a report on a patient with traumatic spondyloptosis of the sixth cervical vertebra which occurred in an adult man when he bumped his head against a standing lorry. The injury of the cervical spine was diagnosed only four weeks after the accident when the patient regained consciousness and the vertebrae were already fixed in a pathological position. Seven years after the injury the patient is satisfied with his health, works in his original occupation, is engaged in sports and leads an active life.

Cauda equina syndrome.

Single or double-level compression of the lumbosacral nerve roots located in the dural sac results in a polyradicular symptomatology clinically diagnosed as cauda equina syndrome. The cauda equina nerve roots provide the sensory and motor innervation of most of the lower extremities, the pelvic floor and the sphincters. Therefore, in a fully developed cauda equina syndrome, multiple signs of sensory disorders may appear. These disorders include low-back pain, saddle anesthesia, bilateral sciatica, then motor weakness of the lower extremities or chronic paraplegia and, bladder dysfunction. Multiple etiologies can cause the cauda equina syndrome. Among them, non-neoplastic compressive etiologies such as herniated lumbosacral discs and spinal stenosis and spinal neoplasms play a significant role in the development of the cauda equina syndrome. Non-compressive etiologies of the cauda equina syndrome include ischemic insults, inflammatory conditions, spinal arachnoiditis and other infectious etiologies. The use of canine, porcine and rat models mimicking the cauda equina syndrome enabled discovery of the effects of the compression on nerve root neural and vascular anatomy, the impairment of impulse propagation and the changes of the neurotransmitters in the spinal cord after compression of cauda equina. The involvement of intrinsic spinal cord neurons in the compression-induced cauda equina syndrome includes anterograde, retrograde and transneuronal degeneration in the lumbosacral segments. Prominent changes of NADPH diaphorase exhibiting, Fos-like immunoreactive and heat shock protein HSP72 were detected in the lumbosacral segments in a short-and long-lasting compression of the cauda equina in the dog. Developments in the diagnosis and treatment of patients with back pain, sciatica and with a herniated lumbar disc are mentioned, including many treatment options available.

Fos protein expression in sacral spinal cord in relation to early phase of cauda equina syndrome in dogs.

1. The aim of the present study is to map the incipient phase of Fos expression in the sacral spinal cord neuronal pools of multiple cauda equina constrictions canine model. 2. Fos-positive neurons were found bilaterally in the lateral portion of superficial dorsal horn layers (Laminae I-III) and along the lateral edge of the dorsal horn accompanied by the lateral collateral pathway, fibers of Lissauer's tract, terminating at the sacral parasympathetic nucleus. Similarly, high Fos expression was detected in the ventral portion of the dorsal sacral commissure and in the dorsomedial portion of the anterior horns at S1-S3 segment level. Finally, a clearly expressed Fos-positivity was disclosed bilaterally in the neuropil of the nucleus Y in the anterior horn. 3. Data from the present study show that continuous stimulation of the central fibers of sacral dorsal root ganglia neurons, i.e., fibers of sacral primary afferents, unlike those using various stimulations of the peripheral fibres offers an unusual pattern of Fos-like immunoreactivity.

[Injuries of the intracranial part of the carotid artery]. / Poranenia intrakraniálneho úseku karotickej tepny.

The objective of the submitted work was to draw attention to different types of injuries of the intracranial portion of the carotid artery and some problems associated with its solution. The investigated group comprised 7 subjects (2 women, 5 men) aged 19 to 76 years who attended between Jan. 1, 1995 and Feb. 29 2000 the Neurosurgical Clinic in Kosice with sequelae of injuries of the intracranial carotid artery. Two patients developed a pseudoaneurysm. In one case it was manifested by subarachnoid haemorrhage on the 24th day after a crash, in one instance by diplopia six weeks after a retrobulbar injection. Injury of the intracavernous portion of the artery was manifested in one instance by profuse epistaxis on the 17th day after a fall from a bicycle, four times by the development of a carotid-cavernous fistula several days to 3 years after the head injury. In the diagnosis classical as well as MR and digital subtraction angiography were used. In the patient with epistaxis classical carotid angiography was 3 times negative. The results are comparable with data in the literature. In three patients the problem was resolved by ligature of the common carotid artery on the neck. In another three it was necessary to use extra-intracranial trapping. One patient will be subjected to endovascular surgery. Two patients died (a 76-year-old woman from bronchopneumonia, a 19-year-old man from meningitis, despite a liquor fistula treated correctly by a patch).

Effect of midthoracic spinal cord constriction on catalytic nitric oxide synthase activity in the white matter columns of rabbit.

The distribution and changes of catalytic nitric oxid synthase (cNOS) activity in the dorsal, lateral and ventral white matter columns at midthoracic level of the rabbit's spinal cord were studied in a model of surgically-induced spinal cord constriction performed at Th7 segment level and compared with the occurrence of nicotinamide adenine dinucleotide phosphate diaphorase expressing and neuronal nitric oxide synthase immunoreactive axons in the white matter of the control thoracic segments. Segmental and white-column dependent differences of cNOS activity were found in the dorsal (141.5 +/- 4.2 dpm/microm protein), lateral (87.3 +/- 11.5 dpm/microm protein) and ventral (117.1 +/- 7.6 dpm/microm protein) white matter columns in the Th5-Th6 segments and in the dorsal (103.3 +/- 15.5 dpm/microm protein), lateral (54.9 +/- 4.9 dpm/microm protein), and ventral (86.1 +/- 6.8 dpm/microm protein) white matter columns in the Th8-Th9 segments. A surgically-induced constriction of Th7 segment caused a disproportionate response of cNOS activity in the rostrally (Th5-Th6) and caudally (Th8-Th9) located segments in both lateral and ventral white matter columns. While a statistically significant decrease of cNOS activity was detected above the constriction site in the ventral columns, a considerable, statistically significant increase of cNOS activity was noted in the white lateral columns below the site of constriction. It is reasoned that the changes of cNOS activity may have adverse effects on nitric oxide (NO) production in the white matter close to the site of constriction injury, thus broadening the scope of the secondary mechanisms that play a role in neuronal trauma.

Incipient cauda equina syndrome as a model of somatovisceral pain in dogs: spinal cord structures involved as revealed by the expression of c-fos and NADPH diaphorase activity.

Segmental and laminar distribution of Fos-like immunoreactive, reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-exhibiting and double-labeled (Fos-like immunoreactive and NADPHd-exhibiting) neurons was examined in lower lumbar and sacral segments of the dog spinal cord using the model of multiple cauda equina constrictions. NADPHd histochemistry was used as marker of nitric oxide synthase-containing neurons. The appearance and the time-course of Fos-like immunoreactive, NADPHd and double-labeled neurons was studied at 2 h and 8 h postconstriction characterized as the incipient phase of cauda equina syndrome. The occurrence of Fos-like immunoreactive and NADPHd-exhibiting neurons in fully developed cauda equina syndrome was studied at five days postconstriction. An increase in Fos-like immunoreactivity in superficial laminae (I-II) and an enhanced NADPHd staining of lamina VIII neurons were found. A statistically significant increase in Fos-like immunoreactive neurons was found in laminae I-II and VIII-X 8 h postconstriction, and in contrast, a prominent decrease in Fos-like immunoreactive neurons was found in laminae I-II, accompanied by a statistically significant increase in Fos-like immunoreactive neurons in more ventrally located laminae VII-X at five days postconstriction. Quantitative analysis of laminar distribution of constriction-induced NADPHd-exhibiting neurons revealed a considerable increase in these neurons in laminae VIII-IX 8 h postconstriction and a statistically highly significant increase in NADPHd-exhibiting neurons in laminae VII-X five days postconstriction. Concurrently, the number of NADPHd-exhibiting neurons in laminae I-II was greatly reduced. While a low number of double-labeled neurons was found throughout the gray matter of lower lumbar and sacral segments at 2 h postconstriction, a statistically significant number of double-labeled neurons was found in lamina X 8 h and in laminae VII-X five days postconstriction. The course and distribution of anterograde degeneration resulting five days after multiple cauda equina constrictions are compared with segmental and laminar distribution of Fos-like immunoreactive and NADPHd-exhibiting neurons. Prominent involvement of the spinal cord neurons appearing in the lumbosacral segments at the early beginning and in fully developed cauda equina syndrome results in a Fos-like immunoreactivity and strongly enhanced NADPHd staining of some neuronal pools. Under such circumstances, an early cauda equina decompression surgery is advisable aimed at decreasing or preventing the derangement of the neural circuits in the lumbosacral segments.