Assessment of the neuroprotective effects of the acetylcholinesterase inhibitor huperzine A in an experimental spinal cord trauma model.

BACKGROUND: Spinal cord injury is nowadays still a challenging disease, and a treatment option aimed at the primary site of injury does not currently exist. Therefore, the management of acute spinal cord injury has recently focused on the reasons behind the aggravation of the initial insult through secondary mechanisms, and the search for pharmacological treatment protocols is generally aimed at reducing and minimizing the neural injury and neurological sequela. The secondary spinal cord injury usually develops following a primary lesion induced by spinal cord contusion and the emergence of apoptotic cells has been found to play an important role in the development of secondary injury. We propose that huperzine A may induce a significant reduction in the number of apoptotic cells because it possesses the ability to protect cells against glutamate, ischemia and staurosporine-induced cytotocity and apoptosis. METHODS: Huperzine A was administered intraperitoneally to male Wistar Albino rats (220-340 g of body weight) after moderate static clip compression (70 g for 60 s) of the spinal cord at T7 level. Neurological functions were assessed using the Basso-Beattle-Breshanan (BBB) motor rating scale until 3th and 7th days before perfusion, following which the spinal cord was harvested for histopathological examinations and apoptotic cell counts. RESULTS: Histopathological evaluations of the spinal cord of the control, trauma and huperzine A treated groups were evaluated. Control group showed normal neuronal and vascular structures of the spinal cord. However, in both trauma groups 3rd- and 7th-day perfusion showed extensive cavitation and hemorrhage, areas of necrosis and edema in gray matter, and degeneration in motor neurons along with patchy areas of necrotic and apoptotic cells. In the group treated with huperzine A, an increased number of normal cells was observed, along with a lower number of necrotic cells, with a significant reduction in the apoptotic cells (P<0.01). The administration of huperzine A improved post-trauma motor performance. Furthermore, BBB scores of all groups showed that there was an improvement of locomotor abilities in the treatment group as compared with the control. CONCLUSIONS: When compared with controls, huperzine A treatment demonstrates a significant reduction in the number of apoptotic cells. In addition, the group treated with huperzine A showed significant and appreciable neurological improvement in rats.

Searching Evidences of Stroke in Animal Models: A Review of Discrepancies A Review of Discrepancies.

So far, animal models have helped us better understand the pathophysiology of the ischemic brain damage but they could not contribute so much to clinical practice. The discrepancies in results regarding neuroprotective agents in animal experiments compared to clinical trials have not been solved. Various animal models of ischemic stroke have proven efficacy of many neuroprotective agents without any considerable result in phase III clinical trials. As is well known, stroke-related focal cerebral ischemia or cardiac arrest related global cerebral ischemia are major causes of disability and death among human subjects. Animal models are essential to evaluate the therapeutic approaches for humans. In this review, we will try to answer two important questions: 1) Which factors endanger the reliability of experimental studies of stroke on animal models? 2) How can we design our experiments to reflect the neurorestoration and/or neuroprotection mechanisms following ischemic injury, when it comes to human disease?

The Effects of Difumarate Salt S-15176 after Spinal Cord Injury in Rats.

OBJECTIVE: In the present study we analyzed neuroprotective and antiapoptotic effect of the difumarate salt S-15176, as an anti-ischemic, an antioxidant and a stabilizer of mitochondrial membrane in secondary damage following spinal cord injury (SCI) in a rat model. METHODS: Three groups were performed with 30 Wistar rats; control (1), trauma (2), and a trauma+S-15176 (10 mg/kg i.p., dimethyl sulfoxide) treatment (3). SCI was performed at the thoracic level using the weight-drop technique. Spinal cord tissues were collected following intracardiac perfusion in 3rd and 7th days of posttrauma. Hematoxylin and eosin staining for histopatology, terminal deoxynucleotidyl transferase dUTP nick end labeling assay for apoptotic cells and immunohistochemistry for proapoptotic cytochrome-c, Bax and caspase 9 were performed to all groups. Functional recovery test were applied to each group in 3rd and 7th days following SCI. RESULTS: In trauma group, edematous regions, diffuse hemorrhage, necrosis, leukocyte infiltration and severe degeneration in motor neurons were observed prominently in gray matter. The number of apoptotic cells was significantly higher (p<0.05) than control group. In the S-15176-treated groups, apoptotic cell number in 3rd and 7th days (p<0.001), also cytochrome-c (p<0.001), Bax (p<0.001) and caspase 9 immunoreactive cells (p<0.001) were significantly decreased in number compared to trauma groups. Hemorrhage and edema in the focal areas were also noticed in gray matter of treatment groups. Results of the locomotor test were significantly increased in treatment group (p<0.05) when compared to trauma groups. CONCLUSION: We suggest that difumarate salt S-15176 prevents mitochondrial pathways of apoptosis and protects spinal cord from secondary injury and helps to preserve motor function following SCI in rats.

Alpha-lipoic acid inhibits peridural fibrosis following laminectomy through the inactivation of TGF-ß1, PDGF, PAI-1 and IL-6 expressions.

AIM: The objective of this study was to investigate the antifibrotic effect of parenteral administration of alpha-lipoic acid (ALA), which has been reported to reduce fibrosis in the liver, oral mucosa, and peritoneum, in laminectomized rabbits as a potential candidate for the prevention of peridural fibrosis. MATERIAL AND METHODS: Twelve adult New Zealand white male rabbits were divided into control (n=6) and ALA treatment groups (n=6). Laminectomy of the lumbar spine was performed in all animals, and ALA was administered intramuscularly in six rabbits composing the treatment group. Total RNA obtained from the paraffin-embedded tissues was analyzed for transforming growth factor-ß1 (TGF-ß1), plateletderived growth factor (PDGF), plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6). RESULTS: mRNA investigations showed that TGF-ß1, PDGF, PAI-1 and IL-6 gene expressions, which constitute strong evidence for the development of fibrosis, were significantly lower in the treatment group compared with the results obtained from the control group. According to the histological peridural grading, the ALA-treated group showed significantly less peridural fibrosis than the control group. CONCLUSION: Intramuscular administration of ALA is a promising treatment for the prevention of peridural fibrosis in the postoperative period.

Tumor-to-tumor metastasis of the central nervous system.

Tumor-to-tumor metastasis is a well recognized phenomenon. Although any tumor may be potential recipient of metastasis, renal cell carcinoma and meningioma are the most common malignant and benign recipients, respectively, whereas the lung and breast are the most common metastatic donors respectively, in both settings. Patients with hereditary cancer syndromes may be at higher risk for the development of tumor-to-tumor metastases. The most common pattern of tumor-to-tumor metastasis for intracranial neoplasms is the type in which an aggressive high-grade malignancy serves as the source of tumor and a more indolent neoplasm serves as the recipient tumor. The development of tumor metastasis from a second primary malignancy is uncommon and remains biologically puzzling. Its low incidence has made its full biological characterization evasive. Although rare, neurosurgeons should be aware of the entity of tumor-to-tumor metastasis.

Scoliosis-Associated Cervical Spine Pathologies.

STUDY DESIGN: A total of 126 scoliosis patients admitted to the hospital were screened for concomitant cervical pathologies. OBJECTIVES: To investigate the prevalence of cervical spine pathologies and the clinical relevance of magnetic resonance imaging (MRI) in the evaluation of patients with neuromuscular, congenital, syndromic, and idiopathic scoliosis. BACKGROUND SUMMARY: With the development of MRI, upper neural axis abnormalities such as syringomyelia and Chiari malformation are increasingly being found in patients with scoliosis, but no report in the literature describes other pathologies in the cervical area seen concomitant with different scoliosis types. METHODS: A total of 126 consecutive patients who were classified as having neuromuscular, congenital, syndromic, and idiopathic scoliosis were retrospectively evaluated. Data regarding cervical neural axis abnormalities obtained from the MRI studies were analyzed and classified into each type of scoliosis group. RESULTS: A total of 126 patients with scoliosis were evaluated for hindbrain and cervical spine anomalies. Patients were divided into 4 groups regarding the type of scoliosis. The cervical spine of all patients was evaluated with MRI and other radiologic methods when needed. The most frequently seen pathology was syringomyelia. Other pathologies found included congenital vertebral anomalies, Chiari malformation, arachnoid cyst, atlanto-axial dissociation, split cord, posterior vertebral fusion, vertebral hypoplasia, neurenteric cyst, myelomalacia, dermoid cyst, and decrease in craniovertebral angle. Cervical pathologies were most frequently seen in neuromuscular scoliosis, followed by congenital and syndromic groups. CONCLUSIONS: Cervical spinal pathologies vary according to the type of scoliosis. The number of cervical spinal pathologies diagnosed in idiopathic scoliosis patients was least compared with neuromuscular and syndromic groups. The most common pathology was syringomyelia, followed by congenital vertebral anomalies and cerebral tonsillar hernia. Preoperative MRI scan provides vital information regarding cervical spinal pathologies encountered in scoliosis patients.

May we use communication as an instrument? A simple neuromonitoring method peripheral nerve tumour resection.

We performed a procedure called awake simple peripheral nerve monitoring of the distal lower extremity. In this procedure we aimed to protect the patient's peroneal nerve during the successful removal of a tumour arising from this nerve. This is the first report that explores the use of communication with the patient during peripheral nerve tumour resection.

Alpha-lipoic acid reduces peridural fibrosis after laminectomy of lumbar vertebrae in rabbits.

BACKGROUND: Peridural fibrosis is an inevitable healing process causing failed back surgery syndrome after lumbar spinal operations. In this study, alpha-lipoic acid (ALA), reported to reduce fibrosis in liver, oral mucosa, and peritoneum, investigated as a potential candidate for prevention of peridural fibrosis. METHOD: Twelve adult New Zealand white male rabbits were divided into control (n = 5) and ALA groups (n = 7). Laminectomy of lumbar spine was performed and ALA was applied on the exposed dura mater topically in ALA group. RESULTS: According to histological peridural grading, the ALA group (median grade 1) showed significantly less peridural fibrosis than the control group (median grade 3, p = 0.005). CONCLUSIONS: ALA is a promising substance in the prevention of peridural fibrosis, especially in early preoperative and postoperative period.

Spondylodiscitis as a spinal complication of transrectal ultrasound-guided needle biopsy of the prostate.

STUDY DESIGN: A case report. OBJECTIVE: To describe the presentation of pyogenic spondylodiscitis as an iatrogenic spinal complication of a transrectal ultrasound-guided needle biopsy of the prostate (TUGNBP), despite prophylactic use of antibiotics, and discuss possible route of infection. SUMMARY OF BACKGROUND DATA: Pyogenic spondylodiscitis is a rare complication of TUGNBP. Several similar case reports, have been previously published, including 1 by the authors of this case report; however, in the present case, spondylodiscitis occurred despite prophylactic antibiotic use. METHODS: A 59-year-old man was admitted to the neurosurgery department, experiencing severe back and bilateral leg pain for 6 weeks. His neurological examination was normal. His medical and surgical histories were unremarkable, except for a TUGNBP performed 2 months ago because of the high serum levels of prostate-specific antigen levels. At the time of the biopsy, he had been given prophylactic oral antibiotic (ciprofloxacin, 500 mg twice a day) for 2 weeks. The day after biopsy, the patient experienced intermittent high fever and fatigue, and a week after biopsy, he complained of progressive back pain. RESULTS: After 2 weeks, whole-body bone scan with Tc99m-MDP revealed hyperactivity at the level of L4 and L5 vertebral bodies. His contrast-enhanced magnetic resonance image of the lumbar spine showed diffuse contrast enhancement vertebral bodies and intervertebral disc of L4 and L5 along with contrast-enhanced circumferential epidural mass extending from S2 to L3 levels. L4 hemilaminectomy and epidural and intradiscal abscess drainage at the L4-L5 levels were performed. The diagnosis was consistent with acute discitis with Gram (-) bacilli, and microbiological culture was positive for Escherichia coli. He received intravenous and oral antibiotics for 6 weeks. CONCLUSION: Acute pyogenic spondylodiscitis should be considered among the major complications of TUGNBP and may occur despite prophylactic antibiotic use.

Posterior epidural migration of herniated lumbar disc fragment.

OBJECT: Posterior epidural migration of a free disc fragment in the lumbar region is a very rare condition that has only been reported in isolated cases to date. Patients with this condition present with radiculopathy or major neurological deficits. Difficulties in diagnosis and the choice and timing of surgical treatment are important in these cases. In this clinical case series, features of cases with posterior epidural migration of free lumbar disc fragments accompanied by cauda equina syndrome are discussed. METHODS: Eight cases (0.27%) of posterior epidural migration of disc fragments were detected among 2880 patients surgically treated for lumbar disc herniation between 1995 and 2008. Seven of these patients had cauda equina syndrome. The mean duration of symptoms in the 8 cases was 4.2 days (range 1-10 days). The group included 6 men and 2 women, with a mean age of 48 years (range 34-72 years). The sequestered disc fragments were at the L3-4 level in 6 patients (75%) and the L4-5 level in 2 (25%). Magnetic resonance imaging showed tumor-like ring contrast enhancement around sequestered fragments in 5 patients. The patients' motor, sensory, sexual, and urological functions were evaluated postoperatively, and modified Odom criteria and a visual analog scale were used in the assessment of postoperative outcomes. RESULTS: A microsurgical approach was used in all cases. Sequestrectomy with minimal hemilaminotomy and removal of the free segments were performed. The patients were followed up for a mean period of 28.5 months. Three patients (37.5%) had excellent results, 3 (37.5%) had good results, 1 patient (12.5%) had fair results, and only 1 patient had poor results according to the Odom criteria. The main factors affecting the long-term outcomes were the presence of cauda equina syndrome and the time period between onset of symptoms and surgery. CONCLUSIONS: Patients with posterior migration of a disc fragment present with severe neurological deficits such as cauda equina syndrome. Because the radiological images of disc fragments may mimic those of other more common posterior epidural space-occupying lesions, definite diagnosis of posteriorly located disc fragments is difficult. All of these lesions can be completely removed with hemilaminotomy and sequestrectomy, and early surgical treatment is important as a first choice to prevent severe neurological deficits.

Postoperative cerebellar mutism and autistic spectrum disorder.

PURPOSE: I read the article "An Inside View of Autism" written by a 44-year-old autistic woman who had a successful international career designing livestock equipment. In this article, she wrote about her life, disease, and experiences as an autistic individual. She stated that "It is interesting that my speech resembled the stressed speech in young children who have had tumors removed from the cerebellum". METHODS: In this article, we intend to review and extensively document both postoperative cerebellar mutism and autistic spectrum disorder. RESULTS: We reviewed the clinical and neurological findings, etio-pathogenesis, neuroanatomy, mechanisms of development, and similarities between the etio-pathogenesis of both diseases. CONCLUSIONS: Cerebellar lesions can produce mutism and dysarthria, symptoms sometimes seen in autistic spectrum disorder. In mammals, cerebellar lesions disturb motivated behavior and reduce social interactions, functions that are disturbed in autistic spectrum disorder and cerebellar mutism. The cerebellum and two regions within the frontal lobes are active in certain language tasks. Language is abnormal in autistic spectrum disorder and cerebellar mutism.

Is clear cell sarcoma a malignant form of psammomatous melanotic schwannoma? Case report.

The authors present a case of clear cell sarcoma (CCS) in which the tumor originated in the S-1 nerve root and had been previously diagnosed as psammomatous melanotic schwannoma (PMS). This is the third case of a spinal nerve root origin for CCS reported in the English-language literature. The similar histogenesis of CCS and malignant melanoma supports the hypothesis that biological agents or immunotherapy are potentially important areas of investigation. The patient underwent S1-3 laminectomy and gross-total resection of the mass lesion. The border of the resection was extended 1 cm distal to the tumor margin. The postoperative period was uneventful. The new histopathological diagnosis was CCS (malignant melanoma of soft tissue). Despite total resection, the patient returned with disseminated disease at the 18-month follow-up visit. His follow-up magnetic resonance image of the lumbar spine revealed sacral L5-S3 involvement of the vertebral bodies along with disseminated cauda equina seeding. A CCS originating from peripheral nerves is quite rare. The histopathological and immunohistochemical appearance of CCSs resembles those of PMSs. Surgery should be the first choice of treatment.

Iatrogenic spondylodiscitis. Case report and review of literature.

Iatrogenic intervertebral disc space infection is encountered following microsurgical discectomy, percutaneous laser disc decompression, automated percutaneous lumbar nucleotomy operations, and discography. The purpose of this paper is to present a case report and review the literature on the uncommon origins of pyogenic spondylodiscitis and to emphasize the significance of prophylactic antibiotic therapy following transrectal ultrasonography-guided needle biopsy of the prostate (TUGNBP). According to the authors, this is the first reported case of pyogenic spondylodiscitis as a complication of TUGNBP in the English language literature.

Expanding occult intrasacral meningocele associated with diastematomyelia and multiple vertebral anomalies. Case report.

The authors report the case of a 7-year-old girl who presented with persistent low-back and left leg pain and was diagnosed with expanding occult intrasacral meningocele (OIM), diastematomyelia, tethered cord, and multiple vertebral anomalies. She was followed for 27 months. Removal of a bone spur and sectioning of the tight terminal filum did not relieve her left leg and back pain. Serial magnetic resonance (MR) imaging after initial detection of the OIM revealed gradual but significant enlargement of the lesion. Fifteen months after terminal filum release and bone spur resection, the OIM was excised. After this surgery, the back and leg pain resolved. No case of OIM reported to date contains documented serial MR imaging confirmation of enlargement of OIM. Furthermore, this is the first report of OIM associated with diastematomyelia. Because most OIMs expand, the authors recommend that, in addition to surgery for associated congenital anomalies, the OIM be totally excised to resolve symptoms completely.

[MRI features of adult tethered cord syndrome]. / Eriskin gergin omurilik sendromunda MRG bulgulari.

PURPOSE: Tethered cord syndrome is a congenital childhood disease, which can also be seen in adults. The aim of this study was to describe magnetic resonance imaging findings of 17 adult patients with tethered cord syndrome and correlate the magnetic resonance images with intraoperative findings. MATERIALS AND METHODS: Between 1994 and 2002, 57 patients with tethered cord syndrome were detected in the neurology and neurosurgery departments in our hospital. Seventeen of these patients were adults and included in this study. The male to female ratio was eleven to six. The mean age was 33.2 years. All patients had physical and neurological examinations and were evaluated with plain films and lumbosacral MRI. All patients underwent surgery and the intraoperative findings were correlated with MRI findings. RESULTS: MRI could delineate the localization of the conus, thickness of the filum terminale and other pathologic conditions. Thick-short filum terminale, diastematomyelia, intradural lipomas and lipomyelomeningoceles were the most common etiological factors. Conus terminalis terminated distal to the level of L2-L3 intervertebral disc space in all patients. Except two patients with thick-short filum terminale, MRI findings were same with the operative findings. Vertebral anomalies could be detected both with plain films and MRI scans. CONCLUSION: MRI is an excellent diagnostic tool in the diagnosis of tethered cord syndrome. Patients with persistent leg and back pain associated with sphincter problems should be evaluated with MRI for a possible tethered cord syndrome.