Prevalence and outcome of congenital heart disease in patients with neural tube defect.

A prospective clinical study was designed to establish the risk factors, the prevalence, and the progress of congenital heart defects in children with neural tube defects. Study included 90 children with a mean age of 13.5 +/- 30.4 months. There were 53 (59%) patients with spina bifida occulta and 37 (41%) patients with spina bifida aperta. The overall prevalence of congenital heart disease was 27.8% (40.5% in spina bifida aperta and 18.9% in spina bifida occulta; P = .024). There was no statistically significant difference for maternal age, usage of periconceptional folate, and maternal diabetes between the patient and control groups. The authors conclude that congenital heart defects are more common than reported in neural tube defects, and screening echocardiograms are warranted. This should be kept in mind especially in patients requiring minor or major surgical procedures. Furthermore, routine obstetric examination and therefore the use of periconceptional folic acid during pregnancy is still lacking in our country.

Do sodium channel blockers have neuroprotective effect after onset of ischemic insult?

OBJECTIVE: Cerebral ischemia causes a series of pathophysiologic events that may result in cerebral infarct. Some neurons are more vulnerable to ischemia, particularly pyramidal neurons in the hippocampal CA1 region. Pharmacologic intervention for treatment of cerebral ischemia aims to counteract secondary neurotoxic events or to interrupt the progression of this process. In the present study, we compare the neuroprotective effects of sodium channel blockers (mexiletine, riluzole and phenytoin) and investigate whether they have neuroprotective effect when given after ischemic insult. METHODS: A transient global cerebral ischemia model was performed in this study by clipping bilateral common carotid arteries during 45 minutes. Riluzole (8 mg/kg), mexiletine (80 mg/kg) and phenytoin (200 mg/kg) were injected into the rats intraperitoneally 30 minutes before or after reperfusion. Lipid peroxidation levels and cerebral water contents were evaluated 24 hours after ischemia. Histopathologic assessment of hippocampal region was determined 7 days after ischemia. RESULTS: Riluzole, mexiletine and phenytoin treatment after global ischemia significantly decreased water content of the ischemic brain (p<0.05 for each). No significant difference was observed in cerebral edema among the drug treatment groups (p>0.05). When pre-treatment and post-treatment groups were compared with each other, only riluzole pre-treatment group revealed better result for cerebral edema (p<0.05). Pre-treatment with these drugs revealed significantly better results for the malonyldialdehyde (MDA) level and the number of survival neuron on the hippocampal region than the post-treatment groups. CONCLUSION: It is demonstrated that riluzole, mexiletine and phenytoin are potent neuroprotective agents in the rat model of transient global cerebral ischemia, but they are more effective when given before onset of the ischemia.

Comparative neuroprotective effect of sodium channel blockers after experimental spinal cord injury.

Spinal cord injury (SCI) results in loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Influx of Na(+) ions into cells has been postulated to be a key early event in the pathogenesis of secondary traumatic and ischemic central nervous system injury. Previous studies have shown that some voltage-sensitive sodium channel blockers provide powerful neuroprotection. The purpose of the present study was to compare the neuroprotective effect of three sodium channel blockers-mexiletine, phenytoin and riluzole--after SCI. Ninety rats were randomly and blindly divided into five groups of 18 rats each: sham-operated group, trauma group (bolus injection of 1 mL physiological saline intraperiteonally [i.p.]), mexiletine treatment group (80 mg/kg, i.p.), phenytoin treatment group (200 mg/kg, i.p.) and riluzole treatment group (8 mg/kg, i.p.). Twenty-four hours after injury, the rats were killed for determination of spinal cord water content and malondialdehyde (MDA) levels. Motor function scores of six rats from each group were evaluated weekly for six weeks. Then the rats were killed for histopathological assessment. Although all the treatment groups revealed significantly lower MDA levels and spinal cord edema than the trauma group (p<0.05), the riluzole and mexiletine treatment groups were better than the phenytoin treatment group. In the chronic stage, riluzole and mexiletine treatment achieved better results for neurobehavioral and histopathological recovery than phenytoin treatment. In conclusion, all the tested Na(+) blockers had a neuroprotective effect after SCI; riluzole and mexiletine were superior to phenytoin.

Central nervous system protection by resveratrol in streptozotocin-induced diabetic rats.

The objective of the present study was to investigate the possible neuroprotective effect of resveratrol against streptozotocin-induced hyperglycaemia in the rat brain and medulla spinalis. Thirty adult male Wistar rats were divided into three groups as follows: control group, streptozotocin-induced diabetic-untreated group, and streptozotocin-induced diabetic resveratrol-treated group. Diabetes was induced by a single injection of streptozotocin (STZ) (60 mg/kg body weight). Three days after streptozotocin injection, resveratrol (10 mg/kg) was injected intraperiteonally daily over 6 weeks to the rats in the treatment group. Six weeks later, seven rats from each group were killed and the brain stem and cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical studies (lipid peroxidation measuring malondialdehyde [MDA], xanthine oxidase [XO], nitric oxide [NO] and glutathione). MDA, XO and NO levels in hippocampus, cortex, cerebellum, brain stem and spinal cord in the streptozotocin-induced diabetic-untreated group increased significantly. Treatment with resveratrol significantly reduced MDA, XO and NO production and increased glutathione levels when compared to the streptozotocin-induced diabetic-untreated group. This study demonstrates that resveratrol is a potent neuroprotective agent against diabetic oxidative damage.

Neuroprotective effect of etomidate in the central nervous system of streptozotocin-induced diabetic rats.

It is well known that hyperglycaemia due to diabetes mellitus leads to oxidative stress in the central nervous system. Oxidative stress plays important role in the pathogenesis of neurodegenerative changes. In the present study we investigated the possible neuroprotective effect of etomidate against streptozotocin-induced (STZ-induced) hyperglycaemia in the rat brain and spinal cord. A total of 40 rats were used in this study. Rats were divided into four groups: sham-control, diabetic, diabetic-etomidate treated and vehicle for etomidate treatment group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Three days after streptozotocin injection, etomidate (2 mg/kg) was injected intraperitoneally for etomidate group and lipid emulsion (10%) for vehicle group was injected with corresponding amount intraperitoneally every day for 6 weeks. Six weeks after streptozotocin injection, seven rats from each group were killed and brain, brain stem and cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for the biochemical analysis (the level of malondialdehyde [MDA], total nitrite, reduced glutathione [GSH], and xanthine oxidase [XO] activity). STZ-induced diabetes resulted in significantly elevation of MDA, XO and nitrite levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the rats (P < 0.05) while etomidate treatment provided significantly lower values (P < 0.05). This study demonstrated that etomidate have neuroprotective effect on the neuronal tissue against the diabetic oxidative damage.

Evaluation of the neuroprotective effects of citicoline after experimental spinal cord injury: improved behavioral and neuroanatomical recovery.

Spinal cord injury (SCI) caused by trauma mainly occurs in two mechanisms as primary and secondary injury. Secondary injury following the primary impact includes various pathophysiological and biochemical events. Methylprednisolone is the only pharmacological agent having clinically proven beneficial effects on SCI. Citicoline has been shown to have clinical and experimental beneficial effects on brain ischemia. This study aims to investigate the neuroprotective effect of citicoline in an experimental SCI model in rats. Sixty adult Wistar albino rats were randomized into five groups. SCI was performed by the weight-drop model. Group 1 underwent laminectomy alone. The Group 2 underwent laminectomy followed by SCI and received no medication. Group3, Group 4 and Group 5 underwent laminectomy followed by SCI and received medication. Group 3 and Group 5 received citicoline and Group 4 and Group 5 received methylprednisolone. The rats were divided into two subgroups for biochemical analysis (sacrificed at 24 h after surgery) and neurobehavioral and histopathological evaluation (sacrificed at 6 weeks after surgery). Malondialdehyde levels, nitric oxide levels and trauma size ratios were lower and reduced glutathione levels were higher in Group 3, Group 4 and Group 5 as compared to Group 2. Posttraumatic neurological recovery after surgery was significantly better in Group 3, Group 4 and Group 5 compared to Group 2. In conclusion, this study demonstrates that citicoline is as effective as methylprednisolone. The efficacy of citicoline combined with methylprednisolone is not superior to either citicoline or methylprednisolone alone.

Neuroprotective effect of etomidate on functional recovery in experimental spinal cord injury.

OBJECTIVE: Primary impact to the spinal cord causes rapid oxidative stress after injury. To protect neural tissue, it is important to prevent secondary pathophysiological mechanisms. Etomidate, a strong antiexcitotoxic agent, stimulates the gamma aminobutyric acid (GABA) receptors. The purpose of this study was to investigate neurobehavioral and histological recovery and to evaluate the biochemical responses to treatment of experimental spinal cord injury (SCI) in rats with etomidate or methylprednisolone (MP) or both etomidate and MP. MATERIAL AND METHODS: Seventy-two rats were randomly allocated into six groups: a control group (laminectomy alone), a trauma group (laminectomy+trauma), a methylprednisolone group (30 mg/kg MP), an etomidate group (2 mg/kg), a methylprednisolone and etomidate combined treatment group (30 mg/kg MP and 2 mg/kg etomidate) and a vehicle group. Six rats from each group were killed at the 24th hour after the injury. Malondialdehyde, glutathione, nitric oxide and xanthine oxidase levels were measured. Neurological functions of the remaining rats were recorded weekly. Six weeks after injury, all of those rats were killed for histopathological assessment. RESULTS: Etomidate treatment revealed similar neurobehavioral and histopathological recovery to MP treatment 6 weeks after injury. Combined treatment did not provide additional neuroprotection. CONCLUSION: Etomidate treatment immediately after spinal cord injury has similar neuroprotection to MP. In spite of different neuroprotection mechanisms, combined treatment with MP and etomidate does not provide extra protection.

Neuroprotective effect of mexiletine in the central nervous system of diabetic rats.

Both experimental and clinical studies suggests that oxidative stress plays an important role in the pathogenesis of diabetes mellitus type 1 and type 2. Hyperglycaemia leads to free radical generation and causes neural degeneration. In the present study we investigated the possible neuroprotective effect of mexiletine against streptozotocin-induced hyperglycaemia in the rat brain and spinal cord. 30 adult male Wistar rats were divided into three groups: control, diabetic, and diabetic-mexiletine treated group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Mexiletine (50 mg/kg) was injected intraperitoneally every day for six weeks. After 6 weeks the brain, brain stem and cervical spinal cord of the rats were removed and the hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical analysis (the level of Malondialdehide [MDA], Nitric Oxide [NO], Reduced Glutathione [GSH], and Xanthine Oxidase [XO] activity). MDA, XO and NO levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group increased significantly, when compared with control and mexiletine groups (P < 0.05). GSH levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group decreased significantly when compared with control and mexiletine groups (P < 0.05). This study demonstrates that mexiletine protects the neuronal tissue against the diabetic oxidative damage.

Post-traumatic early epilepsy in pediatric age group with emphasis on influential factors.

OBJECTIVE: Posttraumatic epilepsy in the pediatric age group is mostly seen within the first week. An acute posttraumatic epileptic fit, which may induce secondary insults, should be hindered. The aim of the study is to define the risk factors for posttraumatic early epilepsy (PTEE) and the indications for prophylactic therapy. METHODS: In this survey, a total of 1,785 pediatric patients--under the age of 16--are studied. The majority of the patients (1,655) were treated in Haydarpasa Numune Hospital within the years 1993-1999. The rest, which consists of 130 patients, were treated in Inönü University Turgut Ozal Medical Center between the years 2001 and 2003. The patients were categorized according to age, gender, neurological manifestations, type of trauma, cranial pathology, number and type of epileptic fits, the interval between trauma and convulsion, electroencephalogram findings, and antiepileptic therapy. All these factors were challenged due to their effect on the evolution of PTEE. RESULTS: Only 149 cases had PTEE (8.4%). There was no correlation between gender and the incidence of PTEE. The data showed that 11.7% of the patients at or under the age of 3 (p=0.00072), 30.8% of the patients with severe head injury (Glasgow Coma Scale=3-8; Children's Coma Scale = 3-8; p=0.00000), 19.3% of the patients with depressed skull fractures (p=0.00038), 13.7% of the patients with intraparenchymal hemorrhage (p=0.0000072), and 21.6% of the patients with cerebral edema (p=0.000008) had PTEE. Only 20% of the patients with PTEE had a Glasgow Outcome Scale (GOS) of 3 or less (p=0.0000075). CONCLUSION: Those patients at or under the age of 3, with severe head injury, cerebral edema, intraparenchymal hemorrhage, or depressed skull fracture, have a higher incidence of PTEE. Moreover, because the GOS of these patients are prone to be worse, antiepileptic therapy in acute stage may be effective in preventing the secondary brain damage.

Mature spinal teratoma associated with thickened filum terminale.

A 30-year-old man presented with an intradural spinal teratoma with thickened filum terminale manifesting as urinary and sexual disturbances, and low back pain persisting for 4 years. Spinal magnetic resonance imaging revealed thickened filum terminale containing a heterogeneously enhanced intradural lesion extending from the L-3 to L-4 levels and in contact with the conus medullaris. The filum terminale was incised and the tumor was totally resected. The histological diagnosis was mature teratoma consisting of three germ cell layers. The patient's complaints had completely resolved 6 months later.

Spinal epidural abscess caused by brucellosis. Two case reports.

Brucellosis is still an important public health problem in the Mediterranean countries, including Turkey, and is most probably underdiagnosed or underreported. Two rare cases of extradural brucellar granuloma causing spinal cord compression in the thoracic and cervical regions were identified by magnetic resonance imaging. The abscesses were totally excised surgically. Medical treatment was given immediately after diagnosis, but delayed neurosurgical intervention resulted in partial neurological recovery in one patient although the other showed complete neurological recovery. Abscess formation may cause myelopathy due to extradural compression of the spinal cord. Failure to correct this condition may cause irreversible impairment of motor functions. Magnetic resonance imaging should be performed periodically in patients with brucellosis and suspected vertebral involvement to monitor for epidural granuloma formation and prevent extradural cord compression.

Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury.

Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Methylprednisolone (MP), by reducing edema and protecting the cell membrane against peroxidation, is the only pharmacological agent with a proven clinically beneficial effect on SCI. Melatonin, known as a free radical scavenger, has been shown to have an effect on lipid peroxidation following experimental SCI. The purpose of this study was to examine the effect of MP and melatonin on neurological, ultrastructural, and electrophysiological recovery. Female albino rats weighing 200-250 g were randomized into five groups of 18 rats each and six rats for the control group. Weight-drop trauma was performed for each group and a 30-mg/kg single dose of MP for rats in group 1, a 10-mg/kg single dose of melatonin for rats in group 2, and MP and melatonin in the same doses for rats in group 3 were administered immediately after trauma. The rats in group 4 were the vehicle group (treated with ethanol) and group 5 was the trauma group. The motor and somatosensory evoked potentials were recorded at the 4th hour, the 24th hour, and on the 10th day of the study for six rats in each group. Posttraumatic neurological recovery was recorded for 10 days using "motor function score" and inclined plane test. After electrophysiological study the rats were terminated for an analysis of lipid peroxidation level of the injured site of the spinal cord. Electron microscopic studies were performed to determine the effects of melatonin, MP, and the combined treatment with MP and melatonin on axons, neurons, myelin, nucleus, and intracytoplasmic edema. The groups treated with MP, melatonin, and a combination of both had significantly enhanced electrophysiological, biochemical, and neurological recovery and also showed better ultrastructural findings than the trauma and vehicle groups. Although combined treatment was significantly more effective on lipid peroxidation than melatonin or MP treatments alone, at the 10th day, neurobehavioral, electrophysiological, and ultrastructural recovery were at the same level. In conclusion, MP, melatonin, and MP and melatonin combined treatment modalities improved functional recovery at the same level. Future studies involving different doses of melatonin and different dose combinations with MP could promise better results since each drug has a different anti-oxidative mechanism of action.

Intraorbital encephalocele: an important complication of orbital roof fractures in pediatric patients.

Orbital roof fractures are uncommon, and traumatic intraorbital encephalocele formation is a very rare complication of this type of injury. We treated 43 pediatric patients with orbital roof fractures at our center over a 4-year period. The aim of this study was to retrospectively investigate conditions that may lead to intraorbital encephalocele formation in children with orbital roof fractures. Each case was reviewed, and the cause of injury, associated clinical and computerized tomography findings, the Glasgow Coma Scale score on admission, neurological status, other bodily injuries, hospitalization time and type and width of the orbital roof fracture were recorded. The findings in 6 patients who developed encephaloceles were compared to corresponding findings in the 37 patients who did not develop this complication. A total of 44 orbital roof fractures were diagnosed by axial and coronal computed tomography scanning. Six of the 43 children developed intraorbital encephaloceles in the first month after head trauma. In each of these cases, magnetic resonance imaging demonstrated the intraorbital cystic lesion in communication with the subarachnoid space. The width of each orbital roof fracture was measured on axial and coronal computed tomography slices and was confirmed by measurements during surgery. The width of the fractures in the encephalocele cases ranged from 2-4 mm. Duraplasty and orbitoplasty were performed in all the patients with encephalocele. Pediatric patients with orbital roof fractures that exhibit more than 2 mm diastasis and are associated with frontal cerebral contusion may be at greater risk for developing intraorbital encephalocele. All such cases should be monitored closely and investigated further with magnetic resonance imaging.