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PubMed2003

Primary motor cortex stimulation within the central sulcus for treating deafferentation pain.

Nine patients with post-stroke pain, six with brachial plexus injuries, two with phantom limb pain, one with spinal cord injury, and one with brain stem injury were treated with a modified motor cortex stimulation (MCS) protocol. Preoperative pharmacological tests were performed with phentolamine, lidocaine, ketamine, thiopental, morphine, and placebo. We placed a grid electrode in the subdural space to decide upon the best stimulation point for pain relief over a few weeks with the purpose of determining the placement of a Resume electrode. In five patients, Resumes were implanted in the interhemispheric fissure to reduce lower extremity pain. In five other patients, Resumes were placed within the central sulcus to stimulate area 4 and area 3b. In addition, electrodes were also placed on the surface of the precentral gyrus. Fourteen of the 19 patients showed pain reduction (6 excellent, 3 good, and 5 fair) using the MCS with our results indicating area 4 within the central sulcus to be the optimal stimulation point for pain relief. We speculate that conventional method may sometimes fail to stimulate area 4 and that focal stimulation of the primary motor cortex within the central sulcus may improve the efficacy of this treatment. Our pharmacological tests show that patients with ketamine sensitivity seem to be good candidates for MCS. Test stimulation with a subdural multi-grid electrode and Resumes in the cetral sulcus were helpful in locating the best stimulation point for pain relief.

Adult↗
PubMed1979

[Primary interhemispheric subdural abscess--case report (author's transl)].

A case of primary interhemispheric subdural abscess was reported, which was not accompanied by abscess formation in other places such as subdural spaces of the convexity or in the brain. A 13-year-old school boy was admitted with 8 days' history of fever, headache and progressive weakness of the left lower extremity. Prior to admission he developed 2 spells of jacksonian seizure initiating from the left leg. Right carotid angiography was performed on admission and separation of the pericallosal and callosomarginal arteries with small avascular area was shown indicating possible abscess formation in the interhemispheric fissure. There was no evidence of purulent infection in the laboratory findings including the CSF and EEG showed diffuse slow wave discharge, more in the right frontocentral leads. He was placed on the vigorous treatment with antibiotics and steroids, and one month later the left lower weakness as well as the EEG abnormality showed some improvement. However, the separation of the anterior cerebral arterial branches became more prominent and formed a lens shaped avascular area, although the pericallosal artery was in the midline. A diagnosis of interhemispheric subdural abscess was made and was confirmed by surgery. Patient showed progressive recovery of the left lower paralysis, and the abscess was totally collapsed in the repeated angiographic follow-up study. Angiographic characteristics of the interhemispheric subdural abscess were described and particular emphasis was placed on the peculiar neurological symptoms referring to the previous reports in the literature.

Adolescent↗
PubMed2000

Interhemispheric subdural hematoma caused by a ruptured internal carotid artery aneurysm: case report.

BACKGROUND: Interhemispheric subdural hematoma (ISH) usually occurs after head trauma; nontraumatic ISH is extremely rare. CASE DESCRIPTION: The authors describe a 62-year-old male presenting with severe headache and ptosis on the left side. Computed tomography (CT) and magnetic resonance imaging disclosed a hematoma in the interhemispheric subdural space without subarachnoid hemorrhage. Cerebral angiography revealed an aneurysm arising from the left internal carotid-posterior communicating artery (IC-PC) junction. The patient underwent emergency clipping of the aneurysm and was discharged without neurological deficit. CONCLUSION: Ruptured aneurysms resulting in ISH without subarachnoid hemorrhage have been reported in only a few cases; this is the second case to describe the association of a ruptured IC-PC aneurysm with an ISH. The etiology of ISH formation due to ruptured aneurysms and the diagnosis are discussed.

Aneurysm, Ruptured↗
PubMed2004

Natural history of chronic subdural haematoma.

This review will clarify the natural history of chronic subdural haematoma (SDH). Chronic SDH has dual origins, one from subdural hygromas (SDG) and the other from acute SDHs. It occurs only in patients with a suitable pre-morbid condition, i.e. sufficient potential subdural space (PSS). In unresolved SDGs, proliferation of dural border cells produces the neomembrane. Unresolved SDGs become chronic SDHs by repeated micro-haemorrhages from fragile new vessels, which were grown into the neomembrane. When PSS is sufficient, acute SDHs may become chronic SDHs. Chronic SDHs enlarge when rebleeding exceeds absorption and they become symptomatic. When the neomembrane is matured, the neocapillary is no longer fragile. If absorption exceeds rebleeding, the haematoma will disappear. Maturation of the neomembrane and stabilization of the neovasculature eventually result in spontaneous resolution. The fate of chronic SDH depends on the pre-morbid status, the dynamics of absorption-expansion and maturation of the neomembrane.

Hematoma, Subdural, Chronic↗
PubMed1999

[Treatment of chronic subdural hematoma with a closed drainage system].

The authors evaluate a group of 92 patients with the diagnosis of chronic subdural haematoma confirmed by CT. All patients were operated from two trepanation bores with insertion of drainage into the subdural space and its connection with the closed drainage system. They used three types of drainage systems. The best clinical results were obtained with the negative pressure suction system of Braun Co in 92%. This system was switched on intermittently only till the patient developed signs of headache. Attention is focused on possible types of complications in different systems. In the remaining 13 patients who did not improve reinsertion of the drain was used, or craniotomy with membranectomy with a 60% improvement. The mentioned negative pressure drainage system in treatment in chSDH seems most suitable and is associated with the least number of complications.

Adult↗
PubMedDate not supplied

Diffusion-weighted MR imaging of subdural empyemas in children.

BACKGROUND AND PURPOSE: Subdural empyema (SDE), an infection of the subdural space, occurs most often in pediatric patients as a complication of meningitis, sinusitis, or otitis media. Diffusion-weighted imaging (DWI) has been used in the past to investigate intracerebral infections. The purpose of this study was to determine the signal intensity characteristics of SDE on DWIs as well as the corresponding apparent diffusion coefficient (ADC) maps. METHODS: MR studies of 10 patients with SDEs were retrospectively reviewed. Included were routine sequences and DWI, which consisted of an axial single-shot echo-planar spin-echo sequence (TR/TE, 4000/110) with b values of 0, 500, and 1000 s/mm(2). Signal-intensity characteristics on routine MR images and DWIs were evaluated. In seven patients, ADC values of the lesions were calculated by using two b values. Follow-up imaging study was performed in seven patients. RESULTS: In nine patients, the empyema was hyperintense on DWIs. In the remaining patient, the empyema showed mixed hyperintensity and hypointensity. ADC values were lower than those of normal cortical gray matter and much lower than those of reactive subdural effusions. In all seven patients with persistent clinical signs of infection, the empyemas were hyperintense on follow-up DWIs. CONCLUSION: SDE had high signal intensity on DWIs and low signal intensity on ADC maps, with an ADC value lower than that of the normal cortical gray matter. Diffusion MR imaging can be valuable in distinguishing SDE from effusion and in the follow-up of subdural collections.

Adolescent↗
PubMed1995

[Chronic subdural hematoma with bleeding tendency; clinical analysis of 11 surgical cases].

Eleven patients with chronic subdural hematoma (CSDH) with bleeding tendency (BT) were surgically treated in the last 12 years. To study the clinical problem of CSDH with BT, 11 surgical cases were divided into 3 groups, Group A; CSDH with primary BT (1 case of hemophilia A), Group B; CSDH with BT secondary to a basic disease (3 cases of leukemia, 2 cases of malignant tumor with DIC, 1 case of chronic renal failure and 1 case of liver cirrhosis), Group C; CSDH with BT by anticoagulants (warfarin) (2 cases of replacement of mitral valve, 1 case of A-C bypass). Evacuation of the hematoma was performed by means of one or two burr holes with irrigation of the hematoma cavity and a drainage tube was placed in the subdural space. The outcome was excellent in Groups A and C. In Group B, two patients with DIC due to gastric cancer and prostatic cancer died, and 3 patients with leukemia recovered dramatically from CSDH, but the poor course of the disease itself resulted in death. The outcome of other patients in Group B was excellent. Since CSDH with BT is often fatal, those patient had usually been treated conservatively. However, from this analysis, we stress that CSDH with BT should be surgically treated after checking the blood conditions carefully to determine whether or not the patient has need for surgery.

Adult↗
PubMed1997

The neuroprotective effect of the forebrain-selective NMDA antagonist CP101,606 upon focal ischemic brain damage caused by acute subdural hematoma in the rat.

The neuroprotective effects of drugs that act against excitotoxic damage, caused by glutamate, are well described in focal ischemia, but behavioral effects, and apparent failure in clinical trials of "first-generation" competitive N-methyl D-aspartate (NMDA) antagonists, such as Selfotel (CGS19755), has led to interest in evaluating newer NMDA antagonists with fewer behavioral effects. We have therefore evaluated the neuroprotective effect of a new forebrain-selective polyamine site NMDA antagonist, CP101,606 in a rat subdural hematoma (SDH) model. An SDH was produced by slow injection of 0.4 ml autologous blood into the parietal subdural space. Brain damage was assessed histologically at eight coronal planes, in animals sacrificed 4 h after induction of hematoma. The drug was infused 30 min after induction of SDH. The reductions of ischemic brain damage achieved by CP101,606, was 29% for the low dose and 37% for the high dose. This novel glutamate antagonist has shown a magnitude of neuroprotection which is comparable with that seen with "first-generation" NMDA antagonists such as MK801, D-CPP-ene and CGS19755, in this same model. This new agent is claimed to have fewer psychomotor and behavioral effects than MK801, D-CPP-ene, and CGS19755.

Animals↗
PubMed2001

Role of dural fenestrations in acute subdural hematoma.

OBJECT: Patients with acute subdural hematomas (ASDHs) have higher mortality and lower functional recovery rates compared with those of other head-injured patients. Early surgical decompression and active intensive care treatment represent, so far, the best way to assist these patients. Paradoxically, one of the factors contributing to poor outcomes in cases of ASDHs could be rapid surgical decompression, owing to the severe extrusion of the brain through the craniotomy defect in response to acute brain swelling. To avoid the deleterious consequences of abrupt decompression of the subdural space with disruption of brain tissue, the authors have adopted a new surgical technique for evacuation of ASDHs. This procedure consists of creating multiple fenestrations of the dura (MFD) in a meshlike fashion and removing clots through the small dural openings that are left open, avoiding the creation of a wide dural opening and the disruption of and additional damage to brain tissue. METHODS: Thirty-one patients (26 male and five female patients with a mean age of 32.5 years) harboring ASDHs were treated using this method. On admission there were 16 patients (51.5%) with Glasgow Coma Scale (GCS) scores of 3 to 5, 11 patients (35.5%) with GCS scores of 6 to 8, and four patients (12.9%) with GCS scores of 9 to 12. Postoperative computerized tomography scans of the brain revealed evacuation of more than 80% of the hematoma in 29 of 31 patients. The overall mortality rate in this group was 51.6%. CONCLUSIONS: This preliminary report of a new surgical approach for patients who have sustained ASDHs should be considered to avoid abrupt disruption of the brain and to allow the gradual and gentle release of subdural clots. This is especially important in cases in which there are severe midline shifts and a tight brain. Further clinical studies should be conducted in a more selected series to estimate the impact of this new procedure on morbidity and mortality rates.

Adolescent↗
PubMed2001

Intracranial meningiomas revealed by non-traumatic subdural haematomas: a series of four cases.

OBJECTIVE: A review of the literature shows 33 cases of ipsilateral subdural haematomas (SDH) associated with meningiomas. We suggest that physiopathological mechanisms could be primary haemorrhages from abnormal vessels in the tumours and the opening of the intratumoral haematomas into the subdural space. Our working hypothesis relies on a series of 300 meningiomas operated upon in our department since 1990; of these, 4 were revealed by SDH. CLINICAL PRESENTATION: The four patients surgically treated in our department had developed a progressive impairment of consciousness. There was no history of trauma, blood dyscrasia or anticoagulant therapy. After diagnosis, the SDH was drained, and the meningeal tumour was totally resected once it had been discovered. In one case, the presence of a tumour was demonstrated by magnetic resonance imaging (MRI) performed only after the evacuation of a recurrent SDH. INTERVENTION: In each case, an acute SDH showing signs of recent bleeding was evacuated. The meningeal tumour discovered proved to be the source of the haemorrhage because of the numerous fresh blood clots both around and inside it. HISTOLOGY: In the four cases histology showed fresh intratumoral haemorrhages (ITH), large blood vessels with thin endothelial linings and haemosiderin deposits. In this review, SDH is associated with other haemorrhage sites in 24 of 37 cases (33+our 4 cases). ITH was present in 14 cases (40%). CONCLUSION: The treatment should consist of the extirpation of the meningioma at the same time as the evacuation of the haematoma. If primary ITH from abnormal vessels is the source of SDH, complete meningioma resection should prevent the recurrence of SDH. Subdural membranes and haematomas should therefore be inspected for their intrinsic pathology, especially when there is no history of trauma.

Aged↗
PubMed2006

Caspase-dependent cell death involved in brain damage after acute subdural hematoma in rats.

Traumatic brain injury is associated with acute subdural hematoma (ASDH) that worsens outcome. Although early removal of blood can reduce mortality, patients still die or remain disabled after surgery and additional treatments are needed. The blood mass and extravasated blood induce pathomechanisms such as high intracranial pressure (ICP), ischemia, apoptosis and inflammation which lead to acute as well as delayed cell death. Only little is known about the basis of delayed cell death in this type of injury. Thus, the purpose of the study was to investigate to which extent caspase-dependent intracellular processes are involved in the lesion development after ASDH in rats. A volume of 300microL blood was infused into the subdural space under monitoring of ICP and tissue oxygen concentration. To asses delayed cell death mechanisms, DNA fragmentation was measured 1, 2, 4 and 7 days after ASDH by TUNEL staining, and the effect of the pan-caspase inhibitor zVADfmk on lesion volume was assessed 7 days post-ASDH. A peak of TUNEL-positive cells was found in the injured cortex at day 2 after blood infusion (53.4+/-11.6 cells/mm(2)). zVADfmk (160ng), applied by intracerebroventricular injection before ASDH, reduced lesion volume significantly by more than 50% (vehicle: 23.79+/-7.62mm(3); zVADfmk: 9.06+/-4.08). The data show for the first time that apoptotic processes are evident following ASDH and that caspase-dependent mechanisms play a crucial role in the lesion development caused by the blood effect on brain tissue.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Chronic subdural hematoma with vasogenic edema in the cerebral hemisphere--case report.

An 80-year-old male with a history of hypertension presented with chronic subdural hematoma manifesting as progressive consciousness disturbance and left hemiparesis. T1-weighted and fluid attenuation inversion recovery (FLAIR) magnetic resonance imaging showed a fresh hematoma in the right subdural space with a midline shift of 15 mm. FLAIR and diffusion-weighted imaging showed a hyperintense area in the right paraventricular white matter compressed by the hematoma. Apparent diffusion coefficients (ADCs) corresponding to the hyperintense area in the central area of the affected cerebral hemisphere on FLAIR images were measured before and one month after the operation. The motion probing gradient was applied in the right-left direction to the body axis. Since the central area in the cerebrum includes nerve fibers perpendicular to the direction of the gradient, the measured ADC appeared to be anisotropic. Preoperative ADC in the right paraventricular white matter was anisotropic and greater than in age-matched normal subjects, so the edema was identified as the vasogenic type. The edema in the right paraventricular white matter resolved promptly with improvement of the midline shift and normalization of the ADC.

Aged↗
PubMed1999

Effect of intracerebral and subdural hematomas on energy-dependent transport across the blood-brain barrier.

Although both intracerebral and subdural hematomas induce brain edema, previous studies have indicated that they may have different cerebrovascular effects. Our own investigations have demonstrated that while subdural hematomas (SDH) are associated with ischemia this is not the case following intracerebral hematomas (ICH). Previous studies have demonstrated a decrease in energy-dependent transport of glutamine across the blood-brain barrier (BBB) following focal cerebral ischemia. The present study investigates this further by examining the effects of SDH, ICH, and intracerebral thrombin injections, an agent involved in ICH-induced injury, on blood to brain glutamine transport. The injection of 200 microL of blood into the subdural space induced a marked reduction in glutamine transport (Ki, influx rate constant) into the cerebral cortex at 4 and 24 h following SDH (sham, 105+/-4% of contralateral cortex; SDH 4 h, 63+/-5%, p<0.01; SDH 24 h, 47+/-12%, p<0.05). There were no significant changes in glutamine Ki in subcortical areas following SDH. Following ICH (200-microL clot); however, there were only modest decreases in glutamine Ki in subcortical areas (sham, 98+/-2% of right cortex; ICH 4 h, 91+/-5%, p<0.01; ICH 24 h, 91+/-2%, p<0.05). Intracerebral injection of thrombin (5U) had minimal effect on glutamine Ki, in subcortical areas, at 4 h and induced a modest decrease in transport at 24 h (sham, 98+/-2% of right cortex; thrombin 4 h, 98+/-2%; thrombin 24 h, 86+/-2%, p<0.05). The present studies demonstrate marked differences in the effects of ICH and SDH on BBB function.

Animals↗
PubMed1999

Subdural haematomas in the elderly: experience with treatment by trephine craniotomy and not closing the dura or replacing the bone plate.

A surgical technique was devised to treat chronic subdural haematomas (SDH) in elderly patients. Initial good results encouraged the author to use this technique in elderly patients with acute SDH. This small group is also reported. The goal was to do definitive, not expectant or incremental surgery on these fragile patients who have a high incidence of co-morbid conditions and cerebral atrophy, and to obliterate the subdural space by allowing the skin to sink into the cranial defect. The surgical technique consists of trephine craniotomy and not closing the dura or replacing the bone plate. Experience with six elderly patients with acute SDH and 23 patients with chronic SDH is reported. Of six patients with acute SDH, mean age 80 years, 2 months, three died, all with a Glasgow Coma Score (GCS) less than 9. Three recovered to preoperative status, one with initial GCS of 7 and the other of 8. Of 23 patients with chronic SDH, mean age 77 years, 21 recovered to preoperative status. The two deaths were in patients with GSC of 5 and 7. There were no recurrent SDH or postoperative surgical or cosmetic complications. All patients were followed for at least 6 months. These excellent results suggest that the procedure could be considered as a first procedure in the elderly patient. At first glance, the operation appears to be overly aggressive, but it is an example of 'aggressive-conservative' treatment which produces good long-term results with few complications and no need for second operations.

Acute Disease↗
PubMed1992

[An autopsy case of spinal subdural abscess in the aged--comparative study with neuroradiological findings].

An 82-year-old woman without previous medical problem noticed vague back pain on December 31, 1989, and was admitted to a hospital because she developed a fever, a rapidly progressive weakness followed by anesthesia of the lower extremities and sphincter disturbance. On myelography and myelo-CT, the spinal cord appeared to be displaced by an extramedullary mass which partially blocked the subdural space at the level of T-9 to L-1. When transferred to our hospital on January 8, 1990, she was febrile and complaining of headache with meningeal signs. Percussion tenderness was present at T-8 to L-1 spinal spinous process. Neurological examination revealed that the patient had mild consciousness clouding, total paraplegia in the legs, sensory disturbance of a partial degree at L-1 to L-3 and totally below L-3, brisk but equal tendon reflexes in the upper extremities, areflexia in the legs with positive bilateral Babinski signs and sphincter disturbance. Otherwise she was neurologically unremarkable. Acute inflammatory reactions were prominent among the laboratory findings on admission. A lumbar tap yielded purulent fluid with more than 170,000 cells/mm3, 5,000 mg/dl of protein, 44 mg/dl of glucose and culture of the fluid isolated Escherichia coli. T1-weighted sagittal MRI disclosed an ill defined mass which showed the same or locally higher with gadopentetate dimeglumine (Gd-DTPA) signal intensity as soft tissue, compressing the spinal cord anteriorly from T-7 to L-3. The lesion was noticed to have a more extensive rostral-caudal extent than was inferred from myelography and myelo-CT.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

[Endoscopic fenestration of median supratentorial cerebrospinal fluid cysts].

Mid-supratentorial liquor cysts are a relatively rare and generally congenital abnormality of the cerebral ventricles and subdural spaces. The data and views available in the literature on rational surgical policy is contradictory. The authors' experience in treating 16 patients was used to consider whether endoscopic techniques can be employed for invasive fenestration of the cysts. The goal of surgery was to remove the masses caused by cystic malformations and their local compression of the brain via fenestration of the walls of the cysts and via communication of their cavities with the ventricles and cisterns. There were solitary cysts in all cases (arachnoidal cysts of the interpedicular cistern and the third ventricle in 9; cysts of the ventricular septum in 4, ependicular cysts of the lateral ventricle in 2, and cysts of the celiac plexus of the third ventricle in other 2 cases, in 1 cases a liquor cyst was located in the midbrain thickness). The clinical picture was characterized by a combination of hypertensive, hydrocephalic and focal symptoms of damages to the hypothalamic and thalamic structures and the adjacent formations of the brain (pyramidal and extrapyramidal disorders, ataxia, chiasmal syndrome, metabolic and endocrine disorders, etc.). In 6 cases these symptoms were persistent despite preimplanted VP anastomosis. Rigid Storz endoscopes (Germany) with an external coat, 6 mm in diameter, and a Codman fibroendoscope (USA), 4 mm in diameter, were employed. Cystic ventriculostomy and cystic ventriculocisternostomies were made in 11 and 6 patients, respectively; one patient underwent endoscopic resection of the walls of an ependymal cyst. In one patient with signs of decreased liquor resorption, endoscopic fenestration was concurrently developed into a ventricle-peritoneal anastomosis. In other 4 anastomosis-dependent patients, the preimplanted mechanically consistent bypass system was left at its site. In 2 of these cases, cystic ventriculostomy was supplemented by ventricular septal fenestration and third-ventricular bottom perforation. Twelve patients were followed up for 6 to 36.5 months (mean 15 months). There has been no information about 6 patients since their discharge. In 12 (66.5%) surgery yielded expected results and the fenestration of cystic walls was followed by their retraction and a steady-state regression of local and/or hypertensive symptoms. In 5 (28%) patients, the complaints and clinical data remained unchanged despite although incomplete but objective cystic relaxation. This was most frequently noted in patients (n = 4) with arachnoidal cysts of the interpedicular cistern and the third ventricle who had endocrine disorders. In one case the operation was stopped due to bleeding. Totally, 5 patients were found to have complications (hemorrhage, ventriculitis). None patient died. Some aspects of indications for endoscopy and surgical techniques are considered. It is concluded that endoscopic internal bypass surgery in patients wit median cystic liquor malformations is the treatment of choice. When equipment is adjusted, fenestration of the membranous walls of these cysts by using an endoscope is reliable and safe. Such patients may be recommended endoscopic technology used as the method of choice.

Adolescent↗
PubMed1988

Successful imaging of human cancer with indium-111-labeled phospholipid vesicles.

Twenty-four patients with proven primary and/or metastatic cancer received single intravenous injections of phospholipid vesicles containing 0.5 mCi of Indium-111. Gamma camera scintigraphy 1 to 72 hours later visualized tumors in 22 patients (92%), including carcinomas of breast, lung, colon, prostate, kidney, cervix, thyroid, and soft tissue sarcoma, lymphoma, and melanoma. Tumor sites that were identified included soft tissues, bone, lung, liver, lymph node, and spinal cord. There were only two false-positive images in metastatic sites and four false-negative images in metastatic sites. Overall sensitivity for tumors in 97 individual sites was 85%, whereas specificity was 96%. Unsuspected areas of malignancy were seen in the lumbar subdural space, pleura, liver, thyroid, and lung. Besides tumor accumulations, homogeneous uptake was observed in normal liver and spleen. Radiation doses to these two organs were 2.2 and 2.9 cGy/0.5 mCi In-111, respectively. Whole body radiation dose was 0.3 cGy/0.5 mCi. The use of Indium-111-labeled vesicles permits a wide variety of human tumors in primary and metastatic sites to be imaged without toxicity and with radiation doses comparable to other radionuclide scanning techniques.

Humans↗
PubMed2001

Distribution of gacyclidine enantiomers after experimental spinal cord injury in rats: possible involvement of an active transport system.

The pharmacokinetics of gacyclidine enantiomers, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, were studied in plasma and spinal cord extracellular fluid (ECF) after experimental spinal cord injury in rats. Spinal cord trauma was produced by introducing an inflatable balloon in the dorsal subdural space. Upon implantation of microdialysis probes in spinal cord (T9) and intravenous (iv) bolus administration of (+/-)-gacyclidine (2.5 mg/kg), concentrations in plasma and ECF were monitored over 5 h and analyzed by a stereospecific gas chromatography-mass spectrometry (GC-MS) assay. In plasma, concentrations of (+)-gacyclidine were approximately 25% higher than those of (-)-gacyclidine over the duration of the experiment and decayed in parallel (t(1/2 alpha) approximately 7 min; t(1/2 beta) approximately 90 min) with no significant difference between the two enantiomers. Clearance (CL) and volume of distribution (Vd) of (-)-gacyclidine were approximately 20% higher than those of its optical antipode (CL: 285 versus 236 mL. kg(-1). min(-1); Vd(beta): 39.3 versus 31.2 l/kg). Protein binding (approximately 91%) was not stereoselective. In spinal cord ECF, both enantiomers were quantifiable within 10 min after drug administration, and their concentration remained stable over the duration of the experiment in spite of changing blood concentrations. Repeated iv bolus injections of gacyclidine did not modify these profiles. Areas under the curves (AUCs) of concentration in ECF versus time were similar for both enantiomers and not correlated with AUCs in plasma. Penetration of (-)-gacyclidine was, however, significantly higher (approximately 30%) than that of (+)-gacyclidine. In summary, the disposition of gacyclidine enantiomers is stereoselective. Both enantiomers exhibit a high affinity for spinal cord tissue, and the drug exchange between plasma and spinal cord ECF involves an active transport system. These findings contribute to the explanation of the discrepancy between drug concentrations in plasma and spinal cord ECF.

Animals↗