Alterations of Norepinephrine Levels in Plasma and CSF of Patients After Traumatic Brain Injury in Relation to Disruption of the Blood-Brain Barrier

Summary  Background. In injured brain tissue with a disrupted blood-brain barrier (BBB) catecholamines such as norepinephrine (NE) are known to enhance glucose consumption and cerebral blood flow but may lead to an energy depletion increasing the risk of ischemia. Therefore it is of great interest whether the exogenous administration of NE used mainly to maintain an adequate cerebral perfusion pressure influences CSF NE levels or not, and whether elevated plasma or CSF leves of NE can influence the actual clinical condition. We addressed this issue by measuring the levels of NE in CSF and plasma and correlating them with the actual clinical condition of the patients.  Methods. In 29 patients with severe TBI (<8 points on the Glasgow Coma cale, GCS) NE levels were analysed by high performance liquid chromatography (HPLC) in paired blood and CSF specimens which were collected from days 1 to 14 after severe TBI (total number of pairs=121). The integrity of the BBB was evaluated by determining the CSF/serum albumin ratio. The clinical condition of the patients was assessed by GCS.  Results. Elevated plasma and CSF NE levels were observed in 50% of all samples, most consistently in patients treated with NE. NE elevation in CSF was independent of whether or not the BBB remained intact. There was no correlation between GCS and the levls of NE in CSF or plasma either in samples from the treated or the untreated group.  Interpretation. Exogenous administration of NE seems to increase NE levels in plasma and CSF. However, in this group of patients with severe TBI there was no clincal evidence that exogenous administration of NE was detrimental to the traumatized patients.     

Indications for computed tomography in patients with mild head injury

The factors affecting outcome were analyzed in 1,064 patients, 621 males and 443 females aged 10 to 104 years (mean 46 +/- 23 years), with mild head injury (Glasgow Coma Scale [GCS] score > or =14) but no neurological signs presenting within 6 hours after injury. Intracranial lesion was found in 4.7% (50/1,064), and 0.66% (7/1,064) required surgical treatment. The Japan Coma Scale (JCS) and GCS assessments were well correlated (r = 0.797). Multivariate analysis revealed significant correlations between computed tomography (CT) abnormality and age > or =60 years, male sex, JCS score > or =1, alcohol consumption, headache, nausea/vomiting, and transient loss of consciousness (LOC)/amnesia. Univariate analysis revealed that pedestrian in a motor vehicle accident, falling from height, and mechanisms of injuries except blows were correlated to intracranial injury. No significant correlations were found between craniofacial soft tissue injury and intracranial injury. Patients with occipital impact, nonfrontal impact, or skull fracture were more likely have intracranial lesions. Bleeding tendency was not correlated with CT abnormality. The following indications were proposed for CT: JCS score >0, presence of accessory symptoms (headache, nausea/vomiting, LOC/amnesia), and age > or =60 years. These criteria would reduce the frequency of CT by 29% (309/1,064). Applying these indications to subsequent patients with GCS scores 14-15, 114 of 168 patients required CT, and intracranial lesions were found in 13. Two refused CT. Fifty-four of the 168 patients did not need CT according to the indications, but 38 of the 54 patients actually underwent CT because of social reasons (n = 21) or patient request (n = 17). These indications for CT including JCS may be useful in the management of patients with mild head injury.     

The Risk of Haemorrhage Associated with Early Postoperative Heparin Administration After Intracranial Surgery

Summary  Background. To analyse the rate of postoperative haemorrhage during a 4-year period of early postoperative administration (<24 hours) of fractionated heparin plus compression stockings in a large cohort of patients undergoing intracranial surgery.  Method. A total of 1564 patients who underwent intracranial surgery at our institution were included in our study. 1197 of the 1564 patients (77%) had major intracranial surgery (group 1). Group 2 was made up of 367 patients in whom ventriculoperitoneal shunting or external ventriculostomy was performed (minor intracranial procedures). All patients were investigated retrospectively for the occurrence of major postoperative haemorrhage confirmed by CT scanning and requiring surgical evacuation. The protocol for prophylaxis of thrombo-embolic events included early (<24 hours) postoperative fractionated low-dose heparin (3×5000 IE subcutaneously) until discharge plus intra- and postoperative compression stockings.  Findings. Major postoperative haemorrhages were observed in 31 of the 1564 patients (2.0%). In three patients, the haemorrhage occurred on the day of surgery before the administration of heparin. The haemorrhage rate of patients receiving heparin was 1.8% (28/1564). All haemorrhages occurred in patients undergoing major intracranial procedures (group 1; 31/1197; 2.6%). There was no haemorrhage in minor intracranial procedures (group 2; 0/367; 0%).  Interpretation. Although retrospective, this is to date the largest study supporting the concept of postoperative pharmacological thrombo-embolic propylaxis in patients undergoing intracranial surgery. The question as to whether pharmacological prophylaxis is beneficial for a given patient can only be answered by weighing the risk reduction of thrombo-embolic events against the risk increase of postoperative haemorrhage associated with different surgical procedures and heparin protocols.     

Prognostic Factors in Postraumatic Severe Diffuse Brain Injury

Summary  It is usually defficult in clinical practice to establish factors affecting final outcome in patients suffering severe diffuse brain injury (SDBI), due to the absence of specific semiology.  Methods. We studied retrospectively 160 consecutive patients with criteria of SDBI. We performed a statistical analysis of epidemiological, clinical and radiological factors, and relationship with final outcome.  Result. 35% of patients with severe head injury presented SDBI. Sixty percent were 15–35 year old and 73% male. More than 45% of the patients presented GCS 3 or 4. On CT performed during the first 24 h, haemorrhagic lesions appeared in white matter in 35% and subarachnoid haemorrhage was observed in 28%. During the first 24 h., 66% of patients presented values of intracranial pressure (ICP) above 20 mm Hg and a 33% below 20 mm Hg. Twenty percent of the patients had ICP>20 mm and no response to treatment. According to the Glasgow Outcome Scale (GOS), mortality of more than 50% and 25% of patients with persistent vegetative state or severe disability were observed.  Conclusions. Clinical evaluation, early CT findings, ICP values and their response to medical treatment and clinical complications were found to be related (p<0.05) to final outcome (GOS).     

Postoperative Pain Therapy After Lumbar Disc Surgery

Summary  Object. This study was undertaken to determine whether a special postoperative pain administration of tramadol and diclofenac provides any benefits in patients who underwent microsurgical lumbar discectomy.  Methods. The study consisted of 60 patients undergoing microsurgical lumbar discectomy. Patients were randomly divided into two groups based on the postoperative pain management: 1) Group A (n=30): no standardized pain therapy; these patients received on demand different analgesics and at variable dosages which were selected by the neurosurgeons; 2) Group B (n=30): standardized pain therapy with specific dosages of tramadol and diclofenac in regular time intervals during the first 48 hours after surgery. After surgery follow-up data from a special standardized questionnaire were obtained for all 60 patients during the first 48–72 postoperative hours. The patients were asked for course and intensity of pain as well as about some specific circumstances of clinical therapy after surgery.  The postoperative pain intensity of patients treated with the special combination of tramadol and diclofenac was significantly diminished (24 hours after surgery: p=0.0002, 48 h: p=0.0047, 72 h: p=0.0034) in relation to the group without standardized pain therapy. Similarly, the frequency of breakthrough pain was significantly reduced (24 h: p=0.0001, 48 h: p=0.003, 72 h: p=0.004).  Conclusions. The results suggest that the application of tramadol and diclofenac during the first 48 hours after lumbar microdiscectomy results in a reduction in postoperative pain without complications. We suggest that the use of this combination can be a beneficial adjunct to lumbar disc surgery.     

Predicting late outcome for patients with traumatic brain injury referred to a rehabilitation programme: a study of 508 Finnish patients 5 years or more after injury

Variables were studied which predict at the acute stage the functional and occupational long term outcome for patients with traumatic brain injury (TBI). Glasgow Coma Scale (GCS) score on hospital admission, length of coma (LOC) and duration of post traumatic amnesia (PTA) were studied in a group of 508 TBI rehabilitation patients, age 0·8-71, mean age 19, followed up between five and over 20 years, mean of 12 years. Information from hospital charts and all data available before and after the injury were gathered and reviewed. The study was carried out among a consecutive sample of Finnish patients with TBI referred to a rehabilitation programme at the out patient neurological clinic of Kauniala Hospital, which specializes in brain injuries in Finland. The patients came from various hospital districts in the country for an evaluation of their educational and vocational problems. Main outcome measures were functional outcome, as measured by the Glasgow Outcome Scale GOS at the end of follow up, and post injury occupational outcome. The patients reemployment on the open job marklet, subsidized employment or inability to work was noted. The GCS score on hospital admission correlated clearly with the functional outcome of the patients at the end of follow up. Length of coma and duration of post traumatic amnesia correlated specifically with the patient s work history after the brain injury and with functional outcome measured by the GOS. Outcomes varied among age groups and seemed to be affected by age at injury. Accordingly, the extent of recovery and quality of life for rehabilitation patients with TBI can be estimated early on by prognostic factors reflecting injury severity in the acute phase. The results suggest that the GCS score, LOC and duration of PTA all have a strong predictive value in assessing functional or occupational outcome for TBI patients.     

Multiple Arteriovenous Malformations with Hemorrhage

Summary  Background. A rare case of a left temporal arteriovenous malformation (AVM) with bleeding 10 days after removal of another hemorrhagic AVM in the frontal lobe is reported.  Method. A 47-year-old man had an attack of headache and vomiting and was admitted to our hospital. On admission, a CT scan showed subcortical hemorrhage in the left frontal lobe. Left carotid angiography revealed four AVMs and a vertebro-basilar angiogram demonstrated a vascular malformation.  Findings. First, a hemorrhagic AVM was removed with a hematoma. Following the operation, left carotid angiograms continued to show, AVMs, particularly a temporal AVM with increased blood flow, and after 10 days this hemorrhaged. This was surgically resected and the remaining small AVMs were treated by stereotactic radiosurgery.  Interpretation. The patient had a high risk of hemorrhage. Adding hemodynamic stress to this situation, hemorrhage would have been expected to occur at an early time after the initial intervention for hemorrhagic AVM. Considering the risk of hemorrhage, other AVMs should undergo surgery as soon as possible after resection of hemorrhagic AVM.     

Traumatic acute subdural haematomas of the posterior fossa: clinicoradiological analysis of 24 patients

Background. We report 24 patients with a traumatic acute subdural haematoma of the posterior fossa managed between 1997 and 1999 at 8 Italian neurosurgical centres. Method. Each centre provided data about patients clinico-radiological findings, management, and outcomes, which were retrospectively reviewed. Findings. A poor result occurred in 14 patients (58.3%). Ten patients (41.7%) had favourable results. Patients were divided into two groups according to their admission Glasgow Coma Scale (GCS) scores. In Group 1 (12/24 cases; GCS score, 8), the outcome was favourable in 75% of cases. In Group 2 (12/12 cases; GCS score, <8), the outcome was poor in 91.6% of cases. Nineteen patients underwent posterior fossa surgery. Factors correlating to outcome were GCS score, status of the basal cisterns and the fourth ventricle, and the presence of supratentorial hydrocephalus. Multivariate analysis showed significant independent prognostic effect only for GCS score (P<0.05). Interpretation. acute posterior fossa subdural haematomas can be divided into two distinct groups: those patients admitted in a comatose state and those with a moderate/mild head injury on admission. Comatose patients present usually with signs of posterior fossa mass effect and have a high percentage of bad outcomes. On the contrary, patients admitted with a GCS of 8 or higher are expected to recover. In these patients the thickness of the haematoma (<1cm) seems to be a guide to indicate surgical evacuation of the haematoma.     

Is the Size of an Epidural Haematoma Related to Outcome?

Summary  Recently we treated 54 patients with acute epidural haematoma, diagnosed by early CT scan and operated on quickly, within 6 hours after trauma.  In 18 cases the volume of the haematoma, calculated by three different methods, was more than 150 cc, and GCS score was equal to or less than 8.  In all 18 patients, as well as in another 36, we obtained good results: all patients survived and 17 fully recovered (only one was left with moderate neurological disability).  Our experience leads us to the conclusion that even volumes of over 150 cc can be compatible not only with survival but also with very low morbidity, if rapid surgical treatment is performed.     

The Therapeutic Effect of Continuous Intracisternal L-Arginine Infusion on Experimental Cerebral Vasospasm

Summary  Background. Recent studies on the pathogenesis of cerebral vasospasm following subarachnoid haemorrhage (SAH) suggest a breakdown of the balance between the vasoconstrictor and vasodilator systems. A shortage of a major cerebral vasodilator, nitric oxide (NO), has been accused of causing this breakdown. We investigated the effect of continuous intracisternal infusion of a NO precursor, L-Arginine, in a rabbit SAH model.  Method. Three experimental groups were designated: Group 1 – Cerebral blood flow (CBF) data was obtained via transorbital Doppler ultrasonography (TDU) in 8 normal rabbits. Group 2 – Intracisternal catheter placement and TDU study during saline infusion were performed in 8 animals at the 4^th day of SAH, Group 3 – SAH occurred in 8 animals. 4 days later, L-Arginine was infused intracisternally for 1 hour, while TDU was performed before and during infusion. CBF parameters which were obtained via TDU measurement or calculations, were compared.  Findings. The results of TDU revealed significant vasospasm in all SAH animals, as well as resolution of vasospasm with L-Arginine infusion. After 20 minutes of infusion, a steady and sustained vasodilation was obtained in the third group. The analysis of CBF data revealed a significant difference in SAH values, and no difference in control animals.  Interpretation. Our results support the contribution of the “NO shortage” concept in the pathogenesis of cerebral vasospasm and overconsumption of L-Arginine during the post-SAH period may cause this shortage. L-Arginine treatment may be useful for the prophylaxis and treatment of cerebral vasospasm. The intracisternal infusion method can eliminate the short action time disadvantage of L-Arginine.     

Nitric Oxide Synthase Inhibition Attenuates Vasoactive Response to Spinal Cord Stimulation in an Experimental Cerebral Vasospasm Model

Summary  Background. The basic mechanism of delayed cerebral vasospasm following subarachnoid haemorrhage (SAH) has been intensively investigated. It is thought that nitric oxide (NO) is a basic mediator of the cerebral vasodilator mechanism. Previous clinical and experimental studies have shown a cerebral vasodilator effect of high cervical spinal cord stimulation (SCS) however, the mechanism of this effect is still controversial. We investigated the contribution of the vasodilator effect of NO to this mechanism in an experimental SAH model using rabbits.  Method. Four experimental groups, were designated: Group 1. Cerebral blood flow (CBF) was evaluated by transcranial Doppler ultrasonography (TDU) in 8 rabbits. Group 2. In 4 animals, intracisternal saline injection and cervical epidural electrode placement without SCS were performed before TDU. Group 3. TDU was performed before and after SCS on the fourth day of SAH in 8 rabbits. Group 4. In 8 animals, N-Nitro-L-Arginine Methyl Esther (L-NAME) was administered intracisternally on the fourth day of SAH, at a dose of 0.6 mg/kg, 45 minutes before SCS. CBF parameters, obtained via measurements or calculations from TDU data, were compared.  Findings. The occurrence of vasospasm after SAH was demonstrated with significant changes in TDU parameters (high peak systolic velocity and positive values of the degree of stenosis). In all SAH animals, SCS resulted in significant vasodilation. Even after the injection of L-NAME, SCS still had a significant vasodilatory effect in SAH animals, but there was also a significant difference in CBF parameters in the SCS-only group when compared with the L-NAME treatment before SCS group.  Interpretation. The mechanism of the cerebral vasodilatory effect of SCS remains controversial. Our results revealed the contribution of a neurohumoral effect which can be partially prevented by use of an NO synthase inhibitor.     

Magnesium therapy after aneurysmal subarachnoid haemorrhage a dose-finding study for long term treatment

Summary.  Background: Magnesium is a neuroprotective agent which might prevent or reverse delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Although the dosage for short-term magnesium therapy is well established, there is lack of knowledge on the dosage for extended use of magnesium. Our aim was to find a dosage schedule of magnesium sulphate to maintain a serum magnesium level of 1.0–2.0 mmol/L for 14 days to cover the period of DCI.  Methods: We prospectively studied 14 patients admitted within 48 hours after aneurysmal subarachnoid haemorrhage (SAH) to our hospital. Magnesium sulphate was administrated intravenously for 14 days, using 3 different dosage schedules. Group A (n=3) received a bolus injection of 16 mmol magnesium sulphate followed by a continuous infusion of 16 mmol/dayly; group B (n=6) a continuous infusion of 30 mmol/dayly; and group C (n=5) a continuous infusion of 64 mmol/dayly. Serum magnesium was measured at least every two days and all patients were under continuous observation during magnesium treatment. Renal magnesium excretion was measured only in group C.  Findings: In treatment group A the mean serum magnesium level during treatment was 1.03±0.14 (range 0.82–1.34) mmol/L, in group B 1.10±0.15 (range 0.87–1.43) mmol/L, and in group C 1.38±0.18 (range 1.11–1.98) mmol/L. The renal magnesium excretion in group C was equal to the administrated doses within 48 hours after treatment had started. All patients in group A reported a flushing sensation during the bolus injection; no other side effects were noted.  Interpretation: With a continuous intravenous dosage of 64 mmol/L per day, serum magnesium levels maintained within the range of 1.0–2.0 mmol/L for 14 days. Published online March 3, 2003 Acknowledgments  We gratefully acknowledge the Netherlands Heart Foundation (grant 99.107) and the Schumacher-Kramer Foundation, for financially supporting this study. Dr. Rinkel is clinically established investigator of the Netherlands Heart Foundation (grant D98.014).  Correspondence: W. M. van den Bergh, M.D., Department of Neurosurgery, Room G03.124, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.     

Vital capacity induction with 8% sevoflurane and N2O causes cerebral hyperemia

Purpose. Little is known about the influence of high-dose sevoflurane on cerebral volume. We evaluated induction time and cerebral blood volume with 8% sevoflurane using the “vital capacity induction” technique. Methods. Thirty-four patients were randomly allocated into three groups. Group P received 2.0 mg·kg⁻¹ of propofol i.v. and inhalation of 67% N₂O/O₂, whereas group S5 and group S8 received inhalation of primed 5% and 8% sevoflurane in 67% N₂O/O₂, respectively. Induction time was measured as the time from the start of inhalation, or from the end of injection, until loss of eyelash reflex. Near-infrared spectroscopy and bispectral index (BIS) were monitored continuously until 3 min after tracheal intubation. Results. Induction time was less in group S8 (17.3 ± 6.4 s, mean ± SD) than in groups P (25.7 ± 8.2 s) and S5 (33.0 ± 16.8 s). There was a significant increase in cerebral blood volume after intubation in group S8, as suggested by higher cerebral oxyhemoglobin and total hemoglobin levels. There were no differences in BIS scores among the groups during the study period. Conclusion. Vital capacity inhalation of 8% sevoflurane produces a faster loss of eyelash reflex than does 5% sevoflurane or propofol, but increases cerebral blood volume. Received: May 20, 2002 / Accepted: August 27, 2002 Address correspondence to: K. Iwasaki     

Hypotension associated with systemic aggregated anaphylaxis is not attenuated by a selective endothelin-A receptor antagonist,BQ 610, in rabbits in vivo

Purpose. The present study was done to investigate the role of endothelin-1 (ET-1) in hypotension and bronchospasm provoked by anaphylaxis in rabbits in vivo. Methods. Forty-five rabbits sensitized to horse serum were randomly allocated to five groups: Group 1 (n = 10) received 0.5 nmol·kg⁻¹ of ET-1; Group 2 (n = 10) received 0.5 nmol·kg⁻¹ of ET-1 and 200 nmol·kg⁻¹ of a selective ET_A receptor antagonist, BQ 610, without anaphylaxis; Group 3 (n = 5) received 200 nmol·kg⁻¹ of BQ 610 alone without anaphylaxis; Group 4 (n = 10) received normal saline alone before being antigen challenged to induce anaphylaxis; Group 5 (n = 10) received 200 nmol·kg⁻¹ of BQ 610 before antigen challenge. Results. Mean arterial pressure (MAP) values were significantly different between Groups 1 and 2. Heart rate (HR), central venous pressure (CVP), dynamic pulmonary compliance (C_dyn), and pulmonary airway resistance (R_L) did not differ significantly between Groups 1 and 2. MAP values were significantly decreased compared with baseline in both Groups 4 and 5; however, the values were not significantly different between two groups. CVP values were significantly different between Groups 4 and 5 only at the 15-min time point following antigen challenge. HR, R_L, and C_dyn values were not significantly different between Groups 4 and 5, nor were the survival rates. Conclusion. BQ 610 does not improve hypotension or survival rates in systemic aggregated anaphylactic rabbits in vivo, implying that circulating ET-1 may not play an important role in anaphylaxis, although direct proof of production of circulating ET-1 or activation of ET_A receptors is lacking in this study. Received: October 15, 2001 / Accepted: August 20, 2002 Address correspondence to: T. Kawakami     

Gamma Knife Radiosurgery of Skull Base Meningiomas

Summary  Background. The standart surgical treatment of meningiomas is total resection of the tumour. The complete removal of skull base meningiomas can be difficult because of the proximity of cranial nerves. Stereotactic radiosurgery (SRS) is an effective therapy, either for adjuvant treatment in case of subtotal or partial tumour resection, or as solitary treatment in asymptomatic meningiomas.  Method. Between September 1992 and October 1995, SRS using the Leksell Gamma Knife was performed on 46 patients (f:m=35:15), ranging in age from 35 to 81 years, with skull base meningiomas at the Neurosurgical Department of the University of Vienna. According to the indication of gamma knife radiosurgery (GKRS) the patients (n=46) were devided into two subgroups. Group I (combined procedure: subtotal resection followed by GKRS as a planned procedure or because of a recurrent meningioma), group II (GKRS as the primary treatment). Histological examination of tumour tissue was available for 31 patients (67%) after surgery covering 25 benign (81%) and 6 malignant (19%) meningioma subtypes.  Findings. The overall tumour control rate after a mean follow-up period of 48 months (ranging from 36 to 76 months) was 96% (97.5% in benign and 83% in malignant meningiomas). Group I displayed a 96.7% tumour control rate, followed by group II with 93.3% respectively. Neurological follow-up showed an improvement in 33%, stable clinical course in 58% and a persistant deterioration of clinical symtoms in 9%. Remarkable neurological improvement after GKRS was observed in group II (47%), whereas in group I (26%) the amelioration of symptoms was less pronounced.  Interpretation. GKRS in meningiomas is a safe and effective treatment. A good tumour control and low morbidity rate was achieved in both groups (I, II) of our series, either as a primary or adjunctive therapeutic approach. The planned combination of microsurgery and GKRS extends the therapeutic spectrum in the treatment of meningiomas. Reduction of tumour volume, increasing the distance to the optical pathways and the knowledge of the actual growing tendency by histological evaluation of the tumour minimises the risk of morbidity and local regrowth. Small and sharply demarcated tumours are in general ideal candidates for single high dose-GKRS, even after failed surgery and radiation therapy, and in special cases also in larger tumour sizes with an adapted/reduced margine dose.     

Clinical features and medical treatment of male prolactinomas

Summary  Background. Prolactinomas found in male patients show distinct clinical features compared to those in female patients, which may warrant a different treatment strategy.  Method. To clarify their clinical features and to evaluate the treatment results, specifically the results of surgical treatment and non-surgical treatment solely with oral bromocriptine, we retrospectively reviewed our experience in male prolactinoma cases.  Findings. From 1988 to 1998, we had 184 pituitary adenoma patients, and thirteen of those were male patients with a pure prolactinoma. Of the thirteen patients, eight underwent transsphenoidal surgery followed by oral bromocriptine (surgical group), and five were treated solely with bromocriptine or terguride (non-surgical group). In both groups, the visual symptoms and signs resolved after the treatment, and the serum prolactin levels were normalised with minimal maintenance dose of bromocriptine. Notably, improvement of the visual symptom in the three non-surgically treated patients was observed within a week following the bromocriptine administration.  Interpretation. Although surgery would continue to play an important part of treatment in some cases with a large tumour, our experience suggests that drug treatment without surgery can be a safe and effective option in the management of male prolactinoma patients.     

Intracranial plasma cell granuloma with genetic analysis

Summary.  Background: Plasma cell granuloma of the central nervous system is rare and less than 30 cases have been reported in literature.  Method/findings: A 64-year-old woman complained of headache, and computed tomography (CT) and magnetic resonance (MR) imaging of the brain revealed a tumour at the right anterior-third parasagittal region which led us to diagnose a parasagittal meningioma. We performed total resection of the tumour and the pathological diagnosis was plasma cell granuloma. Polymerase chain reaction (PCR) analysis of immunoglobulin heavy chain (IgH) gene rearrangements produced no monoclonal band. This patient underwent no supplementary treatment and no recurrent tumour was observed for 3 years.  Interpretation: A case of plasma cell granuloma which is diagnosed with genetic analysis is presented. An analysis of the clonality using the PCR procedure would play an important role in supporting the pathological and clinical diagnosis. Published online March 3, 2003  Correspondence: Mamoru Murakami, M.D., Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.     

Endoscopic percutaneous transforaminal treatment for herniated lumbar discs

Summary.  Background: The prevailing percutaneous treatment options for herniated non-contained lumbar discs have not reliably achieved the same good results as the conventional microsurgical techniques. In this study we evaluated clinical outcome and complication rate following endoscopic percutaneous transforaminal treatment of extruded or sequestrated herniated lumbar discs in 122 patients with a follow-up period of more than one year.  Method: Between October 1997 and December 2000, 86 male and 36 female patients with a median age of 55 years (range 18 to 89 years) underwent endoscopic treatment for non-contained herniated lumbar discs at our department. Neurological controls were conducted after 4 to 8 weeks routinely and the clinical result was reassessed at a follow-up of 15 to 53 months (median 35 months) according to the Macnab scale and Prolo outcome score.  Findings: On follow-up examination, 96 patients were found with permanently ameliorated or normal clinical status following endoscopy alone. The remaining 26 cases with unchanged or only temporarily improved neurological disorders were submitted to conventional microsurgical interventions. Spinal nerve root injury during endoscopic treatment occurred in two patients but no additional neurological deficits or aggravation of pre-existing disorders were observed.  Interpretation: Due to the minimal invasivity, the good functional outcome (78.7% clinical amelioration) and the low complication rate (1.6%), this procedure represents an attractive and efficient treatment alternative especially for foraminal and extraforaminal herniated lumbar discs and reduces the indications for open surgery in selected cases. Published online October 10, 2002 Correspondence: Sandro Eustacchio, M.D., Department of Neurosurgery, Karl-Franzens University, Auenbruggerplatz 29, A-8036 Graz, Austria.     

Cranio-cervical decompression for Chiari type I-malformation,adding extreme lateral foramen magnum opening and expansile duroplasty with arachnoid preservation. Technique and long-term functional results in 44 consecutive adult cases -- comparison with literature data

Summary.  Background: Posterior cranio-cervical decompression by opening at least foramen magnum and C1-lamina usually with corresponding dural and arachnoid opening, is the procedure most currently used for treating Chiari I malformation (alone or in association with syringomyelia). To optimize decompressive effects together with reducing risks, a procedure was developed which consists of a sub-occipital craniectomy and a C1 (or C1/C2) laminectomy, plus an extreme lateral Foramen Magnum opening, a “Y” shaped dural incision with preservation of the arachnoid membrane, and an expansile duroplasty employing autogenous periosteum.  The purpose of the article is: 1. to report the long-term functional results in a consecutive series of 44 adult patients affected by symptomatic Chiari Malformation type I (CM) using the procedure described. 2. and to compare this technical modality with the other modalities reported in the literature.  Method: This series includes 44 patients harboring CM type I and operated on between 1990 and 2000. 15 patients had CM with syringomyelia (34%) and 29 CM alone (66%). Functional status was evaluated by using the Karnofsky disability scale. Before surgery 37 patients (84.1%) were independent (of whom 13 had syringomyelia) and 7 patients (15.9%) were dependent – i.e., they required assistance – (of whom 2 had syringomyelia). Outcomes were analized with follow-up ranging from 1 to 10 years (4 years on average).  Findings: There was no operative mortality, and surgery did not provoke any neurological aggravation. After surgery all the patients were independent. For the patients with CM only, the averaged Karnofsky score was 90 at latest follow up, versus 76 before surgery. For the patients with syringomyelia, the averaged latest Karnofsky score was 89 after surgery, versus 74 before.  Interpretation: The presented technique was compared with the other surgical modalities reported in the literature. This comparative study shows that cranio-cervical decompression with extreme lateral resection of the posterior rim of Foramen Magnum out to the level of the occipital condyles on either side, associated with an enlargement duroplasty with preservation of the arachnoid membrane, achieved the best results with minimal complications and side-effects. Published online October 10, 2002 Acknowledgments  We thank Mrs Brigitte BAUER for her secretariat assistance. Correspondence: Professor Marc Sindou, M.D., D. Sc., Department of Neurosurgery, H?pital Neurologique Pierre Wertheimer, University of Lyon, 59 Bd Pinel, 69003 Lyon, France.     

Combination Chemotherapy Using Carboplatin (JM-8) and Etoposide (JET Therapy) for Recurrent Malignant Gliomas: A Phase II Study

Summary.  Background: To study efficacy and safety of chemotherapy using carboplatin (JM-8) and etoposide (“JET” therapy) for the treatment of recurrent malignant glioma, a phase II study was conducted. Tumour control, survival time, and toxicity/side effects were assessed in patients with recurrent malignant glioma which failed to respond to a postoperative combined auxiliary therapy comprising of IFN-β, ACNU and radiation.  Methods: Twenty-eight patients, fourteen with anaplastic astrocytoma (AA) and fourteen with glioblastoma (GB) were included in this study. The JET regimen consists of the intravenous administration of carboplatin (300 mg/m²) on day 1 and etoposide (60 mg/m²) on day 1 to 5, repeated every 6 weeks.  Findings: Following the therapy, we observed partial response (PR) in five (36%) of 14 patients with AA and two (14%) of 14 with GB, and stabilization of the disease (SD) in six (43%) in each group. The mean survival/survival after recurrence was 51 months/25 months in the AA group, and 17/9 in the GB group.  Interpretations: These results compare favorably with the natural course of recurrent malignant glioma. JET shows signs of efficacy in patients with recurrent malignant glioma, and a randomized trial comparing it to standard therapy is warranted. Published online December 5, 2002  Correspondence: Dr. Kunihiko Watanabe, M.D., D.M.Sc., Division of Neurosurgery, Tochighi Cancer Center, 4-9-13, Yohnan, Utsunomiya, Tochighi, 320-0834, Japan.