Risk analysis of thrombo-embolic and recurrent bleeding events in the management of intracranial haemorrhage due to oral anticoagulation.

PURPOSES: Intracranial haemorrhage (ICH) is a rare but potentially devastating complication of oral anticoagulants (OAC). This raises the difficult clinical choice between either permanent cessation of OAC, or continuing OAC and if so, when to restart. To make this choice, one needs to balance the thrombo-embolic risk after cessation of OAC against the risk of recurrent intracranial haemorrhage when OAC are restarted. There are few published data to base this difficult clinical decision on. METHODS: We present an observational study of a consecutive series of 108 patients, collected prospectively and admitted to our department, with an OAC-related intracranial haemorrhage, in whom we assessed the thrombotic event rate and the recurrent intracranial bleeding rate during follow-up. RESULTS: In the 25 patients in whom OAC were reinstituted no new thrombo-embolic events occurred (0/506 unprotected patient-days). In the group of patients in whom OAC were not restarted (n = 81), the thrombo-embolic event rate was 8/11590 unprotected patient-days, of which only 2 were cerebrovascular thrombo-embolisms. The overall risk of a thrombo-embolic complication can be estimated to be 0.66 events/1000 patient-days at risk (95% exact confidence limits of 0.3 to 1.3 events/1000 patient-days at risk). In three patients the thrombo-embolic event was fatal. We saw recurrent intracranial bleeding in eight patients, 2 of which were fatal. Seven of these occurred before the restarting of the OAC. CONCLUSIONS: In OAC-related intracranial haemorrhages, OAC can be stopped safely for a considerable period, with a very low overall thrombotic event rate. The recurrent bleeding risk after restarting OAC is low. Recurrent bleeding mostly occurred before restarting OAC and is probably caused by insufficient or unsustained correction of the initial coagulation deficit. Immediate reversal of anticoagulation provides the patient with the best possible treatment options including surgery. OAC-related intracranial haemorrhages can therefore be actively treated.

Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study.

Patients with relapsed malignant glioma have a poor prognosis. We developed a strategy of vaccination using autologous mature dendritic cells loaded with autologous tumour homogenate. In total, 12 patients with a median age of 36 years (range: 11-78) were treated. All had relapsing malignant glioma. After surgery, vaccines were given at weeks 1 and 3, and later every 4 weeks. A median of 5 (range: 2-7) vaccines was given. There were no serious adverse events except in one patient with gross residual tumour prior to vaccination, who repetitively developed vaccine-related peritumoral oedema. Minor toxicities were recorded in four out of 12 patients. In six patients with postoperative residual tumour, vaccination induced one stable disease during 8 weeks, and one partial response. Two of six patients with complete resection are in CCR for 3 years. Tumour vaccination for patients with relapsed malignant glioma is feasible and likely beneficial for patients with minimal residual tumour burden.

Jugular foramen schwannoma: surgical experience in six cases.

PURPOSE: Schwannomas of the lower cranial nerves are rare tumours. We have surgical experience in six patients. MATERIAL AND METHODS: We have retrospectively reviewed the files of the six patients with jugular foramen schwannomas that were treated in multidisciplinary collaboration in the departments of neurosurgery and ENT. RESULTS: From a clinical point of view, the most important finding was that these tumours usually mimic a vestibular schwannoma. The imaging findings however always allowed the differentiation. The surgical technique included in all cases a suboccipital approach for the intracranial part. When large, the extracranial extension had to be removed through a lateral cervical or transfacial approach. There was no mortality and minor morbidity, with good functional outcome. In subtotally removed tumours, recurrence occurred. CONCLUSION: A combined neurosurgical and ENT approach allows for safe removal of these often large skull base tumours.

Lhermitte-Duclos disease is a clinical manifestation of Cowden's syndrome.

BACKGROUND: Lhermitte-Duclos disease (LDD) is a hamartomatous overgrowth of cerebellar ganglion cells, which replace granular cells and Purkinje cells. In recent years several cases involving the association between LDD and Cowden's syndrome (CS), an autosomal dominant condition characterized by multiple hamartomas and neoplastic lesions in skin and internal organs, have been reported. METHODS: We reviewed the medical records and imaging studies of six patients with LDD who were treated at our institution, and we looked at other possible symptoms of CS. RESULTS: Other clinical findings suggestive of CS were apparent in five patients: These included mucocutaneous lesions, acral keratosis, thyroid adenoma, fibrocystic disease, ovarian cyst, intestinal polyposis, and arteriovenous malformation. Only in the youngest patient, a 5-year-old boy, were no cutaneous or other signs found, despite extensive clinical and ultrasound examination. CONCLUSION: Our observations strengthen the hypothesis that LDD is a neurological manifestation of CS. Patients with LDD should receive a thorough dermatological and systemic screening, because some of the lesions (breast, etc...) can develop into malignant tumors.

Effect of the serotonin agonist 8-OH-DPAT on the sensorimotor system of the rat.

8-Hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT, 2 mg/kg) is used to induce perseverative behavior in rats in a T-maze as a model for obsessive-compulsive disorder (OCD). Using the open-field test, radiant heat test, and the test with von Frey filaments, we examined whether alterations in sensorimotor functioning could contribute to the perseverative tendencies in this model by measuring differences in left versus right hind paw reactions after 8-OH-DPAT administration (2 mg/kg, sc). Also, the effect of repeated 8-OH-DPAT administration on sensorimotor functioning was tested every third day. 8-OH-DPAT administration induced a significantly decreased sensorimotor performance in the open-field test, an increased threshold for noxious thermal stimulation (increased withdrawal latency, WL, and decreased elevation time, ET) in the radiant heat test, and a decreased nociceptive threshold for mechanical stimulation in the test with von Frey filaments. All changes in sensorimotor functioning were similar for left and right hind paws suggesting that, these changes as measured with the tests in the present study, are not likely to contribute to the perseverative behavior of rats in a T-maze. Further, repeated administration of 8-OH-DPAT had no effect in the radiant heat test and the test with the Frey filaments, but produced a tolerance effect in the open-field test.

Long-term external drainage for subdural collections in infants.

The treatment of subdural collections in infants remains controversial. In order to evaluate the treatment guidelines that we developed on the basis of our earlier experience, we have reviewed the results obtained in 31 consecutive infants with symptomatic chronic and subacute subdural collections treated with external drainage. Using our guidelines for removal of the drains, there was only a very low rate of permanent shunting (4/31), with a low complication rate and good clinical results. However, the long period of external drainage, and therefore of hospitalization, might make if general application of these guidelines problematic.

Posterior fossa decompression in syringomyelia associated with a Chiari malformation: a retrospective analysis of 22 patients.

BACKGROUND: The technique of posterior fossa decompression, nowadays preferred by most neurosurgeons as the first surgical option in the treatment of hindbrain associated syringomyelia, was reintroduced in our center in 1989. We present a retrospective analysis of 22 patients with this pathology who underwent the procedure since then. METHODS: In all patients diagnosis was made by MRI of the craniospinal junction. The operation consisted of a suboccipital craniectomy, removal of the posterior arc of C1, laminectomy of C2 or C3 when necessary and a wide duraplasty at the end. The intradural manipulations (opening of the arachnoid membrane, coagulation or resection of the tonsils) were not uniform. Postoperatively short- and long-term clinical outcome and MRI findings were assessed. RESULTS: Sixteen out of 21 patients (76%) experienced an improvement in the early follow-up period. In the late follow-up period 13 out of 19 patients (68%) were improved, whereas five patients (26%) experienced a marked deterioration. There was no unequivocal effect on all symptoms and signs. Postoperative MR images showed a favorable result in 16 out of 20 patients (80%), consisting of syrinx collapse or reduction of the syrinx diameter. CONCLUSIONS: We conclude that decompression of the posterior fossa is a safe procedure with a considerable chance of clinical improvement. Although total syrinx collapse is not as frequently seen as in syrinx shunting procedures, the clinical outcome may be better. Moreover, there seemed to be no unequivocal correlation between clinical outcome and postoperative syrinx size in the present study.

Results after surgery for lumbosacral lipoma: the significance of early and late worsening.

We retrospectively reviewed 32 patients operated on for lipoma of the conus and lipomyeloschisis, the two main anatomical subtypes of congenital lumbosacral lipomas associated with tethered cord syndrome. Surgery was proposed to patients when they were symptomatic, and in most cases for progressive symptoms. The evolution of the different symptoms was studied separately. In most patients, symptoms improved or stabilized after surgery; in some, however, postoperative worsening, at least of some of the symptoms, was seen. This postoperative worsening became apparent either early or late after the operation, and was not associated with surgical trauma or postoperative complications. We suggest it was caused mainly by the natural course of the disease (especially in the case of the orthopedic deformities), and in some cases by retethering. Our series is not large enough to detect statistical significance for the different symptoms or for the anatomical subgroups. Importantly, according to our analysis by the different symptoms, the operation did not seem to protect the patients from later development of new deficits. This can be interpreted as an argument against prophylactic surgery in asymptomatic patients.

Secondary supratentorial anaplastic astrocytoma following treatment of medulloblastoma.

The development of secondary tumours is a rare but well known late effect of radiation therapy of lesions in the central nervous system. Most radiation-induced tumours are of mesenchymal origin, but on rare occasions gliomas can occur. We describe a patient in whom a supratentorial anaplastic astrocytoma developed 15 years after surgery and radiotherapy for a childhood posterior fossa medulloblastoma. A concise review of the pertinent literature is given.

Treatment of a symptomatic posterior fossa subdural effusion in a child.

We describe the first observation of a child with a posterior fossa subdural effusion with secondary hydrocephalus and tonsillar herniation. We diagnosed this entity in a 14-month-old girl with no history of trauma or coagulation disorder. The patient presented in our emergency department with opisthotonus and raised intracranial pressure resulting from supratentorial hydrocephalus. An emergency ventriculo-peritoneal shunt was placed, which resolved the symptoms only temporarily. Eventually external drainage of the subdural fluid was performed. The collection gradually disappeared, and both the external subdural shunt and the ventriculo-peritoneal shunt were removed. The patient made a complete neurological recovery. We review the physiopathology and treatment of subdural effusions in general, and propose some guidelines for the management of symptomatic effusions occurring in the posterior fossa in particular.

Sciatica caused by a dilated epidural vein: MR findings.

We report the MR imaging findings in a 41-year-old woman presenting with sudden low back pain and sciatica. At surgery a dilated epidural vein was found compressing the nerve root. The MR findings may suggest the diagnosis. Magnetic resonance imaging of a dilated epidural vein or varix causing sciatica has not been reported until now.

Primary brain stem tethering: a rare cause of geniculate neuralgia.

This rare case of brain stem tethering presented with chronic and progressive geniculate neuralgia. In view of the fact that an occipital subcutaneous lipoma had been resected in childhood, it probably concerned a primary tethering, fitting in with an occult occipital dysraphism. Magnetic resonance imaging (MRI) clearly demonstrated an underlying tethering, causing a distortion of the brain stem. Consequently, this led to the hypothesis that the geniculate neuralgia could be explained by traction on the lower cranial nerves secondary to the brain stem displacement. Untethering resulted in a considerable decrease of the neuralgia. MRI proved to be essential in the diagnosis and treatment of this unusual case.

Functional MRI of the brain: localisation of eloquent cortex in focal brain lesion therapy.

The aim of this study was to assess the feasibility of functional MRI (fMRI) in a clinical environment on a large patient group, and to evaluate the pretherapeutic value of localisation of eloquent cortex. Forty patients with focal brain lesions of different origin were studied using fMRI. Functional information was obtained using motor, somatosensory, auditory and phonological stimuli depending on the localisation of the lesions. To obtain information about the spatial accuracy of fMRI, the results were compared with postoperative electrocortical stimulation. Two patients with secondary trigeminal neuralgia were scanned using a motor protocol and were implanted with an extradural plate electrode. Imaging was successful in 40 of 42 patients (including the 2 with trigeminal neuralgia). These patients were analysed for strength of activation, the relation of the lesion to activation sites and the presence of mass effect. The correlation between these data and surgical findings provided significant additional clinical information. Functional MRI can be accurately performed in patients with focal brain lesions using a dedicated approach. Functional MRI offers important clinical information as a contribution to a decrease in posttherapeutic morbidity. The accuracy of the technique can be confirmed by other modalities, including invasive cortical electrostimulation.

Tethered cord syndrome in occult spinal dysraphism: timing and outcome of surgical release.

OBJECTIVE: To investigate the influence of neurosurgical intervention on the appearance of upper motor neuron (UMN) signs in newborns diagnosed with occult spinal dysraphism and tethered cord (TC) during the first month of life. METHODS: A prospective study (1990 to 1996) of 22 consecutive newborns with occult spinal dysraphism monitored for the appearance of UMN signs. Untethering was performed when neurologic or urodynamic investigation indicated the presence of UMN dysfunction. RESULTS: Of 22 patients, 10 remained free of UMN symptoms during follow-up (mean, 67+/-22 months). Untethering was performed in 12 of 22 patients because of the presence of UMN symptoms. In 7 of these 12 patients, there was a documented asymptomatic period of 13+/-11 months before the onset of UMN symptoms. Untethering at a mean age of 18+/-17 months restored normal neurologic and urinary function in all patients (mean postoperative follow-up, 25+/-16 months). Of the 12 children, 5 presented with UMN signs at birth. In these children, untethering was performed at a mean age of 9+/-5 months. In two of these five patients, UMN symptoms did not resolve after surgery, and ongoing conservative bladder treatment was required (mean follow-up, 37+/-14 months). In none of the 12 operated children did signs of retethering occur. CONCLUSIONS: A significant number (10/22) of children born with occult spinal dysraphism and TC did not develop UMN symptoms during follow-up; neurosurgical correction after the appearance of an UMN sign restored normal neurologic and urinary function in all children; and untethering in children presenting at birth with UMN symptoms resulted in poorer outcome.

Epidermoid tumours associated with lumbar punctures performed in early neonatal life.

Three children (ages 5, 7, and 12 years) with epidermoid tumours in the spinal canal, all of whom had a lumbar puncture during the early neonatal period, are reported. A considerable delay occurred from the first symptoms until the diagnosis was made. MRI of the lumbar spine was the method of choice in the diagnostic work-up. All three cases were successfully surgically treated. The link between lumbar punctures and epidermoid tumours and the possible risk factors involved are explored. Because of the variable clinical presentation, the possibility of the existence of these tumours should be considered in the differential diagnosis.

Spontaneous spinal epidural hematoma associated with thrombolysis and anticoagulation therapy: report of three cases.

Three patients with a spontaneous spinal epidural hematoma are presented, one of which is exceptional because it could be attributed to thrombolysis with alteplase. The other two were correlated with oral anticoagulant therapy. Our second case suggests that Morbus Kahler may be an underlying pathology in spinal extradural hematoma. In the third patient neither an obvious 'locus minoris resistentiae' nor a pathological coagulation test could be held responsible for the spontaneous bleeding. All three patients underwent laminectomy and evacuation of the hematoma. Although two of our cases are examples of complete recuperation after late operative intervention, early surgery is preferable. Permanent clinical attention together with a low threshold to perform magnetic resonance imaging (MRI) leads to a quicker diagnosis of spinal epidural hematoma. We show that administration of gadolinium may facilitate correct preoperative localization of the hematoma because there may be contrast enhancement of the hematoma. Finally, the postoperative policy concerning thromboembolic prophylaxis is discussed.

Closed spinal dysraphism: a review on diagnosis and treatment in infancy.

This article reviews the clinical presentation, pathophysiology, diagnostic strategies, and therapeutic management of closed spinal dysraphism in infancy. Four groups of symptoms are distinguished: (1) cutaneous abnormalities, (2) lower motor neuron dysfunction due to congenital spinal and nerve root abnormalities, (3) upper motor neuron dysfunction due to tethering of the spinal cord, and (4) symptoms caused by associated malformations. Guidelines are proposed concerning timing and type of diagnostic investigations in infancy. This essentially encompasses a neurological assessment, including spinal ultrasonography and nuclear magnetic resonance imaging of the spine and the brain, and a urological assessment, including ultrasonography of kidneys and bladder, cystourethrography and a urodynamic study. As to the tethered cord syndrome it is concluded that first, already in infancy, a progressive neurological dysfunction can be detected; second, surgical untethering should be performed only upon appearance of upper motor neuron signs or upon progression of lower motor neuron signs. Despite its frequently asymptomatic course, the diagnosis of a congenital lumbosacral lipoma, and in the more general sense, of a closed spinal dysraphism, implies a periodic, multidisciplinary follow-up for life.

Use of external drainage for posthemorrhagic hydrocephalus in very low birth weight premature infants.

To treat progressive posthemorrhagic hydrocephalus we used early external ventricular drainage (EVD) in 14 premature infants. We think it is important that the catheters in these critically ill infants be inserted in the neonatal intensive care unit, allowing us to keep the infants in an extremely stable environment. Only after prolonged external ventricular drainage (on average 38.4 days) is a ventriculoperitoneal shunt considered, preferably when the child has reached a body weight of 2000 g. There were no infections or other severe drainage-related problems. We report mean daily EVD volumes (which are related to body weight) and EVD duration. The 14 patients included 9 who required permanent shunting. Comparing the mortality, morbidity and follow-up data to at least 3 months of age in this group with similar data for an earlier cohort treated with lumbar punctures and late permanent shunting, we demonstrate the safety of the policy we have recently adopted.