Phase I study of intraventricular recombinant tissue plasminogen activator for treatment of posthaemorrhagic hydrocephalus

AIM: Phase I study to evaluate intraventricular fibrinolytic treatment with recombinant tissue plasminogen activator (tPA) as a method of clearing blood from the cerebrospinal fluid, and thus preventing permanent hydrocephalus. METHODS: Twenty two preterm infants, aged 7 to 26 days, with progressive posthaemorrhagic ventricular dilatation (ventricular width > 4 mm over 97th centile) received one to five intraventricular bolus injections of 1.0 mg or 0.5 mg tPA at intervals of one to seven days. RESULTS: The mean cerebrospinal fluid concentration of tPA 24 hours after 1 mg was 1860 micrograms/ml. The half life of tPA in cerebrospinal fluid was about 24 hours. Twenty one (95%) infants survived, 12 (55%) without shunt surgery. One infant had secondary intraventricular haemorrhage. CONCLUSION: Intraventricular tPA resulted in survival without a shunt for most of the infants, but with some risk. Failure may have been due to plasminogen deficiency, an inhibitor, or late intervention.     

The Yale Geriatric Care Program is not effective in a pilot study in The Netherlands

Brain temperature was measured at various depths beneath the pial surface in patients with hydrocephalus of varying aetiology. Temperature increased gradually with depth in all patients, with the highest temperature found in the ventricle. The difference between intraventricular and rectal temperatures (delta v-r) was greater in patients who underwent continuous ventricular drainage than in patients who underwent ventriculoperitoneal shunt (continuous ventricular drainage; 1.2 (SD 0.40) degrees C, mean (SD), n=5 v ventriculoperitoneal shunt; 0.4 (SD 0.45) degrees C, n=16; p< 0.05). The difference between intracerebral and rectal temperatures (delta b2-r) was also greater in patients with continuous ventricular drainage than in patients with ventriculoperitoneal shunt (continuous ventricular drainage; 0.1 (SD 0.86) degrees C, n=5 v ventriculoperitoneal shunt; -0.7 (0.86) degrees C, n=16; p< 0.05). Among patients with normal pressure hydrocephalus, these differences were greater in the patients with better outcomes after shunt surgery than in the less improved group (delta v-r; 0.7 (SD 0.27) degrees C, n=7 v 0.1 (SD 0.40) degrees C, n=5, p< 0.01, delta b2-r; -0.2 (SD 0.61) degrees C, n=7 v -1.4 (0.90) degrees C, n=5, p< 0.01).     

Role of the pneumo-encephalogram in the diagnosis of spontaneous subarachnoid haemorrhage

The authors have collected eighteen cases of primary intraventricular lesions revealed by a subarachnoid haemorrhage. Among these cases, the most important are the choroid plexus papillomas followed by ependymomas; some cases have no precise histological interpretation. Generally speaking, cerebral arteriography gives only indirect evidence of ventricular dilation and thus does not confirm the presence of a lesion. On the contrary, the pneumoencephalogram is consistantly positive, but does not give the differential diagnosis between intraventricular tumours and primary intraventricular haemorrhages. This test should therefore be given the same importance as spinal cord arteriography in the exploration of subarachnoid haemorrhages with negative cerebral angiograms.     

A study of cerebral perfusion using single photon emission computed tomography in neonates with brain lesions

In this study we used a single photon emission computed tomography technique (SPECT) with radiolabelled 99mTcHMPAO to assess cerebral perfusion in newborn infants with documented cerebral lesions and to determine to what extent brain SPECT might be useful in the neonatal period. A total of 15 newborn infants with the following cerebral pathologies were enrolled: severe parietal bilateral periventricular leucomalacia (PVL, n = 6); moderate parietal bilateral PVL (n = 2); intraventricular haemorrhage grade II with unilateral parietal parenchymal extension (IHV + PE, n = 3); cerebral infarction (CI, n = 2) in the zone of middle cerebral artery; and post-haemorrhagic hydrocephalus (n = 2). Follow-up was available in all infants. Alterations in cerebral perfusion were seen in only 12 of 15 infants and at the location of severe PVL, PE and CI. We have noted that the regions of diminished perfusion extended beyond the apparent extent of cerebral pathology delineated by ultrasound or magnetic resonance imaging. Markedly diminished perfusion was seen in 1 infant with hydrocephalus, which recovered following placement of ventriculo-peritoneal shunt. Regarding outcome, SPECT data failed to provide additional information than that of neuroradiological investigations. We conclude that the use of SPECT, under these conditions, to assess alteration of cerebral perfusion in the neonatal period will not provide any additional information than that of neuroradiological investigations.     

Studies on crude drugs originated from Gentianaceous plants. I. Determination of gentiopicroside, the bitter principle of Gentianae radix and Gentianae scabrae radix (author''s transl)]

A 9-months old patient with a ventricular shunt due to hydrocephalus was treated with intraventricular administration of 5-FC due to Candida ventriculitis with satisfactory clinical response. The intraventricular dose given was 5 mg twice daily for 14 days. The same patient was treated four months later with combined peroral and intraventricular administration of 5-FC also with good clinical response. On both occasions there was no evidence of drug toxicity. The peroral dose given was 100 mg/kg bodyweight/day divided in four doses. A few CSF and serum samples were taken to estimate the concentration of 5-FC. The local installation of 5-FC in an isolated ventriculitis seems to be of special beneficial value whereas fungal septicaemia with ventriculitis needs combination of peroral and intraventricular administration. No increase in resistance against 5-FC could be registered.     

Traumatic intraventricular hemorrhage treated with intraventricular recombinant-tissue plasminogen activator: technical case report

OBJECTIVE AND IMPORTANCE: Traumatic intraventricular hemorrhage (IVH) can result in association with acute obstructive hydrocephalus, repetitive malfunction of external ventricular drains (EVDs), and uncontrollable increased intracranial pressure. We report a case showing the safe and effective use of intraventricular recombinant-tissue plasminogen activator in a child with severe brain injury and acute hydrocephalus from IVH. CLINICAL PRESENTATION: A 15-year-old male patient presented to us after a motor vehicle accident with bilateral extensor posturing, intracerebral and IVH, and acute obstructive hydrocephalus. INTERVENTION: A right EVD was placed and functioned only transiently. A left EVD was placed and functioned only transiently. Because of the inability to maintain ventricular drainage, rising intracranial pressure, and worsening clinical status, 5 mg of recombinant-tissue plasminogen activator was injected through each EVD. Excellent EVD function was obtained quickly, with control of intracranial pressure and improvement in clinical status and without hemorrhagic complication. CONCLUSION: With obstructive hydrocephalus secondary to acute traumatic IVH that cannot be controlled with EVD because of recurrent obstruction from intraventricular blood, intraventricular recombinant-tissue plasminogen activator can be effective and safe, despite preexisting multiple hemorrhagic intracranial injuries.     

Epilepsy in shunt-treated hydrocephalus

Although epilepsy is commonly associated with shunt-treated hydrocephalus, its relation to the shunting procedure and the criteria identifying postoperative epilepsy remain controversial. Of 283 patients shunted at Würzburg University Hospital over a 24-year period (1970 to 1994), 182 were followed up for a minimum of 1 year after shunt insertion and entered the study. The data were analyzed retrospectively in 1995 and 1996. Epilepsy was analyzed in relation to the etiology of hydrocephalus, functional status, time and site of shunt insertion, onset of seizures and seizure type, EEG changes, sex, shunt systems, and shunt revisions. Of the 182 patients studied, 37 (20%) developed epilepsy. The incidence of epilepsy varied according to the etiology of hydrocephalus: posthemorrhagic (5%), postinfectious (4%), connatal/miscellaneous/unknown (3%), myelomeningocele (2%), tumor/arachnoidal cyst/aqueduct stenosis (0%). Early shunting and poor functional status was associated with a higher risk for epilepsy. Epilepsy was not influenced by sex, shunt systems, or number of shunt revisions. Twenty-two (12%) of 182 patients developed epilepsy (generalized N=13, focal N=9) after intracranial shunting. Focal EEG abnormalities (N=16) were located mainly at the anatomical site of the shunt (N=14), but only three patients (2%) presented with focal seizures contralateral and focal EEG abnormalities ipsilateral to the site of the shunt. The presence of epilepsy was determined by the etiology of hydrocephalus rather than by surgical intervention. The incidence of postoperative epilepsy (12%) was low. Onset of epilepsy, clinical presentation of seizures, and EEG changes did not appear to be valid criteria for identifying shunt-related epilepsy. Thus, epilepsy as a complication of intracranial shunting might be overestimated in the literature.     

Epilepsy in children with shunted hydrocephalus

OBJECT: The incidence of epilepsy among children with hydrocephalus and its relation to shunts and their complications, raised intracranial pressure (ICP), and developmental outcome are explored in a retrospective study. METHODS: The authors studied a series of 802 children with hydrocephalus due to varying causes, who were treated by ventriculoperitoneal shunt placement between 1980 and 1990, with a mean follow-up period of 8 years. Patients who had tumoral hydrocephalus and those whose files lacked significant data were excluded. Data extracted from medical records, including history of the hydrocephalus and history of seizures, if any, were analyzed. Thirty-two percent of the children had epilepsy, the onset of which frequently occurred at approximately the same time that the diagnosis of hydrocephalus was made. The majority of the affected children had severe uncontrolled epilepsy. The incidence of epilepsy was significantly affected by the original cause of the hydrocephalus. The presence of radiological abnormalities was also found to be a significant predictor of epilepsy. Similarly, shunt complications predisposed to epilepsy. Episodes of raised ICP related to hydrocephalus or in association with shunt malfunction may also predispose to epileptic seizures. Furthermore, the presence of a shunt by itself seems able to promote an epileptogenic focus. Finally, epilepsy appears to be an important predictor of poor intellectual outcome in hydrocephalic children with shunts. CONCLUSIONS: A prospective study is needed to identify clearly and confirm avoidable factors predisposing to seizures in these children so that we can strive to reduce the incidence of these seizures and, subsequently, improve these children's quality of life.     

Cardiac myocyte membrane wounding in the abruptly pressure-overloaded rat heart under high wall stress

A case of perimesencephalic non-aneurysmal subarachnoid haemorrhage is reported. The patient was a 54-year-old women, after spontaneous subarachnoid haemorrhage with negative cerebral angiography. Internal hydrocephalus due to haemorrhage developed and ventriculo-atrial shunt was inserted. Outcome is presented and the possible causes of bleeding are discussed.     

A preclinical trial of iodoantipyrine safety

Intraluminal coagulation of a ventricular catheter followed by its removal and replacement is a technique used for proximal shunt revision. The authors describe experience leaving the original catheter in place when flow of CSF is established by the coagulation. Advantages of this modification include maintenance of ventricular access when the ventricles are small and the possibility of reducing the incidence of subsequent shunt obstruction by mitigating intraventricular hemorrhage caused by catheter removal.     

Antihypertensive therapy in type 2 diabetes mellitus

Fifty-seven patients with failed sclerotherapy received a mesocaval interposition shunt with an externally supported, ringed polytetrafluoroethylene prosthesis of either 10 or 12 mm diameter. Thirty-one patients had Child-Pugh grade A disease and 26 grade B; all had a liver volume of 1000-2500 ml. Follow-up ranged from 16 months to 6 years 3 months. Three patients (5 per cent) died in the postoperative period. There were two postoperative recurrences of variceal haemorrhage and one recurrent bleed in the second year after surgery. The cumulative shunt patency rate was 95 per cent and the incidence of encephalopathy 9 per cent; the latter was successfully managed by protein restriction and/or lactulose therapy. The actuarial survival rate for the whole group at 6 years was 78 per cent, for those with Child-Pugh grade A 88 per cent and for grade B 67 per cent. Small-lumen mesocaval interposition shunting achieves portal decompression, preserves hepatopetal flow, has a low incidence of shunt thrombosis, prevents recurrent variceal bleeding and is not associated with significant postoperative encephalopathy.     

Vascular injury during lumbar disc surgery. Report of two cases; a review of the literature

Iatrogenic vascular injuries are unusual complications of lumbar disc surgery. The incidence of such injuries is very low but probably underestimated because clinical manifestations may be extremely variable depending on the extension of trauma. Diagnosis is suspected when early signs of retroperitoneal haemorrhage appear, but may often be delayed for weeks or years due to formation of a pseudoaneurysm or an arteriovenous fistula which may be of gradual onset and produce initially only a few symptoms. Prompt diagnosis and aggressive treatment can improve the current mortality rate of more than 50%. Two cases are described that illustrate the full spectrum of acute and chronic manifestations of such injuries. One case of acute haemorrhage due to arterial trauma was immediately detected and the other case with arteriovenous fistula was recognized several years post-operatively.     

The role of endoscopic third ventriculostomy in the management of shunt malfunction

OBJECTIVE: To evaluate the effectiveness of third ventriculostomy as an alternative to shunt revision in the management of shunt malfunction and infection in obstructive hydrocephalus. METHODS: All of the clinical notes of 30 patients treated with third ventriculostomy for malfunctioning or infected shunts between January 1, 1974, and December 31, 1996, were retrospectively reviewed. Third ventriculostomy was performed under fluoroscopic control in the first seven patients and endoscopically in the remainder. A successful outcome was achieved if further shunt revision surgery was avoided. The median follow-up duration was 8.7 years RESULTS: Twenty-three patients (76.7%) experienced successful outcomes, resulting in shunt independence. Of the seven failures, three were technical failures at the time of surgery and the remaining four were manifest within a median of 10 days, resulting in shunt revision. There have been no delayed failures. CONCLUSION: Third ventriculostomy is a valuable alternative to shunt revision in patients affected by obstructive hydrocephalus presenting with shunt malfunction or infection. It should be considered in all suitable cases as the first-line treatment for obstructive hydrocephalus of all causes. Because all failures were manifest within a short time, it is likely that these successes will be durable.     

Periventricular leukomalacia

The present knowledge on periventricular leucomalacia is reviewed. Its incidence is about 10% in preterms infants < 32 gestational weeks. By careful ultrasonographic scanning four stages can be distinguished: Prolonged flares, resolution, cystic leucomalacia, ventriculomegaly. Periventricular leucomalacia (PVL) is much more correlated with later neurologic impairment than intraventricular haemorrhage (apart from grade IV). PVL is caused by ischemia of the periventricular white matter mainly due to arterial hypotension and disturbed regulation of cerebral blood flow. The interactions between blood pressure, pCO2, pO2 and cerebral blood flow are complex and poorly understood. Regarding the clinical management it seems important to avoid hypotension, fluctuating pCO2 and hypoxemia/anemia in order to prevent white matter ischemia. Research should be focussed on the development of monitoring methods (doppler sonography, near infrared spectroscopy, time compressed electroencephalography), which allow to detect ischemic events to prevent neurologic impairment in about 1000 preterm infants per year in Germany.     

Treatment of infected ventriculo-atrial shunts

The paper presents the incidence of infection observed in 108 patients subjected to ventriculoatrial shunting at the Department of Neurosurgery, University Medical Centre of Ljubljana. Infection was established in 17 (15.8%) Pudenz's shunts. It is most likely to develop within the first year following the shunt implantation. The most common clinical symptom associated with the shunt infection is an obscure, moderately elevated body temperature (about 38 degrees C) of several weeks duration. The infected shunt should be removed without delay and replaced by external ventricular drainage with an uniflow valve and an added piece for the intraventricular administration of the antibiotic. Before the results of the cerebrospinal fluid and drainage system cultures are known, the Methicillin therapy of 200 mg/kg daily should be initiated and followed by the adequate antibiotic therapy consistent with the culture findings. Should the antibiotic therapy administered by this route fail to control the infection, additional intraventricular instillation is to be instituted.     

Focal dilation and paradoxical collapse of cortical fissures and sulci in patients with normal-pressure hydrocephalus

OBJECT: The authors describe a subgroup of patients with shunt-proven normal-pressure hydrocephalus (NPH) who presented with focal fissural and sulcal dilation on imaging studies. The specific radiological features and methods of differentiating this condition from cortical atrophy are delineated. METHODS: Normal-pressure hydrocephalus has been described as dilation of the ventricles that is out of proportion to the sulci. Sulcal dilation has been taken as evidence of cortical atrophy and has even been used as a criterion to exclude patients from undergoing a shunting procedure. The authors describe five cases of patients with shunt-proven NPH who presented with focal dilation of cortical fissures and sulci. In three of the cases, there was a paradoxical decrease in the size of the dilated fissures and sulci that paralleled the decrease in the size of the lateral ventricles following successful shunting. CONCLUSIONS: This study demonstrates that focal fissural and sulcal dilation may represent reservoirs of cerebrospinal fluid analogous to the ventricular system. Patients should not be denied a shunting procedure solely on the basis of focally dilated fissures of sulci.     

Successful treatment of postoperative right ventricular heart failure with the HIA-Medos-assist system in a 2-year-old girl

Communicating hydrocephalus can be handled either by the ventriculoperitoneal or, occasionally, the ventriculoatrial shunt. The lumboperitoneal shunt is another option. It does not require a transcranial approach; therefore, it is safer for the patient. We describe a technique that can be performed easily by a skilled laparoscopic surgeon through an anterior approach transabdominally. The lumboperitoneal (LP) shunt is placed laparoscopically under direct videoscopic vision, with the catheter inserted transabdominally through the L3 disc space into the thecal sac. In our patient, the lumboperitoneal shunt was placed at the L3 disc space for communicating hydrocephalus. There were no intraoperative or postoperative complications. The LP shunt can be easily placed by a skilled laparoscopic surgeon. The incidence of infection and complications is lower, and the patency rate is higher. This should be the initial choice for communicating hydrocephalus.     

Acute hydrocephalus after iotrolan lumbar myelography

A 33-year-old woman with cryoglobulinaemia developed acute hydrocephalus 20 h after lumbar myelography using the water-soluble contrast medium iotrolan. After a ventricular drainage, she was free of symptoms and the hydrocephalus resolved. The development of acute hydrocephalus after myelography has not been reported previously.     

Complications of lumboperitoneal shunts. A retrospective study of a series of 195 patients (214 procedures)

BACKGROUND AND PURPOSE: We report our experience with the lumboperitoneal shunt (LPS) in 195 patients. The aim of this retrospective study was to assess and compare the rate of complications and to discuss 4 indications. MATERIAL AND METHOD: Between January 1983 and July 1994, 195 patients including 14 pediatric cases were treated with a LPS. Sex ratio was 1.24. The mean age at insertion was 59.5 years (from 6 months to 88 years) and the follow-up in this series was from 6 months to 12.5 years. The indications for a LPS were: chronic idiopathic hydrocephalus (115 cases), post-hemorrhagic hydrocephalus (37 cases), cerebrospinal fluid fistula (11 cases), post-traumatic hydrocephalus (9 cases), post-surgical hydrocephalus (8 cases), hydrocephalus of the child (6 cases), post-meningitis hydrocephalus (4 cases), benign intracranial hypertension (4 cases), post-radiotherapy hydrocephalus (1). Forty patients (20.5%) presented with at least one complication. A total of 47 complications were observed: chronic subdural effusion (8 cases), meningitis (10 cases), mechanical failures (28 cases), acquired Chiari abnormality (1 case). Mechanical complications varied with the type of shunt. CONCLUSION: Complications of LPS in adults are less frequent than is usually reported after ventricular atrial or peritoneal shunting. In adults, LPS can be used as the first valuable treatment in case of chronic communicating hydrocephalus. LPS is also valuable in the treatment of benign intracranial hypertension or recurrent CSF fistulae. Conversely, in the pediatric cases general and specific complications are frequent, so an indication for LPS must be strictly discussed.     

Post-lumbar puncture headache: clinical features and suggestions for diagnostic criteria

The aim of the present prospective study was to describe clinical features of post-lumbar puncture headache (PPH), and to test the validity of the diagnostic criteria of the International Headache Society (IHS). Eighty-eight of the 239 included patients (36.8%) experienced PPH. Females were affected more frequently than males (45.2% vs 21.4%; p < 0.001). First onset of PPH occurred within the first day in 40 patients (53%), within 2 days in 89%, and never after the fourth day. When PPH occurred for the first time on the day the lumbar puncture was performed, it was usually experienced much later in the day (median 14.00 h) than it first occurred on the second day (median 09.30 h) or later. The median duration of PPH was 6 days (range 1-29 days). Patients with headache performed a "Rising Manoeuvre" twice daily as long as the headache period lasted, and recorded pain and time variables. The severity of PPH was negatively correlated to the time till the headache started or worsened upon rising (T1) and the time from the headache started to increase till it reached its maximum (T2), but was not significantly correlated to the time to restitution upon lying down (T3). The results are in good accordance with the leakage theory. T1 varied from immediate onset to 265 min (median 20 sec). T2 (median 30 sec, range 0-60 min) and T3 (median 20 sec, range 0-15 min) varied considerably as well. During the course of PPH, 45% of the patients occasionally reported non-postural headache or no headache when the Rising Manoeuvre was performed. It is suggested that PPH should be diagnosed in any patient who experiences postural headache at least once within 4 days of lumbar puncture.