The pharmacokinetics of p-Boronophenylalanine.fructose in human patients with glioma and metastatic melanoma.

PURPOSE: To study the biodistribution of p-Boronophenylalanine in patients undergoing surgery for intracranial tumors or metastatic melanoma. METHODS AND MATERIALS: D,L-p-Boronophenylalanine was administered as boronophenylalanine.fructose in an intravenous bolus 1-4 h before the operation. Blood samples were collected for 24 h from the time of administration of the compound, and the blood boron elimination parameters were determined. For the glioma patients tumor samples were obtained and skin, dura, periosteum, and surrounding brain samples were collected whenever possible. For the metastatic melanoma patients tumor, fat, skin, and muscle were collected. Determination of the boron content was performed using inductively coupled plasma-atomic emission spectrometry. Twelve melanoma patients and six glioma patients participated in the study. The melanoma patients included four cases of cutaneous metastatic melanoma, six cases of metastatic melanoma to the lymph nodes and two cases of cerebral metastasis. RESULTS: The results for the metastatic melanoma patients are encouraging with an average tumor:blood boron concentration ratio and standard deviation of about 4.4 +/- 3.2 and a maximum value of 10 for the cerebral metastasis. The glioma patients involved high grade glioma for which the tumor:blood ratio was 2.2 +/- 1.2. CONCLUSION: The tumor:blood ratios for melanoma fulfil requirements for epithermal boron neutron capture therapy for cerebral melanoma metastases, whereas those for high grade glioma do not.

Endoscopic third ventriculostomy.

Long-term extracranial shunting for hydrocephalus has numerous drawbacks related to shunt malfunction and infection. In some cases outcome has been very disappointing. We successfully managed 5 patients with acquired aqueductal stenoses with no significant morbidity by the use of an intracranial cerebrospinal fluid diversion, namely a third ventriculostomy. First advocated by Dandy, ventriculostomy was largely passed over in favor of extracranial procedures. With improved surgical techniques, however, ventriculostomy is now considered to be a viable alternative in selected cases. In a further 19 patients, we subsequently broadened our patient selection to include those with Arnold-Chiari malformations, congenital noncommunicating hydrocephalus, and tumors. Two thirds of these children remain without shunts and apart from 1 child developing hemiplegia postoperatively, there has been no significant morbidity. Although the best results have been seen in the late onset groups, even early onset, noncommunicating hydrocephalus has been successfully managed. Even in patients in whom third ventriculostomy has failed and who have subsequently required ventriculoperitoneal shunts, we anticipate that they will remain less dependent on shunts because their hydrocephalus is now communicating, which tends not to have such a rapid onset or extreme levels of raised intracranial pressure.

Third ventriculostomy for shunt infections in children.

Four children with extracranial shunts for noncommunicating hydrocephalus suffered from recurrent or intractable shunt infections. All patients were resistant to or relapsed after treatment with intravenous and intrathecal antibiotics with change of the shunt apparatus. They were treated with neuroendoscopic third ventriculostomy and the removal of all implants, except for a reservoir in one patient. That child later had the reservoir removed because of persistent proteus infection. All patients received antibiotics for approximately 2 weeks after the operation. There was no morbidity associated with the procedure, and all patients remain shunt independent with follow-up periods of 21 to 46 months (mean, 33 mo), although one has needed another third ventriculostomy. We have shown that third ventriculostomy is a successful surgical intervention for the management of shunt infections in patients with noncommunicating hydrocephalus.

Neuroendoscopic third ventriculostomy. A practical alternative to extracranial shunts in non-communicating hydrocephalus.

The outcomes in 103 patients who have undergone third ventriculostomy for non-communicating hydrocephalus at our institution form 1978-1994 have been analysed. The group has been sub-divided by age, cause of hydrocephalus and whether the third ventriculostomy was the initial definitive procedure or whether progression of their hydrocephalus had been arrested for a long time (usually years) by an extracranial shunt prior to third ventriculostomy. At the time of shunt malfunction (usually blockage) a third ventriculostomy was performed if the anatomy was, or could be made suitable for the safe performance of the procedure. Third ventriculostomy under the age of 6 months was successful in only 8 of 25 patients. Seventeen patients in whom the onset of hydrocephalus was under the age of six months and the ventriculostomy was performed between 6 months and 18 years, 8 were successful. Sixteen of these had had previous long term shunts. In 40 patients in whom the onset of hydrocephalus was over the age of 6 months and the ventriculostomy performed after the age of 19 years, 32 were successful. In 28 patients over the age of 20 years, 13 had previously been shunted and in 8 of these the procedure was successful. In 15 patients not previously shunted, 9 ventriculostomies were successful. Three failed, 2 died before evaluation could be done and one was lost to follow-up. There were no deaths caused by the procedure. Two patients suffered from a hemiparesis, (1 transient) 1 patient suffered mid-brain damage. There were 2 subdural effusions. Two patients had infections, 1 superficial and 1 a ventriculitis.

Hydromyelia and Chiari malformation in children and adolescents.

A series of 24 patients with Chiari malformation and hydromyelia, treated at the Prince of Wales Children's Hospital between 1975 and 1991, is reviewed. The age range of these patients was 3 to 19 years. Eleven had a Chiari 1 malformation and 13 had a Chiari 2 malformation. The follow-up period ranged from 6 months to 16 years with a mean of 5 years. Twenty-one patients had posterior fossa decompression procedures as the primary treatment, with or without plugging of the central canal at the obex. Forty-five per cent of the Chiari 1 patients and 62% of the Chiari 2 patients showed sustained neurological improvement. A further 36% of the Chiari 1 patients and 15% of the Chiari 2 patients had their neurological deficits stabilised. Following operation, sustained radiological collapse of the cavity occurred in 9 out of the 11 cases of Chiari 1 malformation. The follow-up radiology in the Chiari 2 patients has been incomplete. Complications following posterior fossa procedures with plugging of the central canal were transient and there has not been long-term morbidity. Posterior fossa decompression, fourth ventriculostomy, obex plugging and dural grafting is recommended in those cases where the surgical anatomy allows dissection of the tonsils from the brainstem. Plugging of the central canal at the obex is of value if the muscle plug is firmly secured.

Third ventriculostomy for hydrocephalus associated with spinal dysraphism: indications and contraindications.

Twenty-five patients have undergone this procedure at our unit. These constitute 25% of our total experience with endoscopic third ventriculostomy (4). In the patients under 6 months of age, only one out of 11 patients has had a successful long-term result despite initial good fenestration of the floor of the third ventricle. These patients were selected on the basis of their adequate third ventricular size and a relatively slowly progressive hydrocephalus. Fourteen patients had a ventriculostomy performed instead of shunt revision. In 13 patients this has been a success long term. All of these patients had a Heyer-Schulte valve with antisiphon device installed for months, or more often, years, prior to the third ventriculestomy. We believe that the difference in these two groups is due to a very poor cerebrospinal fluid(CSF)-resorptive capability in patients immediately after back closure due to the prior venting of CSF into the amniotic sac. The absorptive capacity seems to improve with the passage of time in our patients who have had a shunt system that maintains a relatively normal intracranial pressure and thus contributes to the development of the patient's CSF-absorptive system.

The current status of endoscopic third ventriculostomy in the management of non-communicating hydrocephalus.

Improvements in the technology have made endoscopic third ventriculostomy safer than earlier technics of open third ventriculostomy as described by Scarf (14). Similarly, it is safer than the stereotactic technics used by Pierre-Kahn (10), Sayers (13), and Hoffman (4). The morbidity and mortality have decreased and the effectiveness has also increased (12, 15). Modern operations are based on Guiot's technique (2). In the management of hydrocephalus third ventriculostomy has to be compared with the treatment with intracranial shunts. Currently in our hands the procedure has a higher morbidity rate than a shunt operation. Our figures include those from our early experience (5)--more recent figures show a lower complication rate. We believe the higher morbidity is acceptable as the chance of being permanently cured is 80% in favourable cases.

Experimental neurogenic disorders of the bladder after section of cauda equina.

Changes in the cystometric pattern and urethral pressure profile after surgical section of the cauda equina have been studied in a group of 20 monkeys (Macaca nemestrinal). The experimental autonomous bladder was characterised by tonic response to filling and with variable urethral dribbling incontinence but without co-ordinated detrusor activity. This pattern developed despite previous urinary diversion to prevent inadvertent overstretch of the bladder. Deliberate "overstretch" of the autonomous bladder was not followed by loss of tonus but was associated with the development of high amplitude regular detrusor contractions which were superimposed upon a steep rising filling cystometrogram. With urinary diversion the resting urethral pressure profiles were preserved after division of the cauda equina but were lower in amplitude after overstretch of the autonomous bladder.

Experimental evaluation of the urethral response to section of the spinal cord or cauda equina and to the electrostimulation of the bladder in non-human primates.

Studies of urethral function in 32 female monkeys indicate a dual innervation of the mid-urethra from sympathetic and somatic supply. The resting urethral pressure profiles were preserved after low level section of the spinal cord or division of the cauda equina. They had lowered amplitude after overstretch or electrostimulation of the autonomous bladder.

Results of ulnar neuropathy at the elbow treated by decompression or anterior transposition.

A retrospective study was conducted on 148 patients with ulnar neuropathy at the elbow, who underwent surgical treatment between 1981 and 1989. Of the 178 nerves operated on, 105 underwent subcutaneous anterior transposition, and 73 were decompressed without transposition. We compared the surgical results of these two groups, and factors influencing prognosis. Overall, 92% of patients improved postoperatively. Pre-operatively, electrophysiological assessment corresponded well to clinical findings, and to macroscopic findings at operation in 95% of cases. The severity of pre-operative clinical findings, advancing age, duration of symptoms and the presence of intraneural fibrosis did not predict an adverse outcome. A satisfactory outcome in 72% of those decompressed compared with 60% of those who were transposed was not statistically significant. However, there was a lower percentage of those with unsatisfactory results in the decompressed series. Thus, we advise that, except where there is persistent deformity or a mass lesion in the region of the ulnar groove, decompression is the operation of choice.

Experience with multiple intracranial haematomas in New South Wales.

A retrospective survey of head injuries in NSW in 1977 and 1978 was conducted by the Trauma Subcommittee of the Neurosurgical Society of Australasia. This paper describes the findings for 129 patients who had more than one significant intracranial haematoma. Overall, the case fatality rate for these patients was 85%. The presence of low or fluctuating blood pressure was associated with a significantly higher mortality than in the rest of the group. Bilateral reacting pupils or an improvement in level of consciousness following decompressive surgery carried a more favourable prognosis. There was 100% fatality if surgery was not carried out or if the bleeding was not found at operation. A subset of patients who died was selected on the basis of a calculated prognostic variable, and compared with a similar subset of survivors. A higher proportion of patients who died had a delay in the provision of definitive treatment and failure to correct shock. This comparison was made on two criteria. Using the first accepted optimal treatment in 1984, nearly all cases were treated suboptimally, as might be expected. Using the second, acceptable treatment in 1977-78, it was calculated that between nine and 12 patients died with MIH in NSW in the 2 years of the survey, whose deaths might have been prevented.

Experience with acute subdural haematomas in New South Wales.

A retrospective survey of head injuries in NSW in 1977 and 1978 was conducted by the Trauma Subcommittee of the Neurosurgical Society of Australasia. Two hundred and ninety patients, who were found to have acute or subacute subdural haematomas, were considered. The mortality rate was 76%, with 19% making a satisfactory recovery. Several factors were found to produce significant improvement in outcome. The availability of neurosurgical facilities at the time of admission made a significant difference. Those patients who had decompressive operations also fared better. No patient survived without operation. Shock, defined as a systolic blood pressure lower than 90 mmHg for more than 60 min was associated with significantly increased mortality. The chance of developing a significant hypotensive episode was greater if two or more other parts of the body were injured. If three other areas were injured, the mortality was 100%. A case control study suggested that some 35 (16%) of all deaths could have resulted from preventable causes, notably delay in instituting definitive treatment and/or inadequate treatment of shock.

Preventable causes of death and disability from neurotrauma.

Preventable causes of death and disability have been studied retrospectively in a series of 1161 cases of neurotrauma occurring in New South Wales in 1977-78, and prospectively in 153 cases of neurotrauma occurring in country districts in South Australia in 1981-82. In the first study, it was found that at least 80 deaths could be attributed to preventable causes; chiefly, transfer to an inappropriate hospital and/or delay in instituting treatment. Apparent failures in initial management of shock and airway obstruction were evident in this study and also in the South Australian study, which identified major deficiencies in cardiorespiratory management in 7% of cases transferred from country areas. These studies confirm that there is a need for better training, at all levels, in the management of neurotrauma. They also provide powerful arguments for the concept of an integrated regional trauma service.

Epidemiology and clinical outcomes of neurotrauma in New South Wales.

This study of 1161 neurotrauma patients in New South Wales hospitals was designed to examine the role of preventable causes of death and disability in cases of spinal injury, extradural, subdural and multiple intracranial haematomas in order to make recommendations for improvements in accident, emergency, ambulance and hospital services. Methods have been developed for standardizing diagnosis in different classes of hospital for the assessment of severity in terms of the patient's age, sex, physical signs, head and spine injuries and other injuries. Estimates have been made of the number of preventable deaths by a case control study of each category of neurotrauma under study.