Post-traumatic hydrocephalus.

BACKGROUND: Surgical treatment of ventricular dilatation following severe head trauma (GCS <8) remains controversial due to the difficulty to distinguish brain atrophy-related ventriculomegaly from active, symptomatic ventricular dilatation. Consequently, the reported incidence of post-traumatic hydrocephalus in literature varies greatly from 0.7-29%. The presence of ventricular dilatation following severe head trauma should be considered and demands investigation, based also on satisfactory results obtained with cerebrospinal fluid (CSP) shunting, METHODS: Ninety-eight patients with post-traumatic hydrocephalus undergoing CSF shunting were selected for this study among 4,044 patients with severe head trauma treated from 1972 to 1999 at the Department of Neurosurgery at the City Hospital of Verona. Patients included 82 (84%) males and 16 (16%) women, ranging from one month to 83 years (mean age; 39 years). In 24 (24%) cases, the brain trauma lesion was single, while in 74 (76%) cases the patient suffered multiple cranio-cerebral lesions. The total number of lesions was 230 including 214 (93%) supratentorial and 16 (7%) posterior cranial fossa (PCF) lesions. Seventy-nine operations were performed on 59 (60%) patients. The onset of hydrocephalus was immediate after trauma in 14 (14%) cases, whereas a delayed onset was observed within 30 days in 44 (45%) cases, between one-four months in 30 (31%) cases and between four-six months in 10 (10%) cases. Of the 98 patients in this study, 15 were treated with an external CSF shunt and 83 underwent internal CSF shunting. RESULTS: Long-term results of the 15 patients with external shunts demonstrated good recovery in 13% while 87% of cases resulted in death. In the 83 cases of internal shunts, despite severe preoperative conditions (75% in coma or persistent coma), the results were as follows: good recovery in 37 (45%) patients, partial disability in nine (11%), persistent coma in 29 (35%) and death in seven (8%) cases. CONCLUSIONS: Post-traumatic hydrocephalus is a complication that must always be considered in cases of severe head trauma (GCS <8) in young patients presenting added neurological deficits, ceased clinical improvement (ceased improvement after initial improvement), increased hypertonia, surgical flap tension or CSF accumulation. The results of this study suggest the necessity to treat post-traumatic ventricular dilatation with aggressive surgery and CSF shunting, based on favorable outcome seen even in coma and persistent coma patients.

Early onset of lipid peroxidation after human traumatic brain injury: a fatal limitation for the free radical scavenger pharmacological therapy?

BACKGROUND: On the basis of the contradiction between data on experimental head trauma showing oxidative stress-mediated cerebral tissue damage and failure of the majority of clinical trials using free radical scavenger drugs, we monitored the time-course changes of malondialdehyde (MDA, an index of cell lipid peroxidation), ascorbate, and dephosphorylated ATP catabolites in cerebrospinal fluid (CSF) of traumatic brain-injured patients. METHODS: CSF samples were obtained from 20 consecutive patients suffering from severe brain injury. All patients were comatose, with a Glasgow Coma Scale on admission of 6 +/- 1. The first CSF sample for each patient was collected within a mean value of 2.95 hours from trauma (SD=1.98), after the insertion of a ventriculostomy catheter for the continuous monitoring of intracranial pressure. During the next 48 hours, CSF was withdrawn from each patient once every 6 hours. All samples were analyzed by an ion-pairing high-performance liquid chromatographic method for the simultaneous determination of MDA, ascorbic acid, hypoxanthine, xanthine, uric acid, inosine, and adenosine. RESULTS: In comparison with values recorded in 10 herniated-lumbar-disk, noncerebral control patients, data showed that all CSF samples of brain-injured patients had high values (0.226 micromol/L; SD=0.196) of MDA (undetectable in samples of control patients) and decreased ascorbate levels (96.25 micromol/L; SD=31.74), already at the time of first withdrawal at the time of hospital admission. MDA was almost constant in the next two withdrawals and tended to decrease thereafter, although 48 hours after hospital admission, a mean level of 0.072 micromol/L CSF (SD=0.026) was still recorded. The ascorbate level was normalized 42 hours after hospital admission. Changes in the CSF values of ATP degradation products (oxypurines and nucleosides) suggested a dramatic alteration of neuronal energy metabolism after traumatic brain injury. CONCLUSIONS: On the whole, these data demonstrate the early onset of oxygen radical-mediated oxidative stress, proposing a valid explanation for the failure of clinical trials based on the administration of oxygen free radical scavenger drugs and suggesting a possible rationale for testing the efficacy of lipid peroxidation "chain breakers" in future clinical trials.

Nosocomial candidemia in non-neutropenic patients at an Italian tertiary care hospital.

In a retrospective study conducted in an Italian tertiary care hospital, the incidence of nosocomial candidemia was evaluated together with causative pathogens, treatment, and risk factors for death. Over a 6-year period (1992-1997), a total of 189 episodes of candidemia occurred in 189 patients (mean age 58+/-19 years), accounting for an average incidence of 1.14 episodes per 10,000 patient-days per year. The most common reasons for hospitalization were solid neoplasia (21%), trauma (17%), abdominal diseases requiring surgery (13%), and cardiovascular diseases (13%). No patient was neutropenic within 3 weeks prior to the onset of candidemia. One hundred thirty patients were hospitalized in intensive care units, 47 patients in surgical wards, and 12 patients in medical wards. Candida albicans was the most frequently isolated pathogen, accounting for 54% of fungal isolates, followed by Candida parapsilosis (23%), Candida glabrata (7%), Candida tropicalis (5%), Candida pelliculosa (4%), Candida lusitaniae (1%), Candida humicula (1%), and other non-albicans Candida spp. (5%). Seventy-six (41%) patients received adequate antifungal therapy. Seventy-one (58%) of the 123 evaluable patients with central venous catheters underwent line removal; 51 of them had catheter-related candidemia. The 30-day crude mortality rate was 45%. Older age, hospitalization in an intensive care unit, a longer duration of candidemia, retention of central lines, and inadequate antifungal therapy were significantly associated with poor outcome. In the present study, nosocomial candidemia was a frequent and relatively underestimated illness. Adequate antifungal therapy and central line removal independently reduced the high mortality of the disease.

Persistence of E2A/PBX1 transcripts in t(1;19) childhood acute lymphoblastic leukemia: correlation with chemotherapy intensity and clinical outcome.

The occurrence of t(1;19) translocation was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) for the E2A/PBX1 hybrid message in a panel of 37 consecutive childhood acute lymphoblastic leukemias (ALLs). Three patients with B-precursor ALL were found to be positive at diagnosis and were re-tested during follow-up to assess the presence of minimal residual disease (MRD). Two of them became PCR-negative during treatment, whereas one remains positive 3 years after diagnosis. Since all three patients are presently in clinical and hematological complete remission, PCR detection of persistent E2A/ PBX1 transcript does not seem to affect significantly the DFS at 3 years. However, the predictivity for an eventual late relapse still remains to be assessed.

[Toxicity of high dose methotrexate repeated infusions in children treated for acute lymphoblastic leukemia and osteosarcoma]. / Tossicità da infusioni ripetute di methotrexate ad alte dosi in bambini trattati per leucemia linfoblastica acuta ed osteosarcoma.

We evaluated and compared hematologic, hepatic and renal cumulative toxicity of high dose methotrexate (HDMTX) repeated courses in two groups of pediatric patients: 22 patients affected by "non B" acute lymphoblastic leukemia (ALL) treated, in consolidation phase, with four courses of HDMTX 5 g/mq given intravenously over 24 hours infusion (for a total of 88 courses) according to the Italian Cooperative Protocols AIEOP LLA-88; 18 patients affected by non metastatic osteosarcoma of extremities (OST) treated, in preoperative and postoperative phases, with five courses of HDMTX 8 g/mq given intravenously over 6 hours infusion (for a total of 90 courses) according to CNR-NEO 2 protocol. Severe myelosuppression (neutropenia < 500/microliters and/or thrombocytopenia < 25000/microliters) was more frequently observed in ALL (7% of infusions) than in OST (3%). Hepatotoxicity (serum transaminase elevation > 350 IU/l) was significantly more frequent (p < 0.001) in OST (32% of courses) than ALL (6%). Nephrotoxicity was assimilable in the two groups and the elevation of serum creatinine was never higher than 1.9 mg/dl. We did not observe any increase of hematologic, hepatic and renal toxicity following the HDMTX courses repetition.

Distribution of TP53 mutations among acute leukemias with MLL rearrangements.

Acute leukemias carrying MLL rearrangements are characterized by a high degree of clinical and immunologic heterogeneity, as demonstrated by variability in their immunophenotype, consistent with lymphoid or myeloid/monoblastic derivation, as well as their occurrence in distinct age groups from infancy to adulthood. Recently, it was shown that inactivation of the TP53 tumor suppressor gene occurs frequently in cases of acute lymphoblastic leukemia carrying MLL rearrangements. In order to assess the extent of TP53 inactivation throughout the immunophenotypic and clinical spectrum of MLL+ acute leukemias, we tested for TP53 mutations 29 cases of MLL+ acute leukemias displaying lymphoid (13 cases) or myeloid/monoblastic (16 cases) features and belonging to different age groups. Mutations were detected in 6/16 myeloid/monoblastic cases and in 3/13 lymphoid cases. Among myeloid/monoblastic leukemias, the TP53 mutations occurred in 3/4 infants, but only in 3/16 cases in other age groups. Overall, our data suggest that (1) TP53 inactivation is a relatively common event in leukemias with MLL rearrangements irrespective of the leukemic phenotype and of the patients' age; (2) at least two genetic lesions (i.e., MLL rearrangement and TP53 mutation) have accumulated in the short time (few weeks after the birth or conception of the child) corresponding to the development of acute leukemias of infancy.

Pre-B acute lymphoblastic leukemia in a patient with partial lipodystrophy and acanthosis nigricans.

In patients with lipodystrophies a post binding defect in insulin action has been described involving phosphorylation of the beta subunit of the insulin receptor, suggesting the presence of a genetically determined defect in insulin action; the receptor gene has been mapped to the distal short arm of chromosome 19 close to the break-point of a specific chromosome translocation frequently found in pre-B Acute Lymphoblastic Leukemia (ALL). We report on a 13 years old female patient with partial lipodystrophy, acanthosis nigricans and insulin resistance who developed a pre-B ALL. Since lipodystrophy and pre-B ALL are rare disorders, a possible causal relationship between the two diseases is suggested possibly mediated by a mutation in the insulin receptor gene.

[Acute lymphoblastic leukemia in adolescents]. / Leucemia linfoblastica acuta negli adolescenti.

Age is an important prognostic factor in acute childhood lymphoblastic leukemia (ALL): intermediate age children (1-9 years) show a better outcome than infants (0-1 year) and adolescents (10-15 years). However recent literature data do not agree about adolescents worse prognosis. We tried to contribute to this issue with a retrospective analysis about presenting features and survival of 302 pediatric patients (65 adolescents and 237 children) with non B ALL enrolled on AIEOP protocols at the Departments of Pediatric Haematology-Oncology (University of Turin) from 1976 to 1992. The last follow up was 30.11.94. We found in adolescents, in spite of higher frequency of unfavourable prognostic factors (Hb > 8 g/dl, mediastinal mass, T cell immunophenotype, L2 morphology), an event free survival similar to children (EFS 52% vs 51%). In conclusion in our population we found that age at diagnosis greater than 10 years does not represent an unfavorable prognostic factor.

Acute lymphoblastic leukemia in a girl treated for osteosarcoma.

Acute lymphoblastic leukemia (ALL) was diagnosed in a 13-year-old girl who had been treated previously for osteosarcoma of the left distal femur (23 months after her first cancer onset and 12 months after the end of treatment). The patient started chemotherapy for ALL and achieved complete remission; she is in continuous complete remission 5 years after the diagnosis of secondary ALL and 7 years after the onset of osteosarcoma.

Efficacy of tropisetron (Navoban) in controlling emesis induced in children by anti-cancer therapy.

AIMS AND BACKGROUND: High doses of metoclopramide are contraindicated to prevent chemotherapy-induced emesis in pediatric patients, since the incidence of extrapyramidal reactions is increased in these patients. The aim of this small study was to evaluate the antiemetic activity and the safety of tropisetron (a new selective antagonist of 5-HT3 receptors) in children who suffered nausea and vomiting during previous chemotherapy courses, despite the administration of an anxiolytic agent (hydroxyzine hydrochloride). METHODS: The children with a malignant neoplasm were treated for emesis with tropisetron (5 mg o.a.d. or b.i.d.) during a total of 20 cycles of chemotherapy with carboplatin combined with other antitumor agents. RESULTS: In 14 cycles (70%), there was no vomiting. There were two or less episodes of vomiting in 2 cycles (10%), 3-4 episodes in 2 cycles (10%), and no inhibition of vomiting at all in 2 cycles (10%). In 8 cycles there were no episodes of nausea (40%), in 5 cycles (25%) there were episodes of moderate nausea, and in 4 (20%) there were episodes of severe nausea. One child had a mild headache during one cycle and moderate hypotension during another. CONCLUSIONS: The results suggest that tropisetron is both efficacious and safe for the treatment of pediatric patients.

[Lipidemic alterations in a child with acute lymphoblastic leukemia in treatment with L-aspariginase]. / Alterazioni lipidiche in una bambina affetta da leucemia linfoblastica acuta (LLA) in trattamento con L-asparaginasi.

The case of a child treated for Acute Lymphoblastic Leukemia (LLA) with high-dose L-asparaginase, (HD L-ase) presented alteration who of lipidemic values (rise of total cholesterol and triglyceride values) without toxicity is described. This finding has previously been reported in only a few patients. Parameters normalized with dietetic regimen. The authors underline the importance of the control, in patient during HD L-ase treatment of lipidic values too, especially when parents also have similar alterations.

Rebleeding, ischaemia and hydrocephalus following anti-fibrinolytic treatment for ruptured cerebral aneurysms: a retrospective clinical study.

350 patients with subarachnoid haemorrhage from aneurysmal rupture--admitted in the years 1966-1983--were selected for a retrospective controlled study on the efficacy of antifibrinolytic therapy (AFT). Patients treated with antifibrinolytics were divided into two groups, according to the day of hospital admission and onset of therapy, respectively between 0 and 3 days (SG 1) and between 4 and 7 days from SAH (SG 2); treated patients (260 cases) received i.v. tranexamic acid (6 gr/day) for at least two weeks. Patients admitted before 1974, not receiving antifibrinolytics (90 cases), were selected as controls and divided into two groups (CG 1 and CG 2), according to the day of admission. In the first study group (admission 0-3 days) the rebleeding rate within 2 weeks was 9% versus 23% in controls (p less than 0.01). The incidence of rebleeding within 3 and 4 weeks was also significantly lower (p less than 0.05) than in controls. No significant difference was observed in the rebleeding rate in treated and untreated patients with late admission (4-7 days). Mortality from rebleeding was 16% in the first study group versus 17% in controls; in the second study group the figure was 6% versus 8% in controls. Seventy-five cases of ischaemic disorders (29%) were registered in treated patients versus 13 cases in controls (14%; p less than 0.01). Thirty-seven patients receiving AFT (14%) developed significant ventricular dilatation requiring shunt insertion, versus one patient in the control groups (1%; p less than 0.001). Final outcome was similar in the 4 groups. In conclusion--according to our data--AFT modifies the behaviour of rebleeding and the patients' course, although it does not modify the outcome after SAH. Clinical use of antifibrinolytic therapy appears still justified in those patients who cannot be operated on in the acute stage after SAH, provided that an associated anti-ischaemic therapy is undertaken.

Spontaneous disappearance of intracranial arterio-venous malformations.

4 cases of spontaneous disappearance of intracranial arteriovenous malformations are reported. All the malformations were in the rolandic-parietal area, and fed in most cases by the MCA. In one case, the malformation was associated with a proximal aneurysm. One malformation was large, one medium-sized, and two small. Venous drainage was towards the longitudinal sinus in all cases. Presenting symptoms consisted of epilepsy in 2 cases, and intracerebral haemorrhage in 2 cases. Disappearance of the AVM was documented by angiography from 1 to 15 years after diagnosis, and was preceded by a new haemorrhage in 2 cases. Acute or gradual thrombosis of the AVM is suggested as the most likely cause of the disappearance of an AVM. Spontaneous thrombosis of an AVM should be considered as an aspect of the pathological entity known as "thrombosed AVM". Guidelines for the management of patients exhibiting spontaneous disappearance of an AVM are briefly discussed.

Cerebral vasospasm after head injury.

Cerebral vasospasm occurs frequently after head injury. Correlation between neurological deterioration and vasospasm has been reported previously, but delayed neurological deterioration secondary to vasospasm in head injury is a rare occurrence. We report the case of a 57-year-old man who, after a motorcycle accident, developed an acute subdural hematoma and a thick subarachnoid deposition of blood in the left sylvian-insular cistern. After surgical evacuation of the hematoma, the patient improved until the 10th postoperative day, when he developed aphasia and a right hemiparesis. Angiography demonstrated multitapering spasm, and a computed tomographic (CT) scan showed persistence of the cisternal deposition of blood. Despite therapy with hypervolemia, the patient improved only slightly. The association of head injury with substantial subarachnoid hemorrhage producing vasospasm has been considered rarely. Delayed posttraumatic vasospasm secondary to blood degradation products seems to play some role in the vasospasm after head injury. CT scanning may be useful in predicting vasospasm in such patients, and digital subtraction angiography might be useful in demonstrating it.

Indications for the surgical treatment of hydrocephalic dementia.

Eighteen patients with chronic hydrocephalic dementia who had a ventriculo-atrial or ventriculo-peritoneal shunt are reported. The indications for operating on this type of dementia are discussed on the basis of the clinical and instrumental protocol and the postoperative results.

Subdural hematoma secondary to CSF ventricular shunt.

The article reports on 8 cases of subdural hematoma consequent on 94 extrathecal CSF shunts inserted in 1977. Neuroradiolgical postoperative monitoning was carried out by CAT Scan and, where the neurological symptomatology required, cerebral angiography. The percentage of diagnosed subdural hematomas in relation to opening valve pressure, CSF opening ventricular pressure during surgery, and the hydrocephalus etiology, are discussed.

Microsurgical treatment of ten arteriovenous malformations in critical areas of the cerebrum.

Ten cases of arteriovenous malformations located in critical areas of the cerebrum, i.e., motor and speech areas, the insular cortex, the corpus callosum, and the basal ganglia, were treated surgically by radical removal of the lesion. In four of the cases a neurologic examination before surgery was negative; five cases exhibited only mild hemiparesis or dysphasia; only one exhibited hemiplegia and stupor. There were no postoperative deaths and a residual permanent deficit was noted in only one patient. Postoperative control angiograms failed to show any filling of the arteriovenous malformations in any of the cases. Recovery of the ability to work was achieved in all of the patients. The operating microscope and controlled hypotension made possible a precise resection at the edges of the lesion, and damage to surrounding important cerebral structures was thus avoided. Based on these results, microsurgery should be considered as an elective therapy for these kinds of arteriovenous malformations, even when preoperative symptoms are minimal.

Neurological results in spinal cord metastases.

Btween 1971 and 1978 140 cases of spinal metastasis treated by decompression or possible removal of secondary neoplasm, were studied. Patients were divided according to their preoperative neurological conditions and then evaluated on the ground of regression of spinal cord and root symptom. The possibility of treating this type of compressive spinal pathology surgically is discussed.

Paraparesis in hereditary multiple exostoses: case report.

The authors report a case of hereditary multiple exostoses (HME) with neurologic complications, and review the literature. A 23-year-old man exhibited a worsening spastic paraparesis with sphincter dysfunction. The cranial nerves and the exteroceptive and deep sensations were apparently undamaged. The family history, the physical examination, and the systemic radiologic examination revealed all the characteristics of HME. The neurologic complication was caused by an exostosis, arising from the C2 right hemilamina, compressing the spinal cord. The patient quickly improved after a laminectomy.