Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).

Language proficiency predictors of code-switching behavior in dual-language-learning children.

Code-switching, switching between different languages within the same conversation, is a prominent feature in bilingual communication. This study aimed to elucidate to what extent the linguistic abilities and age of dual-language-learning preschoolers influence the frequency and purposes of code-switching (compensatory, to bridge linguistic gaps; preferential, to express content as fluently as possible; pragmatic, to phrase something appropriately for the situation). Parental code-switching ratings of 101 German/French-Turkish/Italian dual-language learners aged 32-78 months were analyzed. Generalized linear mixed models revealed positive but no negative effects of societal- and heritage-language skills on children's code-switching frequencies independent of switching purposes and with no evidence of age effects. Hence, code-switching across the preschool age mainly reflects high linguistic competences. Models with linguistically and psychometrically parallelized language scores indicated a strong switching tendency toward the societal language when proficiency in both languages is high and away from the societal language when language proficiencies are low.

A multidrug combination designed for reversing resistance to BCNU in glioblastoma multiforme.

BACKGROUND: Nitrosoureas constitute the main resource of chemotherapy for glioblastoma. However, because of chemoresistance, which is intrinsic or rapidly acquired after the first administration of chemotherapy, there have been few improvements in survival. Because O(6)-alkylguanine-DNA alkyltransferase (AGT) is the main target for increasing cell sensitivity to the nitrosoureas, we postulated that preexposure to other alkylating agents might increase the therapeutic index of the nitrosoureas by saturating all the copies of AGT present in the tumor cells. OBJECTIVE: To investigate the response rate, toxic effects, time from start of chemotherapy to progression of disease or exit from the study for any reason (TTP), and progression-free survival at 6 months (PFS-6) associated with a multidrug combination that could reverse resistance to carmustine (BCNU) through AGT depletion. METHODS: We conducted a phase 2 study of patients with glioblastoma at first relapse or progression after surgery and standard radiotherapy. Patients were treated with 100 mg/m(2) of procarbazine on days 1 to 5, 80 mg/m(2) of BCNU on days 3 to 5, and 1.4 mg/m(2) of vincristine on day 3 every 8 weeks. RESULTS: Fifty-eight patients were enrolled in the study, and all were assessable for response and toxic effects. Six patients (10.3%) had a complete response, 11 (19%) had a partial response, and 17 (29.3%) had stable disease. The median TTP was 4.8 months; 42.3% of patients had PFS-6, and 15.4% had PFS at 12 months. Response to chemotherapy was the only significant prognostic factor for TTP. Neutropenia was grade 3 in 8.6% of patients and grade 4 in 5.2% of patients, and thrombocytopenia was grade 3 in 17.2% of patients and grade 4 in 12% of patients; hepatic and pulmonary toxic effects were grade 3 in 5.2% and 8.6% of patients, respectively. CONCLUSION: This regimen proved active in chemotherapy-naive patients with recurrent glioblastoma even though toxic effects were substantial.

Spontaneous intracerebral hematomas: a new proposal about the usefulness and limits of surgical treatment.

We analyzed the volume of 132 spontaneous supratentorial intracerebral hematomas calculated with computed tomographic (CT) scans and related it to the clinical condition of the patients on admission and to the outcome at their discharge from the hospital (1 to 3 months after the ictus). Fifty patients were operated on, and 82 received only medical treatment. In evaluating outcome, we were more interested in survival than its quality. The main problem is the evaluation and treatment of the many patients who are comatose upon admission (about half of the patients). We concluded that surgical treatment by evacuation of the hematoma increases the percentage of survival of comatose patients with a hematoma volume between 26 and 85 ml.

Computed tomography of epidural fibrosis after discectomy: a comparison between symptomatic and asymptomatic patients.

The evaluation of patients with symptoms recurrent after disc surgery is a difficult diagnostic problem. The most common causes are recurrent herniation and postoperative scarring; routine x-ray and myelographic differentiation between herniation and scarring is difficult or impossible. High resolution computed tomography (CT) has shown some results in the evaluation of postoperative patients, but the role of epidural fibrosis in failed back surgery syndrome (FBSS) is not clear. Some knowledge of the "normal" CT physiological healing and scarring after disc surgery is necessary. We scanned 20 asymptomatic operated patients and 20 patients with recurrent sciatic nerve pain after disc surgery who did not have bony stenosis, recurrent disc herniation, or other causes of FBSS. Our observations showed no important differences in the fibrosis demonstrated by CT between symptomatic and asymptomatic patients. The degree and type of fibrosis are not related to recurrent symptoms.

Breathing alterations in head injured patients.

Breathing abnormalities in patients affected by acute cerebral damage are herein studied as neurological signs of localizing value for the neurological diagnosis of the level of the lesion. Incidence and types of abnormal breathing pattern correlate with neurological syndromes, and in a given neurological syndrome the presence of these alterations entails a more severe outcome. Tachypnea shows the most significant correlations from a diagnostic and prognostic point of view.

Spontaneous healing of cerebral aneurysm at the beginning of left posterior inferior cerebellar artery (PICA). Case report.

We present the clinical and neuroradiological features of a ruptured aneurysm at the beginning of the left PICA suffering from subarachnoid hemorrhage (SAH). The young patient refused surgery, endovascular treatment and also follow-up. After 4 and 5 years she repeated the left vertebral angiography that showed a spontaneous thrombosis of the aneurysm. After 8 years MR angiogram images confirmed the total obliteration of the aneurysm.

The role of decompressive craniectomy in the treatment of uncontrollable post-traumatic intracranial hypertension.

The benefit of decompressive craniectomy for the treatment of uncontrolled post-traumatic intracranial hypertension seems to be encouraging if medical management fails. We present our experience in 22 cases of cerebral edema due to head trauma. The edema alone was rarely the direct consequence of head trauma. Frequently it was associated with an acute subdural or extradural hematoma and contusion (with or without mass effect). First of all we treated the mass effect of the hematoma and contusion when the diameter was more than 3 cm. Intracranial pressure was monitored in the majority of patients. Bone decompression was performed in the operating theatre depending on the values of intracranial pressure. In our series 41% of patients had a good recovery, 18% a severe disability, 23% a vegetative state and 18% died. The findings showed that the bony decompression must be performed early before the situation becomes irreversible. We suggest that if intracranial pressure values remain greater than 30 mmHg with cerebral perfusion pressure below 70 mmHg, despite vigorous anti-edema therapy, decompressive craniectomy should be considered.

Our experiences in early aneurysm operations: a preliminary report.

Twenty-seven patients affected by ruptured aneurysms and operated on within three days of the first haemorrhage, are presented. At operation 22 patients were graded I-II; a six months follow-up showed a 22% mortality rate. Five patients were graded III-IV at operation and none survived. The results of early operation in our series are examined and discussed. In our opinion it is necessary to know the results of other larger series in order to obtain a final evaluation of early operations on aneurysms.

Effects of disuse and nerve stump length on the development of fibrillation in denervated soleus muscle.

Both in normal (control) and in cordotomized (disused) rats, the soleus muscle was denervated either by cutting the sciatic nerve near the trochanter (proximal denervation) or by cutting the soleus nerve near the insertion into the muscle (distal denervation). In the control muscles, the development of fibrillation was not dependent on the level of nerve section. In disused muscles, the development of fibrillation was greater following distal denervation that following the proximal one.

Pressure monitoring inside Meckel's cave during percutaneous microcompression of gasserian ganglion.

During percutaneous microcompression of the gasserian ganglion for the relief of trigeminal neuralgia, a computerized technique for monitoring the pressure inside Meckel's cave was employed in 22 patients. A dedicated transducer connected to a computer records the balloon inflation pressure. Its variations are discernible within tenths of a bar and are plotted in relation to time. The intraoperative pressure inside Meckel's cave is from 0.9 to 2.4 bars. When pressure was low, there was recurrence of pain. The highest values of pressure (1.9-2.4 bars) were observed in most of the patients suffering from untoward side effects. The clinical results seem to be influenced by the level of the intraoperative intracavitary pressure.

Computed tomography after lumbar disc surgery: a comparison between symptomatic and asymptomatic patients.

The evaluation of patients with recurrent symptoms after lumbar disc surgery, is a difficult diagnostic problem. The causes of failure may include recurrent disc herniation, postoperative scarring, arachnoiditis, spinal stenosis, infection and mechanical instability. The most common causes are recurrent herniation and postoperative scarring; the routine x-ray and myelographic differentiation between them is difficult or impossible. High resolution CT has shown some results in the evaluation of the postoperative patients. It requires some knowledge of CT findings of "normal" pictures of the physiologic healing and scarring after disc surgery. We scanned 30 asymptomatic operated patients and 30 patients with recurrent sciatic nerve pain after disc surgery. From our observations result that it is quite impossible to distinguish "normal" scar from asymptomatic fibrosis. The degree and type of fibrosis are not related to recurrent symptoms.

Sclerosing orbital pseudotumor.

Sclerosing orbital pseudotumor is a particular type of idiopathic inflammatory process, frequently located at the orbital apex. Both from clinical and from instrumental examination the diagnosis of these forms is difficult. The ineffectiveness of steroid treatment and the progressive visual loss in these patients favors surgical exploration. We report on 5 patients who underwent exploration yielding the diagnosis of sclerosing orbital pseudotumor. Surgery allowed correct histological diagnosis and improvement of ocular symptoms.

The transcranial Doppler ultrasonography in the evaluation of vasospasm and of intracranial hypertension after subarachnoid hemorrhage.

The transcranial doppler (T.C.D.) is a non-invasive technique useful for the evaluation of vasospasm and intracranial hypertension in patients with subarachnoid hemorrhage (S.A.H.). Eighteen patients with recent S.A.H. were studied by means of T.C.D. device: in 14 patients the source of bleeding was a ruptured aneurysm of the circle of Willis, while the remaining 4 presented a negative four-vessels angiography. All the patients were studied 5 and 10 days after the bleeding. Our data showed that the ultrasonographic demonstration of vasospasm and/or I.C.H. is clearly related to the clinical status of the patients. No significant T.C.D. difference was noticed between the "sine materia" S.A.H. patients and the ones with ruptured aneurysm.

Chemotherapy in patients with recurrent and progressive central neurocytoma.

BACKGROUND: Recurrent central neurocytoma is very rare and to the authors' knowledge data regarding its response to chemotherapy currently are not available. METHODS: Three patients with progressive neurocytoma received chemotherapy after their informed consent was obtained. Disease recurred in two patients after surgery and radiotherapy and in one patient after surgery. The treatment regimen was comprised of etoposide, 40 mg/m(2)/day, for 4 days; cisplatin, 25 mg/m(2)/day, for 4 days; and cyclophosphamide, 1,000 mg/m(2), on Day 4; this cycle was repeated every 4 weeks. RESULTS: Stabilization of disease was observed in 2 patients and complete remission was observed in 1 patient; at last follow-up, these responses had been maintained for 15 months, 18 months, and 36 months, respectively. CONCLUSIONS: In this small series, this therapeutic regimen led to long term disease reduction, and merits further study.

Intra-operative monitoring by means of somatosensory evoked potentials during cerebral aneurysms surgery.

During cerebral aneurysms surgery, brain tissue may suffer for global or local ischemia due to deliberate hypotension and surgical manoeuvres. Somatosensory evoked potentials (SEPs) can detect functional derangements consequent to hypoxia, before a permanent brain damage is produced. Forty two patients, undergoing cerebral aneurysms surgery for treatment of SAH, were evaluated intraoperatively with SEP recordings. It has been stressed that no permanent neurological damage is to be expected if the absolute value of Central Conduction Time (CCT) does not exceed 9.5 ms for 10 min at least and the cortical waves are visible throughout the whole procedure. SEP changes are strictly related with MAP decrease and surgical handlings.