Comparison between VII-to-VII and XII-to-VII coaptation techniques for early facial nerve reanimation after surgical intra-cranial injuries: a systematic review and pooled analysis of the functional outcomes

Neurosurgical Review - The surgical injury of the intracranial portion of the facial nerve (FN) is a severe complication of many skull base procedures, and it represents a relevant issue in terms...     

Targeted therapy with bevacizumab and erlotinib tailored to the molecular profile of patients with recurrent glioblastoma. Preliminary experience

Background

Advances in comprehension of molecular biology of glioblastoma (GBM) have led to the development of targeted therapies. The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM.

Methods

We prospectively enrolled ten adult patients suffering from recurrent GBM who had undergone surgical resection and standard chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by immunohistochemistry. Normal PTEN status was required for inclusion. Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6-week?cycles); patients whose tumor expressed EGFRvIII (4/10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6-month progression-free survival (PFS-6), and safety profile.

Results

The RR and PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with bevacizumab+erlotinib (n?=?4) and bevacizumab (n?=?6), respectively. In the whole cohort (n?=?10), RR and PFS-6 were both 70 % (7/10); median PFS and overall survival (OS) were 8.0 (3.0–31.0) and 9.5 (5.0–31.0) months, respectively. No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation.

Conclusion

To our knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient’s tumor. Although we treated a limited number of patients, we obtained significantly higher RR and PFS-6 than those reported in a previous trial lacking molecular tumor analysis.     

Motoneurons innervating facial muscles after hypoglossal and hemihypoglossal-facial nerve anastomosis in rats

Hypoglossal-facial nerve anastomosis (HFA) is the most popular surgical procedure to reinnervate facial muscles after injury of the facial nerve. Section of the hypoglossus causes paralysis and atrophy of the hemi-tongue. In the attempt to overcome this consequence, the hemihypoglossal-facial nerve anastomosis (HHFA) has been proposed and only a half of the main trunk of the hypoglossus is connected to the distal stump of the facial nerve. In the rat, we have studied experimentally the anatomical nuclear changes after HFA and HHFA with the aim of establishing the quantitative motoneuron innervation of facial muscles obtained with each one of the two operative options. Horseradish peroxidase (HRP) injected in both types of anastomosis labeled not only hypoglossal motoneurons, but also facial motoneurons. HFA appeared to offer a significant quantitative motoneuron innervation higher than HHFA and then a higher probable better functional recovery. Both HFA and HHFA performed immediately after section of the facial nerve in rats did not result in a phenomenon of motor hyperinnervation. In our experimental model, the proximal facial nerve stump was coagulated at the stylomastoid foramen to avoid regeneration. Then, the labeled motoneurons into the facial nucleus could really be the expression of axonal projections from facial motoneurons to the hypoglossus nerve and facial muscles. No labeled motoneurons were seen contralaterally as we observed previously after section and repair of several nerves.     

Simultaneously occurring tumours within the same cerebello-pontine angle: refining literature definitions and proposal for classification

We report on an unusual case of a patient, not affected by neurofibromatosis, harbouring two radiologically spatially contiguous tumours within the same cerebello-pontine angle. Pathological findings were consistent with the diagnosis of two spatially distinct primary tumours, namely a meningioma and a schwannoma. We proposed a classification of tumours occurring at the same location consistent with the different spatial arrangement and histological nature of these conditions. The correct classification of these nosological entities will allow further more accurate evaluations of these cases in order to clarify the pathogenesis, prognosis and best treatment of each one.     

Comparison of combined anterior–posterior and posterior-only approaches for lumbosacral chordomas: a systematic review and meta-analysis of surgical and clinical outcomes

Lumbosacral chordoma is a slow-growing but locally aggressive tumor, resistant to adjuvant treatments and endowed with dismal prognosis. Surgery is the mainstay of treatment but the choice of surgical approach (the posterior-only approach or the combined anterior–posterior approach) remains an open question due to the need of both pursuing a surgical radicality and preserving the neurologic function. The aim of the study was to compare the surgical and clinical outcomes of these approaches in the management of lumbosacral chordomas. A systematic review and meta-analysis in agreement with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines of papers comparing the outcomes of the two approaches was performed. Ten papers met the inclusion criteria. The combined anterior–posterior approach was more frequently performed for tumors with an upper level beyond S2 (p?=?0.012). The 5-year progression-free survival was significantly higher in posterior-only approach compared with the combined anterior–posterior approach (44.7% vs 27.1%, p?=?0.049). Adjuvant radiotherapy was added more frequently after a posterior-only approach (p?=?0.036) and the rate of complications was significantly lower after a posterior-only approach (p?=?0.040). No significant differences in sex, age, tumor diameter, entity of resection, and overall survival were observed. Posterior-only surgical approach may be a reasonable option for lumbosacral chordoma, being associated with comparable entity of surgical resection, reduced complication rate and increased 5-year progression-free survival rate as compared with combined anterior–posterior approach.

     

Long survival in an untreated solitary choroid plexus metastasis from renal cell carcinoma: case report and review of the literature

Brain metastases from renal cell carcinoma (RCC) are rare. Among them, the metastases localized only in the choroid plexus are exceptional and only six cases are reported in the literature. Here we report on a patient with a single choroid plexus metastasis from RCC which presented an unusual biological behaviour. For several years, such metastasis was interpreted as a benign intraventricular tumor and was not treated. Four years after the initial neuroradiological evidence, because of the appearance of symptoms, the brain metastasis was excised. We think that this unusual biological behaviour of the tumor determined the late inset of the neurological symptoms, despite the location at the choroid plexus that usually leads to an early obstructive hydrocephalus. To our knowledge, this 46months survival is the longest survival of a patient affected by a single choroid plexus metastasis from RCC.     

Pathology of the peripheral nervous system

This review deals with papers on important topics in peripheral nerve surgery. Some new diagnostic tools and microsurgical procedures are brought to the attention of neurosurgeons. The first four papers are related to new surgical strategies in treating brachial plexus injury (BPI), particularly root avulsion. Concepts based on experimental studies are applied to clinical practice. Re-establishment of the continuity of interrupted spinal roots or reimplantation of the avulsed spinal roots into the spinal cord are attempted. The authors demonstrate how computed tomography (CT) myelography can be used to plan surgical treatment correctly. The use of reinnervated free-muscle transfer after complete brachial plexus C5-T1 root avulsion is described and critically evaluated. The results obtained after repair of interrupted spinal roots or reimplantation of avulsed spinal roots into the spinal cord are not as clear as described by the authors. Further experimental studies and surgical outcomes are necessary before accepting the efficacy of such surgical procedures in BPI. Reinnervated free-muscle transfer appears to be a promising method for treating such severe lesions. The fifth paper is a case report in which the trapezius branch of the spinal accessory nerve was neurotized with the dorsal branch of the third cervical nerve. This procedure was performed after an injury to the spinal accessory nerve in the neck. The proximal stump of the spinal accessory nerve was available only intracranially. Using this procedure, the risk related to an intracranial approach to the spinal accessory nerve is avoided. A review of one case of primitive neuroectodermal malignant tumor of the median nerve is used to discuss some controversies related to the treatment of malignant tumors involving peripheral nerves.