Renato Conti

Spinal neurinomas: retrospective analysis and long-term outcome of 179 consecutively operated cases and review of the literature

BACKGROUND We present a series of 179 spinal neurinomas consecutively observed at the Department of Neurosurgery at the University of Florence for a period of 30 years (between 1967 and 1997). We decided to limit the retrospective study to obtain at least 5 years of follow-up. Therefore, 20 additional neurinomas treated between 1997 and 2002 were excluded. METHODS All the cases are evaluated under statistical, clinical, neuroradiological, and surgically technical profiles based on data from clinical records and from periodic check-ups after surgery. In particular, the results are analyzed on the basis of an accurate pre- and postsurgical evaluation using Karnofskys scale and Kleklamp-Samiis scoring system. RESULTS We treated 179 spinal neurinomas in 152 (93 male and 59 female) patients. The mean age was 44.3. In 33 cases the neurinoma was sited in the cervical tract, in 59 cases in the dorsal tract, and in 87 cases in the lumbo-sacral tract. Eleven patients harbored Recklinghausens neurofibromatosis (7 NF1 and 4 NF2 of which 1 was intramedullary). In 123 cases the neurinoma was intradural, in 11 cases it was extradural, in 2 intra/extradural, in 9 it had a dumbbell form, and in 2 cases it was intramedullary; the remaining cases had neurofibromatosis. The most common presurgical symptom was segmental pain. Total removal of the lesion was possible in the first operation for 174 neurinomas. We encountered 3 cases of malignant neurinoma of which 1 was in NF2. The result of surgery was recovery in 108 cases; 2 patients with NF2 died, and local recurrence occurred even after total exeresis (excision) and radiotherapy in the cases of malignant neurinoma. CONCLUSIONS Schwannomas represent the most frequent tumor lesions of the spine with prevalence for the cervical-inferior tract and the dorso-lumbar passage. Intramedullary neurinomas are rarely observed. The total surgical removal of neurinomas is often an attainable goal, and clinical improvement is the common outcome with exception to malignant forms and NF2 neurofibromatosis. We describe a series of 179 treated schwannomas.

Genetic and expression profiles of cerebellar liponeurocytomas

Cerebellar liponeurocytoma, a rare, newly identified CNS neoplasm of adults, is characterized by advanced neuronal/neurocytic and focal lipomatous differentiation, low proliferative potential and a favorable clinical prognosis. Despite the different age distribution and benign biological behavior, the cerebellar liponeurocytoma shares several features with the cerebellar medulloblastoma, which may include an origin from the periventricular matrix of the fourth ventricle or the external granular layer of the cerebellum. To establish the genetic profile of cerebellar liponeurocytomas, we have formed an international consortium and collected tumor samples from 20 patients. DNA sequencing revealed TP53 missense mutations in 4 (20%) of 20 cerebellar liponeurocytomas, a frequency higher than in medulloblastomas. There was no case with PTCH, APC, or β‐catenin mutations, each of which may be present in subsets of medulloblastomas. Isochromosome 17q, a genetic hallmark of classic medulloblastomas, was not observed in any of the cases investigated by FISH analysis. cDNA array analyses were carried out on 4 cerebellar liponeurocytomas, 4 central neurocytomas, and 4 classic medulloblastomas. Cluster analysis of the cDNA expression data of 1176 genes grouped cerebellar liponeurocytomas close to central neurocytomas, but distinct from medulloblastomas. These results suggest cerebellar liponeurocytoma as a distinct tumor entity that is genetically different from medulloblastoma. Furthermore, the cDNA expression array data suggest a relationship to central neurocytomas, but the presence of TP53 mutations, which are absent in central neurocytomas, suggests that their genetic pathways are different.

Radiation leukoencephalopathy associated with moderate hydrocephalus: intracranial pressure monitoring and results of ventriculoperitoneal shunting

Abstract. Delayed neurological sequelae of radiotherapy have several manifestations; leukoencephalopathy is one of the most common. Pathogenetic relationships between radiation leukoencephalopathy and other findings of diffuse radiation injury (brain atrophy and progressive ventriculomegaly) are not well defined. Moreover, no guidelines have been established for the treatment of hydrocephalus when associated with radiation leukoencephalopathy. Our study reportsintracranial pressure (ICP) monitoring in two patients with radiation leukoencephalopathy with moderate hydrocephalus. High intraventricular mean pressure and high peaks were found, and marked improvement of clinical status after shunting was achieved. This study, although restricted to only two patients, shows that ventriculoperitoneal shunting insertion is useful in radiation-induced hydrocephalus, when ICP monitoring detects high mean pressure. A hypothesis is advanced concerning radiation-induced hydrocephalus with high ICP, emphasizing periventricular astrocytosis and its connections with cerebral compliance.

Cerebellar Liponeurocytoma: Immunohistochemical and Ultrastructural Study of a Case

The clinical, histopathological, and ultrastructural features of a cerebellar liponeurocytoma are reported. The tumor, a 3-cm mass localized in the right cerebellar hemisphere, was resected from a 61-year-old man clinically presenting with symptoms of intracranial hypertension. The lesion was composed of small, in some areas closely packed, medulloblastoma-like cells with prominent areas of lipidization phenomena. Moreover, mitoses, cellular atypia, and numerous vascular structures were focally observed. Glial and neuronal differentiation was immunohistochemically noted (glial fibrillary acidic protein, synaptophysin, neurofilaments, and neuron-specific enolase positivity). The p53 oncoprotein was detected in the majority of neoplastic cells and a moderate proliferation activity, evaluated by Mib-1 antibody, was focally appreciated. Ultrastructural study did not show evident neuritic processes, synapses, or dense core neuroendocrine granules. This cerebellar tumor previously called lipidized medulloblastoma and recently renamed cerebellar liponeurocytoma is considered an adult neoplasm with excellent prognosis histologically presenting prominent lipidized areas and, at the immunohistochemical and ultrastructural level, both glial and neuronal differentiation. The present study providesthe first description of a less differentiated and histologically more aggressive form of this unusual tumor.The clinical, histopathological, and ultrastructural features of a cerebellar liponeurocytoma are reported. The tumor, a 3-cm mass localized in the right cerebellar hemisphere, was resected from a 61-year-old man clinically presenting with symptoms of intracranial hypertension. The lesion was composed of small, in some areas closely packed, medulloblastoma-like cells with prominent areas of lipidization phenomena. Moreover, mitoses, cellular atypia, and numerous vascular structures were focally observed. Glial and neuronal differentiation was immunohistochemically noted (glial fibrillary acidic protein, synaptophysin, neurofilaments, and neuron-specific enolase positivity). The p53 oncoprotein was detected in the majority of neoplastic cells and a moderate proliferation activity, evaluated by Mib-1 antibody, was focally appreciated. Ultrastructural study did not show evident neuritic processes, synapses, or dense core neuroendocrine granules. This cerebellar tumor previously called lipidized medulloblastoma and recently renamed cerebellar liponeurocytoma is considered an adult neoplasm with excellent prognosis histologically presenting prominent lipidized areas and, at the immunohistochemical and ultrastructural level, both glial and neuronal differentiation. The present study provides the first description of a less differentiated and histologically more aggressive form of this unusual tumor.

Aβ Clearance, “hub” of Multiple Deficiencies Leading to Alzheimer Disease

The role of the amyloid cascade in the pathogenesis of Alzheimer’s disease (AD) is still the subject of passionate debates (Herrup, 2015; Musiek and Holtzman, 2015). According to quite a radical viewpoint (Herrup, 2015), the tendency to try to find a unifying etiopathogenetic pathway has so far hampered the understanding of such a complex disease. Thus, it would be better to reject the amyloid cascade hypothesis since it is neither necessary nor sufficient to drive the development and progression of AD. Herrup (2015) proposes, as food for thought, to relocate the amyloid cascade in a multifactorial context where it represents only one of a number of deficiencies contributing to degenerative escalation in the age-weakened brain (Herrup, 2015). From a more conservative perspective, the amyloid cascade is the necessary key initiator of a complex sequence of pathological changes, especially tau protein hyperphosphorylation, which mediates neurodegeneration (Musiek and Holtzman, 2015). However, owing to the lapse in time between the appearance of amyloid plaques and that of tau protein tangles, neuronal loss and dementia, as well as the absence of an obvious anatomical colocalization between the amyloidogenic process and neurodegeneration areas, the amyloid cascade hypothesis is not sufficient to explain AD pathology unless supported by a series of “wingmen” (Musiek and Holtzman, 2015).

Diastematomyelia and tumor in adults: report of two cases and literature review.

Study Design. Case report and review of the literature. Objective. To report on 2 rare cases of association of diastematomyelia with dysembryogenetic tumors and revision of the literature. Summary of Background Data. Diastematomyelia is an occult spinal diastrophism pathologically characterized by a clefting of the spinal cord with/without its overlying structures. It is often associated with vertebral bony abnormalities, cutaneous lesions, myelomeningocele, hydrocephalus, hydromyelia, Chiari syndrome or Klippel-Feil syndrome. The association of diastematomyelia with dysembryogenetic spinal tumors in adults is extremely rare. Only 13 cases were detected in a literature review since 1951. We report on our experience with 2 new cases. Methods. An 87-year-old man and a 38-year-old woman presented to our department with incomplete cauda equina syndrome. Both patients underwent complete preoperative imaging. Complete surgical removal of the tumor was performed. Details of these were compared with the ones encountered in literature. Results. Both patients presented complete recovery in the follow-up. From the review of 15 adults described in literature including the present cases, the age ranged between 11 and 87 proving an open rage of onset of symptoms. Conclusion. The results of surgery were unclear in literature. In our experience, radical surgery was feasible and good clinical results were obtained.

Assessment of three year experience of a strategy for patient selection and timing of operation in the management of acute thoracic and lumbar spine fractures: a prospective study

SummaryBackground. The purpose of this article is to report experience gained over three years of the use of a protocol for patient selection and timing of operation for acute thoracic and lumbar fractures.Method. At admission, all patients underwent neurological and imaging exams. All patients with a spinal cord lesion scored as ASIA A at any level inferior to T10 and as ASIA B, C or D at any level, were categorized as emergency and operated on within eight hours from trauma. ASIA A cases in the T1–T10 tract and ASIA E cases at any level were treated in the ordinary operative work schedule.Findings. Ninety-four patients with surgically treated lumbar or thoracic fractures took part in this study. On the imaging studies, 12 patients were classified as A, 50 as B and 32 as C following the AO classification. At the neurological exam, 39 patients were scored as ASIA A, nine as B, six as C, two as D and 38 as E. At follow-up, of the 39 patients scored as ASIA A, 13 (33%) improved at least one grade and of the 17 scored as ASIA B, C or D, 11 (64.7%) improved. None of the 38 patients scored as ASIA E deteriorated.Conclusions. The findings show that the strategy in the protocol was safe and followed by satisfactory rates of neurological outcome. Larger prospective studies, preferably randomized, are needed to establish definitively its place in the management of patients with spinal injury.

Large-sized Fetal Striatal Grafts in Huntington's Disease Do Stop Growing: Long-term Monitoring in the Florence Experience.

Development of six large nodules of solid tissue after bilateral human fetal striatal transplantation in four Huntington’s disease patients has raised concern about the safety of this experimental therapy in our setting. We investigated by serial MRI-based volumetric analysis the growth behaviour of such grafts. After 33-73 months from transplantation the size of five grafts was stable and one graft showed a mild decrease in size. Signs neither of intracranial hypertension nor of adjuctive focal neurological deficit have ever been observed. This supports long-term safety of the grafting procedure at our Institution.

A commentary on “Differentiation of pluripotent stem cells into striatal projection neurons: a pure MSN fate may not be sufficient”

Proof-of-concept has long been gained from both Huntingtons disease (HD) animal models and pilot clinical trials that transplantation of fetal striatal tissue has the potential to offer a substitutive therapy to HD patients (Peschanski et al., 1995; Bachoud-Levi et al., 2006; Reuter et al., 2008; Paganini et al., 2014). Nonetheless, in the stem cell era, the body of knowledge so far obtained from fetal tissue as cell source may well be handed over to the clinical exploitation of neural stem cells (Tabar and Studer, 2014).

Symptomatic Vertebral Cavernous Haemangiomas Surgery Alone as Treatment of Choice

Vertebral cavernous haemangiomas are vascular malformations. They are most commonly asymptomatic and often occasionally diagnosed. Four cases of spine cavernomas causing spinal cord compression and neurological disturbances treated in the Neurosurgical Department of Florence are reported. The chosen treatment was surgery, consisting in the removal of only the epidural component responsible for compression with its origin. Anatomoclinical and neuroradiological patterns are described. Therapeutic strategies, considering major complications and results, are discussed.