Severe acute multineuropathy in Churg-Strauss syndrome in a patient with a history of melanoma.

We describe the clinicopathologic features of a 69-year-old man affected with acute onset Churg-Strauss syndrome with major peripheral nerve involvement. At admission the patient presented a one-week history of distal upper-limb asymmetrical paresthesias. Asthma had been present since the age of 55 and treated with leukotriene receptor antagonists (LTAs, Montelukast) for a few years. Multiple pulmonary infiltrates had been diagnosed during follow-up for melanoma. During hospitalization he showed rapidly progressive weakness worsening within a few hours; cerebrospinal fluid analysis, cervical MRI, head CT scan, nerve conduction studies and peripheral nerve and skeletal muscle biopsies were performed. Blood analysis showed leukocytosis and marked eosinophilia; p-ANCA were positive. Sural nerve biopsy showed a marked loss of myelinated fibers, thrombosed vessels surrounded by mononuclear and eosinophilic cells, necrotizing and hyaline degeneration. Eosinophilic infiltrates were shown in May-Grunwald-Giemsa stained sections. The eosinophils mostly occupied the outer zone of the adventitia at the margin of the active lesion. Perivascular cellular infiltrates within the epineurium were immunoreactive for T-lymphocytes and macrophages. Strong HLA-DR immunostaining was present in the perineurium and membrane attack complex deposition was present in a few endoneurial capillaries. Muscle biopsy showed neurogenic changes and one vessel surrounded by mononuclear cells. After a few days of corticosteroid therapy leukocytosis and eosinophilia normalized and the patient's clinical features stabilized.

Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients.

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of a functional dystrophin in muscles results in the fragility of the muscle fiber membrane with progressive muscle weakness and premature death. There is no cure for DMD and current treatment options focus primarily on respiratory assistance, comfort care, and delaying the loss of ambulation. Recent works support the idea that stem cells can contribute to muscle repair as well as to replenishment of the satellite cell pool. Here we tested the safety of autologous transplantation of muscle-derived CD133+ cells in eight boys with Duchenne muscular dystrophy in a 7-month, double-blind phase I clinical trial. Stem cell safety was tested by measuring muscle strength and evaluating muscle structures with MRI and histological analysis. Timed cardiac and pulmonary function tests were secondary outcome measures. No local or systemic side effects were observed in all treated DMD patients. Treated patients had an increased ratio of capillary per muscle fibers with a switch from slow to fast myosin-positive myofibers.

Skin-derived stem cells transplanted into resorbable guides provide functional nerve regeneration after sciatic nerve resection.

The regeneration in the peripheral nervous system is often incomplete and the treatment of severe lesions with nerve tissue loss is primarily aimed at recreating nerve continuity. Guide tubes of various types, filled with Schwann cells, stem cells, or nerve growth factors are attractive as an alternative therapy to nerve grafts. In this study, we evaluated whether skin-derived stem cells (SDSCs) can improve peripheral nerve regeneration after transplantation into nerve guides. We compared peripheral nerve regeneration in adult rats with sciatic nerve gaps of 16 mm after autologous transplantation of GFP-labeled SDSCs into two different types of guides: a synthetic guide, obtained by dip coating with a L-lactide and trimethylene carbonate (PLA-TMC) copolymer and a collagen-based guide. The sciatic function index and the recovery rates of the compound muscle action potential were significantly higher in the animals that received SDSCs transplantation, in particular, into the collagen guide, compared to the control guides filled only with PBS. For these guides the morphological and immunohistochemical analysis demonstrated an increased number of myelinated axons expressing S100 and Neurofilament 70, suggesting the presence of regenerating nerve fibers along the gap. GFP positive cells were found around regenerating nerve fibers and few of them were positive for the expression of glial markers as S-100 and glial fibrillary acidic protein. RT-PCR analysis confirmed the expression of S100 and myelin basic protein in the animals treated with the collagen guide filled with SDSCs. These data support the hypothesis that SDSCs could represent a tool for future cell therapy applications in peripheral nerve regeneration.

TOS pathophysiology and clinical features.

The authors present 280 patients operated on for thoracic outlet syndrome (TOS). In a first group of patients anatomical variants were the striking findings. The underlying factor for TOS development is therefore a well defined structural condition and its pathogenetic mechanism is known to be a nerve fibre compression. In a second group there was no specific salient finding but a postural deviation. The unique pathological features were adhesions of the brachial plexus to the scalenus muscle. Consequently its pathogenetic mechanism is generally recognized as nerve fibre distraction. In all patients neurological, vascular and myofascial pain symptoms were observed before the operation. Neurological and vascular pain disappeared after surgery, while the myofascial pain remained. The authors believe that especially in the second, larger group of patients enhancement of the pain-immobility-fibrosis loop is the central pathogenetic factor on which surgical therapy is successful, and that myofascial hemisyndrome--probably arising from a long-standing postural deviation--is not a TOS dependent symptom. In TOS, therefore, there is a pain loop that cannot be resolved by surgical therapy alone. The connection between myofascial pain syndrome and TOS might explain the many controversial opinions regarding frequency, results and surgical possibilities of this lesion.

Combined treatment of fourth ventricle ependymomas: report of 26 cases.

BACKGROUND: This study investigated the relevance of prognostic factors and the impact of histological features in posterior fossa ependymoma. METHODS: The charts of 26 patients (aged 1-59 years, mean 20.6 years; 11 adults) with posterior fossa ependymoma operated on between January 1983 and December 1994 were reviewed and patients followed up (mean: 93 months). RESULTS: Gross total resection was performed in 18 patients (69%), subtotal in seven patients (27%), biopsy in one patient (4%). One patient (3.8%) developed respiratory complications and died. All patients underwent posterior fossa radiotherapy (5000 cGy) after surgery. Four children first received chemotherapy and then radiotherapy only when at least 3 years old. Eleven patients (42%) received radiotherapy and subsequently chemotherapy. The 5-year survival rate was 90% for adults and 40% for children (

High cerebral perfusion pressure improves low values of local brain tissue O2 tension (PtiO2) in focal lesions.

Arterial hypertension is widely applied to improve regional cerebral blood flow (rCBF). We measured local brain tissue O2 pressure (PtiO2) in low density lesions at computerized tomography (CT) of the head before and after manipulation of mean arterial pressure (MAP) in order to increase cerebral perfusion pressure (CPP). Nine patients, 7 subarachnoid hemorrhage (SAH), 1 severe head injury, 1 meningeoma, were included in our study. A flexible polarographic microcatheter for PtiO2 measurement was placed at the border of the low density area found at CT. PtiO2 was continuously measured for 615 hours. Hypoperfusion in low density areas was detected by perfusional single photon emission computed tomography (SPECT). We recorded 22 episodes of induced or spontaneous increase of MAP. Initial PtiO2 regularly improved after the CPP increase (r2 0.74 in induced episodes). Low PtiO2 showed a greater percent increase for unitary changes of CPP than normal-high PtiO2. Baseline PtiO2 below 20 mm Hg was associated with normal CPPs; 5 readings of PtiO2 below 20 mm Hg normalized when a higher CPP was obtained. Our results show that in ischemic areas PtiO2 is dependent on CPP suggesting both a derangement of pressure autoregulation and high regional cerebrovascular resistences (CVRs). Low PtiO2 was associated with normal CPP, thus indicating that CPP could be an inadequate estimate of rCBF in focal ischemic areas. Arterial hypertension, capable of increasing CPP above normal values, appeared useful in normalizing tissue oxygenation in ischemic areas.

Neuroendocrine, immunohistochemical, and ultrastructural study of pineal region tumors.

Thirteen patients with tumors in the pineal region were submitted to pre- and post-operative blood sampling (08:00, 14:00, 20:00, and 02:00 hr) for three or four consecutive days. A single cerebrospinal fluid (CSF) sample was collected at surgery, and melatonin levels determined. In all patients, serum and CSF beta subunit of human chorionic gonadotrophin (betaHCG), carcino embryonic antigen (CEA), and alpha-fetoprotein (AFP) levels were measured. Histology revealed four pineocytomas, one pineoblastoma, four germinomas, one immature teratoma, one pilocytic astrocytoma, one lymphoma, and one meningioma. Serum and CSF levels of serological biomarkers were normal, except for one of the germinoma cases. In most patients, alteration either in the circadian rhythm or in the melatonin concentration was observed before surgery. In benign neoplasms the circadian rhythm was conserved. In pineoblastoma, lymphoma, and three out of four germinomas, melatonin concentrations were undetectable. In one case of germinoma, melatonin levels were high, with the circadian rhythm being abolished. According to conventional histology, all germinomas were similar. Therefore, in a rare case of pineal germinoma with high melatonin levels, the tissue was subjected to an in depth investigation (immunohistochemical and ultrastructural) in order to determine the pathology and the possible differences from the other typical germinomas. Results were compared to those provided from other pineal neoplasms. Electron microscopy examination detected the presence of clusters of intermediate filaments and numerous electrondense granules only in the case of a germinoma producing melatonin.

Cerebral rhabdomyosarcoma with rhabdoid tumor-like features.

The present paper describes a case of cerebral neoplasm presenting histological-immunohistochemical characteristics of malignant rhabdoid tumor (MRT) and ultrastructural features of both MRT and rhabdomyosarcoma (R). MRT was first described as an aggressive neoplasm of unknown histogenesis of the kidney, then many other sites of onset were reported, including the central nervous system. However, it has been shown that other tumors of known histogenesis can mimic histologic and ultrastructural features of MRT. On the basis of our findings we agree with authors who support the notion that extrarenal MRT has often a different histogenesis from MRT of kidney, and it probably is a 'phenotypic' entity rather than a distinct pathologic entity.

Transcallosal approach to tumors of the third ventricle. Surgical results and neuropsychological evaluation.

A series of 34 patients with tumours of the third ventricle were operated on by a transcallosal route. Basal extrinsic lesions compressing or invading the ventricle as well as tumours located in the pineal area were excluded from this review. Tumours were approached by a transforaminal entry in 16 cases (47%), by an interforniceal route in 11 (32%), by a subchoroidal entry in 4 (14%) and by a combined transforaminal and subchoroidal entry in 3 (9%). Four out of 34 patients were submitted to a second operation, through the same approach corridor: 2 for an incomplete removal of an intrinsic tumour and 2 for a late regrowth. Postoperative mortality rate accounted for 5.8% (2 patients). Major post operative complications were hemiparesis (4 patients) and diabetes insipidus (4 patients), that were transient in 3. Akinetic mutism like status was observed in only 1 patient. Postoperative psychic disturbances were noticed in 5 cases. Nine out of 21 patients (62%) with preoperative hydrocephalus required a permanent CSF shunt. Histology revealed that 21 tumours (62%) were intraaxial (4 pilocitic astrocytoma, 10 low grade glioma, 1 giant cell astrocytoma, 1 subependymoma, 4 ependymoma/ependymoblastoma, 1 neurocitoma) and 13 (38%) were extraaxial (8 colloid cyst, 2 craniopharingioma, 1 ectopic pituitary adenoma, 1 lymphocytic hypophysitis and 1 metastasis). Total excision of third ventricle tumours was achieved in all patients with extraaxial tumours and in 62% and 71% of intraaxial tumours with the first and second surgical procedure respectively. Ten out of 34 patients of this series were submitted to a complete neuropsychological evaluation at an interval of 2-9 years after surgery. Memory tests were pathological in 2. Disconnection signs were constantly absent. Control function were preserved. Transcallosal approach remains the best microsurgical method of third ventricle tumours treatment. This route provides the capability for a superior visualization of the entire cavity of the third ventricle through different corridors. Permanent neurological and neuropsychological deficits are not frequent. Epilepsy, that accounted for 28% in patients submitted to transcortical transventricular approach to third ventricle tumours, was never noticed in this series operated on through a transcallosal route.

Long-term outcome in aqueductal stenosis.

In this study, 78 patients with aqueductal stenosis were submitted to detailed neurodevelopmental assessment with a follow-up of 5-25 years. Sixty-eight percent of patients were categorized as normal; they either attended normal school courses or had regular jobs. Among these, 34% had some motor abnormalities (ataxia, mild hemiparesis, visual disturbances). Twenty-four percent (19 cases) were moderately disabled (trainable retardation) and 8% (6 cases) were severely handicapped. Epilepsy was observed in 13% of the cases. Incidence of recurrent and generalized seizures paralleled neurodevelopmental outcome (5% in normal, 16% in moderately disabled and 50% in severely disabled patients). Endocrine dysfunctions were evident in 28% of the cases and were characterized by precocious or delayed puberty, amenorrhea and somatic underdevelopment. No patient with ventricular enlargement and a cortical mantle width below 20 mm showed a good outcome. Large ventricles were compatible with normal mental development when compensated with a corresponding cranial vault enlargement. In patients with normal mental status and motor abnormalities, long-term CT scan findings revealed the presence of focal brain abnormalities (poroencephaly, brain atrophy, calcifications, extracerebral collections).

A case of optic nerve oligodendroglioma associated with an orbital non-Hodgkin's lymphoma in adult. Case report.

The Authors report a case of optic nerve oligodendroglioma associated with an orbital non-Hodgkin's lymphoma. Its peculiar clinical aspects and neuroradiological appearance are discussed.

Primary intracranial rhabdomyosarcoma: report of two cases.

Primary intracranial rhabdomyosarcoma (RMS) is a rare tumor in infancy and childhood that is found in various locations in the central nervous system. The clinical course worsens rapidly, and the final outcome is poor, with a median survival time of 8-10 months. Invasion of the meninges, spontaneous intratumoral bleeding, spinal leptomeningeal CSF spreading of tumor cells, and early recurrence of the mass are the distinctive features of RMS. Diagnosis of RMS may be missed: immunohistochemical staining using specific markers (myoglobin, myosin, desmin, vimentin, enolase), along with ultrastructural studies, provide the basis for making the final diagnosis. Treatment of RMS includes surgical excision, craniospinal radiation therapy, and chemotherapy. We report two cases of primary RMS in the CNS located in the posterior fossa and frontotemporal area. Both children underwent total surgical removal of the mass. Early recurrence of the tumor mass was noticed in both patients 2 months after surgery. Both children died shortly thereafter.

Ganglioside content and composition in human gliomas.

Many alterations of ganglioside content and distribution have been described in human and experimental tumours. Our previous data showed the presence of lipid alterations in meningiomas, in particular an increased monosialylganglioside content. Therefore we analyzed the distribution and content of gangliosides in various gliomas. The data show that ganglioside content is inversely proportional to tissue malignancy and that the ganglioside pattern can be described as lacking of polysialylgangliosides with increased GD3 content. The amount of GD3 (as percent of total gangliosides sialic acid) increases from 15% in astrocytomas grade I to 60% in grade IV. The GD3 increase seems to be almost specific of glioma. Because anti-GD3 antibodies could be used to localize immunohistochemically the ganglioside and to help the tumour grading, we used a purified preparation of GD3 to produce monoclonal antibodies in balb/c mice. But because some clones did produce anti-GD3 antibodies the low yield requires further experiments to obtain an antibody useful for this purpose.

Cervical vertebral erosion due to tortuous vertebral artery.

A case of cervical vertebral erosion due to tortuous vertebral artery is presented. This entity is rare and only 11 cases have been reported in the literature. The present case is the first to be demonstrated by magnetic resonance imaging. The importance of considering this vascular anomaly in the differential diagnosis of cervical spinal tumors is discussed.