Molecular genetic analysis of ependymal tumors. NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas.

Ependymal tumors are heterogeneous with regard to morphology, localization, age at first clinical manifestation, and prognosis. Several molecular alterations have been reported in these tumors, including allelic losses on chromosomes 10, 17, and 22 and mutations in the NF2 gene. However, in contrast to astrocytic gliomas, no consistent molecular alterations have been associated with distinct types of ependymal tumors. To evaluate whether morphological subsets of ependymomas are characterized by specific genetic lesions, we analyzed a series of 62 ependymal tumors, including myxopapillary ependymomas, subependymomas, ependymomas, and anaplastic ependymomas, for allelic losses on chromosome arms 10q and 22q and mutations in the PTEN and NF2 genes. Allelic losses on 10q and 22q were detected in 5 of 56 and 12 of 54 tumors, respectively. Six ependymomas carried somatic NF2 mutations, whereas no mutations were detected in the PTEN gene. All six of the NF2 mutations occurred in ependymomas of WHO grade II and were exclusively observed in tumors with a spinal localization (P = 0.0063). These findings suggest that a considerable fraction of spinal ependymomas are associated with molecular events involving chromosome 22 and that mutations in the NF2 gene may be of primary importance for their genesis. Furthermore, our data suggest that the more favorable clinical course of spinal ependymomas may relate to a distinct pattern of genetic alterations different from that of intracerebral ependymomas.

Chromosome arm 17p deletion analysis reveals molecular genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumors of the central nervous system.

The current World Health Organization (WHO) classification groups together both infratentorial neoplasms (medulloblastomas) and their supratentorial counterparts as primitive neuroectodermal tumors (PNETs), implying a common origin. Previous analyses of medulloblastoma have shown loss of chromosome arm 17p as the most frequent genetic abnormality: the molecular genetic constitution of supratentorial PNETS has not been systematically studied. We therefore examined 8 hemispheric PNETs and 35 medulloblastomas with 17p restriction fragment length polymorphism (RFLP) and microsatellite markers. We also examined the TP53 tumor suppressor gene by a combined polymerase chain reaction-denaturing gradient gel (PCR-DGGE) technique. Our results showed that all of the 17p markers tested were preserved in all of the supratentorial PNET specimens. In contrast, loss of distal chromosome arm 17p was detected in 37% of the medulloblastomas. Analysis of the TP53 gene showed 2 mutations in the medulloblastomas and no mutations in the supratentorial tumors. These results show that the most common molecular genetic abnormality in infratentorial PNETS is absent in their supratentorial counterparts and suggests that alternative pathways and genetic events may be involved in their etiology.

The activity and size of the nucleus of comet Hale-Bopp (C/1995 O1) [see comment].

Analysis of Hubble Space Telescope (HST) images of comet Hale-Bopp (C/1995 O1) suggests that the effective diameter of the nucleus is between 27 to 42 kilometers, which is at least three times larger than that of comet P/Halley. The International Ultraviolet Explorer and HST spectra showed emissions from OH (a tracer of H2O) and CS (a tracer of CS2) starting in April 1996, and from the CO Cameron system (which primarily traces CO2) starting in June 1996. The variation of the H2O production rate with heliocentric distance was consistent with sublimation of an icy body near its subsolar point. The heliocentric variation in the production rates of CS2 and dust was different from that of H2O, which implies that H2O sublimation did not control the CS2 or dust production during these observations.

Molecular genetic analysis of chromosome arm 17p and chromosome arm 22q DNA sequences in sporadic pediatric ependymomas.

Ependymomas are glial tumors of the brain and spinal cord occurring both sporadically and in a familial syndrome, neurofibromatosis type 2 (NF2). Previous analyses performed on specimens obtained predominantly from adult patients have shown loss of DNA sequences from chromosome arm 22q, which is the location of the NF2 gene. Previously, we documented the consistent loss of chromosome arm 17p DNA in medulloblastoma and astrocytoma, which are the most common brain tumors in children. Although mutation of the TP53 gene located on 17p is the most frequent genetic mutation in all adult tumor types, such mutations are rare in most childhood brain tumors investigated to date. We studied a series of pediatric ependymoma specimens (16 intracranial and 2 spinal) for loss of 17p and 22q DNA sequences and for mutation of the TP53 and NF2 genes. None of the children had the clinical stigmata of NF2. We detected loss of 17p DNA sequences in 9 of the 18 specimens (50%); in 7 of 9 of these specimens (78%), the 144-D6 marker was deleted. In contrast, only 2 of these same 18 specimens (11%) showed loss of 22q DNA. One TP53 gene mutation was detected in a child from a cancer kindred. No mutations were detected in the NF2 gene. Our results suggest that loss of chromosome arm 17p DNA sequences is common in sporadic pediatric ependymomas and that, in contrast to ependymomas in adults, deletion of chromosome arm 22q sequences is rare. Furthermore, TP53 and NF2 gene mutations do not play an important role in the etiology of sporadic pediatric ependymomas.

Entrapment neuropathy at the cubital tunnel: simple decompression is the method of choice.

We present a retrospective study of 41 patients treated by simple decompression for ulnar neuropathy. Pre- and postoperatively, patients were evaluated clinically and electrophysiologically. The median follow-up was 2 years (minimum: 0.5 years, maximum: 5.1 years). The leading pre-operative sign was motor loss in the ulnar distribution (36 patients = 89%) with consecutive atrophy of ulnar innervated muscles (30 patients = 75%). The secondary complaint was sensory impairment in 59% of all cases, less frequently patients presented with pain or paraesthesia. In the majority of cases the aetiology remained unknown (27 patients = 65%). When aetiology was known, previous trauma to the elbow was reported most frequently (9 patients = 22%). Motor nerve conduction velocity (mNCV), compared to the contralateral, non-involved arm, was lower at least for 10 m/s. In cases with atrophy of the ulnar innervated muscles the difference was greater than 15 m/s. In 89%, postoperative results were good or even very good. In 8% (3 patients) no improvement was observed. Worsening due to surgery did not occur. We could demonstrate a significant increase in postoperative mNCV of 7.95 m/s in all patients (p < 0.05). There is still disagreement as to the correct surgical treatment of this disorder. We favour simple decompression (SD) as the appropriate operative technique for cubital tunnel syndrome.

Pure motor hemiparesis with stable somatosensory evoked potential monitoring during aneurysm surgery: case report.

We report a patient who sought treatment for an acute subarachnoid hemorrhage as a result of an intracranial aneurysm. Management included early surgical repair and intraoperative monitoring of evoked potentials. Pan-angiography revealed berry aneurysms of the communicating anterior artery and right middle cerebral artery. Surgery was uneventful, and the somatosensory evoked potential monitoring did not show any abnormalities. Nevertheless, the patient showed a neurological deficit due to a clip-related infarct in the right middle cerebral artery territory characterized by a right hemiparesis with no sensory deficit. This case report supports the possibility of false-negative results in single-mode intraoperative monitoring during aneurysm surgery.