NOGO-A induction and localization during chick brain development indicate a role disparate from neurite outgrowth inhibition.

BACKGROUND: Nogo-A, a myelin-associated protein, inhibits neurite outgrowth and abates regeneration in the adult vertebrate central nervous system (CNS) and may play a role in maintaining neural pathways once established. However, the presence of Nogo-A during early CNS development is counterintuitive and hints at an additional role for Nogo-A beyond neurite inhibition. RESULTS: We isolated chicken NOGO-A and determined its sequence. A multiple alignment of the amino acid sequence across divergent species, identified five previously undescribed, Nogo-A specific conserved regions that may be relevant for development. NOGO gene transcripts (NOGO-A, NOGO-B and NOGO-C) were differentially expressed in the CNS during development and a second NOGO-A splice variant was identified. We further localized NOGO-A expression during key phases of CNS development by in situ hybridization. CNS-associated NOGO-A was induced coincident with neural plate formation and up-regulated by FGF in the transformation of non-neural ectoderm into neural precursors. NOGO-A expression was diffuse in the neuroectoderm during the early proliferative phase of development, and migration, but localized to large projection neurons of the optic tectum and tectal-associated nuclei during architectural differentiation, lamination and network establishment. CONCLUSION: These data suggest Nogo-A plays a functional role in the determination of neural identity and/or differentiation and also appears to play a later role in the networking of large projection neurons during neurite formation and synaptogenesis. These data indicate that Nogo-A is a multifunctional protein with additional roles during CNS development that are disparate from its later role of neurite outgrowth inhibition in the adult CNS.

Early antiepileptic drug reduction following anterior temporal lobectomy for medically intractable complex partial epilepsy.

PURPOSE: To determine the safety, in our practice, of allowing patient preference to influence the timing of antiepileptic drug (AED) reduction, once they became seizure-free after anterior temporal lobectomy (ATL). METHODS: Thirty patients underwent anterior temporal lobectomy for medically intractable complex partial epilepsy at Loma Linda University Medical Center between December 1st 1991 and November 30th 2001. Timing of AED reduction in seizure-free patients was based on patient request. A review of patient records noted seizure status, duration from surgery to AED reduction, AED side effects, seizure recurrence and whether control was regained. RESULTS: Twenty-four (80%) of the 30 patients became seizure-free on their preoperative AEDs after initial ATL; three additional patients after a second operation. AEDs were not reduced in the reoperated patients, the three patients who did not become seizure-free, and in two patients who asked to increase AEDs to control auras. Thus, AEDs were reduced in 22 of the 27 seizure-free patients. Patients were followed an average of 3.4 +/- 2.7 (mean +/- standard deviation) years. AED reduction was initiated 4.6 +/- 7.2 months (range 0-27 months) after surgery. Polytherapy use decreased from 54% preoperatively to 18% at last follow up. Seizures recurred in six patients (27% of 22); three became seizure-free after AED adjustments. CONCLUSIONS: In our practice, using an individualized approach to AED reduction following successful epilepsy surgery resulted in early reduction in AEDs. Our data suggest that early AED reduction can be performed safely and without undue risk of seizure recurrence.

Pigmented villonodular synovitis of the temporomandibular joint: a report of two cases.

Pigmented villonodular synovitis is a benign but locally destructive disease that originates in the synovial membranes of the joints. It is a proliferative disorder of unknown etiology, and it is usually monarthric. Approximately 80% of cases involve the knee; the hip, ankle, foot, hand, elbow, and shoulder account for most other cases. Pigmented villonodular synovitis in the temporomandibular joint is rare. When it does occur, its features include preauricular swelling, trismus, and symptoms of temporomandibular joint dysfunction. It can be diagnosed by a combination of the history, clinical examination, characteristic radiologic findings, and fine-needle aspiration or biopsy results. Wide local excision, including the involved bone, and a total synovectomy are advocated because the lesion can recur if it is not adequately excised. We report two new cases of pigmented villonodular synovitis of the temporomandibular joint, and we review the literature on this subject.

Tortuosity of terminal arterioles in the basal ganglia is increased in status lacunaris.

The goal of this study was to evaluate the participation of small (diameter between 26 microns and 90 microns) and terminal (diameter between 10 microns and 25 microns) arterioles in the status lacunaris of the basal ganglia and to classify tortuous vascular profiles based on morphometry. Paraffin sections, 40 microns thick, of the basal ganglia from autopsied patients over the age of 45, were stained with PAS. A three-dimensional microscope, R400 (edge) was used to evaluate the structure of the blood vessels. Six patterns of the tortuous profiles were identified: simple kink, loop, knot, tangle, coil, and wave, and well as their combinations. Tortuous arterioles in the basal ganglia were present both in control group and status lacunaris cases. However, statistical Student's t-test analysis revealed a significant increment in the number of microfields containing tortuous terminal arterioles in the status lacunaris group (mean 7.50 +/- 4.62) versus the control group (mean 2.92 +/- 1.38) (p = 0.001). A risk for status lacunaris was associated with the increased frequency of tortuous terminal arterioles (Odd ratio = 1.94, 95%-Confidence Interval = 1.17-3.22) (p = 0.008) but not small arterioles (Odd ratio = 1.64, 95%-Confidence Interval = 0.62-4.38) (p = 0.39). Our findings suggest than an increased number of tortuous terminal arterioles is associated with status lacunaris. Six characteristic patterns of the tortuous profiles as well as their combinations were identified.

Primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma of the brain in a patient with acquired immunodeficiency syndrome.

Anaplastic large cell lymphoma is a unique diagnostic subcategory of the T-cell lymphomas in the current World Health Organization classification. Representing approximately 3% of adult and 10% to 30% of childhood non-Hodgkin lymphomas, anaplastic large cell lymphoma classically consists of CD30+ large lymphoid cells with abundant cytoplasm and pleomorphic, often horseshoe-shaped or kidney-shaped nuclei. Among the reported nodal and extranodal sites of occurrence, the gastrointestinal tract and central nervous system have rarely been noted. We report a case of primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma in the brain of a 46-year-old patient with acquired immunodeficiency syndrome. T-cell lineage was confirmed by T-cell receptor gamma chain gene rearrangements using polymerase chain reaction, and extra copies of the anaplastic lymphoma kinase gene of chromosome 2 were demonstrated by fluorescence in situ hybridization analysis. To our knowledge, primary anaplastic large cell lymphoma of the brain has not previously been reported in acquired immunodeficiency syndrome.