Ocular Tonometry and Sporadic Creutzfeldt - Jakob Disease (sCJD): A Confirmatory Case-Control Study.

AIMS: To evaluate the hypothesis that sporadic Creutzfeldt-Jakob disease (sCJD) may be transmitted through ocular tonometry. BACKGROUND: The infectious agent of sCJD may be present in the cornea prior to clinical symptoms. Cornea infectiousness has been documented by cornea transplants in guinea pigs and humans. sCJD is resistant to complete inactivity by conventional sterilization techniques. Thus contact tonometry equipment is not disinfected sufficiently to kill sCJD. We previously hypothesized that contact tonometry is a sCJD risk factor. STUDY DESIGN: Population-based case-control study. PLACE AND DURATION OF STUDY: Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 4 years. METHODOLOGY: An 11-state case-control study of pathologically confirmed definite sCJD cases, individually matched controls, and a sample of control surrogates was conducted. Ocular tonometry histories were obtained from case-surrogates, controls, and a sample of control-surrogates. RESULTS: The odds ratio (OR) for ever vs never having had an ocular tonometry test was statistically significant for matched and unmatched analyses for 15 through 3 years prior to disease onset, using both control self-responses and control surrogates: ORs were ∞ and 19.4 with 1-sided P-values <0.0001 and 0.003 and ORs=∞ and 11.1 with 1-sided P-values <0.003 and 0.02, respectively. ORs increased as the number of tonometry tests increased during this age period: trend test, 2-sided P-value < 0.0001. For ≥5 vs <5 tonometry tests, the OR was 5.8 (unmatched) and 3.7 (matched), 2-sided P-value<0.00005. Respondents generally could not specify the type of tonometry. There was no indication of increased tonometry testing among cases within 2 years of disease onset. CONCLUSIONS: The a priori hypothesis was supported. Contact tonometry, preferred by ophthalmologists, may be capable of transmitting sCJD. Consideration should be given to using disposable instrument covers after each use. The use the disposable covers or non-contact tonometry is preferable in the absence of effective disinfectant processes at this time.

Dietary Risk Factors for Sporadic Creutzfeldt-Jakob Disease: A Confirmatory Case-Control Study.

AIMS: This study's primary purpose was to determine whether earlier findings suggesting an association between sporadic Creutzfeldt-Jakob disease (sCJD), a transmissible spongiform encephalopathy of humans and specific dietary components could be replicated. The a priori hypotheses were that consumption of (i) foods likely to contain organ tissue and (ii) raw/rare meat are associated with increased sCJD risk. STUDY DESIGN: Population-based case-control study. PLACE AND DURATION OF STUDY: Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 4 years. METHODOLOGY: An 11-state case-control study of pathologically confirmed, definite sCJD cases, matched controls, and a sample of control-surrogates was conducted. Ninety-six percent (106/110) of the case data was obtained in 1991-1993, prior to variant CJD publicity. RESULTS: Using control self-responses, consumption of hot dogs, sausage, pepperoni, kielbasa, "other" canned meat, poultry liver, any stomach/intestine, beef stomach/intestine, any organ tissue, and beef organ tissue was individually associated with increased sCJD risk; odds ratios (OR) ranged from 2.4 to 7.2 (0.003

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.

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.

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.

Conformal proton radiation therapy for pediatric low-grade astrocytomas.

BACKGROUND: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). PATIENTS AND METHOD: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephalic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (Cobalt Gray Equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. RESULTS: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. CONCLUSIONS: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment modality. Results are encouraging for central tumors as well as large optic pathway tumors, where dose conformity is of particular importance; yet it is difficult to achieve. Longer follow-up time is needed to fully evaluate the benefits of normal tissue sparing.