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Biomedical subjects

B L Maria

Publications and source records attributed to B L Maria.

At least 19 recordsLinked to original sources
PubMed2001

Quantitative assessment of brainstem development in Joubert syndrome and Dandy-Walker syndrome.

Key features of Joubert syndrome include developmental delay, hypotonia, hyperpnea and apnea, oculomotor apraxia, and the presence of the molar tooth sign on axial imaging through the brainstem isthmus--the junction of the pons and mesencephalon. Interestingly, 1 in 10 patients with Joubert syndrome has abnormal cerebrospinal fluid collections misdiagnosed as Dandy-Walker variants. Because of important differences in patient management, genetic counseling, and prognosis between these conditions, we undertook a study to determine if the brainstem isthmus is normal in Dandy-Walker syndrome. Using standard landmarks, we evaluated development of the isthmus in normal subjects and in subjects with Joubert syndrome and Dandy-Walker syndrome. Four of five brainstem measures increased with age in normal subjects. In subjects with Joubert syndrome, the depth and length of the interpeduncular fossa were increased, and the width of the isthmus was decreased. In subjects with Dandy-Walker syndrome, the width of the brainstem isthmus was normal, and the molar tooth sign was absent. Although the pons can be hypoplastic in Dandy-Walker syndrome, we conclude that the pontomesencephalic junction is normal. Thus, the molar tooth sign can effectively distinguish between Joubert and Dandy-Walker syndromes. Genetic heterogeneity or epigenetic factors may account for abnormal cerebrospinal fluid collections in some cases of Joubert syndrome.

Adolescent↗
PubMed2001

Possible role of high-dose corticosteroids in the treatment of cat-scratch disease encephalopathy.

Approximately 2% of the estimated 24,000 patients in the United States who contract cat-scratch disease annually develop neurologic complications. Between 1989 and 1999, 36 patients were admitted to our hospital with cat-scratch disease; 25% had neurologic complications, and the majority experienced lengthy hospital stays. We describe a case of cat-scratch disease encephalopathy in a 4-year-old girl who responded to high-dose corticosteroid therapy. Further studies are warranted to determine if corticosteroid therapy shortens the duration of symptoms, lessens the severity of disease, and ultimately improves the outcome for patients with cat-scratch disease encephalopathy.

Bartonella henselae↗
PubMed2000

Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant condition characterized by benign tumor (neurofibroma) growth and increased risk of malignancy. Dermal neurofibromas, arising from superficial nerves, are primarily of cosmetic significance, whereas plexiform neurofibromas, typically larger and associated with deeply placed nerves, extend into contiguous tissues and may cause serious functional impairment. Malignant peripheral nerve sheath tumors (MPNSTs) seem to arise from plexiform neurofibromas. The NF1 gene, on chromosome segment 17q11.2, encodes a protein that has tumor suppressor function. Loss of heterozygosity (LOH) for NF1 has been reported in some neurofibromas and NF1 malignancies, but plexiform tumors have been poorly represented. Also, the studies did not always employ the same markers, preventing simple comparison of the frequency and extent of LOH among different tumor types. Our chromosome 17 LOH analysis in a cohort of three tumor types was positive for NF1 allele loss in 2/15 (13%) dermal neurofibromas, 4/10 (40%) plexiform neurofibromas, and 3/5 (60%) MPNSTs. Although the region of loss varied, the p arm (including TP53) was lost only in malignant tumors. The losses in the plexiform tumors all included sequences distal to NF1. No subtle TP53 mutations were found in any tumors. This study also reports the identification of both NF1 "hits" in plexiform tumors, further supporting the tumor suppressor role of the NF1 gene in this tumor type.

Adolescent↗
PubMed1999

Molar tooth sign in Joubert syndrome: clinical, radiologic, and pathologic significance.

Joubert syndrome is a rare autosomal-recessive condition characterized by early hyperpnea and apnea, developmental delay, and truncal ataxia. We previously described key ocular motor signs in Joubert syndrome and the molar tooth sign resulting from dysplasia of the isthmic segment of the brain stem, superior cerebellar peduncles, and vermis. In this study, we obtained clinical and developmental data in 61 cases, and radiologic data in 46 of these, to determine the prevalence of the molar tooth sign in a large sample, and to ensure that magnetic resonance images obtained for study were representative of the Joubert syndrome population at large. We studied the morphology of the isthmic segment of the pontomesencephalic junction, the segment of the brain stem derived from the primitive isthmus. Portions of the cerebellum analyzed included the superior cerebellar peduncles, the anterior and posterior lobes of the vermis, and the flocculonodular lobe. In one case, autopsy of the brain was performed. The average age at diagnosis was 33 months. All patients were hypotonic and developmentally delayed. The molar tooth sign was present in 85% of cases with 13% of these showing additional malformations. All patients without the molar tooth sign had other mimicking conditions such as neocerebellar dysgenesis, isolated vermian atrophy, cerebellar aplasia, and cystic dilation of the cisterna magna. Autopsy showed aplasia of the cerebellar vermis with dysplasia of the dentate nucleus, elongated locus coeruleus, and marked dysplasia of the caudal medulla. A better understanding of the clinical, radiologic, and pathologic features of Joubert syndrome should help uncover the genetic basis for the syndrome.

Abnormalities, Multiple↗
PubMed1999

Clinical features and revised diagnostic criteria in Joubert syndrome.

The clinical presentation of children with Joubert syndrome can include nonspecific features such as hypotonia, ataxia, and developmental delay. Careful examination of the face shows a characteristic appearance, and a neuro-ophthalmologic examination shows the presence of oculomotor apraxia. In the neonatal period, most children have hyperpnea intermixed with central apnea. Neuroimaging of the head in the axial plane demonstrates the "molar tooth sign"--deep posterior interpeduncular fossa, thick and elongated superior cerebellar peduncles, and hypoplastic or aplastic superior cerebellar vermis. The central nervous system malformation spectrum observed in radiologic and neuropathologic studies accounts for many clinical features of Joubert syndrome. The developmental delay and cognitive impairment cannot be fully explained by the hindbrain malformation and probably result from dysfunction of the cerebral hemispheres. Although related conditions with vermian hypoplasia or aplasia (including Arima; Senior-Loken; and cerebellar vermian hypoplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis syndromes) can mimic Joubert syndrome, detailed imaging data are lacking in such cases. We propose a revision in diagnostic criteria for Joubert syndrome.

Abnormalities, Multiple↗
PubMed1999

Cognition, behavior, and development in Joubert syndrome.

This article reports on a series of studies of children with Joubert syndrome who were examined in three investigations from 1994 through 1998. Neuropsychologic screening of 10 of 40 children showed a variety of deficits in cognition, verbal memory, visuomotor, motor, and language-related tasks. Parent report of developmental attainments revealed only 3 of 40 children functioning in the borderline range, with the rest scoring in the severely impaired range. Parent reports of behaviors revealed problems in temperament, hyperactivity, aggressiveness, and dependency, as well as problems in physical development and care that were felt to be related to their neurologic handicaps. Future directions of research with this rare disorder are suggested.

Adolescent↗
PubMed1999

Magnetic resonance imaging features and classification of central nervous system malformations in Joubert syndrome.

This article examines the magnetic resonance imaging features that typify the Joubert malformation. Specific morphologic features include: (1) dysgenesis of the isthmic portion of the brain stem at the pontomesencephalic junction, (2) abnormally thick superior cerebellar peduncles perpendicular to the brain stem, (3) hypoplasia of the cerebellar vermis with consequent enlargement of the 4th ventricle and rostral shift of the fastigium, and (4) sagittal vermic clefting. At least two of these features were present in every patient and all were present in some. The only cerebral anomaly identified was mild prominence of the ventricles and subarachnoid spaces. The "Joubert-plus anomaly" has been defined as the Joubert malformation plus additional anomalies of either the mesencephalon or the caudal 4th ventricle; this likely represents a similar but more extensive embryologic defect. By placing a relative numeric value on each morphologic feature, a classification scheme has been created that can quantitate the extent of the Joubert malformation in any individual case.

Adolescent↗
PubMed1999

Parental burden, coping, and family functioning in primary caregivers of children with Joubert syndrome.

Children with Joubert syndrome have physical and intellectual disabilities. The purpose of this study was to assess the impact of Joubert syndrome on parental burden, coping, and family functioning. Forty-nine primary caregivers were surveyed. Forty-three primary caregivers were mothers and six were fathers; their mean age was 34 years. The following measures were used: Beck Depression Inventory, Child Development Inventory, Caregiver Strain Index, Family Assessment Device, and Ways of Coping Checklist-Revised. The data show that caregiver burden is not related to the severity of the child's illness, but that caregivers report significant burden. Higher burden was associated with the use of palliative coping methods, and family functioning was problematic. The results of this study suggest that for parents of children with Joubert syndrome, degree of parental burden depends more on the parents' coping skills and the level of family functioning rather than on the degree of the child's impairment. These findings highlight the importance of assessing caregiver burden, as well as decreased family functioning or coping abilities, since these problems often can be managed with psychologic intervention.

Activities of Daily Living↗
PubMed1999

Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis.

PURPOSE: To evaluate the efficacy and safety of a slow-release formulation of cytarabine (DepoCyt; Chiron Corp, Emeryville, CA, and Skye Pharma, Inc, San Diego, CA) that maintains cytotoxic concentrations of cytarabine (ara-C) in the CSF of most patients for more than 14 days. PATIENTS AND METHODS: Twenty-eight patients with lymphoma and a positive CSF cytology were randomized to receive DepoCyt 50 mg once every 2 weeks or free ara-C 50 mg twice a week for 1 month. Patients whose CSF cytology converted to negative and who did not have neurologic progression received an additional 3 months of consolidation therapy and then 4 months of maintenance therapy. All patients received dexamethasone 4 mg orally bid on days 1 through 5 of each 2-week cycle. RESULTS: The response rate was 71% for DepoCyt and 15% for ara-C on an intent-to-treat basis (P =.006). All of the patients on the DepoCyt arm but only 53% of those on the ara-C arm were able to complete the planned 1-month induction therapy regimen. Time to neurologic progression and survival trend in favor of DepoCyt (median, 78.5 v 42 days and 99.5 v 63 days, respectively; P >.05). DepoCyt treatment was associated with an improved mean change in Karnofsky performance score at the end of induction (P =.041). The major adverse events on both arms were headache and arachnoiditis, which were often caused by the underlying disease. CONCLUSION: DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative to that produced by free ara-C injected twice a week.

Adult↗
PubMed1998

Medulloblastoma: time-dose relationship based on a 30-year review.

PURPOSE: Time-dose relationships have proven important in many cancer sites. This study evaluates the time factors involved in the successful postoperative radiotherapy of medulloblastoma, based on a 30-year experience in a single institution. METHODS AND MATERIALS: Fifty-three patients with medulloblastoma received postoperative craniospinal radiotherapy with curative intent between 1963 and 1993. Seven patients (13%) underwent biopsy alone, 28 patients (53%) had subtotal excision, and 18 patients (34%) had gross total excision. Eleven patients received adjuvant chemotherapy. The mean posterior fossa dose was 53.1 Gy; most patients received 54.0 Gy (range, 34.3 to 69.6 Gy). For 41 patients receiving once-a-day therapy, the mean dose was 50.6 Gy (range, 34.3 to 56.0 Gy). For 12 patients receiving twice-a-day therapy, the mean dose was 61.8 Gy (range, 52.6 to 69.6 Gy). Minimum follow-up was 2 years, and median follow-up was 10.7 years. Survival, freedom from relapse, and disease control in the posterior fossa were calculated using the Kaplan-Meier method, and multivariate analysis was performed for prognostic factors. Variables related to radiotherapy were examined, including dose to the craniospinal axis, dose to the posterior fossa, fractionation (once-a-day vs. twice-a-day), use of adjuvant chemotherapy, risk group [high (> or =T3b or > or =M1) or low (< or =T3a and M0-MX)], interval between surgery and radiotherapy (excluding patients receiving chemotherapy before radiotherapy), and duration of radiotherapy. RESULTS: At 5 and 10 years, overall survival rates were 68 and 64%, respectively, and freedom-from-relapse rates were 61 and 52%, respectively. Rates of disease control in the posterior fossa at 5 and 10 years were 79 and 68%, respectively. At 5 years, absolute survival rates after biopsy alone, subtotal excision, and gross total excision were 43, 67, and 78%, respectively (p=0.04), and posterior fossa control rates were 27, 89, and 83%, respectively (p=0.004). Duration of the treatment course was the only radiotherapy-related variable with a significant impact on freedom from relapse and posterior fossa control. For patients whose radiation treatment duration was < or =45 days, posterior fossa control was 89% at 5 years, compared with 68% for those treated for >45 days (p=0.01). Duration of treatment also affected freedom from relapse at 5 years: < or =45 days (76%) compared with >45 days (43%), p=0.004. CONCLUSION: Our study demonstrates that if adequate doses are used, then radiotherapy treatment duration will significantly affect the outcome in terms of control of disease in the posterior fossa and freedom from relapse. Fractions of at least 1.75 Gy given once a day, or a twice-a-day regimen should yield optimal local control results.

Adolescent↗
PubMed1998

Ependymoma: results, prognostic factors and treatment recommendations.

PURPOSE: To review the University of Florida experience in treating ependymomas, analyze prognostic factors, and provide treatment recommendations. METHODS AND MATERIALS: Forty-one patients with ependymoma and no metastases outside the central nervous system received postoperative radiotherapy with curative intent between 1966 and 1989. Ten patients had supratentorial lesions, 22 had infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery (stereotactic biopsy, subtotal resection, or gross total resection). Most patients with high-grade lesions received radiotherapy to the craniospinal axis. Low-grade intracranial lesions received more limited treatment. Spinal cord lesions were treated using either partial spine or whole spine fields. RESULTS: Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46% (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%; supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the only factor that influenced absolute survival (p = 0.0004); other factors evaluated included grade, gender, age, duration of symptoms, resection extent, primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and days under radiotherapy treatment. CONCLUSIONS: Patients with supratentorial or infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis fields are used when spinal seeding is radiographically or pathologically evident. Spinal cord tumors are treated using localized fields to the primary site if not completely resected. Failure to control disease at the primary site remains the main impediment to cure.

Adolescent↗
PubMed1998

Outcome after radiotherapy of primary spinal cord glial tumors.

Primary spinal cord tumors are rare, and treatment recommendations are therefore difficult. We reviewed a 22-year experience of postoperative radiotherapy for spinal cord tumors to elucidate prognostic factors and recommendations. Twenty-two patients with spinal cord tumors were treated from 1969-1991. Ten patients had ependymomas, of which two were high grade. Twelve had astrocytomas, of which 4 were high grade. Karnofsky status, age, extent of resection, tumor histology, grade, and radiation dose were evaluated, as well as degree of clinical improvement after treatment based on change in Karnofsky status. Ependymomas achieved 100% local control with postoperative radiotherapy. Grade and dose were of indeterminate significance because of these excellent results. High-grade astrocytomas all recurred and caused death. Disease recurred in 1 of 8 patients with low-grade astrocytic or mixed astrocytic tumors. The only prognostic variables of significance were histology, grade, and change in Karnofsky status after treatment. Radiation of primary spinal cord tumors is rare. In nearly all cases, local fields may be used. Improvement in Karnofsky status after radiotherapy may predict better survival. Treatment recommendations for these rare tumors are discussed.

Adolescent↗
PubMed1998

Comparative value of thallium and glucose SPECT imaging in childhood brain tumors.

Thallium-201 chloride (201Tl) single-photon emission computed tomography (SPECT) detects a high percentage of histologically and anatomically diverse pediatric brain tumors. Thallium-201 chloride SPECT and F-18 fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) are the most commonly used radionuclide techniques in neuro-oncology. Having developed a methodology to image 18F-FDG with SPECT, the authors performed SPECT scans coupled with magnetic resonance imaging to assess the comparative sensitivity of 201Tl and 18F-FDG in 19 children with brain tumors. Tumors were detected using 201Tl SPECT in 14 of 19 patients. Five of five postoperative residual tumors were detected by 201Tl SPECT, and six of seven after irradiation recurrences were detected. F-18 fluoro-deoxy-glucose SPECT detected tumors in only three of 19 patients, all of whom had abnormal 201Tl studies (all three after therapy recurrences). Thallium-201 chloride SPECT could be interpreted in 18 of 19 patients without magnetic resonance imaging confirmation, but none of the 19 18F-FDG SPECT studies could be interpreted without magnetic resonance imaging. Thallium-201 chloride SPECT is more sensitive than 18F-FDG SPECT in the detection of primary or recurrent childhood brain tumors. The failure of 18F-FDG SPECT in follow-up after therapy is primarily a problem of limited fluoro-deoxy-glucose uptake, not spatial resolution. Thallium-201 chloride SPECT is a promising imaging modality in neuro-oncology.

Brain Neoplasms↗