[Simultaneous occurrence of neurofibromatosis and tuberous sclerosis, acquired as neo-mutations]. / Ocurrencia simultánea de neurofibromatosis y esclerosis tuberosa, adquiridas como neomutaciones.

INTRODUCTION: Neurofibromatosis type 1 and tuberous sclerosis are two distinct neurocutaneous syndromes that result of a mutation of tumoral suppressor genes, increasing the risk of tumorigenesis. They both have dominant autosomal hereditariness with half of the cases corresponding to new mutations. They are situations rarely associated. CASE REPORT: A boy without any family history of neurocutaneous disorders who had characteristics of both neurofibromatosis and tuberous sclerosis, as cafe-au-lait patches, six greater than 0.5 cm, macrocephaly, optic nerve glioma, focal alterations of the myelin vacuolization of the white matter from both cerebellar hemispheres, brain stem, basal ganglia, characteristic of type 1 neurofibromatosis. He also presented hypopigmentation spots, infantile spasms, and imagiologic findings of cortical areas with altered mielinization on the white matter, left talamo-caudado sulcus calcifications, cortical tubers, Taylor cortical dysplasia, subependimary nodes, characteristically of tuberous sclerosis. The child also had psycho motor development delay. CONCLUSION: The diagnosis of both disorders was confirmed by genetic study. Parents study was negative, so we can confirm the simultaneous occurrence of two new mutations which is unusually rare.

Ocurrencia simultánea de neurofibromatosis y esclerosis tuberosa, adquiridas como neomutaciones / Simultaneous occurrence of neurofibromatosis and tuberous sclerosis, acquired as neo-mutations

La neurofibromatosis tipo 1 y la esclerosis tuberosa son dos síndromes neurocutáneos distintos, resultadode la mutación de genes supresores tumorales, que aumentan la propensión a la génesis tumoral. Ambas tienen una herencia autosómica dominante y la mitad de los casos corresponden a nuevas mutaciones. Estas enfermedades raramente se presentan asociadas. Caso clínico. Niño sin antecedentes familiares de enfermedades neurocutáneas, que presenta característicasde neurofibromatosis y de esclerosis tuberosa, principalmente manchas ‘café con leche’ (seis de ellas con un diámetro superior a 0,5 cm), macrocefalia, glioma del nervio óptico y alteraciones focales de vacuolización de la mielina en la sustanciablanca de los hemisferios cerebelosos, tronco cerebral y ganglios de la base, características de la neurofibromatosis tipo 1. Por otro lado, presenta manchas hipopigmentadas, espasmos infantiles y evaluación imaginológica de las áreas de alteraciónde la mielinización de la corteza para la sustancia blanca, calcificaciones en el surco talamocaudado a la izquierda, tuberosidades corticales, displasia cortical focal de Taylor y múltiples nódulos subependimarios, características que son compatibles con la esclerosis tuberosa. El niño también presenta retraso en el desarrollo psicomotor. Conclusión. El diagnósticode ambas enfermedades se confirmó gracias al estudio genético. La evaluación de los progenitores fue negativa, por lo que se puede confirmar la presencia de dos neomutaciones concomitantes, un hecho que es excepcionalmente raro

Neurofibromatosis type 1 and tuberous sclerosis are two distinct neurocutaneous syndromes thatresult of a mutation of tumoral suppressor genes, increasing the risk of tumorogenese. They both have dominant autosomal hereditariness with half of the cases corresponding to new mutations. They are situations rarely associated. Case report. A boy without any family history of neurocutaneous disorders who had characteristics of both neurofibromatosis and tuberoussclerosis, as café-au-lait patches, six greater than 0.5 cm, macrocephaly, optic nerve glioma, focal alterations of the myelin vacuolization of the white matter from both cerebellar hemispheres, brain stem, basal ganglia, characteristic of type 1 neurofibromatosis. He also presented hypopigmentation spots, infantile spasms, and imagiologic findings of cortical areaswith altered mielinization on the white matter, left talamo-caudado sulcus calcifications, cortical tubers, Taylor cortical dysplasia, subependimary nodes, characteristically of tuberous sclerosis. The child also had psycho motor development delay.Conclusion. The diagnosis of both disorders was confirmed by genetic study. Parents study was negative, so we can confirm the simultaneous occurrence of two new mutations which is unusually rare

The spectrum of neurologic disease in children with systemic cancer.

To determine the range of neurologic complications in children with systemic cancer, we evaluated prospectively all of the neurologic consultations requested by the pediatric department of Memorial Sloan-Kettering Cancer Center from October 1997 until January 2001. Demographic data, main complaints, diagnosis, cancer status, etiology, and neuroradiologic studies were reviewed for the 528 consultations. Headache was the most frequent complaint (18.3%), followed by altered mental status (8.4%) and back pain (7.1%). Many children with these complaints had underlying structural disorders despite a normal neurologic examination. The symptoms varied with the underlying cancer and tumor status. Headaches were more common in patients with hematologic cancers, and back pain was more common in patients with solid tumors. Chronic headaches were frequent in patients in remission. Iatrogenic complications, particularly related to chemotherapy, constituted the largest etiologic group (27.7%). A high percentage of neuroradiologic studies were abnormal, and 63% of the magnetic resonance imagine studies were diagnostic. The broad spectrum of conditions underlying the neurologic complaints of children with systemic cancer illustrates the complexity of problems presented by these patients and requires a thorough knowledge of pediatric cancer, its effects on the nervous system, and the complications of its treatment from the neurology consultant.

Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: clinical outcome and antineuronal antibodies-a report from the Children's Cancer Group Study.

BACKGROUND: Opsoclonus-myoclonus-ataxia (OMA) is a paraneoplastic neurologic syndrome affecting 2-3% of children with neuroblastoma. Although children with OMA and neuroblastoma may have higher survival, many experience a significant amount of late neurologic impairment, which may be immunologically mediated. The aim of this study was to compare the outcome of neuroblastoma patients with and without OMA, relating to prognostic factors, treatment, and the presence or absence of anti-neuronal antibodies. PROCEDURE: Questionnaires were mailed out requesting information on the current neurologic status of patients who submitted sera at diagnosis to the Children's Cancer Group serum bank from 1980 to 1994. Information was requested on clinical and biological patient characteristics as well as clinical aspects of the patients identified as having OMA syndrome, including presentation and treatment for OMA, late sequelae of OMA, the presence or absence of antineuronal antibodies, and survival. Sera from 16 of the OMA patients and 48 case-controls with neuroblastoma were assayed for anti-neuronal antibodies. RESULTS: Of the 675 responses received, 21 patients had OMA. Ninety percent of OMA patients presented with non-metastatic disease, vs. 35% of non-OMA patients. Estimated 3-year survival for the OMA patients with nonmetastatic disease (stage I, II, III) greater than 1 year of age was 100% vs. 77% for similar non-OMA patients (P = 0.0222). At follow-up, 14/19 evaluable OMA patients displayed some form of developmental or neurologic abnormality. There was no significant correlation of late sequelae with antineuronal antibodies, age, time between OMA symptoms and diagnosis, or treatment given for tumor or OMA. There was a significant correlation of late sequelae with lower stage disease (I and II) compared to more advanced disease (III and IV). CONCLUSIONS: Patients with OMA and neuroblastoma have excellent survival but a high risk of neurologic sequelae. Favorable disease stage correlates with a higher risk for development of neurologic sequelae. The role of anti-neuronal antibodies in late sequelae of OMA needs further clarification.

Intracranial Ewing sarcoma/'peripheral' primitive neuroectodermal tumor of dural origin with molecular genetic confirmation.

Ewing sarcoma/'peripheral' primitive neuroectodermal tumor (ES/pPNET) is the designation given to a family of small cell neoplasms that typically arise in bone or soft tissue and are unified by their common expression of the MIC2 antigen and specific translocations involving a gene on chromosome 22q12 [the most common being t(11;22)(q24;q12)]. ES/pPNET of intracranial origin is extraordinary. We report the case of a 6-year-old boy with a large left frontal region mass that adhered to dura and was extracerebral at surgery. Histologic study revealed a high-grade, undifferentiated-appearing neoplasm of small cell type that was negative on immunostudy for glial fibrillary acidic protein, synaptophysin, desmin, leukocyte common antigen, smooth muscle actin and epithelial membrane antigen, but positive for vimentin and neuron-specific enolase and diffusely labeled by antibody O13 (which recognizes the MIC2 gene product). RNA-based polymerase chain reaction assay confirmed the diagnosis of ES/pPNET by demonstrating fusion transcripts indicative of t(11;22) translocation. Bone scan, computerized tomography of the chest and bone marrow examination revealed no systemic tumor. The limited observations published to date suggest that primary intracranial ES/pPNET is most likely to present in childhood as a circumscribed, contrast-enhancing and dural-based extracerebral mass. It must be distinguished from a variety of small cell neoplasms, particularly PNETs of central neuroepithelial origin.

Acute neurologic complications in children with systemic cancer.

Neurologic complications are common in children with cancer, but the literature dealing with this subject is sparse. Using a symptoms and signs approach, the most common causes for requesting a neurologic evaluation for this population are reviewed. The spectrum of neurologic symptoms in children with cancer differs from adults and requires the consulting neurologist to have a thorough knowledge of childhood cancer and its effects on the nervous system.

Targeted radioimmunotherapy for leptomeningeal cancer using (131)I-3F8.

BACKGROUND: Intrathecal antibody-based targeted therapies may have clinical potential for patients with leptomeningeal (LM) cancer. PROCEDURE: Five patients with GD2-positive LM tumors were injected with 1-2 mCi intra-Ommaya (131)I-3F8, a murine IgG3 antibody specific for GD2. Serial cerebrospinal fluid (CSF) and serum samples and SPECT imagings (4, 24, and 48 hr) were performed to predict radiation doses to the tumor and normal brain and blood prior to the administration of larger therapeutic doses. RESULTS: Side effects included self-limited fever, headache, and vomiting. Focal (131)I-3F8 uptake consistent with tumors was seen along the craniospinal axis in four patients. Calculated radiation dose to the CSF was 14.9-56 cGy/mCi and to blood and other organs outside the CNS less than 2 cGy/mCi. CONCLUSIONS: Intraventricular (131)I-3F8 successfully detected LM disease and resulted in a large favorable CSF/blood ratio. Intraventricular (131)I-3F8 may have clinical utility in the diagnosis and radioimmunotherapy of GD2-positive LM cancers. Med. Pediatr. Oncol. 35:716-718. 2000.

Numb chin syndrome in Ewing sarcoma.

The numb chin syndrome consists of unilateral hypesthesia of the chin and lower lip. In adults, it is often associated with metastatic disease to the mandible, base of the skull, or leptomeninges. In children, it has been associated with infiltration of the inferior alveolar nerve by leukemic cells. We describe two cases of numb chin syndrome in children with Ewing sarcoma. In a child with a solid tumor, this symptom seems to have an ominous meaning and should lead to the investigation of progressive skeletal involvement.

Rolandic encephalopathy and epilepsia partialis continua following bone marrow transplant.

Epilepsia partialis continua (EPC) is a condition defined by prolonged focal myoclonus. Often resistant to therapy, EPC in children is frequently present in Rasmussen encephalitis, a form of chronic encephalitis of uncertain etiology. We discuss a child who developed bilateral EPC 5 months after a bone marrow transplant. Neuroimaging studies showed signal abnormalities on both sensory-motor areas. An extensive search failed to reveal the etiology of the disorder, but treatment with a broad-spectrum anti-viral agent was associated with resolution of the process. An unidentified infectious agent may be responsible for an encephalitis of the motor strip in immunosuppressed patients.

Antineuronal antibodies in patients with neuroblastoma and paraneoplastic opsoclonus-myoclonus.

PURPOSE: To identify serologic markers in children with paraneoplastic opsoclonus-myoclonus (POM). MATERIALS AND METHODS: We examined the sera of 64 children with neuroblastoma (16 with POM and 48 age-matched and stage-matched controls) by immunohistochemistry of rat brain and human cerebellum, and by Western blot analysis of protein extracts from human Purkinje cells, cortical neurons, neuroblastoma cell lines, and HuD. RESULTS: Using immunohistochemistry, IgG reactivity against neurons was identified in 13 of 16 POM sera (81%), and 12 of 48 non-POM sera (25%; P<0.001). IgM antineural antibodies were present in 3 of 16 POM sera (19%) and 11 of 48 (23%) non-POM sera. Except for anti-Hu antibodies detected in 10 sera (4 with POM), no other specific reactivities were identified by Western blot analysis of neuronal or of neuroblastoma protein extracts. CONCLUSIONS: We conclude that: 1) patients with neuroblastoma and POM are more likely to harbor antineuronal antibodies than patients without POM; 2) no specific serologic marker of POM was identified, but the frequent presence of antineuronal antibodies suggests that POM is immune-mediated; and 3) anti-Hu antibodies are present in some sera from patients with neuroblastoma, irrespective of the presence of POM.

Globular glioma of the tectum.

Brainstem gliomas are a heterogeneous group of tumors whose prognosis and treatment depend not only on the histologic features but also on the location within the brainstem. Magnetic resonance imaging allows the recognition of a distinct type of brainstem glioma of the tectal region of the midbrain, leading to aqueductal compression and hydrocephalus. The radiologic appearance of these tumors is usually rather uniform, with a characteristic nonenhancing thickening of the tectal plate. Because of its protracted course, no further treatment is necessary beyond cerebrospinal fluid diversion and close clinicoradiologic follow-up. The authors report two children with tectal plate gliomas of unusual but strikingly similar appearance. They present a clinical picture suggestive of intracranial hypertension without localizing signs. Magnetic resonance images reveal hydrocephalus related to the presence of perfectly circular lesions, hypointense on T1 and hyperintense on T2, which could be mistaken for parasitic cysts or represent dilated rostral portions of the sylvian aqueduct. After the cerebrospinal fluid diversion procedures, no further treatment was given, with one of the patients being monitored for 10 years and the other for 8 months, without tumor progression. These patients demonstrate that tectal gliomas, despite sharing a good prognosis, may have various patterns of growth, leading to unusual radiologic appearances that may pose diagnostic difficulties.

Posterior leukoencephalopathy syndrome may not be reversible.

The association of an acute reversible encephalopathy with transient occipital lobe abnormalities on imaging studies is well known. This condition has been called reversible posterior leukoencephalopathy syndrome. The clinical presentation usually includes seizures, headache, altered mental status, and blindness, often associated with hypertension and immunosuppressants. The authors discuss a two-year-old male with Down syndrome who presented 2 months after allogeneic bone marrow transplantation with severe oculogyric crisis, without other complaints. The patient was being treated for hypertension and was receiving cyclosporine for prophylaxis of graft-vs-host disease. A computed tomography scan of the head revealed marked bilateral lucencies mainly involving the white matter of the occipital lobes, with a few foci of punctate hemorrhage. The condition improved when cyclosporine was discontinued, but an area of leukomalacia was identified on follow-up magnetic resonance imaging. To the authors' knowledge, oculogyric crisis as a presentation of reversible posterior leukoencephalopathy has not been previously described. Recognizing this association is important, because patients receiving cyclosporine are often receiving other medications that can potentially cause dystonic eye movements, possibly leading to a delay in diagnosis and treatment, which can result in an irreversible neurologic deficit.

Neurologic consultations in children with systemic cancer.

The frequency and severity of neurologic symptoms in children with systemic cancer is unknown. The authors reviewed the records of children with systemic cancer for whom a neurologic consultation was requested between 1993 and 1996. The 157 patients had 161 malignancies and 205 consultations. Leukemia (59) and lymphoma (34) were the most common malignancies. The 68 solid tumors included neuroblastoma (13), Ewing's sarcoma, and rhabdomyosarcoma (10 each). In contrast to adults, in whom back pain and altered mental status are the most common reasons for neurologic consultation, headache (33) and seizures (29) were the most common symptoms in children. Structural lesions were present in 84% of patients with headache and focal deficit and in 14% of patients with isolated headache. Structural disease was identified in 37% of children with seizures. Neurologic signs were caused by complications of cancer therapy in 70 instances and to direct tumor invasion of the nervous system in 60. In 71 consultations, neurologic symptoms could not be attributed to cancer or its treatment. The spectrum of neurologic symptoms in children with cancer differs from adults and requires the consulting neurologist to have a thorough knowledge of childhood cancer and its effects on the nervous system.

Brain abscesses in children with cancer.

BACKGROUND: Brain abscesses in pediatric patients are rare events, and the causative organism and prognosis vary with the population under study. Children with cancer seem to be particularly susceptible to the development of brain abscesses because of the immunological changes induced by cancer and its treatment. We reviewed the records of children who developed a brain abscess during treatment of a malignancy to define the clinical characteristics, prognosis, and management of these patients. PROCEDURE: We performed a retrospective review of the clinical and laboratory characteristics of all cancer patients younger than age 20 years who were admitted to our institution between 1980 and 1996 for a brain abscess. RESULTS: Twelve children were identified. Cancer diagnoses were brain tumor in two, systemic PNET in two, and leukemia in eight. Six patients had multiple abscesses. Eleven received prior chemotherapy. Abscesses were surgically excised or aspirated in seven, and empiric antibiotics were given to the other five. At surgery, Listeria monocytogenes, Aspergillus fumigatus (3), Fusarium, and Candida lusitanea were cultured. Aspergillus was identified in other locations in four patients. Abscesses were successfully treated in seven patients, two of whom received antibiotics only; five patients (42%) died from infection. CONCLUSIONS: Mortality is high in this immunosuppressed population, in part due to the preponderance of fungal infection. The finding of very rare organisms suggests that drainage and culture should be performed whenever possible; empiric antibiotics that include an antifungal agent may, on occasion, be successful.

[The use of a multimix as a dietary supplement: study in rats]. / Uso de uma multimistura como suplementação alimentar: Estudo em ratos.

A Multimistura (MM)--sweet cassava (Manihot esculenta Crantz) leaf flour, wheat bran (Tritium aestivum L.), egg shell powder, pumpkin (Cucurbita Spp) and sunflower (Heliantus annus) seed flours--was added to a mixture of Beans, 7% (Phaseolus vulgaris) and Rice, 3% (Oryza sativa) and its effects, were assessed in weanling, male albino (Wistar) rats (n = 60). Animals were divided into 6 groups: groups 1, 2 and 3 were fed beans + rice + multimixture (B + R + MM), beans + rice (B + R) and 10% Casein, respectively; the remaining groups were maintained on a protein-free diet (PFD) for 14 d and then submitted to the same feeding protocol. Microbiological assays were performed in all MM samples. The Coefficient of Digestablity (CD), the Food Efficiency Ratio (FER), Protein Efficiency Ratio (PER), Net Protein Utilization (NPR), serum hemoglobin (Hb) and hematocrit (Ht), carcass total lipids were determined. Rats had their liver, brain, gonads, testes, spleen and left kidney removed for wet dry weights. Liver samples were histologically examined. The Mann-Whitney test was used. The protein content of B + R diet increased slightly after MM addition (0.23 g/100 g). Three out of four MM samples had moulds and yeasts. CD values were 90% and 70% for casein and B + R + MM-fed rats, respectively. The highest values for FER, PER and NPR were seen in the casein-fed rats without protein depletion. The casein-fed group had heavier organs (wet and dry weights) and higher values for carcass fat and serum Hb and Ht. Steatosis was present in both groups, with or without protein depletion. Short or long-term MM consumption, at least under our experimental conditions, had no significant effects on investigated parameters.

Acute infantile thalamic necrosis.

An acute encephalopathy of infancy presenting as seizures and coma following a presumably infectious disease with the distinctive finding of thalamic necrosis was recently described. The authors report a similar case in an 11-month-old infant, and discuss its possible pathogenesis.

Atypical dominance for language in developmental dysphasia.

The authors report an association between developmental language disorder and acquired aphasia in a 13-year-old right-handed boy. Acquired aphasia was caused by a right-frontal abscess (crossed aphasia). It was non-fluent, with a disorder of auditory comprehension, an unusual feature of prerolandic lesions. This case shows that developmental language impairment can be associated not only with an atypical cerebral dominance, but also with unusual patterns of intrahemispheric specialization. The rapid and complete recovery of this boy's aphasia suggests that the cerebral plasticity for acquired lesions can be normal in such cases.

Schinzel-Giedion syndrome. A patient with hypothyroidism and diabetes insipidus.

The Schinzel-Giedion is an autosomal recessive syndrome characterized by midface retraction, hypertrichosis, multiple skeletal anomalies, cardiac and renal malformations and mental retardation. We describe a female child with this syndrome and a clinical status complicated by hypernatremic dehydration, hypothyroidism and diabetes insipidus at the age of 10 months.

[Bean and rice mixtures of high protein value (author's transl)]. / Misturas de feijão e arroz de alto valor protéico.

The optimum content of different rice (Oryza sativa) and bean (Vigna unguiculata L.) combinations was studied in Albino rats. The mixture containing 3 g of rice proteins, corresponding to 41g of rice "in natura", and 7 g of bean protein, corresponding to 59 g of bean "in natura", presented the highest protein efficiency ratio and the feed efficiency ratio. Since the limiting amino acid of this mixture was methionine, new assays using varying levels of this amino acid as a supplement were carried out. The PER of normal rats as well as the "plateau" value of previously protein depleted rats were highest when 0.2% methionine was added to the mixture. The net protein utilization (NPU) confirmed these findings. The values attained after the addition of other amino acids were not higher than those attained by the mixture containing 7 g of bean protein and 3 g of rice protein supplemented with 0.2% methionine. The PER and the NPU values came close to those of milk.