Classification of oligodendroglial tumors based on histopathology criteria is a significant predictor of survival--clinical, radiological and pathologic long-term follow-up analysis.

BACKGROUND: The clinical course of oligodendroglial tumors is variable and there is a lack of consensus with regard to precisely diagnose which minimal criteria are required to make a diagnosis of a high-grade oligodendrial tumor. The aims of the present study are to assess pathologic factors with prognostic significance, in addiction to clinical and neuroradiologic variables, in an attempt to identify reproducible histological parameters that are useful for classification of oligodendroglial tumors. METHODS: 80 oligodendroglial tumors diagnosed between 1977 and 2004 were analyzed. To make a diagnosis of anaplastic tumor we used reproducible parameters: endothelial proliferation, high cellularity, increased mitotic activity and necrosis. Oligoastrocytomas (mixed gliomas) were diagnosed when the astrocytic component was clearly identified as part of the neoplastic cell population. Survival univariate analysis was made constructing survival curves using Kaplan-Meier method and comparing subgroups by log-rank probability test. A Cox regression model was made for multivariable analysis. RESULTS: The histologic diagnosis was low-grade oligodendroglioma in 35 patients (43.75%), anaplastic oligodendroglioma in 23 patients (28.75%), low-grade oligoastrocytoma in 11 patients (13.75%) and anaplastic oligoastrocytoma in 11 patients (13.75%). Median overall survival of the whole series was 80 months. The median overall survival of oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma and anaplastic oligoastrocytoma was 148, 105, 47 and 7 months, respectively (p < 0.0001). Multivariate analysis revealed that age, Karnofsky performance status, histological grade and histological diagnosis (oligodendroglioma vs. oligoastrocytoma) were independently associated with survival. CONCLUSIONS: Clear cut histopathological criteria (endothelial proliferation, high cellularity, mitotic activity and necrosis) allow to establish different oligodendroglial tumor entities with distinct survival outcome.

[Parkinsonism and Camptocormia with focal spinal myopathy: case report and responsiveness to treatment]. / Parkinsonismo y camptocormia con miopatia focal espinal: descripcion de un caso y respuesta al tratamiento.

INTRODUCTION: Camptocormia is characterised by extreme flexion of the thoracolumbar spine. It suffered an increase during walking and it is relieved in supine position. Camptocormia has been described in psychogenic disorders, but in other diseases, including Parkinson's disease as well. It has been recently described several cases with focal spinal myopathy, and we present a patient with this clinical association. CASE REPORT: This 82-year-old man had a 6-year history of parkinsonian symptoms, mostly of rigid-akinetic type. He was in stage 4 on Hoehn & Yahr scale, and he had reached 62 points on Unified Parkinson Disease Rating Scale. Over the past 6-8 months, he developed progressive forward flexion of the trunk with clinical features of camptocormia. He suffered flogotic symptoms and signs on her lower back, and there were no dystonic posture or clinical features. Lumbar computerised tomography showed fat replacement of the paravertebral L3 muscles. A surgical paravertebral muscle examination and biopsy were performed, showing diffuse fat replacement and only a marginal myopathic focus. It was made several therapeutic approaches, with levodopa dose increase, reduction, fractioning, and addition of dopa-agonists. All of these strategies failed. It was determined to try a steroid course, but there were no improvement, so physiotherapy and rehabilitation measures did. He finally was confined to wheelchair. CONCLUSIONS: Physiopathologic and therapeutic aspects of camptocormia in Parkinson's disease are unclear. Their relationship could be casual or causal. Patients with clear inflammatory myopathy could benefit from steroid therapy, but patients with end-stage myopathy probably do not so.

Parkinsonismo y camptocormia con miopatía focal espinal: descripción de un caso y respuesta al tratamiento / Parkinsonism and camptocormia with focal spinal myopathy: case report and responsiveness to treatment

Introducción. La camptocormia es un trastorno caracterizadopor una postura anormal en flexión pronunciada del tronco,que desaparece al tumbarse y empeora al caminar; es de etiologíadiversa. Desde las consideraciones iniciales como trastorno psicogénico,se reconoce ya como un trastorno postural característicode la enfermedad de Parkinson, y se han descrito algunos casos enrelación con miopatías focales lumbares. Presentamos un pacientecon esta asociación clínica. Caso clínico. Varón de 82 años conparkinsonismo rígido-acinético de seis años de evolución, en estadio4 de la escala de Hoehn y Yahr, y 62 puntos en la Unified ParkinsonDisease Rating Scale. En 6-8 meses, desarrolló progresivamenteuna camptocormia dolorosa, sin datos de distonía asociados,y con signos flogóticos dorsolumbares. La tomografía axialcomputarizada lumbar mostró atrofia de los músculos espinales ysustitución grasa. La biopsia de músculos paraespinales mostródegeneración grasa y algún foco miopático marginal. Tras modificacionesinfructuosas de su medicación dopaminérgica (incremento,disminución, fraccionamiento, agonistas dopaminérgicos), serealizó ciclo de tratamiento esteroideo por vía oral, sin observarsemejoría alguna. Tampoco mejoró con rehabilitación o fisioterapia,y quedó confinado a una silla de ruedas. Conclusiones. Los aspectosfisiopatológicos y terapéuticos en la camptocormia con miopatíafocal asociada a la enfermedad de Parkinson son poco claros, ypueden relacionarse de modo causal o casual. Los pacientes conclara miopatía inflamatoria podrían beneficiarse de terapia esteroideaprecozmente, pero no aquellos con estadios finales de miopatíafocal espinal

Introduction. Camptocormia is characterised by extreme flexion of the thoracolumbar spine. It suffered an increaseduring walking and it is relieved in supine position. Camptocormia has been described in psychogenic disorders, but in otherdiseases, including Parkinson’s disease as well. It has been recently described several cases with focal spinal myopathy, andwe present a patient with this clinical association. Case report. This 82-year-old man had a 6-year history of parkinsoniansymptoms, mostly of rigid-akinetic type. He was in stage 4 on Hoehn & Yahr scale, and he had reached 62 points on UnifiedParkinson Disease Rating Scale. Over the past 6-8 months, he developed progressive forward flexion of the trunk with clinicalfeatures of camptocormia. He suffered flogotic symptoms and signs on her lower back, and there were no dystonic posture orclinical features. Lumbar computerised tomography showed fat replacement of the paravertebral L3 muscles. A surgicalparavertebral muscle examination and biopsy were performed, showing diffuse fat replacement and only a marginalmyopathic focus. It was made several therapeutic approaches, with levodopa dose increase, reduction, fractioning, and additionof dopa-agonists. All of these strategies failed. It was determined to try a steroid course, but there were no improvement, sophysiotherapy and rehabilitation measures did. He finally was confined to wheelchair. Conclusions. Physiopathologic andtherapeutic aspects of camptocormia in Parkinson’s disease are unclear. Their relationship could be casual or causal. Patientswith clear inflammatory myopathy could benefit from steroid therapy, but patients with end-stage myopathy probably do not so

[Myopathy with trabecular fibers associated with familiar autoimmune polyglandular syndrome type 1]. / Miopatía con fibras trabeculares asociada a síndrome poliglandular autoinmune tipo 1 familiar.

An association between limb-girdle muscular dystrophy and autoimmune polyglandular syndrome type 1 (APS1), in three sisters born to consanguineous parents, is presented. The components of APS1 in these patients were hypoparathyroidism, autoimmune adrenal insufficiency, primary hypogonadism and mucocutaneous candidiasis. A muscle biopsy performed on the first patient showed over 40 % of trabeculated fibers, suggesting the diagnosis of myopathy with trabeculated fibers (MTF). Intracranial calcification was found in the second patient; and epilepsy, and several other minor components of APS1, in the third; cataracts were found in the last two patients. The clinical manifestations and inheritance of MTF and APS1 are reviewed. While recessive mutations in the AIRE gene (21q22.3) cause APS1, genetic transmission of hereditary MTF has not been investigated in depth. Mutations in CRYAA, a gene that shares the same locus as AIRE, may cause recessive inheritance of cataracts. Thus, the proposal of this article is that linkage of contiguous genes that includes the AIRE gene, might be responsible for the association of both diseases in these three patients. Additional involvement of CRYAA, that possibly causes cataracts in two of the patients, might support this hypothesis, due to the proximity of this gene to AIRE. The genes COL6A1 and COL6A2, localized in 21q22.3, are discarded as transmitters of MTF in these cases, on clinical criteria. The authors wish to draw attention to the association between limb-girdle muscular dystrophy and APS1, since it has been very rarely reported in the medical literature.

Miopatía con fibras trabeculares asociada a síndrome poliglandular autoinmune tipo 1 familiar / Myopathy with trabecular fibers associated with familiar autoinmune polyglandular syndrome type 1

En este trabajo se presenta la asociación de distrofia muscular de cinturas con síndrome poliglandular autoinmune tipo 1 (SPA 1) en tres hermanas, hijas de padres consanguíneos. En las tres pacientes, el SPA 1 estuvo constituido por hipoparatiroidismo, insuficiencia suprarrenal, hipogonadismo primario y candidiasis mucocutánea. La biopsia muscular en una paciente reveló el 40 % de fibras trabeculares, sugiriendo el diagnóstico de miopatía con fibras trabeculares (MFT). Otras manifestaciones fueron calcificaciones intracraneales en la segunda paciente, epilepsia y múltiples componentes adicionales de SPA 1 en la tercera, y cataratas en estas dos. En este estudio se revisan las características clínicas y los mecanismos hereditarios del SPA 1 y la MFT. Mientras que el SPA 1 se transmite con herencia autosómico recesiva por mutaciones en el gen AIRE, localizado en 21q22.3, no se conoce la transmisión genética de la MFT hereditaria. Mutaciones en el gen CRYAA, ubicado en el mismo locus que AIRE, pueden transmitir cataratas con herencia recesiva. Se propone en consecuencia que la asociación de MFT con el SPA 1 en estas tres pacientes fuera transmitida por ligamiento de genes contiguos, que debería incluir el gen AIRE. La participación adicional del gen CRYAA en dos casos apoyaría esta hipótesis por su proximidad con el gen AIRE. Se descarta que estos casos de distrofia muscular estén transmitidos por los genes COL6A 1 y COL6A2, causantes de miopatía y situados en 21 q22.3, en base a criterios clínicos. Se pretende, en suma, destacar la asociación entre SPA 1 y distrofia muscular de cinturas por haber sido muy raramente mencionada en la literatura neurológica

An association between limb-girdle muscular dystrophy and autoimmune polyglandular syndrome type 1 (APS 1), in three sisters born to consanguineous parents, is presented. The components of APS 1 in these patients were hypoparathyroidism, autoimmune adrenal insufficiency, primary hypogonadism and mucocutaneous candidiasis. A muscle biopsy performed on the first patient showed over 40 % of trabeculated fibers, suggesting the diagnosis of myopathy with trabeculated fibers (MTF). Intracranial calcification was found in the second patient; and epilepsy, and several other minar components of APS1, in the third; cataracts were found in the last two patients. The clinical manifestations and inheritance of MTF and APS 1 are reviewed. While recessive mutations in the AIRE gene (21q22.3) cause APS 1, genetic transmission of hereditary MTF has not been investigated in depth. Mutations in CRY AA, a gene that shares the same locus as AIRE, may cause recessive inheritance of cataracts. Thus, the proposal of this article is that linkage of contiguous genes that includes the AIRE gene, might be responsible far the association of both diseases in these three patients. Additional involvement of CRYAA, that possibly causes cataracts in two of the patients, might support this hypothesis, due to the proximity of this gene to AIRE. The genes COL6A1 and COL6A2, localized in 21q22.3, are discarded as transmitters of MTF in these cases, on clinical criteria. The authors wish to draw attention to the association between limb-girdle muscular dystrophy and APS1, since it has been very rarely reported in the medical literature

[Adult-onset subacute sclerosing panencephalitis: clinicopathological findings]. / Panencefalitis esclerosante subaguda de comienzo en la edad adulta: hallazgos clinicopatológicos.

INTRODUCTION: Subacute sclerosing panencephalitis is a disease affecting the central nervous system that is produced by persistent infection by a defective measles virus. This disease is very infrequent and its incidence has gone down even further in western countries since the introduction of generalised measles vaccinations. Onset of the disease is usually during infancy or adolescence. Reports of cases beginning during adulthood are scarce. CASE REPORT: We describe the case of a 30-year-old female with a slowly progressive subacute clinical picture consisting in behavioural disorders, with defrontalisation, cortico-subcortical cognitive impairment, long tract signs and visual disorders, which led the patient into a vegetative state. Four years after the onset of symptoms the patient died. The different electroencephalogram recordings performed did not show any periodic activity and magnetic resonance imaging of the head revealed cerebral atrophy with hyperintense lesions in T2 sequences in white matter. The histological study of the brain showed a chronic inflammatory infiltration with neuronal loss and demyelination, as well as intranuclear inclusions and neurofibrillary degeneration. CONCLUSIONS: The appearance of subacute sclerosing panencephalitis in adulthood is exceptional. Diagnosis requires a high degree of clinical suspicion, above all in the absence of typical symptoms, such as myoclonias or periodic complexes in EEG recordings.

[Mitochondriopathies]. / Mitocondriopatías.

AIMS: The purpose of this study is to review different aspects of mitochondrial myopathies. DEVELOPMENT: Mitochondrial DNA is different to that found in the nucleus and is generally inherited through the mother. There are from 2 to 10 copies per mitochondrion and hundreds or thousands of mitochondria per cell. It contains 37 genes. The oxidative phosphorylation system consists of five enzymatic complexes. Mitochondrial diseases can affect many organs but somewhat more frequent in tissues that are physiologically more demanding as regards oxidative phosphorylation, such as the nervous system, the heart and skeletal muscle. Diagnosis of mitochondrial disease is performed by studying skeletal muscle because it is easily accessible and because of its dependence on oxidative metabolism; moreover, deficits in the respiratory chain are often not expressed in cultivated fibroblasts. CONCLUSIONS: The bioptic muscle specimen must be frozen using isopentane for later histochemical examination. For study under the electron microscope, a small sample must be set in glutaraldehyde or a similar fixative. A 150 mg (5 mm3) fragment which has been frozen without isopentane should be used for the study of the respiratory chain, although fresh muscle tissue is needed for the examination of the complex V. About 50 mg of frozen tissue are required for the study of the mitochondrial mutations.

[Congenital myopathies]. / Miopatías congénitas.

INTRODUCTION: Congenital myopathies include many genetically distinct diseases which have in common the early appearance of symptoms and characteristic morphological findings. AIM: To resume clinical, pathological and genetic findings of the most frequent myopathies in this group. DEVELOPMENT: The most severe of these group is myotubular myopathy; affected boys die frequently in the neonatal period due to respiratory failure. The altered protein, myotubularin, is involved in the metabolism of PI3P. The gene mutated is in Xq28 and more than 140 different mutations have been reported. Centronuclear myopathy is a genetically heterogeneous group, most frequently recessive but sometimes dominant and with a variable clinical course; childhood and adolescent cases usually present facial weakness and ophthalmoplegia together with proximal weakness, while adult forms show symptoms similar to limb girdle dystrophies. The protein responsible of the disease as well as the genetic locus involved are still unknown. Central core disease (CCD) is a scarcely progressive disease frequently associated with skeletal malformations. The inheritance is usually dominant. CCD has an important association with malignant hyperthermia and both diseases share the same gene in 19q13, locus of the RYR1 gene which encodes the ryanodine receptor. Minicore myopathy is a recessive disorder which shows four different phenotypes, the most frequent being the 'classical' one, with axial weakness, scoliosis and severe respiratory insufficiency; some of these cases have mutations in the selenoprotein N gene. Other phenotype with slowly progressive weakness and hand atrophy has a homozygous mutation in the RYR1 gene. Nemaline myopathy shows four different clinical and genetic types according to the age of beginning of symptoms and the type of inheritance. Several different genes have been identified: TPM3 in 1q21, NEB in 2q21 22, ACTA1, TPM2 and TNNT1.

Myotonic dystrophy associated with thyroid disease.

Two patients with hereditary, clinical, electromyographical and histological data typical of myotonic dystrophy are discussed. In both there was a thyroid disorder. The first patient had primary hypothyroidism, and the second a non-toxic multinodular goiter which necessitated total thyroidectomy. The EMG findings and the muscle histopathology of both patients are commented on and compared with the changes described in hypothyroidism. The disease processes in both patients are also discussed in relation to the muscle and metabolic changes described in myotonic dystrophy. The coexistence of these two diseases is not explicable in the light of present knowledge on the basis of a known genetic predisposition. Only two similar cases of myotonic dystrophy and hypothyroidism have been reported.