藤井 克則

Hedgehog (Hh)-Patched1 (Ptch1) signaling plays essential roles in various developmental processes, but little is known about its role in postnatal homeostasis. Here, we demonstrate regulation of postnatal bone homeostasis by Hh-Ptch1 signaling. Ptch1-deficient (Ptch1+/-) mice and patients with nevoid basal cell carcinoma syndrome showed high bone mass in adults. In culture, Ptch1+/- cells showed accelerated osteoblast differentiation, enhanced responsiveness to the runt-related transcription factor 2 (Runx2), and reduced generation of the repressor form of Gli3 (Gli3rep). Gli3rep inhibited DNA binding by Runx2 in vitro, suggesting a mechanism that could contribute to the bone phenotypes seen in the Ptch1 heterozygotes. Moreover, systemic administration of the Hh signaling inhibitor cyclopamine decreased bone mass in adult mice. These data provide evidence that Hh-Ptch1 signaling plays a crucial role in postnatal bone homeostasis and point to Hh-Ptch1 signaling as a potential molecular target for the treatment of osteoporosis.

We describe a 2-year-old girl with refractory macrophage activation syndrome (MAS), which is a serious complication of inflammatory disorders associated with rheumatic disease in children. Although she was treated with intensive immunosuppressive therapies such as immunoglobulin, plasma exchange, dexamethasone, methotrexate, cyclosporine, and etoposide, she subsequently developed motor deficit with the abolition of deep tendon reflexes. Since nerve conduction study revealed low-amplitude compound muscle action potentials and motor conduction slowing, she was diagnosed as having acute motor axonal neuropathy (AMAN) associated with refractory MAS. This is the first report of AMAN occurring during immunosuppressive therapy for extremely refractory MAS, suggesting that hypercytokinemia or activated macrophages may have played a critical role in the pathogenesis of AMAN in this patient. © 2007 Elsevier B.V. All rights reserved.

Small submicroscopic genomic deletions and duplications constitute up to 15% of all mutations underlying human monogenic diseases. In this study, we used newly designed high-resolution oligonucleotide microarrays with a median distance between the probes of 776 bp (average probe interval 2,271 bp) to detect gene deletions in nevoid basal cell carcinoma syndrome (NBCCS) patients. NBCCS, also called Gorlin syndrome, is characterized by developmental defects and tumorigenesis such as medulloblastomas and basal cell carcinomas, caused by mutations of the human patched-1 (PTCH1) gene. Two out of three deletions could not be detected by a conventional chromosomal analysis. A submicroscopic deletion as small as 165 kb was detected affecting only PTCH1, whereas the other two deletions were much larger (5 and 11 Mb). We demonstrated not only the exact number of genes involved in the deletion but also rapidly determined the junction sequences after pinpointing the breakpoint regions in all individuals analyzed. This report of an array-based determination of junction sequences of long deletions circumvented a labor-intensive analysis such as Southern blotting or FISH. Alu-mediated recombination in one case and non-homologous end joining in the other two were probably implicated in the generation of deletions. This method will contribute to the understanding of molecular pathogenesis of gene deletions as well as rapid genetic testing.

Neurologic involvement in nevoid basal-cell carcinoma syndrome includes intracranial calcification, congenital hydrocephalus, intracranial neoplasms, and mental retardation. A few cases of epilepsy with nevoid basal-cell carcinoma syndrome were reported. We report on a patient with nevoid basal-cell carcinoma syndrome and West syndrome. The patient had a heterozygous mutation (insertion of TGGC) in the PTCH gene. This mutation causes a shift of the reading frame, and creates a stop codon predicting the truncation of the PTCH protein. This mutation was not found in previously described patients with nevoid basal-cell carcinoma syndrome. © 2007 Elsevier Inc. All rights reserved.

A considerable fraction of mutations associated with hereditary disorders and cancers affect splicing. Some of them cause exon skipping or the inclusion of an additional exon, whereas others lead to the inclusion of intronic sequences or deletion of exonic sequences through the activation of cryptic splice sites. We focused on the latter cases and have designed a series of vectors that express modified U7 small nuclear RNAs (snRNAs) containing a sequence antisense to the cryptic splice site. Three cases of such mutation were investigated in this study. In two of them, which occurred in the PTCH1 and BRCA1 genes, canonical splice donor sites had been partially impaired by mutations that activated nearby intronic cryptic splice donor sites. Another mutation found in exonic region in CYP11A created a novel splice donor site. Transient expression of the engineered U7 snRNAs in HeLa cells restored correct splicing in a sequence-specific and dose-dependent manner in the former two cases. In contrast, the third case, in which the cryptic splice donor site in the exonic sequence was activated, the expression of modified U7 snRNA resulted in exon skipping. The correction of aberrant splicing by suppressing intronic cryptic splice sites with modified U7 is expected be a promising alternative to gene replacement therapy.

MR imaging of a patient with epilepsy and psychomotor retardation at 5 months revealed parieto-occipital pachygyria with almost normal cortical appearance and thickness in the frontal region this appearance evolved into diffuse pachygyria at 7 years. The change of the MR imaging findings may have resulted from myelination in the intracortical and subcortical fibers. It is important for clinicians to be aware of the longitudinal changes of the cerebral cortex in lissencephaly. © 2007 Elsevier B.V. All rights reserved.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder that is caused by inactivating mutations or a loss of both alleles in the NF2 tumor-suppressor gene. Bilateral vestibular schwannomas are considered to be the hallmark of this disease, with hearing loss and tinnitus which are caused by these tumors, usually presenting as the initial symptoms. In addition to other tumors and ocular findings, skin abnormalities also occur in NF2, however, they are not so characteristic as neurofibromatosis type 1 (NF1). We herein report a case of NF2 which occurred in a 5-year-old boy. He had multiple cutaneous tumors but did not have any symptoms related to vestibular schwannomas. He also had multiple depigmented spots. A histopathological examination revealed these tumors to be plexiform schwannomas we therefore suspected NF2. As a result of magnetic resonance imaging with gadolinium enhancement, bilateral vestibular schwannomas were detected and a final diagnosis of NF2 was thus made. The association between NF2 and multiple depigmented spots is unknown, we therefore consider that multiple cutaneous plexiform schwannomas may strongly suggest an association with NF2. © 2007 Japanese Dermatological Association.

Mutations in the human tumor suppressor gene, Patched-1, are associated with nevoid basal cell carcinoma syndrome characterized by developmental abnormalities and tumorigenesis, such as basal cell carcinoma and medulloblastoma. During the investigation of complex alternative splicing in Patched-1, we identified an alternative exon, exon 12b, located between exon 12 and 13, both in humans and in mice. Since exon 12b has an in-frame stop codon, the mRNA isoform containing this exon (Patched12b) encodes a truncated patched-1 protein. RT-PCR and whole mount in situ hybridization revealed that mouse exon 12b was expressed in the brain and heart, particularly in the cerebellum, in both adults and embryos. We next performed a functional analysis of Patched12b using a GLI-responsive luciferase reporter. Luciferase activity was suppressed when transfected with a plasmid encoding Patched-1, but not with a plasmid for Patched12b. The suppressive activity of Patched-1 was relieved when cotransfected with a plasmid for Patched12b. This implies that the Patched12b protein has a dominant negative effect on Patched-1. Interestingly, Patched12b was found to be expressed in some of the medulloblastoma tissues and cell lines, indicating an important role in the pathogenesis of medulloblastoma as well as brain development. © 2006 Elsevier Inc. All rights reserved.

Guillain-Barré syndrome (GBS) is classified into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), but little is known about the incidence of the subtypes and the prognosis of childhood GBS. To elucidate the features and long-term prognosis, clinical and electrophysiological data for 31 Japanese GBS children were reviewed. By electrodiagnostic criteria, children were classified as having AIDP (35%) or AMAN (48%), or were unclassified (16%). The AMAN children invariably had normal sensory nerve potentials. Between the two groups, age, sex, and clinical disability did not differ significantly, but the AIDP children more frequently had cranial and sensory nerve involvement, and the AMAN children more frequently had preceding gastroenteritis. By 6 months after onset, all the AIDP and 80% of the AMAN children had regained the ability to walk by 2 years, all but one of the AMAN children could walk. In Japanese childhood GBS, the proportion of AIDP and AMAN appears to be similar. Recovery is generally favorable in both subtypes, but some of the AMAN children experienced delayed recovery. © 2006 Wiley Periodicals, Inc.

We describe a 13-year-old boy with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) who experienced a stroke-like episode resulting in severe mental regression and quadriplegia. We tested 14-3-3 protein in the cerebrospinal fluid (CSF) of the patient four times around a stroke-like episode in a magnetic resonance imaging (MRI) study. Detection of the protein in the CSF was well correlated with the clinical course and range of damage of the brain lesion on MRI. Interestingly, 14-3-3 CSF protein was detected at the beginning of mitochondrial encephalopathy without new MRI abnormalities, suggesting that it is a sensitive brain marker. We conclude that 14-3-3 CSF protein is a useful biological marker of brain disruption in MELAS as well as other neurological disorders. © 2005 Elsevier B.V. All rights reserved.

Mutations in the human ortholog of Drosophila patched (PTCH) have been identified in patients with autosomal dominant nevoid basal cell carcinoma syndrome (NBCCS), characterized by minor developmental anomalies and an increased incidence of cancers such as medulloblastoma and basal cell carcinoma. We identified many isoforms of PTCH mRNA involving exons 1-5, exon 10 and a novel exon, 12b, generated by alternative splicing (AS), most of which have not been deposited in GenBank nor discussed earlier. To monitor splicing events of the PTCH gene, we designed oligonucleotide arrays on which exon probes and exon-exon junction probes as well as a couple of intron probes for the PTCH gene were placed in duplicate. Probe intensities were normalized on the basis of the total expression of PTCH and probe sensitivity. Tissue-specific regulation of AS identified with the microarrays closely correlated with the results obtained by RT-PCR. Of note, the novel exon, exon 12b, was specifically expressed in the brain and heart, especially in the cerebellum. Additionally, using these microarrays, we were able to detect disease-associated aberrant splicings of the PTCH gene in two patients with NBCCS. In both cases, cryptic splice donor sites located either in an exon or in an intron were activated because of the partial disruption of the consensus sequence for the authentic splice donor sites due to point mutations. Taken together, oligonucleotide microarrays containing exon junction probes are demonstrated to be a powerful tool to investigate tissue-specific regulation of AS and aberrant splicing taking place in genetic disorders. © The Author 2005. Published by Oxford University Press. All rights reserved.

We present the case of a 6-year-old girl with recurrent bacterial meningitis and cerebrospinal fluid (CSF) rhinorrhea associated with a petrous apex cephalocele (PAC). We diagnosed her by means of three-dimensional computed tomography (CT) and heavily T2-weighted magnetic resonance imaging (MRI). Petrous apex cephaloceles are usually an asymptomatic incidental finding in adults however, they should be considered as a possible cause of CSF rhinorrhea, otorrhea, and recurrent meningitis in children.

Mutations in mouse and human patched (PTCH) genes are associated with birth defects and cancer. PTCH, a 12-pass transmembrane protein, is a receptor for Sonic hedgehog (Shh) signaling proteins. Shh proteins activate transcription of target genes, including PTCH, via GLI transcription factors. Here we identified seven and five isoforms of human and mouse PTCH mRNA, respectively, which are generated by the complex alternative use of five exons as the first exon (exons 1a to 1e in the 5′-to-3′ order). Although expression profiles of these isoforms were highly variable among human tissues, three of them, PTCHa, PTCHb, and PTCHd, were predominantly expressed in most tissues, PTCHd being most ubiquitous. In contrast, PTCHb was always predominant and reached a maximum at E10.5 during mouse development. These three mRNA isoforms encode three PTCH proteins with distinct N-termini, PTCHL, PTCHM, and PTCHS. The expression of these three isoforms was regulated by GLI transcription factors, and at least two functional GLI-binding sequences were identified, one in exon 1a and the other between exon 1a and exon 1b. PTCH L and PTCHM were equally active in terms of suppressing GLI-mediated transcription and inducing apoptosis. PTCHS protein (encoded by PTCHd), lacking the first transmembrane domain, was more unstable than the other two, resulting in a reduced activity. This study may shed light on the mechanism whereby a single PTCH gene plays a role in both tumor cell growth and embryonic development. © 2004 Elsevier Inc. All rights reserved.

Apoptosis signal-regulating kinase 1 (ASK1) is a serine/ threonine kinase that mediates cell stress signaling initiated by diverse stimuli, such as H 2O2 and TNFα. Owing to its critical role in promoting apoptosis, ASK1 activity is highly controlled in cells. Phosphorylation of ASK1 at Thr-845 has been correlated with its activation, while phosphorylation at Ser-967 negatively controls its death promoting activity. Here, we report the identification of a novel phosphorylation site at Ser-1034 in the C-terminal regulatory domain of ASK1. Mutating Ser-1034 to an unphosphorylatable Ala led to increased catalytic activity of ASK1 and enhanced proapoptotic function of ASK1. Thus, the proapoptotic function of ASK1 is suppressed in part by phosphorylation at its C-terminal regulatory domain, which may couple upstream survival kinases to the death regulatory machinery.

Mutations in the human homologue of the Drosophila patched gene (PTCH) are responsible for the hereditary disorder called nevoid basal cell carcinoma syndrome (NBCCS). PTCH has a CGG triplet repeat located 4 bp upstream of the first methionine codon. Here we report a novel polymorphism involving the number of the CGG-repeat. The major allele (86.3%) contained a repeat size of seven, whereas the minor allele contained eight. No significant difference in the distributions of genotypes was observed between normal and NBCCS individuals. However, when the repeat was inserted between a heterologous promoter and the luciferase gene, the longer repeats tended to induce higher luciferase activities, suggesting that the repeat length potentially affects the levels of gene expression. A genome-wide screening revealed that 68 and 146 genes contained a CGG/CCG repeat in the coding region and in the 5'-untranslated region (5'-UTR), respectively. None of the genes had this repeat in 3'-UTR. Interestingly, the number of genes with a CGG repeat in the 5'-UTR was significantly higher than that with a CCG repeat in the 5'-UTR. The localization of a CGG/CCG repeat in PTCH is quite unique in that only four other genes have been found in which the repeat is localized up to 4 bp upstream of the first methionine.

We present the case of a 14-year-old Japanese girl who had both Gorlin syndrome and ulcerative colitis. She had complained of blood stools for 6 months and severe scoliosis from her infancy. Physical examination revealed multiple nevi, palmar and plantar pits, jaw cysts, and calcification of the falx cerebri, leading to the diagnosis of Gorlin syndrome. Total colonoscopy revealed an edematous and spotty bleeding mucosa extending from the anus to the transverse colon. Histological examination was also compatible with ulcerative colitis. Thus, we diagnosed her as having Gorlin syndrome with ulcerative colitis. Gene analysis revealed a mutation, 1247InsT, in the human patched gene (PTCH), resulting in the truncation of PTCH protein. Since Gorlin syndrome and ulcerative colitis are rare disorders in childhood, this association is interesting, suggesting a correlation between the hedgehog signaling and intestinal disorders. © 2003 Wiley-Liss, Inc.

The 14-3-3 proteins are a family of phosphoserine/phosphothreonine-binding molecules that control the function of a wide array of cellular proteins. We suggest that one function of 14-3-3 is to support cell survival. 14-3-3 proteins promote survival in part by antagonizing the activity of associated proapoptotic proteins, including Bad and apoptosis signal-regulating kinase 1 (ASK1). Indeed, expression of 14-3-3 inhibitor peptides in cells is sufficient to induce apoptosis. Interestingly, these 14-3-3 antagonist peptides can sensitize cells for effective killing by anticancer agents such as cisplatin. Thus, 14-3-3 may be part of the cellular machinery that maintains cell survival, and targeting 14-3-3-ligand interactions may be a useful strategy to enhance the efficacy of conventional anticancer agents.

We reported the magnetic resonance imaging of four young patients (13 to 19 years) with nevoid basal cell carcinoma syndrome (NBCCS), which showed empty sella, agenesis of the corpus callosum and empty sella, an interhemispheric lipoma with callosal dysgenesis, and an arachnoid cyst in the posterior fossa, respectively. Calcification of the diaphragma sellae, which is a protective barrier against the pulsating action of the cerebrospinal fluid, may cause the empty sella in NBCCS. Copyright (C) 2000 Elsevier Science B.V.

The authors report a 3-year-old male with glutaric aciduria type II, whose magnetic resonance imaging studies revealed agenesis of the cerebellar vermis and hypoplastic temporal lobes. Proton magnetic resonance spectroscopy in the parietal white matter revealed a markedly increased choline/creatine ratio, suggesting a demyelinating process. Gas chromatographic analysis of urinary organic acids should be studied in any patient with agenesis of the cerebellar vermis and cystic renal disease to exclude glutaric aciduria type II.

We report a mutational and polymorphic analysis of the proteolipid protein gene in members of 27 Japanese families with Pelizaeus-Merzbacher disease. We found causative mutations in 6 members of 27 families (22.2%) 5 of the 6 mutations, including two novel mutations, Leu45Arg and 231 + 2T → G, resulted in the typically severe clinical symptoms. Paradoxically, the Cys219Tyr mutation, presumed to disrupt the tertiary structure of proteolipid protein by removing the disulfide bond between Cys200 and Cys219, was associated with a mild clinical presentation wherein the patient could walk with assistance and speak. It was inferred that the structural change prevented the toxicity associated with a gain of function mutation. Moreover, in one family 3 patients exhibited a intragenic polymorphism that did not segregate with the disease, suggesting a locus heterogeneity for Pelizaeus-Merzbacher disease.

Gorlin syndrome (GS) is an autosomal dominant disorder in which patients are abnormally susceptible to ionizing radiation with radiotherapeutic doses. Radiogenic basal cell carcinomas may develop with a short latent period in patients. The mechanisms underlying the abnormal radiosusceptibility of cells in patients with GS has not been well characterized. In this study we report an increase in the number of nucleoli in fibroblast cells from 3 patients with GS after x-radiation. In GS fibroblasts, the increase in nucleolus number concomitant with the increase of ribonucleoprotein immunoreactive aggregates within the nucleus was observed after x-radiation, whereas significant change was not found in normal fibroblasts derived from healthy donors. This increase disappeared when cells were cultured with the RNA synthesis inhibitor actinomycin D after x-radiation but not when they were cultured with cycloheximide or aphydicolin, which are protein and DNA synthesis inhibitors, respectively. Ultraviolet exposure did not induce remarkable changes in the GS nucleoli. Thus the increase in nucleoli was induced after x-radiation of GS fibroblasts, and this increase seemed to be related to RNA synthesis metabolism.

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by nevi, palmar and plantar pits, falx calcification, vertebrate anomalies and basal cell carcinomas. It is well known in NBCCS that γ-irradiation to the skin induces basal cell carcinomas or causes an enlargement of the tumor size, although the details of the mechanism remain unknown. We have established lymphoblastoid cell lines from three NBCCS patients, and we present here the first evidence of abnormal cell cycle and apoptosis regulations. A novel mutation (single nucleotide deletion) in the coding region of the human patched gene, PTCH, was identified in two sibling patients, but no apparent abnormalities were detected in the gene of the remaining patient. Nevertheless, the three established cell lines showed similar features in the following analyses. Flow cytometric analyses revealed that the NBCCS-derived cells were accumulated in the G2M phase after γ-irradiation, whereas normal cells showed cell cycle arrest both in the G0G1 and G2M phases. The fraction of apoptotic cells after γ-irradiation was smaller in the NBCCS cells. The level of p27 expression markedly decreased after γ-irradiation in the NBCCS cells, although the effects of the irradiation on the expression profiles for p53, p21 and Rb did not differ in normal and NBCCS cells. These findings may provide a clue to the molecular mechanisms of tumorigenesis in NBCCS.

DNA synthesis activity was examined in fibroblasts and isolated nuclei derived from patients with nevoid basal cell carcinoma syndrome (NBCCS) upon exposure to X-ray and ultraviolet (UV). The DNA synthesis activity in NBCCS fibroblasts increased after X-ray irradiation, i.e., to twice that on mock-irradiation, while it decreased in healthy donor-derived fibroblasts. The DNA synthesis activity in isolated nuclei of X-ray irradiated NBCCS fibroblasts also increased, i.e., more than twice that on mock-irradiated. In the experiments using synchronized cells, DNA synthesis activity showed the most marked increase when the fibroblasts at S phase were irradiated with X-rays. In contrast, UV-irradiated NBCCS fibroblasts showed no such increase in DNA synthesis. These results revealed that DNA synthesis is abnormally induced in X-ray irradiated NBCCS cells and that this abnormality might be related with the tendency of tumorigenesis in NBCCS patients after exposure to X-ray.

We described a family of dentatorubral-pallidoluysian atrophy (DRPLA). The mother presented with cerebellar ataxia at 35 years of age and thereafter her neurological symptoms became exacerbated. Her daughter had mental retardation during the preschool period and epilepsy at 10 years. Her son presented with epilepsy at 14 years. Their clinical phenotypes demonstrated maternal anticipation in this family. Genetical analysis of their DNA revealed GAG repeat expansion of the DRPLA gene, the number of which was 61 (mother), 65 (her daughter), and 63 (her son). MR imaging showed disappearance of T2 shortening of the red nucleus in the mother and her daughter in contrast to the normal appearance in her son. MR imaging was effective in evaluating neuropathological changes in the DRPLA patients.

The case of a 5-year-old female with an intradural spinal meningioma is presented. She showed slowly progressive muscle weakness of the lower extremities commencing at 3 years. Spinal magnetic resonance imaging (MRI) demonstrated an intradural mass extending from the eleventh thoracic vertebra to the fifth lumbar vertebra, which was excised totally by means of laminoplasty. The surgical procedure brought a gradual improvement in her gait. This case is unusual because of the tumor's location (lumbar) and origin (cauda equina), and because of the onset at a relatively young age. © 1995 Elsevier Science B.V. All rights reserved.

Two fibroblast cell lines (PG3KT and PG1NA) deruved from Hutchinson-Gilford syndrome (progeria) cases were characterized, at various population doubling levels (PDL), with respect to the capacity of ultraviolet light (UV, mainly 254 nm wavelength)-induced unschedules DNA synthesis (UDS) and plasminogen activator-like protease activity (PA). The UDS levels in PG3KT and PG1NA cells at PDL 2-3 were only slightly less than those in normal fibroblasts. With increasing PDL. both prgeria cell lines exhibited reduction of the UDS levels and undetectable ones at PDL 9-11. Prompt and transient induction of PA was also detectable at less than PDL 5, whereas it was undetectable at higher PDL. However, the levels of UDS and PA induction were increased about 3-7 times after pretreatment with 100 IU/ml human interferon (HuIFN)-β preparations for more than 24 h prior to UV irradiation, although UDS and PA were undetectable at more than PDL 10. These results suggest that cytokines such as HuIFN-β transiently compensate for the decreases in UDS and PA inducibility in progeria cells with aging. © 1995.

A 10-year-old male suffering from acute optic neuritis is reported with multiple silent cerebral lesions, which remained visible only with fluid-attenuated inversion recovery sequences at 3-week intervals. Conventional sequences with magnetic resonance imaging did not visualize the lesions. Fluid-attenuated inversion recovery sequences are highly sensitive for the detection of silent lesions in acute optic neuritis. © 1995.

Purpose: To evaluate the utility and possible increased sensitivity of fluid-attenuated inversion recovery (FLAIR) images for the detection of tubers in patients with tuberous sclerosis, compared with standard T2-weighted images, and to evaluate whether the tubers are correlated with neurologic symptoms. Method: We examined the number, size, and location of tubers in five tuberous sclerosis patients using T2-weighted and FLAIR images. Their intelligence quotients, ages at the onset of the first seizure, seizure types, and epileptic severity also were studied retrospectively. Results: The number of tubers observed ranged from 4 to 17 on T2-weighted images, and from 10 to 33 on FLAIR images. All the tubers, other than the myelination line on T2-weighted images, were remarkably demonstrated as high-intensity lesions on FLAIR images. No correlation was found between the neurologic outcome and the number, size, or location of tubers on FLAIR images. Conclusion: FLAIR images were very sensitive for the detection of tubers, especially small subcortical ones, the number, size, and location of which are not related to the neurologic symptoms.

Two patients with congenital hemiplegia without obvious prenatal, perinatal or neonatal difficulties showed linear low signal intensity lesions along the wall of the dilated lateral ventricles without any parenchymal lesions on T2‐ and proton density weighted MRL Haemosiderin deposition secondary to intra‐uterine subependymal haemorrhage with intraventricular haemorrhage was considered most likely from the signal intensity, distribution and clinical histories. MRI, which is the only means of detecting haemosiderin deposition, could be beneficial for evaluating the pathogenetic cause of congenital hemiplegia. Dépôt d'hémosidérine périyentricitlaire dans l'hémiplégie congénitule Des lésions linéaires traduites par un signal de basse intensité le long de la paroi de ventricules latéraux dilatés, sans autes lésions parenchymateuses, ont été notées chez deux patients avec o hémiplégie congénitale sans difficultés prénatales, périnatales ou néonatales, en imagerie de résonance magnétique (IRM) à densité T2 et proton. L'explication la plus probable de cette anomalie des signaux, de sa localisation ainsi que de l'histoire cliriique est un dépôt d'hémosidérine secondaire à une hémorragie sous‐épendymaire intra‐uterine avec hémorragie intraventriculaire. L'IRM, seul moyen pour déceler des dépôts d'hémosidérine, semble très bénéfiquc pour rechercher la cause d'une hémiplégie congénitale. Perivcntrikuläre Hämosidcrin‐Ablagerungen bei Patienten mit Hemiplegie Zwei Patienten mit kongenitaler Hemiplegie ohne eindeutige prä‐, peri‐oder neonatale Probleme zeigten lineare Läsionen mit niedriger Signalintensität entlang der erweiterten lateralen Ventrikelwände, ohne parenchymal Lasionen im T2 und Protonen gewichteten MRL Hämosiderin‐Ablagerungen durch intra‐uterine subependymale Blutungen mit mtraventrikulärer Blutung wurden aufgrund der Signalintensität, der Verteilung und der Ananmese als sehr wahrscheinlich angenommen. Das MRI, die einzige Untersuchungsmethode mit der Hämosiderin‐Ablugerungen nachgesviesen werden können, konnte zur Beurteilung der Pathogeness der kongenitalen Hemiplegie von Nutzen sein. Depósito periventricular de hemosiderina en pacientes con hemiplegia congénita Dos pacientes con hemiplegia congénita sin ninguna dificultad obvia pre, peri o neonatal, mostraron lesiones lineales con señal de baja densidad a lo largo de las paraedes de los ventrículos laterales dilatados, sin ninguna lesión parenquimalosa en T2 y a la IRM. Se consideró que el depósito de hemosiderina, secundario a una haemorragia subependimaria con hemorragia intraventricular, era la causa más importante de la inensidad de la señal, su distribución y las historias clínicas. La IRM que es el único madio de detectar el depósito de haemosiderina, puede ser beneficiosa para evaluar la patogeoia de la hemiplegia congénita. Copyright © 1995, Wiley Blackwell. All rights reserved