In utero development of symmetric thalamic and brainstem necrosis in a preterm hydropic stillborn.

Focal and symmetric necrotic lesions of the brainstem are thought to result from fetal hypotension or cardiac arrest in the perinatal period and thus occur in the course of postnatal intensive care rather than in utero. Here, we report for the first time on brainstem necrosis in a preterm stillborn demonstrating that brainstem necrosis occurs already in utero. The preterm stillborn of 28 weeks gestation of a mother that suffered from HELLP-syndrome was severely affected by a fetal hydrops with bilateral pleural effusions and lung hypoplasia. Bilateral tegmental brainstem necrosis and thalamic lesions were detected.

[Dermatomyositis]. / Dermatomyositis.

Dermatomyositis (DM) is a systemic inflammatory disease involving skin, muscles and other organs. Immunologically mediated inflammation of small vessels leads to vascular damage, especially of the muscular tissue. Typically DM presents clinically with DM-type local or generalized rash and proximal muscular weakness. Laboratory signs of muscular damage (elevated serum CK, myoglobinuria) may be initially absent. Magnetic resonance tomography frequently shows edema of the involved muscles, while electromyography shows a myopathic pattern with spontaneous activity. Muscle biopsy from involved muscle with histological, immunohistological, histochemical and possibly electron-microscopic examination confirms the diagnosis of inflammatory muscle disease and furthermore of DM-specific muscular findings. Typical findings include the deposition of 5b-9 complement components (membrane attack complex) at the capillaries, perifascicular inflammatory infiltrates composed predominantly of CD4+ T-lymphocytes, B-lymphocytes and plasmacytoid dendritic cells, endothelial swelling and damage, loss of capillaries with perifascicular atrophy and tubuloreticular endothelial inclusions on electron-microscopic examination. Detection of myositis-specific autoantibodies is especially helpful in the diagnosis of early and atypical cases with features of overlapping disease.

A 19-year-old male with generalized seizures, unconsciousness and a deviation of gaze.

Light chain deposition disease (LCDD) is a form of monoclonal immunoglobulin deposition diseases (MIDD) which in contrast to light-chain derived (AL) amyloidosis is characterized by non-congophilic, non-fibrillary monoclonal protein deposits. Systemic organ deposits are common with the kidney being a major target organ. A clonal lymphoplasmocytic proliferation, e.g. plasmacytoma, is present in the majority of cases. Here we report on a 19-year-old male who presented with generalized seizures and an enhancing white matter lesion on MRI scans. A stereotactic brain biopsy revealed a low-grade B cell lymphoma with plasmacellular differentiation as well as lambda light chain deposits without birefringence under polarized microscopy. No systemic lymphoma manifestations or systemic light chain deposits were found, nor was a monoclonal gammopathy detectable in serum and urine. After systemic chemotherapy with three courses high-dose methotrexate the size of the lesion and the condition of the patient have remained stable for 24 months now. This is the first description of cerebral LCDD developing without systemic disease in conjunction with the diagnosis of a cerebral low-grade B cell lymphoma. We present the clinical, laboratory and radiological findings and discuss the pathogenesis of this unusual LCDD manifestation.

Giant intracerebral choroid plexus calcification.

While small calcifications of the choroid plexus are frequent, a large, single intracerebral calcification originating from the choroid plexus is rare. This report presents a 27-year-old woman who was admitted because of right temporal headache which had persisted for months. There was no neurological deficit. Computed tomography demonstrated a mass of calcium density measuring approximately 3 x 3 x 4 cm in the right temporal region, extending to the temporal skull base and to the rostral edge of the petrous bone. At surgery a very hard, poorly vascularised tumour originating from the choroid plexus of the temporal horn of the right lateral ventricle was completely removed. Histological workup yielded the diagnosis of a markedly calcified choroid plexus with no indication of neoplasia or inflammation. Physiological intracranial calcifications resulting from local tissue dystrophy are usually incidental. In the case presented here, a large intracerebral choroid plexus calcification was detected in a patient presenting with episodes of severe headache. The potential pathogenetic mechanism is discussed.

Transscleral resection of a ciliary body leiomyoma in a child: case report and review of the literature.

PURPOSE: To present the case of a patient with leiomyoma of the ciliary body and discuss the histological features and treatment of this rare intraocular tumor. METHODS/CASE REPORT: A 13-year-old boy presented with an asymptomatic tumor of the right eye. Visual acuity was 20/20 in both eyes. Ophthalmoscopy revealed an amelanotic, vascularized ciliary body tumor with exudative retinal detachment and partial transillumination. On ultrasound examination the tumor height was 8 mm and a low internal reflectivity was found. T2-weighted MRI scans showed a hypointense and T1-weighted scans a hyperintense intraocular mass with significant Gd-TPA enhancement. On the assumption that the diagnosis was consistent with an amelanotic ciliary body melanoma, a transscleral resection with adjuvant ruthenium-106 brachytherapy was performed. Visual acuity was 20/40 at 6 months after the operation. RESULTS: Routine stains revealed a pleomorphic tumor composed mainly of spindle cells with palisading in some areas and a prominent intercellular fibrillary background. Immunohistochemistry showed positivity for desmin, vimentin and actin. No reactivity with S-100 and HMB-45 was seen. Intracytoplasmatic filaments and micropinocytotic vesicles were detected by transmission electron microscopy. These findings were consistent with the diagnosis of a ciliary body leiomyoma. CONCLUSION: Typical clinical features of leiomyoma include a dome-shaped configuration and translucency, but the final diagnosis can only be confirmed by histology with the aid of immunohistochemistry and electron microscopy. Though rare, leiomyoma should be considered in the differential diagnosis of amelanotic uveal tumors. Transscleral resection is the treatment of choice of anterior uveal leiomyomas, with a fairly good visual prognosis.

Chronic lumbar epidural haematoma presenting with acute paraparesis.

Chronic spinal epidural haematomas are very rare and have been reported to occur only in the lumbar region. They usually become symptomatic through radicular pain or neurogenic claudication. The epidural bleeding is thought to originate from a rupture of an epidural vein due to a sudden increase in intra-abdominal pressure or due to trauma. The patient reported on here developed acute paraparesis about 8 weeks after a mild fall on the buttocks. MRI showed a spinal epidural mass located dorsolaterally at the level of L3-L5. The mass was surgically removed. Histological and immunohistological studies disclosed an organised haematoma. The clinical, radiological and intra-operative features of this case are described, and the relevant literature is analysed.

The cerebral cortex in fetal Down syndrome.

Brain histopathology of 32 fetuses with Down syndrome was compared to that of 25 age-matched normal controls and 9 brains of fetuses of HIV positive mothers. Four cases of Down syndrome and 1 HIV case showed microdysgenesia of the cerebral cortex. As the pathogenetic background of cortical irregularities is presently not known, we analyzed the neuronal expression of drebrin, an actin-binding protein of neuronal dendritic spines. This protein is thought to play a role in synaptic formation and was recently shown to be manifold reduced in brains of fetuses with Down syndrome. However, immunocytochemistry revealed no differences in drebrin expression pattern between Down patients and controls. We conclude that cerebral cortical microdysgenesia is an infrequent non-specific pathology in fetal Down syndrome.

Isolation of Nocardia paucivorans from the cerebrospinal fluid of a patient with relapse of cerebral nocardiosis.

Nocardia paucivorans represents a new species of the genus Nocardia that has recently been isolated from bronchial secretions of a patient with chronic lung disease. Here, we report on the course of a disseminated infection caused by this species: i.e., cerebral and subsequent meningeal manifestations, isolation from the cerebrospinal fluid, and in vitro susceptibility to various antimicrobial agents.

Expression of Leu-19 (CD56, N-CAM) and nitric oxide synthase (NOS) I in denervated and reinnervated human skeletal muscle.

Neural cell adhesion molecule (N-CAM, Leu-19, CD 56) expression appears during muscle fiber regeneration and after denervation. Sarcolemma-associated nitric oxide synthase (NOS) I, however, disappears from denervated myofibers. The dynamics of expression of both proteins were studied in 5 cases of acute/subacute denervation, 28 cases of chronic denervation with and without collateral reinnervation, 5 cases of the intermediate type spinal muscular atrophy (SMA 2), and in 2 normal biopsies. NOS I and its NADPH diaphorase (NADPHd) activity disappeared from the sarcolemma region shortly after denervation, and before the appearance of denervation atrophy. N-CAM was found diffusely distributed in the sarcoplasm at the most severe phase of denervation atrophy in the majority of highly atrophic fibers. During reinnervation, NOS I expression remained absent and in part of the cases the target/targetoid phenomenon appeared. In parallel with the increase in volume of the reinnervated muscle fibers, the intensity of N-CAM immunoreactivity decreased progressively. After full restitution of muscle fiber caliber, the target/targetoid phenomenon and N-CAM immunostaining disappeared completely, and, finally, NOS I reappeared in the sarcolemma region. The sarcolemmal expression of dystrophin and dystrophin-associated proteins was unchanged during denervation. NOS I was completely absent in children with SMA 2, since the protein does not appear before 5 years of age in skeletal muscle, while N-CAM was very intensely expressed in the sarcoplasm of highly atrophic denervated muscle fibers. In conclusion, this study suggests that innervation is an important factor for selective gene expression and positioning of NOS I and N-CAM in skeletal muscle and gives practical information for the assessment of the phase and developmental stage of the denervation and reinnervation process.

Ultrastructural changes in paravertebral muscles associated with degenerative spondylolisthesis.

STUDY DESIGN: The paravertebral muscle of 30 patients with spondylolisthesis and 30 control patients were investigated histologically. OBJECTIVE: To propose myopathologic paravertebral muscle changes in cases of degenerative lumbar spondylolisthesis. SUMMARY OF BACKGROUND DATA: The stability of the vertebral column is based on both active and passive systems. The passive system is composed of the vertebrae, the intervertebral discs, and the ligaments. Surrounding muscles and tendons constitute the active system. The autochthonous back muscles take over support functions if the passive system is ineffective. In some cases, muscles are overstrained for a long period, ultimately leading to muscular changes. This study was performed to determine the histopathologic correlates of this permanent strain. METHODS: Between July 1998 and July 1999, paravertebral muscle biopsies were performed for 30 patients with monosegmental degenerative spondylolisthesis undergoing posterior lumbar interbody fusion. The tissue samples were submitted to histologic analysis including immune and enzyme histochemistry and electron microscopy. In addition, the muscle fibers were submitted to morphometry. RESULTS: Severe pathologic alterations were found. The findings showed that 22 patients (73.3%) had ragged red fibers with evident ultrastructural mitochondrial anomalies. The cristae appeared irregular in 12 patients (40%) Type 1 paracrystalline inclusions were detected in five samples (16.6%) and dense bodies in eight (26.6%). Fibers with ubiquitin-positive inclusions were detected by immunohistochemistry in 13 patients (43.3%). As shown by the electron microscope, these corresponded to granulofilamentous inclusions and polyglucosan bodies. The samples were submitted to genetical analysis because biochemical studies showed reduced activity of the respiratory chain enzymes. Normal mitochondrial deoxyribonucleic acids of unchanged length were detected. CONCLUSIONS: Apart from nonspecific myopathic changes such as those observed in rimmed vacuoles and rods, increased numbers of polyglucosan bodies were detected. This increase in polyglucosan bodies currently has not been described in patients with otherwise normal muscles.

Fungal brain abscesses in neonates: Sonographic appearances and corresponding histopathologic findings.

Extremely preterm neonates and neonates with predisposing conditions such as congenital or acquired immunodeficiency are at high risk for systemic fungal infection. Abscess formation in the brain is a severe complication that occurs in 70% of neonates with systemic fungal infection. Cerebral sonography can be used to diagnose abscesses in the brain in these patients. We report 2 sonographic presentations of fungal brain abscesses in neonates confirmed by postmortem histopathologic examination. The first patient, an extremely preterm neonate of 23 weeks' gestation with a systemic Candida albicans infection, had multiple small, round, hypoechoic lesions with echogenic rims in both brain hemispheres. The second patient, a term neonate with disseminated aspergillosis and DiGeorge syndrome, had a few large echogenic areas in the right periventricular region. Brain imaging should be considered in the diagnostic workup in neonates with suspected systemic fungal infection. Cerebral involvement can be diagnosed at the bedside with cerebral sonography.

Differentiation, proliferation and apoptosis in primary and recurrent primitive neuroectodermal tumors of childhood.

Primitive neuroectodermal tumors (PNETs) of the CNS are a group of embryonal tumors composed of small undifferentiated or poorly differentiated cells. Infratentorially located PNETs are a synonym for medulloblastomas. In this study 31 PNETs, including 5 recurrent tumors, were examined. All children underwent neurosurgery and chemotherapy according to the HIT and HIT-SKK protocols. The specimens were investigated both for their expression of nine immunohistochemical markers for neuronal, astrocytic, mesenchymal and epithelial differentiation and for their proliferation. Results regarding cellular differentiation were confirmed ultrastructurally. Apoptosis was detected by labeling the 3'OH ends generated by DNA fragmentation and by electron microscopy. Glial differentiation was shown to have a prognostic relevance, with an elevated (twofold) risk of recurrence. Neuronal differentiation also indicated a tendency to poor prognosis. Those tumors that recurred later showed an increased proliferation rate (69%) compared with nonrecurrent tumors (58%). Apoptosis was identified in all tumors examined. The proportion of apoptotic cells could not be related to the effect of therapy. These results indicate that cellular differentiation may be a useful predicative factor for the prognosis of cerebral PNETs.

Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy.

Myogenic factors (MYF) belong to the basic helix-loop-helix (bHLH) transcription factor family and regulate myogenesis and muscle regeneration. The physiological importance of both functions was demonstrated in homozygous Myf knockout mice and mdx mice. Myf5 and Myod are predominantly expressed in proliferating myoblasts while Myf4 and Myf6 are involved in differentiation of myotubes. In a boy with myopathy and an increase of muscle fibres with central nuclei we detected a heterozygous 387G-->T nucleotide transversion in the MYF6 gene (MIM*159991). Protein-protein interaction of mutant MYF6 was reduced, and DNA-binding potential and transactivation capacity were abolished, thus demonstrating MYF6 haploinsufficiency. The boy's father carried the identical mutation and, in addition, an in-frame deletion of exons 45-47 in his dystrophin gene. This mutation is normally associated with a mild to moderate course of Becker muscular dystrophy but the father suffered from a severe course of Becker muscular dystrophy suggesting MYF6 as a modifier.

Hypoxic-ischemic encephalopathy with cystic brain stem necroses and thalamic calcifications in a preterm twin.

A severe and rare ischemic brain lesion in a preterm twin boy is reported. The boy was born after two weeks of anhydramnios and amnionic infection at 24 weeks of gestation. Following a difficult Caesarean section and prolonged umbilical cord compression he developed prenatal acidosis with an umbilical cord pH of 6.96. At the age of 7 h, heart rate variability narrowed due to severely disturbed brain stem function and the patient developed clinical signs of hypoxic-ischemic encephalopathy. Sonography demonstrated extensive symmetrical brain stem and basal ganglia lesions. After a prolonged comatose and apneic state, death occurred at the age of 25 days. Autopsy confirmed columnar bilateral cavitation of basal ganglia, diencephalon, brain stem and spinal gray matter, as well as focal calcifications in the palladium, thalamus, and brain stem. The findings highly resemble those observed after experimental or clinical cardiac arrest.

Charcot-Marie-Tooth neuropathy type 2 and P0 point mutations: two novel amino acid substitutions (Asp61Gly; Tyr119Cys) and a possible "hotspot" on Thr124Met.

Mutations in the gene for the major protein component of peripheral nerve myelin, myelin protein zero (MPZ, P0), cause hereditary disorders of Schwann cell myelin such as Charcot-Marie-Tooth neuropathy type 1B (CMT1B), Dejerine-Sottas syndrome (DSS), and congenital hypomyelinating neuropathy (CHN). More recently, P0 mutations were identified in the axonal type of CMT neuropathy, CMT2, which is different from the demyelinating variants with respect to electroneurography and nerve pathology. We screened 49 patients with a clinical and histopathological diagnosis of CMT2 for mutations in the P0 gene. Three heterozygous single nucleotide changes were detected: two novel missense mutations, Asp61Gly and Tyr119Cys, and the known Thr124Met substitution, that has already been reported in several CMT patients from different European countries. Haplotype analysis for the P0 locus proved that our patients with the 124Met allele were not related to a cohort of patients with the same mutation, all of Belgian descent and all found to share a common ancestor. Our data suggest that P0 mutations account for a detectable proportion of CMT2 cases with virtually every patient harbouring a different mutation but recurrence of the Thr124Met amino acid substitution. The high frequency of this peculiar genotype in the European CMT population is presumably not only due to a founder effect but Thr124Met might constitute a mutation hotspot in the P0 gene as well.

Aqueductal stenosis and hydrocephalus in an infant due to aspergillus infection.

Aqueductal stenosis is a common cause of hydrocephalus during infancy. We report on an infant born with aplasia cutis congenita at the scalp vertex and hypoplastic left heart syndrome developing systemic aspergillosis after cardiac surgery. The infant died at the age of 76 days despite systemic antimycotic therapy with a combination of flucytosine and amphotericin B. Therapy started at post-operative day 17 and was also applied intrathecally. Post-mortem examination revealed meningitis, multiple brain aspergillomas and microabscesses with focal ependymitis, focal bronchopneumonia, and necrotizing enterocolitis. One of the brain aspergillomas was located close to the aqueduct causing an aqueductal stenosis and an obstructive hydrocephalus. Histologically, aspergillus hyphae could only be detected in the aspergilloma of the aqueduct. To the best of our knowledge, this is the first reported case of an aqueductal stenosis caused by an aspergilloma.