Ultramicroscopic structures of the leptomeninx of mice with communicating hydrocephalus induced by human recombinant transforming growth factor-beta 1.
An experimental model of communicating hydrocephalus was developed based on intrathecal injection of human recombinant transforming growth factor-beta 1 (hrTGF-beta 1) in the mouse. To clarify the mechanism of this hydrocephalus model, the ultrastructure of the leptomeninx in the process of ventricular dilation was examined in C57/BL6 mice injected intrathecally with 60 ng of hrTGF-beta 1. The leptomeninx was examined at various periods after injection by light and electron microscopy. Immunostaining for fibroblasts and macrophages was also performed. Leptomeninx within a week after injection showed that the thin cytoplasmic processes of leptomeningeal cells formed a laminated structure with a meshwork, which was almost the same as the controls. In the second week, many cells with a round nucleus appeared in the leptomeninx. Immunohistochemically, these cells were positive for anti-fibroblast antibody and negative for anti-Mac-1 and anti-macrophage BM-8 antibodies. Three weeks later, the laminated structure was disrupted and abundant deposition of collagen fibers was found in the inter-cellular space of the leptomeninx. Such inter-meningeal fibrosis would disturb cerebrospinal fluid flow in the mouse leptomeninx and cause slowly progressive ventricular dilation. (+info)
Transthyretin Leu12Pro is associated with systemic, neuropathic and leptomeningeal amyloidosis.
We report a middle-aged woman with a novel transthyretin (TTR) variant, Leu12Pro. She had extensive amyloid deposition in the leptomeninges and liver as well as the involvement of the heart and peripheral nervous system which characterizes familial amyloid polyneuropathy caused by variant TTR. Clinical features attributed to her leptomeningeal amyloid included radiculopathy, central hypoventilation, recurrent subarachnoid haemorrhage, depression, seizures and periods of decreased consciousness. MRI showed a marked enhancement throughout her meninges and ependyma, and TTR amyloid deposition was confirmed by meningeal biopsy. The simultaneous presence of extensive visceral amyloid and clinically significant deposits affecting both the peripheral and central nervous system extends the spectrum of amyloid-related disease associated with TTR mutations. The unusual association of severe peripheral neuropathy with symptoms of leptomeningeal amyloid indicates that leptomeningeal amyloidosis should be considered part of the syndrome of TTR-related familial amyloid polyneuropathy. (+info)
Meningioangiomatosis. A comprehensive analysis of clinical and laboratory features.
Meningioangiomatosis (MA) is a rare, benign, focal lesion of the leptomeninges and underlying cerebral cortex characterized by leptomeningeal and meningovascular proliferation. It may occur sporadically or in association with neurofibromatosis type 2. Previous reports have emphasized histological and imaging features. Data on the management of these patients are sparse, and electrophysiological features of MA lesions have not been published. We assessed the clinical, electrophysiological, histopathological and imaging features as well as the surgical outcome in MA, and compared MA with and without neurofibromatosis. Seven patients with MA at our centre were investigated and their outcome was assessed. A review of the literature is included. MA exhibits a wide range of clinical, imaging, histopathological and electrophysiological features, making the diagnosis difficult. Sporadic MA cases are not associated with neurofibromatosis and the two disorders are genetically distinct. Medically refractory, localization-related epilepsy is the commonest presentation in sporadic cases, but atypical presentations also occur. Unlike sporadic cases, MA with neurofibromatosis is often found incidentally, does not produce seizures, occurs less frequently (ratio of 1:4), and is multifocal. MRI findings in MA correspond to the histological picture. However, the appearance on imaging is non-specific and may suggest cystic atrophy, angioma and tumours. Several abnormalities have been found in close proximity to MA lesions, i.e. meningioma, oligodendroglioma, arteriovenous malformation, encephalocoel and orbital erosion. In spite of histopathological diversity, MA lesions are either predominantly cellular or vascular. Immunohistochemical results are inconsistent among cases, add little to the diagnosis, and do not support a meningeal origin. Electrocorticographic recordings from the surface and within MA lesions revealed a spectrum of electrophysiological expressions. Intrinsic epileptogenicity of MA lesions was documented in some cases. Epileptogenicity was confined to the perilesional cortex in some patients and it was complex (extralesional, multifocal, generalized) in others. Only 43% of our patients became seizure-free postoperatively compared with 68% previously reported, and >70% of our patients and those in the literature continued to require antiepileptic drugs. This is in keeping with the diverse electrophysiology of MA and suggests a less optimistic postoperative outcome than previously recognized. (+info)
Tumor necrosis factor alpha is a determinant of pathogenesis and disease progression in mycobacterial infection in the central nervous system.
The pathogenesis of tuberculous meningitis, a devastating complication of tuberculosis in man, is poorly understood. We previously reported that rabbits with experimental tuberculous meningitis were protected from death by a combination of antibiotics and thalidomide therapy. Survival was associated with inhibition of tumor necrosis factor alpha (TNF-alpha) production by thalidomide. To test whether cerebrospinal fluid (CSF) levels of TNF-alpha correlated with pathogenesis, the response of rabbits infected in the central nervous system (CNS) with various mycobacterial strains was studied. CNS infection with Mycobacterium bovis Ravenel, M. bovis bacillus Calmette-Guerin (BCG) Pasteur, and M. bovis BCG Montreal were compared. M. bovis Ravenel induced the highest levels of TNF-alpha in the CSF in association with high leukocytosis, protein accumulation, and severe meningeal inflammation. BCG Pasteur had intermediate effects, and BCG Montreal was the least virulent. In addition, M. bovis Ravenel numbers were highest in the brain and CSF and the bacilli also disseminated more efficiently to distant organs, compared with BCG Pasteur and BCG Montreal. In subsequent experiments, rabbits were infected with either recombinant M. bovis BCG Montreal (vector), or BCG Montreal expressing the murine gene for TNF-alpha (BCG mTNF-alpha). BCG Montreal was rendered virulent by the expression of murine TNF-alpha, as demonstrated by high CSF leukocytosis, high protein accumulation, severe meningeal inflammation, persistent bacillary load, and progressive clinical deterioration. Taken together, these results demonstrate that the level of TNF-alpha produced during mycobacterial CNS infection determines, at least in part, the extent of pathogenesis. (+info)
MR of CNS sarcoidosis: correlation of imaging features to clinical symptoms and response to treatment.
BACKGROUND AND PURPOSE: Sarcoidosis is an idiopathic systemic granulomatous disease, recognized in a patient when clinical and radiologic findings are confirmed by histopathologic analysis. The objective was to identify a relationship between MR imaging and clinical findings in CNS sarcoidosis. METHODS: The clinical charts of 461 patients with biopsy-proved sarcoidosis were reviewed retrospectively. Criteria for including patients in the study included those with symptoms referable to the CNS, excluding those with another explanation for their symptoms, those with headaches or other subjective complaints without accompanying objective findings, and those with peripheral neuropathy other than cranial nerve involvement or myopathy without CNS manifestations. Thirty-four of 38 patients whose conditions met the criteria for CNS sarcoidosis underwent a total of 82 MR examinations. The positive imaging findings were divided into categories as follows: pachymeningeal, leptomeningeal, nonenhancing brain parenchymal, enhancing brain parenchymal, cranial nerve, and spinal cord and nerve root involvement. Treatment response, clinical symptomatology, and any available histopathologic studies were analyzed with respect to imaging manifestations in each of the categories. RESULTS: Eighty-two percent of the patients with sarcoidosis with neurologic symptoms referable to the CNS had findings revealed by MR imaging. However, eight (40%) of 20 cranial nerve deficits seen at clinical examination of 13 patients were not seen at contrast-enhanced MR imaging, and 50% of the patients with symptoms referable to the pituitary axis had no abnormal findings on routine contrast-enhanced MR images. In contradistinction, 44% of 18 cranial nerves in nine patients with MR evidence of involvement had no symptoms referable to the involved cranial nerve. Clinical and radiologic deterioration occurred more commonly with leptomeningeal and enhancing brain parenchymal lesions. CONCLUSION: MR imaging can be used to confirm clinical suspicion and to show subclinical disease and the response of pathologic lesions to treatment. (+info)
Multifocal meningioangiomatosis: a report of two cases.
We report the CT and MR findings in two patients with multifocal meningioangiomatosis, neither of whom had a family history or stigmata of neurofibromatosis. All lesions were located in the cortical and subcortical areas and had round dense calcifications with eccentric cysts. The masses were associated with surrounding edema and gliosis. (+info)
Magnetization transfer MR imaging in CNS tuberculosis.
BACKGROUND AND PURPOSE: CNS tuberculosis may simulate other granulomas and meningitis on MR images. The purpose of this study was to improve the characterization of lesions in CNS tuberculosis and to assess the disease load using magnetization transfer (MT) imaging. METHODS: A total of 107 tuberculomas in seven patients with or without meningitis and 15 patients with tuberculosis meningitis alone were studied. Fifteen patients with cysticercus granulomas with T2 hypointensity, five patients each with viral and pyogenic meningitis, and two patients with cryptococcal meningitis were also studied. The MT ratios were calculated from tuberculomas, cysticercus granulomas, and thickened meninges in tuberculous, viral, pyogenic, and cryptococcal meningitis and were compared within each pathologic group and with the MT ratio of different regions of normal brain parenchyma. Detectability of lesions on T1-weighted MT spin-echo (SE) images was compared with that on conventional SE and postcontrast MT-SE images. RESULTS: Thickened meninges appeared hyperintense relative to surrounding brain parenchyma in the basal and supratentorial cisterns on precontrast MT-SE images in all 18 patients with tuberculosis meningitis. These meninges were not seen or were barely visible on conventional SE images, and enhanced on postcontrast MT-SE images. The MT ratio from the thickened meninges of tuberculous meningitis was significantly lower than that from the meninges in cryptococcal and pyogenic disease and significantly higher than the meninges in viral meningoencephalitis. The MT ratio from T2 visible and invisible tuberculomas appeared to be significantly lower than that of normal white matter. The MT ratio of T2 hypointense cysticercus granuloma was significantly higher than that of T2 hypointense tuberculoma. CONCLUSION: Precontrast MT-SE imaging helps to better assess the disease load in CNS tuberculosis by improving the detectability of the lesions. With the use of MT ratios, it may be possible to differentiate tuberculosis from similar-appearing infective lesions on MR images. (+info)
Sclerosing spinal pachymeningitis. A complication of intrathecal administration of Depo-Medrol for multiple sclerosis.
Reported complications of intrathecal steroid therapy include aseptic meningitis, infectious meningitis, and arachnoiditis. We report a case of sclerosing spinal pachymeningitis complicating the attempted intrathecal administration of Depo-Medrol for multiple sclerosis. The lesion is characterised by concentric laminar proliferation of neomembranes within the subdural space of the entire spinal cord and cauda equina, resulting from repeated episodes of injury and repair to the spinal dura mater by Depo-Medrol. There is clinical and laboratory evidence that Depo-Medrol produces meningeal irritation and that the vehicle is the necrotising fraction. (+info)