Susumu Tokiguchi

Myoclonus epilepsy associated with ragged-red fibres (mitochondrial abnormalities): Disease entity or a syndrome? ☆: Light- and electron-microscopic studies of two cases and review of literature

A report is given of an association of dyssynergia cerebellaris myoclonica associated with Friedreichs ataxia and mitochondrial myopathy in 2 patients. They had suffered from gradually increasing bursts of myoclonus since the wage of 14 and childhood, respectively. The other striking clinical features included generalized convulsions, mental deterioration, intention tremor, ataxia, muscular atrophy and deformity of feet. Muscle biopsies revealed ragged-red fibres in both cases. On electron microscopy these fibres contained subsarcolemnal aggregations of abundant abnormal mitochondria with proliferation of inner membranes or paracrystalline inclusions. One of these patients showed elevated blood lactate and pyruvate with an increased lactate/pyruvate ration, apparently of primary origin. These 2 cases resemble those reported briefly by Tsairis et al. (1974). An association of dyssynergia cerebellaris myoclonica associated with Friedreichs ataxia and mitochondrial myopathy in these 2 patients is unlikely to be coincidental but may represent one nosological entity. This myoclonus epilepsy syndrome associated with ragged-red fibres is compared with other possibly related mitochondrial encephalomyopathies.

Corticobasal degeneration : etiopathological significance of the cytoskeletal alterations

We have studied brain tissues from three patients with corticobasal degeneration (CBD) histologically, ultrastructurally and immunohistochemically. Ballooned neurons in the cerebral cortex and severe degeneration of the substantia nigra were observed in them all and weakly basophilic neurofibrillary tangles (NFTs) were distributed widely in the basal ganglia and brain stem. Ultrastructural examination demonstrated that the NFTs comprised characteristic 15-nm-wide straight tubules, which showed positive immunohistochemical staining with an antibody against tau, but not ubiquitin. Tau-immunoreactive neuronal cell bodies without NFTs also were found in the cerebral cortex and subcortical nuclei, predominantly in the brain stem, and the greatest number of tau-positive glial inclusions occurred in the cerebral gray and white matter of the pre- and post-central gyri. These inclusions comprised tubular structures with diameters of about 15 nm and were localized in the oligodendroglial cellular cytoplasm and processes. These findings indicate that there is a close cytoskeletal pathological relationship between CBD and progressive supranuclear palsy.

Diffusion-weighted echo-planar MR imaging in differential diagnosis of brain tumors and tumor-like conditions.

Abstract. We assess diffusion-weighted MR images in the differential diagnosis of intracranial brain tumors and tumor-like conditions. Heavily diffusion-weighted (b = 1100 or 1200 s/mm2) axial images were obtained with single-shot echo-planar technique in 93 patients with pathologically confirmed various intracranial tumors and tumor-like conditions with diffusion gradient perpendicular to the images. We compared signal intensity of the lesions with those of gray and white matter, and cerebrospinal fluid (CSF). In 29 cases (31.1 %) the lesions were isointense to gray and/or white matter. However, 5 cases (5.4 %) showed extremely increased signal intensity: two epidermoid cysts; two chordomas; and one brain abscess. The entire portion of a tumor was markedly hyperintense in 10 cases (10.8 %): four malignant lymphomas; four medulloblastomas; one germinoma; and one pineoblastoma. A CSF-like hypointense signal was seen in many cystic tumors, and cystic or necrotic portions of tumors. A neurosarcoid granulation was the only solid lesion showing characteristically a hypointense signal like CSF. The combination of markedly hyperintense and hypointense signals was seen generally in hemorrhagic tumors. Diffusion-weighted echo-planar MR imaging is useful in the differential diagnosis of brain tumors and tumor-like conditions, and suggests specific histological diagnosis in some cases.

Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy. Influence of CAG repeat size on MRI findings.

To elucidate how the size of the expanded CAG repeat of the gene for dentatorubral pallidoluysian atrophy (DRPLA) and other factors affect the atrophy of the brainstem and cerebellum, and the appearance of high-intensity signals on T2-weighted MRI of the cerebral white matter of patients with DRPLA, we quantitatively analyzed the MRI findings of 26 patients with DRPLA, the diagnosis of which was confirmed by molecular analysis of the DRPLA gene. When we classified the patients into two groups based on the size of the expanded CAG repeat of the DRPLA gene (group 1, number of CAG repeat units≥66; group 2, number of CAG repeat units ≤65), we found strong inverse correlations between the age at MRI and the areas of midsagittal structures of the cerebellum and brainstem in group 1 but not in group 2. Multiple regression analysis, however, revealed that both the patients age at MRI and the size of the expanded CAG repeat correlated with the areas of midsagittal structures. Involvement of the cerebral white matter as detected on T2-weighted images was observed more frequently in patients belonging to group 2 than in group 1 patients. Furthermore it was demonstrated that high-intensity signals can be detected on T2-weighted images of the cerebral white matter of patients with a largely expanded CAG repeat (group 1) in their thirties. These results suggest that patient age as well as the size of the expanded CAG repeat are related to the degree of atrophy of the brainstem and cerebellum, and the white matter changes in patients with DRPLA.

Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia

Germ-cell tumors of the central nervous system generally develop in the midline, but the tumors can also occur in the basal ganglia and/or thalamus. However, MR images have rarely been documented in the early stage of the tumor in these regions. We retrospectively reviewed MR images obtained on admission and approximately 3 years earlier in two patients with germinoma in the basal ganglia, and compared them with CT. In addition to hyperdensity on CT, both hyperintensity on T1-weighted images and a small hyperintense lesion on T2-weighted images were commonly seen in the basal ganglia. These findings may be early MRI signs of germinoma in this region, and the earliest and most characteristic diagnostic feature on MRI was atrophy of the basal ganglia, which was recognizable before development of hemiparesis.

MRI of enlarged endolymphatic sacs in the large vestibular aqueduct syndrome

Abstract We studied ten inner ears of five patients with a bilateral large vestibular aqueduct syndrome, using CT and MRI. Although the large vestibular aqueduct varied in size, a markedly dilated endolymphatic sac extending to the sigmoid sinus was demonstrated bilaterally on MRI in all patients. The cause of hearing loss in this syndrome is unclear. However, it is suggested that reflux of the protein-rich, hyperosmolar endolymph from the enlarged endolymphatic sac (EES) into the cochlea through a widely patent endolymphatic duct may damage the neuroepithelium. CT density and spin-echo MRI signal intensity of the endolymph in EES were markedly higher than those of CSF in eight inner ears of four patients. Increased density and high signal may indicate protein-rich, hyperosmolar endolymph. In some patients with sensorineural hearing loss and EES, the vestibular aqueduct may not appear dilated on CT. MRI is therefore necessary for correct diagnosis of this syndrome, which should more correctly be termed “large endolymphatic duct and sac syndrome”. Prominent EES may predict poor prognosis in this syndrome.

Cytotoxic T cells against a peptide of Yo protein in patients with paraneoplastic cerebellar degeneration and anti-Yo antibody

Anti-Yo antibodies are present in the sera and cerebrospinal fluid of some patients with paraneoplastic cerebellar degeneration (PCD), but there is no evidence that the presence of anti-Yo antibodies causes the Purkinje cell loss seen in PCD patients. We examined the level of cytotoxic T lymphocyte (CTL) activity against a nine-amino acid peptide of the Yo protein using the Human Leukocyte Antigen- (HLA-) based approach called reverse immunogenetics. Mononuclear cells (MNCs) were isolated from the peripheral venous blood and fibroblasts were obtained from the skin of three patients with PCD with anti-Yo antibody. After activating the MNCs of the three patients with the peptide, it showed CTL activity against the Yo protein peptide expressed on autologous fibroblasts. Therefore, CTLs may be involved in the loss of Purkinje cells in PCD.

Imaging of calvarial eosinophil granuloma

Abstract We reviewed the imaging of four pathologically proven calvarial eosinophil granulomas. The diameter of the lesions ranged from 13 to 40 mm; three were biconvex, but the other had a collar-stud appearance. Two lesions were in the frontal and two in the parietal bone. On bone-window CT, a bevelled edge was seen in three cases and button sequestration in one, but no sclerotic rim was shown. Although one lesion had a low-density area, the lesions were slightly denser than grey matter. They were isointense with grey or white matter on T1-weighted MRI and gave heterogeneous high signal on proton-density and T2-weighted images. All enhanced markedly, with a less strongly enhancing portion within them. A tail of dural enhancement and reactive change in the overlying galea or temporal muscle were seen in all cases.

Primary leptomeningeal glioma: ultrastructural and laminin immunohistochemical studies.

SummaryWe studied a case of primary leptomeningeal glioma (PLG) on the left parietal lobe of a 74-year-old woman and compared the tissue with heterotopic glial tissue from another case. The PLG tumor consisted of spindle-shaped cells with marked nuclear atypism, which tended to be arranged in a fascicular pattern, and the majority of its cells were positive for glial fibrillary acidic protein. Ultrastructural examination demonstrated that most of the tumor cells contained intermediate filaments and often junctional complexes were present on their plasma membranes. Frequently, basal lamina-like structures surrounding the tumor, cell surfaces were observed. Laminin immunohistochemistry clearly demonstrated a fine network of linear positive staining around the cytoplasm and processes of the tumor cells. The ultrastructure of the heterotopic glial tissue consisted of many astrocytes partially surrounded by basal lamina. These findings strongly suggest that PLG is a distinct tumor, which arises from the heterotopic astrocytes within the subarachnoid space.

MRI of high-grade astrocytic tumors: early appearance and evolution

The clinical management and prognosis of patients with diffusely infiltrating astrocytomas are dependent on neuropathological grading of the tumors. The characteristics of MR images of high-grade astrocytic tumors are well known, but the early MRI appearance and the MRI evolution of high-grade astrocytic tumors have rarely been examined. We retrospectively reviewed MR images obtained from 4 months to 3 years and 3 months before admission, as well as MR images on admission, for five patients with pathologically proven high-grade astrocytic tumors (two glioblastomas and three anaplastic astrocytomas). In two patients, neoplastic lesions were not detectable on initial MRI, even retrospectively. In the remaining three patients, however, hyperintense areas with little or no mass effect were demonstrated on T2-weighted imaging. These lesions were misinterpreted as non-neoplastic processes, such as ischemic lesion or infarction, or demyelinating processes. All tumors showed gadolinium enhancement on admission, that emerged from the previously existing hyperintense areas on T2-weighted images without gadolinium enhancement, except for one de novo glioblastoma. Development of a small central cyst without gadolinium enhancement was demonstrated in one case before the emergence of an enhancing area.