Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica

Neuromyelitis optica (NMO) is an autoimmune disease targeting aquaporin 4 (AQP4), localized mainly at the astrocytic foot processes. Loss of AQP4 and glial fibrillary acidic protein (GFAP) was reported, but the pathological significance of astrocytopathy is still controversial. Here we show that active lesions in NMO display a wide spectrum of pathology even within a single tissue block of an individual patient. We have distinguished six different lesion types. The first reflects complement deposition at the surface of astrocytes, associated with granulocyte infiltration and astrocyte necrosis and followed by demyelination, global tissue destruction and the formation of cystic, necrotic lesions (lesion type 2). Such destructive lesions lead to Wallerian degeneration in lesion-related tracts (lesion type 3). Around active NMO lesions AQP4 may selectively be lost in the absence of aquaporin 1 (AQP1) loss or other structural damage (lesion type 4). Another pattern is characterized by clasmatodendrosis of astrocytes, defined by cytoplasmic swelling and vacuolation, beading and dissolution of their processes and nuclear alterations resembling apoptosis, which was associated with internalization of AQP4 and AQP1 and astrocyte apoptosis in the absence of complement activation. Such lesions give rise to extensive astrocyte loss, which may occur in part in the absence of any other tissue injury, such as demyelination or axonal degeneration (lesion type 5). Finally, lesions with a variable degree of astrocyte clasmatodendrosis are found, which show plaque-like primary demyelination that is associated with oligodendrocyte apoptosis, but with preservation of axons (lesion type 6). In active multiple sclerosis (MS) lesions astrocytes reveal changes of reactive protoplasmatic or fibrillary gliosis. Only in a subset of lesions, in patients with aggressive disease, loss of AQP4 is observed in the initial stage of their formation, which is associated with retraction of astrocyte processes in the absence of complement deposition, granulocyte infiltration or loss of AQP1 or astrocytes. Our data underline the primary assault of astrocytes in NMO lesions, but also indicate that different mechanisms of tissue injury operate in parallel in the same patient and even within the same lesion.     

Cortical spreading depression augments kynurenate levels and reduces malonate toxicity in the rat cortex

Cortical spreading depression (CSD) is characterized by slowly propagating neuronal and astrocytic depolarization, resulting in transient, heightened resistance to subsequent neuronal injury. This study was designed to examine a possible role of the endogenous neuroprotective agent kynurenate (KYNA) in this phenomenon. Unilateral, consecutive CSDs, induced by topical application of 2 M KCl to the cortical surface of adult male rats, resulted in an ipsilateral increase (201-222% compared to controls) in KYNA levels, which was observed in the frontal, parietal and occipital cortex but not in other brain areas. This effect peaked on day 3 after CSD, and KYNA levels returned to normal on day 7. In separate rats, the lesion caused by an intracortical microinjection of the indirect excitotoxin malonate (500 nmol/0.5 microl) on days 1, 3 or 7 after CSD was reduced by 56-75% in the ipsilateral hemisphere. In normal rats, single or multiple injections of the kynurenine 3-hydroxylase inhibitor 4,5-dichlorobenzoylalanine (PNU 156561; 50 mg/kg, i.p.), which results in selective increases in brain KYNA levels, failed to protect cortical neurons against a focal malonate injection. Taken together, these findings indicate that the observed increase in brain KYNA is not responsible for CSD-induced tolerance to malonate-induced neuronal damage.     

Cavum septi pellucidi in first-episode schizophrenia and first-episode affective psychosis: an MRI study

A high prevalence of abnormal cavum septi pellucidi (CSP) in schizophrenia may reflect neurodevelopmental abnormalities in midline structures of the brain. The relationship, however, between abnormal CSP and clinical symptoms, and with abnormalities in other limbic structures remains unclear, as does the question of whether a similar abnormality is present in affective psychosis. Seventy-four patients at their first hospitalization, 33 with schizophrenia and 41 with affective (mainly manic) psychosis, and 56 healthy control subjects underwent high-spatial-resolution magnetic resonance imaging (MRI). CSP on six slices or more on 0.9375-mm resampled coronal images was categorized as abnormal. The prevalence of abnormal CSP in both schizophrenic patients (26.1%) and affective psychosis patients (18.2%) was significantly higher than was observed in control subjects (8.2%). In schizophrenic patients only, larger CSP was significantly associated with more severe thinking disturbance and smaller left parahippocampal gyrus gray matter volumes. While the relationships between CSP ratings and clinical symptoms did not significantly differ between the two psychosis groups as assessed by the comparison of regression slopes, the association with limbic volumes appeared to be specific to schizophrenic patients. These results suggest that psychosis associated with schizophrenia and affective disorder share, at least to some extent, neurodevelopmental abnormalities involving midline structures and associated psychopathological consequences. However, the association between abnormal CSP and limbic systems may be more specific to schizophrenia.     

Apicortin,a unique protein,with a putative cytoskeletal role,shared only by apicomplexan parasites and the placozoan Trichoplax adhaerens

A new protein, termed apicortin, has been identified, which contains a DCX (doublecortin) and a partial p25-alpha domain. The DCX domains of the doublecortin superfamily are responsible for their microtubule binding and stabilizing properties. The p25-alpha domain occurs in TPPPs (Tubulin Polymerization Promoting Proteins) exhibiting Microtubule Associated Protein (MAP)-like functions. TPPP orthologs can be classified as long- and short-type ones. The latter ones do not contain the partial p25-alpha domain, which is the most conservative part of the long-type TPPPs and was evolutionary-preserved independently from the whole domain. Apicortin seems to occur only in the placozoan animal Trichoplax adhaerens and in each of the apicomplexan parasites, the genomes of which are available. The function of the novel protein can be predicted from the fact that it contains two different microtubule-binding domains. Apicomplexans, important pathogens of humans and animals, possess unique cytoskeletal elements, as subpellicular microtubules and apical polar rings, which are specific for this phylum, extremely stabilized by unknown MAPs. One of the candidates can be the apicortin, which is supported by a recent experimental proteomics analysis. The role of the new protein in T. adhaerens may be similar but needs clarification.     

Identification of the small for gestational age fetus with the use of gestational age-independent indices of fetal growth

This study reviews the roles of sonographic assessment of the rate of growth of the fetal abdominal circumference, the femur length/abdominal circumference ratio, and qualitative determination of amniotic fluid volume as gestational age-independent indices for identification of the small for gestational age fetus. The sensitivity and specificity for single and combinations of test results were evaluated in 50 appropriate for gestational age and 40 small for gestational age fetuses. Positive and negative predictive values were derived for the general population. Our results indicate that either a rate of growth of the fetal abdominal circumference less than or equal to 10 mm/14 days or a femur length/abdominal circumference ratio greater than or equal to 23.5 correctly identifies most small for gestational age fetuses. When the general population is screened, only 15% of small for gestational age fetuses will be missed by this combination of criteria. The presence of a pocket of amniotic fluid less than or equal to 2.0 cm is highly suggestive of a small for gestational age fetus. However, the presence of a pocket of amniotic fluid greater than 2.0 cm does not guarantee an appropriate for gestational age fetus. We conclude that these gestational age-independent indices of fetal growth offer useful tools for differentiating between the small for gestational age and appropriate for gestational age fetus.     

A novel decarboxylation method for the preparation of 5,6,7,8,10-hexahydro-5.9-methanobicyclobenzocyclooctene

Several methods were described earlier for the synthesis of 5,6,7,8,9,10-hexahydro-5,9-methanobicyclobenzocyclooctene (5). A novel simple method is described in this paper by the persulfate (II)/silver (I) ion catalyzed decarboxylation refluxing in water-acetonitrile mixture from corresponding 4 carboxylic acid, which was prepared earlier in four steps starting from tetrahydrophthalic anhydride (1).     

Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study

BACKGROUND: The Heschl gyrus and planum temporale have crucial roles in auditory perception and language processing. Our previous investigation using magnetic resonance imaging (MRI) indicated smaller gray matter volumes bilaterally in the Heschl gyrus and in left planum temporale in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis. We sought to determine whether there are progressive decreases in anatomically defined MRI gray matter volumes of the Heschl gyrus and planum temporale in patients with first-episode schizophrenia and also in patients with first-episode affective psychosis. METHODS: At a private psychiatric hospital, we conducted a prospective high spatial resolution MRI study that included initial scans of 28 patients at their first hospitalization (13 with schizophrenia and 15 with affective psychosis, 13 of whom had a manic psychosis) and 22 healthy control subjects. Follow-up scans occurred, on average, 1.5 years after the initial scan. RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left Heschl gyrus (6.9%) and left planum temporale (7.2%) compared with patients with first-episode affective psychosis or control subjects. CONCLUSIONS: These findings demonstrate a left-biased progressive volume reduction in the Heschl gyrus and planum temporale gray matter in patients with first-episode schizophrenia in contrast to patients with first-episode affective psychosis and control subjects. Schizophrenia but not affective psychosis seems to be characterized by a postonset progression of neocortical gray matter volume loss in the left superior temporal gyrus and thus may not be developmentally fixed.     

Percutaneous transpedicular acrylate vertebroplasty for the treatment of lumbar vertebral hemangioma--case report

The authors present the management of a patient suffering from lumbar vertebral hemangioma. Percutaneous transpedicular acrylate vertebroplasty was performed. This method has widely been used for the treatment of pathological vertebral bodies of different aetiology. A brief review of the literature of previous and current methods is presented. A detailed discussion is given why vertebroplasty was used in contrast to the radiological investigation where the patient's hemangioma proved to be a non-aggressive type. According to the authors' knowledge this is the first Hungarian publication of acrylate vertebroplasty for the treatment of vertebral hemangioma.