Churg-Strauss syndrome complicated by neuropathy: a clinicopathological study of nine cases.

OBJECTIVE: The purpose of this study was to investigate the clinical, electrophysiological and pathological features of Churg Strauss syndrome (CSS) neuropathy. METHODS: Biopsies were selected from over 700 sural nerve biopsies. The diagnosis of vasculitis was based on established clinicopathological criteria. Complete laboratory, clinical, electrophysiological and pathological studies were performed in all cases. RESULTS: Nerve biopsies of 9 patients were diagnosed as Churg-Strauss syndrome. The pathological features were vasculitis with predominant axonal degeneration and a varying pattern of myelinated fiber loss. The vasculitic changes were found mainly in small epineural blood vessels. Mononeuritis multiplex and distal symmetrical and asymmetrical sensorimotor neuropathy, were equally frequent. CONCLUSION: We conclude that, Churg-Strauss syndrome complicated frequently with polyneuropathy, and as remission depends on immunosuppressive therapy, it is important to recognize it in the early stage. The diagnosis of polyneuropathy is based on clinical and electrophysiologic studies, but precise histology, immunolohistochemistry and morphometric study of the peripheral nerve biopsy may be decisive in establishing the diagnosis.

Rare association of sensorimotor polyneuropathy and Klinefelter syndrome (47,XXY): case report.

OBJECTIVES: To describe a case with the rare association of Klinefelter syndrome (47,XXY) and peripheral sensorimotor polyneuropathy. CLINICAL PRESENTATION AND INTERVENTION: A 50-year-old man with Klinefelter syndrome was referred to our neurology clinic complaining of pain, numbness and tingles in both legs, which began 10 years prior to admission. Two years before admission, the patient had difficulty in walking with progressive weakness. CONCLUSION: This report shows a patient with diagnosed Klinefelter syndrome, in whom symmetrical sensorimotor polyneuropathy developed in late adulthood.

Polyneuropathies in teenagers: a clinicopathological study of 45 cases.

The aim of the present study was to investigate the causes of polyneuropathy in teenagers and to describe some characteristic clinical, laboratory, electrophysiological and pathological features. Forty-five patients with peripheral nervous disorders aged 13-19 were studied. Hereditary polyneuropathy of different types was diagnosed in 28 patients (62%); nine showed chronic inflammatory demyelinating polyneuropathy (CIDP) and two showed vasculitic neuropathy. In two more cases polyneuropathy was attributed to toxic agents, while among the rest, one was diagnosed as metachromatic leucodystrophy (juvenile type), one as adrenoleucodystrophy, one as porphyric neuropathy and one as Fabry disease. The high incidence of hereditary neuropathies in teenagers differs from that in adults, but is similar to that encountered in children. In our study, CIDP appears to be a frequent cause of neuropathy in teenagers, while the other causes are broadly similar to those found in studies concerning children rather than adults.

Hereditary neuropathy with liability to pressure palsies: the same molecular defect can result in diverse clinical presentation.

Hereditary neuropathy with liability to pressure palsies (HNPP) is a peripheral nerve disorder characterized by autosomal dominant inheritance, recurrent pressure palsies, reduced motor and sensory conduction velocities and sausage-like swellings (tomacula) of myelin sheaths in nerve biopsy. Two young adult patients are reported as index cases of two families in which HNPP was diagnosed. The first patient presented with recurrent pressure palsies, whereas the second suffered from fasciculations and myokymias in his right hand, with difficulty in writing, and upper and lower limb paraesthesias of 3 years' duration. Electrodiagnostic studies revealed slowing of conduction primarily in common sites of compression in both patients. Sural nerve biopsy revealed the characteristic tomaculous swellings in both patients. DNA analysis showed that both patients have a deletion in chromosome 17p11.2 which is found in the majority of HNPP cases. In light of the common molecular defect, the different clinical symptomatology of the two patients is discussed.

A study of apoptosis in brain tumors by in situ end-labeling method.

Recognition of apoptotic cells has recently been facilitated by in situ end-labeling (ISEL) techniques which identify DNA strand breaks. The ISEL assay has been applied in 26 brain tumors, meningiomas, and gliomas of different grade of malignancy in order to determine the apoptotic index (AI). Apoptotic cells were readily found in all the examined tumors; in most cases the AI values were below 1%. Any significant relationship between AI and grade of malignancy could not be determined. However, the AI mean value of the meningiomas was higher than that of gliomas WHO II and III, respectively. Furthermore, it seemed that in the examined gliomas, with the exception of the glioblastoma group, low grade malignancy was related with higher AI values. The latter decreased gradually in the WHO II and III group of tumors, respectively. Our preliminary results indicate that an apoptotic process may play a significant role in brain tumor kinetics and will probably contribute to our understanding of the biologic behavior of those tumors.

Glutamate levels and activity of the T cell voltage-gated potassium Kv1.3 channel in patients with systemic lupus erythematosus.

OBJECTIVE: Alterations in glutamate homeostasis and Kv1.3 voltage-gated potassium channel function have been independently associated with T cell dysfunction, whereas selective blockade of Kv1.3 channels inhibits T cell activation and improves T cell-mediated manifestations in animal models of autoimmunity. Because low extracellular glutamate concentrations enhance the activity of this channel in normal T cells ex vivo, we undertook this study to examine serum glutamate concentrations and Kv1.3 channel activity in patients with systemic lupus erythematosus (SLE). METHODS: We used high-performance liquid chromatography for glutamate measurements, and we used the whole-cell patch-clamp technique for electrophysiologic studies performed in freshly isolated, noncultured peripheral T cells. RESULTS: Mean +/- SD serum concentrations of glutamate were lower in patients with either clinically quiescent SLE (77 +/- 27 microM [n = 18]) or active SLE (61 +/- 36 microM [n = 16]) than in healthy controls (166 +/- 64 microM [n = 24]) (both P < 0.0001). The intrinsic gating properties of the Kv1.3 channels in lupus T cells were found to be comparable with those in healthy control-derived T cells. Notably, electrophysiologic data from SLE patient-derived T cells exposed to extracellular glutamate concentrations similar to their respective serum levels (50 microM) demonstrated Kv1.3 current responses enhanced by almost 20% (P < 0.01) compared with those subsequently obtained from the same cell in the presence of glutamate concentrations within control serum levels (200 microM). CONCLUSION: Based on the key role of Kv1.3 channel activity in lymphocyte physiology, an enhancing in vivo effect of low serum glutamate concentrations on the functional activity of this channel may contribute to lupus T cell hyperactivity. Studies to further elucidate Kv1.3 responses in SLE, as well as the possible pathogenetic role of this unsuspected metabolic abnormality, may have therapeutic implications for SLE patients.

Polyneuropathies in the elderly: a clinico pathological study of 74 cases.

In elderly patients, peripheral neuropathies are common and may lead to disability. In order to investigate the relative incidence of different polyneuropathies in the elderly focusing on the contribution of nerve biopsy to their diagnosis, the authors studied 74 patients over 65 years of age with clinical, laboratory, electrophysiological, and sural nerve biopsy findings of different types of polyneuropathy. Vasculitic polyneuropathy seemed to be the most common cause of disabling neuropathy in the elderly, followed by paraneoplasia and diabetes. The possible diagnosis of idiopathic axonal neuropathy in the nine cases with neuropathy of unknown origin is discussed.

Use of truncated pyramid representation methodology in three-dimensional reconstruction: an example.

This paper describes a new methodology for three-dimensional (3D) representation of biological structures contained in a series of sections, using an illustrative example. Spatial reconstruction of a specific area of an astrocytoma biopsy was carried out with alignment of the serial sections at an accuracy of 0.01% (or 1 micro m cm(-1)), using the truncated pyramid representation (TPR) methodology. TPR includes: (a) serial tissue sectioning in a ribbon form; (b) alignment of the serial sections based on the properties of a 'truncated pyramid'; (c) identification and localization of structures in every section using a field frame, and representation of the contours of the structures in every section as topographic contours (charting); (d) artificial reconstruction of the missing space between serial sections, by drawing intermediate contours based on the prototype contours of successive sections in order to provide smoother and more elegant representation of the volumes (complementation); and (e) 3D reconstruction. Application of TPR in a selected area of the astrocytoma enabled us to observe the morphology and spatial distribution of neoplastic astrocytic nuclei, which encircled an adjacent blood vessel.

The development of brain tumours produced in rats by the intracerebral injection of neoplastic glial cells: a fine structural study.

Tumours were produced by the intracerebral injection of a clone of glial cells derived from a glioma induced transplacentally by N-ethyl-N-nitrosourea in a BD-IX rat. The injection of 5 X 10(5) cells into the left frontal lobe resulted in a 100% incidence of tumours. To follow the development of the neoplasms, the brains were studied from 1 day to 4 weeks after injection. The tumours maintained their glial characters throughout, but their features changed with time. Ultrastructurally, they were pleomorphic: the proportion of fibrillary astrocytes, undifferentiated and intermediate cell types varied according to tumour size. When smaller (1 and 2 weeks), fibrillary astrocytes predominated, but when larger (3 and 4 weeks), the number of undifferentiated astrocytes considerably increased. A reproducible brain tumour model with a short latency has thus been established and characterized, which may be of use for chemo- and radiotherapeutic studies and for examining the mechanisms of cerebral oedema.

Morphological analysis of malignancy: a comparative study of transplanted brain tumours.

A comparative study of the cellular composition and ultrastructural features of rat brain tumours produced by early and late passage of neoplastic glial cells was carried out. The cells injected intracerebrally were of a clone neoplastic astrocytes (A15A5) derived from a mixed glioma induced transplacentally by N-ethyl-N-nitrosourea (ENU) in a BD-IX rat. The neoplastic cells were maintained for various lengths of time in vitro and then injected (5 X 10(5) cells) into the left frontal lobe of the brains of syngeneic rats, resulting in a 100% tumour yield. Gliomas produced by cells of earlier passages were less malignant and contained better differentiated astrocytes than those produced by cells of later passages. There were also differences in size, shape, extracellular space, presence of haemorrhage and necrosis, vascularity and invasion of the surrounding tissues. Thus the morphological features of transplanted tumours in vivo correlated well with the in vitro behaviour of neoplastic glial cells.

Neuropathy following acute intoxication with Mecarbam (OP ester)

Only a small number of organophosphorous compounds, of the many thousands circulating on the market, has been reported as causing neuropathy with delayed onset. A case is presented of a young male who in an attempt to commit suicide by taking a massive dose of Mecarbam, developed polyneuropathy accompanied by a mild involvement of the CNS. Mecarbam is herewith reported for the first time as an agent which can affect the peripheral nervous system.