Influence of impaired T- and B-cell compartments on efficacy of IVIg in dysimmune neuropathies.

Autoimmune mechanisms are postulated to play a role in the development and progression of dysimmune neuropathies (DN). We investigated the relation between lymphocyte number and marker expression, and disease activity in 20 patients with DN under intravenous immunoglobulins (IVIg) treatment. B- and T-lymphocyte markers were studied by flow cytometry of the expression of CD5, CD25, CD23 and CD38 markers on B cells and of CD3, CD4 and CD8 markers, respectively. These parameters were compared with those obtained from matched healthy volunteers. The proportions of CD38+ B cells were higher in patients compared with those of controls. Proportions of activated CD4+ and CD8+ T cells were comparable in peripheral blood mononuclear cells of patients and controls, but a significant reduction of the absolute numbers of CD3+, CD4+ and CD8+ cells were observed in DN patients. The percentages of CD25+ memory T cells were instead significantly increased in DN patients. Lastly, T-cell reduction and the CD19/CD38 ratio over total B (CD19+) cells directly correlated with a poor response to IVIg therapy. In DN, whereas T-cell number is reduced, activated T and B cells are increased, thus suggesting an intrinsic defect of the immune response.

[Part-time work at a hospital: study of atypical workers]. / Il part time in un'Azienda Ospedaliera: studio sui lavoratori atipici.

According to act 626/1994, employers have the duty to inform and train workers and their representatives. The implementation of training activities requires the following points: planning the training progra according to the needs of the target population, use of the methods aimed at promoting learning and the adoption of safe behaviour, setting-up of evaluation tools. The disciplines of risk perception and communication and adult training may provide useful contribution in this frame. At the light of the preliminary experiences in this field, the importance of the following items for workers, workers representatives and employers is emphasized: probabilistic causality models, role of cognitive and emotional factors in the learning process, definition of carcinogenic according to national and internationals organisation, meaning of TLV with respect to carcinogenic exposure, interaction between carcinogens in the case of multiple exposition, risk evaluation, preventive measures, transfer of carcinogen risk from workplace to domestic environment, due to lack of compliance with basic hygienic rules such proper use of work clothes.

Oligoclonal T cell repertoire in cerebrospinal fluid of patients with inflammatory diseases of the nervous system.

OBJECTIVE: To evaluate the T cell receptor beta chain variable region (TCRBV) gene usage ex vivo in CSF cells and peripheral blood mononuclear cells (PBMCs) collected from patients with autoimmune and inflammatory diseases of the nervous system. METHODS: A novel sensitive seminestedpolymerase chain reaction coupled with heteroduplex analysis was developed. RESULTS: Under these experimental conditions, the minimal number of cells required for the analysis of the whole T cell repertoire was established at 2.5x10(4)-sufficient to evaluate most of the samples collected during diagnostic lumbar punctures. In the 21 patients examined, restrictions in TCRBV gene family usage were not seen. However, using heteroduplex analysis, oligoclonal T cell expansions were found in the CSF of 13 patients and monoclonal expansions in five patients. The T cell abnormalities found did not correlate with intrathecal IgG production or with any clinical variable considered. CONCLUSION: T cell clonal expansions, useful for further characterisation of pathogenetic T cells, can be found during the course of nervous system inflammations, but this abnormality is probably not disease specific.

Expanding lacunae causing triventricular hydrocephalus. Report of two cases.

Two patients are reported in whom the presence of triventricular hydrocephalus and aqueductal obstruction or stenosis due to multiple expanding lacunae in the mesencephalothalamic region possibly corresponds to abnormally dilated perivascular spaces. Placement of a ventriculoperitoneal cerebrospinal fluid (CSF) shunt in one patient and the performance of a third ventricle cisternotomy in the other reversed the hydrocephalic syndrome, but did not modify the complex neuroophthalmological disturbance and rubral tremor presumably related to the compressive effects of the lacunae on adjacent parenchyma. In one patient the number and size of the lacunae were increased 4 years after CSF shunt placement. A review of the literature revealed two cases in which magnetic resonance imaging demonstrated a similar, poorly understood pathological condition.

Syringomyelia in myotonic dystrophy due to spinal hemangioblastoma.

BACKGROUND: Syringomyelia is an uncommon, poorly understood finding in patients with myotonic dystrophy. METHODS: We describe a patient with myotonic dystrophy and neck pain in whom an extensive neuroradiologic diagnostic work-up was carried out. RESULTS: Magnetic resonance imaging revealed a large intramedullary cavity extending from the bulbo-medullary junction to the conus medullaris. After intravenous Gadolinium-DTPA administration, an enhanced nodule was seen at T6. Spinal arteriography showed a single hypervascular nodule and slow flow perimedullary draining veins consistent with hemangioblastoma. After removal of the nodule, a partial collapse of the intramedullary cyst was observed. CONCLUSIONS: Intramedullary tumors can underlie syringomyelia in patients with myotonic dystrophy and have to be actively investigated with modern neuroradiologic investigations.

Detection of skewed T-cell receptor V-beta gene usage in the peripheral blood of patients with multiple sclerosis.

The ex vivo analysis of the T-cell receptor V-beta (TCRBV) gene usage by circulating T lymphocytes in Multiple Sclerosis (MS) patients may contribute to understanding disease pathogenesis. In the present study, TCRBV gene usage was analyzed in freshly collected unstimulated peripheral blood mononuclear cells (PBMC) isolated from 40 MS patients and 20 healthy controls. Nine patients presented abnormal repertoires, with expansion of one or more TCRBV segments. Among these patients, six presented expansion of TCRBV9 chain expression, three also having an expansion of TCRBV1, TCRBV11 and TCRBV22 segments. The most frequently observed TCRBV chain expansion, TCRBV9, was further analyzed and identified as polyclonal. Evaluation of clinical variables showed that median disease duration was shorter in patients with TCRBV gene expression abnormalities. Longitudinal evaluation of five patients with a skewed repertoire showed regression of expanded TCRBV chains expression to normal values. These data indicate that certain MS patients have abnormal TCRBV gene expression. Such abnormalities are caused by polyclonal expansions of T lymphocyte subpopulations that use the same TCRBV gene families, are unstable and preferentially observed early in the course of the disease.

Myotonic dystrophy: an electrophysiological study of cognitive deficits.

Patients with Myotonic Dystrophy (MyD) frequently suffer from a dysfunction of the primary sensory pathways, as documented by abnormalities of short-latency evoked potentials. Impairment of intellectual functions has been less extensively investigated. Short-latency brainstem auditory evoked potentials (BAEPs) as well as long-latency auditory event-related potentials (ERPs) were recorded from 5 female and 6 male patients affected by MyD. A simple discrimination ("oddball") paradigm was used to record ERPs to tones from Fz, Cz, Pz. Both BAEPs and ERPs were significantly altered as compared to normals. BAEP abnormalities were detected in 9 patients and ERP components N2 and P3 were delayed or absent for all patients, who nonetheless correctly discriminated between tones. These data indicate that CNS dysfunction in MyD involves not only primary sensory systems but also neural mechanisms underlying cognitive events and ERP generation.

Plasma-exchange in myasthenia gravis: a study in 20 patients.

Twenty patients with myasthenia gravis (MG) of generalized 2A and 2B types according to the Ossermann classification were treated with a course of nine plasma exchanges (PE) every two days. Before starting of the course, at the fourth exchange, and at the end of the course, the muscle balance was assessed following a special protocol. Other functions, such as respiratory function, stapedial reflex, phonation, and electro-oculographic activity were assessed and a Desmedt test was done. Three patients showed complete remission of symptoms, 8 showed good improvement and 6 mild improvement. Three showed no improvement. In total 85% of patients gained from PE. The onset of improvement was rapid in all patients but in some it lasted only a short time while in others it persisted for several weeks and even months, without the need for immunosuppressive therapy.

Plasma-exchange in idiopathic radiculopolyneuropathies: a study in 62 patients.

The effectiveness of plasma exchange (PE) in the treatment of acute and chronic idiopathic radioculopolyneuropathies (IR) is discussed on the basis of the literature and personal data. Results of controlled trials by Swedish, French and North American groups are favourable to the use of PE in acute forms, whereas one English group found no significant differences between treated patients and controls. Dick et al. (1986) reported significant improvement also in patients with chronic forms after PE. Personal data from a non-controlled series of 62 acute and chronic IR and from a trial group of 12 acute patients and 12 controls indicated that PE--though helpful in Guillain-Barré syndrome--was not so useful in chronic forms.

Becker and limb-girdle muscular dystrophy associated with pituitary dwarfism.

In 1981 a report appeared of a patient with Duchenne muscular dystrophy associated with dwarfism caused by growth hormone deficiency, in whom the muscular disease was unusually benign. The authors suggested that the benign course might be related to the growth hormone deficiency and dwarfism. Other authors later supported this idea, having observed that in dystrophic mice and hamsters with congenital and experimentally induced pituitary dwarfism, respectively, pathological expressions of the dystrophy were markedly reduced. In this paper one case of Becker and one of limb-girdle dystrophy, each associated with short stature and growth hormone deficiency are described. In these cases the disease did not have a particularly benign course. It is concluded that caution is necessary, at least in certain cases, before an association between reduced muscular growth and the dystrophic process can be assumed.

Three-year neuropsychological follow-up of patients with reversible ischemic attacks.

A short neuropsychological test battery designed to measure language, memory and visuospatial abilities was administered to 217 patients with reversible ischemic attacks. Patients were tested twice: the first time more than one month, but less than one year, from the last ischemic episode, and the second time three years later. A comparison between the first and the second testing session did not disclose any significant worsening. The degree of atherosclerosis and the occurrence of further ischemic episodes during the follow-up period were found to be unrelated to change in performance at the test battery. These results seems to challenge the hypothesis that multi-infarct dementia may follow apparently reversible, or even clinically silent, ischemic episodes.

Plasma exchange in myasthenia gravis.

Results obtained with P.E. therapy on 19 myasthenic patients are reported. 15 of them improved during treatment and 4 remained unchanged. We believe P.E. is an useful therapy in M.G. because it produces a rapid improvement in most patients.

Plasma exchange in radiculopolyneuropathies.

The AA. report the results obtained with Plasma Exchange (P.E.) therapy on 24 cases of polyradiculoneuritis; eleven patients had typical Guillain-Barré Syndrome (G.B.S.) ten suffered from a chronic progressive form and three were affected by a relapsing form. The acute patients were selected according to criteria established by the NNCDS Committee (1978) while guidelines laid down by Pineas & Load (1978) were followed in choosing chronic cases. Patients with G.B.S. had four sessions of P.E. at intervals of one or two days while those with chronic forms of polyradiculoneuritis had a total of 6 sessions spaced one to three days apart. P.E. produced no apparent change in chronic progressive patients but two out of three cases with the chronic relapsing form showed rapid and steady improvement resulting in complete cure within a few months. Nine of the eleven G.B.S. patients showed after only one or two sessions a clear and rapid improvement which led to a complete cure within a matter of weeks. The remaining 2 cases showed only partial improvement at first and remained stationary thereafter. The findings confirm the usefulness of P.E. in acute and chronic relapsing radiculopolyneuritis. However, potential side effects and the procedure's high cost suggest that its use should be limited to carefully selected cases, and in particular to those involving respiratory disorders.

[The incidence of the X-linked progressive muscular dystrophies in Tuscany from 1966 to 1974 (author's transl)]. / L'incidenza della distrofia muscolare progressiva X-legata in Toscana negli anni 1966-1974.

An investigation was carried out to establish the incidence of X-linked progressive muscular dystrophies in Tuscany from 1966 to 1974. 52 cases were identified, the incidence being 23,95 X 10(-5) with reference to live-born males. The frequency of new mutations calculated according to Haldane's method was 7,97 X 10(-6). These data practically correspond to those reported by other AA. in Italy and abroad. There was also a remarkable variability in the incidence among individual districts with values ranging from 7,60 X 10(-5) to 41,91 X 10(-5). It was noticed that the number of new cases tended to decrease in the last few years.

[Immunological and therapeutic aspects of myasthenia gravis (author's transl)]. / Aspetti immunopatologici e terapeutici della miastenia gravis.

In the treatment of Myasthenia Gravis (M.G.) new therapeutic techniques have been gradually added to the usual anticholinesterase drugs. Steroids, immunosuppressive drugs, plasma exchange have been employed whereas thymectomy is still the most useful surgical treatment. On the basis of both personal experience and data from the literature the AA. reviewed the therapeutic techniques. Thymectomy is practically indicated for all patients particularly young ones. However there are some reserves in the presence of thymomas as sometimes deterioration may occur. Steroids are mostly employed in cases resistant to other therapies. Immunosuppressive drugs are usually associated with plasma-exchange. The latter has been recently preferred because of the absence of side effects; however its real therapeutic value has not yet been fully assessed.

[Isoelectrofocusing on polyacrilamide gel in the study of gamma-globulin changes during neurological illnesses (author's transl)]. / L'uso dell' isoelettrofocusing nello studio delle proteine liquorali, sua applicazione nella diagnosi delle malattie del sistema nervoso.

Isoelectrofocusing on polyacrilamide gel in the analysis of cerebrospinal fluid proteins is particularly suitable for investigations of gamma-globuline changes in the course of various neurological conditions. This technique makes it possible to recognise three patterns besides the normal one. The first is characterized by a diffuse increase in gamma-globulines with a great number of high density fractions showing uniform distribution in the alkaline pH area. It was observed in a case of Guillain-Barrè syndrome and in two cases of intramedullary tumours. It seems to be due to an alteration in the permeability of the blood-brain barrier. The second pattern shows a diffuse increase in the number of fractions and appears uneven owing to a certain amount of higher density bands which stand out clearly. This was observed in one case of tubercolous meningo-encephalytis, in one case of chickenpox encephalytis and one case of cryptococcal meningitis in a patient affected by lymphogranuloma. This pattern is probably due to an alteration of blood-brain as well as of immunological systems. The third pattern presents a clear fractionation of gamma-globulins gathered in a certain number of highly coloured bands, mainly in the most alkaline area of gel. This was observed in all the ten cases of multiple sclerosis and in the only case of subacute sclerosing panencephalitis. This may be attributed to the intrathecal production of oligoclonal gamma-globulines (Ig.G.).

[On the intrathoracic meningocoele. Diagnostic usefulness of myeloscintigraphy (author's transl)]. / Sul meningocele intratoracico. Utilità diagnostica della mieloscintigrafia.

Intrathoracic meningocoele (I.M.) consists of a bulging out of the meninges in the posterior mediastinum through an intervertebral foramen or a bone defect in the thoracic spine. It is a rare condition generally asymptomatic and often associated with von Recklinghausen's neurofibromatosis, whose aetiopathogenesis and clinical significance have not yet been completely clarified. The AA. describe a case of I.M. in a patient with neurofibromatosis who at 37 years of age presented spastic monoparesis in the left lower limb with subacute onset. In this case two abnormally wide intervertebral foramina and scalloping of the posterior rims of the vertebral bodies close to the meningocoele were observed. These changes seem to point to an alteration in bone development as the chief cause of intrathoracic meningocoele in contrast with other aetiopathogenic hypotheses. Excluding the presence of other expansive lesion, spastic monoparesis might be related to a confined medullary involvment due to compression of arterial or venous vessels by the meningocoele. Finally the AA. emphasize the importance of myeloscintigraphy, wich easily allows correct diagnosis by showing a typical pool of radioactive tracer in the meningocoele bulge lateral to the spine.