Diffusion tensor imaging findings in the multiple sclerosis patients and their relationships to various aspects of disability.

BACKGROUND: The aim of the study was to assess microstructural changes within strategic brain regions in multiple sclerosis (MS) patients, using diffusion tensor imaging (DTI), with regard to various aspects of disability. MATERIAL AND METHODS: The study comprised 50 patients with relapsing-remitting MS (37 women, 13 men, mean age 36.4 yrs) and 27 age- and sex-matched controls. Using DTI, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained within corpus callosum (CC), both thalami (TH) and middle cerebellar peduncles (MCP). Disability was assessed using Expanded Disability Status Scale (EDSS), MS Functional Composite (MSFC), Symbol Digit Modalities Test (SDMT) and Fatigue Severity Scale (FSS). DTI indices were compared between the patients and controls and in the MS group - referred to disability measures. RESULTS: Significant decrease in FA and increase in ADC within CC and both TH were found in MS patients compared to the controls. DTI indices within CC and TH correlated significantly with SDMT score, and within TH and MCP - with MSFC manual dexterity measure. CONCLUSIONS: Changes in DTI measures in normal appearing white and grey matter in the MS patients indicate subtle alterations of the tissue integrity. An occult damage to the strategic brain regions may contribute to various aspects of disability due to MS.

The relationship between epileptiform discharges and background activity in the visual analysis of electroencephalographic examinations in dogs with seizures of different etiologies.

Electroencephalographic (EEG) recordings in 125 outpatient dogs with various epileptiform encephalopathies were acquired under medetomidine sedation using subdermal wire electrodes. The features of canine EEG (background activity [BGA] and epileptiform discharges [EDs]) were assessed, described and compared. The dogs included neurologically healthy controls (N, n = 19), dogs with portosystemic shunt (PSS, n = 9), dogs with intracranial pathologies (IP, n = 27) and dogs with idiopathic epilepsy (IE, n = 70). A visual EEG analysis revealed significantly more pronounced high voltage, low-frequency BGA in the PSS and IP groups in comparison to the N and IE groups (PSS vs. N, PSS vs. IE P <0.0001; IP vs. N, IP vs. IE P = 0.043). At least one ED in the recording was found in 47.37% (n = 9/19) of the individuals in the N group, 88.9% (n = 8/9) of the dogs in the PSS group, 77.78% (n = 21/27) of the dogs in the IP group and 61.43% (n = 43/70) of the dogs in the IE group. The presence of bilateral symmetric triphasic (BST) waves was significantly higher in the PSS group than in the remaining groups. There was a strong prevalence of spike-waves in dogs with idiopathic epilepsy and of BST waves in dogs with portosystemic shunt. None of the dogs in group N had spike-waves or BST activity. EDs were observed more frequently in high and very high voltage, low frequency BGA than in low voltage, high frequency BGA.

In vivo evaluation of brain damage in the course of systemic lupus erythematosus using magnetic resonance spectroscopy, perfusion-weighted and diffusion-tensor imaging.

Twenty-two neuropsychiatric (NPSLE) and 13 systemic lupus erythematosus (SLE) patients with a normal appearing brain on plain magnetic resonance (MR) as well as 20 age-matched healthy controls underwent MR spectroscopy (MRS), perfusion-weighted (PWI) and diffusion-tensor imaging (DTI). In MRS NAA/Cr, Cho/Cr and mI/Cr ratios were calculated from the posterior cingulate cortex and left parietal white matter. In PWI, values of cerebral blood volume (CBV) were assessed from 14 regions, including gray and white matter. In DTI fractional anisotropy (FA) values were obtained from 14 white matter tracts including projection, commissural and association fibers. All MR measurements were correlated with clinical data. SLE and NPSLE patients showed significantly (p < 0.05) lower NAA/Cr ratios within both evaluated regions and FA values within the cingulum, as well as a tendency to cortical hypoperfusion. Compared to SLE, NPSLE subjects revealed lower FA values within a wide range of association fibers and corpus callosum. Advanced MR techniques are capable of in vivo detection of complex microstructural brain damage in SLE and NPSLE subjects regarding neuronal loss, mild hypoperfusion and white matter disintegrity. MRS and DTI seem to show the highest usefulness in depicting early changes in normal appearing gray and white matter in SLE patients.

Stimulated peripheral production of interferon-gamma is related to fatigue and depression in multiple sclerosis.

OBJECTIVES: The aim of the study was to evaluate the stimulated production of interferon-gamma (IFNγ) by peripheral CD3+CD4+ T lymphocytes in patients with multiple sclerosis (MS) with regard to the degree of fatigue, and to investigate relationships between immunological parameters, level of depression and clinical variables. METHODS: Forty MS patients (30 women, 10 men, aged 22-60 years): 20 fatigued and 20 non-fatigued were involved in the study. Fatigue was evaluated using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS), depression level - using Beck Depression Inventory (BDI). Production of IFNγ by stimulated peripheral blood CD3+CD4+ T lymphocytes, assessed using flow cytometry, was compared between MS patients with different levels of fatigue and controls. Correlations were searched out between immunological findings and BDI, age, duration and course of MS, relapse rate, disability (assessed in Expanded Disability Status Scale - EDSS) and its progression. RESULTS: Stimulated production of IFNγ by CD3+CD4+ T lymphocytes was higher in severely fatigued patients in comparison with non-fatigued ones and controls, tended to correlate with FSS and MFIS, and correlated with BDI. No relationships were found between immunological findings and disease-related variables. CONCLUSION: Stimulated production of IFNγ by peripheral CD3+CD4+ T lymphocytes is related to fatigue and depression in MS patients.

Antinuclear and antiphospholipid antibodies in patients with multiple sclerosis.

The prevalence of autoantibodies in multiple sclerosis (MS) patients and their clinical associations differ between various studies. This study investigated antiphospholipid and antinuclear antibodies in 85 patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) with regard to their association with demographic features, MS specific clinical features and symptoms of connective tissue diseases. Autoantibodies tested included antinuclear antibodies (ANA) with their specificities and anticardiolipin (aCL) and anti-beta-2-glycoprotein I (anti-ß2GPI) antibodies. Antinuclear antibodies were more prevalent in MS patients than in controls (63.5% vs. 3.3%; p < 0.01) and in 19% of patients specific antinuclear antibodies were detected. Anti-ß2GPI IgM antibodies were more frequent in MS patients than in the control group (20% vs. 3.3%; p < 0.05). The frequency of anticardiolipin antibodies did not differ between MS patients and controls. MS patients seropositive for ANA and extractable nuclear antigens (ENA) had significantly shorter disease duration than seronegative patients (p < 0.05) and a lower disability score (Expanded Disability Status Score; EDSS) (p < 0.05). Anti-ß2GPI antibodies were more frequent in patients with secondary progressive MS (SP-MS) and specific ANA antibodies were more frequent in patients with clinically isolated syndrome (CIS) (p < 0.05). The presence of autoantibodies was not associated with the predominant site of neurological involvement or the clinical features of connective tissue diseases.

Fas expression on T cells and sFas in relapsing-remitting multiple sclerosis.

OBJECTIVES: To investigate the proportions of peripheral blood CD4+/Fas+ and CD8+/Fas+ cells and serum sFas levels in relapsing-remitting multiple sclerosis (RRMS) patients with relapses (active RRMS), those without relapses (stable RRMS), and controls over 1 year. MATERIAL AND METHODS: Sixteen RRMS patients and 10 controls were tested monthly. Cells were analyzed by dual immunofluorescence and the sFas levels by ELISA. There were 14 relapses which occurred 1223 days after the last control visits. The measurements performed at these visits in the active RRMS patients were considered as relapse-related, while the rest were regarded as relapse-unrelated. RESULTS: In active RRMS patients the median of CD4+ Fas+ to total CD4+ and CD8+ Fas+ to total CD8+ from relapse-related measurements were higher than the median from relapse-unrelated measurements (P=0.003, 0.004, respectively). The median of CD4+ Fas+ to total CD4+ from relapse-unrelated measurements in active RRMS was higher compared with stable RRMS (P = 0.005) and controls (P = 0.004). The sFas level from relapse-unrelated measurements was also higher in active RRMS than in stable RRMS (P = 0.04) and in controls (P = 0.004). CONCLUSIONS: We suggest that increased expression of Fas antigen on CD4+ subset and increased serum sFas level are valuable markers of clinical activity in MS.

Expression of Fas antigen on T cell subpopulations in peripheral blood of patients with relapsing-remitting multiple sclerosis.

BACKGROUND: During the relapse of multiple sclerosis, the activation of T cells, autoreactive to myelin antigens in blood, enhanced and maintained as a result of anomalous mechanisms of their earlier elimination, leads on para- and autocrine basis to the activation of antigen- non-specific cells of immune system. In consequence, activated cells secrete a range of proinflammatory cytokines and display activation antigen expression on their surface, which results in blood-brain barrier damage. The differentiation of lymphocytes into effector cells in blood during MS relapse is to increase the number of cells supporting inflammatory reactions and simultaneously to reduce the number of cells which play a role of suppressors. Fas antigen is present among activation antigens found on T cells. Once this antigen has been combined with the ligand, it transmits apoptic signal to the cell. The presence of Fas antigen on activated peripheral blood T cells may enable us to estimate their activation and it may also indicate a potential to eliminate those cells from blood. The aim of the study was to provide a quantitative assessment of the subpopulations of CD3, CD4 and CD8 lymphocytes in peripheral blood and to investigate Fas antigen expression on these subsets in patients with relapsing-remitting multiple sclerosis, in relation to clinical activation of the disease. MATERIAL AND METHODS: Thirty-five patients participated in the study, including 14 patients finding themselves in clinical relapse of the disease and 21 patients in the state of remission. Additionally, 21 healthy subjects were included. Quantitative assessment of individual subpopulations and Fas co-expression was carried out with the use of monoclonal antibodies anti CD3, CD4 and CD8 as well as anti CD95 antibodies, and flow cytometer Pas/Dako Galaxy. RESULTS: The differences in the percentage of particular lymphocytes between 3 groups proved insignificant. Patients in the relapse of the disease showed significantly greater Fas expression on subpopulations CD3 and CD4 when compared to the results obtained from remission patients and control subjects. This difference was not observed for Fas expression on subset CD8. CONCLUSIONS: The investigation of Fas receptor expression may be useful in order to monitor clinical course of the disease, which is characterised by the periods of exacerbation and remission.

[The comparison of the effectiveness of treatment of multiple sclerosis relapse with high doses of methylprednisolone, alpha-24 corticotropin and cyclophosphamide]. / Porównanie skutecznosci leczenia rzutu stwardnienia rozsianego duzymi dawkami metyloprednizolonu, alpha-24 kortykotropina i cyklofosfamidem.

The effectiveness of treatment was compared in groups of patients with definite multiple sclerosis (MS) given respectively: methylprednisolone, alpha-24 corticotropine and cyclophosphamide combined with corticotropine. Clinical improvement was assessed by means of the expanded disability status scale (EDSS). The significant results were noted in patients treated with methylprednisolon and corticotropine combined with cyclophosphamide (1.5 in EDSS) for the first time, when compared to subsequent treatment. Within the patients in a more advanced stage of the disease, undergoing subsequent treatment, those given corticotropine displayed the best improvement (1.5 in EDSS), but without statistical significance. The authors suggest methylprednisolone or corticotropine combined with cyclophosphamide are the most effective immunosuppressive treatment in the initial phase of MS.

[Congenital defects of the spinal part of the neural tube]. / Wady wrodzone czesci rdzeniowej cewy nerwowej.

The abnormal closure of the neural tube results in defects of the nervous system development, which are referred to as dysraphism. Considering successive steps of the development of the human foetus, it can be estimated that spinal cord malformations arise from pathologies of early foetal development between 17th and 28th day gestational age. This time period comprises a development of the neural plate and subsequently neural tube. The development is completed with a closure of a posterior aperture of the neural tube (caudal neuropore). Congenital malformations are often caused by defective closure of the caudal neuropore. The neural plate develops about 17th day gestational age, the cerebral vesicle appears about 21st day and the neural tube forms between 17th and 20th day. The rostral neuropore closes on the day 25th as does the caudal neuropore on the day 28th. The embryo is 2.5 mm long at the time. Noxious factors acting during that period can affect normal closure of the caudal neuropore and distort the process of spinal cord canalization. The resultant defect is called spina bifida. This is the most severe form of dysraphism-rachischisis. Meninges are also affected in this defect. They cannot cover the neural canal and on the margins of the lesion are replaced by epithelium. In milder types of the defect lack of a complete bony framework is concealed by soft tissues, forming a sac of variable size over the lesion. Spina bifida can be subdivided according to the sac structure: meningocoele, meningocysticoele, meningomyelocoele, meningomyelocystocoele. Central canal pathologies constitute another form of spinal cord malformations presenting as hydromyelia. Abnormal closure of the neural tube may affect development of the vertebral column and spinal cord along their entire length or only at a certain portion. Malformations are seen most frequently in the lumbo-sacral and then cervical regions.

[Evaluation of sweating function, changes in heart function and postural blood pressure in patients with multiple sclerosis]. / Ocena czynnosci wydzielniczej potu, zmiennosci pracy serca i cisnienia tetniczego po pionizacji u chorych na stwardnienie rozsiane.

The aim of the study was electrophysiologic assessment of sudomotor function and some aspects of cardiovascular system function in patients with multiple sclerosis and an attempt of referring assessed variables to duration of the disease and EDSS score. The study included 24 patients with clinically definite, relapsing-remitting multiple sclerosis and 22 healthy, age-matched controls. Autonomic functions were evaluated by means of clinical examination, heart rate variability tests, measures of blood pressure in supine and standing position and skin sympathetic response examination. Clinical symptoms in patients with multiple sclerosis were scarce. Electrophysiologic tests showed no abnormalities in heart rate variability and blood pressure response to standing in studied group. The majority of patients presented with subclinical dysfunction of sudomotor system, indicated by an abnormal sympathetic skin response, which did not correlate with duration of the disease or EDSS score. Sympathetic skin response examination proved to be a sensitive indicator of autonomic disturbances in patients with multiple sclerosis.

[Sarcoidosis with involvement of the central nervous system]. / Sarkoidoza z zajeciem osrodkowego ukladu nerwowego.

Two cases of lungs and mediastinal lymph nodes sarcoidosis with involvement of central and peripheral nervous system were described. In one patient the vascular type of neurosarcoidosis was diagnosed, in another-the inflammatory type, with pyramidal and cerebellar symptoms and severe peripheral changes. Both cases were illustrated with MRI scans.

[Sleep disorders in patients with brain stem lesions]. / Zaburzenia snu u chorych z uszkodzeniami pnia mózgu.

In 10 patients with clinical symptoms of brainstem lesions of various aethiology and different localization within the brainstem polysomnographic records were performed. Patients were divided into two groups (according to age) and the results obtained in each group were compared with the results in control group. In all patients prolongation of I and III+IV phases and reduction of II and the REM phase were noted. In some patients REM was not observed at all. These results may confirm the theory of the localization of the sleep centre in the brainstem, specially the centre of induction of the REM.

[Paroxysmal EEG changes in patients with multiple sclerosis]. / Zmiany napadowe w EEG u chorych na stwardnienie rozsiane.

The electroencephalograms (EEG) and visual evoked potentials (VEP) were recorded in 100 multiple sclerosis patients treated from 1981 to 1989. In 35 cases the EEG records were pathological and in 12 of them they showed paroxysmal changes. Pathological EEG were mostly seen in young patients, during the first relapse, with high degree of Kurtzke's disability score. Patients with paroxysmal changes showed on physical examination brain stem lesions that could be responsible for paroxysmal activity in EEG. The latencies of P100 wave and amplitudes of P100/N120 complex were analysed in two groups of patients (with and without paroxysmal activity in EEG). There was no statistically important difference between two groups, although in the group with paroxysmal changes in EEG some prolongation of the latency of P100 wave and a little higher amplitude of P100/N120 complex were recorded.

[Results of treatment with plasmapheresis in myasthenic crisis and severe polyneuropathy]. / Wyniki leczenia plazmaferezami przelomu miastenicznego i ciezkiej polineuropatii.

Results of plasmapheresis on myasthenic crisis, Guillain-Barre syndrome (GBS) and paraneoplastic polyneuropathy are presented. In the cases of myasthenic crisis which did not respond to steroids addition of plasma exchange (PE) improved dramatically respiratory failure. Also good results were obtained in GBS treated with PE. In the case of paraneoplastic polyneuropathy PE did not influence the course of disease.

Local and diffuse spread of juvenile cerebellar astrocytomas in subarachnoid space. Light and electron microscopic study.

Based on 5 cases of juvenile astrocytomas the unusual behaviour of this type of tumor is described. It is expressed by local and/or diffuse spread of the neoplasms in the subarachnoid space of the brain hemispheres, cerebellum and spinal cord. The light and electron microscopic examinations have revealed the morphological features of well differentiated tumors of astrocytic origin and of fibrillary type which in a great number of cases have a favourable prognosis. The cause of break through into the subarachnoid space, despite its morphology which indicates on a high degree of differentiation of the tumors, is not known. The relation of primary to secondary infiltration of the subarachnoid space or of the leptomeninges is discussed.

Dry drop of blood plasma--a new approach in the diagnosis of neoplastic diseases.

The dried drop of blood plasma and serum was first described by Bialowas in 1967. The dry drop as a method for diagnosis of neoplasms was introduced in 1984 by Hungarian authors from Cancer Research Group. The aim of our investigations was to estimate the usefulness of this method in diagnostic of central nervous system's tumours and lung cancers. We worked out our own modification of dry drop test, i.e., we used the blood plasma instead the blood serum. In 93% of neoplasms the result of test was positive (in 92% of neoplasms of central nervous system and in 83% of lung cancers). In the control group occurred the large number of falsely positive results, as well as in group of patients with lung tuberculosis (70%), multiple sclerosis (63%) and myasthenia (45%). The results of our investigations showed the usefulness of this method in the screening diagnostic of neoplasia. The further investigations are necessary, especially correlation of dry drop test results with erythrocyte sedimentation test and antibodies and fibrinogen's level in the blood.