Multiple sclerosis produces significant changes in urinary bladder innervation which are partially reflected in the lower urinary tract functional status-sensory nerve fibers role in detrusor overactivity.

BACKGROUND: Detrusor overactivity is often observed in patients with multiple sclerosis (MS), and neurotoxins are emerging as second-line therapies albeit with different degrees of success per patient basis. OBJECTIVE: To investigate lower urinary tract (LUT) functional status and bladder innervation (calcitonin gene related peptide [CGRP] and substance P [SP] positive nerve fibers) in patients with MS. METHOD: Eighteen MS patients with LUT symptoms underwent urodynamic investigations, and six non-MS patients undergoing cystoscopy due to microscopic hematuria served as controls. Cold cut bladder biopsies were taken from the bladder trigone region. Neurotransmitter expression was determined by individual immunohistochemical staining. RESULTS: Two distinct groups could be distinguished: group 1 with pronounced neurogenic detrusor overactivity and mild outflow obstruction; group 2 with some degree of neurogenic detrusor overactivity, detrusor hypocontractility during voiding, and high degree of an outflow obstruction. The presence of SP and CGRP immunoreactive + fiber density was observed in greater numbers in group 1. CONCLUSION: Density of CGRP and SP positive nerve fibers within the urinary bladder of patients with MS may be suggestive of functional status of the lower urinary tract, namely denser innervation is observed in patients with mild outflow obstruction and strong detrusor overactivity. This observation could be useful when planning second-line treatment (neurotoxins) in these patients. Patients with denser innervation probably will respond better to such a therapy.

A prospective study of the financial costs of multiple sclerosis at different stages of the disease.

The aim of our study was to estimate the costs of multiple sclerosis (MS) in Poland according to severity of disease. Total, direct and indirect costs were compared in 148 patients divided into three groups categorized by disease severity: stage I Expanded Disability Status Scale (EDSS <3.5), stage II (EDSS 4.0-6.0) and stage III (EDSS >6.5). Cost evaluation was performed from the societal perspective and covered the 5-month period. Simple sensitivity analysis was performed by varying the tariffs and valuing caregiving at 40% of the average wage. The mean total cost/patient for 5 months was estimated at 10,955, 15, 603 and 18, 464 PLN for stage I, II and III, respectively [exchange rate: 4 PLN=1 EUR; purchasing power pariety: 1 EUR=2.05 PLN] (P <0.0001). Regardless of EDSS stage indirect costs exceeded direct costs. Both direct and indirect costs increased with MS progression. For indirect cost the main item was productivity loss. This study confirms that MS represents a high economic burden, with indirect costs greatly exceeding direct costs. As costs increase with disease progression, treatment efforts should focus on patients in the early stages of MS.

[Pseudochoreoathetosis as manifestation of cervical cord lesion. Case report]. / Pseudochoreoatetoza jako objaw uszkodzenia rdzenia kregowego w odcinku szyjnym. Opis przypadków.

The involuntary movements of choreoathetotic type are commonly regarded as a sign of basal ganglia lesion. However, such movements can also occur in pathological processes involving the cervical spinal cord. This condition is referred to as pseudochoreoathetosis. Involuntary movements can be related to lack of proper coordination between agonist and antagonist muscles, their simultaneous activation due to impairment of reciprocal inhibition. The characteristic feature of pseudochoreoathetosis is proprioceptive sensory loss. In this paper we present 4 patients who developed various involuntary limb movements in early stage of the disease. Lesions in the cervical spinal cord were confirmed by MRI. In case 1 the cause was astrocytoma, in cases 2 and 3--demyelination, in case 4 the precise character of the lesion could not be established. Pseudochoreoathetosis is a rare condition which often remains unrecognized. The presented cases emphasise the importance of early and correct diagnosis leading to proper therapeutical procedure.

Evaluation of cerebrospinal fluid for the presense of anticardiolipin antibodies (aCL) in NP-SLE patients.

Many neurological or psychiatric manifestations of SLE (NP-SLE) are related to the presence of anticardiolipin antibodies (aCL) in the patient's sera. The aim of this study was to evaluate the presence of aCL in cerebrospinal fluid (CSF) in SLE patients with NP features. Fifteen SLE patients were studied, all with NP features. CSF was evaluated for intrathecal IgG synthesis, oligoclonal IgG, and blood-brain barrier impairment. Sera and CSF were tested by ELISA for the presence of aCL-IgG and aCL-IgM with and without beta2 glycoprotein (beta2 GPI) cofactor. CSF and sera of 50 low back pain patients served as controls. Six patients were aCL(+) and nine aCL(-). In all patients the general CSF examination was normal. In all patients the value of indices of intrathecal IgG synthesis were normal but oligoclonal protein was present in the CSF of three patients. In none of the patients was the blood-brain barrier impaired. Neither aCL-IgG nor aCL-IgM was detected in the CSF of any NP-SLE patient. Mean levels of aCL in patients without cofactor beta2 GPI and with cofactor were as follows: for IgG class 0.005 and 0.057 OD (negative); for IgM class 0.004 and 0.024 OD (negative). We could not detect aCL in the CSF of patients with NP-SLE, even if sera were positive for aCL.

[The evaluation of humoral immunity response in subacute sclerosing panencephalitis (SSPE)]. / Ocena odpowiedzi humoralnej w podostrym stwardniajacym zapaleniu mózgu (SSPE).

The purpose of the study was the assessment of humoral response markers in 20 patients with SSPE in phase I, II and III of the disease during immunomodulating treatment. In the CSF IgG levels were determined by nephalometric method, with its share in the total protein level, and with determination of the local IgG synthesis in CNS by Reiber method, 24-hour IgG synthesis by Tourtellotte-Boce method, IgG index by Link-Tibbling method and albumin index. Oligoclonal IgG was determined by isoelectrofocusing. All mathematical tests indicating IgG synthesis in CSF were abnormal in all cases, and also in all cases oligoclonal IgG was found (type 3 of electrophoresis separation pattern). The results point to far reaching changes of the humoral immune response in SSPE persisting also during immunomodulating treatment independently of disease phase and duration. In only 10% of cases abnormal values of the albumin index suggested damage to the blood-brain barrier.

Phenotyping analysis of peripheral blood leukocytes in patients with multiple sclerosis.

Multiple sclerosis (MS) is a central nervous disease thought to be elicited by an autoimmune process. Many studies in recent years have concentrated on finding the alterations in the peripheral blood immune profile in MS patients that would reflect disease activity. In the present study, we investigated surface antigen expression on lymphocytes and granulocytes from MS patients and control subjects. We have studied 29 patients suffering from relapsing-remitting or relapsing-progressive forms of MS. The disease was diagnosed in all patients at least 12 months before inclusion into the study. All patients had no attack at the study entry date or within a previous month. The control group included 29 age-matched subjects. Phenotyping of peripheral blood leukocytes was carried out with different fluorescence-conjugated murine monoclonal antibodies. The analysis was performed with three-color flow cytometry. The following antigens were determined [cluster of definition (CD)]: leukocyte common antigen (LCA) (B220, T 200, Ly-5), CD45; LPS-R (lipopolysaccharide receptor), CD14; found on all T cells, CD3; LFA-2 (lymphocyte function associated antigen, T 11), CD2; coreceptor for MHC class II molecules, found on helper T cells, CD4; coreceptor for MHC class I molecules, found on suppressor/cytotoxic T cells, CD8; B4, found on all human B cells, CD19; NCAM (neural cell adhesion molecule), CD56; integrin beta2 subunit, associated with CD11a (CD11a/CD18, LFA-1, alphaLbeta2) and CD11b (CD11b/CD18, Mac-1,CR3, alphaMbeta2), CD18; alphaL, alpha subunit of integrin LFA-1 (alphaLbeta2, CD11a/CD18), CD11a; alphaM, alpha subunit of integrin Mac-1 (CR3, alphaMbeta2, CD11b/CD18), CD11b; ICAM-1 (intercellular adhesion molecule), CD54; H-CAM, Hermes antigen, Pgp-1, CD44; AIM (activation inducer molecule), early activation antigen, CD69; T-cell receptor gammadelta, TCR gammadelta. In the MS group, we have found a significant increased expression of CD54 and CD44 antigens on lymphocytes, and higher percentage CD54(+) and CD11a+CD54(+) lymphocytes out of all lymphocytes compared with the control group. We have also found a significant increased expression of CD11a, CD18 and CD54 antigens on granulocytes, and higher percentage CD11b+CD18(+) granulocytes out of all granulocytes in MS patients compared with control. Higher levels of expression of the adhesion molecules may reflect the activation state of leukocytes in MS patients.

Progressive multifocal leukoencephalopathy (PML) and cerebral toxoplasmosis in an adult patient, with no symptoms of underlying immunosuppressing illness.

We present a case of the coincidence of progressive multifocal leukoencephalopathy (PML) and central nervous system (CNS) toxoplasmosis in an adult patient, without a detectable cause of cell-mediated immunity impairment. The proper diagnosis was made postmortem on the basis of histological changes typical of both pathological processes. PML was characterized by the presence of subcortical focal demyelination, containing enlarged, densely basophilic oligodendrocyte nuclei, often with intranuclear inclusion, and bizarre astrocytes, mimicking neoplastic cells. PML was confirmed by detecting numerous papova virus particles in oligo- and astroglial nuclei by thin-section electron microscopy. Cerebral toxoplasmosis was characterized by the presence of multiple well-circumscribed necrotizing abscesses. Numerous Toxoplasma gondii (T. gondii) cysts and free, non-encysted protozoan parasites were found among the inflammatory infiltrates. The diagnosis of cerebral toxoplasmosis was further confirmed by immunocytochemistry. In order to detect putative immunosuppressive background underlying both pathological processes, HIV infection was taken into consideration, however, no histopathological changes indicative of AIDS either in the CNS or in the peripheral organs were eventually found. Moreover no HIV provirus genome was identified in the formalin-fixed, paraffin embedded brain tissue by the polymerase chain reaction (PCR). Current view on the selected aspects of the pathogenesis of both disorders were discussed.

Oligoclonal expansion of gamma delta T cells in cerebrospinal fluid of multiple sclerosis patients.

We have used a PCR based method to analyse TCR gamma chain repertoire and clonality of gamma delta T cells in the CSF and blood of II MS patients. Samples collected from nine patients with other neurological diseases were used as a control. Five controls had central nervous system inflammation and four had non-inflammatory processes. We have observed a decreased percentage of gamma delta T cells expressing TCR gamma with V gamma 9 and J gamma P fragments in the CSF samples in comparison with the blood. We did not final clonal expansion of the gamma delta T cells in any control case. Clonal expansion of gamma delta T cells occurred in five of II MS cases in the CSF but not in the blood. Two of these clones expressed TCR gamma rearranged with V gamma 9 and J gamma 1 fragments, two others used V gamma 10 and J gamma P1, and one used V gamma 9 and J gamma P fragments. We found no correlation between clonality and clinical state of patients, duration of the disease or number of cells in CSF. Our study provides additional evidence for the possible role of the gamma delta T cells in the MS pathogenesis.

[Detection of oligoclonal immunoglobulin G in the cerebrospinal fluid of patients with multifocal vascular lesions of the CNS]. / Wykrywanie oligoklonalnej immunoglobuliny G w plynie mózgowordzeniowym u chorych z wieloogniskowymi zmianami naczyniowymi OUN.

Vascular diseases of CNS are usually a result of certain risk factors. In a number of cases vascular diseases are caused by inflammatory process within arteries. Establishing the intrathecal synthesis of immunoglobulins is an important indicator of the inflammatory process in the CNS. 16 patients with multifocal vascular lesions in neuroimaging examinations (MRI or CT), were analysed for the frequency of occurrence of inflammatory process within the CNS. The presence of intrathecal synthesis of IgG was established by mathematical formulas and presence oligoclonal IgG bands. In some patients presence of oligoclonal IgG bands was found, and regarded responsible for stroke. In this group the patients were younger, and mainly without other risk factors for vascular diseases. In the majority they were patients with systemic inflammatory process (e.g. SLE). The establishing of inflammatory process within the CNS sometimes has therapeutic implications.

[The application of immunoblotting micromethod for the detection of oligoclonal Igg in cerebrospinal fluid in multiple sclerosis]. / Zastosowanie mikrometody immunoblotingu w wykrywaniu oligoklonalnej immunoglobuliny G w plynie mózgowo-rdzeniowym u chorych na stwardnienie rozsiane.

UNLABELLED: The demonstration of the presence of intrathecal synthesis of immunoglobulins as oligoclonal band (OB) in cerebrospinal fluid (CSF) is considered to be important as an aid to multiple sclerosis diagnosis. We used the Phast System equipment for OB detection in the CSF. Separation was performed on polyacrylamide gels pI 3-9.7. After separation proteins were visualised with silver staining according to manufacturer instruction or transferred electrophoretically on to nitro-cellulose membrane and developed by immunostaining technique. We also calculated indexes of intrathecal synthesis of IgG. We tested CSF of patients with clinically defined multiple sclerosis (n = 29) according to Poser criteria. In all cases IgG indexes were normal. OB were present in 83% with silver staining and in 93% when we used immunoblotting technique. CONCLUSIONS: 1. Detection of OB with Past System is easily performed in routine diagnostic process. 2. Immunoblotting technique increases sensitivity of detection of OB and needs small amounts of CSF. 3. The demonstration of OB in CSF is a method of choice in diagnostic process of inflammatory diseases of nervous system, especially in cases of MS.

[Diagnostic value of oligoclonal band detection in cerebrospinal fluid using PhastSystem device]. / Wartosc diagnostyczna wykrywania pasm oligoklonalnych w plynie mózgowo-rdzeniowym z zastosowaniem aparatu PhastSystem.

The study confirming the presence of oligoclonal IgG in cerebrospinal fluid by isoelectric focusing (IEF) with PhastSystem equipment was carried out in 68 patients with clinically definite MS, in 23 with clinically probable MS and in 23 with other neurological diseases. Other indicators intrathecal synthesis of IgG were olso marked. According to the results it was confirmed that the most sensitive method of detection of intrathecal synthesis of immunoglobulins is finding of the oligoclonal IgG. Using the PhastSystem evidently shorties the diagnostic process. The sensivity of the method equals that of MRI and both have similar clinical value.

[Significance of oligoclonal proteins and magnetic resonance imaging in the diagnosis of multiple sclerosis]. / Znaczenie bialek oligoklonalnych i magnetycznego rezonansu jadrowego w diagnostyce stwardnienia rozsianego.

The new techniques identifying inactive clinical injury, as well as revealing immunological disturbances connected with the CNS, are very helpful for arriving at the correct diagnosis of multiple sclerosis. In their analysis the authors of the work include six cases and emphasize the great practical significance of magnetic resonance imaging and oligoclonal bands in the cerebrospinal fluid in making the diagnosis of multiple sclerosis.