Leptin and ghrelin concentrations and weight loss in Parkinson's disease.

OBJECTIVES: To investigate the role of leptin, ghrelin, GH and IGF-1 in energy balance disturbances in Parkinson's disease (PD). MATERIALS AND METHODS: Thirty-nine patients were included: 11 PD patients with unintentional weight loss, 16 PD patients without weight loss and 12 controls. UPDRS, MMSE, MADRS, appetite scale, BMI, adipose tissue content, plasma leptin and active ghrelin concentrations and serum GH, IGF-1, TSH, T3 and T4, concentrations were evaluated. RESULTS: A lower plasma leptin concentration and a higher serum IGF-1 concentration were found in PD patients with weight loss. BMI and the content of adipose tissue were positively correlated with leptin concentration in all PD patients. Paradoxically, the lower BMI was, the lower plasma active ghrelin concentration was in PD patients with the weight loss. CONCLUSION: These findings confirm that changes of plasma leptin concentration occur in PD patients with loss of weight.

Assessment of relations between clinical outcome of ischemic stroke and activity of inflammatory processes in the acute phase based on examination of selected parameters.

BACKGROUND AND PURPOSES: Inflammatory factors play an important role in the pathogenesis of ischemic stroke. They may influence circulation during the acute phase of stroke and enhance the ischemic region. MATERIALS AND METHODS: We examined 51 patients--36 patients in the early stage of stroke, i.e. the first 24 h after onset. Of these, 15 patients had infection and 21 had no infection during the week preceding stroke. There were 15 patients with noninflammatory diseases in the control group. We analyzed parameters of inflammation such as: activity of serum chitotriosidase by fluorimetric assay, C-reactive proteins (CRP), number of white body cells (WBCs), IgG and fibrinogen. We also assessed the neurological stage according to the Scandinavian Stroke Scale (SSS). RESULTS: In our study, we observed a statistically significant difference (p < 0.05) in the activity of most parameters of inflammation. This difference could be seen in the levels of CRP, number of WBCs and the activity of chitotriosidase, apart from IgG and fibrinogen, between the control group and groups with versus without infection. A significantly increased level of CRP (p < 0.0005) and fibrinogen (p > 0.01) was found on the first day in the stroke group as compared to the control group. The neurological stage on day 4 after stroke, assessed according to the SSS, was significantly worse in the group of patients with infection before stroke than in stroke patients without infection (p < 0.008). CONCLUSION: These results suggest the importance of active inflammatory processes in the pathogenesis of stroke. We observed increased activity of chitotioridase, a parameter of the inflammatory process, in stroke. This study is one more proof that inflammatory processes caused by infection may influence the occurrence of stroke and worsen its outcome. It could be another step towards understanding immunological processes during the acute phase of stroke. The study may also help establish new diagnostic and therapeutic strategies and could be a useful tool for prophylaxis.

The antibodies against Bordetella pertussis in sera of patients with Parkinson's disease and other non-neurological diseases.

OBJECTIVES: It has been reported that the prevalance of parkinsonism might be associated with exposure to whooping cough. METHODS: Examination of levels of antibodies against Bordetella pertussis in serum using enzyme-linked immunosorbent assay (ELISA) tests [presence of IgG antibodies against filamentous hemagglutinin and pertussis toxin (PT)] were performed in 81 persons (including 45 patients with controls) (age-matched groups). RESULTS: Positive results were found in patients with Parkinson's disease (PD), patients with other non-inflammatory diseases, and controls (about 40-45% in each group). A detailed examination of separate responses (IgG and IgA antibodies against PT, and a whole cell immune response) and of the serum level of immunoglobulins IgG, IgA and IgM was also performed. CONCLUSION: Our results demonstrate numerous cases of whooping cough serum antibodies among the adult population (also among PD patients). The results of our research, i.e. a common occurrence of Bordetella pertussis infection do not provide evidence of relationship between PD and the above-mentioned infection.

Lewy body variant of Alzheimer's disease and Alzheimer's disease: a comparative immunohistochemical study.

Immunohistochemistry (IHC) and ultrastructural study were performed on 19 demented autopsy cases of sporadic Alzheimer's disease (AD). Semiquantitative IHC assessment of the pathological changes, according to the criteria of the Consortium to Establish a Registry of Alzheimer's Disease (CERAD) and the Consortium on Dementia with Lewy Bodies, showed morphological hallmarks of AD in 18 demented patients. It was found that 11 of these cases fulfilled criteria for "pure" AD, whereas the remaining 7 cases, with mixed findings, Lewy bodies (LBs) and Lewy-related dystrophic neurites, neuritic plaques (NP) and sometimes neurofibrillary tangles (NFT), met the criteria for Lewy body variant of Alzheimer's disease (LBV). One case with brain stem and cortical LBs but without NP and NFT was finally diagnosed as a pure form of dementia with Lewy bodies (DLB). Regional distribution and semiquantitative assessment frequency of alpha-synuclein-immunoreactive LBs, tau-immunoreactive NFT and beta-amyloid immunoreactive senile plaques, were compared between LBVand AD. Ultrastructural examination confirmed the filamental structure of cortical LBs. In conclusion, IHC study including antibody to alpha-synuclein, the sensitive marker for Lewy bodies, revealed the coexistence of brain stem and cortical LBs and pathological features of AD in a great part of dementia cases. Patients with mixed, LBs, NP and sometimes NFT pathology, fulfilled neuropathological CERAD criteria for LBV. Semiquantitative comparative IHC study, according to LBs- and NFT-scores and CERAD NP-scores showed in the LBV group a significantly lower frequency of NFT coexisting with neocortical LBs than in the group with pure form of AD.

[Social and economic aspects of administration of new antiepileptic drugs]. / Stosowanie nowych leków przeciwpadaczkowych w aspekcie ekonomiczno-spolecznym.

The necessity of analysis of the cost of treatment of patients with epilepsy becomes of primary importance in Poland as a consequence of recent economic transformations affecting the efficiency of health service. The reasons are: high number of patients with epilepsy (approaching 400,000 in a population of about 40 mln) and long time course of illness, taking into account steady, gradual rise of the cost of treatment, even if we accept greater efficiency of the new antiepileptic drugs. However, the analysis of questionnaires provided by patients with epilepsy indicates that optimation of their treatment with introduction of new antiepileptic drugs may be a procedure leading to diminution of the global expenses associated with care of epileptic patients. Identification of factors influencing cost of antiepileptic treatment before and after introduction of new antiepileptic drugs. A group of 150 people chosen at random from a population of persons taking new antiepileptic drugs (vigabatrin, lamotrygin, topiramate, gabapentin, tiagabine) received anonymous questionnaires concerning the time course of their illness. 80 questionnaires were returned. The questions concerned the situation before and after treatment. Statistical analysis included t test for dependent samples-including items such as: number of epileptic seizures and number and days of hospitalization, etc. per year of observation. Significant decrease of the number of epileptic seizures (p < 0.05), number of hospitalizations (p < 0.001), days of hospitalizations (p < 0.001) and neurological consultations (p < 0.001) occurred after optimalization of treatment. Results of our research illustrate significant reduction of direct costs of treatment associated with introduction of new antiepileptic drugs.

Elevated levels of anti-heat shock protein antibodies in patients with cerebral ischemia.

One of the important mechanisms involved in the development of vascular lesions leading to ischemic stroke could be an immune response to heat shock proteins (hsp). For carotid atherosclerosis and myocardial infarction, an association with an increase in anti-hsp 65 antibodies has been demonstrated. The aim of our study was (1) to investigate whether ischemic stroke is associated with a humoral immune response to hsp; (2) to study the connection between anti-hsp antibodies and other stroke risk factors; (3) to estimate if the elevated levels of anti-hsp antibodies could be an independent risk factor for stroke. We examined 180 patients (in the first 48 h after stroke onset) and 64 age-matched healthy controls. The levels of IgG and IgM antibodies to hsp 65 and 70 were measured by ELISA. Ischemic stroke was connected with a significant elevation of anti-hsp 65 and anti-hsp 70 antibody levels (IgG and IgM) compared with controls (p < 0.0001). The multifactorial logistic regression analysis showed that increased levels of anti-hsp 65 and anti-hsp 70 IgG antibodies are independent risk factors for stroke. Our results suggest that humoral immunity to hsp is common in stroke patients and that elevated levels of anti-hsp antibodies could be triggering factors for stroke.

Does Parkinson's disease have an immunological basis? The evidence and its therapeutic implications.

Parkinson's disease (PD) is an age-related neurodegenerative movement disorder of unknown aetiology. Immune abnormalities have been described in PD including the occurrence of autoantibodies against neuronal structures and high numbers of microglia cells expressing the histocompatibility glycoprotein human leucocyte antigen-DR in the substantia nigra. An infectious cause for PD has been discussed for years. Disturbed cellular and humoral immune functions in peripheral blood of patients with PD have been also reported. An elevated gammadelta(+) T cell population and increased immunoglobulin G immunity in CSF to heat shock proteins have been found in PD. Cytokines and apoptosis-related proteins were elevated in the striatum in patients with PD. Activated glial cells may participate in neuronal cell death in PD by providing toxic substances. We may conclude that the immune system is involved in the pathogenesis of PD. However, we are not able to determine whether the disturbances described above constitute a primary or secondary phenomenon. Immunomodulatory agents may have important applications in the development of new therapies for PD.

[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.

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.

Increased expression of adhesion molecule CD18 (LFA-1beta) on the leukocytes of peripheral blood in patients with acute ischemic stroke.

OBJECTIVES: The aim of this study was to investigate whether adhesion molecules play a role in acute ischemic stroke. MATERIAL AND METHODS: Using immunofluorescence phenotyping and flow cytometry, the expression of leukocyte adhesion molecules CD54, CD11a, CD11b and CD18 in peripheral blood were measured within 12 h after onset of ischemia in 20 patients with stroke. Follow-up measurements were performed at 7 and 30 days after ictus. RESULTS: CD18 immunofluorescence was significantly increased on the leukocytes within 12 h after onset in patients with stroke compared with the age-matched control group (20 patients with other neurological diseases). Follow-up measurement of CD18 revealed normal results as found in the control group. CONCLUSION: Our data support the idea that adhesion molecules are involved in tissue injury in ischemic stroke.

[Inflammatory changes and immunological disturbances in stroke]. / Zmiany zapalne i zaburzenia immunologiczne w udarach mózgowych.

During recent years it has been demonstrated that activated leukocytes may play a role in disturbances of flow in microcirculation, such disturbances leading to the enlargement of the necrosis zone and area of ischaemic penumbra. Astrocytes, microglial and endothelium cells are also active in the evolution of ischaemic changes in brain. The above cells are producing cytokines, which upregulate the expression of adhesion molecules being responsible for accumulation of inflammatory cells in injured brain. Very significant is also the secretion of neurotoxic substances such as free radicals, nitric oxide or proteolytic enzymes by leukocytes and glial cells. Pre-stroke infection may increase activation of leukocytes and enhance inflammatory process in ischaemic focus. This paper discusses also the results of a treatment of the experimental brain stroke using therapy which reduces inflammatory and immunological response.

Humoral response to hsp 65 and hsp 70 in cerebrospinal fluid in Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative movement disorder of unknown etiology. In PD immune abnormalities were reported, but the cause of such abnormalities has not been resolved. Recently, the increased proportion of gamma delta + T cells out of all T cells has been found in patients with PD. Heat shock proteins (hsps) could be targets for gamma delta + T lymphocytes. We examined serum and CSF of patients with PD, age-matched patients with other non-inflammatory neurological diseases (OND old), young patients with other non-inflammatory neurological diseases (OND young), and donors of blood (DB). Antibodies were detected using the enzyme-linked immunosorbent assay. The plates were coated with recombinant mycobacterial hsp 65 and hsp 70. The present study showed that the mean ELISA ratio of CSF from patients with PD was significantly greater than that of CSF from patients with OND old (tested against IgG anti-hsp 65 and IgG anti-hsp 70) and OND young (tested against IgG anti-hsp 70). There was no difference between the mean ELISA ratio of sera from patients with PD, OND old and OND young (tested against IgG anti-hsp 65 and IgG anti-hsp 70). The significance of hsps immunity is not completely clear. Increased hsps expression, which is induced by stress, provides cells with protection against the environmental insults. Alternatively, the antibodies may be present as a consequence of prior infections.

V region T cell receptor repertoire in Parkinson's disease.

INTRODUCTION: Restricted usage of V alpha and beta genes has been found in several diseases, which exert autoreactive T cells. So far no information on T cell receptor (TCR) usage in degenerative diseases is available. Since T cells may be involved in pathogenesis of Parkinson's disease, the analysis of the TCR repertoire is of importance. MATERIAL AND METHODS: We have tested the frequency of 6 V beta-subtypes and the most common V alpha-subfamily on peripheral blood lymphocytes in 21 PD patients and 20 controls, separately on CD4+ and CD8+ T cells. For our study Diversi--T, the first available Mab set specific for TCR V regions, was used. RESULTS: As a results, no significant differences were found with one exception, i.e., lower frequency of V beta 8(a) expression on CD8+ T cells in PD patients than in controls. CONCLUSION: The failure of preferential usage or lack of usage of the tested V-chain alleles by CD4+ T cells argues against an involvement of helper T cells in PD induction.

Gamma delta + T cells in Wilson's disease.

Little is currently known about the role of gamma delta + T cells in disease pathogenesis. We have demonstrated elevated levels of gamma delta + T cells in the peripheral blood and cerebrospinal fluid of patients with Wilson's disease compared with other neurological diseases. The percentage of V delta 1 +/ gamma delta + T cells was between 20% and 50% in all patient groups; gamma delta + T cells in blood correlated with copper concentrations. The antigen reactivity of gamma delta + T cells and how the antigens relate to the gamma delta + T cells found in WD remains unknown. It remains unclear whether there is a direct reason for the elevated gamma delta + T cells population found in WD. Immunohistochemistry of frozen autopsy material from brain and liver of WD patients could allow exact localization of gamma delta + T cells and heat shock proteins in future studies.

[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.

[Role of gamma-delta T-cells and heat shock proteins in immunological response and in pathogenesis of neurological diseases]. / Znaczenie komórek T typu gamma delta i bialek szoku cieplnego w odpowiedzi immunologicznej oraz patogenezie chorób neurologicznych.

T cells with gamma delta receptor form small percentage of lymphocytes in healthy individuals, whereas their number increases in persons with immunological disorders. Heat shock proteins (HSPs), which play a central role in protein transformation, could be antigens for gamma delta T cells. HSPs participate in mutual interactions of gamma delta cells and tissue cells, taking part in defense mechanism against infection and auto destruction. There is an interest' in the HSPs' role in modulation of both normal and pathological activity within the nervous system. HSPs can protect cells against undesired stimulation, probably by long-term protein expression. Results of the studies suggest participation of gamma delta T cells and HSPs in pathogenesis of certain diseases, including neurological ones (multiple sclerosis, Alzheimer's disease, Parkinson's disease and cerebrovascular diseases), although detailed explanation of this problem requires further studies.

[The use of gammaglobulin for preventing infection in stroke]. / Gammaglobulina w zapobieganiu infekcjom u chorych z udarem mózgowym.

In the study the influence of giving gammaglobulin on the course of stroke was tested. The trial was double blind, with a control group and with a randomised administering of gammaglobulin and placebo. The condition for including a patient in the trial was clinical diagnosis of stroke, period of time from the onset not longer than five days, and the absence of both clinical and laboratory features of infection. 36 patients were given gammaglobulin (Veinoglobulin Institut Merieux) in 10 g doses at 3-day intervals, 35 patients were given placebo: 10g of albumin. The clinical follow-up lasted 30 days. Three patients from the gammaglobulin group and nine patients from the placebo group died. Administration of gammaglobulin decreased the tisc of death by 74%. The improvement of neurological deficit in 30-day survivals in the treated group was more expressed than in the placebo group. The total number of infections, number of days with increased temperature, number and time of given antibiotics were comparable in both groups. The results obtained suggest that prophylactic treatment with gammaglobulin does not prevent infections but their course is milder with consequent better clinical improvement and lower mortality.

Analysis of CD27 surface expression on T cell subsets in MS patients and control individuals.

Within the peripheral blood, CD4+CD27- T cells only reside within the CD45RA- (memory or primed) T cell subset. Cells with this phenotype have characteristics of specialized effector T cells according to their cytokine secretion profiles and the expression of tissue-specific adhesion molecules. This subset was previously found to be increased in certain diseases that are associated with immune activation. Therefore we analyzed CD27 expression of peripheral blood and CSF T cells in MS patients. Within the CD4+ T cell subset no differences were seen between MS patients and controls in proportions of CD45RA-CD27- cells. However, when the CD3+ T cell compartment was analyzed, CD27- cells were also found within the CD45RA+ subset. These cells, most likely CD8+, are significantly reduced in PBL and CSF of MS patients as compared with OND patients. In MS and OND groups the level of CD27- cells in peripheral blood correlated significantly with that in CSF, indicating a balanced migration of CD27- cells between the two compartments. In OIND patients, however, this equilibrium was lost. The correlation of the level of CD27+ cells with the amount of intrathecally produced IgG in MS patients may suggest that CD27+ cells are responsible for B cell help in this disease.

[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.

Parkinson's disease and immunological abnormalities: increase of HLA-DR expression on monocytes in cerebrospinal fluid and of CD45RO+ T cells in peripheral blood.

The etiology of Parkinson's disease is mainly unknown. Immune abnormalities have been described, but the cause of such abnormalities has not been resolved. We examined by two-colour flow cytometry HLA-DR antigen expression on monocytes from cerebrospinal fluid (CSF) and blood and, moreover, lymphocyte subpopulations (CD4+ CD45RO+, CD4+ CD45RA+, CD8+ CD11b+high) in peripheral blood from patients with Parkinson's disease compared with age-matched patients with other neurological diseases (OND) and tension headache. We found higher HLA-DR expression on CSF monocytes compared with blood monocytes. This difference was restricted to Parkinson's disease patients. T helper cell analysis revealed a decreased percentage of CD45RA+ "naive" and an increased percentage of CD45RO+ "memory" T cell subset from CD4+ T cells in peripheral blood of patients with Parkinson's disease compared with patients with tension headache. The proportions of CD8+ CD11b+high "suppressor" T cells remained unchanged, among the three patient groups compared. A selective loss of CD4+ CD45RA+ cells, previously observed in diseases like multiple sclerosis and Down's syndrome as compared with healthy controls suggests a common immunological abnormality in neurological disorders.