[Neuroleptic malignant syndrome : Rare cause of fever of unknown origin]. / Malignes neuroleptisches Syndrom : Seltene Ursache für Fieber unklarer Genese.

Neuroleptic malignant syndrome (NMS) is a possible cause of fever of unknown origin (FUO) and is a potentially fatal adverse effect of various drugs, especially of neuroleptics. First generation antipsychotics, such as received by the patient described in this article, are more likely to cause NMS than second generation antipsychotics. The key symptoms are the development of severe muscle rigidity and elevated temperature associated with the use of neuroleptic medication. Malignant catatonia (MC) is an important differential diagnosis of NMS. While neuroleptics can trigger NMS and must be immediately discontinued if NMS occurs, neuroleptic therapy represents the first line treatment for MC. This article describes the case of a patient with schizoaffective disorder where initially the diagnosis of NMS was not clear. Eventually, fever and a markedly elevated serum creatine kinase (CK) led to the correct diagnosis and the appropriate therapy with dantrolene, bromocriptine and amantadine. Furthermore, a thorough review of the currently available literature on NMS is provided.

[Parenteral Antipsychotics in the Treatment of Agitation and Aggression]. / Parenteral applizierte Antipsychotika bei Agitation und Aggression.

This overview presents the current scientific data on intramuscular administration of benperidole, aripiprazole, ziprasidone, and haloperidole and on inhaled loxapine with regard to their efficacy and tolerability as well as their pharmacodynamic and pharmacokinetic properties. In addition, the possible advantages and disadvantages of the different substances are compared when administered to patients who show tension, agitation and aggression.

Rituximab in a patient with multiple sclerosis--effect on B cells, plasma cells and intrathecal IgG synthesis.

OBJECTIVE: To study the time course of immunoglobulin, B and plasma cells in the blood and cerebrospinal fluid (CSF) before and during rituximab treatment in a patient with severe relapsing-remitting multiple sclerosis (MS) in relation to clinical and MRI findings. METHODS: Immunoglobulins in the CSF were measured by nephelometry and detected by isoelectrical focussing. CSF and blood cell subtypes from seven time points were analysed by flow cytometry. RESULTS: Treatment with rituximab induced a dramatic and sustained improvement in clinical and MRI findings over a follow-up period of 20 months. By contrast, the initially completely suppressed B and plasma cells in both the blood and CSF reappeared after 5 and 10 months, CSF cells being the first to reappear. Interestingly, intrathecal IgG synthesis persisted throughout the study period. DISCUSSION: Although highly effective in this case, the clinical effect in larger series and the mechanism of rituximab in MS deserves further evaluation.

Relevance and dynamics of myelofibrosis regarding hematopoietic reconstitution after allogeneic bone marrow transplantation in chronic myelogenous leukemia--a single center experience on 160 patients.

A retrospective single center study was performed on 516 trephine biopsies derived from 160 patients with stable phase Ph+-CML and allogeneic BMT. Following morphometric quantification of reticulin-collagen fibers we tried to elucidate (1) the dynamics of bone marrow fibrosis in the post-transplant period; and (2) the influence of manifest myelofibrosis on relevant engraftment parameters. An evaluation of fiber density at standardized endpoints after BMT was carried out on a selected cohort of 124 patients (399 biopsy specimens). A manifest myelofibrosis (more than a three-fold increase compared to the normal fiber content) before BMT was found in 26% of our patients. Concentrating on bone marrow areas with reconstituting hematopoiesis, several findings emerged. Pretransplant myelofibrosis was associated with an initial regression following BMT, but insidiously recurred in the areas of regenerating hematopoiesis or developed in a few patients without increased pregraft fibers during the post-transplant period (mean observation time more than 4 months). Severe acute GVHD (grades III and IV) was significantly correlated with a greater amount of reticulin fibers in the early post-transplant period (9 to 30 days after BMT). Regarding engraftment parameters, a significant delay was detectable in the time to achieve transfusion independence for the patients with manifest myelofibrosis compared to those without pre-transplant fiber increase.

Gender change and its impact on the course of multiple sclerosis.

We report the case of a 22-years old genotypic women suffering from a relapsing-remitting multiple sclerosis (MS) according to the Poser criteria. In this patient, a gender change had been performed by androgen-supplementation and surgical intervention. During gender change, the patient experienced further relapses. Different immunomodulatory and immunosuppressive treatment strategies did not stabilise the course of MS in this patient. Actually, an escalating therapy with mitoxantrone has been initiated. During the observation period the patient received long-term testosterone-supplementation. Testosterone levels were elevated in the serum of this genotypic female MS patient under such a hormonal treatment compared to normal ranges before. The clinical course of the patient is presented in this case. As there are several studies investigating an immunomodulatory impact of hormones on the course of MS or experimental allergic encephalomyelitis, we discuss the presented case and a possible influence of androgens in this patient.

[Measuring fatigue in patients with multiple sclerosis with standardized methods in German speaking areas]. / Messbarkeit von Fatigue bei multipler Sklerose mithilfe standardisierter Methoden im deutschsprachigen Raum.

Fatigue describes the presence of a pronounced and advanced state of weariness. People with fatigue need more energy and it takes more effort to perform different activities than expected when compared to the patients disability. Fatigue can be observed in up to 92 % of patients suffering from multiple sclerosis. In the presented study, the German fatigue severity scale (dFSS) was established following the English "Fatigue Severity Scale". We enrolled 20 patients suffering from a primary relapsing multiple sclerosis and compared them to 20 healthy controls. Fatigue was detected if at least 4 points were reached in the dFSS. The dFSS demonstrated high validity and reliability. The dFSS is able to differentiate patients with fatigue from healthy controls. As consequence, the dFSS can be used to evaluate fatigue in German speaking individuals. The presented data demonstrated a good internal consistence. The scale is able to measure fatigue in an economic and rapid fashion. Therefore, it can be used in clinical situations for measuring fatigue in German speaking individuals.

Stroke after initiation of interferon-beta treatment for relapsing-remitting disseminated white matter disease.

BACKGROUND: Interferon-beta (INF-beta) is effective and used in reducing exacerbation frequency and disease progression in multiple sclerosis. In certain circumstances, INF-beta can lead to rare side effects. AIMS OF THE STUDY: We report the case of a 34-year-old female patient satisfying the McDonald criteria of multiple sclerosis without showing typical pathologic changes in cerebrospinal fluid (CSF). After introduction of INF-beta treatment, she quickly developed further progression of her disseminated neurological symptoms and finally an ischemic cerebral infarction. METHODS: Evaluation of the patient included arterial angiography, magnetic resonance and positron emission tomography, histopathological assessment as well as a broad spectrum of serum and CSF analysis. RESULTS: All diagnostic evaluations and the clinical course revealed evidences for a primary angiitis of the CNS. We discuss the possible worsening due to inappropriate INF-beta treatment in cerebral angiitis promoting severe cerebrovascular insufficiency. CONCLUSION: The authors suggest that all diagnostic multiple sclerosis criteria including typical CSF findings should be ascertained before INF-beta treatment is initiated.

No effect of intravenous immunoglobulins on cytokine-producing lymphocytes in secondary progressive multiple sclerosis.

Intravenous immunoglobulins (IVIG) have been effective in reducing multiple sclerosis (MS) disease activity and improving disability scores. However, the mechanism by which this beneficial effect is achieved remains unclear. An effect of IVIG on pro- and anti-inflammatory cytokines which are thought to play a role in the disease process - has been postulated in a number of animal and ex vivo studies. Hence, we performed a study on 34 patients with secondary progressive (SP) MS being treated with monthly IVIG or placebo for two years according to the protocol of the ESIMS study. Clinical outcome measures and cytokine production (interferon gamma, tumour necrosis factor alpha, interleukin-4 and -10) were recorded in all patients and compared with respect to the treatment group. Against our expectations, IVIG did not reduce the relapse rate or the progression of disability or cytokine production. Our data argue against an enduring immunomodulating effect of IVIG, at least in SPMS.

Difficulties in the differentiation of chronic inflammatory diseases of the central nervous system--value of cerebrospinal fluid analysis and immunological abnormalities in the diagnosis.

OBJECTIVES: A number of neurological syndromes may be evoked by involvement of the nervous system due to systemic diseases such as lupus erythematodes, sarcoidosis, Behçet's disease and Sjögren's syndrome (SS) and may be confounded with another chronic inflammatory disease which is restricted to the central nervous system, e.g. multiple sclerosis (MS). Because of different treatment strategies, it is important to distinguish between these different autoimmune diseases. RESULTS: Neither clinical signs nor additional analyses such as serological findings or cerebrospinal fluid (CSF) analysis are able to differentiate between the diseases with certainty. Nevertheless, taking all findings together, diagnosis may be possible. CONCLUSION: Here we compare typical clinical and CSF findings in MS, neurosarcoidosis, neurolupus, neuro-Behçet and nervous system involving SS with special emphasis on those findings allowing differentiation of the respective diseases by reviewing the literature.

[Differential diagnosis of chronic inflammatory diseases of the central nervous system. Cerebrospinal fluid diagnosis and immunological parameters]. / Differenzialdiagnose chronisch-entzündlicher Erkrankungen des Zentralnervensystems. Liquordiagnostik und immunologische Parameter.

A number of neurological syndromes may be evoked by involvement of the nervous system due to systemic diseases such as lupus erythematosus, sarcoidosis, Behcet's disease, and Sjogren's syndrome. Because of different treatment strategies, it is important to distinguish between these different diseases. Neither clinical signs nor additional analyses such as serological findings or cerebrospinal fluid analysis are able to differentiate between the diseases with certainty. Nevertheless, diagnosis may finally be made taking all findings together. Here we compare typical clinical and cerebrospinal fluid findings in neurosarcoidosis, neurolupus, neuro-Behcet, and nervous system involving Sjogren's syndrome, with special emphasis on those findings allowing differentiation of the respective diseases.

The immunomodulatory properties of in vitro immunoglobulins are dose-dependent.

OBJECTIVES: The mechanism by which intravenous immunoglobulins (immunoglobulin G, IgG) exert their beneficial effect on multiple sclerosis (MS) is unknown. Furthermore, there is uncertainty about the optimal dosage of IgG. Therefore, we investigated the influence of different IgG dosages on cytokine production in MS. MATERIALS AND METHODS: Twenty-five MS patients and 15 healthy controls were enrolled. We measured the production of interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF) and interleukin 10 (IL-10) in peripheral blood lymphocytes by flowcytometry after stimulation without and with IgG in different doses (1, 5 and 10 mg/ml). RESULTS: IFN-gamma and TNF were decreased significantly (P = 0.001) in the untreated and interferon beta (IFN-beta) treated patients after stimulation with IgG. In contrast, IL-10 production was significantly enhanced (P = 0.001) at least in the untreated patient group. The reduction of the pro-inflammatory cytokines IFN-gamma and TNF after stimulation with different IgG doses was clearly dose-dependent in all groups. CONCLUSION: Besides a suppression of the pro-inflammatory cytokines IFN-gamma and TNF, IgG enhances the anti-inflammatory cytokine IL-10. This effect is dose-dependent, speaking in favour of higher IgG doses in the treatment of MS.

Long-term persisting interferon beta-1b neutralizing antibodies after discontinuation of treatment.

OBJECTIVES: Neutralizing antibodies (NAB) against interferon beta (IFNB) with presumably negative impact on treatment outcome have been described in up to 42% of patients undergoing IFNB treatment. However, in most cases NAB decrease despite continuation of IFNB therapy. Observations on NAB after discontinuation of IFNB therapy are lacking. Here, we report for the first time on NAB which now persist for several years following discontinuation of IFNB treatment. MATERIALS AND METHODS: We present two multiple sclerosis patients followed over 8 and 10 years. NAB have been measured repeatedly and are presented together with clinical data. NAB developed after 2 years of treatment and persisted despite discontinuation of treatment at high titers for more than 4 years. CONCLUSION: Our data indicate that IFNB therapy may induce long-term NAB production which persists even after discontinuating IFNB treatment. Possible immunological mechanisms are discussed.