Long-term add-on therapy (compassionate use) with oral artesunate in patients with metastatic breast cancer after participating in a phase I study (ARTIC M33/2).

Background: The antimalarial artesunate (ART), a semisynthetic derivative of artemisinin from the Chinese herb artemisia annua has remarkable anticancer properties in vitro and in vivo. Its excellent safety profile known from short-term therapy in malaria was confirmed in an open phase I trial (ARTIC M33/2) for dose-finding as add-on therapy for four weeks.

Purpose: Patients with metastatic breast cancer, who had not experienced any clinically relevant adverse events (AE) during participation in ARTIC M33/2, were offered to continue ART as compassionate use (CU).

Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2).

Purpose: The antimalarial drug artesunate (ART) is a promising candidate for cancer treatment as it displays anticancer effects in various models. While in short-term treatment of malaria, an excellent safety profile has been found for ART, the potential long-term treatment of cancer patients demands a phase I dose-finding clinical trial determining the daily ART dose which would be well tolerated as add-on therapy.

Methods: Patients with metastatic breast cancer were to receive either 100 or 150 or 200 mg oral ART daily as add-on to their guideline-based oncological therapy for a study period of four weeks with frequent clinical and laboratory monitoring until 4-8 weeks thereafter.

Interferon versus methotrexate in intermediate uveitis with macular edema: results of a randomized controlled clinical trial.

Purpose: To compare interferon (IFN) beta with methotrexate (MTX) in the treatment of intermediate uveitis with macular edema.

Design: Monocentric, prospective, randomized, controlled clinical trial.

Setting: Specialized uveitis center at the University of Heidelberg.

Inflammatory autoimmune neuropathy, presumably induced by bortezomib, in a patient suffering from multiple myeloma.

Bortezomib is a proteasome inhibitor demonstrating substantial activity in multiple myeloma. One of its key toxicities is peripheral neuropathy, which is reversible in most patients. The possibility that bortezomib might in rare cases induce severe neuropathies by auto-inflammatory mechanisms remains controversial.

An unusual case of optic neuritis.

Optic neuritis is a frequent disease with well established tests and therapeutic strategies. However, possible differential diagnoses cover a broad spectrum. Therefore, clinical work-up can be challenging and routine testing and therapies may not be sufficient.

Rippling muscle disease: variable phenotype in a family with five afflicted members.

We report a family with rippling muscle disease (RMD) who had an autosomal dominant mode of inheritance. The father, mother, and one daughter proved to be heterozygous, and two sons were homozygous for the A92T mutation of the caveolin-3 gene. The cardinal features of RMD, particularly percussion-induced rapid contractions, muscle mounding, and muscle rippling, varied considerably among these subjects.

[Intravenous immunoglobulins in multiple sclerosis. An update].

In MS patients with contraindications, intolerance, or failure of established immunomodulatory drugs, intravenous immunoglobulins (IVIG) are increasingly being administered. Several clinical studies recently showed that IVIG are generally safe, well tolerated and only occasionally have serious side effects. While some studies indicated beneficial effects from IVIG in relapsing-remitting MS, the recently published PRIVIG study failed to show any clinical benefit.

Fulminant onset of cerebral immunocomplex vasculitis as first manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE).

Fulminant onset of neuropsychiatric symptoms as first manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE) is rare and diagnosis is difficult if only one organ is involved. Here, we report the case of a previously healthy woman who presented with a clinical syndrome most compatible with acute onset of NPSLE. However, American College of Rheumatology (ACR) criteria were not sufficiently met.

Prospective combined brain and spinal cord MRI in clinically isolated syndromes and possible early multiple sclerosis: impact on dissemination in space and time.

Background: The diagnosis of multiple sclerosis (MS) is based on dissemination in space (DIS) and time (DIT). The aim of the study was to assess the impact of spinal cord (SC) imaging on the evidence of DIS and DIT.

Methods: Thirty-five treatment-naive patients with a first clinical symptom suggestive of MS were examined in a 2-year prospective longitudinal follow-up assessment.

Aquaporin-4 antibody positive longitudinally extensive transverse myelitis following varicella zoster infection.

Longitudinally extensive transverse myelitis (LETM) is a condition shown to confer high risk of conversion into neuromyelitis optica (NMO). Increasing evidence from immunological and histopathological studies suggests that LETM is an autoimmune disorder caused by pathogenic antibodies to aquaporin-4 (AQP4-Ab), the most abundant water channel in the CNS, at least in a subset of patients. However, cases of infectious or parainfectious NMO/LETM (mostly associated with herpes zoster) have been repeatedly reported in the previous literature, raising the question of aetiological diversity in NMO/LETM.

Specific recruitment of regulatory T cells into the CSF in lymphomatous and carcinomatous meningitis.

Whereas regulatory T (Treg) cells play an important role in the prevention of autoimmunity, increasing evidence suggests that their down-regulatory properties negatively affect immune responses directed against tumors. Treg cells selectively express chemokine receptors CCR4 and CCR8, and specific migration occurs following the release of various chemokines. Neoplastic meningitis (NM) resulting from leptomeningeal spread of systemic non-Hodgkin lymphoma (NHL) or carcinoma has a poor prognosis.

Linezolid-induced posterior reversible leukoencephalopathy syndrome.

Objective: To describe a 71-year-old woman who developed clinical and neuroradiological features of posterior reversible leukoencephalopathy syndrome with a compromised blood-brain barrier after 5 days of intravenous linezolid therapy for an infected hip prosthesis.

Design: Case report.

Setting: Academic research.

Subarachnoid hemorrhage due to Borrelia burgdorferi-associated vasculitis.

We report the case history of a patient who suffered a subarachnoid hemorrhage (SAH) in association with early Lyme neuroborreliosis. After a tick bite, this patient developed erythema chronicum migrans and complained of stinging radicular pain in both legs. A computed tomography (CT) scan was performed because of acute headache and nuchal rigidity, which revealed an occipital SAH.

Neuromyelitis optica (Devic's syndrome) as first manifestation of systemic lupus erythematosus.

Neurologic symptoms rarely occur as presenting feature of systemic lupus erythematosus (SLE). We describe a 37-year old woman who presented with several episodes of transverse myelitis and optic neuritis. Clinical, radiologic and laboratory findings were compatible with neuromyelitis optica (NMO).

Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis.

Immunoregulatory T cells of (CD4+)CD25+ phenotype suppress T cell function and protect rodents from organ-specific autoimmune disease. The human counterpart of this subset of T cells expresses high levels of CD25 and its role in human autoimmune disorders is currently under intense investigation. In multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), the activation of circulating self-reactive T cells with specificity for myelin components is considered to be an important disease initiating event.

[Infectious diseases of brain parenchyma in adults: imaging and differential diagnosis aspects].

Infectious diseases of the central nervous system have often to be considered in differential diagnosis, particularly in immunocompromised persons. Neuroimaging, specifically advanced techniques such as diffusion-weighted MRI and perfusion MRI contribute much to the differentiation of various brain infections and to delineation of brain infections from other, for instance, neoplastic diseases. In this review we present the imaging criteria for the most important brain infections in adults and discuss in detail differential diagnostic aspects.

Interferon as a treatment for uveitis associated with multiple sclerosis.

Aim: In addition to optic neuritis (ON), multiple sclerosis (MS) may also involve the eye with a typically bilateral intermediate uveitis. The aim of this pilot study was to evaluate the efficacy of type I interferons (IFN) for the treatment of MS associated uveitis.

Methods: In this non-randomised, retrospective observational case series 13 patients (eight female, five male) with proved MS and associated uveitis from five uveitis centres who were treated with interferon beta1a were included.

Free radical-mediated damage to barrier function is not associated with altered brain morphology in high-altitude headache.

The present study combined molecular and neuroimaging techniques to examine if free radical-mediated damage to barrier function in hypoxia would result in extracellular edema, raise intracranial pressure (ICP) and account for the neurological symptoms typical of high-altitude headache (HAH) also known as acute mountain sickness (AMS). Twenty-two subjects were randomly exposed for 18 h to 12% (hypoxia) and 21% oxygen (O2 (normoxia)) for collection of venous blood (0 h, 8 h, 15 h, 18 h) and CSF (18 h) after lumbar puncture (LP). Electron paramagnetic resonance (EPR) spectroscopy identified a clear increase in the blood and CSF concentration of O2 and carbon-centered free radicals (P<0.

[Postpolio syndrome. Neurologic and psychiatric aspects].

Postpolio syndrome is defined as a clinical syndrome of new pareses in individuals who had been affected by acute paralytic poliomyelitis years before. The objective of this study was to describe neurologic and psychiatric signs of the disease. We evaluated the clinical signs and treatment of 16 patients with postpolio syndrome.

[Leptomeningeal tumor cell infiltrations as a first manifestation of an immunocytoma (Waldenstrom's macroglobulinemia)].

Immunocytoma (Waldenstrom's macroglobulinemia) is a rare chronic lymphoproliferative disorder of B-cell origin. It is characterized by the presence of large amounts of circulating monoclonal immunoglobulin M (IgM) and lymphoplasmocytoid bone marrow infiltration. Affection of the peripheral nervous system is common and causes polyneuropathy (5-10%).

Single-cell PCR analysis of the immunoglobulin heavy-chain CDR3 region for the diagnosis of leptomeningeal involvement of B-cell malignancies using standard cerebrospinal fluid cytospins.

The diagnosis of leptomeningeal B-cell malignancies is based on the identification of malignant B cells in the cerebrospinal fluid (CSF). We have established a polymerase chain reaction (PCR) approach to characterize the clonally diverse gene encoding the immunoglobulin heavy-chain (IgH) third complementarity determining region (CDR3) of single B cells. We demonstrate that single-cell PCR is readily applicable to individual cells derived from routine CSF cytospins and is a powerful method to discriminate monoclonal neoplastic from polyclonal reactive B-cell responses.

Thymic export function and T cell homeostasis in patients with relapsing remitting multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory and possibly autoimmune mediated demyelinating disease of the CNS. Autoimmunity within the CNS may be triggered by dysfunction of peripheral immune tolerance mechanisms via changes in the homeostatic composition of peripheral T cells. We have assessed the release of naive T lymphocytes from the thymus in patients with relapsing remitting MS (RRMS) to identify alterations in the equilibrium of the peripheral T cell compartment.