Robert Patejdl

Insular stroke is associated with acute sympathetic hyperactivation and immunodepression

Post‐stroke immunodepression has been related to brain lesion size but not a specific lesion location. Here, we studied the influence of lesion location within middle cerebral artery (MCA) territory on parameters related to activation of sympathetic adrenomedullar pathway, immunodepression, and associated infection.

Multiple sclerosis and fatigue: A review on the contribution of inflammation and immune-mediated neurodegeneration.

Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) and the leading cause of non-traumatic disability among young and middle-aged adults in the western world. One of its most prevalent and debilitating symptoms is fatigue. Despite the general acceptance of the idea of an immune pathogenesis of MS itself, the role of autoimmunity in the course of MS-fatigue is a matter of debate. Both immune-related processes (acute inflammation, chronic inflammation, immune-mediated neurodegeneration, immune-mediated alterations of endocrine functions related to fatigue) and presumably non-immune-mediated disturbances and factors (sleep disturbances, depression, cognitive alterations, chronic infections, adverse effects of medications) contribute to the clinical picture. Data from in vitro and animal experiments has provided evidence for a role of cytokines as IL-1 and TNF-alpha. This association could not be verified directly in blood samples from humans whereas whole blood stimulation protocols gave some indirect evidence for a role of cytokines in MS-fatigue. MRI being able to detect acute and chronic immune mediated damage to the CNS could depict that global atrophy of gray or white matter does not correlate with fatigue. Rather, distinctive clusters of lesions and atrophy at different locations, mostly bifrontal or in subcortical structures, correlate specifically with fatigue. Regardless of the difficulties in pinpointing the immunogenesis of MS-fatigue, an important role of autoimmunity is strongly supported by an indirect route: A growing amount of data shows that the highly effective immunotherapeutics which have been introduced to MS-treatment over the last years effectively and sustainably stabilize and ameliorate fatigue in parallel to their dampening effects on the neuroinflammatory process. This review summarizes the existing data on the relation between inflammation, patterns of CNS-lesions and the effects of immunotherapeutics on MS-fatigue.

Cerebral MRI lesions and anti-tumor necrosis factor-alpha therapy

We discuss two cases receiving different anti-tumornecrosis-factor alpha antagonists (anti-TNF-α); one for psoriatic arthritis (PA) and the other for ankylosing spondylitis (AS). Due to neurological symptoms cerebral magnetic resonance imaging (MRI) was performed and cerebral lesions were detected. Our interpretations of these cerebral lesions and the resulting diagnostic and therapeutic consequences are presented in regard of data published in the medical literature.

Evidence for the efficacy and effectiveness of THC-CBD oromucosal spray in symptom management of patients with spasticity due to multiple sclerosis

Spasticity, one of the main symptoms of multiple sclerosis (MS), can affect more than 80% of MS patients during the course of their disease and is often not treated adequately. δ-9-Tetrahydrocannabinol-cannabidiol (THC-CBD) oromucosal spray is a plant-derived, standardized cannabinoid-based oromucosal spray medicine for add-on treatment of moderate to severe, resistant multiple sclerosis-induced spasticity. This article reviews the current evidence for the efficacy and safety, with dizziness and fatigue as the most common treatment-related adverse events, being mostly mild to moderate in severity. Results from both randomized controlled phase III studies involving about,1600 MS patients or 1500 patient-years and recently published studies on everyday clinical practice involving more than 1000 patients or more than,1000 patient-years are presented.

Rituximab for secondary progressive multiple sclerosis: a case series.

AbstractBackground: While numerous substances have been developed for the treatment of relapsing-remitting multiple sclerosis over recent years, options are still limited for patients with secondary progressive multiple sclerosis (SPMS). Objectives and Methods: In this observational study we present clinical and CSF findings in three patients with SPMS who were treated with rituximab for at least 15 months. Results: During the observation period, no severe adverse effects occurred and the Expanded Disability Status Scale (EDSS) score stabilized in all patients after a dramatic increase over the previous years. In contrast to other publications, we showed that the time to reoccurrence of B cells was very variable and that serial CSF examinations in the course of treatment revealed a decline in intrathecal IgG synthesis. Conclusion: Rituximab seems to be effective in active SPMS. Restitution of the pathogenic immune response after administration of rituximab is variable. Further studies are needed to determine the optimal dosage and timing for rituximab therapy in multiple sclerosis.

Monoclonal Antibodies in the Treatment of Neuroimmunological Diseases

Over the past 25 years, monoclonal antibodies (mAb) have become important elements in the therapeutic concepts for numerous clinical specialities, including oncology, gastroenterology, hemostaseology and endocrinology. One of the most dynamic fields of their use is the treatment of autoimmune diseases. Although the number of existing mAb interfering with the immune system has increased remarkably and many studies have yielded encouraging results in the treatment of neuroimmunological diseases, their clinical use is still limited compared with standard treatments. The only mAb which has been approved for a neuroimmunological disease by now is natalizumab for the treatment of relapsing-remitting multiple sclerosis (RRMS). This article gives an overview on mAb that are currently in use or under investigation for treating neuroimmunological diseases like multiple sclerosis (MS), neuromyelitis optica (NMO), chronic inflammatory demyelinating polyneuropathy (CIDP), inclusion body myositis (IBM), dermatomyositis, polymyositis, opsoclonusmyoclonus syndrome (OMS), multifocal motor neuropathy (MMN), anti-myelin-glycoprotein neuropathy (Anti-MAG), stiff person syndrome and myasthenia gravis (MG).

Spasticity in multiple sclerosis: Contribution of inflammation, autoimmune mediated neuronal damage and therapeutic interventions

In contrast to other diseases that go along with spasticity (e.g. spinal cord injury), spasticity in chronic autoimmune diseases involving the CNS is complicated by the ongoing damage of neuronal networks that leads to permanent changes in the clinical picture of spasticity. Multiple sclerosis (MS) is the most frequent autoimmune disease of the central nervous system (CNS) and spasticity is one of the most disabling symptoms. It occurs in more than 80% MS patients at some point of the disease and is associated with impaired ambulation, pain and the development of contractures. Besides causing cumulative structural damage, neuroinflammation occurring in MS leads to dynamic changes in motor circuit function and muscle tone that are caused by cytokines, prostaglandins, reactive oxygen species and stress hormones that affect neuronal circuits and thereby spasticity. The situation is complicated further by the fact that therapeutics used for the immunotherapy of MS may worsen spasticity and drugs used for the symptomatic treatment of spasticity have been shown to have the potential to alter immune cell function and CNS autoimmunity itself. This review summarizes the current knowledge on the immunologic pathways that are involved in the development, maintenance, dynamic changes and pharmacological modulation of spasticity in MS.

Posterior reversible encephalopathy syndrome (PRES): An unusual primary manifestation of a diffuse large B-cell lymphoma

Posterior reversible encephalopathy syndrome (PRES), is a clincal entity characterized by headache, nausea, vomiting, seizures, onscious disturbance, and visual disorder associated with neuroadiological findings, predominantly white matter abnormalities f the parieto-occipital lobes [1]. It has been recognized in a ide range of conditions, including hypertensive encephalopathy, rgan transplantation, uremia, preeclampsia/eclampsia, connecive tissue diseases, systemic lupus erythematosus, thrombotic hrombocytopenic purpura, cerebral angiograms, hypertensionnducing treatments such as erythropoietin, blood transfusions, or mmunosuppressive therapy particularly with cyclosporine A and acrolimus, and immunoglobulin, as well as various chemotheraeutic agents such as cisplatin [2]. Usually, if treated early there is a good short-term and long-term rognosis, with complete restitution of clinical and neuroimaging bnormalities in the majority of cases. Occurrence of PRES in assoiation with hematologic disorders has been attributed to effects

Muscle rupture caused by exacerbated spasticity in a patient with multiple sclerosis

We report a case of muscle rupture caused by acute exacerbation of spasticity in a patient with primary chronic progressive multiple sclerosis (PPMS). A complete disruption of the adductor muscles was diagnosed by sonography and still reproducible in a follow-up three months after the clinical event. To our knowledge, this is the first case report of muscle rupture caused by spasticity in a patient with MS. In addition to the clinical case report we give a short overview of morphological and functional changes in spastic muscle and current standards of symptomatic therapy.

Severe acute motor neuropathy after treatment with triple tyrosine kinase inhibitor BIBF 1120 (Nintedanib).

Bilateral ovarian serous cystadenocarcinoma was diagnosed in 59 year-old woman. Staging investigations yielded a progressed tate with peritoneal carcinosis (pT3c, pN1 [2/26] cM0 V0 L1 Pn0 2 G2). After surgical treatment she received the triple – tyrosin kinase inhibitor BIBF 1120 twice daily as an add-on to standard reatment with paclitaxel (175 mg/m2) and carboplatin (adjusted o an AUC of 5), every three weeks [2]. Twelve weeks after initiaion of treatment, she noticed tingling paraesthesias in her feet and ands and limb weakness which progressed to almost complete