Case report: Cerebrospinal fluid neutrophilic pleocytosis upon intrathecal triamcinolone injection.

Intrathecal corticosteroids, initially employed in the 1950s, faced declining use due to complications like arachnoiditis and aseptic meningitis. Triamcinolone, which is nowadays used as intrathecally applied glucocorticoid formulation, has been shown to beneficially influence spasticity without demonstrable influence on disease activity or progression. We here present the case of a patient with recurrent episodes of aseptic cerebrospinal fluid (CSF) neutrophilic pleocytosis over a year following intrathecal triamcinolone treatment.

In mammalian skeletal muscle, phosphorylation of TOMM22 by protein kinase CSNK2/CK2 controls mitophagy.

In yeast, Tom22, the central component of the TOMM (translocase of outer mitochondrial membrane) receptor complex, is responsible for the recognition and translocation of synthesized mitochondrial precursor proteins, and its protein kinase CK2-dependent phosphorylation is mandatory for TOMM complex biogenesis and proper mitochondrial protein import. In mammals, the biological function of protein kinase CSNK2/CK2 remains vastly elusive and it is unknown whether CSNK2-dependent phosphorylation of TOMM protein subunits has a similar role as that in yeast. To address this issue, we used a skeletal muscle-specific Csnk2b/Ck2β-conditional knockout (cKO) mouse model.

A Costa Rican family affected with Charcot-Marie-Tooth disease due to the myelin protein zero (MPZ) p.Thr124Met mutation shares the Belgian haplotype.

The p.Thr124Met mutation in the myelin protein zero (MPZ) causes the Charcot-Marie-Tooth disease type 2J, a peripheral neuropathy with additional symptoms as pupillary alterations and deafness. It was observed in several families around the world originating e.

Peripheral Nerve Society Guideline on the classification, diagnosis, investigation, and immunosuppressive therapy of non-systemic vasculitic neuropathy: executive summary.

Non-systemic vasculitic neuropathy (NSVN) is routinely considered in the differential diagnosis of progressive axonal neuropathies, especially those with asymmetric or multifocal features. Diagnostic criteria for vasculitic neuropathy, classification criteria for NSVN, and therapeutic approaches to NSVN are not standardized. The aim of this guideline was to derive recommendations on the classification, diagnosis, investigation, and treatment of NSVN based on the available evidence and, where evidence was not available, expert consensus.

Health-related quality of life in ALS, myasthenia gravis and facioscapulohumeral muscular dystrophy.

Neuromuscular disorders are rare diseases with a chronic and debilitating course. Unfortunately, data on the health-related quality of life (HRQoL) in neuromuscular diseases are limited. The objective of this multicentre cross-sectional study was to compare the HRQoL in patients with amyotrophic lateral sclerosis (ALS), facioscapulohumeral muscular dystrophy (FSHD) and myasthenia gravis (MG) and to identify the determinants of the HRQoL in these diseases.

Microvasculopathic neuromuscular diseases: lessons from hypoxia-inducible factors.

Dermatomyositis and vasculitic neuropathies are disorders with immune mediated ischemic injuries. Cellular responses to hypoxia include the hypoxia-inducible factor-1 (HIF-1)-induced transcription of genes involved in angiogenesis. To study their possible roles in those disorders, the immunohistochemical expression of HIF-1alpha, HIF-1beta, HIF-2alpha, vascular endothelial growth factor (VEGF), VEGF-receptor (VEGF-R) and erythropoietin-receptor was investigated.

C-fiber axon reflex flare size correlates with epidermal nerve fiber density in human skin biopsies.

The size of the neurogenic axon reflex flare (ARFS) has been proposed to serve as a non-invasive measure of C-fiber neuropathies. This idea is based on the observation that ARFS is often reduced in patients with small-fiber neuropathies. In this study, we compared ARFS and electrically evoked axon reflex sweating with intraepidermal nerve fiber density (IENF) in patients with peripheral neuropathy in order to validate these methods against an objective standard method of diagnosing small-fiber neuropathy.

Socioeconomic burden of amyotrophic lateral sclerosis, myasthenia gravis and facioscapulohumeral muscular dystrophy.

Neuromuscular disorders (NMD) are chronic devastating diseases. The aim of this multicenter cross-sectional study was to evaluate the socioeconomic impact of three NMDs in Germany. Patients (n = 107) with amyotrophic lateral sclerosis (ALS), myasthenia gravis (MG) or facioscapulohumeral muscular dystrophy (FSHD) were recruited consecutively in seven centers in Germany.

Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models.

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous disorder. All mendelian patterns of inheritance have been described. We identified a homozygous p.

Late onset autosomal dominant Charcot-Marie-Tooth 2 neuropathy in a Costa Rican family.

Objective: To describe the clinical, electrophysiologic and morphologic features of a Costa Rican family with an autosomal dominant inherited Charcot-Marie-Tooth (CMT) neuropathy.

Methods: The field study took place in Costa Rica, Central America. Seven patients underwent neurological examinations and standard electrodiagnostic tests, and a sural nerve biopsy was taken from one patient.

Examination of transcript amounts and activity of protein kinase CK2 in muscle lysates of different types of human muscle pathologies.

Motoneurons release the heparansulfate proteoglycan agrin and thereby activate the muscle-specific receptor tyrosine kinase (MuSK), which is the main organizer of subsynaptic specializations at the neuromuscular junction. Recently, we showed that (1) the protein kinase CK2 interacts with the intracellular region of MuSK; (2) the CK2 protein is enriched and co-localized with MuSK at postsynaptic specializations; (3) CK2-mediated phosphorylation of serine residues within a specific MuSK epitope, named the kinase insert, regulates acetylcholine receptor (AChR) clustering; (4) muscle-specific CK2beta knockout mice develop a myasthenic phenotype due to impaired muscle endplate structure and function (see Genes Dev 20(13):1800-1816, 2006). Here, we investigated for the first time if CK2 is modulated in biopsies from human patients.

Activation of the RAGE pathway: a general mechanism in the pathogenesis of polyneuropathies?

Objectives: Binding of ligands to the receptor for advanced glycation end products (RAGE) results in activation of the transcription factor NF-kappaB and subsequent expression of NF-kappaB regulated cytokines and is a possible pathomechanism in diabetic and in vasculitic polyneuropathies (PNP). We wanted to investigate whether the newly discovered RAGE pathway also contributes to the pathogenesis of various other PNP.

Methods: The presence of the RAGE ligand Nepsilon-Carboxymethyllysine (CML), the receptor itself and NF-kappaBp65 was studied in sural nerve biopsies of patients with alcohol-associated PNP (n=5), PNP owing to vitamin B12 deficiency (n=5), chronic inflammatory demyelinating PNP (CIDP, n=10), Charcot-Marie-Tooth disease (CMT) I or II (n= 10), PNP caused by monoclonal gammopathy of unknown significance (MGUS) (n=5), idiopathic PNP (n=10) and five normal controls by immunohistochemistry.

Loss of pain perception in diabetes is dependent on a receptor of the immunoglobulin superfamily.

Molecular events that result in loss of pain perception are poorly understood in diabetic neuropathy. Our results show that the receptor for advanced glycation end products (RAGE), a receptor associated with sustained NF-kappaB activation in the diabetic microenvironment, has a central role in sensory neuronal dysfunction. In sural nerve biopsies, ligands of RAGE, the receptor itself, activated NF-kappaBp65, and IL-6 colocalized in the microvasculature of patients with diabetic neuropathy.

Selective vulnerability in amyotrophic lateral sclerosis: no evidence for a contribution of annexins, a family of calcium binding proteins.

Clinically, amyotrophic lateral sclerosis (ALS) usually presents as a pure motor system disorder, whereas oculomotor and sphincter muscle control of the anus and the bladder appear to be spared. Previously, a lacking expression of calcium binding proteins (CBPs) was demonstrated in vulnerable motor neurons in contrast to spared neuronal populations, e.g.

Annexin expression in inflammatory myopathies.

The pathogenesis of the inflammatory myopathies is still unclear, making their treatment largely empirical. Improved understanding of the molecular mechanisms of inflammatory muscle injury may, however, lead to the development of more specific immunotherapies. To elucidate a possible pathogenic contribution of calcium-binding proteins such as the annexins, we immunohistochemically investigated muscle biopsy specimens from patients with dermatomyositis (10 cases), polymyositis (9 cases), and inclusion-body myositis (4 cases), compared to control cases comprising sarcoid myopathy (3 cases), Duchenne muscular dystrophy (DMD; 4 cases), and normal muscle (3 cases).

Receptor for advanced glycation endproduct (RAGE)-mediated nuclear factor-kappaB activation in vasculitic neuropathy.

Binding of ligands to the receptor for advanced glycation endproducts (RAGE) results in activation of the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) and subsequent expression of NF-kappaB-regulated cytokines. In order to determine whether engagement of RAGE contributes to the pathogenesis of vasculitic neuropathy, we studied the presence of the RAGE ligand N(epsilon)-(carboxymethyl)lysine (CML), the receptor itself, NF-kappaB, and interleukin-6 (IL-6) in sural nerve biopsies of 12 patients with vasculitic neuropathies and 12 controls. In the patients, CML, RAGE, NF-kappaB, and IL-6 were localized in mononuclear cells, epineurial and endoneurial vessels and the perineurium.

Clinical and electrophysiological characteristics of autosomal recessive axonal Charcot-Marie-Tooth disease (ARCMT2B) that maps to chromosome 19q13.3.

Charcot-Marie-Tooth disease (CMT) comprises a heterogeneous group of hereditary motor and sensory peripheral neuropathies. The autosomal recessive axonal form of CMT (ARCMT2) is rare. Eight patients of a large consanguineous family of Spanish ancestry in Costa Rica were diagnosed with ARCMT2B; previous genetic studies of this family revealed linkage to chromosome 19q13.

Expression and localization of cyclooxygenase-1 and -2 in human sporadic amyotrophic lateral sclerosis.

Prostaglandins (PGs) are critical mediators of physiologic processes and inflammation. They are produced by two different isoforms of the cyclooxygenase (COX) enzyme, namely COX-1 and COX-2. In particular COX-2 was demonstrated to be crucial for PG-synthesis in inflammation.

Increased hypoxic blood pressure response in patients with amyotrophic lateral sclerosis.

Objectives: There is evidence of impaired cardiovascular autonomic control and reduced baroreflex sensitivity in patients with amyotrophic lateral sclerosis (ALS). A compromised baroreflex-chemoreflex interaction might result in inadequate responses to chemoreflex activation with progressive hypercapnia and hypoxia and contribute to early fatalities. This study was performed to assess cardiovascular and ventilatory responses to hypercapnic and hypoxic stimulation in ALS patients with impaired baroreflex function.

Charcot-Marie-Tooth disease: a novel Tyr145Ser mutation in the myelin protein zero (MPZ, P0) gene causes different phenotypes in homozygous and heterozygous carriers within one family.

Charcot-Marie-Tooth disease type 1B (CMT 1B) is caused by mutations in the gene coding for peripheral myelin protein zero (MPZ, P0) that plays a fundamental role in adhesion and compaction of peripheral myelin. Here we report a Costa Rican family with a hereditary peripheral neuropathy due to a novel Tyr145Ser MPZ mutation. Four family members were heterozygously affected; two siblings of two heterozygous carriers were homozygous for this mutation.

Burden of care in amyotrophic lateral sclerosis.

Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal disease with unique demands on patients and carers.

Patients And Methods: The total burden of care and burden components in 37 ALS carers were measured using validated questionnaires. Furthermore, influencing factors (functional impairment of the patient, additional carers, participation in support groups) were assessed.

Subjective experience and coping in ALS.

Objective: Amyotrophic lateral sclerosis is a rapidly progressive and fatal disease which has no known cure and limited symptomatic treatment. While coping strategies in more common diseases are widely assessed, coping is poorly understood in ALS.

Methods: We examined 41 ALS patients using a standardised interview, a validated coping self-rating questionnaire and a self-rating depression scale.