0000000000073913
AUTHOR
Wilfred Nix
Lesions of single nerves
The trigeminal nerve exits the brain in its anatomical course in the area of the pons and proceeds to the anterior edge of the petrous bone. There, the nerve forms the trigeminal ganglion – also known as the Gasserian ganglion – which, sheathed by a dural sleeve, gives off three branches (V1–3).
Persistent unilateral tibialis anterior muscle hypertrophy with complex repetitive discharges and myalgia
Unilateral enlargement of the tibialis anterior muscle associated with complex repetitive discharges occurred over several months in two patients and was preceded by pain and numbness in the lower leg. Neuroradiologic investigations excluded a compressive radiculopathy, but pharmacologic and neurophysiologic studies suggested a neurogenic basis for the muscle hypertrophy. Botulinum toxin A injection into the hypertrophied muscles led to a decreased muscle volume and cessation of muscle pain.
The “Mainzer EMF-Wachhund”: results from a watchdog project on self-reported health complaints attributed to exposure to electromagnetic fields
The "Mainzer EMF-Wachhund," a watchdog project, offered a system of self-notification of health complaints attributed to exposures to electromagnetic fields (EMFs) to a population of a part of Germany with about 4 million inhabitants. By using a self-administered questionnaire, which was provided online and for download from the Internet, 192 persons reported such health complaints in the period from October 2003 to March 2005. Of these, 56% classified themselves as electromagnetic hypersensitive (EH). Predictors of this self classification were being affected by all kinds of EMF rather than single EMF sources and being female. On average, EH subjects reported a high degree of suffering, 77…
Clinical aspects of painful conditions
Sudeck’s atrophy, also known by the synonym “reflex sympathetic dystrophy,” is now described by the term “complex regional pain syndrome” (CRPS). This umbrella term has been subdivided into type I and type II.
Acute and chronic pain
Acute or chronic pain is a complex multidimensional neuronal response that draws attention to damaging or potentially damaging situations. A complex cascade of events takes place between the triggering occurrence of irritation and the final result of pain perception. In the beginning the nociceptor transforms the noxious threat into a signal.
A CTLA4high genotype is associated with myasthenia gravis in thymoma patients
Myasthenia gravis (MG) in thymoma patients depends critically on intratumorous generation and export of mature autoreactive CD4+ T cells. Why non-MG thymomas fail to produce CD4+ T cells is unknown. We studied three single-nucleotide polymorphisms of the cytotoxic T-lymphocyte–associated antigen 4(CTLA4) gene in thymoma patients, nonthymoma early-onset MG patients, and control subjects. Surprisingly, the CTLA4high genotype +49A/A, which is protective against several autoimmune diseases, exerted a prominent predisposing effect to paraneoplastic MG in thymoma patients. The unusual disease association with a CTLA4high genotype implies a unique pathogenesis of paraneoplastic MG, with high CTLA4…
Effects of intermittent high frequency electrical stimulation on denervated EDL muscle of rabbit.
This study was performed to determine whether electrical stimulation can retard denervation-induced changes. The denervated extensor digitorum longus of the rabbit, a fast-twitch muscle, was stimulated at a rate mimicking its motoneuron firing pattern. The 100-Hz stimulation given intermittently subjected the muscle to a low mean total daily frequency of 1.6 Hz. Four weeks of stimulation resulted in no effect upon the denervated stimulated muscle. This stimulation protocol, therefore, is unable to substitute for the lost neuronal influence of the nerve. The muscle contralateral to the stimulated side showed physiological changes making it unsuitable to serve as a control.
Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis
Autoimmune associations in myasthenia gravis (MG)-patients and their relatives have not been re-assessed since their separation into early- or late-onset MG (EOMG, LOMG), or thymoma-associated MG. Here, we analysed 226 EOMG-, 97 LOMG-, and 150 thymoma-patients for autoimmune disorders in themselves and their relatives. From 283 of them sera were tested for different organ- and non-organ-specific autoantibodies (autoAbs) by immunofluorescence test (IFT) and ELISA; genotyping was performed in 213 patients. Relatives with autoimmune disorders were reported by more patients with EOMG (40% of 210) than LOMG (20% of 89; p0.01) than thymomas (8% of 150; p0.001). In 150 genotyped EOMG-females, the …
The ageing and myasthenic thymus: a morphometric study validating a standard procedure in the histological workup of thymic specimens.
The thymus is believed to play an important role in the pathogenesis of myasthenia gravis (MG). The 80% of MG patients with anti-acetylcholine receptor autoantibodies fall into three clinical subgroups: 1) thymoma; 2) early-onset MG (<age of 40; EOMG) and 3) late-onset (LOMG; onset after 40). Thymectomy is widely used in EOMG, but its benefits have not been established in randomized controlled trials. A multicenter international trial (MGTX) currently seeks to determine whether thymectomy reduces corticosteroid requirements, and to look for correlations with thymic histology. We here describe the validated, standardized histological workup and reporting system used in this trial.
Reversible esophageal motor dysfunction in botulism
Two cases of botulism with autonomic and neuromuscular system involvement are presented. In both patients, dryness of the mouth and difficulties in swallowing were predominant symptoms. Esophageal manometry revealed a marked decrease in peristaltic amplitude, which was most pronounced in the upper third of the esophagus. These functional abnormalities returned to normal following recovery from the acute disease.
cFLIPoverexpression in T cells in thymoma‐associated myasthenia gravis
OBJECTIVE: The capacity of thymomas to generate mature CD4+ effector T cells from immature precursors inside the tumor and export them to the blood is associated with thymoma-associated myasthenia gravis (TAMG). Why TAMG(+) thymomas generate and export more mature CD4+ T cells than MG(-) thymomas is unknown. METHODS: Unfixed thymoma tissue, thymocytes derived thereof, peripheral blood mononuclear cells (PBMCs), T-cell subsets and B cells were analysed using qRT-PCR and western blotting. Survival of PBMCs was measured by MTT assay. FAS-mediated apoptosis in PBMCs was quantified by flow cytometry. NF-κB in PBMCs was inhibited by the NF-κB-Inhibitor, EF24 prior to FAS-Ligand (FASLG) treatment …
Thymus pathology observed in the MGTX trial
The MGTX trial is the first prospective, randomized clinical trial that aims to evaluate the impact of extended transsternal thymectomy on myasthenic symptoms, prednisone requirements, and quality of life in patients with nonthymomatous, anti-acetylcholine receptor autoantibody-positive myasthenia gravis (MG). Here, we give an overview of the rationale of thymectomy and the standardized macroscopic and histopathological work-up of thymectomy specimens as fixed in MGTX standard operating procedures, including the grading of thymic lymphofollicular hyperplasia and the morphometric strategy to assess thymic involution.
Internalized myofiber capillaries: Observations on their origin and clinical features
Internalized capillaries limited to type 1 muscle fibers were noted in seven patients. They occurred in each case in association with a similar admixture of neurogenic and myopathic features that included atrophic and hypertrophic fibers, internal nuclei, fiber splitting, and endomyseal and perimyseal fibrosis. Internalized capillaries in enlarged type 1 fibers arose from fiber splits on step section study of four patients. They occurred in the gastrocnemius, quadriceps, and soleus muscles from patients with a variety of disorders that included Becker dystrophy, diabetes mellitus and strenuous leg activities, Achilles tendon rupture, and myotonic dystrophy. Exercise-induced myalgias were no…
Late-onset myasthenia gravis - CTLA4(low) genotype association and low-for-age thymic output of naïve T cells.
Abstract Late-onset myasthenia gravis (LOMG) has become the largest MG subgroup, but the underlying pathogenetic mechanisms remain mysterious. Among the few etiological clues are the almost unique serologic parallels between LOMG and thymoma-associated MG (TAMG), notably autoantibodies against acetylcholine receptors, titin, ryanodine receptor, type I interferons or IL-12. This is why we checked LOMG patients for two further peculiar features of TAMG – its associations with the CTLA4 high/gain-of-function +49A/A genotype and with increased thymic export of naive T cells into the blood, possibly after defective negative selection in AIRE-deficient thymomas. We analyzed genomic DNA from 116 …
A Follicular Dendritic Cell Sarcoma of the Mediastinum With Immature T Cells and Association With Myasthenia Gravis
Follicular dendritic cell (FDC) sarcoma is a very rare neoplasm showing morphologic and phenotypic features of FDCs. It occurs primarily in lymph nodes but also in extranodal sites. So far, there have been no reports on FDC sarcoma associated with myasthenia gravis. In the following we will present a case of an FDC tumor of the mediastinum associated with paraneoplastic myasthenia gravis in a 39-year-old man. The tumor contained a major proportion of immature T cells, which may be connected to this patient's very unusual clinical presentation with autoimmune phenomena. Extranodal FDC sarcomas still seem hardly noticed, and their clinical and pathologic characteristics remain to be better de…
Multiple sclerosis patients show an increased spontaneous activity of their peripheral blood monocytes as measured by chemiluminescence
I has been reported that myelin basic protein (BP) reacts extremely sensitively to peroxide, which is formed when monocytes/macrophages are stimulated to produce a "respiratory burst" (RB). We measured the RB activity by means of chemiluminescence in peripheral blood monocytes/macrophages (MO) of 17 MS patients, 5 patients with a viral infection of the CNS, and 14 control persons. The median of the spontaneous RB activity of MS patients compared with the median of our control group showed a highly significant increase (P = 0.0002). All MS patients examined possessed a clearly increased MO activity. The highest values, however, were found in MS patients in a bout (means = 315%, means = 296%)…
The Autoimmune Regulator AIRE in Thymoma Biology: Autoimmunity and Beyond
Thymomas are tumors of thymic epithelial cells. They associate more often than any other human tumors with various autoimmune diseases; myasthenia gravis is the commonest, occurring in 10-50% of thymoma patients, depending on the World Health Organization-defined histologic subtype. Most thymomas generate many polyclonal maturing T lymphocytes but in disorganized microenvironments Failure to induce self-tolerance may be a key factor leading to the export of potentially autoreactive CD4 progeny, thus predisposing to autoimmune diseases. Normally, the master Autoimmune Regulator promotes expression of peripheral tissue-restricted antigens such as insulin by medullary thymic epithelial cells a…
Basics of anatomy
Peripheral nerves contain motor, sensory, and vegetative fibers that are strictly separate, but in close proximity to each other (Figure 1).
Selective loss of regulatory T cells in thymomas
Myasthenia gravis (MG) is the prime autoimmune manifestation of thymomas. We investigated the generation of T cells with a regulatory phenotype (T(R)) in thymomas with and without associated MG. In patients with MG(+) thymomas, maturation and export of T(R) cells but not of other T-cell subsets was significantly reduced. We conclude that imbalance between effector and regulatory T cells in thymomas may be involved in modulation of onset and/or severity of MG.
General therapeutic guidelines
There are currently no methods available that have been proven to promote or accelerate regenerative processes in nerves. This lack often leads to disappointment for both patient and physician.