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Biomedical subjects

T Kuntzer

Publications and source records attributed to T Kuntzer.

At least 19 recordsLinked to original sources
PubMed2006

Autosomal dominant nemaline myopathy: a new phenotype unlinked to previously known genetic loci.

We report a large family with a mild form of autosomal dominant nemaline myopathy and a new phenotype. Onset of symptoms was in infancy with hypotonia and motor delay. Weakness involved neck flexors, abdominal and proximal limb muscles. There was no bulbar, respiratory or foot dorsiflexion weakness and no slowness in movement. Patients had remarkably good physical endurance and no limitation in daily activities, but were slow runners since childhood. Nemaline rods were seen in less than 5% of muscle fibres. No linkage to the five known nemaline myopathy genes (alpha-tropomyosin-3, nebulin, alpha-actin, troponin T1 and beta-tropomyosin), to the ryanodine receptor gene (associated with core-rod myopathy) or to the 15q21-23 locus was found.

Family Health↗
PubMed2006

Painful hand and moving finger treated by wearing a glove.

The authors report a patient with unilateral painful hand and moving finger in whom tactile stimulation interrupted both the movement and the pain. This effect suggests a gating mechanism at a segmental level. The difference between afferent and efferent pathway levels and the delay of several months between trauma and occurrence of symptoms support a central mechanism, most probably involving sensorimotor reorganization at a segmental level.

Female↗
PubMed2006

[Pathogenic mechanisms of neurodegenerative diseases: amyotrophic lateral sclerosis].

Since its description by Charcot in 1869, the mechanism underlying the characteristic selective degeneration and death of motor neurons in amyotrophic lateral sclerosis (ALS) has remained a mystery. There is no effective remedy for this progressive, fatal disorder. Modern genetics have now identified two genes, SODI and ALS2 as primary causes of the disease and has implicated others as potential contributors. These insights have enabled development of model systems to test hypotheses of disease mechanism and potential therapies. Along with errors in the handling of synaptic glutamate and the potential excitotoxic response that it provokes, these model systems underscore the involvement of non-neuronal cells in disease progression and provide new therapeutic strategies.

Amyotrophic Lateral Sclerosis↗
PubMed2006

[Mechanisms leading to muscle degeneration: molecular mechanisms and therapeutical forecasts].

In inclusion body myositis (IBM), there is muscular amyloidogenesis and inflammation. A related disorder is due to alterations in the ubiquitin pathway involving the valsolin-containing protein leading to IBM, dementia and Paget's disease. Alteration in the dystrophin glycoprotein complex leads to several muscular dystrophies (MD), and the pathogenesis of dystrophin related MD as well as certain limb girdle MD are discussed. Therapeutic strategies involving inhibition of proteolytic cascades as well as inhibition of a negative regulator of muscle growth (myostatin) are briefly introduced. Finally, molecular aspects of the most common form of adult myopathy, myotonic MD, are discussed. This disease is caused by an aberrant splicing mechanism and interference thereof may be useful in designing therapeutic strategies.

Humans↗
PubMed2006

[Treatment options for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)].

Limits of treatment in chronic inflammatory demyelinating poly(radiculo)neuropathies (CIDP) patients are better known thanks to recent Cochrane reviews. (1) Randomized controlled trials have only focused on short-term effects, but most patients need long-term therapy, (2) There are three proven effective treatments available (prednisone; intravenous immunoglobulin or IVIg and plasma exchange or PE) which are useful in more than 60 p. 100 of patients, (3) New open studies indicated possible efficacy for mycophenolate, rituximab, etanercept, ciclosporine and interferons, and (4) Whether CIDP variants need specific treatment is still unknown. Many CIDP patients need treatment for years. The fear of side effects during long-term steroid treatment, the high costs of IVIg, the necessity for specialized equipment and the invasive nature of PE, are important factors determining the choice for one of these treatments. In most up-to-date treatment options, patients are initially treated with IVIg at a dosage of 2 g/kg administered for 25 days, clinical improvement can be judged within 10 days. The percentage of patients responding seems to be approximately 70 percent, with a very high chance (approximately 85 percent) that repeated administration of IVIg will be necessary, explaining why most neurologists add an immunosuppressive drug at this stage, but there is no consensus concerning the best drug to be used. Combinations of drugs are most likely to be useful in the next future, using IVIg, prednisone, and a immunosuppressor agent, such as mycophenolate, rituximab, etanercept, or ciclosporine. General measures to rehabilitate patients and to manage symptoms like fatigue and other residual findings are important.

Adrenal Cortex Hormones↗
PubMed2006

[Ganglionopathies: evolving concept and ideas on management].

Sensory ganglionopathies have a frequent association with neoplastic disorders (paraneoplastic subacute sensory neuronopathy, or SSN) or dysimmune disorders, with drugs, such as cisplatin or pyridoxine, and with inherited disorders with degeneration of dorsal root ganglion cells. Unsteady gait and pseudoathetoid movements of the hand are the distinctive signs encountered in these disorders. The chronic disorders are characterized by non-length-dependent abnormalities of sensory nerve action potentials (SNAPs) and differ from other sensory neuropathies in showing a global, rather than distal, decrease in SNAP amplitudes. This review focuses on recent advances in defining the mechanisms involved in sensory ganglionopathies, and describes the differential diagnosis including the rarely encountered hereditary neuronopathies and the infectious causes.

Action Potentials↗
PubMed2006

Favourable outcome of progressive multifocal leucoencephalopathy in two patients with dermatomyositis.

Progressive multifocal leucoencephalopathy (PML), a demyelinating disease caused by the JC virus (JCV), occurs in immunosuppressed patients and carries a poor prognosis. A favourable outcome is reported in two patients with PML and dermatomyositis. Immunosuppressive drugs were stopped in patient 1 but could only be partially tapered in patient 2. The JCV-specific CD8+ T cell response was strong in patient 1 and weak in patient 2. Both were treated with cytosine-arabinoside, and patient 2 was also treated with mirtazapine, a 5HT2A receptor antagonist. Combination of these drugs might be helpful to treat HIV-negative patients with PML.

Adrenergic alpha-Antagonists↗
PubMed2005

Improved sciatic nerve regeneration by local thyroid hormone treatment in adult rat is accompanied by increased expression of SCG10.

Thyroid hormone plays an important role in regulating the development and regeneration of the nervous system. Our previous work showed that local administration of triiodothyronine (T3) at the level of transected rat sciatic nerve increased the number and diameter of regenerated axons, but the mechanism underlying the improved regeneration is still unclear. Here, we have investigated the effect of T3 on the expression of SCG10, a regulator of microtubule dynamics in growth cones. After transection of adult rat sciatic nerves, silicone tubes were implanted and filled with T3 or phosphate-buffered solution. At various time points following surgery, the expression of SCG10 protein and mRNA was analyzed. Semi-quantitative Western blot analysis revealed that sciatic nerve transection induced a more than 20-fold upregulation of SCG10 protein in proximal nerve segments at 1 day post-lesion, while at this time point, SCG10 mRNA in dorsal root ganglion neurons was not increased yet. The increase in SCG10 protein and mRNA could be observed over 30 days. Local T3 treatment significantly enhanced the increase in SCG10 protein levels about two-fold in the different segments of transected nerve during the regeneration period. Also SCG10 mRNA levels in lumbar ganglia were enhanced. Immunohistochemical analysis showed that T3 treatment not only increased the number of SCG10 positive axons but also the intensity of their staining. These results suggest that SCG10 is involved in the regulation of regeneration. The stimulating effect of T3 on SCG10 expression could provide a mechanism by which T3 enhances peripheral nerve regeneration.

Animals↗
PubMed2005

[Immunomodulatory/suppressive treatments in neurology].

Immunomodulatory/suppressive treatments are frequently used in neurological disorders affecting the central and peripheral nervous system. Demyelinating disorders are a good example of a wide application of the various types of existing therapies. Although these therapies are still mostly not disease specific, their combination with more targeted molecules appears most relevant for diseases with multiple pathogenic mechanisms.

Adjuvants, Immunologic↗
PubMed2005

[Mutation of the aprataxin gene presenting with Charcot-Marie-Tooth-like neuropathy and cerebellar ataxia].

BACKGROUND: Phenotype-genotype correlations, generally based on predominant associated signs, are being increasingly used to distinguish different types of autosomal recessive cerebellar ataxias (ARCA). CASE REPORTS: Two brothers developed signs of cerebellar ataxia with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. The examination also showed oculomotor apraxia. Sural nerve biopsy revealed conspicuous reduction in the density of myelinated fibres but preservation of unmyelinated nerve fibres. Blood tests revealed low serum albumin and elevated cholesterol. A homozygous W279X truncating mutation was identified in exon 6 of the APTX gene, confirming the diagnosis of cerebellar ataxia with oculomotor apraxia type 1 (AOA1). CONCLUSIONS: These cases illustrate the presentation of AOA1 type of ARCA and discuss the role of peripheral neuropathy in the differential diagnostic of the ARCAs variants.

Brain↗
PubMed2004

New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis.

BACKGROUND: Periodic paralysis is classified into hypokalemic (hypoPP) and hyperkalemic (hyperPP) periodic paralysis according to variations of blood potassium levels during attacks. OBJECTIVE: To describe new mutations in the muscle sodium channel gene SCN4A that cause periodic paralysis. METHODS: A thorough clinical, electrophysiologic, and molecular study was performed of four unrelated families who presented with periodic paralysis. RESULTS: The nine affected members had episodes of muscle weakness reminiscent of both hyperPP and hypoPP. A provocative test with potassium chloride was positive in two patients. However, repeated and carefully performed tests of blood potassium levels during attacks resulted in normal potassium levels. Remarkably, two patients experienced hypokalemic episodes of paralysis related to peculiar provocative factors (corticosteroids and thyrotoxicosis). Similarly to hyperPP, electromyography in nine patients revealed increased compound muscle action potentials after short exercise and a delayed decline during rest after long exercise as well as myotonic discharges in one patient. With use of molecular genetic analysis of the gene SCN4A, three new mutations were found affecting codon 675. They resulted in an amino acid substitution of a highly conserved arginine (R) to either a glycine (G), a glutamine (Q), or a tryptophan (W). Interestingly, hypoPP is caused by both mutations affecting nearby codons as well as the change of an arginine into another amino acid. CONCLUSION: A potassium-sensitive and normokalemic type of periodic paralysis caused by new SCN4A mutations at codon 675 is reported.

Acetazolamide↗
PubMed2004

Glucocorticoid corticosteroids for Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy is the most common muscular dystrophy of childhood. This incurable disease is characterised by muscle wasting and loss of walking ability leading to complete wheelchair dependence by 13 years of age. Prolongation of walking is one of the major aims of treatment. OBJECTIVES: The aim of this review was to assess whether glucocorticoid corticosteroids stabilize or improve muscle strength and walking in boys with DMD. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group specialised register (October 2003) using the term 'Duchenne muscular dystrophy'. We also searched MEDLINE (January 1966 to October 2003), EMBASE (January 1980 to October 2003), CINAHL and LILACS (January 1982 to October 2003). We wrote to authors of published studies and other experts in this disease to help identify other trials, checked the references in the identified trials and handsearched the abstracts of relevant journals. SELECTION CRITERIA: Types of studies: randomised or quasi-randomised trials. TYPES OF PARTICIPANTS: all patients with a definite diagnosis of Duchenne muscular dystrophy. Types of interventions: glucocorticoids such as prednisone, prednisolone, deflazacort or others, with a minimum treatment period of three months. PRIMARY OUTCOME MEASURE: prolongation of walking (independent walking without long leg calipers). SECONDARY OUTCOME MEASURES: strength outcome measures, manual muscle strength testing using Medical Research Council strength scores, functional outcome measures and adverse events. DATA COLLECTION AND ANALYSIS: We identified five randomised controlled trials that met the inclusion criteria for our review. Two reviewers independently selected the trials for the review and assessed methodological quality. Data extraction and inputting were double-checked. MAIN RESULTS PRIMARY OUTCOME MEASURE: data from one small study used prolongation of walking as an outcome measure and did not show significant benefit. SECONDARY OUTCOME MEASURES: The meta-analysis of the results from three randomised controlled trials showed that glucocorticoid corticosteroids improved muscle strength and function over six months. Improvements were seen in time taken to rise from the floor (Gowers' time), nine metres walking time, four-stair climbing time, ability to lift weights, leg function grade and forced vital capacity. One randomised controlled trial showed that glucocorticoid corticosteroids stabilize muscle strength and function for up to two years. The most effective prednisolone regime appears to be 0.75 mg/kg/day. Not enough data were available to compare efficacy of prednisone with deflazacort.Adverse effects: Excessive weight gain, behavioural abnormalities, cushingoid appearance and excessive hair growth were all more common with glucocorticoid corticosteroids than placebo. Long-term adverse effects of glucocorticoid therapy could not be evaluated because of the short-term duration of the randomised studies.Non-randomised studies: a number of non-randomised studies with important efficacy and adverse effects data are tabulated and discussed. REVIEWERS' CONCLUSIONS: There is evidence from randomised controlled studies that glucocorticoid corticosteroid therapy in Duchenne muscular dystrophy improves muscle strength and function in the short-term (six months to two years). The most effective prednisolone regime appears to be 0.75 mg/kg/day. In the short term, adverse effects were significantly more common but not clinically severe. Long-term benefits and hazards of glucocorticoid treatment cannot be evaluated from the currently published randomised studies. Non-randomised studies support the conclusions of functional benefits but also indicate clinically significant adverse effects of long-term treatment. These benefits and adverse effects have implications for future research studies and clinical practice.

Adrenal Cortex Hormones↗
PubMed2004

[Electrophysiological testing in muscle channelopathies].

Electrodiagnostic testing should always be tailored to the clinical setting; in the muscle channelopathies, provocative tests are essential to demonstrate the modifications of the muscle excitability. When a permanent muscle weakness is present, a post-exercise (or post-tetanic) potentiation should be search to demonstrate a presynaptic neuromuscular channelopathy; when the weakness is fluctuating it is useful to perform repetitive nerve stimulation to see if a decrement is present or if the jitter is prolonged, indicative of a postsynaptic neuromuscular channelopathy; when the weakness is episodic, the prolonged exercise test is the only test to demonstrate the appearance of a late post-exercise decrement (sodium and calcium channelopathies), and when a myotonic reaction is seen to search the myotonic discharges by needle emg. The concomitant presence of myotonic discharges and abnormal decrement of the motor responses during repetitive nerve stimulation train depend on the type of mutations in the chloride gene and the amount of CTG repeats in myotonic dystrophy type 1. In paramyotonia congenita there a prolonged decrement when the tests are carried out with cooling the recorded muscle. Electrophysiological testings appear therefore useful to diagnose muscle channelopathies but also give information about the prognosis of the disorder; they could also be viewed as useful tests to predict response to treatments.

Electrophysiology↗
PubMed2003

Principal mutation hotspot for central core disease and related myopathies in the C-terminal transmembrane region of the RYR1 gene.

The congenital myopathies are a group of disorders characterised by the predominance of specific histological features observed in biopsied muscle. Central core disease and nemaline myopathy are examples of congenital myopathies that have specific histological characteristics but significantly overlapping clinical pictures. Central core disease is an autosomal dominant disorder with variable penetrance which has been linked principally to the gene for the skeletal muscle calcium release channel (RYR1). Two recent reports have identified the 3' transmembrane domain of this gene as a common site for mutations. Two other studies have reported single families that have features of both central core disease and nemaline myopathy (core/rod disease) caused by mutations in RYR1. Screening of the 3' region (exons 93-105) of the RYR1 gene for mutations in 27 apparently unrelated patients with either central core disease or core/rod disease by single strand conformation polymorphism analysis and DNA sequencing identified three described and nine novel mutations in 15 patients.

DNA Mutational Analysis↗
PubMed2002

[Immunopathology and treatments of Guillain-Barré syndrome and of chronic inflammatory demyelinating polyneuropathy].

The concepts of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) have changed over the last decade. The spectrum of GBS ranges from acute inflammatory demyelinating polyneuropathy to pure motor, sensory-motor or bulbar variants and the Miller Fisher syndrome. Also CIDP includes different variants in addition to the typical clinical picture with symmetrical proximal and distal weakness, such as a form with predominant distal weakness, a pure sensory form, an asymmetric form and a form with predominant cranial nerve involvement. Detailed immunopathologic features have been described in GBS and CIDP: most current investigations are centered on the hypothesis of molecular mimicry in GBS and together with the pathogenic role of cell-mediated immunity different antibodies have been discovered in GBS which interfere with nerve impulse conduction on neuromuscular transmission. The immunopathogenesis of CIDP remains fragmentary and insufficient for a unified hypothesis. Activated macrophages and T-cells with the participation of T-1 helper cell related cytokines seem to play a fundamental role in demyelination. The nature of antigen presenting cells, T-cell receptors, adhesion molecules and the proinflammatory cytokines need to be explored to design more specific immunotherapies. Established treatments in GBS include intravenous immunoglobulin and plasma exchange. Randomized trials have shown the efficacy of prednisone, intravenous immunoglobulin and plasma exchange in CIDP. New insight in the pathogenetic role of the cytokine-network in CIDP opens new therapeutical possibilities with the modification of the T-1 helper cell reaction with interferon.

Adrenal Cortex Hormones↗