Continuous muscle activity, Morvan's syndrome and limbic encephalitis: ionic or non ionic disorders?

The early pathophysiologic study showed increasing evidence that autoimmunity is implicated in the pathogenesis of neuromyotonia. Antibodies to voltage gated potassium channel were detected in the serum of patients who had peripheral nerves hyperexcitability and also Morvan's disease or limbic encephalitis. These discoveries offered new approaches to treatments. Recently, antibodies previously attributed to VGKC recognise 2 surface antigens LGI1 and CASPR2 into the VGKC complex. Finally, VGKC antibodies are directed to 2 proteins the first one is a key hippocampic protein containing pre and post synaptic proteins. The second one CASPR2 is an hippocampic and paranodal protein. There clinical significance is different: hyperexcitability, limbic encephalitis without thymoma for LGI1, hyperexcitability, Morvan limbic encephalitis and frequent thymoma for CASPR2. In conclusion, the term NMT--LE--VGKC should be changed to NMT--LE with LGII and CASPR2 antibodies and classified as auto immune synaptic disorders. Mutations in genes encoding both these proteins are found in hereditary epilepsy and other syndromes. Various potassium channelopathies are closely linked to Morvan's syndromes. A new classification of antibodies will be necessary.

[Primary muscle cramps]. / Les crampes musculaires essentielles.

Primary muscle cramps, without known cause, are very frequent especially in the elderly and during the night. They are different from secondary cramps. Likewise they are to be separated from several syndromes erroneously quoted as cramps. The pathophysiological mechanism seems due to result from an initial dysfunction in the distal part of the motoneuron. When the cramps are severe, differential diagnosis with amyotrophic lateral sclerosis may be difficult. Quinine is the best empiric treatment largely used in spite of moderate side effects.

Synthesis and iron-binding properties of quinolobactin, a siderophore from a pyoverdine-deficient Pseudomonas fluorescens.

Quinolobactin is a new siderophore produced by a pyoverdine deficient mutant of Pseudomonas fluorescens. A simple and efficient synthesis of quinolobactin is described, starting from xanthurenic acid. The protonation constants of quinolobactin were determined by potentiometric titrations as pKa2 = 5.50+/-0.07, pKa1 = 10.30+/-0.05. The equilibria of the metal complexes were studied by means of spectrophotometric and potentiometric titrations. The overall stability constants of the quinolobactin-FeIII complexes was found to be log beta111 = 18.60+/-0.10, log beta121 = 32.60+/-0.20, log beta120 = 28.20+/-0.25 resulting in a pFeIII value of 18.2 at pH 7.4. The UV-visible spectral parameters of the [FeL2] are in agreement with a complex containing two ligands coordinated to one Fe3+ cation through the oxygen and nitrogen quinoline atoms.

Neuromuscular diseases associated with antigliadin antibodies. A contentious concept.

Many neurological syndromes associated with antigliadin antibodies have been published. The most frequent are cerebellar ataxia and peripheral neuropathy. Such cases are reported under the title of gluten ataxia or of coeliac neuropathy. However, associations do not prove cause. Herein, a short review is made of the literature and the author's personal experience. Many unsolved questions remain. Gluten sensitivity is probably an immunological response in genetically susceptible individuals with or without enteropathy. Antigliadin antibodies are present in healthy adults, in some idiopathic ataxias and neuropathies. A gluten-free diet is effective on gastrointestinal but not on neurological symptoms. Whether antigliadin antibodies are elevated is more of a waiting classification than a definite diagnosis. Finally, the relationship between antigliadin antibodies and neurological diseases is very weak.

Hydroxyquinolines as iron chelators.

The interest in synthetic siderophore mimics includes therapeutic applications (iron chelation therapy), the design of more effective agents to deliver Fe to plants and the development of new chemical tools for studies of iron metabolism and for a better understanding of iron assimilation processes in living systems. The 8-hydroxyquinoline bidentate chelate moiety offers an alternative to the usual hydroxamic acid, catechol and/or alpha-hydroxycarboxylic acid metal-binding groups encountered in natural siderophores. The promising results obtained by the tris hydroxyquinoline-based ligand O-TRENSOX are summarized. O-TRENSOX exhibits a high and selective affinity for Fe(III) complexation. Its efficiency in delivering Fe to plants as well as its efficiency for iron mobilization, cellular protection and antiproliferative effects have been evidenced. Other chelators of the O-TRENSOX family (mixed catechol / 8-hydroxyquinoline ligands, lipophilic ligands) are also described. Some results question whether the use of partition coefficients is pertinent to foresee the activity of iron chelators. The development of probes (fluorescent, radioactive, spin labelled) based on the O-TRENSOX backbone is in progress. 8-hydroxyquinoline iron chelators seem to have a promising future.

New 8-hydroxyquinoline and catecholate iron chelators: influence of their partition coefficient on their biological activity.

Four new hexadendate chelators, three hydroxyquinoline-based, Csox, O-Trensox, Cox750, and one catecholate-based CacCam-which have comparable skeletal structures and pFe, but widely different partition coefficients, (Kpart), 0.01, 0.02, 1 and 3.2 respectively, have been tested for their iron chelating efficacy in vitro by two methods. First, by their ability to remove iron from ferritin in solution or second, to remove iron from iron-loaded hepatocytes in vitro. Our objective was to ascertain the importance of Kpart and pFe, on the biological efficiency of the molecule. Previous studies proposed that an ideal value of Kpart of 1 should give maximum biological activity. Mobilization of iron by Csox and CacCAM from ferritin was similar and furthermore more efficient than desferrioxamine B. In the iron-loaded hepatocyte cultures, the three hydroxyquinoline chelators, although showing diversity in terms of lipophilicity, appeared to be very similar in their capacity to chelate iron. CacCAM, the unique catecholate, was the most efficient of the molecules tested, as well as being the least toxic in the cellular model despite having the lowest value of pFe. In conclusion, the use of the partition coefficient and pFe, as tools for predicting biological activity of iron chelators should be not generalized. Further studies are required in order to understand the influence of the structure on the biological activity of the molecule.

[An unrecognized cause of camptocormia: proximal myotonic myopathy]. / Une cause méconnue de camptocormie: la myopathie myotonique proximale.

BACKGROUND: The underlying cause of camptocormia, a common condition in adults consisting of forward flexion of the trunk both in stance and gait, is often unrecognized, attributed by some to primary late-onset myopathy. CASE REPORTS: Two patients progressively developed camptocormia. The cause was identified as a relatively new disease, proximal myotonic myopathy. DISCUSSION: The diagnosis of proximal myotonic myopathy is based on clinical findings: myalgia and diffuse pain, gait disorders and progressive weakness of proximal muscles, electrical myotonia, cataracte in some cases, elevated gamma glutamyltranspeptidases. The disease is transmitted by autosomal dominant inheritance. This condition should be entertained as a possible cause in patients presenting an apparently primary camptocormic syndrome.

[Clinical and paraclinical investigations of chronic polyneuropathies]. / Sémiologie clinique et paraclinique des polyneuropathies chroniques.

Given the composition of the nerve fibre, the signs and symptoms of chronic polyneuropathy are not uniform. Clinically, they include sensory, motor and reflex signs and symptoms with, according to the case, association of sensory, either painful or not, motor and sensory-motor forms, with a reflex component. Electrophysiologic tests can usually distinguish initially axonal lesions from those due to initial myelin alteration. Nerve biopsy, although not a routine examination, brings precise information concerning etiology.

MRI of the intracranial corticospinal tracts in amyotrophic and primary lateral sclerosis.

Our aim was to investigate the corticospinal tracts (CST) in motor neurone disease, using MRI, and to correlate findings with clinical data. We studied 31 patients with amyotrophic (ALS) and eight with primary lateral sclerosis (PLS). The signal from the CST was classified into four grades on T2-weighted images, and compared to T2-weighted images of 37 age-matched control subjects. No abnormalities were seen in the CST on T1-weighted images and were rarely evident on proton-density weighting. Variable high signal in the CST was found on T2-weighted images in 35 patients, and in 29 control subjects. Our grades 0 and 1 were more frequent in control subjects, grades 2 and 3 more frequent in patients. We found no correlation between the high signal and clinical data, including the duration of the illness. We therefore conclude that this technique is neither sensitive nor specific except in grade 3 which is quite specific for ALS. In half the patients we found atrophy of the superior parietal gyrus, which merits further study.

Partition coefficients (free ligands and their iron(III) complexes) and lipophilic behavior of new abiotic chelators. Correlation to biological activity.

Partition coefficients between n-octanol and water have been measured for ten tripodal ligands with catecholate or hydroxyquinolinate or pyridinophenolate chelating subunits and for their iron(III) complexes. The abilities of the ligands to cross an octanol phase and to extract ferric ion from its EDTA complex in an aqueous phase are studied. Correlation with biological properties are discussed.