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Biomedical subjects

A Lagueny

Publications and source records attributed to A Lagueny.

At least 19 recordsLinked to original sources
PubMed2005

Epsilon sarcoglycan mutations and phenotype in French patients with myoclonic syndromes.

BACKGROUND: Myoclonus dystonia syndrome (MDS) is an autosomal dominant movement disorder caused by mutations in the epsilon-sarcoglycan gene (SGCE) on chromosome 7q21. METHODS: We have screened for SGCE mutations in index cases from 76 French patients with myoclonic syndromes, including myoclonus dystonia (M-D), essential myoclonus (E-M), primary myoclonic dystonia, generalised dystonia, dystonia with tremor, and benign hereditary chorea. All coding exons of the SGCE gene were analysed. The DYT1 mutation was also tested. RESULTS: Sixteen index cases had SGCE mutations while one case with primary myoclonic dystonia carried the DYT1 mutation. Thirteen different mutations were found: three nonsense mutations, three missense mutations, three splice site mutations, three deletions, and one insertion. Eleven of the SGCE index cases had M-D and five E-M. No SGCE mutations were detected in patients with other phenotypes. The total number of mutation carriers in the families was 38, six of whom were asymptomatic. Penetrance was complete in paternal transmissions and null in maternal transmissions. MDS patients with SGCE mutation had a significantly earlier onset than the non-carriers. None of the patients had severe psychiatric disorders. CONCLUSION: This large cohort of index patients shows that SGCE mutations are primarily found in patients with M-D and to a lesser extent E-M, but are present in only 30% of these patients combined (M-D and E-M).

Adolescent↗
PubMed2005

[Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic strategy. Guidelines of the French CIDP study group].

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) comprises a group of dysimmune neuropathies easily diagnosed in more than half of the patients. Diagnosis is based on clinical, electrophysiological and biological clues. In some patients, diagnosis is unclear because of the debated value of the available clues. In such circumstances, dysimmune neuropathies may not be diagnosed, leading to insufficient treatment. This is an important category of patients because immunomodulatory drugs have proven efficacy. The CIDP spectrum includes a relatively wide range of diseases. Besides the easily recognized classic forms, there are many clinical variants, sometimes with a paucisymptomatic presentation leading to uncertain diagnosis. The French CIDP study group has established guidelines for diagnostic strategy in CIDP patients. The first part of this paper is devoted to the clinical aspects of the disease, classical forms and variants. In the second part, the results of electrophysiological studies are reported. In a third chapter, complementary examinations useful for diagnosis are discussed. The fourth chapter deals with the diagnostic strategy, discussed in relation to the different situations which may be encountered in clinical practice. details the technical modalities of appropriate electrophysiological studies and presents normal results together with those indicating demyelinating neuropathy. Nerve biopsy technique and results are given in appendix II.

Humans↗
PubMed2005

[Cramp-fasciculation syndrome].

The cramp-fasciculation syndrome is a rare clinical entity in comparison with the frequency of cramps and isolated fasciculations in the general population. It is recognized as a benign syndrome without weakness and atrophy, however a few reports suggest that it may precede the occurrence of a motor neuron disease. Most often, the cramp-fasciculation syndrome is idiopathic and may be a component of a hyperexcitable peripheral nerve syndrome including other activities such as myokymia and neuromyotonia where antibodies to voltage-gated potassium channels (VGKCs) appear to be one of the effector mechanisms. The most complete form of this hyperexcitable peripheral nerve syndrome is Isaacs' syndrome. The central nervous system is also concerned with anti-VGKC antibodies found in Morvan's disease and limbic encephalitis which is often a paraneoplastic condition. These findings extend the spectrum of the anti-VGKC syndrome that may be associated with other auto-immune diseases, chiefly myasthenia gravis with thymoma. Carbamazepine and phenytoin cause reduction of the clinical and electrophysiological signs of the nerve hyperexcitability, and plasmapheresis and (or) immunosuppressors are useful when an auto-immune origin is considered.

Humans↗
PubMed2004

[POEMS syndrome (or Crow-Fukase syndrome)].

POEMS is an acronym for polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes. POEMS syndrome is also called Crow-Fukase syndrome, chiefly in Japan. The 5 above mentioned features are not always present at the first examination. The minimal criteria to establish the diagnosis are the presence of a demyelinating and axonal polyneuropathy associated with an IgA or IgG monoclonal gammopathy, the light chain being almost always lambda, and at least 2 of the 8 other features: sclerosing plasmocytoma, endocrinopathy, skin changes, organomegaly, Castleman's disease, anasarca, papillary edema or thrombocytosis. Among these features, only cutaneous glomeruloid angioma are specific. Ultrastructural identification of uncompacted myelin lamellae on the peripheral nerve biopsy is also a strong argument in favor of the diagnosis. An associated "osteosclerotic" bone lesion must be carefully searched, because its treatment may improve the other features of the syndrome, especially the neuropathy. Cytokines and the vascular growth endothelial factor might play a role in the pathogenesis of this rare multisystemic disorder.

Humans↗
PubMed2004

[Single-fibre electromyography].

Single-fibre electromyography (SF-EMG) is the most sensitive electrophysiological test for myasthenia gravis and other neuromuscular junction pathology. It is also useful in the assessment of motor unit morphology in some neuromuscular diseases. A special needle with a 25 microm recording surface is used to record the time-locked potentials of 2 muscle fibers belonging to the same motor unit. Jitter is the variability in the arrival time of action potentials to the recording surface between consecutive discharges. The junctional part of the jitter depends on the amount of Ach released and on the sensitivity of the postsynaptic membrane and is related to the safety margin of neuromuscular transmission. Thus, SF-EMG can detect subclinical impairment of neuromuscular transmission, which cause an increased jitter. However, an increased jitter is not specific of neuromuscular transmission disorders, because it may be due to unstable conduction in motor nerves and muscle fibers. It is the extrajunctional part of the jitter. SFEMG is performed either during slight voluntary contraction (volitional SFEMG) or by axonal stimulation (stimulated SFEMG). Jitter is expressed as the mean of the absolute consecutive differences (MCD) of the latency between the time-locked potentials (volitional SFEMG) or from the stimulus to the negative peak of the potential (stimulated SFEMG). Recording is judged abnormal when more than 10% of the collected pairs are abnormal. On the other hand, single use coaxial needle electrodes which are cheaper could be an alternative for neuromuscular transmission analysis, because the jitter analysed with this type of needle was found highly comparable to that analysed with SF electrode. Moreover, jitter measurements coupled with fiber density estimates provide valuable information on the pathophysiology of the motor units in various neuromuscular disorders.

Electromyography↗
PubMed2003

Serum IgG antibodies to P0 dimer and 35 kDa P0 related protein in neuropathy associated with monoclonal gammopathy.

BACKGROUND: Peripheral neuropathies (PN) associated with monoclonal gammopathy (MG) are widely considered as autoimmune disorders, but the putative role of incriminated antigens is still not understood. OBJECTIVE: Fifty five patients with PN associated with MG were studied to investigate whether new antigens could be found, and to evaluate their relation to clinical manifestations. METHODS: An immunological study was conducted on patient sera to identify autoreactivities against nerve proteins by western blotting. Antigen proteins were purified and analysed by proteomic tools. Correlation with ultrastrucural and clinical features was then studied. RESULTS: Of the 55 patients suffering from PN associated with MG, 17 exhibited IgG autoantibodies directed against peripheral nerve proteins of 35, 58, and 60 kDa. N-terminal microsequencing and mass spectrometry analyses of the 35 kDa protein revealed perfect peptidic matching with 47% of the amino acid sequence of P0, whereas the 58 and 60 kDa proteins were identified as the reduced and non-reduced forms of a P0 dimer. Deglycosylation did not affect IgG binding to the 35 kDa P0 related protein, suggesting a peptidic epitope. In contrast, deglycosylation abolished IgG recognition of the P0 dimer protein, so that a carbohydrate moiety may be implicated in the epitope formation. This confirmed the existence of two different types of IgG, one recognising the 58 and 60 kDa proteins and one directed against the 35 kDa protein. CONCLUSIONS: This is the first report of antibody activity directed against the dimeric association of P0. Although P0 oligomerisation and adhesion properties play a crucial part in the myelin sheath compaction, the pathogenic significance of these autoantibodies needs further investigations to be elucidated.

Animals↗
PubMed2003

[Progressive supranuclear palsy: a clinical, natural history and disability study].

We studied the clinical features, the natural history and disability in 47 progressive supranuclear palsy patients and brain imaging aspects by routinely performed MRI in a subgroup of 25. Unexplained falls together with atypical parkinsonism (symmetric, levodopa unresponsive without resting tremor) are good clinical pointers of the early diagnosis, since they occurred within the first year. Cognitive slowness and unspecific visual complains are also early symptoms, while usual cardinal signs such as supranuclear palsy are more delayed. Blepharospasm and eyelid opening apraxia as well as deep sighs are also quite characteristic clinical features (1/3 of cases). Cardinal signs (falls, pseudobulbar signs, supranuclear gaze palsy) worsened rapidly (20 to 30 months) towards a major disability. In the 20 patients deceased during follow-up, the mean survival time was about 5 years. The MRI study showed typical cortical fronto-temporo-parietal atrophy, mesencephalic and quadrigeminal plate atrophy with third ventricle dilatation. In conclusion, unexplained falls associated with atypical parkinsonism are contributive for the early clinical diagnosis. Non specific visual complains could be useful pointers in the absence of supranuclear ophthalmoplegia. MRI contributes to the clinical diagnosis even in the first 3 years of the disease course.

Age of Onset↗
PubMed2002

Minimal tissue damage after stimulation of the motor thalamus in a case of chorea-acanthocytosis.

Autopsy findings are reported from a patient with chorea-acanthocytosis treated for 2 years by deep brain stimulation (DBS) of the motor thalamus. Postoperative testing showed a progressive improvement in axial truncal spasms. Although relatively high currents were used for 2 years in this patient, postmortem analysis showed minimal tissue damage in the vicinity of the electrode tip. It is concluded that DBS has little impact on the surrounding tissues.

Adult↗
PubMed2002

Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation.

Triple A (3A) syndrome, a rare autosomal recessive disorder, is characterized by adrenocorticotropic hormone-resistant adrenal insufficiency, achalasia of the cardia, alacrima, and variable autonomic and neurologic dysfunction. The gene responsible, AAAS, recently has been identified. We describe the neurologic phenotype of the first adult case of 3A syndrome presenting bulbospinal amyotrophy as the prominent sign in association with a homozygous nonsense mutation identified in the AAAS gene.

Adrenal Gland Diseases↗
PubMed2002

Peripheral neuropathy associated with mitochondrial disorders: 8 cases and review of the literature.

Forty-three cases of peripheral neuropathy (PN) have been reported in the literature with a proven mitochondria (mt) DNA mutation, and 21 had a peripheral nerve biopsy (PNB). We studied 8 patients, 1 of whom had severe sensory PN, 3 mild PN, and 4 subclinical PN. Nerve biopsy was performed in every case; all patients showed axonal degeneration and 4 showed features of primary myelin damage. In addition, there were 2 crystalline-like inclusions in the Schwann cell cytoplasm of a patient with MERRF, and 1 in a patient with multiple deletions on the mtDNA. There are 11 cases of PNB in the literature with axonal lesions, 5 with demyelination, and 4 with mixed lesions. One PNB was not modified. A few crystalline-like inclusions were seen in 1 case of MERRF. Such inclusions were first reported in the Schwann cell cytoplasm of unmyelinated fibers in a patient with Refsum disease and were considered to be modified mitochondria. However, their mitochondrial origin remains debatable.

Adolescent↗
PubMed2002

[Botulinum toxin in the management of spastic hip adductors in non-ambulatory cerebral palsy children].

PURPOSE OF THE STUDY: Spasticity of the hip adductors is a challenging problem for children with severe motor impairment due to cerebral palsy. It inhibits motor development and is also a risk factor for hip dislocation. Botulinum toxin has been found to be an effective means of treating spastic pes equinus in walking cerebral palsy patients and could have other indications. We conducted a prospective study to determine the functional and orthopedic contribution of botulinum toxin in the treatment of spastic hip adductors in non-ambulatory cerebral palsy children. MATERIAL AND METHODS: The study included 11 quadriplegic children with cerebral palsy (mean age 5 years 9 months). Seven of the children had unilateral migration of the hip at study onset (> 40% radiographically). The children were given a single injection of botulinum toxin (Dysport: 20 units/kg/hip) in the adductor muscles (21 treated hips). The children were seen again at months 1, 3, 6 and 12 after treatment (with the exception of one patient not seen after the 6(th) month at the request of the parents). Spasticity was measured with the modified Ashworth scale. The motor level was determined with 8 position and motor items and with the GMFCS classification. Hip x-rays were obtained at study onset and once or twice during the follow-up. RESULTS: There were no adverse effects of the treatment. Spasticity decreased by one point or more on the Ashworth scale in 20 hips at month 1 and remained low at month 3 in 14, and at month 6 in 12 of the 21 hips treated. The effect of the anti-spasticity treatment faded out from the 6(th) to the 12(th) month. Three children who experienced pain in the lower limbs were definitively relieved after treatment. Nine children achieved functional improvement (progress in at least one of the motor items). Three children were able to walk with a walker and two of them improved from level IV to level III on the GMFCS. The best functional responses appeared to occur in the younger children and in those who had good results at months 3 and 6. Among the 7 children whose hip was displaced by more than 40%, 5 had an unfavorable radiological progression and underwent surgery. DISCUSSION: This study demonstrates that the botulinum toxin can be effective against spasticity of the hip adductors and that its effect is still significant 6 months after the injection in more than half the hips treated. It has an analgesic effect. This treatment has a functional impact even in children with severe motor impairment. The benefit has been modest but three children were able to progress to walking with a walker. The best functional results were observed in the younger children and in those whose spasticity had declined at month 3 and 6. It could thus be favored either by innate potential for motor development or by the treatment itself. The botulinum toxin did not improve the orthopedic prognosis of the children: 5 of the 7 with a risk of luxation worsened. Nevertheless, our study suggests that the botulinum toxin is a well-tolerated anti-spasticity treatment that is effective for the hip adductors providing an important contribution to the management of non-ambulatory cerebral palsy children.

Adolescent↗
PubMed2001

Anti-myelin-associated glycoprotein antibodies and endoneurial cryoglobulin deposits responsible for a severe neuropathy.

A 73-year-old man was investigated for a peripheral neuropathy which occurred in the course of a Waldenstrom's macroglobulinemia. Serum immuno-fixation electrophoresis demonstrated two IgM monoclonal gammopathies of the kappa and lambda chain isotypes, and one had the physical characteristics of cryoglobulin. Immunoblot studies on the patient's serum revealed antibodies which reacted with peripheral nervous system proteins of different molecular weights including the myelin-associated glycoprotein (MAG). An immunofluorescence study of a superficial peroneal nerve biopsy revealed not only a binding of IgM and kappa light chain on several myelin sheaths but also the presence of IgM and kappa light chain deposits in the endoneurium. On electron microscopic examination, numerous fibres presented a widely spaced myelin and the endoneurial deposits had the ultrastructure of cryoglobulin. This is the first case presenting features of widely spaced myelin related to serum anti-MAG activity associated with monoclonal cryoglobulin deposits in the endoneurium.

Aged↗
PubMed2001

Sporadic late onset paroxysmal cerebellar ataxia in four unrelated patients: a new disease?

We describe a peculiar form of late onset paroxysmal cerebellar ataxia including clinical features similar to episodic ataxia type 2 (EA2) but unresponsive to acetazolamide. Four unrelated patients were clinically investigated. Neuropathological examination was performed in one patient and molecular analysis in all four. All 47 exons of CACNA1A were screened by a combination of single-strand conformer polymorphism and sequencing analysis in three patients. In addition, the length of the CAG repeat was determined in all four patients. The four patients were in their 60s at the onset of the disease, which was characterized by cerebellar ataxia attacks lasting from a few minutes to 1-2 h and occurring mainly in the morning. In the interictal period a nystagmus was present together with a slowly progressive cerebellar ataxia over the years. The neuropathological examination disclosed a dramatic loss of Purkinje cells mainly in the vermis. Moreover, certain cerebellar granular neurons had a strong cytoplasmic staining at immunopathological examination with an anti-tau protein serum. Search for truncating mutations or CAG repeat expansion in CACNA1A was negative. This late-onset paroxysmal cerebellar ataxia with neuropathological lesions restricted to Purkinje cells and with negative results both for truncating mutations and CAG expansion in the CACNA1A gene represents a new entity. Further studies are needed to delineate the underlying process.

Acetazolamide↗
PubMed2001

Histopathological features of X-linked Charcot-Marie-Tooth disease in 8 patients from 6 families with different connexin32 mutations.

There is still confusion as to whether X-linked Charcot-Marie-Tooth disease (CMTX) is primarily an axonal disorder or is primarily demyelinating. Eight symptomatic patients, 7 males and 1 female, from 6 families with identified connexin32 mutations underwent a superficial peroneal nerve biopsy. Quantitative and ultrastructural studies were performed, and histopathological lesions in these 8 patients proved to be quite homogeneous. The myelinated fiber count was within normal values or only moderately decreased. In 7 cases, the distribution of myelinated fibers was unimodal due to a loss of large fibers, coexisting with numerous clusters of small regenerating fibers. At ultrastructural level, these clusters were often surrounded by flattened Schwann cell processes giving an aspect of "pseudo-onion bulb" formation. There was no "naked axon" (ie, demyelinated axon), and real "onion bulb" formations composed of flattened Schwann cell processes surrounding an isolated myelinated fiber were discrete and not numerous. Macrophages laden with myelin debris were scarce or absent in the endoneurium. Several fibers appeared discretely hypomyelinated and the calculated g-ratio was scarcely higher than the mean control value. Lesions of unmyelinated fibers were absent in 7 cases and mild in one. Given that the primary defect concerns connexin32, we think that the histopathological features observed in our patients correspond to primary hypomyelination rather than to ongoing demyelination. The associated axonal degeneration might be secondary to defective axon-Schwann cell interactions.

Adolescent↗
PubMed2001

Mild recurrent neuropathy in CMT1B with a novel nonsense mutation in the extracellular domain of the MPZ gene.

Clinical, electrophysiological, and neuropathological features are reported associated with a novel heterozygote point mutation in the extracellular domain of the MPZ gene, where a transversion at codon 71 in exon 3 leads to a codon stop: Glu71stop (ie GAA-->TAA). A 36 year old woman developed a mild recurrent neuropathy after intensive manual work. The motor nerve conduction velocities were slow without conduction blocks and the nerve biopsy showed signs of demyelination-remyelination, axonal loss, and regular uncompacted myelin lamellae. She inherited the mutation from her father who displayed the same mutation with a normal phenotype. This nonsense mutation may cause a dosage difference of normal P0, and is probably underrepresented in the current mutation data bases. This report further extends the phenotype of MPZ mutations and also emphasises that mild phenotype of CMT1B may be more frequent than has been appreciated.

Adult↗
PubMed2001

[Inclusion body myositis associated with sacroidosis: a report of 3 cases].

Inclusion body myositis (IBM) is a severe form of idiopathic inflammatory myopathy. A predominantly T CD8+ lymphocytic infiltrate, with focally non-necrotizing muscular fiber invasion, and rimmed-vacuoles are specific histological signs. A few cases of IBM associated with other dysimmune diseases have been reported, but only once with systemic sarcoidosis. We report three cases of muscular sarcoidosis associated with IBM. This very uncommon observation suggests that major complex of histocompatibility, soluble factors, cytokines and adhesion molecules could be involved. Our cases are a novel example of associated dysimmune diseases.

Biopsy↗