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Biomedical subjects

W Camu

Publications and source records attributed to W Camu.

At least 37 records · Page 2Linked to original sources
PubMed1999

Genetics of familial ALS and consequences for diagnosis. French ALS Research Group.

Familial amyotrophic lateral sclerosis (fALS) is a well-recognised condition that accounts for almost 10% of all cases of ALS. Most cases are now known to be transmitted by an autosomal dominant trait. When fALS is compared clinically to sporadic ALS, 20% of cases manifest atypical features such as pain, paraesthesia or urgency micturition. Moreover, a disease duration of over 10 years, with very slow progression, appears to occur almost exclusively in cases of fALS. Studies of superoxide dismutase (SOD1) mutations in fALS have shown that the disease may be multidegenerative, with oculomotor or cerebellar involvement. Molecular genetics has also demonstrated that not all SOD1 mutations have a dominant influence, and the detailed description of the Scandinavian D90A homozygous mutation is very informative in this regard. Misdiagnosis of fALS can be attributed to one of the following situations: (i) atypical phenotype ALS with a multidegenerative profile; (ii) unusually long lasting ALS with mild motor neuron involvement; (iii) significant clinical heterogeneity between affected family members; (iv) low reliability of family history; (v) existence of an unknown or unexpected mode of transmission; and (vi) other multidegenerative disorders with motor neuron involvement. Pedigrees and fALS cases corresponding to these situations are presented.

Adult↗
PubMed1999

Acute hepatitis after riluzole administration.

Riluzole is a new drug representing the first active treatment for amyotrophic lateral sclerosis. We report the cases of two patients who developed acute hepatitis after taking riluzole at the recommended dose (100 mg daily) for 7 and 4 weeks, respectively. In both cases, liver histology showed hepatocellular damage with inflammatory infiltration and microvesicular steatosis without fibrosis. Liver enzymes returned to normal 4 and 8 weeks, respectively, after riluzole withdrawal. In one case, the readministration of riluzole was followed by the relapse of hepatitis. These two observations strongly suggest that riluzole can induce acute hepatitis with associated hepatocellular damage and microvesicular steatosis. They also suggest that liver enzymes should be monitored during treatment with riluzole.

Acute Disease↗
PubMed1998

Hydrogen peroxide-induced motoneuron apoptosis is prevented by poly ADP ribosyl synthetase inhibitors.

The impact of oxidative stress (H2O2) was observed using purified rat motoneuron cultures and H2O2-induced dose-dependent motoneuron death was demonstrated. The apoptotic characteristics of cell death were studied morphologically and using the TUNEL technique. This H2O2-induced motoneuron death was inhibited by the poly ADP ribosyl synthetase (PARS) inhibitors benzamide and nicotinamide. These findings suggest the potential utility of PARS inhibitors in the treatment of neurodegenerative disorders such as amyotrophic lateral sclerosis, in which oxidative stress has been suspected to play an important etiopathogenic role.

Animals↗
PubMed1998

Association between centromeric deletions of the SMN gene and sporadic adult-onset lower motor neuron disease.

The telomeric copy (t) of the survival motor neuron (SMN) gene is homozygously deleted in more than 90% of patients with infantile motor neuron disease (MND). In the general population, no homozygous SMNt deletion has been found, whereas 5% of centromeric SMN (SMNc) deletions can be observed. Although SMNt deletions appear causal for infantile and at least some adult-onset spinal muscular atrophy (SMA) (type IV), the respective role of SMN deletions remains unclear in adult-onset MNDs. We studied SMN gene in three different groups of patients with adult-onset MNDs. In sporadic amyotrophic lateral sclerosis (ALS; n = 177) and familial ALS (n = 66), no SMNt deletion had been found, and the frequency of SMNc deletions was not increased. Conversely, among the 14 patients with sporadic pure lower MND (LMND), we found 2 patients with homozygous SMNt deletions (14%) and 5 patients with homozygous SMNc deletions (36%). These data suggest that (1) SMNt deletions do not account for the major part, if any, of adult-onset LMND cases; and (2) SMNc deletions act as a susceptibility factor for LMNDs in adults. The clinical and genetic heterogeneity of LMND cases, including SMA type IV, are yet to be unexplained. Further studies on large groups of adult-onset LMND patients are warranted to refine its nosology.

Adult↗
PubMed1998

Identification of six novel SOD1 gene mutations in familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the premature death of motor neurons. In approximately 10% of the cases the disease is inherited as autosomal dominant trait (FALS). It has been found that mutations in the Cu/Zn superoxide dismutase gene (SOD1) are responsible for approximately 15% of FALS kindreds. We screened affected individuals from 70 unrelated FALS kindreds and identified 10 mutations, 6 of which are novel. Surprisingly, we have found a mutation in exon 3, which includes most of the active site loop and Zn2+ binding sites, a region where no previous SOD1 mutations have been found. Our data increase the number of different SOD1 mutations causing FALS to 55, a significant fraction of the 154 amino acids of this relatively small protein.

Amino Acid Sequence↗
PubMed1998

Recessive amyotrophic lateral sclerosis families with the D90A SOD1 mutation share a common founder: evidence for a linked protective factor.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neurodegeneration resulting in paralysis and death from respiratory failure within 3-5 years. About 20% of familial cases are associated with mutations in the gene for copper/zinc superoxide dismutase ( SOD1 ), which catalyses the dismutation of the superoxide radical to hydrogen peroxide and oxygen. Experimental evidence suggests mutations act by a toxic gain of function but the mechanism is unknown. There are >60 known SOD1 mutations associated with ALS and all are dominant except for one in exon 4, a D90A substitution which is recessive. D90A pedigrees with dominant inheritance have now been reported and this apparent contradiction needs to be explained. We performed a worldwide haplotype study on 28 D90A pedigrees using six highly polymorphic microsatellite markers. We now show that all 20 recessive families share the same founder (alpha = 0.999), regardless of geographical location, whereas several founders exist for the eight dominant families (alpha = 0.385). This finding confirms that D90A can act in a dominant fashion in keeping with all other SOD1 mutations, but that on one occasion, a new instance of this mutation has been recessive. We propose a tightly linked protective factor which modifies the toxic effect of mutant SOD1 in recessive families.

Amino Acid Substitution↗
PubMed1998

[Cyst of the conus masquerading as motor neuron disease].

We report on a patient presenting with rapidly progressive painless paraplegia, amyotrophy and fasciculations masquerading as motoneuron disease. There were no bowel or bladder involvement but the patient noted mild paresthesia on the external part of the right foot and hypertrophy of the right calve was present. While lumbar CT Scan was normal, MRI showed a large cyst of the conus. Analysis of the cyst concluded to a benign cyst of the conus. Paraplegia resolved after surgery and after one year, no relapse was observed so that an hidden ependymoma appeared unlikely.

Cauda Equina↗
PubMed1997

Somatosensory evoked potentials elicited by stimulation of lower-limb nerves in amyotrophic lateral sclerosis.

To determine lower limb somatosensory modifications in amyotrophic lateral sclerosis (ALS), we studied somatosensory evoked potentials (SEPs) elicited by stimulation of tibial posterior nerves (TP), sural nerves (SN), saphenous internous nerves (SA), and medial plantar nerves (PL) of both limbs in 24 ALS patients, and compared the results with those from 17 normal subjects. Responses were recorded according to the international 10-20 system. Normal sensory conduction velocities of SN, SA and PL and H reflexes in soleus muscles were prerequisites for patient inclusion in this study. The results showed marked alterations in SEPs cortical components of all lower limb nerves, which could be related to abnormal sensory transmission (after spinal N22), or cortical abnormalities. We put forward the hypothesis of impairment of pyramidal control of the sensory system and Clark's column involvement to explain such anomalies. It was concluded that SEPs abnormalities in the lower limbs are a common feature in ALS.

Aged↗
PubMed1997

[Clinical study of familial forms of amyotrophic lateral sclerosis. Review of the literature].

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving both upper and lower motor neurons. The disease is possibly due to several factors, including a genetic one. This is supported by the existence of 5 to 10 p. 100 familial cases. In these pedigrees, the transmission is autosomal dominant, with a high penetrance (> 90 p. 100). We studied the phenotypes of these familial cases, in reviewing the literature on familial ALS (FALS). It has been noted that FALS are heterogeneous, with different age of onset, site of onset and disease duration. Moreover, in FALS, onset is earlier than in the sporadic form (48 vs 60 years, as usually reported in the literature). We also frequently noted sensory disorders (20 p. 100), onset on the lower limbs (46 p. 100) and decreased or absent ankle-jerks (75 p. 100) in FALS patients.

Age Factors↗
PubMed1996

Apolipoprotein E genotyping in sporadic amyotrophic lateral sclerosis: evidence for a major influence on the clinical presentation and prognosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron disorder of unknown etiology. Recently, in Alzheimer's disease (AD) apolipoprotein E (APOE) alleles have been shown to play an important role in disease phenotype. To determine whether APOE have a similar influence in other neurodegenerative disorders, we studied APOE genotypes in 130 sporadic ALS patients, compared with controls. We also analyzed APOE genotypes regarding ALS clinical criteria. The frequency of APOE genotypes was not different between ALS and controls. However, subjects with the APOE2/E3 genotype showed a significantly longer duration of the disease: 51 months vs. 28.5 for APOE3/E3 and 27.5 for APOE3/E4 (p = 0.001 and p = 0.02, respectively). There was a significantly higher proportion of bulbar ALS patients in the APOE3/E4 group (72% of the cases), whereas 90% of patients in the APOE2/E3 group showed limb onset (p = 0.01). In the bulbar group, patients with APOE4 showed earlier onset of the disease: 60 vs. 66 years (mean age, p = 0.05). These results are consistent with a protective role of APOE2 and a deleterious role of APOE4 in ALS as already found for AD. This parallel supports the idea of a general role of APOE in neuronal degeneration or regeneration rather than a specific role in ALS or AD etiopathogenesis.

Age of Onset↗
PubMed1996

Motor evoked potentials (MEPs): evaluation of the different types of responses in amyotrophic lateral sclerosis and primary lateral sclerosis.

We studied different motor evoked potential parameters: cortical threshold (CT), primary response (PR) latency and amplitude and central conduction time (CCT) at rest and after maximal voluntary contraction of the target muscles, silent period (SP) and late muscular responses (LMR) in 21 normal subjects 42- to 75-years old and compared the results to those of 17 patients with motor disease (10 amyotrophic lateral sclerosis, ALS and 7 primary lateral sclerosis (PLS). We report for the first time in patients affected by motor diseases, LMRs were similar to controls. We found abnormalities in both ALS and PLS: enhanced cortical threshold, reduced PR amplitude during maximal voluntary contraction of target muscles compared to rest and shorter SP. CCT was slightly different: in ALS it was normal or undetermined (because of lack of the PR), while it was normal, enhanced or undetermined in PLS. We conclude that except for LMR, additional parameters would be useful for studying motor diseases: CT (reflecting excitability of the central cells), PR amplitudes and SP (disclosing inhibitory pathway disturbances in pyramidal tract diseases).

Adult↗
PubMed1995

Embryonic rat motoneurons express a functional P-type voltage-dependent calcium channel.

Only L- and N-type high voltage-activated calcium currents (HVA ICa) have been demonstrated in identified embryonic spinal motoneurons. However, pharmacological experiments suggest that other HVA ICa, including P-type, govern neurotransmitter release at the adult neuromuscular junction. We sought to analyse if embryonic motoneurons express these other ICa, using the whole-cell voltage-clamp method on motoneurons purified by a new metrizamide-panning technique from E15 rat embryos. In addition to L-type dihydropyridine-sensitive and N-type omega-GVIA-sensitive currents, motoneurons express two other HVA ICa. One has properties related to the P-type channel currents described in Purkinje cells: it is inhibited by the peptide omega-agatoxin-IVA with a maximal effect at 100-200 nM. The inhibited current has a characteristic sustained component during depolarizing test pulses. Furthermore, 50-100 nM concentrations of omega-agatoxin-IVA reduce the increase in cytoplasmic calcium concentration observed after depolarization. The other HVA ICa is resistant to saturating concentrations of verapamil, omega-conotoxin GVIA and omega-agatoxin-IVA which block L, N and P-type HVA ICa, respectively. These results suggest that it is now possible to dissect, using a simple method of purification, the properties of the ICa in embryonic mammalian motoneurons and to provide pharmacological evidence for multiple calcium channels which may be involved in regulation of their activity during development.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Survival of newly postmitotic motoneurons is transiently independent of exogenous trophic support.

We compared the survival requirements of early- and late-born motoneurons from E5 chicken spinal cord. Density gradient centrifugation followed by immunopanning using SC1 antibody allowed us to purify two size classes of motoneuron. Large motoneurons retained by 6.8% metrizamide were shown by BrdU labeling in ovo to be born on average 1.5 d earlier than the small motoneurons recovered from the metrizamide pellet. Large motoneurons were both biochemically and functionally more mature: they expressed higher levels of choline acetyltransferase and low-affinity neurotrophin receptor, and had an acute requirement for trophic support from muscle-derived factors. After 24 hr in culture in basal medium, all early-born motoneurons died, whereas 60% of late-born motoneurons survived. Small motoneurons can develop into large motoneurons in ovo, suggesting that they represent a general transitional stage in motoneuron development. Our results suggest that a defined period elapses between birth of a motoneuron and its acquisition of trophic dependence, possibly corresponding to the time required for target innervation. This property may have important consequences for the timing and regulation of developmental motoneuron death.

Animals↗
PubMed1994

[Somatosensory evoked potentials in amyotrophic lateral sclerosis and primary lateral sclerosis].

Somatosensory evoked potentials (SEPs) were studied in 21 cases of amyotrophic lateral sclerosis (ALS) and 7 cases of primary lateral sclerosis (PLS). Despite the lack of clinical sensory abnormalities, SEPs showed abnormalities in both diseases: lack or delay of some components. In ALS these abnormalities indicate widespread sensory disturbance. In PLS only, the Brodmann area 4 seems to be affected.

Adult↗
PubMed1993

Neurotrophins promote motor neuron survival and are present in embryonic limb bud.

Embryonic spinal motor neurons are thought to depend for survival on unidentified factors secreted both by their peripheral targets and by cells within the central nervous system. The neurotrophins are a family of polypeptides required for survival of discrete central and peripheral neuronal populations in vivo and in vitro. In spite of their ability to reduce motor neuron death in vivo, the known neurotrophins have been thought to be without direct effect on motor neurons. Here we show that picomolar concentrations of three of them, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-5, can prevent the death of cultured embryonic rat spinal motor neurons. Furthermore, messenger RNA coding for neurotrophins is present at appropriate stages in spinal cord and limb bud, and mRNA for their receptors is found in motor neurons. These neurotrophins may therefore be physiological motor neuron growth factors.

Animals↗