Is the P300 deficit in alcoholism associated with early visual impairments (P100, N170)? An oddball paradigm

OBJECTIVE: Studies exploring chronic alcoholism with event-related potentials (ERPs) have shown delayed latency and reduced amplitude of the P300, a long-lasting positive potential reflecting decisional processing. This P300 deficit in alcoholism is generally interpreted as a disturbance in central nervous system inhibition or in memory/attention. The present study aimed at identifying if this electrophysiological deficit is already present on earlier components, and advances a new hypothesis concerning the interpretation of the P300 alteration. METHODS: Patients suffering from alcoholism and matched healthy controls had to detect, in an oddball paradigm, emotional faces among a succession of neutral faces. Behavioral performance and ERP data (recorded from 32 electrodes) were analyzed. RESULTS: In line with previous studies, data showed that alcoholism led to a P300 deficit. Moreover, we observed for the first time that this deficit begins at earlier visual (P100) and face-processing (N170) stages, and we found high positive correlations between P100, N170 and P300 for amplitude and latency values, suggesting cumulative deficits on the cognitive continuum. CONCLUSIONS: We suggest that the P300 deficit observed in chronic alcoholism could be linked to earlier visuo-spatial deficits rather than being an impairment of the specific processes linked to the P300. SIGNIFICANCE: These results call for reconsidering the interpretation of P300 impairments at a fundamental and clinical level, and shows that earlier ERP components must be taken into account in future studies.     

Acquired non hypertrophic pyloric stenosis in children]

Pediatric non hypertrophic pyloric stenosis (NHPS) are uncommon. Their causes and treatments are debated.Material and methodRetrospective review of all cases of NHPS from 3 pediatric surgery services during the period 1984–2002.ResultsSix children, aged 17 months to 15 years, underwent surgery for NHPS. Clinical symptoms, food vomiting and loss of weight, were present for several weeks before the diagnosis of NHPS was made. The diagnosis was peptic stenosis in 3 cases and has not been established in 3 cases. Search for Helicobacter pylori was negative in all cases. Failure of specific medical treatment and endoscopic dilatations led to pyloric resection in 3 cases and pyloroplasty in 3 cases. Post operative course was uneventful with normal oral feeding and normalisation of weight status. Histologic data were aspecific. No recurrence was observed.DiscussionWe discuss the origin of the pyloric stenosis, regarding clinical, operative and pathological data: were the stenosis the cause or consequence of peptic ulcer? Peptic disease is always advocated, but difficult to prove and may be excessively incriminated. Late symptomatic congenital and acquired idiopathic pyloric stenosis should be recalled. In all cases of proved pyloric stenosis, after failure of medical and endoscopic treatment, a simple surgical procedure (pyloroplasty) associated with medical treatment seems to be effective.ConclusionThe diagnosis of NHPS should be suspected in a child with food vomiting and loss of weight if his age is not concordant with hypertrophic pyloric stenosis. Upper gastro-intestinal series and endoscopy are diagnostic. The precise cause of the stenosis is more difficult to asses. When the medical treatment fails, a pyloroplasty is usually curative.     

Dysregulation of human brain microtubule-associated tau mRNA maturation in myotonic dystrophy type 1

Intraneuronal aggregates of hyperphosphorylated tau proteins, referred to as pathological tau, are found in brain areas of demented patients affected by numerous different neurodegenerative disorders. We previously described a particular biochemical profile of pathological tau proteins in myotonic dystrophy type 1 (DM1). This multisystemic disorder is characterized by an unstable CTG repeat expansion in the 3'-untranslated region of the DM protein kinase gene. In the human central nervous system, tau proteins consist of six isoforms that differ by the presence or absence of the alternatively spliced exons 2, 3 and 10. Here we show that the pattern of tau isoforms aggregated in DM1 brain lesions is characteristic. It consists mainly of the aggregation of the shortest human tau isoform. A disruption in normal tau isoform expression consisting of a reduced expression of tau isoforms containing the exon 2 was observed at both the mRNA and protein levels. Large expanded CTG repeats were detected and showed marked somatic heterogeneity between DM1 cases and in cortical brains regions analysed. Our data suggest a relationship between the CTG repeat expansion and the alteration of tau expression showing that DM1 is a peculiar tauopathy.     

Jeune syndrome and liver disease: report of three cases treated with ursodeoxycholic acid

Evidence for a bipolar disorder (BPD) susceptibility locus on chromosome 22q11 has been provided in several studies. One candidate gene that maps to this region is the G-protein alpha subunit gene Galphaz (GNAZ). We have identified a common silent polymorphism in GNAZ exon 2 by single strand conformation polymorphism analysis. The frequency of this polymorphism was determined in a control population (n=84) and in patients with BPD (n=88). The data showed a statistical trend toward a difference in the distribution of alleles in patients with BPD compared with control subjects (chi square=3.2, 1 df, P=0.073, two-tailed). No significant difference was detected when the GNAZ polymorphism was analyzed in control subjects and schizophrenia patients (n=63, P=0.92). These data continue to provide some support for a BPD susceptibility gene on 22q11, possibly in linkage disequilibrium with the GNAZ 309 polymorphism.     

Neonatal status epilepticus due to lamination disorder without significant cell death

Background: Malformations of the cerebral cortex may be associated with severe epilepsy and status epilepticus. It has been shown that status epilepticus models induce excitotoxic cell death. In humans, very few data are available. Case and results: We report a case of a multifocal disorder of the lamination diagnosed in a neonate, borne at 30 weeks’ gestation, who died from a refractory status epilepticus at two months and half. This abnormality was not detected by repeated MRI studies. Only microscopic investigations permitted to identify this disorder of the lamination. We found also little cell death or cell loss. Discussion: Our report highlights the possible false negative results of MRI in a newborn. We can also discuss that immature human brain maybe less sensitive to neuronal injury than mature as described in animal models.     

Tau pathology modulates Pin1 post-translational modifications and may be relevant as biomarker

A prerequisite to dephosphorylation at Ser–Pro or Thr–Pro motifs is the isomerization of the imidic peptide bond preceding the proline. The peptidyl-prolyl cis/trans isomerase named Pin1 catalyzes this mechanism. Through isomerization, Pin1 regulates the function of a growing number of targets including the microtubule-associated tau protein and is supposed to be deregulated Alzheimer's disease (AD). Using proteomics, we showed that Pin1 is posttranslationally modified on more than 5 residues, comprising phosphorylation, N-acetylation, and oxidation. Although Pin1 expression remained constant, Pin1 posttranslational two-dimensional pattern was modified by tau overexpression in a tau-inducible neuroblastoma cell line, in our THY-Tau22 mouse model of tauopathy as well as in AD. Interestingly, in all of these systems, Pin1 modifications were very similar. In AD brain tissue when compared with control, Pin1 is hyperphosphorylated at serine 16 and found in the most insoluble hyperphosphorylated tau fraction of AD brain tissue. Furthermore, in all tau pathology conditions, acetylation of Pin1 may also contribute to the differences observed. In conclusion, Pin1 displays several posttranslational modifications, which are specific in tauopathies and may be useful as biomarker.     

Unusual features of Creutzfeldt–Jakob disease followed-up in a memory clinic

Sporadic Creutzfeldt–Jakob disease (sCJD) generally manifests itself by cognitive or rapidly progressive motor symptoms. An atypical onset or an unusual evolution may delay the diagnosis. Among patients with a confirmed diagnosis of sCJD following a post-mortem neuropathological examination at the Neuropathology Centre of Lille, France, those who had presented with atypical cognitive disorders at onset were included in the study. Four patients were included. The first patient (64-years-old) presented early language disorders, later accompanied by apathy and behavioral disorders. The prolonged course suggested a diagnosis of progressive primary aphasia. The second patient (68-years-old) presented with aphasia, apraxia, and ataxia of the right upper limb with parkinsonian syndrome, suggesting corticobasal degeneration. In the two last patients (58- and 61-years-old), the onset was marked by an anxiety–depression syndrome, falls, visual hallucinations, extra-pyramidal syndrome, and fluctuating cognitive decline. The diagnosis raised was probable Lewy body dementia. The 14.3.3 protein was found in two of the four cases. The clinical elements found may initially suggest focal atrophy or Lewy body dementia. A very rapid clinical deterioration generally suggests sCJD, but in the last case, the evolution was particularly slow. The diagnosis of sCJD must be considered in cases of rapid-onset dementia, even if all of the clinical criteria are not present. The detection of the 14.3.3 protein and multifold increase in total-Tau with normal or slightly increased phosphorylated-Tau in the CSF are additional arguments to reinforce the diagnosis. The post-mortem neuropathological examination is important to confirm the diagnosis.