High-level gait and balance disorders in the elderly: a midbrain disease?

The pathophysiology of gait and balance disorders in elderly people with ‘higher level gait disorders’ (HLGD) is poorly understood. In this study, we aimed to identify the brain networks involved in this disorder. Standardised clinical scores, biomechanical parameters of gait initiation and brain imaging data, including deep white matter lesions (DWML) and brain voxel-based morphometry analyses, were assessed in 20 HLGD patients in comparison to 20 age-matched controls. In comparison to controls, HLGD patients presented a near-normal preparatory phase of gait initiation, but a severe alteration of both locomotor and postural parameters of first-step execution, which was related to ‘axial’ hypokinetic-rigid signs. HLGD patients showed a significant grey matter reduction in the mesencephalic locomotor region (MLR) and the left primary motor cortex. This midbrain atrophy was related to the severity of clinical and neurophysiologically determined balance deficits. HLGD patients also showed a reduction in speed of gait, related to ‘appendicular’ hypokinetic-rigid signs and frontal-lobe-like cognitive deficits. These last two symptoms were correlated with the severity of DWML, found in 12/20 HLGD patients. In conclusion, these data suggest that the gait and balance deficits in HLGD mainly result from the lesion or dysfunction of the network linking the primary motor cortex and the MLR, brain regions known to be involved in the control of gait and balance, whereas cognitive and ‘appendicular’ hypokinetic-rigid signs mainly result from DWML that could be responsible for a dysfunction of the frontal cortico-basal ganglia loops.     

An ERP investigation of item-scene incongruity at encoding on subsequent recognition

The aim of the present study was to investigate how item-scene incongruity at encoding influences subsequent item recognition and the associated event-related potential (ERP) old/new effects. Participants (N = 26) studied pictures showing an item in a scene, either in a congruent condition (e.g., a tent in a field) or an incongruent condition (e.g., a shower cabin in a field). Items were presented alone at test. Behavioral data revealed a benefit of incongruent information, with greater source memory performance but no significant effect on old/new recognition judgments. Longer response times for old compared to new items showed that participants not only evaluated the old-new status of objects during recognition, but also worked already on the scene context decision relative to the source memory judgment. An ERP incongruity effect was found at study, with greater N400 amplitude in the incongruent condition than the congruent condition. During recognition, the results provide evidence that item-scene incongruity at study increases the amplitude of ERP old/new effects. A mid-frontal N400 old/new effect was found in the early time window (300–500 ms), and a right frontal sub-component was modulated by item-scene incongruity at encoding. The modulation observed in the later time window (500–800 ms) confirmed previous studies showing that the parietal old/new effect reflects the retrieval of episodic contextual details. The present study shows that the magnitude of ERP old/new effects is sensitive to item-scene incongruity at encoding from the early time window in the right frontal region to the later retrieval processes.     

Multiplex PCR for Detection of Seven Virulence Factors and K1/K2 Capsular Serotypes of Klebsiella pneumoniae

A single multiplex PCR assay targeting seven virulence factors and the wzi gene specific for the K1 and K2 capsular serotypes of Klebsiella pneumoniae was developed and tested on 65 clinical isolates, which included 45 isolates responsible for community-acquired severe human infections. The assay is useful for the surveillance of emerging highly virulent strains.     

Group A Escherichia coli-Related Purpura Fulminans: an Unusual Manifestation Due to an Unusual Strain?

We describe an exceptional case of life-threatening group A Escherichia coli-induced purpura fulminans. Genotyping of common polymorphisms in genes involved in innate immunity or coagulation did not reveal known susceptibility to such a manifestation. Genetic analysis of the strain revealed an unusual conserved virulence plasmidic region, pointing out its potential virulence.     

Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: A french multicenter study

The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9 years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5 years (range: 1.6-35). Two patients developed Waldenström's macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36 months (range: 2-79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3-4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6 mg/d (range: 5-25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown.     

Circadian rhythm in toxic effects of cystemustine in mice: Relevance for chronomodulated delivery

Cystemustine is a new nitrosourea with high anti-tumor activity and a short plasma half-life in mice. The influence of circadian dosing time upon its toxicities was first investigated in a total of 368 synchronized male B6D2F1 mice. Late survival rate varied from 4% in mice receiving a single dose of cystemustine (conventional lethal dose 50%) at 7 hours after 1ight onset (HALO) up to 88% in mice treated at 15 or at 19 HALO. Target organ toxicities (bone marrow, circulating blood cells, spleen, colon and duodenum) were studied following a single slightly lower dose of cystemustine. Leukopenia was the major hematologic effect encountered. Leukocyte count nadir occurred 7 days after injection and was lowest following cystemustine at 7 HALO as compared to 13 or 19 HALO. Recovery was faster after cystemustine at 19 HALO as compared to other dosing times. Bone-marrow necrotic lesions were more pronounced I day after cystemustine at 7 HALO than after cystemustine at 19 HALO. Thus, a large-amplitude circadian rhythm characterized the toxicity of this nitrosourea in mice. The lowest cystemustine toxicity was found near the middle of the active span of the rest-activity circadian cycle of mice. © 1996 Wiley-Liss, Inc.