Acute Respiratory Failure Involving an R Variant of Mycobacterium abscessus

We report the case of a cystic fibrosis patient colonized with a smooth-morphotype form of Mycobacterium abscessus who developed acute respiratory failure with the emergence of an isogenic rough (R) variant while he was recovering from peritonitis-induced shock. This report emphasizes the role of R forms in severe M. abscessus infections.     

Neuropeptide Y stimulates proliferation, migration and differentiation of neural precursors from the subventricular zone in adult mice

The neuropeptide Y (NPY) is widely expressed in the central nervous system and has been shown to stimulate neurogenesis in the hippocampus and the olfactory epithelium. Here, we demonstrate that intracerebroventricular injection of NPY stimulates proliferation of neural precursors in the mice subventricular zone (SVZ), one the most neurogenic areas of the brain. Newly generated neuroblasts migrate through the rostral migratory stream to the olfactory bulb and also directly to the striatum, as evidenced by BrdU labelling and cell phenotyping. Using knock-out mice, specific NPY receptor agonists and antagonists, we report that this neuroproliferative effect is mediated by the Y1 receptor subtype that we found to be highly expressed in the SVZ both at the mRNA and protein levels. Our data suggest that stimulating endogenous SVZ neural stem cells by NPY may be of a potential interest in cell replacement based therapies of neurodegenerative diseases affecting the striatum such as Huntington's disease.     

Cerebral MRI abnormalities associated with vigabatrin therapy

Purpose:   Investigate whether patients on vigabatrin demonstrated new-onset and reversible T₂-weighted magnetic resonance imaging (MRI) abnormalities.
Methods:   MRI of patients treated during vigabatrin therapy was reviewed, following detection of new basal ganglia, thalamus, and corpus callosum hyperintensities in an infant treated for infantile spasms. Patients were assessed for age at time of MRI, diagnosis, duration, and dose, MRI findings pre-, on, and postvigabatrin, concomitant medications, and clinical correlation. These findings were compared to MRI in patients with infantile spasms who did not receive vigabatrin.
Results:   Twenty-three patients were identified as having MRI during the course of vigabatrin therapy. After excluding the index case, we detected new and reversible basal ganglia, thalamic, brainstem, or dentate nucleus abnormalities in 7 of  22  (32%) patients treated with vigabatrin. All findings were reversible following discontinuation of therapy. Diffusion-weighted imaging (DWI) was positive with apparent diffusion coefficient (ADC) maps demonstrating restricted diffusion. Affected versus unaffected patients, respectively, had a median age of 11 months versus 5 years, therapy duration 3 months versus 12 months, and dosage  170  mg/kg/day versus 87 mg/kg/day. All affected patients were treated for infantile spasms; none of 56 patients with infantile spasms who were not treated with vigabatrin showed the same abnormalities.
Discussion:   MRI abnormalities attributable to vigabatrin, characterized by new-onset and reversible T₂-weighted hyperintensities and restricted diffusion in thalami, globus pallidus, dentate nuclei, brainstem, or corpus callosum were identified in 8 of 23 patients. Young age and relatively high dose appear to be risk factors.     

Pure alexia as a disconnection syndrome: new diffusion imaging evidence for an old concept

Functional neuroimaging and studies of brain-damaged patients made it possible to delineate the main components of the cerebral system for word reading. However, the anatomical connections subtending the flow of information within this network are still poorly defined. Here we study the connectivity of the Visual Word Form Area (VWFA), a pivotal component of the reading network achieving the invariant identification of letter strings, and reproducibly located in the left lateral occipitotemporal sulcus. Diffusion images and functional imaging data were gathered in a patient who developed pure alexia following a small surgical lesion in the vicinity of his VWFA. We had a unique opportunity to compare images obtained before, early after, and late after surgery. Analysis of diffusion images with white matter tractography and voxel-based morphometry showed that the VWFA was mainly linked to the occipital cortex through the inferior longitudinal fasciculus (ILF), and to perisylvian language areas (supramarginal gyrus) through the arcuate fasciculus. After surgery, we observed the progressive and selective degeneration of the ILF, while the VWFA was anatomically intact. This allowed us to establish the critical causal role of this fiber tract in normal reading, and to show that its disruption is one pathophysiological mechanism of pure alexia, thus clarifying a long-standing debate on the role of disconnection in neurocognitive disorders.     

Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure

Anemia is common in patients who have both heart failure and chronic kidney disease, and there is an association between anemia and progression of both diseases. The main causes of anemia are deficient production of erythropoietin (EPO), iron deficiency, and chronic disease with endogenous EPO resistance. EPO has been successfully used for over a decade to treat anemia in patients with chronic kidney disease. Less obvious are the safety and efficacy of EPO treatment in patients with both heart failure and renal disease. Up to 10% of patients receiving EPO are hyporesponsive to therapy and require large doses of the agent. Several mechanisms could explain resistance to endogenous and exogenous EPO. Proinflammatory cytokines antagonize the action of EPO by exerting an inhibitory effect on erythroid progenitor cells and by disrupting iron metabolism (a process in which hepcidin has a central role). EPO resistance might also be caused by inflammation, which has a negative effect on EPO receptors. Furthermore, neocytolysis could have a role. As resistance to exogenous EPO is associated with an increased risk of death, it is important to understand how cardiorenal failure affects EPO production and function.     

New incidence, prevalence, and survival of Aicardi syndrome from 408 cases

We sought to determine the incidence, prevalence, and life expectancy of Aicardi syndrome from 408 cases compiled from multiple international sources. Last known age ranged from less than 1 month to 42 years. The incidence rates per live births for the United States and The Netherlands were 1 per 105 000 and 1 per 93 000, respectively. The prevalence in the United States is greater than 853 cases, and the worldwide estimate is several thousand. Forty-five cases were deceased (age range, 1 month to 33 years), and the risk of death peaked at age 16. The probability of survival at 27 years of age was 0.62 (95% CI, 0.47-0.77). The risk of death by age follows other congenital neurological disorders with a wide range in severity of functional disability. The longer life expectancy found in our study hints at a higher functioning capacity in Aicardi syndrome and may inform counseling to families.