PKA and cAMP/CNG Channels Independently Regulate the Cholinergic Ca(2+)-Response of Drosophila Mushroom Body Neurons

The mushroom bodies (MBs), one of the main structures in the adult insect brain, play a critical role in olfactory learning and memory. Though historical genes such as dunce and rutabaga, which regulate the level of cAMP, were identified more than 30 years ago, their in vivo effects on cellular and physiological mechanisms and particularly on the Ca(2+)-responses still remain largely unknown. In this work, performed in Drosophila, we took advantage of in vivo bioluminescence imaging, which allowed real-time monitoring of the entire MBs (both the calyx/cell-bodies and the lobes) simultaneously. We imaged neuronal Ca(2+)-activity continuously, over a long time period, and characterized the nicotine-evoked Ca(2+)-response. Using both genetics and pharmacological approaches to interfere with different components of the cAMP signaling pathway, we first show that the Ca(2+)-response is proportional to the levels of cAMP. Second, we reveal that an acute change in cAMP levels is sufficient to trigger a Ca(2+)-response. Third, genetic manipulation of protein kinase A (PKA), a direct effector of cAMP, suggests that cAMP also has PKA-independent effects through the cyclic nucleotide-gated Ca(2+)-channel (CNG). Finally, the disruption of calmodulin, one of the main regulators of the rutabaga adenylate cyclase (AC), yields different effects in the calyx/cell-bodies and in the lobes, suggesting a differential and regionalized regulation of AC. Our results provide insights into the complex Ca(2+)-response in the MBs, leading to the conclusion that cAMP modulates the Ca(2+)-responses through both PKA-dependent and -independent mechanisms, the latter through CNG-channels.

West Nile virus-associated flaccid paralysis.

The causes and frequency of acute paralysis and respiratory failure with West Nile virus (WNV) infection are incompletely understood. During the summer and fall of 2003, we conducted a prospective, population-based study among residents of a 3-county area in Colorado, United States, with developing WNV-associated paralysis. Thirty-two patients with developing paralysis and acute WNV infection were identified. Causes included a poliomyelitislike syndrome in 27 (84%) patients and a Guillain-Barré-like syndrome in 4 (13%); 1 had brachial plexus involvement alone. The incidence of poliomyelitislike syndrome was 3.7/100,000. Twelve patients (38%), including 1 with Guillain-Barré-like syndrome, had acute respiratory failure that required endotracheal intubation. At 4 months, 3 patients with respiratory failure died, 2 remained intubated, 25 showed various degrees of improvement, and 2 were lost to followup. A poliomyelitislike syndrome likely involving spinal anterior horn cells is the most common mechanism of WNV-associated paralysis and is associated with significant short- and long-term illness and death.

Diagnosis of Erdheim-Chester disease by using computerized tomography-guided stereotactic biopsy of a caudate lesion. Case report.

The authors present the case of a 27-year-old woman with Erdheim-Chester disease (ECD) and extensive intracranial involvement, in whom the initial diagnosis of ECD was established based on computerized tomography (CT)-guided stereotactic biopsy of a caudate lesion. Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis of unknown origin that is clinically characterized by bone pain, diabetes insipidus, and exophthalmos. The radiological hallmarks of the disease include symmetrical sclerosis of the long bones with epiphysial sparing and increased tracer uptake in lesions seen on scintigraphic imaging. Erdheim-Chester disease is characterized histologically by the presence of infiltrating lipid-laden histiocytes that commonly involve the retroperitoneum, orbits, skin, pericardium, lungs, and long bones. Although the occurrence of diabetes insipidus often precedes the diagnosis of ECD by more than a decade in most patients, magnetic resonance imaging- and CT-documented central nervous system involvement is exceedingly rare. In the setting of neurological involvement, neurosurgical biopsy has been reported seven times in the literature, with only one of these biopsies being the basis for the initial diagnosis of the disease. The authors' case represents only the second time the disease has been diagnosed by means of neurosurgical biopsy, highlighting the diagnostic difficulties that patients with EDC present. Skeletal radiographs were confirmatory in this case and this modality should be emphasized as the simplest and most direct route to the diagnosis. The degree of neurological involvement further distinguishes the case presented from prior reports in the literature. The multiple bilateral intraaxial lesions were intensely enhancing on contrast CT scans, distributed infra- and supratentorially, involving both white and gray matter, and associated with diffuse cerebral edema. The case presented is also remarkable by virtue of the symmetrical involvement of the caudate nuclei, representing the first such example documented in the literature. The diagnosis, treatment, and outcome in this patient are discussed, and a review of the literature is presented.

Clinical and radiologic correlates of frontal intermittent rhythmic delta activity.

To assess the clinical and radiologic correlates of frontal intermittent rhythmic delta activity (FIRDA), the authors reviewed the hospital charts of patients whose EEGs depicted this EEG finding, and recorded their past medical and neurologic history, the reason for hospital admission, and their neurologic status both on admission and during EEG recordings. Laboratory results on admission and concomitant to the EEG recording, computed tomography, or MRI findings during hospital admission were also reviewed. Sixty-eight patients were assessed. The gender ratio was 1:1; mean age was 56 years. Chronic disease occurred in 78% of patients, including hypertension (34%), diabetes (32%), and renal failure (18%). On admission, renal failure (n = 34) and hyperglycemia (n = 22) were most prominent. The majority of patients had at least one abnormal laboratory result. Thirty-eight of 51 patients in whom the level of consciousness was stated during EEG were described as awake. More than half of 58 patients whose EEG background activity was stipulated demonstrated diffuse slowing, mostly in the theta range. MRI was abnormal in 15 of 17 patients. Intrahemispheric lesions, particularly ischemic and hemorrhagic, were most common (n = 10), followed by basal ganglia lacunae (n = 4). Computed tomography was abnormal in 29 of 44 patients. Hemispheric pathology, diffuse or localized, occurred in 22 patients. Frontal intermittent rhythmic delta activity is associated with mild to moderate encephalopathy and is detected principally in awake patients. Most patients in this series had chronic systemic illness. Old ischemic structural brain lesions may predispose some patients to develop FIRDA during acute metabolic derangement, such as uremia and hyperglycemia. Frontal intermittent rhythmic delta activity was not associated with EEG epileptiform activity. Deep midline lesions, posterior fossa tumors, and hydrocephalus were not detected in this series of patients with FIRDA.