Et of neurologic illness. The mechanism by which typhoid fever may

Et of neurologic illness. The mechanism by which typhoid fever may produce neurologic illness is unknown. Rare cases of Salmonella Typhi bacterial meningitis, meningo-encephalitis, and intracranial abscesses have been reported both in CUDC-427 web children and adults [3,33,34]. However, a neuroinvasive bacterial process appears unlikely in our patients; CSF was generally unremarkable and without pleocytosis or protein elevation, features of meningismus were generally 18325633 absent, and CNS tissue from one confirmed case with neurologic illness, as well as brain and spinal cord MRI on 3 acutely ill patients, did not demonstrate signs of MedChemExpress Crenolanib inflammation. This is consistent with prior reports in which neurologic manifestations have largely been unassociated with evidence of CNS inflammation. For these same reasons, a para- or post-infectious immune-mediated inflammatory process in the majority of cases would seem unlikely. An underlying host factor or environmental exposure that may predispose persons to develop neurologic illness in the setting of severe systemic infection due to typhoid is possible. Many of the predominant signs and symptoms observed in these patients, including spasticity, clonus, hyperreflexia, and ataxia, may be seen with micronutrient abnormalities including vitamin B6 toxicity/ deficiency and B12 deficiency [35,36,37,38]. We assessed these micronutrient levels in a subset of persons with and without neurologic signs and did not detect significant differences; however, our sample size was small and variability in the data made it difficult to assess statistical differences. The upper motor neuron findings in this population initially appeared similar to konzo, a neurologic illness seen in tropical areas and associated with thiocyanate toxicity due to consumption of inadequatelycooked bitter cassava [39,40,41]. The ataxia demonstrated by some of our patients resembled tropical ataxic neuropathy, also related to the dietary use of large quantities of cassava over long periods of time [42,43]. Although we considered these etiologies because cassava was part of the local diet, the often dramatic and complete resolution of neurologic signs in 23727046 our patients is inconsistent with konzo or tropical ataxic neuropathy, and measurement of urinary thiocyanate levels did not demonstrate evidence of acute or chronic cyanogen toxicity. Similarly, neurolathyrism seemed unlikely due to improvement in neurologic signs, and we could not obtain a history of consumption of peas or legumes [44,45]. Production of a bacterial toxin may lead to neurologic illness, with toxins produced by Clostridium botulinum and Corynebacterium diphtheriae being fundamental examples [46]. The diffuse nature of neurologic involvement observed with typhoid-associated disease, and the apparent reversibility of these signs may be suggestive of a bacterial toxic etiology. Salmonella Typhi produces a cytolethal toxin, but the role of this toxin in the pathogenesis of typhoid fever is unknown [47,48]. Isolates of Salmonella Typhi obtained from cases in this outbreak, including persons with neurologic illness, did not demonstrate significant differences in genetic or bacteriologic properties from other isolates in central Africa [18]; further investigations into the possible presence of a Salmonella Typhiproduced neurotoxin are ongoing. Some viral and bacterial infections have been proposed to result in a “cytokinemia” in which hyper-reactive pro- and anti-inflammatory cytokines result i.Et of neurologic illness. The mechanism by which typhoid fever may produce neurologic illness is unknown. Rare cases of Salmonella Typhi bacterial meningitis, meningo-encephalitis, and intracranial abscesses have been reported both in children and adults [3,33,34]. However, a neuroinvasive bacterial process appears unlikely in our patients; CSF was generally unremarkable and without pleocytosis or protein elevation, features of meningismus were generally 18325633 absent, and CNS tissue from one confirmed case with neurologic illness, as well as brain and spinal cord MRI on 3 acutely ill patients, did not demonstrate signs of inflammation. This is consistent with prior reports in which neurologic manifestations have largely been unassociated with evidence of CNS inflammation. For these same reasons, a para- or post-infectious immune-mediated inflammatory process in the majority of cases would seem unlikely. An underlying host factor or environmental exposure that may predispose persons to develop neurologic illness in the setting of severe systemic infection due to typhoid is possible. Many of the predominant signs and symptoms observed in these patients, including spasticity, clonus, hyperreflexia, and ataxia, may be seen with micronutrient abnormalities including vitamin B6 toxicity/ deficiency and B12 deficiency [35,36,37,38]. We assessed these micronutrient levels in a subset of persons with and without neurologic signs and did not detect significant differences; however, our sample size was small and variability in the data made it difficult to assess statistical differences. The upper motor neuron findings in this population initially appeared similar to konzo, a neurologic illness seen in tropical areas and associated with thiocyanate toxicity due to consumption of inadequatelycooked bitter cassava [39,40,41]. The ataxia demonstrated by some of our patients resembled tropical ataxic neuropathy, also related to the dietary use of large quantities of cassava over long periods of time [42,43]. Although we considered these etiologies because cassava was part of the local diet, the often dramatic and complete resolution of neurologic signs in 23727046 our patients is inconsistent with konzo or tropical ataxic neuropathy, and measurement of urinary thiocyanate levels did not demonstrate evidence of acute or chronic cyanogen toxicity. Similarly, neurolathyrism seemed unlikely due to improvement in neurologic signs, and we could not obtain a history of consumption of peas or legumes [44,45]. Production of a bacterial toxin may lead to neurologic illness, with toxins produced by Clostridium botulinum and Corynebacterium diphtheriae being fundamental examples [46]. The diffuse nature of neurologic involvement observed with typhoid-associated disease, and the apparent reversibility of these signs may be suggestive of a bacterial toxic etiology. Salmonella Typhi produces a cytolethal toxin, but the role of this toxin in the pathogenesis of typhoid fever is unknown [47,48]. Isolates of Salmonella Typhi obtained from cases in this outbreak, including persons with neurologic illness, did not demonstrate significant differences in genetic or bacteriologic properties from other isolates in central Africa [18]; further investigations into the possible presence of a Salmonella Typhiproduced neurotoxin are ongoing. Some viral and bacterial infections have been proposed to result in a “cytokinemia” in which hyper-reactive pro- and anti-inflammatory cytokines result i.

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