Tremor. Eight patients demonstrated moderate to severe features of parkinsonism, including bradykinesia, postural instability, facial masking, and decreased arm swing. Other commonly observed neurologic features included flaccid dysarthria with hypophonetic purchase TA-01 speech (n = 21) and static/kinetic tremor (n = 4). In addition to neurologic signs, many patients described subjective neurologic symptoms including hearing loss and visual problems. Eleven patients 18325633 had CSF examination; WBC, protein, and glucose levels were within normal limits in all. No routine blood laboratory parameters were consistently abnormal among patients.Results DemographicsBetween March 1 and November 13, 2009, we identified 303 persons meeting the case definition for typhoid fever, including 212 suspected, 45 probable, and 46 confirmed cases. Of these, 40 (13 ) persons had objective, focal neurologic findings documented in the medical chart (n = 6) or elicited on examination (n = 34); an additional 27 persons had encephalopathy or altered mental status but did not demonstrate focal neurologic findings and were not included in subsequent analysis. Twenty-six of the 40 cases with neurologic signs met criteria for a 259869-55-1 site suspected case, 10 for a probable case, and 4 for a confirmed case. The median age 25033180 was 18 years (range: 3?7 years); 53 were female. Age and sex distribution were not significantly different between patients with and without neurologic illness (data not shown). Twenty-seven persons (68 ) with neurologic illness were hospitalized, and there were five (13 ) deaths; one decedent underwent autopsy. Twenty-one (53 ) persons were treated with a variety of antimicrobials at some point during their illness, generally upon hospital admission. The most commonly administered antimicrobials included chloramphenicol (n = 15), lumefantrine-artemether (n = 9), and penicillin G (n = 7).Neurologic Illness Assoc with Typhoid FeverTable 1. Neurologic signs and symptoms among 40 persons with neurologic illness associated with typhoid fever.Neurologic Sign/Symptom Upper Motor Neuron Signs Hyperreflexia Sustained ankle clonus Spasticity Babinski’s sign Dysarthria Ataxia Encephalopathy/altered mental status Headache Hearing loss (subjective) Parkinsonism Tremor doi:10.1371/journal.pone.0046099.tN22 16 10 5 21 22 15 15 9 855 40 25 13 53 
55 38 38 23 20two groups were characterized by a large variance, making it difficult to assess statistical differences. However, the group with neurologic signs did not appear to have lower PLP and 4PA values than the group without neurologic signs. Urinary thiocyanate levels among 16 persons without neurologic illness were significantly higher than in 5 persons with neurologic illness (p = 0.004, Table 2); however, concentrations in all but one (without neurologic signs) were within the established reference range [23], and no urinary thiocyanate concentrations were above those previously associated with health effects [24].Neuroimaging FindingsMRI of the brain and spinal cord was performed on three symptomatic persons (two probable, one suspect) with neurologic signs including spasticity, ataxia, and parkinsonism, during their acute illnesses. No signal abnormalities were present, however all three demonstrated generalized cerebral atrophy disproportionate to age (5, 7, and 18 years) (Figure 2).Short-Term OutcomesSeventeen typhoid fever patients hospitalized with neurologic illness were serially evaluated for at least 1 week following onset. All had u.Tremor. Eight patients demonstrated moderate to severe features of parkinsonism, including bradykinesia, postural instability, facial masking, and decreased arm swing. Other commonly observed neurologic features included flaccid dysarthria with hypophonetic speech (n = 21) and static/kinetic tremor (n = 4). In addition to neurologic signs, many patients described subjective neurologic symptoms including hearing loss and visual problems. Eleven patients 18325633 had CSF examination; WBC, protein, and glucose levels were within normal limits in all. No routine blood laboratory parameters were consistently abnormal among patients.Results DemographicsBetween March 1 and November 13, 2009, we identified 303 persons meeting the case definition for typhoid fever, including 212 suspected, 45 probable, and 46 confirmed cases. Of these, 40 (13 ) persons had objective, focal neurologic findings documented in the medical chart (n = 6) or elicited on examination (n = 34); an additional 27 persons had encephalopathy or altered mental status but did not demonstrate focal neurologic findings and were not included in subsequent analysis. Twenty-six of the 40 cases with neurologic signs met criteria for a suspected case, 10 for a probable case, and 4 for a confirmed case. The median age 25033180 was 18 years (range: 3?7 years); 53 were female. Age and sex distribution were not significantly different between patients with and without neurologic illness (data not shown). Twenty-seven persons (68 ) with neurologic illness were hospitalized, and there were five (13 ) deaths; one decedent underwent autopsy. Twenty-one (53 ) persons were treated with a variety of antimicrobials at some point during their illness, generally upon hospital admission. The most commonly administered antimicrobials included chloramphenicol (n = 15), lumefantrine-artemether (n = 9), and penicillin G (n = 7).Neurologic Illness Assoc with Typhoid FeverTable 1. Neurologic signs and symptoms among 40 persons with neurologic illness associated with typhoid fever.Neurologic Sign/Symptom Upper Motor Neuron Signs Hyperreflexia Sustained ankle clonus Spasticity Babinski’s sign Dysarthria Ataxia Encephalopathy/altered mental status Headache Hearing loss (subjective) Parkinsonism Tremor doi:10.1371/journal.pone.0046099.tN22 16 10 5 21 22 15 15 9 855 40 25 13 53 55 38 38 23 20two groups were characterized by a large variance, making it difficult to assess statistical differences. However, the group with neurologic signs did not appear to have lower PLP and 4PA values than the group without neurologic signs. Urinary thiocyanate levels among 16 persons without neurologic illness were significantly higher than in 5 persons with neurologic illness (p = 0.004, Table 
2); however, concentrations in all but one (without neurologic signs) were within the established reference range [23], and no urinary thiocyanate concentrations were above those previously associated with health effects [24].Neuroimaging FindingsMRI of the brain and spinal cord was performed on three symptomatic persons (two probable, one suspect) with neurologic signs including spasticity, ataxia, and parkinsonism, during their acute illnesses. No signal abnormalities were present, however all three demonstrated generalized cerebral atrophy disproportionate to age (5, 7, and 18 years) (Figure 2).Short-Term OutcomesSeventeen typhoid fever patients hospitalized with neurologic illness were serially evaluated for at least 1 week following onset. All had u.
