The records of 97 children with culture-proven Shigellosis were reviewed in order to assess the frequency and risk factors of convulsions associated with this infection. Thirteen (13.4%) had convulsions, three of whom had additional features suggestive of encephalopathy. Clinical and laboratory data were compared between patients with and without convulsions to define the risk factors for the development of seizures. A high peak temperature and high band forms in excess of 10% of the differential white cell count were significant risk factors. Age, sex, family history of febrile seizure or epilepsy, and the Shigella strain were not significant risk factors.published_or_final_versio

Lau, YL

Low, LCK

Ting, LY

Tsang, AMC

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Title Convulsions and ShigellosisAuthor(s) Tsang, AMC; Ting, LY; Lau, YL; Low, LCKCitation Journal of the Hong Kong Medical Association, 1994, v. 46 n. 3,p. 239-241Issued Date 1994URL http://hdl.handle.net/10722/53457Rights Creative Commons: Attribution 3.0 Hong Kong LicenseConvulsions and ShigellosisA. M. C. Tsang, L. Y. Ting, Y. L. Law and L. C. K. LowAbstractThe records of 97 children with culture-proven Shigellosis were reviewed in order to assess thefrequency and risk factors of convulsions associated with this infection. Thirteen (13.4%) hadconvulsions, three of whom had additional features suggestive of encephalopathy. Clinical andlaboratory data were compared between patients with and without convulsions to define the riskfactors for the development of seizures. A high peak temperature and high band forms in excessof 10% of the differential white cell count were significant risk factors. Age, sex, family history offebrile seizure or epilepsy, and the Shigella strain were not significant risk factors.Keywords: Shigellosis; ConvulsionIntroductionConvulsion is among the most frequent extra-intesti-nal manifestations of Shigellosis. It occurs in 12 to45% of affected children,1-4 which is more frequentthan other common febrile illness. The pathogenesisof such neurological manifestations is not clear. It hasbeen suggested that the factors related to the courseof disease like high fever and electrolyte disturbances5and the production of neurotoxin by the Shigella or-ganism may play a role.6 The aim of this retrospectivestudy was to review the clinical and laboratory fea-tures of children with Shigellosis and to identify therisk factors for the development of convulsions.Subjects and methodsWe reviewed the records of 97 children with culture-proven Shigellosis, who were admitted into theUniversity Paediatric Unit of Queen Mary Hospitalbetween January 1987 and December 1992. The medi-cal history, clinical and laboratory data were analysedand compared between children with and withoutconvulsions. Statistical analysis were performed usingthe Students' t test and chi-square test.Department of Paediatrics, The University of Hong Kong, Queen MaryHospital, Pokfulam,Hong KongA. M. C. Tsang, MB, BS, MRCP(UK)L. Y. Ting, MB, BS, MRCP(UK)Y. L. Lau, MD, FRCP(Edin)L. C. K. Low, MB, ChB, FRCP(Edin and Glasg)Correspondence to: Dr L. C. K. LowResultsThirteen (13.4%) of the 97 children with culture-provenShigella gastroenteritis presented with generalized tonic-clonk convulsions within 24 hours of onset of fever.Five of these patients did not have any diarrhoealsymptoms before admission. The convulsions all lastedfor less than 15 minutes. Two had another attack ofconvulsion (less than 15 minutes) after admission. Three(3%) of them had drowsiness and stupor on presentation.None had clinical signs of meningitis. Lumbar puncturewas performed in six patients (three with encephalo-pathy, two with recurrent convulsions and one whowas seven years old which fell outside the age range forfebrile convulsion) and the cerebrospinal fluid (CSF)findings were normal. Cultures of the CSF were allsterile. Computerised tomography scanning of the brainwas performed in the three patients with encephalopathyand changes of cerebral oedema was only present inone of them. Electroencephalogram showed diffuse slowwaves changes in all three patients. They were startedempirically on intravenous Acyclovir and Cefotaximefor suspected infectious encephalopathy. Acyclovir andCefotaxime were stopped when the stool culture resultswere available. One seven-year-old child developedmyocarditis and heart failure in addition to encephalo-pathy. The encephalopathic changes resolved within 24hours after admission. All the other patients had a benigncourse and recovered uneventfully after treatment.The age distribution of the children with or with-out convulsions is shown in Figure 1. Of the 60children under five years of age, eight (13.3%) hadconvulsion as compared to five (13.5%) of 37 childrenover five years of age.The history, clinical and laboratory data were239240 J Hong Kong Med Assoc Vol. 46, No. 3, September 1994Table 1. Possible Risk factors for convulsions in 97 children with ShigellosisFactor Children with convulsions Children without convulsionsNumberAge (years)Family history of convulsions (%)Individual history of febrile convulsionsM:F ratioTemperature peak (°C)White cell count (109/L)Band form >10% (%)Serum sodium (mmol/l)Serum potassium (mmol/l)PH134.39 ± 2.97'022.25:139.9 + 0.715.8 ±6.3100135.8 + 3.63.6 + 0.37.38 ± 0.05844.57 ±3.54001.27:138.6+ 1.114.1 + 8.032136.6 + 4.33.7 + 0.57.38 + 0.06NSNSNSNS< 0.0001NS< 0.0001NSNSNS" mean + SDNS = not significant (p > 0.05)compared between children with and without con-vulsions for possible risk factors (Table 1). Nodifference was found between the two groups withrespect to age, family history of febrile convulsion orepilepsy, sex ratio, total leucocyte count, serum elec-trolytes and pH. The mean temperature peak wassignificantly higher in children with convulsions thanin those without (39.9 ± 0.7oC vs 38.6 ± 1.1°C, p <0.0001). Among those with convulsion, only one hada temperature below 39°C. Six (46.2%) had a tem-perature between 39.1 to 40°C while six (46.2%) hadtemperature above 40°C. Children with convulsionshad a significantly higher percentage of band formsin their differential white cell counts (28.8 ± 10.4%, p< 0.0001).In the study population, 69 (71%), 27 (28%) and 1<1 %) were infected by Shigella flexneri, Shigella sonneiand Shigella dysenteriae respectively. Among thosewith convulsions, seven were infected by ShigellaD without convulsion• with convulsion0-1 1-2 2-3 3-4 4-5 5-6 6-7 7-8 8-9 9-10 10-11 11-12Age (years)Fig. 1. The age distribution of patients with or withoutconvulsions.flexneri and six by Shigella sonnei. There was nostatistical significance among the different strains ofShigella on the occurrence of convulsions (Table 2).DiscussionNeurological symptoms are the commonest extra-in-testinal manifestations of Shigellosis. In our series,13.4% of the patients had convulsions and 3% hadencephalopathy. This is lower than the prevalence of12 to 45% reported in other series.1-4 Since not all thepatients with Shigellosis are hospitalized, the trueincidence of neurological symptoms may be lower.Young age, a history of convulsions in the patientor family, and a high peak temperature were riskfactors that were associated with higher incidence ofconvulsions in Ashkenazi's series.4 Other factors likethe serum electrolytes, blood glucose, the total whitecell counts, the absolute number of band cells, andthe species of Shigella were not important risk fac-tors. We identified only two factors that wereassociated with higher risk of convulsions: a highpeak temperature and a high band forms of greaterthan 10% of the differential white cell count. 92.4%patients with convulsions had a temperature of higherthan 39°C. All of our patients with convulsions hadgreater than 10% of band forms in their differentialTable 2. Influence of Shigella strain on occurrence ofconvulsionsShigella strainShigella flexneriShigella sonneiShigella dysenteriaeNo ofchildreninfected69271No.(%) ofchildren withconvulsions7 (10%)6 (22%)0 (0%)PNSNSNSTsang et al.: Convulsions and Shigellosis 241white cell count. The high band forms may be anacute stress response to the convulsion or the infec-tion itself, as a result of epinephrine-mediatedreactions and mobilization of the immatureneutrophils into the circulation. Young age was notan important risk factor in our series. 13.3% of chil-dren under five years and 13.5% of children over fiveyears of age developed convulsions associated withShigella infection. In fact, 41.7% of those having con-vulsions were older than five years of age, which felloutside the usual age range for febrile convulsions,with the oldest one being nine years old. A familyhistory of convulsions has not been found to be asignificant risk factor in our patients.Seizure occurs more frequently in Shigellosis thanin other gastrointestinal infections. The underlyingreason is unclear. It has been attributed to the Shigatoxin which possesses neurotoxic, cytotoxic andenterotoxic properties but its exact role remains con-troversial.7 Although Shiga toxin is considered to be aneurotoxin, it does not directly invade neurons, butdamages the endothelial cells, causing vascular dis-turbances in the brain with secondary neurologicaldisturbances. Recently Ashkenazi et al. found a heat-labile cytotoxin with a molecular mass of 100 to 125kDa produced by pathogenic Shigella species, causedreversible neurological dysfunction in experimentalmice.8 Whether other toxic products of Shigella or-ganisms play a role in the pathogenesis of neurologicalmanifestation still needs further studies.In summary, while the pathogenesis of Shigellosis-associated convulsions is still unclear, a high peaktemperature and high band forms in excess of 10% ofthe differential leucocyte count were significant riskfactors for the development of seizures in Shigellosis.References1. Ashkenazi S, Dinari G, Zevulunov A, et al. Convulsionsin childhood Shigellosis: clinical and laboratory featuresin 153 children. Am J Dis Child 1987; 141: 208-10.2. Avital A, Maayan C, Goitein KJ. Incidence of convul-sions and encephalopathy in childhood shigellainfections. Clin Pediatr 1987; 21: 645-8.3. Donald WD, Winkler CH, Bargeron LM Jr. The occur-rence of convulsions in shigella gastroenteritis. ] Pediatr1956; 48: 323-7.4. Ashkenazi S, Dinari G, Weitz R, et al. Convulsions inShigellosis : evaluation of possible risk factors. Am JDis Child 1983; 137: 985-7.5. Keusch GT. Shigella infections. Clin Gastroenterol 1979;8: 645-61.6. Levine MM. Bacterial dysentery : mechanisms andtreatment. Med Clin North Am 1982; 66: 623-38.7. Bartlett AV III, Prado D, Cleary TG, et al. Production ofshiga toxin and other cytotoxins by serogroups ofshigella. J Infect Dis 1986; 154: 996-1002.8. Ashkenazi S, Cleary KR, Pickering LK, et al. The asso-ciation of shiga toxin and other cytotoxins with theneurologic manifestations of Shigellosis. J Infect Dis1990; 161: 961-5.

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