Introduction An acute illness of young children, with brain involvement and high case-fatality, has been plaguing Saharanpur and several neighbouring districts in western Uttar Pradesh (UP) over the past two decades or more 1,2 . It occurs in annual seasonal outbreaks and was earlier diagnosed presumptively as acute encephalitis of unknown viral aetiology 1, 2 . Recent studies have shown the illness to be an acute hepatomyoencephalopathy (HME) syndrome, caused by toxicity from a common weed, Cassia occidentalis 3-8 . The illness develops in Clinical & pathological features of acute toxicity due to Cassia occidentalis in vertebrates V.M. Vashishtha, T.J. John * & Amod Kumar ** Mangla Hospital, Bijnor, * Formerly Department of Clinical Virology, Christian Medical College, Vellore & ** Department of Community Health, St. Stephens Hospital, New Delhi, India Received July 8, 2008 Cassia occidentalis is an annual shrub found in many countries including India. Although bovines and ovines do not eat it, parts of the plant are used in some traditional herbal medicines. Several animal studies have documented that fresh or dried beans are toxic. Ingestion of large amounts by grazing animals has caused serious illness and death. The toxic effects in large animals, rodents and chicken are on skeletal muscles, liver, kidney and heart. The predominant systems involved depend upon the animal species and the dose of the beans consumed. Brain functions are often affected. Gross lesions at necropsy consist of necrosis of skeletal muscle fibres and hepatic centrilobular necrosis; renal tubular necrosis is less frequent. Muscle and liver cell necrosis is reflected in biochemical abnormalities. The median lethal dose (LD 50 ) is 1 g/kg for mice and rats. Toxicity is attributed to various anthraquinones and their derivatives and alkaloids, but the specific toxins have not been identified. Data on human toxicity are extremely scarce. This review summarizes information available on Cassia toxicity in animals and compares it with toxic features reported in children. The clinical spectrum and histopathology of C. occidentalis poisoning in children resemble those of animal toxicity, affecting mainly hepatic, skeletal muscle and brain tissues. The case-fatality rate in acute severe poisoning is 75-80 per cent in children. Key words Animal toxicity - Cassia occidentalis - poisoning children within several hours after eating the beans of C. occidentalis 3-8 . The exact toxin(s) involved are not known. For definitive diagnosis of a toxic disease the toxin has to be identified. Unfortunately, toxicological investigations in children with this syndrome have not been possible 4,5 . We have so far not been able to identify laboratories capable of and willing to investigate for detection and characterization of unspecified toxins. Although several toxicology laboratories were approached, none felt interested or confident to Indian J Med Res 130, July 2009, pp 23-30 Review Article 23
Transcript
Introduction
An acute illness of young children, with braininvolvementandhighcase-fatality,hasbeenplaguingSaharanpur and several neighbouring districts inwesternUttarPradesh(UP)overthepasttwodecadesormore1,2.Itoccursinannualseasonaloutbreaksandwasearlierdiagnosedpresumptivelyasacuteencephalitisofunknownviralaetiology1,2.Recentstudieshaveshownthe illness to be an acute hepatomyoencephalopathy(HME)syndrome,causedbytoxicityfromacommonweed, Cassia occidentalis3-8. The illness develops in
Mangla Hospital, Bijnor, *Formerly Department of Clinical Virology, Christian Medical College, Vellore &**Department of Community Health, St. Stephens Hospital, New Delhi, India
ReceivedJuly8,2008
Cassia occidentalis is an annual shrub found in many countries including India. Although bovines and ovines do not eat it, parts of the plant are used in some traditional herbal medicines. Several animal studies have documented that fresh or dried beans are toxic. Ingestion of large amounts by grazing animals has caused serious illness and death. The toxic effects in large animals, rodents and chicken are on skeletal muscles, liver, kidney and heart. The predominant systems involved depend upon the animal species and the dose of the beans consumed. Brain functions are often affected. Gross lesions at necropsy consist of necrosis of skeletal muscle fibres and hepatic centrilobular necrosis; renal tubular necrosis is less frequent. Muscle and liver cell necrosis is reflected in biochemical abnormalities. The median lethal dose (LD 50) is 1 g/kg for mice and rats. Toxicity is attributed to various anthraquinones and their derivatives and alkaloids, but the specific toxins have not been identified. Data on human toxicity are extremely scarce. This review summarizes information available on Cassia toxicity in animals and compares it with toxic features reported in children. The clinical spectrum and histopathology of C. occidentalis poisoning in children resemble those of animal toxicity, affecting mainly hepatic, skeletal muscle and brain tissues. The case-fatality rate in acute severe poisoning is 75-80 per cent in children.
Key words Animaltoxicity-Cassia occidentalis- poisoning
For definitive diagnosis of a toxic disease thetoxinhastobeidentified.Unfortunately,toxicologicalinvestigationsinchildrenwiththissyndromehavenotbeenpossible4,5.Wehavesofarnotbeenabletoidentifylaboratories capable of and willing to investigatefor detection and characterization of unspecifiedtoxins. Although several toxicology laboratorieswereapproached,none felt interestedorconfident to
In the absence of identified toxin(s) involvedin HME, the aetiological association is based onlyon epidemiological and observational studies4-8. Inordertoenhancethestrengthofevidenceforcausallyassociating C. occidentalis with HME, biologicalplausibility of such association will be helpful.Fortunately a large body of information is availableonclinicalfeaturesandontissuepathologyofCassiapoisoning in animals, due to accidental poisoning aswellasexperimentalstudies.
The weed: Cassia occidentalis
General features: The Cassia spp. (family:Fabaceaesae) are erect, lightlybranched leguminoustrees and shrubs. Cassia shrubs are usually 6 to 8feet tall andaremostlyannual,but somespeciesareperennial.AllCassiaspp.aretoxicorpoisonous,butC. occidentalisandC. obtusifoliaareconsideredtobemoretoxicthanothers9,10.
C. occidentalis is foundasaweedamongvariouscrops(Fig.).InEuropeitisfoundincornandsoybeanfields9.InIndiaitiswidelyprevalentasanopportunistthatgrowsalongroadsides,fencelinesandoverheapsofwastematerial,inadditiontoagriculturalfields9-11.InHindi, theweed isknownasPamaad (Panwaad) and Kasondi.Pamaadisactuallythenameofanothersimilar-looking weed, C. obtusifolia, found less frequentlythanKasondi.C. obtusifolia is lessprolific ingrowth,floweringandpoding10.
The leaves of C. occidentalis are alternate,compoundandpinnate,consistingoffourtofivepairsof leafletswidelyspacedalongacommonstalk.Theleafletsarepointedatthetips,incontrasttotheroundedleafletsofC. obtusifolia.Theflowersareyellowandproducedinlooseclustersintheterminalleafaxils9-11.InIndiathefloweringtimeisaftertheheavymonsoonrains(afterJuly)10.Thefruitsoftheplantareinformof‘pods’-thin,flat,3-4incheslongandpalegreenwhentender,thickanddarkgreenwhenmature.Thepodingtime is from September to November10-11. The podsareslightlycurvedandwithpalerlongitudinalstripesalongtheedges.Eachpodcontainsaround50-60smallbeans (seeds) together weighing 1.9 to 2.25 g. Eachbeanisaboutthesizeofacuminseed,butshorter.Thetender beans are green, soft and juicy and taste like
peas. From December onwards the pods start dryingup,turnbrownandthebeansturndarkbrown10.
Geographic distribution in India: Though C. occidentalisiswidelydistributedalloverthecountry,its density varies in different regions10. ApparentlyeveryIndianlanguagehasitsownvernacularnameforthisplant–forexample,inKeralaandTamilNaduitisknownasthakaraorponthakarai.Sincecattle,sheeporgoatsdonoteatthisplantpeoplerecognizeitasanunwantedweedandregularlyde-weedwhenitgrowsinagriculturalfields.Theweed’sdensityisparticularlyhighinandaroundwesternUP,Uttarakhand,Haryana,andPunjab,whereitgrowsluxuriantlyinallavailablespace,suchasneglectedgardens,roadsidesandunusedgroundsofpublicbuildingsincludinghospitals8.
Traditional medicinal uses: The leaves and roots ofC. occidentalis are used in some traditional herbalmedicines, but its pods or beans are avoided, orused sparingly10,12. Such medicines are considered as
General features: Several animal studies havedemonstratedthetoxicityofthefreshand/ordried/roastedbeans(seeds)9,11-23.Ingestionoflargeamountsoftheseedpodsbygrazinganimalshascausedseriousillness and death11,15,16. Cattle, sheep, goats, horses,pigs, rabbits, and chickens have been shown to besusceptibletopoisoningbyCassiaspp.13-21.Althoughallpartsoftheplantaretoxic,mostpoisoningoccurswhenanimalseatthepodsandbeans,orarefedgreen-chopcontainingCassia plants22,23.
The toxic effects are seen on skeletal muscles,liver, kidney and heart in animals11. The acute toxicdegenerationofliverandmusclescanberapidlyfatalinmostanimals11.Althoughclinicalevidenceofbraindisease is often present, not much studies has beendoneonbrainpathology.
One interesting attribute of C. occidentalispoisoninginanimalsisitspropensitytocausedifferentmanifestationsof toxicityindifferentanimalspecies.However,thephysiologicsystemsinvolvedintoxicitydepend also upon the dose of the beans consumed11.When the dose is low, the animal develops featuresofmildliverdamageandmyodegeneration.Athigherdoses, hepatic degeneration may be rapidly fatalbefore myodegeneration has time to develop14,16,23,24.GroundbeansofC. occidentalisfedtocattleatadoseof5.0g/kgoftheirbodyweightinduceseveremuscledegeneration25.Roastingofthebeanspartiallyreducestheirtoxicitysuchthatgoatsfed2.5g/kgbodyweightof roasted beans were unaffected, whereas unroastedbeansatthisdosagewerefatal18,19,22.
Cassiapoisoningincattlemayoccurwhen4.0to120.0g/kg(0.4-12%)ofbodyweightofthegreenplantiseaten23,25,26.Atlowerdoses,itcancausediarrhoeaanddecreasedweightgain22.Theplantisnotverypalatableandtendstoreducefeedintake.AstheamountofCassiain the animal’s diet increases muscle degenerationbecomesapredominantcharacteristicofthepoisoningand cause of the clinical signs. Experimentally, high
doses of the plant (10 g/kg body weight daily for 3days)induceacuteliverdegenerationanddeathbeforemyodegenerationhastimetodevelop11,13.
Apparently all toxic effects are acute and it isbelieved that the toxins do not accumulate in bodytissues. However, when consumed repeatedly overtime, the ill effectswouldbe seen as chronic, but infactitistheresultofrepeatedacutepoisoningduetotheinclusionofCassiavegetationinfreshgreenfeedinstallfedanimals.
Clinical presentations in animals: Lethargy, jerkyrespiration,tremor,ataxia,hyperpnea,diarrhoea,inco-ordinationandrecumbencyaretheusualmanifestationsof cassia toxicity in most animal species11. In cattlea moderate to severe diarrhoea develops shortlyafter consumption of the plant27. Abdominal pain,straining(tenesmus),anddiarrhoeaare thought tobeduetotheirritanteffectsofanthraquinonesinCassia spp. Depending on the amount of plant or seedsconsumed, muscle degeneration begins after severaldays, causing weakness and recumbency15,16,28,29.Theurinemaybecoffeecolouredduemyoglobinuriafromacute muscle degeneration13,27,30.The levels of serumenzymes creatine kinase and aspartate transaminaseareusuallymarkedlyelevated,reflectingacutemuscledegeneration. Renal failure may develop secondarilyto the myoglobinuria. In severe cases hepatic failuremay be the predominant organ failure leading todeathof theanimal30.Respiratorydifficultydevelopsas a result of the degeneration of the intercostal anddiaphragmmuscles17.Deathmayoccurwithin24-48haftersignsofacuteillnessandisalmostinevitableinanimals thatbecomerecumbent11. Inmoreprolongedsickness, cardiomyopathy and hyperkalemia frommuscle degeneration cause cardiac irregularities andcontributetothedeathoftheanimal21,22,25.
Horsesmaynotexhibit thedigestiveandmuscledegenerative signs of poisoning seen in cattle11,14.Myoglobinuriamaynotdevelopinhorsesbecausetheyapparentlysuccumbtoliverdegenerationsoonerthantothedegenerationofthemusculature11.Poisonedhorsesareseverelyataxicandmaydieearlywithoutshowingother clinical signs14. Serum liver enzymes may beelevatedreflectingacuteliverdegeneration11,14.
Postmortem lesions: Gross lesions at postmortemexaminationconsistprimarilyofpaleskeletalmusclesnecrotic foci similar to those seen in ‘white muscledisease’ associated with selenium and vitamin Edeficiency.Skeletalmusclenecrosisandrenaltubular
VASHISHTAet al:CASSIATOXICITYINVERTEBRATES 25
and hepatic centrilobular necrosis are characteristichistologicfindingsthatdifferentiateCassiapoisoningfrom vitamin E and selenium deficiency15,21,25.Confirmation of the diagnosis should be based onaccesstoandconsumptionofCassia spp.alongwiththe presence of degenerative lesions in the muscles,heart,andliver21,22,31.
Experimental studies on animals: Studies on rats32 andchickens33,34fedarationcontaminatedwithC. occidentalisseeds at different doses had shown histopathologicaland biochemical changes in muscles, liver, and centralnervoussystem.Barbosa-Ferreiraet al32divided40maleWistarratsintofourgroupsof10animalseach,threeofthemrespectively fed rationscontaining1,2and4percent C. occidentalis seeds, and the last one (control)fedcommercialrationforaperiodof2wk.Theratsofthe experimental groups showed lethargy, weakness,recumbency,depressionandemaciation.Histopathologicalstudyshowedfiberdegenerations in theskeletal (tibial,pectoralanddiaphragm)andcardiacmuscles.Intheliverparenchyma, was observed vacuolar degeneration and,inthekidney,mildnecrosisintheproximalconvolutedtubules. All of these alterations occurred in a dose-dependent fashion. Moderate to severe degenerationandspongiosiswasseen in thecentralnervoussystem,especially in cerebellum.Electronmicroscopy revealedmitochondriallesionsinallanalyzedtissues32.
Haraguchi et al33 studied the effects of 0.5, 0.3and0.1percentw/wconcentrationsofC. occidentalis seedsmixedwith commercial ration in18groupsof32broilerchickseach,from1dayto49daysofage.Allbirdswerekilledat49daysofage,andbloodwascollectedfrom10birdsineachgroupforbiochemicalstudies. A complete necropsy was performed on 3birds from each group. No significant differences inthebiochemical parameters in the serumwere foundbetweenthecontrolandexperimentalchicksgiven0.1percentof thebeans.Birds treatedwith0.5percentCassiabeansgainedlessweightthancontrols.Chicksthatreceived0.3or0.5percentCassiabeansdevelopeddegenerative changes in striated skeletal muscles,particularlypectoral,aswellasinthemyocardiumandliver33.
Flory et al34 evaluated feed grains suspected ofcausingdeathinagroupofpigsfortoxicpotentialinchickens.Thecontaminatedgrain (sorghummixture)wasexaminedvisuallyandwas found tocontain3.7percentC. occidentalisand1.6percentC. obtusifoliaseeds,byweight.Chickensreceivingthecontaminatedgrain lost weight rapidly, exhibited clinical signs
typical of intoxication with Cassia spp., and by day16wereseverelydebilitated.NecropsyandhistologicandelectronmicroscopicexaminationsdemonstratedaskeletalandcardiacdegenerativemyopathyconsistentwithtoxiceffectsofC. occidentalis34.
Lethal dose in animals: Thetoxicityofcassiaseed-podsis dose-dependent.The timeof appearanceof illnessanddurationare inverselyproportional to thedose24.Animal experimental studieshavecalculateda lethaldose(LD50)of1g/kgformiceandratswhenaqueousextractoftheplantwasinjectedintraperitoneally35.
Toxins and their actions: Several compounds thatbind strongly to cell membranes occur in Cassiaspp., but the specific toxin(s) responsible formuscledegenerationhavenotbeenidentified13,30,36.Whiletheexact toxic principles are yet to be defined, variousanthraquinones and their derivatives like emodinglycosides,toxalbumins,andotheralkaloidsareusuallyblamedforC. occidentalistoxicity9,12.
Originallyitwasthoughttobeduetouncouplingof oxidative phosphorylation in skeletal musclemitochondria. However, this was disproved sincemitochondrialdamagewasprecededbydegenerationofmyocardialfibers.Themostrecenttheoryindicatesa high blockade of electron transport, rather thanuncouplingofoxidativephosphorylation24,36.
Toxicity in humans
General features: There is no definitive study onhumantoxicityofC. occidentalis. Onlyafewreportson human toxicity are available. According to onereport, repetitive (prolonged) ingestion of a ‘healthdrink’madefromSennaextract(C. acutifolia- anotherherbofCassia genus)resultedinseverehepatotoxicityin an adult37. Another study mentions: “In humans,ingestion of Cassia occidentalis can cause severepurging.Whereas this may produce great discomfortandpain inadults, theresult inachildcanbedeath;hence,whileconsumptionoffewpodsmightnothaveanyilleffectinanadultorolderchild,itcanprovefatalfor a young child”38. However, no further details areavailableonthiscount.
Poisoning in children
Case scenario-1:Threeruralchildrenofajoinfamilyofdailywagesworkersconsumedbeansof C. occidentalisweedwhileplaying‘kitchengame’inthefieldwherethey cooked and consumed a ‘mock dish’.After sixhours of consuming the ‘dish’, the eldest of them,6yroldfemalechildstartedvomitinganddeveloped
The second child of the group, a 4 yr old boydevelopedvomitingandfevernextmorning.ThechildwastakentoManglaHospital,Bijnor,UttarPradesh. Atthetimeofadmission,thechildwasdrowsywithfrothingatmouthandup-rolledeyes,extremelyirritable-biting,scratchingclothsandbodyparts,protrudingandmovinghistongueandlipsinarepetitivestereotypedmanner,throwinghisarmsandlegsinajerky-fashion,buttherewasnofrankseizures.Thechildwaspale,non-icteric,B.P.was88/33/56mmofHg,liverwasjustpalpable,pupilsweredilatedbutreactingtolight,and‘doll’seyemovements’werepreserved.On investigation, serumglucose was 15.5 mg per cent, hemoglobin-12.1 gmpercent,totalleucocytecount(TLC)-3900/c.mmwith66percentpolymorphs,plateletcount-1.55lacs/cmm,serum ALT-3690 units/l, serum AST-3990 units/l,prothrombintime(PT)-24sec(control-13sec),partialthromboplastin time (PTT)-84 sec (control-44 sec),serum bilirubin- 1.8 mg per cent, serum creatinine-0.8mgpercent, creatinephosphokinase (CPK)-355U/Landserumlacticdehydrogenase(LDH)-646U/L,serumNa-136mEq/L,serumK-3.6mEq/L,andserumcalcium-8.2 mg per cent. The cerebrospinal fluid(CSF)examinationwasnormal.Thechildwastreatedwith10percentdextrose,intravenousvitaminK,orallactuloseandretentionenema,frequentbowelwashes,intravenous phenobarbitone, and other supportivetreatment.Thechilddevelopedmoderategradefever,irregularityofrespiration,circulatorycollapseanddiedafter14hofadmission.
The third sibling aged 3.5 yr was admitted 12 hafteradmissionofthesecondchildwithalmostsimilarcomplaintsofvomiting,fever,alteredsensorium,andmarked irritability. On examination, she was in lightcoma,febrile,pale,non-icteric,liverwasnotpalpable,peripheralpulseswerepalpable.Shewasalsotreatedonthesimilarlineaspreviouschildbutafter21hofadmissionshealsosuccumbedtotheillness.
Case scenario-2: A4year8montholdfemalechildofapoorfamilyof labourersconsumedbeansofC. occidentalisweedalongwithtwootherchildrenwhileplaying in thefields.This girl reportedly consumeda largeamountoffreshbeansandafterafewhoursstarted having vomiting, loose stools, fever, andabnormal movements of face. Later, she becameunconscious, developed respiratory irregularity and
abnormalposturingof trunk.Atthisstage, thechildwas brought to the hospital where she was foundpale,febrile,an-icteric,comatosewitheyeballsrolledupward, semi-dilated pupils reacting to light andslightlyenlargedliver.Thechildhadhistoryofpicain the past. Investigations revealed serum glucose-116.7mgper cent,Hb-9.0gmper cent,TLC-4500/cmm with 66 per cent polymorphs, p-count-1.92lacs/cmm, serum ALT-2030 U/L, AST-2160 U/L,serumbilirubin-2.4mg/dlwithdirect-1.3mg/dl,PT-18sec(control-13sec),PTT-76sec(control-44sec),serum CPK-246 U/L, serum LDH- 245 U/L, serumcreatinine-1.1mgpercent,andCSFexaminationwasnormal.Shewas treatedwith intravenousfluids, IVvitaminK,frequentbowelwashes, lactuloseenema,phenobarbitoneandothersupportivetherapy.Duringthe course of treatment she developed high gradefever, myoclonic jerks, irregularity of respiration,decerebrate posturing, fluctuation of BP, and diedafter64hofadmission.
Thetwootherchildren(aged4and6yrold)whohad also consumed cassia beans though in a smallerquantity,alsodevelopedsymptomsofvomiting,loosestools, fever, malaise, giddiness, drowsiness, changeinvoiceandbehaviour,anorexiaandsignsofgeneralweakness.Bothofthemwereadmittedfor24hinthehospitalandrecoveredcompletelyafter3-4days.
Young rural children aged 2-8 yr belonging topoor socio-economic strata seem to be particularlyvulnerable to the poisoning of C. occidentalis3-5. Ahistory of eating beans of C. occidentalis pods isavailableonlyoccasionallyatthetimeofpresentationas theactual incident isusuallynotwitnessedby theparentsandthereisaconsiderablelagperiod(rangingfrom few hours to a day) between consumption ofbeansandonsetofsymptoms4-8.
TheclinicalspectrumofC. occidentalispoisoninginchildrenresemblestoxicityinducedbytheplantinanimals.Thebeansarethemosttoxicpartoftheplantandchildrentendtoeatonlythebeansandnootherpart. As with animals, the clinical features dependupon the amount of beans eaten by the children.While consumption of the beans in 2-3 pods by ayoungchildmaynothaveanydeleterious impact,alarge‘binge’canleadtoseriousdiseaseanddeath4,5,38.Sincesomechildreneatvery fewbeansand remainasymptomatic, people have a tendency to considerthebeansasnon-toxic.Withalarger‘dose’,suchasthebeansin6-7pods,theydevelopanon-fatalillness
VASHISHTAet al:CASSIA TOXICITYINVERTEBRATES 27
with vomiting, loose stools, malaise, giddiness,drowsiness, change in voice and behavior, anorexiaandsignsofgeneralweakness.Thebodymaybewarmtotouch,interpretedbymanyasfever,butwhetherornotoralorrectaltemperaturerisesisnotknown.Theyusually recover after about 3-4 days of illness.Thefatal hepatomyoencephalopathy syndrome ensueswithrelativelylargeramountofbeans-suchaswhatwouldbeequaltoahandfulinthecuppedhandofachild-oracupfulinatoycup5.
The hepatomyoencephalopathy (HME) syndrome
The acute severe C. occidentalis poisoning inchildren affects multiple systems. Functional andbiochemical evidences to show toxic effect on thebrain, liver and striated muscles3-5. Pathologicallythere is acute onset massive zonal necrosis of liverand histopathology evidence of acute muscle fibredegeneration. The degenerative changes in the brainaremild,butbrainoedemaissevereandisbelievedtobe the immediatecauseofdeath3-5.WidefluctuationsofbloodpressureandriseinCK-MBfraction(creatinekinase- isoenzyme of cardiac muscle) of creatinine-phosphokinase (CPK) in some children point towardprobablemyocardialinvolvement3.
Inchildren,likeinmanyanimalspecies,massivehepaticdamagepredominate theclinicalpresentationwith concurrent brain oedema without inflammationor CSF pleocytosis, which closely resembles Reyesyndrome encephalopathy3,6,39. Clinically there isextreme irritability, various degree of brain functiondepressionrangingfrommereconfusiontodecerebratecoma3-8.Histopathologically,onlymildspongiosisandgliosiswithoutanyinflammationhavebeenreported3.Involvement of the brain appears to be secondary tomassive hepatic necrosis. Although liver enzymesare markedly raised, serum bilirubin level is usuallynormalandmostchildrenarenon-icteric3-6.LowserumandCSFglucoselevelsarefrequentfeaturesandserumammonialevelsareraisedintwo-thirdcases3.Allthesepointtowardsacuteandseverelivercellnecrosis.
As Reye syndrome is a well known clinicaldiagnosis40, and since liver enzymes are elevated inthatdiseaseaswellasinHME,thelatterwasearliermistaken for the former. InReye syndrome there isintracellular microvesicular fatty acid accumulationwithout necrosis, while in HME the pathologywas quite different, with massive, dose-dependentcentrilobularnecrosis-afeatureseenconsistentlyinmanyanimalspeciesuponnecropsy11,21,25,32,33.Raised
CPKandlacticdehydrogenase(LDH)levelsarethebiochemical clues of muscle degeneration3-6,8.Apartfrommyalgiaandmuscular twitching,clinicalsignsof myodegeneration are not very pronounced in illchildren.
HMEduetoCassiapoisoningisafataldiseaseinthemajority,inspiteofintensivecareandsupportivetherapy. The case-fatality ratio is 75-80 per cent inchildren who became comatose3-8. Most of them diewithinafewhourstoafewdays(variedfrom1to7days)ofconsumptionofcassiabeans4,5.
Summary and conclusions
On comparing clinical presentation, biochemicalalterations and histopathological changes of Cassia poisoning in children3-8, the very close similarity, ifnot identical to toxicity described in animals can beappreciated11,13-24. In different animal species, hepaticand skeletal muscles systems are mainly affectedin a dose-dependent manner. In some animals, themyocardiumisalsoaffected.Brainfunctionisaffectedduetoacutehepaticencephalopathy.
The similarity of reported clinical, laboratoryand histomorphological features of Cassia poisoningin animals11,13-24 and children along with a strongepidemiological association further strengthen thecausal association of C. occidentalis poisoning withthe acute hepatomyoencephalopathy syndrome inchildren3-5.
Since the specific toxin(s) remain unidentified,the disease cannot be named according to aetiology.Therefore it has been named as a syndrome. ThehighlytoxicnatureoftheputativephytotoxinspresentinC. occidentalis beansunderlies theurgentneed tolaunchmassiveeducationalcampaignstomakepeopleaware of the risk of children eating them. Childrenshould be given adequate common facilities andopportunities for playing, especially in overcrowdedcommunities.PicahasshownstrongcorrelationwithC. occidentalisconsumptionandneedstobediagnosedandtreatedintime.Longtermmeasuresareessentialfor improving economic conditions of marginalizedfamiliesinthevillages.Keytosuccessfulmanagementofecologyultimatelyliesinsafecoexistenceofhumanbeings and all plants including toxic weeds, such asC. occidentalis.Asaleguminousplantitisanitrogenfixer in thesoiland itneedsnotbe targeted for totalelimination.
28 INDIANJMEDRES,JULY2009
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