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Parkinsonism Hyperpyrexia Syndrome Caused by Abrupt Withdrawal of Ropinirole

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Parkinsonism Hyperpyrexia Syndrome Caused by Abrupt Withdrawal of Ropinirole Case RepoRt Parkinsonism hyperpyrexia syndrome caused by abrupt withdrawal of ropinirole Introduction worseningofparkinsonism.Highfeveris the impact that elevated serotonin levels Theparkinsonismhyperpyrexiasyndrome themostfrequentclinicalmanifestationof have on lowering dopamine levels. isararebutpotentiallyfatalcomplication parkinsonismhyperpyrexiasyndrome,fol- Serotonin syndrome may resolve quickly seeninpatientswithParkinson’sdisease.It lowedbyworseningofparkinsonismand butcanbepotentiallyfatal.Likeparkin- ischaracterizedbymentalstatuschanges, thenalteredlevelsofconsciousness. sonismhyperpyrexiasyndrome,therarity muscle rigidity, hyperthermia and auto- Levenson (1985) suggested a defini- and seriousness of serotonin syndrome nomicdysfunction.Mortalityofupto4% tionofneurolepticmalignantsyndrome precludes large randomized trials (Mills, hasbeenreportedbutanadditionalone- using the sum of three major or two 1997). thirdofpatientshavepermanentsequelae. major and four minor criteria in an Rapidly switching between dopamine Thetreatingphysicianshouldbemindful appropriateclinicalsetting(Table 1)and agonists may also lead to parkinsonism oftwoverysimilarandseriousconditions: thesecriteriacanalsobehelpfulindiag- hyperpyrexia syndrome as does dehydra- neurolepticmalignantsyndromeandsero- nosinganeurolepticmalignant-likesyn- tionandmetabolicdisturbances.Thedose toninsyndrome. drome condition, i.e. parkinsonism ofropinirolethatthispatientwasonpre- Parkinsonism hyperpyrexia syndrome hyperpyrexiasyndrome. eventwaslowandthepreparationalong- maybeindistinguishablefromneuroleptic Themajordifferentialdiagnosisissero- acting one (starting dose is 2mg once malignantsyndromeexceptthatitoccurs tonin syndrome and the differences are daily),indicatingthatacuteillness,rapid in patients with pre-existing parkinson- highlighted in Table 2. Serotonin syn- changes in the Parkinson’s disease treat- ism and is often referred as neurolep- drome may have additional clinical fea- ment regimen and dehydration might tic malignant-like syndrome. This is the tures such as myoclonus, hyperreflexia, have contributed to the development of first reported case where withdrawal of seizuresandmoodalteration(restlessness, parkinsonismhyperpyrexiasyndrome. the dopamine-receptor agonist ropinirole elevatedmood).Thisoverlapmayrelateto Althoughwithdrawaloflevodopaisstill alonehasledtoparkinsonismhyperpyrex- themostcommoncauseofparkinsonism iasyndrome,despitethepatientcontinu- Table 1. Diagnostic criteria for hyperpyrexiasyndrome,otheragentscan ing to take levodopa and a monoamine neuroleptic malignant syndrome be implicated, including amantadine, oxidaseinhibitor. dopamine agonists and catechol-O- Criteria Feature methyl-transferaseinhibitors(Kippsetal, Discussion 2005). Major Fever, rigidity, and elevated creatine Parkinsonismhyperpyrexiasyndromeisa kinase level An EMBASE search performed by the neurolepticmalignant-likesyndromeseen ropiniroledrugmanufacturerinJuly2013 inpatientswithParkinson’sdisease.Itisa Minor Tachycardia, abnormal blood pressure, specifically to check for ropinirole with- rare(0.3%ofParkinson’sdiseasepatients/ tachypnoea, altered consciousness, drawalfeaturesdidnotyieldanyreference diaphoresis and leukocytosis year)butapotentiallylethalformcharac- toparkinsonismhyperpyrexiasyndrome. terized by mental status changes, muscle rigidity,hyperthermiaandautonomicdys- Case Report function(NewmanandGrosset,2009). A 67-year-old man with an 8-year history of Parkinson’s disease was admitted with an episode of Parkinsonismhyperpyrexiasyndromeis collapse at home. He was found to have postural hypotension and nitrite-positive urine dip. The labile under-reported,partlybecausetheclinical blood pressure was attributed to his multiple anti-parkinsonian medications (4 mg ropinirole once a day, and laboratory features are non-specific. 100/25 mg co-careldopa 5 times a day and 10 mg selegiline once a day). He only received trimethoprim Mildcasesmaybemislabelledassepsisor for his urinary tract infection and no new medication was added. During the admission his ropinirole was Dr Alok Arora is Acute Medical Registrar in tapered off over 3 days. the Department of Acute Medicine, Frenchay Three days post admission the patient was found in a ‘confused, rigid and hallucinating’ state with Hospital, North Bristol Hospitals NHS Trust, a temperature of 40.2°C. He had increased tremor and stiffness, profuse sweating, tachypnoea and Bristol BS16 1LE and Dr Peter Fletcher is tachycardia. Review of his drug chart and collateral history from the nursing staff confirmed his adherence Consultant Geriatrician in the Department to his usual anti-Parkinson’s disease medications during his hospital stay. of Elderly Care, Cheltenham General A diagnosis of parkinsonism hyperpyrexia syndrome was made. He was cooled via external ice packs Ltd Hospital, Gloucestershire Hospitals NHS and cold intravenous saline. A nasogastric tube was inserted, an additional dose of his usual co-careldopa Foundation Trust, Cheltenham was given and ropinirole was restarted. The creatine kinase was 845 U/litre (50–200 U/litre) and urine Healthcare showed blood on dipstick. The patient started recovering over the next few hours and his muscle tone and MA Correspondence to: Dr A Arora temperature returned to baseline over the next few days. 2013 ([email protected]) © 698 BritishJournalofHospitalMedicine,December2013,Vol74,No12 Case RepoRt clinically significant distress or social or Table 2. Comparison of neuroleptic malignant and similar syndromes occupationaldysfunction,arerefractoryto (parkinsonism hyperpyrexia syndrome) and serotonin syndrome levodopa and other Parkinson’s disease medications,andcannotbeaccountedfor Neuroleptic malignant syndrome Serotonin syndrome by other clinical factors (Rabinak and Onset Acute (minutes to hours) Sub-acute (days) Nirenberg,2010).BJHM Resolution Gradual (average 9 days) Improves in <24 hours Physical examination Altered sensorium (90%) Altered sensorium (50%) FactorSA(2007)FatalParkinsonism-hyperpyrexia syndromeinaParkinson’sdiseasepatientwhile Muscle rigidity (90%) Muscle rigidity (50%) activelytreatedwithdeepbrainstimulation.Mov 22 Autonomic dysfunction (90%) Autonomic dysfunction (50–90%) Disord (1):148–9 KippsCM,FungVS,Grattan-SmithPetal(2005) Hyperthermia (90%) Movementdisorderemergencies.Mov Disord 20(3):322–34 Laboratory Elevated creatine kinase level (90%) Elevated creatine kinase level (20%) KonagayaM,GotoY,MatsuokaYetal(1997) abnormalities Neurolepticmalignantsyndrome-likeconditionin Elevated hepatic transaminase levels (75%) Elevated hepatic transaminase levels (10%) multiplesystematrophy.J Neurol Neurosurg Psychiatry63:120–1 Leukocytosis (90%) Leukocytosis (15%) LevensonJL(1985)Neurolepticmalignant From Mills (1997) syndrome.Am J Psychiatry142(10):1137–45 MillsKC(1997)Serotoninsyndrome:aclinical update.Crit Care Clin13(4):763–83 Parkinsonism hyperpyrexia syndrome Dopamineagonistwithdrawalsyndrome NewmanEJ,GrossetDG(2009)Theparkinsonism- has also been reported in patients with isdefinedasasevere,stereotypedclusterof hyperpyrexiasyndrome. Neurocrit Care 10(1): atypicalparkinsonism,forexamplemulti- physicalandpsychologicalsymptomsthat 136–40 RabinakCA,NirenbergMJ(2010)Dopamine plesystematrophyandprogressivesupra- correlates with dopamine agonist with- agonistwithdrawalsyndromeinParkinson’s nuclearpalsy(Konagayaetal,1997).Itis drawalinadose-dependentmanner,causes disease.Arch Neurol 67(1):58–63 importanttonotethatdeepbrainstimula- tion does not protect the patient from parkinsonism hyperpyrexia syndrome Learning Points (Factor,2007). n Any elevation of body temperature during the course of anti-parkinsonian drug treatment should be Medical complications of parkinsonism considered as parkinsonism hyperpyrexia syndrome until proven otherwise. hyperpyrexiasyndromecanbechronicand n This is the first reported case of parkinsonism hyperpyrexia syndrome associated with withdrawal irreversible, including renal failure from of ropinirole alone and highlights the fact that parkinsonism hyperpyrexia syndrome can develop rhabdomyolysis, respiratory failure from despite the use of other anti-Parkinson’s disease drugs. Parkinsonism hyperpyrexia syndrome has decreasedchestwallcompliance,aspiration been reported with withdrawal of other dopamine agonists and non-dopaminergic medications. pneumonia, and other complications of n In a patient who is ‘nil by mouth’ a nasogastric tube must be placed to administer regular immobility(NewmanandGrosset,1999). Parkinson’s disease medications. The rotigotine transdermal patch and apomorphine as subcutaneous More recently, dopamine agonists have injections are other options. beenshowntoproducebehaviouraladdic- tions,withanestimated14–17%combined n The monoamine oxidase-B inhibitors such as selegiline should be used with caution when combined prevalenceofimpulsecontroldisorderssuch with other antidepressants, including tricyclics and selective serotonin-reuptake inhibitors, because of as pathological gambling, compulsive eat- the risk of causing serotonin syndrome. ing,compulsivebuying,andhypersexuality n Dopamine agonists have a stereotyped withdrawal syndrome that can lead to profound disability in indopamineagonist-treatedpatientsforall a subset of patients. indications(e.g.restlesslegssyndrome). Forthcoming case reports Erythroderma is not all psoriasis: a case of Sézary syndrome Recurrent pneumonia as a result of Mounier–Kuhn syndrome Ltd Audio-vestibular impairment presented as a portent of vertebrobasilar infarction A near death experience Healthcare MA An isolated mid-facial swelling: a cause for an ear, nose and throat referral? 2013 © BritishJournalofHospitalMedicine,December2013,Vol74,No12 699 Copyright of British Journal of Hospital Medicine (17508460) is the property of Mark Allen Publishing Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use..
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