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Emergencies and Critical Issues in Parkinson's Disease REVIEW Pract Neurol: first published as 10.1136/practneurol-2018-002075 on 19 August 2019. Downloaded from Emergencies and critical issues in Parkinson’s disease Cristina Simonet,1,2 Eduardo Tolosa,2,3 Ana Camara,2 Francesc Valldeoriola2,3 1Preventive Neurology Unit, ABSTRACT complications, especially in the inpatient Wolfson Institute of Preventive Complications from Parkinson’s disease may setting. Medicine, London, UK 2Neurology Department, develop over the disease course, sometimes Hospital Clinic de Barcelona, unexpectedly, and require prompt or even EMERGENCIES WITH PROMINENT Barcelona, Spain urgent medical intervention. The most common 3Neuroscience Department, AGGRAVATION OF PARKINSONISM OR are associated with aggravation of motor Institut d'Investigacions DYSKINESIAS symptoms; serious non- motor complications, Biomediques August Pi i Sunyer, Severe parkinsonism (hypokinesia) and Barcelona, Spain such as psychosis, orthostatic hypotension generalised hyperkinesia are common in or sleep attacks, also occur. Here we review Correspondence to people with Parkinson’s disease. These such complications, their clinical presentation, Professor Eduardo Tolosa, disabling motor syndromes usually precipitating factors and management, including Neurology, Hospital Clinic de develop in advanced disease, manifesting Barcelona, Barcelona 8036, those related to using device- aided therapies. as prominent fluctuations associated with Spain; etolosa@ clinic. ub. es Early recognition and prompt attention to these chronic levodopa therapy.3 Motor compli- critical situations is challenging, even for the Accepted 19 July 2019 cations are usually managed initially in an Published Online First Parkinson’s disease specialist, but is essential to outpatient setting but if severe may need 19 August 2019 prevent serious problems. hospitalisation. Rare cases can progress to fever and rhabdomyolysis, resembling neuroleptic malignant syndrome, and INTRODUCTION requiring intensive care unit treatment. People with Parkinson’s disease may develop acute and subacute complications Severe levodopa-related motor that are serious or even life- threatening, complications 1 and require prompt medical attention. Recurrent offs Some emergencies are intrinsic to the Almost everyone taking levodopa may http://pn.bmj.com/ disease, while others result from an inter- develop response fluctuations.4 They action of various medical and surgical typically appear after the so- called treatments with the disease process. These ‘honeymoon’ period, characterised by a conditions often present a diagnostic and favourable and stable levodopa response.5 management challenge. Motor fluctuations comprise recurrent Emergencies may result from motor episodes of parkinsonism (off periods) of on September 25, 2021 by guest. Protected copyright. deterioration, or there may be non- motor variable intensity that occur at different issues such as neuropsychiatric problems, times in relation to levodopa intake autonomic dysfunction syndromes and (wearing off, delayed-on, no-on, unpre- sleep disorders. Occasionally patients dictable off).3 need to be hospitalised and to receive In some patients, especially those with multidisciplinary care.2 Boxes 1 and 2 younger onset or those taking higher provide illustrative examples, drawn from doses of levodopa, motor fluctuations the literature and our experience. become severe, causing great discom- We also discuss complications relating fort.3 Severe off- related parkinsonism can © Author(s) (or their to device- aided therapies, such as deep- manifest with a wide range of symptoms, employer(s)) 2020. Re- use brain stimulation, levodopa- carbidopa especially severe tremor and unmanage- permitted under CC BY- NC. No intestinal gel and subcutaneous apomor- able freezing of gait. These episodes are commercial re- use. See rights and permissions. Published phine, since these are now frequently frequently associated with pain, profuse by BMJ. used in advanced Parkinson’s disease and sweating and tachycardia, abdominal To cite: Simonet C, Tolosa E, can have potentially serious complica- discomfort, and also psychiatric mani- Camara A, et al. Pract Neurol tions. We also make recommendations festations, particularly depression and 2020;20:15–25. to help clinicians minimise or prevent anxiety.6 Simonet C, et al. Pract Neurol 2020;20:15–25. doi:10.1136/practneurol-2018-002075 1 of 12 REVIEW Pract Neurol: first published as 10.1136/practneurol-2018-002075 on 19 August 2019. Downloaded from Box 1 Illustrative case of parkinsonism- Box 2 Illustrative case of acute psychosis hyperpyrexia syndrome An- 80- year old woman with Parkinson’s disease was A- 73-year old man with a 15- year history of Parkinson’s brought by her caregiver to the hospital emergency room disease was admitted for neurosurgical evacuation of trau- because of marked agitation and paranoid ideation. She matic subdural haematoma. His parkinsonism had deteri- had physically attacked a staff member at the nursing orated in the last 3 months despite high daily levodopa home where she had been recently placed. One year dosage (1200 mg). During the postoperative period, his earlier she developed visual hallucinations, initially well bradykinesia and rigidity markedly worsened. There was controlled with quetiapine (75 mg two times per day). In no clear improvement despite increasing the levodopa in the last 6 months she had developed frequent delusions combination with dopamine agonists in several presen- with loss of insight. On admission to the Neurology ward tations (oral, transdermal and subcutaneous). He became she was taking 300 mg per day of levodopa and quetiapine confused, febrile and diaphoretic. On examination, he had (125 mg per day). Her cognitive state was normal. Other marked generalised rigidity and bradykinesia. CT scan medical conditions known to cause acute psychosis were of head was normal. Other factors that may aggravate ruled out. Several treatment changes were tried. First, parkinsonism, such as addition of dopaminergic blockers, levodopa dose was halved without any significant motor and concurrent medical conditions, were ruled out. Blood worsening or improvement in hallucinations or delusions. tests showed high muscle enzyme levels and markers of In consequence, quetiapine was switched to clozapine acute renal failure. Response to dopaminergic therapy (12.5 mg per day), prompting improvement in psychiatric remained minimal. He later developed shortness of breath symptoms. In the end, levodopa was raised back to 300 mg and tachycardia. Pulmonary embolism was diagnosed and a day and clozapine was maintained. A few months later he was admitted to the intensive care unit. Levodopa was she had developed cognitive decline and rivastigmine was administered via a nasogastric tube and intense physio- added. therapy implemented with gradual improvement of his Learning points: Psychosis exacerbation after nursing home health status although daily functioning was still signifi- placement; loss of insight and delusions as severity markers; cantly impaired despite continuous dopaminergic therapy. before adding antipsychotic therapy for psychosis consider dopa- Learning points: Risk (advanced Parkinson’s disease taking high minergic drug reduction, especially in advanced disease stages; dose of levodopa) and contributor factors (recent surgery and after acute episode resolution check cognitive status. hospitalisation) to develop parkinsonism- hyperpyrexia syndrome; benefit of nasogastric levodopa administration in cases with an inappropriate oral intake; the relevance of paying attention to systemic complications. distribution, they can sometimes become generalised and interfere with sitting, walking and basic activities of daily living. This is more common in people with 3 http://pn.bmj.com/ The treatment aims to reduce off time and severity young- onset Parkinson’s disease. Patients then need by providing a more constant delivery of dopami- urgent interventions to prevent consequences, such nergic drug to the brain.6 By the time these prob- as falls and other injuries (ie, bone fractures). More- lems develop, patients are taking multiple doses of over, severe dyskinesias, both peak-dose or diphasic, levodopa and most have tried adjunctive treatments can occur at the end of the day in people taking slow- aiming to prolong levodopa effect: such adjuvant release formulations of oral levodopa, or in those 8 on September 25, 2021 by guest. Protected copyright. treatments include dopamine agonists, catechol- O- receiving levodopa- carbidopa intestinal gel infusions. methyltransferase (COMT) inhibitors, and mono- Treatment of dyskinesia is based on adjusting dopa- amine oxidase B (MAO) inhibitors. Changing the minergic treatments. Peak- dose dyskinesias usually levodopa dose through the day and adjusting the adju- improve with redistributing the total daily levodopa vant medications can minimise the fluctuations and intake into more frequent but smaller doses. Some make them more predictable.5 However, about 10% of patients need a lower total dose of levodopa (or patients have severe medically refractory fluctuations; lower dose of adjunctive therapies such as dopamine such patients require referral to specialised centres for agonists, COMT inhibitors or MAO inhibitors). If consideration of device- aided therapies.3 However, these measures fail, then it is worth considering aman- 7 age, cognitive status and the presence of psychotic tadine (300–400 mg daily). symptoms frequently limit the
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