The dangers of neuroleptic use in Parkinsonian-spectrum illnesses - management of emergent hypodopaminergic syndromes and catatonia

Abstract

IntroductionIn Parkinson disease (PD), the incidence of psychotic symptoms has an estimated rate of 25-30%, a cumulative long term prevalence rate of 60%, with visual hallucinations being the most common type of sensory hallucination. The use of high and low potency, antidopaminergic, antipsychotic medications (AP) have the potential to exacerbate motor symptoms of PD and precipitate neuroleptic malignant syndrome (NMS), neuroleptic malignant-like syndrome in PD known as Parkinson hyperpyrexia syndrome (PHS), and catatonia in at risk population. MethodsHere, we present a clinical case and a review of the current treatment modalities available for movement disorder emergencies in parkinsonian-spectrum illnesses (PSI). Patient was assessed by a multidisciplinary team, including neurology and a geriatric consult-liaison psychiatry service. ResultsThis is a case report of a 79-year-old man with no previous psychiatric history, an initial diagnosis of PD due to early emergence of tremors and motor symptoms responsive to levodopa-carbidopa (LC). This was followed by progressive cognitive impairments, delusional jealousy, and formed visual hallucinations, which prompted concern for cortical lewy body involvement. Pimavanserin was initiated for presumed diagnosis of Parkinson disease psychosis and ameliorated the frequency of visual hallucinations. Patient presented to the hospital for agitation and was positive for COVID-19 on admission; prior to this, he had missed doses of LC and was febrile per family. He received intramuscular haloperidol and ziprasidone for behavioral disturbances and subsequently developed delirium, severe VH's, elevated serum CK, diffuse rigidity, and hyperactive non-purposeful activity, raising concern for NMS.Emergent treatment included bromocriptine, lorazepam, and supportive measures; home dose of LC and pimavanserin were resumed after significant reductions in CK levels. Unfortunately, rigidity and delirium persisted leading to a prolonged hospitalization and requirement of a nasogastric tube for malnutrition. Neurology was concerned for PHS due to clinical overlap with NMS. Psychiatry consult-liaison service suspected protracted delirium and catatonia secondary to recent COVID-19 infection and neuroleptic use.Initial Bush Francis Catatonia Rating Score (BFCRS) was 22. Treatment trials of benzodiazepines, amantadine and memantine were unsuccessful due to adverse effects of excessive sedation, myoclonus, and increase aggression, respectively. Ultimately, bilateral, brief wave, electroconvulsive therapy (ECT) was initiated. Patient had improvements in increased alertness, executive speech, verbal comprehension, appetite, with BFCRS 6 by ninth ECT session, and was more attuned to his surroundings. After twelve ECT sessions and successful treatment of catatonia, despite some residual delirium, family felt comfortable caring for patient at their own home with supportive services. ConclusionThis case demonstrates the nebulous presentation of overlapping syndromes of delirium and catatonia - with NMS and PHS also in the differential - in the setting of acute COVID-19 infection and iatrogenic neuroleptic use in a patient with PSI. NMS and catatonia can be precipitated by dopaminergic blockade, while PHS is most encountered during dopaminergic withdrawal and intercurrent infections. Theorized pathophysiology is due to central dopamine hypofunction, leading to clinical features of altered consciousness, fevers, elevated serum CK, and parkinsonian exacerbation – all of which can be indistinguishable from the above-mentioned diagnoses. These syndromic illnesses appear to occur on an NMS-like spectrum, are a neurological emergency and necessitate prompt treatment with supportive measures, intensive care level monitoring, and restoration of the dopaminergic balance with LC, bromocriptine, and dantrolene. ECT has shown to improve both motor and psychotic symptoms in PD, should be first line in NMS, malignant and benzodiazepine-refractory catatonia, and has even demonstrated effectiveness in a case report of PHS. ECT could be the ideal next step in exacerbated movement disorder emergencies following medication trials and supportive measures. However, the evidence is limited and the logistical nuances of conducting a randomized controlled trial in the geriatric population would be ethically challenging.