Progressive supranuclear palsy - like syndrome induced by amiodarone and flunarizine

Abstract

Progressive supranuclear palsy (PSP) is a taupathy of unknown etiology, representing 7.5% of all cases of Parkinsonism and 50% of atypical Parkinsonism 1,2 . It was first described as a clinicopathological entity by Steele, Richardson and Olszewski 3 in 1964. Clinically, PSP must be considered in any levodopa-unresponsive parkinsonian patient at middle-to-late age with progressive unexplained prominent postural instability with falls and supranuclear vertical gaze palsy 1,2 . The latter is characterized by limitation of upward, downward or lateral gaze, mainly downward. Other features are also important, such as: astonished face, retrocollis, lid freezing, monotonal speech, disartria, dysphagia, dementia and sloppy eaters 1,2 . We report a patient with signs and symptoms suggestive of PSP who markedly improve six months after discontinuation of amiodarone and flunarizine. CASEA 74-year-old Caucasian woman presented rapid progression of an akinetic-rigid syndrome, with frequent falls, and became wheelchair-bound after only four months. At the age of 77 she was first seen by one of the authors (JPM). At that time her medications were levothyroxin (50 mcg/day), captopril (75 mg/ day), trimetadizine (60 mg/day), levodopa + benserazide (600 + 150 mg/day), biperiden (4 mg/day) and amantadine (200 mg/ day). She has a past medical history of hypothyroidism, essential hypertension, ventricular tachycardia with low cardiac output and dizziness. She has taken amiodarone 400 mg/day and flunarizine 10 mg/day since the age of 73 which had been discontinued a month before her first visit. On neurological examination, she was unable to stand or walk without assistance, and she had chin tremor, severe symmetric limb bradikinesia, axial rigidity, dysarthria and marked dysphagia. There were no pyramidal or cerebellar signs, or autonomic failure. Eye movements were normal and vertical gaze was preserved as were cognitive functions. The MRI showed moderate cortical and subcortical atrophy and ventricular enlargement. At that time biperiden and amantadine were discontinued, and pramipexole and tolcapone were titrated up to 3 mg/day and 300 mg/day, respectively. She underwent a percutaneous endoscopic gastrostomy (PEG) after an episode of aspiration pneumonia. In spite of adequate doses of antiparkinsonian medication, there was no improvement in three months. In fact, there was further deterioration of her neurological condition with the presence of retrocollis, vertical and lateral gaze palsy, lid opening apraxia (lid freezing) and cognitive decline. All these features were suggestive of PSP. Pramipexole was discontinued due to side effects (edema and somnolence), and memantine was added up to 20 mg/day. After a few weeks she gradually improved, which was initially attributed to the memantine. After a five month interval with no news, surprisingly she reappeared with dramatic improvement in all her neurological features. She was able to walk without assistance, with slight postural instability. Mild asymmetric rigidity and bradikines...

Cinnarizine- and flunarizine-associated movement disorder: a literature review

“…Other commonly associated MD in descending order of frequency were akathisia, dyskinesia (orofacial, rabbit syndrome, choreoathetotic), and dystonia (oromandibular). Moreover, Mattos and colleagues reported a patient presenting with progressive supranuclear palsy like syndrome [102].…”