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Deletion in the tyrosine hydroxylase gene in a patient with a mild phenotype
Author(s) -
Ormazabal Aida,
Serrano Mercedes,
GarciaCazorla Angels,
Campistol Jaume,
Artuch Rafael,
Castro de Castro Pedro,
BarredoValderrama Estíbaliz,
Armstrong Judith,
Toma Claudio,
Cormand Bru
Publication year - 2011
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.23564
Subject(s) - tyrosine hydroxylase , phenotype , gene , tyrosine 3 monooxygenase , tyrosine , content (measure theory) , genetics , psychology , neuroscience , biology , biochemistry , dopamine , mathematics , mathematical analysis
We present two cases of parkinsonism secondary to adalimumab, a tumor necrosis factor a (TNF-a) inhibitor. Case 1: A 30-year-old woman with rheumatoid arthritis (RA) was started on adalimumab 40 mg monthly, which was increased to 40 mg weekly after 7 months. Within days, she developed gait disturbance, bradykinesia, and cognitive slowing. Brain magnetic resonance imaging (MRI) revealed increased signal in the globus pallidus, putamen, and internal capsule, extending into the subthalamic region (Fig. 1A) with faint putamenal enhancement (Fig. 1B), suggestive of toxic, metabolic or inflammatory causes. Cerebral angiogram showed no evidence of vasculitis. Cerebrospinal fluid examination was normal. The patient continued to deteriorate, and developed urinary incontinence, freezing of gait and falls. High-dose methylprednisone resulted in no improvement. Examination revealed prominent parkinsonian features, including bilateral rigidity and bradykinesia (Video Segment 1). She scored 50 on the motor part of the Unified Parkin-son's Disease Rating Scale (UPDRS). Adalimumab was discontinued and carbidopa/levodopa was started. She improved and was able to walk independently without freezing after 4 months. Her UPDRS motor score improved to 28 (Video Segment 2). L-dopa was ceased due to nausea, with no worsening of parkinsonism. A repeat brain MRI performed 8 months after the initial scan revealed significant resolution of the high signal changes (Fig. 1C,D). Her symptoms resolved over the next 3 years. Case 2: A 31-year-old woman with ankylosing spondylitis was referred for evaluation of arm and leg stiffness causing difficulties with hand dexterity and walking, which developed after treatment with adalimumab 40 mg every 2 weeks for 11 months. She experienced recurrent episodes of right-sided painful toe curling. Examination revealed predominantly right-sided cogwheel rigidity and bradykinesia. MRI of the brain was normal. Ceruloplasmin and copper levels were normal. Carbidopa/L-dopa was started. Although her symptoms have improved, reduction in medication resulted in worsening of bradykinesia and rigidity, and she has remained on L-dopa/ carbidopa 50/200 mg three times per day. Although the use of inhibitors against TNF-a has advanced the treatment of several inflammatory conditions, troublesome adverse effects associated with these drugs have emerged. We describe two women who developed parkinsonism following adalimumab use. The first case was associated with abnormal radiological findings. The second case was associated with dystonia. There was no significant family history. The cause-and-effect relationship between adalimumab and parkinsonism was supported by the onset after the introduction or increased dosages of the drug in both cases, improvement when the drug …