Treatment of Primary Progressive Freezing of Gait With High Doses of Selegiline Carlos Zu ´n ˜iga, MD, Jacobo Lester, MD, Marı ´a Graciela Cerso ´simo, MD, Sergio Dı ´az, MD, and Federico E. Micheli, MD, PhD Abstract: We report the case of a 76-year-old, right-handed woman with progressive primary freezing of gait. Despite several therapeu- tic strategies, she continued to worsen to the point that she became confined to a wheelchair. Treatment with selegiline in doses up to 20 mg/d led to marked improvement of the gait disorder. This case illustrates that selegiline can be an option for patients with freezing of gait other than those with Parkinson’s disease. Key Words: freezing, gait, selegiline (Clin Neuropharmacol 2006;29:20Y21) P rimary progressive freezing of gait (PFG) has been described as an isolated gait disorder where normal walking becomes magnetized and hesitant and the patient experiences multiple motor blocks, accompanied by postural instability and subsequent falls, leading to an important disability. Although these phenomena can be seen in many neurodegenerative diseases, PFG is free of other extra pyramidal signs in most cases. 1 Unfortunately, gait dis- turbances respond poorly to dopaminergic therapy. 2 Selegi- line is a monoamine oxidase type B inhibitor that has been successfully used for the symptomatic treatment of Parkin- son’s disease. 3 However, its usefulness in the treatment of other diseases is still unsettled. We report a case of PFG disorder with a marked response to high doses of selegiline. CASE REPORT This 76 year-old, right-handed woman with a history of left radical mastectomy and local radiotherapy (50 sessions) in 2002 because of cancer in her left breast was brought for an evaluation of a progressive gait disorder without cognitive decline. She has been on tamoxifen (20 mg/d) since then. In late 2003, she insidiously developed gait disorders, postural instability, and unsteady gait. Some months later, her gait was characterized by shuffling, as if she were Bstuck to the floor^ when she tried to walk. This picture grew progressively worse, until she became completely unable to walk. She was treated with levodopa/benserazide (step-up dose from 200/50 mg to 4 pills per day) and ropirinol (2 mg/d), without response. Several other therapeutic strategies failed to provide benefit. Because of her disability, she could walk only with the help of a walking stick during the early stages of her condition, and later, she was confined to a wheelchair. In December 2004, she was examined for the first time. On neurological examination, she was fully oriented to time and space and was cooperative; fundus occuli were normal and visual fields were full. Cranial nerves testing, including ocular movements, were normal. A significant magnetic gait without evidence of parkinsonian signs was evident. The remainder of the neurological examination was normal, and she was put on selegiline (10 mg/d). Four months later, the patient described a significant improvement in her gait, mainly when she was at home and became able to walk without a walking stick or any other aid. At that moment, the patient managed to walk on her own, with a walking stick, presenting occasional motor blocks, but no other disorder, on examina- tion. The daily selegiline dose was increased to 20 mg. Then, the patient described a highly significant improvement in her motor condition in the last months. The transient discontin- uation of selegiline resulted in marked worsening of gait, and the drug had to be reinstalled promptly. To date, no parkinsonian signs or any other nervous system disorders have been observed. Her brain magnetic resonance imaging scan was normal for her age, and no lesions of the basal ganglia were observed. DISCUSSION The symptoms observed in our patient are consistent with PFG, a rare disorder that presents in the elderly, causing an important functional disability with progressive worsening, leading to severe functional disability for the performance of the activities of daily living. Over the past few months, several therapies have failed to provide benefits, but treatment with selegiline resulted in marked functional improvement. In support, an attempt to discon- tinue selegiline was followed by a clear-cut worsening of symptoms within the following days, and treatment had to be restarted. Because of the low prevalence of FPG, treatment trials on this disorder are scarce. Freezing of gait has been more frequently studied in relation to parkinsonism than as a primary disease. Other treatment trials have been conducted for gait freezing, mainly with L-threo-dihydroxyphenylserine, 4 botulinum toxin applied on the soleusYgastrocnemius com- plex, 5Y7 and surgery, 8 with inconsistent results. Similar gait disorders had been observed in vascular parkinsonism, hydrocephalus, drug-induced parkinsonism, and other neurodegenerative diseases, including progressive CASE REPORT 20 Clin Neuropharmacol & Volume 29, Number 1, January - February 2006 Parkinson’s Disease and Movement Disorders Unit, Hospital de Clı ´nicas BJose ´ de San Martı ´n,[ Buenos Aires, Argentina. Reprints: Federico E. Micheli MD, PhD Juncal 1695- P 5 Dpto J (1062), Buenos Aires, Argentina (e-mail: Fmicheli@fibertel.com.ar). 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