ORIGINAL CONTRIBUTION Pharmacological Therapy in Progressive Supranuclear Palsy K. Kompoliti, MD; C. G. Goetz, MD; Irene Litvan, MD; K. Jellinger, MD; M. Verny, MD Background: To our knowledge, previous reports on ticholinergics and selective serotonin inhibitors (1 pa- drug treatment in progressive supranuclear palsy have tient). Positive clinical response was detected in 7 of the not evaluated autopsy-confirmed cases. patients receiving dopaminergic drugs and in 1 patient each receiving tricyclics, methysergide, and 5-hydro- Objective: To evaluate pharmacological treatment re- xytryptophan, respectively. None of the patients re- sponses from detailed clinical records in patients with sponded markedly however, and there was no persis- autopsy-confirmed progressive supranuclear palsy. tent beneficial effect. Use of dopaminergic drugs most frequently improved parkinsonian features, but dis- Subjects and Methods: We reviewed medical records abling adverse effects included orthostatic hypotension for clinical presentation and pharmacological response (6 patients), hallucinations and delusions (3 patients), in 12 patients with autopsy-confirmed progressive supra- gastrointestinal complaints (3 patients), and dizziness nuclear palsy diagnosed using the National Institute of Neu- (1 patient). Only 1 patient developed dyskinesia. rological Disorders and Stroke pathologic criteria. For each drug class, exposure, global positive response, and specific Conclusion: Use of antiparkinsonian medications and positive response (parkinsonism, other movement disor- other neurotransmitter replacement therapies was largely ders, or gaze dysfunction) were recorded. ineffective and caused frequent adverse effects in this se- ries of patients with autopsy-confirmed with progres- Results: Drug classes examined were dopaminergics (all sive supranuclear palsy. patients), tricyclics (3 patients), methysergide maleate (3 patients), 5-hydroxytryptophan (2 patients), and an- Arch Neurol. 1998;55:1099-1102 ROGRESSIVE supranuclear response and detailed clinical records palsy (PSP) is a neurodegen- in a series of patients with autopsy- erative disease character- confirmed PSP assessed by specialists of ized by parkinsonism with movement disorder. prominent axial involve- Pment and postural reflex abnormality, bul- RESULTS bar symptoms, supranuclear ophthal- moplegia, and higher cortical dysfunction. The mean age of the 12 patients was 64 Dysfunction of multiple brain systems has years at onset of symptoms (range, 53-70 complicated attempts to treat the dis- years). Parkinsonism and ocular signs were ease. In PSP there is involvement of the present in all patients, bulbar signs and From the Rush-Presbyterian-St dopaminergic, cholinergic, GABAergic higher cortical dysfunction in 11 patients, Luke’s Medical Center, (g-aminobutyric acid), and to a lesser de- other movement disorders in 10, pyrami- Chicago, Ill (Drs Kompoliti and gree of the serotonergic and noradrener- dal signs in 2, and other signs in 1 patient Goetz); Neuroepidemiology gic systems.1,2 Pharmacological therapy (Table 1). Branch, National Institute of has focused on the manipulation of the Of the parkinsonian signs, bradyki- Neurological Disorders and central dopaminergic,3-6 cholinergic,7-12 nesia, rigidity, and gait abnormalities were Stroke, National Institutes of serotonergic,3,4,13,14 and more recently, nor- present in all, while tremor was found in Health, Bethesda, Md adrenergic systems.15 The clinical over- only 2 of 12 patients. All patients had su- (Dr Litvan); Ludwig Boltzmann Institute of Clinical lap of PSP with other neurodegenerative pranuclear gaze abnormalities, with 2 hav- Neurobiology, Vienna, Austria syndromes is significant, making conclu- ing additional ocular signs, consisting of (Dr Jellinger); and Hoˆpital sions regarding medication responses ten- blepharospasm, which was associated in Charles Foix, Paris, France tative. To identify putatively effective phar- 1 of the patients with eyelid retraction. One (Dr Verny). macotherapies, we assessed clinical patient developed delusional thinking ARCH NEUROL / VOL 55, AUG 1998 1099 ©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 Table 1. Progressive Supranuclear Palsy: Clinical Features* PATIENTS AND METHODS Clinical Features No. of Patients Parkinsonism (n = 12) We collected clinical information on 12 patients from Bradykinesia 12 the Salpe`trie`re Hospital, Paris, France, and the Lud- Rigidity 12 wig Boltzmann Institute of Clinical Neurology, Vi- Tremor 2 enna, Austria. The diagnosis of PSP was made by 2 Gait problems 12 neuropathologists according to the National Insti- Ocular signs (n = 12) tute of Neurological Disorders and Stroke neuro- Supranuclear 12 pathologic criteria for typical PSP.16,17 Other 2 We reviewed the complete medical records of Bulbar function (n = 11) these 12 patients with regard to clinical presenta- Dysarthria 11 tion and response to dopaminergic therapeutic ma- Dysphagia 11 nipulations and exposure to other drugs. The data Both 11 were collected by the primary investigator (K.K.). Higher cortical function (n = 11) Signs were categorized into the following domains: Dementia 11 parkinsonism (at least 2 of bradykinesia, rigidity, Palilalia 7 tremor, and gait abnormalities), other movement dis- Frontal signs 2 orders (dystonia or myoclonus), gaze difficulties, bul- Delusions 1 bar signs, higher cortical signs, pyramidal signs, and Other movement disorders (n = 10) other. Minimal criterion for improvement was im- Dystonia 10 Axial 8 provement in at least 1 domain. Improvement or de- Neck 7 terioration were classified as either absent, modest, Both 6 or marked. Trismus 1 Myoclonus 1 Pyramidal (n = 7) Hyperreflexia 7 Other (n = 1) while receiving a stable dose of levodopa (400 mg/d) in Orthostatic hypotension 1 conjunction with a peripheral decarboxylase inhibitor for many months before the onset of the psychotic phenom- *N = 12. ena. Table 1 shows detailed information of the clinical presentation of this group of patients. The latter consisted of vertical supranuclear gaze palsy. All 12 patients received 1 or several types of dopa- The dyskinesias were observed toward the end of the 2- minergic medication. Treatment was initiated, on aver- year treatment with levodopa, were confined to the face, age, 2 years after onset of symptoms. Improvement from and lasted 2 to 4 months, resolving following discon- 1 dopaminergic agent did not predict response to the other tinuation of levodopa. Subsequently, therapy with bro- dopaminergic agents administered subsequently. Eleven mocriptine mesylate was initiated but without clinical re- received levodopa with a peripheral decarboxylase in- sponse. The patient succumbed to his disease 5 years from hibitor, 6 an agonist, and 5 amantadine (Table 2). Seven onset of symptoms. experienced clinical improvement. Levodopa with a pe- Dopamine agonists were given mostly in the form ripheral decarboxylase inhibitor produced improve- of bromocriptine, except for 1 patient who received piribe- ment in 4 of the 11 patients. This improvement was dil at a dosage of 1250 mg/d for 6 months. This treat- marked in 1 patient and modest in the other 3 patients. ment produced modest improvement of parkinsonism in The features improving were parkinsonism in 4 pa- 1 patient and marked deterioration of the primary con- tients, and dystonia and supranuclear gaze palsy in 1 pa- dition in another patient. tient, respectively. The patient who experienced im- Five patients received amantadine and 2 demon- provement of gaze palsy was treated with levodopa and strated questionable improvement of parkinsonism (both a peripheral decarboxylase inhibitor (400 mg/d of le- patients) and neck dystonia (1 patient). Three patients vodopa) 2 years after onset of disease. The improve- complained of deterioration of their primary condition, ment lasted 3 months. While receiving levodopa therapy, which was modest in 2 and marked in 1. Other medica- 4 patients experienced exacerbation of parkinsonism, bul- tions used were tricyclic antidepressants and methyser- bar symptoms, and higher cortical dysfunction, and 2 ex- gide in 3 patients, 5-hydroxytryptophan in 2, selective perienced exacerbation of supranuclear gaze palsy. serotonin reuptake inhibitors, anticholinergics, and mi- The patient with the levodopa-induced dyskine- anserin hydrochloride in 1 patient each. The tricyclic an- sias was initially diagnosed as having idiopathic Parkin- tidepressants used were amitriptyline hydrochloride in son disease and was started on a regimen of levodopa and 1 patient and chlomipramine in 2 patients. The patient a peripheral decarboxylase inhibitor 1 year after onset receiving amitriptyline experienced modest improve- of symptoms. He experienced a 60% improvement in re- ment of his parkinsonism. sponse to levodopa treatment and this remained stable Three patients received methysergide with modest for 2 years requiring dose increments in regular inter- clinical improvement in one and worsening of the un- vals. Postural instability and falls first occurred 2.5 years derlying condition in another. The elements that im- and supranuclear gaze impairment 3 years after onset. proved were parkinsonism and dystonia and the wors- ARCH NEUROL / VOL 55, AUG 1998 1100 ©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 Table 2. Exposure to Medications and Specific Areas of Improvement* Duration of Improvement