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Levodopa‐Induced Nocturnal Stereotypies with Logorrhea in a Patient with Parkinson's Disease

2015; Wiley; Volume: 2; Issue: 3 Linguagem: Inglês

10.1002/mdc3.12150

2330-1619

Francesca Antonelli, Joan Santamaría, Eduardo Tolosa,

Genetic Neurodegenerative Diseases

Movement Disorders Clinical PracticeVolume 2, Issue 3 p. 301-303 Case ReportFree Access Levodopa-Induced Nocturnal Stereotypies with Logorrhea in a Patient with Parkinson's Disease Francesca Antonelli MD, Francesca Antonelli MD Movement Disorder Unit, Neurology Service, Hospital Clínic Barcelona, Barcelona, SpainSearch for more papers by this authorJoan Santamaria MD, Joan Santamaria MD Sleep Unit, Hospital Clinic Barcelona, Barcelona, Spain IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Barcelona, SpainSearch for more papers by this authorEduardo Tolosa MD, FRCP, Corresponding Author Eduardo Tolosa MD, FRCP Movement Disorder Unit, Neurology Service, Hospital Clínic Barcelona, Barcelona, Spain IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Barcelona, SpainCorrespondence to: Professor, Eduardo Tolosa, Unitat de Parkinson i Trastorns del Moviment, c/Villaroel 171, 08036 Barcelona, Spain; E-mail: etolosa@clinic.ub.esSearch for more papers by this author Francesca Antonelli MD, Francesca Antonelli MD Movement Disorder Unit, Neurology Service, Hospital Clínic Barcelona, Barcelona, SpainSearch for more papers by this authorJoan Santamaria MD, Joan Santamaria MD Sleep Unit, Hospital Clinic Barcelona, Barcelona, Spain IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Barcelona, SpainSearch for more papers by this authorEduardo Tolosa MD, FRCP, Corresponding Author Eduardo Tolosa MD, FRCP Movement Disorder Unit, Neurology Service, Hospital Clínic Barcelona, Barcelona, Spain IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Barcelona, SpainCorrespondence to: Professor, Eduardo Tolosa, Unitat de Parkinson i Trastorns del Moviment, c/Villaroel 171, 08036 Barcelona, Spain; E-mail: etolosa@clinic.ub.esSearch for more papers by this author First published: 28 March 2015 https://doi.org/10.1002/mdc3.12150Citations: 1 Relevant disclosures and conflicts of interest are listed at the end of this article. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat We describe a patient with Parkinson's disease (PD) who presented an unusual nocturnal behavior characterized by hyperkinesias and logorrhea, associated with levodopa overdose. Careful clinical evaluation and video polysomnography (vPSG) were useful for adequate characterization of the problem and its subsequent management. A 77-year-old woman with PD reported during an outpatient clinic visit difficulty sleeping. She had been diagnosed as having PD 8 years previously, and treatment with rasagilina 1 mg and l-dopa 100 mg in 3 divided doses had been started 1 year after diagnosis with good response. Four years after onset of l-dopa therapy she developed l-dopa-induced dyskinesias and later predictable wearing off, requiring an increase of l-dopa up to 900 mg a day (300 mg three times a day). Because of progressive worsening of her mobility associated with gait instability, during the previous year the caregiver had increased, without consulting with the patient's physician, the daily dosage of l-dopa up to 1,800 mg/day (600 mg three times a day). At the time of the current outpatient clinic visit, her caregiver described that during the night, for the last few months, the patient talked incoherently and presented, at the same time, incessant body movements. These behaviors usually started in the evening and continued well into the middle of the night until she fell asleep. In the evening, they occurred while sitting in a chair and later while in bed irrespective of whether the lights of the room were turned on or off. These problems had gradually intensified, were a cause of concern, and seriously interfered with the sleep of both the patient and the caregiver. At the time of the outpatient visit, the patient was alert and oriented. She had no cognitive complains and the Montreal Cognitive Assessment score was of 28/30, falling in attention and delayed recall. She was on a wheelchair and had mild-to-moderate dysarthria as well as global bradykinesia. She was able to stand up alone, however with marked instability (H & Y stage 4). In order to characterize the patient's behavior, the patient was admitted to the hospital, where we administered the same medications she had been taking at home. In the early morning, after an overnight OFF, she was alert and oriented and able to sustain a normal conversation. She was unable to get up from bed because of marked global slowness and postural instability. There was moderate left-hand rest tremor and moderate-to-severe rigidity of her extremities. Two hours after the first dose of l-dopa (600 mg), when she was in her best ON, we observed a global improvement of bradykinesia and tremor, but not of the postural reflexes. In the afternoon, the patient turned ON 2 hours after a 600-mg dose of levoldopa (the second dose of the day) and later developed typical choreiform dyskinesias of the trunk, arms, and legs (see Video, Segment 1). Late in the evening (7 pm), while still having dyskinesias, she started speaking intermittently in an incoherent fashion. She remained alert and oriented, though, and was able to answer appropriately to any questions and denied hallucinations. At 9 pm, she was given the last scheduled l-dopa dose of 600 mg, and at 10 pm a vPSG was started. From 11 pm onward, the choreic movements gradually disappeared while stereotyped involuntary movements appeared occurring periodically every few seconds. These movements involved mostly the trunk and the neck, resembling body rocking movements. To a lesser extent, they involved also the legs and both feet with repeated movements of dorsiflexion of the toes with partial flexion of the ankle and the knee (see Video, Segment 2). During all this time, the patient was talking incessantly. The speech was incoherent and repetitious as well as difficult to understand, in part because of dysarthria. She was alert, oriented, and would responded appropriately to questions, denying hallucinations or delusions or having any inner tension, urge, or necessity to move. She was unable to justify those behaviors, appearing unaware of them. When questioned, the unusual vocal and motor behaviors ceased, but when the feedback by the examiner stopped, the patient would drift again into the same confabulatory-like condition and involuntary movements restarted after a few minutes. At around 2 am the patient fall asleep and the abnormal behaviors described above disappeared (see Video, Segment 3). The vPSG confirmed that the patient was awake during the early hours of the night, at the time of the abnormal behaviors. She fell asleep reaching stage 2 non-rapid-eye movement (N-REM) sleep around 2 am. During sleep, neither periodic leg movements nor REM sleep were recorded (Fig. 1). Only occasional movements of the limbs were recorded during the entire PSG recording, without any clinical significance. After these studies, the dose of l-dopa was reduced to 300 mg three times a day, with a gradual decrease in daytime dyskinesias and disappearance of the stereotyped movements and incessant talking. Figure 1Open in figure viewerPowerPoint Two 30-second segments of the recorded PSG. The study was performed with electro-oculography, EEG (six channels: F3, F4, C3, C4, O1, and O2), chin electromyography (EMG), electrocardiogram (ECG), respiration monitoring with thermistor, including nasal and oral, and respiratory effort bands (thoracic and abdominal), EMG of the upper limb (flexors of the fingers, left and right) and lower limb (tibialis anterior, left and right), and oxyhemoglobin saturation. (A) Polygraph while the patient is having abnormal movements (11 pm). Movement artifacts in the EEG channels and bursts of EMG activity in the chin and limb EMG channels can be observed. (B) Polygraph while the patient was sleeping (3 am). At this time, there is slowing of the EEG frequencies, and K complexes typical of relaxed N2 sleep phase can be observed. EMG channels do not show any burst activity related to movement artifact. Our patient presented an unusual behavior characterized by logorrhea and stereotyped trunk and limb movements, occurring in the evening and during the night, in association with the administration of high doses of l-dopa. In PD, nocturnal vocalizations are uncommon and can be encountered during REM behavior disorder episodes and also as a part of hallucinatory behavior, especially in cases with dementia. Incessant talking during the day has been observed as part of the maniac state.1, 2 However, the patient reported on here was not considered to be hypomaniac or demented. Stereotyped body movements accompanied the logorrheic state in this case. Prominent nocturnal agitation with hyperkinesia is not a common nocturnal problem in PD. Rather than hyperactivity, in fact, most patients report nocturnal immobility along with stiffness.3 It is possible that the abnormal stereotyped movements in our case represented end-of-dose (diphasic) l-dopa-induced dyskinesias. Motor stereotypies can be part of the repertoire of diphasic dyskinesias. However, the repetitive rhythmic, stereotyped trunk flexion movements in our patient were not those typically observed in diphasic, end-of-dose dyskinesias in PD, which are typically ballistic-like and involve the proximal leg muscles, but not the trunk. Moreover, similar movements did not occur during the day following a biphasic pattern. In our patient, the abnormal movement resembled akathisia, a condition known to occur in PD. Body rocking stereotyped movements can occur in akathisia and these movements can be distractible, as they were in our case. However, akathisia is not limited to evening and nocturnal hours, is not associated with l-dopa overdose, and is generally associated with an inner sense of restlessness not present in our patient. The movements occurring in the legs and feet of our patient resembled also periodic leg movement (PLM), but trunkal stereotyped movements occurring every few seconds are not part of the PLM repertoire and PLMs were not recorded during the entire PSG. The development of the abnormal speech and motor behaviors in our patient after an increment in the total daily l-dopa dose, the temporal occurrence of the behaviors 1 to 2 hours after ingestion of a large dose of l-dopa, and their disappearance after a reduction in l-dopa dosage strongly suggest that these behaviors represent an overdose of l-dopa, related either to an exaggerated total dosage or to the large amount of l-dopa of the last dose. A case of a patient who developed psychomotor agitation and logorrhea 5 hours after an acute overdose with controlled release of l-dopa has been previously described. In this case, however, the symptoms were accompanied by visual hallucinations and delirium.4 Clinical and preclinical studies have provided evidence that striatum and the nucleus accumbens have an important role in the generation of stereotypies.5 In particular, these studies emphasized the role of the dorsal and limbic striatal structures and dopamine in the generation of stereotypies.6 The dopamine theory is further corroborated in patients who develop tardive stereotypies, secondary to chronic therapy with dopamine-receptor blocking agents.7 We believe that the bizarre and disabling motor and language behaviors observed in our patient and associated with l-dopa overdose are most unusual. Careful clinical evaluation and vPSG were useful for adequate characterization of the problem and its subsequent management. Author Roles (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. F.A.: 1B, 1C, 3A, 3B J.S.: 1C, 3B E.T.: 1A, 3B Disclosures Funding Sources and Conflicts of Interest: F.A. is a fellow of the European Federation of Neurological Societies. The authors declare that there are no conflicts of interest to report. Financial Disclosures for previous 12 months: E.T. has received honoraria for consultancy from Novartis, Teva, Boehringer Ingelheim, UCB, Solvay, and Lundbeck and received funding for research from Spaniard Network for Research on Deurodegenerative Disorders–Instituto de Salud Carlos III, The Michael J. Fox Foundation for Parkinson's Research, and Fondo de Investigaciones Sanitarias de la Seguridad Social. Supporting Information A video accompanying this article is available in the supporting information here. Filename Description mdc312150-sup-0001-VideoS1.wmvvideo/wmv, 7.9 MB Video. During the first part of the video (Segment 1) choreic l-dopa-induced dyskinesias during ON, in the afternoon, can be observed. During the second video segment (Segment 2), obtained during PSG, stereotyped hyperkinesias in trunk and extremities and incessant, incoherent talkativeness are recorded. The last segment (Segment 3) shows the patient sleeping quietly. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1Kulisevsky J, Berthier ML, Gironell A, Pascual-Sedano B, Molet J, Parés P. Mania following deep brain stimulation for Parkinson's disease. Neurology 2002; 59: 1421– 1424. 2Herzog J, Reiff J, Krack P, Witt K, Schrader B, Müller D, Deuschl G. Manic episode with psychotic symptoms induced by subthalamic nucleus stimulation in a patient with Parkinson's disease. Mov Disord 2003; 18: 1382– 1384. 3Grandas F, Iranzo A. Nocturnal problems occurring in Parkinson's disease. Neurology 2004; 63(8 suppl 3): S8– S11. 4Delmas G, Rothmann C, Flesch F. Acute overdose with controlled-release levodopa-carbidopa. Clin Toxicol 2008; 46: 274– 277. 5Canales JJ, Graybiel AM. A measure of striatal function predicts motor stereotypy. Nat Neurosci 2000; 3: 377– 383. 6Chartoff EH, Marck B, Matsumoto A, Dorsa D, Palmiter R. Induction of stereotypy in dopamine-deficient mice requires striatal D1 receptor activation. Proc Natl Acad Sci USA 2001; 98: 10451– 10456. 7Klawans HL, Goetz CG, Perlik S. Tardive dyskinesias: reviews and update. Am J Psychiatry 1980; 137: 900– 908. Citing Literature Volume2, Issue3September 2015Pages 301-303 FiguresReferencesRelatedInformation