Neurology -- Correspondence for Garcia-Borreguero et al., 61 (7) 1008-1010

Correspondence published:

Reply to Romigi: Diego Garcia-Borreguero, MD (11 November 2003)

L-DOPA–induced excessive daytime sleepiness in PD: A placebo-controlled case with MSLT assessment: Andrea Romigi, Maria Grazia Marciani and Fabio Placidi (11 November 2003)

Reply to Romigi 11 November 2003

Diego Garcia-Borreguero, MD,
Fundacion Jimenez Diaz
Sleep Disorders Unit/ Dept. Of Neurology, Av Reyes Catolicos 2, 20840 Madrid, SPAIN
Send Correspondence to journal:
Re: Reply to Romigi

dgarciaborreguero{at}fjd.es Diego Garcia-Borreguero, MD

We thank Dr. Romigi et al for their comments on our article. [1] They raise the possibility that EDS might have been caused by L-Dopa-induced dyskinesias or by coexisting sleep disorders (Periodic Limb Movements, mild obstructive sleep apnea). Neurological evaluation of both conditions of the double blind pharmacological challenge did not show major differences. UPDRS total score at the time of the double blind challenge was 36 (Hoehn- Yahr stage: 2).
In addition, PLM- and Apnea-Hypopnea Indexes were similar in both overnight sleep studies before the L-DOPA-MSLT challenge and thus an unlikely explanation for the remarkable differences in the MSLT results. It is still unclear whether Periodic Leg Movement Disorder (PLMD) can cause excessive daytime somnolence. [2] This becomes particularly unlikely for mild PLMD. As requested, the PLM arousal-index was low in both active drug and placebo conditions (9.3/hr and 3.3/hr, respectively). Similarly, Apnea-Hypopnea-indexes were low [3] and did not substantially differ between both conditions (see Figure in text). [1]
Regarding the relationship between plasma levels of L-DOPA metabolites and sleep latencies, our study shows lower sleep latencies during higher plasma levels. Understandably, the data obtained in such a study do not allow a more sophisticated analysis.
Although we believe that EDS is caused by a diversity of elements in PD, our case shows that pharmacological factors as L-DOPA might play a crucial role at least in some patients.
References:
1. Garcia-Borreguero, Schwarz C, Larrosa O, De la Llave Y, Garcia De Yebenes J. L-DOPA-induced excessive daytime sleepiness in PD: A placebo-controlled case with MSLT assessment. Neurology 2003;61:1008- 1010.
2. Nicolas A, Lesperance P, Montplaisir J. Is excessive daytime sleepiness with periodic leg movements during sleep a specific diagnostic category? Eur Neurol 1998;40:22-26.
3. Kryger MH, Roth T, Dement WC. Principles and Practice of Sleep Medicine. Third Edition ed. Philadelphia:W.B. Saunders Co., 2000.

L-DOPA–induced excessive daytime sleepiness in PD: A placebo-controlled case with MSLT assessment 11 November 2003

Andrea Romigi,
University of Rome “Tor Vergata” Policlinico Tor Vergata Servizio di Neurofisiopatologia
Policlinico Tor Vergata Servizio di Neurofisiopatologia V.le Oxford 81 Zip code 00133 Rome Italy,
Maria Grazia Marciani and Fabio Placidi
Send Correspondence to journal:
Re: L-DOPA–induced excessive daytime sleepiness in PD: A placebo-controlled case with MSLT assessment

a_romigi{at}inwind.it Andrea Romigi, et al.

We read with interest the article by Garcia-Borreguero et al. The authors focused on an emerging clinical aspect of PD: excessive daytime somnolence (EDS), sleep attacks and antiparkinsonian treatment. Garcia-Borreguero et al. describe a single PD patient diagnosed 12 years earlier showing pathological mean sleep latency under l-Dopa (LD) in contrast to a normal value with placebo. The authors suggest that LD may induce EDS in PD patients. However, the severity of the PD and the clinical picture is not reported in each treatment condition. The patient was also affected by severe PMLS and mild OSAS. Both LD-related adverse events (i.e. dyskinesia, medication effects) and sleep disorders such as periodic limb movements, sleep breathing disorders may have played a role in EDS in the PD patient.
Coleman et al [1] reported PMLS as the primary pathological finding in 11% of hypersomniac patients complaining of EDS. In patients who experienced EDS and PMLS, no correlation was found between PLMI, sleep efficiency and EDS measured by MSLT2. PMLS should be a possible cause of EDS. It would have also been useful to report the PML arousal index. Since PMLI did not exceed the value of 5 during placebo-recording, EDS may be partially correlated to pathological PMLS during both open and double blind LD recordings. Moreover, the patient showed severely pathological PMLI (28/h) during open LD recording, mildly pathological (11.7/h) during double blind LD and normal during placebo.
Montplaisir et al. [3] demonstrated a variability from night to night of PMLI, especially in less severe sleep complaints. How do the authors explain the paradoxical “improvement” of PLMI after LD withdrawal considering LD an effective treatment of PMLS? In addition, a mild OSAS may impair or at least modify EDS.
Garcia-Borreguero et al. suggest an interesting association between the lowest LD plasma levels and the lowest sleep latencies at MSLT as a possible dose-dependent effect of LD on presynpatic D2 autoreceptors. This finding is remarkable but conflict with the recent report of Brodsky et al [4] who showed that the mean daily LD equivalent dose was statistically significant higher in PD patients who experienced EDS.
Even though this report is appealing and well designed, we think that a single patient with a long history of PD affected by concomitant sleep disorders, could not produce enough evidence regarding the role of L-Dopa on sleepiness.
References
1. Coleman RM, Pollak CP, Weitzman ED. Periodic movements in sleep (nocturnal myoclonus): relation to sleep disorder. Ann. Neurol. 1980; 8: 416-421.
2. Mendelson WB. Are periodic leg movements associated with clinical sleep disturbance? Sleep 1996; 19:219-223.
3. Montplaisir J, Boucher S, Poirier G et al. Clinical Polysomnographic and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. Mov Disord. 1996; 12: 61- 65.
4. Brodsky MA, Godbold J, Roth T, Olanow CW. Sleepiness in Parkinson’s Disease: A Controlled Study.Mov Disord 2003 18, (6): 668–672.