mise à jour du
18 février 2002
A trial of subcutaneously injected apomorphine for parkinsonian
Yawning in Parkinson's disease
Neurology january 1999, 52, p428
réponses à Yawning as an aura for an L-Dopa induced "on" in Parkinson's disease
JL Goren JH Friedman Memorial Hospital of Rhode Island Pawtucket USA
Neurology mars 1998, 50, p 823
Carlo Colosimo, MD, Francesco E. Pontieri, MD, Rome, Italy

To the Editor : We read with interest the clinical/scientific Note by Drs. Goren and Friedman on levodopa-induced yawning in PD. They state that "yawning has not been associated with treated or untreated PD" and they suggest that "if yawning is a dopamine mediated phenomenon in humans it should be seen in PD patients treated with levodopa and dopamine agonists". Indeed, this is the case. If is well known that apomorphine, a direct Dl-D2 dopamine receptor agonist, frequently induces yawning just before the onset of the motor effect, both in experimental animals and in patients with PD. Yawning was clearly described since the early clinical trials with apomorphine in the 1950. A More recently this effect was confirmed in the larger clinical series that have marked the revival of this drug as an adjunct therapy for advanced PD, either as intermittent boluses or as a continuous subcutaneous infusion via portable minipumps. Interestingly, the widespread reintroduction of apomorphine in the therapeutic arsenal for PD is due to the observation that pretreatment with the peripheral dopamine receptor blocking agent domperidone could prevent apomorphine-induced nausea, drowsiness, and arterial hypotension, but not yawning. This would confirm that this side effect has a central origin related to dopamine receptor stimulation in the basal ganglia. However, as pointed out by the authors, the pathogenesis is far more complex involving the stimulation of other neurotransmitters in the forebrain.

Virgilio GH. Evidente, MD, Scottsdale, AZ; Katrina Gwinn Hardy, MD, Jacksonville, FL

To the Editor: We read with interest the article by Drs. Goren and Friedman on yawning in PD. The authors state that yawning has not been associated with treated or untreated PD and that it is most likely a dopamine-mediated phenomenon. We wish to point out that idiopathic PD is not the first parkinsonian syndrome reported to be associated with yawning. Yawning was described by Dr. von Economo not only in the acute encephalitic ,"somnolent" stage of encephalitis lethargica (EL) along with sleepiness, but also in postencephalitic parkinsonian (PEP) patients without any accompanying sleep disturbance or somnolence. In the latter case, the yawning was often rhythmic and repetitive, and was viewed as a form of automatism or compulsive tic. We recently published a video collection of early cinematographic cases of PEP seen at the Mayo Clinic in the 1920s, with one case showing a woman with paroxysmal yawning. Like idiopathic PD, PEP is associated with neuronal loss that is most distinct in the substantia nigra and less so in the basal ganglia . Given the neuropathologic involvement of the nigrostriatal system in PEP, the parkinsonism was likely due to dopaminergic dysfunction. We believe that the compulsive yawning in PEP could also possibly be dopamine-mediated, as this symptom or sign often remitted in the few cases of PEP that spontaneously improved.

John D. O'Sullivan, FRACP, Andrew J. Lees, NID, London, UK; Andrew J. Hughes, IMD, Victoria, Australia

To the Editor: We read with interest the report by Drs. Goren and Friedman describing a parkinsonian patient for whom yawning heralded "on" phases after oral levodopa, but were surprised that the same effect following administration of the dopamine agonist apomorphine was not mentioned. The majority of our PD patients who are administered subcutaneous apomorphine to test dopaminergic responsiveness or intermittently to treat parkinsoman motor fluctuations experience yawning, usually coincident with the onset of the motor response. Sedation, wich is also common after apomorphine injections, sometimes but not always accompanies the yawning. The hypothalamic paraventricular nucleus receives afferent projections from the midbrain dopaininergic neurons, and oxytocin release from this area in response to dopaminergic stimulation is thought to mediate both yawning and penile erections in rats following apomorphine. We recently described five patients with PD who experienced apomorphine-induced penile erections, three of whom also yawned after apomorphine administration supporting a similar link in man. Like yawning, the erections were usually transient and occurred as the patients switched from "off"' to "on" suggesting the postsynaptic dopamine receptor mechanisins involved differ from those mediating the more prolonged motor response. Yawning and erections appear to be dose-related and may depend on the number of hypothalamic neurons producing Ocytocin, which have been shown to be reduced in PD. Effects such as yawning and erections associated with dopaminergic agents may be considered irrelevant or embarrassing by patients and go unrecognized without specific questioning. We agree with Drs. Goren and Friedman that such observations may be important to our understanding of the dopaminergic system in PD.

Joseph H. Friedman, MD, Pawtucket, RI; Jessica Goren, PharmD, Kingstown, RI

Reply from the Authors : We appreciate the interest our letter generated. Since reporting the two cases, we have subsequently observed another PD patient who yawned in conjunction with turning "on." He had never made the connection between yawning qnd responding to L-dopa, but in the office he was initially "Off," then began to yawn, and was shortly thereafter able to walk, which had net been the case earlier. The patient, in retrospect, reported that this was a common phenomenon. We acknowledge that yawning occurred in PEP. This, of course, occurred in the absence of medication and was therefore inherent in the condition, as were a number of other movement and behavior disorders. We are unaware that unmedicated patients with PD yawn when not sleepy or bored. The possibility that dopamine is involved is consistent with our report.

Although our letter stated that dopamine agonists and apomorphine in particular have been associated with yawning, we failed to note that apomorphine is known to induce yawning in PD patients. We appreciate this fact being brought to our attention. Because yawning is not keynoted in any of these articles, and apomorphine is not used in the United States, we were unable to retrieve this information from Medline searches and did not know this from personal experience. We do not have a hypothesis to explain why apomorphine induces yawning so commonly whereas L-dopa and the oral dopamine agonists do not.