This case study details a 15-year-old girl with Rett Syndrome who experienced respiratory dysfunction. Her breathing patterns and oxygen saturation levels were monitored before and after receiving buspirone treatment. Before treatment, her average oxygen saturation was 86.9% and she spent over 90% of the time with saturation below 90%. After 5 months of buspirone treatment twice daily, her average saturation improved to 91% and she spent only 52% of the time with saturation below 90%, representing a 42.2% reduction. The improvement in her breathing and oxygen levels suggests buspirone may help treat respiratory issues in Rett Syndrome, though controlled clinical trials are still needed.

1. Case report
Buspirone in Rett syndrome respiratory dysfunction
Daniela K. Andakua,1
, Marcos T. Mercadanteb,2
, Jose´ Saloma˜o Schwartzmanb,*
a
Santo Amaro University Physical Therapy School, Sa˜o Paulo, Brazil
b
Pervasive Developmental Disorder Program, Mackenzie Presbyterian University, Sa˜o Paulo, Brazil
Received 16 September 2003; received in revised form 16 August 2004; accepted 18 September 2004
Abstract
This study details a case of Rett Syndrome where the patient’s respiratory dysfunction was improved after buspirone was administered.
Polygraphic studies in the waking state, before and after treatment with 5 mg of buspirone twice a day, were obtained. Breathing movements,
oxygen saturation and end-tidal carbon were monitored. Average oxygen saturation increased from 86.9 to 91%, and the period of saturation
below 90% was reduced by 42.2%. The oxygen saturation improvement observed in this case suggests that buspirone might be useful in
treating respiratory dysfunction associated with Rett Syndrome. Controlled clinical trials are needed to provide more evidence.
q 2004 Published by Elsevier B.V.
Keywords: Rett syndrome; Respiratory; Dysfunction; Oxygenation; Buspirone
1. Introduction
Rett Syndrome (RS) is a severe pervasive development
disorder, primarily affecting females and characterized by
loss of language and motor skills. The MECP2 gene that
encodes the methyl-CpG binding protein 2 and presumably
acts as a global transcriptional repressor, has been found to
contain a mutation in 80% of classic RS cases [1]. Four
distinct clinical stages have been described: Stage I—early
onset stagnation period, Stage II—rapid destructive stage,
Stage III—pseudostationary stage and Stage IV—late motor
deterioration stage. Although still not well studied, the
respiratory dysfunctions appear to have a significantly
deleterious impact on children suffering from RS as well as
on the quality of life of the child’s family [2].
The associated breathing impairment, which occurs only
during wakefulness, normally consists of periods of breath
holding, shallow breathing, hyperventilation, central
apneas, Cheyne–Stokes breathing, Biot’s breathing and
other pathological breathing patterns [3]. Studies show that
these abnormal breathing patterns may be associated with
oxygen saturation variations with values lower than 60%
[4,5]. However it is not clear if the continuous exposure to
lower levels of oxygen saturation could contribute to the
cerebral functional impairment and/or other clinical
complications.
Julu et al. [3,6] suggest that the multiple respiratory
dysrhythmias could be a consequence of the instability of
the respiratory oscillator in the medulla oblongata and
is probably due to brainstem immaturity. The term
‘immaturity’ in this context is comparable to cardiac vagal
tone observed in 2- to 3-day-old neonates. Among the
abnormal respiratory patterns, the holding of the breath
during inspiration (also called apneusis) has been seen as a
malfunction of inhibitory synaptic process into the brain-
stem. This region is believed to be responsible for the
ending of the cycle of inspiration [3,7].
Buspirone, a serotoninergic type 1A agonist, was
successfully used in the treatment of apneusis secondary
to the surgical removal of pons and medulla oblonga
astrocytoma [8]. It has been suggested that 5-HT1A
receptors control the neuronal processes within the
brainstem that regulate the termination of the cycle of
inspiration. Agonists of these receptors seem to enforce
post-synaptic inhibition through the increased gamma-
aminobutyric acid receptor activity [3]. At the moment,
0387-7604/$ - see front matter q 2004 Published by Elsevier B.V.
doi:10.1016/j.braindev.2004.09.011
Brain & Development 27 (2005) 437–438
www.elsevier.com/locate/braindev
* Corresponding author. Address: Rua Franc¸a Pinto, 941 ZIP 04016-034,
SP/SP Brazil. Fax: C55 11 5571 7743.
E-mail address: josess@terra.com.br (J.S. Schwartzman).
1
Rua Visconde de Inhau´ma 308 (92), ZIP 04145-030, SP/SP, Brazil.
2
Av. BR Campos Gerais, 193 (62), ZIP 05684-000, SP/SP, Brazil.

2. there is a single RS case described by Kerr et al. [9] where
an improvement in the apneusis was reported.
2. Case report
The patient in this case study was a 15-year-old girl with
classic RS (Stage IV, late motor deterioration stage) who
received 5 mg of buspirone twice daily. Her parents first
observed her breathing impairment when she was 4 years
old and, as they described the symptoms, it was clearly a
case of apnea associated with cyanosis. The mother stated
that the respiratory dysfunction became worse after
menarche. Before starting medication, the patient’s parents
received a written and verbal explanation of the procedures.
They subsequently provided written consent for the
procedure as well as for publication of the results.
Before starting medication, a polygraphic study was
administered during the waking state for a period of 75 min.
Breathing movements with thoracic and abdominal strain
gauges were monitored, oxygen saturation was measured by
pulse oxymetry, and end-tidal carbon was measured through
a nasal catheter. The results demonstrated an average
oxygen saturation of 86.9% and the patient stayed 67.7 min
(90.2% of the total time) with oxygen saturation values
lower than 90% (Fig. 1).
After 10 days on buspirone, a dramatic improvement in
patient breathing pattern was observed by the caretakers.
After 5 months of treatment the patient was reassessed using
the same polygraphic methods. The reassessment showed an
improvement in oxygen saturation with average oxygen
saturation of 91%. Values below 90% saturation were
observed for 39.1 min (52% of total time) and a total
reduction of 42.2% of the time compared to the baseline
(Fig. 1). Due to oral breathing no end-tidal carbon data was
obtained.
3. Discussion
This study reports significant improvements with buspir-
one in the breathing pattern and in the saturation values in a
RS adolescent. While it is worth noting that the patient’s
parents and the clinical neurologist also observed a
significant improvement in the social contact and alertness
of the patient, it is not clear if this improvement is related to
the increased level of oxygen saturation or to the improved
function of the other brain regions by the action of the
5HT1A agonist. Controlled clinical trials are recommended
to evaluate the efficacy of buspirone in children with RS.
Outcomes should focus on behavior aspects as well as
breathing patterns.
Acknowledgements
The authors thank Gerar Sono-Centro de Diagno´sticos
do Sono Co. for the research’s technical support and
Mark VanMeter for the manuscript’s review. Supported in
part by a grant from MackPesquisa, grant: 1014 to
Dr Schwartzman.
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Fig. 1. Improvement of oxygen saturation noted by the time (in min) the
patient remained in specific oxygen saturation (SO2) levels before (pre-tx)
and after (tx) treatment with buspirone.
D.K. Andaku et al. / Brain & Development 27 (2005) 437–438438