ARTICLE
Auteur(s) : Piotr Bialasiewicz,
Dariusz Nowak
Sleep and Respiratory Disorders Centre, Department
of Clinical Physiology, Medical University of Lodz, Lodz,
Poland
Article reçu le 15 Février 2009, accepté le 28 Août 2009
A prolonged apnoeic period with subsequent state of confusion
with blunted response to external stimuli observed during sleep,
may pose diagnostic difficulties particularly in patients referred
due to presumptive diagnosis of obstructive sleep apnea syndrome
(OSAS). Epilepsy, because of various clinical presentations, should
be included in the differential diagnosis of witnessed prolonged
apnea.
Case report
In 2003, a 38-year-old male was referred to the Sleep Centre with a
presumptive diagnosis of OSAS. The symptom that made him seek
medical attention, was a nocturnal prolonged apnea with “loss of
consciousness” (according to his spouse) that first occurred in May
of the same year. The patient fell asleep around 11:00 pm; was
later awoken by an ambulance crew at approximately 03:00 am.
His spouse described what appeared to be an episode of prolonged
apnea (lasting more than 5 min) accompanied by a generalized
tonic contraction of muscles with eyes partially open. No clonic
phase, tongue biting, or enuresis was reported. The patient was
unresponsive to stimuli (including pain) and remained in a
semi-comatose state for approximately 30 minutes subsequent to
cessation of the episode. Upon admission to a hospital blood gases
assessment revealed mild respiratory acidosis that subsided by
morning. As sequels of the episode, the patient complained of
generalized muscle pain, and presented, for a few days, with
petechiae over the neck and trunk. The neurological diagnostic
workup (EEG, CT, and NMR) revealed no obvious pathology; therefore
he was referred to the Sleep Centre for further evaluation.
The clinical presentation was somewhat typical: not refreshing
sleep and witnessed apneas but without daily somnolence (4 out
of 24 points on Epworth sleepiness scale). The patient
reported neither chronic diseases nor chronic medication use. The
physical examination revealed a mildly obese patient
(BMI-33.7 kg/m2) with no other apparent
abnormalities.
The polysomnography resulted in the diagnosis of OSAS:
apnea/hypopnea index (AHI) was 49/h (desaturation index - 46/h); no
positional effect, but REM sleep dependence was visible (AHI in REM
- 60/h vs 45/h in non-REM) (figure 1A). Sleep was
fragmented (arousal index - 45/h); with stage N1 dominance,
deprived of slow wave sleep. The patient became eligible to undergo
a nasal-CPAP treatment trial under polysomnographic monitoring
which resulted in significant improvement: AHI along with the
desaturation index declined to 6/h; the sleep structure improved
(reduction of stage N1 and appearance of slow wave sleep), as
well as arousal index (11/h). This was due to the CPAP pressure
reaching 11 mbar in REM, supine (figure 1B).
In October of 2003, CPAP treatment was initiated but the patient
reported no modification in the frequency of night episodes. In
December of 2003 (subsequent to an additional night incident)
the standard EEG registered regular and symmetric alfa rhythm with
the frequency of 9 Hz and amplitude of 60 μV and
scattered slow theta waves (5-6 Hz); furthermore sharp waves
(0.5 s duration) with the sharp-slow wave complex occurred in
temporal leads with the predominance on the left side. They were
augmented by hyperventilation and stroboscopic stimulation. These
findings along with the patient’s history facilitated a final
diagnosis of a rare form of pure sleep epilepsy presenting as
isolated tonic seizures.
For the duration of two hospitalizations in 2004 for
nocturnal seizures, the patient was initially treated with
phenytoin, and then sodium valproate was introduced, without effect
on seizure frequency. By July of 2004, the patient endured
22 episodes of seizures exclusively at night, with an average
frequency of 1.5 per month, separated at times by
2-3 days, or 2-3 weeks. Disappointed by ineffectiveness
of CPAP with regard to the occurrence of nocturnal fits, the
patient discontinued this treatment at his own discretion.
Concurrently, clonazepam (1 mg at bedtime) was introduced by
another neurologist, and was subsequently tapered to 0.5 mg
and discontinued after 6 months. Since the induction of this
treatment there was no relapse of night seizures hitherto.
In September of 2007 the patient was invited to the follow
up visit. His body habitus did not change significantly (BMI -
36.0). He reported no nocturnal seizures since July of 2004. The
control polysomnography revealed a similar pattern of disordered
sleep breathing with REM sleep dependence, however, a mild
improvement in sleep apnea parameters was noted: AHI index dropped
to 19/h (desaturation index to 23/h); similarly to the baseline, no
positional effect but augmentation in REM sleep was present (AHI in
REM - 35/h vs 18/h in non-REM).
Discussion
The difficulty in the attainment of a final diagnosis in our
patient originated from the coexistence of two separate diseases,
symptomatic exclusively at night. Indeed, apnoeic periods are
associated with sleep; however in the preponderance of epilepsy
presentations, this is usually not the case (eventually with the
exception of frontal seizures). At the end of a sleep apnoeic
period, there is usually a defensive mechanism of arousal that
terminates the event preventing from prolonged asphyxia; in
epilepsy such a defensive mechanism is absent. The prolonged,
spurious apnea observed in our patient, was rather due to the tonic
contracture of respiratory muscles compromising the chest wall
compliance and thereby, affecting minute ventilation. Thus, the
presentation of a semi-comatose, confusion phase after such an
event may have the foremost differential value. Nocturnal frontal
lobe epilepsy which should be included in differential diagnosis
presents with episodes of dystonia (Provini et al., 2000),
thus, it is rather not likely that the tonic contracture of axial
musculature observed in our patient may be a form of dystonia; a
subsequent confusional state is also not compatible with this
diagnosis.
It was reported that OSAS evoked seizures in epileptic patients
and its effective treatment decreased the frequency thereof
(Hollinger et al., 2006; Miano et al., 2009); alas the
patient reported no subjective reduction in seizure frequency on
CPAP treatment. Transient respiratory acidosis as a consequence of
alveolar hypoventilation related to OSAS may actually protect the
CNS from seizures; alternatively, frequent arousals from apneas and
related sleep deprivation may facilitate epileptic seizures.
Consequently, effective CPAP treatment prevents respiratory
acidosis and possibly by induction of relative hyperventilation may
enhance neuronal activity promoting seizures, while the reduction
of arousals may induce a contrary effect. Clonazepam, a seemingly
effective treatment in our patient, is thought to enhance sleep
apnea due to its muscle relaxing effect. However, this may not be
the case, as demonstrated in a clinical trial showing its ability
to reduce AHI in OSAS patients in mono-therapy (Noseda et al.,
2002). Thus one can speculate on its possible effectiveness in
treating both conditions in our patient.
Nevertheless, both diseases seemed to be causally dissociated
because effective CPAP treatment of OSAS had no effect on seizure
frequency, so the putative effect of clonazepam on OSAS is
negligible. Apart from the speculative efficacy of clonazepam, the
spontaneous, coincidental remission of seizures cannot be
excluded.
The prevalence of epilepsy in different populations lies between
0.5 and 1%; while pure sleep epilepsy is rare and constitutes
about 6% (95% CI: 4.1-7.7%) of all epilepsy cases (Gibberd and
Bateson, 1974). From these data the prevalence of pure sleep
epilepsy in a population may be estimated as 0.03 to 0.06%.
OSAS with prevalence in adult population around 5%, may be
considered as an independent phenomenon. Thus the coexistence of
pure sleep epilepsy and OSAS may be calculated as up to 3 per
105, but 85% of all cases with pure sleep epilepsy
present as generalized tonic-clonic seizures making the combination
of both disorders with described phenomenology even rarer – i.e. ca
5 per million (D’Alessandro et al., 2004).
Conclusion
We present a case of pure sleep epilepsy that necessitated
discrimination from a coexisting sleep apnea syndrome. To the best
of our knowledge this is the first case reporting the coexistence
of these two diseases, with tonic seizures mimicking apneas. Any
clinical presentation, reminiscent of our case with prolonged
asphyxia due to tonic muscle contracture along with a semi-comatose
state requires a wider diagnostic panel including a full
neurological workup.
Acknowledgments
The authors would like to thank Jeffrey de Graft-Johnson, M.D.,
M.P.A., for his advice and comments.
Disclosure.
The present study was partially founded by the institutional
grant nr: 503-0079-1 of Medical University of Lodz.
None of the authors has any conflict of interest to
disclose.
References
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