Unni
Krishnan1*, Punit S Ramrakha2, Andrew Money-Kyrle2
1Dept
of Cardiology, Royal Liverpool University Hospital, Liverpool, UK. LE3 9QP
2Dept
of Cardiology, Stoke Mandeville Hospital, Aylesbury, UK. HP21 8AL.
*Corresponding
author:
Dr
Unni Krishnan, Dept of Cardiovascular Sciences, Clinical Sciences Wing,
Glenfield Hospital, Leicester, UK. LE3 9QP
Phone: +44 116 2563791, Fax: +44 116 2875792, Email: uk12@le.ac.uk
Acknowledgements: The authors are indebted to Mr Rick Taylor, Sleep Physiologist, Oxford Radcliffe Hospitals NHS Trust for providing us with the MSLT tracings.
SMJ 2009 54(2):
Abstract
Syncope
is a common presenting symptom in cardiology clinics. An accurate and detailed
delineation of the history is important in arriving at the correct underlying
diagnosis. Here we present an instance of syncope, which was initially diagnosed
as neurocardiogenic syncope. On further assessment following persistent
symptoms, this was correctly diagnosed as narcolepsy. We discuss the specific
clues in the history and the diagnostic approach to this rare but important
condition. We also highlight the possibility of coexisting autonomic
disturbances in such cases, which may mislead the clinician if not considered
carefully.
Key
words: neurocardiogenic syncope; narcolepsy; multiple sleep latency test;
modafinil
Case Summary
A
28-year-old woman was referred to cardiology with dizziness and a tendency to
fall followed by loss of consciousness. Her symptoms were provoked by prolonged
standing and she had a prodrome of tinnitus and blurring of vision. There was no
family history of syncope or sudden death. On examination, a postural drop in
blood pressure was noted and a tilt table test reproduced symptoms of dizziness
with significant hypotension and bradycardia (following a 45 degree tilt, the
blood pressure dropped from 110/65 mmHg to 80mmHg systolic and the pulse rate
dropped from 62 bpm to 45 bpm, suggesting a combined vasodepressor and
cardioinhibitory response). Resting 12 lead electrocardiogram, ambulatory heart
rhythm monitor and echocardiogram were normal. A diagnosis of neurocardiogenic
syncope was made at the time. She was advised to consider compression stockings
and was prescribed atenolol 25 mg once daily.
Three
years later, the patient was referred for a cardiology review for recurrent
symptoms and a lack of response to compression stockings and a high salt diet.
She had discontinued atenolol due to lethargy. On eliciting the history, we
noted a change in her symptoms. She suffered from lack of energy in the daytime
and episodes of collapse with diminished awareness of surroundings lasting from
a few seconds to 1-2 minutes without obvious triggers (change in posture,
physical activity) or prodromal symptoms (palpitations, vertigo, tinnitus). A
witness noted muscle twitches during these episodes, although there were no
generalised convulsions or incontinence. She could be easily roused and had no
post-ictal features.
On
examination she was in sinus rhythm with normal cardiac auscultation. There was
no significant postural drop in blood pressure. The spontaneous and
unpredictable loss of posture, without true loss of consciousness in the absence
of obvious triggers, prompted a neurological referral querying the diagnosis of
cataplexy. Multiple sleep latency tests (MSLT) confirmed narcolepsy (figures 1,
2). HLA tests confirmed presence of the HLADQB1*0602 allele which is linked to
narcolepsy with cataplexy. Modafinil 100mg twice daily improved her daytime
tiredness. She was referred to the regional centre for sleep disorders for
further management.
Figure 1: Multiple Sleep Latency Test (MSLT) – onset of sleep
Note the change from a rhythm to q rhythm 3 seconds after closing eyes (normal sleep latency – 10 minutes). Also note the activity of the submentalis muscle (green trace labelled EMG R – EMG L)
Figure 2: Multiple Sleep Latency Test (MSLT) – REM sleep
Arrows indicate the instances of rapid eye movements. Also note tonic inhibition of submentalis (green trace labelled EMG R – EMG L)
Discussion
Gelineau coined the term narcolepsy in 1876 to describe a clinical syndrome of excessive daytime sleepiness associated with cataplexy, hypnagogic hallucinations and sleep paralysis. Prevalence is estimated to be 47/100,000 in European populations. 1 Most patients develop symptoms in the second decade of life. Deficiency of the hypothalamic neurotransmitter orexin (hypocretin-1) is a central event in narcolepsy. 2 The HLA type DQB1*0602 is present in 95% of narcoleptic patients with cataplexy. 3 Dysautonomia including subnormal heart rate and blood pressure and an abnormal valsalva response are reported. 4, 5
There is no single diagnostic test for narcolepsy. MSLT, polysomnography and HLA typing may be useful. 3 MSLT is an objective assessment of the tendency to fall asleep in the day. Two findings on MSLT are significantly associated with narcolepsy: (i) 87% of narcoleptics have a daytime sleep latency period <5 minutes compared to 10% of normal subjects; (ii) 74% of narcoleptics have two or more episodes of sleep onset rapid eye movement periods (SOREMP) during first 15 minutes of sleep compared to 17% of normal subjects. A combination of excessive daytime sleepiness, cataplexy and 2 or more SOREMP on MSLT confirms narcolepsy.
Modafinil (for excessive sleepiness) and Selegiline and Clomipramine (for cataplexy) 3 are useful pharmacological agents. Non-pharmacological measures include patient education and advice regarding career and driving. Referral to a specialist sleep clinic should be considered in all patients with a clinical suspicion of narcolepsy.
Our patient is a useful reminder of the relevance of a clear and thorough history in diagnosing sleep disorders with dysautonomia. Her symptoms started in her early twenties with postural symptoms initially and an abnormal (vasodepressor + cardioinhibitory) tilt table test which suggested neurocardiogenic syncope. It is possible that this phase of dysautonomia was part of the sleep disorder, which manifested three years later as daytime lethargy and collapses. Her loss of posture associated with muscle twitches (with no obvious triggers) were due to cataplexy. The clue in the history, which made us query the initial diagnosis of neurocardiogenic syncope, was a change in symptoms from true loss of consciousness with prodrome to loss of posture with diminished awareness. MSLT and HLA tests confirmed narcolepsy following which further care was arranged at the regional centre for sleep disorders. Educating her about her disease helped her to cope with her episodes better and modafinil improved her daytime somnolence.
References
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2. Nishino S, Ripley B, Overeem S, et al. Hypocretin (orexin) deficiency in human narcolepsy. Lancet. Jan 1 2000;355(9197):39-40.
3. Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet. Feb 10 2007;369(9560):499-511.
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5. Guilleminault C, Heinzer R, Mignot E, et al. Investigations into the neurologic basis of narcolepsy. Neurology. Feb 1998;50(2 Suppl 1):S8-15.