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Sleep disruption following paramedian pontine stroke

Article  in  BMJ Case Reports · April 2009

DOI: 10.1136/bcr.07.2008.0460 · Source: PubMed

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Published 3 April 2009

Cite this as: BMJ Case Reports 2009 [doi:10.1136/bcr.07.2008.0460]
Copyright © 2009 by the BMJ Publishing Group Ltd.

Unusual association of diseases/symptoms

Sleep disruption following paramedian pontine stroke
Matteo Tosato1, Sara Aquila1, Giacomo della Marca2, Raffaele Antonelli Incalzi3 and Giovanni
Gambassi4

1
Università Cattolica del Sacro Cuore, Centro di Medicina dell’Invecchiamento, Largo Agostino
Gemelli 8, Rome 00168, Italy
2
Università Cattolica del Sacro Cuore, Istituto di Neurologia, Largo Agostino Gemelli 8, Rome
00168, Italy
3
Università Campus Biomedico, Divisione di Geriatria, Largo Agostino Gemelli 8, Rome 00168,
Italy
4
Università Cattolica del Sacro Cuore, Centro di Medicina dell’Invecchiamento, Largo Agostino
Gemelli 8, Rome 00168, Italy

Correspondence to:
Matteo Tosato, mtosato@gmail.com

SUMMARY
Pontine structures are critical for the generation of rapid eye movement sleep but there are only a
few reports of the effects of focal pontine lesions on sleep patterns in humans. We report the
case of an 81-year-old man admitted for the acute onset of disordered speech and motor deficit
in the upper right arm who developed hypersomnia within a week. A 24-hour polysomnographic
study revealed a very severe disruption of both circadian rhythm and sleep organisation, and a
brain MRI documented an ischaemic lesion of the anterior left paramedian portion of the pons.
Our observation suggests that even small, paramedian pontine ischaemic lesions can acutely
induce a very severe sleep disorder.

BACKGROUND
A hypersomnolent state is a hallmark of paramedian thalamic strokes in which sleep needs are
markedly increased and the patient’s ability to maintain attention is reduced.1–3 Sleep studies
have shown an increased sleep duration with predominance of superficial sleep stages,
increased sleep fragmentation and decreased sleep spindles.2–4 Hypersomnia has been
considered the result of the disruption of thalamic sleep-generating and arousal-maintaining

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mechanisms.2 Several electrophysiological data suggest that pontine structures are also critical
for the generation of sleep phenomena, especially network organisation in rapid eye movement
(REM) sleep.5 Pontogeniculo-occipital waves generated or propagated in the ponto-
mesencephalic tegmentum are a feature of human REM sleep and are proposed to mediate a
wide variety of sleep-related neural processes.6 Yet, only a few reports of the effects of focal
brainstem lesions on sleep patterns in humans are available in the literature.7

CASE PRESENTATION
An 81-year-old man with a hypertension and diabetes mellitus was admitted to our hospital for
the acute onset of neurological signs. He was currently being treated with ramipril 5 mg once
daily, hydrochlorothiazide 25 mg once daily, aspirin 100 mg once daily, glibenclamide/metformin
400/2.5 mg twice daily and omeprazole 20 mg once daily, and his clinical history was totally
unremarkable.

INVESTIGATIONS
On admission, blood pressure was 140/70 mmHg, pulse rate was regular at 86 bpm, body
temperature was 36.8°C and oxygen saturation was 94%. The neurological examination revealed
disordered speech and a motor deficit in the upper right arm. Acutely, he did not show any
vigilance impairment: the patient was fully awake and well-oriented; cranial nerves and sensory
examination were normal. Other physical examinations were unremarkable. Laboratory tests
revealed a normal blood cell count; serum electrolytes levels were within the normal range.
Fasting serum glucose was 155 mg/dl, haemoglobin A1c was 6.9%; serum creatinine was 1.4
mg/dl with an estimated glomerular filtration rate of 44 ml/min (Cockroft-Gault formula).

A brain CT scan performed 4–6 hours after symptoms onset showed no evidence of acute
haemorrhage, but rather non-specific white-matter vascular lesions. A brain MRI study,
performed within 72 hours of the onset of symptoms, revealed an area of hyperintense signal in
long TR and diffusion-weighted image (DWI) sequences, located in the anterior, left paramedian
portion of the pons (fig 1), without contrast enhancement. This finding was consistent with a
subacute ischaemic lesion.

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Figure 1 Brain MRI performed 72 hours after the onset of symptoms. (A) Diffusion-weighted images (DWI)
showing the area of acute cytotoxic oedema (arrow) in the left paramedian portion of the pons. (B) T2-weighted
images, coronal plan, showing the same lesion (arrow).

In the following week, the patient progressively developed a hypersomnolent state characterised
by repeated sudden episodes of daytime sleep accompanied by severe nocturnal sleep
fragmentation.

A 24-hours polysomnographic (PSG) study was performed following adaptation and the results
are shown in fig 2. No central or obstructive phases of apnoea or other respiratory abnormalities
were detected. The patient did not show any significant nocturnal desaturation. PSG revealed a
very severe disruption of both circadian rhythm and sleep organisation. The study revealed an
irregular succession of episodes of sleep and wakefulness over the 24 hours. Sleep appeared
superficial and fragmented with repeated awakenings; there was a very low prevalence of slow
wave sleep (stages 3 and 4 non-rapid eye movement (NREM)) and an almost total absence of
REM sleep.

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Figure 2 (A) Twenty-four hours sleep hypnogram, recorded 10 days after the onset of symptoms. St. I, II, III
and IV = stage I, II, III and IV non-rapid eye movement. (B) Hypnogram obtained 3 months later. An episode of
nocturnal sleep is evident, with increased duration of rapid eye movement sleep. Daytime sleep duration
appears to be decreased, but three episodes of sleep can still be observed during the daytime. No further
recording of sleep could be performed during follow-up.

OUTCOME AND FOLLOW-UP

By day 10, the patient was in stable clinical conditions and was discharged to a rehabilitation
facility. One month later, a residual motor deficit was still present but speech had greatly
improved; hypersomnia was also still present. While hypersomnia did recover to a large extent at
3 months after the stroke, sleep architecture remained abnormal.

DISCUSSION
The most relevant finding in this patient with a small paramedian pontine ischaemic lesion was
the simultaneous presence of a disruption of the circadian rhythm (with nocturnal insomnia and a
daytime hypersomnolent state) and a severe alteration of the NREM-REM sleep mechanisms.
There have been rare reports of REM sleep disorders in association with lesions within or near

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the pontine tegmentum. Recently, Landau et al described a decreased percentage of REM sleep
in four out of eight patients with isolated brainstem lesions.8 A parasomnia characterised by
intermittent loss of electromyographic atonia during REM sleep with elaborate and violent
behaviour has been reported with unilateral pontine vascular lesions.9,10 The current view on
REM sleep generation indicate that the REM-on region is medial to the locus ceruleus at the
lower/mid level of the pons. In analogy to animal models,11 it is possible that in our case a lesion
to the precoeruleus region was implicated in the REM sleep disorder. To our knowledge, there
has been only a single report of sleep-waking cycle and NREM sleep alterations associated with
pontine ischaemia. Indeed, Tamura et al observed a clinical syndrome characterised by alteration
of the circadian rhythm, absence of REM phases and severely disorganised NREM phases.
However, the patients in this series presented extensive pontine vascular lesions involving the
pontine tegmentum.12

In conclusion, our observation suggests that a relatively small, paramedian pontine ischaemic
lesion can acutely induce a very severe sleep disorder. This can present clinically as an
excessive daytime sleepiness affecting not only REM but also NREM phases. Such impairment in
sleep regulation may result in a global disruption of the circadian sleep-waking rhythm.

Although no medications were used in our case, some of the alterations described might be
amenable to pharmacological treatment with modafinil, tricyclic antidepressants and even
melatonin.

LEARNING POINTS

There have been rare reports of sleep disorders in association with extensive lesions within
or near the pontine tegmentum.
Even small paramedian pontine ischaemic lesions can acutely induce sleep disorders with a
very severe disruption of both circadian rhythm and sleep organisation.
Hypersomnolent state tends to recover within 3 months, but sleep architecture appears to
remain abnormal more persistently.

Competing interests: none.

Patient consent: Patient/guardian consent was obtained for publication.

REFERENCES
1. Lovblad, KO, Bassetti, C, Mathis, J, et al. MRI of paramedian thalamic stroke with sleep
disturbance. Neuroradiology 1997; 39: 693–8.[CrossRef][Medline]

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2. Bassetti, CL, Mathis, J, Gugger, M, et al. Hypersomnia following paramedian thalamic stroke:
a report of 12 patients. Ann Neurol 1996; 39: 471–80.[CrossRef][Medline]
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sleep-wake disturbances after paramedian thalamic stroke. Stroke 2008; 39: 62–8.
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potentials during rapid eye movement sleep. Neuroscience 1996; 72: 209–14.
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geniculo-occipital waves in the human pons. Sleep 2008; 30: 823–7.
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literature and additional new cases. Neurophysiol Clin 2001; 31: 356–75.[CrossRef][Medline]
8. Landau, ME, Maldonado, JY, & Jabbari, B. The effects of isolated brainstem lesions on
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9. Kimura, K, Tachibana, N, Kohymana, J, et al. A discrete pontine ischemic lesion could cause
REM sleep behavior disorder. Neurology 2000; 55: 894–5.[Free Full Text]
10. Xi, Z, & Luning, W. REM sleep behavior disorder in a patient with pontine stroke. Sleep Med
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