Lambeth Healthcare NHS Trust, St Thomas' Hospital, London
Lane Fox Unit, Guy's and St Thomas' Hospital Trust, St Thomas' Hospital, London
Neuropsychiatry and Memory Disorders Clinic, Academic Unit of Psychiatry, St Thomas' Hospital, London
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Correspondence: Dr Nicholas Clarke, Consultant in Old Age Psychiatry, Invicta Community Care NHS Trust, Alexander House, Vines Lane, Hildenborough, Kent TN11 9LY
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ABSTRACT |
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Aims To report on a 74-year-old man with a history of depression and REM sleep behaviour disorder, associated with mild cognitive impairment.
Method Assessment using brain CT, MRI, PET, electroencephalography, neuropsychological testing and nocturnal polysomnography.
Results Depression was treated with sertraline. Sleep laboratory studies supported a diagnosis of REM sleep behaviour disorder, which was treated with clonazepam. Sleep apnoea, revealed later, was treated with nasal continuous positive airways pressure. Brain MRI showed mild atrophy, but neuropsychological testing indicated no progressive cognitive deterioration.
Conclusions This case draws attention to REM sleep behaviour disorder and its potential interaction with depression and cognitive impairment, producing symptoms which can be mistaken for early dementia. The diagnosis of REM sleep behaviour disorder is easily missed, and it requires careful history-taking and sleep investigation in all suspected sufferers. Associated neurological, sleep and psychiatric conditions (including depression and cognitive impairment) may confound the diagnosis.
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INTRODUCTION |
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CASE HISTORY |
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Collateral history
The patient's wife stated that he had become more vague, and that his
previously very good memory had deteriorated, over four years. On further
questioning, she complained bitterly of a change in his sleep behaviour, which
had become increasingly disturbed over the same period. One-and-a-half to two
hours after falling asleep, the patient would thrash his arms and legs about,
talk or shout unintelligibly while sitting up, and exhibit increasingly
violent behaviour towards his wife. On occasion, he knocked or threw bedside
furniture towards her. His snoring had increased greatly, and he reported
menacing dreams. This behaviour occurred for prolonged periods
between the hours of 01.30 and 04.30. The subject was difficult to rouse
during these episodes; on awaking he had no dream recall, appeared confused
and was unaware of what had happened. At no time did he describe to his wife a
dream of a violent nature that could be directly related to his sleeping
behaviour. The patient complained of increased waking during the night.
Personal history
Apart from some night terrors in childhood, there was no significant
personal or family history of psychiatric disorder. An electrical engineer,
the subject retired in 1984 as a director of a multinational company. He
remarried at the age of 40; his wife had never noticed sleep-talking,
sleep-walking, abnormal nocturnal movements, or bruxism until the recent
symptoms. A non-smoker, he drank moderately. He lost consciousness for one
hour in a road traffic accident in 1960, but there was no skull fracture.
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CLINICAL ASSESSMENT, INVESTIGATIONS AND PROGRESS |
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Neuropsychology
Neuropsychological testing at this time showed a high verbal and full-scale
IQ consistent with the patient's predicted premorbid IQ (as measured by using
the National Adult Reading Test-Revised (NART-R;
Nelson & Willison, 1991),
with a 12-point verbal-performance IQ difference (see Tables
1 and
2). Although frontal/executive
test scores were within the normal range, one might expect the subject's FAS
verbal fluency score (Benton,
1968) to have been higher, given his premorbid educational
achievement. The visual memory quotient from the Wechsler Memory Scale -
Revised (WMS-R; Wechsler,
1987) and the score on the words component of the Recognition
Memory Test (RMT; Warrington,
1984) were well above average
(Table 2). However, the verbal
memory quotient and the delayed recall and attention/concentration quotients
on the WMS-R were some 20-30 points below what would be expected on the basis
of the subject's IQ, raising suspicions of an early dementia.
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Investigations
The results of a routine blood screen were normal, as were those of a chest
X-ray, 24-hour electrocardiogram (ECG), daytime and sleep
electroencephalograms (EEGs), pulse oximetry, and fluorodeoxyglucose brain
positron emission tomography (PET). Brain magnetic resonance imaging (MRI)
showed mild cortical atrophy and a slight degree of ventricular
dilatation.
Initial treatment
Before referral to the clinic, dothiepin 150 mg at night had failed to
improve the subject's symptoms. We replaced this treatment with sertraline,
titrated to 150 mg daily. This produced clinical improvement in mood, and his
wife reported that the subject became less withdrawn and irritable. The new
treatment also helped his sleep disturbance, reducing the frequency and
severity of the sleep symptoms. This response was found to be dose-dependent:
the symptoms of thrashing, shouting and disturbed sleep returned within a few
days of the sertraline dose being reduced to 100 mg daily, and improved again
within days of reinstitution of the 150 mg dose.
Further sleep investigation and treatment
After some months, the sleep and behaviour disturbance worsened again
despite the treatment with sertraline, at which time nocturnal polysomnography
was performed, using a conventional montage of EEG
(C1A2, C2A3), sub-mental
electromyelogram (EMG), ECG, respiratory inductance plethysmography,
measurement of oronasal airflow by thermistor, tibial EMG and pulse oximetry.
The important findings were periods of REM without atonia
(Fig. 1), frequent bursts of
periodic leg movements associated with arousal, and normal respiration
throughout without apnoeas or hypopnoeas. Clonazepam 0.5 mg at night was
prescribed and produced a period of asymptomatic sleep, but intermittent motor
activity returned, unresolved by an increase in dose to 0.75 mg. At about this
time, the subject developed loud snoring: repeat nocturnal polysomnography (on
treatment) now demonstrated moderate obstructive sleep apnoea, in addition to
the features previously seen; this was effectively controlled by nasal
continuous positive airways pressure. The latter treatment quickly appeared to
improve the patient's sleep pattern, and in the daytime gave him more
energy, a renewed interest in his hobbies, improved alertness and
reduced irritability. These changes have persisted. He has remained on
continuous pharmacotherapy (sertraline and clonazepam) and continuous positive
airways pressure.
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Further cognitive examination
In-patient investigations in November 1994 and November 1996 included
repeat neuro-psychological testing, a blood screen for dementia, and
neuroimaging. Although the subject showed slight improvements in his IQ and
FAS verbal fluency scores in November 1994 (which were maintained two years
later), there was evidence of decline on the word and face recognition memory
test. By November 1996, the results of this test had also returned to normal
(Tables 1 and
2). On the latter occasion, the
patient's overall memory score on the Doors and People test
(Baddeley et al, 1994)
was at the 75th percentile, equivalent to a memory quotient greater than 115
(i.e. close to his estimated premorbid IQ score). The second brain MRI showed
very minimally increased general cortical atrophy. Results of the repeat blood
dementia screen were normal.
The patient's erythrocyte sedimentation rate, initially normal, rose to 89 at one point in association with symptoms of polymyalgia rheumatica. It responded fully to low-dose prednisolone, which was gradually withdrawn.
Outcome
No further sleep, mood or behavioural abnormalities were observed during
two inpatient assessments with clonazepam and sertraline therapy. By February
1997, the subject's depression had improved and he was off medication (at his
insistence); his memory and frontal test scores had not declined (several of
these scores are well above the population means), while the
verbal-performance IQ discrepancy had narrowed to only two points.
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DISCUSSION |
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Sleep disorder diagnosis
The diagnosis of REM sleep behaviour disorder was made on the basis of the
patient's history and the findings from polysomnography. The violent motor
jerks and apparently coordinated actions and gestures, occurring with cries
and speech in the middle and late stages of the night, when REM sleep was
indicated on sleep staging, clearly indicated this diagnosis. The transient
confusion on waking from this state, the lack of dream recall and the
detection of additional sleep apnoea do not accord with the original
description of the condition by Schenck et al
(1986). However, similar
absence of dream recall, with associated sleep apnoea and daytime
confusion, has been reported by Turner et al
(1997) in a case of REM sleep
behaviour disorder with clinical diffuse Lewy body disease. Although our
patient may represent an interesting parallel, he did not have symptoms
sufficient to make a diagnosis of diffuse Lewy body disease
(McKeith et al, 1994).
The only sleep pathology in depression, reduction in REM latency, is unlikely
to have contributed to the loss of REM atonia. Our patient did not sleepwalk,
and showed no other symptoms suggestive of a partial arousal disorder. His
history of infantile night terrors may represent a vulnerability to sleep
disorders.
Non-progressive cognitive impairment
The subject's cognitive deterioration, which was initially interpreted as
early dementia, showed no further progress. In contrast, many of the later
tests (e.g. FAS verbal fluency) showed normal or improved
scores. This leads us to attribute his initial cognitive decline to normal
ageing aggravated by a combination of depression and REM sleep behaviour
disorder a variant of depressive pseudodementia. This
contrasts with the organic central nervous system pathology
found to be present in up to half the known cases of REM sleep behaviour
disorder to date (Schenck et al,
1996a).
Neurochemistry of REM sleep behaviour disorder and depression
It has been suggested that loss of noradrenergic locus ceruleus neurons may
cause REM sleep behaviour disorder in humans by removing a gate mechanism
responsible for inhibiting the cholinergic mesopontine neurons. The latter are
involved in the reticular activating system, and may drive REM
sleep (Schenck et al,
1996b). The release of our patient's REM
sleep behaviour disorder in association with depression, and the subsequent
response of both conditions to a selective serotonin reuptake inhibitor (SSRI)
antidepressant, may further implicate adrenergic (and serotonergic) brain
dysfunction in the aetiology of REM sleep behaviour disorder.
Drug treatment of the sleep disorder
This case is the first reported instance of a serotonergic antidepressant
drug (transiently) suppressing REM sleep behaviour disorder. Reduction in
duration of REM sleep by SSRIs provides a possible explanation for such an
effect (Sharpley & Cowen,
1995), but the cellular mechanism for this is not understood. With
the use of a benzodiazepine for REM sleep behaviour disorder, the development
of obstructive sleep apnoea could possibly have been predicted. In this age
group, more than 31% of men have more than five apnoeas per hour of sleep
(Young et al, 1993).
The clonazepam might therefore have precipitated clinically significant sleep
apnoea and, with this, the recurrence of thrashing in bed, a
recognised feature of the disorder
(Guilleminault, 1989). Nasal
continuous positive airways pressure is uniformly effective in treating sleep
apnoea and allows the continued use of sedatives. Alleviation of the sleep
disruption caused by obstructive sleep apnoea may also have contributed to the
relief of our patient's depression.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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Received for publication April 28, 1999. Revision received July 16, 1999. Accepted for publication July 21, 1999.