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Involvement of cardiac sympathetic nerve endings in a patient with idiopathic RBD and intact nigrostriatal pathway
Parkinsonism and Related Disorders 15 (2009) 789–791
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Involvement of cardiac sympathetic nerve endings in a patient with idiopathic RBD and intact nigrostriatal pathwayq
We describe a 72-year-old Italian woman with frequent nighttime movement disorders. She was born from consanguineous parents, and she is currently married with three healthy sons. She was seen at our hospital because of a history of sleep disorder that began at the age of 69. She had a past history of hypertension that was very well controlled with drugs and she had a history of mild depression that was never treated with psychotropic medications. She did not have history of epilepsy nor alcohol abuse. During sleep, the patient was noticed to have strong shaking of her limbs and episodes of laughing, talking and screaming; she would also frequently fall out of bed. The patient had noted a change in the nature of her dreams as they had become more vivid and disturbing, and she had started to experience frequent nocturnal nightmares. Moreover, on many occasions she would awaken several times during the night to find herself lying on the floor with bruises or lacerations on her body caused by falling out of bed. For three years these nocturnal episodes had occurred almost every night and mainly in the first part of sleep. She had no excessive daytime sleepiness. There was no familial history of neurological disorders. When she was first admitted to our clinic (May 2008), her neurological examination was normal. She underwent a large battery of cognitive tests (executive functions, short- and long-term verbal memory, visuo-constructive praxis, logical thinking, verbal fluency; Mini Mental State examination (MMSE)), blood tests, chest x-ray, electrocardiogram (ECG), echocardiography, holter blood pressure monitoring and brain magnetic resonance imaging (MRI). Electroencephalograms (EEG) were recorded while the patient was awake and while asleep. A polysomnografic examination (PSG) was performed according to a standard clinical protocol with EEG recordings (electrodes: Fp2, C4, O2, Fp1, C3, O1), electro-oculography, ECG, oronasal and thoracoabdominal airflow and electromyography (EMG) recorded from both mylohyoid and anterior tibial muscles. The patient was also observed with an infrared video to detect movements during REM sleep. The diagnosis of RBD was made according to the International Classification of Sleep Disorders [1]. Olfactory functions have not been investigated. All cognitive tests were normal and MMSE showed a score of 28/30 corrected (n.v. 24/30). The patient did not suffer of orthostatic hypotension. Brain imaging was normal. Few central sleep apnoeas q
The review of this paper was entirely handled by the Co-Editor-in-Chief, Professor R.F. Pfeiffer. 1353-8020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.parkreldis.2009.03.008
were observed during stage II of non-REM sleep lasting between 10 and 20 s. PSG revealed several behavioural episodes with an elevated tonic and phasic muscle tone of the mylohyoid and anterior tibial muscles during the REM sleep stage (Fig. 1). There was no epileptiform activity throughout the recording. We have furthermore performed a cerebral single photon emission computed tomography (DAT-SPECT scan) with 123I-FP-CIT, which came back with normal results (Fig. 2 a); whereas, the myocardial 123metaiodiobenzylguanidine (MIBG) scintigraphy showed a markedly reduced cardiac uptake (Fig. 2 b). A treatment with 0.75 mg per day of clonazepam was started. Here we describe, for the first time, a patient with idiopathic RBD and a marked decrease of cardiac MIBG uptake but normal striatal dopaminergic neurons. RBD is a parasomnia characterized by the suppression of muscular atonia and abnormal, often violent, motor behaviours with a high proportion of aggressive content in the patient’s dreams during REM sleep [1]. RBD can be idiopathic without concomitant neurological disorders, but is mostly reported in patients with neurodegenerative disorders. RBD can be the prodromal symptom of a-synucleinopathies (e.g. Parkinson’s Disease (PD), dementia with Lewy bodies (LBD), multiple system atrophy (MSA) or less frequently, of tauopathies, such as progressive supranuclear palsy (PSP) [2]. DAT-SPECT is a marker of nigrostriatal degeneration used in the diagnostic workup of the parkinsonian syndromes. Patients with idiopathic RBD usually show either normal or decreased striatal dopamine transporter binding, sometimes in the absence of neurological symptoms [2,3]. Similarly to previous reports [3], our patient showed both a normal neurologic examination and a normal DAT-scan. Cardiac MIBG scintigraphy is a useful tool for differentiating patients with Lewy body pathology, such as PD and LBD from those with atypical parkinsonian syndromes (e.g., PSP or MSA) [4]. MIBG uptake reflects presynaptic sympathetic system integrity, and reduced myocardial uptake of the tracer suggests cardiac sympathetic dysfunction or denervation [4]. Indeed, cardiac MIBG uptake has been found markedly reduced in PD and LBD, whereas it was normal in a patient with PSA and MSA. In our patient, cardiac MIBG uptake was markedly decreased, a finding suggestive of Lewy body pathology. In agreement with our data, a recent study showed a marked reduction of the cardiac MIBG uptake in 13 patients with idiopathic RBD, suggesting that idiopathic RBD in older patients may be considered a forme fruste of a-synucleinopathy (PD or LBD) [4]. However, these authors did not perform
790
Letter to the Editor / Parkinsonism and Related Disorders 15 (2009) 789–791
Fig. 1. PSG recording showing REM sleep during nocturnal dream behaviour. Mylohyoid and anterior tibial electromyogram (channels 2 and 10) tones are increased with phasic accentuation. RSWA ¼ REM sleep without atonia; PSG: polysomnography.
DAT-SPECT and we do not know whether their patients that showed decreased MIBG uptake demonstrated also a decreased striatal dopamine transporter binding. Our patient with idiopathic RBD showed markedly reduced MIBG uptake but normal DAT-SPECT. Very recently, Orimo et al., studied cardiac tissues and paravertebral sympathetic ganglia of patients with LBD or PD, demonstrating that the accumulation of a-synuclein aggregates in the distal axons of the cardiac sympathetic nervous system preceded that occurring in neuronal somata or neuritis in the paravertebral sympathetic ganglia,
a finding that heralds centripetal degeneration of the cardiac sympathetic nerve in a-synucleinopathies, such as LBD and PD [5]. On this basis, we can hypothesize that in our RBD patient the evident denervation of cardiac sympathetic nerve endings preceded the damage of striatal presynaptic dopaminergic terminals. Our study shows that a patient with idiopathic RBD and normal DAT-scan had cardiac sympathetic denervation suggesting that these cardiac terminals may be impaired in absence of a detectable damage in the nigrostriatal system.
Fig. 2. a) Dopamine transporter SPECT in our patient showed a normal binding. b) Myocardial 123Metaiodobenzylguanidine (MIBG) planar anterior view (delayed image) showing a markedly decreased MIBG uptake in the early and the delayed images.
Letter to the Editor / Parkinsonism and Related Disorders 15 (2009) 789–791
References [1] Gagnon JF, Postuma RB, Mazza S, Montplaisir J. Rapid-eye-movement sleep behaviour disorder and neurodegenerative disease. The Lancet Neurology 2006;5:424–32. [2] Shenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapideye-movement sleep behaviour disorder. Neurology 1996;46:388–93. [3] Stiasny-Kolster K, Doerr Y, Mo¨ller JC, Ho¨ffken H, Behr TM, Oertel WH, et al. Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 2005;126–37. [4] Miyamoto T, Miyamoto M, Inoue Y, Usui Y, Suzuki K, Hirata K. Reduced cardiac 123 I-MIBG scintigraphy in idiopathic REM sleep behavior disorder. Neurology 2006;67(12):2236–8. [5] Orimo S, Uchihara T, Nakamura A, Mori F, Kakita A, Wakabayashi K, et al. Axonal a-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson’s disease. Brain 2008;131:642–50.
S. Paglionico1 Institute of Neurology, University Magna Græcia, Catanzaro, Italy A. Labate1 Institute of Neurology, University Magna Græcia, Catanzaro, Italy Institute of Neurological Sciences, National Research Council, Piano Lago - Mangone, Cosenza, Italy
1
These authors contributed equally to this work.
791
M. Salsone M. Morelli F. Novellino Institute of Neurology, University Magna Græcia, Catanzaro, Italy G. Cascini Institute of Radiology, University Magna Graecia, Catanzaro, Italy A. Quattrone* Institute of Neurology, University Magna Græcia, Catanzaro, Italy Institute of Neurological Sciences, National Research Council, Piano Lago - Mangone, Cosenza, Italy Correspondence to: Aldo Quattrone, Cattedra ed U.O. di Neurologia, Universita` degli Studi ‘‘Magna Graecia’’, Campus Universitario di Germaneto, Viale Europa, 88100 Catanzaro, Italy. Tel.: þ39 0961 3647071; fax: þ39 0961 3647177. E-mail address: [email protected] (A. Quattrone) 10 February 2009
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Involvement of cardiac sympathetic nerve endings in a patient with idiopathic RBD and intact nigrostriatal pathwayq
We describe a 72-year-old Italian woman with frequent nighttime movement disorders. She was born from consanguineous parents, and she is currently married with three healthy sons. She was seen at our hospital because of a history of sleep disorder that began at the age of 69. She had a past history of hypertension that was very well controlled with drugs and she had a history of mild depression that was never treated with psychotropic medications. She did not have history of epilepsy nor alcohol abuse. During sleep, the patient was noticed to have strong shaking of her limbs and episodes of laughing, talking and screaming; she would also frequently fall out of bed. The patient had noted a change in the nature of her dreams as they had become more vivid and disturbing, and she had started to experience frequent nocturnal nightmares. Moreover, on many occasions she would awaken several times during the night to find herself lying on the floor with bruises or lacerations on her body caused by falling out of bed. For three years these nocturnal episodes had occurred almost every night and mainly in the first part of sleep. She had no excessive daytime sleepiness. There was no familial history of neurological disorders. When she was first admitted to our clinic (May 2008), her neurological examination was normal. She underwent a large battery of cognitive tests (executive functions, short- and long-term verbal memory, visuo-constructive praxis, logical thinking, verbal fluency; Mini Mental State examination (MMSE)), blood tests, chest x-ray, electrocardiogram (ECG), echocardiography, holter blood pressure monitoring and brain magnetic resonance imaging (MRI). Electroencephalograms (EEG) were recorded while the patient was awake and while asleep. A polysomnografic examination (PSG) was performed according to a standard clinical protocol with EEG recordings (electrodes: Fp2, C4, O2, Fp1, C3, O1), electro-oculography, ECG, oronasal and thoracoabdominal airflow and electromyography (EMG) recorded from both mylohyoid and anterior tibial muscles. The patient was also observed with an infrared video to detect movements during REM sleep. The diagnosis of RBD was made according to the International Classification of Sleep Disorders [1]. Olfactory functions have not been investigated. All cognitive tests were normal and MMSE showed a score of 28/30 corrected (n.v. 24/30). The patient did not suffer of orthostatic hypotension. Brain imaging was normal. Few central sleep apnoeas q
The review of this paper was entirely handled by the Co-Editor-in-Chief, Professor R.F. Pfeiffer. 1353-8020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.parkreldis.2009.03.008
were observed during stage II of non-REM sleep lasting between 10 and 20 s. PSG revealed several behavioural episodes with an elevated tonic and phasic muscle tone of the mylohyoid and anterior tibial muscles during the REM sleep stage (Fig. 1). There was no epileptiform activity throughout the recording. We have furthermore performed a cerebral single photon emission computed tomography (DAT-SPECT scan) with 123I-FP-CIT, which came back with normal results (Fig. 2 a); whereas, the myocardial 123metaiodiobenzylguanidine (MIBG) scintigraphy showed a markedly reduced cardiac uptake (Fig. 2 b). A treatment with 0.75 mg per day of clonazepam was started. Here we describe, for the first time, a patient with idiopathic RBD and a marked decrease of cardiac MIBG uptake but normal striatal dopaminergic neurons. RBD is a parasomnia characterized by the suppression of muscular atonia and abnormal, often violent, motor behaviours with a high proportion of aggressive content in the patient’s dreams during REM sleep [1]. RBD can be idiopathic without concomitant neurological disorders, but is mostly reported in patients with neurodegenerative disorders. RBD can be the prodromal symptom of a-synucleinopathies (e.g. Parkinson’s Disease (PD), dementia with Lewy bodies (LBD), multiple system atrophy (MSA) or less frequently, of tauopathies, such as progressive supranuclear palsy (PSP) [2]. DAT-SPECT is a marker of nigrostriatal degeneration used in the diagnostic workup of the parkinsonian syndromes. Patients with idiopathic RBD usually show either normal or decreased striatal dopamine transporter binding, sometimes in the absence of neurological symptoms [2,3]. Similarly to previous reports [3], our patient showed both a normal neurologic examination and a normal DAT-scan. Cardiac MIBG scintigraphy is a useful tool for differentiating patients with Lewy body pathology, such as PD and LBD from those with atypical parkinsonian syndromes (e.g., PSP or MSA) [4]. MIBG uptake reflects presynaptic sympathetic system integrity, and reduced myocardial uptake of the tracer suggests cardiac sympathetic dysfunction or denervation [4]. Indeed, cardiac MIBG uptake has been found markedly reduced in PD and LBD, whereas it was normal in a patient with PSA and MSA. In our patient, cardiac MIBG uptake was markedly decreased, a finding suggestive of Lewy body pathology. In agreement with our data, a recent study showed a marked reduction of the cardiac MIBG uptake in 13 patients with idiopathic RBD, suggesting that idiopathic RBD in older patients may be considered a forme fruste of a-synucleinopathy (PD or LBD) [4]. However, these authors did not perform
790
Letter to the Editor / Parkinsonism and Related Disorders 15 (2009) 789–791
Fig. 1. PSG recording showing REM sleep during nocturnal dream behaviour. Mylohyoid and anterior tibial electromyogram (channels 2 and 10) tones are increased with phasic accentuation. RSWA ¼ REM sleep without atonia; PSG: polysomnography.
DAT-SPECT and we do not know whether their patients that showed decreased MIBG uptake demonstrated also a decreased striatal dopamine transporter binding. Our patient with idiopathic RBD showed markedly reduced MIBG uptake but normal DAT-SPECT. Very recently, Orimo et al., studied cardiac tissues and paravertebral sympathetic ganglia of patients with LBD or PD, demonstrating that the accumulation of a-synuclein aggregates in the distal axons of the cardiac sympathetic nervous system preceded that occurring in neuronal somata or neuritis in the paravertebral sympathetic ganglia,
a finding that heralds centripetal degeneration of the cardiac sympathetic nerve in a-synucleinopathies, such as LBD and PD [5]. On this basis, we can hypothesize that in our RBD patient the evident denervation of cardiac sympathetic nerve endings preceded the damage of striatal presynaptic dopaminergic terminals. Our study shows that a patient with idiopathic RBD and normal DAT-scan had cardiac sympathetic denervation suggesting that these cardiac terminals may be impaired in absence of a detectable damage in the nigrostriatal system.
Fig. 2. a) Dopamine transporter SPECT in our patient showed a normal binding. b) Myocardial 123Metaiodobenzylguanidine (MIBG) planar anterior view (delayed image) showing a markedly decreased MIBG uptake in the early and the delayed images.
Letter to the Editor / Parkinsonism and Related Disorders 15 (2009) 789–791
References [1] Gagnon JF, Postuma RB, Mazza S, Montplaisir J. Rapid-eye-movement sleep behaviour disorder and neurodegenerative disease. The Lancet Neurology 2006;5:424–32. [2] Shenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapideye-movement sleep behaviour disorder. Neurology 1996;46:388–93. [3] Stiasny-Kolster K, Doerr Y, Mo¨ller JC, Ho¨ffken H, Behr TM, Oertel WH, et al. Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 2005;126–37. [4] Miyamoto T, Miyamoto M, Inoue Y, Usui Y, Suzuki K, Hirata K. Reduced cardiac 123 I-MIBG scintigraphy in idiopathic REM sleep behavior disorder. Neurology 2006;67(12):2236–8. [5] Orimo S, Uchihara T, Nakamura A, Mori F, Kakita A, Wakabayashi K, et al. Axonal a-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson’s disease. Brain 2008;131:642–50.
S. Paglionico1 Institute of Neurology, University Magna Græcia, Catanzaro, Italy A. Labate1 Institute of Neurology, University Magna Græcia, Catanzaro, Italy Institute of Neurological Sciences, National Research Council, Piano Lago - Mangone, Cosenza, Italy
1
These authors contributed equally to this work.
791
M. Salsone M. Morelli F. Novellino Institute of Neurology, University Magna Græcia, Catanzaro, Italy G. Cascini Institute of Radiology, University Magna Graecia, Catanzaro, Italy A. Quattrone* Institute of Neurology, University Magna Græcia, Catanzaro, Italy Institute of Neurological Sciences, National Research Council, Piano Lago - Mangone, Cosenza, Italy Correspondence to: Aldo Quattrone, Cattedra ed U.O. di Neurologia, Universita` degli Studi ‘‘Magna Graecia’’, Campus Universitario di Germaneto, Viale Europa, 88100 Catanzaro, Italy. Tel.: þ39 0961 3647071; fax: þ39 0961 3647177. E-mail address: [email protected] (A. Quattrone) 10 February 2009