Letter to the Editor
REM sleep behaviour disorder and “pure” autonomic failure: Presentation of two cases
Trastorno de conducta del sueño REM y fallo autonómico ¿puro? A propósito de 2 casos
B. Tijero
, J.C. Gómez-Esteban, K. Berganzo, J.J. Zarranz
Corresponding author
Servicio de Neurología, Hospital de Cruces, Baracaldo, Bilbao, Spain
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Tijero, J.C. Gómez-Esteban, K. Berganzo, J.J. Zarranz" "autores" => array:4 [ 0 => array:4 [ "nombre" => "B." "apellidos" => "Tijero" "email" => array:1 [ 0 => "beatriz_tijero@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "J.C." "apellidos" => "Gómez-Esteban" ] 2 => array:2 [ "nombre" => "K." "apellidos" => "Berganzo" ] 3 => array:2 [ "nombre" => "J.J." "apellidos" => "Zarranz" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Neurología, Hospital de Cruces, Baracaldo, Bilbao, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Trastorno de conducta del sueño REM y fallo autonómico ¿puro? A propósito de 2 casos" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 585 "Ancho" => 1400 "Tamanyo" => 127122 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Nuclear medicine tests in the first case. The left part of the cardiac-MIBG SPECT shows a significantly low cardiac uptake. The right 123-I-FP-CIT SPECT (DAT-SCAN) is normal.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The need for a diagnosis in the early stages of Parkinson's disease (PD) has led to increasingly more studies about early-stage signs and symptoms being published. A stereotyped and orderly progression of Lewy bodies in the brains of patients with PD<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> has been reported, but this α-synuclein deposit is not necessarily correlated with neuronal dysfunction or death and, therefore, with the symptoms. Thus, the first symptoms of PD can be very varied.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Longitudinal studies have shown that REM sleep behaviour disorder (RBD) can precede the diagnosis of a neurodegenerative disease (α-synucleinopathies), preferentially PD,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> in up to 45% of cases. It is known that autonomic failure is a late complication of PD and dementia with Lewy bodies (DLB), although it can sometimes constitute the presentation symptom.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> We recently described how a carrier of a mutation in the gene for α-synuclein (SNCA) presented dysautonomia as a sign of onset of her disease.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the cases of 2 patients with idiopathic RBD and peripheral autonomic failure without signs or symptoms of neurodegenerative disease. We discuss the risk of developing synucleinopathies and the implications of an early diagnosis.</p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case 1</span>. This patient was a 66-year-old male with no family history of neurodegenerative diseases. In 2004, he attended consultation for a sleep disorder consisting of nightmares, restless sleep and falling from the bed, which the patient referred having suffered for years. A polysomnography recorded during REM sleep found increased phasic phenomena and a loss of the physiological atonia of this phase. We gave a diagnosis of RBD, which improved with clonazepam (0.5<span class="elsevierStyleHsp" style=""></span>mg). Six months later he suffered cough syncope. A vegetative nervous system study showed a fixed heart rate unchanged by the Valsalva manoeuvre, administration of ephedrine or standing. There was also orthostatic hypotension (supine position 148/80<span class="elsevierStyleHsp" style=""></span>mmHg, HR 53; standing 120/65<span class="elsevierStyleHsp" style=""></span>mmHg, HR 53). He presented noradrenaline values while lying of 26<span class="elsevierStyleHsp" style=""></span>pg/ml (VN: 100–750), which rose to 124<span class="elsevierStyleHsp" style=""></span>pg/ml (VN: 200–1700) when standing. Olfactory deficit was not detected (11/12 items identified correctly in the Brief Smell Identification Test, BSIT). There was a marked uptake decrease in myocardial-MIBG SPECT I (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). A brain CT (MRI could not be performed due to the presence of metal particles) was normal. A 123-I-FP-CIT SPECT found no striatal uptake defects (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). This exploration was repeated 2 years later and showed normal values, although the striated/occipital lobe uptake ratios had decreased discretely.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case 2</span>. This patient was a 60-year-old woman who attended consultation due to repeated syncope and orthostatic intolerance, of 10 years’ evolution. She described other dysautonomic symptoms such as constipation and voiding problems: tenesmus and nocturia. She also presented a decrease in olfaction (7/12 in the BSIT). She reported vivid dreams and movement during sleep and the polysomnography found a loss of atonia during REM sleep. The dysautonomic study detected orthostatic hypotension on the tilting table (standing: 103/54<span class="elsevierStyleHsp" style=""></span>mmHg, HR 66; supine position 66/34<span class="elsevierStyleHsp" style=""></span>mmHg, HR 55) and nocturnal arterial hypertension in her blood pressure Holter results. Catecholamine study revealed a significant depletion of noradrenaline (supine position 17<span class="elsevierStyleHsp" style=""></span>pg/ml; standing, 31<span class="elsevierStyleHsp" style=""></span>pg/ml) with an increase of vasopressin during postural changes (supine position 3.9<span class="elsevierStyleHsp" style=""></span>pg/ml, standing 5.1<span class="elsevierStyleHsp" style=""></span>pg/ml). Both the Valsalva ratio (1.8) and the variability of heart rate with breathing were at the lower limit of normality. The reflex-sympathetic skin test was pathological in the lower limbs. The cranial MRI did not detect abnormalities that indicated the presence of multisystem atrophy (MSA). We performed a cardiac-MIBG SPECT with a myocardial/mediastinum ratio at 4<span class="elsevierStyleHsp" style=""></span>h of 1.8 (VN<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>1.7), while the 123-I-FP-CIT SPECT was normal.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The 2 patients described met the criteria for the diagnosis of RBD. The study results of both patients pointed towards a primary autonomic failure with sympathetic and parasympathetic postganglionic involvement.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> This entity includes 3 neurodegenerative diseases: pure autonomic failure (PAF), Parkinson's disease (PD) and multisystem atrophy (MSA).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Autonomic dysfunction in MSA is due to the degeneration of the preganglionic neurons, with α-synuclein cytoplasmic inclusions being found in neurons and glial cells of the brain stem and spine.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The sympathetic ganglia and postganglionic terminals are not affected. In contrast, the involvement of the vegetative nervous system in PD and PAF is predominantly postganglionic. Lewy bodies and neurites are found in the sympathetic ganglia and myenteric plexuses<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and, to a lesser extent, in the intermediolateral horns.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">There have been reports of reduced cardiac MIBG uptake in patients with RBD<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> without other additional symptoms, unlike the cases described above, with no clinical signs of dysautonomia. This shows that hypoperfusion in cardiac-MIBG SPECT may be an early finding and precede the onset of motor manifestations. Olfaction deficit, with the same characteristics as in PD patients, has also been reported in this group of patients.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The hypothesis that neurodegeneration in PD and DLB may begin in the postganglionic autonomic neurons<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> has important therapeutic and diagnostic implications, given that the study of the vegetative nervous system can be a useful tool in identifying patients in premotor stages, prior to neuronal degeneration of the substantia nigra. Recently, synuclein inclusions have been detected in the nerve fibres of cutaneous sweat glands in patients with pure autonomic failure.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The administration of drugs with neuroprotective effects, such as rasagiline, could be indicated in this group of patients. However, we believe that this should be preceded, firstly, by prospective studies that define the values of different biomarkers in these disorders<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and, secondly, by long-term clinical trials with these indications (RBD and pure autonomic failure).</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Tijero B, et al. Trastorno de conducta del sueño REM y fallo autonómico ¿puro? A propósito de 2 casos. Neurología. 2011;27:55–7.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 585 "Ancho" => 1400 "Tamanyo" => 127122 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Nuclear medicine tests in the first case. The left part of the cardiac-MIBG SPECT shows a significantly low cardiac uptake. The right 123-I-FP-CIT SPECT (DAT-SCAN) is normal.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Staging of brain pathology related to sporadic Parkinson's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H. Braak" 1 => "K. del Tredici" 2 => "U. Rub" 3 => "R.A. de Vos" 4 => "E.N. Jansen Steur" 5 => "E. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 0 | 11 |
| 2024 October | 55 | 4 | 59 |
| 2024 September | 54 | 11 | 65 |
| 2024 August | 45 | 9 | 54 |
| 2024 July | 54 | 12 | 66 |
| 2024 June | 49 | 1 | 50 |
| 2024 May | 36 | 5 | 41 |
| 2024 April | 51 | 25 | 76 |
| 2024 March | 63 | 4 | 67 |
| 2024 February | 60 | 8 | 68 |
| 2024 January | 59 | 5 | 64 |
| 2023 December | 56 | 8 | 64 |
| 2023 November | 48 | 9 | 57 |
| 2023 October | 42 | 5 | 47 |
| 2023 September | 38 | 3 | 41 |
| 2023 August | 35 | 11 | 46 |
| 2023 July | 43 | 10 | 53 |
| 2023 June | 40 | 3 | 43 |
| 2023 May | 98 | 9 | 107 |
| 2023 April | 86 | 5 | 91 |
| 2023 March | 52 | 5 | 57 |
| 2023 February | 49 | 5 | 54 |
| 2023 January | 53 | 5 | 58 |
| 2022 December | 53 | 11 | 64 |
| 2022 November | 54 | 12 | 66 |
| 2022 October | 43 | 12 | 55 |
| 2022 September | 56 | 23 | 79 |
| 2022 August | 55 | 21 | 76 |
| 2022 July | 27 | 14 | 41 |
| 2022 June | 33 | 9 | 42 |
| 2022 May | 43 | 10 | 53 |
| 2022 April | 34 | 9 | 43 |
| 2022 March | 55 | 6 | 61 |
| 2022 February | 46 | 6 | 52 |
| 2022 January | 57 | 4 | 61 |
| 2021 December | 58 | 10 | 68 |
| 2021 November | 44 | 12 | 56 |
| 2021 October | 66 | 13 | 79 |
| 2021 September | 49 | 12 | 61 |
| 2021 August | 41 | 5 | 46 |
| 2021 July | 42 | 9 | 51 |
| 2021 June | 35 | 10 | 45 |
| 2021 May | 56 | 11 | 67 |
| 2021 April | 137 | 50 | 187 |
| 2021 March | 102 | 10 | 112 |
| 2021 February | 71 | 11 | 82 |
| 2021 January | 81 | 18 | 99 |
| 2020 December | 71 | 11 | 82 |
| 2020 November | 60 | 5 | 65 |
| 2020 October | 44 | 9 | 53 |
| 2020 September | 46 | 13 | 59 |
| 2020 August | 48 | 8 | 56 |
| 2020 July | 40 | 10 | 50 |
| 2020 June | 21 | 5 | 26 |
| 2020 May | 24 | 7 | 31 |
| 2020 April | 20 | 8 | 28 |
| 2020 March | 35 | 3 | 38 |
| 2020 February | 55 | 4 | 59 |
| 2020 January | 52 | 17 | 69 |
| 2019 December | 45 | 9 | 54 |
| 2019 November | 24 | 10 | 34 |
| 2019 October | 55 | 12 | 67 |
| 2019 September | 38 | 9 | 47 |
| 2019 August | 29 | 7 | 36 |
| 2019 July | 49 | 17 | 66 |
| 2019 June | 80 | 33 | 113 |
| 2019 May | 235 | 46 | 281 |
| 2019 April | 87 | 38 | 125 |
| 2019 March | 29 | 12 | 41 |
| 2019 February | 38 | 10 | 48 |
| 2019 January | 19 | 11 | 30 |
| 2018 December | 21 | 16 | 37 |
| 2018 November | 24 | 7 | 31 |
| 2018 October | 25 | 23 | 48 |
| 2018 September | 23 | 9 | 32 |
| 2018 August | 7 | 10 | 17 |
| 2018 July | 4 | 8 | 12 |
| 2018 June | 13 | 4 | 17 |
| 2018 May | 21 | 8 | 29 |
| 2018 April | 16 | 2 | 18 |
| 2018 March | 7 | 7 | 14 |
| 2018 February | 8 | 4 | 12 |
| 2018 January | 6 | 0 | 6 |
| 2017 December | 7 | 1 | 8 |
| 2017 November | 13 | 6 | 19 |
| 2017 October | 7 | 11 | 18 |
| 2017 September | 15 | 7 | 22 |
| 2017 August | 19 | 9 | 28 |
| 2017 July | 13 | 1 | 14 |
| 2017 June | 18 | 10 | 28 |
| 2017 May | 22 | 11 | 33 |
| 2017 April | 12 | 6 | 18 |
| 2017 March | 7 | 19 | 26 |
| 2017 February | 20 | 5 | 25 |
| 2017 January | 14 | 7 | 21 |
| 2016 December | 23 | 13 | 36 |
| 2016 November | 19 | 11 | 30 |
| 2016 October | 22 | 16 | 38 |
| 2016 September | 18 | 11 | 29 |
| 2016 August | 22 | 7 | 29 |
| 2016 July | 20 | 3 | 23 |
| 2016 June | 37 | 23 | 60 |
| 2016 May | 25 | 27 | 52 |
| 2016 April | 24 | 15 | 39 |
| 2016 March | 40 | 23 | 63 |
| 2016 February | 22 | 26 | 48 |
| 2016 January | 18 | 30 | 48 |
| 2015 December | 17 | 19 | 36 |
| 2015 November | 20 | 18 | 38 |
| 2015 October | 28 | 23 | 51 |
| 2015 September | 16 | 27 | 43 |
| 2015 August | 50 | 17 | 67 |
| 2015 July | 42 | 13 | 55 |
| 2015 June | 17 | 16 | 33 |
| 2015 May | 28 | 29 | 57 |
| 2015 April | 18 | 19 | 37 |
| 2015 March | 20 | 13 | 33 |
| 2015 February | 31 | 21 | 52 |
| 2015 January | 38 | 6 | 44 |
| 2014 December | 53 | 15 | 68 |
| 2014 November | 19 | 1 | 20 |
| 2014 October | 26 | 2 | 28 |
| 2014 September | 26 | 4 | 30 |
| 2014 August | 31 | 4 | 35 |
| 2014 July | 34 | 9 | 43 |
| 2014 June | 18 | 0 | 18 |
| 2014 May | 16 | 2 | 18 |
| 2014 April | 12 | 0 | 12 |
| 2014 March | 22 | 7 | 29 |
| 2014 February | 16 | 3 | 19 |
| 2014 January | 11 | 3 | 14 |
| 2013 December | 25 | 4 | 29 |
| 2013 November | 28 | 5 | 33 |
| 2013 October | 41 | 11 | 52 |
| 2013 September | 36 | 9 | 45 |
| 2013 August | 35 | 5 | 40 |
| 2013 July | 17 | 2 | 19 |
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