ADVERTISEMENT

Issue Navigator

Volume 12 No. 01
Earn CME
Accepted Papers





Sleep Medicine Pearls

A 76 Year-Old Woman with Sleep and Waking Stridor, Sleep Talking, Orthostatic Hypotension, and Imbalance

Erik K. St. Louis, MD1,2,3; Ethan J. Duwell, BA1,2,3; Diana M. Orbelo, PhD4; Eduardo E. Benarroch, MD3; Elizabeth A. Coon, MD3; Bradley F. Boeve, MD1,3; Michael H. Silber, MBChB1,3
1Mayo Center for Sleep Medicine, Mayo Clinic College of Medicine, Rochester, MN; 2Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN; 3Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN; 4Department of Otorhinolaryngology, Mayo Clinic College of Medicine, Rochester, MN

A 76-year-old woman presented with a three-month history of a harsh, high-pitched breathing noise during sleep, which had also recently begun to occur occasionally during the daytime while awake. Sleep talking had been noted for decades but recently had become louder and more agitated in character. No other nocturnal motor activity was noted. Over the last year, she had intermittent urinary urgency and incontinence; softer, imprecise speech; imbalance; and dizziness while standing, with severe supine hypertension. Midodrine was unhelpful. Her only medication was losartan 25 mg daily.

On examination, there was moderate hypomimia, hypokinetic dysarthria, inspiratory and phonatory stridor (Video 1), moderate symmetric rigidity and bradykinesia, and a 30-mm systolic blood pressure drop from sitting to standing. Also noted was loud waking stridor, particularly notable during inspiration, with use of accessory respiratory muscles (sternocleidomastoid and neck strap muscles) indicating increased effort as the patient breathes against dysfunctional vocal cords (Video 1).

Videolaryngoscopy showed significantly reduced vocal fold mobility bilaterally, with failure of abduction and paradoxical movement of true vocal fold tissue during inspiration. Autonomic reflex screen demonstrated severe orthostatic hypotension during head-up tilt table testing, and marked cardiovagal, cardiovascular adrenergic, and patchy postganglionic sympathetic sudomotor abnormalities. Thermoregulatory sweat testing demonstrated severe anhidrosis compatible with central autonomic failure. Brain MRI showed linear hyperintensities along the lateral aspects of the putamen (Figure 1).

Top: Laryngoscopy demonstrated bilateral, near total, vocal fold paralysis, associated with sleep and waking inspiratory and phonatory stridor. Bottom: Thermoregulatory sweat testing showed near complete anhidrosis with only light sweating over the hands. Brain MRI demonstrated linear hyperintensities along the lateral aspects of the putamen bilaterally, right more than left.

jcsm.12.1.143a.jpg

jcsm.12.1.143a.jpg
Figure 1

Top: Laryngoscopy demonstrated bilateral, near total, vocal fold paralysis, associated with sleep and waking inspiratory and phonatory stridor. Bottom: Thermoregulatory sweat testing showed near complete anhidrosis with only light sweating over the hands. Brain MRI demonstrated linear hyperintensities along the lateral aspects of the putamen bilaterally, right more than left.

(more ...)

QUESTION: What diagnosis does the clinical presentation, laryngoscopic, brain MRI, and thermoregulatory sweat testing findings shown in Figure 1 suggest?

  1. Parkinson disease

  2. Huntington disease

  3. Multiple system atrophy

  4. Idiopathic REM sleep behavior disorder

  5. Progressive supranuclear palsy

ANSWER: C. Multiple system atrophy.

Polysomnography recorded stridor during all positions and stages of sleep. Apnea-hypopnea index was 13/h, with oxyhemoglobin saturation nadir of 83%. Nasal continuous positive airway pressure was titrated to 13 cm H2O, eliminating stridor, and further titration to 16 cm H2O eliminated respiratory effort-related arousals. Manually quantified REM sleep without atonia (RSWA) analysis of combined phasic and tonic muscle activity in both submentalis (SM) muscle and tibialis anterior (TA) muscles was 83.5% (with muscle activity calculated as the total number of positively scored REM sleep 3-s mini epochs, divided by the total number of analyzable REM sleep 3-s mini-epochs). Control group combined RSWA muscle activity cutoff was previously defined as 43.4%.1 Manually quantified RSWA tonic muscle activity in the SM and TA muscles was 69.7%, with control group tonic RSWA muscle activity cutoff previously defined as 1.2%.1

Computerized automated REM atonia index (RAI) in the SM EMG assessed using HypnoLab sleep scoring software (ATES Medica Labs, Verona, Italy) was 0.35%. The RAI was scored on a scale of 0–1, with a score of zero indicating complete absence of muscle atonia and one indicating completely preserved muscle atonia. Values < 0.8 are strongly indicative of RSWA, values between 0.81 and 0.90 indicate likely abnormal muscle activity, while an RAI > 0.9 indicates preserved muscle atonia; the diagnostic cutoff determined in our laboratory that best distinguished RBD cases from controls was 0.88.1,2

Nasal CPAP and melatonin 3 mg were initially prescribed; but given daytime stridor and poor vocal fold mobility, tracheostomy with a Passy-Muir valve to permit speech was recommended. Lee Silverman Voice Therapy program for hypokinetic dysarthria was also suggested.

DISCUSSION

Multiple system atrophy (MSA) is a neurodegenerative disorder with predominant brainstem α-synuclein deposition. MSA is clinically characterized by autonomic failure (orthostatic hypotension, bowel and bladder dysfunction, with sweating abnormalities) and motor impairment with parkinsonism (rigidity, bradykinesia, and postural instability) and/or cerebellar ataxia with prominent sleep disturbances including REM sleep behavior disorder (RBD) and sleep disordered breathing (SDB). SDB in MSA may include obstructive or central sleep apnea, central alveolar hypoventilation, and most characteristically, sleep and daytime stridor due to laryngeal weakness or dystonia. Stridor and obstructive and central SDB in MSA likely relate to dysregulation of inspiratory laryngeal and pharyngeal motoneurons and the pontomedullary respiratory network involving the lateral dorsal tegmental, pedunculopontine, parabrachial/Kölliker-Fuse, nucleus of solitary tract, and ventrolateral medulla, as well as degeneration of serotonergic medullary raphe chemosensitive neurons.24

The differential diagnosis for acutely evolving stridor includes allergic reactions, epiglottitis associated with Haemophilus influenzae type b, inhalation injury (e.g., due to cleaning agents, or smoke inhalation), laryngeal tumors, and idiopathic vocal cord dysfunction, although as distinguished from our patient where the temporal course involved initial sleep before waking stridor, most of these other conditions would present with initial waking stridor as well. When stridor is present, visualization of the vocal folds by laryngoscopy is crucial. In our opinion, tracheostomy should be strongly considered to help prevent the risk of sudden death if there is bilateral vocal fold paralysis, if stridor is present during the day, or if nocturnal stridor does not respond to nasal CPAP therapy, as tracheostomy may provide protection against breathing arrest during the awake state, since most patients without ventilatory failure would not choose to utilize CPAP while awake.46 Nasal CPAP is a reasonable alternative when stridor is limited to sleep7 and when vocal folds still demonstrate reasonable function, and even in some cases with complete vocal fold abduction restriction.11 Future multicenter prospective observational and randomized trials between CPAP and tracheostomy will be necessary to define optimal evidence-based treatment approaches for sleep and daytime stridor in MSA.

Repeat laryngoscopy should be performed at regular intervals if CPAP therapy is selected to detect progressive laryngeal dysfunction. Cases of sudden death during sleep have still been reported following treatment with either nasal CPAP or tracheostomy, suggesting that other mechanisms of autonomic dysfunction may still be fatal in MSA.4,6 RBD and REM sleep without atonia characterized by especially prominent excessive tonic muscle activity are frequent in MSA. Melatonin or clonazepam may be offered as therapies, with melatonin preferred to avoid exacerbating SDB and neurological dysfunction.12 Taking a thorough medication history for any medications that could provoke or aggravate RSWA is important in all patients presenting with parasomnia behaviors. Several medications have been associated with RSWA, including tricyclic, selective serotonin reuptake inhibitors, and mixed mechanism antidepressants (i.e., mirtazapine and venlafaxine), and monamine oxidase inhibitors such as seligline.13,14

Unfortunately, no specific therapies to arrest the relentless progression of MSA neurodegeneration exist. Symptomatic treatments include levodopa-carbidopa or a dopamine agonist for parkinsonism (although MSA patients often respond poorly and fail to tolerate dopaminergic therapies due to worsened orthostatism) and midodrine (ProAmatine) or fludrocortisone (Florinef) for orthostatic hypotension.

MSA may present with sleep stridor and RBD in the absence of prominent parkinsonism or cerebellar ataxia,15 so sleep specialists should consider prompt neurological and otorhinolaryngology referral when these signs are encountered.

SLEEP MEDICINE PEARLS

  1. Sleep-related stridor can be the presenting manifestation of MSA and is associated with sudden death.

  2. Sleep-related stridor associated with MSA may respond to nasal continuous positive airway pressure (CPAP) therapy.

  3. The presence of waking stridor signals the need for consideration of prompt elective tracheostomy.

DISCLOSURE STATEMENT

This was not an industry supported study. The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number 1 UL1 RR024150-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr. St. Louis has received research support from Mayo Clinic CCaTS and was on the Data/Safety Monitoring Board for Inspire, Inc. Dr. Boeve has received research support from GE Healthcare, has received royalties from Cambridge Medical, and consulted for Tau Consortium. The other authors have indicated no financial conflicts of interest. Dr. St. Louis was the principal investigator.

ABBREVIATIONS

MSA

multiple system atrophy

RBD

REM sleep behavior disorder

SDB

sleep-disordered breathing

CITATION

St. Louis EK, Duwell EJ, Orbelo DM, Benarroch EE, Coon EA, Boeve BF, Silber MH. A 76 year-old woman with sleep and waking stridor, sleep talking, orthostatic hypotension, and imbalance. J Clin Sleep Med 2016;12(1):143–145.

ACKNOWLEDGMENTS

The authors gratefully acknowledge Ms. Lori Lynn Reinstrom in the Mayo Clinic Department of Neurology for secretarial assistance with manuscript preparation and submission.

REFERENCES

1 

McCarter SJ, St Louis EK, Duwell EJ, et al., authors. Diagnostic thresholds for quantitative REM sleep phasic burst duration, phasic and tonic muscle activity, and REM atonia index in REM sleep behavior disorder with and without comorbid obstructive sleep apnea. Sleep. 2014;37:1649–62. [PubMed Central][PubMed]

2 

Ferri R, Rundo F, Manconi M, et al., authors. Improved computation of the atonia index in normal controls and patients with REM sleep behavior disorder. Sleep Med. 2010;11:947–9. [PubMed]

3 

Benarroch EE, author. Brainstem in multiple system atrophy: clinicopathological corlations. Cell Mol Neurobiol. 2003;23:519–26. [PubMed]

4 

Benarroch EE, author. Brainstem respiratory control: substrates of respiratory failure of multiple system atrophy. Mov Disord. 2007;22:155–61. [PubMed]

5 

Lalich IJ, Ekbom DC, Starkman SJ, Orbelo DM, Morgenthaler TI, authors. Vocal fold motion impairment in multiple system atrophy. Laryngoscope. 2014;124:730–5. [PubMed]

6 

Silber MH, Levine S, authors. Stridor and death in multiple system atrophy. Mov Disord. 2000;15:699–704. [PubMed]

7 

Iranzo A, Santamaria J, Tolosa E, et al., authors. Long-term effect of CPAP in the treatment of nocturnal stridor in multiple system atrophy. Neurology. 2004;63:930–2. [PubMed]

8 

Iranzo A, Santamaria J, Rye DB, et al., authors. Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD. Neurology. 2005;65:247–52. [PubMed]

9 

McCarter SJ, St Louis EK, Boeve BF, authors. REM sleep behavior disorder and REM sleep without atonia as an early manifestation of degenerative neurological disease. Curr Neurol Neurosci Rep. 2012;12:182–92. [PubMed Central][PubMed]

10 

Talley HN, Sandness DJ, McCarter SJ, et al., authors. Quantitative analyses of REM sleep without atonia discriminates between major synucleinopathy phenotypes of Parkinson disease and multiple system atrophy. Sleep. 2015;38(Abstract Suppl):A255.

11 

Iranzo A, Santamaria J, Tolosa E, authors. Continuous positive air pressure eliminates nocturnal stridor in multiple system atrophy. Barcelona Multiple System Atrophy Study Group. Lancet. 2000;356:1329–30. [PubMed]

12 

McCarter SJ, Boswell CL, St Louis EK, et al., authors. Treatment outcomes in REM sleep behavior disorder. Sleep Med. 2013;14:237–42. [PubMed Central][PubMed]

13 

McCarter SJ, St Louis EK, Sandness DJ, et al., authors. Antidepressants Increase REM sleep muscle tone in patients with and without REM sleep behavior disorder. Sleep. 2015;38:907–17. [PubMed Central][PubMed]

14 

Hoque R, Chesson AL Jr, authors. Pharmacologically induced/exacerbated restless legs syndrome, periodic limb movements of sleep, and REM behavior disorder/REM sleep without atonia: literature review, qualitative scoring, and comparative analysis. J Clin Sleep Med. 2010;6:79–83. [PubMed Central][PubMed]

15 

Gaig C, Iranzo A, Tolosa E, Vilaseca I, Rey MJ, Santamaria J, authors. Pathological description of a non-motor variant of multiple system atrophy. J Neurol Neurosurg Psychiatry. 2008;79:1399–400. [PubMed]


Supplemental Material

Supplemental Material

(.mp4 | 29.09 MB)