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Volume 15 No. 01
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Accepted Papers





Case Reports

Occurrence of Stridor During Sleep in a Patient With Spinocerebellar Ataxia Type 17

Kyeong Joon Kim, MD1; Jong-Min Kim, MD2; Yun Jung Bae, MD3; In-Young Yoon, MD4; Yoo Sung Song, MD5; Sang Eun Kim, MD5
1Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Korea; 2Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea; 3Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea; 4Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea; 5Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea

ABSTRACT

Autosomal dominant spinocerebellar ataxia type 17 (SCA17) is known to have various manifestations. Previously, ataxia and autonomic dysfunction have been reported with this disorder, making an overlap with multiple systemic atrophy (MSA). However, respiratory complications, especially stridor during sleep, have not yet been reported with SCA17, in contrast to MSA, in which stridor occurs during sleep and is associated with an increased risk of death. Herein, we report a patient with SCA17, in whom stridor developed during sleep.

Citation:

Kim KJ, Kim JM, Bae YJ, Yoon IY, Song YS, Kim SE. Occurrence of stridor during sleep in a patient with spinocerebellar ataxia type 17. J Clin Sleep Med. 2019;15(1):153–155.


INTRODUCTION

Autosomal dominant spinocerebellar ataxia type 17 (SCA17) is a rare neurologic disorder caused by abnormal CAG/CAA repeat expansions within the TATA-box binding protein (TBP) gene.1 Patients with SCA17 could manifest progressive ataxia and autonomic dysfunction, and therefore may be diagnosed as multiple systemic atrophy (MSA).2 Among the various respiratory complications observed in patients with advanced MSA, stridor and upper airway obstruction are particularly associated with decreased survival.3 However, to the best of our knowledge, there have not been any reported cases of respiratory symptoms associated with SCA17. Herein, we report a patient with SCA17, in whom MSA was diagnosed and stridor developed during sleep.

REPORT OF CASE

A 48-year-old man presented with an insidiously developed progressive gait imbalance. Before the onset of gait imbalance, he had difficulty with urination, constipation, and postural dizziness, and he also suffered from dream enactment and sleep talking, which was reported by his wife, for 3 years. None of his family members had similar symptoms.

Neurologic examination revealed a bilateral, symmetric limb ataxia, and wide-based gait with bilateral swaying. He showed a marked drop in blood pressure without responsive tachycardia (supine: 149/86 – 62/min, 1 minute after standing: 93/53 – 85/min, 3 minutes: 78/47 – 86/min, 5 minutes: 72/47 – 85/min).

On 7 Tesla MRI, there was a loss of nigral hyperintensity in the bilateral substantia nigra4 (Figure 1A, B). On 3 Tesla MRI, atrophy of the brainstem and cerebellum was revealed (Figure 1C). On 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography (123I-FP-CIT SPECT), both putamina showed decreased uptake, with a greater decrease in the left side (Figure 1D). Levodopa was started to relieve gait disturbance, however, with no significant improvement. Based on his clinical features and brain images, the initial diagnosis was MSA.5 At that time, systemic screening for genetic causes of parkinsonism revealed increased 44 CAG/CAA repeats in the TATA box-binding protein (TBP) gene, suggesting SCA17. Genetic tests for spinocerebellar ataxia types 1, 2, 3, 6, and 7 were all negative.

Seven Tesla brain MRI of a healthy control patient and the patient discussed in the case.

(A) A healthy control patient (F/34) and (B) the patient. In contrast to the intact nigral hyperintensity in a healthy control patient (arrows), bilateral loss of nigral hyperintensity was seen in the patient. (C) T1-weighted sagittal MRI of the patient. Mild atrophy in the brainstem and cerebellum was observed. (D) Decreased 123I-FP-CIT uptake in the both sides of striatum, more severe in the left side.

jcsm.15.1.153a.jpg

jcsm.15.1.153a.jpg
Figure 1

Seven Tesla brain MRI of a healthy control patient and the patient discussed in the case.

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During the 2-year-follow-up period, the patient's ataxia and imbalance continued to aggravate, and his wife started to complain of severe snoring during sleep. Neurologic examination revealed masked face, bilateral symmetric bradykinesia, axial rigidity, bilateral gaze-evoked nystagmus, and bilateral limb ataxia. He was unable to walk due to severe imbalance. Laryngoscopic examination, done during wake state, revealed no vocal fold paralysis. To assess snoring, our patient underwent polysomnography, which confirmed severe snoring, sleep apnea, and stridor (Figure 2, Video 1). The episodes of stridor happened at sleep stages 1, 2, and rapid eye movement (REM) sleep stage. He showed transient arterial oxygen desaturation which fell to 78% and improved after applying continuous positive airway pressure. Polysomnography also revealed a sustained elevation of submental electromyography (EMG) activity and phasic submental and limb EMG twitching during REM sleep, compatible with REM sleep behavior disorder: 40.5% for tonic EMG activity and 26.5% for phasic EMG activity among 207 REM sleep epochs.

Polysomnography of the patient at the rapid eye movement sleep stage.

Chin electromyography activity is elevated during eye movement (black arrow), and transient oxygen desaturation occurs with snoring (clear arrow).

jcsm.15.1.153b.jpg

jcsm.15.1.153b.jpg
Figure 2

Polysomnography of the patient at the rapid eye movement sleep stage.

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DISCUSSION

Although our patient showed clinical features of MSA, he also had expanded 44 trinucleotide repeats in the SCA17 locus, and increased repeats in the SCA17 gene were detected in clinical MSA.2 It is noteworthy that severe obstructive apnea and stridor developed during his late stages of the disease. Stridor is the most significant breathing problem during sleep in MSA due to its association with increased mortality and higher incidence of sudden death during sleep.3

The neuropathological substrate of stridor has not been fully elucidated thus far. The pathology of the lower brainstem, especially the nucleus ambiguus and its adjacent structures, has been suspected to cause stridor in MSA.6 Pathologic neuronal loss in the lower brainstem has also been reported in SCA17. A previous report found neuronal loss in the inferior olivary nucleus, which is located anterior to the nucleus ambiguus and raphe nucleus, in a family with SCA17, who manifested ataxia and dystonia with no respiratory symptoms.7 In SCA 17, there has been no report of neuronal loss in the lower brainstem, other than in the inferior olive. Future studies are required to reveal the neuropathological substrate of stridor in SCA17.

Among other types of spinocerebellar ataxias, spinocerebellar ataxia type 1 and spinocerebellar ataxia type 3 have been reported to develop vocal cord paralysis.8,9

In conclusion, we report a patient with SCA17, who manifested clinical features of MSA and developed stridor during sleep. Further neuropathological studies are needed to elucidate the substrate of stridor in SCA17. As shown in our case, when patients with SCA17 manifest MSA, the possibility of respiratory involvement should be considered.

DISCLOSURE STATEMENT

Work for this study was performed at Seoul National University Bundang Hospital. All authors have read and approved this manuscript. All authors declare no conflicts of interest and no financial relationships relevant to this article. Informed consent was obtained from the subject. This study was approved by the Institutional Review Board at Seoul National University Bundang Hospital.

ABBREVIATIONS

EMG

electromyography

MSA

multiple system atrophy

REM sleep

rapid eye movement sleep

SCA17

spinocerebellar ataxia type 17

TBP

TATA-box binding protein

ACKNOWLEDGMENTS

The authors thank the patient who participated in this study.

REFERENCES

1 

Koide R, Kobayashi S, Shimohata T, et al. A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease? Hum Mol Genet. 1999;8(11):2047–2053. [PubMed]

2 

Kim JY, Kim SY, Kim JM, et al. Spinocerebellar ataxia type 17 mutation as a causative and susceptibility gene in parkinsonism. Neurology. 2009;72(16):1385–1389. [PubMed]

3 

Silber MH, Levine S. Stridor and death in multiple system atrophy. Mov Disord. 2000;15(4):699–704. [PubMed]

4 

Kim JM, Jeong HJ, Bae YJ, et al. Loss of substantia nigra hyperintensity on 7 Tesla MRI of Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Parkinsonism Relat Disord. 2016;26:47–54. [PubMed]

5 

Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71(9):670–676. [PubMed Central][PubMed]

6 

Ozawa T, Sekiya K, Aizawa N, Terajima K, Nishizawa M. Laryngeal stridor in multiple system atrophy: Clinicopathological features and causal hypotheses. J Neurol Sci. 2016;361:243–249. [PubMed]

7 

Rolfs A, Koeppen AH, Bauer I, et al. Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17). Ann Neurol. 2003;54(3):367–375. [PubMed]

8 

Isozaki E, Naito R, Kanda T, Mizutani T, Hirai S. Different mechanism of vocal cord paralysis between spinocerebellar ataxia (SCA 1 and SCA 3) and multiple system atrophy. J Neurol Sci. 2002;197(1–2):37–43. [PubMed]

9 

Iranzo A, Munoz E, Santamaria J, Vilaseca I, Mila M, Tolosa E. REM sleep behavior disorder and vocal cord paralysis in Machado-Joseph disease. Mov Disord. 2003;18(10):1179–1183. [PubMed]


Supplemental Material

Video 1

(.mp4 | 2.86 MB)