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Respiratory Insufficiency As the Primary Presenting Symptom of Multiple-System Atrophy

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Respiratory Insufficiency As the Primary Presenting Symptom of Multiple-System Atrophy ORIGINAL CONTRIBUTION Respiratory Insufficiency as the Primary Presenting Symptom of Multiple-System Atrophy Graham A. Glass, MD; Keith A. Josephs, MST, MD; J. Eric Ahlskog, PhD, MD Background: Respiratory stridor, sleep-disordered Main Outcome Measures: Characteristics and clini- breathing, and respiratory insufficiency are part of the cal course of patients. clinical spectrum of multiple-system atrophy (MSA). We have encountered cases where these were presenting Results: Six cases were identified in which substantial res- symptoms, with the diagnosis of MSA being initially un- piratory insufficiency occurred as an early, presenting symp- recognized. tom of MSA. Three patients had been examined emergently for acute respiratory distress before the ultimate diagnosis Objective: To describe cases in which breathing diffi- of MSA; the other 3 patients were diagnosed as having ob- culties were the initial and primary manifestation of MSA. structive sleep apnea unresponsive to therapy, with bilat- eral vocal cord paralysis found on ear, nose, and throat ex- Design: Database review from January 1, 1996, through amination. Stridor was noted early in the course in all. All October 31, 2005. patients required tracheostomy, and all eventually devel- oped features consistent with probable MSA. Setting: Mayo Clinic, Rochester, Minn. Conclusions: Multiple-system atrophy may occasion- Patients: All patients diagnosed as having MSA, cross- ally present as primary respiratory failure or dysfunc- referenced for apnea, hypopnea, or hypoventilation. On tion, with initially mild motor and autonomic symp- review, we included only cases in which respiratory dys- toms. Otherwise unexplained central respiratory failure, function was the primary initial clinical event in MSA, bilateral vocal cord paralysis, stridor, or refractory cen- excluding equivocal cases. tral sleep apnea should prompt consideration of MSA. Interventions: None. Arch Neurol. 2006;63:978-981 ULTIPLE-SYSTEM ATRO- ciency was the initial and most promi- phy (MSA) is a heter- nent feature of MSA. ogeneous, sporadic neurodegenerative dis- METHODS order, with the diag- Mnosis dependent on the clinical presenta- tion. Typically, it presents with motor The Mayo Clinic Rochester Health Sciences da- tabase (Rochester, Minn) was queried for all dysfunction plus dysautonomia. The mo- patients diagnosed as having MSA from Janu- tor syndromes usually take the form of ary 1, 1996, through October 31, 2005, cross- either predominant parkinsonism (some- referenced for apnea, hypopnea, or hypoven- times levodopa refractory) or a spinocer- tilation.4 On review, we included only cases in ebellar syndrome. Respiratory symp- which respiratory dysfunction was the pri- toms, including stridor, sleep-disordered mary initial clinical event in MSA, excluding breathing, and respiratory insufficiency, are equivocal cases. All cases met clinical criteria for the diagnosis of probable MSA.4 known to additionally occur in MSA,1-3 al- though these are not included in the con- sensus diagnostic criteria.4 RESULTS We have encountered patients who presented with a syndrome of prominent We identified 6 cases that met our inclu- respiratory insufficiency plus limited sion criteria. All patients had been exam- motor and autonomic problems. They ined by staff neurologists, including sub- were ultimately recognized to have MSA, specialists in neurodegenerative disease in but the diagnosis was not made until 5 of 6. In addition, all had been exam- Author Affiliations: much later in the course. Herein we ined by sleep specialists and had under- Department of Neurology, Mayo describe 6 patients seen between 1996 gone either polysomnography or over- Clinic, Rochester, Minn. and 2005 in whom respiratory insuffi- night oximetry. Otolaryngologists had (REPRINTED) ARCH NEUROL / VOL 63, JULY 2006 WWW.ARCHNEUROL.COM 978 ©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Table 1. Initial Findings in Cases 3 Through 6 Patient No./ Presenting Pulmonary Additional History Pulmonary/Sleep Neurologic Examination Sex/Age, y Problems at Presentation Evaluation Findings Findings 3/M/70 OSA, CPAP failed; daytime Dysphonia, dysarthria, RBD, bilateral vocal cord Bilateral brisk UE reflexes, hypersomnolence sialorrhea paralysis mildly ataxic gait, nystagmus 4/F/66 Dyspnea on exertion; Constipation, urinary OSA, stridor, bilateral Normal daytime retention, dysphonia vocal cord paralysis hypersomnolence 5/M/60 Dyspnea on exertion; Impotence, subjective Laryngospasm, stridor, Ataxic gait, bilateral brisk acute SOB at night unsteadiness RBD UE reflexes, right Babinski sign 6/M/46 OSA, CPAP failed Erectile dysfunction, RBD, high-pressure CPAP Pancerebellar ataxia, enuresis, requirement nystagmus, bilateral diarrhea/constipation, terminal UE tremor subjective unsteadiness, orthostatic hypotension Abbreviations: CPAP, continuous positive airway pressure; OSA, obstructive sleep apnea; RBD, rapid eye movement sleep behavior disorder; SOB, shortness of breath; UE, upper extremity. Table 2. Follow-up and Confirmation of MSA in Cases 3 Through 6 Patient No./ Sex/Age, y Subsequent Evaluations Additional Findings MSA Features 3/M/70 Hypersomnolence despite Central hypoventilation on PSG Dysautonomia, ataxia, corticospinal tracheostomy, right distal UE tract signs, extrapyramidal signs weakness, bilateral rigid LE, orthostatic hypotension 4/F/66 Dry mouth and eyes, respiratory Central hypoventilation on PSG, Dysautonomia, ataxia improvement with tracheostomy, abnormal autonomic reflex screen, orthostatic hypotension, ataxic gait bilateral LE incoordination, elevated calcium-channel antibodies with normal results of cancer workup and EMG 5/M/60 Urinary retention, diplopia, worsening Central hypoventilation on PSG, Dysautonomia, ataxia, corticospinal gait, pancerebellar ataxia, pancerebellar ataxia, bilateral Babinski tract signs, extrapyramidal signs constipation, heat intolerance, urinary signs, TST suggestive of MSA, urgency with incontinence bilateral LE rigidity, bilateral LE myoclonus 6/M/46 Presyncope Stridor on PSG, bilateral vocal cord Dysautonomia, ataxia, extrapyramidal paralysis, abnormal autonomic reflex signs screen and TST consistent with MSA Abbreviations: EMG, electromyography; LE, lower extremity; MSA, multiple-system atrophy; PSG, polysomnogram; TST, thermoregulatory sweat test; UE, upper extremity. examined these patients as well, either in-house or at an All patients required tracheostomy, although patient 6 re- outside hospital. Two of the cases are described in detail fused. In 3 patients, bilateral vocal cord paralysis may have in the next section to illustrate the presentations. The pre- initially been diagnosed as obstructive sleep apnea unre- sentation of the remaining 4 cases is summarized in sponsive to conventional therapy, although, alternatively, Table 1; these cases evolved into probable MSA, as they may have had simple obstructive sleep apnea for a num- documented in Table 2. All 6 cases ultimately had sub- ber of years and then subsequently developed upper air- stantial dysautonomia by history that was confirmed on way resistance secondary to vocal cord paralysis. autonomic testing.5 The respiratory problems overshadowed the neuro- Respiratory insufficiency was a presenting symptom in logic complaints in all of these cases, and the ultimate all 6 cases, and 3 (patients 1, 2, and 5) had previously been diagnosis of MSA was unsuspected or at least not defi- emergently examined because of acute respiratory dis- nite at presentation. Important early clues to the diag- tress before neurologic evaluations. Patients 2, 3, and 4 all nosis were autonomic symptoms, which were eventu- had visualized bilateral vocal paralysis, although stridor was ally present in all 6 patients, and dream enactment noted in all 6 patients. Patient 1 had definite central res- behavior, which was present in 3 cases. Dream enact- piratory failure, whereas patients 3, 4, and 5 were noted to ment behavior suggests underlying ␣-synuclein neuro- have central apneas during sleep with tracheostomy in place. pathology and is well described in MSA.6 Motor symp- (REPRINTED) ARCH NEUROL / VOL 63, JULY 2006 WWW.ARCHNEUROL.COM 979 ©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 toms and signs were present early but were mild. In her local emergency department, she was intubated Ultimately these declared themselves, with 2 cases evolv- because of hypoventilation, with a PCO2 of 134 mm Hg. ing to a parkinsonian phenotype and 4 cases to a spino- She could not be weaned from the ventilator during the 7 cerebellar phenotype. hospitalization, with elevated PCO2 values (50-70 mm Hg), ultimately requiring tracheostomy. She was discharged with a diagnosis of central hypoventilation. REPORT OF CASES She was reexamined at our institution several months later, and the pulmonologist ultimately concluded that she CASE 1 had hypercapnic respiratory failure secondary to neuro- logic disease. The neurologic history at that time docu- While on vacation, a 54-year-old woman awoke one morn- mented that stridor had been heard by her husband be- ing and told her husband she was tired. An hour or so later, fore tracheostomy, and she had paroxysms of blood pressure he found her unconscious in bed, but with a pulse. In the swings. The neurologic examination again showed find- emergency department she was cyanotic and hypoventi- ings of mild parkinsonism, but
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