https://doi.org/10.5664/jcsm.9390 CASE REPORTS Acute lacunar infarct in an obese adolescent with obstructive sleep apnea Brian Chen, MD1; Sasikanth Gorantla, MD2; Vaishal Shah, MD3 1 Pediatric Institute, Cleveland Clinic, Cleveland, Ohio; 2Department of Neurology, University of Illinois College of Medicine at Peoria and OSF Healthcare Illinois Neurological Institute, Peoria, Illinois; 3Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio Downloaded from jcsm.aasm.org by 37.19.199.141 on April 18, 2024. For personal use only. No other uses without permission. Copyright 2024 American Academy of Sleep Medicine. All rights reserved. Obstructive sleep apnea is associated with an increased risk of acute ischemic cerebrovascular accidents in adults. However, this association has not been well established in the pediatric population. We report a case of acute right internal capsule lacunar infarct manifesting as left-sided hemiplegia in an adolescent with severe obesity. Severe untreated obstructive sleep apnea was identified during the hospital stay. Positive airway pressure therapy, weight loss, and tonsillectomy eventually normalized sleep-disordered breathing. The patient recovered completely without any residual neurological deficits with multidisciplinary care. Lacunar infarcts due to hypertension-related cerebral vasculopathy are a well-known cause of stroke in adults. Untreated obstructive sleep apnea may cause hypertension and potentially predispose even the pediatric population to develop lacunar infarcts. Polysomnography needs to be considered as a part of the diagnostic algorithm in pediatric patients with stroke. Keywords: pediatric obesity, ischemic stroke, obstructive sleep apnea Citation: Chen B, Gorantla S, Shah V. Acute lacunar infarct in an obese adolescent with obstructive sleep apnea. J Clin Sleep Med. 2021;17(8):174 3–174 7. moderately severe stroke. 6 The patient had class III obesity (375 lbs, body mass index 62.1 kg/m2, 99.8th percentile, z score 2.9) at the time of her initial presentation. Magnetic resonance imaging of the brain demonstrated a lacunar infarct in the posterior limb of the internal capsule on the right side, as shown in Figure 1. Computed tomography angiography of the head and neck were negative for flow-limiting stenosis or vasculopathic pattern. Extensive laboratory work, including coagulation and autoimmune panel, were negative. Aside from obesity, past medical history included well-managed intermittent asthma and irregular menses. Prior physician visits earlier in the year did not find abnormally elevated blood pressures. However, the patient’s mother did report loud snoring and frequently witnessed apnea, especially with the patient in the supine position. She does not have a history of sickle cell disease. There was no evidence of elevated low-density lipoprotein cholesterol (78 mg/dL). Echocardiogram and electrocardiogram were negative for structural and conduction abnormalities. The patient was noted to have intermittent hypoxemia while asleep during her hospital stay. The initial split-night study demonstrated severe OSA with an obstructive apnea-hypopnea index (OAHI) of 172 events/h (0 events/h central, 3 events/h mixed) and severe nocturnal hypoxemia (77.2 minutes or 58.4% of sleep time with oxyhemoglobin saturation < 90%, oxyhemoglobin saturation nadir of 60%) as illustrated in Table 1. Transcutaneous CO2 values were within normal limits. Positive airway pressure (PAP) titration and positional therapy normalized OAHI (1 event/h) at a bilevel PAP setting of 19/12 cm H2O (Figure 2). She continued bilevel PAP of 19/12 cm H2O. After 2 months of inpatient rehabilitation and PAP therapy with > 95% adherence (defined as more than 4 hours of use per night), the patient improved with partial resolution of her motor deficits, and she was discharged home. The patient was subsequently managed by a multidisciplinary team, including sleep INTRODUCTION Obstructive sleep apnea (OSA) is known to be associated with potentially life-threatening conditions, including acute coronary syndromes and ischemic cerebrovascular accident (CVA) in adults.1 Approximately 70% of adults with ischemic strokes were identified to have untreated OSA.1 The association between untreated OSA and ischemic CVA is well established in adults, but it is not well investigated in the pediatric population. Ischemic stroke in children is not as common as in adults.2 The common etiologies for pediatric ischemic stroke are congenital heart disease, prothrombotic conditions, sickle cell disease, and arteriopathies.2 Obesity is a known risk factor for OSA.3 The National Health and Nutrition Examination Survey reported that one-third of children in the United States were either overweight or obese, with disproportionately higher rates in African American and Hispanic children.4 The epidemic of pediatric obesity has amplified the incidence of weight-related OSA in children.5 Furthermore, obesity is an established, independent risk factor for stroke in adults.3 In this context, we report a case of an adolescent with severe obesity and untreated OSA who presented with an acute ischemic infarct in the right internal capsule. REPORT OF CASE A 16-year-old White female was brought to the emergency department by her mother for a wake-up stroke (patient going to sleep without neurological deficits and waking up with stroke symptoms) manifested by left-sided hemiplegia involving the face, arm, and leg. The National Institutes of Health Stroke Scale at presentation was 10 (facial palsy 2, left arm 4, left leg 3, and dysarthria 1). National Institutes of Health Stroke Scale scores range from 0–42, and a score of 10 at baseline is considered a Journal of Clinical Sleep Medicine, Vol. 17, No. 8 174 3 August 1, 2021 B Chen, S Gorantla, and V Shah Case report medicine, neurology, rehabilitation medicine, and a structured weight management program. The patient was noted to have 3–4+ tonsils, occupying roughly 75% of the pharyngeal space. At the time of acute presentation, the patient was deemed not to be an ideal candidate for surgery (both adenotonsillectomy [T&A] and bariatric surgery) due to an increased risk of perioperative complications. The patient was enrolled in the medical weight management program. She lost 93 pounds over a span of 1.2 years with diet and exercise. Her body mass index dropped from 62.1 kg/m2 to 47.83 kg/m2. Left-sided weakness had resolved completely by this point. A repeat polysomnogram after weight loss revealed severe OAHI (43 events/h, central apnea-hypopnea index of 0 events/h) but improved oxygenation (2.8% of sleep time with oxyhemoglobin saturation below 90%, oxyhemoglobin saturation nadir of 74%). As mentioned in Table 1, the response to PAP therapy (residual OAHI of 0.4 events/h with a bilevel PAP setting of 14/10 cm H2O) and nocturnal hypoxemia improved significantly. Figure 1—MRI of the brain without contrast showing restricted diffusion lesion in the posterior limb of the internal capsule on the right side. (A) Hyperintense lesion on DWI. (B) Lesion with corresponding hypointensity on ADC sequence. ADC = apparent diffusion coefficient, DWI = diffusion weighted imaging, MRI = magnetic resonance imaging. Downloaded from jcsm.aasm.org by 37.19.199.141 on April 18, 2024. For personal use only. No other uses without permission. Copyright 2024 American Academy of Sleep Medicine. All rights reserved. Table 1—Serial polysomnograms demonstrating OSA improvement with weight loss and T&A. Time from stroke presentation, d PSG Number 1 29 PSG Number 2 325 PSG Number 3 962 Type of study Interim interventions Weight (lbs) BMI (kg/m2) Split-night PSG N/A 367 62.1 Split-night PSG Weight loss 300 48.4 Split-night PSG T&A 291 48.4 99.74, 2.80 99.51, 2.59 99.29, 2.45 132 2.9/43.4/33.1 20.7 182 7.6/68.8/10.0 13.6 213 3.7/63.0/17.1 16.1 91.9% 63.3 175 120 86.9% 0 40 83 88.4% 5.9 5.6 20 170 98.2/1.8/0.0 51.5 60% NA 100/0/0 20.4 74% 24 100/0/0 11.8 90% % time SpO2 < 90% % etCO2 > 50 mm Hg PAP parameters Best bilevel PAP pressure 58.4% 0% 2.8% 0% 0% 0% 19/12 14/10 10/5 AHI at best PAP pressure Oxygen nadir Arousal index % tcPCO2 > 50 mm Hg 1 73% 11.7 0% 0.4 94% 5.6 0% 2.0 93% 2.0 0% BMI percentile, z score Key PSG parameters TST (min) for baseline portion % stage N1/N2/N3 sleep % REM sleep Sleep efficiency % supine Total AHI REM sleep AHI Supine AHI % obstructive/mixed/central Arousal index Oxyhemoglobin nadir Of note for PSG number 1, while the patient was on optimum bilevel PAP, AHI was not normalized in the supine position; however, AHI was normalized in the lateral recumbent position. As such, the patient was recommended for positional therapy in addition to bilevel PAP until the following studies. AHI = apneahypopnea index, BMI = body-mass index, etCO2 = end-tidal carbon dioxide, OSA = obstructive sleep apnea, PAP = positive airway pressure, PSG = polysomnography, REM = rapid eye movement, SpO2 = oxyhemoglobin saturation, T&A = adenotonsillectomy, tcPCO2 = transcutaneous monitoring of carbon dioxide partial pressure, TST = total sleep time. Journal of Clinical Sleep Medicine, Vol. 17, No. 8 174 4 August 1, 2021 B Chen, S Gorantla, and V Shah Case report Downloaded from jcsm.aasm.org by 37.19.199.141 on April 18, 2024. For personal use only. No other uses without permission. Copyright 2024 American Academy of Sleep Medicine. All rights reserved. Figure 2—Hypnogram of the initial split-night study and representative epochs. (continued on following page) Journal of Clinical Sleep Medicine, Vol. 17, No. 8 174 5 August 1, 2021 B Chen, S Gorantla, and V Shah Case report Downloaded from jcsm.aasm.org by 37.19.199.141 on April 18, 2024. For personal use only. No other uses without permission. Copyright 2024 American Academy of Sleep Medicine. All rights reserved. Figure 2— Hypnogram of the initial split-night study and representative epochs.. (continued) (A) Hypnogram of the initial split night study showing severe OSA and severe nocturnal hypoxemia. (B) Two representative epochs of (epoch 1) the severe OSA and (epoch 2) PAP and positional therapy that normalized AHI at a bilevel PAP setting of 19/12 cm of H2O. ADI = apnea disturbance index, AHI = apnea-hypopnea index, APN = apnea, CA = central apnea, CPAP = continuous positive airway pressure, DX = desaturation time, EPAP = expiratory positive airway pressure, act, HDI = hypopnea disturbance index, HYP = hypopnea, IDX = desaturation index, IPAP = inspiratory positive airway pressure, MA = mixed apnea, OA/OSA = obstructive sleep apnea, PAP = positive airway pressure, PS = pressure support. The patient had a T&A 2.5 years after the stroke. A third splitnight study showed remarkable improvement, as shown in Table 1 (baseline OAHI of 5.6 events/h and residual OAHI of 2 events/h with bilevel PAP 10/5 cm H2O). She had not gained significant weight since her previous polysomnogram 2 years previously. PAP therapy abolished snoring and improved daytime sleepiness. Weight loss, T&A, rehabilitation, and PAP therapy facilitated complete recovery from the stroke and OSArelated symptoms. She is currently a full-time college student and continuing with weight loss medical management. DISCUSSION Our case report emphasizes the possible association between obesity, OSA, and CVA in the pediatric population. It also highlights the positive impact of weight loss and OSA treatment on stroke recovery. Untreated OSA is associated with increased risk of ischemic CVA, increased stroke-related mortality, and poor long-term neurological recovery in adults.7 Although the causal effect of untreated OSA on CVA cannot be entirely ascertained, several – Journal of Clinical Sleep Medicine, Vol. 17, No. 8 174 6 August 1, 2021 Downloaded from jcsm.aasm.org by 37.19.199.141 on April 18, 2024. For personal use only. No other uses without permission. Copyright 2024 American Academy of Sleep Medicine. All rights reserved. B Chen, S Gorantla, and V Shah Case report plausible mechanisms support this hypothesis in adults.1,7 9 Hypertension due to increased sympathetic activity, increased inflammatory markers, platelet dysfunction, endothelial disruption, and altered cerebral hemodynamics are some of the postulated mechanisms.1,8,9 Hypertension remains the major and modifiable risk factor for stroke, probably irrespective of age group. In the pediatric population, OSA severity has been associated with hypertension, likely due to increased catecholamine levels.9 Hypertension is known to cause lipohyalinosis of small penetrating vessels in the brain and is a strong risk factor for lacunar infarcts.9 Except for obesity, our patient did not have any other identifiable risk factors for stroke typically seen in the pediatric population. Even though the patient did not have a formal diagnosis of hypertension, it is reasonable to assume that she had untreated hypertension—perhaps due to untreated OSA and obesity—before the stroke. The evidence of lacunar infarct further supports this hypothesis. This case report emphasizes the possibility of a multidimensional relationship between stroke, OSA, and obesity in the pediatric population. Metabolic syndrome, obesity, and weight gain correlate with OSA.1,3 Surgical modalities such as gastric bypass or laparoscopic sleeve gastrectomy result in greater weight loss and are more effective at normalizing sleep-disordered breathing compared with dietary restriction, physical activity, and psychological support.9,10 A longitudinal population-based study predicted a 26% (95% confidence interval, 18%–34%) reduction in the apnea-hypopnea index with 10% weight loss.11 Without surgical management, our patient was able to achieve a significant weight loss of 93 lbs, and the management of obesity with behavioral and nutritional modifications improved OSA in our patient. T&A is often indicated as a first-line treatment option in children with sleep-disordered breathing.9 Obese children who underwent T&A have been shown to have a significant decrease in OSA severity but to a lesser degree than nonobese children.9 As expected in our patient’s case, T&A helped further reduce the severity of OSA. Improved daytime sleepiness due to PAP therapy may enhance participation in rehabilitation and eventually result in enhanced neurologic recovery after a stroke. Treatment of OSA with PAP was shown to improve hypoxemia, hypertension, and outcomes in adults with ischemic stroke. 12 Polysomnography deserves a unique place in the diagnostic algorithm in pediatric patients with ischemic stroke, especially in obese children. PAP therapy should be a part of the treatment plan as it may assist in neurologic recovery. REFERENCES 1. Foldvary-Schaefer NR, Waters TE. Sleep-disordered breathing. Continuum (Minneap Minn). 2017;23(4, Sleep Neurology):1093–1116. 2. Mittal SO, ThatiGanganna S, Kuhns B, Strbian D, Sundararajan S. Acute ischemic stroke in pediatric patients. Stroke. 2015;46(2):e32–e34. 3. Strazzullo P, D’Elia L, Cairella G, Garbagnati F, Cappuccio FP, Scalfi L. Excess body weight and incidence of stroke: meta-analysis of prospective studies with 2 million participants. Stroke. 2010;41(5):e418–e426. 4. Skinner AC, Perrin EM, Skelton JA. Prevalence of obesity and severe obesity in US children, 1999-2014. Obesity (Silver Spring). 2016;24(5):1116–1123. 5. Gozal D, Tan H-L, Kheirandish-Gozal L. Obstructive sleep apnea in children: a critical update. Nat Sci Sleep. 2013;109:109. 6. Lyden P. Using the National Institutes of Health Stroke Scale: a cautionary tale. Stroke. 2017;48(2):513–519. 7. Stahl SM, Yaggi HK, Taylor S, et al. Infarct location and sleep apnea: evaluating the potential association in acute ischemic stroke. Sleep Med. 2015;16(10): 1198–1203. 8. Lv P, Jin H, Liu Y, et al. Comparison of risk factor between lacunar stroke and large artery atherosclerosis stroke: a cross-sectional study in China. PLoS One. 2016;11(3):e0149605. 9. Koren D, Chirinos JA, Katz LEL, et al. Interrelationships between obesity, obstructive sleep apnea syndrome and cardiovascular risk in obese adolescents. Int J Obes Lond. 2015;39(7):1086–1093. 10. Andersen IG, Holm JC, Homøe P. Obstructive sleep apnea in obese children and adolescents, treatment methods and outcome of treatment—a systematic review. Int J Pediatr Otorhinolaryngol. 2016;87:190–197. 11. Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA. 2000;284(23): 3015–3021. 12. Martínez-García MA, Soler-Cataluña JJ, Ejarque-Martínez L, et al. Continuous positive airway pressure treatment reduces mortality in patients with ischemic stroke and obstructive sleep apnea: a 5-year follow-up study. Am J Respir Crit Care Med. 2009;180(1):36–41. SUBMISSION & CORRESPONDENCE INFORMATION Submitted for publication October 13, 2020 Submitted in final revised form April 6, 2021 Accepted for publication April 6, 2021 Address correspondence to: Brian Chen, MD, Cleveland Clinic Children’s Sleep Disorders Center, Neurology Institute, Center for Pediatric Pulmonary Medicine, Cleveland Clinic Children’s, 9500 Euclid Avenue, S73, Cleveland, OH 44195; Tel: (216) 444-2165; Fax: (216) 636-0090 DISCLOSURE STATEMENT All authors have seen and approved the manuscript. The authors report no conflicts of interest. ABBREVIATIONS CVA, cerebrovascular accident OAHI, obstructive apnea-hypopnea index OSA, obstructive sleep apnea PAP, positive airway pressure T&A, adenotonsillectomy Journal of Clinical Sleep Medicine, Vol. 17, No. 8 174 7 August 1, 2021