Sleep Deprivation and Its Consequences.

OBJECTIVE: This article reviews the clinical, cognitive, behavioral, and physiologic consequences of sleep deprivation in relation to general neurology practice. LATEST DEVELOPMENTS: Despite being one of the most common sleep problems in modern society, the role of sleep deprivation is underrecognized and underestimated in clinical medicine and general neurology practice. The recognition, diagnosis, and management of sleep deprivation in neurologic practice have only recently received close attention. The consequences of sleep deprivation involve all aspects of general neurology practice, including individuals with neurologic disease, neurologists, communities, and health care systems. The identification and timely management of sleep deprivation symptoms may help to improve symptoms of underlying primary neurologic disorders. ESSENTIAL POINTS: This article emphasizes complexities related to the identification and evaluation of sleep deprivation in general neurology practice and describes the consequences of sleep deprivation. By recognizing sleep deprivation in patients with neurologic conditions, the neurologist can provide comprehensive care and contribute to improved clinical and neurologic outcomes.

The mobile sleep medicine model in neurologic practice: Rationale and application.

Background: Undiagnosed obstructive sleep apnea (OSA) is prevalent in neurological practice and significantly contributes to morbidity and mortality. OSA is prevalent in US adults and causes poor quality sleep and significant neurocognitive, cardiovascular, and cerebrovascular impairments. Timely treatment of OSA reduces cardio-cerebrovascular risks and improves quality of life. However, most of the US population has limited systematic access to sleep medicine care despite its clinical significance. Focus: We discuss the importance of systematic screening, testing, and best-practice management of OSA and hypoventilation/hypoxemia syndromes (HHS) in patients with stroke, neurocognitive impairment, and neuromuscular conditions. This review aims to introduce and describe a novel integrated Mobile Sleep Medicine (iMSM) care model and provide the rationale for using an iMSM in general neurological practice to assist with systematic screening, testing and best-practice management of OSA, HHS, and potentially other sleep conditions. Key points: The iMSM is an innovative, patient-centered, clinical outcome-based program that uses a Mobile Sleep Medicine Unit-a "sleep lab on wheels"-designed to improve access to OSA management and sleep care at all levels of health care system. The protocol for the iMSM care model includes three levels of operations to provide effective and efficient OSA screening, timely testing/treatment plans, and coordination of further sleep medicine care follow-up. The iMSM care model prioritizes effective, efficient, and patient-centered sleep medicine care; therefore, all parties and segments of care that receive and provide clinical sleep medicine services may benefit from adopting this innovative approach.

Autotitrating Bilevel Positive Airway Pressure in Large Vessel Steno-Occlusive Stroke Patients With Suspected Sleep Apnea: A Multicenter Randomized Controlled Study.

Background: We hypothesized that autotitrating bilevel positive airway pressure (auto-BPAP) favorably affects short-term clinical outcomes in hyperacute ischemic stroke. Methods: In a multicenter, randomized, controlled trial patients with large vessel steno-occlusive stroke and clinically suspected sleep apnea were allocated to auto-BPAP or standard stroke care alone. Auto-BPAP was initiated within 24 h from stroke onset and performed over 48 h during diurnal and nocturnal sleep. Sleep apnea was assessed using cardiorespiratory polygraphy. Primary endpoint was early neurological improvement on National Institutes of Health Stroke Scale (NIHSS) score at 72 h. Safety and tolerability of BPAP, functional independence [modified Rankin Scale (mRS) 0-2], stroke recurrence, and mortality at 90 days were assessed. Results: Due to low recruitment, the trial was prematurely stopped after 24 patients had been randomized (auto-BPAP, n = 14; control, n = 10): median baseline NIHSS 13 (5.5-18), 88% large vessel occlusion, and 12% large vessel stenosis. Polygraphy confirmed sleep apnea in 64% of auto-BPAP and 88% of control patients (p = 0.34). Adherence to auto-BPAP was achieved by 9 of the 14 (64%) patients. Between auto-BPAP and control patients, no differences were observed in early neurological improvement (median NIHSS change: -2.0, IQR = 7 points vs. -0.5, IQR = 3 points), 90 days functional independence (21 vs. 30%, p = 0.67), stroke recurrence (0 vs. 20%, p = 0.16), and death (14 vs. 20%, p = 1.0). No safety concerns were identified. Conclusions: In this prematurely terminated trial, auto-BPAP was safe but did not show an effect on short-term clinical outcomes in selected ischemic stroke patients. Its tolerability, however, may be limited in hyperacute stroke care and needs to be improved before larger trials are conducted. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01812993.

Obstructive sleep apnea intensifies stroke severity following middle cerebral artery occlusion.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep disorder caused by transient obstruction of the upper airway and results in intermittent hypoxia, sleep fragmentation, sympathetic nervous system activation, and arousal which can have an adverse effect on cardiovascular disease. It is theorized that OSA might intensify stroke injury. Our goal here was to develop a new model of experimental OSA and test its ability to aggravate behavioral and morphological outcomes following transient brain ischemia/reperfusion. METHODS: We used a 3D printed OSA device to expose C57BL6 mice to 3 h of OSA (obstructive apnea index of 20 events per hour) for three days. These mice were then subjected to ischemia/reperfusion using the middle cerebral artery occlusion model (MCAO) stroke and examined for overall survival, infarct size and neurological scoring. RESULTS: We found that OSA transiently decreased respiration and reduced oxygen saturation with bradycardia and tachycardia typical of human responses during apneic events. Brain injury from MCAO was significantly increased by OSA as measured by infarct size and location as well as by intensification of neurological deficits; mortality following MCAO was also increased in OSA animals. CONCLUSIONS: Our findings suggest that our new model of OSA alters respiratory and cardiovascular physiological functions and is associated with enhanced ischemia/reperfusion mediated injury in our non-invasive, OSA intensified model of stroke.

The Relationship Between Obstructive Sleep Apnea and Ruptured Intracranial Aneurysms.

STUDY OBJECTIVES: The role of obstructive sleep apnea (OSA) in the overall outcome of ruptured intracranial aneurysms (RIAs) is unknown. We have investigated the role of OSA in overall outcome of RIAs. METHODS: Data from 159 consecutive patients were retrospectively reviewed. A chi-square test and regression analysis were performed to determine the significant difference. A value of P < .05 was considered significant. RESULTS: The prevalence of OSA in RIAs was fivefold higher in the nonaneurysm patient group, P = .002. The number of patients with hypertension (P < .0001), body mass index ≥ 30 (P < .0001), hyperlipidemia (P = .018), chronic heart disease (P = .002) or prior ischemic stroke (P = .001) was significantly higher in the OSA group. Similarly, the number of wide-neck aneurysms (P < .0001) and aneurysm > 7 mm (P = .004), poor Hunt and Hess grade IV-V (P = .005), vasospasms, (P = .03), and patients with poor Modified Rankin Scale scores (3-6) was significantly higher in the OSA group (P < .0001). Interestingly, for the first time in univariate (P = .01) and multivariate (P = .003) regression analysis, OSA was identified as an individual predictor of unfavorable outcome of RIAs. In addition, hypertension (P = .04), smoking (P = .049), chronic heart disease (P = .01), and Hunt and Hess grade IV-V (P = .04) were revealed as predictors of poor outcome of RIAs. CONCLUSIONS: This is a novel study to determine the association between OSA and ruptured cerebral aneurysm in terms of comorbidities, size of aneurysm, severity of symptoms, and outcomes after treatment. In addition, for the first time, OSA is identified as a positive predictor of unfavorable outcome of RIAs.

Cardiorespiratory profiling reveals primary breathing dysfunction in Kcna1-null mice: Implications for sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality, but the relative importance of underlying cardiac and respiratory mechanisms remains unclear. To illuminate the interactions between seizures, respiration, cardiac function, and sleep that contribute to SUDEP risk, here we developed a mouse epilepsy monitoring unit (EMU) to simultaneously record video, electroencephalography (EEG), electromyography (EMG), plethysmography, and electrocardiography (ECG) in a commonly used genetic model of SUDEP, the Kcna1 knockout (Kcna1-/-) mouse. During interictal periods, Kcna1-/- mice exhibited an abnormal absence of post-sigh apneas and a 3-fold increase in respiratory variability. During spontaneous convulsive seizures, Kcna1-/- mice displayed an array of aberrant breathing patterns that always preceded cardiac abnormalities. These findings support respiratory dysfunction as a primary risk factor for susceptibility to deleterious cardiorespiratory sequelae in epilepsy and reveal a new role for Kcna1-encoded Kv1.1 channels in the regulation of basal respiratory physiology.

Coexistence of obstructive sleep apnea worsens the overall outcome of intracranial aneurysm: a pioneer study.

OBJECTIVE Obstructive sleep apnea (OSA) is associated with the progression of abdominal and thoracic aortic aneurysms. However, the role of OSA in the overall outcome of intracranial aneurysms (IAs) has not yet been established. Authors of this report investigated the role of OSA in the overall outcome of IAs. METHODS Radiological and clinical data on patients (from 2010 through 2015) with confirmed IA were retrospectively reviewed. Significant differences between the OSA and non-OSA groups were determined using a chi-square test. Logistic regression analysis was performed to identify the predictors of an unfavorable IA outcome. RESULTS Among the 283 patients with confirmed IAs, 45 patients (16%) were positively screened for OSA, a proportion that was significantly higher than the prevalence of OSA in nonaneurysmal neurosurgical patients (4%, p = 0.008). The percentage of patients with hypertension (p = 0.018), a body mass index ≥ 30 kg/m2 (p < 0.0001), hyperlipidemia (p = 0.034), diabetes mellitus (p = 0.005), chronic heart disease (CHD; p = 0.024), or prior stroke (p = 0.03) was significantly higher in the OSA group than in the non-OSA group. Similarly, the percentage of wide-necked aneurysms (p = 0.00001) and patients with a poor Hunt and Hess Grade IV-V (p = 0.01) was significantly higher in the OSA group than in the non-OSA group. In addition, the percentage of ruptured aneurysms (p = 0.03) and vasospasms (p = 0.03) was significantly higher in the OSA group. The percentage of patients with poor modified Rankin Scale (mRS) scores (3-6) was significantly higher in the OSA group (p = 0.03). A separate cohort of patients with ruptured IAs showed similar results. In both univariate (p = 0.01) and multivariate (p = 0.04) regression analyses, OSA was identified as an individual predictor of an unfavorable outcome. In addition, hypertension and prior stroke were revealed as predictors of a poor IA outcome. CONCLUSIONS Complications of IA such as rupture and vasospasm are often the consequence of uncontrolled OSA. Overall outcome (mRS) of IAs is also affected by the co-occurrence of OSA. Therefore, the coexistence of OSA with IA affects the outcome of IAs. Obstructive sleep apnea is a risk factor for a poor outcome in IA patients.

Changing paradigm in the management of elderly patients with intracranial aneurysms: An institutional review.

Optimal treatment of intracranial aneurysms (IAs) in elderly patients has not yet been well established. We have investigated the clinical and radiological outcomes and predictors of unfavorable outcome of IAs in elderly patients. Radiological and clinical data of 85 elderly patients from 2010 through 2015 were retrospectively reviewed. Significant differences between the groups were determined by a chi-square test. Regression analysis was performed to identify the predictors of unfavorable outcome. Among the 85 patients with IAs, the number of patients with >7mm size aneurysm (p=0.01), diabetes mellitus (DM) (p=0.02), smoking (0.009) and Hunt and Hess grade 4-5 (p=0.003) was significantly higher in the ruptured group compared to the unruptured group. Similarly, the number of patients who underwent clipping was higher in the ruptured aneurysm group (p=0.01). The overall clinical outcome was comparatively better in the unruptured group (p=0.03); however, microsurgical clipping of aneurysms provides a significantly higher rate of complete aneurysmal occlusion (p=0.008). Overall, there was no significant difference in outcome in respect to treatment approach. In regression analysis, hypertension (HTN), obstructive sleep apnea (OSA), prior stroke, ruptured aneurysms and partial occlusion of aneurysms were identified as predictors of unfavorable outcome of IAs. Intracranial aneurysms in elderly patients reveals that endovascular treatment provides better clinical outcome; however, microsurgical clipping yields higher complete occlusion. Retreatment of residual aneurysms was comparatively more in the coiling group. Practice pattern has shifted from clipping to coiling for aneurysms in posterior circulation but not for aneurysms in anterior circulation.

Atypical presentation and outcome of cervicogenic headache in patients with cervical degenerative disease: A single-center experience.

OBJECTIVE: Cervicogenic headache affects a significant portion of the entire population. This type of headache especially with atypical presentation is often hard to diagnose and manage since its etiopathophysiology is not been yet well understood. We have investigated the prevalence of cervicogenic headache with atypical presentation and discussed the etiology of it, and the outcome of surgical intervention on this type of headache in patients with cervical degenerative disease. PATIENTS AND METHODS: Radiological and clinical data of 160 patients (from 2001 through 2016) were retrospectively reviewed. Significant differences between the groups were determined by chi-square test. Logistic regression analysis was performed to identify the predictors of unfavorable outcome. RESULTS: In this study, 10% of the patients had atypical presentation of cervicogenic headache. In overall cohort, after surgical intervention, there was significant improvement in symptoms and pain control, whether the presentation is typical or atypical. Sixty-one percent of the patients had no complaints, and 90% of the patients were headache-free (p<0.0001). Sixty-nine percent of the patients were free of neck, shoulder and extremity pain, and visual analogue scale pain score was reduced by 7 points (pre-op, 8.4 vs. last follow-up, 1.5, p<0.0001). However, number of patients with reduced headache was significantly higher in the group with typical presentation of headache (90.1%) compared to group with atypical (80%) presentation, p=0.04. In this study, female gender, smoking, obesity and depression were identified as predictors of overall unfavourable outcome. In addition, in a separate analysis, smoking and depression were revealed as risk factors for persistent headache. CONCLUSIONS: A notable portion of patients with cervicogenic headache can have an atypical presentation mimicking a primary type headache. However, cervicogenic headaches with atypical presentation can be difficult to diagnose and manage at the initial visit of the patients. Etiopathophysiology of this type of headache could be explained by the theories including discogenic, convergence and sensitization-desensitization theories. When cervicogenic headache is accompanied with CDD, performing ACDF or laminectomy would be the treatment of choice. Surgical intervention can also relieve the accompanying neck, shoulder and extremity pain with minimal complications. Lastly, outcomes of surgical intervention depend on the patients' morbidities including obesity, smoking and depression.

Exploration of screening practices for obstructive sleep apnea in stroke medical community: A pilot study.

BACKGROUND: Frequency of sleep-disordered breathing (SDB) among stroke and transient ischemic attack (TIA) patients ranges from 30-80% and is associated with poor neurological outcomes. Per current stroke prevention guidelines from American Heart Association/American Stroke Association (AHA/ASA), SDB is included in the list of modifiable risk factors for stroke and TIA prevention. Goal of our study is to determine screening practices for SDB in stroke medical community. METHODS: A web-based survey was sent to physicians taking care of stroke patients across North America and Europe. RESULTS: Among 112 total responses, 91 (81%) were stroke physicians, nine (8%) were general neurologists, nine (8%) were from other specialties and three (3%) were sleep medicine physicians. Majority of physicians (72%, n=81) do not use SDB screening questionnaires in their stroke patients. Epworth sleepiness scale is the most used among SDB questionnaires (24%, n=25/105), followed by Berlin sleep questionnaire (10%) and STOP-BANG questionnaire (7%). Only 13% of physicians use screening questionnaires in both in-patients and outpatients, whereas 21% use only in outpatients and 5% use only in acute stroke setting. Only 50% (n=56/111) of physicians would refer their stroke patients to a sleep medicine specialist when patients screen positive for SDB on questionnaires. CONCLUSION: Despite being an independent risk factor for stroke and TIA, majority of physicians in the pilot targeted cohort of medical professionals, who are involved in the management of stroke and TIA, do not screen these patients for SDB. Further work involving systematic, more detailed standardized surveys are needed to be developed to objectively evaluate and improve screening practices for SDB in national and international stroke medical communities.

A pilot study: portable out-of-center sleep testing as an early sleep apnea screening tool in acute ischemic stroke.

INTRODUCTION: Prompt diagnosis of obstructive sleep apnea (OSA) after acute ischemic stroke (AIS) is critical for optimal clinical outcomes, but in-laboratory conventional polysomnograms (PSG) are not routinely practical. Though portable out-of-center type III cardiopulmonary sleep studies (out-of-center cardiopulmonary sleep testing [OCST]) are widely available, these studies have not been validated in patients who have recently suffered from AIS. We hypothesized that OCST in patients with AIS would yield similar results when compared to conventional PSG. METHODS: Patients with AIS had simultaneous type III OCST and PSG studies performed within 72 hours from symptom onset. The accuracy of OCST was compared to PSG using: chi-square tests, receiver operatory characteristic curves, Bland-Altman plot, paired Student's t-test/Wilcoxon signed-rank test, and calculation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Twenty-one out of 23 subjects with AIS (age 61±9.4 years; 52% male; 58% African-American) successfully completed both studies (9% technical failure). Nearly all (95%) had Mallampati IV posterior oropharynx; the mean neck circumference was 16.8±1.6 in. and the mean body mass index (BMI) was 30±7 kg/m(2). The apnea hypopnea index (AHI) provided by OCST was similar to that provided by PSG (19.8±18.0 vs 22.0±22.7, respectively; P=0.49). On identifying subjects by OCST with an AHI ≥5 on PSG, OCST had the following parameters: sensitivity 100%, specificity 85.7%, PPV 93%, and NPV 100%. On identifying subjects with an AHI ≥15 on PSG, OCST parameters were as follows: sensitivity 100%, specificity 83.3%, PPV 81.8%, and NPV 100%. Bland-Altman plotting showed an overall diagnostic agreement between OCST and PSG modalities for an AHI cutoff >5, despite fine-grained differences in estimated AHIs. CONCLUSION: Compared with PSG, OCST provides similar diagnostic information when run simultaneously in AIS patients. OCST is a reliable screening tool for early diagnosis of OSA in AIS patients.

Intracranial atherosclerosis is associated with progression of neurological deficit in subcortical stroke.

BACKGROUND: Progression of neurological deficit (PND) is a frequent complication of acute subcortical ischemic stroke (SCS). The role of intracranial atherosclerosis (IAS) in PND is controversial. Our goal was to evaluate IAS on admission, as predictor of PND in SCS patients. METHODS: SCS patients were identified from our prospective database from 2004 to 2008. Clinical and laboratory data were collected from charts, and radiographic data from original radiographs. The proximal intracranial arteries were graded as patent, irregular, stenotic, or occlusion. IAS was defined as irregularity or stenosis. PND was defined as a change in the National Institutes of Health Stroke Scale >1 point. RESULTS: Two hundred and two SCS patients were identified. In 14%, PND occurred at a median of 2 days from onset. Univariate analysis by infarct location showed the following to be associated with PND: for anterior circulation infarcts (centrum semiovale/basal ganglia), M1 atherosclerosis (p = 0.042); for posterior circulation infarcts, vertebral artery atherosclerosis (p = 0.018). For both groups, we found a non-significant association with age (p = 0.2) and HbA1c levels (p = 0.095). No association was found with admission glucose levels. Multivariate analysis showed the following association with PND: for anterior circulation infarcts, M1 atherosclerosis (OR 4.7; 95% CI 1.2-18.8; p = 0.03); for pontine infarcts, vertebral artery atherosclerosis (OR 5.8; 95% CI 1.1-29.4; p = 0.033). There was an increase in PND likelihood with an increasing number of atherosclerotic vessels. DISCUSSION: In our cohort of SCS patients, PND was associated with IAS of the responsible vessels. These results suggest a role for IAS in the pathogenesis of PNF in SCS patients.

Nonpulsatile cerebral perfusion in patient with acute neurological deficits.

BACKGROUND AND PURPOSE: An extremely low pulsatile cerebral perfusion can result in a massive cerebral infarction and poor outcome. We report a patient who had complete recovery from initial neurological deficits in spite of nonpulsatile perfusion in the middle cerebral artery. METHODS: We used carotid duplex and transcranial Doppler to evaluate cerebral hemodynamics and the National Institutes of Health Stroke Scale (NIHSS) to score the neurological deficits. RESULTS: A 62-year-old man had a sudden chest pain and right hemispheric symptoms with NIHSS score of 18 on arrival. Carotid duplex showed no blood flow in the right common carotid artery. Transcranial Doppler showed a nonpulsatile waveform with slow antegrade flow in right middle cerebral artery. Chest CT angiography revealed type A aortic dissection. After surgical repair for the aortic dissection with brain retroperfusion, the patient had dramatic recovery from the initial neurological deficit, and normal pulsatile cerebral perfusion in the right carotid territory. CONCLUSIONS: Nonpulsatile cerebral perfusion points to a proximal source of arterial flow obstruction that may necessitate interventional treatment or surgery in order to restore brain perfusion and potentially reverse impending stroke.

Heads down: flat positioning improves blood flow velocity in acute ischemic stroke.

BACKGROUND: Acute stroke patients are routinely positioned with the head of the bed (HOB) elevated at 30 degrees despite lack of evidence for increased intracranial pressure. OBJECTIVES: To determine the effect of HOB positions in real time on residual blood flow velocity in acutely occluded arteries causing stroke and whether resistance to residual flow increased with lower HOB positions. METHODS: In a repeated-measures quasi-experiment, the effect of 30, 15, and 0 degrees HOB on middle cerebral artery (MCA) mean flow velocity (MFV) in patients with acute (<24 hours) ischemic stroke was measured with transcranial Doppler using MFV and pulsatility index (PI) of the residual flow signals at the site of persisting acute occlusion. RESULTS: Twenty patients were evaluated (mean age 60 +/- 15 years; median NIH Stroke Scale [NIHSS] score 14 points). MCA MFV increased in all patients with lowering head position (maximum absolute MFV value increase 27 cm/s, range 5 to 96% from baseline values at 30 degrees). On average, MCA MFV increased 20% (12% from 30 to 15 degrees and 8% from 15 to 0 degrees; p < or = 0.025). Mean arterial pressure and heart rate were unchanged throughout the intervention. PI remained unchanged (mean values 0.89 at 30 degrees elevation, 0.91 at 15 degrees elevation, and 0.83 at 0 degrees elevation) at each HOB position, indicating no increase in resistance to blood flow. Immediate neurologic improvement (average 3 NIHSS motor points) occurred in three patients (15%) after lowering head position. CONCLUSION: Acute ischemic stroke patients may benefit from lower head-of-the-bed positions to promote residual blood flow to ischemic brain tissue.

Yield and accuracy of urgent combined carotid/transcranial ultrasound testing in acute cerebral ischemia.

BACKGROUND AND PURPOSE: We routinely perform an urgent bedside neurovascular ultrasound examination (NVUE) with carotid/vertebral duplex and transcranial Doppler (TCD) in patients with acute cerebral ischemia. We aimed to determine the yield and accuracy of NVUE to identify lesions amenable for interventional treatment (LAITs). METHODS: NVUE was performed with portable carotid duplex and TCD using standardized fast-track (<15 minutes) insonation protocols. Digital subtraction angiography (DSA) was the gold standard for identifying LAIT. These lesions were defined as proximal intra- or extracranial occlusions, near-occlusions, > or =50% stenoses or thrombus in the symptomatic artery. RESULTS: One hundred and fifty patients (70 women, mean age 66+/-15 years) underwent NVUE at median 128 minutes after symptom onset. Fifty-four patients (36%) received intravenous or intra-arterial thrombolysis (median National Institutes of Health Stroke Scale (NIHSS) score 14, range 4 to 29; 81% had NIHSS > or =10 points). NVUE demonstrated LAITs in 98% of patients eligible for thrombolysis, 76% of acute stroke patients ineligible for thrombolysis (n=63), and 42% in patients with transient ischemic attack (n=33), P<0.001. Urgent DSA was performed in 30 patients on average 230 minutes after NVUE. Compared with DSA, NVUE predicted LAIT presence with 100% sensitivity and 100% specificity, although individual accuracy parameters for TCD and carotid duplex specific to occlusion location ranged 75% to 96% because of the presence of tandem lesions and 10% rate of no temporal windows. CONCLUSIONS: Bedside neurovascular ultrasound examination, combining carotid/vertebral duplex with TCD yields a substantial proportion of LAITs in excellent agreement with urgent DSA.