hypoxia-related neurological deficits in sleep apnea

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hypoxia-related neurological deficits in sleep apnea

Postby Cece » Sun Jan 16, 2011 5:29 pm

I've been looking into how the brain recovers from hypoxia, if it can recover. Here's some research on hypoxic damage done during sleep apnea and what neurologically recovers after CPAP treatment is begun:
J Clin Exp Neuropsychol. 1993 Mar;15(2):330-41.

Persistent neuropsychological deficits and vigilance impairment in sleep apnea syndrome after treatment with continuous positive airways pressure (CPAP).
Bédard MA, Montplaisir J, Malo J, Richer F, Rouleau I.

Hôpital du Sacré-Coeur and Université de Montréal, Québec, Canada.

Abstract
The obstructive sleep apnea syndrome is characterized by nocturnal sleep disturbance, excessive daytime sleepiness and neuropsychological deficits in the areas of memory, attention, and executive tasks. In the present study, these clinical manifestations were assessed in apneic patients before and 6 months after treatment with nasally applied continuous positive airway pressure (CPAP). CPAP treatment was found to restore normal respiration during sleep and to normalize sleep organization. Daytime vigilance greatly improved with treatment but some degree of somnolence as compared to normal controls persisted. Similarly, most neuropsychological deficits normalized with treatment. The exception was for planning abilities and manual dexterity, two neuropsychological deficits that have been found to be highly correlated with the severity of nocturnal hypoxemia. These results raise the possibility that anoxic brain damage is a pathogenic factor in severe obstructive sleep apnea syndrome.
http://www.ncbi.nlm.nih.gov/pubmed/8491855

Improvements were in daytime vigilance and most neuropsychological deficits but not planning abilities or manual dexterity. These have been shown to be highly correlated with the severity of nocturnal hypoxemia?

With our jugulars being needed when we are lying down, CCSVI is likely causing nocturnal cerebral hypoxemia. This study was only after six months; there have been reports from the Dake patients that in RRMSers fatigue improvements continued to get better and better even up to a year after treatment.

Here is another one that turned up:
CHEST November 1986 vol. 90 no. 5 686-690

Cognitive impairment in patients with obstructive sleep apnea and associated hypoxemia.
L J Findley, J T Barth, D C Powers, S C Wilhoit, D G Boyd, and P M Suratt
Abstract
Twenty-six patients with sleep apnea had neuropsychologic testing prior to nocturnal sleep study in a sleep disorders clinic. The cognitive functioning of patients who had sleep apnea with associated hypoxemia was compared to nonhypoxemic patients with sleep apnea. The patients who had sleep apnea with hypoxemia had more severe cognitive impairment than those with sleep apnea without hypoxemia. The hypoxemic patients with sleep apnea had significantly poorer cognitive functioning on four of eight tests (p less than 0.05). In addition, the patients who had sleep apnea with hypoxemia had mean performance scores in the impaired range on measures of attention, concentration, complex problem-solving, and short-term recall of verbal and spatial information. In contrast, the patients who had sleep apnea without hypoxemia had no mean performance score in the impaired range. The degree of hypoxemia during sleep and wakefulness significantly correlated with the degree of overall cognitive impairment as rated by a neuropsychologist; however, measures of sleep fragmentation did not significantly correlate with overall cognitive impairment in patients with sleep apnea. We conclude that patients who have sleep apnea with associated hypoxemia have cognitive impairment which is more severe than those with sleep apnea without hypoxemia.
http://chestjournal.chestpubs.org/conte ... 6.abstract
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Postby Cece » Sun Jan 16, 2011 6:00 pm

.Optic neuropathy associated with sleep apnea syndrome
Presented in part at the Annual Meeting of the American Academy of Ophthalmology, Chicago, October, 1996.

Objective
The study aimed to determine ocular abnormalities in sleep apnea syndrome (SAS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of cardiovascular and neurologic sequelae.

Design
The study design was a case series.

Participants
Nine patients referred for evaluation of suspected SAS participated.

Intervention
Complete ophthalmologic examination, including computerized perimetry, was performed.

Main outcome measures
Correlations between the respiratory disturbance index (RDI) during night sleep, a value used to diagnose and to grade SAS, and visual field indices using the Spearman rank correlation coefficient (rs) were measured.

Results
One patient was excluded from the statistical analysis because of optic nerve drusen with constricted visual fields, another because of tiled discs with corresponding temporal visual field defects. All three patients with severe SAS and one patient with moderate SAS had relative nasal arcuate visual field defects; two patients with severe SAS also had paracentral relative defects. One patient with normal polysomnographic result and two patients with mild or moderate SAS had normal visual fields. The RDI correlated positively with the mean visual field defect (rs = 0.81, P < 0.05) and with the visual field loss variance (rs = 0.78, P < 0.05). The clinical ophthalmologic examination results were normal in all seven patients. In two of the three patients with severe SAS treated with continuous positive airway pressure (CPAP), visual field defects remained stable over 18 months. The patient with optic nerve drusen also had severe SAS and was, therefore, treated with CPAP. His constricted visual fields improved dramatically after treatment.

Conclusions
Visual fields of patients with SAS showed defects consistent with an optic neuropathy. The CPAP therapy seems to stabilize or even reverse visual field defects.

http://www.ophthalmologyjournaloftheaao ... 61-6420(98)95030-8/abstract

Not sure I understand exactly how this would work. Does the hypoxia of sleep apnea cause optic neuropathy? I include this because of the frequency of optic neuritis in MS patients.
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Postby Cece » Sun Jan 16, 2011 6:12 pm

Sleep. 2007 November 1; 30(11): 1515–1520.
Reduced Cerebral Blood Flow During Wakefulness In Obstructive Sleep Apnea-Hypopnea Syndrome

Eun Yeon Joo, MD,1 Woo Suk Tae, PhD,1 Sun Jung Han, MD,2 Jae-Wook Cho, MD,1 and Seung Bong Hong, MD, PhD11Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

AbstractStudy Objectives:
To investigate changes in regional cerebral blood flow (rCBF) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).
Design:
We compared the 99mTc-ethylcysteinate dimer (ECD) single photon emission computed tomography (SPECT) images of patients with OSAHS with those of age- and sex-matched healthy volunteers.
Setting:
University hospital.
Patients and Participants:
Twenty-seven patients with severe OSAHS and 27 healthy volunteers underwent 99mTc-ECD brain SPECT studies.
Intervention:
For statistical parametric mapping analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 14-mm full-width at half-maximum Gaussian kernel. The Student t test was used for the statistical analysis.Measurements and Results:
The mean age of patients and subjects was 44.3 years (range 31-58). All patients underwent overnight polysomnography. The mean apnea-hypopnea index of patients was 60.4 ± 17.6 per hour (range 33 −104), indicating severe OSAHS. All patients snored heavily and had daytime sleepiness (mean Epworth Sleepiness Scale score, 10.7 ± 3.7, range 6-12). Statistical parametric mapping analysis showed that rCBF in patients with OSAHS was significantly reduced in bilateral parahippocampal gyri and in the right lingual gyrus, as compared with that of healthy volunteers (P < 0.05 with false discovery rate correction). Moreover, apnea-hypopnea indexes of patients were negatively correlated with rCBF in the right pericentral gyrus and right cuneus at uncorrected P < 0.001.
Conclusions:
Our results show the altered rCBF pattern in bilateral parahippocampal gyri, right lingual gyrus, pericentral gyrus, and cuneus in patients with severe OSAHS. These findings may partly explain the deficit in memory, spatial learning, executive function, and attention, which are frequently found in patients with OSAHS.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082095/

So, why do sleep apnea patients have altered cerebral blood flow in these areas? I thought this was curious.
Last edited by Cece on Sun Jan 16, 2011 8:13 pm, edited 1 time in total.
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Postby Cece » Sun Jan 16, 2011 6:18 pm

This one was thorough and well-written, presenting negative results (no gray matter changes as a result of the sleep apnea).
http://tinyurl.com/4gltcb3
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Postby Cece » Sun Jan 16, 2011 6:21 pm

Cerebral hemodynamics in obstructive sleep apnea.
M Siebler and A Nachtmann
+ Author Affiliations

Department of Neurology, Heinrich-Heine-Universität, Düsseldorf, Germany.
Abstract
We have investigated cerebral blood flow velocity (CBVF) in 14 patients with marked obstructive sleep apnea syndrome using transcranial Doppler ultrasonography during sleep. The CBFV increased during apnea, with a mean acceleration of 0.9 cm/s2, followed by a rapid decrease during snoring. The same effect was obtained by voluntary apnea in healthy subjects, showing a smaller acceleration rate (0.6 cm/s2). These results provide evidence for a normal CO2 regulation of cerebral vessels during sleep apnea and do not support the notion of cerebral hypoperfusion during sleep being a risk factor for stroke.

http://chestjournal.chestpubs.org/conte ... 1118.short

negative results again
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Postby Cece » Sun Jan 16, 2011 6:23 pm

Sleep. 2008 July 1; 31(7): 967–977.
Brain Structural Changes in Obstructive Sleep Apnea

Paul M. Macey, PhD,1,2 Rajesh Kumar, PhD,3 Mary A. Woo, DNSc,2 Edwin M. Valladares, BS,3 Frisca L. Yan-Go, MD,4 and Ronald M. Harper, PhD1,31Brain Research Institute
2UCLA School of Nursing,
Departments of 3Neurobiology and
4Neurology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA

Objectives:
Determine whether obstructive sleep apnea (OSA) subjects show indications of axonal injury.
Design:
We assessed fiber integrity in OSA and control subjects with diffusion tensor imaging (DTI). We acquired four whole-brain DTI series from each subject. The four series were realigned, and the diffusion tensor calculated at each voxel. Fractional anisotropy (FA), a measure of fiber integrity, was derived from the diffusion tensor, resulting in a whole brain FA “map.” The FA maps were spatially normalized, smoothed, and compared using voxel-based statistics to determine differences between OSA and control groups, with age as a covariate (P < 0.05, corrected for multiple comparisons).
Setting:
University medical center.
Subjects:
We studied 41 patients with untreated OSA (mean age ± SD: 46.3 ± 8.9 years; female/male: 7/34) with apnea-hypopnea index 15 to 101 (mean ± SD: 35.7 ± 18.1 events/hour), and 69 control subjects (mean age ± SD: 47.5 ± 8.79 years; female/male: 25/44).
Measurements and Results:
Multiple regions of lower FA appeared within white matter in the OSA group, and included fibers of the anterior corpus callosum, anterior and posterior cingulate cortex and cingulum bundle, right column of the fornix, portions of the frontal, ventral prefrontal, parietal and insular cortices, bilateral internal capsule, left cerebral peduncle, middle cerebellar peduncle and corticospinal tract, and deep cerebellar nuclei.
Conclusions:
White matter is extensively affected in OSA patients; the alterations include axons linking major structures within the limbic system, pons, frontal, temporal and parietal cortices, and projections to and from the cerebellum.

White matter changes in sleep apnea. A result of hypoxia?
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Postby Cece » Sun Jan 16, 2011 6:39 pm

J Neurol Neurosurg Psychiatry 2001;71:334-339 doi:10.1136/jnnp.71.3.334
Paper

Cerebral metabolic impairment in patients with obstructive sleep apnoea: an independent association of obstructive sleep apnoea with white matter change

M Kambaa,b, Y Inouec, S Higamid, Y Sutob, T Ogawab, W Chena

Abstract
OBJECTIVES To determine the relation between severity of obstructive sleep apnoea (OSA) and degree of cerebral metabolic impairment.

METHODS Fifty five patients with habitual snoring and excessive daytime sleepiness underwent standard overnight polysomnography and magnetic resonance spectroscopy separately. Proton MR spectra were measured with two dimensional chemical shift imaging (repetition time; 1500 ms, echo time; 135 ms). Severity of cerebral metabolic impairment was assessed by the N-acetylaspartate (NAA)/choline ratios for the cerebral cortex and white matter. Severity of OSA was assessed by the apnoea-hypopnoea index (AHI) and the minimum value of peripheral oxyhaemoglobin saturation. All patients were evaluated for the presence or absence of comobidities including hypertension, cardiac disease, diabetes mellitus, and hyperlipidaemia. Univariate analysis of variance (ANOVA) and mulitple linear regression analysis were used for statistical analyses.

RESULTS Univariate ANOVA disclosed significant effects of AHI, age, and the presence or absence of hypertension on the NAA/choline ratio for cerebral white matter (p=0.011, p=0.028, p=0.0496, respectively). The AHI had a significant negative association with the NAA/choline ratio for cerebral white matter, independent of age and the presence or absence of cardiac disease, in the final multivariate regression model (standardised partial regression coefficient=−0.417, p<0.001). No significant relation was found between severity of OSA and the NAA/choline ratio for the cerebral cortex. Age alone had a significant effect on the NAA/choline ratio for the cerebral cortex on univariate ANOVA (p<0.001) and a significant negative association with the NAA/choline ratio for the cerebral cortex in the regression model (r=−0.552, p<0.001).

CONCLUSIONS A significant relation exists between AHI and the degree of metabolic impairment in cerebral white matter in patients with OSA.

http://jnnp.bmj.com/content/71/3/334.abstract

The hypoxia of sleep apnea is damaging to cerebral white matter.
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Postby Cece » Sun Jan 16, 2011 6:45 pm

Am. J. Respir. Crit. Care Med., Volume 156, Number 1, July 1997, 296-298


Cerebral Metabolism in Sleep Apnea
Evaluation by Magnetic Resonance Spectroscopy
MASAYUKI KAMBA, YUJI SUTO, YOSHIO OHTA, YUICHI INOUE, and EIKEN MATSUDA

Departments of Radiology, Neuropsychiatry, and Otorhinolaryngology, Tottori University Faculty of Medicine, Yonago, Japan

Repeated apneic episodes during sleep may lead to cerebral damage in patients with obstructive sleep apnea (OSA). We performed proton magnetic resonance (MR) spectroscopic studies to examine cerebral metabolism in patients with OSA. We studied 15 healthy subjects and 23 patients with OSA who displayed no anatomical abnormalities on MR imaging. The patients were classified into two groups based on the results of polysomnography: mild OSA (11 patients) or moderate to severe OSA (12 patients). All the subjects were examined with two-dimensional chemical shift imaging. The N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cre), and Cho/Cre ratios for cerebral cortex and white matter were calculated separately. A statistically significant intergroup difference was found for the NAA/Cho ratio in cerebral white matter (p < 0.005). This ratio was significantly lower in patients with moderate to severe OSA than in patients with mild OSA (p < 0.01) and healthy subjects (p < 0.01). Our findings indicate that cerebral metabolic changes occur in normal-appearing brain tissue in patients with moderate to severe OSA. The finding of a decreased NAA/Cho ratio suggests the presence of cerebral damage, probably caused by repeated apneic episodes. Proton MR spectroscopy may be useful for evaluating cerebral damage in patients with OSA.

http://ajrccm.atsjournals.org/cgi/conte ... /156/1/296

Normal-appearing white matter, anyone? NAWM as abbreviated in MS research, where it's shown to be normal in appearance but not normal at all. Same in sleep apnea, with probable cause being the repeated apneic episodes.
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Postby Cece » Sun Jan 16, 2011 6:48 pm

There was another mention of this as well. Increased cerebral blood flow velocity in sleep apnea. No idea if that means anything. Just looking for parallels.
Published online October 2, 2006
PEDIATRICS Vol. 118 No. 4 October 2006, pp. e1100-e1108 (doi:10.1542/peds.2006-0092) ARTICLE

Increased Cerebral Blood Flow Velocity in Children With Mild Sleep-Disordered Breathing: A Possible Association With Abnormal Neuropsychological Function

http://pediatrics.aappublications.org/c ... 18/4/e1100
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Postby Cece » Sun Jan 16, 2011 6:55 pm

Cerebral blood flow is initially reduced during obstructive apnoea, due to intrathoracic negative pressure, and then increases because of changes in first partial pressure of carbon dioxide and then arterial blood pressure 5, 32, 36, 37. The authors postulate that longer apnoeas and apnoeas in REM sleep may be associated with greater swings in cerebral blood flow as well as larger desaturations, so that cerebral blood-flow reductions exacerbate the effect of desaturation on cerebral oxygenation. Cerebral blood flow is more likely to be reduced in longer obstructive events 37, and tissue oxygen extraction may also be increased in longer apnoeas. Cerebral blood flow is increased in REM sleep 32, but this is coupled to an increase in cerebral metabolic rate and tissue oxygen extraction 38. Monitoring of CBFV directly would have assisted the interpretation of the findings in this study.

http://www.ersj.org.uk/content/20/2/444.full
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Postby cheerleader » Sun Jan 16, 2011 6:58 pm

Hi Cece--
an important thread. Interesting connection to optic neuropathy.
You might want to do some research on central sleep apnea (often connected to pwMS and brain lesions, or a neurological condition) as opposed to obstructive sleep apnea (actual physical blockage in airway).

Central sleep apnea-hypoventilation syndromes such as those associated with narcotic use or brainstem lesions are due to disturbances of the central respiratory pattern center or peripheral chemoreceptors or both that may become more evident during sleep because of the suppression of wakefulness or behavior drive.

check out this link....I don't have time to dig in, but I think there's something here regarding the "loop gain" of those with venous hypoxia.
http://emedicine.medscape.com/article/304967-overview


Here's a discussion we had about Jeff's sleep apnea in July--
http://www.thisisms.com/ftopic-12601-0- ... ntral.html

Cece, I don't know how sleep apnea affects oxygenation in the normal population, but my husband, the MSer used to have it--this is what really made Dr. Dake think about what were MS/neurological symptoms, and what symptoms are caused by venous insufficiency and hypoxia.

Jeff used to have horrible sleep apnea. He's had it our whole married life (26 years now!) and since his MS diagnosis, it had gotten really bad. He would wake up, gasping for air. It really scared me, because he would just stop breathing. His doctor had scheduled him for a sleep study, but he ended up going to Stanford before it...

After his angioplasty, the apnea just went away. No more gasping, not even a snore. He sleeps like a baby thru the night, and wakes up refreshed. He remembers his dreams, and fatigue and depression are gone.

Jeff also used to get altitude sickness when hiking or skiing. Since angio, he has gone skiing and snow-shoeing at high altitude, with no problem.

The only thing that is different for him is that he now has jugular return. More studies need to be completed to look at oxygenation levels in MS brain before and after angioplasty


There may be something there regarding cental sleep apnea and the feedback loop that develops due to low O2 while supine...keep digging!
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby Cece » Sun Jan 16, 2011 7:44 pm

I'm wondering if garyak has anything to comment on the optic neuropathy one. It would seem that those were hypoxic-related defects of the visual field that then resolved upon treatment of the hypoxia. Are they similar to the defects seen in optic neuritis?

Thanks for the link, Cheer, I'll read that closely.

I agree that central sleep apnea is more likely to be occurring in people with MS, but since central sleep apnea already would have a neurological cause or component, I was deliberately looking at obstructive sleep apnea with the belief that this would more accurately capture any effects on the CNS of the hypoxia itself. It's imperfect, I know. I wish there were pages upon pages of CCSVI results in google scholar to read up on instead.

My husband also has sleep apnea, I know that scary gasping and thank god for CPAP.
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Postby Cece » Sun Jan 16, 2011 8:02 pm

J Int Neuropsychol Soc. 2004 Sep;10(5):772-85.

Neuropsychological sequelae of obstructive sleep apnea-hypopnea syndrome: a critical review.
Aloia MS, Arnedt JT, Davis JD, Riggs RL, Byrd D.

Brown Medical School, Providence, Rhode Island 02906, USA. Mark_Aloia@Brown.edu

Abstract
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a well-recognized clinical sleep disorder that results in chronically fragmented sleep and recurrent hypoxemia. The primary daytime sequelae of the disorder include patient reports of excessive daytime sleepiness, depression, and attention and concentration problems. It has been well established that OSAHS negatively impacts certain aspects of cognitive functioning. The primary goals of this article are to (1) clarify the pattern of cognitive deficits that are specific to OSAHS; (2) identify the specific cognitive domains that improve with treatment; and (3) elucidate the possible mechanisms of cognitive dysfunction in OSAHS. At the conclusion of the paper, we propose a potential neurofunctional theory to account for the etiology of cognitive deficits in OSAHS. Thirty-seven peer-reviewed articles were selected for this review. In general, findings were equivocal for most cognitive domains. Treatment, however, was noted to improve attention/vigilance in most studies and consistently did not improve constructional abilities or psychomotor functioning. The results are discussed in the context of a neurofunctional theory for the effects of OSAHS on the brain.

http://www.ncbi.nlm.nih.gov/pubmed/15327723

This was a meta-analysis of 37 peer-reviewed research articles. It consistently found that attention and vigilance improved upon treatment of sleep apnea and that constructional abilities and psychomotor functioning did not. So it might be that after CCSVI treatment, in these cognitive domains, we might be likely to see improvements in attention and vigilance but not in constructional abilities and psychomotor functioning, if hypoxia of sleep apnea and hypoxia of CCSVI are indeed similar.

This fits with the first one I posted, which found improvements in daytime vigilance and most neuropsychological deficits but not planning abilities or manual dexterity.
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Postby Billmeik » Mon Jan 17, 2011 10:14 am

I think if they are going to prove the ccsvi is caused by ms the model needs the blood to stop flowing for some reason in the jugs. Apnea would do this, leaving blood full of clenching immune cells to cause stenosis. (not)
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Postby bluesky63 » Mon Jan 17, 2011 4:43 pm

Not thinking on all cylinders right now, but I have wondered if we might get any interest from sleep clinics, etc., from looking at this whole thing as a sleep disorder. I am obviously not the first to talk about this, but a near-universal effect of the procedure seems to be a return of dreaming. A before-and-after sleep study would be enlightening.

How long does the dreaming last? If you lose other benefits, will the dreaming stay? Where is this captured?

P.S. That last study you posted there, Cece, is very funny and fits my experience. Basically, I still can't figure out how to get stuff done, but I am more aware of that fact. :-)
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