The effects of body position on the distribution of obstructive, mixed and central sleep apnoea.

BACKGROUND: Obstructive sleep apnoea is commonly aggravated by the supine body position. The impact of body position on the severity of mixed and central sleep apnoeas is understudied. OBJECTIVES: To evaluate the impact of body position on obstructive, mixed and central apnoea indices in subjects presenting with this triform of sleep apnoea during a single polysomnogram. METHODS: We retrospectively analysed 26 polysomnograms where obstructive, mixed and central apnoeas each occurred at a rate >5/hr. Comparisons between lateral and supine body positions were made for obstructive apnoea index (OAI), mixed apnoea index (MAI), central apnoea index (CAI), apnoea-hypopnoea index (AHI) and obstructive apnoea-hypopnoea index (OAHI). RESULTS: Mean (SD) apnoea indices were significantly lower in lateral v. supine positions, respectively: MAI 15.06 (18.34) v. 32.09 (17.05); p<0.001, CAI 11.82 (11.77) v. 23.82 (14.18); p<0.001, AHI 79.46 (31.17) v. 99.47 (26.33); p<0.001, OAHI 67.87 (28.25) v. 76.00 (23.21); p=0.039. Unexpectedly, the converse was seen for OAI when comparing the lateral v. supine position: 53.10 (30.64) v. 43.58 (25.83); p=0.009, respectively. CONCLUSION: It may be beneficial for subjects with a combination of obstructive, mixed, and central apnoeas to avoid the supine body position. In this triform phenotype, mixed apnoeas are neither purely obstructive nor purely centrally mediated. Furthermore, obstructive, mixed, and central apnoeas may be different representations of a single respiratory abnormality.

Once versus twice daily amikacin in neonates: prospective study on toxicity.

OBJECTIVE: To compare the potentially toxic effects in fullterm neonates of amikacin administered once daily, versus amikacin administered twice daily. METHODOLOGY: A controlled, randomized, prospective study in which one group of fullterm neonatal patients received amikacin 15 mg/kg per dose once daily (n = 20), and the other received amikacin 7.5 mg/kg per dose twice daily (n = 20). Impairment of renal glomerular function was defined as a decline of less than 50% of the expected physiological drop in serum creatinine over time. Brainstem auditory evoked potentials were also evaluated and amikacin blood levels taken. RESULTS: Fifteen patients in the once-daily group and 12 patients in the twice-daily group demonstrated at least one period of renal function impairment while in hospital. This decreased to five of 16 and four of 16 patients during follow-up. These differences were not statistically significant. Brainstem auditory evoked potentials did not find signs of ototoxicity at any time. CONCLUSION: In fullterm neonatal patients, once daily dosing of amikacin is no more toxic than the twice daily regimen.

Short-term antihypertensive medication does not exacerbate sleep-disordered breathing in newly diagnosed hypertensive patients.

It has been speculated for some time that various antihypertensive medications may have a deleterious effect on respiration during sleep and thereby enhance the apparent association between hypertension and sleep apnea/hypopnea (SAH). However, there are few data to support this contention. The present study used a double-blind, randomized, cross-over design to contrast the effects of 6 weeks treatment with alpha-methyldopa and the combination of hydrochlorothiazide and amiloride with that of amlodipine and the combined diuretics in a group of 24 newly diagnosed patients with primary hypertension. All-night polysomnography was performed before the initiation of therapy (baseline) and at the end of the two treatment periods. Respiratory variables failed to reveal any significant differences between the treatments and baseline, or between the two different treatment regimens. The two treatment regimens achieved similar reductions in blood pressure. The prevalence of SAH was 25% before treatment, which is comparable to a prevalence of 20% in a similar group drawn from the same population but receiving various antihypertensive medications. The findings of this study are in agreement with previous reports using other classes of antihypertensive drugs that also failed to detect any tendency for increases in nocturnal respiratory disturbance indices over assessment periods of 8 weeks or shorter.

Hypertension and sleep apnea in black South Africans. A case control study.

Despite relatively consistent findings that patients with hypertension have higher than anticipated prevalences of sleep apnea/hypopnea (SAH), inadequately controlled factors such as age and obesity have been implicated as possibly accounting for these findings. All-night polysomnograms were performed on 20 hypertensive black South Africans, a group with increased risk for this disease. They were matched with a control group of black subjects in respect of age, gender, body mass index (BMI), neck circumference and scores on a sleep questionnaire. While the groups failed to differ significantly in terms of demographic variables, nor in regard to 8/9 anthropometric measures, the hypertensive group had a significantly higher apnea/hypopnea index (AHI) (P = .01), longer duration of AH (P = .01) and lower mean minimum arterial oxygen saturation levels (P = .005). Of the anthropometric measures, only age and neck circumference were found to be cofactors for AHI and were accounted for in the analysis. Five of the hypertensive patients and two of the controls had an AHI > 10, giving a prevalence odds ratio of 3 (95% confidence interval: 0.66-14.50). The present study appears to be the first in black African subjects and with prevalence findings largely comparable to those obtained in other ethnic groups. There was a trend for more severe SAH to occur in this subgroup of five hypertensives (AHI = 14-30) than in controls (maximum AHI = 12). While data are lacking to link antihypertensive medication to SAH in humans, further study is necessary before discarding this factor.

Follow-up of conservatively treated sleep apnoea patients.

Polysomnograms have been recorded at our laboratory since 1985 for the diagnosis of sleep apnoea. Until the recent availability of continuous positive airway pressure devices in Johannesburg, it appeared that some of our subjects were receiving only conservative or no treatment. Structured interviews were conducted with 63 patients with positive polysomnographic findings of sleep apnoea/hypopnoea (SAH), and, where possible, with sleeping partners. Information was obtained about the patients' understanding of the diagnosis by the referring doctor, the recommended treatment and psychosocial consequences. The primary reason for the initial consultation was excessive daytime sleepiness (43%). Diagnoses following polysomnography included SAH (65%) and narcolepsy (6%), while 10% were told they had nothing to be concerned about. Some form of treatment was recommended to 80% of patients, usually weight loss (60%) or medication (59%). Psychosocial consequences were prominent and included a perception of reduced work capacity (62%) and compromised safety (56%). At the time of the interview 90% of patients were experiencing one or more symptoms associated with SAH. These findings support the serious nature of SAH and confirm the need for adequate treatment centres in South Africa.

Neuropsychological test performance and affect in myasthenia gravis.

Neuropsychological test performance, including memory, and affect were investigated in 16 patients with myasthenia gravis (MG) and in a matched control group. Clinical electroencephalograms (EEGs) were recorded from MG patients. Cognitive measures included the Randt Memory Test and a number of tests from the computerized Neurobehavioral Evaluation Battery which included a test of motor speed. Affect was assessed by means of an anxiety questionnaire (IPAT) and a computer based questionnaire similar to the Profile of Mood States (POMS). There were no significant intergroup differences in memory performance and only an isolated significant finding in a timed measure in symbol-digit comparison. The MG group revealed significantly reduced finger tapping. Significantly higher levels of anxiety, tension, anger, fatigue and confusion were associated with the MG group. Abnormal EEGs occurred in 35% of the MG patients, mostly mid-moderate diffuse slowing, but in one case epileptogenic activity was present. The failure to confirm memory deficits in this study appeared not to be related to age or whether patients had generalized or ocular MG. Medication was suggested as a possible factor. These, and other variables, need to be evaluated in further studies.

Multimodal evoked potentials and electroretinography in limb girdle muscular dystrophy.

Evoked potentials (EP) were recorded as part of a complete systems evaluation in 20 strictly selected patients with limb girdle muscular dystrophy. Various abnormalities were detected in 68% (13/19) of patients: 21% (4/19) had visual EP abnormalities; 11% (2/19) had brainstem auditory EP abnormalities; 29% (5/17) and 31% (5/16) had somatosensory EP abnormalities of the median and posterior tibial nerves, respectively. An electroretinogram abnormality was detected in 12% (2/17) of patients. There was no consistent correlation between the number, type or severity of EP abnormality and the age, sex, disease duration or degree of muscle weakness. The significance and etiology of these EP abnormalities need to be established by pathologic studies.

Vitamin B-6 supplementation and theophylline-related effects in humans.

This study investigates whether vitamin B-6 supplementation reduces the stimulatory effects of theophylline (a pyridoxal kinase antagonist) on the nervous system. Twenty young, healthy adults entered this double-blind, randomized, crossover study but only 15 completed the experiment. The dependent measures were a battery of psychomotor tests, electrophysiological tests, and self-report questionnaires. Most tests, including spectral electroencephalography, aspects of the electromyograph, the Sternberg Test of information processing, and questionnaires of sleep quality and daytime sleepiness failed to distinguish between vitamin B-6 and placebo supplementation. However, theophylline-related tremor was markedly reduced (p < 0.01) with vitamin B-6 supplementation after a single dose of theophylline and a similar but nonsignificant trend was observed with repeated doses. There was a tendency for vitamin B-6 supplementation to reduce many side effects related to nervous system function. These findings suggest that vitamin B-6 supplementation with theophylline therapy may have some beneficial effects.

Visual function and long-term chloroquine treatment.

Ophthalmic examinations and selected tests of visual function were performed on 64 patients with rheumatoid arthritis who had received daily doses of 200 mg chloroquine sulphate for periods ranging from 3 to 11 months. Visual fields were determined by Humphrey automated perimetry and Amsler grids and a further battery of four tests of macular function (visual evoked potentials, critical flicker fusion threshold, Cambridge contrast sensitivity and the macular dazzle test) were administered. No case of retinal pigmentary abnormalities plus visual loss was found, but 2 patients were advised to cease chloroquine therapy on the basis of funduscopic findings. A small group of patients with relatively poor scores on one or more tests had normal visual fields and ophthalmic findings. There were no significant partial correlations between test results and the cumulative dose of chloroquine. These results support the opinion that currently recommended doses of chloroquine pose a minimal risk of retinal toxicity.

Induced refractive errors and pattern electroretinograms and pattern visual evoked potentials: implications for clinical assessments.

Refractive errors were induced in normal subjects by means of positive dioptre lenses to reduce visual acuity (VA) from an initial level of 20/20 to 20/100 and then to 20/200. Pattern electroretinograms (PERGs) and pattern visual evoked potentials (PVEPs) were simultaneously recorded at each of these 3 levels of VA using high contrast checkerboard stimuli subtending 11' and 42' of visual arc. Attention was paid to PERG and PVEP variables used for clinical assessments. The findings confirmed the need to take refractive errors into account because, in some cases, latencies and particularly PERG amplitudes fell outside normal limits with decreased VA, especially when using smaller checks.

Recurrent attacks of unconsciousness with diffuse EEG alpha activity.

A 45-year-old patient presented with recurrent attacks of unconsciousness, which resembled sleep. However, EEG recordings during these attacks showed diffuse, frontal-dominant 10-Hz alpha activity. Both the attacks and EEG changes reversed promptly with intravenous flumazenil, but not with methylphenidate, atropine or placebo. The attacks could not be prevented with methysergide, flumazenil, clonidine, piracetam or phenytoin. Laboratory investigations revealed a temporal lobe arachnoid cyst, a distal motor and sensory polyneuropathy, abnormal auditory evoked responses during the attack, an abnormal silent period latency and abnormal melatonin regulation. Similar attacks were reported by history in two siblings and in the proband's late father. It is postulated that the attacks of unconsciousness could involve gamma-aminobutyric acid- (GABA)-mediated mechanisms.

Effect of acute doses of controlled-release carbamazepine on clinical, psychomotor, electrophysiological, and cognitive parameters of brain function.

The neurotoxic effect of acute doses of carbamazepine controlled-release (CBZ-CR) divitabs (800, 1,200, and 1,600 mg) was assessed on clinical, psychomotor, electrophysiological, and cognitive parameters of brain function in 10 healthy volunteers in a double-blind, randomised, placebo-controlled, phase I study. Significant changes compared to placebo were demonstrated for the clinical scales, ataxia (AT), convergence of the near-point (CNP), peak saccadic velocity (PSV), critical flicker fusion (CFF), spectral analysis of the EEG, and brainstem auditory evoked potential (BAEP) tests. Digit repetition, digit symbol substitution, Sternberg memory scanning time, Sternberg choice reaction time, saccadic latency, and saccadic accuracy showed important negative findings. Significant clinical tolerance to side effects developed within 20 to 33 h after CBZ-CR dosage during a period in which the mean CBZ blood levels remained virtually unchanged. CBZ-CR, 800, 1,200, and 1,600 mg yielded low, medium, and high therapeutic blood levels, respectively, for +10 to +33 h after dosage without the development of severe clinical side effects.

The comparison of the effects of multi and single doses of buspirone, chlordiazepoxide and hydroxyzine on psychomotor function and EEG.

This study compares the effects of buspirone (5 mg), chlordiazepoxide (5 mg), hydroxyzine (10 mg) and placebo on psychomotor function and EEG, when taken thrice daily for a period of two weeks, with those after a single dose administration. Nine healthy volunteers participated in the study. The battery of psychomotor tests included peak velocity of saccadic eye movements (SEM), a Sternberg memory scanning and choice reaction time test (SMS-CRT) and critical flicker fusion frequency (CFFF). The peak velocity of saccadic eye movements was significantly impaired by the single dose of hydroxyzine (P = 0.03) in comparison to the multidose results. A similar comparison regarding buspirone only approached significance (P = 0.07). The SMS-CRT and CFFF did not reveal any difference between the multi and single dose regimens. Spectral analysis of the EEG did not distinguish between the multi and single dosage schedules regarding the respective drugs in the low doses administered.

The effects of alprazolam, quazepam and diazepam on saccadic eye movements, parameters of psychomotor function and the EEG.

The effects of a single oral dose of alprazolam (1 mg), quazepam (15 mg) and diazepam (10 mg) on the peak saccadic velocity (PSV) of saccadic eye movements (SEM), the Sternberg memory scanning and choice reaction time (SMS-CRT), critical flicker fusion frequency (CFFF), spectral analysis of the EEG and a mood scale were assessed in 9 healthy volunteers in a double-blind, placebo-controlled cross-over study. Alprazolam revealed greater sedative effects than diazepam in the above-mentioned tests. Quazepam had the least sedative effect of the 3 drugs tested, showed a time lag at the onset of its effects and a more prolonged effect on psychomotor impairment than reported previously.

Somatosensory evoked potential measures of conduction in peripheral and central pathways in children with protein-calorie malnutrition.

The effects of malnutrition on conduction in peripheral and central somatosensory pathways in humans, as measured by short-latency somatosensory evoked potentials (SEPs) have not been previously reported. A group of 28 children with kwashiorkor were compared to a control group of 35 children, aged 6-36 months. The malnourished group had longer reciprocal conduction velocities (ms/m) for pathways between the wrists and the brachial plexi (CL1 response) and between the brachial plexi and the upper cervical region (CL1-CVN). While an individual child with kwashiorkor had abnormal intracranial reciprocal conduction velocities (CVN-N1), the inter-group differences did not attain statistical significance, possibly due to inadequate indices of central pathway lengths. These findings expand the extent of conduction delays revealed by previous studies of peripheral nerve conduction velocities in PCM.

Effects of clobazam and clonazepam on saccadic eye movements and other parameters of psychomotor performance.

The effects of two benzodiazepine anticonvulsants clobazam (20 mg) and clonazepam (2 mg) in a variety of psychomotor performance tests were compared in a placebo controlled double-blind acute oral dose study in ten healthy volunteers. Assessments included critical flicker fusion (CFF) threshold, the Sternberg memory scanning and choice reaction time (CRT), peak saccadic velocity (PSV) and visual analogue scales, all previously shown to be sensitive to the effects of benzodiazepines. Clobazam did not significantly impair saccadic eye movements, CFF threshold, Sternberg memory scanning and CRT compared to placebo. Clonazepam significantly lowered PSV, reduced the CFF threshold, slowed the Sternberg CRT and decreased an alertness factor in the visual analogue scales compared to placebo. Clonazepam significantly increased memory scanning time compared to clobazam. Clobazam was remarkably free of cognitive and psychomotor side-effects.

Auditory brainstem evoked potentials in leprosy.

An electrophysiological study of conduction in the auditory nerve and brainstem auditory pathways using the brainstem auditory evoked potential was undertaken in a group of 47 leprosy patients. There were no statistically significant differences between mean conduction times (interpeak latencies) in the leprosy and the control groups. Abnormal interpeak latencies were encountered in 3 leprosy patients, 1 of whom had a positive serological test for syphilis. In the remaining 2 patients, caudal pathway dysfunction (I-III interpeak latency abnormality) was indicated but specific auditory nerve involvement (an abnormally prolonged I-II interpeak latency) was not demonstrated. An explanation for these findings, other than the patients' disease, was not apparent.

Embolisation of arteriovenous malformation of the spinal cord. A case report.

An arteriovenous malformation of the spinal cord in a 41-year-old man treated by intra-arterial embolisation is reported. The progressive spastic weakness and severe burning pain responded well to treatment. The carefully calculated use of Ivalon particles is essential and is described. Evoked potentials were used to monitor the status of the spinal cord during the procedure. It is essential that a team of clinicians and radiologists be established at major centres to handle such cases.

Brainstem auditory evoked potentials in severely malnourished children with kwashiorkor.

Brainstem auditory evoked potentials (BAEPs) were recorded in a group of 22 children hospitalized for the treatment of severe malnutrition (kwashiorkor). Recordings were repeated after three weeks of treatment. The control group consisted of age- and sex-matched healthy infants. Abnormal BAEP interpeak-latencies (IPLs) were found in 32% of the kwashiorkor group in the initial recording and in 40% of this group in the follow-up recording. Abnormalities were evenly distributed between the I-III, III-V and I-V IPLs and in the majority of cases were unilateral. The influence of increasing stimulus rate was investigated. The findings may reflect defects in myelination of auditory brainstem pathways, however, BAEP abnormalities were not related to several indices of growth retardation or to serum albumin and hemoglobin levels.