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Biomedical subjects

B A Malow

Publications and source records attributed to B A Malow.

At least 19 recordsLinked to original sources
PubMed2003

Rasmussen's syndrome and new-onset narcolepsy, cataplexy, and epilepsy in an adult.

We report a case of new-onset seizures and narcolepsy in a previously healthy 40-year-old man. He developed severe daytime somnolence and cataplexy over the course of a few months. Brain MRI was normal, and polysomnography with multiple sleep latency testing confirmed a diagnosis of narcolepsy. His HLA haplotype is DQB1*0602 and cerebrospinal fluid analysis showed no detectable hypocretin. Approximately 18 months later, he developed complex partial seizures. Further MRI showed a progressively enlarging lesion involving the left frontotemporal and insular areas. Pathology from a partial resection was consistent with Rasmussen's syndrome. Evaluation for tumor, infectious, and paraneoplastic etiologies was negative. There was no further progression of the residual lesion on serial MRI. Although the pathophysiologic bases of narcolepsy and Rasmussen's syndrome are unknown, they may have an autoimmune basis. This unique case of both disorders in a single patient suggests the possibility of a common underlying disease process.

Adult↗
PubMed2002

Sleep deprivation does not affect seizure frequency during inpatient video-EEG monitoring.

OBJECTIVE: To determine whether acute sleep deprivation facilitates seizures during inpatient monitoring in a controlled protocol. METHODS: Eighty-four patients with medically refractory partial epilepsy undergoing inpatient monitoring were assigned in consecutive blocks to either sleep deprivation every other night or to normal sleep. In both groups, subjects were requested to stay awake during the day, from 6 AM to 10 PM. In the sleep deprivation group, patients also stayed awake between 10 PM and 6 AM every other night beginning with Day 2. Patients were removed from sleep deprivation if they had two or more secondarily generalized seizures within 24 hours. Patients were removed from the normal sleep group and were sleep deprived if they did not have a complex partial or secondarily generalized seizure by Day 6 of monitoring. In these patients removed from sleep deprivation or from normal sleep, data were analyzed up to and including the day of removal from the protocol. RESULTS: The sleep deprivation and normal sleep subjects did not differ in age, sex, seizure localization, or percent dosage reduction in antiepileptic drugs from baseline at days 1 to 3 of monitoring. Protocol duration was 6.5 +/- 2.4 days (mean +/- SD) for the sleep deprivation group and 5.8 +/- 2.0 days for the normal sleep group. Seizures per day for complex partial, secondarily generalized, and combined complex partial and secondarily generalized, calculated from admission until end of protocol, did not differ significantly between the two groups. CONCLUSION: Acute sleep deprivation did not affect seizure frequency during inpatient monitoring in our patients with intractable complex partial seizures with secondary generalization.

Adult↗
PubMed2001

Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients.

BACKGROUND: Given that vagal afferents project to brainstem regions that promote alertness, the authors tested the hypothesis that vagus nerve stimulation (VNS) would improve daytime sleepiness in patients with epilepsy. METHODS: Sixteen subjects with medically refractory seizures underwent polysomnography and multiple sleep latency tests (MSLT) and completed the Epworth Sleepiness Scale (ESS), a measure of subjective daytime sleepiness, before and after 3 months of VNS. Most subjects (>80%) were maintained on constant doses of antiepileptic medications. RESULTS: In the 15 subjects who completed baseline and treatment MSLT, the mean sleep latency (MSL) improved from 6.4 +/- 4.1 minutes to 9.8 +/- 5.8 minutes (+/- SD; p = 0.033), indicating reduced daytime sleepiness. All subjects with stimulus intensities of < or =1.5 mA showed improved MSL. In the 16 subjects who completed baseline and treatment ESS, the mean ESS score decreased from 7.2 +/- 4.4 to 5.6 +/- 4.5 points (p = 0.049). Improvements in MSLT and ESS were not correlated with reduction in seizure frequency. Sleep-onset REM periods occurred more frequently in treatment naps as compared to baseline naps (p < 0.008; Cochran-Mantel-Haenszel test). The amount of REM sleep or other sleep stages recorded on overnight polysomnography did not change with VNS treatment. CONCLUSIONS: Treatment with VNS at low stimulus intensities improves daytime sleepiness, even in subjects without reductions in seizure frequency. Daytime REM sleep is enhanced with VNS. These findings support the role of VNS in activating cholinergic and other brain regions that promote alertness.

Adult↗
PubMed2000

Effects of vagus nerve stimulation on respiration during sleep: a pilot study.

BACKGROUND: Vagus nerve stimulation (VNS) is associated with respiratory effects such as hoarseness, dyspnea, and laryngeal irritation. The effects of VNS on sleep-related breathing in humans have not been reported previously. METHODS: Four epilepsy patients underwent polysomnography (PSG) before and after 3 months of treatment with VNS. Two of the four patients also underwent follow-up PSG to assess the effects of changing stimulus parameters on sleep-related breathing. RESULTS: All patients showed consistent sleep-related decreases in airflow and effort coinciding with VNS activation, although most events did not meet laboratory criteria for apneas or hypopneas. Apneas and hypopneas were more frequent during VNS activation than during nonactivation. Apnea-hypopnea index (AHI) for three subjects during VNS treatment PSG was <5 apneas and hypopneas/hour. In one patient with obstructive sleep apnea (OSA) before VNS treatment, AHI rose from 4 (pretreatment) to 11.3 (treatment). In this patient and in another patient without clinically significant OSA, lowering stimulus frequency, but not stimulus intensity, pulse width, or on-time, ameliorated VNS-related apneas and hypopneas. CONCLUSIONS: VNS is associated with adverse changes in respiration during sleep. In patients without preexisting OSA, this VNS effect is probably not clinically significant. In patients with preexisting OSA, VNS should be administered with care. Lowering VNS stimulus frequency or prolonging off-time may prevent exacerbation of OSA.

Adult↗
PubMed2000

Obstructive sleep apnea is common in medically refractory epilepsy patients.

BACKGROUND: Previous reports have documented the coexistence of obstructive sleep apnea (OSA) and epilepsy and the therapeutic effects of treatment on seizure frequency and daytime sleepiness. The authors' objective was to determine the prevalence of OSA and its association with survey items in a group of patients with medically refractory epilepsy undergoing polysomnography (PSG). METHODS: Thirty-nine candidates for epilepsy surgery without a history of OSA underwent PSG as part of a research protocol examining the relationship of interictal epileptiform discharges to sleep state. Subjects also completed questionnaires about their sleep, including validated measures of sleep-related breathing disorders (Sleep Apnea Scale of the Sleep Disorders Questionnaire [SA/SDQ]) and subjective daytime sleepiness (Epworth Sleepiness Scale [ESS]). RESULTS: One-third of subjects had OSA, defined by a respiratory disturbance index (RDI) > or = 5. Five subjects (13%) had moderate to severe OSA (RDI > 20). Subjects with OSA were more likely to be older, male, have a higher SA/SDQ score, and more likely to have seizures during sleep than those without OSA (p < 0.05). Seizure frequency per month, the number or type of antiepileptic drugs (AED) prescribed, the localization of seizures (temporal versus extratemporal), and the ESS were not statistically different between the two groups. CONCLUSIONS: In our sample, previously undiagnosed obstructive sleep apnea was common, especially among men, older subjects, and those with seizures during sleep. The impact of treating OSA on seizure frequency and daytime sleepiness in medically refractory epilepsy patients warrants further controlled study.

Adult↗
PubMed1999

Cost-utility of three approaches to the diagnosis of sleep apnea: polysomnography, home testing, and empirical therapy.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is usually diagnosed with overnight polysomnography in a sleep laboratory. Home sleep studies can be performed at lower cost, but results are somewhat less reliable. Bedside diagnosis of OSAS without any testing has also been discussed. OBJECTIVE: To model the costs and utility of laboratory polysomnography, home study, and no testing during the 5 years after initial evaluation for OSAS. DESIGN: Cost-utility analysis. DATA SOURCES: Published data. TARGET POPULATION: Hypothetical cohort of persons suspected of having OSAS. TIME HORIZON: The 5 years after initial evaluation for OSAS. PERSPECTIVE: Societal. INTERVENTION: Nasal continuous positive airway pressure when OSAS was diagnosed. MEASUREMENTS: Quality of life, survival and charges (as proxies for costs) for each diagnostic method. RESULTS OF BASE-CASE ANALYSIS: Under almost all modeled conditions, polysomnography provided maximal quality-adjusted life-years in the 5 years after the initial diagnostic evaluation. The incremental charges for polysomnography over home study or no testing were about $13,400 and $9200, respectively, per quality-adjusted life-year gained during this period. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the utility of treatment in the absence of OSAS. CONCLUSIONS: The cost-utility of polysomnography instead of home study or no testing in the diagnosis of OSAS compares favorably with that of other procedures for which society judges the added utility per dollar spent to be worthwhile. More precise determination of certain key variables in this model should be a goal of future research.

Cost-Benefit Analysis↗
PubMed1999

Hippocampal sleep spindles revisited: physiologic or epileptic activity?

OBJECTIVE: Few reports have described sleep spindles in intracranial electrode recordings from human hippocampus. Controversy exists regarding whether hippocampal spindles represent a physiologic or epileptic phenomenon. METHODS: We reviewed hippocampal recordings in 8 subjects to characterize events resembling sleep spindles. RESULTS: In 6 subjects, events occurred exclusively during non-rapid eye movement (NREM) sleep, were similar in morphology to surface spindles, occurred simultaneously or independently of surface spindles, and did not show a consistent relationship to the epileptic region. In an additional subject, a proportion of the hippocampal activity recorded differed slightly in morphology from surface spindles, was present during both NREM and rapid eye movement (REM) sleep, occurred in the same channels as isolated interictal epileptiform discharges, attenuated just prior to seizures, and occurred postictally as repetitive discharges. This activity occurred simultaneously or independently of surface spindles, but differed from surface spindles by both visual and signal analysis measures. CONCLUSIONS: Most examples of hippocampal activity resembling spindles are probably physiologic, originating within the hippocampus or propagated from neighboring regions. However, in one subject, spindle activity and epileptiform discharges may have coincided, supporting experimental evidence that neurophysiological processes associated with spindle generation and NREM sleep contribute to the activation of epileptiform discharges.

Adolescent↗
PubMed1999

Lateralizing value of interictal spikes on overnight sleep-EEG studies in temporal lobe epilepsy.

PURPOSE: To determine the lateralizing value of interictal epileptiform discharges (IEDs) recorded during overnight sleep-EEG studies in temporal lobe epilepsy. Because IEDs are more prevalent in non-rapid eye movement (NREM) sleep than in wakefulness, overnight sleep-EEG recordings may contribute additional lateralizing information to the epilepsy surgery evaluation beyond daytime EEGs. METHODS: Twenty-four subjects with medically refractory temporal lobe epilepsy underwent continuous overnight sleep-EEG recordings. Subjects were seizure free > or =24 h before study and receiving stable doses of medication. The IED foci recorded on overnight studies were compared with daytime EEGs, interictal samples, and ictal recordings during long-term monitoring, brain magnetic resonance images (MRIs), and surgical outcome. RESULTS: (a) In all 24 subjects, including 13 without IEDs on daytime EEGs, temporal IEDs were present during NREM sleep and were exclusively or predominantly (>95%) unilateral in 15 and bitemporal in nine. (b) Unilateral NREM IEDs were concordant with surface or depth ictal-onset regions in 14 subjects, even if MRIs were normal (three subjects) or surface ictal-onset regions were bilateral (five subjects). Eleven of 12 subjects with unilateral concordant NREM IEDs who have undergone surgery are seizure free. (c) Bitemporal IEDs were associated with postoperative seizures in all subjects with normal MRIs or widespread MRI abnormalities. However, all subjects with bitemporal IEDs and MRI hippocampal abnormalities concordant with ictal-onset regions had good to excellent surgical outcomes. CONCLUSIONS: When combined with other investigations, IEDs recorded on overnight studies add prognostic data to the epilepsy surgery evaluation not provided by daytime EEGs.

Adult↗
PubMed1998

Interictal spiking increases with sleep depth in temporal lobe epilepsy.

PURPOSE: To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy. METHODS: At the time of study, subjects were seizure-free for > or =24 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2). RESULTS: The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal. CONCLUSIONS: Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.

Adolescent↗
PubMed1997

Relationship of interictal epileptiform discharges to sleep depth in partial epilepsy.

Non-rapid eye movement (NREM) sleep activates interictal epileptiform discharges (spikes) in many epileptic syndromes. To define this phenomenon more precisely, we studied the relationship of spikes to absolute log delta power (LDP), a continuous measure of sleep depth, in 8 patients with partial epilepsy. LDP differed significantly across visually scored sleep stages. Logistic regression analyses of spike occurrence in relation to LDP were carried out on the central-occipital channel contralateral to the dominant spike focus (C4-O2 for left and C3-O1 for right temporal focus). Within NREM sleep, spikes were more likely to occur: (1) at higher levels of LDP, (2) on the ascending limb of LDP, and (3) with more rapid rises in LDP. Spike frequency per minute was 4.6 times higher in NREM than in rapid-eye movement (REM) sleep and diminished with time from sleep onset. When the effect of LDP was controlled for in the analysis, however, there was no significant effect of REM sleep stage or time on spike occurrence. Only 1% of spikes occurred within 10 s of an arousal. These findings suggest that processes underlying the deepening of NREM sleep may contribute to spike activation in partial epilepsy.

Adult↗
PubMed1997

Predictors of sleepiness in epilepsy patients.

Sleepiness, a common complaint of epilepsy patients, is frequently attributed to antiepileptic medications. To determine predictors of subjective sleepiness in epilepsy patients, we gave self-administered, validated surveys of sleepiness [Epworth sleepiness scale (our major outcome measure)] and sleep apnea [sleep apnea scale of the sleep disorders questionnaire (SA/SDQ)] to 158 epilepsy patients and 68 neurology patients without epilepsy (controls). An elevated Epworth score (>10) was more likely in epilepsy patients compared to controls after controlling for age and gender (p < 0.05). When Epworth scores were adjusted for SA/SDQ scores and restless legs symptoms (RLS), however, epilepsy patients showed only a nonsignificant trend toward elevated Epworth scores compared to controls (p = 0.08). SA/SDQ scores (p < 0.005) and RLS (p < 0.007) were significant predictors of elevated Epworth score in both epilepsy patients and controls. Among the epilepsy patients, the number or type of antiepileptic medication, seizure frequency, epilepsy syndrome (partial vs. generalized), and the presence of sleep-related seizures were not significant predictors (p > 0.10) of elevated Epworth score. Before attributing sleepiness in epilepsy patients to antiepileptic medications or uncontrolled seizures, clinicians should consider the possibility of a coexisting sleep disorder.

Adolescent↗
PubMed1997

A direct comparison of PET activation and electrocortical stimulation mapping for language localization.

Mapping eloquent language cortex in presurgical patients typically is accomplished using highly invasive direct cortical stimulation techniques. Functional imaging during language activation using positron emission tomography (PET) is a promising, noninvasive alternative that requires validation. In seven patients undergoing surgical evaluation for intractable epilepsy, we performed both direct cortical stimulation and PET activation mapping of language cortex using identical tasks. MRI, PET, and CT scans were coregistered to directly compare the location of language centers determined by cortical stimulation versus activation PET. We found that cortical regions that showed increased cerebral blood flow during both visual and auditory naming tasks were located in the same regions as subdural electrodes which disrupted language during electrical stimulation. Cortical regions underlying electrodes that did not disrupt language also showed no consistent changes in regional cerebral blood flow during PET activation. Used cautiously, PET activation produces language maps similar to those obtained with direct cortical stimulation, with more complete brain coverage and considerably less invasion.

Adolescent↗
PubMed1997

Usefulness of polysomnography in epilepsy patients.

We reviewed the records of 63 adult epilepsy patients who underwent polysomnograms in our laboratory since 1985 to determine the indications for polysomnography and the results of testing. Reasons for referral included excessive daytime sleepiness, suspected obstructive sleep apnea (OSA), and characterization of nocturnal spells. The most common polysomnographic diagnosis was OSA, although we also found narcolepsy, insufficient sleep syndrome with possible idiopathic hypersomnolence, and previously unrecognized nocturnal seizures. We treated OSA with continuous positive airway pressure in 28 patients, 15 of whom were using the device at follow-up appointments. The majority of patients treated for OSA or other disorders reported an improvement in sleepiness or seizure control. Polysomnography, when indicated, is beneficial in epilepsy patients.

Adult↗
PubMed1997

Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy.

Since its introduction, the multiple sleep latency test (MSLT) has played a major role in the diagnosis of narcolepsy. We assessed its diagnostic value in a series of 2,083 subjects of whom 170 (8.2%) were diagnosed with narcolepsy. The sensitivity of the combination of two or more sleep onset rapid eye movement (REM) periods (SOREMPs) with a mean sleep latency of < 5 minutes on an initial MSLT was 70% with a specificity of 97%, but 30% of all subjects with this combination of findings did not have narcolepsy. In some narcoleptics who had more than one MSLT, the proportion of naps with SOREMPs varied substantially from the initial MSLT to the follow-up test. The highest specificity (99.2%) and positive predictive value (PPV) (87%) for MSLT findings was obtained with the criteria of three or more SOREMPs combined with a mean sleep latency of < 5 minutes, but the sensitivity of this combination was only 46%. The combination of a SOREMP with a sleep latency < 10 minutes on polysomnography yielded a specificity (98.9%) and PPV (73%) almost equal to those obtained from combinations of MSLT findings, but the sensitivity was much lower. Our results suggest that the MSLT cannot be used in isolation to confirm or exclude narcolepsy, is indicated only in selected patients with excessive daytime sleepiness, and is most valuable when interpreted in conjunction with clinical findings.

Adolescent↗
PubMed1996

Felbamate monotherapy has stimulant-like effects in patients with epilepsy.

The objective of this study was to assess the psychiatric effects of the antiepileptic drug (AED) felbamate (FBM) in patients with epilepsy. FBM is a new AED with a novel putative (antiglutaminergic) mechanism. Older AEDs such as carbamazepine and valproate have psychotropic properties, but the psychiatric effects of FBM and other new antiglutamatergic AEDs remain to be determined. Thirty inpatients with refractory epilepsy were openly tapered off all AEDs in conjunction with intensive presurgical monitoring prior to a two week randomized double-blind parallel trial of FBM monotherapy versus placebo, followed by open FBM therapy. Psychopathology was rated with weekly psychiatric rating scales. Anxiety, depression and seizures increased significantly with AED discontinuation. Acute blind FBM monotherapy yielded antiepileptic and stimulant-like effects (insomnia, anorexia, and anxiety), but failed to influence AED withdrawal-emergent psychopathology. Restarting original AEDs resolved such pathology in FBM drop outs. Chronic open FBM also had stimulant-like effects, with half of the patients displaying psychiatric deterioration and the other half modest improvement compared to baseline therapies. Baseline insomnia and anxiety may be markers for poorer psychiatric responses to chronic open FBM. FBM had stimulant-like effects, lacked anxiolytic effects, and failed to attenuate AED withdrawal-emergent psychopathology. Baseline insomnia or anxiety may predict poorer psychiatric responses to FBM. Further studies are required to assess whether the novel psychiatric effects observed with FBM also occur with other new antiglutamatergic AEDs.

Adult↗
PubMed1996

Sleep and epilepsy.

Epileptic seizures during sleep are common. Nocturnal synchronization in thalamocortical networks appears to contribute to the facilitation of sleep-related epilepsy. Specific epileptic syndromes associated with sleep, the differential diagnosis of nocturnal spells, and the use of video-electroencephalographic polysomnography are discussed. The management of sleep-related seizures is outline.

Adult↗