Boris A. Vern

Low-frequency oscillations of cortical oxidative metabolism in waking and sleep.

To study the changes in cortical oxidative metabolism and blood volume during behavioral state transitions, we employed reflectance spectrophotometry of the cortical cytochrome c oxidase (cyt aa3) redox state and blood volume in unanesthetized cats implanted with bilateral cortical windows and EEG electrodes. Continuous oscillations in the redox state and blood volume (∼9/min) were observed during waking and sleep. These primarily metabolic oscillations of relatively high amplitude were usually synchronous in homotopic cortical areas, and persisted during barbiturate-induced electrocortical silence. Their mean amplitude and frequency did not vary across different behavioral/EEG states, although the mean levels of cyt aa3 oxidation and blood volume during rapid eye movement (REM) sleep significantly exceeded those during waking and slow-wave sleep. These data suggest the existence of a spontaneously oscillating metabolic phenomenon in cortex that is not directly related to neuroelectric activity. A superimposed increase in cortical oxidative metabolism and blood volume occurs during REM sleep. Experimental data concerning cerebral metabolism and blood flow that are obtained by clinical methods that employ relatively long sample acquisition times should therefore be interpreted with caution.

BRAIN SPECT IMAGING AND TREATMENT WITH IVIG IN ACUTE POST-INFECTIOUS CEREBELLAR ATAXIA : CASE REPORT

A 19 year-old man presented with pharyngitis and cervical lymphadenopathy, followed by vomiting and acute cerebellar ataxia. Serologic studies were consistent with a recent Epstein-Barr virus infection. Although contrast-enhanced brain computed tomography and MRI scans were normal, brain perfusion single photon emission tomography (SPECT) examination using 99mTc-HMPAO, performed on the 15th day of illness, showed marked cerebellar hyperperfusion, suggesting a diagnosis of acute post-infectious cerebellitis. After treatment with intravenous human immunoglobulin (IVIg, 2 g kg-1 over three days), progressive neurologic improvement occurred over two weeks. A brain SPECT study repeated after two additional weeks demonstrated a normal perfusion pattern. We conclude that brain perfusion SPECT examination is useful in identifying post-infectious cerebellitis and in monitoring its clinical course. In addition, IVIg may be helpful in treating this condition.

Interhemispheric synchrony of slow oscillations of cortical blood volume and cytochrome aa3 redox state in unanesthetized rabbits

In order to study spontaneous, slow oscillations of regional oxidative metabolism and blood flow in the normal, unanesthetized cortex, adult rabbits were implanted with bilateral cortical windows and electrodes for polysomnography. Relative changes in the cortical intramitochondrial redox state of cytochrome aa3 (CYT) and blood volume (CBV) were monitored by dual-wavelength reflectance spectrophotometry. Continuous, non-stationary oscillations (< 0.5 Hz) of both CYT and CBV were observed during waking and non-REM sleep. Cross-correlation analysis revealed a predominant interhemispheric synchrony of these oscillations which were unrelated to the heart rate, breathing, or electrocorticogram pattern. These findings suggest a dynamic linkage of slowly varying metabolic and vascular processes between unanesthetized cortical regions of 50 mm2 surface area.

Effects of Ischemia on the Removal of Extracellular Potassium in Cat Cortex during Pentylenététrazol Seizures

Summary: Changes in cortical extracellular potassium activity ([K+]o), NADH fluorescence, and oxygen consumption were studied in anesthetized cats during pentylenetetrazol seizures. The effects of partial ischemia induced by either hypotension or intermittent carotid artery occlusion on these parameters were investigated. Nonischemic seizures were characterized by gradual generalized decreases in cortical NADH fluorescence and increases in 02 consumption, along with rapid increases in [K+]0, which then usually fell slightly as the ictal discharge continued. Ischemic seizures, on the other hand, were accompanied by complex changes in NADH fluorescence, by smaller delayed maximal increases in O2 consumption that lasted beyond the end of ictal activity, and by more sustained increases in [K+]0. The decay of [K+]0 after the termination of seizures in both nonischemic and moderately ischemic animals was not a monoexponential function: plots of lnΔ[K+]0 versus time showed an initial linear decline (of slope M1) that rather abruptly slowed (to slope M2) after 2 to 5 sec and then often increased to the original rate. Both M, and M2 were proportionately decreased by ischemia. In addition, the rate of [K+]0 removal could be slowed by acute ischemia induced either during or after the end of ictal activity. The initial rate of postictal [K+]0 removal (M1) was found to be linearly and inversely related to the level of cortical NADH fluorescence at the time of seizure termination. The results of this study suggest that an O2‐dependent transport mechanism plays a major role in the removal of [K+]0 during and following the termination of generalized pentylenetetrazol seizures in the cat.

Focal MRI findings in early SSPE

Many investigators have identified localized cortical involvement in subacute sclerosing panencephalitis (SSPE) by clinical and electrophysiologic criteria. Some investigators have reported such abnormalities in the posterior cerebrum early in the course of the disease, but without radiologic correlation. Recently, magnetic resonance imaging has been used to follow the progression of SSPE. The largest reported study of SSPE utilizing magnetic resonance imaging indicated that focal abnormalities were distinctly rare and actually mitigated against the diagnosis of SSPE. We report an SSPE patient with focal cerebral dysfunction and magnetic resonance imaging evidence of distinctly focal inflammatory disease early in the course of the illness.

Health-Related Stigma as a Determinant of Functioning in Young Adults with Narcolepsy

Symptoms of narcolepsy tend to arise during adolescence or young adulthood, a formative time in human development during which people are usually completing their education and launching a career. Little is known about the impact of narcolepsy on the social aspects of health-related quality of life in young adults. The purpose of this study was to examine relationships between health-related stigma, mood (anxiety and depression) and daytime functioning in young adults with narcolepsy compared to those without narcolepsy. Young adults (age 18–35) with narcolepsy (N = 122) and without narcolepsy (N = 93) were mailed a packet that included questionnaires and a self-addressed postage paid envelope. The questionnaire included demographic information and a composite of instruments including the SF 36, Functional Outcomes of Sleep Questionnaire (FOSQ), Fife Stigma Scale (FSS), Epworth Sleepiness Scale (ESS) and Hospital Anxiety and Depression Scale (HADS). Variable associations were assessed using descriptive statistics, ANOVA, Mann-Whitney U Test, correlations, stepwise multiple regression and path analysis. Young adults with narcolepsy perceived significantly more stigma and lower mood and health-related quality of life than young adults without narcolepsy (p<0.01). Health-related stigma was directly and indirectly associated with lower functioning through depressed mood. Fifty-two percent of the variance in functioning was explained by the final model in the young adults with narcolepsy. Health-related stigma in young adults with narcolepsy is at a level consistent with other chronic medical illnesses. Health-related stigma may be an important determinant of functioning in young adults with narcolepsy. Future work is indicated toward further characterizing stigma and developing interventions that address various domains of stigma in people with narcolepsy.

Slow Oscillations of Cytochrome Oxidase Redox State and Blood Volume in Unanesthetized Cat and Rabbit Cortex

The purpose of this study was to determine the frequency characteristics and the degree of interhemispheric synchrony of slow (< 0.5 Hz), spontaneous oscillations of the regional cortical cytochrome oxidase redox state (CYT) and blood volume (CBV) in unanesthetized animals. We implanted bilateral cortical windows and electrodes for polysomnography in 7 cats and 3 rabbits. The animals were atraumatically restrained during multiple 3-6 hour sessions for up to 8 weeks, and relative changes in the cortical CYT and CBV were monitored by dual wavelength reflectance spectrophotometry at 603 nm and 590 nm. Continuous oscillations of CYT and CBV, unrelated to pulse or respiration, were always observed in each animal. Frequency (FFT) analysis over time revealed a nonstationary distribution of frequencies below 0.4 Hz, with most of the spectral power being contained in the 0-0.25 Hz band during both waking and sleep. Although the time-frequency plots of the CYT and CBV signals were similar, an occasional dissociation between the CYT and CBV oscillations was found. Analysis of simultaneous bilateral cortical optical recordings revealed a significant and sustained interhemispheric cross-correlation over time between the CYT as well as the CBV oscillations during stable recordings as long as 60 min. We conclude that: 1) CYT and CBV levels normally oscillate at < 0.4 Hz in the unanesthetized cat and rabbit cortex; 2) these complex oscillations, whose frequencies are non-stationary over time, nevertheless show sustained interhemispheric synchrony between 50 mm2 homotopic cortical regions; and 3) these oscillations may in part represent fluctuations of the metabolic rate.

Hypokalemic periodic paralysis with unusual responses to acetazolamide and sympathomimetics

Five members in three generations of a family were affected by an illness that had many clinical features of the hypokalemic form of periodic paralysis (HPP). The serum potassium was either moderately reduced or normal during attacks, and there was no evidence of myotonia or cold-intolerance. All of the patients improved to a variable degree with oral potassium supplements, and 3 responded favorably to triamterene. The usually beneficial drug acetazolamide, however, invariably caused weakness in these patients, an effect previously described in only one other family with HPP. In addition, amphetamine-like sympathomimetic drugs effectively aborted or prevented paralysis in several members. Muscle biopsy in two patients revealed some unusual features, and electromyography showed myopathic potentials. There was no evidence of diabetes. The urine electrolyte concentrations during glucose tolerance tests, however, were different from those previously reported in HPP. This family may represent a variant form of HPP.

Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial: Effects of Dronabinol in Obstructive Sleep Apnea

Study Objectives There remains an important and unmet need for fully effective and acceptable treatments in obstructive sleep apnea (OSA). At present, there are no approved drug treatments. Dronabinol has shown promise for OSA pharmacotherapy in a small dose-escalation pilot study. Here, we present initial findings of the Phase II PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully blinded parallel groups, placebo-controlled randomized trial of dronabinol in people with moderate or severe OSA. Methods By random assignment, 73 adults with moderate or severe OSA received either placebo (N = 25), 2.5 mg dronabinol (N = 21), or 10 mg dronabinol (N = 27) daily, 1 hour before bedtime for up to 6 weeks. Results At baseline, overall apnea-hypopnea index (AHI) was 25.9 ± 11.3, Epworth Sleepiness Scale (ESS) score was 11.45 ± 3.8, maintenance of wakefulness test (MWT) mean latency was 19.2 ± 11.8 minutes, body mass index was 33.4 ± 5.4 kg/m2, and age was 53.6 ± 9.0 years. The number and severity of adverse events, and treatment adherence (0.3 ± 0.6 missed doses/week) were equivalent among all treatment groups. Participants receiving 10 mg/day of dronabinol expressed the highest overall satisfaction with treatment (p = .04). In comparison to placebo, dronabinol dose-dependently reduced AHI by 10.7 ± 4.4 (p = .02) and 12.9 ± 4.3 (p = .003) events/hour at doses of 2.5 and 10 mg/day, respectively. Dronabinol at 10 mg/day reduced ESS score by -3.8 ± 0.8 points from baseline (p < .0001) and by -2.3 ± 1.2 points in comparison to placebo (p = .05). MWT sleep latencies, gross sleep architecture, and overnight oxygenation parameters were unchanged from baseline in any treatment group. Conclusions These findings support the therapeutic potential of cannabinoids in people with OSA. In comparison to placebo, dronabinol was associated with lower AHI, improved self-reported sleepiness, and greater overall treatment satisfaction. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA.

MRI in intraventricular neurocysticercosis: A case report

SummaryA young Mexican female developed neurocysticercosis presenting as a lymphocytic meningoencephalitis with eosinophilia. Parasitic cysts in the fourth ventricle and pre-pontine cistern were well visualized by magnetic resonance imaging but not by computerized tomography. The meningoencephalitis recurred despite treatment with praziquantel and dexamethasone, and obstructive hydrocephalus eventually developed. The patient remains well one year after excision of the intraventricular cyst. This case emphasizes the distinct advantages of magnetic resonance imaging in the diagnosis of intraventricular neurocysticercosis, and the potential need for surgical rather than medical intervention in this condition.ZusammenfassungBei einer jungen Mexikanerin trat eine Neurozystizerkose unter dem Bild einer lymphozytären Meningoenzephalitis mit Eosiniphilie auf. Mit Kernspintomographie konnten im vierten Ventrikel und der Cisterna chiasmatis deutlich Parasitenzysten dargestellt werden, während die Computertomographie negativ blieb. Die Meningoenzephalitis rezidivierte trotz Behandlung mit Praziquantel und Dexamethason, und es entwickelte sich allmählich ein obstruktiver Hydrocephalus. Ein Jahr nach Exzision der intraventrikulären Zyste ist die Patientin in gutem Zustand. Dieser Fall bestätigt die eindeutigen Vorteile der Kernspintomographie in der Diagnostik der intraventrikulären Neurozystizerkose und die Tatsache, daß bei dieser Erkrankung unter Umständen eher eine chirurgische als eine medikamentöse Behandlung erfolgen sollte.A young Mexican female developed neurocysticercosis presenting as a lymphocytic meningoencephalitis with eosinophilia. Parasitic cysts in the fourth ventricle and pre-pontine cistern were well visualized by magnetic resonance imaging but not by computerized tomography. The meningoencephalitis recurred despite treatment with praziquantel and dexamethasone, and obstructive hydrocephalus eventually developed. The patient remains well one year after excision of the intraventricular cyst. This case emphasizes the distinct advantages of magnetic resonance imaging in the diagnosis of intraventricular neurocysticercosis, and the potential need for surgical rather than medical intervention in this condition. Bei einer jungen Mexikanerin trat eine Neurozystizerkose unter dem Bild einer lymphozytären Meningoenzephalitis mit Eosiniphilie auf. Mit Kernspintomographie konnten im vierten Ventrikel und der Cisterna chiasmatis deutlich Parasitenzysten dargestellt werden, während die Computertomographie negativ blieb. Die Meningoenzephalitis rezidivierte trotz Behandlung mit Praziquantel und Dexamethason, und es entwickelte sich allmählich ein obstruktiver Hydrocephalus. Ein Jahr nach Exzision der intraventrikulären Zyste ist die Patientin in gutem Zustand. Dieser Fall bestätigt die eindeutigen Vorteile der Kernspintomographie in der Diagnostik der intraventrikulären Neurozystizerkose und die Tatsache, daß bei dieser Erkrankung unter Umständen eher eine chirurgische als eine medikamentöse Behandlung erfolgen sollte.