Adenosine and the homeostatic control of sleep: effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness.

The orexinergic neurons of the lateral hypothalamus (LH) are critical for wakefulness [McCarley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8:302-330]. Recent evidence suggests that adenosine (AD), a homeostatic sleep factor, may act via A1 receptor (A1R) to control orexinergic activity and regulate sleep-wakefulness [Thakkar MM, Winston S, McCarley RW (2002) Orexin neurons of the hypothalamus express adenosine A1 receptors. Brain Res 944:190-194; Liu ZW, Gao XB (2006) Adenosine inhibits activity of hypocretin/orexin neurons via A1 receptor in the lateral hypothalamus: a possible sleep-promoting effect. J Neurophysiol]. To evaluate the role of AD in the orexinergic LH and its influences on sleep-wakefulness, we designed two experiments in freely behaving rats: First, we bilaterally microinjected 1,3-dipropyl-8-phenylxanthine (DPX) (1.5 pmol and 15 pmol), a selective A1R antagonist into the LH during the light cycle and examined its effect on spontaneous sleep-wakefulness. Second, we performed 6 h of sleep deprivation. Thirty minutes before the animals were allowed to enter recovery sleep, 15 pmol of DPX was bilaterally microinjected into the LH and its effects on recovery sleep were monitored. Microinjection of DPX into the orexinergic LH produced a significant increase in wakefulness with a concomitant reduction in sleep, both during spontaneous bouts of sleep-wakefulness and during recovery sleep. Local administration of DPX into the LH produced a significant increase in the latency to non-REM sleep during recovery sleep. However, total slow wave (delta) activity during non-REM sleep phase of recovery sleep remained unaffected after DPX treatment. This is the first study that implicates endogenous adenosine to have a functional role in controlling orexinergic tone and influencing the homeostatic regulation of sleep-wakefulness.

Essential versus complex autism: definition of fundamental prognostic subtypes.

Heterogeneity within the autism diagnosis obscures the genetic basis of the disorder and impedes our ability to develop effective treatments. We found that by using two readily available tests, autism can be divided into two subgroups, "essential autism" and "complex autism," with different outcomes and recurrence risks. Complex autism consists of individuals in whom there is evidence of some abnormality of early morphogenesis, manifested by either significant dysmorphology or microcephaly. The remainder have "essential autism." From 1995 to 2001, 260 individuals who met DSM-IV criteria for autistic disorder were examined. Five percent (13/260) were microcephalic and 16% (41/260) had significant physical anomalies. Individually, each trait predicted a poorer outcome. Together they define the "complex autism" subgroup, comprising 20% (46/233) of the total autism population. Individuals with complex autism have lower IQs (P=0.006), more seizures (P=0.0008), more abnormal EEGs (46% vs. 30%), more brain abnormalities by MRI (28% vs. 13%). Everyone with an identifiable syndrome was in the complex group. Essential autism defines the more heritable group with higher sib recurrence (4% vs. 0%), more relatives with autism (20% vs. 9%), and higher male to female ratio (6.5:1 vs. 3.2:1). Their outcome was better with higher IQs (P=0.02) and fewer seizures (P=0.0008). They were more apt to develop autism with a regressive onset (43% vs. 23%, P=0.02). Analysis of the features predictive of poor outcome (IQ<55, functionally non-verbal) showed that microcephaly was 100% specific but only 14% sensitive; the presence of physical anomalies was 86% specific and 34% sensitive. The two tests combined yielded 87% specificity, 47% sensitivity, and an odds ratio of 4.8:1 for poor outcome. Separating essential from complex autism should be the first diagnostic step for children with autism spectrum disorders as it allows better prognostication and counseling. Definition of more homogeneous populations should increase power of research analyses.

Circulating levels of the chemokines JE and KC in female C3H apolipoprotein-E-deficient and C57BL apolipoprotein-E-deficient mice as potential markers of atherosclerosis development.

We have investigated serum chemokines for their suitability as markers of atherosclerosis development in apoE (apolipoprotein E)-deficient ((-/-)) mice. Female C3H apoE(-/-) and C57BL apoE(-/-) mice were fed on either diet W (Western diet; 6 weeks) or normal rodent diet (12 weeks). Serum lipids (0, 6 and 12 weeks) and terminal chemokine levels were measured using commercially available assays, whereas the lesion area was determined using Oil-Red O-stained aortic sections. Serum lipids were higher in C3H apoE(-/-) mice for both diets throughout the study; however, lesions were significantly larger in C57BL apoE(-/-) mice fed on either diet. Chemokine levels were significantly lower in C3H apoE(-/-) mice fed on the normal diet, but no difference was observed between the two groups fed on diet W. We conclude that serum chemokine levels are potential markers for atherosclerosis susceptibility in C3H and C57BL apoE(-/-) mice fed on a normal rodent diet.

Seizures and cortical blindness after meglumine (hypaque) administration: a variant of autonomic dysreflexia.

Autonomic dysreflexia (AD) is a syndrome that consists of facial flushing, excessive sweating, nasal congestion, throbbing headache and paroxysmal hypertension which may occur in response to bladder distension in patients with spinal cord lesions above the T6 level. We report the case of a C2 quadriplegic patient who developed clinical features of AD along with cortical blindness and seizures after administration of meglumine (Hypaque) for diagnostic cystogram.

Pain as a manifestation of seizure disorder.

Seizures can manifest in a variety of different clinical presentations. These include motor signs and symptoms, somatosensory and special sensory, psychic and autonomic signs and symptoms, and loss of impairment of consciousness. However, pain is a very uncommon clinical manifestation of a seizure. We describe a case where paroxysmal, acute-onset, right-sided arm-hand and facial pain was the initial and prominent manifestation of the seizure and was accompanied by interictal and ictal electrographic changes.

Transient recurrent situational insomnia associated with cluster headache.

Headache syndromes are known to occur in association with sleep. Both the clinical and the polysomnographic abnormalities occurring in association with various headache syndromes have been described. We report the occurrence of transient recurrent situational insomnia that occurred in association with chronic cluster headaches and was reversible after the headache cluster subsided. This seems to represent a further degree of sleep disturbance in addition to the previously described insomnia and other abnormal polysomnographic features that may occur in direct association with the headache syndromes.

The neurological aspects of acquired immune deficiency syndrome (AIDS)--a clinical review.

Ten years after it was diagnosed, AIDS is estimated to have affected 10 million people worldwide and about 2-3 million people in the United States. Initially considered to be a disease of coasts (New York, California, Florida), AIDS is making inroad to mid-America as well. It involves the nervous system in a variety of ways. These include direct involvement by the virus, secondary opportunistic infections, and tumors. The spectrum of nervous system involvement is the subject of our review.

Paraneoplastic syndromes of the nervous system: manifestations of the occult and the obvious.

Cancer patients are plagued by a wide variety of medical problems, among them paraneoplastic syndromes of the nervous system. The authors present a review of some of the syndromes these patients endure.

Sleep and headache syndromes: a clinical review.

The relationship between sleep and headache has been known for over a century. Sleep represents the only well documented behavioral state related to the occurrence of some headache syndrome. Liveing in 1873, wrote about the effect of sleep in terminating an attack of headache. Bing also, noted this relationship when he wrote about early morning headaches. Gans reported a decrease in frequency and severity of migraine attacks following selective 'deep-sleep deprivation.' Dreams leading to headache have been reported. Quite obviously, headache also finds a place in the classification of sleep disorders. This very important relationship between sleep and headache is the subject of this clinical review.