Caffeine down-regulates beta adrenoreceptors in rat forebrain

We studied the influence of caffeine treatment (50 mg/kg for 3 doses) on catecholamine utilization and adrenergic receptor binding in female rats. Caffeine enhanced the reduction in forebrain norepinephrine levels following alpha-methyl-p-tyrosine without altering the reduction in dopamine levels. Caffeine reduced the apparent number of beta receptors in forebrain as measured by the Bmax for [3H]dihydroalprenolol binding. No changes in alpha1 or alpha2 receptor binding, as measured with [3H]prazosin and [3H]clonidine, respectively, were noted. These data show that caffeine selectively increases the rate of norepinephrine utilization in rat forebrain and that this is associated with a small, but significant, reduction in beta receptor density in this brain area.     

Cortical excitability and recovery curve analysis in generalized epilepsy.

Seven untreated patients with idiopathic generalized epilepsy were studied with recovery curve analysis using transcranial magnetic stimulation and compared with 16 controls. Patients had a shorter period of inhibition of the test response following a conditioning stimulus and demonstrated a period of increased facilitation of the test response at interstimulus intervals of 200 to 300 msec, which was similar to the mean interdischarge interval of spike-wave activity on EEG. This provides further evidence of cortical hyperexcitability in idiopathic generalized epilepsy.     

De novo mosaic ring chromosome 18 in a child with mental retardation, epilepsy and immunological problems

Ring chromosome 18 [r(18)] is a disorder in which one or both ends of chromosome 18 are lost and joined forming a ring-shaped figures. R(18) patients can therefore show features of 18q-, 18p- syndrome or a combination of both, depending on the size of the 18p and 18q deleted regions. The phenotype of the r(18) is characterized by developmental delay/mental retardation, typical facial dysmorphisms, major abnormalities and immunological problems. Here we report a case of de novo mosaic r(18) with a characterization by array-based comparative genomic hybridization analysis, and discuss the phenotypic correlation in r(18) also through a comparison with previously described cases of the literature.     

Methylphenidate-induced visual hallucinations

An 11-year-old boy with attention deficit/hyperactivity disorder (ADHD) presented with visual hallucinations several years after starting methylphenidate (MPH). The hallucinations resolved upon discontinuation of the drug. Reports of toxic hallucinosis during treatment with MPH are rare. Although the pathogenetic mechanism is unclear, the occurrence of hallucinations may be explained by a chronic increase in synaptic dopamine. Clinicians should be aware of this possible rare adverse manifestation occurring at therapeutic doses.     

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient-control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca(2+)). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death. This increase was consistently blunted by the Ca(2+) chelator ethylene glycol tetraacetic acid; neocortical Ca(2+) levels were significantly higher in all six patients; no difference in AGC transport rates was found in isolated mitochondria from patients and controls following removal of the Ca(2+)-containing postmitochondrial supernatant. Expression of AGC1, the predominant AGC isoform in brain, and cytochrome c oxidase activity were both increased in autistic patients, indicating an activation of mitochondrial metabolism. Furthermore, oxidized mitochondrial proteins were markedly increased in four of the six patients. Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and 17 multiplex families, whereas some unaffected siblings may carry a protective gene variant. Therefore, excessive Ca(2+) levels are responsible for boosting AGC activity, mitochondrial metabolism and, to a more variable degree, oxidative stress in autistic brains. AGC and altered Ca(2+) homeostasis play a key interactive role in the cascade of signaling events leading to autism: their modulation could provide new preventive and therapeutic strategies.     

Attention deficit hyperactivity disorder in children with epilepsy

Attention deficit hyperactivity disorder (ADHD) is more frequent in children with epilepsy than in general pediatric population. Several factors may contribute to this comorbidity, including the underlying brain pathology, the chronic effects of seizures and of the epileptiform EEG discharges, and the effects of antiepileptic drugs. Symptoms of ADHD are more common in some specific types of epilepsies, such as frontal lobe epilepsy, childhood absence epilepsy and Rolandic epilepsy, and may antedate seizure onset in a significant proportion of cases. In epileptic children with symptoms of ADHD, treatment might become a challenge for child neurologists, who are forced to prescribe drugs combinations, to improve the long-term cognitive and behavioral prognosis. Treatment with psychotropic drugs can be initiated safely in most children with epilepsy and ADHD symptoms.