Rett syndrome, EEG and the motor cortex as a model for better understanding of attention deficit hyperactivity disorder (ADHD).

EEG data in Rett syndrome (RS) are quite often characterized by spikes over the central region (especially in sleep). Furthermore, there has been a recent observation of a prominent and peculiar theta (4-6/s) rhythm over the central region and vicinity. In view of the clinical phenomena of RS, it is pointed out that clinical and electrical findings are based upon hyperexcitability of the motor cortex (or a state of motor cortex dyscontrol). States of dyscontrol (disinhibition) are caused by deficits in higher cortical functions. It is reasonable to assume a primary dysfunction for the frontal lobe which is also smaller in size than other cerebral regions. The behavioral (motor) disturbance in RS can be easily explained as the expression of disturbed prefrontal/premotor function with special effect on the "syntax of action". It is further theorized that such a state of fronto-motor cortex uncoupling may also exist in attention deficit hyperkinetic disorder (ADHD) even though there is hardly any structural CNS impairment in that condition. A presumed "lazy frontal lobe" is likely to react favorably to the stimulation provided by methylphenidate (a therapeutic effect which should not be viewed as paradoxical).

Brain magnetic resonance imaging in suspected extrapyramidal cerebral palsy: observations in distinguishing genetic-metabolic from acquired causes.

Experienced clinicians recognize that some children who appear to have static cerebral palsy (CP) actually have underlying genetic-metabolic disorders. We report a series of patients with motor disorders seen in children with extrapyramidal CP in whom brain magnetic resonance imaging abnormalities provided important diagnostic clues in distinguishing genetic-metabolic disorders from other causes. One cause of static extrapyramidal CP, hypoxic-ischemic encephalopathy at the end of a term gestation, produces a characteristic pattern of hyperintense signal and atrophy in the putamen and thalamus. Other signal abnormalities and atrophy in the putamen, globus pallidus, or caudate can point to genetic-metabolic diseases, including disorders of mitochondrial and organic acid metabolism. Progress in understanding and treating genetic diseases of the developing brain makes it essential to diagnose disorders that masquerade as static CP. Brain magnetic resonance imaging is a useful diagnostic tool in the initial evaluation of children who appear to have CP.

Attention-deficit hyperactivity disorder (ADHD) and frontal-motor cortex disconnection.

Attention-Deficit Hyperactivity Disorder (ADHD) is a very common pediatric-neuropsychiatric entity of still unknown etiology, and is thus a topic of controversy. A neurological concept is presented in order to attain a better conceptualization of ADHD. This concept focuses on the frontal lobe as the inhibitor of excessive motor activity. This inhibitory function is presumed to be most active during childhood. The concept of a disturbed frontal-motor cortex connection was first developed in view of a completely different and rare disorder of childhood: Rett Syndrome (RS) with smallness of the frontal lobe, excessive motor activity and EEG abnormalities often confined to the Rolandic region. Accordingly, what is due to structural damage in RS, might be caused by simple dysfunction in ADHD under essential ly benign circumstances. Not a damaged but a "lazy" frontal lobe results in disinhibited motor activity and also in disturbed attention ( a predominantly frontal lobe function). In the light of this concept, the calming effect of methylphenidate in ADHD is quite logical (frontal stimulation improving motor inhibition) and not paradoxical. It is the "lazy" frontal lobe that responds to "the whip" whereas a truly sick frontal lobe as in RS would be unable to respond.

Unusual EEG theta rhythms over central region in Rett syndrome: considerations of the underlying dysfunction.

In 10 female patients (age 2-26 years) with clinical evidence of Rett Syndrome (RS), unusual and prominent rhythmical theta activity (4-5/sec or 5-6/sec) proved to be the outstanding EEG feature. This pattern was present in waking state and/or sleep. When it was noted in the waking state, the localization (vertex, central region and vicinity) and blocking responses to active or passive movements suggested a slow equivalent of Rolandic mu rhythm (in two patients associated with a posterior 10-12/sec alpha rhythm). In sleep, rhythmical theta activity was either Rolandic or more diffuse, sometimes independently occurring with central spikes. The prominent rhythmical 4-5/sec or 5-6/sec activity and its relationship to Rolandic mu rhythm suggest a dysfunction of the motor cortex in RS. This would be congruent with the frequent observation of central spikes. EEG evidence of motor cortex dysfunction might be helpful in the understanding of this enigmatic disorder and conducive to the following hypothesis: RS is characterized by motor cortical dyscontrol due to primary frontal lobe dysfunction. The usefulness of EEG, however, is limited to insights into the (secondary) motor-cortex dysfunction.

Rett syndrome.

Rett syndrome (RS) is a neurological disorder that mainly, and possibly exclusively, affects girls. After its description in 1966 by Andreas Rett in the Wiener Klinische Wochenschrift, awareness and interest in RS were enhanced by the 1983 report of Hagberg et al. in the Annals of Neurology. Diagnosis, and indeed the hypothesis that it exists, continue to be based upon a consistent constellation of clinical features observed in thousands of female patients world-wide. A diagnostic marker has not been identified. Notwithstanding this serious limitation, it is generally agreed that RS is a distinct entity and that it is genetically determined. Although it is associated with devastating loss of function between infancy and the fifth year of life, its course becomes relatively static thereafter, setting it apart from most of the genetic neurodegenerative disorders of childhood. Neuropathological and neurochemical studies call attention to RS as a neurodevelopmental disorder. Clarification of its pathogenesis may provide new insight into normal brain development. This report summarizes existing information and concepts about RS, and presents recent advances.