Arthur S. Walters

Dopaminergic therapy in children with restless legs/periodic limb movements in sleep and ADHD

The long-term effects of monotherapy with levodopa or the dopamine agonist pergolide on the motor/sensory, behavioral, and cognitive variables in seven children with restless legs syndrome/periodic limb movements in sleep (RLS/PLMS) and attention-deficit-hyperactivity disorder (ADHD) were investigated. Five of the seven children had previously been treated with stimulants that had either been determined to be ineffective or to have intolerable side effects. Dopaminergic therapy improved the symptoms of RLS and reduced the number of PLMS per hour of sleep (P = 0.018) and associated arousals (P = 0.042) for the entire group. After treatment, three children no longer met the criteria for ADHD, and three reverted to normal on the Test of Variable Attention. ADHD improved in all seven as measured by the Connors parent rating scale (P<0.04) and the Child Behavior Checklist (P<0.05). A significant improvement also occurred in the visual, but not verbal, memory scores on the Wide Range Assessment of Memory and Learning (P<0.001). Five of seven children continue on dopaminergic therapy 3 years after treatment initiation, with good response. We postulate that the improvement in ADHD may be the result of the amelioration of RLS/PLMS and its associated sleep disturbance. Alternatively, ADHD and RLS/PLMS may share a common dopaminergic deficit.

Studies of penetrance and anticipation in five autosomal-dominant restless legs syndrome pedigrees

Restless legs syndrome (RLS) can occur with an autosomal‐dominant mode of inheritance. To determine if there are distinguishing features of RLS pedigrees which might clarify molecular mechanisms of pathogenesis, five pedigrees with 81 affected members were analyzed for age of onset, sex ratio, and transmission pattern. One‐factor analysis of variance of ages of onset between generations was carried out, and segregation ratios were calculated for each generation. These kindreds showed an autosomal‐dominant mode of inheritance and a male:female ratio of 1:1.4 (p = 0.15). One of the five analyzed pedigrees shows some evidence of reduced penetrance. In two of the five analyzed pedigrees, there is statistical support for anticipation (p < 0.05). These variations in penetrance and anticipation suggest possible genetic heterogeneity.

The Johns Hopkins telephone diagnostic interview for the restless legs syndrome: preliminary investigation for validation in a multi-center patient and control population.

STUDY OBJECTIVESnTo develop and validate a telephone diagnostic interview (the Johns Hopkins telephone diagnostic interview for restless legs, abbreviated TDI) for diagnosis of the restless legs syndrome (RLS).nnnDESIGN AND METHODSnUsing the International RLS Study Group diagnostic criteria, specific questions were developed reflecting the diagnostic features of RLS. Seventy-five subjects (37 previously diagnosed RLS patients and 38 controls self-reported to be free of RLS) were interviewed by three expert interviewers blinded to each others interviews and the patients clinical status. The interviewers diagnosed each subject based on responses to the TDI.nnnRESULTSnThe interviewers overall correctly diagnosed 72 of 75 individuals. Minimum interviewer sensitivity and specificity were 97 and 92%, respectively. The intraclass correlation coefficient (ICC) was used to quantify inter-rater reliability for the three interviewers. The ICC for diagnosis was 0.95. The ICC calculated on other key items in the interview exceeded 0.80 in all cases. The patients were predominantly older individuals with long-standing RLS; 19 of them scored at the highest level of severity on the Johns Hopkins Restless Legs Severity Scale (JHRLSS). The interviewers had more difficulty with assessing the controls accurately, some of whom were probably incorrectly self-categorized as not having RLS.nnnCONCLUSIONSnThe TDI is a sensitive, specific, and reliable instrument for diagnosing RLS by experienced interviewers in a brief, anonymous telephone encounter.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration to C57-black mice leads to parallel decrements in neostriatal dopamine content and tyrosine hydroxylase activity

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57-black mice (4 doses of 20 mg/kg, at 2 h intervals) led to a large decrement in the neostriatal content of dopamine (92%) and a parallel decrease in tyrosine hydroxylase activity (91%). MPTP administration also caused highly significant but lesser decrements in the neostriatal content of dihydroxyphenylacetic acid (84%) and homovanillic acid (68%). These data are consistent with other observations which suggest that MPTP administration to mice results in a destruction of the dopaminergic nigrostriatal pathway.

Chapter 28 – Motor Functions and Dysfunctions of Sleep

Publisher Summary This chapter focuses on motor functions and dysfunctions of sleep. Motor disturbances associated with sleep can be loosely sorted into two categories. In the first category, there are motor disturbances—diurnal movement disorders—present during the daytime that may have an impact on sleep, either directly through their motor effects or indirectly through a variety of other mechanisms. These are the typical movement disorders that are seen by a movement disorder specialist. In the second category, there are motor disturbances that are predominantly associated with sleep. They may be motor activity similar to what is normally found during waking hours that intrudes upon sleep or abnormal motor activity that does not occur during the wake state but is aroused by sleep. These are generally classified as sleep disorders and primarily are treated by a sleep disorder specialist. These two main categories are by no means completely unique, and it is not unusual for a patient with a disorder in one category to be seen by a specialist in the other category.