The problem of augmentation, or enhancement of the restless leg syndrome with the long-term use of dopaminergic drugs has led to studies of alternatives, mainly gabapentin, pregabalin, but also diazepines such as clonazepam (0.5 to 2.0 mg), or temazepam (30 mg), taken 30 min before retiring. A clinical trial conducted by Allen and associates showed that pregabalin was as effective as pramipexole in reducing restless leg symptoms and had similar rates of augmentation as pramipexole 0.25 mg but lower rates than 0.5 mg. Suicidal ideation may have been more frequent as an adverse event with pregabalin. Other drugs—for example, baclofen, opioids, carbamazepine seem to be helpful in certain patients, but they are infrequently required. The lengthy list of medications that have been effective is given in Earley’s review. It is sometimes useful to give a medication in two divided doses, the first early in the evening, and the second just before sleep or, in severe cases, during the night by setting an alarm clock before the anticipated time of symptoms.
Disorders of Sleep Related to Neurologic Disease
Many neurologic conditions seriously derange the total amount and patterns of sleep. Lesions in the upper pons, near the locus ceruleus, are particularly prone to do so. Markand and Dyken have described the most substantial of these, pontine infarction with involvement of the tegmental raphe nuclei. The clinical abnormality took the form of diminished NREM sleep and near abolition of REM sleep lasting for weeks or months. Bilateral lacunar infarctions in the pontine tegmentum also appear to be the basis of some instances of the REM sleep behavior disorder (Culebras and Moore) described further on with the other parasomnias. Bilateral paramedian thalamic infarctions are a potent cause of hypersomnolence as the result of disruption of both arousal mechanisms and NREM sleep (Bassetti et al).
Medullary lesions may affect sleep by altering automatic ventilation; the most extreme examples occur with bilateral tegmental lesions that may completely abolish breathing during sleep (“Ondine’s curse,” as described in Chap. 25). Lesser degrees of tegmental damage—as might occur with Chiari malformations, unilateral medullary infarction, syringobulbia, or poliomyelitis—may cause sleep apnea, and daytime drowsiness. Patients with large hemispheric strokes may also be left with daytime lethargy on the basis of inversion of sleep–wake rhythm. Certain instances of mesencephalic infarction that are characterized by vivid visual hallucinations (peduncular hallucinosis) may be associated with disruption of sleep.
von Economo encephalitis, now an extinct illness, was usually associated with a hypersomnolent state but caused persistent insomnia in some instances. The latter was related to a predominance of lesions in the anterior hypothalamus and basal frontal lobes, in distinction to hypersomnia, which was related to lesions mainly in dorsal hypothalamus and subthalamus. This subject and other forms of hypersomnia are elaborated further on under “Hypersomnia” (pathologic excessive sleep).