Sinemet and the treatment of Parkinsonism.

Sinemet (a combination of levodopa with carbidopa, a dopa-decarboxylase inhibitor) has replaced levodopa for early treatment of parkinsonism. The blocking of the systemic uptake of dopamine has eliminated the previous complications of nausea, vomiting, and cardiac and respiratory arrhythmias; pyridoxine need not now be avoided. However, the earlier appearance of abnormal involuntary movements, hallucinations, occasional psychosis, and a dopa-resistant state limits treatment efficacy. In all-over experience the combination drug offers the best relief for rigidity and akinesia. It has improved the quality of life and reduced mortality by one half. The greatest benefits appear in the first 3 years; then complications set in. The relation of complications to dosage is now better understood, and the ratio of dopa-decarboxylase inhibitor to levodopa inhibitor to levodopa of 1:4 is better than the previous 1:10. Levodopa with or without dopa decarboxylase is not a cure for parkinsonism. Some agonist drugs (bromocryptine, lisuride) are showing promise in the testing stage. The evolving knowledge about neurotransmitters and peptide messengers offers hope for the growing number of patients with parkinsonism.

Frequency and cooccurrence of vocal tract dysfunctions in the speech of a large sample of Parkinson patients.

In this study, the frequency of occurrence of speech and voice symptoms in 200 Parkinson patients was defined by two expert listeners from high-fidelity tape recordings of conversational speech samples and readings of the sentence version of the Fisher-Logemann Test of Articulation Competence. Specific phonemes that were misarticulated were catalogued. Other vocal-tract dysfunctions, including laryngeal disorders, rate disorders, and hypernasality, were also recorded. Cooccurrence of symptoms in each patient was tabulated. Examination of the patterns of cooccurring dysfunctions permitted classifying the 200 patients into five groups: Group 1 (45% of the patients) with laryngeal dysfunction as their only vocal-tract symptom; Group 2 (13.5% of the patients) with laryngeal and back-tongue involvement; Group 3 (17% of the patients) with laryngeal, back-tongue, and tongue-blade dysfunction; Group 4 (5.5% of the patients) with laryngeal dysfunction, back-tongue involvement, tongue-blade dysfunction, and labial misarticulations; and Group 5 (9% of the patients) with laryngeal dysfunction and misarticulations of the back tongue, tongue blade, lips, and tongue tip. Disfluencies and hypernasality did not follow a systematic pattern of cooccurrence with other vocal-tract dysfunctions.

Speech and swallowing evaluation in the differential diagnosis of neurologic disease.

Examination of the speech mechanism (the vocal tract) frequently provides information about certain neurologic lesions. The speech, swallowing and respiratory patterns of patients with cerebellar, upper motor neuron, lower motor neuron and extra-pyramidal lesions (parkinsonism) were studied, 10 of each category. The patient's lingual, labial and velar movement was examined cineradiographically during production of four short speech samples and the oral, through esophageal structures, during chewing and swallowing. Videotape, with simultaneous voice recording, and 16 mm. film were used. Oral, pharyngeal and esophageal transit times during swallowing were determined. These quantified tests reveal distinctive differences in vocal tract physiology between patient groups. The specific physiologic patterns characteristic of each neurological lesion were discussed and illustrated with films. Each patient group in this study exhibited a distinctive profile distinguishing it from every other. The results also indicate that if only a portion of these studies was completed, the disorder might be erroneously classified. The findings emphasize the need for complete and detailed physiologic studies of the speech and swallowing of patients with neurologic lesions, as an aid to accurate diagnosis.

Molecular biology of neurological and psychiatric disorders. I. Effect of parkinsonism, age, sex and L-dopa on platelet monoamine oxidase.

Since there is substantial evidence for a nigrostriatal dopamine defect in Parkinson's disease and since monoamine oxidase (MAO) appears to be essential for the degradation of dopamine, we investigated whether this enzyme is involved in the pathogenesis of this disease or in the therapeutic action of L-dopa. To gain a solid basis for our analysis we studied some properties of platelet MAO, at present the only practical in vivo source for human MAO. Substrate and inhibitor pattern clearly pointed to a predominant B-type character of this enzyme. By using 3 substrates, m-iodobenzylamine, p-methoxybenzylamine, and tyramine, we found a marked age and sex difference in MAO activity. In untreated parkinsonian patients, platelet MAO was slightly reduced as compared with age- and sex-matched controls. Treatment with L-dopa induced a further reduction of platelet MAO activity in both sexes, but more in men than in women. We conjecture that the action of L-dopa on parkisonian patients is twofold: L-dopa is known to enhance the release of gonadotropins and thus to increase the production of sex hormones which in turn are capable of reducing MAO activity. Dopamine, formed from L-dopa, may thus have a better chance for survival in reaching the dopaminergic receptor. A new form of therapy, based on this concept, is proposed.

Transient eyelid retraction in myasthenia gravis.

Three patients with myasthenia gravis had transient retraction of the upper eyelids which usually followed prolonged upgaze and which persisted for many seconds. This could result from post-tetanic facilitation, myotonia, or a transient contracture. Retraction of this type is to be distinguished from both the long-standing unilateral retraction associated with ptosis of the contralateral eyelid and the fleeting lid twitch sign.

Comparison of speech and swallowing function in patients with tremor disorders and in normal geriatric patients: a cinefluorographic study.

In a study of vocal tract and esophageal function during speech and swallowing, unmedicated Parkinson patients were found to have specific disorders in oral and esophageal stages of deglutition and a predictable sequence of deterioration in speech. To determine whether these disorders are exclusive to parkinsonism or are typical of all patients with tremor or of geriatric patients in general, a cinefluoroscopic study was initiated to examine the physiology of speech and swallowing in these other patients. Subjects were 10 normal geriatric patients and 10 patients with essential tremor. Results of the studies for these two groups were compared with data from earlier studies on unmedicated Parkinson patients. Parkinson patients showed most severely disordered swallowing and speech function. Patients with essential tremor showed only slight slowing in esophageal transit during swallowing and vocal tremor during speech, but no progressive deterioration. Normal geriatric patients revealed no swallowing or speech disturbances.