Biomedical subjects
Publications and source records attributed to R Kurlan.
Sensory tics are localized uncomfortable sensations for which patients attempt to obtain relief by producing movements or vocalizations. We report 3 patients with Tourette's syndrome (TS) and sensory tics to illustrate this poorly recognized symptom. A survey of 34 randomly selected TS patients indicates that sensory tics are common and should be considered part of a clinical spectrum of tics and associated sensory phenomena.
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A 74-year-old man with parkinsonism developed progressive cognitive and behavioral dysfunction suggesting coexistent Alzheimer's disease. The intellectual and behavioral disturbances were reversed following withdrawal of his anticholinergic antiparkinsonian medication. This case demonstrates that anticholinergic drugs used to treat parkinsonism may mimic or exacerbate the clinical signs of Alzheimer's disease and suggests that these medications should be withdrawn for all parkinsonian patients who develop significant impairments of cognition or behavior.
Patients with Huntington's disease (HD) commonly have concomitant depressive disorders. Prompted by reports of elevated corticotropin releasing factor (CRF) and reduced 5-hydroxyindoleacetic acid (5-HIAA) concentrations in lumbar cerebrospinal fluid (CSF) of patients with major depression, these CSF constituents were examined in 56 nonmedicated patients who were in the early stages of HD. Elevated CRF concentrations were found in patients with HD in comparison with a control group of 21 subjects without neurologic illness. The CSF 5-HIAA concentrations in patients with HD did not differ from that in four normal volunteers. Patients with HD who had depressive disorders (major depression or dysthymia) did not differ from those without depression with respect to CSF 5-HIAA or CRF concentration. However, a positive correlation was observed between severity of major depression and CRF concentration. These findings suggest that the depression associated with HD may differ neurochemically from that seen in other major depressive disorders, and support the notion that clinically significant depressive symptoms reflect heterogeneous pathophysiologic conditions with different neurochemical correlates.
Transient tic disorder (TTD) has not generally been considered part of the spectrum of Tourette's syndrome (TS). We studied a large kindred affected by TS and identified two family members with TTD who are very likely obligate carriers of the TS gene. Our observations indicate that TTD is a possible expression of the TS gene and that individuals with TTD may transmit TS to their offspring.
To clarify the influence of gastric emptying on levodopa-related motor fluctuations in Parkinson's disease, we assessed mobility and plasma levodopa concentrations in 10 patients during five modes of levodopa administration: (1) standard intermittent oral (SIO), (2) intermittent duodenal (ID), (3) continuous duodenal infusion (CDI), (4) continuous gastric infusion (CGI), and (5) controlled-release Sinemet (CR-4). The rank order from greatest to least for both percentage of time "on" and average mobility score was CDI, CGI, ID, CR-4, and SIO. The rank order for variance of means, a measure of fluctuation, from least to greatest for mobility was CDI, CGI, CR-4, ID, SIO, and for plasma levodopa concentrations was CDI, CGI, ID, SIO, and CR-4. The results demonstrate that it is possible to produce very steady plasma concentrations of levodopa with a corresponding reduction in motor fluctuations by continuous intraduodenal administration of the drug. This mode of delivery is an ideal model for the development of optimal continuous-release preparations of levodopa. Other enteral routes have produced a more variable plasma levodopa concentration and clinical response.
In Huntington's disease (HD), normal or decreased levels of homovanillic acid (HVA) in cerebrospinal fluid (CSF) have been reported but have not been analyzed with respect to severity of parkinsonism, which in certain cases may be a predominant feature of the illness. We obtained CSF by lumbar puncture from four groups of nonmedicated subjects: (1) those with HD in the earliest stages of illness (n = 51), (2) those with parkinsonism, including idiopathic (n = 10) and atypical forms (n = 4), (3) those with nonparkinsonian movement disorders (n = 19), and (4) normal volunteers (n = 4). HVA was determined by high-pressure liquid chromatography with electrochemical detection, and motor signs were assessed in standardized fashion. The parkinsonian group had reduced levels of CSF HVA, but the other groups showed no significant differences. For those with HD, no correlation was found between HVA level and severity of parkinsonism, and there were no differences in HVA level between those subjects with (n = 14) or without (n = 37) prominent parkinsonism or between subjects whose age at illness onset was 30 years or less (n = 16) and those whose age at onset was over 30 (n = 35). Our findings indicate that in early, untreated HD, CSF HVA is in the normal range and does not correlate with the severity of parkinsonism. This observation supports neuropathological findings suggesting that parkinsonian features in HD are largely related to the loss of postsynaptic striatal dopamine receptors rather than to presynaptic nigral degeneration.
The concentration of the endogenous excitotoxin quinolinic acid was determined in the cerebrospinal fluid of drug-free patients suffering from Huntington's disease or schizophrenia (control group). In both diseases, quinolinic acid concentrations were highly variable (less than 4-48 nM) but the mean levels for each disease group were not significantly different from each other or from the quinolinic acid concentration of normal cerebrospinal fluid. Analysis of steady-state cerebrospinal fluid quinolinic acid concentration is unlikely to be of value as a diagnostic tool in Huntington's disease.
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The Research Diagnostic Criteria were applied to 16 depressed patients with Parkinson's disease and 20 depressed multiple sclerosis patients. Diagnoses of anxiety and panic disorder were significantly more frequent among the patients with Parkinson's disease. These patients may experience atypical depression.
The pathogenesis of "random" fluctuations in parkinsonian mobility, which are not clearly related to the dosing schedule of levodopa, has not been determined. We rated parkinsonian mobility and assayed plasma dopa in one patient with clinically random fluctuations during two modes of administration of levodopa/carbidopa: (1) standard oral route and (2) direct duodenal delivery via nasoduodenal tube. During oral therapy, mobility varied unpredictably in relation to levodopa dosing, suggesting a clinically random pattern. During duodenal delivery, however, a predictable and dramatic pattern of recurrent end-of-dose deterioration was observed; each intraduodenal levodopa dose resulted in 60 to 90 minutes of benefit. Plasma dopa levels correlated closely with mobility ratings for both modes of administration. Our findings indicate that erratic gastric emptying of levodopa is responsible for apparently "random" oscillations in mobility in at least one patient with Parkinson's disease and probably in others.
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An accurate prevalence rate for Tourette's syndrome (TS) has not been established. To assess severity of illness, a potential source of bias in determining prevalence rate, we administered standardized questionnaires and examinations to 159 members of a large Mennonite kindred showing apparent autosomal dominant transmission of motor and vocal tics (TS) or chronic motor tics (CMTs). Fifty-four family members were diagnosed as having definite or probable TS or CMTs. For these 54 subjects, 30% (n = 16) were unaware of tics noted by the examiners and only 18.5% (n = 10) had sought medical care. Our findings suggest that most cases of TS and CMTs are mild and do not come to medical attention. These tic disorders are probably much more prevalent than generally appreciated.
We studied five patients with a combination of Meige's syndrome (blepharospasm-oromandibular dystonia) and myasthenia gravis. The coexistence of two disorders impairing eyelid opening led to diagnostic confusion and delayed appropriate therapy. Detailed oculographic monitoring of one patient indicated that eye position drifting due to myasthenic oculomotor fatigue was corrected by eye blinks, and that blinks tended to occur with slower saccades. Our observations suggest that fatigue of extraocular muscles may lead to synkinetic blinking and perhaps eventually to autonomous blepharospasm.
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We interviewed and examined 12 members of a single family affected by paroxysmal dystonic choreoathetosis. Three subjects experienced characteristic painful dystonic spasms, often precipitated by cold and prolonged physical activity. Three other family members suffered painful cramping of their limbs, without involuntary movement, following physical exertion. Based on the clinical features of affected subjects, we suggest that exertional cramping may represent a "forme fruste" of paroxysmal dystonia.