Exaggerated growth hormone response to arginine infusion in Huntington's disease.

Growth hormone regulation was studied in 10 patients with Huntington's disease after intravenous administration of arginine. In 20 control subjects arginine infusion resulted in a rise of plasma growth hormone levels from a mean baseline value of 3.2+/-0.6 ng/ml to a peak level of 17.6+/-2.7 ng/ml at 60 min. Growth hormone rise in the majority of patients with Huntington's disease was clearly intact and significantly greater than normal in magnitude, increasing from the baseline level of 2.6+/-0.5 ng/ml to a peak level of 28.3+/-3.7 ng/ml at 60 min (P = less than 0.05). Carbohydrate tolerance of these patients was previously examined, and 4 with normal glucose tolerance and normal insulin responses to arginine infusion had growth hormone levels significantly higher than controls at 30 min. Six patients with impaired carbohydrate tolerance and exaggerated insulin responses to arginine had significantly higher growth hormone responses at 30 min and also at 60 min. Neuronal degeneration of several hypothalamic nuclei has been reported in Huntington's disease. The observations that growth hormone responds in an exaggerated fashion to stimulation by arginine infusion or falling glucose levels as previously described may be explained by intrahypothalamic dysfunction such as impairment of somatostatin secretion.

Dysphagia in Huntington's disease.

Dysphagia is a common complication of Huntington's disease (HD) that is frequently responsible for the potentially lethal respiratory events of aspiration or asphyxiation. Twelve patients who had HD and a history of dysphagia underwent extensive multidisciplinary clinical examinations. All of the patients, regardless of the clinical severity of their disease, demonstrated impaired control of many voluntary aspects of food intake that affected swallowing efficiency. Abnormalities of the rate of food consumption, mastication, bolus transfer, respiration, and swallow initiation seem to be responsible for most dysphagic symptoms in HD. Less prominent abnormalities of the pharyngoesophageal phases of ingestion were also noted. Dysphagia therapy was initiated in 11 of 12 patients. All of the patients' conditions improved; a majority (8/11) of the patients returned to an unrestricted diet. This improvement persisted for as long as three years, while other clinical features of HD intensified.

Prolonged metoclopramide-induced dyskinetic reaction.

Metoclopramide is an effective non-phenothiazine antiemetic that acts, in part, by blockade of the dopamine receptors. The extrapyramidal complications of metoclopramide are similar to those of the phenothiazines. A patient is reported who developed a metoclopramide-induced acute dystonic reaction lasting 53 days. Acute and chronic treatment with anticholinergic drugs suppressed but did not eliminate the adventitious movements. The features of acute dystonic reactions secondary to metoclopramide therapy are reviewed.

An alphabetical 'WORLD'. A new version of an old test.

The Mini-Mental State Examination (MMSE) is a standardized test used by neurologists to screen patients for impaired cognition. Despite its ease of use, one major limitation of the MMSE is a possible ceiling effect or a lower sensitivity in patients with advanced education. Patients (n = 97) undergoing diagnostic neuropsychological testing also completed one subtest of the MMSE, the spelling of "world." In addition to its forward and backward spelling, patients were asked to reorder these letters in alphabetical sequence. Our preliminary data indicate that our modified WORLD test is a rapid and simple test to identify patients with cognitive impairment. When measured against the diagnosis of dementia as determined by neuropsychological testing, the modified WORLD test has a sensitivity of 85%, a specificity of 88%, and a positive predictability value of 95%. Other variables examined include patient age, sex, education, and cutoff scores on the Mattis Dementia Rating Scale.

Laryngeal deglutition movement in Parkinson's disease.

Laryngeal muscle function is defective in Parkinson's disease (PD) patients; the intrinsic group (vocal cords) is defective during phonation and the extrinsic group (laryngeal strap muscles) is slow during deglutition. There are no studies of vocal cord motility during deglutition in PD. We investigated laryngeal motility during deglutition in 71 patients with PD in a videofluoroscopic swallowing study. Patients were subdivided into two groups by the Hoehn and Yahr disability scale, stages II and III (n = 38) and stages IV and V (n = 33). At least one abnormality of laryngeal movement was present in 68 of 71 patients (95.8%); most patients had multiple abnormalities. There was statistically significant slowing of vertical laryngeal excursion; true vocal cord closure; or delayed, incomplete, or absent opening of the true vocal cords. Patients with more advanced disease manifested more deficits of laryngeal movement. Laryngeal dysmotility in PD may be related to defective descending basal ganglionic control of medullary deglutory and phonatory motor functions.

Absence of sleep-related growth hormone elevations in myotonic dystrophy.

There is evidence that in myotonic dystrophy, the endocrine and central nervous systems are affected. To study a possible relationship between both defects, we investigated nocturnal sleep patterns and associated growth hormone secretion in two men and three women with myotonic dystrophy. In three patients who were clinically the most severely affected by myotonic dystrophy, plasma growth hormone elevations related to the slow-wave phase of sleep were absent. The two least severely affected patients had plasma growth hormone increases of low magnitude and brief duration (from 0.4 ng per milliliter to 13.0 ng per milliliter). These data suggest a failure of integration at a subcortical level of the slow-wave phase of sleep with the hypothalamic-pituitary mechanisms of growth hormone secretion. Thalamic neuronal lesions occurring in myotonic dystrophy could be responsible for such failure.

Binding of [99mTc]TRODAT-1 to dopamine transporters in patients with Parkinson's disease and in healthy volunteers.

UNLABELLED: [99mTc]TRODAT-1 is a radiolabeled tropane that binds dopamine transporters. The primary goal of this study was to determine whether its regional cerebral distribution could differentiate between patients with Parkinson's disease and healthy human volunteers. METHODS: The sample consisted of 42 patients with Parkinson's disease, 23 age-matched controls, and 38 healthy adults younger than 40 y old. SPECT scans of the brain were acquired on a triple-head gamma camera 3-4 h after the intravenous injection of 740 MBq (20 mCi) [99mTc]TRODAT-1. Mean counts per pixel were measured manually in subregions of the basal ganglia and normalized to the mean background counts to give specific uptake values ([SUVs] approximately k3/k4). Patient and control groups were also compared with automated statistical parametric mapping techniques. Logistic discriminant analyses were performed to determine the optimum uptake values for differentiating patients from age-matched controls. RESULTS: Quantitative image analysis showed that the group mean SUVs in patients were less than the mean values in controls for all regions (all Ps < 0.000001). There was overlap in the caudate as well as in the anterior-most portion of the putamen, but not in the posterior putamen, even when the asymptomatic sides of 5 patients with clinically defined hemi-Parkinson's disease were factored in. CONCLUSION: The findings indicate that Parkinson's disease can be detected with [99mTc]TRODAT by simply inspecting the images for uptake in the posterior putamen. Appropriate asymmetries seem to be visible with quantification in patients with clinically defined hemi-Parkinson's disease, even though changes in the putamen contralateral to the clinically unaffected side in these patients appear to precede the development of symptoms.

Paroxysmal facial neuralgia secondary to a posterior communicating artery aneurysm.

Paroxysmal facial neuralgia, typified by classical tic douloureux, may be secondary to intermittent compression of the trigeminal nerve by pulsating vascular structures. The critical area of compression, at least for producing true trigeminal neuralgia, is felt to be the dorsal root entry zone. One case of paroxysmal facial neuralgia, secondary to more distal compression of the trigeminal nerve by a large posterior communicating artery aneurysm, is reported here. The location of the compression may be important in producing the atypical characteristics of paroxysmal facial neuralgia that is not classical tic douloureux. The pain was relieved by clipping the aneurysm without excision or rupture of the sack.

Dysphagia in drug-induced parkinsonism: a case report.

Dysphagia complicates both idiopathic Parkinson's disease (IPD) and drug-induced parkinsonism (DIP). Although parkinsonism of DIP and IPD are often clinically indistinguishable, there is no assurance that their abnormalities of swallowing will be similar. We evaluated a patient with DIP who complained of difficulty chewing and swallow initiation. The dysphagia evaluation demonstrated abnormalities during all stages of ingestion. However, the prepharyngeal stages were disproportionately affected when compared with patients with IPD and similar levels of parkinsonian functional disability. This case gives additional support for a significant basal ganglia influence on motor deglutitive functions.

Gaze-induced laughter.

Pathological laughter was stimulated by pursuit eye movements with a large extramedullary brainstem tumour. Laughter was also evoked by intense direct light. The mechanism by which visual stimuli could induce pathological laughter is discussed.

Risperidone treatment of drug-related psychosis in patients with parkinsonism.

Risperidone, a novel neuroleptic with approximately equal D2 and 5HT2A receptor blocking properties, has been used to treat drug-related hallucinations in patients with Parkinson's disease. However, the results of only small numbers of patients have been reported with the drug demonstrating limited usefulness. We report our experience with this drug in 39 patients (25 women and 19 men) with parkinsonism. Monitored clinical data included duration of disease, Hoehn and Yahr score, Mini-Mental State Score, Unified Parkinson's Disease Rating Scale (UPDRS) prior to drug administration and after 3 and 6 months of treatment, and response to treatment. Twenty-three patients with Parkinson's disease had either complete or near-complete resolution of hallucinations whereas an unsatisfactory response (N = 6) or worsening of parkinsonism (N = 6) was noted in 12 patients, only six of whom had Parkinson's disease. Excluding patients with diffuse Lewy body disease, there was no significant worsening of the UPDRS scores after either 3 or 6 months of treatment. The presence of dementia did not predict response to treatment. Our results suggest that risperidone is a useful treatment for hallucinations in patients with parkinsonism.

Dysphagia in progressive supranuclear palsy: radiologic features.

Progressive supranuclear palsy (PSP) is a progressive degenerative extrapyramidal disease that often masquerades as Parkinson's disease (PD). Similar to PD, dysphagia frequently complicates the course of PSP. Because there is only one published report characterizing dysphagia in PSP, we reviewed the neurologic features and dynamic videofluoroscopic swallowing function study results in 10 dysphagic PSP patients. Abnormalities during multiple stages of ingestion were recorded in each patient. Uncoordinated lingual movements, absent velar retraction or elevation, impaired posterior lingual displacement, and copious pharyngeal secretions were noted in all patients. Tongue-assisted mastication, noncohesive lingual transfer, excessive oral bolus lingual leakage to the pharynx prior to active transfer, vallecular bolus retention, abnormal epiglottic positioning, and hiatal hernias were noted in at least half of the cohort. Although ingestion abnormalities in PSP are similar to those previously reported in PD, the number of studied patients and observed differences were too few to clearly differentiate the two diseases.

Swallowing, ingestion and dysphagia: a reappraisal.

Abnormalities of swallowing are unappreciated complications of many neurologic disorders. However, the standard phases of swallowing, with their emphasis on reflex aspects, inadequately account for dysphagia in many neurologic patients. Disorders of oral activity prior to swallow initiation may also be responsible for dysphagic symptoms. Therefore, the inclusion of the phases of deglutition within the more encompassing process of ingestion is proposed. The volitional component of food intake is stressed and its relationship to dysphagia in the neurologic patient is discussed. A general diagnostic and therapeutic approach is included.

Dysphagia in Huntington's disease: a 16-year retrospective.

Degenerative diseases of the basal ganglia are commonly complicated by dysphagia. In 35 patients with Huntington's disease (HD), a hereditary neurodegenerative basal ganglia disease characterized by chorea, dementia, and emotional changes, an extensive battery of clinical and radiologic procedures helped to identify numerous abnormalities of deglutition. The results permitted the classification of our patients with HD into hyperkinetic (HD-h) or rigid-bradykinetic (HD-rb) groups. Although the two groups share multiple abnormalities, statistically significant intergroup differences were observed. Clinical assessment of the HD-h cohort (30 patients) demonstrated rapid lingual chorea, swallow incoordination, repetitive swallows, prolonged laryngeal elevation, inability to stop respiration, and frequent eructations. In the HD-rb group (five patients), frequently observed abnormalities included mandibular rigidity, slow lingual chorea, coughing on foods, and choking on liquids. Videofluoroscopic swallowing studies (VFSS) using a variety of barium-impregnated foods and liquids confirmed the abnormalities noted on the clinical assessment. Respiratory and laryngeal chorea, pharyngeal space retention, and aspiration were also identified. Numerous compensatory techniques introduced during videofluoroscopy benefited all patients.

Pharyngo-esophageal dysphagia in Parkinson's disease.

The radiologic characteristics of pharyngoesophageal (PE) dysfunction in Parkinson's disease (PD) are not well established, partly because most previous studies have examined only small numbers of patients. We administered a dynamic videofluoroscopic swallowing function study to 71 patients with idiopathic PD. Using the Hoehn and Yahr disease severity scale, patients were subdivided into those with mild/moderate disease, subgroup I (n = 38), and advanced PD disease, subgroup II (n = 33). From pharyngeal ingestion to gastric emptying, bolus transport was normal in only 2 patients. The most common abnormalities occurring during pharyngeal ingestion included impaired motility, vallecular and pyriform sinus stasis, supraglottic and glottic aspiration, and deficient epiglottic positioning and range of motion. Esophageal abnormalities were multiple but most commonly included delayed transport, stasis, bolus redirection, and tertiary contractions. Typical aberrations of lower esophageal sphincter (LES) function included an open or delayed opening of the LES and gastro-esophageal reflux. A pathogenesis linking PE with the pathology of PD is proposed.

Dysphagia--ingestion or deglutition?: a proposed paradigm.

The current classifications of dysphagia are based on local structural or central nervous system pathology causing dysfunction of the aerodigestive tract. The result is a clinical science grounded in the analysis of the swallow with its lingual, pharyngeal, and esophageal stages. Adding bolus preparation to the swallowing paradigm improves but still constrains the study of dysphagia and treatment of the dysphagic patient. Those pre-oral facets of mealtime behavior that may evoke or exacerbate dysphagia remain beyond the existing classification boundaries imposed by the conceptual swallow and anatomic aerodigestive tract. We offer a more inclusive strategy for investigating dysphagia based on a five-stage process of ingestion: pre-oral (anticipatory), preparatory, lingual, pharyngeal, and esophageal. The first stage considers the interaction of pre-oral motor, cognitive, psychosocial, and somataesthetic elements engendered by the meal. The limited literature regarding the interaction of the pre-oral stage with other ingestion stages, in both normal subjects and patients with cortical, basal ganglia, and psychogenic diseases, is reviewed. The neurophysiologic and clinical justifications for embracing a pre-oral stage, and thus for the paradigm shift from deglutition to ingestion, are presented.