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.     

Autonomic nervous function in progressive supranuclear palsy--comparison with Parkinson's disease and healthy controls

This study evaluated the autonomic nervous function in 6 patients with progressive supranuclear palsy (PSP). The autonomic nervous functions in PSP patients were compared with those in 17 patients of Parkinson's disease (PD) and 9 age-matched healthy control subjects. Results were that all PSP patients and 59% of PD patients had sympathetic skin response (SSR) abnormalities. Significant abnormalities in cardiovascular response observed in PD patients suggested the presence of sympathetic and parasympathetic disturbances. There were no significant differences between PSP patients and control subjects in cardiovascular responses. But some of PSP patients showed abnormal cardiovascular responses compared with the results from the control subjects. In PSP patients mild disturbances in cardiovascular responses and sudomotor dysfunction were suggested. We consider that the high incidence of SSR abnormality is at least partially related to the presence of disturbances in the frontal lobes.     

Differential distribution of striatal [123I]beta-CIT in Parkinson's disease and progressive supranuclear palsy, evaluated with single-photon emission tomography

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [123I]beta-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24+/-2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3"). ANOVA revealed a global reduction of V3" in all ROIs of PD and PSP patients compared with normal controls (P<0. 0001). A Mann-Whitney U test showed that the difference between PD and PSP patients was statistically significant for the caudate region only (Z value: 2.6; P<0.01). By subtracting V3" caudate values from those of the putamen, differentiation from PSP was possible in 10/13 PD patients. In conclusion, analysis of [123I]beta-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP.     

Concentration of neural thread protein in cerebrospinal fluid from progressive supranuclear palsy and Parkinson's disease

We measured the concentration of neural thread protein (NTP) in cerebrospinal fluid (CSF) by an automatized microparticle enzyme immunoassay from 11 progressive supranuclear palsy (PSP) patients and 11 Parkinson's disease (PD) patients and 7 patients with cervical spondylosis as controls. The mean levels did not differ significantly among the groups. In the PSP group, however, the levels correlated significantly with the severity of motor symptoms, signs and functional disability but not with dementia, while the opposite was true in the PD group. The elevated levels in PSP cases may reflect an increase with progression of the disease in such pathological structures as neurofibrillary tangles or neuropil threads, while in PD such levels may indicate associated Alzheimer-type pathology.     

Expression of apolipoprotein E in normal and diverse neurodegenerative disease brain

Brains from 21 patients with Alzheimer's disease (AD), nine with diffuse Lewy body disease (DLBD), six with progressive supranuclear palsy (PSP) and five with Parkinson's disease (PD) as well as 20 normal subjects were examined to detect apolipoprotein E (ApoE) by immunohistochemistry and immunoblotting. ApoE antigenicity was optimally preserved in Bouin-fixed tissues compared with those fixed in neutral-buffered formalin, 70% ethanol or denatured by microwave energy. ApoE immunoreactivity was prominent in senile plaques and in intra- and extra-neuronal tangles, as well as in a diverse neurones and their processes and astroglial cells. Notably, tangles in PSP and Lewy bodies in PD and DLBD were both devoid of ApoE immunoreactivity. Western blots of cerebral cortex revealed an immunoreactive ApoE band with mol. wt of 34 kDa. Our results suggest that ApoE is not a crucial factor in the development of neuronal inclusions in DLBD, PSP and PD.     

Nigral glutathione deficiency is not specific for idiopathic Parkinson's disease

The consistent findings of decreased levels of the major antioxidant glutathione in substantia nigra of patients with idiopathic Parkinson's disease (PD) has provided most of the basis for the oxidative stress hypothesis of the etiology of PD. To establish whether a nigral glutathione deficiency is unique to PD, as is generally assumed, or is present in other Parkinsonian conditions associated with nigral damage, we compared levels of reduced glutathione (GSH) in postmortem brain of patients with PD to those with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). As compared with the controls, nigral GSH levels were decreased in the PD and PSP patient groups (P < 0.05 for PD [-30%], PSP [-21%]), whereas a similar decrease in the MSA patient group did not reach statistical significance (P = 0.078, MSA [-20%]). GSH levels were normal in all examined normal and degenerating extra-nigral brain areas in PSP and MSA. A trend for decreased levels of uric acid (antioxidant and product of purine catabolism) also was observed in nigra of all patient groups (-19 to -30%). These data suggest that glutathione depletion, possibly consequent to overutilisation in oxidative stress reactions, could play a causal role in nigral degeneration in all nigrostriatal dopamine deficiency disorders, and that antioxidant therapeutic approaches should not be restricted to PD.     

Treatment of progressive supranuclear palsy with amitriptyline: therapeutic and toxic effects

BACKGROUND: Progressive supranuclear palsy (PSP) is a parkinsonian-like disorder characterized by postural instability, rigidity, bradykinesia, supranuclear ocular palsy, dysarthria, dysphagia, and dementia. There is no satisfactory treatment. Two patients with advanced (PSP) reported here had clinically meaningful improvement in motor function on low dose amitriptyline (AMI) but developed cognitive and behavioral disturbances at higher doses. CASE REPORTS: During 11 weeks of upward dose titration, a 65-year-old man was partially relieved of severe bradykinesia, dysarthria, and dysphagia at an optimal dose of 40 mg bid (plasma AMI 39 ng/mL) such that he could feed himself, swallow easily, and transfer from wheelchair to toilet. Nocturnal confusion and urinary incontinence appeared at 70 mg bid, then resolved at 40 mg bid. Benefits were sustained during the next 14 months. A 77-year-old man had substantial relief of severe rigidity, bradykinesia, poor balance, and blepharospasm at 10 mg bid, such that he could feed himself and walk independently. At 40 mg bid (plasma AMI 62 ng/mL) 3 weeks later, he became aggressive, irritable, and increasingly confused. He reverted to his untreated state with drug withdrawal, then improved when AMI was reintroduced at 10 mg bid (plasma AMI 17 ng/mL). CONCLUSION: Low dose AMI may improve severe motor dysfunction in PSP significantly. Dosing must be individualized for optimal response and minimal toxicity.     

Superantigen-induced stromelysin production from rheumatoid synovial cells

Positron emission topographic studies on local cerebral glucose metabolism in Parkinson's disease (PD) including our own data were reviewed. In our 18F-FDG PET studies, local or global metabolic change was not found in 9 patients with non-demented PD, with respect to 5 normal controls. Moreover, there was not an apparent difference between severe PD group (Hoehn-Yahr III-IV) and mild PD group (Hoehn-Yahr I-II). In other PD patients with dementia or autonomic failure, parietal dominant hypometabolism was found likely to those of Alzheimer disease, but lenticular nucleus was well preserved. Furthermore 18F-FDG PET findings of atypical parkinsonian syndromes, such as SND and PSP were reviewed. They showed relative hypometabolism in the basal ganglia in PET images. PET study with FDG provides a clue to differential diagnosis of parkinsonian patients.     

Analysis of Parkinson's disease and related syndromes using 123I-IMP-SPECT with the ARG method

We studied regional cerebral blood flow (rCBF) in 8 patients with non-demented Parkinson's disease (PD). 1 patient with progressive supranuclear palsy (PSP), 1 patient with multiple system atrophy (MSA), and 7 normal control subjects using single photon emission computed tomography (SPECT) with the IMP-ARG method. Regions of interest were studied in the cerebral cortex (upper frontal, lower frontal, temporal, occipital, parietal), thalamus, basal ganglia, and cerebellum. In patients with PD, rCBF was normal in 4/8, and decreased in occipital lobe in 4/8. In patient with PSP, rCBF was decreased in the upper and lower frontal lobes, and in the cerebellum. In patient with MSA, rCBF was diminished in the cerebellum. The results of our study were almost compatible with the conventional rCBF study by positron emission tomography (PET), however, the decrease of rCBF in occipital lobe had rarely been reported, suggesting that might be related to visuospatial dysfunction in Parkinson's disease.     

Solid bolus swallowing in the radiologic evaluation of dysphagia

Patients with dysphagia, heartburn and chest pain are regularly referred for radiologic evaluation of swallowing. The liquid barium swallow has been of great value for the biphasic evaluation of the pharynx and esophagus. Though many patients complain of dysphagia specifically for solids, solid bolus swallow is usually not part of the evaluation. For the present study we therefore included the use of a solid bolus with a diameter of 13 mm and interviewed the patients carefully for any symptoms during this tablet swallow. Of 200 patients examined, the tablet passed through the esophagus without delay in 102. In the 98 patients with delayed passage, the solid bolus arrest occurred in the pharynx in 5 and in the esophagus in 93. Arrest in the esophagus was due to esophageal dysmotility in 48 patients. Twenty of these were symptomatic during the tablet swallow. A narrowing was the cause in 45, of whom 9 had symptoms. In 18 patients (9%) the solid bolus added key information to the radiologic evaluation. We therefore recommend that the solid bolus is included in the routine radiologic work-up of patients with dysphagia. Careful attention to symptoms during the tablet swallow is important.     

Ectopic lingual thyroid. Apropos of 3 cases

Lingual thyroid is a rare cause of upper airway obstruction, dysphagia or hypothyroidism symptoms. This report describes three cases of lingual thyroid arising in women. One was in pregnancy and developed a lingual goiter and hemorrhages with hypothyroidy. The second case have been diagnosed because of a dysphagia and the third was asymptomatic and have been diagnosed during physical examination for cervical nodes. Diagnosis and possible therapeutic options are discussed regarding these three cases. Surgical therapy is appropriate for patients with clinical signs of upper airway obstruction or when malignant degeneration is suspected. Without of clinical sign, substitutive therapy with thyroid hormone allows the stabilization or the regression of the ectopic thyroid.     

Persistent dysphagia after laser uvulopalatoplasty: a videoradiographic study of pharyngeal function

In a follow-up study of 79 patients two years after laser uvulopalatoplasty 21 (27%) reported persistent postoperative dysphagia, with aspiration symptoms in 22%. None of the patients had suffered from recurrent pneumonia. A total of 4% of the patients regretted the treatment because of their dysphagia problems. The objective of this study was to examine oral and pharyngeal function videoradiographically during swallowing in the patients with persistent dysphagia, to determine whether the subjective symptoms of dysphagia correlated with objective signs of pharyngeal dysfunction. Pharyngeal function during swallowing was deviant in 76% of the dysphagic patients. In 52% of the dysphagic patients premature leakage of bolus down to different levels of the pharynx, from the tongue base to sinus piriformis, was observed before the swallowing reflex was elicited. In the dysphagic patients substantial bolus retention was observed on the epiglottis or in the valleculae alter the propagation wave had passed (43%) as well as epiglottal dysmotility (24%). Of the dysphagic patients, 10% could not avoid aspiration during the examination. These findings could explain the symptoms reported by the patients.     

Efficiency of video-assisted thoracic surgery for primary and secondary spontaneous pneumothorax

BACKGROUND: The objective of the study was to analyze the efficiency of video-assisted thoracic surgery (VATS) for the treatment of primary (PSP) or secondary (SSP) spontaneous pneumothorax in an initial series of 99 patients. METHODS: From April 1992 to December 1995, 74 men and 25 women with a median age of 31 years (range, 17 to 85 years) were treated by VATS for persistent (n = 40) or recurrent (n = 59) PSP (n = 65) or SSP (n = 34). Postoperative parameters such as use of analgesics, length of hospital stay, and duration of drainage were compared with those of a control group of 100 patients treated by lateral thoracotomy between January 1988 and December 1991. RESULTS: Conversion to lateral thoracotomy was necessary in 6 (9.2%) patients with PSP and in 10 (29.4%) patients with SSP, in most cases because of adhesions. Postoperative complications occurred in 1 (1.7%) patient with PSP and in 6 (25%) patients with SSP. There were no operative deaths. After a median follow-up period of 29 months, 4 (4.8%) recurrences were noted. All recurrences occurred in patients with PSP and during the first year of our experience. Compared with lateral thoracotomy, treatment by VATS resulted in a significantly shorter hospital stay and drainage duration in patients with PSP but not in patients with SSP. The use of analgesics was reduced in all patients treated by VATS independent of the type of pneumothorax. CONCLUSIONS: Surgical treatment by VATS is a viable alternative to lateral thoracotomy in patients with PSP. The usefulness of VATS in patients with SSP remains to be defined.     

Treatment of lung metastases from malignant melanoma with IL-2 inhalation therapy

Seven patients with pulmonary metastases of malignant melanoma were treated with inhalation therapy with 36 million IU interleukin-2 for six months. Inhalation therapy was combined with four bolus infusions of DTIC at a dose of 850 mg/m2 once every four weeks. Response rates were 71.4% with 2 patients achieving a complete remission (CR), 2 partial remissions (PR), 1 stable disease (SD), and 2 progressing disease (PD). Therapy was well tolerated with low toxicity. Six of the patients developed cough; one patient was slightly feverish. We conclude that inhalation therapy of lung metastases is a promising addition to the therapeutic arsenal against malignant melanoma.     

Myopathology of the intrinsic laryngeal muscles in neurodegenerative diseases, with reference to the mechanism of vocal cord paralysis

To investigate the mechanism of the vocal cord abductor paralysis (VCAP) in the neurodegenerative diseases, the intrinsic laryngeal muscles (the crycothyroid, the interarytenoid, and the posterior crycoarytenoid muscles) from 41 autopsied cases were histologically examined: 10 cases of amyotrophic lateral sclerosis (ALS), 10 of Parkinson's disease (PD), 9 of multiple system atrophy (MSA), 4 of Machado-Joseph disease (MJD), 4 of progressive supranuclear palsy (PSP), 1 of familial amyloidotic polyneuropathy (FAP), and 3 of cerebrovascular diseases as a control. According to the distribution of the neurogenic changes among above-described three intrinsic laryngeal muscles, three forms were raised: 1. The totally paralytic form showing that all the three muscles developed neurogenic atrophy. This form includes ALS, MJD, and FAP. 2. The posterior muscle-paralytic form showing that only the posterior crycoarytenoid muscle was selectively involved. This form includes MSA. 3. The nonparalytic form showing no morphological abnormalities in any of the intrinsic laryngeal muscles. This type includes PD and PSP. In this nonparalytic form, supranuclear mechanism such as pyramidal or extrapyramidal tract involvement may cause VCAP through the increased laryngeal muscles tone. Considering that VCAP can be seen in any of the above-described forms, our results indicate that the mechanism of VCAP is different among the neurological disorders.     

The effect of cisapride on delayed colonic transit time in patients with idiopathic Parkinson's disease

Disorders of autonomic regulation are common in patients with Parkinson's disease (PD). Patients most frequently complain of dysphagia and therapy resistant constipation, as far as the gastrointestinal tract is concerned. These symptoms have to be attributed to a neuronal degeneration. In a pilot study we therefore investigated the effect of stimulation of the myenteric plexus by cisapride. 11 women and 13 men were examined, the average age was 67.3 years, the Webster rating 17 points. In 2 out of 24 patients, colonic transit was prolonged up to the limit, both with and without therapy. The other 22 patients showed an acceleration in transit on response to cisapride. On average the colonic transit of 130 hours was reduced to 79 hours. This objective improvement was associated with a subjective improvement. Central side effects or a worsening of Parkinsonian symptoms were not found. We conclude that cisapride is effective in the treatment of constipation in idiopathic PD.     

Effects of a startling acoustic stimulus on reaction time in different parkinsonian syndromes

BACKGROUND: The functional assessment of the startle circuit is usually done by analyzing the acoustic startle response (ASR). However, a startling acoustic stimulus (SAS) also induces changes in the excitability of neural structures that can be demonstrated by studying the SAS-induced change in the behavior of certain neurophysiologic responses. OBJECTIVE: To examine the effects induced by an SAS on voluntary reaction time in patients with parkinsonian syndromes (StartReact effect) and to compare the results with those obtained in a group of age-matched healthy volunteers. METHODS: Twelve patients with idiopathic PD (IPD), seven patients with progressive supranuclear palsy (PSP), seven patients with multisystem atrophy (MSA), and seven healthy age-matched control volunteers performed a simple visual reaction time task and received SAS together with the "go" signal in random trials. RESULTS: Baseline reaction time was significantly slower in PSP patients than in control subjects and MSA patients. The SAS induced a significant shortening of the reaction time in control subjects and in patients with IPD and MSA, but not in patients with PSP. The percentage of reaction time shortening with regard to the baseline values also differed significantly between PSP patients and the other groups of subjects. The StartReact effect was consistent throughout the experiment and showed reduced habituation with repeated testing. CONCLUSIONS: The results are consistent with an abnormal function of the startle circuit in patients with PSP and agree with previous studies using the ASR. The reduced habituation of the StartReact effect favors its clinical applicability in the assessment of differences between patients with parkinsonian syndromes.     

ApoE and CYP2D6 polymorphism with and without parkinsonism-dementia complex in the people of Chamorro, guam

Parkinsonism-dementia complex (PDC), a neurodegenerative disorder in the Chamorro, Guam population, has been epidemiologically ascribed to the ingestion of the neurotoxin cycasin. This disease is characterized neuropathologically by the presence of abundant neurofibrillary tangles (NFTs). We analyzed a genetic risk factor of Alzheimer's disease (AD), apolipoprotein E, hypothesized to be linked to NFT formation, and a genetic risk factor of Parkinson's disease (PD), CYP2D6 mutation, linked to slower metabolism of exogenous toxins, in Chamorro, Guam individuals with and without PDC. The representation of the G-to-C mutation in exon 9 of the CYP2D6 gene was higher in Chamorro and Filipino than in Caucasian individuals, but this mutant allele had similar high frequencies in both PDC patients and healthy Chamorro individuals. We found no alleles of these genes associated with AD or PD to be overrepresented among those with PDC.     

Parkinson's dementia and Alzheimer's dementia: an evoked potential comparison

Auditory endogenous event-related potentials (ERPs) and flash visual evoked potentials (VEPs) were recorded in 26 elderly patients with idiopathic Parkinson's disease (PD), 14 with dementia and 12 non-demented, 16 elderly patients with Alzheimer dementia (AD) and 15 cognitively intact controls. ERP P3 and flash-VEP N2, P2 and delta (P2-P1) latency measures were significantly increased in the demented PD group compared with controls. The ERP P3 latency was also significantly delayed in the AD group compared with controls, but the differences in the flash-VEP measures from controls were not significant. No significant differences were noted between the PD groups, except for a significantly shorter flash-VEP N1 latency in the demented PD group; this was also the only significant evoked potential difference between the AD and PD dementia groups, which were otherwise electrophysiologically similar.     

Aberrant methylation of p16INK4a and deletion of p15INK4b are frequent events in human esophageal cancer in Linxian, China

Esophageal transit scintigraphy seems to be a valid methodology to assess impaired esophageal motility in early stages of disease. The purpose of this study was to discriminate patients with primary Raynaud's phenomenon (RP) and patients with systemic sclerosis (SSc) from healthy subjects by esophageal scintigraphy with a semisolid meal. METHODS: We studied 32 patients with primary RP, 18 with SSc and 13 healthy subjects. Dysphagia, acid regurgitation and heartburn were scored. After an overnight fast, all subjects underwent esophageal scintigraphy, using a semisolid orally ingested bolus (10 mL apple puree) labeled with 99mTc-sulfur colloid. Esophageal transit and emptying time and integral value were evaluated with the subjects in the upright (sitting) and supine positions. Transit time was defined as the time from the entry of 50% of radioactivity into the upper esophagus until the clearance of 50% of the bolus from the whole esophagus. Emptying time was defined as the time from the entry of 50% of radioactivity into the upper esophagus, until the clearance of 100% of the bolus from the whole esophagus. Integral value was defined as the total counts under the time-activity curve normalized to the maximum. RESULTS: Esophageal transit and emptying time and integral value, evaluated in both positions, were significantly higher in patients with SSc than in healthy subjects and than in patients with RP. Moreover, patients with RP had all three parameters, assessed in supine position, significantly longer compared to healthy subjects. Clinical scores regarding dysphagia, acid regurgitation and heartburn were not significantly different between patients with RP and SSc. CONCLUSION: Esophageal transit and emptying time and integral value appear to be able to discriminate patients with primary RP from patients with SSc and patients with RP from healthy subjects, suggesting an early mild esophageal dysfunction in RP.