Nur Yüceyar

Electrophysiological evaluation of pharyngeal phase of swallowing in patients with Parkinson's disease

We studied the various physiological aspects of oropharyngeal swallowing in Parkinsons disease (PD). Fifty‐eight patients with PD were investigated by clinical and electrophysiological methods that measured the oropharyngeal phase of swallowing. All patients except 1 had mild to moderate degree of disability score. Dysphagia was demonstrated in 53% of all patients in whom the test of dysphagia limit was abnormal. All PD patients with or without dysphagia displayed the following abnormalities: (1) the triggering of the swallowing reflex was prolonged probably due to inadequate bolus control in the mouth and tongue and/or a specific delay in the execution of the swallowing reflex; (2) the duration of the pharyngeal reflex time was extremely prolonged due to slowness of the sequential muscle movements, especially those of the suprahyoid‐submental muscles; (3) cricopharyngeal muscle of the upper oesophageal sphincter was found to be electrophysiologically normal; and (4) the electrophysiological phenomena in PD patients could not be strongly correlated with the degree of the disability and clinical score of the PD. It was concluded that various motor disorders of PD have considerable influence on oropharyngeal swallowing: hypokinesia, reduced rate of spontaneous swallowing, and the slowness of segmented but coordinated sequential movements rather than any abnormalities in the central pattern generator of the bulbar center. Some compensatory mechanisms in the course of PD may explain the benign nature of swallowing disorder until the terminal stage of the disease. Similarly, the swallowing problems of PD are not only related with the dopamine deficiency; some other nondopaminergic mechanisms may also be involved.

Piecemeal deglutition and dysphagia limit in normal subjects and in patients with swallowing disorders.

OBJECTIVE: Before the advanced evaluation of deglutition and selection of a treatment method, objective screening methods are necessary for patients with dysphagia. In this study a new electroclinical test was established to evaluate patients with dysphagia. METHODS: This test is based on determining piecemeal deglutition; which is a physiological phenomenon occurring when a bolus of a large volume is divided into two or more parts which are swallowed successively. The combined electrophysiological and mechanical method used to record laryngeal movements detected by a piezoelectric transducer, and activities of the related submental integrated EMG (SM-EMG)-and sometimes the cricopharyngeal muscle of the upper oesophageal sphincter (CP-EMG)-were performed during swallowing. Thirty normal subjects and 66 patients with overt dysphagia of neurogenic origin were investigated after detailed clinical evaluation. Twenty patients with a potential risk of dysphagia, but who were normal clinically at the time of investigation, were also evaluated to determine the specificity of the test. All subjects were instructed to swallow doses of water, gradually increasing in quantity from 1 ml to 20 ml, and any recurrence of the signals related to swallowing within the eight seconds was accepted as a sign of dysphagia limit. RESULTS: In normal subjects as well as in the patients without dysphagia, piecemeal deglutition was never seen with less than 20 ml water. This volume was therefore accepted as the lower limit of piecemeal deglutition. In patients with dysphagia, dysphagia limits were significantly lower than those of normal subjects. CONCLUSION: The method is a highly specific and sensitive test for the objective evaluation of oropharyngeal dysphagia even in patients with suspected dysphagia of neurogenic origin. It can also be safely and simply applied in any EMG laboratory.

Electrodiagnostic methods for neurogenic dysphagia

OBJECTIVE Swallowing mechanisms and neurogenic dysphagia have not been systematically studied by the EMG technique. It is desirable to evaluate neurogenic dysphagia for diagnostic and possibly for therapeutic purposes using electrophysiological methods. METHODS The following methods were described: mechanical upward/downward movements of the larynx were detected using a piezoelectric sensor, while submental integrated EMG activity was recorded during dry and wet swallowing. The EMG activity of cricopharyngeal muscle of the upper oesophageal sphincter was also recorded in some normal subjects and patients. Piecemeal deglutition and the dysphagia limit were determined in all patients to detect dysphagia objectively. In this study 75 normal subjects and 177 neurological patients with various degrees of dysphagia were investigated. RESULTS Voluntarily triggered oropharyngeal swallowing was commonly pathological in the majority of patients, with or without overt dysphagia. The dysphagia limit appeared to be an objective measure of the degree of dysphagia in more than 90% of patients. Pathophysiological mechanisms were different in at least three groups of patients with neurogenic dysphagia. In the group of patients with muscular disorders, laryngeal elevators were involved while the CP-sphincter was intact. The second group included patients with the clinical signs of corticobulbar fibre involvement such as amyotrophic lateral sclerosis and pseudobulbar palsy. In these patients, there was incoordination between paretic laryngeal elevators and hyperreflexic CP-sphincter. In the third group (patients with Parkinsons disease), the swallowing reflex was delayed and prolonged. CONCLUSIONS EMG methods described in the present study are very useful for the diagnosis of neurogenic dysphagia, objectively and quickly. They are important to understand the physiological mechanisms for deglutition and its disorders.

An Electronic Device Measuring the Frequency of Spontaneous Swallowing: Digital Phagometer

A new and protable electronic device called the “Digital Phagometer” is described for the time-based counting of spontaneous swallowing. This device is composed of a piezoelectric sensor and a digital event counter/recorder which can be downloaded to any IBM-compatible PC. The sensor of Digital Phagometer is placed and fixed on the coniotomy region between the cricoid and thyroid cartilage. In this way, it is capable of sensing each upward and downward movement of the larynx produced by spontaneous movement as a function of time. Spontaneous swallowing was measured 1–4 h after lunch in 21 normal subjects and 21 patients with Parkinsons disease (PD). The mean frequency of spontaneous swallowing was 0.8 counts/min in PD patients and 1.18 counts/min in normal subjects (p<0.05). During the intake of 200 ml water, the mean frequency of voluntary swallowing did not differ significantly between the two groups (24.6 counts/min in normals vs. 22.3 counts/min in PD patients), but the time necessary to swallow the same volume of water was longer in the PD group.

Clinical and electrophysiological evaluation of dysphagia in myasthenia gravis

OBJECTIVE To evaluate dysphagia at the oropharyngeal stage of swallowing and to determine the pathophysiological mechanisms of dysphagia in patients with myasthenia gravis. METHODS Fifteen patients with myasthenia gravis with dysphagia and 10 patients without dysphagia were investigated by a combined electrophysiological and mechanical method described previously. Laryngeal movements were detected by a piezoelectric transducer and the related submental EMG (SM-EMG) and sometimes the EMG of cricopharyngeal muscle of the upper esophageal sphincter (CP-EMG) were recorded during dry or wet swallowing. The results of these electrophysiological variables were compared with those of normal age matched control subjects. RESULTS In patients with myasthenia gravis with dysphagia, it was found that the time necessary for the larynx to remain in its superior position during swallowing and swallowing variability in successive swallows increased significantly compared with normal subjects and with patients with myasthenia gravis without dysphagia. The total duration of SM-EMG activity was also prolonged in both groups but more severely in the dysphagic patients. Electromyographic activity of the CP sphincter was found to be normal in the dysphagic patients investigated. All the patients with myasthenia gravis with dysphagia had pathological dysphagia limits (<20 ml water) whereas other patients except two, were within normal limits. CONCLUSIONS Because the electrophysiological variables related to oropharyngeal swallowing were prolonged even in patients with myasthenia gravis without dysphagia, it is concluded that the submental and laryngeal elevators are involved subclinically in myasthenia gravis and, because of compensating mechanisms, the patient may not be dysphagic. As the CP-EMG behaviour was found to be normal, a coordination disorder between normal CP sphincter muscle and the affected striated muscles of the laryngeal elevators may be one of the reasons for dysphagia in myasthenia gravis. This method also made it possible to investigate the myasthenic involvement in the laryngeal elevators that cannot be evaluated by other electrophysiological methods in myasthenia gravis.

Oropharyngeal dysphagia in polymyositis/dermatomyositis

The nature of the oropharyngeal dysphagia in polymyositis/dermatomyositis (PM/DM) has been investigated by EMG methods. Nineteen patients with PM/DM were studied. The oropharyngeal phase of swallowing was evaluated by the electrophysiological methods measuring the laryngeal relocation time, pharyngeal transit time and the triggering of the pharyngeal phase of swallowing reflex. The EMG of cricopharyngeal muscle of the upper esophageal sphincter was also recorded in 10 patients. The patients have been compared with a group of 22 healthy controls matched with age and gender. Dysphagia limit was also measured for all patients and control subjects. Fourteen out of 19 patients could not swallow 20 ml or less amount of water at one go and divided the bolus into two or more pieces (piecemeal deglutition) in comparison to normal subjects. In PM/DM patients, the triggering of the swallowing reflex for the voluntarily initiated swallow was normal while the pharyngeal phase of swallowing was significantly prolonged. The cricopharyngeal sphincter muscle EMG demonstrated severe abnormalities in halves of the patients investigated. These findings demonstrated the weakness of the striated oropharyngeal muscles. Cricopharyngeal sphincter muscle was affected less frequently and showed either hyperreflexic or hyporeflexic states during swallowing. It is concluded that the pharyngeal stage of oropharyngeal swallowing is mainly involved in patients with PM/DM.

Electrophysiological evaluation of oropharyngeal swallowing in myotonic dystrophy

OBJECTIVE Oropharyngeal dysphagia is a common feature of patients with myotonic dystrophy and is not usually perceived due to their emotional deficits and lack of interest. The aim was to show the existence and frequency of subclinical electrophysiological abnormalities in oropharyngeal swallowing and to clarify the mechanisms of dysphagia in myotonic dystrophy. METHODS Eighteen patients with myotonic dystrophy were examined for oropharyngeal phase of swallowing by clinical and electrophysiological methods. Ten patients had dysphagia whereas 11 patients had signs and symptoms reflecting CNS involvement. Four patients with myotonia congenita and 30 healthy volunteers served as controls. Laryngeal movements were detected by means of a piezoelectric sensor. EMG activities of the submental muscle (SM-EMG) and needle EMG of the cricopharyngeal muscle of the upper eosophageal sphincter (CP-EMG) were also recorded during swallowing. RESULTS In about 70% of the patients with myotonic dystrophy, the existence of oropharyngeal dysphagia was indicated objectively by means of the technique of “dysphagia limit” and by clinical evaluation. Duration of the swallowing reflex as defined by the laryngeal relocation time (0–2 time interval) and submental muscle excitation as a part of the swallowing reflex (A-C interval) were significantly prolonged in patients with myotonic dystrophy, especially in dysphagic patients. Triggering time of the swallowing reflex (A-0 interval) also showed significant prolongation, especially in the patients having both dysphagia and CNS involvement. During swallowing, CP muscle activity was abnormal in 40% of the patients with myotonic dystrophy. CONCLUSION Both myopathic weakness and myotonia encountered in oropharyngeal muscles play an important part in the oral and the pharyngeal phases of swallowing dysfunction in myotonic dystrophy. It was also suggested that CNS involvement might contribute to the delay of the triggering of the swallowing reflex and some abnormal EMG findings in the CP sphincter, resulting in oropharyngeal dysphagia in myotonic dystrophy.

Serum and cerebrospinal fluid nitrite and nitrate levels in relapsing-remitting and secondary progressive multiple sclerosis patients

Nitric oxide (NO) has been implicated in immune mediated cellular cytotoxicity and inflammatory processes including multiple sclerosis (MS). We aimed to assess NO production in MS patients and to delineate its involvement in different stages. The stable end-products of NO; nitrite(NO2-) and nitrate(NO3-) were analysed both in serum and CSF (cerebrospinal fluid) of patients with MS and non-inflammatory neurological diseases. Nitrite levels were quantified by calorimetric assay based on the Griess reaction. Nitrate levels were examined spectrophotometrically. MS patients exhibited significantly increased serum and CSF levels of NO2-+NO3- compared with the control subjects. CSF NO2-+NO3- levels were raised significantly in MS patients with both relapsing remitting (RR) and secondary progressive (SP) course. There was no significant difference between RR and SP MS patients with regard to NO metabolites. No significant correlation was found between NO metabolites and disability score, disease progression index, MRI (magnetic resonance imaging) activity and development of cortical atrophy on MRI. This study provides further evidence for excessive NO production both in CSF and peripheral blood of MS patients. Excessive CSF NO2-+NO3- levels being more increased than the levels in sera supports pathological inflammatory process within CNS (central nervous system) in both stages of MS. Another implication for the role of NO and INOS inhibitors in the treatment of MS patients with both RR and SP courses was also suggested.

Increased Cerebrospinal Fluid and Serum Nitrite and Nitrate Levels in Amyotrophic Lateral Sclerosis

Abnormal glutamate metabolism is implied in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS) and cerebrospinal fluid (CSF) glutamate levels appear to be elevated. Since nitric oxide (NO) inhibits glutamate transport, excessive amounts of nitrie oxide could underlie the glutamate induced neurotoxicity in ALS. Stable metabolites of NO (NO−2 + NO−3) levels were determined in serum and CSF of sporadic ALS patients and control subjects. NO−2 + NO−3 levels were higher in ALS, in males and in serum samples compared to controls, females and CSF, respectively. Furthermore, while the difference between serum and CSF NO−2 + NO−3 levels was significant in males (higher in serum) no such difference was observed in females. Our results suggest that nitrie oxide may be involved in the pathogenesis of ALS directly or indirectly and in a sexually dimorphic manner.

Identification of a locus for an autosomal recessive hyaline body myopathy at chromosome 3p22.2 -p21.32

Hyaline body myopathy is a rare congenital disease with distinctive histopathological features. We performed homozygosity mapping in a family with two affected sibs and identified a gene locus with a maximum homozygosity region of 5.35 centi Morgans or 5.59 Megabases at chromosome 3p22.2-p21.32. The best candidate responsible for the disease is a novel gene that exhibits homology to the myosin heavy chain.