Barbara C. Sonies

Treatment of inclusion-body myositis with IVIg A double-blind, placebo-controlled study

Article abstract-We randomized 19 patients with inclusion-body myositis (IBM) to a double-blind, placebo-controlled, crossover study using monthly infusions of 2 g/kg intravenous immunoglobulin (IVIg) or placebo for 3 months. Patients crossed over to the alternate treatment after a washout period. We evaluated responses at baseline and at the end of each treatment period using expanded (0-10) MRC scales, the Maximum Voluntary Isometric Contraction (MVIC) method, symptom and disability scores, and quantitative swallowing studies. We calculated the differences in scores between IVIg and placebo from baseline to end of treatment. Of the 19 patients, 9 (mean age, 61.2 years; mean disease duration, 5.6 years) were randomized to IVIg and 10 (mean age, 66.1 years; mean disease duration, 7.4 years) to placebo. During IVIg the patients gained a mean of 4.2 (-16 to +39.8) MRC points, and during placebo lost 2.7 (-10 to +8) points (p < 0.1). These gains were not significant. Similar results were obtained with the MRC and MVIC scores when the patients crossed to the alternate treatment. Six patients had a functionally important improvement by more than 10 MRC points that declined when crossed over to placebo. Limb-by-limb analysis demonstrated that during IVIg the muscle strength in 39% of the lower extremity limbs significantly increased compared with placebo (p < 0.05), while a simultaneous decrease in 28% of other limbs was detected. The clinical importance of these minor gains is unclear. The duration of swallowing functions measured in seconds with ultrasound improved statistically in the IVIg-randomized patients (p < 0.05) compared with placebo. Although the study did not establish efficacy of IVIg, possibly because of the small sample size, the drug induced functionally important improvement in 6 (28%) of the 19 patients. Whether the modest gains noted in certain muscle groups justify the high cost of trying IVIg in IBM patients at a given stage of the disease remains unclear. NEUROLOGY 1997;48: 712-716

Effects of Surface Electrical Stimulation Both at Rest and During Swallowing in Chronic Pharyngeal Dysphagia

We tested two hypotheses using surface electrical stimulation in chronic pharyngeal dysphagia: that stimulation (1) lowered the hyoid bone and/or larynx when applied at rest, and (2) increased aspiration, penetration, or pharyngeal pooling during swallowing. Bipolar surface electrodes were placed on the skin overlying the submandibular and laryngeal regions. Maximum tolerated levels of stimulation were applied while patients held their mouth closed at rest. Videofluoroscopic recordings were used to measure hyoid movements in the superior-inferior and anterior-posterior dimensions and the subglottic air column position while stimulation was on or off. Patients swallowed 5 ml liquid when stimulation was off, at low sensory stimulation levels, and at maximum tolerated levels (motor). Speech pathologists, blinded to condition, tallied the frequency of aspiration, penetration, pooling, and esophageal entry from videofluorographic recordings of swallows. Only significant (p = 0.0175) hyoid depression occurred during stimulation at rest. Aspiration and pooling were significantly reduced only with low sensory threshold levels of stimulation (p = 0.025) and not during maximum levels of surface electrical stimulation. Those patients who had reduced aspiration and penetration during swallowing with stimulation had greater hyoid depression during stimulation at rest (p = 0.006). Stimulation may have acted to resist patients’ hyoid elevation during swallowing.

Durational aspects of the oral-pharyngeal phase of swallow in normal adults

We present durational data on normal oral-pharyngeal swallows in adults obtained using ultrasound imaging. The effects of normal aging on the oral-pharyngeal phase of swallowing were studied in 47 healthy adults. Timing of the oralpharyngeal phase of swallow was determined from frame-by-frame analysis of ultrasound videos of the motion of the tongue and hyoid bone from initial rest to final resting position. Duration of unstimulated (dry) swallows was compared to stimulated (wet) swallows across four age groups and by sex and age. For most subjects, dry swallows were longer than wet swallows; moreover, swallow duration was longest for older women than any other group. As age increased (55+), oral swallows were accompanied by extralingual gestures. Ability to produce a timed series of continuously dry swallows was somewhat influenced by age. Findings are suggestive of an age change more typical in women, with a pattern of multiple lingual gestures commonly seen after age 55 in both sexes. We suggest that subtle, subclinical, oral neuromotor changes occur with normal aging to cause these findings.

Clinical spectrum of Niemann‐Pick disease type C

Analysis of the neurologic symptomatology in 22 patients with Niemann-Pick disease type C revealed 3 phenotypes: (1) an early-onset, rapidly progressive form associated with severe hepatic dysfunction and psychomotor delay during infancy and later with supranuclear vertical gaze paresis, ataxia, marked spasticity, and dementia; (2) a delayed-onset, slowly progressive form heralded by the appearance, usually in early childhood, of mild intellectual impairment, supranuclear vertical gaze paresis, and ataxia, and later associated with dementia and, variably, seizures and extrapyramidal deficits; (3) a late-onset, slowly progressive form distinguished from the 2nd pattern by later age of onset (adolescence or adulthood) and a much slower rate of progression. The existence of the 1st and 2nd phenotypes within the same sibship suggests that they are variant expressions of the same clinicopathologic disorder. Niemann-Pick disease type C should be considered not only in infants and children who present with organomegaly and a progressive neurodegenerative course, but also in adolescents and adults who have insidiously progressive neurologic dysfunction and only slight organomegaly. Associated with the disease is a marked deficiency in the ability of cultured fibroblasts to esterify exogenously supplied cholesterol. Assay of this deficiency is particularly useful for confirming the diagnosis in patients with atypical presentation.

Emergence of oropharyngeal, laryngeal and swallowing activity in the developing fetal upper aerodigestive tract: an ultrasound evaluation

The developing fetal upper aerodigestive system provides the structural support for respiratory and ingestive functions necessary to sustain life at birth. This study investigated prenatal development of upper aerodigestive anatomy and the association of emerging functions as predictors of postnatal feeding skills. Biometric measures of oral, lingual, pharyngeal and laryngeal structures were obtained in fetuses 15-38 weeks gestational age using a four-plane sonographic technique. Accompanying ingestive behaviors were tallied across development. The data from 62 healthy controls were compared to seven cases at risk for postnatal feeding and swallowing dysfunction (Type II Arnold Chiari Malformation, trisomy 18, polyhydramnios, intrauterine growth restriction, Brachmann-de Lange Syndrome). Significant (p<0.001) linear regressions occurred in pharyngeal and lingual growth across gestation while ingestive behavior such as suckling emerged in a sequence of basic to complex movement patterns. Jaw and lip movements progressed from simple mouth opening to repetitive open-close movements important for postnatal suckling. Lingual movements increased in complexity from simple forward thrusting and cupping to anterior-posterior motions necessary for successful suckling at term. Laryngeal movements varied from shallow flutter-like movements along the lumen to more complex and complete adduction-abduction patterns. Fetal swallowing primarily occurred in the presence of concomitant oral-facial stimulatory activity. Significant variations (p<0.01) in the form and function of the ingestive system occurred in comparisons of gestational age-matched controls to at-risk cases. We postulate that prenatal developmental indices of emerging aerodigestive skills may guide postnatal decisions for feeding readiness and, ultimately, advance the care of the premature, medically fragile neonate.

Ultrasound analysis of tongue, hyoid, and larynx activity during swallowing.

Using real-time ultrasound, the motions of the tongue, hyoid bone, and larynx were monitored and timed during swallowing in ten normal subjects. A well-defined propulsive wave of the tongue was observed during swallowing a 5-cc water bolus. The body of the hyoid bone was identified on the ultrasound scan as a high echogenic area with posterior acoustic shadowing at the tongue base. As the water bolus reached the pharynx, hyoid elevation was visible. Laryngeal motion was monitored by an externally applied pressure transducer and its pressure tracing incorporated into the ultrasound video image.

Effects of systematic bolus viscosity and volume changes on hyoid movement kinematics.

Using ultrasonography with head and transducer stabilization, this study examined the effects of maximally controlled, systematic changes in bolus viscosity (thin juice-like, 7 cP; nectar-like, 243–260 cP; honey-like, 724–759 cP; spoon-thick, 2760–2819 cP) and volume (5, 10, 20, 30 cc) on hyoid kinematics in 31 healthy subjects (16 male, 15 female) in three age groups (20–39, 40–59, 60–79 years). Frame-by-frame hyoid displacements were tracked from digitized images of 612 swallows. Measures of movement durations, maximal amplitudes, total distances, and peak velocities were subjected to repeated measures multivariate analyses of variance with viscosity, volume, age, and gender as factors. Results showed that (1) spoon-thick swallows had the greatest preswallow gesture and total movement durations; (2) larger-volume swallows had significantly greater maximal amplitudes, forward peak velocity, and total vertical distance; (3) older subjects had longer start-to-max duration (though shorter preswallow gesture and total movement durations), greater maximal vertical amplitude, longer total vertical distance, and greater backward peak velocity than younger subjects; (4) males had greater values for all kinematic parameters except preswallow gesture, hyoid-at-max, and max-to-end durations. The results illustrate the importance of examining the interrelations among kinematic variables to better understand task accommodation and motor control strategies. The evidence also supports the concept of suprahyoid–infrahyoid functional adaptation and compensation in the healthy elderly.

DYSPHAGIA IN PATIENTS WITH THE POST-POLIO SYNDROME

BACKGROUND AND METHODS Dysphagia may develop in some patients many years after an attack of acute paralytic poliomyelitis. To identify clinical or subclinical signs of oropharyngeal dysfunction, we examined 32 patients (mean age, 48.9 years) with the post-polio syndrome (defined by new weakness in the limbs). Of the 32 patients, 14 had symptoms of new swallowing difficulties, and 18 were asymptomatic in this respect; 12 had a history of bulbar involvement during acute poliomyelitis. Swallowing function was assessed objectively by ultrasonography, videofluoroscopy, and an oral motor index score for 10 components of oral function. RESULTS All but 1 of the 32 patients, regardless of whether they had new symptoms or previous bulbar involvement, had some abnormality on detailed testing of oropharyngeal function; only 2 patients had any signs of aspiration. The mean oral motor index score (a quantitative measure of oral sensorimotor function) in the patients was higher than that in age-matched normal subjects (P less than 0.001). Videofluoroscopy showed abnormalities of varying severity, including unilateral bolus transport through the pharynx, pooling in the valleculae or pyriform sinuses, delayed pharyngeal constriction, and impaired tongue movements. On ultrasonography, the mean (+/- SD) duration of wet swallows was significantly longer in the symptomatic patients than in the asymptomatic patients (2.67 +/- 0.70 vs. 1.65 +/- 0.42 seconds). The four patients who were reexamined two years later had objective signs of worsening oropharyngeal function and corresponding new symptoms. CONCLUSIONS In patients with the post-polio syndrome, the bulbar muscles often have clinical or subclinical signs of dysfunction. These abnormalities suggest that in bulbar neurons there is a slowly progressive deterioration similar to that in the muscles of the limbs.

Oral-pharyngeal dysphagia: A common sequela of salivary gland dysfunction

Saliva plays a critical role in alimentary events, allowing food to be initially processed, formed into a bolus, and subsequently transported through the oral cavity. Patients with salivary gland hypofunction often present with dysphagic complaints. We therefore evaluated the possible relationship between salivary performance and swallowing ability in such patients. Patients subjectively reporting difficulty in swallowing had significantly lower salivary flow rates (1/6–1/3 less) than persons without such complaints. Similarly, patients with documented salivary hypofunction displayed significantly increased duration (more than two-fold) of the oral phase of swallowing for several experimental swallowing conditions. Our results support the hypothesis that dysphagia can result from conditions leading to salivary gland hypofunction.

Soft tissue anatomy of the tongue and floor of the mouth: An ultrasound demonstration

Ultrasound technology has not been used extensively in the study of normal and abnormal oral physiology and speech. Features such as soft tissue detail, real-time motion display, and subject safety make ultrasound ideal for imaging the tongue and the floor of the mouth. This study demonstrates visualization of the muscles of the tongue and floor of the mouth for a normal subject using ultrasound imaging. By employing submandibular transducer placement of realtime sector scanners, tongue anatomy and motion were continuously visualized in sagittal or coronal planes. In addition to the entire tongue surface, much of the intrinsic anatomy was identified including: the genioglossus, geniohyoid, mylohyoid, and digastric muscles; fascial boundaries such as the median fibrous septum, floor intermuscular septum, and paramedian septums; and the hyoid bone. A tongue excised from a human cadaver was scanned using ultrasound and dissected to confirm the anatomy seen in the live tongue. Tongue surface shape and configuration of the intrinsic tissue structures were observed and compared for the phonemes /k/, /u/, and /i/. Anatomical landmarks in the resting and speaking tongue are discussed as well as applications in the fields of speech science and speech pathology.