A mouse model of pharyngeal dysphagia in amyotrophic lateral sclerosis.

We recently established that the SOD1-G93A transgenic mouse is a suitable model for oral-stage dysphagia in amyotrophic lateral sclerosis (ALS). The purpose of the present study was to determine whether it could serve as a model for pharyngeal-stage dysphagia as well. Electrophysiological and histological experiments were conducted on end-stage SOD1-G93A transgenic mice (n = 9) and age-matched wild-type (WT) littermates (n = 12). Transgenic mice required a twofold higher stimulus frequency (40 Hz) applied to the superior laryngeal nerve (SLN) to evoke swallowing compared with WT controls (20 Hz); transgenic females required a significantly higher (P < 0.05) stimulus frequency applied to the SLN to evoke swallowing compared with transgenic males. Thus, both sexes demonstrated electrophysiological evidence of pharyngeal dysphagia but symptoms were more severe for females. Histological evidence of neurodegeneration (vacuoles) was identified throughout representative motor (nucleus ambiguus) and sensory (nucleus tractus solitarius) components of the pharyngeal stage of swallowing, suggesting that pharyngeal dysphagia in ALS may be attributed to both motor and sensory pathologies. Moreover, the results of this investigation suggest that sensory stimulation approaches may facilitate swallowing function in ALS.

An animal model of oral dysphagia in amyotrophic lateral sclerosis.

Relatively little is known about the underlying neuropathology of dysphagia in amyotrophic lateral sclerosis (ALS); thus, effective treatments remain elusive. Tremendous progress toward understanding and treating dysphagia in ALS may be possible through the use of an animal model of dysphagia in ALS research; however, no such animal model currently exists. The most logical candidate to consider is the SOD1-G93A transgenic mouse, the most widely investigated animal model of ALS. To investigate whether this animal model develops dysphagia, oral behaviors (lick and mastication rates) of SOD1-G93A transgenic mice (n = 30) were evaluated at three time points based on hind limb motor function: asymptomatic (60 days), disease onset (approximately 110 days), and disease end-stage (approximately 140 days). Age-matched nontransgenic littermates (n = 30) served as controls. At each time point, lick and mastication rates were significantly lower (p < 0.05) for transgenic mice compared with controls. Histologic analysis of the brainstem showed marked neurodegeneration (vacuolation) of the trigeminal and hypoglossal nuclei, two key motor components involved in mastication and licking behaviors. These results demonstrate a clinicopathologic correlation of oral dysfunction in SOD1-G93A transgenic mice, thereby establishing the SOD1-G93A transgenic mouse as a bona fide animal model of oral dysphagia in ALS.

Mild traumatic brain injury: effects on naming in word retrieval and discourse.

PRIMARY OBJECTIVE: To investigate differences between a group with mild traumatic brain injury (MTBI) and a control group relative to standard scores and error type during word retrieval in both naming and discourse tasks. METHODS AND PROCEDURES: Ten participants with MTBI were age-, gender- and education-matched with 10 participants without injury. Pre-experimental tasks for the participants with MTBI included the Scales of Cognitive Ability for Traumatic Brain Injury and the Raven's Coloured Progressive Matrices and both groups received the Peabody Picture Vocabulary Test-III. Experimental tasks included the Test of Adolescent/Adult Word Finding and the Test of Word Finding in Discourse. MAIN OUTCOMES AND RESULTS: Few participants (three on each experimental task) demonstrated psychometrically-based word retrieval deficits (standard score < 85); however, a significant difference in performance for the TAWF as compared to the TWFD was observed between groups. More word finding errors occurred with confrontational naming than with discourse tasks for both groups, with latency as the primary error type. CONCLUSIONS: Confrontational naming tasks may be more sensitive to subtle language difficulties occurring after MTBI. The study of adults with MTBI and their performance on semantically-based tasks offers important information for the advancement of therapeutic intervention and education.