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Pompe disease is a lysosomal storage disease resulting from absence or deficiency of acid α-glucosidase (GAA). Tongue-related disorders including dysarthria, dysphagia, and obstructive sleep apnea are common in Pompe disease. Our purpose was to determine if designer receptors exclusively activated by designer drugs (DREADDs) could be used to stimulate tongue motor output in a mouse model of Pompe disease. An adeno-associated virus serotype 9 (AAV9) encoding an excitatory DREADD (AAV9-hSyn-hM3D(Gq)-mCherry, 2.44 × 10

Inadequate tongue muscle activation contributes to dysarthria, dysphagia, and obstructive sleep apnea. Thus, treatments which increase tongue muscle activity have potential clinical benefit. We hypothesized that lingual injection of an adeno-associated virus (AAV) encoding channelrhodopsin-2 (ChR2) would enable light-induced activation of tongue motor units during spontaneous breathing. An AAV serotype 9 vector (pACAGW-ChR2-Venus-AAV9, 8.29 × 10

Dysfunction and/or reduced activity in the tongue muscles contributes to conditions such as dysphagia, dysarthria, and sleep disordered breathing. Current treatments are often inadequate, and the tongue is a readily accessible target for therapeutic gene delivery. In this regard, gene therapy specifically targeting the tongue motor system offers two general strategies for treating lingual disorders. First, correcting tongue myofiber and/or hypoglossal (XII) motoneuron pathology in genetic neuromuscular disorders may be readily achieved by intralingual delivery of viral vectors. The retrograde movement of viral vectors such as adeno-associated virus (AAV) enables targeted distribution to XII motoneurons via intralingual viral delivery. Second, conditions with impaired or reduced tongue muscle activation can potentially be treated using viral-driven chemo- or optogenetic approaches to activate or inhibit XII motoneurons and/or tongue myofibers. Further considerations that are highly relevant to lingual gene therapy include (1) the diversity of the motoneurons which control the tongue, (2) the patterns of XII nerve branching, and (3) the complexity of tongue muscle anatomy and biomechanics. Preclinical studies show considerable promise for lingual directed gene therapy in neuromuscular disease, but the potential of such approaches is largely untapped.

Purpose Hyoid bone and laryngeal approximation aid airway protection (laryngeal vestibule closure) while moving toward their peak superior and anterior positions during swallowing. Submental surface electrical stimulation (SES) is a therapeutic technique that targets the muscles that move the hyoid bone during swallowing. It is unknown whether submental SES only increases peak hyoid bone swallowing positions but not peak laryngeal swallowing positions, which could require faster or greater laryngeal movement to achieve adequate laryngeal vestibule closure. Method We examined the effects of submental SES on hyo-laryngeal kinematics in 30 healthy adults who swallowed 50 times using an error-based learning paradigm. Results Submental SES did not alter any hyo-laryngeal swallowing kinematic. However, submental SES significantly changed the starting position of the hyoid bone just prior to the swallow onset (more anterior; p = .003). On average, submental SES immediately prior to swallow onset can position the hyoid approximately 20% closer to its peak swallowing point. Conclusions These findings indicate that electrical stimulation of the agonists for hyoid movement might not alter swallowing outcomes tested in this study. However, submental SES could have clinical utility by minimizing swallowing impairments related to reduced hyoid swallowing range of motion in individuals with dysphagia.

There are multiple descending neural pathways, including the corticospinal pathway (CS) and the corticobulbar pathway (CB). The corticospinal pathway has been shown to exhibit within-pathway (CS-to-CS) motor transfer. However, motor transfer across each pathway (CS-to-CB or CB-to-CS) has yet to be studied in depth. The aim of the present study was to examine the effects of cross-pathway motor transfer between the ankle (CS) and tongue (CB) after training with a ballistic goal-directed motor task. Twelve healthy participants were recruited for this two-day experimental study. Six participants performed a ballistic goal-directed task with their ankle on Day 1 (ankle dorsiflexion), then tongue on Day 2 (elevate tongue against IOPI). The other 6 participants performed the same task with their tongue on Day 1, then ankle on Day 2. Both the ankle and tongue tasks (50 trials each) required matching force and time to a visual target. Our findings indicate that participants who underwent ankle training on Day 1 exhibited decreased tongue force error on Day 2 compared with participants who completed the tongue training on Day 1, with no prior ankle training (p = 0.02) (i.e. greater accuracy). This finding suggests that cross-pathway transfer from the corticospinal pathway to the corticobulbar pathway occurred with respect to force error. In other words, training of the ankle (CS) translated to improved training performance of the tongue (CB) through a reduction in force error. However, the reverse was not true – training the tongue did not elicit improved performance of the ankle. Nonetheless, if training with the corticospinal pathway can lead to improved corticobulbar pathway functioning, incorporating multi-pathway rehabilitation techniques might be valuable for clinicians across medical disciplines.

Although movement is controlled by different descending pathways, it remains unknown whether the integration of visual feedback and motor learning differs for movements controlled by different descending pathways. Here, we compare motor control and learning of the ankle joint and tongue because they are primarily controlled by the corticospinal and corticobulbar pathways, respectively. Twelve young adults (19.63 ± 2.11 years, 6 females) practiced a tracking task (combination of 0.02, 0.37, 0.5, and 1 Hz) with ankle dorsiflexion and with tongue elevation for 100 trials. The participants practiced each effector (ankle and tongue) in different days and the order of the effector was counterbalanced. Following practice, participants performed the same tracking task with concurrent contractions of the tongue and ankle (dual tracking task; transfer) with three different visual feedback conditions (no visual feedback, visual feedback only for ankle, visual feedback only for tongue). We quantified the force accuracy (RMSE) from each effector during the practice and transfer periods. During practice, the force accuracy and performance improvement to the visuomotor task was greater for the ankle dorsiflexion than tongue elevation. During the transfer task, the ankle dorsiflexion was more accurate than tongue elevation, independent of whether visual feedback was given for the ankle or tongue. The greater performance improvement for the ankle dorsiflexion during practice was related to superior transfer performance. These findings suggest that the corticospinal pathway integrates visual feedback more efficiently than the corticobulbar pathway, which enhances performance and learning of visuomotor tasks.

Swallowing dysfunction is common after stroke. More than 50% of the 665 thousand stroke survivors will experience dysphagia acutely of which approximately 80 thousand will experience persistent dysphagia at 6 months. The physiologic impairments that result in post-stroke dysphagia are varied. This review focuses primarily on well-established dysphagia treatments in the context of the physiologic impairments they treat. Traditional dysphagia therapies including volume and texture modifications, strategies such as chin tuck, head tilt, head turn, effortful swallow, supraglottic swallow, super-supraglottic swallow, Mendelsohn maneuver and exercises such as the Shaker exercise and Masako (tongue hold) maneuver are discussed. Other more recent treatment interventions are discussed in the context of the evidence available.

The appearance of a vesicular rash in the anogenital area of a child should alert the practitioner to the possibility of herpes simplex virus (HSV) infection and potential sexual abuse. However, careful attention to other sources of infection must be made to avoid unfounded suspicion of abuse. The rash of primary varicella zoster has been demonstrated to mimic HSV infection.1,2 In two published case studies, varicella vesicles began in the anogenital region before progressing to a more typical diffuse distribution of lesions. In these cases the diagnosis of suspected child abuse was made before the eruption of the nongenital rash. Herpes zoster (HZ), although uncommon in healthy children, must also be included in the differential diagnosis of painful genital or anal vesicular rash. Reactivation of the varicella zoster virus (VZV) along sacral dermatomes can result in highly suggestive painful vesicles. Although viral culture is the standard of reference for viral identification, rapid direct immunofluorescence assay (DFA) of vesicular contents is a clinically useful way to determine the infectious cause of a suspicious rash. A previously healthy 9½-year-old girl presented to her primary care physician with a complaint of a painful perianal rash with dyschezia for 4 days. She was afebrile and denied abdominal pain, vomiting, diarrhea, dysuria, pruritis, or a generalized skin rash. Perianal vesicles were identified and considered to be highly suspicious for HSV. The possibility of sexual abuse was discussed with the family. The child's parents had no concern about sexual abuse, and the child denied any prior sexual assault. Because of the presumptive diagnosis of HSV, a report of suspected child sexual abuse was made to the local child welfare …