Respiratory therapies for Amyotrophic Lateral Sclerosis: A state of the art review.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition noteworthy for upper and lower motor neuron death. Involvement of respiratory motor neuron pools leads to progressive pathology. These impairments include decreases in neural activation and muscle coordination, progressive airway obstruction, weakened airway defenses, restrictive lung disease, increased risk of pulmonary infections, and weakness and atrophy of respiratory muscles. These neural, airway, pulmonary, and neuromuscular changes deteriorate integrated respiratory-related functions including sleep, cough, swallowing, and breathing. Ultimately, respiratory complications account for a large portion of morbidity and mortality in ALS. This state-of-the-art review highlights applications of respiratory therapies for ALS, including lung volume recruitment, mechanical insufflation-exsufflation, non-invasive ventilation, and respiratory strength training. Therapeutic acute intermittent hypoxia, an emerging therapeutic tool for inducing respiratory plasticity will also be introduced. A focus on emerging evidence and future work underscores the common goal to continue to improve survival for patients living with ALS.

Exploring inspiratory occlusion metrics to assess respiratory drive in patients under acute intermittent hypoxia.

Patients living with Amyotrophic Lateral Sclerosis (ALS) experience respiratory weakness and, eventually, failure due to inspiratory motor neuron degeneration. Routine pulmonary function tests (e.g., maximum inspiratory pressure (MIP)) are used to assess disease progression and ventilatory compromise. However, these tests are poor discriminators between respiratory drive and voluntary respiratory function at rest. To better understand ALS disease progression, we can look into compensatory strategies and how patients consciously react to the occlusion and the effort produced to meet the ventilatory challenge of the occlusion. This ventilatory challenge, especially beyond the P0.1 (200 ms and 300 ms), provides information regarding the patient's ability to recruit additional respiratory muscles as a compensatory strategy. Utilizing a standard P0.1 protocol to assess respiratory drive, we extend the occlusion time analysis to 200 ms and 300 ms (Detected Occlusion Response (DOR)) in order to capture compensatory respiratory mechanics. Furthermore, we followed an Acute Intermittent Hypoxia (AIH) protocol known to increase phrenic nerve discharge to evaluate the compensatory strategies. Inspiratory pressure, the rate of change in pressure, and pressure generation normalized to MIP were measured at 100 ms, 200 ms, and 300 ms after an occlusion. Airway occlusions were performed three times during the experiment (i.e., baseline, 30 and 60 minutes post-AIH). Results indicated that while AIH did not elicit change in the P0.1 or MIP, the DOR increased for ALS patients. These results support the expected therapeutic role of AIH and indicate the potential of the DOR as a metric to detect compensatory changes.

Intra-Arterial, but Not Intrathecal, Baclofen and Codeine Attenuates Cough in the Cat.

Centrally-acting antitussive drugs are thought to act solely in the brainstem. However, the role of the spinal cord in the mechanism of action of these drugs is unknown. The purpose of this study was to determine if antitussive drugs act in the spinal cord to reduce the magnitude of tracheobronchial (TB) cough-related expiratory activity. Experiments were conducted in anesthetized, spontaneously breathing cats (n = 22). Electromyograms (EMG) were recorded from the parasternal (PS) and transversus abdominis (TA) or rectus abdominis muscles. Mechanical stimulation of the trachea or larynx was used to elicit TB cough. Baclofen (10 and 100 µg/kg, GABA-B receptor agonist) or codeine (30 µg/kg, opioid receptor agonist) was administered into the intrathecal (i.t.) space and also into brainstem circulation via the vertebral artery. Cumulative doses of i.t. baclofen or codeine had no effect on PS, abdominal muscle EMGs or cough number during the TB cough. Subsequent intra-arterial (i.a.) administration of baclofen or codeine significantly reduced magnitude of abdominal and PS muscles during TB cough. Furthermore, TB cough number was significantly suppressed by i.a. baclofen. The influence of these drugs on other behaviors that activate abdominal motor pathways was also assessed. The abdominal EMG response to noxious pinch of the tail was suppressed by i.t. baclofen, suggesting that the doses of baclofen that were employed were sufficient to affect spinal pathways. However, the abdominal EMG response to expiratory threshold loading was unaffected by i.t. administration of either baclofen or codeine. These results indicate that neither baclofen nor codeine suppress cough via a spinal action and support the concept that the antitussive effect of these drugs is restricted to the brainstem.

Attention demands of language production in adults who stutter.

OBJECTIVE: We investigated whether language production is atypically resource-demanding in adults who stutter (AWS) versus typically-fluent adults (TFA). METHODS: Fifteen TFA and 15 AWS named pictures overlaid with printed Semantic, Phonological or Unrelated Distractor words while monitoring frequent low tones versus rare high tones. Tones were presented at a short or long Stimulus Onset Asynchrony (SOA) relative to picture onset. Group, Tone Type, Tone SOA and Distractor Type effects on P3 amplitudes were the main focus. P3 amplitude was also investigated separately in a simple tone oddball task. RESULTS: P3 morphology was similar between groups in the simple task. In the dual task, a P3 effect was detected in TFA in all three distractor conditions at each Tone SOA. In AWS, a P3 effect was attenuated or undetectable at the Short Tone SOA depending on Distractor Type. CONCLUSIONS: In TFA, attentional resources were available for P3-indexed processes in tone perception and categorization in all distractor conditions at both Tone SOAs. For AWS, availability of attentional resources for secondary task processing was reduced as competition in word retrieval was resolved. SIGNIFICANCE: Results suggest that language production can be atypically resource-demanding in AWS. Theoretical and clinical implications of the findings are discussed.