Transcranial, Non-Invasive Evaluation of Potential Misery Perfusion During Hyperventilation Therapy of Traumatic Brain Injury Patients.

Hyperventilation (HV) therapy uses vasoconstriction to reduce intracranial pressure (ICP) by reducing cerebral blood volume. However, as HV also lowers cerebral blood flow (CBF), it may provoke misery perfusion (MP), in which the decrease in CBF is coupled with increased oxygen extraction fraction (OEF). MP may rapidly lead to the exhaustion of brain energy metabolites, making the brain vulnerable to ischemia. MP is difficult to detect at the bedside, which is where transcranial hybrid, near-infrared spectroscopies are promising because they non-invasively measure OEF and CBF. We have tested this technology during HV (∼30 min) with bilateral, frontal lobe monitoring to assess MP in 27 sessions in 18 patients with traumatic brain injury. In this study, HV did not lead to MP at a group level (p > 0.05). However, a statistical approach yielded 89 events with a high probability of MP in 19 sessions. We have characterized each statistically significant event in detail and its possible relationship to clinical and radiological status (decompressive craniectomy and presence of a cerebral lesion), without detecting any statistically significant difference (p > 0.05). However, MP detection stresses the need for personalized, real-time assessment in future clinical trials with HV, in order to provide an optimal evaluation of the risk-benefit balance of HV. Our study provides pilot data demonstrating that bedside transcranial hybrid near-infrared spectroscopies could be utilized to assess potential MP.

Comparative analysis between available challenge tests in the hyperventilation syndrome.

BACKGROUND: The hyperventilation syndrome (HVS) is characterized by somatic/ psychological symptoms due to sustained hypocapnia and respiratory alkalosis without any organic disease. OBJECTIVE: The purpose of this study was to compare ventilatory parameters and symptoms reproducibility during the hyperventilation provocation test (HVPT) and cardiopulmonary exercise test (CPET) as diagnostic tools in patients with HVS, and to identify the most frequent etiologies of the HVS by a systematic assessment. METHODS: After exclusion of organic causes, 59 patients with HVS according to Nijmegen's questionnaire (NQ) score ≥23 with associated hypocapnia (PaCO2/PETCO2<35 mm Hg) were studied. RESULTS: The most frequent comorbidities of HVS were anxiety and asthma (respectively 95% and 73% of patients). All patients described ≥3 symptoms of NQ during the HVPT vs 14% of patients during the CPET (p<0.01). For similar maximal ventilation (61 L/min during HVPT vs 60 L/min during CPET), the median level of PETCO2 decreased from 30 mmHg at baseline to 15 mmHg during hyperventilation and increased from 31 mmHg at baseline to 34 mmHg at peak exercise (all p<0.01). No significant difference for the ventilatory parameters was found between patients with HVS (n = 16) and patients with HVS + asthma (n = 43). CONCLUSIONS: In term of symptoms reproducibility, HVPT is a better diagnostic tool than CPET for HVS. An important proportion of patients with HVS has an atypical asthma previously misdiagnosed. The exercise-induced hyperventilation did not induce abnormal reduction in PETCO2, suggesting that the exercise could be a therapeutic tool in HVS.

Habituation or Normalization? Experiential and Respiratory Recovery From Voluntary Hyperventilation in Treated Versus Untreated Patients With Panic Disorder.

Psychophysiological theories postulate respiratory dysregulation as a mechanism contributing to panic disorder (PD). Additionally, symptomatic and respiratory recovery from voluntary hyperventilation (HVT-recovery) have been shown to lag in PD and it is unclear if HVT-recovery normalizes with treatment. Thirty-seven panic disorder patients were randomized to hypoventilation therapy (TX, n = 20) or waitlist control (WL, n = 17) (Meuret et al., 2008). In a secondary analysis, their HVT-recovery was analyzed at pre- and post-TX/WL, compared to 29 healthy controls (HC). HVT included three phases: 5-min baseline, 3-min hyperventilation, and 8-min recovery. HVT-elicited symptom severity and anxiety were rated following each phase, and end-tidal PCO2 and respiratory rate (RR) were recorded throughout. Treatment, compared to WL, was highly effective in reducing PD pathology (d=2.21, Meuret et al., 2008). At pre-TX/WL, PD demonstrated delayed HVT-recovery PCO2 and higher RR. Treated patients demonstrated normalization of HVT-recovery for PCO2 and RR; however, improvements of HVT-recovery for symptom severity and anxiety did not differ between TX and WL. Results replicate pretreatment HVT respiratory recovery abnormalities in PD and further demonstrate normalization, comparable to HC, following successful treatment. The results provide support for respiratory dysregulation as a feature of PD and demonstrate the utility of HVT respiratory recovery as treatment outcome measure for respiration-based PD therapy.

Breathlessness and dysfunctional breathing in patients with postural orthostatic tachycardia syndrome (POTS): The impact of a physiotherapy intervention.

Postural orthostatic tachycardia syndrome (POTS) is a chronic, multifactorial syndrome with complex symptoms of orthostatic intolerance. Breathlessness is a prevalent symptom, however little is known about the aetiology. Anecdotal evidence suggests that breathless POTS patients commonly demonstrate dysfunctional breathing/hyperventilation syndrome (DB/HVS). There are, however, no published data regarding DB/HVS in POTS, and whether physiotherapy/breathing retraining may improve patients' breathing pattern and symptoms. The aim of this study was to explore the potential impact of a physiotherapy intervention involving education and breathing control on DB/HVS in POTS. A retrospective observational cohort study of all patients with POTS referred to respiratory physiotherapy for treatment of DB/HVS over a 20-month period was undertaken. 100 patients (99 female, mean (standard deviation) age 31 (12) years) with a clinical diagnosis of DB/HV were referred, of which data was available for 66 patients pre - post intervention. Significant improvements in Nijmegen score, respiratory rate and breath hold time (seconds) were observed following treatment. These data provide a testable hypothesis that breathing retraining may provide breathless POTS patients with some symptomatic relief, thus improving their health-related quality of life. The intervention can be easily protocolised to ensure treatment fidelity. Our preliminary findings provide a platform for a subsequent randomised controlled trial of breathing retraining in POTS.

Effects of GB34 acupuncture on hyperventilation-induced carbon dioxide reactivity and cerebral blood flow velocity in the anterior and middle cerebral arteries of normal subjects.

OBJECTIVES: To determine whether acupuncture at GB34 affects cerebral blood flow (CBF) via the anterior cerebral arteries (ACAs) and middle cerebral arteries (MCAs). METHODS: This study included 10 healthy young male volunteers. CBF velocity and cerebrovascular reactivity (CVR) were measured using transcranial Doppler sonography (TCD). The changes in hyperventilation-induced carbon dioxide (CO2) reactivity and modified blood flow velocity at 40 mm Hg (CV40) were observed for both ACAs and MCAs before and after GB34 acupuncture treatment. Blood pressure and heart rate were also measured before and after GB34 acupuncture treatment. RESULTS: The CO2 reactivity of the ipsilateral MCA significantly increased after GB34 acupuncture treatment, compared with that at baseline (P=0.007). In contrast, the CO2 reactivity of both ACAs and the contralateral MCA remained unchanged. The CV40 of both ACAs and MCAs did not change after GB34 acupuncture treatment and neither did the mean arterial blood pressure and heart rate. CONCLUSIONS: GB34 acupuncture treatment increased CO2 reactivity specifically in the ipsilateral MCA, but had no effect on either the ACAs or the contralateral MCA. These data suggest that GB34 acupuncture treatment improves the vasodilatory potential of the cerebral vasculature to compensate for fluctuations caused by changes in external conditions and could potentially be useful for the treatment of disorders of the ipsilateral MCA circulation.

The Effect of a Brief Mindfulness Training on Distress Tolerance and Stress Reactivity.

Poor distress tolerance (DT) is considered an underlying facet of anxiety, depression, and a number of other psychological disorders. Mindfulness may help to increase DT by fostering an attitude of acceptance or nonjudgment toward distressing experiences. Accordingly, the present study examined the effects of a brief mindfulness training on tolerance of different types of distress, and tested whether trait mindfulness moderates the effect of such training. Undergraduates (n = 107) naïve to mindfulness completed a measure of trait mindfulness and underwent a series of stress tasks (cold pressor, hyperventilation challenge, neutralization task) before and after completing a 15-minute mindfulness training or a no-instruction control in which participants listened to relaxing music. Participants in the mindfulness condition demonstrated greater task persistence on the hyperventilation task compared to the control group, as well as a decreased urge to neutralize the effects of writing an upsetting sentence. No effect on distress ratings during the tasks were found. Overall trait mindfulness did not significantly moderate task persistence, but those with lower scores on the act with awareness facet of mindfulness demonstrated greater relative benefit of mindfulness training on the hyperventilation challenge. Mediation analyses revealed significant indirect effects of mindfulness training on cold pressor task persistence and urges to neutralize through the use of the nonjudge and nonreact facets of mindfulness. These results suggest that a brief mindfulness training can increase DT without affecting the subjective experience of distress.

Diagnosis and management in Pitt-Hopkins syndrome: First international consensus statement.

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, specific facial features, and marked autonomic nervous system dysfunction, especially with disturbances of regulating respiration and intestinal mobility. It is caused by variants in the transcription factor TCF4. Heterogeneity in the clinical and molecular diagnostic criteria and care practices has prompted a group of international experts to establish guidelines for diagnostics and care. For issues, for which there was limited information available in international literature, we collaborated with national support groups and the participants of a syndrome specific international conference to obtain further information. Here, we discuss the resultant consensus, including the clinical definition of PTHS and a molecular diagnostic pathway. Recommendations for managing particular health problems such as dysregulated respiration are provided. We emphasize the need for integration of care for physical and behavioral issues. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimization of diagnostics and care.

Hypoventilation Therapy Alleviates Panic by Repeated Induction of Dyspnea.

BACKGROUND: Previous research has shown that hypoventilation therapy reduces panic symptoms in part by increasing basal partial pressure of carbon dioxide (PCO2) levels. We tested an additional pathway by which hypoventilation therapy could exert its therapeutic effects: through repeated interoceptive exposure to sensations of dyspnea. METHODS: A total of 35 patients with panic disorder were trained to perform exercises to raise their end-tidal PCO2 levels using a portable capnometry device. Anxiety, dyspnea, end-tidal PCO2, and respiratory rate were assessed during each exercise across 4 weeks of training. Mixed-model analysis examined whether within-exercise levels of dyspnea were predictive of reduction of panicogenic cognitions. RESULTS: As expected, within-exercise anxiety and respiratory rate decreased over time. Unexpectedly, PCO2 dropped significantly from the beginning to the end of exercise, with these drops becoming progressively smaller across weeks. Dyspnea increased and remained consistently above basal levels across weeks. As hypothesized, greater dyspnea was related to significantly lower panicogenic cognitions over time even after controlling for anxiety and PCO2. Additional exploratory analyses showed that within-exercise increases in dyspnea were related to within-exercise increases in anxiety but were not related to within-exercise increases in PCO2. CONCLUSIONS: In support of the interoceptive exposure model, we found that greater dyspnea during hypoventilation exercises resulted in lower panicogenic cognitions even after the effect of PCO2 was taken into account. The findings offer an additional important target in panic treatment.

Inhibiting the Physiological Stress Effects of a Sustained Attention Task on Shoulder Muscle Activity.

OBJECTIVE: The objective of this study was to investigate if a breathing technique could counteract the effects of hyperventilation due to a sustained attention task on shoulder muscle activity. BACKGROUND: The trend towards higher levels of automation in industry is increasing. Consequently, manufacturing operators often monitor automated process for long periods of their work shift. Prolonged monitoring work requires sustained attention, which is a cognitive process that humans are typically poor at and find stressful. As sustained attention becomes an increasing requirement of manufacturing operators' job content, the resulting stress experienced could contribute to the onset of many health problems, including work related musculoskeletal disorders (WRMSDs). METHODS: The SART attention test was completed by a group of participants before and after a breathing intervention exercise. The effects of the abdominal breathing intervention on breathing rate, upper trapezius muscle activity and end-tidal CO2 were evaluated. RESULTS: The breathing intervention reduced the moderation effect of end-tidal CO2 on upper trapezius muscle activity. CONCLUSIONS: Abdominal breathing could be a useful technique in reducing the effects of sustained attention work on muscular activity. APPLICATION: This research can be applied to highly-automated manufacturing industries, where prolonged monitoring of work is widespread and could, in its role as a stressor, be a potential contributor to WRMSDs.

Pitt-Hopkins Syndrome: A Review of Current Literature, Clinical Approach, and 23-Patient Case Series.

Pitt-Hopkins syndrome (PTHS) is a rare, genetic disorder caused by a molecular variant of TCF4 which is involved in embryologic neuronal differentiation. PTHS is characterized by syndromic facies, psychomotor delay, and intellectual disability. Other associated features include early-onset myopia, seizures, constipation, and hyperventilation-apneic spells. Many also meet criteria for autism spectrum disorder. Here the authors present a series of 23 PTHS patients with molecularly confirmed TCF4 variants and describe 3 unique individuals. The first carries a small deletion but does not exhibit the typical facial features nor the typical pattern of developmental delay. The second exhibits typical facial features, but has attained more advanced motor and verbal skills than other reported cases to date. The third displays typical features of PTHS, however inherited a large chromosomal duplication involving TCF4 from his unaffected father with somatic mosaicism. To the authors' knowledge, this is the first chromosomal duplication case reported to date.

Effects of massage therapy on anxiety, depression, hyperventilation and quality of life in HIV infected patients: A randomized controlled trial.

INTRODUCTION: HIV infection is often preceded or accompanied by psychiatric comorbidities. These disorders improve with complementary therapies. The aim of this study was to measure the effect of massage therapy on anxiety, depression, hyperventilation and quality of life in HIV infected patients. METHOD: Adult HIV-infected patients were randomized (n=29) in massage therapy group (one hour a week during four weeks) and control group. Anxiety and depression (HADS-A and HADS-D), hyperventilation (Nijmegen questionnaire) and quality of life (WHOQOL-HIV) were evaluated at inclusion and after 4 weeks. RESULTS: At inclusion, 51% and 17% of the patients had a positive HADS-A and HADS-D score respectively. Two facets from WHOQOL-HIV ("Home environment" and "Death and dying" (p=0.04)) were different between groups. After the four week massage therapy, a significant improvement was observed only for Nijmegen questionnaire (p=0.01) and HADS-A (p=0.04) contrarily to WHOQOL-HIV and HADS-D. Domains of the WHOQOL-HIV did not improve following the massage therapy. Only "Pain and discomfort" facet improved after massage therapy (p=0.04). CONCLUSION: This study highlights the positive impact of a four week massage therapy on anxiety and hyperventilation in HIV infected patients. However, neither benefit of this program was observed on depression and quality of life.

[Which treatments for the hyperventilation syndrome in adults?] / Quels traitements proposer dans le syndrome d'hyperventilation chez l'adulte ?

The hyperventilation syndrome is a complex entity whose management is poorly codified. We report a synthesis about the management of adult patients diagnosed with hyperventilation syndrome. A systematic literature review has identified fifteen articles dealing, among them three studies about drug treatment and the others about non-pharmacological approaches. Among the last ones, a re-educational approach based on abdominal ventilation and regulation of the ventilatory rate seems and an educative approach seems to be the most effective. Methodological biases did not permit a conclusion on the efficacy of these treatments. Practically, teaching abdominal ventilation and respiratory rate regulation, associated with a personalized therapeutic education, seems to be a pertinent management approach. Other clinical studies should explore this issue.

A 56-Year-Old, Otherwise Healthy Woman Presenting With Light-headedness and Progressive Shortness of Breath.

A 56-year-old white woman was referred to the pulmonary clinic for evaluation of unexplained shortness of breath. She enjoyed good health until 3 months prior to this visit when she reported experiencing recurrent episodes of shortness of breath and oppressive retrosternal chest discomfort with radiation to the neck. Episodes lasting 5 to 10 min often occurred at rest and were inconsistently related to physical activity. These symptoms became progressively worse and were often associated with light-headedness and presyncope. Her past medical history was uneventful apart from a prior diagnosis of breast cysts and suspected prolactinoma. Her symptoms escalated to such a level that she was forced to seek urgent medical attention at our institutional ED on two separate occasions in the preceding weeks. These visits precipitated a number of investigations and, eventually, a referral to the pulmonary clinic.

Feasibility and Efficacy of an mHealth Game for Managing Anxiety: "Flowy" Randomized Controlled Pilot Trial and Design Evaluation.

OBJECTIVE: Meeting the complex needs of patients with chronic common mental health disorders (CMHDs) may be the greatest challenge facing organized medical practice. On the basis of a well-established and proven theoretical foundation for controlled respiration as a behavioral intervention for CMHDs, as well as preliminary evidence that gamification can improve health outcomes through increasing patient engagement, this randomized controlled pilot study evaluated the feasibility and clinical efficacy of a mobile health game called "Flowy" ( www.flowygame.com ) that digitally delivered breathing retraining exercises for anxiety, panic, and hyperventilation symptom management. MATERIALS AND METHODS: We designed an unblinded, Web-based, parallel-group randomized controlled trial focusing on feasibility, clinical efficacy, and design proof of concept. In the intervention condition (n = 31), participants received free access to "Flowy" for 4 weeks. In the control condition (n = 32), participants were placed on a waitlist for 4 weeks before being offered free access to "Flowy." Online measurements using psychological self-report questionnaires were made at 2 and 4 weeks post-baseline. RESULTS: At trial conclusion, participants found "Flowy" acceptable as an anxiety management intervention. "Flowy" engaged participants sufficiently to endorse proactive gameplay. Intent-to-treat analysis revealed a reduction in anxiety, panic, and self-report hyperventilation scores in both trial arms, with the intervention arm experiencing greater quality of life. Participants perceived "Flowy" as a fun and useful intervention, proactively used "Flowy" as part of their care, and would recommend "Flowy" to family and friends. CONCLUSIONS: Our results suggest that a digital delivery of breathing retraining exercises through a mobile health game can manage anxiety, panic, and hyperventilation symptoms associated with CMHDs.

Restoring heat stress-associated reduction in middle cerebral artery velocity does not reduce fatigue in the heat.

Heat-induced hyperventilation may reduce PaCO2 and thereby cerebral perfusion and oxygenation and in turn exercise performance. To test this hypothesis, eight volunteers completed three incremental exercise tests to exhaustion: (a) 18 °C ambient temperature (CON); (b) 38 °C (HEAT); and (c) 38 °C with addition of CO2 to inspiration to prevent the hyperventilation-induced reduction in PaCO2 (HEAT + CO2 ). In HEAT and HEAT + CO2 , rectal temperature was elevated prior to the exercise tests by means of hot water submersion and was higher (P < 0.05) than in CON. Compared with CON, ventilation was elevated (P < 0.01), and hence, PaCO2 reduced in HEAT. This caused a reduction (P < 0.05) in mean cerebral artery velocity (MCAvmean ) from 68.6 ± 15.5 to 53.9 ± 10.0 cm/s, which was completely restored in HEAT + CO2 (68.8 ± 5.8 cm/s). Cerebral oxygenation followed a similar pattern. V ˙ O 2   m a x was 4.6 ± 0.1 L/min in CON and decreased (P < 0.05) to 4.1 ± 0.2 L/min in HEAT and remained reduced in HEAT + CO2 (4.1 ± 0.2 L/min). Despite normalization of MCAvmean and cerebral oxygenation in HEAT + CO2 , this did not improve exercise performance, and thus, the reduced MCAvmean in HEAT does not seem to limit exercise performance.