Hyperventilation-Induced Nystagmus in Acute Unilateral Vestibulopathy: A Correlation with Vestibulo-ocular Reflex Gain and Clinical Implication.

Hyperventilation-induced nystagmus test (HINT) is capable of generating a response in 77.2% of cases of acute unilateral vestibulopathy (AUVP); both nystagmus toward the affected side (excitatory pattern) and toward the healthy side (inhibitory pattern) have been described. The aim of the study is to investigate the clinical and prognostic role of the test by evaluating its correlation with vestibulo-ocular reflex (VOR) gain. We evaluated 33 AUVP patients by performing the HINT and video head impulse test (V-HIT) during the acute phase and then at 15 and 90 days after the onset of the symptoms. The correlation between the VOR gain of the affected side and test responses was evaluated first, phase by phase, and then considering the pattern shown during the first assessments. Patients with a negative HINT had a higher mean VOR gain than patients with a positive test at both 15 and 90 days. Patients who showed an inhibitory pattern at the first assessment had a continuous improvement in V-HIT performance, while patients with an initial excitatory response had a transient decrease in gain at the subsequent evaluation (P=.001). No difference between these 2 groups emerged at 90 days (P=.09). The finding of a negative HINT during the follow-up correlates with good V-HIT performance and could be an indicator of good recovery. The inhibitory pattern is associated with a subsequent improvement; and it would be indicative of compensation. but, despite this, the prognostic value of the test is limited.

Clinical Reasoning: Hyperventilation-Induced Alternating Hemiplegia With Concomitant Hemispheric EEG Slowing in a 7-Year-Old Girl With Headache.

A 7-year-old right-handed girl presented to the pediatric neurology outpatient clinic after 5 episodes of headache over the previous 3 months. Her family history was positive for migraine in the mother and maternal grandmother and for febrile seizures in the older sister. The neurologic examination and cognitive profile were normal. Five seconds after the end of hyperventilation, video-EEG showed high-amplitude delta waves predominantly over the left hemisphere with concomitant acute aphasia and right-sided weakness. After the event, which self-resolved over 8 minutes, the girl showed intact recall. A second instance of hyperventilation evoked the appearance of pseudo-rhythmic slow activity localized to the right hemisphere, associated with left-sided weakness, 20 seconds after the end of the test. This event spontaneously resolved in 3 minutes and was followed by headache.An exaggerated physiologic response to hyperventilation, the possible epileptic nature of the events, and a migraine variant were all considered in the differential. Nonetheless, the EEG slowing is shorter in duration and generalized in physiologic and paraphysiological conditions. A clear ictal morphology and evolution of the EEG activity were lacking in this case, and migraine attacks induced by hyperpnea have not been reported to date. Instead, EEG alterations similar to that observed in our patient are described in association with vascular abnormalities. We report the clinical presentation and diagnostic workup of a rare cerebrovascular disorder, highlighting the key features in the differential. Our case emphasizes the clinical value of the EEG rebuild-up phenomenon, which can help the clinician in achieving a prompt diagnosis.

Effects of sodium bicarbonate ingestion on ventilatory and cerebrovascular responses in resting heated humans.

Hyperthermia stimulates ventilation in humans. This hyperthermia-induced hyperventilation may be mediated by the activation of peripheral chemoreceptors implicated in the regulation of respiration in reaction to various chemical stimuli, including reductions in arterial pH. Here, we investigated the hypothesis that during passive heating at rest, the increases in arterial pH achieved with sodium bicarbonate ingestion, which could attenuate peripheral chemoreceptor activity, mitigate hyperthermia-induced hyperventilation. We also assessed the effect of sodium bicarbonate ingestion on cerebral blood flow responses, which are associated with hyperthermia-induced hyperventilation. Twelve healthy men ingested sodium bicarbonate (0.3 g/kg body weight) or sodium chloride (0.208 g/kg). One hundred minutes after the ingestion, the participants were passively heated using hot-water immersion (42°C) combined with a water-perfused suit. Increases in esophageal temperature (an index of core temperature) and minute ventilation (V̇E) during the heating were similar in the two trials. Moreover, when V̇E is expressed as a function of esophageal temperature, there were no between-trial differences in the core temperature threshold for hyperventilation (38.0 ± 0.3 vs. 38.0 ± 0.4°C, P = 0.469) and sensitivity of hyperthermia-induced hyperventilation as assessed by the slope of the core temperature-V̇E relation (13.5 ± 14.2 vs. 15.8 ± 15.5 L/min/°C, P = 0.831). Furthermore, middle cerebral artery mean blood velocity (an index of cerebral blood flow) decreased similarly with heating duration in both trials. These results suggest that sodium bicarbonate ingestion does not mitigate hyperthermia-induced hyperventilation and the reductions in cerebral blood flow index in resting heated humans.NEW & NOTEWORTHY Hyperthermia leads to hyperventilation and associated cerebral hypoperfusion, both of which may impair heat tolerance. This hyperthermia-induced hyperventilation may be mediated by peripheral chemoreceptors, which can be activated by reductions in arterial pH. However, our results suggest that sodium bicarbonate ingestion, which can increase arterial pH, is not an effective intervention in alleviating hyperthermia-induced hyperventilation and cerebral hypoperfusion in resting heated humans.

The effect of acute respiratory demand on postural control: A systematic review.

BACKGROUND: Postural control can be challenged by breathing. RESEARCH QUESTION: What is the effect of an acute increase in respiratory demand on postural control compared to quiet breathing? METHODS: A systematic review was conducted. Electronic databases were systematically searched until October 18, 2022 on studies reporting changes in center of pressure (CoP) motion related to an acute manipulation of respiratory demand compared to quiet breathing during upright standing in healthy participants and/or participants with a clinical condition. RESULTS: Twenty-one studies in healthy participants showed that voluntary (not metabolic-induced) hyperventilation or inspiratory resistive loading significantly increased CoP motion, while breath-holding decreased CoP motion, compared to quiet breathing (p< 0.05). Manipulating respiratory rate or breathing patterns did not reveal consistent results. Four studies showed that people with low back pain showed similar CoP responses to increasing respiratory demand (p> 0.05), except for breathing at different rates, whereas they showed greater CoP motion during quiet breathing. SIGNIFICANCE: The extent of postural disturbance depended on the breathing mode and how it was quantified (i.e., CoP coupled with breathing movement or overall CoP measures). Voluntary hyperventilation and inspiratory resistive loading increased postural sway. For voluntary hyperventilation, this could be explained by CoP motion being directly coupled to chest wall movements whereas metabolic-induced hyperventilation did not increase CoP motion or CoP coupling with breathing. Breath-holding decreased postural sway. Patients with low back pain show greater postural sways than pain-free individuals during quiet breathing, although they exhibit similar postural adaptations to respiratory-related challenges as controls.

Skeletal muscle vulnerability in a child with Pitt-Hopkins syndrome.

BACKGROUND: TCF4 acts as a transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5 motif. Dominant variants in TCF4 are associated with the manifestation of Pitt-Hopkins syndrome, a rare disease characterized by severe mental retardation, certain features of facial dysmorphism and, in many cases, with abnormalities in respiratory rhythm (episodes of paroxysmal tachypnea and hyperventilation, followed by apnea and cyanosis). Frequently, patients also develop epilepsy, microcephaly, and postnatal short stature. Although TCF4 is expressed in skeletal muscle and TCF4 seems to play a role in myogenesis as demonstrated in mice, potential myopathological findings taking place upon the presence of dominant TCF4 variants are thus far not described in human skeletal muscle. METHOD: To address the pathological effect of a novel deletion affecting exons 15 and 16 of TCF4 on skeletal muscle, histological and immunofluorescence studies were carried out on a quadriceps biopsy in addition to targeted transcript studies and global proteomic profiling. RESULTS: We report on muscle biopsy findings from a Pitt-Hopkins patient with a novel heterozygous deletion spanning exon 15 and 16 presenting with neuromuscular symptoms. Microscopic characterization of the muscle biopsy revealed moderate fiber type I predominance, imbalance in the proportion of fibroblasts co-expressing Vimentin and CD90, and indicate activation of the complement cascade in TCF4-mutant muscle. Protein dysregulations were unraveled by proteomic profiling. Transcript studies confirmed a mitochondrial vulnerability in muscle and confirmed reduced TCF4 expression. CONCLUSION: Our combined findings, for the first time, unveil myopathological changes as phenotypical association of Pitt-Hopkins syndrome and thus expand the current clinical knowledge of the disease as well as support data obtained on skeletal muscle of a mouse model.

Factors Affecting the Activation and Appearances of Epileptiform Abnormalities in Routine Electroencephalography by Different Provocation Methods.

OBJECTIVE: The objective of this study was to observe the effects of various clinical factors on the activation and appearance of epileptiform abnormalities (EAs) in routine electroencephalography (rEEG) by different provocation methods. METHODS: This observational study involved a review of 136 patients presented for EEG recording due to various indications and their EEG showing EAs during various provocation methods. RESULTS: Generalized spike-wave discharges (GSWDs) were the most frequent activated epileptiform pattern observed in, 81 (59.1%) recordings. This pattern was seen mainly in females 49 (P = 0.00), in patients with generalized seizures 48 (P = 0.00), in prolonged EEG records 3 (P = 0.03), and in both genetic 35 (P = 0.00) and lesional epilepsies 21 (P = 0.00). Focal sharp waves with bilateral synchrony (FSWSBS) were the most activated ictal pattern (P = 0.00). Ictal EAs after hyperventilation (HV) (P = 0.03) and intermittent photic stimulation (IPS) (P = 0.01) were mainly observed in patients with uncontrolled seizures (P = 0.00), and immune-mediated epilepsy (P = 0.02). Females sex (odds ratio [OR]: 1.33, confidence interval [CI]: 0.6-2.6; P = 0.25), bilateral tonic-clonic seizures (OR: 1.17, CI: 0.5-2.4; P = 0.31) and lesional epilepsies (OR: 1.45, CI: 0.7-2.9; P = 0.20) had risk of activation of EAs by provocation methods; however this risk was not statistically significant. While sleep deprivation (SD) (OR: 6.33, CI: 2.2-18.2; P = 0.00), nonrapid eye movement sleep (NREM) (OR: 2.41, CI: 1.0-5.4; P = 0.00), and prolong EEG recording (OR: 1.91, CI: 0.9-3.9; P = 0.04) were leading to a statistically significant risk of activation and appearances of EAs due to provocation. CONCLUSION: Different provocation methods can activate and augment the variety of EEG patterns of diverse clinical significance. Detection of activated ictal EAs is dependent on various patient factors, including seizure control, and the provocation method applied. Further larger prospective cohort studies with adequate sample sizes are warranted.

Résumé Objectif:L'objectif de cette étude était d'observer les effets de différents facteurs cliniques sur l'activation et l'apparition d'épileptiformes. anomalies (EA) dans l'électroencéphalographie (EEG) de routine par différentes méthodes de provocation.Méthodes:Cette étude observationnelle impliquait une examen de 136 patients présentés pour un enregistrement EEG en raison de diverses indications et de leurs EEG montrant des EA au cours de diverses méthodes de provocation.Résultats:Les décharges épileptiformes généralisées étaient le schéma épileptiforme activé le plus fréquemment observé dans 81 enregistrements (59,1 %). Cele schéma a été observé principalement chez les femmes 49 (P = 0,00), chez les patients présentant des crises généralisées 48 (P = 0,00), dans les enregistrements EEG prolongés 3 (P = 0,03), et dans les épilepsies génétiques 35 (P = 0,00) et lésionnelles 21 (P = 0,00). Les ondes aiguës focales avec synchronie bilatérale étaient les ondes critiques les plus activées motif (P = 0,00). Les AE ictales après hyperventilation (P = 0,03) et stimulation photique intermittente (P = 0,01) ont été principalement observées chez les patients avec crises incontrôlées (P = 0,00) et épilepsie à médiation immunitaire (P = 0,02). Sexe féminin (oddsratio [OR] : 1,33, intervalle de confiance [IC] :0,6­2,6; P = 0,25), crises tonico-cloniques bilatérales (OR : 1,17, IC : 0,5­2,4; P = 0,31) et épilepsies lésionnelles (OR : 1,45, IC : 0,7­2,9; P = 0,20) avait un risque d'activation des EA par des méthodes de provocation; cependant, ce risque n'était pas statistiquement significatif. Alors que la privation de sommeil (OR : 6,33, IC : 2,2­18,2; P = 0,00), sommeil à mouvements oculaires non rapides (OR : 2,41, IC : 1,0­5,4; P = 0,00) et prolonger l'enregistrement EEG (OR : 1,91, IC : 0,9­3,9; P = 0,04) entraînaient un risque statistiquement significatif d'activation et d'apparition d'AE par provocation.Conclusion:Différent les méthodes de provocation peuvent activer et augmenter la variété des schémas EEG de signification clinique diverse. La détection des EA ictaux activés est dépend de divers facteurs liés au patient, y compris le contrôle des crises et la méthode de provocation appliquée. D'autres études de cohorte prospectives plus importantes avec des tailles d'échantillons adéquates sont justifiées.

Hypocapnia in women with fibromyalgia.

OBJECTIVES: The purpose of this study was to investigate whether people with fibromyalgia (FM) have dysfunctional breathing by examining acid-base balance and comparing it with healthy controls. METHODS: Thirty-six women diagnosed with FM and 36 healthy controls matched for age and gender participated in this cross-sectional study. To evaluate acid-base balance, arterial blood was sampled from the radial artery. Carbon dioxide, oxygen, bicarbonate, base excess, pH and lactate were analysed for between-group differences. Blood gas analyses were performed stepwise on each individual to detect acid-base disturbance, which was categorized as primary respiratory and possible compensation indicating chronicity. A three-step approach was employed to evaluate pH, carbon dioxide and bicarbonate in this order. RESULTS: Women with FM had significantly lower carbon dioxide pressure (p = 0.013) and higher lactate (p = 0.038) compared to healthy controls at the group level. There were no significant differences in oxygen pressure, bicarbonate, pH and base excess. Employing a three-step acid-base analysis, 11 individuals in the FM group had a possible renally compensated mild chronic hyperventilation, compared to only 4 among the healthy controls (p = 0.042). CONCLUSIONS: In this study, we could identify a subgroup of individuals with FM who may be characterized as mild chronic hyperventilators. The results might point to a plausible dysfunctional breathing in some women with FM.

Temporal association of ventricular arrhythmias and respiratory events in heart failure patients with central sleep apnoea.

In contrast to obstructive sleep apnoea, the peak of sympathetic tone in central sleep apnoea occurs during the hyperventilation phase. To explore the temporal association of premature ventricular complex (PVC) burden in the context of the apnoea/hypopnoea-hyperpnoea cycle, the duration of apnoea/hypopnoea was defined as 100 %. We assessed the PVC burden throughout the apnoea/hypopnoea-hyperpnoea cycle during the periods of ±150 % in 50 % increments before and after the apnoea/hypopnoea phase. In this subanalysis of 54 SERVE-HF patients, PVC burden was 32 % higher in the late hyperventilation period (50-100 % after apnoea/hypopnoea) compared to the apnoea/hypopnoea phase.

Inaugural Review Prize 2023: The exercise hyperpnoea dilemma: A 21st-century perspective.

During mild or moderate exercise, alveolar ventilation increases in direct proportion to metabolic rate, regulating arterial CO2 pressure near resting levels. Mechanisms giving rise to the hyperpnoea of exercise are unsettled despite over a century of investigation. In the past three decades, neuroscience has advanced tremendously, raising optimism that the 'exercise hyperpnoea dilemma' can finally be solved. In this review, new perspectives are offered in the hope of stimulating original ideas based on modern neuroscience methods and current understanding. We first describe the ventilatory control system and the challenge exercise places upon blood-gas regulation. We highlight relevant system properties, including feedforward, feedback and adaptive (i.e., plasticity) control of breathing. We then elaborate a seldom explored hypothesis that the exercise ventilatory response continuously adapts (learns and relearns) throughout life and ponder if the memory 'engram' encoding the feedforward exercise ventilatory stimulus could reside within the cerebellum. Our hypotheses are based on accumulating evidence supporting the cerebellum's role in motor learning and the numerous direct and indirect projections from deep cerebellar nuclei to brainstem respiratory neurons. We propose that cerebellar learning may be obligatory for the accurate and adjustable exercise hyperpnoea capable of tracking changes in life conditions/experiences, and that learning arises from specific cerebellar microcircuits that can be interrogated using powerful techniques such as optogenetics and chemogenetics. Although this review is speculative, we consider it essential to reframe our perspective if we are to solve the till-now intractable exercise hyperpnoea dilemma.

Seizure provocation in EEG recordings: A data-driven approach.

OBJECTIVE: Recording seizures on video-EEG has a high diagnostic value. However, bilateral convulsive seizures constitute a risk for the patients. Our aim was to investigate the diagnostic yield and associated risks of provocation methods in short-term video-EEGs. METHODS: We extracted data on seizures and provocation methods from a large database of short-term video-EEGs with standardized annotations using SCORE (Standardized Computer-based Organized reporting of EEG). RESULTS: 2742 paroxysmal clinical episodes were recorded in 11 919 consecutive EEGs. Most epileptic seizures (54%) were provoked. Hyperventilation provoked most of typical absence seizures (55%), intermittent photic stimulation (IPS) provoked myoclonic seizures (25%) and most of bilateral convulsive seizures (55%), while 43% of focal seizures were precipitated by sleep. All but one of the 16 bilateral convulsive seizures were provoked by IPS or sleep. Latency between start of generalized photoparoxysmal EEG response and bilateral convulsive seizures were ≤3 s in all but one patient. SIGNIFICANCE: The large, structured database provides evidence for the diagnostic utility of various provocation methods in short-term video-EEGs. The risk of bilateral convulsive seizures is relatively small, but it cannot be prevented by stopping IPS after 3 s. A priori knowledge about seizure semiology helps planning patient-tailored provocation strategy in short-term video-EEGs.

Respiratory muscles's thermographic analysis in asthmatic youth with and without bronchospasm induced by eucapnic voluntary hyperpnea.

OBJECTIVE: To compare the thermographic pattern of regions of interest (ROI) of respiratory muscles in young asthmatics with and without bronchospasm induced by eucapnic voluntary hyperpnea (EVH). MATERIALS AND METHODS: Cross-sectional study carried out with 55 young (55% male and 45% females) aged 12.5 ± 3.3 years, divided in nine nonasthmatics, 22 asthmatics without exercise-induced bronchospasm compatible response (EIB-cr) and 24 asthmatics with EIB-cr. The diagnosis of EIB was given to subjects with a fall in forced expiratory volume in the first second (FEV1) ≥ 10% compared to baseline. Thermographic recordings of respiratory muscles were delimited in ROI of the sternocleidomastoid (SCM), pectoral, and rectus abdominis intention area. Thermal captures and FEV1 were taken before and 5, 10, 15 and 30 min after EVH. RESULTS: Twenty-four (52.1%) of asthmatics had EIB-cr. There was a decrease in temperature at 10 min after EVH test in the SCM, pectoral and rectus abdominis ROIs in all groups (both with p < 0.05). There was a decrease in temperature (% basal) in asthmatic with EIB-cr compared to nonasthmatics in the rectus abdominis area (p < 0.05). CONCLUSION: There was a decrease in temperature in the ROIs of different muscle groups, especially in asthmatics. The greater drop in FEV1 observed in individuals with EIB-cr was initially associated with a decrease in skin temperature, with a difference between the nonasthmatics in the abdominal muscle area. It is likely that this decrease in temperature occurred due to a temporary displacement of blood flow to the most used muscle groups, with a decrease in the region of the skin evaluated in the thermography.

Short-term mild hyperventilation on intracranial pressure, cerebral autoregulation, and oxygenation in acute brain injury patients: a prospective observational study.

Current guidelines suggest a target of partial pressure of carbon dioxide (PaCO2) of 32-35 mmHg (mild hypocapnia) as tier 2 for the management of intracranial hypertension. However, the effects of mild hyperventilation on cerebrovascular dynamics are not completely elucidated. The aim of this study is to evaluate the changes of intracranial pressure (ICP), cerebral autoregulation (measured through pressure reactivity index, PRx), and regional cerebral oxygenation (rSO2) parameters before and after induction of mild hyperventilation. Single center, observational study including patients with acute brain injury (ABI) admitted to the intensive care unit undergoing multimodal neuromonitoring and requiring titration of PaCO2 values to mild hypocapnia as tier 2 for the management of intracranial hypertension. Twenty-five patients were included in this study (40% female), median age 64.7 years (Interquartile Range, IQR = 45.9-73.2). Median Glasgow Coma Scale was 6 (IQR = 3-11). After mild hyperventilation, PaCO2 values decreased (from 42 (39-44) to 34 (32-34) mmHg, p < 0.0001), ICP and PRx significantly decreased (from 25.4 (24.1-26.4) to 17.5 (16-21.2) mmHg, p < 0.0001, and from 0.32 (0.1-0.52) to 0.12 (-0.03-0.23), p < 0.0001). rSO2 was statistically but not clinically significantly reduced (from 60% (56-64) to 59% (54-61), p < 0.0001), but the arterial component of rSO2 (ΔO2Hbi, changes in concentration of oxygenated hemoglobin of the total rSO2) decreased from 3.83 (3-6.2) µM.cm to 1.6 (0.5-3.1) µM.cm, p = 0.0001. Mild hyperventilation can reduce ICP and improve cerebral autoregulation, with minimal clinical effects on cerebral oxygenation. However, the arterial component of rSO2 was importantly reduced. Multimodal neuromonitoring is essential when titrating PaCO2 values for ICP management.

Hyperventilation testing in the diagnosis of vasospastic angina: A clinical review and meta-analysis.

BACKGROUND: Given the limited access to invasive vasospastic reactivity testing in Western Countries, there is a need to further develop alternative non-invasive diagnostic methods for vasospastic angina (VSA). Hyperventilation testing (HVT) is defined as a class IIa recommendation to diagnose VSA by the Japanese Society of Cardiology. METHODS: In this systematic review and meta-analysis reported according to the PRISMA statement, we review the mechanisms, methods, modalities and diagnostic accuracy of non-invasive HVT for the diagnostic of VSA. RESULTS: A total of 106 articles published between 1980 and 2022 about VSA and HVT were included in the systematic review, among which 16 were included in the meta-analysis for diagnostic accuracy. Twelve electrocardiogram-HVT studies including 804 patients showed a pooled sensitivity of 54% (95% confidence intervals [CI]; 30%-76%) and a pooled specificity of 99% (95% CI; 88%-100%). Four transthoracic echocardiography-HVT studies including 197 patients revealed a pooled sensitivity of 90% (95% CI; 82%-94%) and a pooled specificity of 98% (95% CI; 86%-100%). Six myocardial perfusion imaging-HVT studies including 112 patients yielded a pooled sensitivity of 95% (95% CI; 63%-100%) and a pooled specificity of 78% (95% CI; 19%-98%). Non-invasive HVT resulted in a low rate of adverse events, ventricular arrhythmias being the most frequently reported, and were resolved with the administration of nitroglycerin. CONCLUSIONS: Non-invasive HVT offers a safe alternative with high diagnostic accuracy to diagnose VSA in patients with otherwise undiagnosed causes of chest pain.

Hyperventilation Induced Seizures in Focal Epilepsy: Two Cases and a Review of Literature.

We report two cases of temporo-perisylvian epilepsy with habitual seizures consistently inducible by hyperventilation (HV). One case was non-lesional, while the other was a lesional temporo-perisylvian epilepsy. Both underwent surgical resection and were seizure-free or nearly seizure-free thereafter. We discuss the pathophysiological changes evoked by HV in healthy brains, and those with generalized and focal epilepsy. We provide a comprehensive and critical review of the literature on the role of HV in focal epilepsy. We suggest HV should be considered an activation method for patients with focal epilepsy during epilepsy monitoring unit admissions and may help in the localization of the epileptogenic network/zone.

Two types of early epileptic encephalopathy in a Pitt-Hopkins syndrome patient with a novel TCF4 mutation.

INTRODUCTION: Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by mutations in TCF4. Seizures have been found to vary among patients with PTHS. We report the case of a PTHS patient with a novel missense mutation in the gene TCF4, presenting with two types of early epileptic encephalopathy. CASE REPORT: The patient was a Japanese boy. His first seizure was reported at 17 days of age, with twitching of the left eyelid and tonic-clonic seizures on either side of his body. An ictal electroencephalogram (EEG) showed epileptic discharges arising independently from both hemispheres, occasionally resembling migrating partial seizures of infancy (MPSI) that migrated from one side to the other. Brain magnetic resonance imaging revealed agenesis of the corpus callosum. His facial characteristics included a distinctive upper lip and thickened helices. His seizures were refractory, and psychomotor development was severely delayed. At the age of 10 months, he developed West syndrome with spasms and hypsarrhythmia. After being prescribed topiramate (TPM), his seizures and EEG abnormalities dramatically improved. Also, psychomotor development progressed. Whole-exome sequencing revealed a novel de novo missense mutation in exon 18 (NM_001083962.2:c.1718A > T, p.(Asn573Ile)), corresponding to the basic region of the basic helix-loop-helix domain, which may be a causative gene for epileptic encephalopathy. CONCLUSIONS: To our knowledge, this is the first report of a patient with PTHS treated with TPM, who presented with both MPSI as well as West syndrome. This may help provide new insights regarding the phenotypes caused by mutations in TCF4.

Exercise hyperventilation and pulmonary gas exchange in chronic thromboembolic pulmonary hypertension: Effects of balloon pulmonary angioplasty.

BACKGROUND: Excessive ventilation (V̇E) and abnormal gas exchange during exercise are features of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) improves symptoms and exercise capacity. How BPA affects exercise hyperventilation and gas exchange is poorly understood. METHODS: In this longitudinal observational study, symptom-limited cardiopulmonary exercise tests and carbon monoxide lung diffusion (DLCO) were performed before and after BPA (interval, mean (SD): 3.1 (2.4) months) in 36 CTEPH patients without significant cardiac and/or pulmonary comorbidities. RESULTS: Peak work rate improved by 20% after BPA whilst V̇E at peak did not change despite improved ventilatory efficiency (lower V̇E with respect to CO2 output [V̇CO2]). At the highest identical work rate pre- and post-BPA (75 (30) watts), V̇E and alveolar-arterial oxygen gradient (P(Ai-a)O2) decreased by 17% and 19% after BPA, respectively. The physiological dead space fraction of tidal volume (VD/VT), calculated from measurements of arterial and mixed expired CO2, decreased by 20%. In the meantime, DLCO did not change. The best correlates of P(Ai-a)O2 measured at peak exercise were physiological VD/VT before BPA and DLCO after BPA. CONCLUSIONS: Ventilatory efficiency, physiological VD/VT, and pulmonary gas exchange improved after BPA. The fact that DLCO did not change suggests that the pulmonary capillary blood volume and probably the true alveolar dead space were unaffected by BPA. The correlation between DLCO measured before BPA and P(Ai-a)O2 measured after BPA suggests that DLCO may provide an easily accessible marker to predict the response to BPA in terms of pulmonary gas exchange.

Enhancement of self-sustained muscle activity through external dead space ventilation appears to be associated with hypercapnia.

We reported that external dead space ventilation (EDSV) enhanced self-sustained muscle activity (SSMA) of the human soleus muscle, which is an indirect observation of plateau potentials. However, the main factor for EDSV to enhance SSMA remains unclear. The purpose of the present study was to examine the effects of EDSV-induced hypercapnia, hypoxia, and hyperventilation on SSMA. In Experiment 1 (n = 11; normal breathing [NB], EDSV, hypoxia, and voluntary hyperventilation conditions) and Experiment 2 (n = 9; NB and normoxic hypercapnia [NH] conditions), SSMA was evoked by electrical train stimulations of the right tibial nerve and measured using surface electromyography under each respiratory condition. In Experiment 1, SSMA was significantly higher than that in the NB condition only in the EDSV condition (P < 0.05). In Experiment 2, SSMA was higher in the NH condition than in the NB condition (P < 0.05). These results suggest that the EDSV-enhanced SSMA is due to hypercapnia, not hypoxia or increased ventilation.

The involvement of the central cholinergic system in the hyperventilation effect of centrally injected nesfatin-1 in rats.

We recently demonstrated that peripheral and central administration of nesfatin-1 in fasting and satiety states generate hyperventilation activity by increasing tidal volume (TV), respiratory rate (RR), and respiratory minute ventilation (RVM). The present study aimed to investigate the mediation of central cholinergic receptors effective in respiratory control in the hyperventilation activity of nesfatin-1. Besides this, we intended to determine possible changes in blood gases due to hyperventilation activity caused by nesfatin-1 and investigate the mediation of central cholinergic receptors in these changes. Intracerebroventricular (ICV) administration of nesfatin-1 revealed a hyperventilation response with an increase in TV, RR, RMV, and pO2 and a decrease in pCO2 in saturated Sprague Dawley rats. ICV pretreatment with the muscarinic receptor antagonist atropine partially blocked the RR, RMV, pO2, and pCO2 responses produced by nesfatin-1 while completely blocking the TV response. However, central pretreatment with nicotinic receptor antagonist mecamylamine blocked the respiratory and blood gas responses induced by nesfatin-1. The study's conclusion demonstrated that nesfatin-1 had active hyperventilation effects resulting in an increase in pO2 and a decrease in pCO2. The critical finding of the study was that activation of central cholinergic receptors was involved in nesfatin-1-evoked hyperventilation and blood gas responses.

Effects of hyperventilation with face mask on brain network in patients with epilepsy.

OBJECTIVES: During the ongoing pandemic of COVID-19, wearing face masks was recommended, including patients with epilepsy doing the hyperventilation (HV) test during electroencephalogram (EEG) examination somewhere. However, evidence was still limited about the effect of HV with face mask on cortical excitability of patients with epilepsy. The motivation of this work is to make use of the graph theory of EEG to characterize the cortical excitability of patients with epilepsy when they did HV under the condition wearing a surgical face mask. METHODS: We recruited 19 patients with epilepsy and 17 normal controls. All of participants completed two HV experiments, including HV with face mask (HV+) and HV without a mask (HV). The interval was 30 min and the sequence was random. Each experiment consisted of three segments: resting EEG, EEG of HV, and EEG of post-HV. EEG were recorded successively during each experiment. Participants were asked to evaluate the discomfort degree using a questionnaire when every HV is completed. RESULTS: All of the participants felt more uncomfortable after HV + . Moreover, not only HV decreased small-worldness index in patients with epilepsy, but also HV + significantly increased the clustering coefficient in patients with epilepsy. Importantly, the three-way of Mask*HV*Epilepsy showed interaction in the clustering coefficient in the delta band, as well as in the path length and the small-worldness index in the theta band. CONCLUSIONS: The results of this study indicated that patients with epilepsy showed the increased excitability of brain network during HV + . We should pay more attention to the adverse effect on brain network excitability caused by HV + in patients with epilepsy. In the clinical practice under the COVID-19 pandemic, it is important that the wearing face mask remain cautious for the individuals with epilepsy when they carried out HV behavior such as exercise (e.g., running, etc.).