Congenital central hypoventilation syndrome (CCHS) is an autosomal dominant disease that is caused by heterozygous mutations in the paired-like homeobox 2B gene (PHOX2B). Madani et al. described an abnormally high degree of not only central apnea but also obstructive and mixed apnea in Phox2b27Ala/+newborn mice. Newborns with CCHS must undergo polysomnography for obstructive respiratory events in order to guide the optimal ventilation strategy if oxygen desaturation, bradycardia, and malaise persist under noninvasive ventilation. Newborns and infants with CCHS must be systematically tested for obstructive apnea, especially in cases of inefficient noninvasive ventilation.

ADPRHL2 is involved in posttranslational modification and is known to have a role in physiological functions such as cell signaling, DNA repair, gene control, cell death, and response to stress. Recently, a group of neurological disorders due to ADPRHL2 variants is described, characterized by childhood-onset, stress-induced variable movement disorders, neuropathy, seizures, and neurodegenerative course. We present the diagnostic pathway of two pediatric patients with episodic dystonia and ataxia, who later had a neurodegenerative course complicated by central hypoventilation syndrome due to the same homozygous ADPRHL2 variant. We conducted a systematic literature search and data extraction procedure following the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 statement in terms of patients with ADPRHL2 variants, from 2018 up to 3 February, 2023. In total, 12 articles describing 47 patients were included in the final analysis. Median age at symptom onset was 2 (0.7-25) years, with the most common presenting symptoms being gait problems (n = 19, 40.4%), seizures (n = 16, 34%), ataxia (n = 13, 27.6%), and weakness (n = 10, 21.2%). Triggering factors (28/47; 59.5%) and regression (28/43; 60.4%), axonal polyneuropathy (9/23; 39.1%), and cerebral and cerebellar atrophy with white matter changes (28/36; 77.7%) were the other clues. The fatality rate and median age of death were 44.6% (n = 21) and 7 (2-34) years, respectively. ADPRHL2 variants should be considered in the context of episodic, stress-induced pediatric and adult-onset movement disorders and seizures.

To provide an overview of the discovery, presentation, and management of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD). To discuss a search for causative etiology spanning multiple disciplines and continents.
The literature (1965-2022) on the diagnosis, management, pathophysiology, and potential etiology of ROHHAD was methodically reviewed. The experience of several academic centers with expertise in ROHHAD is presented, along with a detailed discussion of scientific discovery in the search for a cause.
ROHHAD is an ultra-rare syndrome with fewer than 200 known cases. Although variations occur, the acronym ROHHAD is intended to alert physicians to the usual sequence or unfolding of the phenotypic presentation, including the full phenotype. Nearly 60 years after its first description, more is known about the pathophysiology of ROHHAD, but the etiology remains enigmatic. The search for a genetic mutation common to patients with ROHHAD has not, to date, demonstrated a disease-defining gene. Similarly, a search for the autoimmune basis of ROHHAD has not resulted in a definitive answer. This review summarizes current knowledge and potential future directions.
ROHHAD is a poorly understood, complex, and potentially devastating disorder. The search for its cause intertwines with the search for causes of obesity and autonomic dysregulation. The care for the patient with ROHHAD necessitates collaborative international efforts to advance our knowledge and, thereby, treatment, to decrease the disease burden and eventually to stop, and/or reverse the unfolding of the phenotype.

Neuromuscular diseases (NMD) are indications for long-term home mechanical ventilation (HMV). Noninvasive ventilation is preferred to HMV. However, invasive mechanical ventilation (IMV) is more appropriate if the patient has uncontrollable airway secretions, the possibility of aspiration, failure to wean, or severe weakness of the respiratory muscles. But if the patient undergoes multiple intubation or tracheotomy, it will be more painful and unbearable. For some end-stage NMD patients who need long-term tracheostomy, HMV using noninvasive ventilator via tracheotomy may be a conservative care option. An 87-year-old male with myasthenia gravis underwent repeated IMV and failed to wean. We used a noninvasive ventilator connected to a tracheostomy tube for mechanical ventilation. One and a half years later, the patient weaned successfully. However, there was a lack of evidence-based medicine and standardized guidelines in such areas as indications, contraindications, and ventilator parameter setting. For the systematic review, a literature search was performed in PubMed, Embase, Cochrane, and CNKI (China National Knowledge Infrastructure) to identify reported cases of using noninvasive ventilator in patients undergoing tracheostomy. A total of 72 cases who performed ventilation via tracheotomy tube were identified. The main diagnoses included NMD, chronic obstructive pulmonary disease (COPD), pneumonia, and congenital central hypoventilation syndrome (CCHS). Indications included dysfunctional ventilatory weaning response (DVWR), apnea and cyanosis. Clinical outcome was as follows: 33 patients were weaned, and 24 patients underwent HMV. A total of 288 cases who performed ventilation through the mask after blocking the tracheostomy tube were identified. The primary diagnoses included COPD, NMD, thoracic restriction, spinal cord injured (SCI), and CCHS. Indications included DVWR, apnea and cyanosis, routine weaning. Clinical outcome was as follows: successful tracheostomy tube decannulations were performed in 254 patients and failed in 33 patients. So, in patients requiring HMV, selection of noninvasive ventilation (NIV) or IMV should be individualized. Tracheostomy preservation should be considered in some patients with advanced NMD if there is respiratory muscle weakness or the risk of aspiration. And attempts can be made to use a noninvasive ventilator because of its advantages of portability, ease of operation, and low cost. Noninvasive ventilators can be used in patients with tracheotomy, whether direct connection tracheotomy or mask ventilation after the tube is capped, especially in weaning and tracheostomy tube decannulation.

Only 15 patients of autoimmune encephalitis with metabotropic glutamate receptor 5 (mGluR5) antibodies have been reported worldwide since 2011, mostly from western countries. Patients with different genetic backgrounds are necessary to further clarify the clinical phenotype and prognosis of this rare disease.
We initially describe a case series from China to confirm the previous findings, expand the clinical phenotype, and identify the prognostic factors of autoimmune encephalitis with mGluR5 antibodies.
Observational data with follow-up were prospectively collected from autoimmune encephalitis patients with mGluR5 antibodies. Clinical information and outcomes on current and previously reported cases were combined and analyzed.
We identified five patients (median age 35 years); two were female. The main clinical manifestations were behavioral/personality changes (five of five, 100%) and cognitive disorders (four of five, 80%), accompanied with other neurologic symptoms. Hypoventilation occurred in two (40%) patients, which was life-threatening. One patient had meningoencephalitis, suggesting a new phenotype in anti-mGluR5 encephalitis. All patients received immunotherapy. At the last follow-up (median 18 months), two (40%) patients showed complete recovery, two (40%) patients showed partial recovery, and one (20%) patient died. One (20%) patient had multiple relapses. Together with the 15 previously reported cases, associated tumors occurred in seven of 12 (58%) Western patients vs. one of eight (13%) Chinese patients. Modified Rankin Scale (mRS) scores at the last follow-up (median 31 months) were available in 16 patients. Patients with bad outcomes (mRS > 2, n = 4) were more likely to have hypoventilation at onset and higher mRS scores at peak of the disease.
In patients with different genetic background, as Chinese, the clinical phenotype of anti-mGluR5 encephalitis is similar. Fewer paraneoplastic cases were observed in Chinese patients. Most patients showed good responses to immunotherapy and cancer treatment. The clinical outcomes were favorable in most patients.

Individuals with biallelic TBCK pathogenic variants present in infancy with distinctive facial features, profound hypotonia, severe intellectual impairment and epilepsy. Although rare, it may mimic other neurogenetic disorders leading to extensive investigations. Improved understanding of the clinical phenotype can support early monitoring of complications due to respiratory insufficiency. We present six individuals who were found to have pathogenic biallelic TBCK variants. The clinico-radiological and diagnostic records were reviewed. Five individuals were diagnosed with hypoventilation, requiring respiratory support, highlighting the need for early respiratory surveillance. Characteristic brain imaging in our cohort included periventricular leukomalacia-like changes. We recommend screening for TBCK in hypotonic children with periventricular leukomalacia-like changes, particularly in the absence of prematurity.

Hypertension is a widespread disease that, if persistent, increases the risks of coronary heart disease mortality and morbidity. Slow breathing is a recommended blood pressure-lowering strategy though the mechanisms mediating its effects are unknown.
This review aims to evaluate autonomic and vascular function as potential mediators driving BP adaptive responses with slow breathing.
We searched EBSCO host, Web of Science, Cochrane Central Register of Controlled Trials, and PubMed using key words for optimized search results.
Nineteen studies were included in this review (11 device-guided; 8 non-device-guided breathing). Though some studies showed increased vagally mediated components of heart rate variability during slow breathing, results from acute and long-term studies were incongruent. Increases in baroreflex sensitivity (BRS) following a single device-guided slow breathing bout were noted in normotensive and hypertensive adults. Long-term (4 weeks to 3 months) effects of slow breathing on BRS were absent. Device-guided breathing resulted in immediate reductions in muscle sympathetic nerve activity (MSNA) in normo- and hyper-tensive adults though results from long-term studies yielded inconsistent findings. Non-device-guided slow breathing posed acute and chronic effects on vascular function with reductions in arterial stiffness in adults with type I diabetes and increases in microvascular endothelial function in adults with irritable bowel syndrome. Non-device guided breathing also reduced pro-inflammatory cytokines in healthy and hypertensive adults in acute and chronic studies. No adverse effects or non-adherence to treatment were noted in these trials.
Device-guided slow breathing is a feasible and effective modality in improving BRS, HRV, and arterial stiffness though its long-term effects are obscure. Though less evidence exists supporting the efficacy of non-device-guided slow breathing, acute and chronic studies demonstrate improvements in vascular function and inflammatory cytokines. More studies are needed to further explore the long-term effects of slow breathing in general and non-device-guided breathing in particular.

Perry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP-43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease.
Data on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed.
Parkinsonism was symmetrical, progressed rapidly and was poorly responsive to L-Dopa; nonetheless, a trial with high doses of L-Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L-Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP-43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1-related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play.
Perry disease and other DCTN1-related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy.

Obstructive sleep apnoea (OSA) now affects one-seventh of the world\'s population. Treatment of even mild OSA can improve daytime sleepiness and quality of life. Recent modifications to uvulopalatopharyngoplasty may make it a more widely applicable treatment option in selected patients with OSA. Diet and exercise have effects on sleep apnoea severity independent of weight loss. Insomnia has become increasingly common during the coronavirus disease 2019 (COVID-19) pandemic.

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation (ROHHAD) syndrome is a rare disease with unknown and debated etiology, characterized by precipitous obesity in young children, hypoventilation and autonomic dysregulation with various endocrine abnormalities. Neuroendocrine tumors can be associated in more than half of the cases. This rare condition has a severe outcome because of high morbidity and mortality. We provide a comprehensive description of the etiopathogenetic theories of the disease, clinical presentation, diagnostic workup and treatment possibilities.