Quality of Life and Respiratory Performance in the Laryngectomized Patient: Role of the HME Filters during Physical Activity.

Background: Permanent tracheostomy because of total laryngectomy surgery entails significant consequences for patients regarding respiratory physiopathology, such as the loss of the filtering, humidifying, and heating of air by the nose. The use of special stomal filters can provide adequate protection of the tracheal-bronchopulmonary system with a reduction in respiratory pathologies. In fact, in most cases, laryngectomy patients are first cigarette smokers who for this reason also already have respiratory diseases such as chronic obstructive pulmonary disease (COPD). Despite the availability of tracheal filters, as reported in the literature, patients often tend to limit their use due to reported breathing difficulties, especially in conditions of intense breathing. Methods: The objective of this clinical study was to evaluate the most suitable stomal filter for laryngectomy patients during physical activity. The filters studied were an INHEALTH device (Blom-Singer SpeakFree HME); two ATOS devices (Provox® Life™ Energy HME and Provox® Life™ Home HME); and an FAHL device (Laryvox HME Sport). Results: For this purpose, the performances of 31 laryngectomy patients, subjected to medium-high physical effort, were analyzed through a standardized pneumological test, the Six Minute Walking Test (6MWT), which involves a sustained walk lasting six minutes, with an evaluation of heart rate, oxygen saturation, and meters traveled every 60 s; furthermore, we examined two subjective indices, namely, the basal and final dyspnea index and the initial and final muscular fatigue index. Conclusions: The multidisciplinary approach of the laryngectomee patient must also take pulmonary rehabilitation into consideration. It is the task of the medical team and speech therapy support to help the patient in the correct choice of HME filters taking into account daily needs.

Sport in the Laryngectomized Patient: A Literature Review and Single Case Presentation.

BACKGROUND: Total laryngectomy is an operation that involves numerous problems for the patient, especially in daily life: loss of the fact, loss of voice, evident scars and persistence of the tracheostoma. Much is known about rehabilitation programs involving the voice, swallowing, shoulder girdle rehabilitation; less explored is the field of sport and sports rehabilitation in the laryngectomized patient. METHODS: We conduced systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in order to evaluate the possibilities of practicing sports for the patient after total laryngectomy. RESULTS: From an initial search of 4191 papers, we have come to include six papers for this literature review. We have also reported one of our clinical cases referring to a laryngectomized patient who swims competitively at an amateur level even after surgery with a particular device. The purpose of this work is to understand the role and importance of sport in rehabilitation and the possibilities that a frail patient like the laryngectomized patient has in practicing sport. Surely the best results are obtained in subjects who practiced sports before surgery. CONCLUSION: It is evident that sport is important in the psychological and motor recovery of the laryngectomized patient. There is still a lack of clear rehabilitation protocols, especially for water sports, which allow all laryngectomized patients to return to sports. We believe that early resumption of physical activity makes the experience of the disease less dramatic.

Extracapsular Tonsillectomy versus Intracapsular Tonsillotomy in Paediatric Patients with OSAS.

OBJECTIVE: The objective of our study was to compare our experience of intracapsular tonsillotomy performed with the help of a microdebrider usually used for adenoidectomy with results obtained from extracapsular surgery through dissection and from adenoidectomy in cases of people affected with OSAS, linked to adeno-tonsil hypertrophy, observed and treated in the last 5 years. METHODS: 3127 children with adenotonsillar hyperplasia and OSAS-related clinical symptoms (aged between 3 and 12 years) underwent tonsillectomy and/or adenoidectomy. A total of 1069 patients (Group A) underwent intracapsular tonsillotomy, while 2058 patients (Group B) underwent extracapsular tonsillectomy, from January 2014 to June 2018. The parameters considered in order to evaluate the effectiveness of the two different surgery techniques taken into consideration were as follows: the presence of possible postoperative complications, represented mainly by pain and perioperative bleeding; the level of postoperative respiratory obstruction compared with the original obstruction through night pulse oximetry, performed 6 months before and after the surgery; tonsillar hypertrophy relapse in Group A and/or the presence of residues in Group B with clinical evaluation performed 1 month, 6 months, and 1 year after the surgery; and postoperative life quality, evaluated through submitting to parents the same survey proposed before the surgery 1 month, 6 months, and 1 year after the surgery. RESULTS: Regardless of the technique used (extracapsular tonsillectomy or intracapsular tonsillotomy), there was a clear improvement in both the obstructive respiratory symptomatology and quality of life in both patient groups, as highlighted by the pulse oximetry and the OSA-18 survey submitted later. CONCLUSIONS: Intracapsular tonsillotomy surgery has improved in terms of a reduction in postoperative bleeding cases and pain reduction, with an earlier return to patients' usual lifestyle. Lastly, using a microdebrider with the intracapsular technique seems to be particularly effective in removing most of the tonsillar lymphatic tissue, leaving only a thin border of pericapsular lymphoid tissue and preventing lymphoid tissue regrowth during one year of follow-up.

Subjective Perception and Psychoacoustic Aspects of the Laryngectomee Voice: The Impact on Quality of Life.

PURPOSE: A retrospective study is presented to correlate the inter-judge consistency for the different psycho-perceptual parameters of the recently proposed Impression Noise Fluency Voicing (INFVo) perceptual rating scale for substitution voices, and the vocal function as perceived by the patient. METHODS: The scale Voice-Related Quality of Life (V-RQoL) and the Self Evaluation of Communication Experiences After Laryngectomy scale (SECEL)-a self-evaluation questionnaire of communicative experience after laryngectomy surgery-were administered to 89 total laryngectomees, subdivided in four groups depending on their type of alaryngeal voice (i.e., tracheoesophageal and esophageal speakers, electro larynx users, voiceless patients), in order to evaluate the impact of the impairment of the phonatory function on the quality of life. RESULTS: No significant differences exist among the various groups on their perception of QoL using subjective questionnaires, whereas the INFVo scale has proven to be a useful tool for the description and analysis of the psychoacoustic characteristics of the vocal signal and a reliable instrument to correctly classify the patients. It is also notable that the judgement of the patients on their own voice and those of the referees are highly significant. CONCLUSION: Although speech rehabilitation for the acquisition of a substitution voice offers a new way of communication for the laryngectomized patients, nonetheless, their QoL is not significantly related to the type of substitution voice. Therefore, improving the patient's adaptation to the new phonatory condition is mandatory.

Voice rehabilitation and quality of life in laryngectomized patients.

BACKGROUND: Total laryngectomy represents the surgical procedure necessary for the treatment of some advanced neoplasms of the hypopharyngeal-laryngeal district and involves strong functional, physical and emotional repercussions. This research investigated the way in which the rehabilitation methods, used to improve the communicative needs of laryngectomized patients, influence their perceived quality of life. METHOD: The questionnaires "V-RQoL" and "SECEL" were administered to 45 patients divided into four groups on the basis of the type of vicarious voice: group TE (27 patients), group E (7 patients), group EL (2 patients), group NV (9 patients). RESULTS: Patients using electrical or tracheo-esophageal prostheses reported a better quality of life than patients with an erythromophonic voice. Regarding postoperative satisfaction, the group with esophageal voice was the most satisfied. CONCLUSIONS: The results lead us to emphasize the importance of preoperative counseling to make the patient as aware as possible of his future condition. KEY WORDS: Cancer, Laryngectomy, Vicarious Voice, Voice Rehabilitation, Quality of Life.

Loss-Driven Topological Transitions in Lasing.

We experimentally observe lasing in a hexamer plasmonic lattice and find that, when tuning the scale of the unit cell, the polarization properties of the emission change. By a theoretical analysis, we identify the lasing modes as quasi-bound-states in continuum of topological charges of zero, one, or two. A T-matrix simulation of the structure reveals that the mode quality (Q) factors depend on the scale of the unit cell, with highest-Q modes favored by lasing. The system thus shows a loss-driven transition between lasing in modes of trivial and high-order topological charge.

Novel CTNNB1 variant leading to neurodevelopmental disorder with spastic diplegia and visual defects plus peripheral neuropathy: A case report.

Pathogenic variants in the ß1-catenin (CTNNB1) gene have been identified in patients with various diseases, including syndromic intellectual disability, autism spectrum disorder, familial exudative vitreoretinopathy, and neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV). We report on the clinical, genetic, neuroimaging, and neurophysiological data of a 15-year-old patient with complex hereditary spastic paraplegias with exotropia, dyskinesia, and cerebellar signs and a so-far unreported demyelinating (mainly sensory) polyneuropathy in her lower limbs. She carries the novel, de novo, likely pathogenic heterozygous c.603_605delinsAATA, p.(Met202Ilefs*6) frameshift variant in the CTNNB1 gene. Although peripheral neuropathy was not previously associated with NEDSDV, in light of the role of ß1-catenin as a junction protein in the peripheral as well as in the central nervous system documented in experimental studies, it might represent a causally linked and under-reported finding to be further explored.

Oncological and psychological evaluation of laryngectomized patients, pre and post implantation of voice prostheses. A single center experience.

BACKGROUND: In our study we evaluated from an oncological and psychological point of view, a group of patients who had previously undergone total laryngectomy and candidates for the placement of a vocal prosthesis, which allows to recover the voice using the air that passes from the trachea to the esophagus, thus vibrating a segment of the cervical esophagus. For the placement of the prosthesis and the oncological follow-up, we used the support of videoendoscopy, to exclude any recurrence or secondary tumors. At the same time, we subjected patients to a psychological evaluation before and after the implantation of the prostheses, to understand the behavioral changes in the two phases, and the possible achievement of the result of total autonomy, social reintegration, and recovery of oral communication, in the post-surgical phase. METHODS: We performed a complete esophagogastroduodenoscopy and psychological evaluation on 42 patients who had previously undergone a total laryngectomy, before proceeding to the creation of a tracheoesophageal fistula and the placement of a phonatory prosthesis. After six months, we re-evaluated the same patients, both from an oncological and psychological point of view. RESULTS: At the preimplantation control of the prosthesis, in endoscopy we detected three neoplastic relapses that did not allow the placement of a prosthesis, and four patients who had grade B esophagitis according to the Los Angeles classification, in the remaining 35 patients there were no complications. At the psychological evaluation, most of the patients had psychosocial disorders, with phenomena of anxiety and depression. At the check-up six months after implantation, none of the patients had relapses, and the voice prosthesis was not fully functional in a single patient. From a psychological point of view, voice recovery has significantly improved relationships both in the family and in the social sphere. CONCLUSIONS: Our experience has confirmed the interesting and advantageous use of videoendoscopy in patients undergoing total laryngectomy and candidates for the placement of a tracheoesophageal vocal prosthesis, in the evaluation of neoplastic relapses and secondary lesions of the esophagus. The role of the psychologist both in the pre and post prosthetic phase is fundamental in assessing the discomfort of these patients by helping them solve some problems such as isolation and anxiety. KEY WORDS: Anxiety, Depression, Total laryngectomy, Voice prosthesis.

Isolated neurofibromas of the great auricular nerve: A rare localization in a pediatric patient with neurofibromatosis type-1.

Peripheral nerve sheath tumors encompass a spectrum of well-defined clinicopathologic entities, ranging from benign tumors, such as neurofibromas, to high grade malignant neoplasms termed malignant peripheral nerve sheath tumors. Morphologic variability of these tumors is wide, and they engender some of the most controversial, difficult differential diagnoses. Localized neurofibromas often involve a major nerve and result typically in fusiform expansion of the nerve trunk (intraneural subtype). We report a case of circumscribed solitary neurofibromas in a 14-year-old boy with NF1 who presented to our department with a left neck swelling. The neurofibromas lesion involved the anterior branch of the great auricular nerve. The sensory symptoms initially reported by the patient (paresthesia and hyperesthesia) in the lower preauricular region. Surgical treatment represents the therapeutic method of choice in the approach to neurofibromas, considering functional disorders and possible aesthetic deformities. The case described presented difficulties in surgical excision, based on risk of functional and aesthetic results.

Quasi-BIC Mode Lasing in a Quadrumer Plasmonic Lattice.

Plasmonic lattices of metal nanoparticles have emerged as an effective platform for strong light-matter coupling, lasing, and Bose-Einstein condensation. However, the full potential of complex unit cell structures has not been exploited. On the other hand, bound states in continuum (BICs) have attracted attention, as they provide topologically protected optical modes with diverging quality factors. Here, we show that quadrumer nanoparticle lattices enable lasing in a quasi-BIC mode with a highly out-of-plane character. By combining theory with polarization-resolved measurements of the emission, we show that the lasing mode has a topological charge. Our analysis reveals that the mode is primarily polarized out-of-plane as a result of the quadrumer structure. The quality factors of the out-of-plane BIC modes of the quadrumer array can be exceedingly high. Our results unveil the power of complex multiparticle unit cells in creating topologically protected high-Q modes in periodic nanostructures.

Refining the mutational spectrum and gene-phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study.

BACKGROUND: Pontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes. METHODS: We performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASK rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters. RESULTS: A genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which accounted for nearly half cases (45%) and was mutated in females and occasionally in males. The European founder mutation p.Ala307Ser in TSEN54 and pathogenic variants in EXOSC3 accounted for 18% and 9% of cases, respectively. VLDLR, TOE1 and RARS2 were mutated in single patients. We were able to confirm only few previously reported associations, including jitteriness and clonus with TSEN54 and lower motor neuron signs with EXOSC3. When considering multiple features simultaneously, a clear association with a phenotypic cluster only emerged for EXOSC3. CONCLUSION: CASK represents the major PCH causative gene in Italy. Phenotypic variability associated with the most common genetic causes of PCH is wider than previously thought, with marked overlap between CASK and TSEN54-associated disorders.

SPG6 (NIPA1 variant): A report of a case with early-onset complex hereditary spastic paraplegia and brief literature review.

SPG6, caused by NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome) gene pathogenic variants, is mainly considered as a pure autosomal dominant hereditary spastic paraplegia (AD-HSP), even if descriptions of complex cases have also been reported. We detected the common c.316G > A, p.(Gly106Arg) pathogenic de novo substitution in a 10-year-old patient with HSP and drug-resistant eyelid myoclonia with absences. In order to assess the significance of this association, we reviewed the literature to find that 25/110 (23%) SPG6 cases are complex, including a heterogeneous spectrum of comorbidities, in which epilepsy is most represented (10%), but also featuring peripheral neuropathy (5.5%), amyotrophic lateral sclerosis (3.6%), memory deficits (3.6%) or cognitive impairment (2.7%), tremor (2.7%) and dystonia (0.9%). From this literature review and our single case experience, two main conclusions can be drawn. First, SPG6 is an AD-HSP with both pure and complex presentation, and frequent occurrence of epilepsy within the spectrum of genetic generalized epilepsies (absences, bilateral tonic-clonic, bilateral tonic-clonic with upper limbs myoclonic seizures and eyelid myoclonia with absences). Second, opposed to previous descriptions, seizures might not always be drug responsive.

Infantile-Onset Charcot-Marie-Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature.

Background: Charcot-Marie-Tooth (CMT) is the most frequent group of inherited neuropathies and includes several heterogeneous phenotypes. Over 80 causative genes have been described so far. Variants in the microrchidia family CW-type zinc finger 2 (MORC2) gene have been described in several axonal polyneuropathy (CMT2) patients with childhood or adult onset. Occasionally more complex phenotypes with delayed milestones, severe hypotonia, intellectual disability, dystonic postures, pyramidal signs, and neuroimaging abnormalities have been reported. Case Presentation: We report on a patient with a de novo MORC2 gene variant (c.1181A>G p.Tyr394Cys) with a history of developmental delay, axial hypotonia, progressive gait disorder with dystonic features, and intentional tremor. At the age of 8 years, he showed bilateral pyramidal signs (clonus, increased tendon reflexes, and Babinski sign) and bilateral pes cavus. The first neuroimaging performed at the age of 3 years demonstrated white matter abnormalities in the posterior periventricular zone, in the frontal lobes bilaterally and at the midbrain, stable during childhood and adolescence. Nerve conduction studies (NCS) were negative until the age of 15 years, when a sensory axonal neuropathy appeared. The association between pyramidal signs and neuropathy due to the MORC2 gene variant is increasingly being highlighted, although a neuroradiological correlate is evident only in about half of the cases. Longitudinal nerve conduction velocity (NCV) are helpful to identify late-onset features and provide useful information for diagnosis in patients with rare neurogenetic disorders. Conclusions: Characterization of complex neurological disorders is important to delineate the expanding phenotypic spectrum of MORC2-related disease, to confirm if possible the pathogenicity of the variants and to deepen the genotype-phenotype correlation.

Beneficial effects of the ketogenic diet on drug-resistant epileptic encephalopathy associated with a de novo NBEA pathogenic variant.

Although neurobeachin (NBEA) de novo genetic variants have been mainly reported in patients with neurodevelopmental disorders (NDD), they have also been recently associated with early childhood epilepsy. We report an 11-year-old boy who was first evaluated at 34 months of age because of drug-resistant epileptic encephalopathy. He also had developmental delay and prominent autistic features. Whole-exome sequencing (WES) disclosed a pathogenic NBEA c.5258_5279del, p.(Ala1753Valfs*13) variant, occurring de novo and a paternally-inherited heterozygous NBEA c.416T>C p.(Met139Thr) variant of uncertain significance (VUS). The patient showed good response to the ketogenic diet, suggesting that this therapy may be an effective option for patients with seizures who carry NBEA variants.

Posterior Lissencephaly Associated with Subcortical Band Heterotopia Due to a Variation in the CEP85L Gene: A Case Report and Refining of the Phenotypic Spectrum.

Lissencephaly describes a group of conditions characterized by the absence of normal cerebral convolutions and abnormalities of cortical development. To date, at least 20 genes have been identified as involved in the pathogenesis of this condition. Variants in CEP85L, encoding a protein involved in the regulation of neuronal migration, have been recently described as causative of lissencephaly with a posterior-prevalent involvement of the cerebral cortex and an autosomal dominant pattern of inheritance. Here, we describe a 3-year-old boy with slightly delayed psychomotor development and mild dysmorphic features, including bitemporal narrowing, protruding ears with up-lifted lobes and posterior plagiocephaly. Brain MRI at birth identified type 1 lissencephaly, prevalently in the temporo-occipito-parietal regions of both hemispheres with "double-cortex" (Dobyns' 1-2 degree) periventricular band alterations. Whole-exome sequencing revealed a previously unreported de novo pathogenic variant in the CEP85L gene (NM_001042475.3:c.232+1del). Only 20 patients have been reported as carriers of pathogenic CEP85L variants to date. They show lissencephaly with prevalent posterior involvement, variable cognitive deficits and epilepsy. The present case report indicates the clinical variability associated with CEP85L variants that are not invariantly associated with severe phenotypes and poor outcome, and underscores the importance of including this gene in diagnostic panels for lissencephaly.

Further delineation of PIGB-related early infantile epileptic encephalopathy.

Pathogenic variants in phosphatidylinositol glycan anchor biosynthesis class B (PIGB) gene have been first described as the cause of early infantile epileptic encephalopathy 80 (EIEE-80) in 2019. This disorder, an inherited glycosylphosphatidylinositol deficiency, is associated with a complex neurologic phenotype, including developmental delay, early-onset epilepsy and peripheral neuropathy. We report on a 5 year-old girl born from consanguineous parents, manifesting severe global developmental delay with absent speech, mixed peripheral polyneuropathy, hypotonia, bilateral equino-varo-supinated-cavus foot, early-onset scoliosis, elevated serum alkaline phosphatase and a single episode of febrile status epilepticus. Hypomyelination was documented on brain MRI. Whole-exome sequencing (WES) disclosed the likely pathogenic biallelic PIGB NM_004855.4: c.463G > C, p.(Asp155His) missense variant. In our patient, while other characteristic clinical, neuroimaging and laboratory findings (as described in the first research paper) were present, seizures were not a major clinical issue, thus contributing to our knowledge on this ultra-rare disorder.

Pharmacological Treatment of Severe Breathing Abnormalities in a Case of HNRNPU Epileptic Encephalopathy.

Abnormal breathing patterns are a typical feature of Rett and Pitt-Hopkins syndrome and their variants. Their treatment can be challenging, with a risk of long-term detrimental consequences. Early infantile epileptic encephalopathy (EIEE) type 54 is a rare epileptic encephalopathy caused by pathogenic variants in the heterogeneous nuclear ribonucleoprotein U (HNRNPU) gene. Only one case has been described in the literature with episodes of hyperventilation and apnea, but treatment was not discussed. We describe the clinical and genetic features and treatment strategies in a case of EIEE type 54 and severely abnormal breathing pattern. A novel and likely pathogenic c.2277dup, p.(Pro760Serfs*5) variant in the HNRNPU gene was found in a male patient with severe episodes of hyperventilation and apnea, leading to syncope. Combination therapy with acetazolamide, alprazolam and aripiprazole led to significant clinical improvement. Although HNRNPU has not been implicated in breathing control, pathogenic variants in this gene can be associated with the development of abnormal breathing patterns reminiscent of Rett and Pitt-Hopkins syndrome. Its function as a gene expression regulator and its interaction with transcription factors offers a potential pathogenetic link between these 3 disorders. Based on our experience, treatment strategies can be similar to those already applied for patients with Pitt-Hopkins and Rett syndrome.

Laryngeal Candidiasis Mimicking Supraglottic Carcinoma by Prolonged Inhaled Steroid Therapy: A Case Report and Review of the Literature.

Candidiasis is a rare entity reported as an isolated and primary laryngeal disease. In this condition, inhaled steroids were the single most common predisposing factor. Also mycotic infections of larynx are frequently seen in patients with immune insufficiency, although they have also been reported in individual with normal immune status. We report a case of isolated laryngeal Candidiasis in an immunocompetent individual, with an unusual presentation with exophytic lesion, edema, ulceration, white plaque, and pseudomembranous formation mimicking supraglottic carcinoma, to highlight the clinical of this condition and provide a review of the literature.