Age-Specific Clinical Features of Pediatric Malignant Hyperthermia: A Review of 187 Cases Over 60 Years in Japan.

BACKGROUND: Malignant hyperthermia (MH) is an inherited muscle disorder induced by volatile anesthetics and depolarizing muscle relaxants. While the incidence of MH is high in young, there are few reports on the clinical features of pediatric MH. In this study, we selected pediatric cases from an MH database and analyzed the clinical findings by age group. We hypothesized that there would be age-related differences in the clinical characteristics. METHODS: A retrospective analysis of MH data collected in our database during 1960 to 2020 was performed to identify pediatric subjects (≤18 years) with a Clinical Grading Scale of ≥35, indicating "very likely" or "almost certain" MH. We compared clinical characteristics among the 0 to 24 month, 2 to 12 year, and 13 to 18 year (youngest, middle, and oldest, respectively) age groups. RESULTS: Data were available for 187 patients: 15 in the youngest age group, 123 in the middle-aged group, and 49 in the oldest age group. Of these, 55 patients (29.4%) had undergone muscle biopsy and muscle contracture test. The mortality rates during the study period were 13.3%, 13.8%, 20.4%, and 15.5% in the youngest, middle, and oldest cohorts and overall, respectively. In contrast, the overall mortality rate from 2000 to 2020 was 8.8%. The most frequent initial symptoms of MH were elevated temperature (46.7%) and generalized muscular rigidity (26.7%) in the youngest cohort, masseter spasm (35.0%) and generalized muscular rigidity (19.5%) in the middle cohort, and elevated end-tidal carbon dioxide (26.5%) and tachycardia (22.4%) in the oldest cohort. Physical examination revealed that elevated temperature, sinus tachycardia, and respiratory acidosis occurred frequently in all groups. The middle cohort had high frequencies of masseter spasm (58.4%; P = .02) and dark urine (75.5%; P = .01) compared to those in the oldest groups, and had a higher peak creatine kinase level compared to those in the 3 groups. Skeletal muscle symptoms tended to be more common in patients administered succinylcholine (generalized muscular rigidity, P = .053; masseter spasm, P < .0001; dark urine, P < .0001). In particular, masseter spasm and dark urine were more common in the middle cohort when succinylcholine was administered (masseter spasm: versus youngest cohort, P = .06, versus oldest cohort, P = .027; dark urine: versus youngest cohort, P = .0072, versus oldest cohort, P = .0015). CONCLUSIONS: The clinical characteristics of pediatric patients with MH vary according to age group. The difference in initial symptoms of MH depending on age group is noteworthy information for the early diagnosis of MH.

Comparison Between Primary and Secondary Method of Closing Surgical Wound After Tooth Extraction: A Split-Mouth Study

ABSTRACT Objective: To compare and assess the primary and secondary closure techniques following extraction of impacted third molars for post-operative complications. Material and Methods: In total, 30 patients ranging between 18-30 years of age and of either sex who had bilaterally impacted mandibular third molars were randomly selected. Split mouth study method was used so that the participants served as their own control. Group 1 consisted of primary closure of left mandibular impacted third molars and Group 2 consisted of secondary closure of right mandibular impacted third molars. Basement evaluations were recorded for each patient along with subjective and objective evaluations for postoperative 7 days. Data analysis was carried out by SPSS 17.0 software using Mann-Whitney U test, Wilcoxon matched-pairs test and t-test. A p-value ≤ 0.05 was assigned as statistically significant. Results: When compared to group 1, group 2 revealed statistically less pain and swelling following the secondary closure of wound from day 1 to 7. There was a significant improvement in mouth opening in Group 2 at day 1 (p=0.0005) and at day 7 (p=0.00001). Conclusion: Secondary wound closure after disimpaction of mandibular third molar results in better postoperative recovery than primary closure.

[Localised tetanus with no obvious entry site: about a case in Bamako (Mali)]. / Tétanos localisé sans porte d´entrée apparente: à propos d´un cas à Bamako (Mali).

Tetanus is a major public health problem in sub-Saharan Africa. Localised tetanus is rare, unlike generalized tetanus which has been sufficiently described in the literature. We report a case of localised tetanus with no obvious entry site managed in the Department of Infectious Diseases in Bamako. The study involved a retired nurse aged 59 years who had not undergone tetanus booster immunisation within the last 10 years, corresponding to the date of her last delivery. She was referred to our Hospital with dysphagia associated with inability to open the buccal cavity. Patient's history was characterized by long-term therapy associated with many specialized consultations without any improvement. The diagnosis of localised tetanus with no obvious entry site was retained after having excluded any other local disorder. Outcome was favorable ten days after adequate management. Underdiagnosed or unknown to health-care providers, localised tetanus may mimic other diseases delaying diagnosis and management. Targeted campaign to build awareness should be implemented in order to improve adherence with immunization schedules.

Crisponi/cold-induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts.

Crisponi/cold-induced sweating syndrome (CS/CISS) is an autosomal recessive disease characterized by hyperthermia, camptodactyly, feeding and respiratory difficulties often leading to sudden death in the neonatal period. The affected individuals who survived the first critical years of life, develop cold-induced sweating and scoliosis in early childhood. The disease is caused by variants in the CRLF1 or in the CLCF1 gene. Both proteins form a heterodimeric complex that acts on cells expressing the ciliary neurotrophic factor receptor (CNTFR). CS/CISS belongs to the family of "CNTFR-related disorders" showing a similar clinical phenotype. Recently, variants in other genes, including KLHL7, NALCN, MAGEL2 and SCN2A, previously linked to other diseases, have been associated with a CS/CISS-like phenotype. Therefore, retinitis pigmentosa and Bohring-Optiz syndrome-like (KLHL7), Congenital contractures of the limbs and face, hypotonia, and developmental delay syndrome (NALCN), Chitayat-Hall/Schaaf-Yang syndrome (MAGEL2), and early infantile epileptic encephalopathy-11 syndrome (SCN2A) all share an overlapping phenotype with CS/CISS, especially in the neonatal period. This review aims to summarize the existing literature on CS/CISS, focusing on the current state of differential diagnosis, pathogenesis and treatment concepts in order to achieve an accurate and rapid diagnosis. This will improve patient management and enable specific treatments for the affected individuals.

Measurement properties of patient-reported outcome measures in radiotherapy-induced trismus.

Trismus or lockjaw is the reduction in mouth opening. Radiotherapy-induced trismus occurs when the masticatory muscles are within range of radiation treating head and neck cancer, resulting in muscular fibrosis and trismus. We aim to assess the measurement properties of available validated patient-reported outcome measures relevant to radiotherapy-induced trismus in head and neck cancer patients. Systematic electronic searches were performed in MEDLINE and EMBASE databases to identify studies validating radiotherapy-induced trismus with patient-reported outcome measures up to January 2018. Two reviewers independently rated the methodological quality of identified validation studies, using the consensus-based standards for the selection of health status measurement instrument (COSMIN) checklist. The level of evidence for measurement properties was then summarised based upon pre-defined criteria. Only one of the 280 retrieved studies were deemed fit for inclusion. The Gothenburg Trismus Questionnaire was assessed and found to have a good methodological quality of measurement properties except for reliability, which was poor. There was a moderate level of evidence supporting internal consistency, content validity, structural validity and hypothesis testing. The evidence for test-retest reliability remains unknown in the population of interest. The Gothenburg Trismus Questionnaire is the only patient-reported outcome measure in the field of showing some good measurement properties, and it may therefore represent a useful instrument for the assessment of radiotherapy-induced trismus in head and neck cancer patients. However, further validation studies are needed especially with respect to the reliability, measurement error and the responsiveness of this instrument.

Bi-allelic c.181_183delTGT in BTB domain of KLHL7 is associated with overlapping phenotypes of Crisponi/CISS1-like and Bohring-Opitz like syndrome.

Biallelic pathogenic variants in KLHL7 are known to result in Crisponi syndrome (CS)/cold-induced sweating syndrome type 1 (CISS1) like phenotype and Bohring-Opitz-like syndrome. In this report, a trio whole-exome sequencing (WES) was performed in proband with cold-induced sweating, microcephaly, facial dysmorphism, spasticity, failure to thrive, pigmentary abnormalities of the retina, hypoplasia of corpus callosum and periventricular nodular heterotopia. A novel homozygous in-frame deletion was identified in exon 2 of KLHL7, affecting the BTB domain of the protein. Our findings expand the clinical and molecular spectrum of KLHL7-related disorders.

Trismus surgical release and free flap reconstruction after radiation therapy in oral and oropharyngeal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: This study aims to review our experience in trismus release followed by free flap reconstruction after radiotherapy in oral and oropharyngeal cancer, describe the results obtained in long-term follow-up and identify possible predictors of outcome. METHODS: Patients' demographics, tumor characteristics and treatment where retrieved. Surgical release and reconstructive procedures were detailed. Interincisor distances (IIDs) where measured preoperatively (PO-IID), intraoperatively after release (IO-IID) and in the last follow-up (FU-IID). Potential predictors of outcome in terms of interincisor long-term gain (LT-gain) and postoperative loss (PO-loss) were analyzed. RESULTS: Twenty-eight patients were included in our study. The mean LT-gain was 8.9 ± 7.0 mm, and the PO-loss was 22.14 ± 7.27 mm. Patients with a PO-IID of 10 mm or less had a significant higher LT-gain (P = 0.038). Predictors of worse outcome included having received a previous maxillectomy during tumor ablation (lower LT-gain, P = 0.035), and previous buccal mucosa resection (higher PO-loss, P = 0.044). CONCLUSIONS: Trismus release and free flap reconstruction after radiotherapy in oral and oropharyngeal cancer patients seems to be associated with modest long term results and a high incidence of trismus recurrence, particularly in cases of prior buccal resections or maxillectomy. Patients should be adequately informed and carefully selected before indicating the procedure.

Preoperative evaluation and surgical technique of functional and cosmetic aspects in zygomatic complex fracture patients.

The zygomatico-maxillary complex functions as the principle buttress of the face and is the cornerstone to an individual’s aesthetic appearance. Its fracture not only creates cosmetic deformities owing to its position and facial contour, but can also cause disruption of ocular and mandibular functions. The aim of this study was to evaluate the quality, efficacy and impact of internal fixation of zygomatic complex fractures on functional and cosmetic outcomes. A prospective study was carried out on 100 patients who were divided according to the classification and the severity of injury. Subjective evaluation was submitted based on the patient’s perception of signs and symptoms in the preoperative and postoperative periods. Intraoperative and postoperative assessment of bone reduction quality was made according to the type of the fracture and related difficulties; also, the difference between these groups was observed as functional and esthetic outcome. To optimize the treatment of zygomatic bone fractures, a pre-designed questionnaire was used for subjective evaluation of symptoms and treatment outcome. In 70% of cases, ophthalmologic consultation was taken and was most common in type VII fractures (100% cases). Neurosensory disturbance was the most common finding (60%), followed by diplopia (56R%), pain upon mouth opening (54%) and malar depression (50%). Out of all possible 400 fracture sites in 100 patients of zygomatic complex fractures, 266 (66.5%) fractures were detected by clinical examination, in contrast to 330 (82.5%) on radiological examination, which were highest at zygomatic-maxillary buttress (93%) followed by infraorbital rim (91%) and almost equal among fronto-zygomatic site (72%) and zygomatic arch (74%). The scores from the questionnaire for annoyance were significantly higher for paraesthesia (23%) than for trismus (10%), pain (8.5%), or deformity (8.25%). Residual deformity and pain significantly influenced the total satisfaction. Conclusively, there are many treatment modalities available for zygomatic complex fractures, and the preferred methods should be selected on the basis of fracture type, fracture severity, pre-operative signs and symptoms. Regarding the requirements of fracture site exposure and actual fixation, one priority should be to minimize postoperative complications, morbidity and residual deformities.

First case of bilateral coronoid hyperplasia in monozygotic twin sisters-a new aetiological perspective?

BACKGROUND: Mandibular coronoid hyperplasia is a rare condition associated with gradual reduction in mouth opening. Its aetiology is unknown but increased temporalis activity, endocrine stimulus, trauma and familial causes have been proposed. CASE REPORT: In this article, we present a case of bilateral coronoid hyperplasia presenting with limited mouth opening in 16-year-old Caucasian twin sisters. DISCUSSION: This report gives a new perspective to the aetiology of coronoid hyperplasia since it describes its occurrence in monozygotic twins and hence provides a strong argument in support of a genetic aetiology.

Decreased radiation doses to tongue with "stick-out" tongue position over neutral tongue position in head and neck cancer patients who refused or could not tolerate an intraoral device (bite-block, tongue blade, or mouthpiece) due to trismus, gag reflex, or discomfort during intensity-modulated radiation therapy.

PURPOSE: To assess changes in oral cavity (OC) shapes and radiation doses to tongue with different tongue positions during intensity-modulated radiation therapy (IMRT) in patients with head and neck squamous cell carcinoma (HNSCC) but who refused or did not tolerate an intraoral device (IOD), such as bite block, tongue blade, or mouthpiece. RESULTS: Tongue volume outside of OC was 7.1 ± 3.8 cm3 (5.4 ± 2.6% of entire OC and 7.8 ± 3.1% of oral tongue) in IMRT-S. Dmean of OC was 34.9 ± 8.0 Gy and 31.4 ± 8.7 Gy with IMRT-N and IMRT-S, respectively (p < 0.001). OC volume receiving ≥ 36 Gy (V36) was 40.6 ± 16.9% with IMRT-N and 33.0 ± 17.0% with IMRT-S (p < 0.001). Dmean of tongue was 38.1 ± 7.9 Gy and 32.8 ± 8.8 Gy in IMRT-N and IMRT-S, respectively (p < 0.001). V15, V30, and V45 of tongue were significantly lower in IMRT-S (85.3 ± 15.0%, 50.6 ± 16.2%, 24.3 ± 16.0%, respectively) than IMRT-N (94.4 ± 10.6%, 64.7 ± 16.2%, 34.0 ± 18.6%, respectively) (all p < 0.001). Positional offsets of tongue during the course of IMRT-S was -0.1 ± 0.2 cm, 0.01 ± 0.1 cm, and -0.1 ± 0.2 cm (vertical, longitudinal, and lateral, respectively). MATERIALS AND METHODS: 13 patients with HNSCC underwent CT-simulations both with a neutral tongue position and a stick-out tongue for IMRT planning (IMRT-N and IMRT-S, respectively). Planning objectives were to deliver 70 Gy, 63 Gy, and 56 Gy in 35 fractions to 95% of PTVs. Radiation Therapy Oncology Group (RTOG) recommended dose constraints were applied. Data are presented as mean ± standard deviation and compared using the student t-test. CONCLUSIONS: IMRT-S for patients with HNSCC who refused or could not tolerate an IOD has significant decreased radiation dose to the tongue than IMRT-N, which may potentially reduce RT related toxicity in tongue in selected patients.

An intriguing case of locked jaw secondary to melioidosis.

A 56-year-old woman presented with fever, pain and restriction of movement of the right temporomandibular joint. She was premorbidly diagnosed to have type 2 diabetes mellitus and rheumatoid arthritis. Local examination revealed a poorly demarcated severely tender, erythematous swelling in the right preauricular region. All haematological and biochemical investigations were within normal limits. MRI of the neck revealed the presence of a masticator space infection with intramuscular abscess involving the masseter and the temporalis muscles along with intracranial extension. Osteomyelitic changes were detected in the right mandibular condyle, temporal bone and in the temporomandibular joint. Melioidosis was suspected due to this unique clinical presentation of an abscess at an unusual and atypical site. Blood cultures identified the Gram-negative bacilli Burkholderia pseudomallei, which established the diagnosis of Melioidosis. Remarkable improvement was attained with antibiotics meropenem and cotrimoxazole, deferring the need for any surgical intervention.

Thoraco dorsal artery perforator flap for trismus release in a young girl.

Trismus is a frequent complication occurring after treatment of tumors of the pterygomaxillary fossa. Local flaps and full-thickness skin grafts fail to release it because they usually lead to scar contracture in previously irradiated tissues. We propose to release it with a thoracodorsal artery perforator flap, which is feasible in children like other perforator flaps. It is interesting because it is thinner than the anterolateral thigh flap and its scar may be less disgraceful and easier to hide.

[DIAGNOSTICS OF POSITION OF THE MOTOR AND TRIGGER POINTS: OF THE CHEWING MUSCLES FOR ZYGOMATIC COMPLEX FRACTURES].

Existing treatment methods of zygomatic complex fractures, which are complicated by contrac- ture of the masseter as a result of displaced bone fragments, have to be improved. Lack of muscle relaxation leads to the formation of local hypertonicity. In spasmodic muscle fibers varies perfusion and hypoxia occurs, which is accompanied by the release of inflammatory mediators and activation of pain receptors. Over time, areas formed local hypertonicity specific trigger points that contain multiple sensory loci and include one or more sensitive nerve endings. A device for the effective electromyographic study of masseters as a source of their condition and the dynamics of changes in masticatory muscles during patient treatment by improving the fixation system on the face of the patient and the introduction of more perfect spatial coordinate system for mathematical calculations masseter motor position (or triggered) point. Patients were examined before and in the dynamics of treatment according to our methodology, which included proper masseter relaxation, reposition and fixation of bone fragments and further medical therapy.

[Limited mouth opening - what now?]. / Eingeschränkte Mundöffnung – was nun?

This case report illustrates a rare complex of symptoms leading to limited mouth opening in a young woman. The 28-year old suffered from a progressively limited mouth opening over several years that finally resulted in restricted alimentation and made dental treatment impossible. Clinical findings suggest a structural alteration, including a hyperplastic mandibular angle and marked hypertrophy of the masseter muscle. Further radiologic investigations reveal a thickened aponeurosis of the masticatory muscles and hyperplastic coronoid processes that are not interfering with the zygomatic bone. Primary therapeutic options for such conditions are mainly surgical, including reduction of the masseter muscles volume and aponeurorectomy as well as bony reductions, such as coronoidectomy and mandibular angle reduction. With this treatment, the outcome and prognosis are good. Long-term results depend on concomitant physical therapy. A uniform nomenclature for this condition is yet lacking and propositions such as “masticatory muscle tendon-aponeurosis hyperplasia” have been made. However, knowledge of this condition and its typical clinical signs can make the diagnosis and treatment straightforward, thus leading to an improved quality of life of affected patients.

Case report of recurrent temporomandibular joint open lock associated with abrupt reduction of displaced articular disk.

PATIENT: This report describes the case of a 51-year-old male patient who initially presented at age 23 with a habitual intermittent open lock (at >35mm) in the left temporomandibular joint (TMJ). The patient was able to manage this affliction through rapid-repetition jaw opening and closing. Tomography of the joint showed no irregular morphology, but intraoral examination revealed an occlusal interference at the mandibular left third molar during leftwards excursion. For this patient, alteration of lateral guidance using a palatal plate attached to the maxillary left canine precluded this intermittent open lock, but at 22 years of age, the open lock recurred and could not be relieved by the patient, who was unable to assume an occlusal position. Because conservative treatment was ineffective, a pumping manipulation technique was applied to reduce the open lock, after which the patient has maintained good jaw function. MRI taken before and after repositioning indicated that abrupt reduction of a displaced articular disk was the cause of the open lock, and that this articular disk was restored to its proper position during the manipulation. DISCUSSION: Most TMJ open locks occur as anterior dislocation, where the mandibular head becomes trapped anterior to the articular eminences, causing excessive opening and difficulty closing. Our clinical findings from this patient indicate that open lock can occur through abrupt reduction of a displaced articular disk, particularly in patients with chronic internal derangement of the TMJ. CONCLUSION: TMJ open lock can occur following abrupt reduction of a displaced articular disk.

Expanding the mutational spectrum of CRLF1 in Crisponi/CISS1 syndrome.

Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis, and cold-induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia associated with death in most cases in the first years of life. To date, 24 distinct CRLF1 mutations have been found either in homozygosity or in compound heterozygosity in CS/CISS1 patients, with the highest prevalence in Sardinia, Turkey, and Spain. By reporting 11 novel CRLF1 mutations, here we expand the mutational spectrum of CRLF1 in the CS/CISS1 syndrome to a total of 35 variants and present an overview of the different molecular and clinical features of all of them. To catalog all the 35 mutations, we created a CRLF1 mutations database, based on the Leiden Open (source) Variation Database (LOVD) system (https://grenada.lumc.nl/LOVD2/mendelian_genes/variants). Overall, the available functional and clinical data support the fact that both syndromes actually represent manifestations of the same autosomal-recessive disorder caused by mutations in the CRLF1 gene. Therefore, we propose to rename the two overlapping entities with the broader term of Crisponi/CISS1 syndrome.

Coronoid hyperplasia in chronic progressive trismus.

Hyperplasia of the coronoid process of the mandible has been observed in conditions like Oral submucous fibrosis, TMJ ankylosis, etc. The etiopathogenesis of this coronoid overgrowth has not been clearly sequenced or adequately hypothesized, and no definite mechanism has so far been advocated to explain this elongation of the coronoid process in the above mentioned conditions. Coronoid hyperplasia is seen in both these conditions despite being completely unrelated etiologically. However, progressive hypomobility of the mandible seems to be the common underlying condition in both the cases. We attempt to hypothesize a mechanism of coronoid hyperplasia, which appears to be independent of the underlying etiological factor causing trismus in these conditions.

Evaluation of the Pentax-AWS(®) and the Macintosh laryngoscope in difficult intubation: a manikin study.

BACKGROUND: The Pentax-AWS (AWS(®)), a new video laryngoscope, has been shown to be useful in cases of difficult intubation. We hypothesized that the AWS(®) would be more useful in the settings of a narrow upper airway than the Macintosh laryngoscope. We compared each device in simulated scenarios of representative difficulty of tracheal intubation using a manikin. The primary endpoint was the rate of successful intubation. METHODS: With each device, 23 anesthesiologists performed tracheal intubation in a SimMan(®) manikin in the following scenarios: (1) normal airway, (2) tongue edema, (3) cervical spine rigidity, (4) pharyngeal obstruction, (5) jaw trismus, (6) tongue edema with pharyngeal obstruction. The intubation time and success rate were measured. Each participant was asked to rate the difficulty of intubation (1=very easy; 5=very difficult). RESULTS: In the scenarios of tongue edema and tongue edema with pharyngeal obstruction, the AWS(®) yielded a higher success rate (100% vs. 34.8%; P<0.001, 65.2% vs. 21.7%; P=0.006), a shorter intubation time [14.6 (7.0) vs. 33.4 (13.0) s; P<0.001, 24.5 (12.0) vs. 37.6 (11.9); P=0.047; mean (standard deviation)], and a lower difficulty score [2 (1-4) vs. 5 (1-5); P<0.001, 4 (2-5) vs. 5 (3-5); P<0.001; median (range)], compared with the Macintosh laryngoscope. CONCLUSION: The AWS(®) has an advantage over the Macintosh laryngoscope in simulated tongue edema and tongue edema with pharyngeal obstruction. Further studies in a clinical setting are necessary to confirm these findings.

MRI findings in patients with severe trismus following radiotherapy for nasopharyngeal carcinoma.

The aim of the study was to document MRI findings in masticator structures in patients with trismus developing after radiotherapy for nasopharyngeal carcinoma (NPC). MRI neck examinations were reviewed in 35 patients with marked trismus, defined as an interincisal gap of 25 mm or less, post-radiotherapy for NPC. Patients with trismus before treatment, infiltration of masticator structures at the time of trismus, or previous surgery involving the masticator structures were excluded. Sixteen patients had no significant abnormality in their masticator structures (46%). Nineteen patients (54%) had abnormalities comprising radiotherapy-induced masticator muscle fibrosis (n = 19), denervation atrophy of the masticator muscles secondary to mandibular nerve damage (n = 1), mandibular ramus signal abnormalities (n = 5), mandibular condyle sclerosis with or without capsular thickening (n = 5), perimasticator fibrosis extending into the masticator space (n = 3) and inflammation secondary to severe sinusitis extending into the masticator space (n = 2). Nine patients (26%) had more than one type of abnormality. Twenty-two patients (63%) had concomitant skull base osteoradionecrosis which extended into the pterygoid bases in 16 patients (45%). The presence of several MRI abnormalities in the masticator structures of patients with trismus after radiotherapy suggests that trismus is multifactorial. This study advances the understanding of mechanisms behind this debilitating side effect of radiotherapy.