Trismus in head and neck cancer: translation and validation of the Chinese version of the Gothenburg Trismus Questionnaire-2 (C-GTQ-2).

OBJECTIVES: Trismus, marked by restricted mouth opening, significantly affects patients with temporomandibular disorder (TMD) and head and neck cancer (HNC). Despite its prevalence, specialized questionnaires for trismus assessment are scarce. This study aims to fill this gap by translating and validating the Gothenburg Trismus Questionnaire version 2 (GTQ-2) into Chinese (C-GTQ-2), enhancing the evaluation of trismus in HNC and TMD patients. MATERIALS AND METHODS: The study involved 78 HNC patients, 75 TMD patients, and a control group of 150 individuals without trismus symptoms. Participants were asked to complete the C-GTQ-2 and other health-related quality of life (HRQL) instruments. A subset of 30 individuals retook the questionnaire within two weeks to assess test-retest reliability. RESULTS: The C-GTQ-2 demonstrated remarkable reliability, with Cronbach's alpha values exceeding 0.70 in three of the four domains, indicating high internal consistency. The instrument also showcased high intra-class correlations in the test-retest, affirming its reliability. Furthermore, it exhibited strong convergent validity, aligning well with other HRQL instruments, and effectively discriminated between patients with and without trismus, establishing its discriminant validity. CONCLUSIONS: The C-GTQ-2 emerges as a valid and reliable tool for assessing trismus in HNC and TMD patients, promising to significantly enhance both clinical and research approaches to managing trismus-related complications in the Chinese-speaking demographic. CLINICAL RELEVANCE: C-GTQ-2 proves effective for trismus assessment in head and neck cancer and temporomandibular disorder patients, offering enhanced clinical and research utility.

A case of conversion disorder presenting as chronic trismus.

Trismus can be the symptom of several diseases. For the most part, the inability to open the mouth is due to an articular disorder but occasionally, the cause may be extra-articular. In this case, being reported, non-articular hysterical trismus caused the jaw to lock in an 11-year-old boy for 3 months. During this period the jaw was completely locked and the locking was associated with moderate to severe pain. After three sessions of therapy the patient was able to open his mouth 33 mm and his eating was back to normal. Conversion disorders often present with dramatic physical presentation including trismus and jaw lock. This report highlights the importance of complete history taking and a thorough clinical examination to make a correct diagnosis in a patient with trismus.

A novel method for the remote measurement of trismus in clinical trials using mobile phone cameras.

OBJECTIVE: To evaluate the reliability and validity of a novel method for remotely measuring trismus. MATERIALS AND METHODS: We recruited 60 volunteers who took three types of photographs at a fixed restricted jaw position mimicking limited mouth opening, including one selfie and one portrait with or without a reference frame. Additionally, the interincisal distance and the width of the upper central incisors were measured with a ruler, as per common practice. Measurements of trismus were made using image analysis software comparing different types of photos and calibration methods. Intraclass correlation coefficient (ICC) and 95% limits of agreement (LoA) with 95% confidence interval were calculated to evaluate reliability and validity. RESULTS: The proposed method demonstrated high reliability (ICC 0.998; 95% CI 0.997, 0.999). Calibration of photographs using at least a baseline photograph with an external reference frame yielded unbiased measurements and minimised variability. The use of selfies compared to portrait photos also increased variability. CONCLUSION: The measurement of trismus can be performed using images taken remotely by patients using their mobile phone cameras. The proposed method is highly accurate, with best results obtained by using a reference frame for calibration of portrait photographs. CLINICAL RELEVANCE: We propose an easy, cheap, and accurate method that allows for remote and frequent monitoring of trismus in clinical studies using patients' mobile phones.

Trismus, health-related quality of life, and trismus-related symptoms up to 5 years post-radiotherapy for head and neck cancer treated between 2007 and 2012.

PURPOSE: Radiotherapy-induced trismus is present in up to 40% of patients treated radiotherapeutically for head and neck cancer (HNC) and impacts health-related quality of life (HRQL) negatively. This prospective study aimed to investigate the development of trismus and its influence on HRQL and trismus-related symptoms in HNC patients for up to 5 years post-radiotherapy completion as no such follow-up studies exist. METHODS: Patients (n = 211) were followed prospectively from pre-radiotherapy to 12 and 60 months post-radiotherapy. At each follow-up, maximum interincisal opening (MIO) was measured, and patients filled in the European Organization for Treatment of Cancer Quality-of-Life Questionnaire Core-30 (EORTC QLQ-C30), Head and Neck-35 (EORTC QLQ-HN35), and Gothenburg Trismus Questionnaire (GTQ). Trismus was defined as an MIO ≤ 35 mm. RESULTS: At 1 year post-radiotherapy, a total of 27% met the trismus criterion, and at 5 years post-radiotherapy, the corresponding figure was 28%. Patients in the trismus group scored significantly worse compared to the patients without trismus on 8/15 domains at 1 year post-radiotherapy on EORTC QLQ-C30, further worsening in 11/15 domains at 5 years post-radiotherapy. Similar results were found for EORTC QLQ-HN35. Patients with trismus reported more trismus-related symptoms according to the GTQ at both timepoints compared to those without trismus. CONCLUSION: This study highlights that HNC patients suffering from radiotherapy-induced trismus report poorer HRQL and more trismus-specific symptoms compared to patients without trismus. These differences persist and increase up to at least 5 years following treatment completion. Hence, our results highlight that radiotherapy-induced trismus affects long-term HRQL, jaw symptoms, and pain, further stressing the need for early and structured intervention.

Novel Mutations in CRLF1: Case Reports with Crisponi Syndrome.

Crisponi syndrome (CS) is a rare autosomal recessive syndrome, characterized by episodic facial muscle contraction with trismus, abundant salivation along with intermittent hyperthermia, feeding difficulties, characteristic facial dysmorphism, and camptodactyly. Here the authors report two South Indian neonates with confirmed diagnosis of Crisponi syndrome, caused by novel pathogenic variants in cytokine receptor-like factor 1 (CRLF1) gene. The classical clinical findings observed in the present cases were feeding difficulty, facial dysmorphism, tachypnea, contractures, camptodactyly, opisthotonus, hyperthermia, poor growth, and facial muscle contraction resembling probable tetanus. The patients with variants identified in the signal peptide domain had typical spasms from day one of life as compared to the variants in other domains who had later onset at neonatal period. The authors provide a review of the cases described, so far, from India highlighting that no common variants attribute to this rare syndrome. Recognizing this syndrome is crucial to differentiate it from infective conditions and for effective genetic counseling. Though tetanus is almost eradicated in developing countries, genetic causes should be suspected in new cases.

Temporomandibular disorder as risk factor for radiation-induced trismus in patients with head and neck cancer.

OBJECTIVES: The aim of this study was to investigate if patients with temporomandibular disorders (TMD) prior to head and neck cancer (HNC) treatment are at higher risk of developing trismus after oncological treatment. MATERIALS AND METHODS: Eighty-three study patients underwent detailed dental examination prior oncological treatment and 6 months after radiotherapy completion, including evaluation of temporomandibular jaw function, palpation of the jaw muscles, and measurement of mouth opening capacity. TMD criteria were based on both clinical examination findings and patient-reported symptoms. TMD at baseline was used in regression analysis in order to predict restricted mouth opening. RESULTS: At the 6 months follow-up more than a third of the patients (35%) were examined with reduced mouth opening of >20% compared to baseline. A majority of the patients had bilateral tenderness of both the temporal and the masseter muscle. At the 6 months follow-up, 42% of the study patients reported mouth opening problems. About one-third of the patients suffered from fatigue and stiffness of the jaw as well as pain when mowing the jaw. Two questions from the validated symptom-specific Gothenburg Trismus Questionnaire were found to be related to a statistically significant increased risk of restricted mouth opening after radiotherapy; "During the last week, have you felt: Pain on moving the jaw?" (OR [95% CI] 5.9 (1.2-29.4) [p = 0.030]) and "During the last week, have you felt pain and tenderness in the muscles of mastication?" (OR [95% CI] 5.90 [1.19-29.40] [p = 0.030]). CONCLUSIONS: TMD is common amongst HNC patients. Patients who suffer from pain in the jaw muscles and pain when moving the jaw before start of treatment are at higher risk of radiation-induced trismus after 6 months. Clinicians should strive for optimizing the patients pain treatment and oral health before, during, and after radiotherapy.

Tetanus presenting as painful muscle spasms, dysphagia and delirium in an older adult.

While tetanus is now a rare disease in the UK, it remains an important differential diagnosis for trismus and muscle spasms. Even more so in older adults, as this population is less likely to have received full vaccination. Hence, the highest incidence of tetanus in England is seen in older adults. Written informed consent for publication of their clinical details was obtained from the patient proxy.

Three new cases of Crisponi /cold induced sweating syndrome (CS/CISS1) in Turkish families.

Crisponi syndrome/Cold Induced Sweating Syndrome 1 (CS/CISS1) is a rare, autosomal recessive, multisystemic disease. Hyperthermia attacks, abnormal contractions in the muscles of the face and oropharynx, respiratory distress, camptodactyly, and swallowing difficulty are the main features of the condition in the neonatal period. Patients experience cold-induced sweating attacks and progressive kyphoscoliosis in childhood and adolescence. Mutations in the cytokine receptor like factor 1 (CRLF1) gene causes the CISS1 (Cold- induced sweating syndrome type 1) disease (over 95% of patients). CRLF1 is located in the ciliary neurotrophic factor receptor (CNTFR) pathway, which plays an important role in development and maintenance of neurons in the nervous system. In this study three patients from Turkey, clinically and molecularly diagnosed with CS/CISS1, are presented. Hyperthermia, swallowing difficulty, camptodactyly and pursing of the lips were present in all patients, and foot deformity in one patient. In the first patient a homozygous nonsense mutation NM_004750.5: c.531G > A; p.(Trp177Ter) in the 4th exon was detected. In the second patient a homozygous nonsense mutation NM_004750.5: c.776C > A; p.(Ser259Ter) in the 5th exon was detected. The third patient was homozygous for a missense mutation NM_004750.5: c.935G > T; p.(Arg312Leu) in the 6th exon. Early diagnosis is very important in this syndrome since most patients die in the neonatal period. Therefore, physicians should be suspicious for this disease in patients with dysmorphic features, hyperthermia attacks, camptodactyly, pursing of lips while crying, and swallowing difficulty.

Jaw Pain and Oromandibular Dysfunction After a Complex Hospital Course: A Clinical Vignette.

ABSTRACT: A 38-yr-old man presented to the emergency department with severe chest pain and was found to have a type A aortic dissection. Forty-eight hours after an emergency mechanical Bentall and ascending hemiarch replacement, the patient developed agitation prompting administration of high-dose haloperidol. He was found to have evidence of multiple acute infarcts on head computed tomography/computed tomography angiography and brain magnetic resonance imaging. Four days later, he began to complain of jaw pain and difficulty opening his mouth. After admission to inpatient rehabilitation, he was found to have strong activity in the masseters bilaterally at rest on electromyography, indicating a diagnosis of oromandibular dystonia. Starting in the intensive care unit, the patient reported jaw pain and dysfunction for 40 days before having a diagnosis of oromandibular dystonia. At this point, treatment with onabotulinumtoxinA injections and baclofen did not provide relief. Because of an extended delay in diagnosis, it is believed that the patient has developed joint contractures. Oromandibular dystonia is an important diagnosis to consider in patients who experience jaw pain or difficulty with mouth opening. Treatment of this condition can decrease pain and trauma to oral structures as well as improve ability to perform oral hygiene, eat, and communicate.

Tetanus of suspected dental causality.

Tetanus infection by Clostridium tetani is a major health problem in many developing countries, including India. Significant morbidity and mortality is attributed to lack of awareness, hygiene and incomplete vaccination. The most common cause of tetanus infection follows cutaneous injury or infection. However, a localized point of entry cannot always be determined. Tetanus has been associated with tooth extraction, root canal therapy, gross caries, periodontal abscess and intraoral soft tissue trauma. The classic symptoms of trismus and risus sardonicus may result in an initial presentation to an oral and maxillofacial surgeon. Due to the rarity of this infection, the dentist or the health care provider may fail to corroborate the findings and be unsuspecting of the diagnosis. Prompt recognition is the key in such a scenario due to the inherent risk of rapid progress of symptoms, progressive deterioration of the health condition and catastrophic complications. A sound knowledge of the effects of tetanospasmin, the disease process, prevention and vaccination against tetanus with its management is essential for health care workers. The authors hereby present a case of tetanus with a suspected dental etiology to make the dental fraternity aware of this lurking malady.

Adenoid cystic carcinoma with dedifferentiation/expansion of the luminal cell component and preserved biphasic morphology - Early high-grade transformation.

We present two patients (29 and 67 years) with histomorphologic and immunohistochemical evidence of early high-grade transformation of adenoid cystic carcinoma in the nasal cavity and floor of mouth, respectively. The component of early high-grade transformation was characterized by 1) selective expansion of the luminal (CK7+, c-kit+, p63-) cell component with severe cytologic atypia and significantly increased Ki-67 proliferation index, and 2) retained albeit attenuated abluminal (CK7-, c-kit-, p63+) cells, surrounding nests of high-grade luminal cells.

Further validation of the Gothenburg Trismus Questionnaire (GTQ).

This study aimed to update and, if necessary, revise the Gothenburg Trismus Questionnaire (GTQ), the only existing trismus-specific questionnaire, and retest its psychometric properties. Semi-structured interviews were performed with 10 trismus patients of which 5 had head and neck cancer (HNC) and 5 suffered from benign temporomandibular disorders. Trismus was defined as a maximal incisal opening of ≤ 35mm. An expert panel discussed and revised the GTQ based on interview information, expertise knowledge and the original questionnaire. The revised questionnaire was then tested in a study sample consisting of benign jaw-related conditions (n = 26), patients treated for HNC (n = 90) and an age- and gender-matched control group with no trismus (n = 116). The revised version of the GTQ (GTQ 2) was well accepted by patients. The original three domains continued to show high internal consistency (Cronbach's alpha 0.74-0.94) and construct validity. Two dually posed single items were split into four questions and the wording was altered in another three items. Moreover, a new domain (Facial pain) was identified, which had excellent internal consistency (α = 0.96) and good construct validity. The revision of the original Gothenburg Trismus Questionnaire (GTQ 1) with inclusion of patient-input, resulted in splitting of ambiguous items, identifying a fourth domain named Facial pain and the recall time shortened for some items. Additionally, the remaining domains and items were re-confirmed as strong in the psychometric analysis. Henceforth, the new version, GTQ 2 should be used.

[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.

Trismus and oral haematoma, a rare presentation of tetanus / Trismo y hematoma oral, una presentación rara del tétanos

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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.

Development of Normal Tissue Complication Probability Model for Trismus in Head and Neck Cancer Patients Treated With Radiotherapy: The Role of Dosimetric and Clinical Factors.

BACKGROUND/AIM: The aim of this study was to develop a normal tissue complication probability (NTCP) model for trismus in head and neck cancer (HNC) patients treated with radiotherapy (RT). PATIENTS AND METHODS: Prospective measurements of maximum inter-incisal opening (MIO) were performed at baseline and 6 months after definitive RT in 132 HNC patients. The primary endpoint of this study was defined when a patient fulfilled both of the following criteria: 1) MIO at 6 months after RT ≤35 mm and 2) MIO at 6 months after RT ≤80% of baseline MIO. Eleven clinical factors and a wide range of dosimetric factors (mean dose, maximum dose, V5, V10, V20, and V40) in twelve organs at risk (OARs) were chosen as candidate prognostic variables. RESULTS: Thirty out of 132 patients (23%) developed the primary endpoint. Multivariate logistic regression analysis revealed that the mean dose to the contralateral mandible joint (p=0.001) and baseline MIO (p=0.027) were independent prognostic factors. CONCLUSION: A multivariable NTCP model for trismus in HNC patients treated with RT was established including the mean dose to contralateral mandible joint and baseline MIO.

Exome sequencing in Crisponi/cold-induced sweating syndrome-like individuals reveals unpredicted alternative diagnoses.

Crisponi/cold-induced sweating syndrome (CS/CISS) is a rare autosomal recessive disorder characterized by a complex phenotype (hyperthermia and feeding difficulties in the neonatal period, followed by scoliosis and paradoxical sweating induced by cold since early childhood) and a high neonatal lethality. CS/CISS is a genetically heterogeneous disorder caused by mutations in CRLF1 (CS/CISS1), CLCF1 (CS/CISS2) and KLHL7 (CS/CISS-like). Here, a whole exome sequencing approach in individuals with CS/CISS-like phenotype with unknown molecular defect revealed unpredicted alternative diagnoses. This approach identified putative pathogenic variations in NALCN, MAGEL2 and SCN2A. They were already found implicated in the pathogenesis of other syndromes, respectively the congenital contractures of the limbs and face, hypotonia, and developmental delay syndrome, the Schaaf-Yang syndrome, and the early infantile epileptic encephalopathy-11 syndrome. These results suggest a high neonatal phenotypic overlap among these disorders and will be very helpful for clinicians. Genetic analysis of these genes should be considered for those cases with a suspected CS/CISS during neonatal period who were tested as mutation negative in the known CS/CISS genes, because an expedited and corrected diagnosis can improve patient management and can provide a specific clinical follow-up.

Criterion for trismus in head and neck cancer patients: a verification study.

PURPOSE: Several cut-off points for trismus in head and neck cancer patients have been used. A mouth opening of 35 mm or less is most frequently used as cut-off point. Due to the variation in cut-off points, prevalence, risk factors and treatment outcomes of trismus cannot be studied in a uniform manner. To provide uniformity, we aimed to verify the cut-off point of 35 mm or less. Additionally, we aimed to determine associated covariates with reported difficulties when opening the mouth. METHODS: In a cross-sectional design, we measured the mouth opening in 671 head and neck cancer patients at the Department of Oral and Maxillofacial Surgery, at the University Medical Center Groningen. The cut-off point was determined using the receiver operating characteristic curve and Youden index, with reported difficulties when opening the mouth as criterion for trismus. Cut-off points for significant covariates were also determined. RESULTS: The Youden index was highest at 35 mm, with a sensitivity of 0.71 and a specificity of 0.86. Of the covariates analysed, type of treatment modality was significantly associated with reported difficulties when opening the mouth. The highest Youden index for patients treated with surgery alone was 37 mm and for patients treated with radiotherapy alone 33 mm. CONCLUSIONS: The cut-off point of 35 mm or less for trismus was confirmed in a head and neck cancer population and is recommended to be used in future studies. Patients receiving different treatment modalities experience difficulty when opening the mouth differently.