Nusinersen Initiation After Onset of Weakness Does Not Prevent Progression of Hip Instability.

BACKGROUND: We report changes in the natural history of hip instability with nusinersen treatment among patients with spinal muscular atrophy (SMA) type II after onset of weakness, historically wheelchair-bound but now potentially ambulatory in the era of disease-modifying therapy. METHODS: Patients with genetically confirmed diagnoses of SMA type II who received intrathecal nusinersen from January 1, 2018, to June 30, 2022, were screened for inclusion. Patients with less than 6 months of follow-up, or prior hip surgeries were excluded. Primary clinical outcome measures included scores from Hammersmith motor functional scale expanded (HMFSE), revised upper limb module (RULM), 6-minute walk test (6MWT), and ambulatory status. Radiographic outcomes, including Reimer migration index, the presence of scoliosis, and pelvic obliquity, were also assessed. Secondary outcomes involved comparisons with a historical cohort of SMA type II patients treated at our institution who never received nusinersen. RESULTS: Twenty hips from 5 boys and 5 girls were included in the analysis, with a mean follow-up of 3 years and 8 months. The median age at time of nusinersen initiation was 6.8 years old, ranging between 2.5 and 10.3 years. All patients developed lower limb motor weakness before nusinersen initiation. After treatment with nusinersen, 1 previously stable hip (5%) developed subluxation, 15 hips (75%) remain subluxated, 3 hips (15%) remain dislocated, and 1 hip (5%) remained stable, with a statistically significant difference between the pretreatment and posttreatment groups ( P <0.01). Six patients (60%) were ambulatory at latest follow-up. Six patients (60%) had improved ambulatory ability; 2 had static ambulatory ability (20%); and 2 had deterioration in their walking ability. The median HFMSE score improved from 18.5 (range 0 to 46) to 22 (range 0 to 49) ( P =0.813), whereas the median RULM score improved from 17 (range 2 to 28) to 21.5 (range 5 to 37), which was statistically significant ( P =0.007). CONCLUSIONS: Hip instability persists despite treatment with nusinersen among patients with SMA type II who received nusinersen after onset of lower limb weakness. LEVEL OF EVIDENCE: Therapeutic Level IV.

Arterial tortuosity syndrome causing recurrent transient ischemic attacks in young adult: a case report.

BACKGROUND: Arterial Tortuosity Syndrome (ATS) is a rare autosomal recessive disorder characterized by elongated and tortuous arteries. Although ATS showed a significant clinical and pathophysiological overlap with other syndromes involving connective tissues, only few cases of cerebrovascular events related to this syndrome have been described so far. CASE PRESENTATION: We report the case of a 33-years-old male diagnosed with ATS since childhood, that experienced three sudden episodes of expressive aphasia and right hemiparesis with spontaneous resolution. He was treated with recombinant tissue plasminogen activator (r-TPA) at a dosage of 0.9 mg/kg with a complete recovery. Brain Magnetic Resonance Imaging (MRI) showed the absence of acute ischemic lesions and the patient was diagnosed with recurrent transient ischemic attacks (TIA). Intracranial and supra-aortic trunks Magnetic Resonance Angiography (MRA) and Angio-CT scan of the thoracic and abdominal aorta showed marked vessel tortuosity without stenosis. To our knowledge, this is the first reported case of an ATS patient with TIA in young age that was treated with intravenous thrombolysis with recombinant plasminogen activator. CONCLUSION: Our report strengthens the relationship between ATS and juvenile cerebrovascular events, suggesting that an extensive study of body vessels in order to detect potential stenoses or occlusions in these cases is needed. The greater predisposition to cerebrovascular events in ATS could benefit from a more aggressive primary and secondary prevention therapy.

Hypermobility in individuals with Kabuki syndrome: The effect of growth hormone treatment.

Kabuki syndrome (KS) is a multiple congenital malformation syndrome which has been described across all ethnic groups. Most KS patients possess two genetic subtypes: KMT2D-associated, autosomal-dominant KS type 1 (KS1; OMIM 147920); and KDM6A-associated, X-linked-dominant KS type 2. Generalized joint hypermobility is one feature of KS, but its exact incidence and pattern is not well described in the literature. As part of our prospective study on the metabolic and growth effect of GH treatment, we assessed children from our Dutch Kabuki cohort who were eligible for growth hormone therapy. We assessed severity and pattern of joint hypermobility, both before and after 24 months of growth hormone replacement therapy. The prevalence of hypermobility was 31% in boys and 14% in girls using the Beighton score and 69% in boys and 57% in girls using the Bulbena score. This varies from the general population where girls are more affected. After 2 years of growth hormone treatment, there was a statistically significant decrease in the presence of joint hypermobility to 6% using the Bulbena score and none with respect to the Beighton score. We hypothesized that this result suggests a direct effect of growth hormone on connective tissue in patients with KS.

Characterizing adolescents with heavy menstrual bleeding and generalized joint hypermobility.

Patients with generalized joint hypermobility (JHM) may experience excessive bruising/bleeding, with heavy menstrual bleeding (HMB) commonly reported. We performed a retrospective review of 30 adolescents seen in a Young Women's Hematology Clinic with both HMB and JHM. We found that (1) a significant delay (mean 36 months, range 5-72) occurred between menarche and referral to specialty care, (2) HMB had moderate to severe impact on school and physical activities in 60% of patients, and (3) most patients (68%) required escalation of their initial therapy. We suggest providers consider JHM as a risk factor for a more complex clinical course.

Predictors for progression of two different types of cervical lesions in rheumatoid arthritis treated with biologic agents.

BACKGROUND: Biologic agents (BAs) enabled not only a reduction of disease activity but also a slowing down of structural damage to the joints in patients with rheumatoid arthritis (RA). However, the incidence of cervical lesions in patients with RA is still high. PURPOSE: To elucidate the predictors for the progression of two different cervical lesions in patients with RA under BA treatment. METHODS: Of 151 subjects who received more than two years of continuous BA treatment, 101 subjects who had cervical X-ray images taken at baseline and final visit were enrolled. The mean disease duration and mean radiography interval were 10.6 years and 4.4 years, respectively. The existence and progression of cervical lesions (atlanto-axial subluxation [AAS], vertical subluxation [VS], and subaxial subluxation [SS]) were investigated. And predictors for the AAS or VS progression were analyzed by multivariate logistic regression analysis. RESULTS: The incidence of cervical lesions at baseline were no pre-existing cervical lesion (none) in 50 cases (50%), AAS only in 32 (32%), both AAS and VS in 12 (12%), and VS only in 7 cases (7%). In the none group, only 4 cases of AAS progression (8%) was observed during the follow-up. In contrast, in the groups with pre-existing cervical lesions, a high incidence of VS progression was observed (63% in the AAS only group, 58% in the AAS + VS group, and 71% in the VS only group). Multivariate regression analysis demonstrated that the DAS-CRP value at baseline (odds ratio [OR] = 9.23) and matrix metaloprotease-3 level at baseline (OR = 1.01) were significant predictors for the progression of AAS, and pre-existing AAS (OR = 18.38) was a sole significant predictor for the progression of VS. CONCLUSIONS: Cervical lesions progressed irrespective of disease activity after AAS development. Strict disease control before the development of AAS is crucial for preventing further progression and development of cervical lesions.

The efficacy of dextrose prolotherapy over placebo for temporomandibular joint hypermobility: A systematic review and meta-analysis.

OBJECTIVE: The aim of the systematic review was to analyse the available evidence in order to assess the efficacy of dextrose prolotherapy in improving outcomes in temporomandibular joint (TMJ) hypermobility patients as compared to placebo. METHODS: An electronic search of PubMed, Scopus, CENTRAL and Google scholar databases was performed for English language papers published up to February 2018. Randomised clinical trials (RCTs) and controlled clinical trials (CCTs) comparing dextrose prolotherapy with placebo for TMJ hypermobility were included. RESULTS: Three RCTs were included in the review. Frequency of subluxation/dislocation was reported by two trials which found no difference between dextrose and placebo. A statistical significant difference in reduction of MMO with the use of dextrose prolotherapy was seen on pooling of data (random: MD = -3.32, 95% CI -5.26 to -1.28; P = 0.0008; I2  = 0%). A statistical significant difference in pain reduction was also seen with dextrose as compared to placebo (random: MD = -1, 95% CI -1.58 to -0.42; P = 0.0007; I2  = 0%). CONCLUSION: Within the limitations of the study, dextrose prolotherapy may cause significant reduction in mouth opening and pain associated with TMJ hypermobility. Conclusions with regard to reduction of episodes of subluxation/dislocation cannot be drawn. There is a need of more high-quality RCTs with larger sample size and homogenous prolotherapy protocol to draw stronger conclusions on the effect of dextrose prolotherapy in patients with TMJ hypermobility.

[THE ROLE OF TRANSFORMING GROWTH FACTOR-B IN IMMUNOPATHOGENESIS OF DISEASES OF CONNECTIVE TISSUE].

The recent studies of molecular physiology of fibrillin and pathophysiology of inherent disorders of structure and function of connective tissue such as dissection and aneurysm of aorta, myxomatously altered cusps and prolapses of mitral valve, syndrome of hyper-mobility of joints, demonstrated that important role in development of these malformations play alterations of transfer of signals by growth factors and matrix cellular interaction. These conditions under manifesting Marfan's syndrome can be a consequence of anomalies of fibrillin-1 which deficiency unbrakes process of activation of transforming growth factor-ß (TGFß). The involvement of TGFß in pathogenesis of Marfan's syndrome permits consider antagonists of angiotensin-transforming enzymes as potential pharmaceuticals in therapy of this disease. The article presents analysis of publications' data related to this problem.

Diffuse neonatal hemangiomatosis in a very low-birthweight infant treated with erythropoietin.

Diffuse neonatal hemangiomatosis (DNH) is a rare condition characterized by the concomitant development of multiple cutaneous infantile hemangiomas (IH) and visceral hemangiomas. Recently, an association between erythropoietin treatment and an increased incidence of infantile hemangioma was noted. A Japanese male infant was born via cesarean section at 27 weeks of gestation. Following the commencement of erythropoietin treatment for anemia of prematurity, he developed multiple cutaneous hemangiomas, high cardiac output heart failure and hepatomegaly. Abdominal imaging indicated comorbidity of diffuse infantile hepatic hemannigomas, resulting in the final diagnosis of DNH. The discontinuation of erythropoietin treatment and long-term therapy with propranolol improved the hepatic lesions and cutaneous hemangiomas. The possibility of multiple organ involvement and the exacerbating effects of erythropoietin treatment should be considered in cases in which multiple cutaneous hemangiomas develop in preterm infants receiving erythropoietin treatment.

Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically induced model of osteoarthritis in mice.

OBJECTIVE: To investigate the chondroprotective effect of cyclooxygenase 2 (COX-2) inhibition in experimental osteoarthritis (OA). METHODS: The expression of prostaglandin E2 synthetic enzymes was examined by immunostaining of tibial cartilage from mice with surgically induced knee joint instability and from OA patients undergoing total knee arthroplasty. The effect of orally administered celecoxib (10 mg/kg/day and 30 mg/kg/day) or vehicle alone in mice was examined 12 weeks after the induction of OA. To investigate the involvement of COX-1 and COX-2 in OA development, we also created the model in COX-1-homozygous-knockout (Ptgs1-/-) mice and COX-2-homozygous-knockout (Ptgs2-/-) mice. OA severity was assessed using a grading system developed by our group and by the Osteoarthritis Research Society International scoring system. RESULTS: In mouse and human OA cartilage, the expression of the inducible enzymes COX-2 and microsomal prostaglandin E synthase 1 (mPGES-1) was enhanced, while that of the constitutive enzymes COX-1, cytosolic PGES, and mPGES-2 was suppressed. Daily celecoxib treatment did not prevent cartilage degradation or osteophyte formation during OA development in the mouse model. Furthermore, neither Ptgs1-/- mice nor Ptgs2-/- mice exhibited any significant difference in OA development as compared to wild-type littermates. CONCLUSION: The two COX enzymes differ in terms of regulation of their expression during OA development. Nevertheless, experiments using inhibitor and genetic deficiency demonstrated a lack of chondroprotective effect of COX-2 inhibition in the mouse surgical OA model.

Perioperative opioid-minimization approach as a useful protocol in the management of patients with Ehlers-Danlos syndrome-hypermobility type, craniocervical instability and severe chronic pain who are to undergo occipito-cervical fixation.

Patients suffering from connective tissue disorders like Ehlers-Danlos syndrome hypermobility type/joint hypermobility syndrome (EDS-HT/JHS) may be affected by craniocervical instability (CCI). These patients experience myalgic encephalomyelitis, chronic fatigue, depression, extreme occipital-cervical pain, and severe widespread pain that is difficult to relieve with opioids. This complex and painful condition can be explained by the development of chronic neuroinflammation, opioid-induced hyperalgesia, and central sensitization. Given the challenges in treating such severe physical pain, we evaluated all the analgesic methods previously used in the perioperative setting, and updated information was presented. It covers important physiopathological aspects for the perioperative care of patients with EDS-HT/JHS and CCI undergoing occipital-cervical/thoracic fixation/fusion. Moreover, a change of paradigm from the current opioid-based management of anesthesia/analgesia in these patients to the perioperative opioid minimization strategies used by the authors was analyzed and proposed as follow-up considerations from our previous case series. These strategies are based on total-intravenous opioid-free anesthesia, multimodal analgesia, and a postoperative combination of anti-hyperalgesic coadjuvants (lidocaine, ketamine, and dexmedetomidine) with an opioid-sparing effect.

A protocol for a randomized clinical trial assessing the efficacy of hypertonic dextrose injection (prolotherapy) in chronic ankle instability.

BACKGROUND: Lateral ankle sprain (LAS) is a common injury. Conservative care is not uniformly effective. Chronic ankle instability (CAI) results in up to 70% of patients with LAS in the physically active population. LAS, together with subsequent osteochondral lesions and pain in many patients, leads to the development of post-traumatic osteoarthritis, resulting in a substantial direct and indirect personal and societal health burden. Dextrose prolotherapy (DPT) is an injection-based therapy for many chronic musculoskeletal conditions but has not been tested for CAI. This protocol describes a randomized controlled trial to test the efficacy of DPT versus normal saline (NS) injections for chronic ankle instability (CAI). METHODS AND ANALYSIS: A single-center, parallel-group, randomized controlled trial will be conducted at a university-based primary care clinic in Hong Kong. A total of 114 patients with CAI will be randomly allocated (1:1) to DPT and NS groups. The primary outcome will be the Cumberland Ankle Instability Tool scores at 1 year. The secondary outcomes will be the number of re-sprains in 1 year, the Star Excursion Balance Test, the 5-level of EuroQol 5-dimension questionnaire, and the Foot and Ankle Ability Measure. All outcomes will be evaluated at baseline and at 16, 26, and 52 weeks using a linear mixed model. DISCUSSION: We hypothesized the DPT is a safe, easily accessible, and effective treatment for patients with CAI. This RCT study will inform whether DPT could be a primary non-surgical treatment for CAI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040213 . Registered on 25 November 2020.

The efficacy of dextrose prolotherapy for temporomandibular joint hypermobility: a preliminary prospective, randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: The aim of this study was to assess the efficacy of dextrose prolotherapy for the treatment of temporomandibular joint (TMJ) hypermobility. PATIENTS AND METHODS: A prospective, randomized, double-blind clinical study using a placebo control was carried out. Twelve patients with painful subluxation or dislocation of the TMJ were randomly assigned to 1 of 2 equal-sized groups. Patients in the active group received 4 injections of dextrose solution (2 mL of 10% dextrose and 1 mL of 2% mepivacaine) for each TMJ, each 6 weeks apart, whereas patients in the placebo group received injections of placebo solution (2 mL of saline solution and 1 mL of 2% mepivacaine) on the same schedule. A verbal scale expressing TMJ pain on palpation, maximal mouth opening (MMO), clicking sound, and frequency of luxations (number of locking episodes per month) were assessed at each injection appointment just before the injection procedure and 3 months after the last injection. The collected data were then statistically analyzed. RESULTS: By the end of the study, each group showed significant improvement in TMJ pain on palpation and number of locking episodes and insignificant improvement in clicking sound. With the exception of the MMO, there were no statistically significant differences throughout the study intervals between the active and placebo groups. The active group showed a significant reduction in MMO at the 12th week postoperatively. Differences compared with mean baseline value remained significant at the end of the follow-up period. On the other hand, the placebo group showed an insignificant difference in MMO throughout the study periods. For the last 2 intervals, the placebo group showed statistically significantly higher mean MMO values than the active group. By the end of the 12th postoperative week, the percentages of decrease in MMO were significantly greater in the active group. CONCLUSION: Prolotherapy with 10% dextrose appears promising for the treatment of symptomatic TMJ hypermobility, as evidenced by the therapeutic benefits, simplicity, safety, patients' acceptance of the injection technique, and lack of significant side effects. However, continued research into prolotherapy's effectiveness in patient populations with large sample sizes and long-term follow-up is needed.

Perioperative Botulinum Toxin A in the Surgical Management of Seizure-Related Shoulder Instability: A Case Report.

CASE: A 20-year-old woman presented with recurrent bilateral shoulder instability concurrent with severe, treatment-refractory epilepsy. Imaging revealed glenoid bone loss of 25% to 28% and large Hill-Sachs defects bilaterally. Bone graft augmentation of the glenoid and infill of the Hill-Sachs defects was performed bilaterally. Perioperative neuromuscular paralysis of shoulder girdle muscles with botulinum toxin was performed to facilitate recovery. Both shoulders at 2.5 and 4 years, respectively, demonstrate excellent stability and radiographic union despite continued seizure activity. CONCLUSION: Perioperative neuromuscular paralysis with botulinum toxin may provide early graft protection after the surgical treatment of glenohumeral instability because of seizures.

Vague Posterior Knee Discomfort in a Soccer Player: A Clinical Vignette.

A 24-yr-old male soccer player presented with a 7-yr history of left posterior knee "looseness." Evaluation 7 yrs ago, at the time of initial injury, revealed atraumatic anterior and posterior cruciate ligament sprains. On representation, the patient described the pain as a constant, dull ache, 3/10, but his biggest complaint was this feeling of "instability" and looseness where his knee would "buckle" 3-4 times a week. Physical examination was positive for grade 1 posterior drawer and grade 1 posterior sag signs. Reverse KT-1000 testing showed a 3-mm side-to-side difference. Sonographic evaluation confirmed magnetic resonance imaging findings of posterior cruciate ligament laxity and buckling and a small cystic lesion abutting the posteromedial margin of the distal 1/3 of the posterior cruciate ligament. After a trial of physical therapy, the patient elected to undergo experimental injection of dextrose hyperosmolar solution. This resulted in resolution of the cyst and reverse KT-1000 measurements improved to a side-to-side difference of 1 mm. The patient's subjective feeling of looseness and instability resolved by 7 wks.

Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing.

BACKGROUND AND PURPOSE: Corticosteroids are intra-articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial-based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak drug concentrations. EXPERIMENTAL APPROACH: The applicability of prolonged corticosteroid exposure was examined in a rat model of anterior cruciate ligament and medial meniscus transection (ACLT + pMMx) with ensuing degenerative changes. KEY RESULTS: Intra-articular injection of a bolus of the corticosteroid triamcinolone acetonide (TAA) resulted in enhanced joint instability in 50% of the joints, but neither instability-induced OA cartilage degeneration, synovitis, nor the OA-related bone phenotype was affected. However, biomaterial microsphere-based extended TAA release enhanced instability in 94% of the animals and induced dystrophic calcification and exacerbation of cartilage degeneration. In healthy joints, injection with TAA releasing microspheres had no effect at all. In vitro, TAA inhibited cell migration out of joint tissue explants, suggesting inhibited tissue healing in vivo as mechanisms for enhanced instability and subsequent cartilage degeneration. CONCLUSIONS AND IMPLICATIONS: We conclude that short-term TAA exposure has minor effects on surgically induced unstable joints, but its extended presence is detrimental by extending instability and associated joint degeneration through compromised healing. This supports a contraindication of prolonged corticosteroid exposure in tissue damage-associated joint instability, but not of brief exposure.

Comparison of botulinum toxin type A injection and soft-tissue surgery to treat hip subluxation in children with cerebral palsy.

OBJECTIVE: To compare the effects of botulinum toxin type A (BTX-A) injection into the hip adductor muscles on hip displacement with soft-tissue surgery and assess the factors related to a favorable outcome after intervention in children with bilateral spastic cerebral palsy (CP). DESIGN: Retrospective chart review with regard to radiographic findings. SETTING: University hospital. PARTICIPANTS: Children with CP (N=194). INTERVENTIONS: BTX-A injection and soft-tissue surgery into the hip adductor muscles. MAIN OUTCOME MEASURE: The Reimers hip migration percentage (MP). RESULTS: Sixty-nine children did not receive any therapeutic intervention for hip displacement, whereas 60 children underwent soft-tissue surgery and 65 children took BTX-A injection for the spasticity of their hip muscles. MP was measured on each radiograph of the pelvis. The annual change of MP was improved in both the soft-tissue surgery and BTX-A groups, whereas it worsened in the nonintervention group. The annual improvement of MP in the BTX-A group did not differ significantly from that of the soft-tissue surgery group. The improvement in hip displacement after therapeutic intervention was greater in young children and high-functioning groups compared with older children and low-functioning groups. Hip displacement was progressive in the severely hip subluxated group despite therapeutic intervention. CONCLUSIONS: Comparable effects of BTX-A injection to soft-tissue surgery in our study suggest that BTX-A injection, if timely reinjected, may replace soft-tissue surgery as a prophylactic procedure against progressive hip subluxation or dislocation in children. Age at intervention, functional level, and initial MP before therapeutic intervention were the factors affecting the outcomes.

The effect of ketorolac on anteroposterior knee laxity after anterior cruciate ligament reconstruction.

UNLABELLED: This study investigated the effect of ketorolac on anteroposterior laxity after anterior cruciate ligament (ACL) reconstruction. A total of 168 ACL reconstructions performed between July 2003 and November 2004 were reviewed. The 6-week KT-1000 manual maximum differences between the ACL-reconstructed knee and nonoperative knee were compared for patients who received ketorolac and those who did not. Mean manual maximum difference in anterior displacement was 0.6 mm in the ketorolac group and -0.6 mm in the non-ketorolac group (P=.03). When bone-patellar tendon grafts were analyzed as a separate group, mean manual maximum difference was 0.5 mm in the ketorolac group and -1.4 mm in the non-ketorolac group (P=.007). When hamstring grafts were analyzed separately, mean manual maximum difference was 0.7 mm in the ketorolac group and 0.4 mm in the non-ketorolac group (P=.59). The use of ketorolac during bone-patellar tendon autograft ACL reconstruction was associated with increased AP laxity at 6 weeks postoperatively. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Pharmacological resources, diagnostic approach and coordination of care in joint hypermobility-related disorders.

INTRODUCTION: Joint hypermobility (JH) is the hallmark of many hereditary soft connective tissue disorders, including Ehlers-Danlos syndromes and related disorders, disorders of the TGFß-pathway, lateral meningocele syndrome, arterial tortuosity syndrome, and cutis laxa syndromes. Contemporary practice separates individuals with isolated, non-syndromic JH from patients with Mendelian syndromes and those with hypermobility spectrum disorders. The latter is a new nosologic entity grouping together individuals with JH and related musculoskeletal manifestations, but lacking inclusion criteria for well-defined and/or single-gene disorders. Area covered: Nomenclature of JH and JH-related disorders are summarized on a practically oriented perspective. Critical areas of clinical management comprise pain; cardiovascular and respiratory issues; fatigue and dysautonomia; bone fragility; and capillary, skin and soft tissue fragility. Medical management stands on low-evidence data. Ongoing preclinical and clinical studies are aimed to reach a more personalized pharmacological approach to the management of the cardiovascular risk, musculoskeletal pain, and reduced bone mass. Expert commentary: Correct classification of patients with JH-related disorders needs a systematic approach, in which a wide array of molecular tests should be intermingled with strong clinical competences in highly specialized settings. A multispecialty, hierarchical approach should be encouraged for optimal coordination of care in systemic phenotypes.

OK-432 (Picibanil) sclerotherapy for recurrent dislocation of the temporomandibular joint in elderly edentulous patients: Case reports.

Dislocation of the temporomandibular joint (TMJ) is a thorny problem not only for a patient but also a doctor. Especially for the elderly edentulous patients, it is very hard to treat the condition although there are many surgical and non-surgical procedures. We successfully treated it in two elderly edentulous patients by injection of OK-432 as a sclerosing agent.