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Effect of Multiple Injections of Botulinum Toxin into Painful Masticatory Muscles on Bone Density in the Temporomandibular Complex

Raphael, Karen G; Janal, Malvin N; Tadinada, Aditya; Santiago, Vivian; Sirois, David A; Lurie, Alan G
BACKGROUND:Adverse effects of masticatory muscle injections of Botulinum Toxin (Btx) have been noted in animal and, less dramatically, human studies. OBJECTIVE:Among women treated in multiple community-based private practices, to compare TMJ bone density and mandibular condylar volume between patients with myofascial TMJD receiving multiple masticatory muscle Btx treatments and similarly diagnosed women not receiving such treatment. METHODS:Cohorts consisted of women whose treatment charts indicated a diagnosis of myofascial TMJD: 35 received at least 2 Btx treatment cycles; 44 received none. Bone density at prespecified regions of interest (ROI) was defined by grey scale values from Cone Beam CT, adjusting for a fixed density phantom included in each scan. Mean bone density and mandibular condyle volume were compared between groups. Dose response effects were tested within the Btx-exposed group. RESULTS:The mean density of primary and secondary ROIs was similar between exposure groups, as was condylar volume. Among Btx-exposed women, increasing dose of Btx to the temporalis muscle was inversely proportional to the density of the trabecular area of the mandible body. Many Btx-exposed women received smaller doses of Btx to the masseter muscles than in most TMJD Btx clinical trials. CONCLUSION/CONCLUSIONS:Masticatory muscle injections of Btx failed to produce clinically significant TMJ bone-related changes. Should Btx receive regulatory approval for treatment of myofascial TMJD, a phase IV study is recommended to evaluate potential adverse effects of Btx on bone and muscle when administered at higher doses and/or for more treatment cycles.
PMID: 32885475
ISSN: 1365-2842
CID: 4583612

Depressive Symptoms Account for Differences between Self-reported Versus Polysomnographic Assessment of Sleep Quality in Women with Myofascial TMD

Dubrovsky, Boris; Janal, Malvin N; Lavigne, Gilles J; Sirois, David A; Wigren, Pia E; Nemelivsky, Lena; Krieger, Ana C; Raphael, Karen G
BACKGROUND: Temporomandibular disorder (TMD) patients report poor sleep quality on the Pittsburgh Sleep Quality Index (PSQI). However, polysomnographic (PSG) studies show meager evidence of sleep disturbance on standard physiological measures. OBJECTIVE: The present aim was to analyze self-reported sleep quality in TMD as a function of myofascial pain, PSG parameters, and depressive symptomatology. METHODS: PSQI scores from 124 women with myofascial TMD and 46 matched controls were hierarchically regressed onto TMD presence, ratings of pain intensity and pain-related disability, in-lab PSG variables, and depressive symptoms (Symptoms Checklist-90). RESULTS: Relative to controls, TMD cases had higher PSQI scores, representing poorer subjective sleep, and more depressive symptoms (both P < 0.001). Higher PSQI scores were strongly predicted by more depressive symptoms (P < 0.001, R2 = 26%). Of 19 PSG variables, two had modest contributions to higher PSQI scores: longer REM latency in TMD cases (P = 0.01, R2 = 3%) and more awakenings in all participants (P = 0.03, R2 = 2%). After accounting for these factors, TMD presence and pain ratings were not significantly related to PSQI scores. CONCLUSION: These results show that reported poor sleep quality in TMD is better explained by depressive symptoms than by PSG-assessed sleep disturbances or myofascial pain. As TMD cases lacked typical PSG features of clinical depression, the results suggest a negative cognitive bias in TMD and caution against interpreting self-report sleep measures as accurate indicators of PSG sleep disturbance. Future investigations should take account of depressive symptomatology when interpreting reports of poor sleep.
PMID: 28853162
ISSN: 1365-2842
CID: 2679452

Trigeminal neuropathic pain and orofacial neuralgias

Chapter by: Sirois, David A.; Jorns, Teekayu P.
in: Orofacial Disorders: Current Therapies in Orofacial Pain and Oral Medicine by
[S.l. : s.n.], 2017
pp. 213-222
ISBN: 9783319515076
CID: 4039742

Thermal temporal summation and decay of after-sensations in temporomandibular myofascial pain patients with and without comorbid fibromyalgia

Janal, Malvin N; Raphael, Karen G; Cook, Dane B; Sirois, David A; Nemelivsky, Lena; Staud, Roland
INTRODUCTION: Chronic myofascial temporomandibular disorders (TMD) may have multiple etiological and maintenance factors. One potential factor, central pain sensitization, was quantified here as the response to the temporal summation (TS) paradigm, and that response was compared between case and control groups. OBJECTIVES: As previous research has shown that fibromyalgia (FM) is diagnosed in20% of TMD patients, Aim 1 determined whether central sensitization is found preferentially in myofascial TMD cases that have orofacial pain as a regional manifestation of FM. Aim 2 determined if the report of after-sensations (AS) following TS varied depending on whether repeated stimuli were rated as increasingly painful. METHODS: One hundred sixty-eight women, 43 controls, 100 myofascial TMD-only cases, and 25 myofascial TMD + FM cases, were compared on thermal warmth and pain thresholds, thermal TS, and decay of thermal AS. All cases met Research Diagnostic Criteria for TMD; comorbid cases also met the 1990 American College of Rheumatology criteria for FM. RESULTS: Pain thresholds and TS were similar in all groups. When TS was achieved (~60%), significantly higher levels of AS were reported in the first poststimulus interval, and AS decayed more slowly over time, in myofascial TMD cases than controls. By contrast, groups showed similar AS decay patterns following steady state or decreasing responses to repetitive stimulation. CONCLUSION: In this case-control study, all myofascial TMD cases were characterized by a similar delay in the decay of AS. Thus, this indicator of central sensitization failed to suggest different pain maintenance factors in myofascial TMD cases with and without FM.
PMID: 27672341
ISSN: 1178-7090
CID: 2261872

Validity of self-reported sleep bruxism among myofascial temporomandibular disorder patients and controls

Raphael, K G; Janal, M N; Sirois, D A; Dubrovsky, B; Klausner, J J; Krieger, A C; Lavigne, G J
Sleep bruxism (SB), primarily involving rhythmic grinding of the teeth during sleep, has been advanced as a causal or maintenance factor for a variety of oro-facial problems, including temporomandibular disorders (TMD). As laboratory polysomnographic (PSG) assessment is extremely expensive and time-consuming, most research testing this belief has relied on patient self-report of SB. The current case-control study examined the accuracy of those self-reports relative to laboratory-based PSG assessment of SB in a large sample of women suffering from chronic myofascial TMD (n = 124) and a demographically matched control group without TMD (n = 46). A clinical research coordinator administered a structured questionnaire to assess self-reported SB. Participants then spent two consecutive nights in a sleep laboratory. Audiovisual and electromyographic data from the second night were scored to assess whether participants met criteria for the presence of 2 or more (2+) rhythmic masticatory muscle activity episodes accompanied by grinding sounds, moderate SB, or severe SB, using previously validated research scoring standards. Contingency tables were constructed to assess positive and negative predictive values, sensitivity and specificity, and 95% confidence intervals surrounding the point estimates. Results showed that self-report significantly predicted 2+ grinding sounds during sleep for TMD cases. However, self-reported SB failed to significantly predict the presence or absence of either moderate or severe SB as assessed by PSG, for both cases and controls. These data show that self-report of tooth grinding awareness is highly unlikely to be a valid indicator of true SB. Studies relying on self-report to assess SB must be viewed with extreme caution.
PMID: 26010126
ISSN: 1365-2842
CID: 1602322

World Workshop on Oral Medicine VI: a systematic review of the treatment of mucocutaneous pemphigus vulgaris

McMillan, R; Taylor, J; Shephard, M; Ahmed, R; Carrozzo, M; Setterfield, J; Grando, S; Mignogna, M; Kuten-Shorrer, M; Musbah, T; Elia, A; McGowan, R; Kerr, A R; Greenberg, M S; Hodgson, T; Sirois, D
OBJECTIVE: To determine the efficacy and safety of interventions for pemphigus vulgaris (PV). STUDY DESIGN: We conducted a systematic review from 2003 to 2013 according to the Cochrane Collaboration methodology. Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) and observational studies were conducted along with diagnosis confirmed by clinical, histopathologic, and immunofluorescence criteria. Primary outcomes were disease remission and mortality; several relevant secondary outcomes were also included. RESULTS: Fourteen RCTs or CCTs and 110 observational studies were included in the final analyses. RCTs or CCTs demonstrated considerable heterogeneity in outcome measures, and all had a high risk of bias for at least 1 of 8 domains. Of the studies, 96.8% (120) described the use of oral corticosteroids. Azathioprine and mycophenolate-mofetil were the most commonly cited treatments. An increasing number of studies described biologic therapies (rituximab, intravenous immunoglobulin [IVIg]). Evidence supporting recent comprehensive treatment guidelines was reviewed. CONCLUSIONS: We found persisting wide variations in treatment practice and inadequate quality of research supporting optimal PV treatment.
PMID: 25934414
ISSN: 2212-4411
CID: 1556022

World Workshop on Oral Medicine VI: a systematic review of the treatment of mucous membrane pemphigoid

Taylor, J; McMillan, R; Shephard, M; Setterfield, J; Ahmed, R; Carrozzo, M; Grando, S; Mignogna, M; Kuten-Shorrer, M; Musbah, T; Elia, A; McGowan, R; Kerr, A R; Greenberg, M S; Hodgson, T; Sirois, D
OBJECTIVE: To determine the efficacy and safety of interventions for mucous membrane pemphigoid (MMP). STUDY DESIGN: We conducted a systematic review from 2003 to 2013 according to the Cochrane Collaboration methodology. Randomized controlled trials (RCTs) or controlled clinical trials and observational studies were included, with diagnosis confirmed by clinical, histopathologic, and immunofluorescence criteria. The primary outcome was lesion remission or healing; several relevant secondary outcomes were also included. RESULTS: In the final analysis, 1 RCT and 32 observational studies were included. The one included RCT with a high risk of bias in multiple domains found limited evidence that pentoxifylline, combined with corticosteroid and cyclophosphamide, was more effective than standard therapy (corticosteroid + cyclophosphamide alone) for ocular MMP. We summarize here the outcomes from 32 observational studies examining 242 patients across 19 unique treatments. Interventions that show promise include rituximab and intravenous immunoglobulin. CONCLUSIONS: This systematic review is the most recent since 2003-2009. There is still lack of high-quality research providing evidence-based MMP treatments.
PMID: 25953640
ISSN: 2212-4411
CID: 1568362

Development of a Disease Registry for Autoimmune Bullous Diseases: Initial Analysis of the Pemphigus Vulgaris Subset

Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A
Pemphigus vulgaris (PV) is a rare, potentially life threate-ning, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, email, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation.
PMID: 24691863
ISSN: 0001-5555
CID: 922652

Neuromuscular diseases

Chapter by: Sirois, David
in: Burket's oral medicine by Glick, Michael (Ed)
Shelton, Connecticut : People's Medical Publishing House USA, 2015
pp. ?-?
ISBN: 9781607952800
CID: 4039832

Osteopenic consequences of botulinum toxin injections in the masticatory muscles: a pilot study

Raphael, K G; Tadinada, A; Bradshaw, J M; Janal, M N; Sirois, D A; Chan, K C; Lurie, A G
Patients with temporomandibular muscle and joint disorder (TMJD) increasingly seek and receive treatment for their pain with botulinum toxin (BoNTA; botulinum toxin A). Used intramuscularly in therapeutic doses, it produces localised paresis. Such paresis creates risk of reduced bone mineral density, or 'disuse osteopenia'. Animal studies have frequently used BoNTA as a model of paralysis to induce bone changes within short periods. Osteopenic effects can be enduring in animals but have yet to be studied in humans. This is the first study in humans to examine bone-related consequences of BoNTA injections in the masticatory muscles, comparing oral and maxillofacial radiologists' ratings of trabecular bone patterns in the condyles of patients with TMJD exposed to multiple masticatory muscle injection sessions with BoNTA to a sample of patients with TMJD unexposed to masticatory muscle injections with BoNTA. Cone-beam computed tomography (CBCT)-derived images of bilateral condyles were evaluated in seven patients with TMJD receiving 2+ recent BoNTA treatment sessions for facial pain and nine demographically matched patients with TMJD not receiving BoNTA treatment. Two oral and maxillofacial radiologists evaluated CBCT images for evidence of trabecular changes consistent with osteopenia. Both evaluators noted decreased density in all participants exposed to BoNTA and in none of the unexposed participants (P < 0.001). No other abnormalities associated with reduced loading were detected. These findings need replication in a larger sample and over a longer time period, to ensure safety of patients with TMJD receiving multiple BoNTA injections for their pain.
PMID: 24836732
ISSN: 0305-182x
CID: 1004612