Papers by Cynthia Comella
Frontiers in Neurology, 2020
Background: Botulinum toxin-A (BoNT-A) injections are first-line treatment for adult spasticity. ... more Background: Botulinum toxin-A (BoNT-A) injections are first-line treatment for adult spasticity. Prior patient surveys have reported that BoNT-A treatment improves quality of life but that symptoms usually recur before the next injection. We aimed to explore, in-depth, patient perceptions of the impact of spasticity and the waning of BoNT-A therapeutic effects.Methods: An internet-based survey was conducted through Carenity, an online patient community, from May to September 2019 in France, Germany, Italy, UK and USA. Eligible respondents were adult patients with spasticity due to stroke, traumatic brain injury (TBI) or spinal cord injury (SCI) who had ≥2 previous BoNT-A injections.Results: Two hundred and ten respondents (mean 47.2 years) met screening criteria and had their responses analyzed. Overall, 43% of respondents had spasticity due to stroke, 30% due to TBI and 27% due to SCI. The mean [95% CI] injection frequency for spasticity management was 3.6 [3.4–3.7] injections/year...
Ear, Nose & Throat Journal, 2011
Dystonias are a group of disorders characterized by muscle contractions that can produce twisting... more Dystonias are a group of disorders characterized by muscle contractions that can produce twisting and repetitive movements or abnormal postures. Dystonias of the head and neck region, except for spasmodic dysphonia, are rarely described in the otolaryngology literature. Ironically, it is the otolaryngologic surgeon's knowledge of anatomy and physiology of the head and neck that can be of greatest benefit for patients suffering from these disorders. Medical and surgical treatment options are available in treating this disorder. This article is intended to serve as an introduction and overview of dystonias for the otolaryngologist-head and neck surgeon.
Ear, Nose & Throat Journal, 2011
The objective of this study was to investigate quality-of-life outcomes in patients with jaw-open... more The objective of this study was to investigate quality-of-life outcomes in patients with jaw-opening oromandibular dystonia who had received treatment with botulinum neurotoxin injections. The Glasgow Benefit Inventory (GBI) was used as a post-intervention questionnaire to measure patient benefit. Twenty-five questionnaires were sent to patients. Of the 12 patients who returned the form (48% response rate), the mean scores for the general GBI subscore (p = 0.001), the social support GBI subscore (p = 0.031), and the physical health GBI subscore (p = 0.002) demonstrated statistically significant benefit from the injections. No scores demonstrated a negative impact. Botulinum neurotoxin injections were demonstrated to benefit the quality of life in patients suffering from jawopening oromandibular dystonia.
Neurology, Jan 10, 2016
To update the 2008 American Academy of Neurology (AAN) guidelines regarding botulinum neurotoxin ... more To update the 2008 American Academy of Neurology (AAN) guidelines regarding botulinum neurotoxin for blepharospasm, cervical dystonia (CD), headache, and adult spasticity. We searched the literature for relevant articles and classified them using 2004 AAN criteria. Blepharospasm: OnabotulinumtoxinA (onaBoNT-A) and incobotulinumtoxinA (incoBoNT-A) are probably effective and should be considered (Level B). AbobotulinumtoxinA (aboBoNT-A) is possibly effective and may be considered (Level C). CD: AboBoNT-A and rimabotulinumtoxinB (rimaBoNT-B) are established as effective and should be offered (Level A), and onaBoNT-A and incoBoNT-A are probably effective and should be considered (Level B). Adult spasticity: AboBoNT-A, incoBoNT-A, and onaBoNT-A are established as effective and should be offered (Level A), and rimaBoNT-B is probably effective and should be considered (Level B), for upper limb spasticity. AboBoNT-A and onaBoNT-A are established as effective and should be offered (Level A) ...
Neurology. Genetics, 2016
To characterize the clinical and genetic features of cervical dystonia (CD). Participants enrolle... more To characterize the clinical and genetic features of cervical dystonia (CD). Participants enrolled in the Dystonia Coalition biorepository (NCT01373424) with initial manifestation as CD were included in this study (n = 1,000). Data intake included demographics, family history, and the Global Dystonia Rating Scale. Participants were screened for sequence variants (SVs) in GNAL, THAP1, and Exon 5 of TOR1A. The majority of participants were Caucasian (95%) and female (75%). The mean age at onset and disease duration were 45.5 ± 13.6 and 14.6 ± 11.8 years, respectively. At the time of assessment, 68.5% had involvement limited to the neck, shoulder(s), and proximal arm(s), whereas 47.4% had dystonia limited to the neck. The remaining 31.5% of the individuals exhibited more extensive anatomical spread. A head tremor was noted in 62% of the patients. Head tremor and laryngeal dystonia were more common in females. Psychiatric comorbidities, mainly depression and anxiety, were reported by 32...
Movement Disorders Clinical Practice, 2015
We present the methodology utilized for development and clinimetric testing of the Comprehensive ... more We present the methodology utilized for development and clinimetric testing of the Comprehensive Cervical Dystonia (CD) Rating scale, or CCDRS. The CCDRS includes a revision of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-2), a newly developed psychiatric screening tool (TWSTRS-PSYCH), and the previously validated Cervical Dystonia Impact Profile (CDIP-58). For the revision of the TWSTRS, the original TWSTRS was examined by a committee of dystonia experts at a dystonia rating scales workshop organized by the Dystonia Medical Research Foundation. During this workshop, deficiencies in the standard TWSTRS were identified and recommendations for revision of the severity and pain subscales were incorporated into the TWSTRS-2. Given that no scale currently evaluates the psychiatric features of cervical dystonia (CD), we used a modified Delphi methodology and a reiterative process of item selection to develop the TWSTRS-PSYCH. We also included the CDIP-58 to capture the impact of CD on quality of life. The three scales (TWSTRS2, TWSTRS-PSYCH, and CDIP-58) were combined to construct the CCDRS. Clinimetric testing of reliability and validity of the CCDRS are described. The CCDRS was designed to be used in a modular fashion that can measure the full spectrum of CD. This scale will provide rigorous assessment for studies of natural history as well as novel symptom-based or disease-modifying therapies.
Journal of the neurological sciences, Jan 15, 2014
Typically, botulinum toxin injections for blepharospasm or cervical dystonia (CD) are administere... more Typically, botulinum toxin injections for blepharospasm or cervical dystonia (CD) are administered at approximately 3-month intervals, reflecting concerns that shorter intervals might increase the risk of adverse events (AEs) and development of neutralizing antibodies. These post-hoc analyses investigated flexible incobotulinumtoxinA (Xeomin®) injection intervals (6-20 weeks) in patients with blepharospasm or CD. Patients received up to 6 injections at intervals ≥ 6 weeks, as determined by physician assessment upon patient request. The blepharospasm study permitted flexible doses (≤ 50 U/eye). The CD study employed fixed dosing using incobotulinumtoxinA 120 U, 240 U, or placebo for the first treatment followed by subsequent randomization to 120 U or 240 U for the extension period. Standard safety assessments were performed. Intervals <12 weeks were employed in 207 of 461 (44.9%) treatment cycles for blepharospasm and in 369 of 821 (44.9%) treatment cycles for CD. The most frequen...
Toxicon, 2009
This is a review on the use of injections of botulinum toxin for the treatment of focal dystonias... more This is a review on the use of injections of botulinum toxin for the treatment of focal dystonias. Disorders covered include cranial dystonia, cervical dystonia, spasmodic dysphonia, and focal hand dystonia. Considered are clinical aspects, alternative treatment strategies and principles of use of botulinum toxin injections.
Journal of the Neurological Sciences, 2015
Background: The Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy... more Background: The Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE; NCT00836017) is a prospective, observational, multicenter, real-world registry designed to assess the safety, effectiveness, and treatment utilization following multiple treatments of onabotulinumtoxinA. Methods: Subjects were naïve to botulinum toxin, new to practice, or had not received toxin in ≥16 weeks if in a clinical trial. Dosages and treatment intervals varied due to the real-world design. Descriptive and inferential statistics evaluated changes over 3 treatments. Results: 1046 subjects enrolled. Subjects were 74.4% female, 63.5% toxin-naïve, mean age 58.0 ± 14.7 years. The mean dose over 2481 treatment sessions was 189.8 ± 87.1 U, with average treatment intervals of 14.6 and 15.1 weeks. The mean Toronto Western Spasmodic Torticollis Rating Scale Total score in subjects who completed all assessments (n = 479) decreased from 39.2 at baseline to 27.1 at final visit (P b .0001). A high percentage of physicians reported improvement in Clinician Global Impression of Change after initial assessment; this significantly increased at final assessment (n = 479, 91.2% vs 95.0%; P b .0001). Similarly, a high percentage of subjects reported improvement in Patient Global Impression of Change after initial assessment, which significantly increased at final assessment (n = 470, 83.0% vs 91.7%; P b .0001). Significant reductions in all Cervical Dystonia Impact Profile-58 scores were observed (n = 407). Overall, 26.2% of subjects reported adverse events, including muscular weakness (7.0%) and dysphagia (6.4%). Conclusions: Results indicate robust improvement in clinical ratings and excellent tolerability following onabotulinumtoxinA treatment of CD.
Journal of Neurology, 2015
This was an international survey undertaken to assess cervical dystonia (CD) patients own percept... more This was an international survey undertaken to assess cervical dystonia (CD) patients own perceptions of their illness and its management. A total of 1,071 selfidentified respondents with CD in 38 countries completed the online survey between March and December 2012. The mean time since diagnosis was 9.6 years and over half (54 %) of patients surveyed were not diagnosed in the first year. When asked how the symptoms of CD affected them, two-thirds (66 %) of patients reported they experienced a lot of pain, and 61 % said that they suffered depression and mood alterations; only 7 % reported no impact on their lives. Despite problems with the diagnosis, almost 70 % of respondents reported being satisfied with the overall relationship with their doctor. Patient treatment expectations were high, with 63 % expecting freedom from spasms and 62 % expecting freedom from pain. Over half (53 %) expected to be able to return to a normal routine (53 %). The most common treatment reported was botulinum toxin (BoNT) (86 %), followed by oral medication (58 %) and physiotherapy/physical therapy (37 %). Among patients treated on BoNT, 56 % were fairly/very satisfied, 25 % were fairly/very dissatisfied and 20 % were neither satisfied nor dissatisfied with the outcome. In conclusion, this international survey highlights the broad impact of CD on several aspects of patient life. Taken overall, the survey suggests that that patients need to be better informed about their condition, treatments available and the limitations of those treatments. It may be that realistically managing patient expectations of treatment would reduce the dissatisfaction of some patients.
Neurotherapeutics, 2013
With advances in the understanding of the pathophysiology of dystonia, novel therapeutics are bei... more With advances in the understanding of the pathophysiology of dystonia, novel therapeutics are being developed. Such therapies will require clinical investigation ranging from exploratory studies to examine safety, tolerability, dosage selection, and preliminary efficacy to confirmatory studies to evaluate efficacy definitively. As dystonia is a rare and complex disorder with clinical and etiological heterogeneity, clinical trials will require careful consideration of the trial design, including enrollment criteria, concomitant medication use, and outcome measures. Given the complexities of designing and implementing efficient clinical trials, it is important for clinicians and statisticians to collaborate closely throughout the clinical development process and that each has a basic understanding of both the clinical and statistical issues that must be addressed. To facilitate designing appropriate clinical trials in this field, we review important general clinical trial and regulatory principles, and discuss the critical components of trials with an emphasis on considerations specific to dystonia. Additionally, we discuss designs used in early exploratory, late exploratory, and confirmatory phases, including adaptive designs.
JAMA Neurology, 2014
IMPORTANCE Data on the long-term cognitive outcomes of patients with PARKIN-associated Parkinson ... more IMPORTANCE Data on the long-term cognitive outcomes of patients with PARKIN-associated Parkinson disease (PD) are unknown but may be useful when counseling these patients. OBJECTIVE Among patients with early-onset PD of long duration, we assessed cognitive and motor performances, comparing homozygotes and compound heterozygotes who carry 2 PARKIN mutations with noncarriers. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of 44 participants at 17 different movement disorder centers who were in the Consortium on Risk for Early-Onset PD study with a duration of PD greater than the median duration (>14 years): 4 homozygotes and 17 compound heterozygotes (hereafter referred to as carriers) and 23 noncarriers. MAIN OUTCOMES AND MEASURES Unified Parkinson Disease Rating Scale Part III (UPDRS-III) and Clinical Dementia Rating scores and neuropsychological performance. Linear regression models were applied to assess the association between PARKIN mutation status and cognitive domain scores and UPDRS-III scores. Models were adjusted for age, education, disease duration, language, and levodopa equivalent daily dose. RESULTS Carriers had an earlier age at onset of PD (P < .001) and were younger (P = .004) at time of examination than noncarriers. They performed better than noncarriers on the Mini-Mental State Examination (P = .010) and were more likely to receive lower scores on the Clinical Dementia Rating (P = .003). In multivariate analyses, carriers performed better than noncarriers on the UPDRS-III (P = .02) and on tests of attention (P = .03), memory (P = .03), and visuospatial (P = .02) cognitive domains. CONCLUSIONS AND RELEVANCE In cross-sectional analyses, carriers demonstrated better cognitive and motor performance than did noncarriers with long disease duration, suggesting slower disease progression. A longitudinal follow-up study is required to confirm these findings.
Parkinsonism & Related Disorders, 2011
Background-Mutations in parkin are a known genetic risk factor for early-onset Parkinson's diseas... more Background-Mutations in parkin are a known genetic risk factor for early-onset Parkinson's disease (EOPD) but their role in non-motor manifestations is not well established. Genetic factors for depression are similarly not well characterized. We investigate the role of parkin mutations in depression among those with EOPD and their relatives. Methods-We collected psychiatric information using the Patient Health Questionnaire and Beck Depression Inventory II on 328 genotyped individuals including 88 probands with early onset PD (41 with parkin mutations, 47 without) and 240 first and second degree relatives without PD. Results-Genotype was not associated with depression risk among probands. Among unaffected relatives of EOPD cases, only compound heterozygotes (n=4), and not heterozygotes, had significantly increased risk of depressed mood (OR=14.1; 95% CI 1.2-163.4), moderate to severe depression (OR=17.8; 95% CI 1.0-332.0), depression (score ≥15) on the Beck Depression Inventory II (BDI-II) (OR=51.9; 95% CI 4.1-657.4), and BDI-II total depression score (β=8.4; 95% CI 2.4-11.3) compared to those without parkin mutations. Conclusions-Relatives of EOPD cases with compound heterozygous mutations and without diagnosed PD may have a higher risk of depression compared to relatives without parkin mutations. These findings support evidence of a genetic contribution to depression and may extend the phenotypic spectrum of parkin mutations to include non-motor manifestations that precede the development of PD.
Parkinsonism & Related Disorders, 2006
One factor, which may contribute to slowed movement in dystonia, is impairment in controlling the... more One factor, which may contribute to slowed movement in dystonia, is impairment in controlling the voluntary rate of motor output. This study examined the ability of patients with focal hand dystonia to rapidly turn force on and off at the wrist and elbow joints. Dystonic patients were slower than controls in rapidly turning on force from rest at both joints, passively relaxing force and rapidly reversing force output from a steady-state flexion contraction. Adding a preload did not improve the ability of dystonic subjects to rapidly turn on force. These results support the idea that dystonia is a disorder of impaired motor cortical activation, possibly due to basal ganglia dysfunction.
Neurology, 2010
Background: While Parkinson disease (PD) is consistently associated with impaired olfaction, one ... more Background: While Parkinson disease (PD) is consistently associated with impaired olfaction, one study reported better olfaction among Parkin mutation carriers than noncarriers. Whether olfaction differs between Parkin mutation heterozygotes and carriers of 2 Parkin mutations (compound heterozygotes) is unknown. Objective: To assess the relationship between Parkin genotype and olfaction in PD probands and their unaffected relatives. Methods: We administered the University of Pennsylvania Smell Identification Test (UPSIT) to 44 probands in the Consortium on Risk for Early-Onset Parkinson Disease study with PD onset Յ50 years (10 Parkin mutation heterozygotes, 9 compound heterozygotes, 25 noncarriers) and 80 of their family members (18 heterozygotes, 2 compound heterozygotes, 60 noncarriers). In the probands, linear regression was used to assess the association between UPSIT score (outcome) and Parkin genotype (predictor), adjusting for covariates. Among family members without PD, we compared UPSIT performance in heterozygotes vs noncarriers using generalized estimating equations, adjusting for family membership, age, gender, and smoking. Results: Among probands with PD, compound heterozygotes had higher UPSIT scores (31.9) than heterozygotes (20.1) or noncarriers (19.9) (p Ͻ 0.001). These differences persisted after adjustment for age, gender, disease duration, and smoking. Among relatives without PD, UPSIT performance was similar in heterozygotes (32.5) vs noncarriers (32.4), and better than in heterozygotes with PD (p ϭ 0.001). Conclusion: Olfaction is significantly reduced among Parkin mutation heterozygotes with PD but not among their heterozygous relatives without PD. Compound heterozygotes with PD have olfaction within the normal range. Further research is required to assess whether these findings reflect different neuropathology in Parkin mutation heterozygotes and compound heterozygotes. Neurology ® 2011;76:319-326 GLOSSARY AAO ϭ age at onset; CORE-PD ϭ Consortium on Risk for Early-Onset Parkinson Disease study; EOPD ϭ early-onset Parkinson disease; GEE ϭ generalized estimating equation; MMSE ϭ Mini-Mental State Examination; PD ϭ Parkinson disease; UPSIT ϭ
Neurology, 2003
This assessment evaluates the clinical utility, efficacy, and safety of quantitative sensory test... more This assessment evaluates the clinical utility, efficacy, and safety of quantitative sensory testing (QST). Methods: By searching MEDLINE, Current Contents, and their personal files, the authors identified 350 articles. Selected articles utilized computer operated threshold systems, manually operated threshold systems, and electrical threshold devices. The authors evaluated the use of normal values and the degree of reproducibility between the same and different systems. Articles were rated using a standard classification of evidence scheme. Results: Because of differences between systems, normal values from one system cannot be transposed to others. Reproducibility of results was also an important concern, and there is no consensus on how it should be defined. The authors identified no adequately powered class I studies demonstrating the effectiveness of QST in evaluating any particular disorder. A number of class II and III studies demonstrated that QST is probably or possibly useful in identifying small or large fiber sensory abnormalities in patients with diabetic neuropathy, small fiber neuropathies, uremic neuropathies, and demyelinating neuropathy. Conclusions: QST is a potentially useful tool for measuring sensory impairment for clinical and research studies. However, QST results should not be the sole criteria used to diagnose pathology. Because malingering and other nonorganic factors can influence the test results, QST is not currently useful for the purpose of resolving medicolegal matters. Well-designed studies comparing different QST devices and methodologies are needed and should include patients with abnormalities detected solely by QST.
Neurology, 2012
Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with e... more Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). Methods: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age-and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed. Results: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale-III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p ϭ 0.035), and on the memory (p ϭ 0.017) and visuospatial (p ϭ 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p Ͻ 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p Ͻ 0.001), and a clinical diagnosis of either MCI or dementia (p ϭ 0.004). Conclusion: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD.
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Neurology, 2008
Objective: To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin... more Objective: To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of movement disorders.Methods: A literature search was performed including MEDLINE and Current Contents for therapeutic articles relevant to BoNT and selected movement disorders. Authors reviewed, abstracted, and classified articles based on American Academy of Neurology criteria (Class I–IV).Results: The highest quality literature available for the respective indications was as follows: blepharospasm (two Class II studies); hemifacial spasm (one Class II and one Class III study); cervical dystonia (seven Class I studies); focal upper extremity dystonia (one Class I and three Class II studies); focal lower extremity dystonia (one Class II study); laryngeal dystonia (one Class I study); motor tics (one Class II study); and upper extremity essential tremor (two Class II studies).Recommendations: Botulinum neurotoxin should be offered as a treatment option for the t...
Muscle & Nerve, 2004
Botulinum toxins are among the most potent neurotoxins known to humans. In the past 25 years, bot... more Botulinum toxins are among the most potent neurotoxins known to humans. In the past 25 years, botulinum toxin has emerged as both a potential weapon of bioterrorism and as a powerful therapeutic agent, with growing applications in neurological and non-neurological disease. Botulinum toxin is unique in its ability to target peripheral cholinergic neurons, preventing the release of acetylcholine through the enzymatic cleavage of proteins involved in membrane fusion, without prominent central nervous system effects. There are seven serotypes of the toxin, each with a specific activity at the molecular level. Currently, serotypes A (in two preparations) and B are available for clinical use, and have been shown to be safe and effective for the treatment of dystonia, spasticity, and other disorders in which muscle overactivity gives rise to symptoms. This review focuses on the pharmacology, electrophysiology, immunology, and application of botulinum toxin in selected neurological disorders.
Movement Disorders, 2012
Objective-To determine the reliability of a new scale for the clinical assessment of essential tr... more Objective-To determine the reliability of a new scale for the clinical assessment of essential tremor. Background-The Essential Tremor Rating Assessment Scale contains nine performance items that rate action tremor in the head, face, voice, limbs and trunk 0-4 in half-point intervals. Head and limb tremor ratings are defined by specific amplitude ranges in centimeters. Design/Methods-Videos of 44 patients and 6 controls were rated by 10 specialists on two occasions, 1-2 months apart. Inter-and intra-rater reliabilities were assessed with a two-way random effects intraclass correlation, using an absolute agreement definition. Results-The inter-and intra-rater intraclass correlations for head and upper limb tremor ranged from 0.86 to 0.96, and the intraclass correlations for the total score were 0.94 and 0.96. The intraclass correlations for voice, face, trunk and leg were less robust. Conclusions-This scale is an exceptionally reliable tool for the clinical assessment of essential tremor.
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Papers by Cynthia Comella