Skip to main content

HD-PRO-TRIAD™ Validation: a Patient-Reported Instrument for the Symptom Triad of Huntington Disease

Background: Few valid, disease‐specific measures of health‐related quality of life (HRQOL) capture the spectrum of symptoms associated with Huntington's disease (HD). The HD‐PRO‐TRIAD™ is a new, HD‐specific, patient‐reported outcome (PRO) instrument of the HD symptom triad (cognitive decline, emotional/behavioral dyscontrol, and motor dysfunction) designed for clinical research and practice. The objective was to validate the HD‐PRO‐TRIAD™ through a cross‐sectional sample of individuals with HD and caregivers.

Methods: Development of the HD‐PRO‐TRIAD™ has been described elsewhere. A total of 132 individuals with HD and 40 HD caregivers, comprising 29 dyads, participated in the cross‐sectional psychometric validation of this instrument. Participants provided responses to the HD‐PRO‐TRIAD™ and other HRQOL and disease severity instruments (EuroQOL 5D, Short Form 12, Neuro‐QOL Item Banks, PROMIS Global Health, and self‐reported Unified Huntington's Disease Rating Scale Total Functional Capacity and Independence Scales). Internal consistency, construct validity, and patient–caregiver proxy consistency were evaluated.

Results: Internal consistency of the three domains and overall HD‐PRO‐TRIAD™ instrument was supported by Cronbach's alpha values ≥0.94. Construct validity was supported by significant correlations between HD‐PRO‐TRIAD™ domain scores and other measures of the same domains (e.g., significant positive correlations between HD‐PRO‐TRIAD™ Anxiety with Neuro‐QOL Anxiety), as well as slightly weaker but still strong correlations with other HRQOL instruments (e.g., HD‐PRO‐TRIAD™ Anxiety and UHDRS Independence; all p less than 0.01). Consistency between patient self‐report and caregiver proxy report was supported by an intra‐class correlation coefficient ≥0.92 for all three domains and the overall instrument.

Discussion: These data indicate that HD‐PRO‐TRIAD™ is a reliable and valid HRQOL instrument that captures the typical triad of HD symptoms.

Publication type: 
Author: 
Noelle E. Carlozzi
David Victorson
Victor Sung
Jennifer L. Beaumont
Wendy Cheng
Brian Gorin
Mei Sheng Duh
David Samuelson
David Tulsky
Sandra Gutierrez
Cindy J. Nowinski
Allison Mueller
Vivienne Shen
Samuel Frank
Subjects: 
Neurosciences
Title string: 
HD-PRO-TRIAD™ Validation: a Patient-Reported Instrument for the Symptom Triad of Huntington Disease
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:179309

Observational Study of IncobotulinumtoxinA for Cervical Dystonia or Blepharospasm (XCiDaBLE): Interim Results for the First 170 Subjects with Blepharospasm

Background: XCiDaBLE is a large, prospective, observational “naturalistic” study evaluating Xeomin® for Cervical Dystonia or BLEpharospasm in the United States. We report the interim results from the blepharospasm cohort of XCiDaBLE.

Methods: Subjects (≥18 years old) with blepharospasm were followed for two treatment cycles of incobotulinumtoxinA and monitored for 4 weeks after injection via interactive voice/web response system (IVRS/IWRS). The investigator‐reported scale includes the Clinical Global Impression Scale‐Severity subscale (CGI‐S). Patient‐reported outcome measures include the Patient Global Impression Scale‐Severity (PGI‐S) and ‐Improvement (PGI‐I) subscales, Jankovic Rating Scale (JRS), SF‐12v2® health survey, and Work Productivity and Activity Impairment questionnaire. Subjects are seen by the investigator at baseline (including the first injection), during the second injection, and at a final study visit (12 weeks after the second injection).

Results: One hundred seventy subjects were included in this interim analysis. The majority of subjects were female (77.1%) and white (91.8%), and had previously been treated with botulinum toxins (96.5%). The mean total dose (both eyes) was 71.5 U of incobotulinumtoxinA for the first injection. PGI‐S, PGI‐I, and JRS scores were significantly improved 4 weeks after treatment (all p less than 0.0001). No differences were noted in either quality of life (QoL) or work productivity in this short assessment period. No unexpected adverse events occurred.

Discussion: This is an interim study and assessment method based on an IVRS/IWRS. In this predominantly toxin‐experienced cohort, significant benefits in specific and global measures of disease severity were seen in the immediate post‐incobotulinumtoxinA injection period. It will be interesting to see if there are improvements in QoL with consistent individualized injections over a longer period.

Publication type: 
Author: 
Hubert H. Fernandez
Joseph Jankovic
John B. Holds
Daniel Lin
John Burns
Amit Verma
Kapil Sethi
Eric J. Pappert
XCiDaBLE Study Group
Subjects: 
Neurosciences
Title string: 
Observational Study of IncobotulinumtoxinA for Cervical Dystonia or Blepharospasm (XCiDaBLE): Interim Results for the First 170 Subjects with Blepharospasm
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:179255

Mild Cognitive Impairment, Dementia, and Affective Disorders in Essential Tremor: A Prospective Study

Background: It is now reported that non‐motor features, cognitive and affective problems, are becoming a major factor in essential tremor (ET). The aim of this study was to investigate the prevalence of cognitive and affective dysfunction in ET and to prospectively follow‐up changes in the subjects. Methods: Fifty‐two persons over the age of 50 years were recruited from the Movement Disorder Clinic. The subjects underwent baseline neurological, cognitive, and mood assessments and repeat assessment 2 years later. Results: The mean age was 68 years, with an average age of ET onset of 55.8 years and with a mean disease duration of 11.7 years. At initial cognitive assessment using various instruments and the Clinical Dementia Rating Scale, 69.2% had mild cognitive impairment (MCI). There were disturbances in phonemic fluency, verbal memory, concentration, and semantic fluency; 25% suffered from anxiety and 17.6% from depression. During the 2 years there was an annual 8.4% conversion rate to dementia, with all convertors initially suffering from MCI. Another 25% converted from no initial cognitive impairment to MCI within 2 years. At follow‐up the same percentage was still suffering from anxiety. Discussion: The study confirms our hypothesis that ET patients suffer from MCI and anxiety. Though a control group was not used, the conversion rates for patients without ET and with/without MCI are known. The uniqueness of this study is that at follow‐up, those with ET and MCI had a similar conversion rate to dementia to those suffering from MCI only. Additionally, persons with ET and no initial cognitive impairment were found to be at greater risk for developing MCI than the normal population. Clinicians must increase their awareness of cognitive impairment and anxiety in persons with ET and begin immediate treatment when indicated.

Publication type: 
Author: 
Gary Sinoff
Samih Badarny
Subjects: 
Neurosciences
Title string: 
Mild Cognitive Impairment, Dementia, and Affective Disorders in Essential Tremor: A Prospective Study
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:179267

The Non-motor Features of Essential Tremor: A Primary Disease Feature or Just a Secondary Phenomenon?

Essential tremor (ET) is a pathologically heterogeneous neurodegenerative disorder with both motor and increasingly recognized non-motor features. It is debated whether the non-motor manifestations in ET result from widespread neurodegeneration or are merely secondary to impaired motor functions and decreased quality of life due to tremor. It is important to review these features to determine how to best treat the non-motor symptoms of patients and to understand the basic pathophysiology of the disease and develop appropriate pharmacotherapies. In this review, retrospective and prospective clinical studies were critically analyzed to identify possible correlations between the severities of non-motor features and tremor. We speculated that if such a correlation existed, the non-motor features were likely to be secondary to tremor. According to the current literature, the deficits in executive function, attention, concentration, and memory often observed in ET are likely to be a primary manifestation of the disease. It has also been documented that patients with ET often exhibit characteristic personality traits. However, it remains to be determined whether the other non-motor features often seen in ET, such as anxiety, depression, and sleep disturbances are primary or secondary to motor manifestations of ET and subsequent poor quality of life. Finally, there is evidence that patients with ET can also have impaired color vision, disturbances of olfaction, and hearing impairments, though there are few studies in these areas. Further investigations of large cohorts of patients with ET are required to understand the prevalence, nature, and true significance of the non-motor features in ET.

Publication type: 
Author: 
Ketan Jhunjhunwala
Pramod K. Pal
Subjects: 
Neurosciences
Title string: 
The Non-motor Features of Essential Tremor: A Primary Disease Feature or Just a Secondary Phenomenon?
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:179240

The GABA Hypothesis in Essential Tremor: Lights and Shadows

Background: The gamma‐aminobutyric acid (GABA) hypothesis in essential tremor (ET) implies a disturbance of the GABAergic system, especially involving the cerebellum. This review examines the evidence of the GABA hypothesis. Methods: The review is based on published data about GABA dysfunction in ET, taking into account studies on cerebrospinal fluid, pathology, electrophysiology, genetics, neuroimaging, experimental animal models, and human drug therapies. Results: Findings from several studies support the GABA hypothesis in ET. The hypothesis follows four steps: 1) cerebellar neurodegeneration with Purkinje cell loss; 2) a decrease in GABA system activity in deep cerebellar neurons; 3) disinhibition in output deep cerebellar neurons with pacemaker activity; and 4) an increase in rhythmic activity of the thalamus and thalamo‐cortical circuit, contributing to the generation of tremor. Doubts have been cast on this hypothesis, however, by the fact that it is based on relatively few works, controversial post‐mortem findings, and negative genetic studies on the GABA system. Furthermore, GABAergic drug efficacy is low and some GABAergic drugs do not have antitremoric efficacy. Discussion: The GABA hypothesis continues to be the most robust pathophysiological hypothesis to explain ET. There is light in all GABA hypothesis steps, but a number of shadows cannot be overlooked. We need more studies to clarify the neurodegenerative nature of the disease, to confirm the decrease of GABA activity in the cerebellum, and to test more therapies that enhance the GABA transmission specifically in the cerebellum area.

Publication type: 
Author: 
Alexandre Gironell
Subjects: 
Neurosciences
Title string: 
The GABA Hypothesis in Essential Tremor: Lights and Shadows
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:179258

Change in Non-motor Symptoms in Parkinson’s Disease and Essential Tremor Patients: A One-year Follow-up Study

Background: Non‐motor symptoms (NMS) in Parkinson's disease (PD) differ from those in essential tremor (ET), even before a definitive diagnosis is made. It is not clear whether patient's knowledge of the diagnosis and treatment influence their subsequent reporting of NMS. Methods: 1 year after a clinical and instrumental diagnosis, we compared the motor impairment (Movement Disorders Society (MDS)‐Unified Parkinson's Disease Rating Scale‐III) and non‐motor symptoms (NMSQuest) in PD (n = 31) and ET (n = 21) patients. Results: PD patients reported more NMS than did the ET patients (p = 0.002). When compared to their baseline report, at follow‐up, PD patients reported less nocturia (p = 0.02), sadness (p = 0.01), insomnia (p = 0.02), and restless legs (p = 0.04) and more nausea (p = 0.024), unexplained pain (p = 0.03), weight change (p = 0.009), and daytime sleepiness (p = 0.03). When compared to their baseline report, ET patients reported less loss of interest (p = 0.03), anxiety (p = 0.006), and insomnia (p = 0.02). Differences in reported weight change (p less than 0.0001) and anxiety (p = 0.001) between PD and ET patients were related to pharmacological side effects or to a reduction in the ET individuals.

Publication type: 
Author: 
Maurizio Giorelli
Junia Bagnoli
Luigi Consiglio
Pasquale Difazio
Daniela Zizza
Giovanni Bosco Zimatore
Subjects: 
Neurosciences
Title string: 
Change in Non-motor Symptoms in Parkinson’s Disease and Essential Tremor Patients: A One-year Follow-up Study
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:179303

Identifying Motor, Emotional-Behavioral, and Cognitive Deficits that Comprise the Triad of HD Symptoms from Patient, Caregiver, and Provider Perspectives

Background: The objective of this study was to identify important attributes associated with the triad of symptoms (cognition, emotional–behavioral, and motor) of Huntington's disease (HD) from patient, caregiver, and medical provider perspectives to facilitate development of a new disease‐specific, health‐related quality of life (HRQOL) instrument. Methods: We conducted a targeted literature review of HD and HRQOL instruments, expert surveys, and patient and caregiver phone‐based interviews to extract information on the symptoms and issues most relevant to the HD symptom triad (HD triad). The data collected from these sources were used to generate themes and subdomains and to develop an integrated schema that highlights the key dimensions of the triad. Results: The search identified the following areas: emotional functioning/behavioral changes (e.g., positive emotions, sadness/depression); cognitive functioning (e.g., memory/learning, attention/comprehension); physical functioning (e.g., motor functioning, medication); social functioning (e.g., leisure, interpersonal relationships); end‐of‐life concerns/planning; and gene testing. Fifteen individuals diagnosed with HD and 16 HD caregivers, recruited from several Huntington's Disease Society of America support group networks, completed phone interviews. Nineteen US medical providers who specialize in HD completed the online survey. Twenty‐six subdomains of the HD symptom triad (seven cognition, 12 emotional–behavioral, and seven motor) emerged relatively consistently across patient, caregiver, and provider samples. These included movements/chorea, memory impairment, depression, and anxiety. Discussion: Based on an integrated, mixed‐methods approach, important HD triad symptom were identified and organized into a guiding schema. These patient‐, caregiver‐, and provider‐triangulated data served as the basis for development of a HD‐specific HRQOL instrument, the HD‐PRO‐TRIAD™.

Publication type: 
Author: 
David Victorson
Noelle E. Carlozzi
Samuel Frank
Jennifer L. Beaumont
Wendy Cheng
Brian Gorin
Mei Sheng Duh
David Samuelson
David Tulsky
Sandra Gutierrez
Cindy J. Nowinski
Allison Mueller
Vivienne Shen
Victor Sung
Subjects: 
Neurosciences
Title string: 
Identifying Motor, Emotional-Behavioral, and Cognitive Deficits that Comprise the Triad of HD Symptoms from Patient, Caregiver, and Provider Perspectives
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:179306

Lessons Learned from Open‐label Deep Brain Stimulation for Tourette Syndrome: Eight Cases over 7 Years

Background
Deep brain stimulation (DBS) remains an experimental but promising treatment for patients with severe refractory Gilles de la Tourette syndrome (TS). Controversial issues include the selection of patients (age and clinical presentation), the choice of brain targets to obtain optimal patient‐specific outcomes, and the risk of surgery‐ and stimulation‐related serious adverse events.

Methods
This report describes our open‐label experience with eight patients with severe refractory malignant TS treated with DBS. The electrodes were placed in the midline thalamic nuclei or globus pallidus, pars internus, or both. Tics were clinically assessed in all patients pre‐ and postoperatively using the Modified Rush Video Protocol and the Yale Global Tic Severity Scale (YGTSS).

Results
Although three patients had marked postoperative improvement in their tics (>50% improvement on the YGTSS), the majority did not reach this level of clinical improvement. Two patients had to have their DBS leads removed (one because of postoperative infection and another because of lack of benefit).

Discussion
Our clinical experience supports the urgent need for more data and refinements in interventions and outcome measurements for severe, malignant, and medication‐refractory TS. Because TS is not an etiologically homogenous clinical entity, the inclusion criteria for DBS patients and the choice of brain targets will require more refinement.

Publication type: 
Author: 
Maria G. Motlagh
Megan Smith
Angeli Landeros-Weisenberger
Andrew J. Kobets
Joan Miravite
de LotbinièAlain C. re
Ron L. Alterman
Alon Y. Mogilner
Michael H. Pourfar
Michael S. Okun
Robert A. King
Subjects: 
Neurosciences
Title string: 
Lessons Learned from Open‐label Deep Brain Stimulation for Tourette Syndrome: Eight Cases over 7 Years
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:169958

Prospective Study Evaluating IncobotulinumtoxinA for Cervical Dystonia or Blepharospasm: Interim Results from the First 145 Subjects with Cervical Dystonia

Background: We report the interim results from XCiDaBLE: A large prospective, observational "naturalistic" study evaluating Xeomin® (incobotulinumtoxinA) for cervical dystonia or blepharospasm in the United States.
Methods: Subjects with CD are followed for 2 treatment cycles and monitored via Interactive Voice/Web Response. Subject-reported scales include the Subject Global Impression-Severity and Improvement; Cervical Dystonia Impact Profile (CDIP-58); and Work Productivity and Quality of Life (QoL) are assessed by means of an employment questionnaire and work history and the SF-12v2.
Results: This ongoing study includes 145 subjects with a diagnosis of CD. The majority were female (82.3%) and White (91.0%) and had previously been treated with botulinum toxins (77.2%). There were 106 employed at the time of onset of the disease, but 12.6 years later only 44% were still employed at the time of enrolment into the study and 20% were either receiving or seeking disability benefits. However, only 44% were still employed at the time of recruitment for study participation. The mean total dose/treatment of CD was 225.2 units for the 1st injection. The CDIP-58 total score was significantly improved at four weeks post the first injection compared to baseline (p less than or equal to 0.0001). Most subjects noted improvement in their global impression assessment. No new or unexpected adverse events occurred.
Discussion: The results from these interim analyses confirm previous controlled single-dose studies of incobotulinumtoxinA in terms of efficacy and safety.

Publication type: 
Author: 
Hubert H. Fernandez
Fernando Pagan
Fabio Danisi
David Greeley
Joseph Jankovic
Amit Verma
Kapil Sethi
Eric J. Pappert
XCiDaBLE Study Group
Subjects: 
Neurosciences
Pharmaceutical sciences
Medicine
Title string: 
Prospective Study Evaluating IncobotulinumtoxinA for Cervical Dystonia or Blepharospasm: Interim Results from the First 145 Subjects with Cervical Dystonia
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:166238

Pages