This study shows that the General Symptom Questionnaire-30 (GSQ-30) is a valid and reliable self-report instrument that clinicians and researchers could use to assess the multi-system symptom burden and response to treatment among patients with acute and post-treatment Lyme disease. The GSQ-30 may prove valuable in future precision medicine studies as a quantitative clinical measure for assessing the clinical relevance of biomarkers and effectiveness of treatments.
Why was this study done?
Clinicians and researchers have lacked a valid and reliable instrument to measure the multi-symptom burden of Lyme disease patients, that can be debilitating and include rheumatologic, neurologic, infectious, cardiac, psychiatric, and neurocognitive problems. This study validates the GSQ-30 as a sensitive measure of symptom burden that quantifies, detects changes after treatment, and demonstrates clinically relevant profile differences between early and post treatment Lyme disease symptoms and between Lyme disease and health.
The research also examines whether the symptom profile of post-treatment Lyme disease differs from two similarly disabling conditions with multi-system symptom burden: depression and traumatic brain injury (TBI).
How was this study done?
The GSQ-30 is a brief 30 item questionnaire developed to assess symptom burden over a two week time period. Modeled after measures of somatic symptom burden in primary care (PHQ-15 and SSS-8), the GSQ-30 asks: “how much have you been bothered by any of the following?” with five options: “not at all,” “a little bit,” “somewhat,” “quite a bit,” and “very much” (scored 0–4); total score ranges from 0 to 120. The two week timeframe was selected to account for the waxing and waning nature of Lyme disease symptoms.
The GSQ-30 reflects physical and neuropsychiatric symptoms commonly reported by patients with Lyme disease. An additional question (not included in the scoring) asks whether any of the 30 GSQ symptoms have impaired work, social, or family functioning, and asks the rank order of severity (up to seven items) to identify the symptoms of most concern to the individual.
The GSQ-30 assessment was administered to 342 participants: healthy controls (37) and 4 patient cohorts [erythema migrans (EM) rash patients (53), post-treatment Lyme disease (124), traumatic brain injury (51), and depression (36)] and included 6 month reassessment after treatment of the EM group.
Internal consistency of the data was assessed using Cronbach’s alpha for the total GSQ-30 scale. Construct validity and factorial validity were scrutinized using rigorous statistical analysis methods.
What were the major findings?
The study substantiates the GSQ-30 instrument as a valid sensitive measurement of multi-symptom burden in Lyme disease patients.
The research identified four core domains: pain/fatigue, neurologic, neuropsychiatric, and viral-like symptoms. These are common symptom clusters reported by patients impacted by Lyme disease.
Patients with post-treatment Lyme disease had a significantly greater burden of pain/fatigue, neuropsychiatric and neurologic symptoms than those with early (EM) Lyme disease. The GSQ-30 total score for post-treatment Lyme disease was nearly 2x higher than for EM. These scores support the clinical impression that patients with post-treatment Lyme disease have a much greater symptom burden than those with early (EM) Lyme disease.
GSQ-30 total scores for traumatic brain injury and depression were also high and not significantly different from post-treatment Lyme disease. The GSQ-30 total score predicted functional impairment over and above symptoms of anxiety/depression.
The GSQ-30 total score correlated strongly with functional impairment. Reduction in the GSQ-30 over time corresponded with improvement in functional status. These findings support the conclusion that the GSQ-30 detects symptom impact (i.e. burden) and not just symptom presence. Traumatic brain injury, depression and post treatment Lyme disease exhibited high GSQ-30 scores with high functional impairment and great symptom burden.
What is the impact of this work?
Lyme disease patients with persistent symptoms pose a challenge to clinicians as their symptoms vary across multiple medical domains, including rheumatologic, neurologic, infectious, cardiac, psychiatric, and neurocognitive. This diversity of symptoms can make it difficult to assess symptom severity and treatment progress. The General Symptom Questionnaire-30 (GSQ-30) is a valid and reliable self-report instrument that assesses the multi-system symptom burden of Lyme disease patients. Given the clinician’s limited time with each patient, a brief self-report screening instrument covering multiple symptom domains would allow a rapid quantification of symptom burden, facilitate the monitoring of symptom changes over time, and highlight other disease-relevant symptoms that require attention.
The questionnaire has the advantages of brevity, ease of administration and scoring, and sensitivity to change after treatment.
The GSQ-30 is not a diagnostic instrument, but rather is a measure of symptom burden, and could be a useful instrument to complement clinical judgment. The GSQ-30 may prove valuable in future precision medicine studies as a quantitative clinical measure for assessing the clinical relevance of biomarkers and treatment efficacy.
- Regular administration of the GSQ-30 may improve patient care by highlighting for the clinician the symptoms of greatest burden to the patient which may prompt a different treatment approach.
- Future research is needed to determine:
- If clinical outcome can be improved by using the GSQ-30 to guide treatment
- If high GSQ-30 at initial evaluation may identify a subgroup of EM patients in need of treatment augmentation to increase the likelihood of improved long-term outcome
- If high GSQ-30 scores may correspond with particular biomarkers, such as inflammatory cytokines
- Whether high GSQ-30 scores at 6+ months are being driven by persistent infection, post-infectious processes, and/or re-infection
- Whether GSQ-30 may be useful for monitoring a variety of multi-system medical conditions
Fallon BA, Zubcevik N, Bennett C, Doshi S, Rebman AW, Kishon R, Moeller JR, Octavien NR and Aucott JN (2019) The General Symptom Questionnaire-30 (GSQ-30): A Brief Measure of Multi-System Symptom Burden in Lyme Disease. Front. Med. 6:283. doi: 10.3389/fmed.2019.00283
This research was supported by:
Specific support for this project was provided by Oxford Immunotec, Inc. General support for research was provided by the Steven and Alexandra Cohen Foundation, Inc., the Global Lyme Alliance, Inc., the Lyme Disease Association, Inc., and the Cohen Foundation, Inc. NZ’s work at the Spaulding site was supported by Mark and Eileen Lovell. The funding organizations and sponsors had no role in any of the following aspects of the study: design and conduct of the study; data collection, management, analysis, or interpretation; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.