Objective: To determine if excitatory/inhibitory balance (E/I) within the sensorimotor network is linked to motor symptoms in two distinct subtypes of isolated focal dystonia.
Background: Cervical dystonia (CD) and blepharospasm (BSP) are focal dystonias characterized by involuntary muscle contractions of the neck and eye muscles, respectively. Prior studies suggest an E/I imbalance may underlie motor symptoms in focal dystonia,1-2 however it remains unclear whether different subtypes share a similar pathophysiology.3
Method: Magnetic resonance spectroscopy using PRESS and MEGA-PRESS pulse sequences was used to estimate levels of excitatory (glutamate + glutamine [Glx]) and inhibitory (GABA) neurotransmitters in the sensorimotor cortex (SMC), basal ganglia (BG), and cerebellum (CBL) of individuals with CD and BSP as well as healthy controls (HC). Dystonia severity was assessed using the Burke-Fahn-Marsden Rating Scale (BFMRS) and Global Dystonia Rating Scales (GDRS). E/I was estimated as the ratio of Glx to GABA. ANOVAs were used to compare E/I between the three cohorts. Pearson’s coefficients were used to analyze E/I balance related to symptom severity and duration.
Results: To date, 15 CD patients (3M:12F; 59.0±12.7 yrs), 21 BSP patients (6M:15F; 62.2±9.6 yrs), and 11 HC (2 M:9F; 55.4±16.2 yrs) have been enrolled. CD and BSP had similar disease durations (171.4±118.9 mos vs. 101.6±140.1 mos, p=0.15), but different severity (BFMRS: 2.9±0.6 vs. 10.1±4.7, p<0.00001; GDRS: 4.1±1.6 vs. 6.7±3.8, p=0.01). ANOVA analysis suggested E/I differences in the CBL (F=2.5; df=41; p=0.09) and pairwise t-tests revealed E/I differences between CD and BSP in the CBL (p<0.05) with a trend toward a difference in the SMC (p<0.06). No differences in E/I were seen between HC and dystonia subtypes. In CD, E/I did not correlate with BFMRS, GDRS, or disease duration in any brain region. In BSP, however, E/I in the BG positively correlated with BFMRS (r=0.48, p<0.05) and GDRS (r=0.47, p<0.05), and E/I in the SMC was positively associated with disease duration (r=0.80, p<0.0001).
Conclusion: Our preliminary data suggest E/I balance changes within the sensorimotor network may be more relevant for symptomatology in BSP as opposed to CD. Additionally, E/I within the BG of individuals with BSP may be able to serve as a marker of dystonia severity.
References: 1. Hallett, M. Neurophysiology of dystonia: The role of inhibition. Neurobiol Dis 42, 177–184 (2011).
2. Groth, C. L. et al. Cervical Dystonia Is Associated With Aberrant Inhibitory Signaling Within the
Thalamus. Front Neurol 11, 575879 (2020).
3. Berardelli A. New advances in the pathophysiology of focal dystonias. Brain. 2006;129(1):6-7.
doi:10.1093/brain/awh717
To cite this abstract in AMA style:
C. Dintino, N. Mukhopadhyay, C. Groth, B. Berman. Excitatory/inhibitory Balance Differences Suggests Distinct Pathophysiology Between Blepharospasm and Cervical Dystonia [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/excitatory-inhibitory-balance-differences-suggests-distinct-pathophysiology-between-blepharospasm-and-cervical-dystonia/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/excitatory-inhibitory-balance-differences-suggests-distinct-pathophysiology-between-blepharospasm-and-cervical-dystonia/