Rush, Beth

Background Difficulty tolerating the uncertainty of ambiguous or unpredictable situations may influence how patients with functional motor disorder (FMD) respond to treatment. However, only one study has examined the role of intolerance of uncertainty (IU) in FMD treatment. Objectives This study sought to expand on prior findings in a larger sample of patients with FMD who completed an intensive motor-retraining programme. Methods A consecutive cohort of 109 patients with FMD completed a 1-week intensive outpatient motor-retraining programme. Patients rated their IU using the Intolerance of Uncertainty Scale-12 and functional motor outcomes using three empirical measures before and after treatment. Univariate and multivariable analyses were conducted to (1) characterise the rate of elevated IU, (2) evaluate potential changes in IU across the programme, (3) examine whether changes in IU predict improvements in motor functioning and (4) determine if IU incrementally predicts functional improvements in patients with clinically elevated IU. Results Findings revealed that clinically elevated IU was common (yielding a base rate of 44%) and that the ‘prospective’ subtype of IU significantly decreased with 1 week of FMD treatment. Change in IU was not significantly associated with improved functional outcomes across the sample. However, change in prospective IU did predict patient-specific functional outcomes among those with clinically elevated IU ( R 2 =11%). Conclusions Findings support prior work suggesting that certain subtypes of IU are common, modifiable and related to treatment outcomes in FMD. The ‘prospective’ subtype of IU may represent an operative factor that can enhance the efficacy of existing FMD rehabilitation programmes.

Functional neurological disorder (FND) is a prevalent neurologic condition, yet existing treatment approaches yield inconsistent outcomes. We propose a unifying framework that conceptualizes FND as a disorder triggered and perpetuated by individuals lacking targeted tools to reconcile the cumulative impact of intolerance of uncertainty (IU) and multidimensional allostatic overload. Expanding upon predictive coding and IU theories from neuroscience and psychology research, we argue that during times of uncertainty, individuals with FND exhibit a higher rate of prediction error but lack the energy, resources, and adaptive capacity to respond. This sustained hyperactivation of the brain and body trigger and perpetuate FND. We propose that FND treatment requires a strategic and progressively tiered behavioral approach. First, the individual with FND must be taught behavioral skills to gain immediate symptom control and shift automatic, hyperactive processes into conscious awareness. Only then, can practices from Acceptance and Commitment Therapy, Dialectical Behavioral Therapy, and Mindfulness Therapy be leveraged. These practices help explicitly identify sources of uncertainty and teach how to effectively respond to hyperactive processes with skills that optimize function, commitment to values, and well-being. This framework offers testable hypotheses and a pathway to more effective, individualized care for FND.

Background Intolerance of Uncertainty (IU) has never been explored in functional motor disorder (FMD) or any functional neurological disorder but perceptions of control are theoretically relevant. Objective To evaluate if IU changes in people with FMD completing intensive 1-week motor retraining treatment, and if IU change associates with outcome. Methods A consecutive cohort of 45 FMD patients completed a 1-week intensive outpatient motor retraining treatment. At program beginning and end, patients self-rated IU using the Intolerance of Uncertainty Scale-12 (IUS-12) and four functional impairment measures. Paired t-tests analyzed program changes in IU and functional outcomes. Linear regressions analyzed association strength between IU change and outcome. Results IU improved with FMD treatment (p < 0.001). Pre- to post-treatment IU was improved in 32/45 (71%), stable in 5/45 (11%), and worsened in 8/45 (18%). Age, symptom duration, and FMD phenotype did not predict IU improvement. Self-rated function improved across measures with treatment (p < 0.001). Program change in IU positively predicted outcome on 3 of 4 measures. Conclusions IU improves with FMD rehabilitation, even without explicit psychological focus of treatment, regardless of age or FMD phenotype. Improving IU associates with positive FMD treatment outcomes suggesting an important treatment target in FMD.

AbstractBackgroundColony‐stimulating factor‐1 receptor (CSF1R)‐related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease‐modifying treatment.ObjectiveThe objective of this study was to determine the effect of HSCT on disease progression.MethodsWe collected all available clinical data from a cohort of 7 patients with CSF1R‐related leukoencephalopathy who underwent HSCT at our institutions. Clinical data included detailed neurological examination by a board‐certified neurologist, serial cognitive screens, formal neuropsychological evaluations, and serial brain magnetic resonance imaging (MRI).ResultsOur patients had an average disease duration of 27.6 months at the time of transplant, and we have 87 months of total posttransplant follow‐up time (median, 11; range, 2–27). One patient died in the periprocedural period. The remaining patients showed a variable response to treatment, with 6 of 7 patients trending toward stabilization on motor examination, cognitive scores, and/or MRI abnormalities, especially with white matter lesion burden.ConclusionsThis is the largest series of patients with CSF1R‐related leukoencephalopathy receiving HSCT. We conclude that HSCT can stabilize the disease in some patients. Variability in patient responsiveness suggests that measures of disease heterogeneity and severity need to be considered when evaluating a patient's candidacy for transplant. HSCT appears to be the first disease‐modifying therapy for CSF1R‐related leukoencephalopathy. This milestone may serve as a foothold toward better understanding the disease's pathomechanism, thus providing new opportunities for better disease‐specific therapies. © 2021 International Parkinson and Movement Disorder Society