Sleepiness and comorbid sleep disorders in functional motor disorders: a comparative study with central hypersomnia.

Sleep symptoms, including excessive sleepiness, are frequently reported by patients with functional motor disorders (FMD). We aimed to classify the comorbid sleep disorders in FMD, and to investigate the relationship between subjective sleepiness and objective measures of hypersomnia, comparing them with data from people with central hypersomnia. A total of 37 patients (mean [SD] age 46.4 [11.2] years) with clinically definite FMD, and 17 patients (mean [SD] age 41.1 [11.6] years) with central hypersomnia underwent structured medical and sleep history, neurological examination, polysomnography, multiple sleep latency test (MSLT), and questionnaires assessing sleepiness, fatigue, and depression. In all, 23 patients with FMD (62%) reported excessive daytime sleepiness. Evidence of specific sleep disorders was identified in our cohort, with 35% having restless legs syndrome; 49% obstructive sleep apnea; and 8% periodic limb movements in sleep; however, the presence of these disorders was not correlated with subjective sleepiness. Patients with FMD with self-reported sleepiness reported higher fatigue (p = 0.002), depression (p = 0.002), and had longer sleep latencies in the MSLT (p < 0.001) compared to the patients with central hypersomnia. No correlation was found between subjective and objective sleepiness in either group. Fatigue positively correlated with self-reported sleepiness in patients with FMD (p < 0.001). This study did not find objective correlates of increased sleepiness in patients with FMD. While sleep abnormalities were found to be common in FMD, they were not correlated with self-reports of excessive sleepiness. Positive correlations between self-reported sleepiness and fatigue support the current unified model of non-motor symptoms in FMD.

Increased Frequency of Self-Reported Obsessive-Compulsive Symptoms in Patients with Functional Movement Disorders.

Background: Functional movement disorders (FMD) are associated with a high prevalence of psychiatric comorbidities. Objective: To assess the frequency of obsessive-compulsive symptoms (OCS) in FMD. Methods: A total of 167 consecutive patients with clinically definite FMD (mean age = 44.4 years, standard deviation [SD] = 12.0, 119 females) and 145 healthy controls (mean age = 43.2 years, SD = 11.8, 103 females) completed the Obsessive-Compulsive Inventory-Revised (OCI-R), which is a widely used tool for assessing OCS. The cutoff score ≥21 is indicative of clinically significant obsessive-compulsive disorder (OCD). Motor symptom severity was assessed using the Simplified FMD Rating Scale (S-FMDRS). All subjects completed questionnaires for depression, anxiety, pain, fatigue, cognitive complaints, health-related quality of life, and childhood trauma. Personality traits were assessed using the Big Five questionnaire. Results: FMD patients had higher mean OCI-R score and higher proportion of individuals with OCI-R ≥ 21 42%, 95% confidence interval (CI) = (30.2, 54.6) versus 16%, 95% CI = (8.2, 28.2) in controls, P < 0.001. Patients had higher scores in three domains: checking, ordering, and obsessing (P < 0.001). FMD patients with OCI-R score ≥21 had higher depression, anxiety, cognitive complaints, and lower quality of life compared to those with score <21 (P < 0.001). No correlation between OCI-R and S-FMDRS scores was found. Conclusions: FMD patients reported higher rates of OCS compared to controls, along with higher rates of non-motor symptoms and lower quality of life. This finding may have clinical implications and raises the possibility of shared risk factors and common pathophysiological mechanisms in FMD and OCD.

The complex syndrome of functional neurological disorder.

BACKGROUND: Patients with functional neurological disorders (FND) often present with multiple motor, sensory, psychological and cognitive symptoms. In order to explore the relationship between these common symptoms, we performed a detailed clinical assessment of motor, non-motor symptoms, health-related quality of life (HRQoL) and disability in a large cohort of patients with motor FND. To understand the clinical heterogeneity, cluster analysis was used to search for subgroups within the cohort. METHODS: One hundred fifty-two patients with a clinically established diagnosis of motor FND were assessed for motor symptom severity using the Simplified Functional Movement Disorder Rating Scale (S-FMDRS), the number of different motor phenotypes (i.e. tremor, dystonia, gait disorder, myoclonus, and weakness), gait severity and postural instability. All patients then evaluated each motor symptom type severity on a Likert scale and completed questionnaires for depression, anxiety, pain, fatigue, cognitive complaints and HRQoL. RESULTS: Significant correlations were found among the self-reported and all objective motor symptoms severity measures. All self-reported measures including HRQoL correlated strongly with each other. S-FMDRS weakly correlated with HRQoL. Hierarchical cluster analysis supplemented with gap statistics revealed a homogenous patient sample which could not be separated into subgroups. CONCLUSIONS: We interpret the lack of evidence of clusters along with a high degree of correlation between all self-reported and objective measures of motor or non-motor symptoms and HRQoL within current neurobiological models as evidence to support a unified pathophysiology of 'functional' symptoms. Our results support the unification of functional and somatic syndromes in classification schemes and for future mechanistic and therapeutic research.

Attention impairment in motor functional neurological disorders: a neuropsychological study.

OBJECTIVE: Our objective was to assess cognitive functioning across multiple cognitive domains using a standardised neuropsychological battery in patients with motor functional neurological disorders (mFND). METHODS: Thirty patients with clinically established mFND and 30 age-, sex- and education-matched control subjects underwent a thorough neuropsychological assessment evaluating (1) attention including processing speed, (2) executive functions including working memory, (3) short-term memory, (4) speech and language and (5) visuospatial functions. Performance validity tests (PVT) and self-report measures of depression, anxiety and cognitive complaints were included in the assessment. Only patients with valid test performance were included in the analysis. RESULTS: Three patients scored below the cut-off scores in PVT. Patients performed significantly worse than controls in the following areas: (1) the attention domain which included a slow processing speed (p = 0.005, Cohen's d = 0.89), (2) executive functions (p = 0.01, Cohen's d = 0.88) and (3) speech and language domains (p = 0.025, Cohen's d = 0.77). Patients with mFND showed greater intra-individual variability in cognitive performance (p = 0.005, Cohen's d = 0.94). Cognitive impairments were independent of depressive symptoms, which were higher in mFND patients. CONCLUSION: This study revealed both subjective and objective cognitive impairment in patients with mFND. The neuropsychological profile in mFND was characterised primarily by attentional impairment including a slow processing speed and a high intra-individual variability in cognitive performance. Cognitive impairment was associated with a valid test performance, highlighting that the deficits observed were not likely to be explained by a lack of effort in the patient group. Attention is considered to play a key role in mFND pathophysiology, and the results suggest that such impairments are objectively measurable.

Bridging structural and functional biomarkers in functional movement disorder using network mapping.

BACKGROUND: There are gaps in our neurobiological understanding of functional movement disorder (FMD). OBJECTIVES: We investigated gray matter volumetric profiles in FMD, and related findings to resting-state functional connectivity (rsFC) profiles using Human Connectome Project data. METHODS: Volumetric differences between 53 FMD patients and 50 controls were examined, as well as relationships between individual differences in FMD symptom severity and volumetric profiles. Atrophy network mapping was also used to probe whether FMD-related structural alterations preferentially impacted brain areas with dense rsFC. RESULTS: Compared to controls without neurological comorbidities (albeit with mild depression and anxiety as a group), the FMD cohort did not show any volumetric differences. Across patients with FMD, individual differences in symptom severity negatively correlated with right supramarginal and bilateral superior temporal gyri volumes. These findings remained significant adjusting for FMD subtype or antidepressant use, but did not remain statistically significant adjusting for depression and anxiety scores. Symptom severity-related structural alterations mapped onto regions with dense rsFC-identifying several disease epicenters in default mode, ventral attention, and salience networks. CONCLUSIONS: This study supports that FMD is a multinetwork disorder with an important role for the temporoparietal junction and its related connectivity in the pathophysiology of this condition. More research is needed to explore the intersection of functional neurological symptoms and mood.

Testing the Analytical Rumination Hypothesis: Exploring the Longitudinal Effects of Problem Solving Analysis on Depression.

Depression is a mental health condition for which individuals commonly seek treatment. However, depressive episodes often resolve on their own, even without treatment. One evolutionary perspective, the analytical rumination hypothesis (ARH), suggests that depression occurs in response to complex problems. According to this perspective, depressive symptoms promote analytical rumination, i.e., distraction-resistant thoughts about the causes of problems [causal analysis (CA)] and how they can be solved [problem-solving analysis (PSA)]. By helping individuals solve complex problems, analytical rumination may contribute to remission from depression. The aim of this study was to investigate (1) whether clinically-depressed individuals have more complex problems and engage in more CA and PSA than non-depressed and (2) the effects of CA and PSA on decreases in problem complexity, depressive symptoms, and remission from the depression. Samples of 85 patients were treated for depression with antidepressants and psychotherapy, and 49 healthy subjects were assessed three times over a 4-month period (at Weeks 1, 5, and 16). At each assessment, they completed measures of depression, analytical rumination, and problem complexity. Depressed individuals reported having more complex problems and engaging in more CA than non-depressed participants. The two groups engaged in a similar degree of PSA. Findings from a multiple regression suggested that more PSA at Week 1 was related to a decrease in depressive symptoms at Week 5, even after controlling for baseline depression, problem number, and complexity. PSA at Week 1 did not predict the remission after hospitalization or at follow-up; however, having less complex problems at the baseline made it more likely that a patient would later remit. Engaging in more CA or PSA at Week 1 did not affect perceived problem complexity at Week 5 or at follow-up. However, these findings were not statistically significant when influential observations (or outliers) were included in the analysis. Our findings suggest that PSA may contribute to a decrease in symptoms of depression over time. However, alleviations in problem complexity and remission might only be achieved if problems are initially less complex. Future directions involve exploring how PSA might contribute to decreases in depressive symptoms and other mechanisms underlying remission from depression.

Prepulse inhibition of the blink reflex is abnormal in functional movement disorders.

BACKGROUND: Patients with functional movement disorders also typically have functional somatic symptoms, including pain, fatigue, and sensory disturbance. A potentially unifying mechanism for such symptoms is a failure in processing of sensory inputs. Prepulse inhibition is a neurophysiological method that allows for the study of preconscious somatosensory processing. OBJECTIVE: The objective of this study was to assess prepulse inhibition in patients with functional movement disorders and healthy control subjects. METHODS: We analyzed the effect of a weak electrical stimulus to the index finger (prepulse) on the magnitude of the R2 response of the blink reflex induced by electrical stimuli delivered to the supraorbital nerve in 22 patients with clinically established functional movement disorders and 22 matched controls. Pain, depression, anxiety, and obsessive-compulsive symptoms were assessed using self-rated questionnaires. In addition, in patients we assessed motor symptom severity. RESULTS: Prepulses suppressed the R2 response of the blink reflex in both groups, by 36.4% (standard deviation: 25.6) in patients and by 67.3% (standard deviation: 16.4) in controls. This difference was significant (P < 0.001). There was no significant correlation between motor and nonmotor symptom measures and prepulse inhibition size. CONCLUSIONS: Impaired prepulse inhibition of the blink reflex suggests an abnormal preconscious processing of somatosensory inputs, which can be interpreted within predictive coding accounts of both functional movement disorders and functional somatic syndromes. Our results, along with previous findings of a reduced prepulse inhibition in fibromyalgia syndrome, support a possible unified pathophysiology across functional neurological and somatic syndromes with noteworthy implications for diagnostic classification and development of novel biomarkers and treatments. © 2019 International Parkinson and Movement Disorder Society.

The impact of non-motor symptoms on the health-related quality of life in patients with functional movement disorders.

OBJECTIVE: Pain, fatigue, cognitive complaints and psychiatric comorbidities are common in patients with functional movement disorder and may significantly affect their quality of life. The aim of the study was to assess the impact of motor and non-motor symptoms on health-related quality of life in patients with functional movement disorder. METHODS: Sixty-one patients with clinically established functional movement disorder and 61 matched healthy controls completed standardized questionnaires for depression, anxiety, cognitive complaints, fatigue, pain, sleepiness, apathy and health-related quality of life. Motor disorder severity was assessed using The Simplified Functional Movement Disorders Rating Scale. Personality traits were assessed using the 44-Item Big Five Inventory. RESULTS: Compared to controls, patients reported significantly lower health-related quality of life and higher levels of all assessed non-motor symptoms except for apathy. No difference was found in personality traits. In both groups, health-related quality of life scores negatively correlated with depression, anxiety, pain, cognitive complaints, apathy, and neuroticism. No correlation was found between health-related quality of life and motor symptom severity in patients with functional movement disorder. Multiple regression analysis of the predictors of health-related quality of life showed significant impact of trait anxiety and cognitive complaints scores. CONCLUSIONS: Multiple non-motor symptoms but not motor symptom severity correlated with impaired health-related quality of life in patients with functional movement disorder. Impaired health-related quality of life was predicted by anxiety and cognitive complaints. Our results highlight the importance of assessing and treating both motor and non-motor symptoms in patients with functional movement disorder.