Changes in interoceptive accuracy related to emotional interference in somatic symptom disorder.

OBJECTIVE: The somatic symptom disorder (SSD) is characterized by one or more distressing or disabling somatic symptoms accompanied by an excessive amount of time, energy and emotion related to the symptoms. These manifestations of SSD have been linked to alterations in perception and appraisal of bodily signals. We hypothesized that SSD patients would exhibit changes in interoceptive accuracy (IA), particularly when emotional processing is involved. METHODS: Twenty-three patients with SSD and 20 healthy controls were recruited. IA was assessed using the heartbeat perception task. The task was performed in the absence of stimuli as well as in the presence of emotional interference, i.e., photographs of faces with an emotional expression. IA were examined for correlation with measures related to their somatic symptoms, including resting-state heart rate variability (HRV). RESULTS: There was no significant difference in the absolute values of IA between patients with SSD and healthy controls, regardless of the condition. However, the degree of difference in IA without emotional interference and with neutral facial interference was greater in patients with SSD than in healthy controls (p = 0.039). The IA of patients with SSD also showed a significant correlation with low-frequency HRV (p = 0.004) and high-frequency HRV (p = 0.007). CONCLUSION: SSD patients showed more significant changes in IA when neutral facial interference was given. These results suggest that bodily awareness is more affected by emotionally ambiguous stimuli in SSD patients than in healthy controls.

Frontal alpha asymmetry is associated with chronic stress and depression, but not with somatoform disorders.

Cardinal characteristics of somatoform disorders (SFDs) are worry of illness, and impaired affective processing. We used relative frontal alpha asymmetry (FAA), a method to measure functional lateralization of affective processing, to investigate psychobiological correlates of SFDs. With alpha activity being inversely related to cortical network activity, relative FAA refers to alpha activity on the right frontal lobe minus alpha activity on the left frontal lobe. Less relative left frontal activity, reflected by negative FAA scores, is associated with lower positive and greater negative affectivity, such as observed in depression. Due to its negative affective component (illness anxiety), we expected to find less relative left frontal activity pattern in SFDs, and positive associations with self-reported chronic stress and depression symptoms. We recorded resting-state EEG activity with 64 electrodes, placed in a 10-10 system in 26 patients with a primary SFD, 23 patients with a major depressive disorder and 25 healthy control participants. The groups did not differ in FAA. Nevertheless, across all participants, less relative left frontal activity was associated with chronic stress and depression symptoms. We concluded that FAA may not serve as an indicator of SFDs. As the relationship of FAA and depressive symptoms was fully mediated by chronic stress, future studies have to clarify whether the association between FAA and chronic stress may represent a shared underlying factor for the manifestation of mental health complaints, such as depression.

The Association of Emotion Regulation and Somatic Symptoms.

OBJECTIVE: People with functional somatic symptoms have difficulties in various stages of the emotion regulation (ER) process. As an adaptive and flexible use of ER strategies is a core tenet of emotional health, having difficulties in this area is often assumed to be the key mechanism behind functional somatic symptoms. Following a dimensional population-based sampling approach, we investigated ER abilities across a broad range of people and tested possible associations with somatic symptom reporting, habitual ER use, and various subclinical constructs (such as alexithymia and anxiety). METHODS: In a sample of N = 254 persons, somatic symptom distress (Patient Health Questionnaire-15, Hierarchical Taxonomy of Psychopathology somatoform spectrum), trait ER facets (Emotion Regulation Questionnaire, Emotion Reactivity Scale), and the ER abilities (suppression and reappraisal) were assessed. Correlations (frequentist and Bayesian), ANOVAs, and structural equation models were used to analyze the data. RESULTS: Correlational and structural equation model analyses revealed that general symptom severity (both on the somatoform Hierarchical Taxonomy of Psychopathology and Patient Health Questionnaire-15) was not significantly associated with ER effectiveness, general arousal, or general valence. The sensory components of pain symptoms ( r = -0.708, p = .023) and health anxiety ( r = -0.443, p = .028) were significantly negatively associated with effective ER. CONCLUSIONS: ER effectiveness seems independent of general somatic symptom distress. We make recommendations for clinical interventions in light of these complex findings.

Leptin promoter methylation in female patients with painful multisomatoform disorder and chronic widespread pain.

BACKGROUND: Different functional somatic syndromes (FSS), fibromyalgia (FMS) and other unexplained painful conditions share many common clinical traits and are characterized by troubling and functionally disabling somatic symptoms. Chronic pain is most frequently reported and at the center of patients' level of disease burden. The construct of multisomatoform disorder (MSD) allows to subsume severely impaired patients suffering from FSS, FMS and other unexplained painful conditions to be examined for common underlying processes. Altered leptin levels and a pathological response of the HPA-axis as a result of chronic stress and childhood trauma have been suggested as one of the driving factors of disease development and severity. Previous studies have demonstrated that methylation of the leptin promoter can play a regulatory role in addiction. In this study, we hypothesized that methylation of the leptin promoter is influenced by the degree of childhood traumatization and differs between patients with MSD and controls. A cohort of 151 patients with MSD and 149 matched healthy volunteers were evaluated using clinical and psychometric assessment while methylation level analysis of the leptin promoter was performed using DNA isolated from whole blood. RESULTS: In female controls, we found CpG C-167 to be negatively correlated with leptin levels, whereas in female patients CpG C-289, C-255, C-193, C-167 and methylation cluster (C-291 to C-167) at putative bindings sites for transcription factors Sp1 and c/EBPalpha were negatively correlated with leptin levels. Methylation levels were significantly lower in female patients CpG C-289 compared with controls. When looking at female patients with chronic widespread pain methylation levels were significantly lower at CpG C-289, C-255 and methylation cluster (C-291 to C-167). CONCLUSION: Our findings support the hypothesis that epigenetic regulation of leptin plays a role in the regulation of leptin levels in patients with MSD. This effect is more pronounced in patients with chronic widespread pain.

Effect of psychosocial trauma and stress on sexual dysfunction in women with endometriosis.

BACKGROUND: Endometrial tissue plays an important role in the regulation of female fertility and there is evidence that endometrial pathology (including endometriosis) is closely related to endocrine disorders. On the other hand, various neuroendocrine changes can be significantly affected by psychosocial stress. In connection with these findings, we tested the relationship between neuroendocrine changes, sexual dysfunction, psychosocial/traumatic stress, and dissociative symptoms in women with endometriosis. METHODS: A total of 65 patients with endometriosis were included in the study. Clinical examinations were focused on the biochemical analysis of neuroendocrine markers of endometriosis (cancer antigen 125 [CA 125] and cancer antigen 19-9 [CA 19-9]), estradiol, psychometric evaluation of sexual dysfunction, psychosocial/traumatic stress, and dissociative symptoms. RESULTS: The results showed significant Spearman correlations between the values of the revised range of sexual difficulties for sexual dysfunction (Revised Female Sexual Distress Scale), psychosocial/traumatic stress (Trauma Symptoms Checklist) (R = 0.31), and dissociative symptoms (Somatoform Dissociation Questionnaire) (R = 0.33). Positive correlations were also found between CA 125 and CA 19-9 (R = 0.63), and between CA 125 and the results of the values of the revised scale of sexual difficulties for sexual dysfunction (Revised Female Sexual Distress Scale) (R = 0.29). Also psychosocial/traumatic stress (Trauma Symptoms Checklist) significantly correlated with CA 125 (R = 0.38) and with CA 19-9 (R = 0.33). CONCLUSION: These results represent the first findings regarding the relationship of the neuroendocrine markers CA 125 and CA 19-9 and sexual dysfunction with trauma/stress-related symptoms and dissociative symptoms in women with endometriosis.

Theory of Mind in Somatization and Depression: Is It Cause or Phenomenon?

ABSTRACT: Although mentalization is important in somatic symptom disorder (SSD) and major depressive disorder (MDD), it is not fully understood. In this study, we aimed to investigate the relation between somatic and depressive symptoms with mentalization. A total of 48 patients diagnosed with SSD, 50 patients diagnosed with MDD, and 50 healthy individuals, participated the study. The Montgomery-Asperg Depression Scale, Symptom Checklist-90 Revised, and Reading the Mind in the Eyes Test (RMET) were applied to the participants. The patients with SSD showed significantly the lowest performance of theory of mind. There was no significant difference between MDD and healthy controls. High somatization score was found to be a predictor for low RMET scores (95% confidence interval, -0.339; p = 0.014). Mentalization deficit seems to be associated with somatization rather than depression.

Does physical activity and BMI mediate the association between DCD and internalizing problems in early childhood? A partial test of the Environmental Stress Hypothesis.

BACKGROUND AND PURPOSE: Young children with Developmental Coordination Disorder (DCD) are more likely to experience internalizing problems, such as depression and anxiety, than typically developing (TD) children. Currently, the underlying mechanisms resulting in increased internalizing problems in DCD remains unknown; however, a previous study based on the Environmental Stress Hypothesis (ESH) indicated that physical inactivity and obesity may mediate the relationship between DCD and internalizing problems. The purpose of this study is to investigate the relationships among DCD, internalizing problems, physical activity, and BMI, and the role of sex in these relationships in preschool children, a population for which we currently have very limited data. METHODS: Young children between the ages of 4 and 5 years enrolled in the Coordination and Activity Tracking in CHildren (CATCH) study comprised the sample (n = 589). Of these, 288 (193 boys, 67.0%) were classified as at risk for DCD (rDCD), based on scoring at or below 16th percentile on the Movement Assessment Battery for Children - Second Edition. Physical activity was measured using accelerometers and height and weight were measured by trained research assistants, while parents completed the Child Behavior Checklist to rate internalizing problems. The mediating effects of physical activity and BMI were tested on the relationship between rDCD and internalizing problems. RESULTS: Children with rDCD reported more internalizing problems than TD children. While there was a direct effect of rDCD on internalizing problems, neither physical activity nor BMI were found to mediate this relationship. CONCLUSION: The findings from this study support co-occurring internalizing problems in preschool children with DCD, and extend these findings to demonstrate that this relationship is not explained by physical activity or BMI in early childhood. Further research should be directed toward other psychosocial factors identified in the ESH to better understand the underlying mechanisms between DCD and co-occurring internalizing problems.

Functional and Idiopathic Cervical Dystonia in Two Family Members: A Challenging Diagnosis.

Background: Cervical dystonia (CD) often occurs in the same family. Case report: A 40-year-old woman presented with a longstanding history of CD and signs of inconsistency at history taking and neurological examination; her 65-year-old mother was diagnosed instead with idiopathic CD, which had begun 7 years after the onset of CD in her daughter. Discussion: Idiopathic and functional CD share common clinical and endophenotypic traits, making the differential diagnosis particularly challenging. A complete examination is warranted.

Palatal Tremor - Pathophysiology, Clinical Features, Investigations, Management and Future Challenges.

Background: Palatal tremor is involuntary, rhythmic and oscillatory movement of the soft palate. Palatal tremor can be classified into three subtypes; essential, symptomatic and palatal tremor associated with progressive ataxia. Methods: A thorough Pubmed search was conducted to look for the original articles, reviews, letters to editor, case reports, and teaching neuroimages, with the keywords "essential", "symptomatic palatal tremor", "myoclonus", "ataxia", "hypertrophic", "olivary" and "degeneration". Results: Essential palatal tremor is due to contraction of the tensor veli palatini muscle, supplied by the 5th cranial nerve. Symptomatic palatal tremor occurs due to the contraction of the levator veli palatini muscle, supplied by the 9%th and 10%th cranial nerves. Essential palatal tremor is idiopathic, while symptomatic palatal tremor occurs due to infarction, bleed or tumor within the Guillain-Mollaret triangle. Progressive ataxia and palatal tremor can be familial or idiopathic. Symptomatic palatal tremor and sporadic progressive ataxia with palatal tremor show signal changes in inferior olive of medulla in magnetic resonance imaging. The treatment options available for essential palatal tremor are clonazepam, lamotrigine, sodium valproate, flunarizine and botulinum toxin. The treatment of symptomatic palatal tremor involves the treatment of the underlying cause. Discussion: Further studies are required to understand the cause and pathophysiology of Essential palatal tremor and progressive ataxia and palatal tremor. Similarly, the link between tauopathy and palatal tremor associated progressive ataxia needs to be explored further. Oscillopsia and progressive ataxia are more debilitating than palatal tremor and needs new treatment approaches.

Cranial Functional Movement Disorders: A Case Series with Literature Review.

Background: Cranial functional movement disorders (CFMDs) affect the face, eyes, jaw, tongue, and palate. Objectives: We aimed to examine our large series of functional movement disorders (FMDs) patients where the cranial muscles were involved to determine their phenomenology and other clinical features. Methods: This is a chart review of 26 patients who presented with CFMDs. Results: There were 16 (61.53%) females and 10 (38.46%) male patients. The mean ± [standard deviation (SD)] age at the presentation was 33.96 ± 16.94 (Range: 11-83) years. The duration of symptoms ranged from one day to 6 years (Mean ±SD: 402.03 ±534.97 days). According to the Fahn-Williams criteria, CFMDs were documented in 24 patients and clinically established in two patients. The facial [38.46% (10/26)] involvement was the most common in our CFMDs patients. Oromandibular [19.23% (5/26)], ocular [15.38% (4/26)], lingual [15.38% (4/26)], speech [15.38% (4/26)] and palatal [(3.85; 1/26)] involvement was also seen. 10 (38.46%) patients also had associated FMD in the extracranial regions. Precipitating factors were present in 84.61% (22/26) of the patients and associated illnesses were present in 42.30% (11/26) of the patients. At 3 months follow-up, 9 (34.61%) patients had improved, 13 (50%) had partial improvement and 4 (15.38%) had no improvement. Conclusions: There was a slight female preponderance in our patients. CFMDs are more likely to involve facial muscles. Associated medical conditions like neuropsychiatric disturbances and headaches are frequently present in CFMDs patients. Early clinical diagnosis will avoid unnecessary investigations and allow the patient to seek the right treatment.

Electrophysiological Evidence for Functional (Psychogenic) Essential Palatal Tremor.

Background: There is little published work describing the electrophysiological characteristics of essential palatal tremor, a condition now believed by many to be a functional (psychogenic) movement disorder. Case Report: Here we combine electroencephalography and electromyography with time-locked video recordings to document two cases of essential palatal tremor in which a definitive diagnosis is achieved using these electrophysiological tools. Discussion: We believe that sharing how these objective tools can be used to diagnose a functional movement disorder, as well as providing more published evidence to support the functional origin of essential palatal myoclonus, will help to diagnose this condition in the future.

Dissociated motor learning and de-adaptation in patients with functional gait disorders.

Walking onto a stationary platform that had been previously experienced as moving generates a locomotor after-effect-the so-called 'broken escalator' phenomenon. The motor responses that occur during locomotor after-effects have been mapped theoretically using a hierarchal Bayesian model of brain function that takes into account current sensory information that is weighted according to prior contextually-relevant experiences; these in turn inform automatic motor responses. Here, we use the broken escalator phenomenon to explore motor learning in patients with functional gait disorders and probe whether abnormal postural mechanisms override ascending sensory information and conscious intention, leading to maladaptive and disabling gait abnormalities. Fourteen patients with functional gait disorders and 17 healthy control subjects walked onto a stationary sled ('Before' condition, five trials), then onto a moving sled ('Moving' condition, 10 trials) and then again onto the stationary sled ('After' condition, five trials). Subjects were warned of the change in conditions. Kinematic gait measures (trunk displacement, step timing, gait velocity), EMG responses, and subjective measures of state anxiety/instability were recorded per trial. Patients had slower gait velocities in the Before trials (P < 0.05) but were able to increase this to accommodate the moving sled, with similar learning curves to control subjects (P = 0.87). Although trunk and gait velocity locomotor after-effects were present in both groups, there was a persistence of the locomotor after-effect only in patients (P < 0.05). We observed an increase in gait velocity during After trials towards normal values in the patient group. Instability and state anxiety were greater in patients than controls (P < 0.05) only during explicit phases (Before/After) of the task. Mean 'final' gait termination EMG activity (right gastrocnemius) was greater in the patient group than controls. Despite a dysfunctional locomotor system, patients show normal adaptive learning. The process of de-adaptation, however, is prolonged in patients indicating a tendency to perpetuate learned motor programmes. The trend to normalization of gait velocity following a period of implicit motor learning has implications for gait rehabilitation potential in patients with functional gait disorders and related disorders (e.g. fear of falling).

Attentional Processing and Interpretative Bias in Functional Neurological Disorder.

OBJECTIVE: Altered attentional processing (automatically attending to negative or illness-relevant information) and interpretative biases (interpreting ambiguous information as negative or illness relevant) may be mechanistically involved in functional neurological disorder (FND). Common mechanisms between FND and chronic fatigue syndrome (CFS) have been proposed but not compared experimentally. METHODS: We compared the cognitive task performance of FND, CFS, and healthy control (HC) groups. The tasks assessed attentional bias toward illness-relevant stimuli (visual probe task), attentional control (attention network task), and somatic interpretations (interpretative bias task), alongside self-reported depression, anxiety, fatigue, and general health. RESULTS: Thirty-seven participants diagnosed with FND, 52 participants diagnosed with CFS, and 51 HC participants were included. Although participants with CFS showed attentional bias for illness-relevant stimuli relative to HC (t = -3.13, p = .002, d = 0.624), individuals with FND did not (t = -1.59, p = .118, d = 0.379). Both the FND (t = 3.08, p = .003, d = 0.759) and CFS (t = 2.74, p = .007, d = 0.548) groups displayed worse attentional control than did the HC group. Similarly, the FND (t = 3.63, p < .001, d = 0.801) and CFS groups (t = 4.58, p < .001, d = 0.909) showed more somatic interpretative bias than did the HC group. CONCLUSIONS: Similar attentional control deficits and somatic interpretative bias in individuals with FND and CFS support potential shared mechanisms underlying symptoms. Interpretative bias toward somatic and illness-relevant stimuli in functional disorders may prove a therapeutic target.

Somatic symptom and related disorders in pediatric patients: Associations with parent psychiatric and substance use histories.

Parental response to pediatric patients with somatic symptom and related disorders (SSRDs) can impact symptom presentation. However, little is known about the impact of parent psychiatric and substance use disorder (SUD) history on the functional status and medical healthcare utilization of patients with SSRDs. The current study explored the associations between parent psychiatric & SUD history and patient somatic symptoms, functional disability, and hospital course in a medically hospitalized sample of pediatric patients with SSRDs. The electronic medical records of 375 pediatric patients with SSRDs, ages 5 to 18, admitted at a tertiary pediatric hospital were retrospectively reviewed. Parent psychiatric histories were identified in 45.1% of the sample. Parent SUD history and maternal psychiatric history were associated with more patient reported somatization. Parent psychiatric and SUD history were not associated with pediatric patients' level of functional disability or healthcare utilization during admission, including admission length, number of tests, and number of consultations obtained. This study has implications regarding reduction of potential stigma towards parents with psychiatric or SUD histories whose children are hospitalized with SSRDs. While such histories may provide insights regarding somatization presentation of pediatric patients with these disorders, it may not necessarily impact level of functional disability or hospital course.

Breakdown of the affective-cognitive network in functional dystonia.

Previous studies suggested that brain regions subtending affective-cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective-cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS-fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]). FC of brain regions of interest, known to be involved in affective-cognitive processes, and independent component analysis of RS-fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective-cognitive seeds of interest and the fronto-subcortical and limbic circuits; enhanced FC between the right affective-cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective-cognitive seeds of interest and the sensorimotor and high-order function ("cognitive") areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective-cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.

Distinct associations of DSM-5 Somatic Symptom Disorder, the Diagnostic Criteria for Psychosomatic Research-Revised (DCPR-R) and symptom severity in patients with irritable bowel syndrome.

OBJECTIVE: The clinical management of high symptom severity is a challenging task with patients with functional somatic disorders. We investigated the extent to which DCPR-revised (DCPR-R) syndromes and the DSM-5 category of Somatic Symptom Disorder (SSD) were able to predict symptom severity in 203 consecutive tertiary care patients with irritable bowel syndrome (IBS). METHOD: Semistructured interview were used for assessing DCPR-R and validated scales for SSD (combining PHQ-12 and WI-7), severity of symptoms (IBS-SSS), psychological distress (HADS), and psychosocial functioning (SF-12). RESULTS: Compared to moderate severity (IBS-SSS = 175-300), patients in the high range of severity (IBS-SSS > 300) had significantly more DCPR-R syndromes (particularly alexithymia and persistent somatization), higher psychological distress, and poorer psychosocial functioning, but showed no difference for SSD. DCPR-R, particularly alexithymia and persistent somatization, significantly and independently predicted IBS severity by explaining 18.5% of the IBS-SSS variance with large effect size (d = 1.18), after controlling for covariables. Conversely, SSD was not able to significantly predict IBS severity. CONCLUSIONS: This study highlights the need of an integrative approach in the medical setting. Psychosomatic factors play a relevant role in the individual perception of symptom severity and should be carefully evaluated for clinical management of functional syndromes.

Making Sense of "Somatization": A Systematic Review of its Relationship to Pediatric Pain.

OBJECTIVES: Pain and other physical symptoms commonly co-occur in childhood. There is debate about the relevance of somatization in understanding pain. The present review critically appraised and synthesized the extant literature on the relationship between pediatric pain and somatization. METHODS: A systematic review (PROSPERO registration #95956) was conducted in Medline, PsycINFO, EMBASE, and CINAHL using search terms related to pain and somatization in children and adolescents. A total of 156 articles were eligible for inclusion in the review. For studies that measured somatization using a symptom questionnaire, descriptions of "somatization" were extracted. Data regarding the relationship between pain and somatization were extracted for studies measuring somatization using a diagnostic category (e.g., Somatic Symptom and Related Disorders [SSRDs]). RESULTS: While many studies using somatic symptom questionnaires described somatization as having a psychological component, this was not always captured in measurement tools. Pain was reported as a common symptom in patients with an SSRD diagnosis, though rates varied depending on the specific diagnosis and pain location. Rates of SSRD diagnoses among pain patients were less frequent than rates of pain amongst SSRD patients. CONCLUSIONS: SSRDs and pain commonly co-occur, though rates differ depending on diagnosis and pain location. Understanding the relationship between pain and somatization is complicated by the discrepancy between how somatization is defined and measured in questionnaire studies. A comprehensive and measurable definition of somatization is needed so researchers can better identify the shared and unique contributions of pain and somatization in pediatric populations.

The effect of spontaneous osteoarthritis on conditioned pain modulation in the canine model.

Endogenous Pain Modulation (EPM) impairment is a significant contributor to chronic pain. Conditioned pain modulation (CPM) testing assesses EPM function. Osteoarthritic (OA) dogs are good translational models, but CPM has not been explored. Our aim was to assess EPM impairment in OA dogs compared to controls using CPM. We hypothesized that CPM testing would demonstrate EPM impairment in OA dogs compared to controls. Dogs with stifle/hip OA and demographically-matched controls were recruited. The pre-conditioning test stimulus, using mechanical/thermal quantitative sensory testing (MQST or TQST), were performed at the metatarsus. A 22N blunt probe (conditioning stimulus) was applied to the contralateral antebrachium for 2 minutes, followed by MQST or TQST (post-conditioning test stimulus). The threshold changes from pre to post-conditioning (∆MQST and ∆TQST) were compared between OA and control dogs. Twenty-four client-owned dogs (OA, n = 11; controls, n = 13) were recruited. The ∆MQST(p < 0.001) and ∆TQST(p < 0.001) increased in control dogs but not OA dogs (∆MQST p = 0.65; ∆TQST p = 0.76). Both ∆MQST(p < 0.001) and ∆TQST(p < 0.001) were different between the OA and control groups. These are the first data showing that EPM impairment is associated with canine OA pain. The spontaneous OA dog model may be used to test drugs that normalize EPM function.

Heart rate variability in patients with somatic symptom disorders and functional somatic syndromes: A systematic review and meta-analysis.

This research is aimed to systematically review heart rate variability (HRV) findings of functional somatic syndromes (FSSs) and somatic symptom disorders (SSDs), and to compare the HRV values between FSSs/SSDs patients and healthy individuals. We included clinical studies assessing HRV (including baseline HRV and HRV reactivity) in FSSs/SSDs and healthy participants. We searched PubMed, Embase, PsycINFO, MEDLINE, and Web of Science databases from the earliest available date to June 2019. Eighty-five studies comprising 3242 FSSs/SSDs patients and 2321 controls were included in the main meta-analysis; the baseline HRV value was significantly lower compared to healthy individuals (Hedges'g, -0.43; 95 % CI, -0.54 to -0.30; p < .001), with the largest effect size in fibromyalgia patients. A significant lower HRV was also found for total variability (Hedges'g, -0.56; 95 % CI, -0.77 to -0.36) and specific parasympathetic indices (Hedges'g, -0.41, 95 % CI; -0.54 to -0.30). HRV reactivity was significantly lower in FSSs/SSDs patients (Hedges'g, -0.42; 95 % CI, -0.64 to -0.20). Our results support the notion that FSSs/SSDs patients have significantly lower HRV than healthy individuals.

How to distinguish seizures from non-epileptic manifestations.

The first and most important step in establishing diagnosis of epilepsy consists of careful history taking from patients and witnesses. The clinical evaluation of the event will lead the indication for further diagnostic tests including e.g. EEG and MRI. Hence, identifying the paroxysmal event as epileptic or non-epileptic is the very first step in the diagnostic process. Paroxysmal events pose a clinical challenge, as these are unpredictable and do not usually occur in the doctor's office. History taking, hunting for witness reports and home-video recordings are the main tools to conclude whether a paroxysmal event is a seizure or not. In this review, we describe the most common differential diagnoses of epileptic seizures, including syncope, psychogenic non-epileptic seizures, as well as a variety of paroxysmal conditions and behaviours of all age groups. Misdiagnosis of non-epileptic events as epilepsy may not only defer the correct diagnosis and treatment but also poses additional risk by prescribing antiepileptic drugs unnecessarily. Moreover, missing the diagnosis of epilepsy implies risk of additional seizures and therefore possibly injuries, sudden death in people with epilepsy, or status epilepticus. Studies have shown that patient and witness accounts are unreliable in a high percentage of cases. Therefore, the core competency of doctors and medical professionals assessing paroxysmal events is knowledge of the clinical features that help define the different aetiologies, thus empowering them to establish the most accurate appraisal of an event. [Published with video sequences].