Social affective behaviors among female rats involve the basolateral amygdala and insular cortex.

The ability to detect, appraise, and respond to another's emotional state is essential to social affective behavior. This is mediated by a network of brain regions responsible for integrating external cues with internal states to orchestrate situationally appropriate behavioral responses. The basolateral amygdala (BLA) and the insular cortex are reciprocally connected regions involved in social cognition and prior work in male rats revealed their contributions to social affective behavior. We investigated the functional role of these regions in female rats in a social affective preference (SAP) test in which experimental rats approach stressed juvenile but avoid stressed adult conspecifics. In separate experiments, the BLA or the insula were inhibited by local infusion of muscimol (100ng/side in 0.5µL saline) or vehicle prior to SAP tests. In both regions, muscimol interfered with preference for the stressed juvenile and naive adult, indicating that these regions are necessary for appropriate social affective behavior. In male rats, SAP behavior requires insular oxytocin but there are noteworthy sex differences in the oxytocin receptor distribution in rats. Oxytocin (500nM) administered to the insula did not alter social behavior but oxytocin infusions to the BLA increased social interaction. In sum, female rats appear to use the same BLA and insula regions for social affective behavior but sex differences exist in contribution of oxytocin in the insula.

Social affective behaviors among female rats involve the basolateral amygdala and insular cortex.

The ability to detect, appraise, and respond to another's emotional state is essential to social affective behavior. This is mediated by a network of brain regions responsible for integrating external cues with internal states to orchestrate situationally appropriate behavioral responses. The basolateral amygdala (BLA) and the insular cortex are reciprocally connected regions involved in social cognition and prior work in male rats revealed their contributions to social affective behavior. We investigated the functional role of these regions in female rats in a social affective preference (SAP) test in which experimental rats approach stressed juvenile but avoid stressed adult conspecifics. In separate experiments, the BLA or the insula were inhibited by local infusion of muscimol (100ng/side in 0.5µL saline) or vehicle prior to SAP tests. In both regions, muscimol interfered with preference for the stressed juvenile and naive adult, indicating that these regions are necessary for appropriate social affective behavior. In male rats, SAP behavior requires insular oxytocin but there are noteworthy sex differences in the oxytocin receptor distribution in rats. Oxytocin (500nM) administered to the insula did not alter social behavior but oxytocin infusions to the BLA increased social interaction. In sum, female rats appear to use the same BLA and insula regions for social affective behavior but sex differences exist in contribution of oxytocin in the insula.

Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Over 80 monogenic causes of very early onset inflammatory bowel disease [VEOIBD] have been identified. Prior reports of the natural history of VEOIBD have not considered monogenic disease status. The objective of this study is to describe clinical phenotypes and outcomes in a large single-centre cohort of patients with VEOIBD and universal access to whole exome sequencing [WES]. METHODS: Patients receiving IBD care at a single centre were prospectively enrolled in a longitudinal data repository starting in 2012. WES was offered with enrollment. Enrolled patients were filtered by age of diagnosis <6 years to comprise a VEOIBD cohort. Monogenic disease was identified by filtering proband variants for rare, loss-of-function, or missense variants in known VEOIBD genes inherited according to standard Mendelian inheritance patterns. RESULTS: This analysis included 216 VEOIBD patients, followed for a median of 5.8 years. Seventeen patients [7.9%] had monogenic disease. Patients with monogenic IBD were younger at diagnosis and were more likely to have Crohn's disease phenotype with higher rates of stricturing and penetrating disease and extraintestinal manifestations. Patients with monogenic disease were also more likely to experience outcomes of intensive care unit [ICU] hospitalisation, gastrostomy tube, total parenteral nutrition use, stunting at 3-year follow-up, haematopoietic stem cell transplant, and death. A total of 41 patients [19.0%] had infantile-onset disease. After controlling for monogenic disease, patients with infantile-onset IBD did not have increased risk for most severity outcomes. CONCLUSIONS: Monogenic disease is an important driver of disease severity in VEOIBD. WES is a valuable tool in prognostication and management of VEOIBD.

Association Between Diaphragmatic Paralysis and Ipsilateral Cervical Spondylosis on MRI.

PURPOSE: Diaphragmatic paralysis (DP) is an important cause of dyspnea with many underlying etiologies; however, frequently no cause is identified despite extensive investigation. We hypothesized that cervical spondylosis (CS), as manifest by cervical neuroforaminal stenosis on magnetic resonance imaging (MRI), is an underrecognized cause of unilateral DP. METHODS: A retrospective study was performed assessing cervical spine imaging utilization in the investigation of unilateral DP, and the contribution of CS to its pathogenesis. To assess the relationship between CS and DP, comparison was made between severity of ipsilateral and contralateral foraminal stenosis on cervical spine MRI in individuals with idiopathic DP, and to controls with DP of known etiology. RESULTS: Record searches identified 334 individuals with DP who were classified as idiopathic (n = 101) or DP of known etiology (n = 233). Of those with idiopathic DP, only 37% had undergone cervical spine imaging. Cervical spine MRIs, available for 32 individuals from the total cohort identified (n = 15 idiopathic DP, n = 17 DP of known etiology), were reviewed and severity of CS graded (0-2). In idiopathic DP, CS was significantly more severe (grade 2 stenosis) on the side of DP at C3-C4 (73% affected vs 13% unaffected side; p = 0.031) and C4-C5 (60% affected vs 20% unaffected side; p = 0.0039), while no difference was observed in DP of known etiology. Overall severity of CS across all cervical spine levels was significantly worse in idiopathic DP versus those with DP of known etiology. CONCLUSIONS: In unilateral idiopathic DP, severity of CS is associated with DP laterality and is an underrecognized cause of diaphragmatic dysfunction. We propose that evaluation of 'idiopathic' DP should routinely include cervical spine imaging, preferably by MRI.

Gender Differences in Skin Biopsy Findings in Small Fiber Neuropathy: A Retrospective Chart Review.

OBJECTIVES: To determine whether there are gender differences in the clinical presentation or skin biopsy measures of nerve fiber density in patients with small fiber neuropathy (SFN). METHODS: Retrospective chart review of subjects with suspected SFN. RESULTS: Of 218 cases (137 women and 81 men) with suspected SFN, 96 (44%), including 63% of the men and 33% of the women (P < 0.05), had low epidermal nerve fiber density (ENFD) or sweat gland nerve fiber density (SGNFD). There were no differences in the clinical presentation between men and women. In those with abnormal findings, low ENFD alone was more frequent in women than men (51.1% vs. 7.8%, P < 0.05), whereas abnormal SGNFD alone was more frequent in men than women (68.6% vs. 11.1%, P < 0.05). Both SGNFD and ENFD were low in 23.5% of men and 33.3% of women. Skin biopsy findings were independent of clinical presentation or etiology. CONCLUSIONS: The clinical presentation of SFN is similar in men and women. In skin biopsy studies, low ENFD is more common in women and low SGNFD in men.

Big Five aspects of personality interact to predict depression.

OBJECTIVE: Research has shown that three personality traits-Neuroticism, Extraversion, and Conscientiousness-moderate one another in a three-way interaction that predicts depressive symptoms in healthy populations. We test the hypothesis that this effect is driven by three lower-order traits: withdrawal, industriousness, and enthusiasm. We then replicate this interaction within a clinical population for the first time. METHOD: Sample 1 included 376 healthy adults. Sample 2 included 354 patients diagnosed with current major depressive disorder. Personality and depressive tendencies were assessed via the Big Five Aspect Scales and Personality Inventory for DSM-5 in Sample 1, respectively, and by the NEO-PI-R and Beck Depression Inventory-II in Sample 2. RESULTS: Withdrawal, industriousness, and enthusiasm interacted to predict depressive tendencies in both samples. The pattern of the interaction supported a "best two out of three" principle, in which low risk scores on two trait dimensions protects against a high risk score on the third trait. Evidence was also present for a "worst two out of three" principle, in which high risk scores on two traits are associated with equivalent depressive severity as high risk scores on all three traits. CONCLUSIONS: These results highlight the importance of examining interactive effects of personality traits on psychopathology.

Abnormal Nutritional Factors in Patients Evaluated at a Neuropathy Center.

Abnormal concentrations of nutritional factors were found in 24.1% of 187 patients with neuropathy who were newly seen at our academic neuropathy referral center over a 1-year period. All patients presented with sensory axonal or small fiber neuropathy. In 7.3%, they were present in association with at least one other identifiable cause for neuropathy. Elevated levels of pyridoxal phosphate or mercury occurred more frequently than deficiencies in vitamins B1, B12, or B6. The nutritional abnormalities are amenable to correction by dietary intervention.

Ten aspects of the Big Five in the Personality Inventory for DSM-5.

Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) includes a dimensional model of personality pathology, operationalized in the Personality Inventory for DSM-5 (PID-5), with 25 facets grouped into 5 higher order factors resembling the Big Five personality dimensions. The present study tested how well these 25 facets could be integrated with the 10-factor structure of traits within the Big Five that is operationalized by the Big Five Aspect Scales (BFAS). In 2 healthy adult samples, 10-factor solutions largely confirmed our hypothesis that each of the 10 BFAS would be the highest loading BFAS on 1 and only 1 factor. Varying numbers of PID-5 scales were additional markers of each factor, and the overall factor structure in the first sample was well replicated in the second. Our results allow Cybernetic Big Five Theory (CB5T) to be brought to bear on manifestations of personality disorder, because CB5T offers mechanistic explanations of the 10 factors measured by the BFAS. Future research, therefore, may begin to test hypotheses derived from CB5T regarding the mechanisms that are dysfunctional in specific personality disorders.

Consensus statement: Using laryngeal electromyography for the diagnosis and treatment of vocal cord paralysis.

INTRODUCTION: The purpose of this study was to develop an evidence-based consensus statement regarding use of laryngeal electromyography (LEMG) for diagnosis and treatment of vocal fold paralysis after recurrent laryngeal neuropathy (RLN). METHODS: Two questions regarding LEMG were analyzed: (1) Does LEMG predict recovery in patients with acute unilateral or bilateral vocal fold paralysis? (2) Do LEMG findings change clinical management in these individuals? A systematic review was performed using American Academy of Neurology criteria for rating of diagnostic accuracy. RESULTS: Active voluntary motor unit potential recruitment and presence of polyphasic motor unit potentials within the first 6 months after lesion onset predicted recovery. Positive sharp waves and/or fibrillation potentials did not predict outcome. The presence of electrical synkinesis may decrease the likelihood of recovery, based on 1 published study. LEMG altered clinical management by changing the initial diagnosis from RLN in 48% of cases. Cricoarytenoid fixation and superior laryngeal neuropathy were the most common other diagnoses observed. CONCLUSIONS: If prognostic information is required in a patient with vocal fold paralysis that is more than 4 weeks and less than 6 months in duration, then LEMG should be performed. LEMG may be performed to clarify treatment decisions for vocal fold immobility that is presumed to be caused by RLN. Muscle Nerve 53: 850-855, 2016.

Comparison of 2-limb versus 3-limb electrodiagnostic studies in the evaluation of chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: European Federation of Neurological Societies/Peripheral Nerve Society electrodiagnostic (EDx) criteria for the definite diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) require the presence of demyelinating findings (DF) in at least 2 nerves. Data are lacking, however, regarding the optimal number of nerves to test. METHODS: We retrospectively reviewed EDx data from 53 patients with CIDP and compared the number of DF found on 2- and 3-limb testing. RESULTS: A median of 3 (range 2-5) DF were found on 2-limb testing compared with 5 (range 4-7) DF when 3 limbs were evaluated. Two-limb EDx studies were sufficient to diagnose definite CIDP in 92.3% of typical, 84.2% of asymmetric, and 66.7% of distal phenotypes. Testing a third limb increased diagnostic certainty in 11 patients (20.8%) to definite CIDP. CONCLUSIONS: Three-limb testing may increase diagnostic sensitivity of definite CIDP, especially in patients with atypical phenotypes. Larger prospective studies are needed to better assess the benefit of performing 3-limb EDx studies.

A novel technique for clinical assessment of laryngeal nerve conduction: normal and abnormal results.

OBJECTIVES/HYPOTHESIS: To describe a novel conduction study of the laryngeal nerves, including normal values and abnormal findings. STUDY DESIGN: Prospective nonrandomized. METHODS: Seventeen healthy adult volunteers, as well as three patients with clinically identified laryngeal neuropathy, underwent low-level brief electrical stimulation of the laryngeal mucosa by means of a wire inserted via a transnasal flexible laryngoscope. Bilateral hookwire electrodes recorded the result in the laryngeal adductor muscles. RESULTS: This study yields an early response ipsilateral to the side of stimulation (LR1), which is uniform and consistent (right = 13.2 ± 0.80 msec; left = 15.2 ± 1.20 msec), and late bilateral responses (ipsilateral LR2 [LR2i] and contralateral LR2 [LR2c]), which exhibit greater variation in latency and morphology (right LR2i = 50.5 ± 3.38 msec; left LR2i = 52.2 msec; right LR2c = 50.7 ± 4.26; left LR2c = 50.6 ± 4.07). Findings in abnormal patients differ significantly from normal, consistent with the distribution of neuropathy. CONCLUSIONS: We describe a novel, clinically applicable conduction study of laryngeal nerves. Normative electrodiagnostic values and variations of the reflex responses of the laryngeal adductor muscles in response to irritative stimulation of the laryngeal mucosa (Laryngeal Closure Reflex) are proposed. By enabling the determination of electrophysiological parameters of the superior laryngeal and recurrent laryngeal branches of cranial nerve X (CN X), this procedure, which is used as an adjunct to laryngeal electromyography, may provide earlier and more accurate information regarding the extent and grade of nerve injury. Because injury grade relates directly to prognosis, the information derived from this test may have clinical relevance in determining optimal treatment.

A novel electrodiagnostic assessment of the laryngeal closure reflex.

INTRODUCTION: We describe a novel, clinically applicable conduction study of the laryngeal nerves. METHODS: Seventeen normal volunteer subjects were included. Activation of the sensory territory of the superior laryngeal nerve was performed by administration of low level brief electrical stimuli. The laryngeal closure reflex (LCR) evoked by this stimulus was recorded by needle electrodes. Mean minimal latencies were calculated for each response, and proposed values for the upper limit of normal were determined. RESULTS: Uniform, consistent early ipsilateral responses and late bilateral responses, which exhibit greater variation in latency and morphology, were recorded. Significant side-to-side differences in latencies were observed, consistent with the length discrepancy between right and left recurrent laryngeal nerves. CONCLUSIONS: This technique yields clear, quantifiable data regarding neurologic integrity of laryngeal function, heretofore unobtainable in the clinical setting. This study may yield clinically relevant information regarding severity and prognosis in patients with laryngeal neuropathic injury.

Prolongation of the tibialis anterior CMAP duration in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: To assess the duration of the distal compound muscle action potential (dCMAP) recording from the tibialis anterior (TA) as a supportive electrodiagnostic feature in chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: We performed peroneal motor conduction studies with recording from the TA in 35 CIDP patients, 30 normal controls, and 21 disease controls. The normal cut-off for the TA dCMAP duration was determined to be 14 ms. RESULTS: Prolonged TA dCMAP durations were detected in 34% of CIDP patients (12/35) and in 33% (2/6) of patients in whom only one demyelinating lesion was identified by conventional motor conduction studies. Prolonged TA dCMAP durations were present in 28% (5/18) of patients with normal duration dCMAPs recorded from the abductor hallucis (AH) and in 42% (5/12) of patients with normal duration dCMAPs recorded from the extensor digitorum brevis (EDB). In patients with AH or EDB dCMAP amplitudes <1 mV, TA dCMAP durations were prolonged in 28% and 23% of patients, respectively. CONCLUSIONS: Determination of TA dCMAP duration appears to be useful for detecting demyelination in CIDP, especially when there is significant coexisting axon loss. SIGNIFICANCE: In patients with potential CIDP and limited electrodiagnostic abnormalities by routine studies, the finding of additional demyelinating findings, such as increased TA dCMAP duration, could allow for improved diagnostic sensitivity.

Laryngeal electromyography for prognosis of vocal fold palsy: a meta-analysis.

OBJECTIVES/HYPOTHESIS: To analyze existing evidence regarding utility of laryngeal electromyography (LEMG) for prognosis in cases of vocal fold palsy (VFP). STUDY DESIGN: Meta-analysis of studies reporting LEMG results and clinical outcomes in 503 patients with of VFP identified by literature search. METHODS: Studies were identified by literature search. Method of diagnosis, interval to LEMG, criteria for prognostication, and outcome were assessed. Criteria for prognosis were standardized to the extent possible across all studies, and studies were checked for consistency in outcome measures and assessments. Pooled data were subjected to statistical analysis. RESULTS: A total of 296/503 patients (58.8%) had findings predictive with poor prognosis, whereas 207/503 (41.2%) had findings of recovery. According to laryngoscopic examination, 269/296 patients with predicted poor recovery had poor recovery (positive predictive value=90.9%), whereas 27/296 (9.1%) had good recovery. In patients with findings consistent with recovery, 115/207 (negative predictive value=55.6%) noted return of motion, whereas 88/207 (44.4%) did not. The odds ratio was 11.56 with 95% confidence interval of 7.10-18.81. CONCLUSIONS: LEMG is a good predictor of poor recovery in patients with VFP and is clinically useful in identifying candidates for early definitive intervention.

A comparison of personality disorder characteristics of patients with nonepileptic psychogenic pseudoseizures with those of patients with epilepsy.

We sought to determine the type of personality disorder cluster associated with patients with nonepileptic psychogenic seizures (NES) compared with that of patients with epileptic seizures (ES). Consecutive adult patients admitted for video/EEG monitoring found to have NES were compared with a simultaneously admitted patient with confirmed epilepsy. Personality was assessed using the Structured Clinical Interview for DSM-IV-TR Axis II Personality Disorders. Personality disorders were then divided into personality clusters described in the DSM-IV-TR: A = paranoid, schizotypal, schizoid; B = borderline, histrionic, antisocial, narcissistic; or C = avoidant, dependent, obsessive-compulsive. Thirteen of 16 patients with NES and 12 of 16 patients with ES met criteria for personality disorders. Patients with NES were more likely to meet criteria for a personality disorder in Cluster A or B, compared with patients with ES, who were more likely to have Cluster C personality disorders (chi(2) test, P=0.007). We propose that the personality traits of patients with NES contribute to the development of nonepileptic psychogenic seizures. However, the large proportion of patients with ES with Cluster C personality disorders was unexpected, and further, for the patients with epilepsy, the direction of the association of their personality traits with the development of epilepsy is unknown.