Proteomics based markers of clinical pain severity in juvenile idiopathic arthritis

Introduction Juvenile idiopathic arthritis (JIA) is a cluster of autoimmune rheumatic diseases occurring in children 16 years of age or less. While it is well-known that pain may be experienced during inflammatory and non-inflammatory states, much remains ambiguous regarding the molecular mechanisms that may drive JIA pain. Thus, in this pilot study, we explored the variability of the serum proteomes in relation to pain severity in a cohort of JIA patients. Methods Serum samples from 15 JIA patients (male and female, 12.7 ± 2.8 years of age) were assessed using liquid chromatography/mass spectrometry (LC/MS). Correlation analyses were performed to determine the relationships among protein levels and self-reported clinical pain severity. Additionally, how the expression of pain-associated proteins related to markers of inflammation (Erythrocyte Sedimentation Rate (ESR)) or morphological properties of the central nervous system (subcortical volume and cortical thickness) implicated in JIA were also evaluated. Results 306 proteins were identified in the JIA cohort of which 14 were significantly (p < 0.05) associated with clinical pain severity. Functional properties of the identified pain-associated proteins included but were not limited to humoral immunity (IGLV3.9), inflammatory response (PRG4) and angiogenesis (ANG). Associations among pain-associated proteins and ESR (IGHV3.9, PRG4, CST3, VWF, ALB), as well as caudate nucleus volume (BTD, AGT, IGHV3.74) and insular cortex thickness (BTD, LGALS3BP) were also observed. Conclusions The current proteomic findings suggest both inflammatory- and non-inflammatory mediated mechanisms as potential factors associated with JIA pain. Validation of these preliminary observations using larger patient cohorts and a longitudinal study design may further point to novel serologic markers of pain in JIA.

Sex Hormone-Specific Neuroanatomy of Takotsubo Syndrome: Is the Insular Cortex a Moderator?

Takotsubo syndrome (TTS), a transient form of dysfunction in the heart’s left ventricle, occurs predominantly in postmenopausal women who have emotional stress. Earlier studies support the concept that the human circulatory system is modulated by a cortical network (consisting of the anterior cingulate gyrus, amygdala, and insular cortex (Ic)) that plays a pivotal role in the central autonomic nervous system in relation to emotional stressors. The Ic plays a crucial role in the sympathovagal balance, and decreased levels of female sex hormones have been speculated to change functional cerebral asymmetry, with a possible link to autonomic instability. In this review, we focus on the Ic as an important moderator of the human brain–heart axis in association with sex hormones. We also summarize the current knowledge regarding the sex-specific neuroanatomy in TTS.

Descending Cephalic to Epigastric Sensation in a Patient with Mesial Temporal Lobe Epilepsy: A Novel Observation

One of the most frequent type of auras in mesial temporal lobe epilepsy (MTLE) is epigastric sensation. Until now the site of the symptomatogenic zone of the epigastric aura remains controversial. The temporal lobe as well as insular cortex has been implicated. Our case is that of a 29-year-old young woman who presented with an aura of descending cephalic to epigastric sensation as opposed to the prototypical ascending aura. Interictal and ictal recording favored a mesial temporal pattern. Magnetic resonance imaging brain showed left mesial temporal lobe sclerosis. Interictal positron emission tomography showed concordant findings. The patient underwent selective amygdalohippocampectomy following which she remains seizure-free. This previously unreported clinical expression of MTLE and its origins is discussed.

Organic Hallucinosis in Non-Hemorrhagic Stroke Caused by Thrombosis Process: A Case Report

Background/aim: Hallucinations are the special ability to experience phenomena that are not visible to normal individuals. Hallucinations, delusions, and confabulations are common symptoms between neurology and psychiatry. Nervous disease that manifests with hallucinatory symptoms like this is one of them due to right hemispheric stroke. The authors report cases of new-onset organic hallucinosis. and stroke in brain regions similar to the salience network (insular cortex, parietal cortex, and striatum). Case: A 43-year-old man comes to the ER Sanglah Hospital Denpasar, Bali Indonesia with complaints of slurred speech using an incomprehensible language, and repeating the same words. Talking about seeing a shadow following him but actually not there. Patients often experience sleep disorders, from the results of neurological physical examination found right eye ptosis, pupil anisokor, nerve III dextra complete lesion, supranuclear left NVII paresis, supranuclear left NXII paresis, left flaccid hemiparesis. Psychiatric status obtained unnatural appearance, looks confused, verbal and visual contact is sufficient, mood dysphoric, confused affect and there is no harmony. The thought process obtained realistic, coherent, preoccupation with pain. Perceptual disturbances in the form of visual and auditory hallucinations. Insomnia mixed type and there is hypobulia. Psychomotor calm on examination, history increases. Narcissistic personality traits and defense mechanisms of ego repression. Grade 4 view. CT scan of the head with and without contrast shows subacute ischemic cerebral infarction in the right internal capsule to the right thalamus and midbrain. Conclusion: Organic hallucinosis occur in non-hemorrhagic stroke caused by thrombosis process if an infarction is found in the right hemisphere. Keywords: organic hallucinations, ischemic cerebral infarction, non-hemorrhagic stroke, right hemisphere.

A Comprehensive Overview of Broca’s Aphasia after Ischemic Stroke

Aphasia denotes an acquired central disorder of language, which alters patient’s ability of understanding and/or producing spoken and written language. The main cause of aphasia is represented by ischemic stroke. The language disturbances are frequently combined into aphasic syndromes, contained in different vascular syndromes, which may suffer evolution/involution in the acute stage of ischemic stroke. The main determining factor of the vascular aphasia’s form is the infarct location. Broca’s aphasia is a non-fluent aphasia, comprising a wide range of symptoms (articulatory disturbances, paraphasias, agrammatism, anomia, and discrete comprehension disorders of spoken and written language) and is considered the third most common form of acute vascular aphasia, after global and Wernicke’s aphasia. It is caused by a lesion situated in the dominant cerebral hemisphere (the left one in right-handed persons), in those cortical regions vascularized by the superior division of the left middle cerebral artery (Broca’s area, the rolandic operculum, the insular cortex, subjacent white matter, centrum semiovale, the caudate nucleus head, the putamen, and the periventricular areas). The role of this chapter is to present the most important acquirements in the field of language and neurologic examination, diagnosis, and therapy of the patient with Broca’s aphasia secondary to ischemic stroke.

Investigating the Relationship between White Matter Connectivity and Motivational Circuits in Subjects with Deficit Schizophrenia: A Diffusion Tensor Imaging (DTI) Study

Deficit schizophrenia is a subtype of schizophrenia presenting primary and enduring negative symptoms (NS). Although one of the most updated hypotheses indicates a relationship between NS and impaired motivation, only a few studies have investigated abnormalities of motivational circuits in subjects with deficit schizophrenia (DS). Our aim was to investigate structural connectivity within motivational circuits in DS. We analyzed diffusion tensor imaging (DTI) data from 46 subjects with schizophrenia (SCZ) and 35 healthy controls (HCs). SCZ were classified as DS (n = 9) and non-deficit (NDS) (n = 37) using the Schedule for Deficit Syndrome. The connectivity index (CI) and the Fractional Anisotropy (FA) of the connections between selected brain areas involved in motivational circuits were examined. DS, as compared with NDS and HCs, showed increased CI between the right amygdala and dorsal anterior insular cortex and increased FA of the pathway connecting the left nucleus accumbens with the posterior insular cortex. Our results support previous evidence of distinct neurobiological alterations underlying different clinical subtypes of schizophrenia. DS, as compared with NDS and HCs, may present an altered pruning process (consistent with the hyperconnectivity) in cerebral regions involved in updating the stimulus value to guide goal-directed behavior.

Nicotine Exposure during Adolescence Leads to Changes of Synaptic Plasticity and Intrinsic Excitability of Mice Insular Pyramidal Cells at Later Life

To find satisfactory treatment for nicotine addiction, synaptic and cellular mechanisms should be investigated comprehensively. Synaptic transmission, plasticity and intrinsic excitability in various brain regions are known to be altered by acute nicotine exposure. However, it has not been addressed whether and how nicotine exposure during adolescence alters these synaptic events and intrinsic excitability in the insular cortex in adulthood. To address this question, we performed whole-cell patch-clamp recordings to examine the effects of adolescent nicotine exposure on synaptic transmission, plasticity and intrinsic excitability in layer V pyramidal neurons (PNs) of the mice insular cortex five weeks after the treatment. We found that excitatory synaptic transmission and potentiation were enhanced in these neurons. Following adolescent nicotine exposure, insular layer V PNs displayed enhanced intrinsic excitability, which was reflected in changes in relationship between current strength and spike number, inter-spike interval, spike current threshold and refractory period. In addition, spike-timing precision evaluated by standard deviation of spike timing was decreased following nicotine exposure. Our data indicate that adolescent nicotine exposure enhances synaptic transmission, plasticity and intrinsic excitability in layer V PNs of the mice insular cortex at later life, which might contribute to severe nicotine dependence in adulthood.

FAAH polymorphism (rs324420) modulates extinction recall in healthy humans: an fMRI study

Gold standard treatments for anxiety- and trauma-related disorders focus on exposure therapy promoting extinction learning and extinction retention. However, its efficacy is limited. Preclinical and particularly animal research has been able to demonstrate that homozygosity for the fatty acid amide hydrolase (FAAH) C385A allele, similar to FAAH inhibition, is associated with elevated concentrations of anandamide (AEA) and facilitates extinction learning and extinction recall. However, in humans, the underlying neurobiological processes are less well understood, and further knowledge might enhance the development of more effective therapies. In this functional magnetic resonance imaging (fMRI) study, a fear conditioning, fear extinction and extinction recall paradigm was conducted with 55 healthy male adults. They were genotyped for the FAAH single-nucleotide polymorphism (SNP) rs324420 to investigate differences related to extinction recall in neural activation and State–Trait Anxiety Inventory (STAI) ratings between AC heterozygotes and CC homozygotes (FAAH C385A SNP). Differential brain activation upon an unextinguished relative to an extinguished stimulus, was greater in AC heterozygotes as compared to CC homozygotes in core neural structures previously related to extinction recall, such as the medial superior frontal gyrus, the dorsal anterior cingulate and the anterior and middle insular cortex. Furthermore, AC heterozygotes displayed higher AEA levels and lower STAI-state ratings. Our data can be interpreted in line with previous suggestions of more successful extinction recall in A-allele carriers with elevated AEA levels. Data corroborate the hypothesis that the endocannabinoid system, particularly AEA, plays a modulatory role in the extinction of aversive memory.