Abnormal Irritability Research Articles

A network approach to the investigation of childhood irritability: probing frustration using social stimuli.

Self-regulation in early childhood develops within a social context. Variations in such development can be attributed to inter-individual behavioral differences, which can be captured both as facets of temperament and across a normal:abnormal dimensional spectrum. With increasing emphasis on irritability as a robust early-life transdiagnostic indicator of broad psychopathological risk, linkage to neural mechanisms is imperative. Currently, there is inconsistency in the identification of neural circuits that underlie irritability in children, especially in social contexts. This study aimed to address this gap by utilizing a functional magnetic resonance imaging (fMRI) paradigm to investigate pediatric anger/frustration using social stimuli. Seventy-three children (M = 6 years, SD = 0.565) were recruited from a larger longitudinal study on irritability development. Caregivers completed questionnaires assessing irritable temperament and clinical symptoms of irritability. Children participated in a frustration task during fMRI scanning that was designed to induce frustration through loss of a desired prize to an animated character. Data were analyzed using both general linear modeling (GLM) and independent components analysis (ICA) and examined from the temperament and clinical perspectives. ICA results uncovered an overarching network structure above and beyond what was revealed by traditional GLM analyses. Results showed that greater temperamental irritability was associated with significantly diminished spatial extent of activation and low-frequency power in a network comprised of the posterior superior temporal sulcus (pSTS) and the precuneus (p < .05, FDR-corrected). However, greater severity along the spectrum of clinical expression of irritability was associated with significantly increased extent and intensity of spatial activation as well as low- and high-frequency neural signal power in the right caudate (p < .05, FDR-corrected). Our findings point to specific neural circuitry underlying pediatric irritability in the context of frustration using social stimuli. Results suggest that a deliberate focus on the construction of network-based neurodevelopmental profiles and social interaction along the normal:abnormal irritability spectrum is warranted to further identify comprehensive transdiagnostic substrates of the irritability.

Characterizing the spectrum of irritability in preadolescence: Dimensional and pragmatic applications.

Characterize the dimensional spectrum of preadolescent (PA) irritability, a robust transdiagnostic vulnerability marker, using the youth version of the Multidimensional Assessment Profiles Temper Loss (MAPS-TL-Youth) scale including common and with developmentally specific items. Based on this, derive and validate a clinically optimized irritability screener to flag psychopathology risk in preadolescents. The normal:abnormal irritability spectrum was modeled using MAPS-TL-Youth data from the Multidimensional Assessment of Preschoolers Study (MAPS) Study PA wave (n=340) via item response theory. Both cross-cutting core items from the MAPS scales and developmentally specific items were used to generate this dimension. Stepwise logistic regression was then used to optimize MAPS-TL-Youth irritability items in relation to Kiddie Schedule of Affective Disorders and Schizophrenia impairment to generate a clinically optimized irritability screener. Receiver operator characteristic analysis identified the irritability threshold for the screener. For the first time, youth self-report of their own irritability on the MAPS-TL was also modeled via the MAPS-TL-Youth-Self-Report (MAPS-TL-Youth-SR). Irritability was unidimensional and ranged from mild and common to severe and rare behaviors. Developmentally specific items allowed detection of more severe irritability. Items for the screener were identified in relation to concurrent impairment. These included low frustration tolerance and pathognomonic severe behaviors. The clinically optimized screener demonstrated very good sensitively (87%) and specificity (81%) in regard to concurrent irritability-related DSM disorders. Modeling of the MAPS-TL-Youth-SR yielded similar results. Characterizing the normal: abnormal spectrum of irritability in preadolescence advances application of Research Domain Criteria methods to this developmental period. This foundational work yielded two developmentally specified tools for irritability characterization in preadolescence: a nuanced dimensional scale to precisely characterize the full normal-abnormal irritability spectrum, and a pragmatic, clinically optimized screener suitable for real world use. Future application in mechanistic and clinical studies will be important for establishing validity and incremental utility.

Developmentally specified characterization of the irritability spectrum at early school age: Implications for pragmatic mental health screening.

Developmentally specified measures that identify clinically salient irritability are needed for early school-age youth to meaningfully capture this transdiagnostic risk factor for psychopathology. Thus, the current study modeled the normal:abnormal irritability spectrum and generated a clinically optimized screening tool for this population. The irritability spectrum was modeled via the youth version of the Multidimensional Assessment Profile Scales-Temper Loss Scale (MAPS-TL-Youth) in children (n=474; 6.0-8.9years) using item response theory (IRT). Both cross-cutting core irritability items from the early childhood version and new developmentally specific items were included. Items uniquely associated with impairment were identified and used to derive a brief, clinically optimized irritability screener. Longitudinal data were then utilized to test the predictive utility of this clinically optimized screener in preadolescence (n=348; 8.0-12.9years). Most children exhibit irritability regularly, but daily occurrence was rare. Of the top 10 most severe items from the IRT analyses, 9 were from the developmentally specific items added for the MAPS-TL Youth version. Two items associated with concurrent impairment were identified for the clinically optimized irritability screener ("Become frustrated easily" and "Act irritable"). The MAPS-TL-Youth clinically optimized screener demonstrated good sensitivity (69%) and specificity (84%) in relation to concurrent DSM 5 irritability-related diagnoses. Youth with elevated scores on the screener at early school age (ESA) had more than 7x greater odds of irritability-related psychopathology at pre-adolescence. The MAPS-TL-Youth characterized the developmental spectrum of irritability at ESA and a clinically optimized screener showed promise at predicting psychopathology risk. Rigorous testing of clinical applications is a critical next step.

Assessing pediatric mental health in the family medicine setting, with a focus on irritability - A qualitative study

Primary care practitioners are often called upon to differentiate normal from abnormal irritability, but little education is provided to prepare them to do so. Assessing the mental health of a child is a challenging task. This study used appreciative inquiry to answer the question, “How do family medicine practitioners assess and treat irritability in school aged children?” To gain an initial perspective on how practitioners in Family Medicine (FM), Pediatrics (PED), and Psychiatry (PSY) evaluate and treat school-aged children, 17 volunteers participated in in-depth interviews. The participants in primary care expressed frustration over the lack of time and specialized knowledge they had to accurately assess children, even though they were often the first clinician consulted when problems arose. There were clear and sometimes contradictory differences between how practitioners with a general vs. specialized practice assessed mental health status in the clinic setting. In addition, input on treatment approaches revealed that medication prescription was more common in primary care and therapy preferred by the PSY participants. School referrals were common pathways to the FM and PED clinic, where practitioners often focused on assessing functional status to assess normal vs. abnormal irritability. Based on the initial assessment, FM and PED participants often referred the child to more specialized treatment, particularly when complex medication prescription was involved.

Evidence of Non-Linear Associations between Frustration-Related Prefrontal Cortex Activation and the Normal:Abnormal Spectrum of Irritability in Young Children.

Burgeoning interest in early childhood irritability has recently turned toward neuroimaging techniques to better understand normal versus abnormal irritability using dimensional methods. Current accounts largely assume a linear relationship between poor frustration management, an expression of irritability, and its underlying neural circuitry. However, the relationship between these constructs may not be linear (i.e., operate differently at varying points across the irritability spectrum), with implications for how early atypical irritability is identified and treated. Our goal was to examine how the association between frustration-related lateral prefrontal cortex (LPFC) activation and irritability differs across the dimensional spectrum of irritability by testing for non-linear associations. Children (N=92; ages 3-7) ranging from virtually no irritability to the upper end of the clinical range completed a frustration induction task while we recorded LPFC hemoglobin levels using fNIRS. Children self-rated their emotions during the task and parents rated their child's level of irritability. Whereas a linear model showed no relationship between frustration-related LPFC activation and irritability, a quadratic model revealed frustration-related LPFC activation increased as parent-reported irritability scores increased within the normative range of irritability but decreased with increasing irritability in the severe range, with an apex at the 91st percentile. Complementarily, we found children's self-ratings of emotion during frustration related to concurrent LPFC activation as an inverted U function, such that children who reported mild distress had greater activation than peers reporting no or high distress. Results suggest children with relatively higher irritability who are unimpaired may possess well-developed LPFC support, a mechanism that drops out in the severe end of the irritability dimension. Findings suggest novel avenues for understanding the heterogeneity of early irritability and its clinical sequelae.

Resective surgery in the treatment of super-refractory partial status epilepticus secondary to NMDAR antibody encephalitis

BackgroundAnti-NMDAR encephalitis is an increasingly described clinical entity in children, comprising 40% of all cases. We present a case of super-refractory status epilepticus secondary to anti-NMDAR encephalitis treated with emergent resective surgery. Case studyA 7 years-old boy presented with progressive abnormal irritability. On the day after admission he had multiple seizures, characterized by head and eye version to the right. EEG revealed left parietal-occipital continuous paroxysmal activity. Anti-NMDAR antibodies were positive in CSF and serum. After almost 3 months in the Intensive Care Unit, in barbituric coma, and given the failure of all treatment regimens, a preoperative evaluation was conducted. Ictal SPECT showed significant hiperperfusion and brain FDG-PET a cortical hypometabolism in the left occipital lobe; a left occipital lobectomy was performed. In the next days it was possible to progressively suspend Thiopental. Currently, patient presents right homonymous hemianopsia, eats by his own hand but needs help in almost all other activities. DiscussionStatus epilepticus (SE) in the setting of anti-NMDAR encephalitis is unusual but described. Whilst the role of surgery in the management of refractory focal epilepsy is established, it is seldom used in the treatment of SE. In the patient with refractory SE (RSE), awareness of surgery as a potentially life saving treatment is an important issue. To our knowledge, this is the first report of a partial RSE secondary to anti-NMDAR encephalitis treated with resective surgery and illustrates the need to consider anti-NMDAR encephalitis as a cause of super-refractory SE.

P-165 - A case of hydrocephalus occlusus presenting as a manic episode

Normal Pressure Hydrocephalus(Hakim-Adams Syndrome)is a dilation of the ventricles without an increase of intracranial pressure.It corresponds to he classic triade of are gait disturbance, memory/cognitive problems,and urinary incontinence. Manic and depressive symptoms can be related to hydrocephalus occlusus even in the absence of neurological symptoms.These symptoms disappear after neurosurgery or pharmacological treatment. A 26 year old-male,from Cabo Verde,is interviewed in the Emergency Department in June 2011 presenting disturbance of general behaviour.He is being aggressive and presents flight of ideas.The diagnosis: “Hypomanic state” treated with lorazepam 6 mg/day and Olanzapine 5 mg/day. August 2011, the patient is reevaluated because of his behaviour:soliloquies,laughs,expansive mood, abnormal irritability, easily excited to enthusiasm and irritable humor. He also presents psychomotor agitation associated to delusion of persecution.He has not been taking his medication. No other neurological symptoms are detected. In Hospital he receives Risperidone 6 mg/day, Clorazepate Dipotassium45mg/day and Lormetazepam 2 mg /day disappearing most of the symptoms. A MRI was done, presenting triventricular hydrocephalus with absence of intraparenchymal damage.After monitoring the intracranial pressure, Neurosurgery decides not to perform surgery. In the case of not responding to Risperidone, studies have been published that Aripiprazole (atypical antipsychotic with a unique partial agonistic effect at D2receptors)is effective and safe in the treatment of manic episode. Some publications about the reduction of D2receptors demonstrated that the binding of striatal was reduced in NPH. Sometimes imaging tests are needed in patients with behavioural disturbance as manic symptoms in order to avoid misdiagnosis and it is crucial for the correct medical and chirurgical treatment.

Epidermoid cyst involving the medial temporal lobe: Surgical pathologic features of the epileptogenic lesion

Epidermoid cysts in the middle fossa are rare and may involve the temporal lobe and lateral ventricle. Affected patients often suffer from seizures, but the pathomechanisms underlying the epileptogenic lesions have remained unclear. Here we report the surgical pathological features of the hippocampus in a 31-year-old woman with mesial temporal lobe epilepsy (mTLE), in whom an epidermoid cyst involving the right basal cistern and inferior horn of the lateral ventricle was evident. The ictal electrocorticogram indicated seizure onset at the parahippocampal gyrus. An anterior temporal lobectomy and amygdalohippocampectomy were performed. Histologically, the hippocampus showed marked atrophy with severe loss of pyramidal neurons in the cornu Ammonis subfields and granule cell loss in the dentate gyrus. At the ventricular surface of the hippocampus, there were small granulomatous lesions with spicularly anchored keratin substance. These features indicated multiple and chronic stab wounds by the cyst contents and consequent local inflammatory responses within the parenchyma. The predisposition to adhesion between the tumor and hippocampus may have caused neurons to develop abnormal irritability to certain chemical mediators present in the cyst. Epileptogenicity involving the atrophic hippocampus and medial temporal lobes nearby may have developed in association with these processes. This case appears to provide information that is useful for surgical planning in patients with mTLE and epidermoid cysts involving the medial temporal lobe.

HYPERTENSIVE ENCEPHALOPATHY INDUCED BY MERCURY POISONING; A REPORT OF 3 CASES (IN AN IRANIAN FAMILY)

Objective Mercury poisoning is one of the important recent causes of mortality and mortality in children worldwide, particularly in industrial environments; mercury is a poisonous metal, especially harmful to the nervous and immune systems and the kidneys and can even be fatal. Elemental mercury is present in thermometers, barometer batteries, sphygmomanometers and latex paints. Inorganic mercury salts are found in antiseptics, pesticides, pigments and explosives and are used as preservatives in medicine. Mercury was once used to stop fever, and this worked because the immune system was so weakened that it could no longer sustain the attack for which the fever was created. Some medical drugs still contain mercury chloride and mercurous chloride and certain forms of mercury are still used in some laxatives. Mercury toxicity of the nervous system causes anorexia, ataxia, lack of ability to coordinate voluntary muscle movements, dementia, depression, dizziness, emotional instability, erethism (abnormal irritability in response to stimulation), incoordination, insomnia, irritability, loss of ability to speak, memory impairment, numbness, saresthesias (sensation of prickling, tingling or creeping on the skin), psychosis, tremors, drowsiness, fatigue and weakness. Other organ damages include kidney failure, headaches, hearing impairment, visual impairment, hypertension, dermatitis, digestive tract problems, colitis, diarrhea, stomatitis and excessive salivation, loss of teeth, metallic taste, chromosomal damage, birth defects and ensuing organ failure. Chronic mercury poisoning can cause Acrodynia (Pink disease). Mercury poisoning is a rare cause of hypertension in children. Herein we report 3 cases, the first a child with hypertensive encephalopathy due to severe mercury poisoning and his two siblings with moderate symptoms. Case report A 10 year old boy was admitted in psychiatric ward of Imam Hossein Hospital with behavioral disorder, irritability, mood change and convulsion. Because of his blood pressure which was 160/120 he was referred and admitted to the Pediatric Nephrology department. On arrival, for his hypotonia and the pink discoloration of his fingers a diagnosis of Acrodynia (Pink disease) was considered; his history showed that he has played with a ball of mercury, taken from a laboratory. He and his 2 siblings received British Anti Lewisite(BAL) and D-penicillamin; at follow-up all symptoms had gradually disappeared and they are well now. Keywords: Mercury poisoning, Children, Renal complications, Hypertensive encephalopathy

Presence of irritability during depressive episodes in bipolar disorder.

This study examined the prevalence of irritability in patients with bipolar I disorder during an episode of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) major depression who do not meet criteria for a mixed episode. A chart review of 111 patients with bipolar I disorder treated at the Massachusetts General Hospital Bipolar Clinic between 1998 and 2000 identified 34 patients who met criteria for a DSM-IV major depressive episode in the absence of (1) mood elevation and/or (2) irritability associated with any additional above threshold DSM-IV symptoms of mania. Data gathered from the charts utilized prospective ratings made routinely at each clinic visit using the Clinical Monitoring Form (CMF), a structured assessment instrument which includes modified versions of the mood modules of the Structured Clinical Interview for DSM-IV. Data from these 34 patients were reviewed to determine the presence of irritability. The frequency of abnormal irritability in these 34 patients followed a bimodal distribution: 26% of the patients showed abnormal irritability > or =75% of the time, compared with 68% of the patients with abnormal irritability < or =30% of the time. Of the high-irritability patients, psychomotor agitation was rated as definitely present to a significant degree in 44%. Talkativeness and distractibility were rated present but subthreshold in one patient each. All other symptoms of DSM-IV mania were absent. Approximately 25% of patients with bipolar I disorder who meet criteria for a DSM-IV major depressive episode also experienced substantial irritability in the absence of associated symptoms of mania. Our results suggest that abnormal irritability is not limited to mania or mixed states.

Gastroesophageal reflux.

1. Susan R. Orenstein, MD* 1. 2. *Professor of Pediatrics, Children’s Hospital of Pittsburgh, Division of Pediatric Gastroenterology, Pittsburgh, PA. 3. Dr. Orenstein receives research grant support from the Janssen Research Foundation. Thirty years ago, gastroesophageal reflux disease was virtually unknown; today, it seems necessary to consider it a potential cause of an enormous range of symptoms. Not long ago, reflux was diagnosed simply by ordering an upper gastrointestinal barium study; now the complexity of differentiating between gastroesophageal reflux (GER) episodes and gastroesophageal reflux disease (GERD) mandates an understanding of the strengths and weaknesses of a variety of tests. Several decades ago, few options for therapy of reflux existed, and those that did were not very effective or even frankly detrimental; currently, the range of proven therapeutic options is greater, and the pediatrician must exercise finesse in prescribing these options. It has been useful to consider the symptoms, diagnostic complexity, and therapy of reflux as an“ iceberg” (Figure⇓ ). The largest section at the bottom represents common, easily diagnosed, and easily treated cases; the tip of the iceberg represents those cases that occur less frequently, provide considerable diagnostic and therapeutic challenges, and require subspecialist consultation. Exactly where the demarcation occurs between these sections of the iceberg depends on the individual pediatrician’s expertise and the local availability of subspecialty expertise. Each section that follows will consider both infantile GERD (which is more common) and childhood GERD. Figure 1. The GERD iceberg. Reprinted with permission from Orenstein SR. Di Lorenzo C, Hyman P, Flores A. Pediatric Gastroesophageal Reflux: A Guide for Primary Care Physicians . Slide-lecture program sponsored and distributed by American Pseudo-obstruction and Hirschsprung’s Disease Society, Inc., Medfore MA, 1996. ### INFANTS Regurgitation is the classic symptom of reflux in infancy. However, we now understand that infantile regurgitation is not necessarily GERD (reflux disease) and that GERD may occur without any regurgitation, even in infancy. Other symptoms also should prompt the pediatrician to consider the possibility of GERD affecting an infant (Table 1⇓ ). ### CHILDREN During …

Intractable Hiccup

Hiccup previously was thought to be due to a single disease that produced an abnormal irritation of the phrenic nerve or of the higher centers. A study of 220 cases of intractable hiccup suggests that there may be several exciting causes that one must elucidate in the same patient.

THE RELATION OF THE ENDOCRINE GLANDS TO THE DISORDERS OF THE EAR, NOSE AND THROAT

One group of diseases of the ear, nose and throat are mechanical results of physical deformities, sometimes congenital, sometimes secondary effects of infections or other destructive agencies, sometimes the results of glandular hyperplasias or abnormal growth of cartilage and connective tissues. A second group of diseases of these regions are the infections. A third group seems to be due essentially to disturbances in the circulation. This applies particularly to the nose, and in some cases to the middle ear. With these circulatory disturbances are frequently associated abnormal irritability of sensory nerves leading to excess reflexes of various kinds. We have what may be called primary hypertrophy of the lymphoid tissues of the nose and throat, that is, the adenoids and the tonsils. The hypertrophy is at times of obscure origin, possibly dietary or irritative, but not certainly related to acute infections. Finally, there is the so-called sclerosis of the internal

THE SIGNIFICANCE OF CARDIAC IRREGULARITIES

REPORT OF CASES AND COMMENT By Dr. Straus Cardiac irregularities in cases of gallbladder disease are not infrequent; many are functional. During the last few months I have operated in four cases (three cases of gallbladder disease and one of duodenal ulcer) in which the pulse before operation showed a permanent irregularity consisting of premature contractions. In only one of the cases was there any enlargement of the heart; none of the others showed any other evidence of organic disease. In these four cases the extrasystoles may have been due to a vagus reflex phenomenon. While it is generally agreed that extrasystoles are abnormal systoles of a portion of the heart due to impulses which originate, independent of the pacemaker and the Purkinje system, in certain heterogenic zones in the heart itself, and are due to conditions of abnormal irritability, in the cases I report this increased local irritability may