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1.  Abdominal epilepsy in chronic recurrent abdominal pain 
Background:
Abdominal epilepsy (AE) is an uncommon cause for chronic recurrent abdominal pain in children and adults. It is characterized by paroxysmal episode of abdominal pain, diverse abdominal complaints, definite electroencephalogram (EEG) abnormalities and favorable response to the introduction of anti-epileptic drugs (AED). We studied 150 children with chronic recurrent abdominal pain and after exclusion of more common etiologies for the presenting complaints; workup proceeded with an EEG. We found 111 (74%) children with an abnormal EEG and 39 (26%) children with normal EEG. All children were subjected to AED (Oxcarbazepine) and 139 (92%) children responded to AED out of which 111 (74%) children had an abnormal EEG and 27 (18%) had a normal EEG. On further follow-up the patients were symptom free, which helped us to confirm the clinical diagnosis.
Context:
Recurrent chronic abdominal pain is a common problem encountered by pediatricians. Variety of investigations are done to come to a diagnosis but a cause is rarely found. In such children diagnosis of AE should be considered and an EEG will confirm the diagnosis and treated with AED.
Aims:
To find the incidence of AE in children presenting with chronic recurrent abdominal pain and to correlate EEG findings and their clinical response to empirical AEDs in both cases and control.
Settings and Design:
Krishna Institute of Medical Sciences University, Karad, Maharashtra, India. Prospective analytical study.
Materials and Methods:
A total of 150 children with chronic recurrent abdominal pain were studied by investigations to rule out common causes of abdominal pain and an EEG. All children were then started with AED oxycarbamezepine and their response to the treatment was noted.
Results:
111 (74%) of the total 150 children showed a positive EEG change suggestive of epileptogenic activity and of which 75 (67.56%) were females and 36 (32.43%) were male, majority of children were in the age of group of 9-12 years. Temporal wave discharges were 39 (35.13%) of the total abnormal EEG's. All the children were started on AEDs and those with abnormal EEG showed 100% response to treatment while 27 (18%) children with normal EEG also responded to treatment. Twelve (8%) children did not have any improvement in symptoms.
Conclusions:
A diagnosis of AE must be considered in children with chronic recurrent abdominal pain, especially in those with suggestive history, and an EEG can save a child from lot of unnecessary investigations and suffering.
doi:10.4103/1817-1745.106468
PMCID: PMC3611899  PMID: 23559997
Abdominal epilepsy; chronic recurrent abdominal pain; electroencephalogram
2.  Characteristics of late-onset epilepsy and EEG findings in children with autism spectrum disorders 
Korean Journal of Pediatrics  2011;54(1):22-28.
Purpose
To investigate the clinical characteristics of late-onset epilepsy combined with autism spectrum disorder (ASD), and the relationship between certain types of electroencephalography (EEG) abnormalities in ASD and associated neuropsychological problems.
Methods
Thirty patients diagnosed with ASD in early childhood and later developed clinical seizures were reviewed retrospectively. First, the clinical characteristics, language and behavioral regression, and EEG findings of these late-onset epilepsy patients with ASD were investigated. The patients were then classified into 2 groups according to the severity of the EEG abnormalities in the background rhythm and paroxysmal discharges. In the severe group, EEG showed persistent asymmetry, slow and disorganized background rhythms, and continuous sharp and slow waves during slow sleep (CSWS).
Results
Between the two groups, there was no statistically significant difference in mean age (P=0.259), age of epilepsy diagnosis (P=0.237), associated family history (P=0.074), and positive abnormal magnetic resonance image (MRI) findings (P=0.084). The severe EEG group tended to have more neuropsychological problems (P=0.074). The severe group statistically showed more electrographic seizures in EEG (P=0.000). Rett syndrome was correlated with more severe EEG abnormalities (P=0.002). Although formal cognitive function tests were not performed, the parents reported an improvement in neuropsychological function on the follow up checkup according to a parent's questionnaire.
Conclusion
Although some ASD patients with late-onset epilepsy showed severe EEG abnormalities, including CSWS, they generally showed an improvement in EEG and clinical symptoms in the long-term follow up. In addition, severe EEG abnormalities tended to be related to the neuropsychological function.
doi:10.3345/kjp.2011.54.1.22
PMCID: PMC3040362  PMID: 21359057
Autism spectrum disorder; Epilepsy; Electroencephalography; Regression; Child
3.  Duloxetine in panic disorder with somatic gastric pain 
Panic disorder is the most common type of anxiety disorder, and its most common expression is panic attacks characterized with sudden attacks of anxiety with numerous symptoms, including palpitations, tachycardia, tachypnea, nausea, and vertigo: ie, cardiovascular, gastroenterologic, respiratory, and neuro-otologic symptoms. In clinical practice, panic disorder manifests with isolated gastroenteric or cardiovascular symptoms, requiring additional clinical visits after psychiatric intervention. The first-line treatment for anxiety disorders, and in particular for panic disorder, is the selective serotonin reuptake inhibitors. However, these drugs can have adverse effects, including sexual dysfunction, increased bodyweight, and abnormal bleeding, that may be problematic for some patients. Here we report the case of a 29-year-old Caucasian woman affected by panic disorder with agoraphobia who was referred to our clinic for recurrent gastroenteric panic symptoms. The patient reported improvement in her anxiety symptoms and panic attacks while on a selective serotonin reuptake inhibitor, but not in her gastric somatic problems, so the decision was taken to start her on duloxetine, a serotonin-norepinephrine reuptake inhibitor. After 6 months of treatment, the patient achieved complete remission of her gastric and panic-related symptoms, and was able to stop triple gastric therapy. Other authors have hypothesized and confirmed that duloxetine has greater initial noradrenergic effects than venlafaxine and is effective in patients with panic disorder. This case report underscores the possibility of tailoring therapeutic strategies for the gastroenteric expression of panic disorder.
doi:10.2147/NDT.S35922
PMCID: PMC3842215  PMID: 24294001
anxiety disorder; panic attacks; palpitations; tachycardia; tachypnea; nausea; vertigo
4.  Panic Disorder and Serotonin Reuptake Inhibitors Predict Coupling of Cortical and Cardiac Activity 
Neuropsychopharmacology  2013;39(2):507-514.
Panic attacks, the cardinal symptom of panic disorder (PD), are characterized by intense physiological reactions including accelerated heart activity. Although cortical processes are thought to trigger and potentiate panic attacks, it is unknown whether individuals with PD have a general tendency to show elevated cortico–cardiac interactions, which could predispose them for brain-driven modulations of heart activity during panic. Consistent with this hypothesis, serotonin, a highly relevant neurotransmitter for panic and PD presumably affects the cortical control of the heart. The current study thus aimed to test whether PD and serotonin reuptake inhibitor (SRI) intake are related to cortico–cardiac interactions in the absence of acute panic. Human participants with PD (N=22), major depression (MD, clinical control group, N=21) or no psychiatric diagnosis (healthy control group, N=23) performed a gambling task. To measure cortico–cardiac coupling, the within-subject covariation of single-trial EEG after feedback presentation and subsequent changes in heart period was determined. As in prior studies, there was a significant time-lagged covariation of EEG and heart activity indicating that trial-by-trial fluctuations of feedback-evoked EEG amplitude determined how much heart activity accelerated seconds later. Importantly, this covariation pattern was significantly potentiated in PD vs control participants. Moreover, concurrent SRI intake further augmented brain–heart covariation in individuals with PD and MD. The present findings demonstrate that PD and serotonin are associated with altered brain–heart interactions in a non-panic situation. Future work should clarify whether brain–heart coupling has a causal role in PD, for example by facilitating panic attacks.
doi:10.1038/npp.2013.224
PMCID: PMC3870782  PMID: 23985783
Biological Psychiatry; cardiovascular; Depression; Unipolar/Bipolar; feedback; Mood/Anxiety/Stress Disorders; panic; Serotonin; heart rate; P300; brain–heart coupling; depression; feedback
5.  Panic attacks and supraventricular tachycardias: the chicken or the egg? 
Netherlands Heart Journal  2012;21(2):74-77.
Panic attacks occur in about 2 % of the population. Symptoms include a racing or pounding heart beat, chest pain, dizziness, light-headedness, nausea, difficulty in breathing, tingling or numbness in the hands, flushes or chills, dreamlike sensations or perceptual distortions. The symptoms of paroxysmal supraventricular tachycardia (PSVT) may be similar. A PSVT is often difficult to document on the ECG since it has often ceased before the patient comes to medical attention. Besides, a tachycardia may still be present and even be documented but interpreted as a phenomenon secondary to the panic attack. In addition, ECG abnormalities between episodes can often not be identified. The evidence that in some patients paroxysmal SVT is the cause, but not the consequence of a panic attack, is based on observations that catheter ablation was able to cure patients presenting with panic disorders. To better establish the prevalence of SVT as the underlying mechanism of a panic attack, there is a need for prospective studies and/or registries. Whereas gastric ulcer has in some patients changed from a psychosomatic disorder to an infectious disease, we may hypothesise that a certain proportion of panic disorders may mutate into an underlying arrhythmia rather than a primary psychiatric disorder.
doi:10.1007/s12471-012-0350-2
PMCID: PMC3547429  PMID: 23179613
Panic attacks; Panic disorder; Paroxysmal supraventricular tachycardia
6.  The Correlation between Electroencephalography Amplitude and Interictal Abnormalities 
Objectives:
The aim of this study was to establish the relationship between background amplitude and interictal abnormalities in routine electroencephalography (EEG).
Methods:
This retrospective audit was conducted between July 2006 and December 2009 at the Department of Clinical Physiology at Sultan Qaboos University Hospital (SQUH) in Muscat, Oman. A total of 1,718 electroencephalograms (EEGs) were reviewed. All EEGs were from patients who had been referred due to epilepsy, syncope or headaches. EEGs were divided into four groups based on their amplitude: group one ≤20 μV; group two 21–35 μV; group three 36–50 μV, and group four >50 μV. Interictal abnormalities were defined as epileptiform discharges with or without associated slow waves. Abnormalities were identified during periods of resting, hyperventilation and photic stimulation in each group.
Results:
The mean age ± standard deviation of the patients was 27 ± 12.5 years. Of the 1,718 EEGs, 542 (31.5%) were abnormal. Interictal abnormalities increased with amplitude in all four categories and demonstrated a significant association (P <0.05). A total of 56 EEGs (3.3%) had amplitudes that were ≤20 μV and none of these showed interictal epileptiform abnormalities.
Conclusion:
EEG amplitude is an important factor in determining the presence of interictal epileptiform abnormalities in routine EEGs. This should be taken into account when investigating patients for epilepsy. A strong argument is made for considering long-term EEG monitoring in order to identify unexplained seizures which may be secondary to epilepsy. It is recommended that all tertiary institutions provide EEG telemetry services.
PMCID: PMC4205058  PMID: 25364549
Electroencephalography, abnormalities; Epilepsy
7.  Improved Diagnosis in Children with Partial Epilepsy Using a Multivariable Prediction Model Based on EEG Network Characteristics 
PLoS ONE  2013;8(4):e59764.
Background
Electroencephalogram (EEG) acquisition is routinely performed to support an epileptic origin of paroxysmal events in patients referred with a possible diagnosis of epilepsy. However, in children with partial epilepsies the interictal EEGs are often normal. We aimed to develop a multivariable diagnostic prediction model based on electroencephalogram functional network characteristics.
Methodology/Principal Findings
Routinely performed interictal EEG recordings at first presentation of 35 children diagnosed with partial epilepsies, and of 35 children in whom the diagnosis epilepsy was excluded (control group), were used to develop the prediction model. Children with partial epilepsy were individually matched on age and gender with children from the control group. Periods of resting-state EEG, free of abnormal slowing or epileptiform activity, were selected to construct functional networks of correlated activity. We calculated multiple network characteristics previously used in functional network epilepsy studies and used these measures to build a robust, decision tree based, prediction model. Based on epileptiform EEG activity only, EEG results supported the diagnosis of with a sensitivity and specificity of 0.77 and 0.91 respectively. In contrast, the prediction model had a sensitivity of 0.96 [95% confidence interval: 0.78–1.00] and specificity of 0.95 [95% confidence interval: 0.76–1.00] in correctly differentiating patients from controls. The overall discriminative power, quantified as the area under the receiver operating characteristic curve, was 0.89, defined as an excellent model performance. The need of a multivariable network analysis to improve diagnostic accuracy was emphasized by the lack of discriminatory power using single network characteristics or EEG's power spectral density.
Conclusions/Significance
Diagnostic accuracy in children with partial epilepsy is substantially improved with a model combining functional network characteristics derived from multi-channel electroencephalogram recordings. Early and accurate diagnosis is important to start necessary treatment as soon as possible and inform patients and parents on possible risks and psychosocial aspects in relation to the diagnosis.
doi:10.1371/journal.pone.0059764
PMCID: PMC3614973  PMID: 23565166
8.  Clinical neurophysiological assessment of sepsis-associated brain dysfunction: a systematic review 
Critical Care  2014;18(6):674.
Introduction
Several studies have reported the presence of electroencephalography (EEG) abnormalities or altered evoked potentials (EPs) during sepsis. However, the role of these tests in the diagnosis and prognostic assessment of sepsis-associated encephalopathy remains unclear.
Methods
We performed a systematic search for studies evaluating EEG and/or EPs in adult (≥18 years) patients with sepsis-associated encephalopathy. The following outcomes were extracted: a) incidence of EEG/EP abnormalities; b) diagnosis of sepsis-associated delirium or encephalopathy with EEG/EP; c) outcome.
Results
Among 1976 citations, 17 articles met the inclusion criteria. The incidence of EEG abnormalities during sepsis ranged from 12% to 100% for background abnormality and 6% to 12% for presence of triphasic waves. Two studies found that epileptiform discharges and electrographic seizures were more common in critically ill patients with than without sepsis. In one study, EEG background abnormalities were related to the presence and the severity of encephalopathy. Background slowing or suppression and the presence of triphasic waves were also associated with higher mortality. A few studies demonstrated that quantitative EEG analysis and EP could show significant differences in patients with sepsis compared to controls but their association with encephalopathy and outcome was not evaluated.
Conclusions
Abnormalities in EEG and EPs are present in the majority of septic patients. There is some evidence to support EEG use in the detection and prognostication of sepsis-associated encephalopathy, but further clinical investigation is needed to confirm this suggestion.
doi:10.1186/s13054-014-0674-y
PMCID: PMC4277650  PMID: 25482125
9.  Panic disorder 
Clinical Evidence  2008;2008:1010.
Introduction
Panic disorder occurs in up to 3% of the adult population at some time, and is associated with other psychiatric and personality disorders, and with drug and alcohol abuse. The risk of suicide and attempted suicide has been found to be higher in people with panic disorder than in people with other psychiatric illness, including depression.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug treatments for panic disorder? What are the effects of drug treatments for panic disorder? What are the effects of combined drug and psychological treatments for panic disorder? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 36 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: applied relaxation; benzodiazepines; breathing retraining; brief dynamic psychotherapy; buspirone; client-centred therapy; cognitive behavioural therapy (CBT) (alone or plus drug treatments); cognitive restructuring; couple therapy; exposure (external or interoceptive); insight-orientated therapy; monoamine oxidase inhibitors (MAOIs); psychoeducation; selective serotonin reuptake inhibitors (SSRIs); self-help; and tricyclic antidepressants (imipramine).
Key Points
Panic disorder is characterised by recurrent, unpredictable panic attacks, making people worry about or change their behaviour to avert subsequent panic attacks or their consequences. Panic disorder occurs in up to 3% of the adult population at some time, and is associated with other psychiatric and personality disorders, and with drug and alcohol abuse.The risk of suicide and attempted suicide has been found to be higher in people with panic disorder than in people with other psychiatric illness, including depression.
CBT is effective in reducing symptoms of panic disorder over 6 months or longer, but we don't know whether it is more effective than other psychological treatments. CBT is more effective than waiting list and other controls in reducing symptoms in panic disorder with or without mild to moderate agoraphobia. We don't know whether CBT alone is more effective than antidepressants alone, but weak evidence suggests that the effects of CBT may last longer. Combined treatment with CBT plus antidepressants has shown to be more effective than CBT alone or antidepressants alone in reducing symptoms in the short term.
Other forms of psychotherapy can also be beneficial in reducing symptoms associated with panic disorder, with or without drug treatments. Applied relaxation, client-centred therapy, cognitive restructuring, and exposure to the panic-inducing stimulus are all likely to be effective in reducing symptoms. Self-help using CBT techniques may be as effective as therapist-based CBT. Breathing retraining, couple therapy, insight-orientated therapy, psychoeducation, and brief dynamic psychotherapy may be beneficial, but we found insufficient evidence to be sure.
SSRIs and tricyclic antidepressants are also effective at reducing the symptoms of panic disorder. Benzodiazepines can be effective in reducing symptoms in panic disorder, but their adverse-effect profile makes them unsuitable for long-term treatment.We don't know whether buspirone or MAOIs are effective.
PMCID: PMC2907935  PMID: 19445787
10.  Smoking Behavior and Alcohol Consumption in Individuals With Panic Attacks 
Individuals with anxiety often report greater smoking and drinking behaviors relative to those without a history of anxiety. In particular, smoking and alcohol use have been directly implicated among individuals experiencing panic attacks, diagnosed with panic disorder, or high on panic-relevant risk factors such as anxiety sensitivity. Less is known, however, about specific features of panic that may differentiate among those who do or do not use cigarettes or alcohol. The purpose of the current study was to replicate previous research findings of an association between panic symptomatology, cigarette smoking, and alcohol consumption, as well as extend findings by examining whether specific symptoms of panic attacks differentiated among those who do or do not use cigarettes or alcohol. Participants (n = 489) completed the Panic Attack Questionnaire-IV, a highly detailed assessment of panic attacks and symptoms, as well as self-report measures of smoking history and alcohol use. Consistent with previous research, participants who reported a history of panic attacks (n = 107) were significantly more likely to report current daily or lifetime daily cigarette smoking, and significantly greater hazardous or harmful alcohol use than participants with no panic history (n = 382). Although smoking and hazardous alcohol use were highly associated regardless of panic status, participants with panic attacks showed elevated hazardous alcohol use after controlling for daily or lifetime smoking. Surprisingly, although participants who reported having had at least one panic attack were more likely to smoke, panic attack symptoms, intensity, or frequency did not differentiate panickers who did or did not smoke. Furthermore, panic-related variables were not shown to differentially relate to problematic drinking among panickers. Implications for understanding the complex relationship between panic attacks and smoking and drinking behaviors are discussed.
doi:10.1891/0889-8391.25.1.61
PMCID: PMC3170754  PMID: 21915160
smoking; alcohol; panic attacks; comorbidity
11.  The Experience of Panic Symptoms across Racial Groups in a Student Sample 
Journal of anxiety disorders  2010;24(8):873-878.
While there is general agreement that, across cultures, panic disorder appears to be characterized by sudden onset of bodily sensations, such as dizziness and heart palpitations, followed by catastrophic misinterpretations of these symptoms, there remains a need for research investigating ethnic/cultural differences in the experience of panic attacks. In addition to investigating ethnic differences in the experience of panic, it is important to assess whether increased endorsement of panic symptoms translates into increased dysfunction. The present study investigated differences in the experience of panic attacks and examined the relation between symptom endorsement and overall distress and impairment in a large multiracial/ethnic student population. Preliminary analyses indicated that although overall endorsement of panic symptoms was similar across groups, differences did emerge on specific symptoms. Participants identifying as Asian tended to endorse symptoms such as dizziness, unsteadiness, choking, and feeling terrified more frequently than those identifying as Caucasian, and individuals identifying as African American reported feeling less nervous than those identifying as Caucasian. Participants of Hispanic/Latino(a) descent showed no differences from any other group on symptom endorsement. Panic symptom severity was not found to differ across racial/ethnic groups; however, the correlation between panic symptoms and panic severity was stronger for Asian and Caucasian participants than for African Americans. These results suggest that symptoms of panic may be experienced differently across racial/ethnic groups, and highlight the need for clinicians and researchers to assess panic symptoms within the context of culture.
doi:10.1016/j.janxdis.2010.06.010
PMCID: PMC2956784  PMID: 20621442
12.  Catastrophic misinterpretations as a predictor of symptom change during treatment for panic disorder 
Objective
Cognitive models of panic disorder suggest that change in catastrophic misinterpretations of bodily sensations will predict symptom reduction. To examine change processes, a repeated measures design was used to evaluate whether the trajectory of change in misinterpretations over the course of 12-week cognitive behavior therapy is related to the trajectory of change in a variety of panic-relevant outcomes.
Methods
Participants had a primary diagnosis of panic disorder (N=43; 70% female; Mean Age: 40.14 years old). Race or ethnicity was reported as 91% Caucasian, 5% African-American, 2.3% Biracial, and 2.3% “Other.” Change in catastrophic misinterpretations (assessed with the Brief Body Sensations Interpretations Questionnaire) was used to predict a variety of treatment outcomes, including overall panic symptom severity (assessed with the Panic Disorder Severity Scale; PDSS), panic attack frequency (assessed with the relevant PDSS item), panic-related distress/apprehension (assessed by a latent factor, including peak anxiety in response to a panic-relevant stressor - a straw breathing task), and avoidance (assessed by a latent factor, which included the Fear Questionnaire-Agoraphobia subscale).
Results
Bivariate latent difference score modeling indicated that, as expected, change in catastrophic misinterpretations predicted subsequent reductions in overall symptom severity, panic attack frequency, distress/apprehension, and avoidance behavior. However, change in the various symptom domains was not typically a significant predictor of later interpretation change (except for the distress/apprehension factor).
Conclusions
These results provide considerable support for the cognitive model of panic and speak to the temporal sequence of change processes during therapy.
doi:10.1037/a0021067
PMCID: PMC3299495  PMID: 20954759
panic disorder; catastrophic misinterpretations; cognitive behavior therapy; avoidance
13.  The development of agoraphobia is associated with the symptoms and location of a patient's first panic attack 
Background
The place where a patient experiences his/her first panic attack (FPA) may be related to their agoraphobia later in life. However, no investigations have been done into the clinical features according to the place where the FPA was experienced. In particular, there is an absence of detailed research examining patients who experienced their FPA at home. In this study, patients were classified by the location of their FPA and the differences in their clinical features were explored (e.g., symptoms of FPA, frequency of agoraphobia, and severity of FPA).
Methods
The subjects comprised 830 panic disorder patients who were classified into 5 groups based on the place of their FPA (home, school/office, driving a car, in a public transportation vehicle, outside of home), The clinical features of these patients were investigated. Additionally, for panic disorder patients with agoraphobia at their initial clinic visit, the clinical features of patients who experienced their FPA at home were compared to those who experienced their attack elsewhere.
Results
In comparison of the FPAs of the 5 groups, significant differences were seen among the 7 descriptors (sex ratio, drinking status, smoking status, severity of the panic attack, depression score, ratio of agoraphobia, and degree of avoidance behavior) and 4 symptoms (sweating, chest pain, feeling dizzy, and fear of dying). The driving and public transportation group patients showed a higher incidence of co-morbid agoraphobia than did the other groups. Additionally, for panic disorder patients with co-morbid agoraphobia, the at-home group had a higher frequency of fear of dying compared to the patients in the outside-of-home group and felt more severe distress elicited by their FPA.
Conclusion
The results of this study suggest that the clinical features of panic disorder patients vary according to the place of their FPA. The at-home group patients experienced "fear of dying" more frequently and felt more distress during their FPA than did the subjects in the other groups. These results indicate that patients experiencing their FPA at home should be treated with a focus on the fear and distress elicited by the attack.
doi:10.1186/1751-0759-6-12
PMCID: PMC3349583  PMID: 22494552
Place of first panic attack; Panic attack symptoms; Subtype of panic disorder; Agoraphobia
14.  Traumatic Brain Injury Detection Using Electrophysiological Methods 
Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI). This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from an electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: (1) Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. (2) ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are non-disclosing. (3) The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including non-linear dynamical analysis, complexity measures, analysis of causal interactions, graph theory, and information dynamics. (4) Reports of high specificity in qEEG evaluations of TBI must be interpreted with care. High specificities have been reported in carefully constructed clinical studies in which healthy controls were compared against a carefully selected TBI population. The published literature indicates, however, that similar abnormalities in qEEG measures are observed in other neuropsychiatric disorders. While it may be possible to distinguish a clinical patient from a healthy control participant with this technology, these measures are unlikely to discriminate between, for example, major depressive disorder, bipolar disorder, or TBI. The specificities observed in these clinical studies may well be lost in real world clinical practice. (5) The absence of specificity does not preclude clinical utility. The possibility of use as a longitudinal measure of treatment response remains. However, efficacy as a longitudinal clinical measure does require acceptable test–retest reliability. To date, very few test–retest reliability studies have been published with qEEG data obtained from TBI patients or from healthy controls. This is a particular concern because high variability is a known characteristic of the injured central nervous system.
doi:10.3389/fnhum.2015.00011
PMCID: PMC4316720
event-related potentials; EEG; traumatic brain injury; qEEG; non-linear dynamical analysis
15.  Which electroencephalography (EEG) for epilepsy? The relative usefulness of different EEG protocols in patients with possible epilepsy 
Background and aim
Electroencephalography (EEG) is an essential investigative tool for use in young people with epilepsy. This study assesses the effects of different EEG protocols on the yield of EEG abnormalities in young people with possible new epilepsy.
Methods
85 patients presenting to the unit underwent three EEGs with differing protocols: routine EEG (r‐EEG), sleep‐deprived EEG (SD‐EEG), EEG carried out during drug‐induced sleep (DI‐EEG). The yield of EEG abnormalities was compared using each EEG protocol.
Results
98 patients were recruited to the study. Of the 85 patients who completed the study, 33 (39%) showed no discernible abnormality on any of their EEG recordings. 36 patients (43%) showed generalised spike and wave during at least one EEG recording, whereas 15 (18%) had a focal discharge evident at some stage. SD‐EEG had a sensitivity of 92% among these patients, whereas the sensitivity of DI‐EEG and r‐EEG was 58% and 44%, respectively. The difference between the yield from SD‐EEG was significantly higher than that from other protocols (p<0.001). Among the 15 patients showing focal discharges, SD‐EEG provoked abnormalities in 11 (73%). r‐EEG and DI‐EEG each produced abnormalities in 40% and 27%, respectively. 7 patients (47%) had changes seen only after sleep deprivation. In 2 (13%), the only abnormalities were seen on r‐EEG. In only 1 patient with focal discharges (7%) was the focal change noted solely after drug‐induced sleep. These differences did not reach significance.
Conclusion
EEG has an important role in the classification of epilepsies. SD‐EEG is an easy and inexpensive way of increasing the yield of EEG abnormalities. Using this as the preferred protocol may help reduce the numbers of EEGs carried out in young patients presenting with epilepsy.
doi:10.1136/jnnp.2005.084871
PMCID: PMC2077738  PMID: 16801353
16.  Recurrent diarrhea as a manifestation of temporal lobe epilepsy 
A woman with temporal lobe epilepsy manifesting with repeated episodes of sudden diarrhea and loss of consciousness is reported. A 63-year-old, right-handed female presented with chief complaints of sudden diarrhea and loss of consciousness for almost three decades. The first attack occurred in her 30s, and similar attacks repeated several times in a year. Her attacks comprised abrupt abdominal discomfort, diarrhea, sudden emergence of old memories relating to when she had played with her brother in her childhood, and loss of consciousness during defecation. She had no convulsion or automatism and fully recovered in a few minutes. Every time she was transferred to emergency hospital by ambulance, she had examinations such as blood test, head computed tomography, electrocardiogram, abdominal ultrasound, and electroencephalography (EEG), but no specific diagnosis was made. On admission to our hospital, vital signs, neurological examination, and blood tests did not show abnormal findings. During long-term video-EEG monitoring for 40 h, she had no habitual event. Interictal EEG showed intermittent irregular delta waves and sharp regional transients in the left anterio-midtemporal area. Sharp transients were not as outstanding from background activities as to be defined as epileptiform discharges, but they were reproducible in morphology and distribution and appeared not only in sleep but also in wakefulness. Brain magnetic resonance imaging was unremarkable. Single-photon emission computed tomography showed a decrease of blood flow in the left frontal and temporal lobes. Wechsler Adult Intelligence Scale—III showed a decline of verbal comprehension. We concluded that the patient was suffering from partial epilepsy originating from the left temporal lobe. Carbamazepine markedly improved her seizures. Temporal lobe epilepsy can manifest with diverse autonomic symptoms and signs. Abdominal sensations often herald the onset of epileptic seizures. Among them is an uncommon syndrome called abdominal epilepsy in which gastrointestinal complaints are the primary or the sole manifestation of epileptic seizures. In patients who present with diarrhea and other autonomic symptoms otherwise unexplained, a possible diagnosis of epilepsy should be considered.
doi:10.1016/j.ebcr.2014.03.007
PMCID: PMC4308087  PMID: 25667870
Recurrent diarrhea; Semiology; Temporal lobe epilepsy
17.  Genetic and Disorder-Specific Aspects of Resting State EEG Abnormalities in Schizophrenia 
Schizophrenia Bulletin  2008;35(4):826-839.
We evaluated whether abnormal frequency composition of the resting state electroencephalogram (EEG) in schizophrenia was associated with genetic liability for the disorder by studying first-degree biological relatives of schizophrenia patients. The study included a data-driven method for defining EEG frequency components and determined the specificity of resting state EEG frequency abnormalities by assessing schizophrenia patients, bipolar disorder patients, and relatives of both patient groups. Schizophrenia patients and their relatives, but not bipolar patients or their relatives, exhibited increased high-frequency activity (beta) providing evidence for disturbances in resting state brain activity being specific to genetic liability for schizophrenia. Schizophrenia patients exhibited augmented low-frequency EEG activity (delta, theta), while bipolar disorder patients and the 2 groups of relatives generally failed to manifest similar low-frequency EEG abnormalities. The Val158Met polymorphism for the catechol-O-methyl transferase (COMT) gene was most strongly associated with delta and theta activity in schizophrenia patients. Met homozygote schizophrenia patients exhibited augmented activity for the 2 low-frequency bands compared with control subjects. Excessive high-frequency EEG activity over frontal brain regions may serve as an endophenotype that reflects cortical expression of genetic vulnerability for schizophrenia. Low-frequency resting state EEG anomalies in schizophrenia may relate to disorder-specific pathophysiology in schizophrenia and the influence of the COMT gene on tonic dopamanergic function.
doi:10.1093/schbul/sbn021
PMCID: PMC2696373  PMID: 18381357
electroencephalography; endophenotype; catechol-O-methyl transferase
18.  Clozapine response and pre-treatment EEG-is there some kind of relationship 
Industrial Psychiatry Journal  2014;23(1):18-22.
Background:
Clozapine has been used widely in the management of treatment-resistant schizophrenia. The present study aims at determining whether pre-treatment electroencephalography (EEG) abnormalities would serve as a marker for response to clozapine treatment.
Subjects and Methods:
This was a cross-sectional study done in a tertiary care center in Mumbai where patients diagnosed with schizophrenia using DSM-IV criteria and resistant schizophrenia using Kane criteria were assessed using EEG prior to starting clozapine treatment. They were rated for symptomatic improvement using the Positive and Negative Syndrome Scale (PANSS) along with Clinical Global Improvement for Severity (CGI-S). The results were statistically analysed and presented.
Results:
55 out of the 80 patients in the study showed baseline EEG abnormalities. The mean duration of illness in the patients were 2.65 years. Slow wave and background EEG abnormalities were common in pre-treatment EEG. 36.4% patients in the study showed clinical response. Patients with negative symptoms and baseline EEG abnormalities showed better response.
Conclusions:
The study was circumscribed and had many limitations due to a small sample size. The relation between pre-treatment EEG abnormalities and clozapine response could not be statistically correlated and it could not be ascertained to be a marker for response to clozapine therapy.
doi:10.4103/0972-6748.144951
PMCID: PMC4261208  PMID: 25535440
Clozapine; electroencephalography; electroencephalography abnormalities; schizophrenia; treatment resistant schizophrenia
19.  Panic Disorder Among Cambodian Refugees Attending a Psychiatric Clinic 
General hospital psychiatry  2000;22(6):437-444.
This study surveys Khmer refugees attending two psychiatric clinics to determine both the prevalence of panic disorder as well as panic attack subtypes in those suffering panic disorder. A culturally valid adaptation of the SCID-panic module, the Cambodian Panic Disorder Survey (CPDS), was administered to 89 consecutive Cambodian refugees attending these psychiatric clinics. Utilizing culturally sensitive panic probes, the CPDS provides information regarding both the presence of panic disorder and panic-attack subtypes during the month prior to interview. Of 89 patients surveyed at two psychiatric clinics, 53 (60%) currently suffered panic disorder. Among the 53 patients suffering panic disorder, the most common panic attack subtypes during the previous month were the following: “sore neck” [51% of the 53 panic disorder patients (PDPs)], orthostatic dizziness (49% of PDPs), gastro-intestinal distress (26% of PDPs), effort induced (21% of PDPs), olfactory induced (21% of PDPs), and “while-sitting dizziness” (16% of PDPs).
PMCID: PMC2749726  PMID: 11072060
20.  Absence of early epileptiform abnormalities predicts lack of seizures on continuous EEG 
Neurology  2012;79(17):1796-1801.
Objective:
To determine whether the absence of early epileptiform abnormalities predicts absence of later seizures on continuous EEG monitoring of hospitalized patients.
Methods:
We retrospectively reviewed 242 consecutive patients without a prior generalized convulsive seizure or active epilepsy who underwent continuous EEG monitoring lasting at least 18 hours for detection of nonconvulsive seizures or evaluation of unexplained altered mental status. The findings on the initial 30-minute screening EEG, subsequent continuous EEG recordings, and baseline clinical data were analyzed. We identified early EEG findings associated with absence of seizures on subsequent continuous EEG.
Results:
Seizures were detected in 70 (29%) patients. A total of 52 patients had their first seizure in the initial 30 minutes of continuous EEG monitoring. Of the remaining 190 patients, 63 had epileptiform discharges on their initial EEG, 24 had triphasic waves, while 103 had no epileptiform abnormalities. Seizures were later detected in 22% (n = 14) of studies with epileptiform discharges on their initial EEG, vs 3% (n = 3) of the studies without epileptiform abnormalities on initial EEG (p < 0.001). In the 3 patients without epileptiform abnormalities on initial EEG but with subsequent seizures, the first epileptiform discharge or electrographic seizure occurred within the first 4 hours of recording.
Conclusions:
In patients without epileptiform abnormalities during the first 4 hours of recording, no seizures were subsequently detected. Therefore, EEG features early in the recording may indicate a low risk for seizures, and help determine whether extended monitoring is necessary.
doi:10.1212/WNL.0b013e3182703fbc
PMCID: PMC3475619  PMID: 23054233
21.  Early intervention in panic: randomized controlled trial and cost-effectiveness analysis 
Trials  2008;9:67.
Background
Panic disorder (PD) is a common, severe and persistent mental disorder, associated with a high degree of distress and occupational and social disability. A substantial proportion of the population experiences subthreshold and mild PD and is at risk of developing a chronic PD. A promising intervention, aimed at preventing panic disorder onset and reducing panic symptoms, is the 'Don't Panic' course. It consists of eight sessions of two hours each. The purpose of this study is to evaluate the effectiveness of this early intervention – based on cognitive behavioural principles – on the reduction of panic disorder symptomatology. We predict that the experimental condition show superior clinical and economic outcomes relative to a waitlisted control group.
Methods/design
A pragmatic, pre-post, two-group, multi-site, randomized controlled trial of the intervention will be conducted with a naturalistic follow-up at six months in the intervention group. The participants are recruited from the general population and are randomized to the intervention or a waitlist control group. The intervention is offered by community mental health centres. Included are people over 18 years of age with subthreshold or mild panic disorder, defined as having symptoms of PD falling below the cut-off of 13 on the Panic Disorder Severity Scale-Self Report (PDSS-SR). Primary outcomes are panic disorder and panic symptoms. Secondary outcomes are symptoms of agoraphobia, anxiety, cognitive aspects of panic disorder, depressive symptoms, mastery, health-related quality of life, and cost-effectiveness. We will examine the following variables as potential mediators: cognitive aspects of panic disorder, symptoms of agoraphobia, anxiety and mastery. Potential moderating variables are: socio-demographic characteristics, panic disorder, agoraphobia, treatment credibility and mastery.
Discussion
This study was designed to evaluate the (cost) effectiveness of an early intervention based on cognitive behavioural principles. The strong external validity is one of the strengths of the study design.
Trial registration
Current Controlled Trials ISRCTN33407455.
doi:10.1186/1745-6215-9-67
PMCID: PMC2630960  PMID: 19038038
22.  Overgeneralization of Conditioned Fear as a Pathogenic Marker of Panic Disorder 
Objective
Classical conditioning features prominently in many etiological accounts of panic disorder. According to such accounts, neutral conditioned stimuli present during panic attacks acquire panicogenic properties. Conditioned stimuli triggering panic symptoms are not limited to the original conditioned stimuli but are thought to generalize to stimuli resembling those co-occurring with panic, resulting in the proliferation of panic cues. The authors conducted a laboratory-based assessment of this potential correlate of panic disorder by testing the degree to which panic patients and healthy subjects manifest generalization of conditioned fear.
Method
Nineteen patients with a DSM-IV-TR diagnosis of panic disorder and 19 healthy comparison subjects were recruited for the study. The fear-generalization paradigm consisted of 10 rings of graded size presented on a computer monitor; one extreme size was a conditioned danger cue, the other extreme a conditioned safety cue, and the eight rings of intermediary size created a continuum of similarity from one extreme to the other. Generalization was assessed by conditioned fear potentiating of the startle blink reflex as measured with electromyography (EMG).
Results
Panic patients displayed stronger conditioned generalization than comparison subjects, as reflected by startle EMG. Conditioned fear in panic patients generalized to rings with up to three units of dissimilarity to the conditioned danger cue, whereas generalization in comparison subjects was restricted to rings with only one unit of dissimilarity.
Conclusions
The findings demonstrate a marked proclivity toward fear overgeneralization in panic disorder and provide a methodology for laboratory-based investigations of this central, yet understudied, conditioning correlate of panic. Given the putative molecular basis of fear conditioning, these results may have implications for novel treatments and prevention in panic disorder.
doi:10.1176/appi.ajp.2009.09030410
PMCID: PMC2806514  PMID: 19917595
23.  Auditory evoked potentials in panic disorder. 
Neuroimaging studies of behavioral-induced anxiety in non-patients and of lactate-induced anxiety in panic disorder patients have indicated that normal and pathological anxiety may share a common pathway involving the temporal poles. As panic-related anxiety may reflect faulty temporopolar evaluative processing of input, the objective of this study was to examine sensory reactivity in panic disorder patients via scalp recordings of the late auditory evoked 'vertex' potential (LAEP) which appears to have a predominantly temporal lobe origin. Twelve patients diagnosed according to DSM-III criteria as panic disorder and ten normal controls served as subjects in this study. EEG was recorded from 16 scalp sites using a monopolar fronto-occipital derivation and LAEPs were separately averaged in response to four acoustic intensities. Analysis focused on group and electrode-site differences in the negative (N1) and positive (P2) component amplitudes of the LAEPs. Panic disorder patients were found to exhibit significantly larger N1 amplitudes across all stimulus intensities and across all recording sites. No significant group differences were observed with P2. Although the results provide indirect support for a temporal focus, other modulating influences must be considered in data interpretation.
Images
PMCID: PMC1188339  PMID: 1786264
24.  Quantitative Analysis of Simultaneous EEG Features during PET Studies for Childhood Partial Epilepsy 
Yonsei Medical Journal  2013;54(3):572-577.
Purpose
To demonstrate the significance of simultaneous electroencephalography (EEG) recording during 2-deoxy-2-[18F] fluoro-D-glucose (FDG)-positron emission tomography (PET) in childhood partial epilepsy.
Materials and Methods
We included 46 children with partial epilepsy who underwent simultaneous EEG during PET. We compared the epileptogenic area of several EEG features including epileptiform discharges, focal polymorphic slow waves, and electrographic seizures, with the abnormal metabolic region on PET. We also compared the epileptogenic area of simultaneous EEG and PET with findings on magnetic resonance imaging (MRI) and video/EEG, as well as the histopathological diagnosis of the resected cortical area, in eight patients who underwent surgical resection of the epileptogenic area.
Results
Hypometabolic regions on interictal PET were concordant with epileptogenic areas of epileptiform discharges and focal polymorphic slow waves, according to their frequency and/or severity, with odds ratios of 1.35 and 1.81, respectively (p<0.05). Hypermetabolic PET was also concordant with epileptogenic areas of ictal events longer than 20 seconds during the period of FDG uptake. Among the eight patients who underwent surgical resection, six patients, including two with non-lesional MRI, had concordant EEG and PET findings, were confirmed pathologically, and became seizure-free after surgery.
Conclusion
Simultaneous EEG is useful in identifying epileptogenic areas due to a high concordance with abnormal PET metabolic areas. Moreover, simultaneous EEG may also prevent false lateralization of PET from postictal and mixed metabolism during ictal events, as well as abnormal hypermetabolism, during frequent interictal epileptiform discharges.
doi:10.3349/ymj.2013.54.3.572
PMCID: PMC3635630  PMID: 23549798
Positron-emission tomography; electroencephalography; epilepsy
25.  Validity and reliability of the Structured Clinical Interview for Depersonalization–Derealization Spectrum (SCI-DER) 
This study evaluates the validity and reliability of a new instrument developed to assess symptoms of depersonalization: the Structured Clinical Interview for the Depersonalization-Derealization Spectrum (SCI-DER). The instrument is based on a spectrum model that emphasizes soft-signs, sub-threshold syndromes as well as clinical and subsyndromal manifestations. Items of the interview include, in addition to DSM-IV criteria for depersonalization, a number of features derived from clinical experience and from a review of phenomenological descriptions. Study participants included 258 consecutive patients with mood and anxiety disorders, 16.7% bipolar I disorder, 18.6% bipolar II disorder, 32.9% major depression, 22.1% panic disorder, 4.7% obsessive compulsive disorder, and 1.5% generalized anxiety disorder; 2.7% patients were also diagnosed with depersonalization disorder. A comparison group of 42 unselected controls was enrolled at the same site. The SCI-DER showed excellent reliability and good concurrent validity with the Dissociative Experiences Scale. It significantly discriminated subjects with any diagnosis of mood and anxiety disorders from controls and subjects with depersonalization disorder from controls. The hypothesized structure of the instrument was confirmed empirically.
PMCID: PMC2626926  PMID: 19183789
depersonalization; derealization; mood disorders; anxiety disorders

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