"My mind goes dead I cannot speak": an expression of DPD.

INTRODUCTION: Here we present a case of Depersonalisation-Derealisation Disorder which involves an unusual environmental trigger and profile of symptoms in a patient with an underlying left frontal encephalomalacia. METHODS: The clinical information has been collected from multiple neurological, psychiatric, neuropsychological examinations and from the patient's medical records. RESULTS: The neuropsychiatric assessment showed depersonalisation, derealisation, de-somatisation and de-affectualisation, along with a good response to SSRI + Lamotrigine; all typical features of DPD. The neuropsychological assessment showed language problems, and other mild cognitive difficulties that may provide a neuropsychological foundation contributing to the DPD episodes. DISCUSSION AND CONCLUSION: Given Mr R's underlying neuropsychological deficit, hearing voices without speech-associated gestures might place excessive demands on his ability to process the information, exacerbating his feelings of threat. This sets up the pattern of suppressed insula activation, and possibly the suppression of the auditory cortex leading to the presented unusual DPD symptoms.

Epilepsy, anti-seizure medication, intellectual disability and challenging behaviour - Everyone's business, no one's priority.

PURPOSE: People with Intellectual Disability (ID) and epilepsy are more likely to experience psychiatric conditions, challenging behaviour (CB), treatment resistance and adverse effects of anti-seizure medications (ASM) than those without. This population receives care from various professionals, depending on local care pathways. This study evaluates the training status, confidence, reported assessment and management practices of different professional groups involved in caring for people with ID, epilepsy and CB. METHODS: A cross sectional survey using a questionnaire developed by expert consensus which measured self-reported training status, confidence, and approaches to assessment and management of CB in people with ID and epilepsy was distributed to practitioners involved in epilepsy and/or ID. RESULTS: Of the 83 respondents, the majority had either a psychiatry/ID (n = 39), or Neurology/epileptology background (n = 31). Psychiatry/ID and Neurology/epileptology had similar confidence in assessing CB in ID-epilepsy cases, but Psychiatry/ID exhibited higher self-rated confidence in the management of these cases. While assessing and managing CB, Psychiatry/ID appeared more likely to consider mental health aspects, while Neurology/epileptology typically focused on ASM. CONCLUSION: Psychiatry/ID and Neurology/epileptology professionals had varying training levels in epilepsy, ID and CB, had differing confidence levels in managing this patient population, and considered different factors when approaching assessment and management. As such, training opportunities in ID should be offered to neurology professionals, and vice versa. Based on the findings, a best practice checklist is presented, which aims to provide clinicians with a structured framework to consider causal explanations for CB in this population.

The effect of depression and side effects of antiepileptic drugs on injuries in patients with epilepsy.

BACKGROUND AND PURPOSE: People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression. METHODS: Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy. RESULTS: Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor. CONCLUSIONS: Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects.

Clinical correlates of memory complaints during AED treatment.

OBJECTIVES: To investigate clinical correlates of memory complaints (MC) during anti-epileptic drug (AEDs) treatment in adults with epilepsy with special attention to the role of depression, using user-friendly standardized clinical instruments which can be adopted in any outpatient setting. MATERIALS & METHODS: Data from a consecutive sample of adult outpatients with epilepsy assessed with the Neurological Disorder Depression Inventory for Epilepsy (NDDIE), the Adverse Event Profile (AEP) and the Emotional Thermometer (ET) were analysed. RESULTS: From a total sample of 443 patients, 28.4% reported MC as 'always' a problem. These patients were less likely to be seizure free (18.3% vs 34.3%; P < 0.001), had a high number of previous AED trials (4 vs 3; P < 0.001) and high AEP total scores (49 vs 34.2; P < 0.001). There was no correlation with specific AED type or combination. Depression was the major determinant with a 2-fold increased risk (95%CI 1.15-3.86; P = 0.016). When depression was already known and under treatment, patients with MC were less likely to be in remission from depression despite antidepressant treatment (11.9% vs 1.6% P < 0.001). Among patients without depression, those reporting MC presented with significantly high scores for depression (3.3 vs 2; t = 3.07; P = 0.003), anxiety (4.5 vs 2.7; t = 4.43; P < 0.001), anger (3 vs 2; t = 2.623; P = 0.009) and distress (3.8 vs 2.2; t = 4.027; P < 0.001) than those without MC. CONCLUSIONS: Depression has to be appropriately treated and full remission from depression should represent the ultimate goal as subthreshold or residual mood and anxiety symptoms can contribute to MC.

The relevance of neuropsychiatric symptoms and cognitive problems in new-onset epilepsy - Current knowledge and understanding.

Neurobehavioral and cognition problems are highly prevalent in epilepsy, but most research studies to date have not adequately addressed the precise nature of the relationship between these comorbidities and seizures. To address this complex issue and to facilitate collaborative, innovative research in the rising field of neurobehavioral comorbidities and cognition disturbances in new-onset epilepsy, international epilepsy experts met at the 3rd Halifax International Epilepsy Conference & Retreat at White Point, South Shore, Nova Scotia, Canada from September 18 to 20, 2014. This Conference Proceedings provides a summary of the conference proceedings. Specifically, the following topics are discussed: (i) role of comorbidities in epilepsy diagnosis and management, (ii) role of antiepileptic medications in understanding the relationship between epilepsy and neurobehavioral and cognition problems, and (iii) animal data and diagnostic approaches. Evidence to date, though limited, strongly suggests a bidirectional relationship between epilepsy and cognitive and psychiatric comorbidities. In fact, it is likely that seizures and neurobehavioral problems represent different symptoms of a common etiology or network-wide disturbance. As a reflection of this shared network, psychiatric comorbidities and/or cognition problems may actually precede the seizure occurrence and likely get often missed if not screened.

More than seizures: improving the lives of people with refractory epilepsy.

As captured by the proposed new definition, epilepsy is increasingly recognized as a disorder characterized not only by an enduring predisposition to recurrent seizures but explicitly also by the neurobiological, cognitive, psychological and social consequences of this condition. Further, both in the estimated 15 million people worldwide who have ongoing seizures despite optimal management and in a substantial proportion of those in remission, the consequences and comorbidities of epilepsy are the major determinants of quality of life. These include mood disorders such as anxiety and depression, dose related and longer term effects of antiepileptic drugs, including on prenatal development and bone health, and neurobehavioural effects. Whilst separating those that are part of an underlying condition or have unrelated contributors from those that are potentially remediable can be difficult, given the range of tools now available to assist with screening and management there is no excuse for not at least trying as part of standard care for people with epilepsy. Managing epilepsy well is about much more than controlling seizures and this needs to be recognized in planning and delivering services, as well as in prioritizing research.

Validation of the Hamilton Rating Scale for Depression in adults with epilepsy.

PURPOSE: Mood disorders represent a frequent psychiatric comorbidity among patients with epilepsy, having a major impact on their quality of life and contributing considerably to the global burden of the disease. The availability of standardized clinical instruments validated in populations with epilepsy has important implications in terms of diagnosis and treatment. This aimed to validate the Hamilton Rating Scale for Depression (HRSD) in adult patients with epilepsy. METHODS: A consecutive sample of 120 adult outpatients with epilepsy was assessed using the Mini International Neuropsychiatric Inventory (MINI) Plus version 5.0.0 and the HRSD. RESULTS: Cronbach's alpha coefficient was 0.824 for the 17-item version and 0.833 for the 21-item version. Receiver operating characteristic analysis showed an area under the curve of 0.896 and 0.899, respectively, for the two versions. However, the HRSD-17 demonstrated the best psychometric properties compared to the HRSD-21 and, with a cutoff score of 6, showed a sensitivity of 94%, a specificity of 80%, a positive predictive value of 46%, and a negative predictive value of 99%. CONCLUSIONS: The HRSD proved to be reliable and valid in the epilepsy setting and will stimulate further research in this area.

Validation of the Italian version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E).

The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was developed for the rapid detection of a major depressive episode in people with epilepsy. It has been proven to be a user-friendly screening instrument. This study describes the development, validation, and psychometric properties of the Italian version of the NDDI-E. A consecutive sample of 120 outpatients with epilepsy has been assessed using the M.I.N.I. Plus version 5.0.0 and the NDDI-E. All patients had no major difficulties in understanding or answering the questions of the Italian version. Cronbach's alpha coefficient was 0.851. Receiver operating characteristic analysis showed an area under the curve of 0.943 (CI95%=0.902-0.985; SE 0.021; p<0.001), a cut off score of 13, a sensitivity of 86.2%, a specificity of 89%, a positive predictive value of 71.4%, and a negative predictive value of 95.3%.

Recognize and manage psychiatric comorbidities in patients with epilepsy.

The management of patients with epilepsy, especially those with drug refractory syndromes, may be complicated by psychiatric comorbidities that significantly affect prognosis, morbidity and mortality. In general terms, a careful distinction between true psychiatric manifestations and seizure-based phenomena (i.e. peri-ictal psychiatric symptoms) is crucial, having implications in terms of prognosis and treatment. Guidelines of treatment for psychiatric disorders in epilepsy are still lacking. In general terms, internationally adopted guidelines of treatment outside epilepsy may be considered taking into account a number of special issues related to the underlying brain disorder. New compounds are generally well tolerated and reasonably safe in patients with epilepsy. SSRIs, especially citalopram, are considered first line agents in mood and anxiety disorders and new antipsychotics, especially olanzapine, quetiapine and risperidone, in interictal psychoses. The potential for drug interactions is generally minimized although drug dosages need to be adjusted according to clinical response in patients taking inducers (e.g. carbamazepine, barbiturates or phenytoin). Long term tolerability need to be balanced with long term side effects such as weight gain and sedation. Comprehensive treatment of people with epilepsy requires that psychiatric comorbidities are recognized and taken into account in the overall management. Continued clinical research is needed to obtain further knowledge about the optimal use of the expanding antiepileptic armamentarium and on how to tailor treatment to each individual patient according to clinical circumstances.

Progressive multifocal leucoencephalopathy after autologous bone marrow transplantation: a treatment option.

A patient with multiple myeloma was treated with high-dose chemotherapy followed by two autologous bone marrow transplantations (ABMTs). Nine months after the second ABMT the patient complained of severe left hemiparesis, paraesthesias, left homonymous visual field defects and gait ataxia. She was diagnosed with progressive multifocal leucoencephalopathy (PML) confirmed by detection of JC virus (JCV) DNA and prescribed cidofovir every other week and mirtazapine daily. Her symptoms and signs remained stable and after 6 months the JCV DNA was undetectable in the cerebrospinal fluid. Repeated MRI scans demonstrated the stabilisation of demyelinating lesion volume; after more than 2 years of follow-up the patient's neurological examination does not show significant variations. Combination of cidofovir and mirtazapine may be helpful in the treatment of PML in HIV-negative patients.

Panic disorder as a risk factor for post-partum depression: Results from the Perinatal Depression-Research & Screening Unit (PND-ReScU) study.

BACKGROUND: Although the role of anxiety disorders on the development of Post-partum Depression (PPD) have already been studied in literature, that of individual anxiety disorders has not received specific attention. The aim of this study is to investigate the role of Panic Disorder (PD) and family history for PD as risk factors for PPD. METHODS: Six hundred women were recruited in a prospective, observational study at the 3rd month of pregnancy and followed up until the 6th month after delivery. At baseline, risk factors for PPD, Axis-I disorders and family history for psychiatric disorders were assessed. We investigated minor and major depression (mMD) occurred at 1st, 3rd and 6th months post-partum. Logistic regression models were used to estimate the association between PD, family history for PD and PPD. RESULTS: Forty women had mMD in the post-partum. PD during pregnancy (RR=4.25; 95%CI:1.48-12.19), a history of PD (RR 2.47; 95%CI:1.11-5.49) and family history for PD (RR=2.1; 95%CI:1.06-4.4) predicted PPD after adjusting for lifetime depression and risk factors for PPD. LIMITATIONS: The response rate is moderately low, but it is similar to other studies. The drop out rate is slightly high, however the 600 women who completed the 6th month follow-up did not differ from the presence of PD at baseline. CONCLUSIONS: PD is an independent risk factor for PPD, underscoring need to assess PD symptoms during pregnancy. Furthermore, PD represents an important risk factor for the development of PPD and should be routinely screened in order to develop specific preventive interventions.

Health-related quality of life measures and psychiatric comorbidity in patients with migraine.

BACKGROUND AND PURPOSE: The identification of factors associated to health-related quality of life (HRQoL) measures in patients with migraine has major implications in terms of prognosis and treatment. This study aimed at investigating associations between HRQoL and comorbid mood and anxiety disorders. METHODS: Consecutive adult outpatients with a diagnosis of migraine with or without aura were assessed using the Mini International Neuropsychiatric Interview (M.I.N.I.) Plus version 5.0.0 and the Migraine-Specific Quality-of-Life Questionnaire (MSQ). RESULTS: Data of 112 patients (82 females), 69 without aura, mean age 41.2 +/- 13.3 years were analyzed. According to the M.I.N.I., 50% patients had a lifetime or current DSM-IV diagnosis of mood or anxiety disorder. There was no between-groups difference in MSQ total and subscale scores in relation to the presence/absence of psychiatric comorbidity, independently whether that was current or lifetime. In the group of subjects with psychiatric disorders, age at onset of migraine correlated with MSQ-total (rho = -0.407 P = 0.002), and subscale scores (Role Function-Restrictive, rho = -0.397, P = 0.002; Emotional Function, rho = -0.487, P < 0.001). CONCLUSIONS: Our findings suggest that current and/or lifetime psychiatric comorbidities are not associated with HRQoL measures in patients with migraine. However, patients with migraine and psychiatric comorbidities may represent a specific subgroup deserving particular attention for targeted interventions.

The factor structure of lifetime depressive spectrum in patients with unipolar depression.

BACKGROUND: While previous attempts to elucidate the factor structure of depression tended to agree on a central focus on depressed mood, other factors were not replicated across studies. By examining data from a large number of items covering the range of depressive symptoms, the aim of the present study is to contribute to the identification of the structure of depression on a lifetime perspective. METHODS: The study sample consisted of 598 patients with unipolar depression who were administered the Mood Spectrum Self-Report (lifetime version) in Italian (N=415) or English (N=183). In addition to classical exploratory factor analysis using tetrachoric correlation coefficients, an IRT-based factor analysis approach was adopted to analyze the data on 74 items of the instrument that explore cognitive, mood and energy/activity features associated with depression. RESULTS: Six factors were identified, including 'Depressive Mood', 'Psychomotor Retardation', 'Suicidality', 'Drug/Illness related depression', 'Psychotic Features' and 'Neurovegetative Symptoms', accounting overall for 48.3% of the variance of items. LIMITATIONS: Clinical information on onset of depression and duration of illness is available only for 350 subjects. Therefore, differences between sites can only be partially accounted using available data. CONCLUSIONS: Our study confirms the central role of depressed mood, psychomotor retardation and suicidality and identifies the factors 'Drug/Illness related depression', 'Psychotic features' and the neurovegetative dysregulation not captured by the instruments most frequently used in previous studies. The identification of patients with specific profiles on multiple factors may be useful in achieving greater precision in neuroimaging studies and in informing treatment selection.

The structure of lifetime panic-agoraphobic spectrum.

The heterogeneity of the clinical presentation of panic disorder (PD) has prompted researchers to describe different subtypes of PD, on the basis of the observed predominant symptoms constellation. Starting from a dimensional approach to panic disorder, an instrument to assess lifetime panic-agoraphobic spectrum (PAS) available in interview or self-report form (SCI-PAS, PAS-SR) was developed which proved to have sound psychometric properties and the ability to predict delayed response to treatment in patients with mood disorders. However, the structure of the instrument was defined a priori and an examination of its empirical structure is still lacking. Aim of the present report is to analyse the factor structure of the PAS taking advantage of a large database of subjects with panic disorders (N=630) assessed in the framework of different studies. Using a classical exploratory factor analysis based on a tetrachoric correlation matrix and oblique rotation, 10 factors were extracted, accounting overall for 66.3% of the variance of the questionnaire: panic symptoms, agoraphobia, claustrophobia, separation anxiety, fear of losing control, drug sensitivity and phobia, medical reassurance, rescue object, loss sensitivity, reassurance from family members. The first two factors comprise the DSM-IV criteria for panic disorder and agoraphobia. The other factors had received limited empirical support to date. We submit that these symptoms profiles might be clinically relevant for tailoring drug treatments or psychotherapeutic approaches to specific needs. Future perspectives might include the use of these factors to select homogeneous subgroups of patients for brain-imaging studies and to contribute to elucidating the causes and pathophysiology of panic disorder at molecular level.

The structure of lifetime manic-hypomanic spectrum.

BACKGROUND: The observation that bipolar disorders frequently go unrecognized has prompted the development of screening instruments designed to improve the identification of bipolarity in clinical and non-clinical samples. Starting from a lifetime approach, researchers of the Spectrum Project developed the Mood Spectrum Self-Report (MOODS-SR) that assesses threshold-level manifestations of unipolar and bipolar mood psychopathology, but also atypical symptoms, behavioral traits and temperamental features. The aim of the present study is to examine the structure of mania/hypomania using 68 items of the MOODS-SR that explore cognitive, mood and energy/activity features associated with mania/hypomania. METHODS: A data pool of 617 patients with bipolar disorders, recruited at Pittsburgh and Pisa, Italy was used for this purpose. Classical exploratory factor analysis, based on a tetrachoric matrix, was carried out on the 68 items, followed by an Item Response Theory (IRT)-based factor analytic approach. RESULTS: Nine factors were initially identified, that include Psychomotor Activation, Creativity, Mixed Instability, Sociability/Extraversion, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Inflated Self-esteem, Euphoria, Wastefulness/Recklessness, and account overall for 56.4% of the variance of items. In a subsequent IRT-based bi-factor analysis, only five of them (Psychomotor Activation, Mixed Instability, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Euphoria) were retained. CONCLUSIONS: Our data confirm the central role of Psychomotor Activation in mania/hypomania and support the definitions of pure manic (Psychomotor Activation and Euphoria) and mixed manic (Mixed Instability and Mixed Irritability) components, bearing the opportunity to identify patients with specific profiles for a better clinical and neurobiological definition.

Measuring the level and content of consciousness during epileptic seizures: the Ictal Consciousness Inventory.

Ictal alterations of the level of general awareness and subjective content of consciousness play a pivotal role in the clinical phenomenology of epilepsy, and reflect the pathological involvement of different neurobiological substrates. However, no self-reported measures have been proposed for patients experiencing altered conscious states during seizures. This study describes the development and validation of a new scale for the quantitative assessment of the level and content of ictal consciousness, the Ictal Consciousness Inventory (ICI). The ICI is a 20-item questionnaire generated on the basis of interviews with patients, literature review, and consultation with experts. It was tested on a sample of 110 patients attending three different epilepsy clinics in Northern Italy, who also completed standardized clinical scales. Standard psychometric methods were used to demonstrate that this scale satisfies criteria for acceptability, reliability, and validity. The ICI is proposed as a user-friendly and clinically sound instrument for the measurement of ictal alterations of consciousness in patients with epilepsy.

The structured assessment of depression in brain-damaged individuals: translation and validation study of the Italian version.

The aim of this study was to translate the structured assessment of depression in brain-damaged individuals (SADBD) questionnaire into the Italian language, validate, and test reliability and validity of the Italian version. Consecutive patients with stroke were screened in the Department of Neurology, Avogadro University in Novara and the Department of Neurorehabilitation, Maugeri Foundation, Veruno, Italy. Thirty patients were included in the study. The internal consistency ranged between 0.78 and 0.87. The intra-rater test-retest reliability was 0.93 for BDIderived items and 0.82 for HRSD-derived items; while the inter-rater test-retest reliability was 0.94 for BDI-derived items and 0.93 for HRSD-derived items. Correlation between the SADBD diagnosis made by the physician and the nurse was 0.51; correlation between caregiver and physician diagnosis was 0.60. The Italian version of the SADBD was demonstrated to be acceptable, reliable and a valid measure of depression in patients with stroke.

Progression of MRI abnormalities in herpes simplex encephalitis despite clinical improvement: natural history or disease progression?

Herpes simplex virus encephalitis (HSVE) is associated with a high mortality rate and a high probability of neurological sequelae. Good results are obtained when HSVE is promptly diagnosed and treated with acyclovir. We present a 71-year-old woman with clinically diagnosed HSVE, confirmed by PCR detection of HSV-1 DNA in the cerebrospinal fluid. She was treated with acyclovir (30 mg/kg day) for two weeks. Clinical and neuropsychological assessments 6 months after admission were normal; however MRI at 2, 6 and 12 months showed progressive deterioration with extensive white matter and cortical damage. Imaging studies of a cohort of patients surviving PCR-confirmed HSVE are needed to determine whether this pattern is occasional or a frequent form of progression.

Psychiatric adverse events during levetiracetam therapy.

The prevalence and psychopathologic features of psychiatric adverse events (PAE) in 517 patients taking levetiracetam (LEV) were investigated. Fifty-three (10.1%) patients developed PAE. A significant association was found with previous psychiatric history, history of febrile convulsions, and history of status epilepticus, whereas lamotrigine co-therapy had a protective effect. PAE were not related to the titration schedule of LEV, and certain patients seem to be biologically more vulnerable.