Metaphoric language in the differential diagnosis of epilepsy and psychogenic non-epileptic seizures: Time to move forward.

Conversation analysis (CA) to identify metaphoric language (ML) has been proposed as a tool for the differential diagnosis of epileptic (ES) and psychogenic nonepileptic seizures (PNES). However, the clinical relevance of metaphoric conceptualizations is not clearly defined. The current study aims to investigate the ML utilized by individuals with ES and PNES in a pulled multi-country sample. Two blinded researchers examined the transcripts and videos of 54 interviews of individuals (n = 29, Italy; n = 11, USA; n = 14, Russia) with ES and PNES, identifying the patient-seizure relationship representative of the patient's internal experience. The diagnoses were based on video-EEG. Metaphors were classified as "Space/place", "External force", "Voluntary action", and "Other". A total of 175 metaphors were identified. No differences between individuals with ES and PNES were found in metaphoric occurrence (χ2 (1, N = 54) = 0.07; p = 0.74). No differences were identified when comparing the types of metaphors utilized by participants with ES and those with PNES. Patients with PNES and ES did not demonstrate differences in terms of occurrence and categories in ML. Therefore, researchers and clinicians should carefully consider the use of metaphor conceptualizations for diagnostic purposes.

Heart rate and autonomic biomarkers distinguish convulsive epileptic vs. functional or dissociative seizures.

OBJECTIVE: 20-40% of individuals whose seizures are not controlled by anti-seizure medications exhibit manifestations comparable to epileptic seizures (ES), but there are no EEG correlates. These events are called functional or dissociative seizures (FDS). Due to limited access to EEG-monitoring and inconclusive results, we aimed to develop an alternative diagnostic tool that distinguishes ES vs. FDS. We evaluated the temporal evolution of ECG-based measures of autonomic function (heart rate variability, HRV) to determine whether they distinguish ES vs. FDS. METHODS: The prospective study includes patients admitted to the University of Rochester Epilepsy Monitoring Unit. Participants are 18-65 years old, without therapies or co-morbidities associated with altered autonomics. A habitual ES or FDS is recorded during admission. HRV analysis is performed to evaluate the temporal changes in autonomic function during the peri­ictal period (150-minutes each pre-/post-ictal). We determined if autonomic measures distinguish ES vs. FDS. RESULTS: The study includes 53 ES and 46 FDS. Temporal evolution of HR and autonomics significantly differ surrounding ES vs. FDS. The pre-to-post-ictal change (delta) in HR differs surrounding ES vs. FDS, stratified for convulsive and non-convulsive events. Post-ictal HR, total autonomic (SDNN & Total Power), vagal (RMSSD & HF), and baroreflex (LF) function differ for convulsive ES vs. convulsive FDS. HR distinguishes non-convulsive ES vs. non-convulsive FDS with ROC>0.7, sensitivity>70%, but specificity<50%. HR-delta and post-ictal HR, SDNN, RMSSD, LF, HF, and Total Power each distinguish convulsive ES vs. convulsive FDS (ROC, 0.83-0.98). Models with HR-delta and post-ictal HR provide the highest diagnostic accuracy for convulsive ES vs. convulsive FDS: 92% sensitivity, 94% specificity, ROC 0.99). SIGNIFICANCE: HR and HRV measures accurately distinguish convulsive, but not non-convulsive, events (ES vs. FDS). Results establish the framework for future studies to apply this diagnostic tool to more heterogeneous populations, and on out-of-hospital recordings, particularly for populations without access to epilepsy monitoring units.

Mortality in patients with psychogenic non-epileptic seizures a population-based cohort study.

OBJECTIVES: To compare mortality, comorbidities and causes of death in people with psychogenic non-epileptic seizures (PNES), epilepsy and the general population. METHODS: Using linkage of multiple Swedish national registers, we identified individuals with incident diagnosis of PNES, epilepsy and conversion disorder with motor symptoms or deficits, and 10 controls for each. Main outcome was all-cause mortality. Causes of death were categorised into non-natural (eg, suicide, injuries) and natural. Conditional Cox regression models were used to estimate HRs and 95% CIs for mortality. HRs were adjusted for socioeconomic factors and psychiatric comorbidities. RESULTS: Included were 885 individuals with PNES, 50 663 with epilepsy and 1057 with conversion disorder and motor symptoms or deficits. We found 32 (3.6%) deaths among individuals with PNES, compared with 46 (0.5%) deaths in controls, giving an adjusted HR of 5.5 (95% CI 2.8 to 10.8). Patients with epilepsy had a 6.7 times higher risk of death (95% CI 6.4 to 7.0) compared with individuals without epilepsy. The association between conversion disorder with motor symptoms or deficits was non-significant after adjusting for psychiatric comorbidities. PNES carried a higher risk of natural (HR 8.1, 95% CI 4.0 to 16.4) and non-natural causes of death (HR 15.3, 95% CI 3.0 to 78.6). Suicide ranked high in patients with PNES (18.8%) and conversion disorder with motor symptoms and deficits. The association between PNES diagnosis and all-cause mortality varied with age and time since diagnosis. CONCLUSION: Like epilepsy, PNES carries a higher than expected risk of both natural and non-natural causes of death. The high proportion of suicides requires further investigation.

Psychodynamic interpretation of linguistic findings in patients with epileptic and psychogenic non-epileptic seizures: the role of metaphors.

This work points out the main differences in the semantic expressions used by patients with psychogenic non-epileptic seizures (PNES) and epileptic seizures (ES). In reference to the body as a phenomenological entity, in ES the concept of the body-object prevails while in PNES the body, with all its life attributes, predominates. In description of seizures and in similitudes and metaphors used, ES patients focus on the description of the attack, trying to close the "gap" with a big effort, while patients with PNES concentrate on the context and on the presence of bystanders. Patients with PNES are unable to describe their own attack, since this it is not at the core of their distress, but rather the manifestation of something else, which is hiding the extreme anguish associated with experiences of the past that cannot be revealed (expressed). In the case of ES, instead, the ability to talk and the willingness to elaborate on the emotions become useful tools for facing the disease, an entity perhaps unsurmountable but at least manageable, to the benefit of everyone. In general, we can say that the experience of a disease (real or symbolic) deserves constant attention because it gives us the opportunity not only to probe the depth of the emotional experiences but also the psychic structure of the individual in front of us. A cure would not be a cure without considering such fundamental elements. It would become a sterile exercise of prescribing medications without paying attention to the person, which is the best way of preserving dignity in a state of illness.

Improved ictal assessment performance in the epilepsy monitoring unit via standardization.

OBJECTIVE: To determine whether the standardization and implementation of an ictal testing protocol in the Epilepsy Monitoring Unit (EMU) leads to improvements in ictal testing performance. METHODS: Ictal assessments completed in the EMU from a single center were retrospectively reviewed over a two-month period. Each assessment was evaluated to determine whether 8 high-yield aspects of the ictal assessment were performed. Following observation of performance, a standardized ictal testing protocol was developed based on a root cause analysis and review of consensus guidelines. This protocol was disseminated to staff in conjunction with an annual epilepsy education seminar. Ictal assessment performance was re-assessed during the subsequent two months (short-term follow-up) and again during a five- to seven-month period (long-term follow-up) beyond the initial intervention. For sub-group analysis, event characteristics (event type, time of assessment) and patient characteristics (age, gender) were also evaluated and analyzed in relation to ictal testing performance. RESULTS: All eight individual ictal testing elements were more likely to be assessed in short-term and long-term follow-up periods when compared to pre-intervention assessments. The cumulative difference in ictal testing was 20.4% (95% CI 3.7-37.2, p = 0.02) greater for the short-term period and 16.7% (95% CI -0.3% to 33.8%, p = 0.05) greater in the long-term period when compared to baseline testing. CONCLUSIONS: Utilization of a standardized ictal testing battery in conjunction with staff education leads to an objective improvement in ictal assessment performance. Further research is warranted to assess the replicability of our findings.

History of violence/maltreatment and psychogenic non-epileptic seizures.

PURPOSE: To study the association of earlier violence/maltreatment with the occurrence of PNES in a nationwide population sample. METHODS: This is a nested case-control study performed using Swedish nationwide registers. Cases were all individuals born in Sweden between 1941 and 2009 with incident PNES between 2001 and 2013 while resident in Sweden according to the Swedish Patient Register. For each case, 10 controls, alive and PNES-free at time of PNES diagnosis of the matched case, were randomly selected from the Swedish Total Population Register, matched on age and sex. To test the specificity of the association, we conducted two similar analyses for epilepsy and dissociative disorder with motor symptoms or deficit, as comparators to PNES. Registers were examined in search of all coded diagnoses of child maltreatment or violence episodes before the index date among the cases and controls. RESULTS: 885 patients received a first diagnosis of PNES. 7.6 % of cases had a history of violence/maltreatment, compared to 1.1 % of controls, giving a crude OR of 7.9 (95 % CI: 3.7-11.0). The ORs decreased but remained significant after adjustment for socio-economic factors (OR = 6.3, 95 % CI: 4.4-9.0) and psychiatric comorbidities (OR = 5.2, 95 % CI: 3.5-7.9). The association was also evident for epilepsy and dissociative disorder, although of lower magnitude. CONCLUSION: Patients with PNES have a history of violence/maltreatment more frequently than the rest of the population. This association can be influenced by socio-economic factors and the presence of concurrent psychiatric disturbances.

Self-Report questionnaires for the diagnosis of psychogenic non-epileptic seizures in clinical practice. A comprehensive review of the available instruments.

We searched Medline from 1946 to 2019 for reports exploring differences between PNES and other comparable paroxysmal events using clinical instruments, few of which focused on the differential diagnosis using broad-based questionnaires covering multiple aspects of this condition. The majority investigated single items to highlight specific differences, either qualitative or quantitative, between groups and to elucidate some of the pathogenetic mechanisms of PNES. We selected all variables that proved to be useful for differentiating PNES from other types of paroxysmal events and classified them by category, by instrument utilized and method of investigation. This body of data will constitute the basis for assembling a new set of evidence-based questionnaires for patients and eyewitnesses to facilitate the differential diagnosis of these disorders, especially in resource-poor clinical settings. This will require a skillful translation of the content of each selected variable into clear and intuitive questions, appropriate for lay responders. Predictive variables found by more than one investigator, especially if using different approaches, have greater diagnostic weight and should be prominent in future questionnaires. However, even variables so far found to be predictive by one investigator will deserve consideration. Once the preliminary text of the questionnaires is consolidated, the instrument will need extensive testing and validation in large prospective studies before becoming available for clinical use in its definitive format.

Self-reporting versus clinical scrutiny: the value of adding questionnaires to the routine evaluation of seizure disorders. An exploratory study on the differential diagnosis between epilepsy and psychogenic nonepileptic seizures.

Questionnaires or symptom lists have proved effective for differentiating epileptic seizures (ES) from psychogenic nonepileptic seizures (PNES). However, monitoring the events, corroborated by medical history gathered by experts, remains the gold standard. We directly compared symptoms and characteristic of the events self-reported by patients/eyewitnesses (Questionnaire A/B) with the information contained in the clinical charts of 50 patients with undefined diagnosis undergoing long-term monitoring. Data extracted from medical records were reformatted to fit the questionnaires' templates (A1/B1) for comparison. Quantitatively, self-reported information was considerably greater and more complete. Calculating sensitivity (SE) and specificity (SP) of all variables in the group with confirmed diagnosis, we identified those above the preset thresholds with the potential to discriminate between ES and PNES. Eight predictive variables were common to both methods: head injury, physical/emotional abuse, chronic fatigue (A); talked out of seizures, eyes closed, apnea, and collapsing (B). Eleven predictive variables were specific to direct questioning: preictal headache, bright light, feeling overwhelmed, heart racing, tingling and numbness, postictal trouble speaking, physical pain, history of gastro-esophageal reflux disease (GERD), self-inflicted injuries (A); on/off shaking, and side-to-side head movements (B). Thirteen predictive variables were generated by chart review: sleep deprivation, strong emotions/anxiety, preictal headache (warning), nausea/vomiting, history of PNES, cholecystectomy, depression, medications for behavioral problems (A1), sudden start/sudden stop of shaking, both sides shaking, falling during the seizure, feeling confused and disoriented postictally (B1). CONCLUSION: Self-reporting and clinical scrutiny are complementary. Structured questionnaires increase the range of predictive variables and should be utilized routinely to facilitate clinicians' quest for the correct diagnosis.

Patients' and caregivers' contributions for differentiating epileptic from psychogenic nonepileptic seizures. Value and limitations of self-reporting questionnaires: A pilot study.

PURPOSE: Questionnaires investigating semiology and comorbidities of psychogenic non-epileptic seizures (PNES) have been used mainly to help physicians expedite referrals to epilepsy centres for confirmation of diagnosis rather than as alternative diagnostic tool when video-EEG monitoring (VEM), the current gold standard, is not available or is inconclusive. METHODS: We developed one structured questionnaire for patients, exploring subjective experiences and vulnerabilities and one for eyewitnesses, focused on features observable during typical events to study prospectively 50 consecutive adult patients with PNES or epileptic seizures (ES) admitted for VEM. A list of variables representing specific signs, symptoms and risk factors was obtained from each question. Specificity (SP) and sensitivity (SE) of each variable were calculated analyzing patient's and witness' responses against the final diagnosis. Statistical significance was assessed using the Fisher's exact test. RESULTS: Twenty-eight patients' questionnaires (17 PNES, 11 ES) were eligible for analysis. Seven variables with high SE and SP, of which 5 statistically significant, emerged as diagnostic predictors. They comprised three historical items: head injury, physical abuse and chronic fatigue; two warning signs: heart racing and tingling or numbness; one triggering sign: headache; one postictal symptom: physical pain. Sixteen witness questionnaires (6 PNES, 10 ES) were available. Side-to-side head movements and eyes closed were the statistically significant variables. CONCLUSION: Pending further refinements, ad hoc questionnaires specifically designed for patients and eyewitnesses, may represent a practical tool for distinguishing ES from PNES in settings without sophisticated facilities or when VEM is inconclusive.

Engaging psychiatrists in the diagnosis of psychogenic nonepileptic seizures. What can they contribute?

PURPOSE: To investigate if psychiatrists could predict the diagnosis of psychogenic nonepileptic seizures (PNES) by reviewing videos of seizures of various types and to compare the accuracy and the criteria leading to the diagnosis used by psychiatrists with those used by epileptologists. METHODS: Four board-certified psychiatrists were asked to review 23 videos capturing representative events of 21 unselected consecutive patients admitted to an epilepsy center for long-term video-EEG monitoring. All raters were blind to EEG and clinical information. They were requested to (1) rate the videos for quality and content; (2) choose among four diagnoses: (a) epileptic seizures; (b) PNES; (c) Other nonepileptic seizures (syncope, movement disorder, migraine, etc.); (d) "Cannot Say"; and (3) explain in their own words the main reasons leading to the diagnosis of choice. The results were compared to those of four blind epileptologists who independently reviewed the same cases. The inter-rater reliability was tested with the Kappa statistic. RESULTS: All psychiatrists were concordant and correct in 3/23 video-events, compared to 8/23 among epileptologists. Despite widespread disagreement among themselves and frequent failures as a group, individual psychiatrists scored a comparable number of correct diagnoses as did individual epileptologists. The comments provided to justify the diagnosis of choice differed from neurologists, varied among raters, and reflected considerable attention to body movements and body language. CONCLUSION: Psychiatrists, as a group, are less reliable than neurologists in differentiating seizure types on video but, as individuals, can be quite accurate in making the correct diagnosis because they are more attuned to capture the subtleties of human behaviour, of subjective experiences, as the effects of hidden internal conflicts and can contribute a new lexicon in defining PNES.

Antiepileptic drug discontinuation by people with epilepsy in the general population.

OBJECTIVE: Rate, reasons, and predictors of antiepileptic drug (AED) discontinuation were investigated in a well-defined cohort of people with epilepsy to verify efficacy and tolerability of treatment up to 20 years from treatment initiation. METHODS: The history of AED usage in children and adults with epilepsy registered with 123 family physicians in an area of Northern Italy between 2000 and 2008 was recorded. Cumulative probabilities of AED withdrawal for specific reasons were estimated using cumulative incidence functions. The probabilities of withdrawing for terminal remission, and of achieving sustained remission while still on treatment, were also evaluated. The roles of sex, age at diagnosis, seizure types, duration at diagnosis, and syndrome were assessed with hazard ratios and 95% confidence intervals. RESULTS: Seven hundred thirty-one of 747 individuals were treated with one or more AEDs during the disease course. The three commonest drugs were valproate, carbamazepine, and phenobarbital. Reported reasons for AED withdrawal were, in decreasing order, terminal remission, ineffectiveness, and adverse events. The probability of withdrawing the first AED for terminal remission was 1.0% at 1 year and increased to 20.0% at 20 years. Corresponding rates were 2.9% and 12.6% for ineffectiveness and 0.5% and 3.3% for adverse events. Reasons for withdrawal varied with individuals' age, sex, disease characteristics, and drugs. SIGNIFICANCE: The initial AED given was retained in the majority of cases. Terminal remission, lack of efficacy, and adverse effects were, in decreasing order, the commonest reasons for AED discontinuation. Withdrawal could be predicted by age at diagnosis, sex, and clinical characteristics and varies among drugs.

The semiology of psychogenic nonepileptic seizures revisited: Can video alone predict the diagnosis? Preliminary data from a prospective feasibility study.

OBJECTIVE: To investigate if, when, and to what extent visual information contained in a video-recorded event allows experienced epileptologists to predict the diagnosis of psychogenic nonepileptic seizures (PNES) without the aid of electroencephalography (EEG). METHODS: Five neurologists actively practicing in epilepsy centers in Italy and the United States were asked to review 23 videos capturing representative events of 21 unselected consecutive patients admitted for long-term video-EEG monitoring (VEM). Four raters were blind to EEG and clinical information; one rater was not. They were requested to (1) rate the videos for quality and content; (2) choose among four diagnoses: (a) epileptic seizures (ES); (b) PNES; (c) Other nonepileptic seizures (NES; (syncope, movement disorder, migraine, etc.); (d) "Cannot Say"; and (3) explain in their own words the main reasons leading to the diagnosis of choice. RESULTS: All raters predicted the diagnosis correctly in 7 of 23 videos (all ES or PNES) (30.4%), whereas all raters failed in 5 of 23 cases (three Other NES, one PNES, one Cannot Say) (21.7%). The conditions that facilitate, and those that interfere with, a confident diagnosis were predictable. Degree of accuracy among raters was not uniform and was consistently better in three raters. Two among the four blind raters were as accurate as the rater who was not blinded. Interrater agreement was "moderate" (k = 0.52) for the overall group; "moderate" for ES (k = 0.53); "substantial" for PNES (k = 0.63); "fair" for Other NES (k = 0.21)-similar to the results obtained in a previous study evaluating the reliability of combined video-EEG. SIGNIFICANCE: In about one third of cases, a confident diagnosis of PNES/ES can be established on clinical grounds based on video data alone. Our results benefit all affected patients, particularly those with no access to video-EEG monitoring units.

A population-based study of active and drug-resistant epilepsies in Northern Italy.

Drug-resistant epilepsy (DRE) is defined by the International League Against Epilepsy as a failure of adequate trials of two tolerated, appropriately chosen, and used antiepileptic drugs to achieve sustained seizure freedom. Our aim was to calculate the following: (1) the prevalence of active epilepsy and DRE in a well-defined population of Northern Italy and (2) the proportion of incident cases developing DRE. The study population (146,506; year 2008) resided in the province of Lecco, Northern Italy. The medical records of 123 general practitioners were reviewed to identify patients with epilepsy, diagnosed by a neurologist during the period 2000-2008. The point prevalence of active epilepsy and DRE was calculated on December 31, 2008. A total of 747 prevalent patients with epilepsy, 684 patients with active epilepsy, and 342 incident cases were identified. The frequency of DRE was 15.6% (107/684) of all active epilepsies and 10.5% (36/342) of incident cases. The point prevalence was 0.73 per 1000. The standardized prevalence of DRE was 0.7 per 1000 (Italian population) and 0.8 per 1000 (world population). Our data indicate that 1/6 patients with active epilepsy in the general population has DRE, and 1/10 patients with newly diagnosed epilepsy will develop DRE within nine years from the diagnosis.

Characteristic Features of the Interictal EEG Background in 2 Patients With Malignant Migrating Partial Epilepsy in Infancy.

PURPOSE: To describe chronological electrographic features of the interictal EEG background observed in two patients with malignant migrating partial epilepsy in infancy from neonatal to early infantile period. METHODS: EEGs of two patients who fulfilled diagnostic criteria for malignant migrating partial epilepsy in infancy were acquired over the period of 6 months to monitor treatment efficacy and characterize seizures and other paroxysmal events. RESULTS: Both patients followed a similar sequential pattern. A distinctive evolution from a dysmature term neonatal EEG pattern to an asynchronous suppression burst pattern was observed before the interictal background becoming continuous. CONCLUSIONS: Physicians providing care to infants with intractable epilepsy and burst suppression EEG pattern should be alert to the possibility of malignant migrating partial epilepsy in infancy. An earlier diagnosis of malignant migrating partial epilepsy in infancy would help to guide diagnostic workup including genetic testing.

The perceived burden of epilepsy: Impact on the quality of life of children and adolescents and their families.

PURPOSE: The assessment of the quality of life (QoL) is relevant for a comprehensive treatment of patients with epilepsy. In children and adolescents, an impact of epilepsy on the QoL of the entire family is expected. METHODS: We asked 293 parents of children and adolescents with epilepsy, included in an observational study on treatment satisfaction, to evaluate the impact of the disease on several aspects of the QoL of the whole family using a specifically organized questionnaire (IEQoL). RESULTS: The degree of parents' concerns about epilepsy and the severity of the disease correlated with a deterioration of QoL in both the children and the family. This involved all aspects of QoL (conflicts within the family, job, leisure activities, peer relationship, economy) although to a different degree. Parents frequently admitted increased apprehensiveness, even when not justified by the low severity of the disease. There was general agreement between parents and their adolescent children, although in a few cases adolescents overrated their school and daily performance in respect to the parents, suggesting a tendency to overlook their problems. CONCLUSION: Epilepsy impairs all aspects of QoL, although at different degree, both in children/adolescents and in their families. Parental apprehensiveness appears to have a role on this, and it may not reflect the severity of the disease.

Acceptance of epilepsy surgery in the pediatric age - what the parents think and what the doctors can do.

Epilepsy surgery (ES) in pediatrics is safe and effective but can be underutilized. Possible barriers could be parental resistance and doctor inertia. We surveyed 138 parents of pediatric patients with epilepsy and found that 25.2% were opposed to this treatment. However, upon completing the questionnaire that contained factual information about ES, 50.4% of the responders stated that they had become more favorable vs. 3.3% more contrary and 46.3% unchanged. Parents of prepubescent patients were most receptive (p=0.0343) and more likely to shift to a more favorable attitude. Thus, pediatric neurologists should not hesitate to discuss ES as soon as indicated, providing all necessary information to increase acceptance. However, among 60 child neurologists surveyed, 60% did not fully comply with guidelines or follow accepted standards of practice, indicating that they may not be apt to provide proper parental guidance. We conclude that education of both practicing neurologists and parents is needed to facilitate the process.