Dual diagnosis of epilepsy and dissociative seizures: Prescription patterns, feasibility and safety of rationalising antiseizure medication.

BACKGROUND: Patients with a dual-diagnosis of epilepsy and dissociative seizures (DS) have received far less attention than those with single pathology. Anti-seizure medication (ASM) prescription patterns and safety of rationalisation have not been reviewed. METHODS: We undertook a retrospective cohort study of all patients with a dual-diagnosis admitted to the Scottish Epilepsy Centre between 2012-2020. ASM frequencies were compared across admission, discharge and follow-up and emergency hospital attendances compared a year before and after admission. Demographic data, seizure characteristics and mortality data were also reviewed. RESULTS: Across the 139 patients included in our study, ASM frequency at follow-up was significantly lower than on admission (mean 2.51 vs 2.14, Z = -2.11 p = 0.035, r = -0.215). Total hospital attendances in the year following admission were significantly lower than in the year before (mean 1.27 vs 0.77, Z = 2.306, p = 0.021, r = -0.262). Those with inactive epilepsy had their medications reduced to a greater extent that those with active epilepsy. 44 patients had their ASM frequency reduced during admission with a similar trend of reduced hospital attendances (mean 1.29 vs 0.43 Z = -3.162 p = 0.002). There was one epilepsy related death. CONCLUSIONS: Clinicians should consider the development of co-morbid DS in patients with epilepsy not responding to an escalation of ASM, especially if presenting with a new seizure type. Patients with a dual-diagnosis of epilepsy and DS, particularly those with well controlled epilepsy, are likely overtreated with ASM. Medication review in a tertiary epilepsy centre allows for safe rationalisation of ASM and likely contributes to the need for fewer hospital attendances.

Subjective seizure symptom reporting in functional/dissociative seizures and epilepsy: Effects of sampling technique and patient characteristics.

BACKGROUND: Differences in subjectively reportable ictal experiences between epilepsy and functional/dissociative seizures (FDS) have received less attention than visible manifestations. Patients with FDS (pwFDS) tend to report seizure symptoms differently than patients with epilepsy (pwE). The effects of symptom elicitation method and mediation by psychopathological traits have not been examined and may aid in differentiating the disorders. METHOD: Analysis of responses of 24 pwE and 28 pwFDS in interviews exploring ictal experiences through open questioning followed by structured closed questioning using possible symptom prompts (74-item modified Psychosensory-Psychomotor Phenomena Interview, PPPI); self-report of psychological profile (HADS-A, HADS-D, PHQ-15, DES-T, THQ, PCL-C). RESULTS: Symptom prompting with PPPI elicited three times more seizure symptoms than open questions in pwE (median 34 vs. 11.5, p = 0.005) and over four times more in pwFDS (42.5 vs. 11, p = 0.001). Intra-ictal symptoms were reported freely more frequently by pwE (median 6.5 vs. 4, p = 0.005), while pwFDS reported more pre-ictal symptoms after prompts (median 6 vs 14.5, p = 0.004). The difference between freely reported and PPPI-elicited symptoms correlated with different psychopathological traits in pwE and pwFDS. Symptoms of anxiety (HADS-A) correlated more strongly with prompted symptoms among pwE than pwFDS (z = 2.731, p = 0.006). CONCLUSION: Prompting generates more detailed ictal symptom profiles than simply encouraging patients to narrate their subjective seizure experiences. While pwFDS freely reported fewer symptoms related to the intra-ictal period compared to pwE, pwFDS reported more pre-ictal symptoms than pwE when prompted. Differences in the psychopathological traits associated with the number of peri-ictal symptoms captured by symptom prompting in pwE and pwFDS possibly reflect etiological or psychological differences between these patient groups.

Alcohol and the central nervous system.

Ethanol use is common to most cultures but with varying doses and to varying extents. While research has focused on the effects on the liver, alcohol exerts a range of actions on the function and structure of the nervous system. In the central nervous system (CNS) it can provoke or exacerbate neurological and psychiatric disease; its effects on the peripheral nervous system are not included in this review. Sustained alcohol intake can predispose to acute neurochemical changes which, with continued ingestion and incomplete treatment, can lead to chronic structural changes in the CNS: these include generalised cortical and cerebellar atrophy, amnesic syndromes such as Korsakoff's syndrome, and specific white matter disorders such as central pontine myelinolysis and Marchiafava-Bignami syndrome. Alcohol in pregnancy commonly and significantly affects fetal health, though this receives less medical and political attention than other causes of fetal harm. This review looks at the range of disorders that can follow acute or chronic alcohol use, and how these should be managed, and we provide a practical overview on how neurologists might diagnose and manage alcohol addiction.

Peri-ictal responsiveness to the social environment is greater in psychogenic nonepileptic than epileptic seizures.

OBJECTIVE: To look for evidence of peri-ictal social interaction in psychogenic nonepileptic seizures (PNES) and epileptic seizures exploring the notion of PNES as a form of nonverbal communication. METHODS: Video recordings of typical seizures experienced by patients with epilepsy and PNES were obtained in a naturalistic social setting (residential epilepsy monitoring unit). Video analysis by three nonexpert clinicians identified 18 predefined semiological and interactional features indicative of apparent impairment of consciousness or of peri-ictal responsiveness to the social environment with assessment of interrater reliability using Fleiss κ. Features were compared between epileptic seizures and PNES. RESULTS: One hundred eighty-nine seizures from 50 participants (24 epilepsy, 18 PNES, eight combined) were analyzed. At least fair (κ > 0.20) interrater agreement was achieved for 14 features. The PNES and epileptic seizures compared were of similar severity in terms of ictal impairment of consciousness (κ = 0.34, odds ratio [OR] = 1.11, 95% confidence interval [CI] = 0.62-1.96) and responsiveness (κ = 0.52, OR = 1.01, 95% CI = 0.55-1.86). PNES were more likely to be preceded by attempts to alert others (κ = 0.52, OR = 12.4, 95% CI = 3.2-47.7, P < .001), to show intensity affected by the presence of others (κ = 0.44, OR = 199.4, 95% CI = 12.0-3309.9, P < .001), and to display postictal behavior affected by the presence of others (κ = 0.35, OR = 91.1, 95% CI = 17.2-482.1, P < .001). SIGNIFICANCE: Nonexpert raters can, with fair to moderate reliability, rate features characterizing ictal impairment of consciousness and responsivity in video recordings of seizures. PNES are associated with greater peri-ictal responsiveness to the social environment than epileptic seizures. These findings are consistent with a potential communicative function of PNES and could be of differential diagnostic significance.

Medically unexplained symptoms in patients with PNES: Do they explain poor employment outcome in patients with good seizure outcomes?

BACKGROUND: Many patients with psychogenic nonepileptic seizures (PNES) have other medically unexplained symptoms (MUS). In order to assess their long-term contribution to ill-health and unemployment, we recorded MUS, employment, healthcare utilization, and seizure outcomes in a cohort of patients with PNES. METHODS: We had complete computerized healthcare records and employment information in 120 patients with PNES, 5-10years postdiagnosis. We analyzed these data to assess the contribution of MUS to ill-health and to determine whether MUS could explain differences among seizure, employment, and healthcare utilization outcomes in PNES. RESULTS: At 5-10years, 41/120 patients (34.2%) were attending primary or secondary care for seizures, 42/120 patients (35.0%) had MUS other than PNES, and 36/120 patients (30.0%) were employed. Unemployment was predicted by age at presentation (OR: 0.90 (0.86-0.94), p<0.001), presenting to primary or secondary care with seizures (OR: 0.16 (0.05-0.52), p=0.003), and contact with psychiatric services at 5-10years (OR: 0.16 (0.05-0.58), p=0.005). No outcome measures were predicted by additional MUS, though MUS themselves were predicted by psychiatric contact (OR: 2.27 (1.01-5.01), p=0.048). CONCLUSIONS: Our data suggest that MUS do not contribute independently to unemployment in the population with PNES, whereas psychiatric morbidity appears to do so. Nonetheless, MUS and psychiatric morbidity persist in the long term in a substantial minority of patients with PNES. We found no evidence that seizures in patients whose PNES have resolved are replaced with other MUS.

Healthcare resource utilization after medium-term residential assessment for epilepsy and psychogenic nonepileptic seizures.

INTRODUCTION: Epilepsy and epilepsy mimics may lead to high healthcare resource utilization (HRU) including diagnostic resources. The William Quarrier Scottish Epilepsy Centre (SEC) provides medium-term residential assessment (MTRA; average length of stay: 28days) and treatment for complex presentations of epilepsy and related conditions (principally psychogenic nonepileptic seizures, PNES). We studied the effect of MTRA on HRU in a defined health board area in Scotland. METHODS: A retrospective audit of individuals admitted to the SEC from a defined health board area using SEC and health board medical records. Neurological HRU assessed included emergency department visits, hospital admissions, outpatient clinic appointments, and brain imaging prior to and post-MTRA. Healthcare resource utilization was also compared with individuals referred but not admitted to the SEC because of individual circumstances and choice. RESULTS: Seventy-three individuals (51 female, average age: 37.51; 22 men, average age: 43.72) were identified from three years of admissions (1st April 2010 to 31st March 2013). Final diagnosis was epilepsy (ES), 32; ES and psychogenic nonepileptic seizures (ES+PNES), 17; and PNES alone, 24. Twenty-two individuals were identified as a comparison group (8 men, 14 women; average age: 37.21 and 43.90, respectively). Total average contacts per patient per year (CPY) was significantly different pre- and post-MTRA (4.16 vs. 1.32; t(72)=6.11, p<.0001, d=.72). Comparison of HRU in the first year of baseline and last full year of follow-up showed a post-MTRA reduction in HRU for PNES of 92.28%, for ES of 46.81%, and for ES+PNES of 28.3%. During the course of follow-up, PNES CPY continued to drop (1.13 first year vs. 0.10 at 3years post-MTRA). For individuals with epilepsy (with or without PNES), HRU use dropped significantly in the year after admission, and these gains remained stable (total first vs. third postdischarge CPY, 1.74 vs. 1.29). The participants in the comparison group, who were not admitted, had no comparable drop across the study period and were using significantly more resources at each follow-up point than those in the admitted group (F (1, 48)=44.45, p<.01, ηp(2)=.49). CONCLUSION: Medium-term residential assessment is associated with sustained reduction in HRU especially in patients with PNES. Overall HRU reduction was 68.27% following admission (d=.72). This suggests benefit from the MTRA model for people with complex presentations.

Primary and secondary care attendance, anticonvulsant and antidepressant use and psychiatric contact 5-10 years after diagnosis in 188 patients with psychogenic non-epileptic seizures.

BACKGROUND AND OBJECTIVES: There have been few studies of long-term outcome in psychogenic non-epileptic seizures (PNES), and none of long-term healthcare utilization. METHODS: We studied attendance with seizures, healthcare use and employment over a 6-month period from the family doctors of 260 consecutive patients with psychogenic non-epileptic seizures (PNES), 5-10 years after diagnosis. RESULTS: We obtained clinical data in 188/260 patients (72.3%), of whom 60 (31.9%) had attended primary or secondary care with seizures in the previous 6 months. Predictors of attendance with seizures included a diagnosis of epilepsy+PNES (OR 5.7, p=0.009), work status (OR 3.9, p=0.027) and social security payments (OR 6.3, p=0.003). Latency to diagnosis was not predictive. Emergency admission data were available in 187 patients, of whom 25 (13.4%) had emergency hospital attendances. Prescription data were available for 172 patients, of whom 154 had 'PNES only'. Of these, 17 (11.0%) remained on antiepileptic medication (AED). 68/172 patients (39.5%) were prescribed antidepressant (AD) drugs. We had psychiatric contact data in 185 patients, of whom 49 (26.5%) had accessed psychiatric services in the last 6 months. CONCLUSIONS: Surprisingly few of our patients had presented with seizures during the study period. Early reductions in both AED use and healthcare use were sustained long term. Although psychiatric and employment outcomes were less encouraging, some aspects of PNES outcome may be better than previously thought.

Neurologist assessment of reactions to the diagnosis of psychogenic nonepileptic seizures: relationship to short- and long-term outcomes.

PURPOSE: To determine the relationship between neurologist assessment of reactions to the diagnosis of PNESs and outcomes at 6-12 months and at 5-10 years. METHODS: Two hundred thirty-eight patients with psychogenic nonepileptic seizures (PNES) were recruited into a long-term follow-up study. At diagnosis and 6-12 months post diagnosis, doctors recorded their assessments of patient and caregiver reactions to the diagnosis of PNESs. RESULTS: At baseline, 92/238 patients (38.7%) and 73/106 caregivers (68.9%) were assessed as having understood and accepted the diagnosis, while 6.7% of patients and 10.4% of caregivers reacted with anger. At 6-12 months, patient acceptance rose to 57.7%, with caregiver acceptance static at 70.8%. Attendance at follow-up was predicted by the presence of a caregiver at baseline: only one patient who came with a caregiver at baseline did not attend at 6-12 months (OR: 123.80, p < 0.001). Outcome at 6-12 months was predicted by patient acceptance at baseline (OR: 2.85, p = 0.006) and at 6-12 months (OR: 13.83, p < 0.001) and by caregiver acceptance at 6-12 months (OR: 10.77, p < 0.001). Presentation to primary or secondary care with attacks at 5-10 years was predicted by caregiver acceptance at 6-12 months (OR: 3.50, p = 0.007). CONCLUSION: Patient understanding and acceptance of the diagnosis of PNESs are linked to outcome at 6-12 months. The beliefs of caregivers may be important for outcome in the longer term, particularly with respect to health-care use.

Outcome at 5-10 years in psychogenic nonepileptic seizures: what patients report vs. what family doctors report.

OBJECTIVES: We previously found that family doctor records indicated that 78.1% of 188 patients with PNES were not accessing medical care for their attacks at 5-10 years after diagnosis. We wanted to determine whether this represented a better-than-expected outcome or whether patients had just ceased to access medical care for their attacks. METHODS: We sent a postal questionnaire to 221 patients with PNES. We compared the responses with information obtained from family doctors. RESULTS: Seventy-five (33.9%) patients responded to the survey, and, of those, 36.5% reported that they were free of attacks. However, in 52.1% of responders, the date of last attack was more than 6 months previously, and in 39.4%, more than 12 months previously. Comparison with baseline data suggested a substantial long-term reduction in attack frequency in almost all patients. Comparison with family doctor-acquired data showed that 6 patients who reported that they were free of attacks were seeking medical attention for PNES and that 27 patients reported having attacks but were not seeking medical attention for them. CONCLUSION: There appeared to be a wide variation in what patients regarded as 'free of attacks', suggesting that PNES outcomes based on simply asking patients if they are free of attacks should be interpreted with caution. Reduction in frequency of PNES may explain why some patients who report continuing attacks nonetheless cease to access medical services for them.

Teratogenic risk and contraceptive counselling in psychiatric practice: analysis of anticonvulsant therapy.

BACKGROUND: Anticonvulsants have been used to manage psychiatric conditions for over 50 years. It is recognised that some, particularly valproate, carbamazepine and lamotrigine, are human teratogens, while others including topiramate require further investigation. We aimed to appraise the documentation of this risk by psychiatrists and review discussion around contraceptive issues. METHODS: A retrospective review of prescribing patterns of four anticonvulsants (valproate, carbamazepine, lamotrigine and topiramate) in women of child bearing age was undertaken. Documented evidence of discussion surrounding teratogenicity and contraceptive issues was sought. RESULTS: Valproate was most commonly prescribed (n=67). Evidence of teratogenic risk counselling at medication initiation was sub-optimal--40% of individuals prescribed carbamazepine and 22% of valproate. Documentation surrounding contraceptive issues was also low- 17% of individuals prescribed carbamazepine and 13% of valproate. CONCLUSION: We found both low rates of teratogenic risk counselling and low rates of contraception advice in our cohort. Given the high rates of unplanned pregnancies combined with the relatively high risk of major congenital malformations, it is essential that a detailed appraisal of the risks and benefits associated with anticonvulsant medication occurs and is documented within patients' psychiatric notes.

Do patients whose psychogenic non-epileptic seizures resolve, 'replace' them with other medically unexplained symptoms? Medically unexplained symptoms arising after a diagnosis of psychogenic non-epileptic seizures.

BACKGROUND: In clinical practice, it is sometimes observed that patients in whom psychogenic non-epileptic seizures (PNES) cease, develop another medically unexplained symptom (MUS). METHODS: In order to determine how many patients develop new MUS post diagnosis and whether patients whose attacks cease are more likely to do so, new MUS were recorded 6-12 months after the diagnosis of PNES in 187 consecutive patients. RESULTS: Compared with baseline, the overall proportion of patients with MUS increased slightly, from 70.1% to 76.5%, with 44/187 patients (23.5%) developing new MUS. There were no significant differences between attack free and non-attack free patients. Binary logistic regression analysis showed that predictors of new MUS diverged between attack free and non-attack free patients. Among patients continuing to have attacks, those with previous health related psychological trauma were 18.00 times more likely to develop new MUS (p<0.0005). In patients who became attack free, patients drawing disability benefits were 5.04 times more likely to have new MUS (p = 0.011). CONCLUSIONS: The results suggest that almost 25% of patients develop new MUS following a diagnosis of PNES, although most of those have MUS pre-diagnosis. Patients with a history of health related psychological trauma whose attacks continue after diagnosis are at particularly high risk of developing new MUS. The data do not support the hypothesis that PNES that resolve are likely to be 'replaced' by other MUS.

Anti-NMDAR encephalitis for psychiatrists: the essentials.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis predominantly presents with psychiatric symptoms. Psychiatrists need to be alert to this diagnostic possibility, especially in female adolescents and young adults, as exemplified by the real (de-identified) case outlined below. Earlier diagnosis and immunotherapy improves long-term outcomes. Collaboration with neurology colleagues is essential for optimal care. 'Red flags' for autoimmune encephalitis and 'diagnostic clues' act as helpful aide memoires for this uncommon condition. The gold standard for testing is the detection of NMDAR antibodies in cerebrospinal fluid, but serum can be tested as a more accessible (but less reliable) preliminary step. The results of routine blood tests, magnetic resonance imaging of the head and electroencephalograms can be normal or show non-specific changes. Diagnostic criteria exist to define probable and definite cases. Immunotherapy for anti-NMDAR encephalitis is effective for many patients, but recovery is prolonged and relapses can occur.

How to do things with words: Two seminars on the naming of functional (psychogenic, non-epileptic, dissociative, conversion, ) seizures.

Amongst the most important conditions in the differential diagnosis of epilepsy is the one that manifests as paroxysms of altered behaviour, awareness, sensation or sense of bodily control in ways that often resemble epileptic seizures, but without the abnormal excessive or synchronous electrical activity in the brain that defines these. Despite this importance, there remains little agreement - and frequent debate - on what to call this condition, known inter alia as psychogenic non-epileptic seizures (PNES), dissociative seizures (DS), functional seizures (FS), non-epileptic attack disorder (NEAD), pseudoseizures, conversion disorder with seizures, and by many other labels besides. This choice of terminology is not merely academic - it affects patients' response to and understanding of their diagnosis, and their ability to navigate health care systems.This paper summarises two recent discussions hosted by the American Epilepsy Society and Functional Neurological Disorders Society on the naming of this condition. These discussions are conceptualised as the initial step of an exploration of whether it might be possible to build consensus for a new diagnostic label.

An exploratory randomized controlled trial of immediate versus delayed withdrawal of antiepileptic drugs in patients with psychogenic nonepileptic attacks (PNEAs).

PURPOSE: To determine whether withdrawal of antiepileptic drugs (AEDs) in patients with psychogenic nonepileptic attacks (PNEAs) improves outcome. METHODS: Randomized controlled trial of AED withdrawal in patients with PNEAs. Patients were randomized to immediate or delayed (9 months) withdrawal of AEDs. We recorded spell frequency, changes in work status, use of emergency medical services, and psychological status at baseline, 9 months, and 18 months. RESULTS: Of 193 patients screened, 38 fulfilled entry criteria, 13 declined participation, and 25 were randomized. Fourteen patients were randomized to immediate withdrawal (IW) and 11 patients to delayed withdrawal (DW). There was a significant reduction in spell frequency from baseline to 9 months in the IW group but not in the DW group (p = 0.028). There was a significantly greater reduction in use of rescue medication in the IW group compared to the DW group between baseline and 9 months (p = 0.002). Emergency health care utilization dropped to zero in both groups by the end of the study. Psychological measures reflecting internal locus of control increased significantly more in the IW group (p = 0.005). DISCUSSION: Stringent diagnostic criteria and an increasing tendency for patients to be referred before AED prescription limited the recruitment and the power of the study. Our data nonetheless provide evidence that some outcomes are improved by AED withdrawal in patients with PNEAs.

Modafinil in the rehabilitation of a patient with post-surgical posterior fossa syndrome: a lesson to be learned?

Disorders of the cerebellum may present with motor, cognitive, behavioral and affective symptoms. There is a growing interest in developing neuroanatomical models of symptoms generation that involve the cerebellum and the cerebello-cortical connections. We describe an exciting first case report of successful use of Modafinil in an adult patient with post-operative posterior fossa syndrome. Following resection of a melanoma metastasis in the cerebellum the patient developed striking affective and behavioral symptoms in the form of withdrawn flat mood and disengagement. This neurobehavioral presentation severely impacted on his quality of life, independence, and ability to engage in the neuro-rehabilitative program. Pharmacological treatment with Modafinil ameliorated these emotional and behavioral aspects, and also fatigue. Treatment with Modafinil hence affected recovery and outcome for the patient. To our knowledge, this is the first description of a successful pharmacological intervention in an adult with post-surgical posterior fossa syndrome and negative neurobehavioral presentation. Our findings illustrate the variability of the presentation of post-operative posterior fossa syndrome in adults, and the importance of delivering targeted treatment to maximize the benefits of neurorehabilitation. The manuscript highlights the following points: 1. post-operative consequences currently under the wide umbrella of posterior fossa syndrome, can indeed manifest in adults; 2. a wide spectrum of neurobehavioral symptoms can occur, including a presentation with predominantly negative features; 3. the type of neurobehavioral presentation should guide the treatment choice with particular consideration of drugs that potentially modulate the cerebello-frontal connections; 4. Modafinil can be a candidate for effective treatment in presentations with predominantly negative behavioral symptoms.

The misdiagnosis of epilepsy: Appraising risks and managing uncertainty.

PURPOSE: To present evidence from the literature on the rates, underlying causes and consequences of the misdiagnosis of epilepsy and place these meaningfully within a practical framework of risk appraisal and managed diagnostic uncertainty towards informing a clinical practice that might make misdiagnosis less likely. METHOD: Narrative review. RESULTS: Misdiagnosis of epilepsy remains common and the consequences for the individual significant. Evidence and critical appraisal are presented as regards the absolute level of risk associated with the false positive diagnosis epilepsy, and reasons as to why those risks need to be appraised against the risks associated to false negative diagnosis. CONCLUSIONS: Diagnostic error is not entirely avoidable and a degree of uncertainty, and perforce risk, is intrinsic to the diagnostic process of epilepsy. The risks of a false negative diagnosis of epilepsy must be appraised against the also significant risks of a false positive diagnosis.