Breathing control training for functional seizures: A multi-site, open-label pilot study.

There are no well-validated treatments for functional seizures. While specialist psychotherapy is usually recommended, the evidence for its benefit is qualified, and it can be difficult to obtain. Given the association between hyperventilation and functional seizures we explored an alternative modality, breathing control training, in a multi-site open label pilot trial. Participants with functional seizures over the age of 16 received an hour of breathing training from a respiratory physiotherapist, with a half-hour booster session a month later. Seizure frequency and Nijmegen scores (a measure of hyperventilation) were reported at baseline and follow-up, 3-4 months later. Eighteen subjects were recruited, and 10 completed follow-up. Seven of these 10 had improved seizure frequency, and 3 did not (Wilcoxon signed rank test, p = 0.09), with seizure frequency correlating with Nijmegen score (Spearman's rank correlation = 0.75, p = 0.034). The intervention was well tolerated, with no adverse events reported. These preliminary results support a potentially new approach to treating functional seizures that should prove cost-effective and acceptable, though require confirmation by a randomised controlled trial.

Aneurysmal bone cysts: A UK wide tumor center experience.

BACKGROUND AND OBJECTIVES: This multicenter retrospective series of consecutive extra-spinal aneurysmal bone cysts aims to identify risk factors for treatment failure. METHODS: Aneurysmal bone cysts treated within seven collaborating centers with over 12-months follow-up were eligible for inclusion. Survival analyses were performed to identify variables associated with recurrence using log-rank tests and Cox proportional hazard regression. RESULTS: One hundred and fifteen (M:F 60:55) patients were included. Median age at presentation was 13 years and median follow-up was 27 months. Seventy-five patients underwent surgical curettage and 27% of these required further intervention for recurrence. Of the 30 patients who underwent biopsy with limited percutaneous curettage as initial procedure, 47% required no further treatment. Patients under 13 years (log-rank p = 0.006, HR 2.3, p = 0.011) and those treated who had limited curettage (log-rank p = 0.001, HR 2.7, p = 0.002) had a higher risk of recurrence/persistence. CONCLUSIONS: There is a high risk of recurrence following surgical treatment for aneurysmal bone cysts and this risk is higher in young patients. However, the cyst heals in a substantial number of patients who have a limited curettage at the time of biopsy.

Adverse life events in patients with functional seizures: Assessment in clinical practice and association with long-term outcome.

BACKGROUND: A history of adverse life events (ALE) is a risk factor for functional seizures (FS). Their influence on long-term outcome remains unclear. International guidelines recommend assessing ALE in patients presenting with associated disorders. It is not clear to what extent patients evaluated for FS are regularly asked about ALE. OBJECTIVES: We hypothesised that the presence of ALE would relate to worse outcome at follow-up and, that the rate of detection of ALE in clinical work-up would be inferior to that based on self-report questionnaires. METHODS: 53 patients with FS from the National Centre for Epilepsy in Norway, aged 16-62 years were included. Symptom severity, health-related quality of life (HRQoL), and antecedent ALE were assessed at baseline. Medical records were examined for disclosure of ALE. At a mean of 70.45 (SD 29.0, range 22-130) months after inclusion, participants were inquired about FS status, FS-related health care utilization and HRQoL. FINDINGS: A history of emotional abuse documented in the medical record was an independent risk factor for worse HRQoL at follow-up. Prevalence of ALE documented in medical records was lower compared with rates measured by a self-report questionnaire. CONCLUSIONS: These findings indicate an association between antecedent ALE and HRQoL years after diagnosis. A substantial proportion of the adverse life events by a self-report questionnaire had not been documented in the clinical records. CLINICAL IMPLICATIONS: The supplemental use of a self-report questionnaire in the diagnostic work-up of patients with FS may be valuable for detecting ALE.

Glycogen storage disease type IV without detectable polyglucosan bodies: importance of broad gene panels.

Glycogen storage disease type IV (GSD IV) is caused by mutations in the glycogen branching enzyme 1 (GBE1) gene and is characterized by accumulation of polyglucosan bodies in liver, muscle and other tissues. We report three cases with neuromuscular forms of GSD IV, none of whom had polyglucosan bodies on muscle biopsy. The first case had no neonatal problems and presented with delayed walking. The other cases presented at birth: one with arthrogryposis, hypotonia, and respiratory distress, the other with talipes and feeding problems. All developed a similar pattern of axial weakness, proximal upper limb weakness and scapular winging, and much milder proximal lower limb weakness. Our cases expand the phenotypic spectrum of neuromuscular GSD IV, highlight that congenital myopathy and limb girdle weakness can be caused by mutations in GBE1, and emphasize that GSD IV should be considered even in the absence of characteristic polyglucosan bodies on muscle biopsy.

The effect of attachment style on long-term outcomes in psychogenic nonepileptic seizures: Results from a prospective study.

INTRODUCTION: Insecure and fearful attachment styles have been reported in psychogenic nonepileptic seizures (PNES). We have investigated associations between long-term clinical outcome in PNES, parenting and attachment styles and demographic, clinical, and neuropsychiatric factors. MATERIAL AND METHODS: Patients aged at least 16 years and with documented PNES, according to criteria from the International League Against Epilepsy, were prospectively recruited to this study. They were assessed at baseline to determine clinical characteristics, experience of attachment and perceptions of experienced parenting styles, trauma history, dissociation, and health-related quality of life. At a mean of 70.45 (SD 29.0, range 22-130) months after inclusion, participants were contacted by telephone and asked about their current medical status and psychiatric/psychological interventions. RESULTS: Of 53 patients included in the study, 51 (96 %) provided follow-up data. Most (84.9 %) patients were female, and the mean age of PNES onset was 25.6 years. At follow-up, 20 patients (39 %) were free of PNES. Those patients that had achieved PNES freedom at follow-up had lower levels of attachment anxiety (p = 0.01) and reported to have experienced their fathers as less controlling (p = 0.02) and their mothers as more caring (p = 0.04) at baseline compared with those patients still suffering from PNES. Seizure freedom at follow-up was predicted by male gender, younger age at PNES onset, and less attachment anxiety. CONCLUSION: In our cohort from a tertiary epilepsy center the long-term prognosis of PNES is poor. Attachment anxiety is a risk factor for persistent PNES. It may be of therapeutic relevance to assess attachment patterns in patients with PNES.

From left to right: an unusual presentation of Tolosa-Hunt syndrome with bilateral eye involvement.

Here we discuss a presentation of Tolosa-Hunt syndrome (THS) in a 44-year-old female with new right-eye ptosis, ophthalmoplegia and headache. Four days prior, she had almost identical ptosis and ophthalmoplegia in her left eye, which resolved. Cavernous sinus inflammation and symptom improvement with glucocorticoid treatment indicated THS with bilateral eye involvement, a presentation which may be undervalued by the current THS classification.

Incidence and prevalence of psychogenic nonepileptic seizures in a Norwegian county: A 10-year population-based study.

OBJECTIVE: This study was undertaken to measure the incidence and prevalence of active psychogenic nonepileptic seizures (PNES) in a Norwegian county. METHODS: Using the Norwegian patient registry, we identified patients in Møre and Romsdal County in Norway diagnosed with F44.5 (conversion disorder with seizures or convulsions) or R56.8 (convulsions, not elsewhere classified) in the period January 2010 to January 2020. A review of the patients' medical records and an assessment of diagnostic validity were performed. PNES were diagnosed according to the recommendations by the International League Against Epilepsy Nonepileptic Seizures Task Force. Point prevalence of PNES on January 1, 2020 and incidence rates for the period 2010-2019 were determined. RESULTS: Based on PNES within the past 5 years, we found a PNES prevalence of 23.8/100 000 (95% confidence interval [CI] = 17.9-29.6), including all levels of diagnostic certainty. For the highest level of diagnostic certainty (video-electroencephalographically confirmed), the prevalence was 10.6/100 000 (95% CI = 6.7-14.5). The highest prevalence was found in the age group 15-19 years, at 59.5/100 000 (95% CI = 22.6-96.3). The mean annual incidence rate between 2010 and 2019 was 3.1/100 000/year (95% CI = 2.4-3.7). SIGNIFICANCE: We report for the first time a population-based estimate of the prevalence of PNES. Our findings suggest that the prevalence of PNES is within the range of estimates from non-population-based data. We found a strikingly high prevalence of PNES in the 15-19-year age group.

Routine Use of Tenecteplase for Thrombolysis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients. METHODS: We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0-2) at day 90. RESULTS: There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% [95% CI, 0.4-5.3]) tenecteplase patients compared with 7 (2.7% [95% CI, 1.1-5.7]) alteplase patients (P=0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 [2.4%; 95% CI, 0.7-6.2] versus 1 [0.4%; 95% CI, 0.01-2.2], P=0.08) or 90-day functional independence (100 [61%] versus 140 [57%], P=0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 [95% CI, 0.14-2.80], P=0.53) or functional independence (odds ratio tenecteplase, 1.20 [95% CI, 0.74-1.95], P=0.46). CONCLUSIONS: Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.

Functional neurological disorders presenting as emergencies to secondary care.

BACKGROUND: Functional neurological disorders (FND) represent a significant proportion of presentations to outpatient adult neurology services. There is little information relating to patients presenting to acute inpatient care. METHODS: We identified patients presenting as acute admissions with FND to Christchurch Hospital, Christchurch, New Zealand, from 2016 to 2018. We analyzed relevant demographic and clinical data from electronic records and measured incidence of presentation to secondary care and healthcare utilization. RESULTS: One hundred sixty-two patients presented on 173 occasions with FND, representing 9% of all admissions to the neurology service during the 3-year study period. The mean age was 40 (SD 17) years, 111 (69%) patients were female and the median length of stay was 3 (IQR 2-4) days. A total of 92 computed tomography brain scans, 77 magnetic resonance imaging brain scans and 42 electroencephalograms were carried out. On 22 (13%) occasions, patients were referred for outpatient psychological therapy. In the 3 years prior to each patient's last presentation in the study period, these 162 patients had a total of 671 presentations to the emergency department. Healthcare demand did not decrease after the index admission. The rate of acute inpatient admission for FND was 10 per 100,000 per year for the total Christchurch Hospital catchment, 6/100,000/year in rural areas, and 11/100,000/year in urban areas. CONCLUSION: FND represented almost 1 in 10 acute neurology admissions with significant inpatient healthcare resource utilization.

Endovascular thrombectomy: 31 hours from symptom onset.

Endovascular thrombectomy is an effective intervention for symptomatic intracranial large-vessel occlusion. This treatment has proven benefit up to 24 hours following onset in selected patients with prestroke functional independence. Limited case reports suggest that thrombectomy beyond 24 hours may also be effective. We describe a young woman managed with endovascular thrombectomy beyond 24 hours.

Psychogenic nonepileptic seizures that remit when the diagnosis is given: Just good luck?

OBJECTIVE: Some patients with psychogenic nonepileptic seizures (PNES) remit when given the diagnosis. It is not realistically possible to test this potential therapeutic effect in an Randomized Controlled Trial (RCT) so we aim to statistically demonstrate it using the temporal relationship between the communication of the diagnosis and the timing of remission. METHOD: Re-analysis of data from a study of PNES, where diagnosis was communicated, and outcomes recorded in 54 patients. Making conservative assumptions and using the binomial distribution, the Poisson distribution and the chi-squared test distribution, we calculated likelihoods of the null hypothesis: that communication of the diagnosis and remission of seizures had occurred in random temporal relationship. RESULTS: Remission occurred in the week following communication of the diagnosis in 15 out of 54 patients. The χ2 test assigned this result a p value of <0.00001. Binomial and Poisson distribution calculations also indicated that remission was highly unlikely to have occurred by chance and that, in a dataset similar to ours, was unlikely to be due to chance if occurring in more than 9 patients (16.7%). CONCLUSIONS: We showed that the observed remissions were highly unlikely to be due to chance. Where an intervention is 'short and sharp' and the outcome can be measured with reasonable temporal acuity, then this type of method may provide an alternative to RCT methodology when the latter is impracticable.

The aetiology of psychogenic non-epileptic seizures: risk factors and comorbidities.

Psychogenic non-epileptic seizures (PNES), also known as dissociative seizures, are paroxysms of altered subjective experience, involuntary movements and reduced self-control that can resemble epileptic seizures, but have distinct clinical characteristics and a complex neuropsychiatric aetiology. They are common, accounting for over 10% of seizure emergencies and around 30% of cases in tertiary epilepsy units, but the diagnosis is often missed or delayed. The recently proposed "integrative cognitive model" accommodates current research on experiential, psychological and biological risk factors for the development of PNES, but in view of the considerable heterogeneity of presentations and medical context, it is not certain that a universal model can capture the full range of PNES manifestations. This narrative review addresses key learning objectives of the ILAE curriculum by describing the demographic profile, common risk factors (such as trauma or acute stress) and comorbid disorders (such as other dissociative and functional disorders, post-traumatic stress disorder, depressive and anxiety disorders, personality disorders, comorbid epilepsy, head injury, cognitive and sleep problems, migraine, pain, and asthma). The clinical implications of demographic and aetiological factors for diagnosis and treatment planning are addressed.

Medically Unexplained Symptoms and Antecedent Sexual Abuse: An Observational Study of a Birth Cohort.

OBJECTIVE: Medically unexplained symptoms (MUS) are common and associated with high consumption of health care resources. Cross-sectional studies in selected and clinical populations show consistent linkages between history of childhood sexual abuse (CSA) and presentation with MUS and somatization. However, there are almost no well-controlled prospective studies in population samples. METHODS: Data were gathered in a longitudinal study of a New Zealand birth cohort born in 1977. Hospital e-record data for the period 2008-2015 (age, 30-38 years) were searched for a subsample of 408 study participants who were resident in one District Health Board region, and details of MUS contacts were recorded. Retrospective reports of CSA (<16 years) were obtained at ages 18 and 21 years. Associations between CSA and MUS were sequentially adjusted using logistic regression methods for both childhood confounders assessed before age 16 years and potential mediating mental health/family context up to age 30 years. RESULTS: Twenty (4.9%) participants were classified as having MUS, of whom 11 had a history of CSA. Severe CSA involving attempted/completed sexual penetration was strongly associated with risk of MUS (odds ratio = 11.6, 95% confidence interval = 4.3-31.7, p < .001). A substantial association remained after statistically adjusting for confounding and mediating mental health/family context (adjusted odds ratio = 5.1, 95% confidence interval = 1.2-21.3, p = .024). This strong association was specific to severe CSA (as opposed to childhood physical abuse) and to MUS rather than medically explained symptoms. CONCLUSIONS: CSA involving attempted/completed penetration was strongly associated with attendance at secondary level care for MUS. Implications for prevention and treatment of MUS are discussed.

Hiding in Plain Sight: Functional Neurological Disorders in the News.

OBJECTIVE: Functional movement and seizure disorders are still widely misunderstood and receive little public and academic attention. This is in stark contrast to their high prevalence and levels of associated disability. In an exploratory observational study, the authors examined whether the relative lack of media coverage of functional neurological disorders is in part due to misidentification in "human interest" news stories. METHODS: Thirteen recent news stories from high-impact English-language media outlets that portrayed patients with complex symptoms either attributed to other diagnoses or presented as medical mysteries were identified using online keyword searches. All selected news stories contained video or still images displaying relevant symptoms. Cases were categorized into movement disorders or seizure disorders and were then independently assessed by 10 respective expert raters. For each category, one story of a patient whose symptoms were due to a well-recognized neurological disease was also included. Both the diagnostic category and the respective confidence level were reported by each rater for each case. The interrater agreement was calculated for each group of disorders. RESULTS: The raters confirmed almost unanimously that all presented news stories except the negative control cases portrayed misidentified functional movement or seizure disorders. The interrater agreement and average diagnostic confidence were high. CONCLUSIONS: Functional neurological disorders are often wrongly considered a rare medical curiosity of the past. However, these findings suggest that, while they are largely absent from public discourse, they often appear in the news incognito, hiding in plain sight.

Generating the perception of choice: the remarkable malleability of option-listing.

The normative view that patients should be offered more choice both within and beyond the UK's National Health Service (NHS) has been increasingly endorsed. However, there is very little research on whether - and how - this is enacted in practice. Based on 223 recordings of neurology outpatient consultations and participants' subsequent self-reports, this article shows that 'option-listing' is a key practice for generating the perception of choice. The evidence is two-fold: first, we show that neurologists and patients overwhelmingly reported that choice was offered in those consultations where option-listing was used; second, we demonstrate how option-listing can be seen, in the interaction itself, to create a moment of choice for the patient. Surprisingly, however, we found that even when the patient resisted making the choice or the neurologist adapted the practice of option-listing in ways that sought acceptance of the neurologist's own recommendation, participants still agreed that a choice had been offered. There was only one exception: despite the use of option-listing, the patient reported having no choice, whereas the neurologist reported having offered a choice. We explore this deviant case in order to shed light on the limits of option-listing as a mechanism for generating the perception of choice.

Helsinki Stroke Model Is Transferrable With "Real-World" Resources and Reduced Stroke Thrombolysis Delay to 34 min in Christchurch.

BACKGROUND: Christchurch hospital is a tertiary hospital in New Zealand supported by five general neurologists with after-hours services provided mainly by onsite non-neurology medical residents. We assessed the transferrability and impact of the Helsinki Stroke model on stroke thrombolysis door-to-needle time (DNT) in Christchurch hospital. METHODS: Key components of the Helsinki Stroke model were implemented first in 2015 with introduction of patient pre-notification and thrombolysis by the computed tomography (CT) suite, followed by implementation of direct transfer to CT on ambulance stretcher in May 2017. Data from the prospective thrombolysis registry which began in 2012 were analyzed for the impact of these interventions on median DNT. RESULTS: Between May and December 2017, 46 patients were treated with alteplase, 25 (54%) patients were treated in-hours (08:00-17:00 non-public holiday weekdays) and 21 (46%) patients were treated after-hours. The in-hours, after-hours, and overall median (interquartile range) DNTs were 34 (28-43), 47 (38-60), and 40 (30-51) minutes. The corresponding times in 2012-2014 prior to interventions were 87 (68-106), 86 (72-116), and 87 (71-112) minutes, representing median DNT reduction of 53, 39, and 47 minutes, respectively (p-values <0.01). The interventions also resulted in significant reductions in the overall median door-to-CT time (from 49 to 19 min), CT-to-needle time (32 to 20 min) and onset-to-needle time (168 to 120 min). CONCLUSION: The Helsinki stroke model is transferrable with real-world resources and reduced stroke DNT in Christchurch by over 50%.