The natural history of epilepsy and nonepileptic seizures in Sturge-Weber syndrome: A retrospective case-note review.

OBJECTIVE: Patients with Sturge-Weber Syndrome (SWS) experience varying degrees of neurological problems - including epilepsy, hemiparesis, learning disability (LD), and stroke-like episodes. While the range of clinical problems experienced by children with SWS is well recognized, the spectrum of clinical presentation and its treatment during adulthood has been relatively neglected in the literature to date. This study explored the natural history of epileptic and nonepileptic seizures into adulthood in patients with SWS, and their treatment, and investigated whether any clinical factors predict which symptoms a patient will experience during adulthood. METHODS: A retrospective case-note review of a cohort of 26 adults with SWS at the National Hospital for Neurology and Neurosurgery (NHNN). Childhood data were also recorded, where available, to enable review of change/development of symptoms over time. RESULTS: The course of epilepsy showed some improvement in adulthood - seventeen adults continued to have seizures, while six patients gained seizure freedom, and no one had adult-onset seizures. However, seizures did worsen for some patients. Although no factors reached statistical significance regarding predicting continued epilepsy in adulthood, being male, more severe LD, having required epilepsy surgery, and bilateral cortical involvement may be important. Nonepileptic seizures (NES) also began during adulthood for four patients. SIGNIFICANCE: By adulthood, there is some degree of improvement in epilepsy overall; while NES may occur for the first time. While the majority of the results did not survive adjustments for multiple comparisons, some interesting trends appeared, which require further investigation in a multicenter national audit. Patients with more neurologically severe presentations during childhood may continue to experience seizures. Careful monitoring and screening are needed during adulthood, to detect changes and newly developing symptoms such as NES, and target treatment promptly.

Sleep and epilepsy: A snapshot of knowledge and future research lines.

Sleep and epilepsy have a reciprocal relationship, and have been recognized as bedfellows since antiquity. However, research on this topic has made a big step forward only in recent years. In this narrative review we summarize the most stimulating discoveries and insights reached by the "European school." In particular, different aspects concerning the sleep-epilepsy interactions are analysed: (a) the effects of sleep on epilepsy; (b) the effects of epilepsy on sleep structure; (c) the relationship between epilepsy, sleep and epileptogenesis; (d) the impact of epileptic activity during sleep on cognition; (e) the relationship between epilepsy and the circadian rhythm; (f) the history and features of sleep hypermotor epilepsy and its differential diagnosis; (g) the relationship between epilepsy and sleep disorders.

Exploratory pilot study of exogenous sustained-release melatonin on nocturia in Parkinson's disease.

INTRODUCTION: Nocturia is one of the commonest non-motor symptoms in Parkinson's disease (PD). Nocturia has evolved from being understood as a symptom of urological disorders or neurogenic bladder dysfunction to being considered as a form of circadian dysregulation. Exogenous melatonin is known to help circadian function and can be an effective strategy for nocturia in PD. METHODS: In this open-label, single-site, exploratory, phase 2 pilot study, adults with PD and nocturia underwent assessments using standardized questionnaires, urodynamics studies and a bladder scan. This was followed by completion of a frequency volume chart (FVC) and 2-week sleep diary. Sustained-release melatonin 2 mg was then administered once-nightly for 6 weeks. A repeat assessment using questionnaires, the FVC and sleep diary was performed whilst on treatment with melatonin. Companion or bed partners filled in sleep questionnaires to assess their sleep during the intervention. RESULTS: Twenty patients (12 males; mean age 68.2 [SD = 7.8] years; mean PD duration 8.0 [±5.5] years) with PD reporting nocturia were included. Administration of melatonin was associated with a significant reduction in the primary outcome bother related to nocturia measured using the International Consultation on Incontinence Questionnaire Nocturia (ICIQ-N) (p = 0.01), number of episodes of nocturia per night (p = 0.013) and average urine volume voided at night (p = 0.013). No serious adverse events were reported. No significant improvement was noted in bed partner sleep scores. CONCLUSIONS: In this preliminary open-label study, administration of sustained-release melatonin 2 mg was found to be safe for clinical use and was associated with significant improvements in night-time frequency and nocturnal voided volumes in PD patients.

Expert Opinion: Managing sleep disturbances in people with epilepsy.

Poor sleep and daytime sleepiness are common in people with epilepsy. Sleep disorders can disrupt seizure control and in turn sleep and vigilance problems can be exacerbated by seizures and by antiepileptic treatments. Nevertheless, these aspects are frequently overlooked in clinical practice and a clear agreement on the evidence-based guidelines for managing common sleep disorders in people with epilepsy is lacking. Recently, recommendations to standardize the diagnostic pathway for evaluating patients with sleep-related epilepsies and comorbid sleep disorders have been presented. To build on these, we adopted the Delphi method to establish a consensus within a group of experts and we provide practical recommendations for identifying and managing poor night-time sleep and daytime sleepiness in people with epilepsy. We recommend that a comprehensive clinical history of sleep habits and sleep hygiene should be always obtained from all people with epilepsy and their bed partners. A psychoeducational approach to inform patients about habits or practices that may negatively influence their sleep or their vigilance levels should be used, and strategies for avoiding these should be applied. In case of a suspected comorbid sleep disorder an appropriate diagnostic investigation should be performed. Moreover, the possible presence of sleep fragmentation induced by sleep-related seizures should be ruled out. Finally, the dose and timing of antiepileptic medications and other co-medications should be optimized to improve nocturnal sleep and avoid daytime sedation.

Standard procedures for the diagnostic pathway of sleep-related epilepsies and comorbid sleep disorders: A European Academy of Neurology, European Sleep Research Society and International League against Epilepsy-Europe consensus review.

BACKGROUND: Some epilepsy syndromes (sleep-related epilepsies [SRE]) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. PURPOSES: To define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2). METHODS: The project was conducted under the auspices of the European Academy of Neurology (EAN), the European Sleep Research Society (ESRS) and the International League against Epilepsy (ILAE) Europe. The framework of the document entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For literature search a step-wise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library. RESULTS: Scenario 1: despite a low quality of evidence, recommendations on anamnestic evaluation, tools for capturing the event at home or in the laboratory are provided for specific SRE. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizures control. CONCLUSIONS: Definitive procedures for evaluating patients with SRE are lacking. We provide advice that could be of help for standardising and improving the diagnostic approach of specific SRE. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined.

The effect of posterior hypothalamus region deep brain stimulation on sleep.

BACKGROUND: Early observations by von Economo showed that the posterior part of the hypothalamus (PH) plays a prominent role in sleep-wake regulation. The PH is a candidate area involved in cluster headaches and other trigeminal autonomic cephalalgias (TACs) and is targeted for deep brain stimulation (DBS). CASE REPORTS: Sleep studies in two men, 69- and 39-years-old, with pre-existing sleep disorders, before and after PH-DBS for pharamacoresistant cluster headache and SUNCT syndrome showed that PH-DBS led to a dramatic alteration of the patients' sleep patterns. This coincided with an improvement of the predominantly diurnal TACs, suggesting a PH-DBS-induced change in sleep patterns. Hypnograms after DBS demonstrated disrupted sleep and a prolonged period of wakefulness after midnight in both patients, which was reproduced the second night. CONCLUSIONS: PH-DBS, a promising treatment for severe refractory TACs, affects sleep quality and pre-existing sleep disorders. This needs to be considered when treating patients with PH-DBS.

Risk Factors Associated with Asthma Control and Quality of Life in Patients with Mild Asthma Without Preventer Treatment, a Cross-Sectional Study.

Purpose: To study risk factors for uncontrolled asthma and insufficient quality of life (QoL) in patients with mild asthma, ie those without preventer treatment. Patients and Methods: Patients aged 18-75 years with a doctor's diagnosis of asthma randomly selected from primary and secondary care in Sweden. Mild asthma was defined as self-reported current asthma and no preventer treatment. Data were collected from self-completed questionnaires in 2012 and 2015. Well-controlled asthma was defined as Asthma Control Test (ACT) ≥20 points and no exacerbation and uncontrolled asthma as ACT<20 points and/or at least one exacerbation in the previous six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ), where a total mean score of ≥ 6 indicated sufficient and < 6 insufficient QoL. Multivariate logistic regression analyses were performed using asthma control and Mini-AQLQ as dependent variables. Asthma control was dichotomized as controlled and uncontrolled asthma and the Mini-AQLQ as sufficient QoL (mean score ≥6) and insufficient QoL (mean score <6). Results: Among 298 patients, 26% had uncontrolled asthma, 40% insufficient QoL and 20% both uncontrolled asthma and insufficient QoL. Age ≥60 years, obesity, daily smoking, rhinitis and inadequate knowledge of asthma self-management were independently associated with poor asthma control. Factors independently associated with insufficient QoL were age ≥60 years, overweight, obesity, rhinitis, sinusitis and inadequate knowledge of asthma self-management. Age ≥60 years, obesity, rhinitis and inadequate knowledge of asthma self-management were independently associated with both uncontrolled asthma and insufficient QoL. Conclusion: Among asthma patients without preventer medication, 26% had uncontrolled asthma and 40% had insufficient asthma-related QoL. Older age, obesity, and rhinitis were risk factors for both poor asthma control and a reduced QoL, but having good knowledge of asthma self-management reduced this risk. Our findings suggest that this group of patients requires further attention and follow-up.

Many patients with little symptoms of asthma do not take asthma-preventer medication as their asthma is recognized as mild. Still, it is well-known that in this group there are patients with frequent and severe symptoms and acute attacks of asthma, defined as uncontrolled asthma. Quality of life (QoL) is less studied in these patients. Our aim was to study patient characteristics and factors with a higher risk for uncontrolled asthma and insufficient QoL in patients with mild asthma. We studied patients with asthma diagnosis 18­75 of age in Sweden who reported asthma and no asthma preventer medication. They answered questionnaires about characteristics, knowledge of asthma, asthma symptoms, acute asthma attacks and QoL. A test for asthma symptom control, the Asthma Control Test (ACT), was answered, where 20 points or more meant good asthma symptom control. Patients were regarded as having uncontrolled asthma if they had less than 20 points and/or at least one acute asthma attack the last six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire. A mean score of 6 or more meant sufficient and less than 6 insufficient QoL. Of the 298 patients, 26% had uncontrolled asthma, 40% had insufficient QoL and 20% had both. Patients with risk for both uncontrolled asthma and insufficient QoL were 60 years and over, with obesity, rhinitis and those who reported insufficient knowledge of how to handle asthma. Our results suggest that patients with mild asthma need more attention, better management and follow-ups.

Imaging the interaction: epileptic discharges, working memory, and behavior.

Interictal generalized epileptiform discharges may impair cognition. We used simultaneous video-electroencephalography and functional imaging to quantify changes, induced by epileptiform discharges, in the task-related activations during a spatial working-memory paradigm. The number of epileptiform discharges increased during the task with its level of complexity, but were not significantly associated with wrong responses during the task. We observed hemodynamic responses in working-memory related frontal-lobe-network, motor-cortex, precuneus, and parietal lobes in the absence of epileptiform discharges. In the presence of epileptiform discharges during the task, task-related hemodynamic changes were seen only in motor-cortex, precuneus, and parietal lobes. These findings suggest that generalized epileptiform discharges during a high demanding working memory task may change the working memory-related hemodynamic responses in frontal-lobe-network.

Experiences of frostbite injury from recreational use of nitrous oxide canisters in a UK burns center: Not a laughing matter.

Nitrous oxide is used as a recreational drug. Contact frostbite injury from compressed gas canisters has previously been described in the literature, but an increased number of such cases has been noted in our busy regional burns center in the UK. A single-center prospective case series of all patients referred and treated for frostbite injury secondary to misuse of nitrous oxide compressed gas canisters between January and December 2022 is presented. Data collection was performed through a referral database and patient case notes. Sixteen patients, of which 7 were male and 9 were female, satisfied the inclusion criteria. Mean patient age was 22.5 years. The median TBSA was 1%. In total, 50% of patients in the cohort had a delayed initial presentation to A&E of greater than 5 days. Eleven patients were reviewed at our burns center for further assessment and management. In total, 11 patients had bilateral inner thigh frostbite injuries, of which 8 had necrotic full-thickness injury, including subcutaneous fat. Seven patients were reviewed at our burns center and offered excision and split-thickness skin graft. Four patients presented with contact frostbite injury to the hand and one patient to the lower lip. This subgroup was managed successfully with conservative management alone. The reproducible pattern of frostbite injury secondary to the abuse of nitrous oxide compressed gas canisters is demonstrated in our case series. The distinct pattern of injury, patient cohort, and anatomical area affected presents an opportunity for targeted public health intervention in this group.

Group Cognitive Behavioural Therapy for Non-Rapid Eye Movement Parasomnias: Long-Term Outcomes and Impact of COVID-19 Lockdown.

Prior to the COVID-19 pandemic, we demonstrated the efficacy of a novel Cognitive Behavioural Therapy programme for the treatment of Non-Rapid Eye Movement Parasomnias (CBT-NREMP) in reducing NREM parasomnia events, insomnia and associated mood severities. Given the increased prevalence and worsening of sleep and affective disorders during the pandemic, we examined the sustainability of CBT-NREMP following the U.K.'s longest COVID-19 lockdown (6 January 2021-19 July 2021) by repeating the investigations via a mail survey in the same 46 patient cohort, of which 12 responded. The survey included validated clinical questionnaires relating to NREM parasomnia (Paris Arousal Disorder Severity Scale), insomnia (Insomnia Severity Index) and anxiety and depression (Hospital Anxiety and Depression Scale). Patients also completed a targeted questionnaire (i.e., Impact of COVID-19 Lockdown Questionnaire, ICLQ) to assess the impact of COVID-19 lockdown on NREM parasomnia severity, mental health, general well-being and lifestyle. Clinical measures of NREM parasomnia, insomnia, anxiety and depression remained stable, with no significant changes demonstrated in questionnaire scores by comparison to the previous investigatory period prior to the COVID-19 pandemic: p (ISI) = 1.0; p (HADS) = 0.816; p (PADSS) = 0.194. These findings support the longitudinal effectiveness of CBT-NREMP for up to three years following the clinical intervention, and despite of the COVID-19 pandemic.

Evaluation and Treatment in Urology for Nocturia Caused by Nonurological Mechanisms: Guidance from the PLANET Study.

Patients with nocturia are commonly referred to urology clinics, including many for whom a nonurological medical condition is responsible for their symptoms. The PLanning Appropriate Nocturia Evaluation and Treatment (PLANET) study was established to develop practical approaches to equip healthcare practitioners to deal with the diverse causes of nocturia, based on systematic reviews and expert consensus. Initial assessment and therapy need to consider the possibility of one or more medical conditions falling into the "SCREeN" areas of Sleep medicine (insomnia, periodic limb movements of sleep, parasomnias, and obstructive sleep apnoea), Cardiovascular (hypertension and congestive heart failure), Renal (chronic kidney disease), Endocrine (diabetes mellitus, thyroid disease, pregnancy/menopause, and diabetes insipidus), and Neurology. Medical and medication causes of xerostomia should also be considered. Some key indicators for these conditions can be identified in urology clinics, working in partnership with the primary care provider. Therapy of the medical condition in some circumstances lessens the severity of nocturia. However, in many cases there is a conflict between the two, in which case the medical condition generally takes priority on safety grounds. It is important to provide patients with a realistic expectation of therapy and awareness of limitations of current therapeutic options for nocturia. PATIENT SUMMARY: Nocturia is the symptom of waking at night to pass urine. Commonly, this problem is referred to urology clinics. However, in some cases, the patient does not have a urological condition but actually a condition from a different speciality of medicine. This article describes how best the urologist and the primary care doctor can work together to assess the situation and make sensible and safe treatment suggestions. Unfortunately, there is sometimes no safe or effective treatment choice for nocturia, and treatment needs to focus instead on supportive management of symptoms.

Association of Sleep Disorders with Nocturia: A Systematic Review and Nominal Group Technique Consensus on Primary Care Assessment and Treatment.

CONTEXT: Sleep disorders affect responsiveness to sensory information and can cause nocturnal polyuria and reduced sleep depth; hence, these are potentially influential in understanding the mechanism of nocturia. OBJECTIVE: To report the systematic review (SR) and expert consensus for primary care management of nocturia in sleep disorders. EVIDENCE ACQUISITION: Four databases were searched from January to April 2020. A total of 1658 titles and abstracts were screened, and 23 studies potentially applicable were included for full-text screening. The nominal group technique (NGT) was used to derive a consensus on recommendations for management using an expert panel with public involvement. EVIDENCE SYNTHESIS: Thirteen studies met the SR inclusion criteria, all of which studied obstructive sleep apnoea (OSA), with ten evaluating the effect of continuous positive airway pressure. The NGT consensus discussed the assessment of OSA with other key sleep disorders, notably insomnia, restless legs syndrome/periodic limb movements of sleep, and parasomnias, including non-rapid eye movement (non-REM) parasomnias and REM sleep behaviour disorder (RBD). The NGT considered that the use of screening questions to reach a clinical diagnosis is a sufficient basis for offering conservative therapy within primary care. Reasons for referral to a sleep clinic are suspected sleep disorder with substantially impaired daytime function despite conservative treatment. Suspected RBD should be referred, and if confirmed, neurology opinion is indicated. Referrals should follow local guidelines. Persisting nocturia is not currently considered an indication for referral to a sleep clinic. CONCLUSIONS: Sleep disorders are potentially highly influential in nocturia, but are often overlooked. PATIENT SUMMARY: People with sleep disorders can experience nocturia due to easy waking or increased bladder filling. We looked at published research, and information was limited to one form of sleep disturbance-obstructive sleep apnoea. We assembled a group of experts, to develop practical approaches for assessing and treating nocturia in the potentially relevant sleep disorders.

Epilepsy and sleep.

PURPOSE OF REVIEW: There is a complex relationship between epilepsy, sleep and sleep disorders. Recent studies have provided new insights into the links between the disorders that may facilitate differential diagnosis and treatment but may also improve our understanding of underlying pathophysiological mechanisms. RECENT FINDINGS: Sleep and sleep deprivation have long been recognized to influence interictal epileptiform discharges and seizures. More recent studies have shown that primary sleep disorders such as obstructive sleep apnoea may worsen epilepsy and treatment of these sleep disorders can lead to improved seizure control. Seizures may interfere with night-time sleep structure and cause excessive day-time somnolence (EDS). Antiepileptic drugs may also cause EDS or influence sleep. Despite more frequent use of video-electroencephalographic telemetry and polysomnography, the differential diagnostic challenges between nonrapid eye movement parasomnia and nocturnal frontal lobe epilepsy remain. There is also ongoing debate regarding the possibility of a common pathogenic background for parasomnias and nocturnal seizures that is summarized in the review. SUMMARY: Accurate identification and diagnosis of sleep disorders as well as epilepsy is clinically important to ensure optimal treatment of both epilepsy and sleep disorders. Further studies of these nocturnal events may advance our understanding of underlying pathological mechanisms and the complex relationship between sleep and epilepsy.

Temporal lobe sclerosis associated with hippocampal sclerosis in temporal lobe epilepsy: neuropathological features.

Widespread changes involving neocortical and mesial temporal lobe structures can be present in patients with temporal lobe epilepsy and hippocampal sclerosis. The incidence, pathology, and clinical significance of neocortical temporal lobe sclerosis (TLS) are not well characterized. We identified TLS in 30 of 272 surgically treated cases of hippocampal sclerosis. Temporal lobe sclerosis was defined by variable reduction of neurons from cortical layers II/III and laminar gliosis; it was typically accompanied by additional architectural abnormalities of layer II, that is, abnormal neuronal orientation and aggregation. Quantitative analysis including tessellation methods for the distribution of layer II neurons supported these observations. In 40% of cases, there was a gradient of TLS with more severe involvement toward the temporal pole, possibly signifying involvement of hippocampal projection pathways. There was a history of a febrile seizure as an initial precipitating injury in 73% of patients with TLS compared with 36% without TLS; no other clinical differences between TLS and non-TLS cases were identified. Temporal lobe sclerosis was not evident preoperatively by neuroimaging. No obvious effect of TLS on seizure outcome was noted after temporal lobe resection; 73% became seizure-free at 2-year follow-up. In conclusion, approximately 11% of surgically treated hippocampal sclerosis is accompanied by TLS. Temporal lobe sclerosis is likely an acquired process with accompanying reorganizational dysplasia and an extension of mesial temporal sclerosis rather than a separate pathological entity.

Cortical neuronal loss and hippocampal sclerosis are not detected by voxel-based morphometry in individual epilepsy surgery patients.

Voxel-based morphometry (VBM) has detected differences between brains of groups of patients with epilepsy and controls, but the sensitivity for detecting subtle pathological changes in single subjects has not been established. The aim of the study was to test the sensitivity of VBM using statistical parametric mapping (SPM5) to detect hippocampal sclerosis (HS) and cortical neuronal loss in individual patients. T1-weighted volumetric 1.5 T MR images from 13 patients with HS and laminar cortical neuronal loss were segmented, normalised and smoothed using SPM5. Both modulated and non-modulated analyses were performed. Comparisons of one control subject against the rest (n = 23) were first performed to ascertain the smoothing level with the lowest number of SPM changes in controls. Each patient was then compared against the whole control group. The lowest number of SPM changes in control subjects was found at a smoothing level of 10 mm full width half maximum for modulated and non-modulated data. In the patient group, no SPM abnormalities were found in the affected temporal lobe or hippocampus at this smoothing level. At lower smoothing levels there were numerous SPM findings in controls and patients. VBM did not detect any abnormalities associated with either laminar cortical neuronal loss or HS. This may be due to normalisation and smoothing of images and low statistical power in areas with larger inter-individual differences. This suggests that the methodology may currently not be suitable to detect particular occult abnormalities possibly associated with seizure onset zone in individual epilepsy patients with unremarkable standard structural MRI.

Increasing the accuracy of 3D EEG implantations.

OBJECTIVEThe accuracy of stereoelectroencephalography (SEEG) electrode implantation is an important factor in maximizing its safety. The authors established a quality assurance (QA) process to aid advances in implantation accuracy.METHODSThe accuracy of three consecutive modifications of a frameless implantation technique was quantified in three cohorts comprising 22, 8, and 23 consecutive patients. The modifications of the technique aimed to increase accuracy of the bolt placement.RESULTSThe lateral shift of the axis of the implanted bolt at the level of the planned entry point was reduced from a mean of 3.0 ± 1.6 mm to 1.4 ± 0.8 mm. The lateral shift of the axis of the implanted bolt at the level of the planned target point was reduced from a mean of 3.8 ± 2.5 mm to 1.6 ± 0.9 mm.CONCLUSIONSThis QA framework helped to isolate and quantify the factors introducing inaccuracy in SEEG implantation, and to monitor ongoing accuracy and the effect of technique modifications.

Sleep symptoms in syndromes of frontotemporal dementia and Alzheimer's disease: A proof-of-principle behavioural study.

Sleep disruption is a key clinical issue in the dementias but the sleep phenotypes of these diseases remain poorly characterised. Here we addressed this issue in a proof-of-principle study of 67 patients representing major syndromes of frontotemporal dementia (FTD) and Alzheimer's disease (AD), in relation to 25 healthy older individuals. We collected reports on clinically-relevant sleep characteristics - time spent overnight in bed, sleep quality, excessive daytime somnolence and disruptive sleep events. Difficulty falling or staying asleep at night and excessive daytime somnolence were significantly more frequently reported for patients with both FTD and AD than healthy controls. On average, patients with FTD and AD retired earlier and patients with AD spent significantly longer in bed overnight than did healthy controls. Excessive daytime somnolence was significantly more frequent in the FTD group than the AD group; AD syndromic subgroups showed similar sleep symptom profiles while FTD subgroups showed more variable profiles. Sleep disturbance is a significant clinical issue in major FTD and AD variant syndromes and may be even more salient in FTD than AD. These preliminary findings warrant further systematic investigation with electrophysiological and neuroanatomical correlation in major proteinopathies.