Expert advice for prescribing cannabis medicines for patients with epilepsy-drawn from the Australian clinical experience.

There is international interest for consensus advice for prescribers working in the field of drug resistant epilepsy intending to trial potential therapies that are nonregistered or off-label. Cannabinoids are one such therapy. In 2017, the New South Wales State Government (Australia) set up a cannabinoid prescribing guidance service for a wide variety of indications, based on known pharmacology together with the relevant new literature as it became available. Increasing interest in cannabis medicines use outside this State over the following 5 years together with a paucity of registration-standard clinical trials, lack of information around dosing issues, drug interactions and biological plausibility meant there remained a large unmet need for such advice. To address the unmet need in epilepsy, and until medicines were registered or regulator quality data were available, it was agreed to bring together a working group comprising paediatric and adult epilepsy specialists, clinical pharmacists., clinical pharmacologists and cannabis researchers from across Australia to develop interim consensus advice for prescribers. Although interim, this consensus advice addresses much of the current practice gap by providing an informed overview of the different cannabis medicines currently available for use in the treatment of epilepsy in paediatric and adult settings, with information on dose, drug interactions, toxicity, type of seizure and frequency of symptom relief. As such it supplements the limited evidence currently available from clinical trials with experience from front-line practice. It is expected that this consensus advice will be updated as new evidence emerges and will provide guidance for a subsequent Guideline.

Association Between Migraine Comorbidity and Psychiatric Symptoms Among People With Newly Diagnosed Focal Epilepsy.

OBJECTIVE: Little is known about psychiatric symptoms among patients with migraine and newly diagnosed focal epilepsy. The investigators compared symptoms of depression, anxiety, and suicidality among people with newly diagnosed focal epilepsy with migraine versus without migraine. METHODS: The Human Epilepsy Project is a prospective multicenter study of patients with newly diagnosed focal epilepsy. Depression (measured with the Center for Epidemiologic Studies Depression Scale), anxiety (measured with the 7-item Generalized Anxiety Disorder scale), and suicidality scores (measured with the Columbia-Suicide Severity Rating Scale [C-SSRS]) were compared between participants with versus without migraine. Data analysis was performed with the Kolmogorov-Smirnov test for normality assessment, the Mann-Whitney U test, chi-square test, and linear regression. RESULTS: Of 349 patients with new-onset focal epilepsy, 74 (21.2%) had migraine. There were no differences between the patients without migraine versus those with migraine in terms of age, race, and level of education. There were more women in the group with migraine than in the group without migraine (75.7% vs. 55.6%, p=0.0018). The patients with epilepsy and comorbid migraine had more depressive symptoms than the patients with epilepsy without migraine (35.2% vs. 22.7%, p=0.031). Patients with epilepsy with comorbid migraine had more anxiety symptoms than patients with epilepsy without migraine, but this relation was mediated by age in logistic regression, with younger age being associated with anxiety. Comorbid migraine was not associated with C-SSRS ideation or behavior. CONCLUSIONS: Among a sample of patients with newly diagnosed focal epilepsy, 21.2% had migraine. Migraine comorbidity was associated with higher incidence of depressive symptoms. Future studies should be performed to better assess these relationships and possible treatment implications.

First seizure presentations in adults: beyond assessment and treatment.

Almost 10% of people will experience at least one seizure over a lifetime. Although common, first seizures are serious events and warrant careful assessment and management. First seizures may be provoked by acute or remote symptomatic factors including life-threatening metabolic derangements, drug toxicity or structural brain lesions. An unprovoked first seizure may herald the onset of epilepsy and may be accompanied by medical and psychiatric illnesses. Accidents, injuries and death associated with first seizures are likely under-reported. The cognitive and emotional impact of first seizures is often neglected. Evaluation of a patient presenting with a first seizure requires careful history-taking and early specialist assessment, however optimal management strategies have not been extensively investigated. Further, advances in technology and the role of eHealth interventions such as telemedicine may be of value in the care of patients who have experienced a first seizure. This article reviews the impact and implications of first seizures beyond the scope provided in current guidelines which tend to focus on assessment and management. It examines the effect of first seizures on the well-being of patients; assesses morbidity and premature mortality in first seizures and discusses current and future directions to optimise safety and health of people with first seizures, with a focus on adult patients. Recognition of these issues is essential to provide adequate care for people with first seizures.

Bilateral volume reduction in posterior hippocampus in psychosis of epilepsy.

OBJECTIVE: Psychosis of epilepsy (POE) occurs more frequently in temporal lobe epilepsy, raising the question as to whether abnormalities of the hippocampus are aetiologically important. Despite decades of investigation, it is unclear whether hippocampal volume is reduced in POE, perhaps due to small sample sizes and methodological limitations of past research. METHODS: In this study, we examined the volume of the total hippocampus, and the hippocampal head, body and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy and generalised epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP). RESULTS: Compared with EC the POE group had smaller total left hippocampus volume (13.5% decrease, p<0.001), and smaller left hippocampal body (13.3% decrease, p=0.002), and left (41.5% decrease, p<0.001) and right (36.4% decrease, p<0.001) hippocampal tail volumes. Hippocampal head volumes did not differ between groups. CONCLUSION: Posterior hippocampal volumes are bilaterally reduced in POE. Volume loss was observed on a posteroanterior gradient, with severe decreases in the tail and moderate volume decreases in the body, with no difference in the hippocampal head. Posterior hippocampal atrophy is evident to a similar degree in PIP and IP. Our findings converge with those reported for the paradigmatic psychotic disorder, schizophrenia, and suggest that posterior hippocampal atrophy may serve as a biomarker of the risk for psychosis, including in patients with epilepsy.

Increased cortical thickness in nodes of the cognitive control and default mode networks in psychosis of epilepsy.

OBJECTIVE: To explore the cortical morphological associations of the psychoses of epilepsy. METHODS: Psychosis of epilepsy (POE) has two main subtypes - postictal psychosis and interictal psychosis. We used automated surface-based analysis of magnetic resonance images to compare cortical thickness, area, and volume across the whole brain between: (i) all patients with POE (n = 23) relative to epilepsy-without psychosis controls (EC; n = 23), (ii) patients with interictal psychosis (n = 10) or postictal psychosis (n = 13) relative to EC, and (iii) patients with postictal psychosis (n = 13) relative to patients with interictal psychosis (n = 10). RESULTS: POE is characterised by cortical thickening relative to EC, occurring primarily in nodes of the cognitive control network; (rostral anterior cingulate, caudal anterior cingulate, middle frontal gyrus), and the default mode network (posterior cingulate, medial paracentral gyrus, and precuneus). Patients with interictal psychosis displayed cortical thickening in the left hemisphere in occipital and temporal regions relative to EC (lateral occipital cortex, lingual, fusiform, and inferior temporal gyri), which was evident to a lesser extent in postictal psychosis patients. There were no significant differences in cortical thickness, area, or volume between the postictal psychosis and EC groups, or between the postictal psychosis and interictal psychosis groups. However, prior to correction for multiple comparisons, both the interictal psychosis and postictal psychosis groups displayed cortical thickening relative to EC in highly similar regions to those identified in the POE group overall. SIGNIFICANCE: The results show cortical thickening in POE overall, primarily in nodes of the cognitive control and default mode networks, compared to patients with epilepsy without psychosis. Additional thickening in temporal and occipital neocortex implicated in the dorsal and ventral visual pathways may differentiate interictal psychosis from postictal psychosis. A novel mechanism for cortical thickening in POE is proposed whereby normal synaptic pruning processes are interrupted by seizure onset.

Ophthalmoplegia in tiger snake envenomation.

Herein, we present the case of a 67-year-old grazier who was bitten by a tiger snake and developed coagulopathy and respiratory distress. The patient required intubation and ventilation in intensive care. There was delayed detection of snake envenomation and administration of antivenom. On extubation several days later, gross external ocular paresis was noted. Clinical testing indicated that the ocular pathology was secondary to neurotoxin-mediated presynaptic blockade. The paresis was partially resolved by the time of discharge one week later. The present case report discusses the possible mechanisms for the delayed development of ophthalmoplegia.

The use of chromophore and fluorophore degradation to quantitate UV dose: FD&C dyes as chemical identicators for UV sterilization.

The accurate measurement of ultraviolet (UV) irradiation, especially within a container or vessel is one of the challenges facing the broad implementation of UV sterilization. Currently, biological indicators are the best method to determine whether an applied UV dose has the necessary efficacy to achieve sterilization. To overcome some of the challenges of using a biological indicator, chemical indicators based upon the degradation of food, drug and cosmetic (FD&C) dyes were developed. In this work, the relationship between UV dose and dye degradation was elucidated and used to create standard curves which could be used as a quantitative measurement system. The use of dye degradation as a measurement of UV dose is especially useful when the levels of UV irradiation within a container cannot be measured directly. Additionally, due to the highly colored nature of the FD&C dyes, the visual changes present upon dye irradiation can be used as a qualitative visual indicator of the UV dose.

Evidence of primary transmission of multidrug-resistant tuberculosis in the Western Province of Papua New Guinea.

OBJECTIVE: To review patient outcomes and the molecular epidemiology of multidrug-resistant tuberculosis (MDR-TB) strains isolated from patients living in the Western Province of Papua New Guinea (PNG) seeking treatment in Australia. DESIGN, SETTING AND PARTICIPANTS: Review of all cases of MDR-TB among people living in the open border region between the Western Province of PNG and the Torres Strait Islands of Australia who presented to health clinics in the region between 2000 and 2006. All cases of suspected TB were bacteriologically confirmed at the time of presentation by the Mycobacterium Reference Laboratory in Brisbane. MAIN OUTCOME MEASURES: Drug resistance patterns; drug use and duration; molecular typing of TB strains; patient outcomes. RESULTS: Between 2000 and 2006, 60 patients from the Western Province of PNG were diagnosed with TB, of which 15 had MDR-TB. Mortality was high, although no patient who was able to maintain access to supervised therapy died. All 15 MDR-TB isolates were Beijing-family strains showing the same unique mycobacterial interspersed repetitive unit (MIRU) profile, with the exception of a single strain that differed by a single repeat at one locus. Restriction fragment length polymorphism (RFLP) typing on 10 of these strains further differentiated them into two distinct clusters. CONCLUSION: Transmission of MDR-TB is occurring in the Western Province of PNG. Additional resources are urgently needed to interrupt the ongoing transmission of MDR-TB from the Western Province of PNG to the Torres Strait Islands. Good supervision and management of patient treatment, which includes ensuring a regular supply of second-line anti-TB drugs, are essential elements of TB control.