Leigh syndrome: an adult presentation of a paediatric disease.

A previously healthy 27-year-old man was admitted to the acute neurology ward with events involving his face, throat and upper limb, which video telemetry later confirmed were refractory focal seizures. He also had progressive pyramidal features, dysarthria and ataxia. MR scans of the brain identified progressive bilateral basal ganglia abnormalities, consistent with Leigh syndrome. However, extensive laboratory and genetic panels did not give a unifying diagnosis. A skeletal muscle biopsy showed no histopathological abnormalities on routine stains. Sequencing of the entire mitochondrial genome in skeletal muscle identified a well-characterised pathogenic variant (m.10191T>C in MT-ND3; NC_012920.1) at 85% heteroplasmy in skeletal muscle. We discuss the clinical and molecular diagnosis of an adult presenting with Leigh syndrome, which is more commonly a paediatric presentation of mitochondrial disease, and how early recognition of a mitochondrial cause is important to support patient care.

A library of quantitative markers of seizure severity.

OBJECTIVE: Understanding fluctuations in seizure severity within individuals is important for determining treatment outcomes and responses to therapy, as well as assessing novel treatments for epilepsy. Current methods for grading seizure severity rely on qualitative interpretations from patients and clinicians. Quantitative measures of seizure severity would complement existing approaches to electroencephalographic (EEG) monitoring, outcome monitoring, and seizure prediction. Therefore, we developed a library of quantitative EEG markers that assess the spread and intensity of abnormal electrical activity during and after seizures. METHODS: We analyzed intracranial EEG (iEEG) recordings of 1009 seizures from 63 patients. For each seizure, we computed 16 markers of seizure severity that capture the signal magnitude, spread, duration, and postictal suppression of seizures. RESULTS: Quantitative EEG markers of seizure severity distinguished focal versus subclinical seizures across patients. In individual patients, 53% had a moderate to large difference (rank sum r > .3 , p < .05 ) between focal and subclinical seizures in three or more markers. Circadian and longer term changes in severity were found for the majority of patients. SIGNIFICANCE: We demonstrate the feasibility of using quantitative iEEG markers to measure seizure severity. Our quantitative markers distinguish between seizure types and are therefore sensitive to established qualitative differences in seizure severity. Our results also suggest that seizure severity is modulated over different timescales. We envisage that our proposed seizure severity library will be expanded and updated in collaboration with the epilepsy research community to include more measures and modalities.

Cancer and motor neuron disease-causal or coincidental? Two contrasting cases.

INTRODUCTION: Motor neuron disease (MND) can occur in patients with cancer, but there is minimal evidence that this is more than by chance. We contrast two cases of motor neuronopathies occurring in the context of systemic malignancy and argue that in one case the cause was most likely paraneoplastic, while in the other it was not. CASE 1: A 61-year-old woman developed progressive walking difficulties over 9 months with weakness and stiffness in her legs. EMG showed fibrillations and positive sharp waves in multiple lower limb muscles bilaterally, with neurogenic units and a reduced recruitment pattern. An invasive ductal carcinoma of the breast was identified and she continued to deteriorate neurologically with worsening mobility, upper limb spasticity and fasciculations. She died approximately 26 months after symptom onset. CASE 2: A 57-year-old woman developed weight loss and weakness of her right arm without any sensory symptoms. At presentation, she had wasting and fasciculations in her right upper limb muscles, with normal reflexes, normal left upper limb and lower limb examination. Over the following week, she developed left upper limb weakness and fasciculations, brisk knee reflexes, and flexor plantar responses. Her EMG showed upper and lower limb denervation. She was found to have anti-Hu and anti-CV2 antibodies present in serum. A PET-CT showed active uptake in lymph nodes in the right hilum. Biopsy confirmed a small cell lung cancer. She had chemoradiation therapy and the tumour went into remission. She has remained well on follow-up 24 months later, regaining weight and strength after her chemotherapy. She continues to be monitored for cancer recurrence, but thus far appears to be in remission. CONCLUSION: In cases with rapidly progressive MND, particularly of upper limb onset, consideration should be given to testing anti-neuronal antibodies and searching for an occult tumour.

Capturing Disruptions to Food Availability After Disasters: Assessing the Food Environment Following Hurricanes Florence and María.

OBJECTIVE: The aim of this study was to describe the results of food environment assessments completed after Hurricane Florence in North Carolina (2018) and Hurricane María in Puerto Rico (2017), and provide recommendations for assessing disaster food environments. METHODS: Adapted structured observation protocols were used to conduct rapid assessments of the availability, price, and quality of specific foods in retail markets. RESULTS: In both settings, unhealthful food items (soda, chips, fruit-flavored drinks) and milk were widely available and at lower prices than domestic averages. The adapted instrument in Puerto Rico allowed for documentation of greater availability of canned items compared with fresh or frozen foods. In both settings, researchers noted the inability of the instrument to document items that are important to assess postdisaster: ready-to-heat and ready-to-eat foods; food preparation facilities and supplies; hygiene supplies; and empty shelf-space. CONCLUSIONS: The instruments, despite their limitations, were able to capture food availability issues in postdisaster environments. Future instrument adaptation is necessary to capture availability of all major food groups, healthful and unhealthful options, shelf-stable, ready-to-eat, and ready-to-heat foods versus other formats (fresh, frozen), and cooking and hygiene supplies.

Drug withdrawal in the epilepsy monitoring unit - The patsalos table.

Investigation of possible candidates for epilepsy surgery will usually require inpatient EEG to capture seizures and allow full operative planning. Withdrawal of antiepileptic drugs increases the yield of this valuable diagnostic information and the benefits of this should justify any increase in the risk of harm associated with these seizures This paper outlines our opinion on what would constitute proposed best practice for management of antiepileptic drug (AED) dosing when patients are admitted for monitoring of seizures to an epilepsy monitoring unit (EMU). In the vast majority of cases EMU admissions are safe and, even if seizures occur, will pass off without complication. Previous guidance has concentrated on ensuring practice around technical aspects of EEG monitoring itself and staffing within the unit. In this guidance we aim to outline optimally safe ways of ensuring that EMUs ensure the minimisation of risk to the patients admitted under their care. We propose an algorithm for enhancing the safety of AED withdrawal in VT admissions while ensuring adequate seizure yields. Risk minimisation requires planned management of drug dosing (with reduction if appropriate), provision of adequate rescue medication, and adequate supervision to allow rapid response to generalised seizures. This algorithm is accompanied by a table which uses knowledge of the clinical and pharmacological properties of each AED to ensure dose withdrawal and reduction is timely and safe taking into account the severity and frequency of the individual's seizures.

Sodium valproate versus lamotrigine: a randomised comparison of efficacy, tolerability and effects on circulating androgenic hormones in newly diagnosed epilepsy.

We have performed a randomised, prospective study to compare the efficacy and tolerability of sodium valproate (VPA) and lamotrigine (LTG) monotherapy, and their effects on circulating androgenic hormones, in newly diagnosed epilepsy. A total of 225 patients (116 male; median age 35 years, range 13-80 years) were followed-up at 6-weekly intervals until they reached an end-point (12 months' seizure freedom; withdrawal due to intolerable side-effects; lack of efficacy despite adequate dosing). Twelve month seizure-free rates were identical (47%) in the VPA (n=111) and LTG (n=114) treatment arms. More patients taking VPA withdrew from the study due to adverse events (26 VPA versus 15 LTG; p=0.046). Eight patients, all taking VPA, dropped out during the first 6 months due to weight gain. There were no changes in mean serum concentrations of testosterone, sex-hormone binding globulin and androstenedione or in the free androgen index after 6 or 12 months' treatment with either drug in 112 patients who fulfilled the criteria for hormone analysis. No difference in efficacy was found between VPA and LTG in our patients with newly diagnosed epilepsy. LTG appeared to be better tolerated. Neither drug appeared to alter the circulating levels of androgenic hormones.