Investigating the Neuroprotective Effect of Oral Omega-3 Fatty Acid Supplementation in Type 1 Diabetes (nPROOFS1): A Randomized Placebo-Controlled Trial.

This randomized, double-masked, placebo-controlled trial evaluated the effects of oral omega-3 (n-3) fatty acid supplementation on peripheral nerves in type 1 diabetes. Participants with type 1 diabetes were assigned (1:1) to n-3 (1,800 mg/day fish oil) or placebo (600 mg/day olive oil) supplements for 180 days. The primary outcome was change from baseline in central corneal nerve fiber length (CNFL) at day 180. Secondary outcomes included change in other corneal nerve parameters, corneal sensitivity, peripheral small and large nerve fiber function, and ocular surface measures. Efficacy was analyzed according to the intention-to-treat principle. Safety assessments included diabetic retinopathy grade and adverse events. Between July 2017 and September 2019, 43 participants received n-3 (n = 21) or placebo (n = 22) supplements. All participants, except for two assigned to placebo, completed the trial. At day 180, the estimated increase in CNFL in the n-3 group, compared with placebo, was 2.70 mm/mm2 (95% CI 1.64, 3.75). The Omega-3 Index increased relative to placebo (3.3% [95% CI 2.4, 4.2]). There were no differences in most small or large nerve fiber functional parameters. Adverse events were similar between groups. In conclusion, we found in this randomized controlled trial that long-chain n-3 supplements impart corneal neuroregenerative effects in type 1 diabetes, indicating a role in modulating peripheral nerve health.

Corneal Epithelial Dendritic Cell Response as a Putative Marker of Neuro-inflammation in Small Fiber Neuropathy.

We report a case of a 41-year old female with systemic lupus erythematosus and Sjögren's syndrome, who developed symptoms of painful small fiber neuropathy (SFN). Examination using in vivo confocal microscopy (IVCM) revealed dense accumulations of putative dendritic cells in the central cornea that was postulated to represent a peripheral neuro-inflammatory response. Interventions with higher dose prednisolone, and then intravenous immunoglobulin resulted in substantial, progressive improvements in her symptoms, which were paralleled by cumulative reductions in corneal dendritic cell density (DCD). This case identifies corneal DCD as a potential non-invasive marker of symptomatic SFN due to inflammatory causes.

Assessment of the relationship between hypoglycaemia awareness and autonomic function following islet cell/pancreas transplantation.

BACKGROUND: This study assesses the autonomic function of patients who have regained awareness of hypoglycaemia following islet cell or whole pancreas transplant. METHODS: Five patients with type 1 diabetes and either islet cell (four patients) or whole pancreas (one patient) transplant were assessed. These patients were age-matched and gender-matched to five patients with type 1 diabetes without transplant and preserved hypoglycaemia awareness and five healthy control participants without diabetes. All participants underwent (i) a battery of five cardiovascular autonomic function tests, (ii) quantitative sudomotor axonal reflex testing, and (iii) sympathetic skin response testing. RESULTS: Total recorded hypoglycaemia episodes per month fell from 76 pre-transplant to 13 at 0- to 3-month post-transplant (83% reduction). The percentage of hypoglycaemia episodes that patients were unaware of decreased from 97 to 69% at 0-3 months (p < 0.001, Fisher's exact test) and to 20% after 12 months (p < 0.0001, Fisher's exact test). This amelioration was maintained at the time of testing (mean time: 4.1 years later, range: 2-6 years). Presence of significant autonomic neuropathy was seen in all five transplanted patients (at least 2/3 above modalities abnormal) but in only one of the patients with diabetes without transplantation. CONCLUSIONS: The long-term maintenance of hypoglycaemia awareness that returns after islet cell/pancreas transplantation in patients with diabetes is not prevented by significant autonomic neuropathy and is better accounted for by other factors such as reversal of hypoglycaemia-associated autonomic failure.

Fibular motor nerve conduction studies: Investigating the mechanism for compound muscle action potential amplitude drop with proximal stimulation.

INTRODUCTION: The compound muscle action potential (CMAP) amplitude of extensor digitorum brevis can show a drop with proximal stimulation in normal fibular nerves. METHODS: We assessed the contribution of the far-field potential recorded by the reference electrode (R-CMAP) to the fibular CMAP. Negative R-CMAP amplitude, peak-to-peak amplitude, and negative area were measured and correlated with the amplitude decrease. Fibular motor nerves from 14 healthy participants were studied. RESULTS: The mean CMAP amplitude drop with proximal stimulation was 14.0 ± 9.3%, including a >30% reduction in 1 study. All measured R-CMAP parameters correlated with the degree of amplitude drop. CONCLUSIONS: A greater R-CMAP contribution to the fibular CMAP leads to greater phase cancellation and temporal dispersion. The resulting amplitude drop seen in the proximal CMAP can be large enough to be classified incorrectly as "probable conduction block" by several different diagnostic criteria.

Exercise-induced seizures and lateral asymmetry in patients with temporal lobe epilepsy.

OBJECTIVE: The objective of this case report is to better characterize the clinical features and potential pathophysiological mechanisms of exercise-induced seizures. METHODS: We report a case series of ten patients from a tertiary epilepsy center, where a clear history was obtained of physical exercise as a reproducible trigger for seizures. RESULTS: The precipitating type of exercise was quite specific for each patient, and various forms of exercise are described including running, swimming, playing netball, dancing, cycling, weight lifting, and martial arts. The level of physical exertion also correlated with the likelihood of seizure occurrence. All ten patients had temporal lobe abnormalities, with nine of the ten patients having isolated temporal lobe epilepsies, as supported by seizure semiology, EEG recordings, and both structural and functional imaging. Nine of the ten patients had seizures that were lateralized to the left (dominant) hemisphere. Five patients underwent surgical resection, with no successful long-term postoperative outcomes. CONCLUSIONS: Exercise may be an underrecognized form of reflex epilepsy, which tended to be refractory to both medical and surgical interventions in our patients. Almost all patients in our cohort had seizures localizing to the left temporal lobe. We discuss potential mechanisms by which exercise may precipitate seizures, and its relevance regarding our understanding of temporal lobe epilepsy and lateralization of seizures. Recognition of, as well as advice regarding avoidance of, known triggers forms an important part of management of these patients.

Evaluating the use of prolonged video-EEG monitoring to assess future seizure risk and fitness to drive.

OBJECTIVE: The use of prolonged video-electroencephalography monitoring (VEM), rather than routine electroencephalography (EEG), in predicting the risk of future seizures in patients with epilepsy is not well studied. A longer period of monitoring could be more likely to capture either ictal or interictal epileptiform activity. This information may better assist clinical decision making on driving fitness. The goal of this study was to evaluate the use of 6-hour prolonged VEM versus routine EEG in the assessment of future seizure risk and driving fitness for patients with epilepsy. METHODS: Data on consecutive patients referred for 6-hour prolonged VEM were retrospectively analyzed. Criteria were developed that combined EEG findings and clinical factors to determine each patient's fitness to drive. Seizure relapse outcomes were followed over 2 years. RESULTS: Of 34 patients, 27 were considered safe to drive following prolonged VEM. Five (19%) of these 27 patients had seizure relapses; all had an obvious precipitant(s) identified including sleep deprivation, excessive alcohol, and missed medication doses. Seven of the 34 patients were deemed unsafe to drive. All seven (100%) had seizure relapses, with unprovoked seizures in four patients. The relative risk of seizure in patients deemed unfit to drive was 5.4 (P=0.00015). If only the routine EEG component of the recordings were used with the criteria, the relative risk would have been 3.4 (P=0.037), with nearly double the number of active drivers having seizures. The majority of patients (76%) in this study had idiopathic generalized epilepsy, with a relative seizure risk of 4.0 (P=0.002) for patients deemed unfit to drive in this subgroup. The focal epilepsy group was small (eight patients) and did not quite achieve statistical significance. CONCLUSION: Six-hour VEM improves the evaluation of driving fitness by better predicting the risk of subsequent seizure relapse for idiopathic generalized epilepsy and possibly focal epilepsy. Prolonged monitoring is superior to routine EEG. Ongoing avoidance of seizure-provoking factors remains paramount to driving safety.

Severe and disabling constipation: an adverse effect of pregabalin.

The incidence of constipation as an adverse effect of pregabalin has previously been reported as low, with all cases described as either mild or moderate. From the experience of a tertiary referral epilepsy hospital center, we report several cases of severe and disabling constipation after initiating pregabalin, and resolving only on drug withdrawal. Of 80 consecutive patients, six (7.5%) developed significant constipation within 1-2 weeks of commencing pregabalin. Constipation was the most frequent adverse effect that required pregabalin to be withdrawn (6.3% of patients). The severity of symptoms was dose dependent. Pregabalin can cause marked constipation in some patients, and can lead to multiple unnecessary investigations and procedures if the clinician is not aware of this entirely reversible side effect.