Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. METHODS: This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. RESULTS: Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. CONCLUSIONS: The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation.

Epidemiology of aquaporin-4-IgG-positive NMOSD in Sardinia.

PURPOSE: The Italian Island of Sardinia (population, 1,578,146) is recognized for the high risk of multiple sclerosis (MS) but the epidemiological burden of other less common demyelinating diseases of the central nervous system (CNS), such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD), is unknown. In this study, we determined the incidence and prevalence of AQP4-IgG+NMOSD in Sardinia over a ten-year study period (2013-2022). METHODS: Patients with a diagnosis of AQP4-IgG+NMOSD (per 2015 IPND diagnostic criteria) were retrospectively identified using two sources: (1) Archives of the reference and only laboratory for AQP4-IgG testing in Sardinia; and (2) medical records of the four MS units in the island. Incidence (January 2013-December 2022) and prevalence (December 31, 2022) were calculated. RESULTS: A total of 45 cases were included: incident, 31; prevalent, 41. The median age (range) at disease presentation was 51 (6-78) years; female/male ratio was 9:1. The crude (95 % CI) incidence and prevalence were 1.9 (1.3-2.7) per million and 2.6 (1.9-3.5) per 100,000, respectively. Prevalence increased from 2013 (1.1 per 100,000) to 2022 (2.6 per 100,000); p = 0.002. After age-standardization to the world, incidence and prevalence (95 % CI) decreased to 1.3 (0.7-2) per million and 1.8 (1.3-2.3) per 100,000, respectively. Coexisting immune-mediated disorders, mostly autoimmune thyroiditis, were reported in 50 % of patients. CONCLUSIONS: The epidemiology of AQP4-IgG+NMOSD in Sardinia is overall in line with other Caucasian populations. The high MS risk in the island seems disease-specific and not associated with an increased risk of other CNS demyelinating disorders, confirming different pathophysiology.

Percutaneous Endoscopic Transgastric Jejunostomy (PEG-J) Tube Placement for Levodopa-Carbidopa Intrajejunal Gel Therapy in the Interventional Radiology Suite: A Long-term Follow-up.

BACKGROUND: Percutaneous endoscopic gastrojejunostomy (PEG) and radiologically inserted gastrojejunostomy (RIG) are both safe and effective techniques for gastrojejunal tube placement. The authors compared these 2 procedures in patients with advanced Parkinson's disease (PD) who required the continuous intrajejunal delivery of a levodopa/carbidopa gel suspension (LCIG). METHODS: Outcomes were retrospectively collated from 30 PEG and 12 RIG procedures performed at 2 centers in patients with advanced PD for the delivery of LCIG. RESULTS: Baseline clinical characteristics, incidence of early severe adverse events, late major complications, dropout, and the mean time-lapse of tube replacements were comparable in the PEG and RIG groups. CONCLUSION: The current results suggest that, in patients with PD, the RIG technique is as safe and effective as the endoscopic procedure, and it can be considered a valid option for patients who require LCIG when the endoscopic procedure is not available or unfeasible.

Posterior Reversible Encephalopathy Syndrome with Bilateral Independent Epileptic Foci Precipitated By Guillain-Barrè Syndrome.

We report the case of a 56-year-old woman who developed status epilepticus (SE) related to independent occipital foci as clinical manifestation of posterior reversible encephalopathy syndrome (PRES) in the background of Guillain-Barrè syndrome (GBS). SE resulted from a series of focal seizures clinically characterized by left- and rightward deviations of the head and consequent oculoclonic movements. Electroencephalography recorded independent seizure activity in both occipital regions with alternate involvement of the two cerebral hemispheres. The epileptic foci corresponded topographically to parenchymal abnormalities of PRES in the occipital lobes. The manifestation of bilateral, independent occipital seizures with alternate deviations of the head and oculoclonic movements, previously not reported in patients with PRES, highlights the acute epileptogenicity of the cerebral lesions in this syndrome. Despite the variable clinical expression of seizures due to occipital damage in PRES, the development of independent seizure activity in both occipital lobes might represent a distinctive epileptic phenomenon of this encephalopathy.

Partial status epilepticus related to independent occipital foci in posterior reversible encephalopathy syndrome (PRES).

Posterior reversible encephalopathy syndrome (PRES) is an acute disorder characterised by a variable association of neurologic symptoms with potentially reversible oedematous abnormalities mainly in the parieto-occipital regions of the brain. Despite the significant incidence of seizures, the EEG characteristics of epileptic disorders related to PRES have rarely been investigated. We report the case of an 85-year-old man who presented with generalised tonic-clonic seizures and prolonged disturbances of consciousness as clinical manifestations of PRES due to moderate exacerbation of chronic hypertension. An EEG performed during an alteration of mental function displayed a pattern of partial status epilepticus (SE) in both temporo-parieto-occipital regions. The seizure activity originated from two independent epileptic foci located in the occipital area of each hemisphere and could be related to the parenchymal abnormalities of PRES. The EEG pattern of partial SE related to independent occipital foci illustrates a distinctive seizure disorder that could be characteristic of PRES in adult patients.