Levodopa-Carbidopa-Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience.

BACKGROUND: For Parkinson disease (PD) patients who have been diagnosed with advanced disease that can no longer be effectively controlled with optimized oral or transdermal medications, a range of device-aided therapies (DAT) are available, comprising either deep brain stimulation or infusion therapies providing continuous dopaminergic stimulation. Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is the latest DAT for advanced PD (APD) that was approved in Romania in 2021. STUDY QUESTION: What is the experience to date in real-world clinical practice in Romania regarding the efficacy and tolerability of LECIG in APD? STUDY DESIGN: A retrospective evaluation of 74 APD patients treated with LECIG at 12 specialized APD centers in Romania. MEASURES AND OUTCOMES: Demographic data and various clinical parameters were recorded, including Mini Mental State Evaluation score or Montreal Cognitive Assessment Test score. Levodopa-equivalent daily dose and the administered doses of levodopa and other PD medications were evaluated at baseline and after starting LECIG treatment. The efficacy of LECIG in reducing daily hours of off time, motor fluctuations, and dyskinesias were assessed. Any percutaneous endoscopic gastrojejunostomy system or device complications after starting LECIG treatment were noted. RESULTS: At baseline, patients were taking oral levodopa for a mean of 5.3 times per day, with a high proportion also taking concomitant add-on therapies (dopamine agonists, 86%, monoamine oxidase type-B inhibitors, 53%; catechol-O-methyltransferase inhibitors, 64%). LECIG treatment significantly reduced daily off time versus baseline from 5.7 h/d to 1.7 hours per day ( P < 0.01). Duration and severity of dyskinesias was also significantly reduced versus baseline, and improvements were observed in Hoehn and Yahr Scale scores. LECIG treatment also allowed a significant reduction in the use of concomitant oral medications. CONCLUSIONS: These findings suggest that LECIG treatment is an effective DAT option in APD that can simplify the treatment regimen.

Low Fluctuation of Symptoms May Delay Diagnosis of Myasthenia Gravis: A Case Series.

INTRODUCTION: Myasthenia gravis is an autoimmune disorder affecting neuromuscular transmission, and its hallmark is fluctuating muscular weakness affecting the ocular, bulbar, respiratory, or limb muscles. Our objective is to highlight the difficulties encountered in diagnosing this disorder in patients lacking this characteristic phenomenon. METHODS: Three cases of patients presenting with progressive weakness of bulbar and ocular muscles, in whom a lack of fluctuation delayed the diagnosis of myasthenia gravis, are described. RESULTS: Amyotrophic lateral sclerosis was considered in two of the patients, while cavernous sinus thrombosis was initially diagnosed in the third. Electrodiagnostic, pharmacologic, and serologic testing ultimately established the diagnosis of myasthenia gravis. CONCLUSION: While the typical clinical pattern of myasthenia gravis is well known and easily recognizable, there are cases when the diagnosis, and thus the treatment, is delayed because of low or absent fluctuation of symptoms. The acknowledgment of this probably underestimated presentation is important for expeditious management.

Anticoagulation-refractory strokes and selective infarction pattern: What's the link?

Stroke etiology in the form of a CAP should be actively explored, especially in the context of previous negative work-up and anticoagulant-refractory strokes. Dual antiplatelet therapy proved superior to anticoagulation for secondary prevention.

Clinical characteristics in patients with hereditary amyloidosis with Glu54Gln transthyretin identified in the Romanian population.

BACKGROUND: In Romania, 23 patients have been diagnosed with hereditary transthyretin amyloidosis (ATTRh), 18 of whom have the Glu54Gln mutation. This retrospective cohort included all patients with Glu54Gln-mutated ATTRh who were diagnosed in Romania from 2005 to 2018. RESULTS: Of 18 patients, 10 were symptomatic, five were asymptomatic carriers and three died during the study. All originated from North-East Romania. Median age at symptom onset was 45 years; median age at death was 51 years. All patients had cardiac involvement, including changes in biomarkers (mean N-terminal-pro B-type natriuretic peptide: 2815.6 pg/ml), electrocardiography (15% atrial fibrillation, 38% atrioventricular block, 31% right bundle block), and echocardiography (mean interventricular septum: 16 mm, mean left ventricular ejection fraction: 49%). Scintigraphy showed myocardial radiotracer uptake in all patients. In addition, 92% of patients had polyneuropathy at diagnosis and 53% had carpal tunnel syndrome; 69% exhibited orthostatic hypotension and 31% suffered from diarrhea. No renal or liver involvement was observed. CONCLUSIONS: This is the largest Glu54Gln-mutated ATTRh cohort diagnosed to date, and to our knowledge the first describing this variant worldwide. Clinical features of this variant are early onset, neurological and cardiac involvement, aggressive disease progression and short survival. Early diagnosis and therapeutic intervention have potential to improve prognosis in ATTRh.

Opsoclonus-Myoclonus Syndrome Associated With West-Nile Virus Infection: Case Report and Review of the Literature.

Opsoclonus-myoclonus syndrome (OMS) is a very rare condition with different autoimmune, infectious and paraneoplastic aetiologies or in most cases idiopathic. We report the case of a 75-year-old woman who was admitted in our department in early fall for altered mental status, opsoclonus, multifocal myoclonus, truncal titubation and generalized tremor, preceded by a 5 day prodrome consisting of malaise, nausea, fever and vomiting. Brain computed tomography and MRI scans showed no significant abnormalities and cerebrospinal fluid changes consisted of mildly increased protein content and number of white cells. Work-up for paraneoplastic and autoimmune causes of OMS was negative but serologic tests identified positive IgM and IgG antibodies against West Nile virus (WNV). The patient was treated with Dexamethasone and Clonazepam with progressive improvement of mental status, myoclonus, opsoclonus and associated neurologic signs. Six months after the acute illness she had complete recovery. To our knowledge this is the 14th case of WNV associated OMS reported in the literature so far. We briefly describe the clinical course of the other reported cases together with the different treatment strategies that have been employed.

Duodopa infusion treatment: a point of view from the gastroenterologist.

In patients with advanced Parkinson's disease, the continuous delivery to the small intestine via a jejunal tube of levodopa/carbidopa, formulated as a gel suspension (Duodopa) represents a new treatment method. The continuous release results in less variability in levodopa concentrations and fewer motor fluctuations and dyskinesias than with oral administration. The method which requires a very good collaboration between the neurologist and the gastroenterologist is used with increasing frequency in selected centres especially in severe patients. First, a classic PEG gastrostomy kit is placed under propofol sedation. This allows the passage of a pig tail catheter which is deployed in the jejunum and it is attached to a portable pump via a special tubing system. We present our experience of seven cases (5 males, mean age 60 years) with a follow up of one year. One patient died due to respiratory failure and aspiration pneumonia probably related to the endoscopic procedure. At one year, all patients agreed that the neurological benefit offsets the procedure related problems and the technical issues related to the enteral infusion system.

Cutting the Gordian knot: the blockage of the jejunal tube, a rare complication of Duodopa infusion treatment.

We present the case of a 21-year-old man with advanced refractory Parkinson's disease treated with Duodopa continuous infusion. With this therapy, the patient had a spectacular recovery but after six months, he experienced an aggravation of his symptoms. A failure of his pumping system was suspected but we discovered that the jejunal tube was blocked due to a knot around a bezoar. This is the first complication of this kind described with the Duodopa infusion technique.

An immunological approach to cerebral ischemia (I). Immune cells and adhesion molecules.

Ischemic stoke is a major cause of death and an important source of disability in industrialized countries. Since there is no ideal treatment for cerebral ischemia, any approach aiming to limit the devastating consequences of the ischemic process is justified. Concerning immune responses, it has become clear in the latest years that actors of the immune system are involved in multiple and various neurobiological processes such as cerebral ischemia, neurodegeneration, neuroprotection and neuroregeneration. An immunological approach to cerebral ischemia can distinguish, besides the implication of inflammation in the developing of atherothrombosis thus leading to stroke, the clear involvement of immune cells and mediators in processes continuing the initial stage of ischemia, having consequences on recovery or lesion extent. Cerebral infarctions develop within minutes to hours of cessation of the cerebral blood flow, but may expand over subsequent days. There is increasing evidence that leukocytes, cytokines, cell adhesion molecules, and other immune mediators contribute to secondary infarction growth, but inflammatory cytokines are also involved in signaling pathways leading to neuroprotection related to ischemic pre-conditioning. The aim of this review is to show some aspects concerning the complex and diverse functions of immune modifications occurring in cerebral ischemia. This first part will focus on the involvement of immune cells, adhesion molecules and immunological transcription factors in the development of ischemic lesion.

Antiphospholipid antibodies and migraine: a retrospective study of 428 patients with inflammatory connective tissue diseases.

The antiphospholipid syndrome (APS) is defined by the presence of antiphospholipid antibodies (aPL), associated with thrombosis or recurrent spontaneous abortions. APS can occur alone or secondary to other conditions, especially associated to inflammatory systemic autoimmune diseases. Among the neurological manifestations associated with aPL, only ischemic stroke is recognized by the actual classification criteria for APS. Other neurological manifestations have been, however, repeatedly reported in case studies of APS patients. Headache, and especially migraine, was commonly reported in APS patients and is one of the classical features described by Hughes as related to aPL, but studies failed to confirm this association. We studied retrospectively the association between headache syndromes and aPL in 428 patients with inflammatory connective tissue diseases admitted in the Neurology and Internal Medicine Departments of Colentina Hospital-Bucharest. We found that migraine alone, not headache of all types, is significantly associated with aPL in patients with systemic immune disease. We studied the presence of cerebral ischemia in patients with headache and aPL. In SLE patients, headache (all types) is significantly associated with positive titers of aPL, and cerebral ischemic lesions are significantly encountered. Even if both migraine and aPL are conditions with high frequency in patients with immune systemic disease and their association may be coincidental, the presence of ischemic lesions in patients showing this association suggests the need to define a sub-group at risk, for whom headache can be a marker and anticoagulants can be discussed.