Economic evaluation of subcutaneous versus intravenous immunoglobulin therapy in chronic inflammatory demyelinating polyneuropathy: a real-life study.

OBJECTIVES: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired peripheral neuropathy of immunological origin with a clinical presentation and course that are extremely variable. The therapeutic approach generally includes corticosteroid drugs, intravenous immunoglobulins (IVIGs) or plasmapheresis alone or in combination as first line therapy, and immunosuppressants. In 2014 the Italian regulatory agency included subcutaneous immunoglobulins (SCIGs) in the list of off-label drugs reimbursed by the national health service. Our aim is to compare costs and outcomes of IVIG versus SCIG therapy. METHODS: Patients medical records and therapeutic plans were retrospectively analysed to collect data on IVIG treatments 1 year before the switch to SCIG, and after 1 year of treatment with SCIG. A budget impact analysis was conducted through resource identification and quantification, and healthcare and non-health care costs evaluation. RESULTS: 13 of 34 patients affected by CIDP who were referred to our neurophysiopathological unit and treated with IVIG were switched to home-based SCIG. After 1 year of receiving SCIG, 12 patients remained neurologically stable and reported good outcomes. Considering the cost of IVIG (€30.97/g) and adding to this the direct and indirect healthcare costs, the total cost of IVIG treatment for the 12 patients in a year was €371 417.06, compared with the cost of SCIG (€51.57/g) for a total annual cost of €631 745.16, not including indirect costs. CONCLUSIONS: We observe a higher cost for SCIG treatment versus IVIG, which is not in line with data in the literature. However, SCIGs offer some important safety benefits and improvements in patient quality of life.

Dynamic transperineal ultrasonography correlates with prolonged pudendal nerve latency in female with fecal incontinence.

The pelvic floor is a complex anatomical entity and its neuromuscular assessment is evaluated through debated neurophysiological tests. An innovative approach is the study of pelvic floor through dynamic transperineal ultrasound (DTU). The aim of this study is to evaluate DTU sensitivity in recognizing patients with fecal incontinence and to evaluate its concordance with the results of the motor latency studied via pudendal nerve terminal motor latency (PNTML). Female patients affected by FI addressed to our center of coloproctology were prospectively assessed. After a coloproctological evaluation, comprising the PNTML assessment to identify pudendal neuropathy, patients were addressed to DTU to determine anterior and posterior displacement of puborectalis muscle by a blinded coloproctologist. In order to compare the data, a cohort of female healthy volunteers was enrolled. Sixty-eight subjects (34 patients and 34 healthy volunteers) were enrolled. The sensitivities of anterior displacement, posterior displacement and either anterior or posterior displacement in determining the fecal incontinence were 82%, 67% and 91%, respectively. A further high correlation of either anterior or posterior displacement with PTNML was also noted (88%). DTU is an indirect, painless and reproducible method for the identification of the pelvic floor neuromuscular integrity. Its findings seem to highly correlate with FI symptoms and with PNTML results. In the near future, after larger comparative studies, DTU would be considered a potential reliable non-invasive and feasible indirect procedure in the identification of fecal incontinence by pudendal neuropathy. Trial registration number is NCT03933683.

Vacuolated PAS-positive lymphocytes as an hallmark of Pompe disease and other myopathies related to impaired autophagy.

Autosomal recessive Pompe disease is a lysosomal disorder caused by mutations of the acid-α-glucosidase (GAA) gene. Deficiency of GAA enzyme leads to glycogen accumulation and autophagy impairment in cardiac and skeletal muscles, but also in lymphocytes. Since an effective therapy is available, a rapid, sensitive, and specific test is crucial to early identify affected subjects. Number of lymphocytes containing PAS-positive vacuoles was evaluated on blood films from 72 consecutive adult patients with hyperckemia and/or muscle weakness, 13 genetically confirmed late-onset-Pompe-disease (LOPD) and 13 of their offspring. GAA activity, measured on dried blood spot (DBS) in all patients inversely correlated with number of PAS-positive lymphocytes. More than 4 PAS-positive lymphocytes were found in 11 out of the 72 patients (6 new diagnosis of LOPD, 3 different glycogen storage myopathies, 1 glucose-6-phosphate dehydrogenase deficiency, 1 caveolinopathy), in all 13 LOPD patients and in the 13 LOPD offspring. These latter resulted to have all a single GAA mutation but low GAA levels. Immunostaining with the autophagy markers LC3 and p62 confirmed the autophagic nature of lymphocytes vacuoles. ROC curve assessment of PAS-positive lymphocytes disclosed 100% of sensitivity and 94% of specificity in recognizing both compound heterozygous and heterozygous GAA carriers. The other myopathies with more than 4 PAS-positive lymphocytes appeared to be all related to impaired autophagy, which seems to be responsible of PAS-positive vacuolated lymphocytes formation. Quantification of PAS-positive lymphocytes in blood films is useful to identify autophagic vacuolar myopathies and should be routinely used as first level test for Pompe disease.

Diagnostic contribution of magnetic resonance imaging in an atypical presentation of motor neuron disease.

Motor neuron disease (MND) is a neurodegenerative disease determining progressive and relentless motor deterioration involving both upper and lower motor neurons (UMN and LMN); several variants at onset are described. Here we describe a case of MND presenting as pure spastic monoparesis in which magnetic resonance imaging (MRI) gave a substantial contribution in confirming the diagnosis and assessing the severity of UMN involvement. An isolated pyramidal syndrome, with complete absence of LMN signs, is a rare phenotype in the context of MND (less than 4% of total cases), especially if restricted to only one limb. Several other elements made this case an unusual presentation of MND: the late age of onset (8th decade), the subacute evolution of symptoms (raising the suspicion of an ischemic or inflammatory, rather than degenerative, etiology), the patient's past medical history (achalasia, erythema nodosum), the increase of inflammatory indices. Conventional MRI showed no focal lesions that could explain the clinical features; therefore, we used advanced MR sequences. Diffusion tensor imaging (DTI) evaluation evidenced bilateral impairment of corticospinal tract (CST) diffusion metrics, with clear right-left asymmetry, pointing to a neurodegenerative etiology, which clinically appeared less likely at that time. Magnetic resonance spectroscopy (MRS) showed a significant reduction of NAA/Cho + Cr ratio in the motor cortex (MC), further supporting the hypothesis of UMN degeneration. In conclusion, in this particular case of MND, whose nosographic framing has not been fully defined, advanced MRI techniques with DTI and MRS proved to be of great usefulness in confirming a diffuse UMN involvement, possibly at a more advanced stage than its clinical expression.

Chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: treatment update.

PURPOSE OF REVIEW: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy usually respond to immune therapies including steroids and plasma exchange for CIDP and high-dose intravenous immunoglobulins (IVIgs) for both diseases. Other immune therapies have been used to reduce the costs or the side-effects of these therapies, but their efficacy was only recently assessed in randomized controlled trials (RCTs). RECENT FINDINGS: The prolonged efficacy of IVIg in CIDP has been confirmed in a 48-week RCT. Two other RCTs showed that oral methotrexate or intramuscular interferon beta were not more effective than placebo in improving the efficacy or reducing the dose of IVIg or steroids. In multifocal motor neuropathy, a RCT showed that oral mycophenolate mofetil was not more effective than placebo in increasing the efficacy or reducing the dose of IVIg. Other immune therapies were assessed in open trials in both diseases, but their efficacy remains unclear, even if in some patients a possible efficacy of rituximab was reported. Some preliminary studies suggest that subcutaneous immunoglobulin may be as effective as IVIg in the maintenance therapy of CIDP and multifocal motor neuropathy. SUMMARY: After several years of anecdotal reports, a number of RCT have now appeared in CIDP and multifocal motor neuropathy, but their results are still insufficient to support the use of new therapies in these diseases.