Digital health and Clinical Patient Management System (CPMS) platform utility for data sharing of neuromuscular patients: the Italian EURO-NMD experience.

BACKGROUND: The development of e-health technologies for teleconsultation and exchange of knowledge is one of the core purposes of European Reference Networks (ERNs), including the ERN EURO-NMD for rare neuromuscular diseases. Within ERNs, the Clinical Patient Management System (CPMS) is a web-based platform that seeks to boost active collaboration within and across the network, implementing data sharing. Through CPMS, it is possible to both discuss patient cases and to make patients' data available for registries and databases in a secure way. In this view, CPMS may be considered a sort of a temporary storage for patients' data and an effective tool for data sharing; it facilitates specialists' consultation since rare diseases (RDs) require multidisciplinary skills, specific, and outstanding clinical experience. Following European Union (EU) recommendation, and to promote the use of CPMS platform among EURO-NMD members, a twelve-month pilot project was set up to train the 15 Italian Health Care Providers (HCPs). In this paper, we report the structure, methods, and results of the teaching course, showing that tailored, ERN-oriented, training can significantly enhance the profitable use of the CPMS. RESULTS: Throughout the training course, 45 professionals learned how to use the many features of the CPMS, eventually opening 98 panels of discussion-amounting to 82% of the total panels included in the EURO-NMD. Since clinical, genetic, diagnostic, and therapeutic data of patients can be securely stored within the platform, we also highlight the importance of this platform as an effective tool to discuss and share clinical cases, in order to ease both case solving and data storing. CONCLUSIONS: In this paper, we discuss how similar course could help implementing the use of the platform, highlighting strengths and weaknesses of e-health for ERNs. The expected result is the creation of a "map" of neuromuscular patients across Europe that might be improved by a wider use of CPMS.

Pimozide and pancreatic cancer in diabetic chorea: a case report.

PURPOSE/AIM: Diabetic chorea is a rare movement disorder associated with diabetes mellitus. We report the case of a patient that benefited from pimozide and died of pancreatic cancer. CASE REPORT: A 70-year-old woman presented with pollakiuria and involuntary movements of left limbs since three months. Laboratory tests revealed high serum levels of glycemia and glycated haemoglobin. She was admitted to internal medicine department and discharged one week later: insulin was administered with normalization of blood glucose levels and the involuntary movements gradually disappeared. Three weeks later she was admitted to neurological department due to the recurrence of the involuntary movements. Glycemia and other routine laboratory tests were normal. Neurological examination showed choreic movements involving left limbs. MRI showed a hyperintensity on T1- and T2-weighted sequences of right putamen and caudate nucleus head. Haloperidol was administered without improvement, it was successively substituted with tetrabenazine and the patient was discharged with an unvaried clinical picture. Two months later tetrabenazine was discontinued because of inefficacy and pimozide was started. The choreic movements considerably diminished after few days. Four months later, a pancreatic cancer was diagnosed and the patient died in the same month. CONCLUSION: Clinical and radiological features were suggestive of diabetic chorea. Our patient benefited exclusively from pimozide, it could be reasonable to use pimozide in resistant form and also propose it as first choice treatment. Another important element is the diagnosis of pancreatic cancer some months after chorea onset: a causal link could exist.

Methotrexate as a Steroid-Sparing Agent in Myasthenia Gravis: A Preliminary Retrospective Study.

OBJECTIVES: Treatment approach of myasthenia gravis (MG) is still debated; corticosteroids alone or in combination with immunosuppressive agents are the most used drugs. Azathioprine (AZA) has been shown to be effective for MG with a significant steroid-sparing activity, although burdened by side effects. Few studies on methotrexate (MTX) administration showed controversial results. In this cohort, we evaluated the role of MTX as a effective steroid-sparing agent. METHODS: Fifteen MG patients treated with MTX, previously treated with AZA for at least 12 months, with poor benefits and uncomfortable side effects AZA related, have been selected. Each patient was evaluated through MG-Activity of Daily Living and Quantitative MG scores 5 times/yr. RESULTS: Patients treated with MTX had a significant improvement of MG-Activity of Daily Living and Quantitative MG scores. Furthermore, all patients reduced prednisone dosage, and none complained of side effects. CONCLUSIONS: We suggest MTX is effective and well tolerated and could be considered as a steroid-sparing agent in MG treatment.

Benefit and danger from immunotherapy in myasthenia gravis.

In the last years, significant advances have improved the knowledge of myasthenia gravis (MG) immunopathogenesis and have enabled to realize new molecules with a selective action targeting compounds of the immunological system. This review discusses emerging treatments for MG, including complement inhibitors, neonatal Fc receptor targeting agents, and B cell interfering drugs, focusing on benefit and danger. In the second section of the review, several related adverse events of immunotherapy, including MGonset, are debated.

Endocrine myopathies: clinical and histopathological features of the major forms.

Endocrinopathies, such as thyroid and parathyroid diseases, disorders of the adrenal axis, and acromegaly are included among the many causes of myopathy. Muscle disturbances caused by endocrine disorders are mainly due to alterations in the protein and carbohydrate metabolisms. Either a deficiency or excess of hormones produced by the glands can cause muscle dysfunction that can be reversed by starting hormone replacement therapy or acting on hormone dysfunction. The diagnosis is usually easy if a muscle disorder occurs in an overt endocrinopathy; however, in few patients, myopathy could be the first manifestation of the underlying endocrinopathy. In this article we discuss pathophysiology, clinical features and management of muscle involvement related to the major endocrine diseases.

Effect of exercise on telomere length and telomere proteins expression in mdx mice.

In Duchenne muscular dystrophy (DMD), telomere shortening has been postulated to contribute to the failure of regenerative activity promoting the premature senescence of satellite cells. The aim of the present study was to investigate the telomere length and the expression of telomeric repeat-binding factor-1 (TRF1), poly (ADP-ribose) polymerase-1 (PARP1) and mouse telomerase reverse transcriptase (MTERT) in gastrocnemius, tibialis anterior and diaphragm muscles of the murine model of DMD, the mdx mouse and whether a chronic protocol of forced exercise impacts on them. Our results confirmed a telomere shortening in mdx muscles, more evident in the diaphragm, in which exercise induced a greater shortening than in wild-type mice. Moreover, we showed for the first time in mdx an increased TRF1 and PARP1 expression and an augmented activity of MTERT, further enhanced by exercise. These results reinforce the hypothesis that a deregulation of mechanisms involved in telomere length occurs and may pave the way for the test of compounds targeting proteins modulating telomere maintenance as a novel strategy to treat dystrophinopathies.

Myasthenia gravis after etanercept and ustekinumab treatment for psoriatic arthritis: A case report.

A 35-year-old man was diagnosed with psoriatic arthritis treated with methotrexate and cyclosporine, the latter was then interrupted. Subsequently, etanercept was introduced, administered for 10 years and then replaced with ustekinumab. Six months after treatment with ustekinumab, patient underwent a chest CT scan for pneumonia, showing an anterior mediastinal mass which turned out to be a thymoma. He was referred to our department with fatigue, difficulty in raising arms and transient episodes of diplopia after exertion. Clinical history revealed that these symptoms had begun about 7 years previously but were ascribed to psoriatic arthritis. A diagnosis of anti-acetylcholine receptor antibodies positive myasthenia gravis was made; a higher dosage of methotrexate and prednisone were started with regression of symptoms. Our case increases the number of clinical reports of myasthenia gravis onset in patients with a history of rheumatic disease treated with anti-TNFα drugs. We speculate that ustekinumab could contribute to clinical worsening.