Using Redcap to Support the Development of a Learning Healthcare System for Patients with Multiple Sclerosis.

Multiple Sclerosis is a neurodegenerative disease which shows different phenotypes making difficult for clinicians to make short-term decisions related with treatment and prognosis. Diagnosis is usually retrospective. Learning Healthcare Systems (LHS) can support clinical practice as they are devised as constantly improving modules. LHS can identify insights which allow evidence-based clinical decisions and more accurate prognosis. We are developing a LHS with the aim of reducing uncertainty. We are using ReDCAP to collect patients' data, both from Clinical Reported Outcomes (CRO) and from Patients Reported Outcomes (PRO). Once analyzed, this data will serve as a foundation to our LHS. We conducted bibliographical research to select those CRO and PRO collected in clinical practice or identified as possible risk factors. We designed a data collection and management protocol based on using ReDCAP. We are following a cohort of 300 patients for 18 months. At the moment, we have included 93 patients and received 64 complete responses and 1 partial response. This data will be used to develop a LHS, able to accurate prognosis as well as to automatically include new data and improve its algorithm.

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry.

OBJECTIVE: To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. METHODS: An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. RESULTS: Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. CONCLUSIONS: The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.

Immunological profile of patients with primary progressive multiple sclerosis. Expression of adhesion molecules.

Adhesion molecules are important in the trafficking of peripheral leucocytes into the central nervous system, a major event in the pathogenesis of multiple sclerosis, which is an inflammatory and demyelinating disease. The latest MRI evidence supports clinical divergence between forms of multiple sclerosis with relapses and the primary progressive form without relapses, which shows fewer and smaller inflammatory lesions. With the aim of elucidating whether different pathogenic mechanisms are involved in primary progressive multiple sclerosis, we compared membrane expression of the adhesion molecules ICAM-1 (CD54), LFA-1alpha (CD11a), VLA-4 [alpha(4)/beta(1) integrin (CD49d/CD29)], L-selectin (CD62L) and ICAM-3 (CD50) in peripheral blood and the serum-soluble forms ICAM-1, L-selectin, VCAM-1 and ICAM-3 in 89 patients (39 with the primary progressive form, 25 with the secondary progressive form and 25 with the relapsing-remitting form) and 38 healthy controls. We found a significant decrease in leucocyte surface expression of most of the adhesion molecules tested and an increase in soluble ICAM-1 and L-selectin levels in secondary progressive and relapsing-remitting multiple sclerosis compared with primary progressive multiple sclerosis, which gave results similar to those in controls. These results, which are supported by MRI evidence, show that trafficking of autoreactive leucocytes through the blood-brain barrier is crucial to the pathogenesis of secondary progressive and relapsing-remitting forms of multiple sclerosis, whereas other mechanisms leading to progressive axonal damage would account for primary progressive forms of the disease.

Neurological impairment in alpha-mannosidosis: a longitudinal clinical and MRI study of a brother and sister.

Neurological development over a period of 25 years and MRI findings are reported in two members of the same family affected by mannosidosis type II. Progressive axial and appendicular cerebellar syndrome, moderate hearing loss and deterioration of gait were present in both patients. Neuropsychological deficiency was severe, but progression over the years was not observed except in the woman's speech capacity. Neither of the patients showed clinical improvement. A progressive corticosubcortical atrophy stands out in the brain neuroimaging studies, especially at the vermian cerebellar level. The osseous cranial deformities are very characteristic and include brachycephaly, thickening of the calvaria at the expense of the diploe, and poor pneumatization of the sphenoid. Neither of our cases showed an empty sella turcica.

[Optic neuritis, brain stem syndromes and myelitis: rapid conversion to multiple sclerosis]. / Neuritis óptica, síndromes del tronco y mielitis: conversión temprana a esclerosis múltiple.

BACKGROUND: To establish the early risk of multiple sclerosis (MS) following isolated demyelinating syndromes. PATIENTS AND METHOD: 36 patients with optic neuritis, 24 with brainstem syndromes, 27 with spinal cord syndromes and 8 patients with a poliregional syndrome were included in a prospective protocol: including clinical data, immunological determinations, oligoclonal bands, visual, somestesic and brainstem evoked potentials and a magnetic resonance imaging (MRI) study. RESULTS: MRI showed the presence of signal abnormalities in 70% of the patients. The conversion rate (CR) was 18.5%. In patients with a normal MRI, CR was 4% compared to 26% in patients with an abnormal MRI (p = 0.05). CONCLUSIONS: The early conversion rate to MS is significantly increased when MRI is abnormal.

Low-dose steroids reduce flu-like symptoms at the initiation of IFNbeta-1b in relapsing-remitting MS.

To determine whether low-dose prednisone reduces flu-like symptoms at the initiation of interferon beta 1-b (IFNbeta-1b), we studied 71 patients with clinically definite, relapsing-remitting multiple sclerosis who were started on IFNbeta-1b. Patients were randomized to receive prednisone plus paracetamol or only paracetamol and were monitored for side effects. Systemic side effects were minimal in the steroid group compared with the nonsteroid group during the first 15 days of treatment (p=0.005). At 3 months, both groups showed a similar frequency of flu-like symptoms. No differences in local reaction between the two groups were observed throughout the study.

[Ocular myasthenia: clinical course and strategies for treatment]. / Miastenia ocular: evolución clínica y estrategia terapéutica.

INTRODUCTION: Ocular myasthenia gravis is a localized form of myasthenia in which only the extra-ocular muscles are clinically affected, namely the levator palpebrae superioris and orbicularis oculi. Two years after onset of the ocular condition, it became generalized in 44-53% of the patients. OBJECTIVE: 1. To describe the clinical features, diagnostic characteristics and clinical course of seven patients who fulfilled the criteria for diagnosis of ocular myasthenia and in whom the condition did not become generalized: 2. Review recent papers on this. Material and methods. We studied seven patients (two men and two women) diagnosed as having ocular myasthenia gravis, and followed them up for at least three years. RESULTS: The average age was 56.5. The clinical findings were of ptosis of the eyelids and diplopia. All seven patients were treated with pyridostigmine. In six cases prednisone was also given and in one patient thymectomy was done. There was a satisfactory result in all cases. CONCLUSIONS: The basic treatment of ocular myasthenia is with anticholinesterases and corticosteroids. Occasionally other immunosuppressives may be required. Prednisone seems to reduce the number of patients who go on to develop the generalized form.

[Profile of efficacy and safety in the treatment of remittent-recurrent multiple sclerosis with interferon beta-1b]. / Perfil de eficacia y seguridad en el tratamiento de la esclerosis múltiple remitente-recurrente con interferón beta-1b.

BACKGROUND: Interferon beta 1b (IFN beta-1b) has showed a reduction of exacerbation rate and a decrease in multiple sclerosis activity as evidenced by MRI. After the approval of IFN beta-1b in our country more than 1,000 patients are under treatment, however the experience is limited. The purpose of this study is to describe the clinical results and the tolerance of IFN beta-1b during the postmarketing period in our country. MATERIAL AND METHODS: We studied 95 patients treated with IFN beta-1b. An exhaustive follow-up has been performed in order to assess the tolerance and the efficacy of the drug. We registered the haematological and biochemical abnormalities, secondary effects, relapses, clinical evolution and drop-outs. RESULTS: Mean age was 32.5 +/- 9 years, and the mean follow-up was 13.2 months. Seventy patients (74%) have been followed for more than one year. Haematological abnormalities are frequent, lymphopenia being the most common finding (37%). Flulike symptoms appear in 90% of the patients and skin reaction in the 70%. We have observed a drop-out rate of 7%. One patient developed depressive symptoms and the treatment was temporally discontinued. We have observed a significant decrease in relapses of the disease, however disability has not changed in the first year after treatment. CONCLUSIONS: IFN beta-1b has been well tolerated in the postmarketing period. The profile of secondary effects is similar, although not identical to that reported. The patient awareness of secondary effects and the realistic expectations of the drug are important in order to decrease the drop-out rate.

["Locked-in" syndrome due to hyperglycemia]. / Síndrome de cautiverio por hipoglucemia.

INTRODUCTION: Hypoglycemia can cause a diffuse brain malfunction and sometimes a focal neurological deficiency, that could lead to a mistaken diagnosis of cerebrovascular disease. CLINICAL CASE: We describe the case of a 67 year old man, with diabetes mellitus type II treated with glibenclamide, that was referred to our hospital due to worsening of his chronic obstructive pulmonary disease. On the fifth day following admission he developed acute weakness in the right extremities and experienced difficulty in talking: six hours later he was conscious, with normal eye movements, but there was an absence of spontaneous facial motility and to pain; he showed complete cuadraplegia and bilateral Babinski. A determination of glycemia was made with the result of 24 mg/dl; after immediate treatment with glucose solution intravenously the patient recovered in a few minutes. CONCLUSION: This clinical observation reminds us of the importance of determining blood glucose in the assessment of any acute neurological dysfunction.

[Phenotype variability in adrenoleukodystrophy. Presentation of three new cases and a review of literature]. / Variabilidad fenotípica de la adrenoleucodistrofia. Presentación de tres casos y revisión de literatura.

INTRODUCTION: Adrenoleukodystrophy is a hereditary recessive sex-linked disorder with very variable phenotype expression, including classical infantil ALD, adrenomyeloneuropathy (AMN) in adults and sex-linked Addison's disease. Clinical observations. Three affected patients are presented. The first showed signs of myeloneuropathy from the age of 38 and diagnosis was made by showing raised serum and fibroblasts levels of very long chain fatty acids (C26:0). In the second case symptoms started at the age of 13 and cerebral and peripheral nervous system changes developed progressively. This patient's brother was the third case, showing symptoms when he was 21 and developing cerebral, medullary and peripheral nervous system involvement. In the latter two cases, diagnosis was made by showing intracytoplasmatic trilaminary inclusions in the nervous system. CONCLUSIONS: It is important to recognize the different varieties of this disease in view of the possibilities of genetic counselling and of the therapeutic implications which are currently being evaluated.

[Cerebral arterio-venous malformations in children under 10 years]. / Malformaciones arteriovenosas cerebrales en ninos menores de 10 anos.

INTRODUCTION: Arteriovascular malformations are anomalies of the embryonic development of cerebral vessels. They usually appear at between 10 and 30 years of age, being infrequent in infants. OBJECTIVE: Describe our experience of angiomas in small children. MATERIAL AND METHOD: The histories of all children under 10 years of age with the diagnosis of arteriovenous malformation admitted to our department between November 1984 and May 1995 were reviewed. RESULTS: Nine patients, aged between 3 months and 10 years; seven cases presented as intracranial haemorrhage, one with epileptic crises and another with general clumsiness and a hemicerebellar syndrome. The diagnosis was confirmed by angiography and/or study by the pathologist in all cases. Six patients were treated surgically and the other three by embolization. Of the latter, two also received radiosurgical treatment. The complications seen were; two children died, one during the acute phase and the other four years later as direct consequence of the haemorrhage. Six patients had residual neurological defects. One child had no complications. CONCLUSIONS: Intra-parenchymatous haemorrhage is the commonest manifestation of angiomas in children under 10 years of age. The high risk and serious consequences of bleeding make it necessary for treatment to be as radical as possible.