Javier Pablo Hryb

Disease onset in familial and sporadic multiple sclerosis in Argentina

UNLABELLED The present study was carried out to assess if there is an anticipation of age at onset in younger generations of familial multiple sclerosis (FMS) vs. sporadic MS (SMS) in Argentina. METHODS multicenter study that included patients from 14 MS Centers of Argentina. Patients were considered as FMS if they had in their family at least one relative of first or second degree diagnosed with MS; otherwise, patients were considered to have SMS. We compared the age at onset between familial and sporadic cases as well as the age at onset between relatives from different generations in FMS vs. SMS. RESULTS 1333 patients were included, 97 of them were FMS (7.3%). A lower age at onset in the younger generations of FMS cases was found compared with older generations of FMS as well as. SMS cases (24.1±3.7 years vs. 30.3±5.7 years, and 32.4±9.4 respectively; p<0.001). No differences were observed between older generations of FMS vs. SMS cases (p=0.12). CONCLUSION we observed an anticipation of age at onset of MS in younger generations of patients with FMS vs. older generations of FMS and SMS.

Frequency of brain MRI abnormalities in neuromyelitis optica spectrum disorder at presentation: a cohort of Latin American patients

BACKGROUND Brain magnetic resonance imaging (BMRI) lesions were classically not reported in neuromyelitis optica (NMO). However, BMRI lesions are not uncommon in NMO spectrum disorder (NMOSD) patients. OBJECTIVE To report BMRI characteristic abnormalities (location and configuration) in NMOSD patients at presentation. METHODS Medical records and BMRI characteristics of 79 patients with NMOSD (during the first documented attack) in Argentina, Brazil and Venezuela were reviewed retrospectively. RESULTS BMRI abnormalities were observed in 81.02% of NMOSD patients at presentation. Forty-two patients (53.1%) showed typical-NMOSD abnormalities. We found BMRI abnormalities at presentation in the brainstem/cerebellum (n = 26; 32.9%), optic chiasm (n = 16; 20.2%), area postrema (n = 13; 16.4%), thalamus/hypothalamus (n = 11; 13.9%), corpus callosum (n = 11; 13.9%), periependymal-third ventricle (n = 9; 11.3%), corticospinal tract (n = 7; 8.8%), hemispheric white matter (n = 1; 1.2%) and nonspecific areas (n = 49; 62.03%). Asymptomatic BMRI lesions were more common. The frequency of brain MRI abnormalities did not differ between patients who were positive and negative for aquaporin 4 antibodies at presentation. CONCLUSION Typical brain MRI abnormalities are frequent in NMOSD at disease onset.

Longitudinally extensive transverse myelitis immune-mediated in aquaporin-4 antibody negative patients: Disease heterogeneity

BACKGROUND Longitudinally extensive transverse myelitis (LETM) is a frequent manifestation of neuromyelitis optica spectrum disorder (NMOSD). However, it can also occur in other immune-mediated diseases of the central nervous system (CNS). Positive aquoporin-4 antibodies (AQP4-ab) predict higher relapse rate after LETM. OBJECTIVE To assess clinical and brain/spinal cord magnetic resonance imaging (MRI) features of LETM immune-mediated at onset and to compare AQP4-ab negative (N-LETM) with AQP4-ab positive (P-LETM) patients. METHODS Thirty LETM patients remitted for consideration of inflammatory CNS diseases were included. Demographics, clinical, serological, disability and neuroimaging features at onset we reviewed retrospectively and divided into two groups according to serological status. AQP4-ab were tested using indirect immunofluorescence. RESULTS Twenty-one patients were N-LETM. We did not find significant differences between both groups as regards gender, age at onset, dysfunction (motor, sensory, bladder/bowel) or disability. However, recurrences (p=0.04) of myelitis and number of relapses (p=0.03) were associated to P-LETM. N-LETM was associated with normal brain MRI (p=0.04) at onset. AQP4-ab positive were only observed in NMOSD patients. N-LETM (24%) and P-LETM (56%) patients had relapses of optic neuritis (ON) during the follow-up. CONCLUSION LETM at onset is a heterogeneous syndrome with similar clinical and neuroimaging features between both groups. N-LETM displayed a lower relapse rate of myelitis and ON.

Gender ratio trends over time in multiple sclerosis patients from Argentina

Several studies in multiple sclerosis (MS) suggest a trend of increasing disease frequency in women during the last decades. A direct comparison of gender ratio trends among MS populations from Argentina remains to be carried out. The objective of the study was to compare gender ratio trends, over a 50-year span in MS populations from Argentina. METHODS multicenter study that included patients from 14 MS Centers of Argentina. Patients with definite MS with birth years ranging from 1940 to 1989 were included. Gender ratios were calculated by five decades based on year of birth and were adjusted for the F/M born-alive ratio derived from the Argentinean national registry of births. The F/M ratios were calculated using a multivariate logistic regression per five decades by the year of birth approach. Analyses were performed using Stata 10.1. RESULTS 1069 patients were included. Gender ratios showed a significant increase from the first to the last decade in the whole MS sample (from 1.8 to 2.7; p value for trend=0.023). The Gender ratio did not show differences considering MS subtype. CONCLUSION our study showed a modest increase of the F/M ratio (from 1.8 to 2.7) over time among patients affected by MS in Argentina.

Diagnósticos diferenciales y pronóstico de las mielitis longitudinales extensas en Buenos Aires, Argentina

INTRODUCTION Longitudinally extensive myelitis (LETM) has classically been grouped with the full or limited neuromyelitis optica spectrum disorders (NMOSD). However, differential diagnosis reveals a wide range of aetiologies. OBJECTIVE To report on differential diagnosis and prognosis for LETM observed in a group of patients in Buenos Aires, Argentina. PATIENTS AND METHODS Cross-sectional and retrospective multicentre study in two hospitals in Buenos Aires from June 2008 to June 2014. INCLUSION CRITERIA medullary syndrome associated with spinal cord lesion extending for 3 or more contiguous spinal segments in magnetic resonance imaging (MRI). Clinical, radiological, and biochemical data were collected and subjects were rated on the Hughes functional disability scale (WHFDS) at 3 months. RESULTS We evaluated 27 patients, 74% of whom were women; mean age was 35.22 years. The NMO-IgG antibody test was performed in 66.6% and oligoclonal band testing in 71%. NMO-IgG seropositivity was found exclusively in NMOSD patients (75%). Brain MRI was normal in 59.2% and revealed a mean of 7.9 affected spinal segments. Differential diagnoses revealed NMOSD (37%), idiopathic LETM (22.2%), lupus (11.1%), tumour (11.1%), dural fistula (7.4%), acute disseminated encephalomyelitis (7.4%), and a single case of multiple sclerosis (3.7%). Patients with lesions to ≥ 7 spinal segments showed poor recovery at 3 months (P<.001); these cases were associated with neoplastic, vascular, idiopathic, and lupus-related aetiologies. CONCLUSIONS The most frequent causes of LETM in our cohort were NMOSD followed by idiopathic cases. Neoplastic, vascular, lupus-related, and idiopathic LETM may constitute a critical group with a distinct prognosis and other treatment needs.

Diagnostic Utility of Systematic Aquaporin-4 Antibodies Determination in the First Event of Immune-Mediated Optic Neuritis

Background: Antibodies against aquaporin-4 (AQP4-ab) have diagnostic and prognostic value. However, little is known to date about their utility in the first event of optic neuritis (ON). Objective: To evaluate the utility of systematic AQP4-ab determination in a retrospective cohort of patients with a first onset of ON. Patients and Methods: All patients (n = 42) were tested for AQP4-ab in the following context: typical ON (TON) and atypical ON (AON). Clinical, radiological and biochemical data were collected; patients with TON vs. AON and AQP4-ab positive vs. negative were compared. Results: The proportion of AQP4-ab seropositive patients was 40% in the TON group vs. 40.9% in the AON group. Visual acuity (VA) at baseline was poor in AON patients (p = 0.02) and these patients were associated with worse VA outcome (p < 0.001) at 6 months compared with TON patients, with a median follow-up of 3.27 ± 1.79 years. Brain MRI with dissemination in space criteria (p < 0.001), spinal cord partial lesions (p < 0.001) and oligoclonal bands (p = 0.02) were associated with the initial stages of TON. VA severity, number of myelitis attacks and ON relapses did not differ significantly between seropositive and seronegative patients. AQP4-ab were detected only in neuromyelitis optica spectrum disorders patients. Conclusion: This study showed a high seropositivity for AQP4-ab in TON patients, suggesting that it could diagnostic utility at the onset of ON.

Short-segment transverse myelitis lesions in a cohort of Latin American patients with neuromyelitis optica spectrum disorders

Study designMulticenter retrospective study.ObjectivesThe aim was to determine the frequency and magnetic resonance imaging (MRI) features of short-segment transverse myelitis (STM) in patients with neuromyelitis optica spectrum disorders (NMOSD) during a myelitis attack.SettingLatin American diagnostic centres (Neuroimmunology Unit). A multicenter study from Argentina, Brazil and Venezuela was performed.MethodsSeventy-six patients with NMOSD were included. We analyzed 346 attacks and reviewed spinal cord MRIs performed within 30 days from spinal attack onset. Sagittal and axial characteristics on cervical and thoracic MRI (1.5 tesla) were observed. Demographics, clinical, serological, and disability data were collected.ResultsAmong the 76 patients with NMOSD, isolated STM was observed in 8% (n = 6), multisegmental lesions (longitudinally extensive transverse myelitis (LETM) + STM) in 28% (n = 21; 13 had at least one STM), LETM in 42% (n = 32), and normal spinal MRI in 22% (n = 17). However, isolated STM was increased by 10% in patients with NMOSD with spinal lesions (6 out of 59) with mean attacks of 2.5 (±0.83) and last follow-up expanded disability status scale (EDSS) of 3.1 (±2.63). Positive aquaporin 4 antibodies (AQP4-ab) were found in 50%. Upper-cervical lesion was most frequently observed (5 out of 6). Myelitis was preceded by ON in all isolated patients with STM. Only one had a positive gadolinium lesion and none of these had asymptomatic spinal cord lesion.ConclusionIsolated STM does not exclude NMOSD diagnosis. Therefore, APQ4-ab testing could be useful during a myelitis attack with STM.

Mielitis y lupus: clínica, diagnóstico y tratamiento. Revisión

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Myelopathy is one of 19 neuropsychiatric syndromes related to SLE defined by the American College of Rheumatology. Although infrequent, it is a severe manifestation, leading to motor and sensory deficits, and sphincter dysfunction. The pathogenesis is not clearly known, but may be related to arterial thrombosis and vasculitis. Diagnosis is based on clinical findings, laboratory tests and the use of gadolinium-enhanced magnetic resonance imaging. The standard therapy is the combination of intravenous cyclophosphamide and glucocorticoids. In refractory disease, other treatments such as plasmapheresis or rituximab have been used.

Myelitis in systemic lupus erythematosus: clinical features, immunological profile and magnetic resonance imaging of five cases.

Myelopathy is one of the neuropsychiatric lupus syndromes. In this article, an original series of related lupus myelitis is reported and analyzed. We employed a retrospective chart review and identified all patients who were admitted to a general hospital in Buenos Aires, Argentina, with SLE and myelitis during the period 2007–2014. Five patients were observed, all women. The mean age was 25.4 years (19–39). In three of five cases, myelitis was one of the initial SLE manifestations. The SLE Disease Activity Index was variable (3/5 with high activity). Time to nadir ranged from 6 to 72 h. All had severe impairment, with motor deficit, sensory level and urinary retention. Magnetic resonance imaging was abnormal in all cases, 3/5 presented a longitudinally extensive myelitis. Serum analysis revealed positive antinuclear antibodies at a high titer in all patients, 4/5 had low complement levels and 3/5 had anti-phospholipids positive. The treatment (methylprednisolone and, in some cases, cyclophosphamide, anticoagulation and/or plasmapheresis) produced partial improvement or no benefits. One patient died due to sepsis. The others showed significant disability at 6 months (European Database for Multiple Sclerosis grading scale=6–8). In view of these results, myelitis associated with lupus shows heterogeneity of the clinical, radiological and serological features. In our experience, the cases were severe and with poor response to treatment. Further studies are required to understand this disease and establish a more efficient treatment.

Contents Vol. 76, 2016

Basel • Freiburg • Paris • London • New York • Chennai • New Delhi • Bangkok • Beijing • Shanghai • Tokyo • Kuala Lumpur • Singapore • Sydney Founded 1897 as ‘Monatsschrift für Psychiatrie und Neurologie’, continued 1957–1967 as ‘Psychiatria et Neurologia’ Founders: C. Wernicke and Th. Ziehen. Successors: K. Bonhoeffer (1912–1938), J. Klaesi (1939–1967), E. Grünthal (1953–1967), H.E. Kaeser (1968–1993)