Late onset neuromyelitis optica spectrum disorders (LONMOSD) from a nationwide Portuguese study: Anti-AQP4 positive, anti-MOG positive and seronegative subgroups.

INTRODUCTION: Several neuroimmunological disorders have distinct phenotypes according to the age of onset, as in multiple sclerosis or myasthenia gravis. It is also described that late onset NMOSD (LONMOSD) has a different phenotype. OBJECTIVE: To describe the clinical/demographic characteristics of the LONMOSD and distinguish them from those with early onset (EONMOSD). METHODS: From a nationwide Portuguese NMOSD study we analyzed the clinical/demographic characteristics of the LONMOSD. RESULTS: From the 180 Portuguese patients 45 had disease onset after 50 years old, 80% were female. 23 had anti-AQP4 antibodies (51.1%), 13 anti-MOG antibodies (28.9%) and 9 were double seronegative (20.0%). The most common presenting phenotypes in LONMOSD were transverse myelitis (53.3%) and optic neuritis (26.7%), without difference from EONMOSD (p = 0.074). The mean EDSS for LONMOSD was 6.0 (SD=2.8), after a mean follow-up time of 4.58 (SD=4.47) years, which was significantly greater than the mean EDSS of EONMOSD (3.25, SD=1.80)(p = 0.022). Anti-AQP4 antibodies positive LONMOSD patients had increased disability compared to anti-MOG antibodies positive LONMOSD (p = 0.022). The survival analysis showed a reduced time to use a cane for LONMOSD, irrespective of serostatus (p<0.001). CONCLUSIONS: LONMOSD has increased disability and faster progression, despite no differences in the presenting clinical phenotype were seen in our cohort.

Neuromyelitis optica spectrum disorders: A nationwide Portuguese clinical epidemiological study.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits. OBJECTIVE: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics. METHODS: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included. RESULTS: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome. CONCLUSION: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries.

Plasma exchange in severe acute relapses of multiple sclerosis - Results from a Portuguese cohort.

BACKGROUND: Relapses in Multiple Sclerosis (MS) are often associated with significant disability impairment which is resultant from poor response to corticosteroids. In such severe cases, plasma exchange (PLEX) may be used, although only a few studies with MS patients have been reported. Our objective was to evaluate the effectiveness of PLEX in severe relapses of MS. METHODS: Retrospective study of MS patients treated with PLEX in acute relapses. Data regarding EDSS, annualized relapse rate (ARR), treatment with corticosteroids, number of PLEX sessions, adverse events, and gadolinium enhancement in brain MRI were analysed. RESULTS: Included 46 patients, 76.09% female (n = 35) with mean age of 38.76 years and mean disease duration of 5.99 years, of which 84.78% had a Relapsing Remitting MS (n = 39), 15.22% Secondary Progressive MS (n = 7). The previous ARR was 1.1 and in 28.26% of the cases (n = 13) PLEX was used in the relapse that led to MS diagnosis. The majority of relapses had motor impairment (69.6%, n = 32), with a median EDSS increase of 1.5 points from baseline (maximum of 6.5) and higher than 1.5 points in 45.65% of cases (n = 21). Brain MRI was available in 69.57% of the cases (n = 32), and gadolinium enhancing lesions were present in 68.75% of cases (n = 22). Corticosteroids were used before PLEX in all patients for a mean of 6.09 days, without any immediate benefit in 41.30% of cases (n = 19), with the remaining cases showing only mild disability recovery. After a mean of 7.39 PLEX sessions, there was clinical benefit with complete EDSS recovery in 41.30% of patients (n = 19), and partial in 39.13% (n = 18). There were no adverse events related to PLEX in 89.13% of patients (n = 41) and in the remaining patients the reported adverse events included deep venous thrombosis (n = 1), anaemia (n = 1), fever (n = 1), hypoalbuminemia (n = 1) and arterial hypotension (n = 1). CONCLUSION: Our results support the use of PLEX in severe relapses unresponsive to corticosteroids, since it was an effective and relatively safe treatment for most of our patients.

Neurosonology Accuracy for Isolated Acute Vestibular Syndromes.

OBJECTIVES: The clinical approach to acute vestibular syndromes is often complex for the physician. Neurosonology offers a noninvasive method to study the cervicocephalic circulation when a vascular etiology is suspected. We aim to evaluate the diagnostic accuracy of a vascular neurosonological exam in isolated acute vestibular syndrome. METHODS: All patients submitted to cerebrovascular ultrasound and magnetic resonance imaging during the period between 2011 and 2015 with acute isolated vestibular syndrome. Those with any clinical sign of brainstem lesion on presentation were excluded. All patients performed the neuroimaging study (brain computed tomography and magnetic resonance imaging) and neurologic surveillance. Neurosonological exam included all intra- and extracranial segments of the vertebrobasilar circulation. Positive ultrasound exam was defined as the presence of stenotic or occlusive disease in any of these segments related to the infarcted area. RESULTS: A total of 108 patients were included: 60 (53.6%) were males (mean age: 60.75 years (standard deviation, 14.17)). In 27 patients (25.0%) a cerebral ischemic lesion was found to be the cause of the vertigo. Neurosonological assessment showed a sensitivity of 40.7% (95% confidence interval (CI): 22.4; 61.2), specificity of 100% (95% CI: 95.5; 100.0), positive predictive value (PPV) of 100% (95% CI: 71.5; 100.0), and negative predictive value (NPV) of 83.5% (95% CI: 74.6; 90.3). CONCLUSIONS: Our study suggests that cerebrovascular ultrasound is a highly specific method for the diagnosis of cerebrovascular vertigo. However, its low sensitivity makes it a poor candidate for screening.

Neuromyelitis optica in Portugal (NEMIPORT) - A multicentre study.

BACKGROUND: Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease of the CNS. There have been few epidemiologic studies on NMO, none in Portugal. OBJECTIVE: To analyze the clinical, biological and MRI characteristics from a cohort of Portuguese patients who fulfilled the Wingerchuk 2006 NMO/NMOSD criteria. To identify and characterize those who had concomitant autoimmune disease or circulating autoantibodies. METHODS: We performed an observational, retrospective, multicenter study in 5 Hospital Centers in Portugal. RESULTS: Sixty-seven patients fulfilled the inclusion criteria. They were mainly Caucasian, 55 female. Median age at onset was 32.0 years and mean follow-up 7.4±6.0 years. Twenty-one patients were definite NMO and optic neuritis (ON) the most frequent initial presentation. Forty-six were classified as NMO spectrum disorders. The main subtypes were recurrent ON and single longitudinally extensive transverse myelitis. Twenty-four patients had positive AQP4-IgG. Twenty-three had other circulating autoantibodies. Fifteen out of 67 patients had concomitant autoimmune disease. There was a significant correlation between the presence of autoimmune disease and the positivity for AQP4-IgG. Five patients died, all definite NMO. CONCLUSION: This is the first study about this rare disease in Portugal. Demographic features were similar to other studies. The existence of concomitant autoimmune disease was significantly associated with seropositivity for AQP4-IgG.

Progressive multifocal leukoencephalopathy in a patient with chronic lymphocytic leukaemia treated with alemtuzumab.

A 69-year-old Caucasian woman with a 15-year history of refractory chronic lymphocytic B-cell leukaemia (CLL), treated with alemtuzumab in the past 10 months presented with a subacute right foot drop. Initial evaluation with a brain CT scan, lumbosacral MRI, nerve conduction studies and LP was negative. In the following months, progressive right hemibody weakness and dysarthria developed. Brain MRI showed a bilateral parasagittal frontal lesion. Alemtuzumab treatment was withdrawn. Progressive multifocal leukoencephalopathy (PML) was confirmed by PCR. Attempted antiviral therapies proved fruitless. Inexorable clinical deterioration ensued and the patient passed away 10 months after the presentation. This case report intends to call attention for PML as a potential fatal complication of severe immunosuppression, including the possible role of new monoclonal antibodies (such as alemtuzumab) in its pathogenesis.

[Atrial fibrillation in cerebrovascular disease: national neurological perspective]. / Fibrilhação Auricular na Doença Cerebrovascular: A Perspectiva Neurológica Nacional.

BACKGROUND: Cardioembolism due to atrial fibrillation assumes a dominant etiologic role in cerebrovascular diseases due to its growing incidence, high embolic risk and particular aspects of clinical events caused. Our objectives are to analyze the frequency of atrial fibrillation in patients with ischemic stroke, study the vital and functional impact of stroke due to different etiologies and evaluate antithrombotic options before and after stroke. METHODS: We conducted a retrospective study including patients admitted in a central hospital due to ischemic stroke in 2010 (at least one year of follow-up). Etiology of stroke was defined using the Trial of ORG 10172 in Acute Stroke (TOAST) classification, and functional outcome by modified Rankin scale. We performed a descriptive analysis of different stroke etiologies and antithrombotic medication in patients with atrial fibrillation. We then conducted a cohort study to evaluate the clinical impact of antithrombotic options in secondary prevention after cardioembolic stroke. RESULTS: In our population (n = 631) we found superior frequency of cardioembolism (34.5%) to that reported in the literature. Mortality, morbidity and antithrombotic options are similar to other previous series, confirming the severity of cardioembolic strokes and the underuse of vitamin K antagonists. Oral anticoagulation was effective in secondary prevention independently from post-stroke functional condition. CONCLUSIONS: Despite unequivocal recommendations, oral anticoagulation is still underused in stroke prevention. This study confirms the clinical efficacy of vitamin K antagonists in secondary prevention independently from residual functional impairment.

Introdução: A cardioembolia por fibrilhação auricular assume particular destaque etiológico nas doenças vasculares cerebrais devido à sua crescente incidência, elevado risco embólico e particularidades dos eventos clínicos causados. São objectivos deste trabalho analisar a frequência da fibrilação auricular numa população de doentes com acidente vascular cerebral isquémico observados num hospital nacional, estudar o impacto vital e funcional dos acidentes vasculares cerebrais causados por diferentes etiologias, e avaliar as opções antitrombóticas prévias e posteriores ao acidente vascular cerebral. Metodologia: Realizámos um estudo observacional retrospectivo incluindo todos os doentes internados num hospital central por acidente vascular cerebral isquémico em 2010 (pelo menos um ano de seguimento). A etiologia do acidente vascular cerebral foi definida pela classificação Trial of ORG 10172 in Acute Stroke (TOAST) modificada e o resultado funcional pela escala Rankin modificada. Realizámos análise descritiva das diferentes etiologias de acidente vascular cerebral e das prescrições antitrombóticas a doentes com fibrilhação auricular. Realizámos ainda um estudo de coorte para estudar o impacto clínico das opções antitrombóticas em prevenção secundária após acidente vascular cerebral cardioembólico. Resultados: Na nossa população (n = 631) encontramos frequência de cardioembolia (34,5%) superior à relatada na literatura. Os valores de mortalidade e morbilidade além das opções terapêuticas antitrombóticas em pré e pós-Doença Vascular Cerebral são semelhantes aos de outras séries, confirmando a gravidade dos acidentes vasculares cerebrais cardioembólicos e a subutilização dos antagonistas da vitamina K. A anticoagulação oral foi eficaz em prevenção secundária independentemente do estado funcional sequelar após acidente vascular cerebral. Conclusões: Apesar das recomendações terapêuticas inequívocas a anticoagulação oral continua a ser subutilizada em prevenção de Doença Vascular Cerebral. Confirmamos a eficácia clínica dos antagonistas da vitamina K em prevenção secundária, independentemente das limitações funcionais sequelares.