Joseph Bruno Bidin Brooks

Two Cases of Lesions in Brainstem in Multiple Sclerosis and Refractory Migraine

We report on 2 cases of multiple sclerosis in patients with refractory migraine as one of the initial manifestations of the disease. In both cases, the magnetic resonance image showed lesions in the brainstem that could be implicated in the genesis of such migraine attacks.

Leflunomide and teriflunomide: altering the metabolism of pyrimidines for the treatment of autoimmune diseases

Leflunomide modulates T-cell responses and induces a shift from the Th1 to Th2 subpopulation. This process results in a beneficial effect in diseases in which there is good evidence that T cells play a major role in both initiation and perpetuation of the inflammatory condition. Leflunomide has been successfully used for treating rheumatoid arthritis and psoriatic arthritis for many years. The active metabolite of leflunomide is teriflunomide, which has been approved for treating multiple sclerosis. Teriflunomide, just like the mother drug, inhibits dihydro-orotate dehydrogenase and synthesis of pyrimidine. The present review presents and discusses the safety profiles of leflunomide and teriflunomide, two drugs that are indeed the same, considering that much can be learned from the reported side effects of both.

The real-life experience with cardiovascular complications in the first dose of fingolimod for multiple sclerosis

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.

Assessment of cognition using the Rao's Brief Repeatable Battery of Neuropsychological Tests on a group of Brazilian patients with multiple sclerosis

UNLABELLED To assess the cognition of patients with multiple sclerosis (MS) using the Raos Brief Repeatable Battery of Neuropsychological Tests (BRB-N). METHOD BRB-N was translated and adapted for control subjects. Subsequently, it was applied to a group of patients with relapsing-remitting (RR) MS. RESULTS The assessment on the healthy controls (n=47) showed that the correlation between tests on the same cognitive domain was high and that there was a five-factor solution that explained 90% of the total variance. Except for the Word List Generation subset of tests, the performance of patients with RRMS (n=39) was worse than that of the healthy controls. CONCLUSION BRB-N is a relatively simple method to assess cognition of patients with MS in the daily clinic. It does not take long to apply and does not require special skills or equipment.

Paced auditory serial addition test (PASAT): a very difficult test even for individuals with high intellectual capability

OBJECTIVE To assess the difficulty of paced auditory serial addition test (PASAT) in a population of high intellectual level, under ideal cognitive testing circumstances. METHOD One hundred medical students underwent PASAT testing. They had slept well the night before, they had eaten before the assessment, they were not using any drugs that could affect the central nervous system and they did not have depression, anxiety or any chronic disease. RESULTS The average result from the three-second version of PASAT was 57.5% and, from the two-second version, it was 44.3%. CONCLUSION Even under ideal circumstances, PASAT is a very difficult test for the general population. It may not be ideal for neurologists to screen, assess and follow up patients with cognitive function in multiple sclerosis.

Neuromyelitis optica with onset in childhood and adolescence.

BACKGROUND Neuromyelitis optica with onset before the age of 18 years is a relatively rare, yet potentially devastating condition. The objective of the present study was to contribute to the study of early-onset neuromyelitis optica with a case series. PATIENTS Data were collected from medical records of Brazilian neurologists caring for patients with neuromyelitis optica occurring in childhood and adolescence. RESULTS Twenty-nine patients with neuromyelitis optica occurring before the age of 18 years and fulfilling the diagnostic criteria were identified. The average age at disease onset was 13 years and the patients had had an average disease duration of 6 years. The expanded disability scale score at the latest consultation was, on average, 4.7, and one patient had died from the disease. The 29 patients had had an average 4.5 relapses during the disease, accounting for 0.75 relapses per year, irrespective of the medication used. All patients were using one or more of the following medications: azathioprine, prednisone, immunoglobulin, and glatiramer acetate. CONCLUSIONS Neuromyelitis optica with onset in childhood and adolescence is a poorly understood condition that is often disabling and difficult to manage.

Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South Americans: A Descriptive, Multicenter, Cross-Sectional Study

The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been investigated among different populations, and the results have indicated a low relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS) cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%-27.5%) living in areas of low MS prevalence. South America (SA) was colonized by Europeans from the Iberian Peninsula, and their miscegenation with natives and Africans slaves resulted in significant racial mixing. The current study analyzed the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its population. A cross-sectional multicenter study was performed. Only individuals followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria were considered eligible. Patients’ demographic, clinical and laboratory data were collected. In all, 1,917 individuals from 22 MS centers were included (73.7% female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main disease categories and their associated frequencies were MS (76.9%), NMO (11.8%), other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy (0.4%). Females predominated in all main categories. The white ethnicity also predominated, except in NMO. Except in ADEM, the disease onset occurred between 20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in 8.9%. The long-term morbidity after a mean disease time of 9.28±7.7 years was characterized by mild disability in all categories except in NMO, which was scored as moderate. Disease time among those with MS was positively correlated with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This correlation was not observed in people with NMO or those with other NMO spectrum disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using indirect immunofluorescence (IIF) with a composite substrate of mouse tissues in 200 NMOSD cases was positive in people with NMO (95/162; 58.6%), longitudinally extensive transverse myelitis (10/30; 33.3%) and bilateral or recurrent optic neuritis (8/8; 100%). No association of NMO-IgG antibody positivity was found with gender, age at onset, ethnicity, early or late onset forms, disease course, or long-term severe disability. The relative frequency of NMO among relapsing-remitting MS (RRMS) + NMO cases in SA was 14.0%. Despite the high degree of miscegenation found in SA, MS affects three quarters of all patients with IIDD, mainly white young women who share similar clinical characteristics to those in Western populations in the northern hemisphere, with the exception of ethnicity; approximately one-third of all cases occur among non-white individuals. At the last assessment, the majority of RRMS patients showed mild disability, and the risk for secondary progression was significantly superior among those of African ethnicity. NMO comprises 11.8% of all IIDD cases in SA, affecting mostly young African-Brazilian women, evolving with a recurrent course and causing moderate or severe disability in both ethnic groups. The South-North gradient with increasing NMO and non-white individuals from Argentina, Paraguay, Brazil and Venezuela confirmed previous studies showing a higher frequency of NMO among non-white populations.

Report of three cases of herpes zoster during treatment with natalizumab.

While there is no doubt that natalizumab is a very effective treatment for multiple sclerosis (MS) [1], the worries about the safety of this drug continue. Natalizumab (Tysabri ; Biogen Idec, Cambridge, MA, USA, and Elan Pharmaceuticals, Dublin, Ireland) was the first FDA-approved monoclonal antibody for the treatment of MS. Natalizumab is a humanized monoclonal IgG4j antibody that selectively binds to the a4-integrin (subunit of the leukocyte adhesion molecules a4b1 and a4b7) component of adhesion molecules found on lymphocytes, monocytes, and eosinophils. Natalizumab inhibits the interaction of a4b1 with VCAM-1 and of a4b7 with MAdCAM-1. VCAM-1 and MAdCAM-1 are found on endothelial cells and interact with a4b1 and a4b7 on leukocytes for firm adherence of leukocytes to endothelial cells, which is a requisite step for their extravasation into inflamed tissue [2]. The main concern regarding the association of natalizumab and opportunistic infections is in relation to progressive multifocal leukoencephalopathy (PML) [3] caused by the JC virus (JCV). Doctors prescribing natalizumab are well aware of this potential complication, and JCV testing is now frequently used by neurologists to establish the potential risks of prescribing natalizumab to a given patient. However, although extremely rare, other viral infections have been described in patients using natalizumab, particularly herpes simplex virus (HSV) meningitis [4] and encephalitis [5]. Varicella zoster virus (VZV) reactivation has not been described in patients using natalizumab, although it has been known to affect patients using fingolimod, which is another new drug for MS. In fact, YZV reactivation was found to be fatal in a patient receiving fingolimod [6], but only at unusually high doses [7]. To the best of our knowledge, there have been no case reports on the association of natalizumab and herpes zoster in patients with MS. The purpose of the present study was to report on three cases of herpes zoster manifestation in patients undergoing treatment with natalizumab. Case 1 – Female, 62 years old with a 20-year history of MS, still presenting relapses of demyelination and therapeutic failure with first-line drugs for the treatment of MS (interferon beta and glatiramer acetate). Her neurological disability assessed using the expanded disability status scale (EDSS) [8] was 5.0, meaning that she had moderate difficulty in walking unaided. After the fourth monthly infusion of natalizumab, the patient developed herpes zoster in the cervical region and natalizumab was withdrawn and glatiramer acetate was restarted. Case 2 – Female, 28 years old, presenting frequently relapses of demyelination of the central nervous system without response to first-line therapy for the treatment of MS. The degree of disability of this patient was 3.5 on the EDSS scale, meaning that she had mild difficulty in walking long distances. After the seventh monthly infusion, the patient presented severe intercostal herpes zoster, leading to discontinuation of the drug. The patient continued with monthly pulses of corticosteroid during the short followup, because she moved to another MS service. Case 3 – Male, 54 years old, presenting therapeutic failure with first-line treatments of MS. Disability degree rated as 4.5 on the EDSS scale, meaning the patient had moderated difficulty to walk. After the 28th infusion, the patient presented intercostal herpes zoster. The patient continued on natalizumab. The patients described above were receiving the medication at the appropriate dose and posology. They were treated with

Multiple sclerosis starting before the age of 18 years: the Brazilian experience

Multiple sclerosis (MS) starting in childhood and adolescence poses a challenge for diagnosis and management of the disease. The aim of the present study was to assess the characteristics of early onset MS in Brazilian patients. Methods Retrospective data collection from specialized MS units. Results From 20 MS units in 11 Brazilian states, 117 cases of MS starting before the age of 18 years were collected. These patients had an average of 10 years of disease duration, still typically with low disability and one relapse every 2.5 years. The mean age for disease onset was 13.7 years. Conclusion The present study introduces a large series of Brazilian cases of pediatric MS. Although some patients presented a very severe form of MS, on the whole the group of patients with MS starting in childhood or adolescence presented a relatively mild form of this disease in Brazil.

Neurological complications following bariatric surgery

OBJECTIVE It was to report on Brazilian cases of neurological complications from bariatric surgery. The literature on the subject is scarce. METHOD Cases attended by neurologists in eight different Brazilian cities were collected and described in the present study. RESULTS Twenty-six cases were collected in this study. Axonal polyneuropathy was the most frequent neurological complication, but cases of central demyelination, Wernicke syndrome, optical neuritis, radiculits, meralgia paresthetica and compressive neuropathies were also identified. Twenty-one patients (80%) had partial or no recovery from the neurological signs and symptoms. CONCLUSION Bariatric surgery, a procedure that is continuously increasing in popularity, is not free of potential neurological complications that should be clearly presented to the individual undergoing this type of surgery. Although a clear cause-effect relation cannot be established for the present cases, the cumulative literature on the subject makes it important to warn the patient of the potential risks of this procedure.