Sidney Gomes

Severe depression, suicide attempts, and ideation during the use of interferon beta by patients with multiple sclerosis.

Background:Interferon (IFN) beta is a safe and efficient drug for treating multiple sclerosis (MS). It is widely accepted that previously depressed patients may get worse when using IFN-beta. There are few reports on the association of IFN-beta and severe depression among patients without previous psychiatric history. Methods:Discussion of a case of a patient with MS who developed severe depression and attempted suicide while using IFN-beta encouraged us to review the subject. A group of neurologists in Brazil retrospectively gathered together their similar cases for the present paper. Results:The present paper reports on 11 cases of severe depression with suicide attempts or ideation among patients with MS who were using IFN-beta. These patients had no previous history of any psychiatric disease. Nine patients developed the symptoms over a relatively short period (4 months, on average). Two patients developed severe depression after more than 1 year of treatment with IFN-beta. Phobic, aggressive, behavioral, psychotic, and manic symptoms also were observed in these patients, thus suggesting the existence of a complex mood-behavior disorder associated with this drug. Interferon beta withdrawal led to complete remission of symptoms. The Naranjo algorithm established a highly probable association between IFN-beta and this adverse reaction in these patients. Conclusions:Although uncommon, severe depression with suicide ideation or attempts may be observed during treatment of MS with IFN-beta. This association should not discourage the use of this drug, but physicians need to be aware of this possible adverse event from IFN-beta.

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.

Restless legs syndrome and multiple sclerosis: a Brazilian multicenter study and meta-analysis of the literature

OBJECTIVE The increased prevalence of restless legs syndrome (RLS) in multiple sclerosis (MS) has recently been the subject of a few papers. The present study investigated the prevalence of RLS symptoms in MS patients and in controls in four Brazilian cities. Additionally, a systematic review and meta-analysis of the literature was carried out on the subject of RLS-MS. METHOD MS patients and controls were investigated regarding the presence of the four typical symptoms of RLS. A questionnaire assessing RLS severity was also used for patients and controls presenting the four RLS symptoms criteria. The systematic review and meta-analysis on the subject were carried out according to the strict international criteria. RESULTS In the present report, the RLS-MS association was confirmed as being more than fortuitous in Brazilian MS patients, in a multicenter case-control study. MS patients also presented RLS symptoms of greater severity than did the control population. A systematic review and meta-analysis of the literature showed that MS patients had a fourfold higher chance of presenting RLS than did the controls. CONCLUSION Although underlying mechanisms to explain the association RLS-MS are still a matter of discussion, there is a clear association of these two neurological conditions.

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.

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.

Natalizumab adverse events are rare in patients with multiple sclerosis

OBJECTIVE To assess the prevalence and the profile of adverse events (AE) of natalizumab in patients with multiple sclerosis (MS). METHODS Data collection from neurologists attending to patients with MS at specialized units in Brazil. RESULTS Data from 103 patients attending the infusion centers of 16 MS units in 9 Brazilian states were included in the study. The total number of infusions was 1,042. Seventy-nine patients (76.7%) did not present any AE. Twenty-four patients (23.3%) presented only mild AE. There were three major AE, including two deaths. These three occurrences, although not necessarily being drug-related, must be taken into consideration. CONCLUSION The profile of AEs for natalizumab shows that 97% of patients have none or only mild AE. However, still due to safety worries, the use of this medication should be restricted to MS units under the care of specialized neurologists.

Persistent Headache in Patients With Multiple Sclerosis Starting Treatment With Fingolimod

It is difficult to think of a medication that does not have “headache” as a potential adverse event listed by the manufacturer. However, this symptom is not described in detail by the pharmaceutical companies, and no considerations are made regarding the acceptable duration of this side effect or how to manage it, should it occur. This letter concerns 12 potential cases of headache associated with use of fingolimod, a new and very efficient drug for treating multiple sclerosis (MS). Upon starting with fingolimod, these patients presented persistent headache that resembled new daily persistent headache (NDPH) but were, in fact, attributable to a new substance. Fingolimod is an orally bioavailable compound that antagonizes the sphingosine 1-phosphate (SP1) receptor. In vivo, fingolimod is phosphorylated to fingolimod-phosphate, which resembles naturally occurring S1P. Through binding to SP1 sites in lymphocytes, fingolimod prevents these cells from leaving the lymph nodes. The first dose of fingolimod may be associated with bradycardia, fatigue, gastrointestinal disturbance, headache, and upper respiratory tract infection. Other adverse events in patients using fingolimod that are more serious but rare include atrioventricular block, herpetic viral infections, and macular edema. Although headache is described as a potential side effect of fingolimod and many other drugs for the treatment of MS, the present cases caught our attention because of the characteristics that these patients presented. These patients comprised 8 males and 3 females, of mean age 33.5 years (range 23 to 46 years), who are undergoing treatment for MS. Fingolimod was prescribed due to suboptimal response to other drugs. One patient had a previous history of episodic migraine. They were not using any drugs other than immunomodulatory treatments for MS. In all patients, their headache started within the first week of use of fingolimod and persisted for at least 3 months. In all cases, the pain was bilateral, non-pulsatile, of moderate intensity, and persistent From the MS Reference Center, Universidade Metropolitana de Santos, SP, Brazil (Y.D. Fragoso); MS Reference Center, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil (T. Adoni); Department of Neurology, Hospital Beneficencia Portuguesa de Sao Paulo, Sao Paulo, SP, Brazil (S. Gomes); MS Unit, Centro Hospitalar Unimed, Joinville, SC, Brazil (M.V.M. Goncalves); Department of Neurology, Hospital Universitario Antônio Pedro, Universidade Federal Fluminense, Niterói, RJ, Brazil (A.P.C. Matta); Department of Neurology, Medical School, Irmandade de Misericordia da Santa Casa de Sao Paulo, Sao Paulo, SP, Brazil (M.F. Mendes); Department of Neurology, Universidade Regional de Blumenau, Blumenau, SC, Brazil (F. Siquineli).

Nearly one-half of Brazilian patients with multiple sclerosis using natalizumab are DNA-JC virus positive

OBJECTIVE Natalizumab is a new and efficient treatment for multiple sclerosis (MS). The risk of developing progressive multifocal leukoencephalopathy (PML) during the use of this drug has created the need for better comprehension of JC virus (JCV) infection. The objective of the present study was to assess the prevalence of JCV-DNA in Brazilian patients using natalizumab. METHOD Qualitative detection of the JCV in the serum was performed with real-time polymerase chain reaction (PCR). RESULTS In a group of 168 patients with MS who were undergoing treatment with natalizumab, JCV-DNA was detectable in 86 (51.2%) patients. DISCUSSION Data on JCV-DNA in Brazil add to the worldwide assessment of the prevalence of the JCV in MS patients requiring treatment with natalizumab.