Paulo Diniz da Gama

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 Brazilian database on pregnancy in multiple sclerosis

OBJECTIVESnTo report the results from the Brazilian database on multiple sclerosis (MS) and pregnancy.nnnMETHODSnRetrospective data from MS patients who became pregnant at any time of their disease were sent to a Brazilian database, using a specific file for this purpose.nnnRESULTSnData on 128 women (142 pregnancies) from 30 neurologists working in 21 cities in Brazil were collected. Patients average age at pregnancy was 29.8 years (range 16-42). EDSS at start of pregnancy was 1.5±1.4; and the relapse rate in the year preceding pregnancy was 1.2±1.5. Exposure to medication at any time during pregnancy was high (69.7%): 48.6% to interferon beta; 14.1% to glatiramer acetate; and 7% to other immunomodulatory and immunosuppressive drugs. There was a significant decrease in relapse rate during pregnancy. The prevalence of complications was relatively low, with 4.9% of obstetric and 1.4% neonatal unfavorable outcomes.nnnCONCLUSIONSnOur patients had low degrees of disability, short histories of disease, high drug exposure, and relatively high relapse rate in the year previous to pregnancy. Obstetric and neonatal outcomes were successful in over 90% of our patients.

The effects of long-term exposure to disease-modifying drugs during pregnancy in multiple sclerosis

BACKGROUND AND OBJECTIVEnWomen with multiple sclerosis (MS) who intend to get pregnant are often advised to discontinue disease modifying therapy (DMT) prior to conception. This recommendation is not based on medical evidence and may interfere with disease control by immunomodulatory drugs. The present study was designed to help discuss the effect of DMT for MS on pregnancy and on disease course.nnnPATIENTS AND METHODSnRetrospective data from 152 pregnancies of 132 women with MS were collected by the physician in charge of the case. All data were entered into a specific file for qualitative and quantitative statistical analysis.nnnRESULTSnFrom the total group of patients, 89 pregnancies occurred without any exposure to MS drugs, while 61 pregnancies occurred with at least eight weeks of exposure to MS immunomodulatory drugs. The rate of obstetric and neonatal complications was similar in both groups, except for the newborn weight and height which was smaller for mothers receiving medications. Mothers post-delivery relapse rate and EDSS scores in the follow-up period were significantly higher in the absence of treatment.nnnCONCLUSIONnIt is possible that, with further such supportive data, international guidelines on MS treatment in young women who intend to get pregnant may need to be revised.

Pregnancy and multiple sclerosis: the initial results from a Brazilian database

PURPOSEnPregnancy management poses an extra challenge to physicians and their multiple sclerosis (MS) patients. There are few papers reporting databases on the subject.nnnMETHODnBrazilian database from nine MS clinical and research units, with complete data on 47 pregnant women (49 pregnancies).nnnRESULTSnDespite relatively high exposure to MS medications, no birth defects were reported. Low birth weight and prematurity were similar to those for developing countries. Three complications may have been associated with these medications, while three others were considered to be of purely obstetric nature.nnnCONCLUSIONnOur results confirm previous findings on lower relapse rate during pregnancy and add to the present literature informing on data related to drug exposure.

Recommendations on diagnosis and treatment of depression in patients with multiple sclerosis

Multiple sclerosis (MS) is frequently associated with depression. Yet there are few clinical trials on treating depression in MS and no agreed recommendations for its assessment and follow-up. We present evidence-based recommendations for several aspects of depression in MS, including screening for depression, recognition of other concomitant psychiatric conditions, suicide risk, disability, fatigue, cognition, adherence to treatment, the effect of drugs used to treat MS on depression and possible pharmacological treatments for depression in MS.

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.

Natalizumab adverse events are rare in patients with multiple sclerosis

OBJECTIVEnTo assess the prevalence and the profile of adverse events (AE) of natalizumab in patients with multiple sclerosis (MS).nnnMETHODSnData collection from neurologists attending to patients with MS at specialized units in Brazil.nnnRESULTSnData 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.nnnCONCLUSIONnThe 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.

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

OBJECTIVEnNatalizumab 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.nnnMETHODnQualitative detection of the JCV in the serum was performed with real-time polymerase chain reaction (PCR).nnnRESULTSnIn a group of 168 patients with MS who were undergoing treatment with natalizumab, JCV-DNA was detectable in 86 (51.2%) patients.nnnDISCUSSIONnData on JCV-DNA in Brazil add to the worldwide assessment of the prevalence of the JCV in MS patients requiring treatment with natalizumab.

How do we manage and treat a patient with multiple sclerosis at risk of tuberculosis

Tuberculosis continues to be a serious health problem worldwide. The disease continues to be underdiagnosed and not properly treated. In conditions that affect the immune system, such as multiple sclerosis (MS), latent tuberculosis may thrive and reactivate during the use of immunomodulatory and immunosuppressive drugs. Among the best treatment options for patients with latent or active tuberculosis who have MS are IFN-β, glatiramer acetate and mitoxantrone. Drugs leading to a reduced number and/or function of lymphocytes should be avoided or used with caution. Tuberculosis must always be investigated in patients with MS and treated with rigor.