Postpartum Treatment With Immunoglobulin Does Not Prevent Relapses of Multiple Sclerosis in the Mother.

Multiple sclerosis (MS) is a chronic, neurological, immune-mediated disease that can worsen in the postpartum period. There is no consensus on the use of immunoglobulin for prevention of disease relapses after delivery. We have shown that the controversial beneficial effect of immunoglobulin given immediately after birth could not be observed in patients with MS.

Alice in Wonderland syndrome: "Who in the world am I?"

Alice in Wonderland syndrome (AIWS) is a paroxysmal, perceptual, visual and somesthetic disorder that can be found in patients with migraine, epilepsy, cerebrovascular disease or infections. The condition is relatively rare and unique in its hallucinatory characteristics. OBJECTIVE To discuss the potential pathways involved in AIWS. Interest in this subject arose from a patient seen at our service, in which dysmetropsia of body image was reported by the patient, when she saw it in her son. METHODS We reviewed and discussed the medical literature on reported patients with AIWS, possible anatomical pathways involved and functional imaging studies. RESULTS A complex neural network including the right temporoparietal junction, secondary somatosensory cortex, premotor cortex, right posterior insula, and primary and extrastriate visual cortical regions seem to be involved in AIWS to varying degrees. CONCLUSIONS AIWS is a very complex condition that typically has been described as isolated cases or series of cases.

Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis.

Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). OBJECTIVE: To identify the serologic profile of JCV in patients with MS. METHODS: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. RESULTS: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. CONCLUSION: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

Critical analysis on the present methods for brain volume measurements in multiple sclerosis.

OBJECTIVE: The treatment of multiple sclerosis (MS) has quickly evolved from a time when controlling clinical relapses would suffice, to the present day, when complete disease control is expected. Measurement of brain volume is still at an early stage to be indicative of therapeutic decisions in MS. METHODS: This paper provides a critical review of potential biases and artifacts in brain measurement in the follow-up of patients with MS. RESULTS: Clinical conditions (such as hydration or ovulation), time of the day, type of magnetic resonance machine (manufacturer and potency), brain volume artifacts and different platforms for volumetric assessment of the brain can induce variations that exceed the acceptable physiological rate of annual loss of brain volume. CONCLUSION: Although potentially extremely valuable, brain volume measurement still has to be regarded with caution in MS.

Superficial siderosis of the central nervous system is a rare and possibly underdiagnosed disorder.

METHODS: Series of cases collected from Brazilian centers. RESULTS: We studied 13 cases of patients presenting with progressive histories of neurological dysfunction caused by SS-CNS. The most frequent clinical findings in these patients were progressive gait ataxia, hearing loss, hyperreflexia and cognitive dysfunction. The diagnoses of SS-CNS were made seven months to 30 years after the disease onset. CONCLUSION: SS-CNS is a rare disease that may remain undiagnosed for long periods. Awareness of this condition is essential for the clinician.

Safety of switching from natalizumab straight into fingolimod in a group of JCV-positive patients with multiple sclerosis.

OBJECTIVE: To assess safety of the switch between natalizumab and fingolimod without a washout period. METHODS: Prospective data on 25 JCV positive patients who underwent this medication switch were collected and analyzed. RESULTS: After a median period of nine months from the medication switch, there were no safety issues to report. The patients had good disease control and no adverse events were reported. CONCLUSION: Washout may not be necessary in daily practice when switching from natalizumab to fingolimod. Expertise on multiple sclerosis management, however, is essential for drug switching.

Cerebrum-cervical arterial dissection in adults during sports and recreation.

UNLABELLED: Dissection of cervical arteries constitutes a medical emergency. Although relatively rarely, activities classified as sports and recreation may be a cause of arterial dissection independently of neck or head trauma. The purpose of the present paper was to present a series of cases of cerebrum-cervical arterial dissection in individuals during or soon after the practice of these sports activities. METHODS: Retrospective data on patients with arterial dissection related to sports and recreation. RESULTS: Forty-one cases were identified. The most frequently affected vessel was the vertebral artery. A large variety of activities had a temporal relationship to arterial dissection, and jogging was the most frequent of these. This is the largest case series in the literature. CONCLUSION: Arterial dissection may be a complication from practicing sports.

Real-life experience with fampridine (Fampyra®) for patients with multiple sclerosis and gait disorders.

BACKGROUND: Fampridine is a broad-spectrum voltage-dependent potassium channel blocker that enhances synaptic transmission. The drug has been shown to be able to ameliorate conduction in demyelinated axons, thereby leading to improved gait in patients with multiple sclerosis (MS). OBJECTIVE: To assess the "real-life" efficacy and safety of fampridine prescribed for gait disorders in MS. This was an observational and prospective study carried out at MS Units participating in the Brazilian Multiple Sclerosis Study Group. METHODS: Patients with MS and gait disorders were prescribed fampridine (10 mg twice a day), irrespectively of the degree of disability determined by MS. Neurological disability determined by MS was assessed with the expanded disability scale score (EDSS). Outcomes for efficacy and safety of the drug were evaluated by the 25 foot-walk test and by the adverse events of fampridine. RESULTS: The time taken to walk 25 feet decreased by 20% or more in 62 patients (70%). Twenty-five patients were considered to be non-responders to this treatment. Improvement in walking speed was independent of improvement of disability. Mild or moderate adverse events were reported in 8% of patients. CONCLUSION: Fampridine is an efficient and safe therapeutic option for patients with MS and gait disorders.

Alternatives for reducing relapse rate when switching from natalizumab to fingolimod in multiple sclerosis.

Natalizumab is a therapeutic option for treating multiple sclerosis (MS) and is particularly efficacious for patients with highly active disease. A long washout period has been recommended between withdrawal of natalizumab and start of fingolimod (another option for treating MS). This long washout period has been associated with a significant increase in MS activity. In the present study, a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs, or monthly corticosteroid pulse therapy if longer washout periods were recommended. This therapeutic approach led to the lowest reported relapse rate so far, among patients with MS switching from natalizumab to fingolimod (8.3%). No complications from short withdrawal were observed in this group of patients.

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.

There is still a role for the blink reflex in the diagnosis and follow-up of multiple sclerosis.

OBJECTIVE: The evolution of the diagnostic criteria for multiple sclerosis (MS) has essentially evolved to clinical manifestations and magnetic resonance imaging. Inexpensive, quick to apply, non-invasive, quantitative and reliable neurophysiological tests are rare in daily practice and absent in clinical trials. METHOD: The blink reflex was assessed in 50 patients with remitting-relapsing MS (RRMS) and 100 matched controls. RESULTS: Patients with RRMS had abnormalities in the blink reflex waves in relation to controls. If only RRMS patients were considered, these abnormalities were more pronounced in patients with longer disease duration, higher disability and for those with clinical or image lesions in the brainstem. CONCLUSION: Neurophysiological tests, such as the blink reflex, can be used for helping the diagnosis and follow-up of patients with RRMS, since the reflex can identify dissemination in time and in space in a clear and quantitative manner. SIGNIFICANCE: Potential good methods for diagnosis and follow-up of MS should be considered for clinical trials and daily practice.

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.

Alice in Wonderland syndrome: "Who in the world am I?" / Síndrome de Alice no País das Maravilhas: "Quem sou eu no mundo?"

ABSTRACT Alice in Wonderland syndrome (AIWS) is a paroxysmal, perceptual, visual and somesthetic disorder that can be found in patients with migraine, epilepsy, cerebrovascular disease or infections. The condition is relatively rare and unique in its hallucinatory characteristics. Objective: To discuss the potential pathways involved in AIWS. Interest in this subject arose from a patient seen at our service, in which dysmetropsia of body image was reported by the patient, when she saw it in her son. Methods: We reviewed and discussed the medical literature on reported patients with AIWS, possible anatomical pathways involved and functional imaging studies. Results: A complex neural network including the right temporoparietal junction, secondary somatosensory cortex, premotor cortex, right posterior insula, and primary and extrastriate visual cortical regions seem to be involved in AIWS to varying degrees. Conclusions: AIWS is a very complex condition that typically has been described as isolated cases or series of cases.

RESUMO Síndrome de Alice no País das Maravilhas (SAPM) é uma condição paroxística visual perceptiva e somestésica que pode ser encontrada em pacientes com enxaqueca, epilepsia, doença cerebrovascular ou infecções. A condição é relativamente rara e tem características alucinatórias peculiares. Objetivo: Discutir as potenciais vias envolvidas na SAPM. O interesse pelo assunto surgiu com um caso de nosso serviço, onde a distropsia da imagem corporal foi relatada pela paciente, que via isto em seu filho. Métodos: Os autores revisaram e discutiram a literatura médica de casos relatados de SAPM, possíveis vias anatômicas envolvidas e estudos de imagem funcional. Resultados: Uma complexa rede neural incluindo junção temporoparietal direita, córtex somatossensitivo secundário, córtex pré-motor, região posterior da ínsula direita, e regiões do córtex visual primário e extra-estriatal têm diferentes graus de envolvimento na SAPM. Conclusão: SAPM é uma condição complexa que tipicamente foi descrita apenas com casos isolados ou séries de casos.

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-ß, 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.

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.

The blink reflex test does not show abnormalities in a large group of patients with chronic migraine.

UNLABELLED: The blink reflex - a simple, non-invasive and inexpensive test - may be indicative of lesions or dysfunctions of the brainstem, and particularly assesses the trigeminal-facial arch. Results from alterations of the blink reflex in patients with headaches have provided controversial data. METHOD: Registration of the waves R1 and R2 (ipsilateral to the stimulus) and R2c (contralateral to the stimulus) by electroneuromyography. RESULTS: A large number of controls (n=160) and patients with chronic migraine (n=160) were studied. No significant differences were observed between the two groups. CONCLUSION: It is possible that this relatively simple and primitive reflex is not affected unless there is significant damage to the brainstem.

Neuromyelitis optica and pregnancy.

Less than a hundred cases of pregnancies in women with neuromyelitis optica (NMO) have been published in the world. The aim of the present study was to add the Brazilian experience to this subject. Cases of women with NMO who became pregnant, or who developed NMO soon after pregnancy, were included. Retrospective analysis of medical data from these patients was carried out by the neurologist responsible for the case. Seventeen cases of pregnancies (16 full-term pregnancies, one miscarriage) were identified. The relapse rate of demyelinating events in the first trimester after pregnancy was significantly higher than at any other time. Disability progression was significantly worse 1 year after delivery. Pregnancy negatively influenced the disease course of NMO in these women. These results are similar to those of other authors, although the total number of cases so far described is still small. Obstetricians must be aware of the potential complications of a pregnancy in a woman who has NMO.

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.

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.

Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis / Perfil sorológico do vírus John Cunningham (JCV) em pacientes com esclerose múltipla

ABSTRACT Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). Objective: To identify the serologic profile of JCV in patients with MS. Methods: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. Results: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. Conclusion: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

RESUMO As opções terapêuticas para esclerose múltipla (EM) modificaram-se ao longo dos últimos anos, trazendo uma nova categoria de drogas com melhor perfil de eficácia. No entanto, estas drogas vieram com um novo perfil de potenciais eventos adversos que exigem que o neurologista os reconheça bem e rapidamente. Uma das complicações mais temidas destes tratamentos para a EM é a leucoencefalopatia multifocal progressiva (LEMP), causada pela reativação do vírus John Cunningham (JCV). Objetivo: Identificar o perfil sorológico de JCV em pacientes com EM. Métodos: Dados sorológicos de JCV foram obtidos através do ensaio por enzimas imuno-adsorvidas (ELISA) fornecido pelo programa STRATIFY-JCV. Resultados: Um total de 1.501 testes sanguíneos foram obtidos de 1.102 pacientes com EM. O grupo teve 633 pacientes (57,1%) soropositivos para anticorpos anti-JCV e 469 pacientes negativos (42,9%). Vinte e três pacientes se tornaram posivitos após resultados iniciais negativos para anticorpos anti-JCV. A taxa de soroconversão foi 18,5% em 22 meses. Conclusão: O perfil sorológico do JCV e a soroconversão nos pacientes brasileiros foi semelhante àquela descrita em outros países.