Plasma exchange in inflammatory demyelinating disorders of the central nervous system: reasonable use in the clinical practice.

Plasma exchange (PLEX) is a therapeutic apheresis modality in which the plasma is separated from inflammatory factors such as circulating autoreactive immunoglobulins, the complement system, and cytokines, and its therapeutic effect is based on the removal of these mediators of pathological processes. Plasma exchange is well established for various neurological disorders, and it is applied successfully in central nervous system inflammatory demyelinating diseases (CNS-IDD). It mainly modulates the humoral immune system; thus, it has a greater theoretical effect in diseases with prominent humoral mechanisms, such as neuromyelitis optica (NMO). However, it also has a proven therapeutic effect in multiple sclerosis (MS) attacks. Several studies have suggested that patients with severe attacks of CNS-IDD have poor response to steroid therapy but show clinical improvement after the PLEX treatment. Currently, PLEX is generally established only as a rescue therapy for steroid unresponsive relapses. However, there are still research gaps in the literature regarding plasma volume, number of sessions, and how early the apheresis treatment needs to started. Thus, in the present article, we summarize the clinical studies and meta-analyses, especially about MS and NMO, outlining clinical data regarding the experience with therapeutic PLEX in severe attacks of CNS-IDD, the clinical improvement rates, the prognostic factors of a favorable response, and highlighting the likely role of the early apheresis treatment. Further, we have gathered this evidence and suggested a protocol for the treatment of CNS-IDD with PLEX in the routine clinical practice.

Plasmaférese (PLEX) é um procedimento em que o plasma é separado de fatores inflamatórios como imunoglobulinas autorreativas circulantes, sistema complemento e citocinas, e seu efeito terapêutico se baseia na remoção desses mediadores de processos patológicos. A PLEX está bem estabelecida no tratamento de diversos distúrbios neurológicos, e é utilizada com sucesso em surtos de doenças desmielinizantes inflamatórias do sistema nervoso central (CNS-IDD). A PLEX modula principalmente o sistema imunológico humoral; assim, tem efeito teórico maior em doenças com mecanismos patológicos humorais proeminentes, como a neuromielite óptica (NMO). No entanto tem também efeito terapêutico comprovado em surtos de esclerose múltipla (EM). Estudos sugerem que a corticoterapia é pouco eficaz em pacientes com surtos graves de CNS-IDD, e que estes apresentam melhora clínica após o tratamento com PLEX. Atualmente, a PLEX está geralmente estabelecida apenas como terapia de resgate para surtos não responsivos a corticosteroides. No entanto, há lacunas na literatura sobre a quantidade de troca de volume plasmático, o número de sessões, e o tempo de início da aférese terapêutica. Dessa forma, resumimos neste artigo estudos clínicos e metanálises, especialmente sobre EM e NMO, e delineamos os dados clínicos sobre a experiência com o uso de PLEX em surtos graves de CNS-IDD, as taxas de melhora clínica, os fatores prognósticos para uma resposta favorável, e destacamos o provável papel do tratamento precoce nestes casos. Em um segundo momento, reunimos essas evidências em uma sugestão de protocolo de tratamento de CNS-IDD com PLEX na prática clínica rotineira.

Plasma exchange in inflammatory demyelinating disorders of the central nervous system: reasonable use in the clinical practice / Plasmaférese em doenças inflamatórias desmielinizantes do sistema nervoso central: uso coerente na prática clínica

Abstract Plasma exchange (PLEX) is a therapeutic apheresis modality in which the plasma is separated from inflammatory factors such as circulating autoreactive immunoglobulins, the complement system, and cytokines, and its therapeutic effect is based on the removal of these mediators of pathological processes. Plasma exchange is well established for various neurological disorders, and it is applied successfully in central nervous system inflammatory demyelinating diseases (CNS-IDD). It mainly modulates the humoral immune system; thus, it has a greater theoretical effect in diseases with prominent humoral mechanisms, such as neuromyelitis optica (NMO). However, it also has a proven therapeutic effect in multiple sclerosis (MS) attacks. Several studies have suggested that patients with severe attacks of CNS-IDD have poor response to steroid therapy but show clinical improvement after the PLEX treatment. Currently, PLEX is generally established only as a rescue therapy for steroid unresponsive relapses. However, there are still research gaps in the literature regarding plasma volume, number of sessions, and how early the apheresis treatment needs to started. Thus, in the present article, we summarize the clinical studies and meta-analyses, especially about MS and NMO, outlining clinical data regarding the experience with therapeutic PLEX in severe attacks of CNS-IDD, the clinical improvement rates, the prognostic factors of a favorable response, and highlighting the likely role of the early apheresis treatment. Further, we have gathered this evidence and suggested a protocol for the treatment of CNS-IDD with PLEX in the routine clinical practice.

Resumo Plasmaférese (PLEX) é um procedimento em que o plasma é separado de fatores inflamatórios como imunoglobulinas autorreativas circulantes, sistema complemento e citocinas, e seu efeito terapêutico se baseia na remoção desses mediadores de processos patológicos. A PLEX está bem estabelecida no tratamento de diversos distúrbios neurológicos, e é utilizada com sucesso em surtos de doenças desmielinizantes inflamatórias do sistema nervoso central (CNS-IDD). A PLEX modula principalmente o sistema imunológico humoral; assim, tem efeito teórico maior em doenças com mecanismos patológicos humorais proeminentes, como a neuromielite óptica (NMO). No entanto tem também efeito terapêutico comprovado em surtos de esclerose múltipla (EM). Estudos sugerem que a corticoterapia é pouco eficaz em pacientes com surtos graves de CNS-IDD, e que estes apresentam melhora clínica após o tratamento com PLEX. Atualmente, a PLEX está geralmente estabelecida apenas como terapia de resgate para surtos não responsivos a corticosteroides. No entanto, há lacunas na literatura sobre a quantidade de troca de volume plasmático, o número de sessões, e o tempo de início da aférese terapêutica. Dessa forma, resumimos neste artigo estudos clínicos e metanálises, especialmente sobre EM e NMO, e delineamos os dados clínicos sobre a experiência com o uso de PLEX em surtos graves de CNS-IDD, as taxas de melhora clínica, os fatores prognósticos para uma resposta favorável, e destacamos o provável papel do tratamento precoce nestes casos. Em um segundo momento, reunimos essas evidências em uma sugestão de protocolo de tratamento de CNS-IDD com PLEX na prática clínica rotineira.

Roberto Melaragno's scientific contributions to Brazilian Neurology.

Roberto Melaragno Filho, an associate professor of neurology at the School of Medicine of Universidade de São Paulo and head of the neurology service at Hospital do Servidor Público Estadual Francisco Morato Oliveira (HSPE-FMO), had a significant scientific career. He is recognized as a reference in the 20th century Brazilian neurology in addition to having a notable international career.

Encefalite herpética associada a mieloma múltiplo: desafio diagnóstico / Herpetic encephalitis associated with multiple myeloma: a diagnostic challenge

O mieloma múltiplo é a segunda neoplasia onco-hematológica mais comum, correspondendo a 1% das neoplasias malignas. Trata-se de uma condição subdiagnosticada, assim como a encefalite herpética. Entretanto, é comum a relação do mieloma com infecções, em decorrência do acometimento da imunidade humoral. A encefalite viral herpética tem como principal agente o vírus do herpes simples 1. O caso foi descrito baseado em um raciocínio clínico, visando contribuir para uma melhor caracterização do quadro clínico e do diagnóstico de duas entidades clínicas que possuem baixa suspeição diagnóstica e elevada morbimortalidade. Durante o curso da investigação, foram propostas variadas etiologias como responsáveis pelo rebaixamento do nível de consciência, levando a uma pesquisa de um espectro mais amplo de hipóteses diagnósticas, as quais precederam a confirmação do diagnóstico final. O quadro clínico atípico descrito apresentou obstáculos à suspeição diagnóstica correta, pois a ausência dos sinais e sintomas característicos de ambas as doenças levaram à pesquisa de um arsenal mais amplo de diagnósticos diferenciais. Assim, o atraso no diagnóstico e o início tardio do tratamento foram fatores que contribuíram para o prognóstico reservado do paciente. A associação dessas doenças é pouco descrita na literatura, de modo que mais estudos acerca do assunto se fazem necessários. (AU)

Multiple myeloma is the second most common onco-hematologic neoplasm, accounting for 1% of malignant neoplasms. As herpetic encephalitis, it is an underdiagnosed condition. However, the relation of myeloma with infections is common, due to the involvement of humoral immunity. Herpetic encephalitis has as its main etiological agent the herpes simplex virus 1. The case was described based on a clinical reasoning, aiming to contribute to a better characterization of the clinical picture and diagnosis of two entities that have low rates of diagnostic suspicion and high rates of morbidity and mortality. During the course of investigation, several etiologies were proposed as responsible for the decreased level of consciousness, leading to a search for a broader range of diagnostic hypotheses, which preceded confirmation of the final diagnosis. The atypical clinical picture described presented obstacles to the correct diagnostic suspicion, as the absence of symptoms and signs characteristic of both diseases led to the search for a broader arsenal of differential diagnoses. Thus, delayed diagnosis and late treatment were factors that contributed to the patient's reserved prognosis. The association of these diseases is poorly described in the literature, so further studies on that subject are required. (AU)

Parkinson's disease delays predictable visual cue processing without affecting complex and unpredictable visual cue processing in postural control.

This study examined the influence of visual information of different complexities and predictability on the body sway of individuals with Parkinson's disease (PD) during upright stance. Twenty-one individuals at initial stages of PD (62.1 ± 7.2 years), under dopaminergic medication, and 21 controls (62.3 ± 7.1 years) stood inside a moving room, performing 10 trials of 60 s. In the first trial, the room remained motionless. Then, the room oscillated in an anterior-posterior direction. There were three blocks of three trials. In the first block, the room oscillated at 0.2 Hz (periodic simple condition); in the second block, periodic frequencies of 0.1, 0.3, and 0.5 Hz were combined (periodic complex condition); in the third block, non-periodic frequencies of 0.1, 0.3, and 0.5 Hz were combined (non-periodic complex condition). Participants were not informed about the room movement. The displacement of the room and trunk were registered using an OPTOTRAK system. Postural sway was examined using mean sway amplitude, and the relationship between visual information and body sway used coherence, gain, and phase. There was no group difference when the room remained motionless. Upon visual manipulation, the PD group displayed larger sway magnitude in the non-periodic complex condition. Individuals with PD also lagged behind the moving room (lower phase values) compared to controls, only in the periodic simple condition. In the remaining measures, there was no group difference. These results suggest that individuals with PD use complex and unpredictable visual information, similar to controls, during upright stance. However, PD might affect the predictable visual cues processing.

The functional assessment Berg Balance Scale is better capable of estimating fall risk in the elderly than the posturographic Balance Stability System.

The purpose of this study was to verify which instrument better identifies recurrent falls in the elderly. Ninety-eight old people, with an average age of 80 ± 4 years, were submitted to an assessment of balance and fall risk by means of the Berg Balance Scale (BBS) and the posturographic Balance Stability System (BSS). The BBS was correlated with the BSS (r=-0.27; p=0.008), age (r=-0.38; p<0.001) and number of falls (r=-0.25; p=0.013) and the analysis of logistical regression showed that the elderly classified with fall risk on the BBS presented 2.5 (95%CI 1.08-5.78) more chance of identifying who had two falls or more over the last year. The BBS identified that the greater the age the worse the functional balance and demonstrated a greater capacity to identify falls risk suffered over the last year when compared with the BSS.

The functional assessment Berg Balance Scale is better capable of estimating fall risk in the elderly than the posturographic Balance Stability System / A avaliação funcional Berg Balance Scale é capaz de estimar melhor o risco de quedas em idosos do que a posturografia Balance Stability System

The purpose of this study was to verify which instrument better identifies recurrent falls in the elderly. Ninety-eight old people, with an average age of 80±4 years, were submitted to an assessment of balance and fall risk by means of the Berg Balance Scale (BBS) and the posturographic Balance Stability System (BSS). The BBS was correlated with the BSS (r=-0.27; p=0.008), age (r=-0.38; p<0.001) and number of falls (r=-0.25; p=0.013) and the analysis of logistical regression showed that the elderly classified with fall risk on the BBS presented 2.5 (95%CI 1.08-5.78) more chance of identifying who had two falls or more over the last year. The BBS identified that the greater the age the worse the functional balance and demonstrated a greater capacity to identify falls risk suffered over the last year when compared with the BSS.

A proposta do estudo foi verificar o instrumento que melhor identifica o risco de quedas recorrentes em idosos. O estudo incluiu 98 idosos, com média de idade de 80±4 anos, submetidos à avaliação do equilíbrio e risco de quedas por meio da Berg Balance Scale (BBS) e da posturografia Balance Stability System (BSS). A BBS foi correlacionada com a BSS (r=-0,27; p=0,008), com a idade (r=-0,38; p<0,001) e com o número de quedas (r=-0,25; p=0,013). A análise de regressão logística mostrou que idosos classificados com risco de quedas na BBS apresentaram 2,5 (95%IC 1,08-5,78) mais chances de identificar quem teve duas quedas ou mais no último ano. A BBS identificou que quanto maior a idade pior é o equilíbrio funcional e demonstrou maior capacidade de identificar o risco de quedas sofridas no último ano quando comparada a BSS.

Depression in Parkinson's disease: clinical-epidemiological correlates and comparison with a controlled group of non-parkinsonian geriatric patients.

OBJECTIVE: To evaluate and compare the frequency and severity of major depression in patients with Parkinson's disease and in individuals older than 60 years without neurological, rheumatological and/or oncological comorbidities. METHOD: We studied 50 patients with Parkinson's disease older than 60 years and 50 geriatric patients. Subjects with scores of Mini Mental State Examination indicating cognitive impairment were excluded. We used Diagnostic Statistical Manual of Mental Diseases-IV criteria to diagnose major depression and the Hamilton Depression Scale and the Beck Depression Inventory to rate it. The Unified Parkinson's Disease Rating Scale part 3 and the Hoehn and Yahr Scale were used to evaluate the motor severity of Parkinson's disease. RESULTS: Major depression was found in 42% of Parkinson's disease patients and in 10% of the geriatric patients (p < 0.001). The scores of the Hamilton Depression Scale and the Beck Depression Inventory were higher in Parkinson's disease patients (p < 0.001). Depressed Parkinson's disease patients had longer duration of Parkinson's disease (p = 0.020) and higher scores on the Unified Parkinson's Disease Rating Scale part 3 (p = 0.029) and the Yahr Scale (p = 0.027). CONCLUSIONS: The frequency (42%) and severity of major depression were higher in Parkinson's disease patients. Longer duration of Parkinson's disease, higher scores on the Unified Parkinson's Disease Rating Scale part 3 and the Hoehn and Yahr Scale were significantly associated with major depression.

Depression in Parkinson's disease: clinical-epidemiological correlates and comparison with a controlled group of non-parkinsonian geriatric patients / Depressão na doença de Parkinson: análise clínico-epidemiológica e comparação com um grupo de pacientes geriátricos não parkinsonianos

OBJECTIVE: To evaluate and compare the frequency and severity of major depression in patients with Parkinson's disease and in individuals older than 60 years without neurological, rheumatological and/or oncological comorbidities. METHOD: We studied 50 patients with Parkinson's disease older than 60 years and 50 geriatric patients. Subjects with scores of Mini Mental State Examination indicating cognitive impairment were excluded. We used Diagnostic Statistical Manual of Mental Diseases-IV criteria to diagnose major depression and the Hamilton Depression Scale and the Beck Depression Inventory to rate it. The Unified Parkinson's Disease Rating Scale part 3 and the Hoehn and Yahr Scale were used to evaluate the motor severity of Parkinson's disease. RESULTS: Major depression was found in 42 percent of Parkinson's disease patients and in 10 percent of the geriatric patients (p < 0.001). The scores of the Hamilton Depression Scale and the Beck Depression Inventory were higher in Parkinson's disease patients (p < 0.001). Depressed Parkinson's disease patients had longer duration of Parkinson's disease (p = 0.020) and higher scores on the Unified Parkinson's Disease Rating Scale part 3 (p = 0.029) and the Yahr Scale (p = 0.027). CONCLUSIONS: The frequency (42 percent) and severity of major depression were higher in Parkinson's disease patients. Longer duration of Parkinson's disease, higher scores on the Unified Parkinson's Disease Rating Scale part 3 and the Hoehn and Yahr Scale were significantly associated with major depression.

OBJETIVO: Avaliar e comparar a freqüência e intensidade de depressão em um grupo com doença de Parkinson e um grupo sem doença de Parkinson, sem doença neurológica, reumatológica e/ou oncológica acompanhados na Universidade Federal de São Paulo. MÉTODO: Avaliaram-se 50 indivíduos com doença de Parkinson (grupo Parkinson) e 50 indivíduos sem doença de Parkinson (grupo controle) acima de 60 anos. Excluíram-se indivíduos que demonstravam alterações cognitivas pelo Mini Exame Estado Mental. Todos foram submetidos à entrevista estruturada para depressão maior do Diagnostic Statistical Manual of Mental Diseases-IV, Escala de Depressão de Hamilton e Inventário de Depressão de Beck. O grupo Parkinson foi submetido à avaliação física por Unified Parkinson Disease Rating Scale 3 e Hoehn-Yahr. RESULTADOS: 42 por cento do grupo Parkinson e 10 por cento do grupo controle (p < 0,001) apresentaram depressão maior, segundo os critérios do Diagnostic Statistical Manual of Mental Diseases-IV. As médias de pontuação da Escala de Depressão de Hamilton e do Inventário de Depressão de Beck foram maiores no grupo Parkinson (p < 0,001). Em tempo de doença (p = 0,020), as médias dos escores de Hoehn-Yahr (p = 0,027) e Unified Parkinson Disease Rating Scale 3 (p = 0,029) foram maiores nos parkinsonianos com depressão. CONCLUSÕES: A freqüência (42 por cento) e a intensidade de depressão maior foram maiores no grupo Parkinson. A depressão maior também esteve significativamente relacionada à pior função motora dos parkinsonianos.

Quality of life scale in Parkinson's disease PDQ-39 - (Brazilian Portuguese version) to assess patients with and without levodopa motor fluctuation.

Quality of life (QoL) is an important treatment outcome indicator in Parkinson's disease (PD). The aim of this study is to assess the usefulness of the Parkinson's disease questionnaire--PDQ-39 (Brazilian Portuguese Version) in measuring QoL of PD patients with or without motor fluctuations. Fifty-six PD patients with mean disease duration of 7.4 years were assessed and 41 of them (73.3%) had motor fluctuations. The PDQ-39 has eight dimensions ranging from 0 to 100; being the higher the score, the worse the QoL. Comparing groups with and without motor fluctuations showed that the dimensions mobility, activities of daily living (ADL), communication and bodily discomfort scored higher in the fluctuating group. There was a tendency to see that the higher the Hoehn and Yahr (HY) scale stages, the higher the PDQ-39 scores. Patients suffering from the disease for more than five years had worse PDQ-39 scores only in the items ADL and communication, when compared with those with the disease for < 5 years. The PDQ-39 is an instrument that detects decrease in QoL of PD patients and the presence of motor fluctuations predicts QoL reduction.

Quality of life scale in parkinson's disease PDQ-39 - (Brazilian Portuguese version) to assess patients with and without levodopa motor fluctuation

Quality of life (QoL) is an important treatment outcome indicator in Parkinson's disease (PD). The aim of this study is to assess the usefulness of the Parkinson's disease questionnaire - PDQ-39 (Brazilian Portuguese Version) in measuring QoL of PD patients with or without motor fluctuations. Fifty-six PD patients with mean disease duration of 7.4 years were assessed and 41 of them (73.3 percent) had motor fluctuations. The PDQ-39 has eight dimensions ranging from 0 to 100; being the higher the score, the worse the QoL. Comparing groups with and without motor fluctuations showed that the dimensions mobility, activities of daily living (ADL), communication and bodily discomfort scored higher in the fluctuating group. There was a tendency to see that the higher the Hoehn and Yahr (HY) scale stages, the higher the PDQ-39 scores. Patients suffering from the disease for more than five years had worse PDQ-39 scores only in the items ADL and communication, when compared with those with the disease for < 5 years. The PDQ-39 is an instrument that detects decrease in QoL of PD patients and the presence of motor fluctuations predicts QoL reduction.

A qualidade de vida (QdV) é um item importante para se mensurar o sucesso do tratamento na doença de Parkinson (DP). O objetivo deste estudo foi o de avaliar a utilidade do questionário sobre a doença de Parkinson - PDQ-39 (versão em língua portuguesa falada no Brasil) para mensurar a QdV dos pacientes parkinsonianos com e sem flutuação motora. Nós avaliamos 56 pacientes com DP com tempo médio da doença de 7,4 anos, e destes 41 (73,3 por cento) apresentavam flutuação motora. A PDQ-39 tem oito domínios que variam de 0 a 100 e quanto maior o escore pior a QdV. A comparação dos grupos de pacientes com e sem flutuação motora mostrou que os domínios: mobilidade, atividades de vida diária, comunicação e desconforto corporal tinham escores maiores nos flutuadores. Quanto maiores os estágios de Hoehn e Yahr (HY) da doença, maiores os escores da PDQ-39. Pacientes com mais de 5 anos de evolução da doença mostraram escores piores da PDQ39 apenas nos itens atividades da vida diária e comunicação se comparados a pacientes com 5 anos ou menos de doença. A PDQ-39 é um instrumento capaz de detectar declínio da QdV de pacientes com DP e a presença de flutuação motora é um preditor para redução na QdV.