Increasing the incidence of the Guillain-Barre syndrome in Curacao

OBJECTIVE: To confirm an observed increase in the occurrence of Guillain-Barre syndrome (GBS) in patients in Curacao. DESIGN AND METHODS: Between 1987 and 1999, medical records of all patients who fulfilled the National Institute of Neurological Communicative Disorders and Stroke (NINCDS) criteria for GBS were reviewed. RESULTS: Forty-nine patients were diagnosed as GBS resulting in an incidence rate (IR) of 2.53/100,000 inhabitants (95 percent CI 1.87-3.35). From 1987 to 1991, the IR remained stable, whereas from 1992 to 1999, there was a linear increase in the IR. There was a high IR in the colder months and a low IR in the warmer months. Patients showed a low percentage of sensory involvement (17 percent, generally 65 percent), rapid progression of the disease (83 percent, generally 30 percent), high percentage of artificial respiration (31 percent, generally 17 percent) and high mortality rate (23 percent, generally 3-5 percent). Fifty-five percent of the patients reported a preceding gastroenteritis (GE); 9/10 serum samples showed evidence of a recent Campylobacter jejuni infection. CONCLUSIONS: This is the first report of an increase in IR of GBS over a longer period, associated with low percentage of sensory involvement, a more severe course and a high mortality rate. The characteristics suggest a role for C jejuni. Prospective research is needed to show whether the increase in GBS is due to an overall increase in IR of C. jejuni infections on the island.(Au)

Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala

Male Wistar rats were trained in one-trial step-down inhibitory avoidance using a 0.4-mA footshock. At various times after training (0, 1.5, 3,6 and 9 h for the animals implanted into the CA1 region of the hippocampus; 0 and 3 h for those implanted into the amygdala), these animals received microinfusions of SKF38393 (7.5 mug/side), SCH23390 (0.5 mug/side), norepinephrine (0.3 mug/side), timolol (0.3 mug/side), 8-OH-DPAT (2.5 mug/side), NAN-190 (2.5 mug/side), forskolin (0.5 mug/side), KT5720 (0.5 mug/side) or 8-Br-cAMP (1.25 mug/side). Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Again, at 9 h after training, all treatments were inffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory cosolidation at 3 and 6 h after training, which is regulated by D1, Beta, and 5HT1A receptors. This correlates with data on increased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h) in rat hippocampus after training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.

Involviment of the hippocampus, amygdala, entorhinal cortex and posterior parietal cortex in memory consolidation

A total of 182 young adult male Wistar rats were bilaterally implanted with cannulae into the CA1 region of the dorsal hippocampus and into the amygdaloid nucleus, the entorhinal cortex, and the posterior parietal cortex. After recovery, the animals were trained in a stepdown inhibitory avoidance task. At various times after training (0, 30, 60 or 90 min) the animals received a 0.5-mul microinfusion of vehicle (saline) or O.5 mug of muscimol dissolved in the vehicle. A retention test was carried out 24 h after training. Retention test performance was hindered by muscimol administered into both the hippocampus and amygdala at 0 but not at 30 min posttraining. The drug was amnestic when given into the entorhinal cortex 30, 60 or 90 min after training, or into the parietal cortex 60 or 90 min after training, but not before. These findings suggest a sequential entry in operation, during the posttraining period, of the hippocampus and amygdala, the entorhinal cortex, and the posterior parietal cortex in memory processing.

High dose immunoglobulins and plasma exchange in the Guillain-Barré Syndrome

The background, design and preliminary results of the Dutch Guillain-Barré trial comparing high-dose immunoglobulins (IgIV) with plasma-exchange (PE) are described. This randomized trial was conservative in that the main aim was to show equal effect of both treatments within certain predefined limits. This approach was appropriate since IgIV is quickly and easily applicable, whereas PE is much more combersome leading to treatment delays and a considerable dropout rate. Moreover PE is not available in all hospitals. For these reasons IgIV would be preferable if the two treatments have a similar effect. We originally estimated that 200 patients would be needed to demonstrate a comparable effect of IgIV and PE (type I error = 0.05 and type II error = o.2). At the interim analysis after 150 patients the stopping criterion has been met. Four weeks after randomization 52.7 per cent in the IgIV group was functionally improved and 34.2 per cent in the PE-group, and advantage of 18.5 per cent for IgIV (p = 0.024)

Prognosis in the Guillain-Barre syndrome / Prognosis in the Guillain-Barre syndrome

Estudamos 147 pacientes, participantes do estudo multicentrico holandes, para comparacao da efetividade de altas doses de imunoglobulina humana com a da plasmaferese na sindrome de Gillain-Barre, com o objetivo de verificar a influencia dos seguintes fatores no prognostico da sindrome: idade, duracao (menor igual 7 dias), respiracao artificial, potencial de acao muscular composto (PAMC) menor 3mV (20 por cento) - identificdos como fatores prognosticos em estudos previos - e graduacao funcional, graduacao pelo somatorio da escala do Medical Research Council 9mRC), anticorpos anti GMI e sorologia positiva para Campilobacter jejuni - explorados no presente estudo. Utilizamos, para gradacao da gravidade da sindrome, a seguinte escala de graduacao funcional (F): 0, normal; 1, sintomas e sinais menores, sendo o paciente completamente capaz de exercer tarefas manuais; 2, capaz de caminhar mais de 10 metros sem assistencia; 3, capaz de andar mais de 10 metros com assistencia; 4, restrito ao leitor ou a cadeira; e, ventilacao assistida requerida por, pelo menos, parte do dia; 6, morte. O criterio principal de prognostico foi definido como melhora ate o final da quarta semana em pelo menos um grau da escala. O criterio secundario de prognostico foi definido como os periodos de tempo: para haver melhora de um grau e para adquirir locomocao independente (F-2). A avaliacao funcional foi tambem efetivada, de uma maneira mais sutil, atraves da medida de forca muscular em seis grupos musculares individuais, em ambos os lados do corpo, usando a escala do MRC. A soma das 12 gradacoes, variando de 0 a 5, oferece uma pontuacao de 60, normal, a 0, tetraplegia. Os fatores que influenciam o prognostico estao relacionados a seguir Alteracao da graduacao para melhor, igual ou maior que IF, ate o final da quarta semana: idade, imunoglobulina humana endovenosa, anticorpos contra GMI e sorologia positiva para Campilobacter. Periodo de tempo para a graduacao se alterar para melhor, de IF ou mais idade, PAMC, GMI, somatorio pela escala do MRC. Periodo de tempo para se atingir 2F de melhora: idade, GMI, somatorio pela escala MRC. Estamos ainda analisando como os fatores determinados podem ser utilizados para predicao da evolucao de cada paciente, individualmente. Podemos, de momento, dizer que se um paciente tem menos de 50 anos de idade, se nao sao detectados anticorpos contra GMI e o somatorio na escala do MRC esta acima de 40, ha mais que 90 por cento de probabilidade de que o paciente consiga andar independentemente antes dos seis meses de idade (grau funcional 2). Se os tres fatores forem diferentes do que foi referido acima, a probabilidade cai para 30 por cento.

High dose immunoglobulins and plasma exchange in the Guillain-Barre Syndrome / High dose immunoglobulins and plasma exchange in the Guillain-Barre Syndrome

Apresentamos o desenho metodologico e comunicamos os resultados e comunicamos os resultados iniciais do estudo multicentrico holandes, comparando o tratamento da sindrome de Guillain-Barre com imunoglobulinas humanas endovenosas em altas doses (IgIV) e plasmaferese (PE). O estudo multicentrico e randomico e conservador no sentido de que a principal finalidade e demonstrar um efeito igual de ambas as terapeuticas dentro de certos limites pre-definidos. Esta abordagem foi adequada, uma vez que IgIV e facil e rapidamente aplicavel, enquanto que a PE e terapeutica complexa, o que pode conduzir a demoras e numero insuficiente de sessoes. IgIV seria preferivel se os dois tratamentos tivessem efeito semelhante. Inicialmente estimamos que 200 pacientes seriam necessarios para a demonstracao de efeito comparavel dos dois tratamentos IgIV x PE (erro do tipo I igual 0,05 e do tipo II igual a 0,2). Na analise preliminar, apos o tratamento de 150 pacientes, o criterio de ponto final foi atingido. Quatro semanas apos a randomizacao 52,7 por cento de pacientes no grupo que utilizou PE apresentaram melhora funcional. A diferenca a favor da IgIV foi de 18,5 por cento (P igual 0,024).