Diagnostic delay and outcome in immunocompetent patients with primary central nervous system lymphoma in Spain: a multicentric study.

INTRODUCTION: To assess the management of immunocompetent patients with primary central nervous system lymphomas (PCNSL) in Spain. METHODS: Retrospective analysis of 327 immunocompetent patients with histologically confirmed PCNSL diagnosed between 2005 and 2014 in 27 Spanish hospitals. RESULTS: Median age was 64 years (range: 19-84; 33% ≥ 70 years), 54% were men, and 59% had a performance status (PS) ≥ 2 at diagnosis. Median delay to diagnosis was 47 days (IQR 24-81). Diagnostic delay > 47 days was associated with PS ≥ 2 (OR 1.99; 95% CI 1.13-3.50; p = 0.016) and treatment with corticosteroids (OR 2.47; 95% CI 1.14-5.40; p = 0.023), and it did not improve over the years. Patients treated with corticosteroids (62%) had a higher risk of additional biopsies (11.7% vs 4.0%, p = 0.04) but corticosteroids withdrawal before surgery did not reduce this risk and increased the diagnostic delay (64 vs 40 days, p = 0.04). Median overall survival (OS) was 8.9 months [95% CI 5.9-11.7] for the whole series, including 52 (16%) patients that were not treated, and 14.1 months (95%CI 7.7-20.5) for the 240 (73.4%) patients that received high-dose methotrexate (HD-MTX)-based chemotherapy. Median OS was shorter in patients ≥ 70 years (4.1 vs. 13.4 months; p < 0.0001). Multivariate analysis identified age ≥ 65 years, PS ≥ 2, no treatment, and cognitive/psychiatric symptoms at diagnosis as independent predictors of short survival. CONCLUSIONS: Corticosteroids withdrawal before surgery does not decrease the risk of a negative biopsy but delays diagnosis. In this community-based study, only 73.4% of patients could receive HD-MTX-based chemotherapy and OS remains poor, particularly in elderly patients ≥ 70 years.

Dosis bajas frente a dosis altas de topiramato en el tratamiento preventivo de la migraña / Low versus high doses of topiramate in the preventive treatment of migraine

ntroducción. La eficacia de topiramato en la profilaxis de la migraña está bien demostrada. Los ensayos clínicos indican que la dosis de 100 mg/día es la ideal en términos de eficacia, si bien dosis tan bajas como 50 mg/día pueden ser eficaces, lo que podría mejorar su tolerabilidad en algunos pacientes. Objetivo. Analizar el comportamiento de las diferentes dosis de topiramato en condiciones de práctica clínica diaria. Pacientes y métodos. Los pacientes con migraña con y sin aura frecuente que recibieron topiramato en nuestra consulta fueron tratados con una pauta homogénea. Se les indicó inicialmente 50 mg/día (habitualmente en dosis única nocturna) en pauta ascendente en 2- 3 semanas. La eficacia del fármaco se evaluó a las 6-8 semanas. Si no se constataba mejoría (reducción del número de crisis >50%) incrementamos la dosis de topiramato a razón de 25 mg/semana hasta 100 mg/día. Los pacientes fueron revisados al menos una vez cada 3 meses. Resultados. Esta serie incluye a 182 pacientes. En global, un 75% de los pacientes respondieron al topiramato, un 14% no respondieron y un 11% no toleraron el fármaco. Una cuarta parte de los pacientes (44 casos) respondieron a dosis bajas, mientras que 92 pacientes (51%) respondieron a dosis de 100 mg/día. La tolerabilidad empeoró ligeramente al incrementar la dosis. Conclusiones. Estos datos indican que dosis bajas de topiramato pueden ser útiles en una cuarta parte de pacientes con migraña en condiciones de práctica clínica, si bien la mitad de los pacientes necesitarán dosis de 100 mg/día. Dada la mejor tolerabilidad de las dosis bajas, recomendamos hacer un intento de tratamiento inicial con dosis bajas antes de administrar dosis más elevadas, que serán necesarias en la mitad de los pacientes (AU)

Introduction. The efficacy of topiramate in the preventive treatment of migraine is well demonstrated. Clinical trials indicate that the dose of 100 mg/daily is the ideal in terms of efficacy, but doses as low as 50 mg/ daily show some efficacy, which could improve its tolerability in some patients. Objetive. To analyse the behaviour of the different doses of topiramate in daily clinical practice. Patients and methods. Patients with frequent migraine with or without aura episodes who received topiramate in our clinic were treated in a homogeneous way. Initially they were given 50 mg/daily (usually as a nocturnal dose), after increasing the dose in 2-3 weeks. The efficacy was evaluated after 6-8 weeks. If no response (decrease in frequency by at least 50%) was observed the dose of topiramate was increased (25 mg/week) up to 100 mg/daily, The patients were seen at least once every 3 months. Results. This series includes 182 patients. Globally, 75% of the patients responded, 14% did not respond and 11% did not tolerate the drug. One-quarter of patients (44 cases) responded to low doses, while 92 patients (51%) responded to the 100 mg/dose. Tolerability slightly decreased on increasing the dose. Conclusions. These data indicate that one-quarter of the patients respond to low doses in daily clinical practice, though about half of these patients will need doses of 100 mg/day. Given the higher tolerability of low doses, we recommend trying first low doses before giving higher doses, which will be necessary in half of the patients (AU)

[Low versus high doses of topiramate in the preventive treatment of migraine]. / Dosis bajas frente a dosis altas de topiramato en el tratamiento preventivo de la migraña.

INTRODUCTION: The efficacy of topiramate in the preventive treatment of migraine is well demonstrated. Clinical trials indicate that the dose of 100 mg/daily is the ideal in terms of efficacy, but doses as low as 50 mg/ daily show some efficacy, which could improve its tolerability in some patients. OBJECTIVE: To analyse the behaviour of the different doses of topiramate in daily clinical practice. PATIENTS AND METHODS: Patients with frequent migraine with or without aura episodes who received topiramate in our clinic were treated in a homogeneous way. Initially they were given 50 mg/daily (usually as a nocturnal dose), after increasing the dose in 2-3 weeks. The efficacy was evaluated after 6-8 weeks. If no response (decrease in frequency by at least 50%) was observed the dose of topiramate was increased (25 mg/week) up to 100 mg/daily, The patients were seen at least once every 3 months. RESULTS: This series includes 182 patients. Globally, 75% of the patients responded, 14% did not respond and 11% did not tolerate the drug. One-quarter of patients (44 cases) responded to low doses, while 92 patients (51%) responded to the 100 mg/dose. Tolerability slightly decreased on increasing the dose. CONCLUSIONS: These data indicate that one-quarter of the patients respond to low doses in daily clinical practice, though about half of these patients will need doses of 100 mg/day. Given the higher tolerability of low doses, we recommend trying first low doses before giving higher doses, which will be necessary in half of the patients.

[Pentoxifylline: is it useful in multiple sclerosis?]. / Pentoxifilina: es útil en la esclerosis múltiple ?

INTRODUCTION: Pentoxifylline (PTX) is a phosphodiesterase inhibitor which has been found in studies in vitro to inhibit the production of Th-1 cytokines. It has been postulated that it might be used as a possible coadjuvant treatment for interferon in patients with multiple sclerosis. This would also reduce the potential side effects of interferon. OBJECTIVE. To show the efficacy of PTX in reducing the side effects of interferon, and in the functional improvement of these patients. PATIENTS AND METHODS: We studied 18 patients with remitting-relapsing multiple sclerosis over a period of 18 months; nine patients were given PTX and interferon 800 mg/day simultaneously, and nine patients were treated with interferon alone. The clinical condition was evaluated every three months using the Expanded Disability Status Scale (EDSS) and the Neurological Score (NRS) scales. RESULTS: We found no statistical improvement in the clinical course of EDSS and NRS in either group of patients after treatment for 18 months. The patients treated with PTX have fewer secondary effects due to interferon (fever and myalgia) during the first three months, but these differences between the groups subsequently disappear. In two patients PTX caused transient gastralgias and nauseas. CONCLUSIONS: PTX may be useful as a coadjuvant drug with interferon during the first three months of treatment since some of the side effects of interferon may thus be reduced. However, there seems no justification for using PTX for a longer period since there is no functional improvement.

Pentoxifilina: ¿es útil en la esclerosis múltiple? / Pentoxifylline: is it useful in multiple sclerosis?

Introducción. La pentoxifilina (PTX) es un inhibidor de la fosfodiesterasa que en estudios in vitro inhibe la producción de citocinas Th-1 y se ha postulado como posible tratamiento coadyuvante del interferón (IFN) en los pacientes con esclerosis múltiple, disminuyendo además los posibles efectos secundarios de este fármaco.Objetivos. Comprobar la eficacia de la PTX en la reducción de los efectos secundarios del IFN y en la evolución funcional de los pacientes. Pacientes y métodos. Estudiamos 18 pacientes con esclerosis múltiple remitente-recurrente durante un período de 18 meses; nueve pacientes recibieron simultáneamente 800 mg/día de PTX e IFN y otros nueve enfermos fueron tratados sólo con IFN. Se evaluó su estado clínico cada tres meses aplicando las escalas del estado de incapacidad ampliada (EDSS) y la Neurological Score (NRS). Resultados. No apreciamos mejoría estadísticamente significativa en la evolución de la EDSS y NRS entre ambos grupos de pacientes después de 18 meses de tratamiento. Los pacientes que reciben PTX tienen menos efectos secundarios del IFN (fiebre y mialgias) durante los tres primeros meses, pero estas diferencias entre ambos grupos desaparecen posteriormente. En dos pacientes la PTX produjo transitoriamente gastralgias y náuseas. Conclusiones. La PTX podría ser útil como fármaco coadyuvante del IFN durante los tres primeros meses de tratamiento al reducir algunos efectos secundarios del mismo, pero no parece justificado mantenerlo más tiempo al no existir mejoría del estado funcional (AU)

Body iron stores and early neurologic deterioration in acute cerebral infarction.

BACKGROUND: Iron-dependent free radicals formation has been related to greater damage in cerebral ischemia. The authors analyzed whether increased body iron stores were associated with early neurologic worsening and excitatory amino acid release in patients with acute ischemic stroke. METHODS: Ferritin, total iron, and glutamate concentrations in plasma and CSF were measured on admission in 100 consecutive patients with a cerebral infarction of <24 hours' duration. The authors diagnosed progressing stroke when the Canadian Stroke Scale score decreased one or more points between admission and 48 hours. Cranial CT was performed on admission and repeated on days 4 to 7 of hospitalization. RESULTS: Ferritin concentrations in plasma (median 391, range 119 to 500 versus 148, 21 to 399 ng/mL) and in CSF (17.4, 6.8 to 82, versus 4.8, 0.6 to 14 ng/mL) were significantly higher in the 45 patients with subsequent progressing stroke than in those with nonprogressing stroke (p < 0.001). There was a positive correlation between ferritin and glutamate concentrations in plasma (r = 0.81, p < 0.001) and CSF (r = 0.64, p < 0.001). Plasma ferritin concentrations >275 ng/mL in plasma (OR, 33.5; 95% CI, 4.7 to 235) and >11 ng/mL in CSF (OR, 11.4; 95% CI, 3. 1 to 41) were independently and significantly related to early neurologic worsening. The effect was reduced by >60% after controlling for glutamate concentrations, but remained significant. CONCLUSIONS: High plasma and CSF ferritin concentrations within the first 24 hours from the onset of ischemic stroke are associated with early neurologic deterioration. Increased body iron stores may contribute to stroke progression by enhancing the cytotoxic mechanisms in cerebral ischemia.

[Lewy bodies dementia: new data for the understanding of neuroimaging]. / Demencia con cuerpos de Lewy: nuevas aportaciones al conocimiento de la neuroimagen.

INTRODUCTION: The criteria for diagnosis of dementia with Lewy bodies (DLB) do not include neuroimaging, and few reports have been published on this. OBJECTIVE: To report our observations of cerebral CAT and MR studies in 25 patients with probable DLB. PATIENTS AND METHODS: Measurement of the surface of the cerebral lobes and the hippocampal region in two axial sections on CAT and MR and three coronal sections on MR. Our controls were 27 persons with probable Alzheimer's disease and 30 healthy persons of the same age group. RESULTS: The size of the frontal, parietal and temporal lobes in DLB is intermediate between the values found in Alzheimer's disease and those found in asymptomatic persons, but without significant differences from these. Atrophy of the hippocampal region seen in DLB is significant as compared with healthy persons, but not when compared with those with Alzheimer's disease, in whom it was greater still. In the patients in whom DLB was still not an advanced stage, there was no atrophy of the occipital lobes, in spite of other observers having found hypoactivity of these lobes on SPECT and PET. CONCLUSION: In the sample studied, structural imaging techniques were not useful in the diagnosis of DLB.

[Hospital mortality in ischemia: influence of two vascular risk factors]. / Mortalidad hospitalaria en el ictus: influencia de los factores de riesgo vascular.

INTRODUCTION: Acute cerebrovascular disease is a serious neurological problem. Mortality is between 6% and 30%. Most studies are in agreement that advanced age, type of ictus, size of lesion and clinical deterioration are factors determining mortality. However, its relationship to vascular risk factors is not completely clear. OBJECTIVE: To analyze the repercussion of different vascular risk factors on mortality during the acute phase of ictus. PATIENTS AND METHODS: We studied all patients with ictus admitted to the Servicio de Neurología of the Hospital Xeral de Galicia de Santiago de Compostela over a period of 3 years (n = 915). We recorded vascular risk factors and analyzed the causes of mortality whilst in hospital. RESULTS: Hospital mortality due to ictus was 16.8%. Mortality was 14.5% in cerebral infarct, 23.2% in intracerebral haemorrhage and 19.4% in subarachnoid haemorrhage. A total of 20.8% of the patients died of neurological causes, 24.7% of vascular causes, 26% due to infection and of uncertain causes in the remaining 28.6%. There was a neurological cause of death in 46.1% of the patients with subarachnoid haemorrhage, 25.5% with intracerebral haemorrhage and 14.8% with cerebral infarcts. Vascular risk factors associated with greater mortality were age (p < 0.001) and a history of cardiopathy (p < 0.05). CONCLUSIONS: Vascular risk factors which indicated worse prognosis were: age, type of ictus and a history of cardiopathy.

[Progressive degenerative aphasia: clinical and neuroradiological observations in 18 cases]. / Afasia progresiva degenerativa: observaciones clínicas y neurorradiológicas en 18 casos.

INTRODUCTION: In some types of degenerative dementia aphasia is the main disorder. In primary progressive aphasia. (PPA) atrophy is limited to the dominant peri-sylvan region. We present 18 cases of progressive aphasia of degenerative origin, with or without dementia. MATERIAL AND METHODS: We describe the clinical and neuro-radiological findings in 3 patients with 'aphasic dementia and motor neuron disease (ADMND)', 7 with 'semantic dementia' (DS), and 4 with 'fronto-temporal dementia' with 'marked non-fluent aphasia' (AFTD). Criteria published in recent years were used. RESULTS: In patients with ADMND non-fluent aphasia progressed to global aphasia, with dementia occurring after 2-9 months, and death after an average of 17 months. In cases with SD, initial anomic aphasia progressed to transcortical sensory or global aphasia, and in patients with AFTD, Broca's aphasia or motor transcortical aphasia progressed to global aphasia. Seven of these patients had been initially diagnosed as having PPA and became demented after two years or more. In most of the cases the cognitive disorder had the characteristics of fronto-temporal dementia. All cases had cortical atrophy or asymmetrical cortical or cortico-subcortical atrophy. The 4 cases of non-fluent PPA were not demented after 21 months-6 years of illness, and showed perisylvan and left fronto-temporopolar atrophy. CONCLUSIONS: The PPA may correspond to the initial form of at least three varieties of dementia, usually the fronto-temporal type. Dementia occurs after two years or more, except in patients with motor neurone disease, when there is a latent period of less than one year.