Globular glial tauopathy caused by MAPT P301T mutation: clinical and neuropathological findings.

OBJECTIVE: To describe the clinical, biochemical, and neuropathological findings of an autosomal dominant globular glial tauopathy caused by the P301T mutation at the MAPT gene. METHODS: Five patients from two unrelated pedigrees underwent clinical evaluation. Genetic analysis, brain pathological examination, and biochemical analysis of tau were performed. RESULTS: The patients studied were 3 men and 2 women with a mean age at onset of 52.2 years and mean disease duration of 5.2 years. Three patients presented a corticobasal syndrome, one patient an asymmetric pyramidal syndrome compatible with primary lateral sclerosis, and one patient a frontotemporal dementia. In both pedigrees (4 patients) Sanger sequencing showed the p.P301T mutation in exon 10 of the MAPT gene. Neuropathological findings consisted of atrophy of frontal and temporal lobes with marked spongiosis and astrogliosis, and abundant phosphorylated tau protein deposits in the frontal and temporal cortex, limbic area, basal ganglia, and brain stem. The most striking finding was the presence of oligodendroglial 4R phospho-tau globular positive inclusions in the white matter and cortex. Globose-type neurofibrillary neuronal tangles, and in particular astrocytic globular inclusions and coarse tufts, were present in the grey matter. Biochemical analysis of sarkosyl-insoluble fractions revealed two tau bands of 64 and 68 kDa and case-dependent bands of lower molecular weight. CONCLUSION: This is the first pathological and biochemical study of the MAPT p.P301T mutation showing variable clinical manifestation and neuropathological phenotype of globular glial tauopathy not only among different families but also within families.

Prevalence and concordance between the clinical and the post-mortem diagnosis of dementia in a psychogeriatric clinic. / Prevalencia y concordancia entre diagnóstico clínico y anatomopatológico de demencia en una clínica psicogeriátrica.

INTRODUCTION: The aim of our study is to describe the types of dementia found in a series of patients and to estimate the level of agreement between the clinical diagnosis and post-mortem diagnosis. MATERIAL AND METHODS: We conducted a descriptive analysis of the prevalence of the types of dementia found in our series and we established the level of concordance between the clinical and the post-mortem diagnoses. The diagnosis was made based on current diagnostic criteria. RESULTS: 114 cases were included. The most common clinical diagnoses both at a clinical and autopsy level were Alzheimer disease and mixed dementia but the prevalence was quite different. While at a clinical level, prevalence was 39% for Alzheimer disease and 18% for mixed dementia, in the autopsy level, prevalence was 22% and 34%, respectively. The agreement between the clinical and the autopsy diagnoses was 62% (95% CI 53-72%). CONCLUSIONS: Almost a third of our patients were not correctly diagnosed in vivo. The most common mistake was the underdiagnosis of cerebrovascular pathology.

Impact of initial FDG PET/CT in the management plan of patients with locally advanced head and neck cancer.

OBJECTIVE: To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). MATERIALS AND METHODS: We retrospectively reviewed the records of 72 consecutive patients (2007-2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36 %), oral cavity (17 patients, 24 %), oropharynx (16 patients, 22 %), nasopharynx (12 patients, 17 %), and others (2 %). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. RESULTS: FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12 % of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25 %) of patients, upstaging N stage in 90 % of patients with low impact. CONCLUSIONS: Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients.

Clinical characteristics of tuberculosis in immigrants and autochthonous populations, in 2 hospitals of Catalonia. / Características clínicas de la tuberculosis incidente en inmigrantes y autóctonos, en 2 hospitales de Cataluña (2000-2011).

BACKGROUND AND OBJECTIVES: Tuberculosis is a difficult-to-control endemic, and its incidence rate in Spain is greater than that of neighboring countries. In recent years, this has been due to an increased number of foreigners infected with the disease. The aim of this study was to compare the characteristics of this disease between immigrant and native populations in the last decade. PATIENTS AND METHOD: Observational, retrospective (2000-2011) multicenter study in 2 urban areas of Catalonia comparing the clinical presentation (risk factors, location and infectivity), the diagnostic delay and the completion of tuberculosis treatment between immigrants and natives. RESULTS: A total of 503 patients (181 immigrants and 322 Spaniards) were included. The immigrants were younger (mean age of 31 versus 46 years; P<.001), and 70.8% had lived in Spain for less than 5 years. Pulmonary tuberculosis was the most common clinical presentation (61.4%), with similar frequencies in immigrants and natives. Only osteoarticular involvement was significantly more common in immigrants from sub-Saharan Africa. The median diagnostic delay was 32 days, with no differences compared with the Spanish population. Proper adherence to the tuberculostatic treatment tended to be lower for immigrants (84.3% vs. 88.3%, P=.051). Treatment dropout was more common in immigrants (8 dropouts, P<.001). CONCLUSION: The main clinical characteristics and the diagnostic and therapeutic handling of immigrant patients with tuberculosis included in this study were similar to those of the native population.

[News on venous thromboembolic disease]. / Novedades en la enfermedad tromboembólica venosa.

This paper brings together the latest developments that have occurred in different aspects of venous thromboembolism (VTE): VTE prophylaxis in high-risk orthopedic surgery and acutely ill hospitalized medical patients; therapeutic advances in pulmonary embolism and superficial vein thrombosis and VTE future prospects. It summarizes the reviews that five speakers made in-depth for the Second Day in New Anticoagulant Treatment, held in Madrid on November 18, 2011, organized by the Foundation for the Study of Thromboembolic Disease in Spain and endorsed by the Spanish Society of Internal Medicine, Spanish Society of Pneumology and Thoracic Surgery, Spanish Society of Cardiology, Spanish Society of Thrombosis and Haemostasis and the Spanish Society of Angiology and Vascular Surgery.

Multiprotein deposits in neurodegenerative disorders: our experience in the tissue brain bank of Navarra.

The prevalence of neurodegenerative disorders increases dramatically with advancing age. Although in recent decades the study of many neurodegenerative disorders has evolved greatly, the concept of neurodegeneration still remains elusive. Although neurodegenerative disorders are classified according to the major components of protein deposits, coexpression of several abnormal proteins in the brain tissue is more common than that was previously thought. The aim of this report is to describe the type of protein deposits found in brains with neuropathological diagnosis of neurodegenerative disease. The report shows the experience obtained in the Brain Bank of Navarra (Spain). The target population for this retrospective descriptive study comprised 178 brains autopsied in the "Hospital of Navarra" in Pamplona between 1994 and 2004 and 201 brains donated to the Brain Bank of Pamplona between 2004 and 2009. The diagnosis of the 201 brains from the Brain Bank was 62 (30.8%) Alzheimer's disease (AD), 43 (21.3%) multiprotein deposit, 31 (15.4%) α-synucleinopathies, 31 (15.4%) frontotemporal lobar degeneration (FTLD), 17 (8.4%) tauopathies, 9 (4.4%) prion disease, 6 (2.9%) vascular dementia (VD), and 2 (0.9%) Huntington's disease. Among the 43 cases with multiprotein deposits, we found 35 brains with deposits of 3 proteins (tau, ß-amyloid, and α-synuclein). In these two series of brains, the high incidence of deposition of multiple proteins in neurodegenerative disorders is shown. Our results are in agreement with previous findings showing that tau, ß-amyloid, and α-synuclein are the proteins most frequently deposited together.

[Leptomeningeal dissemination in an intestinal-type sinonasal adenocarcinoma: an uncommon presentation]. / Diseminación leptomeníngea en un carcinoma nasosinusal de tipo intestinal: una forma de presentación inusual.

We present the case of a patient with a 30-year history of exposure to sawdust who was diagnosed with mucinous intestinal-type sinonasal adenocarcinoma after histological examination. The patient presented with neurological symptoms; moreover, intra- and extra-cranial leptomeningeal involvement, which is exceedingly rare in this type of tumors, was observed at the time of diagnosis.

[Fatal familiar insomnia: clinical, neurophysiological and histopathological study of two cases]. / Insomnio letal familiar: estudio clínico, neurofisiológico e histopatológico de dos casos.

INTRODUCTION: Family prion diseases are caused by mutations in the gene coding the prion protein (PrP), originating an altered isoform called prion. One of the most uncommon is the fatal familial insomnia (FFI), an entity characterized by sleep disorders and that is associated to a mutation in codon 178. METHODS: We have studied two male patients, aged 43 and 49 years respectively, from the same family. RESULTS: The most significant symptoms were sleep disorders with agitation, fractionated sleep, snoring and daytime sleepiness. The evolution was brief, the patient dying at a few months of the clinical debut. Sleep registries showed destructuration with total loss of the normal cycle of the phases and great decrease of the sleep spindles and K complexes in both cases. The polygraphy showed tachycardia and apnea pauses. In the molecular study, a mutation in the codon 178 was detected, both being methionine/methionine homozygotes at position 129. The most outstanding neuropathological abnormalities were located in the thalamus with gliosis and neuronal loss of anterior and dorsomedial ventral nuclei and also intense neuronal loss in olive of the first case. CONCLUSIONS: This study describes two new cases of FFI with genotype D178N-129M and short course classical phenotype. The polysomnography is essential in the diagnostic strategy of this disease whose neuropathological substrate is the thalamic alterations and of the inferior olive. Molecular biology permits an exact diagnosis of FFI although there is still controversy on the phenotypal variability and physiopathogenic mechanisms.

The influence of extreme body weight on clinical outcome of patients with venous thromboembolism: findings from a prospective registry (RIETE).

BACKGROUND: Data evaluating the safety of using weight-based dosing of low-molecular-weight heparin (LMWH) in either underweight or obese patients with venous thromboembolism (VTE) are limited. Thus, recommendations based on evidence from clinical trials might not be suitable for patients with extreme body weight. PATIENTS AND METHODS: Patients with objectively confirmed, symptomatic acute VTE are consecutively enrolled into the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. For this analysis, data from patients in the following ranges of body weight were examined: <50, 50-100, and >100 kg. Patient characteristics, underlying conditions, treatment schedules and clinical outcomes during the first 15 days of treatment were compared. RESULTS: As of August 2004, 8845 patients with acute VTE were enrolled from 94 participating centers. Of these, 169 (1.9%) weighed <50 kg, 8382 (95%) weighed 50-100 kg and 294 (3.3%) weighed >100 kg. Patients weighing <50 kg were more commonly females, were taking non-steriodal antiinflammatory drugs (NSAIDs), and had severe underlying diseases more often than patients weighing 50-100 kg. Their incidence of overall bleeding complications was significantly higher than in patients weighing 50-100 kg (odds ratio 2.2; 95% CI: 1.2-4.0). Patients weighing >100 kg were younger, most commonly males, and had cancer less often than those weighing 50-100 kg. Incidences of recurrent VTE, fatal pulmonary embolism or major bleeding complications were similar in both groups. CONCLUSIONS: Patients with VTE weighing <50 kg have a significantly higher rate of bleeding complications. The clinical outcome of patients weighing over 100 kg was not significantly different from that in patients weighing 50-100 kg.

[Systemic mastocytosis with skin manifestation versus indolent mastocytosis]. / Mastocitosis sistémica con afectación de piel versus mastocitosis indolente.

We have analyzed the clinical, analytical, radiologic, therapeutic an evolutive of cases of systemic mastocytosis (SM) skin lesions. The diagnostic of MS is difficult in the absence of skin lesions.

Efficacy and safety of oral and early-switch therapy for community-acquired pneumonia: a randomized controlled trial.

PURPOSE: We sought to determine the safety, efficacy, and cost of oral therapy for patients with community-acquired pneumonia. In patients with nonsevere pneumonia, conventional (parenteral) treatment was compared with the oral route; in patients with severe pneumonia, conventional treatment was compared with early switch from parenteral to oral therapy. SUBJECTS AND METHODS: We randomly assigned 85 hospitalized patients with nonsevere pneumonia to one of two groups: 41 received oral antimicrobials from admission, and 44 received parenteral antimicrobials until they had been afebrile for 72 hours before switching to oral treatment. We randomly assigned 103 patients with severe pneumonia who had initially been treated with parenteral antimicrobials to one of two groups: 48 were switched to oral therapy after 48 hours of treatment (early switch), and 55 received a full 10-day course of parenteral antibiotics. RESULTS: Among patients with nonsevere pneumonia, there were no deaths in the oral treatment group, and one death (2%) in the parenteral treatment group (95% confidence interval [CI] for between-group [oral minus parenteral] difference: -7% to 2%, P = 0.3). The time to resolution of morbidity was < or =5 days in 34 (83%) patients in the oral treatment group and 39 (88%) patients in the parenteral treatment group (P = 0.5); there were treatment failures in 4 (10%) patients in the oral treatment group and 14 (32%) patients in the parenteral treatment group (P = 0.02). Among patients with severe pneumonia, there was one (2%) death in the early-switch group and no deaths in the full course of parenteral antibiotics groups (95% CI for between-group [early switch vs. full course] difference: -2% to 6%, P = 0.5). The time to resolution of morbidity was < or =5 days in 38 (79%) patients in the early-switch group and 41 (75%) in the full-course group (P = 0.3). There were 12 (25%) treatment failures in the early-switch group and 13 (24%) in the full-course group (P = 0.9). There were fewer adverse events in the oral and early-switch groups, primarily due to lower rates of infusion-related phlebitis. Significant cost savings, mainly due to a shorter hospitalization, occurred among patients with severe pneumonia in the early-switch group. CONCLUSION: Inpatients with nonsevere community-acquired pneumonia can be effectively and safely treated with oral antimicrobials from the time of admission, whereas those with severe pneumonia can be treated with early-switch therapy.

[Clinical and neuropathological study of two brothers with Cockayne syndrome]. / Estudio clínico y neuropatológico en dos hermanos con síndrome de Cockayne.

INTRODUCTION: Cockayne syndrome (CS) is a rare autosomal recessive disease which is characterized by physical and mental retardation, progressive neurological disfunction, photosensitivity and other cutaneous features. Usually they present ophthalmologic abnormalities as well as other heterogenous clinical, radiological and pathologic features as leucodistrophy and calcifications in central nervous system and segmental demyelination in peripheral nervous system. CLINICAL CASES: Two brothers, sons of healthy unrelated parents, are presented. The first patient was referred at 8 months of age because of psychomotor retardation and the second one at 5 months old because of a cataract. At the age of 2 years both presented a complex clinical picture with photosensitivity, growth and mental retardation, peripheral neuropathy, neurosensorial deafness, and cerebral atrophy and calcifications in neuroimaging diagnosis tests. In the following years the older brother presented signs of renal failure, cataracts and retinopathy, and died at 9 years old because of a respiratory infection. The neuropathologic study showed a discrete neuronal loss and diffuse demyelination with calcium deposits in cerebral white matter and basal ganglia. Today the second patient is 8 years old and shows a clinical course similar to that of his brother. CONCLUSIONS: Clinical, radiologic and pathologic features in our patients support the diagnosis of CS type II.

Differential diagnosis between community-acquired pneumonia and non-pneumonia diseases of the chest in the emergency ward.

Background: The differential diagnosis of community-acquired pneumonia and some non-pneumonia diseases involving the chest may sometimes be cumbersome. Adding some objective variables to the diagnostic strategy may be helpful.We evaluated the main objective variables that are usually available in the emergency ward and that may be valuable in this differential diagnosis. Methods: We recorded epidemiological, clinical, and analytical data, as well as that obtained from physical examination, from 284 consecutive patients diagnosed in the emergency ward as having community-acquired pneumonia. The diagnosis was reviewed by the investigators applying pre-set diagnostic criteria. Statistical analysis was then performed comparing data from patients with a definitive diagnosis of community-acquired pneumonia with those with a final diagnosis of non-pneumonia disease excluding acute exacerbations of chronic bronchitis. Results: In the univariate analysis, C-reactive protein (difference of means 93 mg/l; 95% C.I. 47, 140), erythrocyte sedimentation rate (d.m. 19 mm/h; 95% C.I. 3, 35), leukocyte count (d.m. 3.5x10(9)/l; 95% C.I. 0.5, 6.4), and temperature (d.m. 0.5 degrees C; 95% C.I. 0.1, 0.9) discriminated between community-acquired pneumonia and non-pneumonia diseases. In the multivariate analysis, only C-reactive protein remained in the equation. Conclusions: C-reactive protein, erythrocyte sedimentation rate, leukocyte count, and temperature were measurable variables that proved to be useful in the differential diagnosis between community-acquired pneumonia and non-pneumonia diseases. C-reactive protein appears to be the most suitable for this purpose.

[Andersen syndrome. Description of a case] . / Síndrome de Andersen. Descripción de un caso.

A 17 year-old man, with periodic muscular weakness since the age of 6 years, is presented. The episodes of periodic paralysis were of variable duration, from 1 to 3 days, and were induced by physical exercise or by stress. Weakness was generalised, although predominant in anterior compartment of the legs, with foot drop. Interictal neurological examination was absolutely normal. He showed dysmorphic features, with micrognatia. Cardiac examination revealed continuous arrhythmia. Basal EKG and 24 hours EKG-Holter confirmed the existence of abundant ventricular extrasystoles, with episodes of ventricular tachycardia, without clinical manifestations. Echocardiogram was normal. Ictal and interictal ENG-EMG, and muscle and nerve biopsies were normal. Serum potassium levels during the episodes ranged from 3 to 3.6 mEq/l (N: 3.5-4.5 mEq/l), being normal interictally (4-5 mEq/l). Oral administration of potassium did not prevent the development of episodic weakness. He had no familial history of similar symptoms. This association of periodic paralysis, cardiac arrhythmia and dysmorphic features correspond to a rare entity named Andersen's syndrome.