Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain.

BACKGROUND AND PURPOSE: Chitinase 3-like 1 (CHI3L1) and neurofilament light chain (NF-L) are promising biomarkers of disability in multiple sclerosis (MS). However, their role in cognitive dysfunction remains elusive. Here, we aimed to correlate cerebrospinal fluid (CSF) levels of CHI3L1 and NF-L with cognitive status in MS. METHODS: Fifty one recently diagnosed patients were cognitively evaluated and CSF was collected. Levels of CHI3L1 and NF-L were determined by ELISA. Spearman's partial correlation coefficient was performed. RESULTS: After adjusting cognitive scores by age, anxiety and EDSS, association was detected between CHI3L1 levels and Trail Making Test A (rs = 0.348; p = 0.016) and between NF-L levels and Word List Generation (rs = -0.324; p = 0.025). CONCLUSION: High levels of CSF CHI3L1 and NF-L are associated with cognitive impairment in the early phases of MS.

Neuroinflammation in obesity: circulating lipopolysaccharide-binding protein associates with brain structure and cognitive performance.

BACKGROUND/OBJECTIVES: Growing evidence implicates neuroinflammation in the pathogenesis of diet-induced obesity and cognitive dysfunction in rodent models. Obesity is associated with reduced white matter integrity and cognitive decline. Circulating lipopolysaccharide binding protein (LBP) concentration is known to be increased in patients with obesity. Here, we aimed to evaluate whether circulating LBP is associated longitudinally with white matter structure and cognitive performance according to obesity status. SUBJECTS/METHODS: This longitudinal study analyzed circulating LBP (ELISA), DTI-metrics (axial diffusivity (L1), fractional anisotropy (FA) and radial diffusivity (RD)) in specific regions of the white matter of 24 consecutive middle-aged obese subjects (13 women) and 20 healthy volunteers (10 women) at baseline and two years later. Digit Span Test (DST) was used as a measure of working memory/short-term verbal memory. RESULTS: Circulating LBP concentration was associated with FA and L1 values of several white matter regions both at baseline and follow-up. The associations remained significant after controlling for age, BMI, fat mass and plasma high sensitivity C-reactive protein. Importantly, the increase in LBP over time impacted negatively on FA and L1 values and on DST performance. CONCLUSIONS: Circulating LBP associates with brain white matter integrity and working memory/short-term verbal memory in both obese and non-obese subjects.

[Clinical and demographic characteristics of the cases of dementia diagnosed in the Health District of Girona throughout the period 2007-2010: data from the Girona Dementia Registry (ReDeGi)]. / Caracteristicas clinicas y demograficas de los casos de demencia diagnosticados en la Region Sanitaria de Girona durante el periodo 2007-2010: datos del Registro de Demencias de Girona (ReDeGi).

INTRODUCTION: The Girona Dementia Registry (ReDeGi, from Spanish: Registro de Demencias de Girona) is a population-based epidemiological surveillance mechanism that registers the cases of dementia diagnosed by the reference centres in the Girona Health District. AIM: To report on the frequency of the diagnoses and their clinical and sociodemographic characteristics, as well as to compare differences depending on the different subtypes of dementia. PATIENTS AND METHODS: The method used consisted in a consecutive standardised register of the diagnoses involving dementia in specialised procedures in the Girona Health District between 2007 and 2010. RESULTS: A total of 2814 cases were registered, which represents a clinical incidence of 6.6 cases per 1000 persons/year. Of this total number, 69.2% were primary degenerative dementias, 18.9% were dementias secondary to a vascular pathology, 5.4% were other secondary dementias and 6.5% were non-specific dementias. The mean age was 79.2 ± 7.6 years (range: 33-99 years) and 59.3% were females. The mean time elapsed since the onset of symptoms and clinical diagnosis was 2.5 ± 1.7 years. The mean score on the Blessed dementia scale was 7.7 ± 4.5 points and in the minimental test it was 17.6 ± 5.4 points. A family history of dementia was present in 26.6% of cases and 69.6% presented one or more cardiovascular risk factors. In 60.6% of cases they were cases of mild dementia, 28.5% were moderate and 10.9% were severe cases. CONCLUSIONS: The epidemiological surveillance activity carried out by the ReDeGi throughout the period 2007-2010 has made it possible to record information that is extremely valuable for the planning and management of health care resources.

A kindred with cerebellar ataxia and thermoanalgesia.

OBJECTIVE: To characterise the clinical, neurophysiological, neuropathological and genetic features of a family with cerebellar autosomal dominant ataxia. DESIGN: Patients were submitted to clinical, neuroradiological and neurophysiological examinations. Molecular studies were undertaken to exclude SCAs 1-3, 6-8, 12 and 17. Studies were performed to rule out linkage to SCA4 on chromosome 16, and for all still uncharacterised SCA loci. Neuropathological examination of the proband was performed with immunocytochemistry. RESULTS: These patients presented a late onset cerebellar ataxia with thermoanalgesia and deep sensory loss. Unlike in SCA4, reflexes were preserved. MRI revealed cerebellar, medullar and spinal cord atrophy. Neurophysiological studies showed absence or marked reduction of the sensory nerve action potentials and somatosensory evoked potentials in lower and upper limbs but preservation of the soleus H reflex. No triplet repeat expansion mutations in the studied SCA genes were identified. Our studies ruled out linkage of the disease to the SCA4 locus on chromosome 16 and the remaining reported SCA loci. The neuropathological study of the proband revealed severe loss of Purkinje cells and dentate neurons. The inferior olive and lower cranial nerve nuclei also showed extensive cell loss. Posterior columns and spinocerebellar tracts were demyelinated. Ubiquitin immunoreactive intranuclear inclusions were absent. CONCLUSION: This kind of cerebellar ataxia, associated with thermoanalgesia as well as deep sensory loss with retained reflexes, does not associate to any known SCA loci. Therefore, we identify and describe a new form of late onset dominant spinocerebellar ataxia.

Paroxysmal dystonia and pathological laughter as a first manifestation of multiple sclerosis.

Paroxysmal dystonia is an uncommon but well-established feature of multiple sclerosis (MS). Attacks can occur in established MS and may even occasionally be the initial symptom of this disorder. Pathological laughter is usually seen as a pseudobulbar palsy in some diffuse neurological diseases, but cases have been described, mostly in ischaemic attacks or tumours, where it is presented as bursts of laughter of variable duration. The pathogenesis of neither of the two phenomena has been fully established but both have been reported as being positive phenomena resulting from ectopic activation with ephaptic spread. We describe the first reported case of a paroxysmal hemidystonia together with bursts of pathological laughter as the first manifestation of MS.

¿Existe relación entre el colesterol y el deterioro cognitivo? / Does a relationship exist between cholesterol and cognitive deterioration?

La población envejece y, como consecuencia de ello, en las próximas décadas se producirá un incremento espectacular de las enfermedades que se relacionan con la edad. Los procesos neurodegenerativos y la arteriosclerosis serán los fenómenos más prevalentes en esta población. La conservación del árbol vascular y un control adecuado de los factores de riesgo preponderantes pueden disminuir la incidencia de estas enfermedades invalidantes. Diversas investigaciones poblacionales, en animales de laboratorio y en humanos, ofrecen datos esperanzadores sobre el papel que desempeña el colesterol plasmático en el deterioro cognitivo. Los fármacos inhibidores de la HMG-CoA reductasa pueden convertirse, en un futuro no muy lejano, en el tratamiento de elección en pacientes con factores de riesgo vasculares (AU)

Populations age and, as a consequence, in the next few decades there will be a spectacular increase in age-related diseases. Neurodegenerative processes and atherosclerosis will be the most prevalent phenomena in this population. Conservation of the vascular tree and adequate control of the main risk factors could reduce the incidence of these incapacitating diseases. Several population-based studies in laboratory animals and humans provide hopeful data on the role played by plasma cholesterol in cognitive deterioration. In the not too distant future, HMG-CoA reductase inhibitors could become the treatment of choice in patients with vascular risk factors (AU)