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Liver growth factor (LGF) is a hepatic mitogen purified some years ago that promotes proliferation of different cell types and the regeneration of damaged tissues, including brain tissue. Considering the possibility that LGF could be used as a therapeutic agent in Parkinson’s disease, we analyzed its potential neuroregenerative and/or neuroprotective activity when peripherally administered to unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. For these studies, rats subjected to nigrostriatal lesions were treated intraperitoneally twice a week with LGF (5 microg/rat) for 3 weeks. Animals were sacrificed 4 weeks after the last LGF treatment. The results show that LGF stimulates sprouting of tyrosine hydroxylase-positive terminals and increases tyrosine hydroxylase and dopamine transporter expression, as well as dopamine levels in the denervated striatum of 6-OHDA-lesioned rats. In this structure, LGF activates microglia and raises tumor necrosis factor-alpha protein levels, which have been reported to have a role in neuroregeneration and neuroprotection. Besides, LGF stimulates the phosphorylation of MAPK/ERK1/2 and CREB, and regulates the expression of proteins which are critical for cell survival such as Bcl2 and Akt. Because LGF partially protects dopamine neurons from 6-OHDA neurotoxicity in the substantia nigra, and reduces motor deficits in these animals, we propose LGF as a novel factor that may be useful in the treatment of Parkinson’s disease.

En estos momentos se encuentra en plena expansion la llamada secuenciacion paralela o de siguiente generacion -next generation sequencing (NGS)-, que establece un salto de varios ordenes de magnitud en la longitud de los fragmentos secuenciados y la rapidez de su secuenciacion. La NGS permite la secuenciacion de un genoma humano completo en el tiempo y el coste economico de secuenciar dos o tres genes grandes con la tecnica de Sanger. Mediante la NGS se pasa de examinar genes especificos seleccionados mediante estudio del fenotipo a explorar genomas enteros de grupos humanos o de otras especies. Esto esta permitiendo conocer no solo como es un genoma individual, sino como cambia el genoma humano de persona a persona, como difieren los genomas entre diferentes grupos humanos, e incluso como difiere el genoma de un tumor respecto del genoma sano del huesped.

The oculo-auricular phenomenon consists of coactivation of the ocular rectus lateralis and the posterior muscles of both ears (transverse auriculae and obliquus auriculae muscles). This coactivation produces a bilateral curling of auricles during extreme lateral gaze that can be observed in as much as an 80% of the normal population. We herein describe a 26-year-old man who presented a transient oculo-auricular phenomenon in the course of a vestibular vertigo.

Isolated continuous lingual myoclonus is an exceptional entity, poorly documented and understood. A patient with a nonepileptic continuous rhythmical myoclonus, affecting the anterior portion of the tongue, as an independent involuntary disorder, is reported. Electromyography showed low frequency (2-4 Hz) bursts of genioglossus muscles activity. The EEG, visual, auditory and somatosensory evoked responses were normal. Imaging techniques like CT and MRI failed to reveal any brainstem or cerebellar lesion. Lingual myoclonus showed a very good response to sodium valproate.

Variability of age at onset (AO) of Alzheimer disease (AD) among members of the same family is important as a biological clue and because of its clinical effects.To evaluate which clinical variables influence the discrepancy in AO among affected relatives with familial AD.Clinical genetic project of Spanish kindred with AD conducted by 4 academic hospitals in Madrid, Spain.Age at onset of AD in 162 families and discrepancy in AO in intragenerational and intergenerational affected pairs were analyzed in relation to age, sex, maternal or paternal transmission, pattern of inheritance, and apolipoprotein E genotype.Maternal transmission of AD was significantly more frequent than paternal transmission (P.001). In 27% of the affected individuals, AO occurred before the patient was 65 years old. Discrepancy in AO among siblings was within 5 years in 44% of the families, 6 to 10 years in 29%, and more than 10 years in 27% (range, 0-22). This discrepancy was independent of the sex of the sibling pairs and was significantly lower with maternal transmission of AD (P = .02). Segregation analysis showed no differences in the inheritance pattern between families with low (or =5 years) or high (5 years) AO discrepancy. Age at onset in carriers of the apolipoprotein E epsilon4 allele was slightly younger. However, among siblings, an extra apolipoprotein E epsilon4 allele was not consistently associated with earlier onset of AD. Eighty percent of patients, independent of sex or mode of transmission, were already affected at their parents' reported AO.There is a wide discrepancy in AO in affected siblings that is not clearly explained by a single clinical variable or apolipoprotein E genotype. The interaction of many factors probably determines AO in each affected individual. However, maternal transmission of AD seems to result in a similar AO in offspring, and the risk of developing dementia after the parent's reported AO decreases significantly.

We present a patient with palsy of the third nerve nuclear complex secondary to cerebral toxoplasmosis. There was a unique lesion by magnetic resonance and there were no other neurological symptoms. A complete radiographic and clinical resolution was obtained by specific treatment. Such neurological symptoms in cases of toxoplasmosis have not been reported previously.

We report the clinical features of, and the molecular study performed on, a Spanish family with essential tremor (ET), late onset epilepsy and autosomal dominant hypokalemic periodic paralysis (hypoPP). The presence of hypoPP in this kindred suggested an ion channel as a candidate gene for ET. Our study identified an Arg528His CACNL1A3 mutation in patients with hypoPP, and excluded this mutation as the cause of tremor or epilepsy in this kindred.

Objective: To determine the prevalence and causes of meningitis in patients with human immunodeficiency virus (HIV) infection. Design: A prospective study of HIV-associated neurologic complications carried out from 1988 to 1992. Setting: A tertiary care university hospital in Madrid, Spain. Patients: A total of 142 patients, 65% of whom were injecting drug users. Results: Thirty-six episodes of meningitis were diagnosed in 33 patients (23%). Of these, 17 cases (47%) were tuberculous meningitis (5 definite and 12 probable) and 7 (19%) corresponded to cryptococcal meningitis. Comparative studies of the tuberculous and cryptococcal meningitis cases showed injecting drug use as the most common form of HIV transmission in the tuberculous meningitis (P=.03) and a lower mean CD4+cell count in the cryptococcal meningitis group (P=.02). Conclusions: Tuberculous meningitis was the prime type of meningitis, which was associated with HIV transmission by injecting drug use. Cryptococcal meningitis appears in more advanced stages of HIV infection, which determines its characteristic presentation.

Liver growth factor (LGF) is a hepatic mitogen purified by our group in 1986. In the following years we demonstrated its activity both in "in vivo" and "in vitro" systems, stimulating hepatocytes mitogenesis as well as liver regeneration in several models of liver injury. Furthermore, we established its chemical composition (albumin-bilirubin complex) and its mitogenic actions in liver. From 2000 onwards we used LGF as a tissue regenerating factor in several models of extrahepatic diseases. The use of Liver growth factor as a neural tissue regenerator has been recently protected (Patent No US 2014/8,642,551 B2). LGF administration stimulates neurogenesis and neuron survival, promotes migration of newly generated neurons, and induces the outgrowth of striatal dopaminergic terminals in 6-hidroxydopamine-lesioned rats. Furthermore, LGF treatment raises striatal dopamine levels and protects dopaminergic neurons in hemiparkinsonian animals. LGF also stimulates survival of grafted foetal neural stem cells in the damaged striatum, reduces rotational behaviour and improves motor coordination. Interestingly, LGF also exerts a neuroprotective role both in an experimental model of cerebellar ataxia and in a model of Friedrich´s ataxia. Microglia seem to be the cellular target of LGF in the CNS. Moreover, the activity of the factor could be mediated by the stimulation of MAPK´s signalling pathway and by regulating critical proteins for cell survival, such as Bcl-2 and phospho-CREB. Since the factor shows neuroprotective and neurorestorative effects we propose LGF as a patented novel therapeutic tool that may be useful for the treatment of Parkinson´s disease and cerebellar ataxias. Currently, our studies have been extended to other neurological disorders such as Alzheimer's disease (Patent No: US 2014/0113859 A1).