Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation, Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice.

Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson's disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Graphical Abstract MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.

[Bone marrow stem cell transplantation in amyotrophic lateral sclerosis: technical aspects and preliminary results from a clinical trial]. / Terapia celular para la esclerosis lateral amiotrófica: aspectos técnicos y resultados preliminares del estudio CMN/ELA.

Patients with amyotrophic lateral sclerosis (ALS) experience progressive and irreversible paralysis as a result of the continued loss of motor neurons, which leads to death in less than five years. To date, there is no treatment that can change the progression of this disease. Bone marrow stem cells have shown neural regenerative and neural repairing properties. Specifically, our group showed in a murine model of the disease that these cells, when injected in the spinal cord, can rescue motor neurons through the secretion of GDNF. Based on these results, we designed a phase I/II clinical trial for the purpose of demonstrating the viability of the intraspinal injection of autologous bone marrow mononuclear cells in patients with bulbar onset ALS, with an evolution between 6 and 36 months, with a forced vital capacity (FVC) 50% and T90 29%. This article describes the technique for extracting 60 mL of bone marrow used for the intervention, processing it by density gradient, and the neurosurgical technique used for implanting it. After 6 months of follow-up, the few adverse events reported in the first seven patients included seem to show that the procedure is safe and viable. Most of these patients, including two with a rapid deterioration, have stabilized the progression of their FVC and the neurologic scales measured. The data obtained so for seem to justify the design of new trials more oriented toward the efficacy of the procedure.

[Acute respiratory insufficiency as onset form of Lambert-Eaton's syndrome associated with pulmonary small cell carcinoma]. / Insuficiencia respiratoria aguda como forma de debut de síndrome de Lambert-Eaton asociado a carcinoma pulmonar de células pequeñas.

The Lambert-Eaton myasthenic syndrome is a rare disorder of neuromuscular transmission, usually presenting as a paraneoplastic process associated with a small cell lung cancer. Recently, respiratory muscular impairment has been described in these patients. Acute respiratory failure as a presenting symptom has been reported in few cases. We present a case of acute ventilatory failure as the first manifestation of Lambert-Eaton myasthenic syndrome associated with small cell lung cancer and discuss the main features of this disease, including its treatment. The Lambert-Eaton myasthenic syndrome should be considered in cases of unexplained acute respiratory failure and clinical evidence of neoplasic disease. We thought that electromyographic studies could reveal the real involvement of respiratory muscles, including diaphragm, in this condition.

Insuficiencia respiratoria aguda como forma de debut de síndrome de Lambert-Eaton asociado a carcinoma pulmonar de células pequeñas / Lambert-Eaton myasthenic syndrome presenting as acute respiratory failure in a patient with small cell lung cancer

El síndrome de Lambert-Eaton (SLE) es un trastorno raro de la transmisión neuromuscular que se presenta habitualmente como un proceso paraneoplásico frecuentemente asociado al carcinoma pulmonar de células pequeñas. Varios estudios han demostrado la existencia de disfunción de la musculatura respiratoria en estos pacientes. La insuficiencia respiratoria aguda como presentación del SLE ha sido descrita de forma excepcional. Se describe un caso de insuficiencia respiratoria aguda como forma de debut de SLE asociado a un carcinoma microcítico de pulmón, repasando las principales características del cuadro y su tratamiento. El SLE debería ser considerado en casos de insuficiencia respiratoria aguda sin causa aparente y sospecha de enfermedad neoplásica de base. Proponemos la realización de estudios electromiográficos que detecten alteraciones en la función muscular respiratoria, incluyendo el diafragma, para descartar su existencia (AU)

A comparison of electrophysiological tests for the early diagnosis of diabetic neuropathy.

Clinical criteria and several electrophysiological parameters for detecting nerve damage were compared in 99 patients with diabetes mellitus type 1 and type 2. Abnormal results were found in sural/radial amplitude ratio (51%), minimal F-wave latency of the tibial nerve (36.4%), sensory conduction velocity of the sural nerve (29.8%), and sural sensory nerve action potential amplitude (29.3%) when pooling data from all patients and comparing them to age- and height-matched normal control subjects. Analysis of all the parameters revealed large differences between the diabetes mellitus type 1 and type 2 groups, suggesting that the type of diabetes must be taken into account when comparing the sensitivity of nerve conduction tests. In diabetes mellitus type 1, the sural/radial ratio had the clearest correlation with course of illness and was the first parameter to show a significant reduction. We conclude that the simple ratio between sural and radial amplitudes is a very sensitive parameter and abnormalities in this ratio provide the means for earliest detection of neuropathy in diabetes mellitus type 1.

[Early infantile epileptic encephalopathy and glycine encephalopathy]. / Encefalopatía epiléptica infantil precoz y encefalopatía glicinémica.

INTRODUCTION: Early infantile epileptic encephalopathy (EIEE) with suppression burst activity in EEG (Ohtahara syndrome) is a rare type of epileptic encephalopathy in infancy and represents the earliest type of age-related symptomatic generalized epilepsy. The main etiologic factors associated to EIEE are cerebral dysgenesia and metabolopathies, principally nonketotic hyperglycinemia. CLINICAL CASE: We report a neonate with EIEE secondary to glycine encephalopathy, diagnosed by increased of LCR/plasma glycine index.

[Variations in cerebral blood flow in various states of severe neonatal hypoxic-ischemic encephalopathy]. / Variaciones del flujo sanguíneo cerebral en diversos estadios de la encefalopatía hipóxico-isquémica neonatal severa.

The clinical applications of Doppler sonography are numerous in pediatric practice. Of the all the measurements of arterial signals available, the one that has been most useful used and has proved to be of practical benefit is the Pourcelot resistance index (PI). The change in PI is more sensitive than the real-time image for documentation of the cerebral insult in full-term asphyxia. The PI is much lower and stays lower for several days in the more severely asphyxiated infants and is thus extremely useful for predicting outcome as well. But multiple factors affect the waveform and PI, and it is important to understand how physiological and pathological variables influence chances in the Doppler signal in order to better understand changes in newborn with neurological problems. We present the changes of cerebral blood flow by Doppler ultrasound in a newborn with severe perinatal asphyxia and hypoxic-ischemic encephalopathy, associated with other neurological problems; coma, seizures and hydrocephalus.

Retrograde migration of the abdominal catheter as a complication of ventriculoperitoneal shunts: the fishhook sign.

Three cases of retrograde migration of the distal catheter of ventriculoperitoneal shunts into the subcutaneous fibrous tract of the thoracic wall are reported. To the authors' knowledge this is the first time that this complication of ventriculoperitoneal shunts has been described.