Roberto E.P. Sica

Normal anatomy of the developing fetal brain. Ex vivo anatomical-magnetic resonance imaging correlation.

Fetal brain Magnetic Resonance Imaging (MRI) is a new technique of growing interest, with a high potential to detect prenatal central nervous system abnormalities. This requires an accurate knowledge of the normal morphological sequence of brain development. In this paper we studied the cortical development of post-mortem normal fetal brains, correlating MRI estimations of fetal age with in vitro anatomical and anthropometric measurements. Ten post-mortem fetal heads were submitted to MRI. Maturational state of sulci and gyri and gray-white matter differentiation were analysed in the MRIs and by dissection of the brains. The findings were correlated with the previously estimated ages of the fetuses, which varied between 17 and 38 weeks. Consistency between methods was assessed employing intraclass correlation coefficient and Bland-Altman plots, with a 95% confidence interval. Estimations of fetal age obtained by MRI were very similar to those achieved by anthropometric measurements or by considering anatomical parameters. Gyral development proved to be more precise than gray-white matter differentiation for this purpose. Fetal MRI proved to be as reliable as the macroscopic anatomical examination for depicting normal cortical developmental sequence and age, suggesting that this technique may be a suitable option for achieving precise information about the morphology of human brains along the gestational period.

Sporadic amyotrophic lateral sclerosis: new hypothesis regarding its etiology and pathogenesis suggests that astrocytes might be the primary target hosting a still unknown external agent

This article briefly describes the already known clinical features and pathogenic mechanisms underlying sporadic amyotrophic lateral sclerosis, namely excitoxicity, oxidative stress, protein damage, inflammation, genetic abnormalities and neuronal death. Thereafter, it puts forward the hypothesis that astrocytes may be the cells which serve as targets for the harmful action of a still unknown environmental agent, while neuronal death may be a secondary event following the initial insult to glial cells. The article also suggests that an emergent virus or a misfolded infectious protein might be potential candidates to accomplish this task.

Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System

Along the last years it has been demonstrated that non-neural cells play a major role in the pathogenesis of the primary degenerative disorders (PDDs) of the human central nervous system. Among them, astrocytes coordinate and participate in many different and complex metabolic processes, in close interaction with neurons. Moreover, increasing experimental evidence hints an early astrocytic dysfunction in these diseases. In this mini review we summarize the astrocytic behavior in PDDs, with special consideration to the experimental observations where astrocytic pathology precedes the development of neuronal dysfunction. We also suggest a different approach that could be consider in human investigations in Alzheimer’s and Parkinson’s disease. We believe that the study of PDDs with human brain samples may hold the key of a paradigmatic physiopathological process in which astrocytes might be the main players.

Epidemiology of amyotrophic lateral sclerosis patients in a centre in Buenos Aires

UNLABELLED Sporadic amyotrophic lateral sclerosis (sALS) is considered a multifactorial disease with genetic and environmental factors causing motor neuron degeneration. OBJECTIVE To describe the epidemiological and occupational characteristics of patients with sALS who attended the Ramos Mejía Hospital at Buenos Aires, Argentina. METHOD We analyzed the medical records of sALS patients diagnosed between 2001 and 2008. All occupations were coded according to the International Standard Classification of Occupation (ISCO). RESULTS 187 patients were assessed, 38.5% were women and 61.5% men. Mean age at diagnosis was 55 years. 16% of them came from rural areas; 68% of the studied population had no health insurance. 40% were employed in elementary occupations, 19 were technicians and 8 handicraftsmen. CONCLUSION The most represented profession was elementary occupation. A large proportion of patients came from rural areas, which might suggest an increased risk of environmental exposure to an unknown agent in those regions.

Prenatal cerebral magnetic resonance imaging

UNLABELLED Ultrasonography (USG) is the preferred screening method for fetal brain examination. It has some technical limitations and a relatively low sensibility and specificity for many central nervous system (CNS) malformations. Fetal cerebral magnetic resonance imaging (MRI) offers better resolution and sensibility, with scarce limitations. OBJECTIVES To determine the fetal age according to cortical maturation as seen in MRI, correlating these data with those obtained by means of USG measurements; to correlate USG pathological findings with the MRIs and to determine how the sequence of cortical maturation varies in abnormal brains. MATERIALS AND METHODS 50 pregnant women were submitted to USG and fetal brain MRI. Fifteen carried out normal pregnancies. In the remaining 35, the USG, the clinical assessment or both, raised the suspicion of a CNS malformation. Facts studied were: the gestational age calculated by USG, analysis of the cortical gyral development by MRI (cortical age), the presence of CNS abnormalities and the correlation between the cortical maturation and the presence of CNS pathologies. Statistical analysis included the Students t test for paired samples, the Pearsons correlation coefficient (r) and linear regression curves. RESULTS In the control group, fetal age highly correlated with the cortical age estimated by MRI. In the abnormal group, a wide variety of pathologies could be found, with higher sensibility and specificity than USG when applying MRI techniques. Cortical age did not correlate with the gestational age in this group; moreover, its estimation could not be achieved in severely malformed brains. DISCUSSION MRI allows a detailed study of the CNS before birth. It proved to be more reliable and specific than USG, with fewer technical limitations. Cortical maturation can be accurately assessed by this method in normal or slightly abnormal fetuses. However, USG is better than MRI for diagnosing skull bony defects.

Síndrome cerebeloso por amiodarona

Amidarone (AMD) is an antiarrhythmic drug with side effects on the nervous system. Cerebellum is seldom involved: We describe the case of a 56 years old male patient with a history of 4 month of cerebellar involvement characterized by gait unsteadiness, ataxia, nistagmus and vertigo. He was on treatment with AMD because of ventricular arrythmia. The cerebellar syndrome progressively disappeared after drug withdrawal and he was symptoms-free 4 months later. Similar symptoms appeared after another one month of automedication with the same drug. Structural lesions, metabolic, nutritional deficiencies or toxics were excluded. Mechanisms of cerebellar toxicity of AMD are yet unknown. The knowledge of the toxic effects of this drug, widely used in our country, would allow its early recognition.Amidarone (AMD) is an antiarrhytmic drug with side effects on the nervous system. Cerebellum is seldom involved. We describe the case of a 56 years old male patient with a history of 4 month of cerebellar involvement characterized by gait unstadiness, ataxia, nistagmus and vertigo. He was on treatment with AMD because of ventricular arrythmia. The cerebellar syndrom progressively disappeared after drug whitdrawal and he was symptoms-free 4 months later. Similar symptoms appeared after another one month of automedication with the same drug. Structural lesions, metabolic, nutritional deficiencies or toxics were excluded. Mechanisms of cerebellar toxicity of AMD are yet unknown. The knowledge of the toxic effects of this drug, widely used in our country, would allow its early recognition.

Ataxia cerebelosa persistente despues de la administracion toxica de difenilhidantoina

Diphenylhydantoin (DFH) is known to yield cerebellar ataxia in chronically treated epileptic patient due to cerebellar atrophy with loss of Purkinje cells. Little attention has been paid in the literature to the acute DFH intoxication bearing cerebellar symptoms. We report a patient afflicted with complex partial seizures due to a left temporal cyst, who has been treated during the last two years with DFH 100 mg/day.Due to the refractory characteristics of his seizures he was put on DFH 400 mg daily, and developed a pancerebellar syndrome. After surgical removal of the cyst his seizures entirely faded away and his cerebellar signs improved. Nevertheless his neurological examination still showed trunkal and lower limbs ataxia. After one year of follow up his neurological picture did not change, while he was seizures free. TC and MRI did not show cerebellar atrophy.La intoxicacion cronica con difenilhidantoina (DFH) es bien conocida como causa de ataxia irreversible en pacientes epilepticos debida a atrofia cerebelosa con perdida de celulas de Purkinje. No es asi con la intoxicacion aguda, puesto que sus signos y sintomas son reversibles. Presentamos un paciente con convulsiones parciales complejas, secundarias a un quiste temporal, que habia sido tratado irregularmente con DFH durante dos anos con dosis variables que oscilaban en los 100 mg/dia. Dada la refractariedad de su cuadro convulsivo en una entrevista previa a su ingreso se le indico un aumento brusco de la dosis del farmaco que alcanzo a los 400 mg/dia. Ello ocasiono un sindrome pancerebeloso severo que motivo su internacion. Posteriormente a la suspension de la DFH y la exeresis del quiste temporal mejoro su cuadro convulsivo, aunque quedo con ataxia de miembros inferiores y asinergia de tronco, cuadro con el que fue dado de alta. Un ano despues, el paciente se encontraba libre de convulsiones, pero su sindrome cerebeloso no se habia modificado. El estudio por imagenes no evidencio atrofia cerebelosa.: Diphenylhydantoin (DFH) is known to yield cerebellar ataxia in chronically treated epileptic patient due to cerebellar atrophy with loss of Purkinje cells. Little attention has been paid in the literature to the acute DFH intoxication bearing cerebellar symptoms. We report a patient afflicted with complex partial seizures due to a left temporal cyst, who has been treated during the last two years with DFH 100 mg/day. Due to the refractory characteristics of his seizures he was put on DFH 400 mg daily, and developed a pancerebellar syndrome. After surgical removal of the cyst his seizures entirely faded away and his cerebellar signs improved. Nevertheless his neurological examination still showed trunkal and lower limbs ataxia. After one year of follow up his neurological picture did not change, while he was seizures free. TC and MRI did not show cerebellar atrophy.

Estudio comparativo de las funciones ejecutivas entre pacientes con enfermedad de Parkinson y pacientes con enfermedad degenerativa cerebelosa

OBJECTIVE To compare executive functions (EF) in non-demented mild to moderate Parkinsons disease (PD) (Hoehn and Yahr < or =3) and pure degenerative cerebellar disease (CD) in order to evaluate the relative contribution and differential role of basal ganglia and cerebellum in those functions. METHOD 14 patients with PD and 14 patients with CD matched by sex, education, diseases duration and MMSE were selected. A standardized neuropsychological battery and the Wisconsin Card Sorting Test (WCST) were administered. Z scores were compared for both groups through t-test for independent samples were used. RESULTS The cerebellar group showed significant lower performance in measures of attention and EF, with a significant increase in both perseverative and non perseverative errors during the WCST. On the other hand the PD group showed a selective increase of non perseverative errors, without reaching significant between group difference. CONCLUSION The CD group appears to have greater deficits in EF with a pattern of prefrontal dysfunction.

Percutaneous cervical stimulation: effects on intraspinal structures

Changes in the amplitude of motor evoked potentials (MEPs) from percutaneous cervical stimulation (PCS) obtained at rest in the thenar muscles, and smaller than 0.8 mV, were studied under 3 different experimental conditions. A significant enhancement was observed mainly with a conditioning subthreshold transcranial stimulus and when MEPs were obtained in coincidence with weak voluntary contraction of the target muscle. Subthreshold stimulation of Ia fibers of the median nerve seemed to have a smaller facilitatory effect. It is generally accepted that PCS excites the spinal motoneuron (SMN) axons at the spinal nerve. However, our results show that other SMNs, usually not recruited, may be triggered by PCS when they receive excitatory postsynaptic potentials from the pyramidal tract (PT) or Ia fibers. This behavior suggests that low intensity PCS also exerts subthreshold excitation of the PT fibers and, perhaps, of the incoming spindle afferents, which adds its effects to the conditioning stimuli.

Progesterone and cortisol levels in sporadic amyotrophic lateral sclerosis (sALS): correlation with prognostic factors

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Worse prognostic factors in ALS are: (a) advanced age, (b) bulbar onset, and (c) short time between onset and diagnosis. Progesterone (PROG) has been associated with neuroprotective and promyelinating activities in injury, ischemia and degeneration of the central and peripheral nervous system. Cortisol is connected to the response to stress situations and could contribute to neuronal damage. The goals of this study were: (i) to investigate whether PROG levels are modified by ALS prognostic factors and (ii) to determine whether cortisol follows the same pattern. We determined serum steroid levels in 27 patients with sporadic ALS (sALS) and 21 controls. Both steroid hormones showed significantly increased levels in ALS patients versus controls (mean±SEM: PROG ALS vs. control: 0.54±0.05 vs. 0.39±0.04 ng/mL, p<0.05; cortisol ALS vs. control: 17.02±1.60 vs. 11.83±1.38 μg/dL, p<0.05).1 A trend towards higher levels of PROG were demonstrated in spinal onset patients compared with bulbar onset (p=0.07), positive correlation with survival time (RRho=0.43, p=0.04) and a trend towards significance with time to diagnosis (RRho=0.36, p=0.06). These correlations have not been demonstrated for cortisol. Elevated serum steroid levels in sALS were probably due to hyperfunction of the hypothalamic-pituitary-adrenal axis. However, only PROG correlated with better prognostic factors. Future studies will determine if the different behavior of PROG and cortisol relate to any particular role they might play during the course of this motor neuron degenerative disease. 1Conversion factors from conventional units to SI units: Progesterone ng/mL to nmol/L=3.18 Cortisol μg/dL to nmol/L=27.59