The human olfactory system in two proteinopathies: Alzheimer's and Parkinson's diseases.

Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative disorders. Their etiologies are idiopathic, and treatments are symptomatic and orientated towards cognitive or motor deficits. Neuropathologically, both are proteinopathies with pathological aggregates (plaques of amyloid-ß peptide and neurofibrillary tangles of tau protein in Alzheimer's disease, and Lewy bodies mostly composed of α-synuclein in Parkinson's disease). These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages. Both disorders present a long prodromal period, characterized by preclinical signs including hyposmia. Interestingly, the olfactory system, particularly the anterior olfactory nucleus, is initially and preferentially affected by the pathology. Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes. It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding (seeding), which then propagates through neurons and glia (spreading). Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading. Connectomic approaches reveal a number of hubs in the olfactory system (anterior olfactory nucleus, olfactory entorhinal cortex and cortical amygdala) that are key interconnectors with the main hubs (the entorhinal-hippocampal-cortical and amygdala-dorsal motor vagal nucleus) of network dysfunction in Alzheimer's and Parkinson's diseases.

Cranial Pair 0: The Nervus Terminalis.

Originally discovered in elasmobranchs by Fritsh in 1878, the nervus terminalis has been found in virtually all species, including humans. After more than one-century debate on its nomenclature, it is nowadays recognized as cranial pair zero. The nerve mostly originates in the olfactory placode, although neural crest contribution has been also proposed. Developmentally, the nervus terminalis is clearly observed in human embryos; subsequently, during the fetal period loses some of its ganglion cells, and it is less recognizable in adults. Fibers originating in the nasal cavity passes into the cranium through the middle area of the cribiform plate of the ethmoid bone. Intracranially, fibers joint the telencephalon at several sites including the olfactory trigone and the primordium of the hippocampus to reach preoptic and precommissural regions. The nervus terminalis shows ganglion cells, that sometimes form clusters, normally one or two located at the base of the crista galli, the so-called ganglion of the nervus terminalis. Its function is uncertain. It has been described that its fibers facilitates migration of luteinizing hormone-releasing hormone cells to the hypothalamus thus participating in the development of the hypothalamic-gonadal axis, which alteration may provoke Kallmann's syndrome in humans. This review summarizes current knowledge on this structure, incorporating original illustrations of the nerve at different developmental stages, and focuses on its anatomical and clinical relevance. Anat Rec, 302:394-404, 2019. © 2018 Wiley Periodicals, Inc.

Efficacy of long-term continuous subcutaneous apomorphine infusion in advanced Parkinson's disease with motor fluctuations: a multicenter study.

Continuous subcutaneous apomorphine infusion (CSAI) is, at present, an alternative option for advanced Parkinson's disease (PD) with motor fluctuations. We studied the evolution of patients with PD and severe motor fluctuations long-term treated with CSAI. We reviewed data from 82 patients with PD (mean age, 67 +/- 11.07; disease duration, 14.39 +/- 5.7 years) and severe motor fluctuations referred to 35 tertiary hospitals in Spain. These patients were long-term treated (for at least 3 months) with CSAI and tolerated the procedure without serious side effects. We compared the baseline data of these 82 patients (before CSAI) with those obtained from the last follow-up visit of each patient. The mean follow-up of CSAI was 19.93 +/- 16.3 months. Mean daily dose of CSAI was 72.00 +/- 21.38 mg run over 14.05 +/- 1.81 hours. We found a statistically significant reduction in off-hours, according to self-scoring diaries (6.64 +/- 3.09 vs. 1.36 +/- 1.42 hours/day, P < 0.0001), total and motor UPDRS scores (P < 0.0001), dyskinesia severity (P < 0.0006), and equivalent dose of antiparkinsonian therapy (1,405 +/- 536.7 vs. 800.1 +/- 472.9 mg of levodopa equivalent units P < 0.0001). CSAI is an effective option for patients with PD and severe fluctuations, poorly controlled by conventional oral drug treatment.

Freezing of gait in Parkinson's disease: functional neuroimaging studies of the frontal lobe.

OBJECTIVE: The objective of the study is to study a group of patients with Parkinson's disease (PD) with and without freezing of gait (FOG) and analyze neuropsychological differences, especially regarding executive functions, according to their performance in a set of tests, and potential anomalies in functional positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-d-glucose integrated with computed tomography (18F-FDG PET/CT) neuroimaging results of the frontal lobe. METHODS: The study recruited 23 patients. We performed an 18F-FDG PET/CT scan for 17 patients (9 with FOG and 8 without FOG) and 6 controls. Frontal functions were evaluated in all the patients during their 'on' situation. RESULTS: In FDG PET studies, PD patients differed from controls in that they presented hypometabolic areas in the parietal and bilateral occipital regions, as well as in the bilateral frontal region, especially on the right side. Compared to patients without FOG, patients with FOG displayed more pronounced frontal and predominantly right-sided hypometabolism. Both groups of patients displayed a poorer performance than the control population in the frontal cognitive tests. A greater executive disfunction was found in patients with FOG. CONCLUSIONS: Our study revealed greater hypometabolism in FDG PET studies, predominantly in right-sided-specific motor regions of the frontal lobe in FOG patients and greater frontal disfunction in neuropsychological tests in PD patients with FOG. These data suggest that FOG may be related to functional impairment of the circuits connecting the frontal lobe and the basal ganglia.

Structural and functional alterations of the heart in Parkinson's disease.

Parkinson's disease (PD) patients have most frequently heart failure. The cause of this increased prevalence is not known. We designed a study to assess the cardiac function and cardiac structure in patients with PD compared to a control group. METHODS: Cross-sectional study with 50 PD patients and 50 healthy matched controls. We performed electro and echocardiograms to all patients and controls. The measurements were blind. In addition, we performed a neurological assessment. RESULTS: PD patients had higher left ventricular mass index (114.2 ± 38.4 vs. 94.1 ± 26.4 g/m2; P = 0.003) and higher left atrial volume (30.1 ± 7.9 vs. 26.7 ± 6.2 ml/m2; P = 0.01). PD was an independent risk factor for elevated left ventricular filling pressures (OR = 2.7, CI 95% 2.2-6.3; P = 0.004). Concentric remodeling and left ventricular hypertrophy were associated with more advanced Hoehn and Yahr stages. Moreover, patients with more dysautonomia symptoms showed more left ventricular hypertrophy. Finally, PD group had longer QT interval than control group regardless of the drugs. CONCLUSIONS: PD is significantly associated with increased concentric left ventricular hypertrophy and diastolic dysfunction. Advanced stages of PD are associated with a more severe cardiac affection. These findings can explain the increase of heart failure in PD patients. Cardiomyopathy could be a non-motor parkinsonian symptom.

[Supra-on state freezing of gait: two case reports]. / Congelacion de la marcha en supra-on: a proposito de dos casos.

INTRODUCTION: Over recent years, several types of freezing of gait (FOG) have been described, mainly according to their response to levodopa. FOG in Parkinson's disease presents in a variety of ways due to differences within the underlying pathophysiology. In a number of patients, increasing the dopaminergic stimulation may not improve this condition, and may even worsen it. CASE REPORTS: We present two patients with Parkinson's disease who were evaluated during off, on and supra-on periods. Motor function was assessed with Unified Parkinson's Disease Rating Scale III, tapping test on lower limbs and quantification of FOG episodes during each of these periods. Both patients presented FOG episodes while in off period, experiencing a significant improvement during on period. However, when increasing the dopaminergic stimulation in order to try to improve their motor response, FOG episodes worsened to the point of impairing gait. CONCLUSIONS: FOG episodes are not always a consequence of akinesia or rigidity. Regarding the pathophysiology, the lack of an appropriate response to treatment would be explained by the involvement of structures exceeding the substantia nigra and the dopaminergic deficit. FOG worsening during periods of dopaminergic overstimulation could be related to a neurotransmitters disbalance affecting other nuclei involved in postural and gait control.

TITLE: Congelacion de la marcha en supra-on: a proposito de dos casos.Introduccion. Durante los ultimos años se han descrito diversos tipos de congelacion de la marcha (CDM), definidos fundamentalmente por su respuesta o no al tratamiento con levodopa. El fenomeno de la CDM en la enfermedad de Parkinson es de presentacion muy variable de unos pacientes a otros, con sustrato fisiopatologico diverso. En algunos pacientes, el aumento del estimulo dopaminergico no solo no mejora, sino que puede empeorar este problema. Casos clinicos. Se presentan dos pacientes con enfermedad de Parkinson que fueron evaluados en situacion off, on y supra-on. Para la evaluacion motora se utilizo la Unified Parkinson's Disease Rating Scale III (bilateral) y el tapping test en las extremidades inferiores, y se cuantificaron los episodios de CDM que presentaban los pacientes en las tres situaciones. Ambos pacientes sufrian episodios de CDM en situacion off que no mejoraban significativamente durante el on. Al aumentar el estimulo dopaminergico, en un intento de mejorar la respuesta motora, empeoraron significativamente los episodios de CDM, hasta el punto de imposibilitar la marcha por graves bloqueos. Conclusiones. Los episodios de CDM no siempre son una mera consecuencia de la acinesia o la rigidez. En la fisiopatologia de la CDM podrian intervenir estructuras que desbordan la sustancia negra y el deficit dopaminergico, lo cual podria explicar la falta de respuesta adecuada al tratamiento e incluso el empeoramiento por desequilibrio de los neurotransmisores, en relacion con la sobreestimulacion dopaminergica, en otros nucleos implicados en el control postural y de la marcha.

[Abnormal movements of peripheral origin: seven case reports]. / Movimientos anormales de origen periferico: a proposito de siete casos.

INTRODUCTION: Movement disorders induced by central nervous system trauma are well recognized. The relation between peripheral injury and the subsequent development of movement disorders has been documented in many reports, specially dystonia and tremor. Pathophysiological mechanisms underlying these movement disorders are not well understood. CASE REPORTS: We report a group of seven patients with movement disorders induced by peripheral trauma. The inclusion criteria used for the patients were: the trauma was well documented for the patient and the medical history, and the onset of the movement disorder was anatomically and temporally related to the injury. We describe seven patients presenting respectively oromandibular dystonia, radicular myoclonus, tremor, segmental dystonia, lower limbs dystonia, segmental myoclonus and tremor, of the body parts previously exposed to traumatic injuries. CONCLUSIONS: Individual predisposition and central changes with pathological reorganization in response to peripheral injury have been considered in the pathogenesis of peripherally induced movements disorders.

Síndromes conversivos en neurología: características clínicas de 16 pacientes / Conversion syndromes in neurology: clinical characteristics of 16 patients

El trastorno de conversión (término que describe lo que anteriormente se llamaba histeria) se refiere a los síntomas motores, sensitivos o ambos, que se asemejan a una enfermedad neurológica, pero que no tienen origen en una enfermedad física conocida, ni se pueden explicar por ella, dándose la particularidad de que el enfermo no es consciente de lo que le ocurre. La incapacidad funcional para los pacientes a veces es mayor que la observada en los casos en los que, con una semiología similar, hay un sustrato orgánico. Material y método: Presentamos 16 pacientes, valorados en consulta externa de neurología, con un trastorno motor o sensitivo, sin evidencia de enfermedad orgánica subyacente, con al menos un año de seguimiento. Discusión: Se comentan las características semiológicas. La fisiopatología de los síndromes conversivos está todavía en discusión. Las técnicas de neuroimágenes funcionales parecen mostrar alteraciones que nos permiten acercarnos a la fisiopatología de estos trastornos. Es importante señalar que aunque la fisiopatología de los síndromes conversivos está todavía en discusión, lo cierto es que se trata de pacientes de diagnóstico difícil, pero posible; es responsabilidad del médico intentar entender el sustrato neurológico de un problema que implica una gran incapacidad funcional e instaurar un tratamiento adecuado, buscando, si es necesario, la colaboración de un psiquiatra con experiencia en el abordaje de estos trastornos...

Movimientos anormales de origen periférico: a propósito de siete casos / Abnormal movements of peripheral origin: seven case reports

Introducción. Los movimientos involuntarios desencadenados por lesiones en el sistema nervioso central están bien reconocidos. La relación entre lesión o traumatismos periféricos y movimientos involuntarios, fundamentalmente distonía y temblor, se ha documentado en numerosos trabajos. Los mecanismos fisiopatológicos no están aún bien definidos. Casos clínicos. Se presenta una serie de siete pacientes con movimientos involuntarios inducidos por traumatismo periférico. Los criterios de inclusión fueron traumatismo o lesión bien documentados por el paciente y el historial clínico, y una clara relación anatómica y temporal entre la lesión periférica y el movimiento involuntario. Los pacientes desarrollaron, respectivamente, distonía oromandibular, mioclonías radiculares, temblor, distonía segmentaria, distonía en las extremidades inferiores, mioclonías segmentarias y temblor, tras haber sufrido algún tipo de lesión o traumatismo periférico. Conclusión. Una predisposición individual y cambios en la plasticidad neuronal en el sistema nervioso central, inducidos por el traumatismo periférico, podrían ser el sustrato fisiopatológico de este tipo de movimientos involuntarios (AU)

Introduction. Movement disorders induced by central nervous system trauma are well recognized. The relation between peripheral injury and the subsequent development of movement disorders has been documented in many reports, specially dystonia and tremor. Pathophysiological mechanisms underlying these movement disorders are not well understood. Case reports. We report a group of seven patients with movement disorders induced by peripheral trauma. The inclusion criteria used for the patients were: the trauma was well documented for the patient and the medical history, and the onset of the movement disorder was anatomically and temporally related to the injury. We describe seven patients presentingrespectively oromandibular dystonia, radicular myoclonus, tremor, segmental dystonia, lower limbs dystonia, segmental myoclonus and tremor, of the body parts previously exposed to traumatic injuries. Conclusions. Individual predisposition and central changes with pathological reorganization in response to peripheral injury have been considered in the pathogenesis of peripherally induced movements disorders (AU)

Evolución de la enfermedad de Parkinson. Revisión crítica de estudios longitudinales / The course of Parkinson's disease. A critical review of longitudinal studies

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Hiponatremias recurrentes como inicio de un quiste de la bolsa de Rathke / No disponible

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