Clínica de animais de companhia

O presente relatório é resultado do estágio curricular, 11º semestre do Mestrado Integrado em Medicina Veterinária. Este decorreu em duas instituições de referência veterinária em Barcelona (Hospital ARS Veterinária e Hospital Veterinari Montjuïc) e permitiu melhorar e integrar os conhecimentos adquiridos ao longo do curso. O relatório é composto por três partes: introdução, que situa temporal e espacialmente, relatório de casuística, que abrange todas as atividades realizadas e assistidas, e monografia. A monografia consiste na descrição de uma afeção neurológica, muito comum em Cavalier king charles spaniel, designada de siringomielia. A monografia inicia-se com uma revisão bibliográfica e termina com o relato de quatro casos clínicos acompanhados no Hospital ARS Veterinário; ABSTRACT: Small animal practice This report is the result of the traineeship in the 11th semester of the Integrated Master degree in Veterinary Medicine. It took place in two veterinary reference institutions in Barcelona (hospital ARS veterinary and hospital Veterinari Montjuïc) and contributed to improve and integrate the knowledge acquired throughout the course. The report consists in three parts: Introduction, which locates temporally and spatially, the sample report covering all activities, and monograph. The monography is the description of a neurological disorder, very common in Cavalier king charles spaniel, designated syringomyelia. The monography begins with a literature review and ends with the description of four clinical cases followed in ARS veterinary hospital.

Effect of host genotype and prion strain on the phenotypic heterogeneity of Creutzfeldt-Jakob disease: the peripheral nervous system involvement and the spectrum of the genetic form

The first study was designed to assess whether the involvement of the peripheral nervous system (PNS) belongs to the phenotypic spectrum of sporadic Creutzfeldt-Jakob disease (sCJD). To this aim, we reviewed medical records of 117 sCJDVV2, 65 sCJDMV2K, and 121 sCJDMM(V)1 subjects for symptoms/signs and neurophysiological data. We looked for the presence of PrPSc in postmortem PNS samples from 14 subjects by western blotting and real-time quaking-induced conversion (RT-QuIC) assay. Seventy-five (41.2%) VV2-MV2K patients, but only 11 (9.1%) MM(V)1, had symptoms/signs suggestive of PNS involvement and neuropathy was documented in half of the VV2-MV2K patients tested. RT-QuIC was positive in all PNS samples, whereas western blotting detected PrPSc in the sciatic nerve in only one VV2 and one MV2K. These results support the conclusion that peripheral neuropathy, likely related to PrPSc deposition, belongs to the phenotypic spectrum of sCJDMV2K and VV2, the two variants linked to the V2 strain. The second study aimed to characterize the genetic/molecular determinants of phenotypic variability in genetic CJD (gCJD). To this purpose, we compared 157 cases of gCJD to 300 of sCJD. We analyzed: demographic aspects, neurological symptoms/signs, histopathologic features and biochemical characteristics of PrPSc. The results strongly indicated that the clinicopathological phenotypes of gCJD largely overlap with those of sCJD and that the genotype at codon 129 in cis with the mutation (i.e. haplotype) contributes more than the latter to the disease phenotype. Some mutations, however, cause phenotypic variations including haplotype-specific patterns of PrPSc deposition such as the “dense” synaptic pattern (E200K-129M), the intraneuronal dots (E200K-129V), and the linear stripes perpendicular to the surface in the molecular layer of cerebellum (OPRIs-129M). Overall, these results suggest that in gCJD PRNP mutations do not cause the emergence of novel prion strains, but rather confer increased susceptibility to the disease in conjunction with “minor” clinicopathological variations.

Epileptic and developmental encephalopathies: clinical and genetic study of adult patients attending a tertiary Epilepsy Centre

Objectives: To fully re-evaluate patients with early-onset epilepsy and intellectual disability with neurological, neurophysiological and neuropsychological examination in order to contribute to expanding the phenotypic spectrum of known epileptic encephalopathy (EE)-related genes and to identify novel genetic defects underlying EEs. Methods: We recruited patients with epilepsy and intellectual disability (ID) referring to our Epilepsy Centre. Patients underwent full clinical and neurophysiologic evaluation. When possible they underwent neuroradiologic investigations. Selected cases also underwent genetic analysis. Results: We recruited 200 patients (109 M, 91 F; mean age 36 years old). Mean age at epilepsy onset was 4 years old. The degree of ID was borderline in 4.5% of patients, mild in 25%, moderate in 38% and severe in 32.5%. EEG showed epileptiform abnormalities in 79.5% of patients. One hundred and thirty-one patients out of the 200 recruited (65.5%) did not have an aetiological diagnosis. All the patients underwent full clinical reassessment and when necessary they performed neuroradiologic and genetic investigations as well. We identified 35 patients with a genetic aetiology. In 8 cases a structural brain lesion was observed. In 33 patients, a genetic aetiology was identified. In 2 patients with drug-resistant seizures video-EEG allowed the identification of non-epileptic seizures, and in one patient we discontinued anti-epileptic drugs. In these patients, the aetiological diagnosis was made after 30 years (range 9-60 years) from the disease onset. Conclusions: In a population of 200 adult patients with epilepsy and ID, an aetiological cause was identified in 45 patients after 30 years from the disease onset. Aetiological diagnosis, especially if genetic, has significant positive implications for patients, even if it has been made after years from the beginning of the disease. Benefits include better-focused antiepileptic drug (AED) choice, sparing of further unnecessary investigations and improved knowledge of comorbidities.

Sleep disorders in Multiple System Atrophy: a longitudinal study

Introduction: A higher frequency of sleep and breathing disorders in Multiple System Atrophy (MSA) populations is documented in literature. The analysis of disease progression and prognosis in patients with sleep and breathing disorders could shed light on specific neuropathology and pathophysiology of MSA. Objective: To characterize sleep disorders and their longitudinal modifications during disease course in MSA patients, and to determine their prognostic value. Methods: This is a retrospective and prospective cohort study including 182 MSA patients (58.8% males). Type of onset was defined by the first reported motor or autonomic symptom/sign related to MSA. The occurrence of symptoms/signs and milestones of disease progression and their latency were collected. REM sleep behaviour disorder (RBD) and stridor were video-polysomnography (VPSG)-confirmed. VPSG recordings were analysed in a standardized fashion during the disease course. Survival data were based on time to death from the first symptom of disease. Results: Isolated RBD represented the first MSA symptom in 30% of patients, preceding disease onset according to international criteria with a median of 3(1–5) years. Patients developing early stridor or presenting with RBD at disease onset showed a more rapid and severe disease progression. These features had independent negative prognostic value for survival. Sleep architecture was characterized by peculiar features which could represent negative markers in MSA prognosis. Patients with stridor treated with tracheostomy showed a reduced risk of death. Conclusions: This is one of the first studies focusing on longitudinal progression of sleep in MSA. Sleep disorders are key features of disease, playing a role in presentation, prognosis and progression. In our MSA cohort, RBD represented the most frequent mode of disease presentation. Moreover, some specific clinical and instrumental sleep features could represent a hallmark of MSA and could be involved in prognosis and, in particular, in sudden death and death during sleep.

Ruolo della proteina OPA3 nella patogenesi di malattie neurodegenerative

OPA3 è una proteina codificata dal genoma nucleare che, grazie a una sequenza di targeting mitocondriale, viene indirizzata ai mitocondri dopo la sua sintesi. Le mutazioni nel gene OPA3 sono associate a due patologie neurodegenerative: la Sindrome di Costeff, causata da mutazioni recessive, e una forma di atrofia ottica dominante che si manifesta con cataratta e spesso sordità. L’esatta funzione e regolazione della proteina non sono ancora state completamente chiarite, così come la sua localizzazione nella membrana mitocondriale esterna o interna. Lo scopo di questa tesi era quello di fare luce sulla funzione della proteina OPA3, con particolare interesse alla dinamica mitocondriale e all’autofagia, sulla sua localizzazione subcellulare ed infine di definire il meccanismo patogenetico nelle patologie neurodegenerative causate da mutazioni in questo gene. A questo scopo abbiamo utilizzato sia una linea di neuroblastoma silenziata stabilmente per OPA3 che linee cellulari primarie derivate da pazienti. I risultati del presente studio dimostrano che la riduzione di OPA3, indotta nelle cellule del neuroblastoma e presente nei fibroblasti derivati dai pazienti, produce alterazioni nel network mitocondriale con uno sbilanciamento a favore della fusione. Questo fenomeno è probabilmente dovuto all’aumento della forma long della proteina OPA1 che è stato riscontrato in entrambi i modelli cellulari. Inoltre, seppur con direzione apparentemente opposta, in entrambi i modelli abbiamo osservato un’alterata regolazione dell’autofagia. Infine, abbiamo confermato che OPA3 localizza nella membrana mitocondriale interna ed è esposta per gran parte nella matrice. Inoltre, un segnale della proteina è stato trovato anche nelle mitochondrial associated membranes, suggerendo un possibile ruolo di OPA3 nel trasferimento dei lipidi tra i mitocondri e il reticolo endoplasmatico. Abbiamo rilevato un’interazione della proteina OPA3 con l’acido fosfatidico che non era mai stata evidenziata fino ad oggi. Queste osservazioni sono compatibili con le alterazioni della dinamica mitocondriale e la disregolazione dell’autofagia documentate nei modelli studiati.

Circadian rhythms, sleep and autonomic function in progressive supranuclear palsy: characteristic features and reciprocal interactions

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative condition. The aims of this study were to evaluate the association between sleep, the circadian system and autonomic function in a cohort of PSP patients. Methods: Patients with PSP diagnosed according to consensus criteria were recruited prospectively and retrospectively and performed the following tests: body core temperature (BcT), sleep-wake cycle, systolic and diastolic blood pressure (SBP, DBP) continuous monitoring for 48 h under controlled environmental conditions; cardiovascular reflex tests (CRTs). The analysis of circadian rhythmicity was performed with the single cosinor method. For state-dependent analysis, the mean value of variables in each sleep stage was calculated as well as the difference to the value in wake. Results: PSP patients presented a reduced total duration of night sleep, with frequent and prolonged awakenings. During daytime, patients had very short naps, suggesting a state of profound sleep deprivation across the 24-h. REM sleep behaviour disorder was found in 15%, restless legs syndrome in 46%, periodic limb movements in 52% and obstructive sleep apnea in 54%. BcT presented the expected fall during night-time, however, compared to controls, mean values during day and night were higher. However BcT state-dependent modulation was maintained. Increased BcT could be attributed to an inability to properly reduce sympathetic activity favoured by the sleep deprivation. At CRTs, PSP presented mild cardiovascular adrenergic impairment and preserved cardiovagal function. 14% had non-neurogenic orthostatic hypotension. Only 2 PSP presented the expected BP dipping pattern, possibly as a consequence of sleep disruption. State-dependent analysis showed a partial loss of the state-dependent modulation for SBP. Discussion: This study showed that PSP presented abnormalities of sleep, circadian rhythms and cardiovascular autonomic function that are likely to be closely linked one to another.

Evaluation of alpha-synuclein RT-QuIC for an early and differential diagnosis of Lewy body disease

Synucleinopathies are a group of neurodegenerative diseases characterized by tissue deposition of insoluble aggregates of the protein α-synuclein. Currently, the clinical diagnosis of these diseases, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), is very challenging, especially at an early disease stage, due to the heterogeneous and often non-specific clinical manifestations. Therefore, identifying specific biomarkers to aid the diagnosis and improve the clinical management of patients with these disorders represents a primary goal in the field. Pursuing this aim, we applied the α-Syn Real-Time Quaking-Induced Conversion (RT-QuIC), an ultrasensitive technique able to detect minute amounts of amyloidogenic proteins, to a large cohort of 953 CSF samples from clinically well-characterized (“clinical” group), or neuropathologically verified (“NP” group) patients with parkinsonism or dementia. Of significance, we also studied patients with prodromal synucleinopathies (“prodromal” group), such as pure autonomic failure (PAF) (n = 28), isolated REM sleep behavior disorder (iRBD) (n = 18), and mild cognitive impairment due to probable Lewy body (LB) disease (MCI-LB) (n = 81). Our findings show that α-syn RT-QuIC can accurately detect α-Syn seeding activity across the whole spectrum of LB-related disorders (LBD), exhibiting a mean sensitivity of 95.2% in the “clinical” and “NP” group, while ranging between 89.3% (PAF) and 100% (RBD) in the “prodromal group”. Moreover, we observed 95.1% sensitivity and 96.6% specificity in the distinction between MCI-LB patients and cognitively unimpaired controls, demonstrating the solid diagnostic potential of α-Syn RT-QuIC in the early phase of the disease. Finally, 13.3% of MCI-AD patients also had a positive test, suggesting an underlying LB co-pathology. This work demonstrated that α-Syn RT-QuIC is an efficient assay for accurate and early diagnosis of LBD, which should be implemented for clinical management and recruitment for clinical trials in memory clinics.

Whole Exome Sequencing widens the genetic landscape of Hereditary Optic Neuropathies

Hereditary optic neuropathies (HON) are a genetic cause of visual impairment characterized by degeneration of retinal ganglion cells. The majority of HON are caused by pathogenic variants in mtDNA genes and in gene OPA1. However, several other genes can cause optic atrophy and can only be identified by high throughput genetic analysis. Whole Exome Sequencing (WES) is becoming the primary choice in rare disease molecular diagnosis, being both cost effective and informative. We performed WES on a cohort of 106 cases, of which 74 isolated ON patients (ON) and 32 syndromic ON patients (sON). The total diagnostic yield amounts to 27%, slightly higher for syndromic ON (31%) than for isolated ON (26%). The majority of genes found are related to mitochondrial function and already reported for harbouring HON pathogenic variants: ACO2, AFG3L2, C19orf12, DNAJC30, FDXR, MECR, MTFMT, NDUFAF2, NDUFB11, NDUFV2, OPA1, PDSS1, SDHA, SSBP1, and WFS1. Among these OPA1, ACO2, and WFS1 were confirmed as the most relevant genetic causes of ON. Moreover, several genes were identified, especially in sON patients, with direct impairment of non-mitochondrial molecular pathways: from autophagy and ubiquitin system (LYST, SNF8, WDR45, UCHL1), to neural cells development and function (KIF1A, GFAP, EPHB2, CACNA1A, CACNA1F), but also vitamin metabolism (SLC52A2, BTD), cilia structure (USH2A), and nuclear pore shuttling (NUTF2). Functional validation on yeast model was performed for pathogenic variants detected in MECR, MTFMT, SDHA, and UCHL1 genes. For SDHA and UCHL1 also muscle biopsy and fibroblast cell lines from patients were analysed, pointing to possible pathogenic mechanisms that will be investigated in further studies. In conclusion, WES proved to be an efficient tool when applied to our ON cohort, for both common disease-genes identification and novel genes discovery. It is therefore recommended to consider WES in ON molecular diagnostic pipeline, as for other rare genetic diseases.

Integrating omics in prion diseases as a model to explore the strain paradigm in neurodegenerative diseases

This project aims at deepening the understanding of the molecular basis of the phenotypic heterogeneity of prion diseases. Prion diseases represent the first and clearest example of “protein misfolding diseases”, that are all the neurodegenerative diseases caused by the accumulation of misfolded proteins in the central nervous system. In the field of protein misfolding diseases, the term “strain” describes the heterogeneity observed among the same disease in the clinical and pathologic progression, biochemical features of the aggregated protein, conformational memory and pattern of lesions. In this work, the two most common strains of Creutzfeldt-Jakob Disease (CJD), named MM1 and VV2, were analyzed. This thesis investigates the strain paradigm with the production of new multi omic data, and, on such data, appropriate computational analysis combining bioinformatics, data science and statistical approaches was performed. In this work, genomic and transcriptomic profiling allowed an improved characterization of the molecular features of the two most common strains of CJD, identifying multiple possible genetic contributors to the disease and finding several shared impaired pathways between the VV2 strain and Parkinson Disease. On the epigenomic level, the tridimensional chromatin folding in peripheral immune cells of CJD patients at onset and of healthy controls was investigated with Hi-C. While being the first application of this very advanced technology in prion diseases and one of the first in general in neurobiology, this work found a significant and diffuse loss of genomic interactions in immune cells of CJD patients at disease onset, particularly in the PRNP locus, suggesting a possible impairment of chromatin conformation in the disease. The results of this project represent a novelty in the state of the art in this field, both from a biomedical and technological point of view.

Myotonic syndromes: analysis of factors with pathogenetic and prognostic significance

Background: The natural history of Myotonic Dystrophy type 1 is largely unclear, longitudinal studies are lacking. Objectives: to collect clinical and laboratory data, to evaluate sleep disorders, somatic and autonomic skin fibres, neuropsychological and neuroradiological aspects in DM1 patients. Methods: 72 DM1 patients underwent a standardized clinical and neuroradiological evaluation performed by a multidisciplinary team during 3 years of follow-up. Results: longer disease duration was associated with higher incidence of conduction disorders and lower ejection fraction; higher CVF values were predictors for a reduced risk of cardiopathy. Lower functional pulmonary values were associated with class of expansion and were negatively associated with disease duration; arterial blood gas parameters were not associated with expansion size, disease duration nor with respiratory function test. Excessive daytime sleepiness was not associated with class of expansion nor with any of the clinical parameters examined. We detected apnoea in a large percentage of patients, without differences between the 3 genetic classes; higher CVF values were predictors for a reduced risk of apnoea. Skin biopsies demonstrated the presence of a subclinical small fibre neuropathy with involvement of the somatic fibres. The pupillometry study showed lower pupil size at baseline and a lower constriction response to light. The most affected neuropsychological domains were executive functions, visuoconstructional, attention and visuospatial tasks, with a worse performance of E1 patients in the visuoperceptual ability and social cognition tasks. MRI study demonstrated a decrease in the volumes of frontal, parietal, temporal, occipital cortices, accumbens, putamen nuclei and a more severe volume reduction of the isthmus cingulate, transverse temporal, superior parietal and temporal gyri in E2 patients. Discussion: only some clinical parameters could predict the risk of cardiopathy, pulmonary syndrome and sleep disorders, while other clinical aspects proved to be unpredictable, confirming the importance of periodic clinical follow-up of these patients.

Neuro-ophthalmological and electrophysiological characterization of mitochondrial diseases.

Aims and methods: 1) characterization of patients with Dominant Optic Atrophy (DOA) associated with mutations in AFG3L2 and ACO2 genes in comparison with classical OPA1-DOA; 2) characterization of patients with mtDNA mutations causing MELAS and MERRF syndromes and correlation with heteroplasmy; 3) longitudinal evaluation of subacute m.11778G>A/MTND4 Leber’s Hereditary Optic Neuropathy (LHON) patients co-treated with rAAV2/2-ND4 gene therapy and idebenone. We performed a comprehensive neuro-ophthalmological assessment coupled with electrophysiological examination. Results: 1) We described and compared 23 ACO2 and 13 AFG3L2 patients with 72 OPA1 patients. All patients presented temporally predominant optic atrophy, with ACO2 showing higher RNFL and GCL thicknesses at OCT, while AFG3L2 was virtually-indistinguishable from OPA1. 2) Retinopathy was the most common manifestation in 17/33 MELAS patients, conversely, optic atrophy was the most common finding in 7/8 MERRF patients. Correlation of heteroplasmy with neuro-ophthalmological parameters failed to disclose any significance in MELAS, while it negatively correlated with OCT parameters in MERRF. 3) We compared modifications in visual acuity, OCT and electrophysiological parameters at 3 timepoints in 9 LHON patients. We observed significant decrease of RNFL thickness and reduction of PhNR amplitude. Visual acuity improved of about -0.37 LogMAR, correlating significantly with time from onset and from injection, but not with idebenone therapy duration. Discussion: 1) ACO2 seems associated to better preservation of retinal ganglion cells, depending on a different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2 which is involved in OPA1 processing. 2) MELAS and MERRF patients presented with a clearly distinct ocular phenotype, possibly reflecting a selective susceptibility of different retinal cell types to global energy defect or oxidative stress. 3) Follow up of LHON patients treated with gene therapy confirmed the deterioration in OCT and electrophysiological parameters, while the amount of visual improvement was similar to the one observed in recent clinical trials.

Skin as a promising biomatrix for the early detection of misfolded proteins by RT-QuIC in neurodegenerative diseases

Real-Time Quaking-Induced Conversion (RT-QuIC) is an ultrasensitive assay capable of detecting pathological aggregates of misfolded proteins in biospecimens. In recent years, efforts have been made to find a more feasible and convenient biomatrix as an alternative to CSF, and skin biopsy may be a suitable candidate. This project aimed to evaluate the diagnostic performance of skin RT-QuIC in 3 different cohorts of patients: 1. Creutzfeldt-Jakob disease (CJD), 2. Lewy body disease (LBD), and 3. Isolated REM sleep behavior disorder (iRBD). We studied 71 punch skin samples of 35 patients with CJD, including five assessed in vitam, using 2 two different substrates: Bank vole 23-230 (Bv23-230) and Syrian hamster 23-231 (Ha23-231) recombinant prion protein. Skin prion RT-QuIC showed a 100% specificity with both substrates and a higher sensitivity with the Bv23-230 than Ha23-231 (87.5% vs. 65.6%, respectively). Forty-one patients underwent both lumbar puncture (LB) and skin biopsy; CSF and skin RT-QuIC showed a high level of concordance (38/41, 92.7%). Then, we analyzed samples taken in vitam (n=69) or postmortem (n=49) from patients with Parkinson’s disease (PD), dementia with Lewy bodies (DLB), incidental Lewy body pathology, and neurological controls. Skin α-syn RT-QuIC distinguished LBD patients with an overall accuracy of 94.1% in the two cohorts (sensitivity, 89.2%; specificity, 96.3%). Seventy-nine patients underwent both CSF and skin α-syn RT-QuIC, and the two assays yielded similar diagnostic accuracy (skin, 97.5%; CSF, 98.7%). Finally, we studied 91 iRBD patients and 41 control. In the skin, RT-QuIC showed a sensitivity of 76.9%, specificity of 97.6%, and 82.0% accuracy. 128 participants (88 patients plus 40 controls) underwent both CSF and skin RT-QuIC. The two protocols showed 99.2% of concordance. These works confirmed that skin punch biopsies might represent a valid and convenient alternative to CSF analysis for an early diagnosis of prion diseases and LB-related pathologies.

Evaluation of the transcriptomic response of an Alzheimer's disease murine model induced at different ages: searching for predictors

Alzheimer’s disease (AD) is a chronic, progressive neurodegenerative disease, characterized by the impairment of mnesic and cognitive functions, that represents the most frequent type of dementia in older people worldwide. Aging is the most important risk factor for the sporadic form of the pathology and it is associated to the progressive impairment of the proteostasis network. The endoplasmic reticulum (ER), the main cellular actor involved in proteostasis, appears significantly compromised in AD due to the accumulation of β-amyloid (Aβ) protein and phosphorylated-tau protein. Increasing proteins misfolding activates a specific cellular response known as Unfolded Protein response (UPR) which orchestrates the recovery of ER function. The aim of the present study was to investigate the role of UPR and aging process in a murine model of AD induced by intracerebroventricular (i.c.v.) injection of Aβ1-42 oligomers at 3 or 18 months. The oligomers injection in aged animals caused the increased of memory impairment, oxidative stress, and the depletion of glutathione reserve. Furthermore, the RNA-sequencing analysis was performed and the bioinformatic analysis showed the enrichment of several pathways involved in neurodegeneration and protein regulations. The following analysis highlighted the significant dysregulation of the three branches of the UPR, the protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF-6). In turn, ER stress affected the PI3K/Akt/Gsk3β and MAPK/ERK pathways, highlighting Mapkapk5 as a potential marker of the neurodegenerative process, which regulation could lead to the definition of new pharmacological and neuroprotective strategies to counteract AD.

Disorders of arousal: a physiopathological window to explore the mechanisms regulating sleep arousal

Disorders of Arousal (DoA) belong to NREM parasomnias and are characterized by motor and emotional episodes arising from incomplete awakenings from NREM sleep. DoA episodes embody at the same time the double nature of the arousal process, that is preserving sleep as well as respond to sleep perturbations, thus being an ideal model to study sleep arousal. In the first part of this work, we performed a spectral whole scalp EEG analysis exploring the neurophysiologic correlates of the pre-motor onset of the episodes in a large sample of patients with DoA, disclosing the co-existence of both slow and fast EEG frequencies over overlapping areas before DoA episodes, suggesting an alteration of local sleep mechanisms. Episodes of different complexity were preceded by a similar EEG activation, implying that they possibly share a similar pathophysiology. In the second part of this work, we performed a spectral whole scalp EEG analysis comparing the pre-motor onset of the episodes and normal arousals from healthy sleepers, disclosing the persistence of slow frequencies as well as sigma band (expression of sleep spindles) in DoA episodes. Overall, these results might subtend a higher tendence to preserve sleep and a more defective mechanism toward developing a complete arousal in patients with DoA. In the last part of our work, we evaluated 15 patients with DoA with 15 controls in a functional MRI study during wakefulness in addition to a proton magnetic resonance spectroscopy (1H-MRS) focused on cingulate cortex. We disclosed subtle alterations on posterior cingulate cortex as well as an increased connectivity in sensory-motor network, possibly representing a trait-functional feature responsible for the dysfunctional arousal process in DoA patients

Zika Vírus: manifestações neurológicas do adulto

A Organização Mundial de Saúde reconhece a coincidência espaço-temporal entre surtos de Zika e a incidência de algumas síndromes neurológicas, mas diante da escassez de dados, ainda não estabelece um vínculo direto entre as doenças. No Brasil, a relação entre essas síndromes neurológicas e o Zika Vírus foi percebida em estados da região Nordeste que apresentaram aumento atípico dessas síndromes. O objetivo desta videoaula foi o de abordar as possíveis relações entre o Zika Vírus e algumas síndromes neurológicas do adulto.