Academic literature on the topic 'Neurologisk status'

In 2013, the term disaster neurology was introduced to describe a new practice opportunity for neurologists interested in providing needed, nonsurgical neurologic care in regions affected by natural or human-influenced disasters. Although previously presented as an option for interested neurologists, the coronavirus disease 2019 (COVID-19) pandemic has made it clear that every neurologist should be prepared to take on the unique challenges of disaster neurology. Examining the role of neurologists on the frontlines of the COVID-19 pandemic response represents an opportunity to review and apply key features of disaster neurology, including recognizing the categories of neurologic cases expected to be seen during a disaster, adapting inpatient and outpatient workflows, and accommodating the needs of vulnerable populations. Relating principles of disaster neurology to the response of neurologists to the current pandemic informs best practices for neurologic care as COVID-19 cases continue to surge throughout the United States and abroad.

Objective:To evaluate racial and ethnic differences in the utilization of neurologic care across a wide range of neurologic conditions in the United States.Methods:We analyzed nationally representative data from the 2006–2013 Medical Expenditure Panel Survey (MEPS), including information on demographics, patient-reported health conditions, neurology visit rates, and costs. Using diagnostic codes, we identified persons with any self-identified neurologic disorder except back pain, as well as 5 subgroups (Parkinson disease, multiple sclerosis, headache, cerebrovascular disease, and epilepsy). To assess disparities in neurologic care utilization, we performed logistic regression analyses of outpatient department neurologic care visit rates and expenditures for each racial ethnic group controlling for age, sex, health status, socioeconomic characteristics, and geographic region of care.Results:Of the 279,103 MEPS respondents, 16,936 (6%) self-reported a neurologic condition; 5,890 (2%) received a total of 13,685 outpatient neurology visits. Black participants were nearly 30% less likely to see an outpatient neurologist (odds ratio [OR] 0.72, confidence interval [CI] 0.64–0.81) relative to their white counterparts, even after adjustment for demographic, insurance, and health status differences. Hispanic participants were 40% less likely to see an outpatient neurologist (OR 0.61, CI 0.54–0.69). Among participants with known neurologic conditions, blacks were more likely to be cared for in the emergency department, to have more hospital stays, and to have higher per capita inpatient expenditures than their white counterparts.Conclusions:Our findings highlight racial and ethnic inequalities in the utilization of neurologic care in the United States.

Objective:To compare neurologist and patient perceptions of multiple sclerosis (MS)-related health status.Methods:MS patients (n=99) were recruited from six sites in Canada. Following a consultation with their neurologist, patients estimated their relapse frequency, rated their general health and quality of life (QoL), reviewed descriptions of eight health domains and selected the three most important, and completed a utility assessment using the standard gamble (SG). Concurrently, neurologists independently used the same instruments to rate their patients' health status. Assessments were compared on the basis of paired mean values of both groups and the degree of exact agreement quantified by intraclass coefficient (ICC) and kappa analyses, which yield values of 1.0 with 100% agreement.Results:There were significant differences (p<0.001) between patient and neurologist ratings for relapses in the last year (0.86 vs. 0.4, respectively), QoL (61.2 vs. 69.7 (maximum score = 100) and utility (0.864 vs. 0.971); ICC analysis revealed moderate to poor levels of agreement (0.56 for QoL to 0.03 for SG). There was little concordance in identification of important health domain and the only significant associations were in bodily pain and social functioning (kappa statistic = 0.24, p = 0.026 for both). Neurologists identified physical functioning domains as important, while patients placed more emphasis on mental health domains.Conclusions:Discrepancies between neurologist and patient perceptions of MS were observed. The study identifies a need to educate neurologists on the recognition of MS health domains that are important in the definition of patient QoL.

Background and Purpose: We sought to determine the proportion of patients with ischemic stroke evaluated by vascular neurologists in the United States. Methods: Using 2009 to 2015 claims from a 5% nationally representative sample of Medicare beneficiaries, we identified patients ≥65 years of age who were hospitalized for ischemic stroke. We ascertained the proportion of patients evaluated during the hospitalization or within 90 days of discharge by nonvascular and vascular neurologists. We assessed the relationship between county-level socioeconomic status and the likelihood of neurologist evaluation and between neurologist evaluation and diagnostic testing. Results: Among 66 989 patients with ischemic stroke, 37 820 (56.5%) were evaluated by a nonvascular neurologist and 11 700 (17.5%) by a board-certified vascular neurologist. Across increasing quartiles of county socioeconomic advantage, the proportion of patients evaluated by a vascular neurologist was 12.2%, 16.5%, 19.8%, and 23.0%. Relative to evaluation by a nonvascular neurologist, evaluation by a vascular neurologist was associated with a higher likelihood of postdischarge heart rhythm monitoring (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.6-1.9), echocardiography (OR, 1.4; 95% CI, 1.3-1.4), cervical vessel imaging (OR, 1.3; 95% CI, 1.2-1.3), and intracranial vessel imaging (OR, 2.1; 95% CI, 2.0-2.2). Conclusions: In a nationally representative cohort of Medicare beneficiaries, we found that about three quarters of patients with ischemic stroke were evaluated by a neurologist, and about one-sixth were evaluated by a vascular neurologist. Patients who were evaluated by a vascular neurologist were significantly more likely to undergo diagnostic testing.

Latar Belakang: Komplikasi neurologis terjadi pada lebih dari 40% pasien dengan infeksi HIV. Kelainan neurologis yang terkait dengan infeksi HIV meliputi infeksi sistem saraf pusat, neoplasma, komplikasi vaskular, neuropati perifer, dan miopati.Penelitian ini bertujuan untuk mengetahui manifestasi klinis gangguan neurologis terkait HIV pada pasien terdiagnosis HIV yang dirawat di RSUP Dr. Kariadi Semarang tanggal 1 Januari 2014- 31 Desember 2016. Metode: Penelitian ini adalah studi deskriptif retrospektif observasional yang dilakukan di Rumah Sakit Umum Dr. Kariadi, Semarang, Jawa Tengah. Data diambil dari Rekam medis, dianalisis manifestasi neurologis terkait HIV. Hasil: Subyek adalah 115 pasien dengan HIV-AIDS, 64 laki-laki (56%) dan 51 perempuan (44%). Usia rata-rata 32,06 tahun (4 sampai 68 tahun). Dari 115 kasus, 40 subyek (34,78%) memiliki manifestasi neurologis terkait HIV. Manifestasi neurologis terkait HIV meliputi toksoplasmosis otak (60%), meningoencephalitis(20%), st non hemoragik (5%),abses serebral (5%) dan vertigo (5%). Kesimpulan. Infeksi HIV dan kaitannya dengan tingkat keparahan imunodefisiensi bertanggung jawab atas sejumlah besar gangguan neurologis. Analisis faktor risiko serta status imunitas harus dilakukan pada semua pasien dengan gangguan neurologis untuk tujuan penyaringan hiv. Kata kunci: HIV, AIDS, Kelainan neurologis Background: Neurologic complications occur in more than 40% of patients with HIV infection. Neurologic disorders associated with HIV infection include central nervous system infections, neoplasms, vascular complications, peripheral neuropathies, and myopathies. This study was aimed to identify clinical manifestation of HIV-associated neurologic disorders in Patients with AIDS treated in Dr. Kariadi General Hospital from 1 January 2014 to 31 December 2016. Methods: This is a descriptive retrospective observational study conducted in neurology clinic,Dr. Kariadi General Hospital, Semarang,between 1 January 2014 and 31 December 2016.Each patient”s medical record was studied in detail and then analyzed specifically in regard to the clinical manifestation of HIV-associated neurologic disorders. Results: One hundred fifteen patients were included, 64 males (56%) and 51 females (44%). The average age was 32,06 years (4 to 68 years). Of the 115 cases, 40 (34,78 %) had neurologic manifestation.The manifestation include brain toxoplasmosis (60%), meningoencephalitis (20%), non hemorragic stroke (5%),cerebral abces (5%) and vertigo (5%). Conclusions. HIV infection and their association with the severity of immunodeficiency is responsible for a large number of neurologic disorders. Analysis of risk factors as well as imunnological status should be made in all patients with neurologic disorders for the purpose of hiv screening. Keywords: HIV, AIDS, neurologic disorders

BackgroundEffective communication between patients and their health care providers is recognized as critically important to improve the quality of health services for individuals with epilepsy. We aimed to describe in-office neurologist–patient conversations about epilepsy and focus on disease identification, shared decision-making, and care planning.MethodsTranscripts and audio recordings of conversations between patients and neurologists in the United States, Spain, and Germany were analyzed linguistically in the topic areas of epilepsy identification and diagnosis, disease education, treatments, and care planning. Analyses included word-level assessments, topic switching, strategies of information elicitation, identification of topics discussed, quantification of questions asked, and assessment of types of questions asked.ResultsConversations of 17 neurologists in the United States, 12 in Spain, and 6 in Germany, with 50, 20, and 16 patients, respectively, were analyzed. Neurologists tended to utilize an event-based, patient-friendly vocabulary to refer to seizures, and in the United States, they avoided using the term “epilepsy.” Regardless of who initiated the treatment discussion, the neurologists in all 3 countries were unilaterally responsible for the treatment decision and choice of medication. When describing a new medication, neurologists most often discussed potential side effects but did not review potential benefits. Neurologists rarely defined seizure control and did not ask patients what seizure control meant to them.ConclusionsWe identified opportunities related to vocabulary, decision-making, and treatment goal setting that could be targeted to improve neurologist–patient communication about epilepsy, and ultimately, the overall treatment experience and outcomes for patients.

Background Smartphone technology is ubiquitous throughout neurologic practices, and numerous apps relevant to a neurologist’s clinical practice are now available. Data from other medical specialties suggest high utilization of smartphones in routine clinical care. However, the ways in which these devices are used by neurologists for patient care–related activities are not well defined. Objective This paper aims to characterize current patterns of smartphone use and perceptions of the utility of smartphones for patient care–related activities among academic neurology trainees and attending physicians. We also seek to characterize areas of need for future app development. Methods We developed a 31-item electronic questionnaire to address these questions and invited neurology trainees and attendings of all residency programs based in the United States to participate. We summarized descriptive statistics for respondents and specifically compared responses between trainees and attending physicians. Results We received 213 responses, including 112 trainee and 87 attending neurologist responses. Neurology trainees reported more frequent use of their smartphone for patient care–related activities than attending neurologists (several times per day: 84/112, 75.0% of trainees; 52/87, 59.8% of attendings; P=.03). The most frequently reported activities were internet use, calendar use, communication with other physicians, personal education, and health care–specific app use. Both groups also reported regular smartphone use for the physical examination, with trainees again reporting more frequent usage compared with attendings (more than once per week: 35/96, 36.5% of trainees; 8/58, 13.8% of attendings; P=.03). Respondents used their devices most commonly for the vision, cranial nerve, and language portions of the neurologic examination. The majority of respondents in both groups reported their smartphones as “very useful” or “essential” for the completion of patient care–related activities (81/108, 75.0% of trainees; 50/83, 60.2% of attendings; P=.12). Neurology trainees reported a greater likelihood of using their smartphones in the future than attending neurologists (“very likely”: 73/102, 71.6% of trainees; 40/82, 48.8% of attendings; P=.005). The groups differed in their frequencies of device usage for specific patient care–related activities, with trainees reporting higher usage for most activities. Despite high levels of use, only 12 of 184 (6.5%) respondents reported ever having had any training on how to use their device for clinical care. Regarding future app development, respondents rated vision, language, mental status, and cranial nerve testing as potentially being the most useful to aid in the performance of the neurologic examination. Conclusions Smartphones are used frequently and are subjectively perceived to be highly useful by academic neurologists. Trainees tended to use their devices more frequently than attendings. Our results suggest specific avenues for future technological development to improve smartphone use for patient care–related activities. They also suggest an unmet need for education on effectively using smartphone technology for clinical care.

Background: With few evidence-based disease-modifying therapies being available for patients with progressive multiple sclerosis (PMS), how can neurologists best care for their patients? Little is known about the perspectives of patients with respect to the role they would like their neurologist to play in their care. We hereby report an update to our abstract presented at the Canadian Neurological Sciences Federation’s annual congress in 2016. Methods: Patients with PMS having an Expanded Disability Status Scale (EDSS) score of 6 or more were invited to participate. Semi-structured interviews were conducted with patients and their caregivers, and written questionnaires were completed by all participants. Collected data was subjected to thematic coding. Results: We have now interviewed a total of 18 patients (compared to 10 in 2016) and have reached thematic saturation. The majority of patients identified the neurologist as a useful figure in their care. Three main reasons were identified: (1) The neurologist provides information about new research and therapies (2) The neurologist educates patients about their disease and available services (3) The neurologist is viewed as an important supportive figure. Conclusions: Despite a lack of disease-modifying treatments for progressive multiple sclerosis, patients with PMS view the neurologist as an essential provider of care.

Neurologic disorders are among the most frequent causes of morbidity and mortality in the United States. Moreover, the current shortfall of neurologists is expected to worsen over the coming decade. As a consequence, many patients with neurologic disorders will be treated by physicians and primary care providers without formal neurologic training. Furthermore, a pervasive and well-described fear of neurology, termed neurophobia, has been identified in medical student cohorts, residents, and among general practitioners. In this article, members of the American Academy of Neurology A.B. Baker Section on Neurological Education review current guidelines regarding neurologic and neuroscience education, contextualize the genesis and the negative consequences of neurophobia, and provide strategies to mitigate it for purposes of mentoring future generations of health care providers.

AbstractIn the United States, there is a prescription medication misuse crisis including increases in unintentional drug overdose deaths, medications obtained on the illicit market (i.e., diversion), and in the number of individuals seeking treatment for addiction to prescription medications. Neurologists manage patients suffering from conditions (e.g., pain, seizures, spasticity) where the prescriptions of medications with misuse potential are indicated. It is therefore imperative that neurologists understand which medications are liable to misuse and institute strategies to minimize the harm associated with these medications. The authors review the most common medications prescribed by neurologist with misuse potential, and briefly discuss the behaviors that are suggestive of medication misuse and tools for monitoring patients to minimize medication-related harm from misuse.

Background: Examinations with the intent to assess neurological functions and level of conciousness are common in neurocritical care, but the effect on the patient is not entirely researched. Aim: The purpose of this study was to describe the patient’s situation at the neurological wake-up test concerning the environment, nursing interventions and the possibility given the patient to become awake, and if these conditions affect the outcome of the wake-up test. Methods: A quantitative observational study took place at a neurocritical care unit, where 20 patients were observed from interruption of sedation to the neurological assessment, which was performed by a neurosurgeon or a specialized critical care registered nurse. Nursing interventions, environmental factors and physiological parameters were documented. Result: Twelve intervention varieties to control patients’ physiological parameters were used. CPP > 80 mmHg was found in 90 % of observations. Adjustment of the patient’s body position was found in 45 % of observations. The patients were considered sufficiently awake for the neurological assessment in 74 % of observations. The level of consciousness at the point of the neurological assessment was different depending on if it took place in the mornings, performed by neurosurgeons or in the afternoon, performed by nurses. The patients were not agitated and 60 % of patients appeared pain-free. Conclusion: The observed patients were given good conditions concerning environmental factors and nursing interventions for a neurological wake-up test with a fair neurological assessment. NWT as a method didn´t generally cause the observed patients discomfort, such as pain or agitation.
Bakgrund: Undersökningar för att avgöra neurologisk funktion och medvetandegrad är vanliga inom neurointensivvården, men hur patienten påverkas av undersökningarna är relativt utforskat. Syfte: Studiens syfte var att beskriva förhållandena kring patienten vid neurologiskt wake-up test med avseende på miljö, åtgärder som utförs och möjligheten patienten ges att bli tillräckligt vaken, samt om dessa förhållanden påverkar utfallet i wake-up-testet. Metod: En kvantitativ observationsstudie genomfördes på en neurointensivvårdsavdelning, där 20 patienter observerades från sederingsstopp till bedömning av neurologisk status, vilken utfördes av neurokirurg eller intensivvårdssjuksköterska. Omvårdnadsåtgärder, miljöfaktorer och fysiologiska parametrar dokumenterades. Resultat: Tolv varianter av omvårdnadsåtgärder användes för att hålla patienternas fysiologiska parametrar inom gränsvärden. Högt CPP > 80 mmHg förekom i 90 % av observationerna och den omvårdnadsåtgärd som noterades vid flest observationer var justering av patientens kroppsposition (45 %). Vid 74 % av bedömningarna av neurologisk status ansågs patienten ha hunnit vakna tillräckligt mycket. Vakenhetsgraden vid bedömning av neurologisk status skilde sig åt beroende på om bedömningen utfördes på morgon av läkare eller på eftermiddag av intensivvårdssjuksköterska. Patienterna var inte agiterade och bedömdes vid 60 % av observationerna inte visa tecken på smärta innan bedömning av neurologisk status. Slutsats: Patienterna i studien gavs goda förutsättningar med avseende på miljö och omvårdnadshandlingar för ett neurologiskt wake-up test med rättvisande bedömning av neurologisk status. För de observerade patienterna var NWT en metod som generellt sett inte verkade orsaka obehag som smärta eller agitation.

La ligne directrice de nos expériences a été l'hypothèse que l'apparition et/ou la persistance des fluctuations de longue durée entre les états silencieux et actifs dans les réseaux néocorticaux et une excitabilité neuronale modifiée sont les facteurs principaux de l'épileptogenèse, menant aux crises d’épilepsie avec expression comportementale. Nous avons testé cette hypothèse dans deux modèles expérimentaux différents. La déafférentation corticale chronique a essayé de répliquer la déafférentation physiologique du neocortex observée pendant le sommeil à ondes lentes. Dans ces conditions, caractérisées par une diminution de la pression synaptique et par une incidence augmentée de périodes silencieuses dans le système cortico-thalamique, le processus de plasticité homéostatique augmente l’excitabilité neuronale. Par conséquent, le cortex a oscillé entre des périodes actives et silencieuses et, également, a développé des activités hyper-synchrones, s'étendant de l’hyperexcitabilité cellulaire à l'épileptogenèse focale et à des crises épileptiques généralisées. Le modèle de stimulation sous-liminale chronique (« kindling ») du cortex cérébral a été employé afin d'imposer au réseau cortical une charge synaptique supérieure à celle existante pendant les états actifs naturels - état de veille ou sommeil paradoxal (REM). Dans ces conditions un mécanisme différent de plasticité qui s’est exprimé dans le système thalamo-corticale a imposé pour des longues périodes de temps des oscillations continuelles entre les époques actives et silencieuses, que nous avons appelées des activités paroxysmiques persistantes. Indépendamment du mécanisme sous-jacent de l'épileptogenèse les crises d’épilepsie ont montré certaines caractéristiques similaires : une altération dans l’excitabilité neuronale mise en évidence par une incidence accrue des décharges neuronales de type bouffée, une tendance constante vers la généralisation, une propagation de plus en plus rapide, une synchronie augmentée au cours du temps, et une modulation par les états de vigilance (facilitation pendant le sommeil à ondes lentes et barrage pendant le sommeil REM). Les états silencieux, hyper-polarisés, de neurones corticaux favorisent l'apparition des bouffées de potentiels d’action en réponse aux événements synaptiques, et l'influence post-synaptique d'une bouffée de potentiels d’action est beaucoup plus importante par rapport à l’impacte d’un seul potentiel d’action. Nous avons également apporté des évidences que les neurones néocorticaux de type FRB sont capables à répondre avec des bouffées de potentiels d’action pendant les phases hyper-polarisées de l'oscillation lente, propriété qui peut jouer un rôle très important dans l’analyse de l’information dans le cerveau normal et dans l'épileptogenèse. Finalement, nous avons rapporté un troisième mécanisme de plasticité dans les réseaux corticaux après les crises d’épilepsie - une diminution d’amplitude des potentiels post-synaptiques excitatrices évoquées par la stimulation corticale après les crises - qui peut être un des facteurs responsables des déficits comportementaux observés chez les patients épileptiques. Nous concluons que la transition incessante entre des états actifs et silencieux dans les circuits cortico-thalamiques induits par disfacilitation (sommeil à ondes lentes), déafférentation corticale (épisodes ictales à 4-Hz) ou par une stimulation sous-liminale chronique (activités paroxysmiques persistantes) crée des circonstances favorables pour le développement de l'épileptogenèse. En plus, l'augmentation de l’incidence des bouffées de potentiels d’actions induisant une excitation post-synaptique anormalement forte, change l'équilibre entre l'excitation et l'inhibition vers une supra-excitation menant a l’apparition des crises d’épilepsie.
The guiding line in our experiments was the hypothesis that the occurrence and / or the persistence of long-lasting fluctuations between silent and active states in the neocortical networks, together with a modified neuronal excitability are the key factors of epileptogenesis, leading to behavioral seizures. We addressed this hypothesis in two different experimental models. The chronic cortical deafferentation replicated the physiological deafferentation of the neocortex observed during slow-wave sleep (SWS). Under these conditions of decreased synaptic input and increased incidence of silent periods in the corticothalamic system the process of homeostatic plasticity up-regulated cortical cellular and network mechanisms and leaded to an increased excitability. Therefore, the deafferented cortex was able to oscillate between active and silent epochs for long periods of time and, furthermore, to develop highly synchronized activities, ranging from cellular hyperexcitability to focal epileptogenesis and generalized seizures. The kindling model was used in order to impose to the cortical network a synaptic drive superior to the one naturally occurring during the active states - wake or rapid eye movements (REM) sleep. Under these conditions a different plasticity mechanism occurring in the thalamo-cortical system imposed long-lasting oscillatory pattern between active and silent epochs, which we called outlasting activities. Independently of the mechanism of epileptogenesis seizures showed some analogous characteristics: alteration of the neuronal firing pattern with increased bursts probability, a constant tendency toward generalization, faster propagation and increased synchrony over the time, and modulation by the state of vigilance (overt during SWS and completely abolished during REM sleep). Silent, hyperpolarized, states of cortical neurons favor the induction of burst firing in response to depolarizing inputs, and the postsynaptic influence of a burst is much stronger as compared to a single spike. Furthermore, we brought evidences that a particular type of neocortical neurons - fast rhythmic bursting (FRB) class - is capable to consistently respond with bursts during the hyperpolarized phase of the slow oscillation, fact that may play a very important role in both normal brain processing and in epileptogenesis. Finally, we reported a third plastic mechanism in the cortical network following seizures - a decreasing amplitude of cortically evoked excitatory post-synaptic potentials (EPSP) following seizures - which may be one of the factors responsible for the behavioral deficits observed in patients with epilepsy. We conclude that incessant transitions between active and silent states in cortico-thalamic circuits induced either by disfacilitation (sleep), cortical deafferentation (4-Hz ictal episodes) and by kindling (outlasting activities) create favorable circumstances for epileptogenesis. The increase in burst-firing, which further induce abnormally strong postsynaptic excitation, shifts the balance of excitation and inhibition toward overexcitation leading to the onset of seizures.

Un problema important en el maneig de l’Estat Epiléptico (EE) és el diagnòstic precoç d’aquest. Se sap que l’activitat epilèptica causa un augment de la demanda metabòlica a nivell cerebral, que s’acompanya d’un augment temporal de la perfusió cerebral, per això investiguem si la TC cerebral de perfusió (TC-P) podia ser una eina de diagnòstic útil per a pacients amb EE. Realitzem un estudi de pacients amb EE, diagnosticats per semiologia clínica i EEG, en els quals es va realitzar de manera prospectiva un TC-P en fase crítica. Es va realitzar una anàlisi visual i quantitatiu dels mapes de perfusió. Es van calcular els índexs de asimetría-(IA) per al flux cerebral regional-(rCBF), el volum-(rCBV), el temps a l’pic-(TTP) i el temps de trànsit mig-(MTT). En 9 dels casos es va realitzar una TC-P de seguiment un cop resolt el EE i es van comparar amb les TC-P realitzades en fase crítica. A més, incloem un grup de control en els quals també es va realitzar un TC-P. Incloem 19 pacients. L’anàlisi visual dels mapes de perfusió durant la fase crítica, va mostrar àrees de hiperperfusión en el 78,9% dels pacients. L’anàlisi quantitativa va mostrar un augment significatiu dels valors de rCBF (p=0.002) i rCBV (p=0.004), i una disminució de TTP (p <0.001) MTT (p=0.001) en les àrees corticals de el costat afectat versus el costat no afectat. Dels 9 pacients amb una TC-P de seguiment, 8 van mostrar disminució de la intensitat, rCBV (p=0.035) i rCBF (p=0.024) en les àrees de hiperperfusión. La sensibilitat de la detecció de hiperperfusión per al diagnòstic d’EE va ser 78.95%, i l’especificitat de l’90%. L’anàlisi quantitativa comparativa dels índexs de asimetria per rCBF, rCBV i MTT entre les TC-P crítiques i el grup control va mostrar diferències significatives per a tots els paràmetres (rCBF p=0.001; rCBV p=0.002; TTP p=0.001 i MTT p=0.001) En aquest estudi vam demostrar que la TC-P pot proporcionar informació diagnòstica valuosa en pacients amb EE i complementar a l’EEG. D’altra banda, la identificació de factors clínics que puguin predir l’evolució dels pacients en EE és important. L’escala STESS-(Status-epilepticus-Severity-Score) és una eina per predir la mortalitat en el EE. No obstant això, aquesta escala no té en compte la situació funcional prèvia de l’malalt. Per això en el nostre segon estudi vam voler valorar si l’Rankin modificat-(mRS) podria ser un factor pronòstic en el EE i si afegint aquesta variable a l’STESS es podria millorar la predicció de el pronòstic en aquests pacients. Es va realitzar un registre retrospectiu dels pacientes≥16 anys que van presentar un EE. Realitzem corbes ROC i models de regressió logística per estimar les puntuacions d’una nova escala “”mSTESS””(modified STESS) i comparem amb els resultats de l’STESS. Es van incloure 136 pacients. La capacitat de l’STESS per predir la mortalitat va ser de l’74,3%, mentre que la capacitat de l’mRS per predir la mortalitat va ser de l’65,2%. El model de regressió logística i les corbes ROC van permetre classificar el mRS en tres grups: 0 (mRS=0); 1 (mRS=1 a 3) i 2 (mRS> 3). Aquests valors van ser afegits als altres ítems de l’STESS, resultant una nova escala, el mSTESS, amb puntuacions entre 0 i 8 punts. La capacitat de l’mSTESS per predir la mortalitat va ser de l’80,1%. Un mSTESS> 4 va establir una precisió general de 81.8% per predir la mortalitat, que va ser considerablement més gran que la precisió general de l’STESS≥3 (59.6%). Concloem que el mRS basal s’associa amb un alt risc de mortalitat, i que el mSTESS, podria ser una escala més precisa per predir el pronòstic de pacients amb EE.
Un problema importante en el manejo del Estado Epiléptico (EE) es el diagnóstico precoz del mismo. Se sabe que la actividad epiléptica causa un aumento de la demanda metabólica en la corteza cerebral, que se acompaña de un aumento temporal de la perfusión cerebral, por ello investigamos si la TC cerebral de perfusión (TC-P) podía ser una herramienta de diagnóstico útil para pacientes con EE. Realizamos un estudio de pacientes con EE, diagnosticados por semiología clínica y EEG, en los que se realizó de forma prospectiva una TC-P en fase crítica. Se realizó un análisis visual y cuantitativo de los mapas de perfusión. Se calcularon los índices de asimetría-(IA) para el flujo cerebral regional-(rCBF), el volumen-(rCBV), el tiempo al pico-(TTP) y el tiempo de tránsito medio-(MTT). En 9 de los casos se realizó una TC-P de seguimiento una vez resuelto el EE y se compararon con las TC-P realizadas en fase crítica. Además, incluimos un grupo de control en los que también se realizó un TC-P. Incluimos 19 pacientes. El análisis visual de los mapas de perfusión durante la fase crítica, mostró áreas de hiperperfusión en el 78,9% de los pacientes. El análisis cuantitativo mostró un aumento significativo de los valores de rCBF (p=0.002) y rCBV (p=0.004), y una disminución de TTP (p <0.001) MTT (p=0.001) en las áreas corticales del lado afectado versus el lado no afectado. De los 9 pacientes con una TC-P de seguimiento, 8 mostraron disminución de la intensidad, rCBV (p=0.035) y rCBF (p=0.024) en las áreas de hiperperfusión. La sensibilidad de la detección de hiperperfusión para el diagnóstico de EE fue 78.95%, y la especificidad del 90%. El análisis cuantitativo comparativo de los índices de asimetría para rCBF, rCBV y MTT entre las TC-P críticas y el grupo control mostró diferencias significativas para todos los parámetros (rCBF p=0.001; rCBV p=0.002; TTP p=0.001 y MTT p=0.001) En este estudio demostramos que la TC-P puede proporcionar información diagnóstica valiosa en pacientes con EE y complementar al EEG. Por otro lado, la identificación de factores clínicos que puedan predecir la evolución de los pacientes en EE es importante. La escala STESS (Status-Epilepticus-Severity-Score) es una herramienta para predecir la mortalidad en el EE. Sin embargo, esta escala no tiene en cuenta la situación funcional previa del enfermo. Por ello en nuestro segundo estudio quisimos valorar si el Rankin modificado (mRS) podría ser un factor pronóstico en el EE y si añadiendo esta variable al STESS se podría mejorar la predicción del pronóstico en estos pacientes. Se realizó un registro retrospectivo de los pacientes≥16 años que presentaron un EE. Realizamos curvas ROC y modelos de regresión logística para estimar las puntaciones de una nueva escala “mSTESS”(modified STESS) y comparamos con los resultados del STESS. Se incluyeron 136 pacientes. La capacidad del STESS para predecir la mortalidad fue del 74,3%, mientras que la capacidad del mRS para predecir la mortalidad fue del 65,2%. El modelo de regresión logística y las curvas ROC permitieron clasificar el mRS en tres grupos: 0 (mRS=0); 1 (mRS=1 a 3) y 2 (mRS> 3). Estos valores fueron añadidos a los otros ítems del STESS, resultando una nueva escala, el mSTESS, con puntajes entre 0 y 8 puntos. La capacidad del mSTESS para predecir la mortalidad fue del 80,1%. Un mSTESS> 4 estableció una precisión general de 81.8% para predecir la mortalidad, que fue considerablemente mayor que la precisión general del STESS≥3 (59.6%). Concluimos que el mRS basal se asocia con un alto riesgo de mortalidad, y que el mSTESS, podría ser una escala más precisa para predecir el pronóstico de pacientes con EE.
One challenge in SE management is establishing the diagnosis, particularly in patients with nonconvulsive seizures. It is known that epileptic activity causes an increase in the metabolic demand of the affected cerebral cortex, and this is accompanied by a transient increase in blood perfusion of the region, Therefore, we wanted to evaluate if the PCT cerebral perfusion could a be of value for diagnosing a SE. We included SE patients, diagnosed by EEG and clinical semiology, who prospectively underwent a PCT study in the ictal phase. Visual and quantitative analysis of the perfusion maps were performed. Asymmetry index-(AI) between affected and unaffected hemispheres were calculated for regional-cerebral blood flow-(rCBF), regional-cerebral blood volume-(rCBV), time to peak-(TTP), and mean transit time-(MTT). Nine patients underwent a follow-up PCT after SE resolution, and the corresponding maps were compared to the ictal maps. In addition, we included a control group, who also underwent acute PCT during the study period. We included 19 patients. On visual analysis of parametric perfusion maps during the ictal phase, regional cortical hyperperfusion was depicted in 78.9% of patients. Quantitative analysis showed significantly increased rCBF (p=0.002) and rCBV (p=0.004) values, and decreased TTP (p<0.001) MTT (p=0.001) in cortical areas of the affected versus the unaffected side. In the 9 patients with a follow-up PCT, 8 showed decreased intensity, rCBV (p=0.035), and rCBF (p=0.024) in the hyperperfusion areas. The sensitivity of hyperperfusion detection for the diagnosis of SE was 78.95%, specificity 90%. Comparative quantitative analysis of asymmetry indices for rCBF, rCBV, and MTT between ictal PCT and control patients showed significant differences for all parameters (rCBF p=0.001; rCBV p=0.002; TTP p=0.001 and MTT p=0.001). In this study we demonstrate that PCT may provide valuable diagnostic information in patients with SE and complement the diagnostic value of EEG. On the other hand, identifying the clinical factors that predict the outcome of patients with SE is important. The Status Epilepticus Severity Score (STESS) is a score for predicting mortality in SE. However, this scale does not consider the previous functional situation of the patient. Therefore, in our second study we wanted to assess if the baseline modified Rankin Scale (mRS) might be a prognostic factor for assessing the short-tem outcomes of SE and whether its addition to STESS can improves the prediction of mortality. We recruited consecutive patients with SE >16 years. We developed ROC curves and a logistic regression model to estimate the scores of the new score, designated as modified STESS (mSTESS) and subsequently compared it with the STESS. We included 136 patients. The capacity of STESS to predict mortality was 74.3% (IC:63.8-81.8%), while the capacity of the mRS to predict mortality was 65.2% (IC:54.2-76.2%). The logistic regression model and ROC curves enabled the classification of mRS as follows: 0 (mRS=0); 1 (mRS=1 to 3) and 2 (mRS>3). These values, when added to the other items of the STESS, resulted in the mSTESS with scores between 0 and 8 points. The capacity of the mSTESS to predict mortality was 80.1%. A mSTESS>4 established an overall accuracy of 81.8% for predicting mortality, which was considerably higher than the overall accuracy of STESS≥3 (59.6%). In this second study, we conclude that the baseline mRS was associated with high mortality risk and we propose to use mSTESS to improve the prediction of mortality risk in SE.

Spontaneous activity in the cerebral cortex changes in different brain states. During desynchronized brain states (e.g. wakefulness, REM sleep), populations of neurons in the cerebral cortex fire action potentials in a stochastic and uncorrelated manner. In contrast, during synchronized states (e.g. slowwave sleep, anesthesia) cortical neurons display the alternation between quiescent periods (DOWN) and periods of spiking activity (UP) coherently across cortical layers. In recent years, the view has emerged that brain states are not defined in discrete categories, but rather form a continuum of possible states. In this thesis, we address three main questions regarding this phenomenon: How is the oscillatory activity at high frequencies (10-100 Hz) distributed across the cortical laminae during UP states? What are the mechanisms underlying UP and DOWN dynamics in neocortex in vivo? How do brain states shape the statistics of cortical spontaneous activity? First, we analyzed laminar local field potential recordings of spontaneous activity in the visual cortex in vivo and characterized the laminar profile of fast oscillatory activity present during UP states, which showed overall similar spectral properties across layers but were generated independently in two different compartments determined by superficial and deep cortical layers. In order to explore whether this laminar profile of fast oscillatory activity was generated intrinsically by cortical circuitry or by external inputs, we performed simultaneous local field potential recordings in spontaneously active cortical slices in vitro. By manipulating the slices pharmacologically, we concluded that neural excitability can control inter-laminar couplings and oscillatory dynamics in cortical circuits. Second, we made a quantitative analysis of UP and DOWN dynamics in vivo by analyzing multiple single-unit cortical recordings during synchronized states. The classic view about what causes cortical UP and DOWN dynamics during synchronized states implicates a "fatigue" or adaptation process (such as spike frequency adaptation or synaptic depression), but our results were inconsistent with a dominant role for this mechanism. Using a low dimensional modeling approach, we proposed a rate model that displays UP and DOWN dynamics, in which bistability can be obtained at arbitrarily low rates. With this model we explored the role and interplay of adaptation and external fluctuations in shaping the statistics of UP and DOWN state dynamics, and determined that a regime of weak adaptation and strong fluctuations is necessary to qualitatively reproduce the statistical features of the experimental data. Finally, we studied the impact of brain states in cortical dynamics. Under urethane anesthesia, spontaneous transitions between synchronized states (with UP and DOWN state dynamics) and desynchronized states (with sporadic or absent DOWN states) are observable, and these transitions resemble those observed from slow-wave to REM sleep states. Investigating multiple single-unit recordings during these transitions, we found that the statistics of UP and DOWN states are largely determined by the brain state in a continuous manner, consistently across experiments and cortical areas. This constrains the possible cortical mechanisms modulated during transitions between desynchronized and synchronized states, as revealed in a low-dimensional firing rate network model.
La actividad espontánea en la corteza cerebral cambia en diferentes estados cerebrales. Durante estados desincronizados (e.g. estado de vigilia, sueño MOR), las poblaciones de neuronas en los potenciales de acción en una manera aparentemente estocástica y no correlacionada. Por el contrario, durante estados sincronizados (e.g. sueño de ondas lentas, anestesia) las neuronas corticales muestran la alternancia entre periodos de reposo (DOWN) y los períodos de actividad (UP) de manera coherente a través de las capas corticales. En los últimos años, ha emergido la visión de que los estados cerebrales no están definidos en categorías discretas, sino que forman un continuo de estados posibles. En esta tesis, nos dirigimos a tres preguntas principales con respecto a este fenómeno: ¿Cómo es la actividad oscilatoria a altas frecuencias (10-100 Hz) distribuída a través de las capas de la neocorteza durante los períodos UP? ¿Cuáles son los mecanismos que subyacen a la dinámica UP y DOWN en el neocórtex in vivo? ¿Cómo se determinan los estados cerebrales estadísticas de actividad espontánea cortical? En primer lugar, analizamos registros de potencial de campo local en la corteza visual in vivo y caracterizamos el perfil laminar de actividad oscilatoria rápida durante los estados UP, que mostraron en general propiedades espectrales similares a través de las distintas capas, pero generadas de forma independiente en dos compartimentos distintos determinados por capas corticales superficiales y profundas. Con el fin de explorar si este perfil laminar de la actividad oscilatoria rápida es generada intrínsecamente por los circuitos corticales o por inputs externos, se realizaron registros de potencial de campo local en rebanadas corticales espontáneamente activas in vitro. Mediante la manipulación farmacológica in vitro, se concluyó que la excitabilidad neuronal puede controlar los acoplamientos entre capas y dinámica oscilatoria en los circuitos corticales. En segundo lugar, realizamos un análisis cuantitativo de la dinámica UP y DOWN in vivo mediante el análisis de registros corticales múltiples de una sola unidad durante estados sincronizados. El punto de vista clásico sobre las causas de esta dinámica durante los estados sincronizados implica un mecanismo de "fatiga" o proceso de adaptación (e.g. adaptación de frecuencia disparo o depresión sináptica), pero los resultados que observamos resultan inconsistentes con un papel dominante de este mecanismo. Utilizando un enfoque de modelado de baja dimensión, propusimos un modelo que muestra dinámica UP y DOWN, en la que biestabilidad se puede conseguir a tasas de descarga arbitrariamente bajas. Con este modelo hemos explorado el papel y la interacción de la adaptación y las fluctuaciones externas en la conformación de las estadísticas de la dinámica del estado UP y DOWN, y determinamos un régimen de adaptación débil pero con fluctuaciones fuertes es necesario para reproducir cualitativamente la estadística de los datos experimentales. Por último, transiciones espontáneas entre estados sincronizados (con la dinámica del estado UP y DOWN) y estados desincronizados (con los períodos DOWN esporádicos o ausentes) son observables bajo la influencia del anestésico uretano, y estas transiciones se asemejan a las observadas a partir de ondas lentas de los estados de sueño REM. Investigando registros múltiples de una sola unidad durante estas transiciones, encontramos que la estadísticas de la dinámica UP y DOWN está determinada en gran medida por el estado del cerebro de forma continua, de manera consistente a través de experimentos y áreas corticales. Esto limita los posibles mecanismos corticales modulados durante las transiciones entre estados desincronizados y sincronizados, tal como lo revela el uso de un modelo de baja dimensión.

Electroencephalogram (EEG) recordings provide insight into the changes in brain activity associated with various states of anesthesia, epilepsy, brain attentiveness, sleep disorders, brain disorders, etc. EEG's are complex signals whose statistical properties depend on both space and time. Their randomness and non-stationary characteristics make them impossible to be described in an accurate way with a simple technique, requiring analysis and characterization involves techniques that take into account their non-stationarity. For that, new advanced techniques in order to improve the efficiency of the EEG based methods used in the clinical practice have to be developed. The main objective of this thesis was to investigate and implement different methods based on nonlinear techniques in order to develop indexes able to characterize the frequency spectrum, the nonlinear dynamics and the complexity of the EEG signals recorded in different state of consciousness. Firstly, a new method for removing peak and spike in biological signal based on the signal envelope was successfully designed and applied to simulated and real EEG signals, obtaining performances significantly better than the traditional adaptive filters. Then, several studies were carried out in order to extract and evaluate EEG measures based on nonlinear techniques in different contexts such as the automatic detection of sleepiness and the characterization and prediction of the nociceptive stimuli and the assessment of the sedation level. Four novel indexes were defined by calculating entropy of the Choi-Williams distribution (CWD) with respect to time or frequency, by using the probability mass function at each time instant taken independently or by using the probability mass function of the entire CWD. The values of these indexes tend to decrease, with different proportion, when the behavior of the signals evolved from chaos or randomness to periodicity and present differences when comparing EEG recorded in eyes-open and eyes-closed states and in ictal and non-ictal states. Measures obtained with time-frequency representation, mutual information function and correntropy, were applied to EEG signals for the automatic sleepiness detection in patients suffering sleep disorders. The group of patients with excessive daytime sleepiness presented more power in ¿ band than the group without sleepiness, which presented higher spectral and cross-spectral entropy in the frontal zone in d band. More complexity in the occipital zone was found in the group of patients without sleepiness in ß band, while a stronger nonlinear coupling between the occipital and frontal regions was detected in patients with excessive daytime sleepiness, in ß band. Time-frequency representation and non-linear measures were also used in order to study how adaptation and fatigue affect the event-related brain potentials to stimuli of different modalities. Differences between the responses to infrequent and frequent stimulation in different recording periods were found in series of averaged EEG epochs recorded after thermal, electrical and auditory stimulation. Nonlinear measures calculated on EEG filtered in the traditional frequency bands and in higher frequency bands improved the assessment of the sedation level. These measures were obtained by applying all the developed techniques on signals recorded from patients sedated, in order to predict the responses to pain stimulation such as nail bad compression and endoscopy tube insertion. The proposed measures exhibit better performances than the bispectral index (BIS), a traditional indexes used for hypnosis assessment. In conclusion, nonlinear measures based on time-frequency representation, mutual information functions and correntropy provided additional information that helped to improve the automatic sleepiness detection, the characterization and prediction of the nociceptive responses and thus the assessment of the sedation level.
El registro de la señal Electroencefalografíca (EEG) proporciona información sobre los cambios en la actividad cerebral asociados con varios estados de la anestesia, la epilepsia, la atención cerebral, los trastornos del sueño, los trastornos cerebrales, etc. Los EEG son señales complejas cuyas propiedades estadísticas dependen del espacio y del tiempo. Sus características aleatorias y no estacionarias hacen imposible que el EEG se describa de forma precisa con una técnica sencilla requiriendo un análisis y una caracterización que implica técnicas que tengan en cuenta su no estacionariedad. Todo esto aumenta la necesidad de desarrollar nuevas técnicas avanzadas con el fin de mejorar la eficiencia de los métodos utilizados en la práctica clínica que son basados en el análisis de EEG. En esta tesis se han investigado y aplicado diferentes métodos utilizando técnicas no lineales con el fin de desarrollar índices capaces de caracterizar el espectro de frecuencias, la dinámica no lineal y la complejidad de las señales EEG registradas en diferentes estados de conciencia. En primer lugar, se ha desarrollado un nuevo algoritmo basado en la envolvente de la señal para la eliminación de ruido de picos en las señales biológicas. Este algoritmo ha sido aplicado a señales simuladas y reales obteniendo resultados significativamente mejores comparados con los filtros adaptativos tradicionales. Seguidamente, se han llevado a cabo varios estudios con el fin de extraer y evaluar las medidas de EEG basadas en técnicas no lineales en diferentes contextos. Se han definido nuevos índices mediante el cálculo de la entropía de la distribución de Choi-Williams (DCW) con respecto al tiempo o la frecuencia. Se ha observado que los valores de estos índices tienden a disminuir, en diferentes proporciones, cuando el comportamiento de las señales evoluciona de caótico o aleatorio a periódico. Además, se han encontrado valores diferentes de estos índices aplicados a la señal EEG registrada en diferentes estados. Diferentes medidas basadas en la representación tiempo-frecuencia, la función de información mutua y la correntropia se han aplicado al EEG para la detección automática de la somnolencia en pacientes que sufren trastornos del sueño. Se ha observado en la zona frontal que la potencia en la banda θ es mayor en los pacientes con somnolencia diurna excesiva, mientras que la entropía espectral y la entropía espectral cruzada en la banda δ es mayor en los pacientes sin somnolencia. En el grupo sin somnolencia se ha encontrado más complejidad en la zona occipital, mientras que el acoplamiento no lineal entre las regiones occipital y frontal ha resultado más fuerte en pacientes con somnolencia diurna excesiva, en la banda β. La representación tiempo-frecuencia y las medidas no lineales se han utilizado para estudiar cómo la adaptación y la fatiga afectan a los potenciales cerebrales relacionados con estímulos térmicos, eléctricos y auditivos. Analizando el promedio de varias épocas de EEG grabadas después de la estimulación, se han encontrado diferencias entre las respuestas a la estimulación frecuente e infrecuente en diferentes períodos de registro. Todas las técnicas que se han desarrollado, se han aplicado a señales EEG registradas en pacientes sedados, con el fin de predecir las respuestas a la estimulación del dolor. Un conjunto de medidas calculadas en señales EEG filtradas en diferentes bandas de frecuencia ha permitido mejorar la evaluación del nivel de sedación. Las medidas propuestas han presentado un mejor rendimiento comparado con el índice bispectral, un indicador de hipnosis tradicional. En conclusión, las medidas no lineales basadas en la representación tiempofrecuencia, funciones de información mutua y correntropia han proporcionado informaciones adicionales que contribuyeron a mejorar la detección automática de la somnolencia, la caracterización y predicción de las respuestas nociceptivas y por lo tanto la evaluación del nivel de sedación.

Antecedents: Hi ha escassa informació disponible sobre l’atròfia cerebral global i de substància gris i blanca (SG i SB) en l'esclerosi múltiple primària progressiva (EMPP) i en la seva relació amb paràmetres clínics i de ressonància magnètica (RM); per altra banda, les anomalies en el teixit cerebral d’aparença normal poden contribuir a la discapacitat. Objectiu: Avaluar els mecanismes subjacents a la progressió de la malaltia en les primeres fases de l'EMPP emprant eines de volumetria cerebral i calculant les concentracions de metabòlits mitjançant la imatge de RM per espectroscòpica de protons (IRME) a l'inici de l'estudi i després d'un any de seguiment, i avaluant la seva relació amb els paràmetres clínics i radiològics convencionals. Mètodes: Quaranta-tres pacients amb EMPP dins dels 5 anys primers anys de malaltia i 45 subjectes sans s’inclogueren a l'inici de l'estudi per a l’anàlisi volumètric; després d'un any 31 pacients tingueren un segon examen de RM volumètrica; per als estudis d’IRME, hi havia 41 pacients amb EMPP i 44 subjectes sans disponibles a l'inici de l'estudi i després d'un any es disposava de 21 parells d’estudis (basal – 12 mesos) de pacients amb vòxels de SG cortical i 24 parells d’estudis de pacients amb vòxels de substància blanca d’aparença normal (SBAN) utilitzables. Per als estudis d'atròfia, es va adquirir una seqüència 3D inversion-prepared fast spoiled gradient recall (3DFSPGR); les dades d’IRME es varen adquirir d’un volum situat immediatament superior al sostre dels ventricles laterals emprant una seqüencia point resolved spectroscopy (PRESS). Els anàlisis volumètrics es van realitzar emprant els programes SPM99 (Statistical Parametric Mapping 99) i SIENA (Structural Imaging Evaluation, using Normalization, of Atrophy). Les imatges cerebrals varen ser segmentades en SB, SG, i líquid cefaloraquidi, calculant-se els valors de les fraccions de parènquima cerebral total (FPC), SB (FSB), i SG (FSG). Utilitzant SIENA es va obtenir el percentatge de canvi de volum cerebral (PBVC). Les concentracions de colina (Cho), fosfocreatina (Cr), myo-inositol (Ins), N-acetil-aspartat total (tNAA), i glutamat-glutamina (Glx) es van estimar a través del programari Linear Combination Model (LCModel). Es varen determinar els volums de lesió en seqüències ponderades en T2 i en T1 que realçaven amb gadolini. Es varen obtenir les puntuacions en les escales Expanded Disability Status Scale (EDSS) i Multiple Sclerosis Functional Composite (MSFC) per a cada pacient. Les anàlisis estadístiques es varen realitzar utilitzant les proves apropiades en cada moment per tal d’investigar l'associació entre els paràmetres volumètrics i metabòlics i els corresponents a les valoracions clíniques i de RM convencional, i per avaluar el canvi en aquests paràmetres després d'un any. Resultats i conclusions: S’ha observat pèrdua de volum cerebral global, que afecta tant la FSG com la FSB, als pacients amb EMPP a l'inici de la malaltia per damunt el que s’observa en una mostra de controls sans. Tant la FSG com la FSB s’associen als paràmetres clínico-radiològics convencionals. S’observen disminucions significatives en FPC i FSG al cap de l’any, però no en FSB. Els canvis en FSB es poden predir per la quantitat d'inflamació visible per RM a l'inici de l'estudi, mentre que els canvis en FSG no es poden predir per cap paràmetre. A la SG cortical, les concentracions de tNAA i Glx són més baixes en pacients que en controls. A la SBAN, el tNAA s'ha trobat reduït (encara que en menor mesura) i l’Ins elevat en pacients en comparació amb controls. A la SG cortical el tNAA i a la SBAN l’INS s'han trobat associats amb els paràmetres clínics i radiològics. No s'han detectat canvis significatius de concentració de cap dels metabòlits a cap teixit al cap d’un any.
Background: There is little information available on global and on grey and white matter (GM and WM) atrophy in primary progressive multiple sclerosis (PPMS) and on their relationship with clinical and with other magnetic resonance imaging (MRI) measures; on the other hand abnormalities in normal-appearing brain tissues may contribute to disability in PPMS, where fewer lesions are seen on conventional imaging. Aim: To evaluate the mechanisms underlying disease progression in the early phase of PPMS, focusing on axonal loss as assessed by volumetric MRI measures of WM and GM, and by measuring metabolite concentrations in normal-appearing white matter (NAWM) and cortical GM using proton magnetic resonance spectroscopic imaging (MRSI) at baseline and after one year of follow-up and to assess their relationship with clinical outcomes. Methods: Forty-three patients with PPMS within 5 years of symptom onset and 45 control subjects were included at baseline for the volumetric study; after one year 31 patients returned for a second volumetric MRI examination; for the MRSI examinations 41 patients with PPMS and 44 control subjects were available at baseline (final availability of usable voxels vary according to tissue and group) and 21 pairs of patients yielded usable cortical GM voxels and 24 patients yielded usable NAWM voxels after one year. For atrophy studies, a 3D inversion-prepared fast spoiled gradient recall (3DFSPGR) sequence was acquired; for spectroscopy studies, MRSI data were acquired from a volume located superior to the roof of the lateral ventricles using a point resolved spectroscopy (PRESS) localization sequence. Volumetric analyses were performed at baseline and follow-up using SPM99 (Statistical Parametric Mapping 99) and SIENA (Structural Imaging Evaluation, using Normalization, of Atrophy) software; brain scans were segmented into WM, GM, and cerebrospinal fluid, and brain parenchymal (BPF), WM (WMF), and GM fractions (GMF) normalized against total intracranial volumes were estimated. Using SIENA the percentage brain volume change (PBVC) over one year was obtained. Concentrations of choline-containing compounds (Cho), phosphocreatine (Cr), myo-inositol (Ins), total N-acetyl-aspartate (tNAA), and glutamate-glutamine (Glx) were estimated using proton MRSI using the Linear Combination Model (LCModel) software. T2-weighted and T1-weighted gadolinium-enhancing lesion volumes were also determined. Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores were recorded in all patients. Statistical analyses were performed using appropriate tests to investigate the association between volumetric and metabolic parameters with those obtained from clinical and conventional MRI assessments, and to evaluate change in these parameters after one year. Results & conclusions: Brain atrophy, affecting both GMF and WMF, has been found to be present early in the course of PPMS exceeding what is observed in a sample of healthy controls after adjusting for significant variables. Both GMF and WMF are related to clinical and MRI lesion-related parameters. Significant decreases in BPF and GMF can be observed after one year, but cannot be detected in the WMF. WMF changes can be predicted by the amount of MRI-visible inflammation at baseline, whereas GMF changes cannot be predicted by any clinical or MRI parameter investigated. In cortical GM, concentrations of tNAA and Glx have been found to be lower in patients as compared to control subjects. In NAWM, tNAA has also been found to be reduced (although to a lower extent) and Ins to be increased in patients as compared to control subjects. In cortical GM tNAA and, in NAWM, Ins levels have been found to correlate with clinical parameters. No changes have been detected in either cortical GM or NAWM for any of the metabolite concentrations after one year of follow-up.

Tese de doutoramento, Medicina (Neurologia), Universidade de Lisboa, Faculdade de Medicina, 2016
Parkinson`s disease (PD) is an age-related neurodegenerative disorder with progressive disability. Its incidence is expected to increase substantially owing to ageing of world population. Better general healthcare, and better understanding of complications and clinical management of PD is likely to increase in the future the prevalence of PD patients in very advanced stages of disease, when disability is most severe. These very advanced patients will represent an important burden for families and the healthcare and social systems, and a new challenge for healthcare personnel. Nevertheless, the clinical characteristics of these late-stage PD (LS-PD) patients have been only partially described in the pre-levodopa or post-levodopa era. Since knowledge of the health needs of these patients is crucial to plan effective health resources that cover patients and caregivers needs, we aimed to study the clinical features and handicap of LS-PD patients attending two tertiary centres, selected on the basis of motor disability. We also aimed to study whether the handicap of LS-PD patients differs from that of classical advanced stage PD patients, i.e., patients manifesting disabling levodopa-induced motor complications, and, if so, whether that modifies the way we conceive today the natural history of PD. Finally, we reviewed the pharmacological and non-pharmacological interventions available to treat the non-motor symptoms of LS-PD, using a systematic approach. Participants were LS-PD (stage 4 or 5 of Hoehn & Yahr scale in on state) and advanced stage PD patients (patients with disabling levodopa-induced motor complications selected to deep brain stimulation), and their informal caregivers. Cross-sectional data were obtained using comprehensive clinical assessment. Handicap was assessed using the London Handicap Scale (LHS). Descriptive and regression analysis was performed. To review the treatment available for non-motor symptoms in LS-PD, we extracted the controlled clinical trials for PD dementia, psychosis, falls, bone fractures, joint and skeletal deformities, pain, orthostatic hypotension, gastrointestinal abnormalities and urological dysfunction; we chose these symptoms because they were considered as the most disabling for LS-PD patients, based on our results and published data. 50 LS-PD patients (mean age 74.1 years and mean disease duration 17.9 years) were studied. Severe akinetic symmetric parkinsonism was present in most, with negligible rigidity and tremor, and most patients were wheelchair-bound. Postural instability and freezing of gait, causing frequent falls and fractures, and prominent dysarthria and dysphagia dominated the motor syndrome. Levodopa, used as monotherapy in one-third of the cases, remained partially effective in most patients but with limited clinical relevance. Dosage of antiparkinsonian drugs was probably influenced by the frequent occurrence of neuropsychiatric symptoms. Motor fluctuations and dyskinesias were frequent but not disabling. All had neuropsychiatric and dysautonomic symptoms, namely dementia and visual hallucinations in half and depression in two-thirds of the patients. Lack of tremor and absence of depression were independently associated with dementia. Greatest impact on perceived health status was due to motor and non-motor levodopa-resistant symptoms. The LHS was easy to use in these patients and their caregivers. Handicap was severe and determined by dementia, behavioural complaints and the severity of non-dopaminergic motor features. Most affected domain of handicap was Orientation. Co-morbidities and past medical conditions were frequent. Patients visited doctors infrequently and made low use of health resources, while unpaid caregivers reported a high burden which correlated with patients’ handicap. The LHS was also easily completed by 100 advanced stage PD patients (mean age 61 years and mean disease duration 12.2 years) and their carers. Handicap was moderate-to-severe, although less than that of LS-PD patients. In contrast to the latter, Physical Independence and Social Integration were the most affected domains, and the determinants of handicap were disability in ADL and dyskinesias. The clinical features, severity and determinants of handicap of PD patients in late-stage differ from those in advanced stage, although they are nowadays classified under the generic category of advanced stage patients. LS-PD patients are severely handicapped from axial motor and non-motor symptoms unresponsive to levodopa, and they are very dependent on caregivers. Data suggest that LS-PD is a very distinct sub-group of advanced stage PD, and we propose an operational definition for LS-PD that anchors on (lack) of functionality regardless the cause is motor or non-motor symptomatology, using the Schwab and England scale in on. Unfortunately, few controlled clinical trials are available to treat most non-motor symptoms that disable LS-PD patients. Best evidence exists for the treatment of dementia, psychosis, osteoporosis and prevention of fractures, and sialorrhea. The present study provides cross-sectional evidence that LS-PD is a distinct sub-group of advanced stage PD, and that LS-PD patients manifest a clinical picture dominated by a severe akinetic symmetric non-dopaminergic motor phenotype and by severe non-motor features, which are overall poorly responsive to levodopa. LHS is easily completed by PD patients and handicap can be further explored as a patient-centred outcome in PD. Caregivers have a high burden that is correlated with patients’ handicap. In face of an expected increase in the prevalence of LS-PD and lack of efficacious therapies for most disabling symptoms, future research and allocation of funds should focus on non-levodopa responsive aspects of the disease and the needs of caregivers.

Introduction: Guillain-Barré syndrome (GBS) is a neurological disease caused by an autoimmune attack on the peripheral nerves. The main symptoms are loss of motor and sensory skills in the upper and lower extremities. Autonomic dysfunction also occurs.Aim: To identify which parameters in neurography examination that are showing pathology at three different stages from the onset of symptoms. To practically perform and evaluate different electrode placements at RR-intervals.Materials and methods: The first part of this study was a retrospective study with results from 58 patients which were diagnosed with GBS in 2010-2020 at the University Hospital in Uppsala. The second part of this study included measurement of the heart rate variation with RR-intervals at different electrode placement in ten healthy volunteers. Results: In part 1 of the project, there were no significant differences between the groups at distal latency in the ulnar nerve, F-latency in the tibial nerve and in the conduction velocity in the sural nerve. However, there were significant differences in the amplitude of the radial nerve. In part 2 of the project, there were significant differences between the electrode placements, and most artifacts were found with electrodes placed on the shoulders.Conclusion: Examination with neurography and RR-intervals plays an important role in the diagnosis of GBS. As the amplitude in the radial nerve was the only one that showed significant differences between the groups, the nerve is recommended to be examined bilaterally. With a high presence of artifacts in RR-intervals with electrodes placed on the shoulders and wrists, placement on the chest is to be recommended.

Theory of mind is the ability to have mental states about mental states. Among theories concerning the structure and role of theory of mind is the view that theory of mind is the cognitive component of empathy. It is proposed that there is partial dissociation within theory of mind between emotional state representation and non-emotional state representation. In trying to test this hypothesis, an instrument was developed and implemented in a pilot study. Current theory of mind tests are reviewed and design features discussed in relation to the new hypothesis. The instrument aims to measure emotional and non-emotional state representation on separate subscales, as well as coding representations from emotional stories and non-emotional stories separately. The instrument was administered to 33 third level or higher students from the University of KwaZulu-Natal. Groups were chosen from science major (n = 9) and humanities major (n = 24) students. The findings fail to show the group performance patterns reported in literature, for example that humanities students tend to score higher in ToM tests than science students. A number of factors might contribute to the finding, but principally, low sample size and unequal general cognitive ability between groups are proposed as vital. Problems with the pilot study are identified and improvements suggested for subsequent testing.
Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2010.

The video in this chapter discusses neurologic emergencies, including the symptoms of increased intracranial pressure leading to herniation, subarachnoid haemorrhage (can be due to aneurysm, vascular malformation, or reversible cerebral vasoconstriction syndrome, and definition and management of status epilepticus.

This chapter on “Asymmetry” examines the topic of normal neurological asymmetries and their implications for disease states. Neurologists encounter asymmetry daily. They regularly see asymmetry of pupil diameter, and alpha rhythm amplitude differences are frequently found between the right and left sides on a scalp recording. Not all of the asymmetries are important. However, neurologists must be aware of the anatomic asymmetries that occur. Within limited ranges, these asymmetries are “physiologic.” Asymptomatic developmental asymmetries can become important when disease is superimposed on congenital vascular variants. This chapter comprises discussion of several topics about central nervous system asymmetries and their importance to the neurologist.

Over the past decade, there has been increasing interest in alternative methods of treatment for many diseases. Physicians have recognized the limitations in the conventional use of pharmaceuticals and surgical intervention. Integrative approaches to patient care combine evidence-based conventional care with the best of evidence-based alternative care. Neurologists, in particular, manage many patients who have difficult-to-treat symptoms and disorders and can greatly benefit from integrative medicine. Many neurologists in practice have been incorporating alternative means of treatment in conjunction with current standards of care and experiencing improved patient response and satisfaction. This text covers some of the more commonly seen disease states in neurology and discusses integrative approaches to treatment and management. It also addresses the importance of self-care for the neurologist as stress and burnout are problematic for neurologists, further impairing patient care and the critical patient–doctor relationship.

Over the past decade, there has been increasing interest in alternative methods of treatment for many diseases. Physicians have recognized the limitations in the conventional use of pharmaceuticals and surgical intervention. Integrative approaches to patient care combine evidence-based conventional care with the best of evidence-based alternative care. Neurologists, in specific, manage many difficult-to-treat symptoms and disorders and can greatly benefit from integrative medicine. Many neurologists in practice have been incorporating alternative means of treatment in conjunction with current standards of care and experiencing improved patient response and satisfaction. This text covers some of the more common disease states in neurology and discusses integrative approaches to treatment and management. It also addresses the importance of self-care for the neurologist as stress and burnout are problematic for neurologists, further impairing patient care and the critical patient–doctor relationship.

More than half a million babies are born prematurely in the United States, and the rate of preterm birth (PTB) is on the rise [1]. Infants born prematurely account for a high percentage of perinatal mortalities, and preterm infants that survive are at risk for long-term morbidities including neurologic, respiratory, cardiovascular and gastrointestinal complications [2]. Altered mechanical and biochemical properties of the uterine cervix are suspected to cause premature and spontaneous cervical dilation, which is associated with a leading cause of PTB known as cervical insufficiency (CI). The impact of this condition is unknown because diagnosing CI remains controversial. Multiple etiologies are believed to lead to an insufficient cervix, or a soft cervix. Yet, there is no standard method to quantify the mechanical strength of the cervix, limiting the ability to discern these etiologies, to stage the progression of labor, and to identify and manage high-risk CI patients.

Traumatic brain injury (TBI) is a leading cause of death and disability, affecting 1.7 million Americans annually, 50,000 of whom die [1]. Victims who survive the initial injury often suffer debilitating neurologic deficits. The total annual cost of TBI in the United States has been estimated at $60 billion [2]. While damage to brain tissue is of primary concern in TBI, nearly all head trauma includes some element of vascular injury or dysfunction [3], putting neural tissue uninjured in the primary event at subsequent risk. Contusion, which includes injury to both brain and vessel tissue in the cortex, is considered the hallmark of head injury, but little is known about the specific mechanisms of vascular injury in contusion. Previous efforts to elucidate mechanisms and thresholds for contusion, including inanimate gel, animal, and computational models [e.g. 4–7], have defined bulk tissue deformations that are associated with contusion, but the relationship to vascular injury is not clear. In order to address this question, our laboratory is studying acute disruption of the blood-brain barrier using a controlled cortical impact (CCI) mouse model. The objective of this study was to compare acute vascular injury in CCI with cortical mechanics predicted by a computational model of the experiment. This comparison is then discussed in the context of results from isolated vessels testing in our laboratory.