Parkinson's Disease: A Multisystem Disorder / 神经科学通报·英文版

The way sporadic Parkinson's disease (PD) is perceived has undergone drastic changes in recent decades. For a long time, PD was considered a brain disease characterized by motor disturbances; however, the identification of several risk factors and the hypothesis that PD has a gastrointestinal onset have shed additional light. Today, after recognition of prodromal non-motor symptoms and the pathological processes driving their evolution, there is a greater understanding of the involvement of other organ systems. For this reason, PD is increasingly seen as a multiorgan and multisystemic pathology that arises from the interaction of susceptible genetic factors with a challenging environment during aging-related decline.

Influence of migration on the thought process of individuals at ultra-high risk for psychosis

Objective: To assess the influence of migration on the psychopathological presentation of individuals at ultra-high risk for psychosis (UHR) in São Paulo, Brazil. Methods: This study is part of the Subclinical Symptoms and Prodromal Psychosis (SSAPP) project, a cohort study in São Paulo, Brazil, designed to follow individuals at UHR. After screening with the Prodromal Questionnaire (PQ) and a clinical interview, the Global Assessment of Functioning (GAF) was administered, a neuropsychological assessment was performed, sociodemographic and migration data were obtained. We then analyzed UHR individuals who had migration data to see if migration had any effect on their cognition and psychopathology. Chi-square tests were used for categorical variables, and Student's t test or analysis of variance (ANOVA) were used for nonparametric and parametric distributions, respectively. Results: The sample was composed of 42 at-risk subjects, of whom 5 had a migration history in the past two generations. Those with migration history showed significantly more formal thought disturbances (p = 0.012) and sleeping problems (p = 0.033) compared to those without. Conclusions: Our data reinforce migration as a risk factor for psychosis in developing countries as well, and highlights the importance of studying the specific effect of this factor in UHR psychopathology.

Signo del atolón o signo del halo invertido en covid-19: a propósito de un caso / Covid-19 Atoll sign or inverted halo sign: about a case

La Sociedad Fleishner define el signo del halo invertido o signo del atolón como un área focal redondeada con la densidad de un "vidrio esmerilado", rodeada por un anillo más o menos completo de consolidación. Este signo fue descrito inicialmente en pacientes con neumonía organizada criptogénica por Voloudaki y Kim. Ha sido descrito en: 1) enfermedades infecciosas (la paracoccidioidomicosis, la aspergilosis, la mucormicosis y virales), 2) síndromes linfoproliferativos (la granulomatosis linfomatoidea), y 3) enfermedades inflamatorias no infecciosas ni neoplásicas (el síndrome de Churg-Strauss, la neumonía intersticial no específica y la granulomatosis de Wegener).

The Fleishner Society defines the inverted halo sign or Atoll sign as a rounded focal area with a "ground glass" density, surrounded by a more or less complete ring of consolidation. This sign was initially described in patients with organizing cryptogenic pneumonia by Voloudaki and Kim. It has been described in: 1) infectious diseases (paracoccidioidomycosis, aspergillosis, mucormycosis, and virals), 2) lymphoproliferative diseases (lymphomatoid granulomatosis), and 3) non-infectious and neoplastic inflammatory diseases (Churg-Strauss syndrome, non-specific interstitial pneumonia, and Wegener's granulomatosis).

COVID -19: una nueva enfermedad respiratoria y una posible amenaza mundial / COVID-19: a new respiratory disease and a possible global threat

A fines de 2019, la Organización Mundial de la Salud (OMS) comunicó la aparición, en la ciudad de Wuhan, situada en la provincia china de Hubei, de varios casos de enfermedad respiratoria aguda con neumonía producidos por un virus distinto a los conocidos . El 7 de enero de 2020, las autoridades chinas confirmaron que habían identificado un nuevo coronavirus al que denominaron provisoriamente, 2019-nCoV (Novel Coronavirus 2019)

Biological and Clinical Markers in Panic Disorder

OBJECTIVE: Classifying mental disorders on the basis of objective makers might clarify their aetiology, help in making the diagnosis, identify “at risk” individuals, determine the severity of mental illness, and predict the course of the disorder. This study aims to review biological and clinical markers of panic disorder (PD). METHODS: A computerized search was carried out in PubMed and Science Direct using the key words: “marker/biomarker/clinical marker/neurobiology/staging” combined using Boolean AND operator with “panic.” In addition, the reference lists from existing reviews and from the articles retrieved were inspected. Only English language papers published in peer-reviewed journals were included. RESULTS: Structural changes in the amygdala, hippocampus, cerebral blood level in the left occipital cortex, serotonin 5-TH and noradrenergic systems activation, aberrant respiratory regulation, hearth rate variability, blood cells and peripheral blood stem cells, hypothalamic–pituitary–adrenal axis dysregulation were identified as potential candidate biomarkers of PD. Staging was identified as clinical marker of PD. According to the staging model, PD is described as follows: prodromal phase (stage 1); acute phase (stage 2); panic attacks (stage 3); chronic phase (stage 4). CONCLUSION: The clinical utility, sensitivity, specificity, and the predictive value of biomarkers for PD is still questionable. The staging model of PD might be a valid susceptibility, diagnostic, prognostic, and predictive marker of PD. A possible longitudinal model of biological and clinical markers of PD is proposed.

The Effect of Clinical Characteristics and Subtypes on Amyloid Positivity in Patients with Amnestic Mild Cognitive Impairment

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Amyloid deposits in positron-emission tomography (PET) imaging of MCI patients imply a higher risk for advancing to dementia, with rates of 10%–15% yearly. The purpose of this study was to investigate the clinical characteristics of subgroups of amnestic MCI (aMCI) that may have a higher impact on amyloid positivity.METHODS: We recruited 136 aMCI patients. All patients underwent a 20-minute F-18 florbetaben or flutemetamol PET scan. We classified amyloid PET images as positive or negative according to a semi-quantitative method. We evaluated the amyloid positivity of subgroups of aMCI (early vs. late type, single vs. multiple amnestic type, verbal vs. verbal, and visual amnestic type), and compared baseline clinical characteristics including key risk factors, apolipoprotein E4 (apoE4) genotype, and neuropsychological assessments with amyloid positivity in aMCI.RESULTS: The amyloid positivity in total aMCI was 41%. The positivity rate according to subgroup of aMCI were as follow: Late aMCI (49%) vs. early aMCI (33%) (p=0.13), multiple aMCI (40%) vs. single aMCI (38%) (p=0.51), and verbal and visual aMCI (59%) vs. verbal aMCI (35%) (p=0.01), respectively. The mean age and the frequency of apoE4 allele of the amyloid-positive group was higher than that of the amyloid-negative group in aMCI (p< 0.01).CONCLUSIONS: We found that the amyloid positivity was related to patterns of clinical subtypes, characteristics, and risk factors in patients with aMCI.

Rapid Eye Movement Sleep Behavior Disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by sleep interruption or trauma due to abnormal behaviors that occur during REM sleep. The pathophysiology of RBD is known to be a dysfunction of brainstem circuit that causes the loss of skeletal muscle atonia during REM sleep. The diagnosis of RBD is needed to confirm REM sleep without atonia in the polysomnography. The management of RBD includes not only drug treatment, but also to prevent injury from RBD and to follow-up on neurodegenerative diseases that may occur later. RBD is thought to be a prodromal stage of neurodegenerative disease associated with α-synucleoinopathy, such as Parkinson's Disease or multiple system atrophy. This article reviews the symptoms, epidemiology, diagnosis and treatment of RBD, the relevance of neurodegenerative diseases, and recent research trends.

Prevalence of Operation Room-Related Syncope and Presyncope among Medical Students / 의학교육논단

Attending the operation room is an essential part of surgical clerkships. Syncope or presyncopal attacks in the operation room may negatively affect students' learning and career development. This study set out to identify the prevalence of syncope and presyncopal attacks in the operation room during medical students' surgical clerkships. Data from 420 medical students (303 men and 117 women) in their 3rd year of clerkship were collected between 2014 and 2017. An anonymous questionnaire was distributed to assess the prevalence and degree of syncope and presyncopal symptoms. A total of 27% of the respondents had experienced syncope or presyncopal symptoms, 49.6% of the female students and 18.8% of the male students (p < 0.001). Fifty students (43.5%) had been attending as observers at the time of the syncopal attack, while 65 students (56.5%) had been participating as assistants. Thirty-four students (29.6%) had recently eaten at the time of the syncopal attack, while 81 students (70.4%) had not recently eaten. Prodromal symptoms included the urge to sit down (21.2%), sweating (19.3%), nausea (16.9%), a feeling of warmth (13.3%), darkened vision (12.6%), yawning (11.7%), palpitation (11.0%), ear fullness (10.2%), black spots in one's vision (7.6%), and hyperventilation (7.1%). This study showed the prevalence of syncope and presyncopal symptoms in the operation room during surgical clerkships. For students' safety and effective clerkship learning, thorough proactive education on syncopal attacks is required.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Orientación de Enfermería para detectar síntomas prodrómicos y evitar reingreso psiquiátrico temprano / Nursing guidance to detect prodromal symptoms and avoid early psychiatric readmission

A partir de una reflexión sobre los espacios académicos que tiene actualmente el problema de la puerta giratoria y el abordaje de la persona con trastorno mental desde la Enfermería, se logra desarrollar en el presente documento, un lineamiento teórico, histórico y práctico, en forma de orientación, dirigido al profesional de enfermería en salud mental, facilitando la detección temprana de síntomas prodrómicos psiquiátricos, teniendo en cuenta, los diferentes momentos en que se pueda exacerbar dicha sintomatología (prehospitalización, hospitalización y egreso) así como, sugerir un adecuado abordaje a cada uno de los actores participes en el tratamiento ( Familia, Sociedad, Instituciones, Profesionales) previniendo el reingreso psiquiátrico institucional de la persona con trastorno mental.

Having in count the reflection about the different academic meetings that has the early revolving door problem and the psychiatric nursing approach, it is possible to develop this paper, a theorical, historical and practical lineament, in orientation form, addressed to mental health nursing professionals, facilitating the psychiatric prodromal symptom's early detection, having in count, the different moments when it could exacerbate this symptomatology (pre-hospitalization, hospitalization and discharge) ) preventing patient's psychiatric reentry.

Increased Levels of C1q in the Prefrontal Cortex of Adult Offspring after Maternal Immune Activation: Prevention by 7,8-Dihydroxyflavone

OBJECTIVE: Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: a tropomyosin receptor kinase B [TrkB] agonist) was also examined. METHODS: Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed. 7,8-DHF or vehicle was given from 4 to 8-weeks old. RESULTS: Expression of C1q in the prefrontal cortex (PFC) of adult offspring from poly(I:C)-treated pregnant mice was significantly higher than that of control group. Early treatment with 7,8-DHF during juvenile and adolescent stages could prevent an increase of C1q in the PFC of adult offspring after MIA. CONCLUSION: Therefore, it is likely that increased C1q expression in the frontal cortex may play a role in the behavioral abnormalities of adult offspring after MIA. Furthermore, supplementation with a TrkB agonist such as 7,8-DHF during the prodromal stage may have prophylactic effects on the behavioral abnormalities after MIA.

Manifestaciones psiquiátricas por priones. Una revisión narrativa / Psychiatric manifestations by prions. A narrative review

Las enfermedades priónicas son un grupo de enfermedades neurodegenerativas raras y rápidamente progresivas que causan síntomas neuropsiquiátricos diversos. Estas enfermedades se describieron hace más de 200 arios, y con el tiempo se reconoció que los animales eran portadores de esta alteración; sin embargo, hasta finales de los noventa este problema conmocionó Europa, ya que para entonces la enfermedad había cruzado la barrera de especie y podía afectar al hombre. La polémica fue mayor al atribuirse la alteración a una proteína con capacidad infecciosa. El proceso patológico común se caracteriza por la conversión de la proteína priónica celular normal (PsPc) a una forma anómala y patológica (PrPSc). En el ser humano se han clasificado como padecimientos idiopáticos, hereditarios o adquiridos por la exposición a material exógeno con contenido priónico. La manifestación neurológica más sobresaliente de las prionopatías consiste en la aparición de una demencia rápidamente progresiva asociada a mioclonías y ataxia cerebelosa, además de síntomas extrapiramidales. Los síntomas psiquiátricos ocurren en etapas tempranas de la enfermedad y su presencia, además de la valoración de factores de riesgo, puede contribuir al diagnóstico oportuno de este síndrome. Clásicamente los síntomas psiquiátricos se han agrupado en tres categorías: síntomas afectivos, alteraciones de la motricidad y síntomas psicóticos. Este tipo de manifestaciones suele aparecer durante un periodo prodrómico previo a los signos neurológicos y consiste en la aparición de aislamiento social, ideas delirantes, irritabilidad/agresión, alucinaciones predominantemente visuales, ansiedad y depresión, así como otros menos frecuentes. El diagnóstico definitivo requiere de un estudio post mortem. La posibilidad de que un número mayor de casos pueda ocurrir en los próximos años o que en muchos pacientes no se haya considerado el diagnóstico es una realidad. En opinión de los autores de este trabajo, los psiquiatras debemos tener conocimiento de los síntomas de esta enfermedad. El objetivo de esta investigación es evaluar las alteraciones neuropsiquiátricas presentes en las prionopatías y, en particular, determinar si las manifestaciones psiquiátricas en conjunto integran un cuadro clínico que apunte al diagnóstico de estas enfermedades, aunque en primer término se revisan aspectos taxonómicos, patogénicos y patológicos. Como elemento agregado en este trabajo, los autores hacen algunas consideraciones diagnósticas basadas en la evidencia científica disponible hasta el momento. Los descriptores controlados aplicados a la búsqueda bibliográfica son los utilizados para indexación de artículos científicos en las bases de datos. Las bases de datos y EMBASE, aunque también se empleó PsycInfo. Los descriptores empleados son: enfermedades priónicas, trastornos psicóticos, depresión, trastornos afectivos, patología, clasificación, proteína priónica, historia, manifestaciones neurológicas y manifestaciones psiquiátricas. Los criterios de selección de material fueron cualitativos. Como conclusión y con base en la extensa bibliografía revisada, los autores plantean que el periodo en que hay más evidencia de alteraciones en la esfera mental se denomine «fase de síntomas psiquiátricos¼, la cual puede extenderse por algunos meses (hasta 4). Los síntomas afectivos son los más característicos de dicha fase. Como conclusiones, se considera que la identificación de estos síntomas en un paciente con factores de riesgo de sufrir esta enfermedad contribuiría a la identificación temprana del padecimiento y normaría qué pautas seguir ante la sospecha del diagnóstico de este grupo de trastornos, sobre todo con la idea de mejorar la calidad de vida de estos pacientes.

Prion diseases are a group of rare and rapidly progressive neurodegenerative conditions that may cause neuropsychiatric symptoms. This group of diseases has been described since the 18th century, but they were recognized decades later, when it became clear that the humans were affected by infected animals. There was controversy when the problem was attributed to a single protein with infective capacity. The common pathological process is characterized by the conversion of the normal cellular prion protein into an abnormal form. In humans, the illness has been classified as idiopathic, inherited and acquired through exposure to exogenous material containing abnormal prions. The most prominent neurological manifestation of prion diseases is the emergence of a rapidly progressive dementia, mioclonus associated with cerebellar ataxia and also extra pyramidal symptoms. Psychiatric symptoms occur in early stages of the illness and can contribute to timely diagnosis of this syndrome. Psychiatric symptoms have traditionally been grouped in three categories: affective symptoms, impaired motor function and psychotic symptoms. Such events usually occur during the prodromal period prior to the neurological manifestations and consists in the presence of social isolation, onset of delusions, irritability/aggression, visual hallucinations, anxiety and depression, and less frequent first-rank symptoms among others. Definite diagnosis requires post mortem examination. The possibility that a large number of cases may occur in the next years or that many cases have not been considered with this diagnosis is a fact. In our opinion, psychiatrists should be aware of symptoms of this disease. The main objective of this research consisted of assessing the correlation between this disturbance and neuro-psychiatric symptoms and particularly if this psychiatric manifestations integrate a clinical picture suggestive for the diagnosis of these diseases, but firstly reviewed taxonomic, pathogenic and pathological aspects. The authors of this project also added an element in relation to some diagnostic considerations based on scientific evidence. For the search controlled descriptors applied to the research for indexing scientific articles in databases were used. The electronic data bases used were PubMed, EMBASE and also PsycInfo. The descriptors were prion diseases, psychotic disorders, depression, mood disorders, pathology, classification, prion protein, history, neurological manifestations, and psychiatric manifestations. The selection criteria for the material were qualitative. To conclude, and based on the extensive literature review, the authors propose that the period where the evidence is more robust for mental impaired is named "psychiatric symptoms phase, which can be extended for a few months, being the psychiatric affective symptoms the most characteristic of this phase. In conclusion, we considered that the identification of these symptoms in a patient with risk factors for developing the disease will contribute to the early identification, and would regulate the guidelines in suspected diagnosis of this group of disorders. The intention is provide a better quality of life to the sick people.

Craniofacial pain can be the sole prodromal symptom of an acute myocardial infarction: an interdisciplinary study / El dolor cráneo-facial puede ser el único síntoma prodrómico de un infarto agudo de miocárdio: estudio interdisciplinario

We recently found craniofacial pain to be the sole symptom of anacute myocardial infarction (AMI) in 4% of patients. Wehypothesized that this scenario is also true for symptoms ofprodromal (pre-infarction) angina. We studied 326 consecutivepatients who experienced myocardial ischemia. Intra-individualvariability analyses with respect to ECG findings and paincharacteristics were performed for those 150 patients whoexperienced at least one recurrent ischemic episode. AMI patients(n=113) were categorized into two subgroups: “abrupt onset”(n=81) and “prodromal angina” (n=32). Age, gender and riskfactor comparisons were performed between groups. Craniofacialpain constituted the sole prodromal symptom of an AMI in 5% ofpatients. In those who experienced two ischemic episodes, womenwere more likely than men to experience craniofacial pain in bothepisodes (p<0.01). There was no statistically significant differencebetween episodes regarding either ECG findings or the use of thetwo typical pain quality descriptors “pressure” and “burning”. This study is to our knowledge the first to report that craniofacialpain can be the only symptom of a pre-infarction angina.Craniofacial pain constitutes the sole prodromal AMI symptomin one out of 20 AMI patients. Recognition of this atypicalsymptom presentation is low because research on prodromalAMI symptoms has to date studied only patients with chest pain.To avoid a potentially fatal misdiagnosis, awareness of thisclinical presentation needs to be brought to the attention ofclinicians, researchers and the general public.

En un estudio previo encontramos que un dolor en la región cráneo-facial puede ser el único síntoma de un infarto agudo de miocardio (IAM) en el 4 por ciento de los casos. En el presentetrabajo la hipótesis fue que este escenario es cierto también para la angina pre-infarto o angina prodrómica.En el estudio se incluyeron 326 pacientes consecutivos con isquemia cardiaca sintomática. Se realizó un análisis intraindividual con respecto a características del dolor y hallazgoselectrocardiográficos en los 150 pacientes que presentaron episodios recurrentes de isquemia cardiaca. Los pacientes con infarto agudo se categorizaron en dos grupos: “comienzoabrupto” (n=81) y “angina prodrómica” (n=32). Se realizaron comparaciones entre grupos con respecto a edad, género y factores de riesgo cardiovasculares. El dolor en la región cráneofacial constituyó el único síntoma prodrómico (pre-infarto) de un IAM en el 5 por ciento de los casos. En aquellos pacientes que experimentaron dos episodios isquémicos, las mujeres tuvieron una mayor prevalencia de dolor cráneo-facial en los dos episodios (p<0.01). No se detectaron diferencias estadísticas entre episodios con respecto a hallazgos electrocardiográ ficos o al empleo de los descriptores verbales del dolor de origen cardíaco “opresivo” y “quemante”.Este es el primer estudio de investigación en documentar queel dolor en la región cráneo-facial puede ser el único síntoma de una angina pre-infarto. En efecto, esto ocurre en uno decada 20 casos de IAM. El reconocimiento de esta presentación clínica es baja debido a que históricamente los criterios de inclusión de los estudios de angina pre-infarto incluyeron únicamente pacientes con dolor de pecho. Para evitar el error diagnóstico con consecuencias fatales para el paciente, es importante que esta información llegue tanto a los clínicos como al público en general.

Early Detection and Intervention of Autism Spectrum Disorder / 한양의대학술지

Autism spectrum disorder (ASD) is a neurodevelopmental disorder typically identified in early toddlerhood. Both retrospective and prospective follow up studies of high risk infants reveal early risk signs of ASD at 12-24 months of age. The most frequently replicated early signs of ASD are atypical visual tracking and coordination, lack of social reciprocity, abnormal social communication and unusual patterns of manipulating objects, atypical sensory exploration, expressed as uncoordinated eye contact, unresponsiveness to naming, lack of social smile, delayed development of nonverbal communication and joint attention, less sharing interest, and unusually repetitive use of objects. Early intervention, before 2 years of age, appears to change the underlying developmental trajectories of the brain in individuals with ASD. In this review, the early risk signs of ASD in infancy and toddlerhood, along with early intervention and their implications, are discussed.

Clinical characteristics and influence of childhood trauma on the prodrome of bipolar disorder

Objectives: To describe the onset pattern, frequency, and severity of the signs and symptoms of the prodrome of the first hypomanic/manic episode and first depressive episode of bipolar disorder (BD) and to investigate the influence of a history of childhood maltreatment on the expression of prodromal symptoms. Methods: Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), information regarding prodromal symptoms was assessed from patients with a DSM-IV diagnosis of BD. History of childhood maltreatment was evaluated using the Childhood Trauma Questionnaire (CTQ). Results: Forty-three individuals with stable BD were included. On average, the prodrome of mania lasted 35.8±68.7 months and was predominantly subacute or insidious, with rare acute presentations. The prodrome of depression lasted 16.6±23.3 months and was also predominantly subacute or insidious, with few acute presentations. The prodromal symptoms most frequently reported prior to the first hypomanic or manic episode were mood lability, depressive mood, and impatience. A history of childhood abuse and neglect was reported by 81.4% of participants. Presence of childhood maltreatment was positively associated with prodromal symptoms, including social withdrawal, decreased functioning, and anhedonia. Conclusions: This study provides evidence of a long-lasting, symptomatic prodrome prior to first hypomanic/manic and depressive episode in BD and suggests that a history of childhood maltreatment influences the manifestations of this prodrome.

Clinical Biomarkers of Neurodegeneration in REM Sleep Behavior Disorder

Rapid eye movement sleep behavior disorder (RBD) is currently considered as a prodromal stage of alphasynucleinopathies neurodegeneration. The update data suggested that over 80% patients with idiopathic RBD eventually developed neurodegenerative disease after a mean of 14 years interval from the onset of RBD. A series of potential biomarkers have been identified to predict the development of neurodegeneration in idiopathic RBD, including olfactory loss, color vision deficit, depression, mild cognitive impairment, excessive daytime sleepiness, dopamine dysfunction, and tonic electromyographic activity. Early recognition of the predictive markers of neurodegeneration in idiopathic RBD is essential for development of intervention or prevention strategies at the presymptomatic stage. Nonetheless, the current literature is lacking biomarkers that might reflect the alpha-synuclein neuropathology at the earliest stages. Future studies with large samples and systematic follow-up are needed to confirm more potential markers of neurodegeneration at its early stages.

Atypical Femoral Fracture: 2015 Position Statement of the Korean Society for Bone and Mineral Research

Bisphosphonate (BP) is a useful anti-resorptive agent which decreases the risk of osteoporotic fracture by about 50%. However, recent evidences have shown its strong correlation with the occurrence of atypical femoral fracture (AFF). The longer the patient takes BP, the higher the risk of AFF. Also, the higher the drug adherence, the higher the risk of AFF. It is necessary to ask the patients who are taking BP for more than 3 years about the prodromal symptoms such as dull thigh pain. Simple radiography, bone scan, and magnetic resonance imaging (MRI) are good tools for the diagnosis of AFF. The pre-fracture lesion depicted on the hip dual energy X-ray absorptiometry (DXA) images should not be missed. BP should be stopped immediately after AFF is diagnosed and calcium and vitamin D (1,000 to 2,000 IU) should be administered. The patient should be advised not to put full weight on the injured limb. Daily subcutaneous injection of recombinant human parathyroid hormone (PTH; 1-34) is recommended if the patient can afford it. Prophylactic femoral nailing is indicated when the dreaded black line is visible in the lateral femoral cortex, especially in the subtrochanteric area.

Fever of Unknown Origin: An Unusual Presentation of Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Encephalitis associated with antibodies to the N-methyl-D-aspartate receptor (NMDAR) has variable clinical manifestations. Patients are often diagnosed with infectious processes because of prodromal symptoms and autonomic manifestations. Approximately 70% of patients have prodromal symptoms consisting of headache, fever, nausea, vomiting, and diarrhea, along with frequent autonomic manifestations, including tachycardia, and fluctuating blood pressure. A 36-year-old woman presented with uncontrolled fever and skin and soft tissue infections. She had shown psychiatric symptoms and abnormal behavior, and had been diagnosed with bipolar disorder. Antibodies to NMDAR were positive in cerebrospinal fluid (CSF) and serum samples, and pelvic computed tomography detected a large ovarian teratoma. The patient improved dramatically after removal of the teratoma and administration of corticosteroid therapy. When confronted with a young woman with uncontrolled fever and acute psychiatric symptoms, physicians should suspect anti-NMDAR encephalitis.

Depresión en la tercera edad como factor de riesgo y su posible rol como pródromo de demencia / Depression and dementia in the mental health of old age

Depresión y demencia, sobre todo enfermedad de Alzheimer (EA) son entidades críticas en la salud mental de la tercera edad. Ambas condiciones disminuyen la calidad de vida e incrementan el deterioro de actividades de vida diaria de individuos de la tercera edad. EA tiene pobre pronóstico al ser una enfermedad neurodegenerativa; mientras que la depresión es básicamente reversible. Los estudios de seguimiento longitudinal y de caso-control reportan una estrecha asociación entre depresión de inicio tardío y deterioro cognitivo progresivo, pues se ha demostrado riesgo de incremento en 2 a 5 veces para desarrollar demencia en pacientes con depresión de inicio tardío. Por otro lado, la depresión de inicio precoz ha demostrado en forma consistente ser también un factor de riesgo para demencia, y escasas probabilidades de ser pródromo de demencia.La naturaleza de la asociación (si depresión es un pródromo o consecuencia de demencia, o un factor de riesgo para desarrollar demencia) permanece aún sin ser esclarecida. Independiente de ello, las estrategias para tratar depresión podrían alterar el riesgo de desarrollar demencia.

Depression and dementia, in particular Alzheimer´s disease (AD) are critically important issues in the mental health of old age. Both conditions apparently reduce quality of life and increase the impairment of activities of daily living for elderly persons. AD usually shows poor prognosis owing to progressive neuronal degeneration, while depression is basically reversible. Longitudinal follow-up and case-control studies reported a strong association between late-onset depression and dementia, and therefore increased risk was observed in 2-5 times to develop dementia in patients with late-onset depression. Furthermore, early-onset depression have also consistenly demonstrated to be a risk factor for dementia and unlikely to be prodromal to dementia. The nature of this association (if depression is a prodrome or consequence of, or risk factor for dementia) remains unclear. Regardless of this, treatment strategies for depression could alter the risk of dementia.