The Efficacy of Cervical Pedicle Screw Is Enhanced When Used With 5.5-mm Rods for Metastatic Cervical Spinal Tumor Surgery.

OBJECTIVE: The cervical spine presents challenges in treating metastatic cervical spinal tumors (MCSTs). Although the efficacy of cervical pedicle screw placement (CPS) has been well established, its use in combination with 5.5-mm rods for MCST has not been reported. This study aimed to evaluate the efficacy of CPS combined with 5.5-mm rods in treating MCST and compare it with that of CPS combined with traditional 3.5-mm rods. METHODS: This retrospective study analyzed 58 patients with MCST who underwent posterior cervical spinal fusion surgery by a single surgeon between March 2012 and December 2022. Data included demographics, surgical details, imaging results, numerical rating scale score for neck pain, Eastern Cooperative Oncology Group performance status, and Spine Oncology Study Group Outcomes Questionnaire responses. RESULTS: Preoperative Spinal Instability Neoplastic Scores were significantly higher in the 5.5-mm rod group. Greater kyphotic changes in the index vertebra were observed in the 3.5-mm rod group. Neck pain reduction was significantly better in the 5.5-mm rod group. CONCLUSION: CPS with 5.5-mm rods provides superior biomechanical stability and effectively resists forward bending momentum in posterior MCST fusion surgery. These findings support the use of 5.5-mm rods to enhance surgical outcomes.

A Validation Study of Mental Health Monitoring Through a Mobile Application.

OBJECTIVE: Face-to-face evaluation is the most important in psychiatric evaluation, but smart healthcare, including non-face-to-face evaluation, can be beneficial considering the situation in which face-to-face evaluation is limited or the preventive aspect of mental illness. In this paper, we aimed to check whether mental health screening tests have the same significance as paper-based tests even when collected through mobile applications. METHODS: A smart mental healthcare screening test was conducted on the 1,327 community subjects. We measured two indicators of depression (Patient Health Questionnaire 9-item scale, PHQ-9) and anxiety (Generalized Anxiety Disorder 7-item scale, GAD-7) to check mental health conditions. RESULTS: The average Cronbach's alpha value of the PHQ-9 questionnaire was good at 0.870. As a result of PHQ-9's principal component analysis, one component with an eigenvalue of 1 or more was identified, which is suitable to be described as a single factor. The average Cronbach's alpha value of the GAD-7 was 0.919. The structural validity of the GAD-7 was confirmed through principal component analysis. CONCLUSION: Our results show that PHQ-9 and GAD-7 scales performed through mobile applications can have the same meaning as paper-based tests. Surveys using a tablet PC, or smartphone application can monitor residents' mental health and accumulate data. Based on these data, smart mental health management can check the mental health of residents and treat mental illness in connection with medical services.

Parastomal Hernia Rates and Exercise After Ostomy Surgery.

BACKGROUND: Parastomal hernias are common and negatively affect patient's lives. We hypothesized that physical activity (or lack thereof) might be associated with the presence of parastomal hernia. If so, this might be an actionable target for prevention. OBJECTIVE: The objective was to determine rates of and risk factors for parastomal hernias in patients with a permanent ostomy. DESIGN: This was a retrospective cohort and survey study. Postal survey included questions about parastomal hernia, symptoms, lifestyle, and validated instruments to measure stoma quality of life and physical activity. Medical record abstraction was conducted for clinical comorbidities. SETTINGS: This study was conducted in a single large academic medical center. PATIENTS: Patients who underwent operations that included a permanent urostomy, colostomy, and/or ileostomy between 2014 and 2018 were included. MAIN OUTCOME MEASURES: Parastomal hernia (self-reported) and physical activity, measured in total metabolic equivalent-minutes/week, were our main outcome measures. RESULTS: A total of 443 of 724 patients responded (response rate, 61.2%). Two hundred twelve patients (47.9%) had urostomies, 160 (36.1%) had colostomies, and 99 (22.3%) had ileostomies. One hundred twenty-eight patients (29.7%) had a parastomal hernia, with rates of 27.1% for urostomy, 40.0% for colostomy, and 23.7% for ileostomy. There was a statistically significant association between less exercise and higher incidence of parastomal hernia (median, 579 metabolic equivalent-minutes/week for those with parastomal hernias vs 1689 metabolic equivalent-minutes/week for those without; p = 0.001). LIMITATIONS: The association between physical activity and parastomal hernia may be confounded by obesity or the possibility that patients with parastomal hernia may be limited physically by their hernia. CONCLUSIONS: Parastomal hernia rates remain high in modern surgical practice. This study shows an association between patients' physical activity and the presence of a parastomal hernia, with a higher rate among patients who exercise less. See Video Abstract at http://links.lww.com/DCR/B910 . TASAS DE HERNIA PARAESTOMAL Y EJERCICIO DESPUS DE LA CIRUGA DE OSTOMA: ANTECEDENTES:Las hernias paraostomales son complicaciones comunes después de la cirugía de ostomía y afectan la calidad de vida de los pacientes. Nuestra hipótesis es que la actividad física de los pacientes (o la falta de ella) podría estar asociada con la presencia de hernia paraostomal. Si es así, este podría ser un objetivo utilizable para la prevención.OBJETIVO:Determinar las tasas y los factores de riesgo de las hernias paraostomales en pacientes que se sometieron a una cirugía que resultó en una ostomía permanente.DISEÑO:Estudio retrospectivo de cohorte y encuesta. La encuesta postal incluyó preguntas sobre hernia paraostomal, síntomas, estilo de vida e instrumentos validados para medir la calidad de vida del paciente ostomizado y la actividad física. Se realizó la confección de gráficos para las comorbilidades clínicas.ESCENARIO:Centro médico académico de gran tamañoPACIENTES:Pacientes que se sometieron a operaciones que incluyeron una urostomía permanente, colostomía y/o ileostomía entre 2014 y 2018.PRINCIPALES MEDIDAS DE RESULTADO:La hernia paraostomal (autoinformada) y la actividad física, medidas en equivalente metabólico de actividad total-minutos/semana, fueron nuestras principales medidas de resultado. También se evaluó la calidad de vida.RESULTADOS:Un total de 443 de 724 pacientes respondieron a la encuesta (tasa de respuesta 61,2%). 212 pacientes (47,9%) tenían urostomías, 160 (36,1%) colostomías y 99 (22,3%) ileostomías. 128 pacientes (29,7%) tenían hernia paraostomal, con tasas de 27,1% para urostomía, 40,0% para colostomía y 23,7% para ileostomía. Hubo una asociación estadísticamente significativa entre menos ejercicio y una mayor incidencia de hernia paraostomal (mediana: 579 equivalentes metabólicos - minutos/semana para aquellos con hernias paraostomales versus 1689 para aquellos sin hernias; p = 0,001).LIMITACIONES:La asociación entre la actividad física y la hernia paraostomal puede confundirse con la obesidad o con el hecho de que los pacientes con hernia paraostomal pueden tener menos actividad física debido a su hernia.CONCLUSIONES:Las tasas de hernia paraostomal siguen siendo altas en la práctica quirúrgica moderna y las hernias se asocian con una peor calidad de vida. Este estudio muestra una asociación entre la actividad física de los pacientes y la presencia de una hernia paraostomal, con una tasa más alta entre los pacientes que hacen menos ejercicio. Consulte Video Resumen en http://links.lww.com/DCR/B910 . (Traducción-Dr. Felipe Bellolio ).

The Role of Decreased Cortical Thickness and Volume of Medial Temporal Lobe Structures in Predicting Incident Psychosis in Patients With Alzheimer's Disease: A Prospective Longitudinal MRI Study.

OBJECTIVE: To investigate the effect of decreased cortical thickness or volume of medial temporal lobe structures on the risk of incident psychosis in patients with AD. DESIGN, SETTING, AND PARTICIPANTS: This hospital-based prospective longitudinal study enrolled 109 patients with AD. All patients with AD were evaluated at 3-month intervals to investigate the effect of decreased cortical thickness or volume of medial temporal lobe structures on the risk of incident psychosis in patients with AD. OUTCOME MEASURE: The main outcome measure was time-to-progression from AD to incident psychosis. The thickness or volume of medial temporal lobe structures (i.e., the hippocampus, entorhinal cortex, and parahippocampus) were measured using magnetic resonance imaging and the Freesurfer automated segmentation pipeline at baseline. RESULTS: Multivariate Cox proportional hazards regression analysis revealed that a decreased cortical thickness or volume of medial temporal region was associated with a higher risk of incident psychosis in patients with AD. The hazard ratios for decreased cortical thickness of the left entorhinal cortex and decreased cortical volume of the right hippocampus were 4.291 (95% confidence interval [CI], 1.196-15.384) and 2.680 [(CI, 1.003-1.196]), respectively. CONCLUSION: Our study revealed that decreased cortical thickness or volume of medial temporal sub-regions is a risk factor for incident psychosis in patients with AD. A careful assessment of the thickness or volume of the medial temporal lobe structures in AD may improve early detection and intervention of psychosis in AD.

Interactive Training Program Improves Surgeon and Pathologist Comfort Level With Total Mesorectal Excision Grading for Rectal Cancer.

BACKGROUND: Total mesorectal excision for rectal cancer has been shown to decrease local recurrence and improve survival, and specimen grading is recommended as a best practice. However, specimen grading remains underutilized in the United States potentially because of the lack of surgeon and pathologist training in the technique. OBJECTIVE: This study aimed to determine whether an interactive webinar improves physician comfort with mesorectal grading. DESIGN: To test the effect of the program, participants completed a survey before and after participating. SETTINGS: Twelve Michigan Surgical Quality Collaborative hospitals volunteered to participate in a Total Mesorectal Excision Project. PARTICIPANTS: Total mesorectal excision grading training program participants were surgeons, surgery residents, pathologists, and pathology assistants from 12 hospitals. MAIN OUTCOME MEASURES: Comfort with grading total mesorectal excision specimens was our main outcome measure. Prewebinar surveys also measured familiarity, previous experience, and training in grade assignment, as well as interest in the training program. Postwebinar surveys measured webinar relevance and effectiveness as well as participant intention to use content in practice. RESULTS: A total of 34 participants completed the prewebinar survey and 28 participants completed the postwebinar survey. The postwebinar overall median comfort level with specimen grading of 3.64 was significantly higher than the prewebinar overall median comfort level of 2.94 (95% CI, 3.32-3.96 versus 95% CI 2.56-3.32; p = 0.007). When evaluated separately, both surgeons and pathologists reported significantly higher comfort levels with total mesorectal excision grading after the webinar. LIMITATIONS: Six participants did not complete the postwebinar survey. Surgery residents and pathology assistants were analyzed with practicing surgeons and pathologists. The pre- and postwebinar surveys were deidentified, so paired analysis was not possible. CONCLUSIONS: Our total mesorectal excision grading training program improved the comfort level of both surgeons and pathologists with specimen grading. Survey results also demonstrate that providers are interested in receiving training in rectal cancer specimen grading. See Video Abstract at http://links.lww.com/DCR/B766.PROGRAMA DE ENTRENAMIENTO INTERACTIVO MEJORA EL NIVEL DE COMODIDAD DEL CIRUJANO Y DEL PATÓLOGO CON LA CLASIFICACIÓN DE LA ESCISIÓN TOTAL DEL MESORRECTO PARA EL CÁNCER DE RECTO. ANTECEDENTES: Se ha demostrado que la escisión total del mesorrecto para el cáncer de recto disminuye la recurrencia local y mejora la supervivencia, y se recomienda la clasificación de la muestra como buena práctica de rutina. Sin embargo, sigue siendo poco utilizado en los Estados Unidos debido principalmente a la falta de formación en la técnica de cirujanos y patólogos. OBJETIVO: Determinar si un seminario interactivo en línea mejora la comodidad del médico con la clasificación mesorrectal. DISEO: Para probar el efecto del programa, los participantes completaron una encuesta antes y después de haber participado de la misma. MARCO: Doce hospitales en cooperación sobre la calidad quirúrgica de Michigan se ofrecieron como voluntarios para participar en el proyecto de Escisión Total de Mesorrecto. PARTICIPANTES: Los participantes del programa de entrenamiento en la clasificación de escisión total de mesorrecto fueron cirujanos, residentes de cirugía, patólogos y asistentes de patología de doce hospitales. PRINCIPALES RESULTADOS MEDIDOS: La comodidad con la clasificación de las muestras de escisión total de mesorrecto fue nuestro principal resultado de medición. Las encuestas previas al seminario en línea también midieron la familiaridad, la experiencia y entrenamiento previo en la clasificación, así como el interés en el programa de entrenamiento. Las encuestas posteriores midieron la relevancia y la eficacia del seminario web, así como la intención de los participantes de utilizar en la practica el contenido. RESULTADOS: Un total de 34 participantes completaron la encuesta previa, y 28 de ellos la completaron con posterioridad al seminario en línea.La mediana del nivel de comodidad general, posterior al seminario en línea, con respecto a la clasificación de la pieza de 3,64 fue significativamente mayor con respecto al valor de 2,94 previo al seminario (IC del 95%: 3,32 - 3,96 versus IC 2,56 - 3,32, respectivamente; valor de p = 0,007).Cuando fueron evaluados de manera separada, tanto los cirujanos como los patólogos reportaron niveles de comodidad significativamente más altos con la clasificación de escisión total de mesorrecto (TME) después del seminario en línea. LIMITACIONES: Seis participantes no completaron la encuesta posterior al seminario en línea. Los residentes de cirugía y los asistentes de patología fueron analizados conjuntamente con los cirujanos y patólogos en ejercicio, respectivamente. Las encuestas previas y posteriores al seminario en línea fueron anónimas, anulándose la identificación, por lo que no fue posible realizar un análisis por pares. CONCLUSIONES: Nuestro programa de entrenamiento en la clasificación de escisión total de mesorrecto mejoró el nivel de comodidad tanto de los cirujanos como de los patólogos con la clasificación de las muestras. Los resultados de la encuesta también demuestran que el personal involucrado está interesado en recibir capacitación en la clasificación de muestras de cáncer de recto. Consulte Video Resumen en http://links.lww.com/DCR/B766. (Traducción-Dr Osvaldo Gauto).

The Relationship of Plasma Transthyretin Level with Global or Regional Amyloid Beta Burden in Subjects with Amnestic Mild Cognitive Impairment: Cross-Sectional Amyloid PET Study.

Background: To investigate the relationships of plasma transthyretin levels with amyloid beta deposition and medial temporal atrophy in amnestic mild cognitive impairment. Methods: This is a cross-sectional study of association of subjects with amnestic mild cognitive impairment. Plasma transthyretin levels, brain magnetic resonance imaging, and 18F-florbetaben positron emission tomography were simultaneously measured in subjects with amnestic mild cognitive impairment. Results: Plasma transthyretin levels were positively associated with amyloid beta deposition in global (r = 0.394, P = .009), frontal cortex (r = 0.316, P = .039), parietal cortex (r = 0.346, P = .023), temporal cortex (r = 0.372, P = .014), occipital cortex (r = 0.310, P = .043), right posterior cingulate (r = 0.350, P = .021), left precuneus (r = 0.314, P = .040), and right precuneus (r = 0.398, P = .008). No association between plasma transthyretin level and medial temporal sub-regional atrophies was found. Conclusions: Our findings of positive association of plasma transthyretin levels with global and regional amyloid beta burden suggest upregulation of transthyretin level as a reactive response to amyloid beta deposition during the early stages of the Alzheimer's disease process.

Reduced Thickness of the Anterior Cingulate Cortex as a Predictor of Amnestic-Mild Cognitive Impairment Conversion to Alzheimer's Disease with Psychosis.

BACKGROUND: A long-term follow-up study in patients with amnestic mild cognitive impairment (aMCI) is needed to elucidate the association between regional brain volume and psychopathological mechanisms of Alzheimer's disease with psychosis (AD + P). OBJECTIVE: The purpose of this study was to investigate the effect of the thickness of the angular cingulate cortex (ACC) on the risk of AD + P conversion in patients with aMCI. METHODS: This was a hospital-based prospective longitudinal study including 174 patients with aMCI. The main outcome measure was time-to-progression from aMCI to AD + P. Subregions of the ACC (rostral ACC, rACC; caudal ACC, cACC) and hippocampus (HC) were measured as regions of interest with magnetic resonance imaging and the Freesurfer analysis at baseline. Survival analysis with time to incident AD + P as an event variable was calculated with Cox proportional hazards models using the subregions of the ACC and HC as a continuous variable. RESULTS: Cox proportional hazard analyses showed that the risk of AD + P was associated with sub-regional ACC thickness but not HC volume: reduced cortical thickness of the left cACC (HR [95%CI], 0.224 [0.087-0.575], p = 0.002), right cACC (HR [95%CI], 0.318 [0.132-0.768], p = 0.011). This association of the cACC with the risk of AD also remained significant when adjusted for HC volume. CONCLUSION: We found that reduced cortical thickness of the cACC is a predictor of aMCI conversion to AD + P, independent of HC, suggesting that the ACC plays a vital role in the underlying pathogenesis of AD + P.

Smaller hippocampal volume in APOE ε4 carriers independent of amyloid-ß (Aß) burden.

OBJECTIVE: To investigate the association of the APOE ε4 genotype with hippocampal volume, independent of Aß burden. METHOD: This cross-sectional study included 71 participants with mild cognitive impairment or mild AD. All participants were divided into carriers or non-carriers of the ε4 allele. The main outcome was hippocampal volume measured using structural magnetic resonance imaging; 18F-florbetaben positron emission tomography was additionally performed to investigate the association of APOE ε4 genotype with hippocampal volumes, independently of Aß burden. Analysis of covariance was conducted to compare the differences in hippocampal volumes between carriers and non-carriers of the ε4 allele after controlling for global Aß burden or local hippocampal Aß burden. RESULTS: The APOE ε4 genotype was associated with a smaller right and total hippocampal volume (right: 3160.16 ± 365.71 vs. 3365.24 ± 434.88, p < 0.05; total: 6257.48 ± 790.60 vs. 6599.52 ± 840.58, p < 0.05), independent of Aß burden. CONCLUSION: Our findings on the association of APOEε4 genotype with hippocampal volume independent of Aß burden suggest that the APOEε4 genotype may contribute to hippocampal neurodegeneration through an Aß-independent mechanism.

Ocular Manifestations of Hospitalized COVID-19 Patients in a Tertiary Care Academic Medical Center in the United States: A Cross-Sectional Study.

PURPOSE: Studies have identified a wide range of ocular signs and symptoms in coronavirus disease 2019 (COVID-19) patients; however, these studies were often conducted outside of the United States. We aim to investigate the ocular manifestations of hospitalized COVID-19 patients at a tertiary care medical center in the United States. PATIENTS AND METHODS: A retrospective, cross-sectional study was conducted on individuals aged 18 and over who were hospitalized for COVID-19 between March 10, 2020 and April 13, 2020. The electronic health record was reviewed for all patients, and a follow-up phone survey was conducted on patients who were discharged home. Data on patient history, physical exam, laboratory results, and hospital disposition were collected and analyzed. RESULTS: A total of 400 patients were included. The mean patient age was 61.7 years (SD 15.5) and 233 (58.3%) were males. Ocular signs and symptoms were noted in 38 (9.5%) patients. The most common ocular abnormality was conjunctival injection, followed by vision changes and ocular irritation. Among the 38 patients, 30 (79.0%) developed ocular involvement prior to day 30 of onset of their COVID symptoms. Univariate analysis showed that age, gender, ocular history, fever, mechanical ventilation, and increasing inflammatory markers were not significantly associated with the presence or development of ocular symptoms. CONCLUSION: In this study, 9.5% of hospitalized COVID-19 patients exhibited ocular signs and symptoms. Factors associated with severe systemic COVID-19 disease were not associated with developing ocular abnormalities. The rate of ocular manifestations of COVID-19 should not be ignored, and thus physicians should routinely evaluate for ocular involvement in hospitalized COVID-19 patients.

Anger-Related Characteristics According to Chronotypes in Bipolar or Depressive Disorders.

OBJECTIVE: Though anger was highly associated with eveningness in general population, there is no study on the relationship between chronotype and anger-related characteristics in bipolar or depressive disorders. This study aimed to investigate the difference of anger-related characteristics according to chronotypes in bipolar or depressive disorders. METHODS: Patients with bipolar or depressive disorders (n=238) were included in this study. Their chronotypes and anger-related characteristics were assessed with a self-evaluation of the Composite Scale of Morningness (CSM), the State Trait Anger Expression Inventory (STAXI) and the Anger Coping Scale (ACS). RESULTS: The eveningness group in patients with mood disorders showed the highest scores of anger-trait (p<0.001), anger-expression (p=0.002) and anger-in (p<0.001) in STAXI subscales, verbal aggression (p=0.010) in ACS subscales among three groups, but the morningess group showed the lowest scores of these subscales among three groups. However, there were no significant differences in all subscales of the STAXI and ACS according to diagnostic subtypes in the Friedman test. CONCLUSION: The results of this study suggested that eveningness in patients with mood disorders might be related to anger proneness and maladaptive anger coping. To manage anger emotion in the patients with mood disorders, therapeutic interventions to modulate eveningness might be helpful.

Whole genome sequencing and rare variant analysis in essential tremor families.

Essential tremor (ET) is one of the most common movement disorders. The etiology of ET remains largely unexplained. Whole genome sequencing (WGS) is likely to be of value in understanding a large proportion of ET with Mendelian and complex disease inheritance patterns. In ET families with Mendelian inheritance patterns, WGS may lead to gene identification where WES analysis failed to identify the causative single nucleotide variant (SNV) or indel due to incomplete coverage of the entire coding region of the genome, in addition to accurate detection of larger structural variants (SVs) and copy number variants (CNVs). Alternatively, in ET families with complex disease inheritance patterns with gene x gene and gene x environment interactions enrichment of functional rare coding and non-coding variants may explain the heritability of ET. We performed WGS in eight ET families (n = 40 individuals) enrolled in the Family Study of Essential Tremor. The analysis included filtering WGS data based on allele frequency in population databases, rare SNV and indel classification and association testing using the Mixed-Model Kernel Based Adaptive Cluster (MM-KBAC) test. A separate analysis of rare SV and CNVs segregating within ET families was also performed. Prioritization of candidate genes identified within families was performed using phenolyzer. WGS analysis identified candidate genes for ET in 5/8 (62.5%) of the families analyzed. WES analysis in a subset of these families in our previously published study failed to identify candidate genes. In one family, we identified a deleterious and damaging variant (c.1367G>A, p.(Arg456Gln)) in the candidate gene, CACNA1G, which encodes the pore forming subunit of T-type Ca(2+) channels, CaV3.1, and is expressed in various motor pathways and has been previously implicated in neuronal autorhythmicity and ET. Other candidate genes identified include SLIT3 which encodes an axon guidance molecule and in three families, phenolyzer prioritized genes that are associated with hereditary neuropathies (family A, KARS, family B, KIF5A and family F, NTRK1). Functional studies of CACNA1G and SLIT3 suggest a role for these genes in ET disease pathogenesis.

Right hippocampus atrophy is independently associated with Alzheimer's disease with psychosis.

AIM: The purpose of this study was to determine whether regionally distributed medial temporal cortex thickness (or hippocampal volume) and frontal lobe volume are independently associated with the onset of Alzheimer's disease (AD) with psychosis. METHODS: We identified 26 AD patients with psychosis (AD+P) and 48 AD patients without psychosis (AD-P) from the Memory Impairment Clinic at Pusan National University Hospital in South Korea. They were matched for age, gender, duration of AD, and Clinical Dementia Rating sum of box score. All participants met the National Institute of Neurological and Communication Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for probable AD. Psychosis was diagnosed according to Jeste and Finkel's proposed diagnostic criteria for psychosis of AD. All participants underwent 3-T magnetic resonance imaging, and 3-D magnetization-prepared rapid gradient echo sequence was acquired for each. The FreeSurfer version 5.1 software package was used to analyze cortical thickness and volume on 3-D T1 -weighted images. anova was used to investigate the differences in cortical thickness and the volume of the total frontal cortex, total temporal cortex, and subregions of the medial temporal cortex between groups after age, gender, years of education, Clinical Dementia Rating sum of box score, duration of AD, and total intracranial volume were controlled for. Furthermore, we added the total frontal volume as an additional variable to investigate whether the association between the medial temporal cortex and AD+P is independent of the frontal cortex. RESULTS: We found that both left and right hippocampal volume were smaller in AD+P than in AD-P. In particular, there was a significant difference in right hippocampal volume between the AD+P and AD-P groups after total frontal volume was added as an additional variable. CONCLUSION: We found that more severe hippocampal atrophy is associated with AD+P than with AD-P. In addition, atrophy of the right hippocampus remained significant among AD+P after adjustment for frontal volume. These findings suggest that right hippocampal atrophy is independently associated with AD+P.

Protein Kinase C Activity and Delayed Recovery of Sleep-Wake Cycle in Mouse Model of Bipolar Disorder.

OBJECTIVE: Previous studies reported the delayed recovery group after circadian rhythm disruption in mice showed higher quinpiroleinduced locomotor activity. This study aimed to compare not only Protein Kinase C (PKC) activities in frontal, striatal, hippocampus and cerebellum, but also relative PKC activity ratios among brain regions according to recovery of circadian rhythm. METHODS: The circadian rhythm disruption protocol was applied to eight-week-old twenty male Institute Cancer Research mice. The circadian rhythm recovery patterns were collected through motor activities measured by Mlog system. Depressive and manic proneness were examined by forced swim test and quinpirole-induced open field test respectively. Enzyme-linked immunosorbent assay was employed to measure PKC activities. RESULTS: The delayed recovery group presented greater locomotor activities than the early recovery group (p=0.033). The delayed recovery group had significantly lower frontal PKC activity than the other (p=0.041). The former showed lower frontal/cerebellar PKC activity ratio (p=0.047) but higher striatal/frontal (p=0.038) and hippocampal/frontal (p=0.007) PKC activities ratios than the latter. CONCLUSION: These findings support potential mechanism of delayed recovery after circadian disruption in bipolar animal model could be an alteration of relative PKC activities among mood regulation related brain regions. It is required to investigate the PKC downstream signaling related to the delayed recovery pattern.

Genetic Testing Preferences of Individuals in Families with Essential Tremor.

Background: The search for essential tremor (ET) genes is active, and it is only a matter of time before genetic tests become available. Genetic testing preferences in families have been studied in numerous other neurological disorders but there are no published data about ET. Methods: We surveyed 34 ET probands and their relatives (43 affected, 28 unaffected) enrolled in our Family Study of Essential Tremor to assess their interest in genetic testing. We examined whether clinical factors influenced their interest in testing. Clinical utility ("Your physician will be able to use the information obtained to improve your care") and penetrance ("How likely an individual who carries an ET gene is to develop ET") were defined for participants. Results: Interest in genetic testing was high in ET families (90/105 [85.7%]). There was a significant difference between affected (including probands and affected relatives) and unaffected relatives in terms of their interest in genetic testing, with the former being more interested (70/77 [90.9%] vs. 20/28 [71.4%] p = 0.04). Participants were more likely to want testing in the scenarios with high clinical utility; disease penetrance was not a determining factor (all p < 0.05). Sixteen hypothetical factors were identified that might influence a participant's decision to undergo genetic testing for ET. Discussion: Interest in genetic testing was high in ET families. While genetic testing is not currently available for ET, the hunt for ET genes is ongoing, and this is a highly familial disorder. Understanding genetic testing preferences will greatly aid clinicians once a genetic test becomes available.

Can Residual Symptoms During Inter-Episode Period after Partial Remission in Bipolar I Disorder Have Cyclic Patterns with Specific Frequencies?

This case report aimed to describe cyclic patterns of residual mood symptoms in partially remitted bipolar I patient. In a 24-year-old woman with bipolar I disorder, residual mood symptoms measured by self-rated daily mood chart for 18 months were analyzed using wavelet analysis. A 146-day periodicity was prominent for the first 100 days after discharge. Between 100-200 days, 146-day periodicity was progressively diminished and 21- and 8-day periodicity was prominent. Between 200-516 days, 21-day periodicity was diminished and 85-day periodicity became prominent. This case suggest that bipolar patients might have cyclic residual symptoms with specific frequencies.

Action Tremor Asymmetry Profile Does Not Aggregate in Families with Essential Tremor.

BACKGROUND: Action tremor is the hallmark feature of essential tremor (ET). While the tremor typically is mildly asymmetric, in some patients, it is markedly asymmetric. There are few data on factors that influence this asymmetry. ET is also a highly familial disease. Whether the tremor asymmetry profile (i.e., differential expression of tremor in each arm in a given patient) is similar across family members is not known. The alternative possibility is that this feature is not heritable. There are no published data addressing this issue. The aim of this study was to determine whether the extent of action tremor asymmetry ran in ET families. METHODS: ET probands and relatives were enrolled in a genetic study at Yale and Columbia Universities. An in-person evaluation included a videotaped neurological examination, including a detailed assessment of tremors. A senior movement disorders neurologist reviewed all videotaped examinations, and the severity of postural and kinetic arm tremors was rated on 12 examination items using a reliable rating scale. The tremor asymmetry index = right arm tremor score - left arm tremor score. We used a bivariate linear regression model to assess the predictors of the tremor asymmetry index in relatives; this model used the tremor asymmetry index in the proband as a primary predictor of interest. In an analysis of variance (ANOVA), we tested for heterogeneity across families in the tremor asymmetry index (i.e., to see whether there was a significant family effect). RESULTS: There were 187 enrollees (59 probands, 128 affected relatives). In a bivariate linear regression model, the tremor asymmetry index in the proband was not a predictor of the tremor asymmetry index in their relatives (p = 0.66). In an ANOVA, family grouping did not explain a significant proportion of the total variance in the tremor asymmetry index (p = 0.56). CONCLUSION: Tremor asymmetry did not aggregate in families with ET. Therefore, this does not seem to be a disease feature that is heritable. These data will provide added value to the clinical dialog, giving patients one more piece of information about the way the disease manifests within families.

Early Head Tremor in Essential Tremor: A Case Series and Commentary.

BACKGROUND: Classically, the onset of head tremor in essential tremor (ET) patients follows that of hand tremor, such that there is a somatotopic spread of involved areas. Here we present a series of seven self-reportedly "unaffected" relatives of ET cases. These seven were clinically asymptomatic and had normal levels of arm tremor on examination, yet each evidenced a transient head wobble on examination. We estimate the prevalence of this phenotype within the two studies from which cases were ascertained. METHODS: ET cases and their self-reportedly affected and unaffected relatives, enrolled in two family studies, underwent a medical history and videotaped neurological examination. RESULTS: In seven self-reportedly "unaffected" relatives, a transient and subtle head wobble was seen, always during sustained phonation, speech, or reading aloud. Total tremor score (a measure of arm tremor) ranged from 5 to 12 (i.e., mild tremor within the range of normal). The prevalence of this phenotype of early head tremor was 3.7% in one study and 23.1% in the other. DISCUSSION: We present a series of seven individuals who had early head tremor in an evolving transition state from normal to ET. These cases raise a number of broad clinical, phenotypic, and pathophysiological issues about ET.

Familial Aggregation of the Cerebellar Signs in Familial Essential Tremor.

BACKGROUND: Although the hallmark feature of essential tremor (ET) is kinetic tremor, patients may exhibit additional motor features (e.g., intention tremor and mild gait ataxia) that are markers of an underlying abnormality of cerebellar function. ET is also a highly familial disorder, but we do not know whether the presence and expression of cerebellar signs are similar across family members. There are simply no published data. The alternative possibility is that these features are not heritable. We tested the specific hypothesis that the presence of cerebellar signs (i.e., intention tremor, tandem gait difficulty) ran in ET families. METHODS: ET probands and relatives enrolled in a genetic study at Yale and Columbia universities underwent a detailed videotaped neurological examination. RESULTS: There were 187 enrollees (59 probands, 128 affected relatives). In a bivariate logistic regression model, the presence of intention tremor in the proband was not a predictor of the presence of intention tremor in the relatives (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.28-1.27, p = 0.18). In a similar model, the presence of greater tandem gait difficulty (i.e., a tandem gait score in the upper quartile) in the proband was not a predictor of the presence of such difficulty in the relatives (OR = 1.22, 95% CI = 0.41-3.66, p = 0.73). DISCUSSION: The presence of cerebellar signs did not aggregate in families with ET. In the current dataset, these did not seem to be disease features that were heritable.

Worse and Worse and Worse: Essential Tremor Patients' Longitudinal Perspectives on Their Condition.

BACKGROUND: Essential tremor (ET) patients regularly inquire about their prognosis. Therefore, physicians have cause to review available medical literature for meaningful answers. Longitudinal studies are ideally suited to provide a glimpse into the evolution of tremor. Despite its high prevalence, there are surprisingly few longitudinal clinical studies of ET. Furthermore, none of them provide data from the patients' perspective. Understanding the patient vantage point is valuable as it is the starting point of personalized medicine. Given the progressive nature of ET, we hypothesized that many patients will experience an increase in symptom severity over time. However, due to a lack of clinical data, the exact nature of this progression is unclear. For example, whether patients experience a worsening at each time interval is simply not known. In this longitudinal study, we assessed whether ET patients felt that their symptoms had worsened between each follow-up evaluation and try to identify specific clinical characteristics associated with this experience. METHODS: A cohort of 164 ET cases enrolled in a prospective, longitudinal research study. After a baseline in-person assessment, they received regular telephone evaluations for up to 5.25 years, beginning in 2009. During each follow-up evaluation, cases answered the question, "has your ET worsened since our last call?" RESULTS: Two-thirds [104 (63.4%)] of ET cases reported worsening at one-half or more of their follow-up evaluations. Furthermore, one in four cases [44 (26.8%)] reported worsening at every follow-up evaluation. Self-reported worsening was not associated with any of the baseline clinical variables assessed, including age, gender, tremor duration, age at tremor onset, or total tremor score. CONCLUSION: Little has been written from the patients' perspective on progression of ET. When followed longitudinally at regular intervals, a majority of ET cases we studied reported worsening one-half or more of the time; furthermore, one in four cases reported worsening at each and every assessment, indicating that they felt they were inexorably getting worse and worse with time. That there is so much self-reported worsening in ET argues against the notion that this is a static and benign condition. It suggests that patients experience it as a condition that worsens regularly and consistently.

Decreased gray matter volume is associated with the subtypes of psychotic symptoms in patients with antipsychotic-naïve mild or moderate Alzheimer's disease: A voxel-based morphometry study.

The purpose of this study was to investigate the association between brain regional gray matter volume and two subtypes of psychotic symptoms, namely paranoid and misidentification subtypes, in antipsychotic-naïve mild or moderate Alzheimer's disease (AD) patients. Forty AD patients with psychotic symptoms and 25 AD patients without psychotic symptoms were assessed for cognitive and functional impairment. Presence and subtype of psychotic symptoms were assessed by using the delusion and hallucination subscale of the Korean Neuropsychiatric Inventory (K-NPI). Structural MRI images were acquired on a 3 T scanner, and were analyzed using voxel-based morphometry (VBM) for automated analysis. The misidentification subtype is associated with more severe gray matter atrophy, and paranoid subtype is associated with less severe gray matter atrophy compared to non-psychosis group. These results suggest that the misidentification, the paranoid subtype and the non-psychosis group have a distinct neural correlation.