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.
Humans ; Parkinson Disease/pathology* ; Gastrointestinal Tract ; Risk Factors ; Gastrointestinal Microbiome ; Prodromal Symptoms ; alpha-Synuclein

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.
Amygdala ; Biomarkers ; Blood Cells ; Diagnosis ; Hippocampus ; Mental Disorders ; Occipital Lobe ; Panic Disorder ; Panic ; Prodromal Symptoms ; Sensitivity and Specificity ; Serotonin ; Stem Cells

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.
Alleles ; Amyloid ; Apolipoprotein E4 ; Dementia ; Genotype ; Humans ; Methods ; Mild Cognitive Impairment ; Plaque, Amyloid ; Positron-Emission Tomography ; Prodromal Symptoms ; Risk Factors

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.
Anonyms and Pseudonyms ; Clinical Clerkship ; Ear ; Education ; Female ; Humans ; Hyperventilation ; Learning ; Male ; Nausea ; Operating Rooms ; Prevalence ; Prodromal Symptoms ; Students, Medical ; Surveys and Questionnaires ; Sweat ; Sweating ; Syncope ; Yawning

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.
Brain Stem ; Diagnosis ; Epidemiology ; Follow-Up Studies ; Multiple System Atrophy ; Muscle, Skeletal ; Neurodegenerative Diseases ; Parasomnias ; Parkinson Disease ; Polysomnography ; Prodromal Symptoms ; REM Sleep Behavior Disorder ; Sleep, REM

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.
Adolescent ; Adult Children* ; Adult* ; Animals ; Blotting, Western ; Brain ; Brain-Derived Neurotrophic Factor ; Complement System Proteins ; Frontal Lobe ; Humans ; Mice ; Phosphotransferases ; Prefrontal Cortex* ; Prodromal Symptoms ; Psychotic Disorders ; Schizophrenia ; Tropomyosin

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.
Autistic Disorder* ; Brain ; Child ; Autism Spectrum Disorder* ; Early Intervention (Education) ; Early Medical Intervention ; Follow-Up Studies ; Humans ; Infant ; Joints ; Nonverbal Communication ; Prodromal Symptoms ; Prospective Studies ; Retrospective Studies

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.
Absorptiometry, Photon ; Calcium ; Diagnosis ; Extremities ; Femoral Fractures* ; Hip ; Humans ; Injections, Subcutaneous ; Magnetic Resonance Imaging ; Osteoporotic Fractures ; Parathyroid Hormone ; Prodromal Symptoms ; Radiography ; Thigh ; Vitamin D

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.
alpha-Synuclein ; Biomarkers* ; Color Vision ; Depression ; Dopamine ; Follow-Up Studies ; Humans ; Mild Cognitive Impairment ; Neurodegenerative Diseases ; Parkinson Disease ; Prodromal Symptoms ; REM Sleep Behavior Disorder* ; Sleep, REM*

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.
Adult ; Anti-N-Methyl-D-Aspartate Receptor Encephalitis* ; Antibodies ; Bipolar Disorder ; Blood Pressure ; Cerebrospinal Fluid ; Dermoid Cyst ; Diarrhea ; Encephalitis ; Female ; Fever ; Fever of Unknown Origin* ; Headache ; Humans ; N-Methylaspartate ; Nausea ; Prodromal Symptoms ; Skin ; Soft Tissue Infections ; Tachycardia ; Teratoma ; Vomiting