Objective: The presence of elevated dopamine (DA) and its major metabolites in the cytosol of neurons has been associated with their vulnerability in Parkinson's disease (PD). Over 99% of the cell's amines are confined to secretory vesicles (SVs), making these structures fundamental in the regulation of cytosolic DA levels. SVs of platelets use similar, if not the same mechanisms to accumulate serotonin in SVs as dopaminergic neurons do to store DA. Hence, any functional defects in platelets probably mirrors events in DA neurons.Methods: We have isolated fresh platelets from the blood of 75 PD patients, 116 matched controls and 24 patients with Parkinsonism, assaying serotonin handling (basal content, accumulation, secretion and spontaneous leakage).Results: We found a dramatic decrease in the serotonin content and uptake by SVs, as well as decreased thrombin‐induced release by platelets from PD patients but not in those from most Parkinsonism cases. Platelets from PD patients also failed to retain serotonin in SVs.Interpretation: These findings indicate a functional impairment in the handling of amines by SVs in PD patients. This defect may serve as a biomarker of PD, and the approach described here may be potentially used for the subclinical detection of PD and to establish a platform to assay disease modifying drugs. ANN NEUROL 2022

Background: Anti-NMDA receptor encephalitis is an autoimmune disease characterized by severe neuropsychiatric disturbances, often misdiagnosed as a primary psychiatric disorder. Early diagnosis is crucial, as delayed immunotherapy is associated with worse outcomes. Electroencephalography (EEG) is a widely available tool for detecting abnormalities that may aid in early detection of cases that should undergo a thorough approach. Although EEG has high sensitivity, its specificity remains a challenge. Methods: This case-control study was carried out in the National Institute of Neurology and Neurosurgery of Mexico and included 241 patients with acute or subacute neuropsychiatric disturbances, raising the suspicion of autoimmune encephalitis and leading to the determination of NMDA receptor antibodies in the cerebrospinal fluid (CSF). EEG patterns were analyzed to determine the frequency of abnormal findings and their diagnostic value. Results: 140 patients were diagnosed as having definite anti-NMDA receptor encephalitis, whereas 101 had a negative determination of NMDA receptor antibodies. Psychosis was very frequent in both groups. However, severe cognitive dysfunction and catatonia were significantly more frequent in anti-NMDA receptor encephalitis patients. EEG abnormalities were significantly more frequent in patients with anti-NMDA receptor encephalitis patients (87.2% vs. 61.2%, p < 0.001). Diffuse slowing (75.7% vs. 46.6%, p < 0.001) and the extreme delta brush pattern (8.8% vs. 0%, OR = 20.6, p = 0.002) were significantly associated with anti-NMDA receptor encephalitis. Logistic regression analysis confirmed that an abnormal EEG remained strongly associated with anti-NMDA receptor encephalitis after adjusting for confounders. Conclusions: EEG abnormalities, particularly diffuse slowing and the extreme delta brush pattern, provide important diagnostic clues in patients with a clinical suspicion of anti-NMDA receptor encephalitis. While EEG has high sensitivity, its specificity is enhanced by recognizing distinct patterns. These findings support the integration of EEG into diagnostic algorithms to guide early detection and management of autoimmune encephalitis.

Background: Brain MRI abnormalities in anti-NMDA receptor encephalitis (ANMDARE) are classically described in limbic structures, particularly the medial temporal lobe. Paralimbic, neocortical, and meningeal abnormalities have been less consistently reported. Objective: The objective was to evaluate the diagnostic value of brain MRI abnormalities in patients with definite ANMDARE. Methods: We conducted a case–control study including 115 patients with ANMDARE and 115 controls with primary psychotic disorders or antibody-negative autoimmune encephalitis. Structural MRI studies were systematically reviewed by an expert neuroradiologist blinded to clinical diagnosis. Results: ANMDARE patients were younger and more frequently presented with seizures, dyskinesia, severe neuropsychiatric disturbances, abnormal cerebrospinal fluid and EEG findings, and worse outcomes, including mortality. T2-T2-FLAIR abnormalities commonly involved medial temporal limbic structures, paralimbic regions (anterior cingulate and insular cortices), and neocortical areas (parieto-occipital cortices). Pachymeningeal enhancement was observed in 26.1% of patients. MRI findings clearly differentiated ANMDARE from primary psychotic disorders but largely overlapped with antibody-negative autoimmune encephalitis, except for limited parietal and occipital differences. Conclusions: T2-FLAIR MRI abnormalities involving medial temporal, paralimbic, and posterior neocortical regions are common in ANMDARE. Pachymeningeal enhancement is not rare. While useful for distinguishing ANMDARE from primary psychotic disorders, a substantial overlap with antibody-negative autoimmune encephalitis was observed.

Background: Brain MRI abnormalities in anti–NMDA receptor encephalitis (ANMDARE) are classically described in limbic structures, particularly the medial temporal lobe. Paralimbic, neocortical, and meningeal abnormalities have been less consistently reported. Objective: To evaluate the diagnostic value of brain MRI ab-normalities in patients with definite ANMDARE. Methods: We conducted a case–control study including 115 patients with ANMDARE and 115 controls with primary psychotic disorders or antibody-negative autoimmune encephalitis. Structural MRI studies were systematically reviewed by an expert neuroradiologist blinded to clinical diagnosis. Results: ANMDARE patients were younger and more frequently presented with seizures, dyskinesia, severe neuropsychiatric disturbances, abnormal cerebrospi-nal fluid and EEG findings, and worse outcomes, including mortality. T2-T2-FLAIR abnormalities commonly involved medial temporal limbic structures, paralimbic re-gions (anterior cingulate and insular cortices), and neocortical areas (parieto-occipital cortices). Pachymeningeal enhancement was observed in 26.1% of patients. MRI find-ings clearly differentiated ANMDARE from primary psychotic disorders but largely overlapped with antibody-negative autoimmune encephalitis, except for limited parie-tal and occipital differences. Conclusions: T2-FLAIR MRI abnormalities involving me-dial temporal, paralimbic, and posterior neocortical regions are common in ANMDARE. Pachymeningeal enhancement is not rare. While useful for distinguishing ANMDARE from primary psychotic disorders, a substantial overlap with anti-body-negative autoimmune encephalitis was observed.