BackgroundNeural autoantibody-associated dementia (NABD) is an increasing phenomenon in memory clinics with a high impact on later therapy. Biomarkers are lacking that differentiate this type of dementia from neurodegenerative dementia such as Alzheimer’s dementia (AD). Our aim is to analyze neurodegeneration markers and their relationship to progressing cognitive dysfunction in NABD and AD to test for tools differentiating these two forms of dementia prior to neural autoantibody testing.MethodsIn our retrospective, observational study, we investigated 14 patients with dementia and serum and/or cerebrospinal fluid (CSF) neural autoantibodies as well as 14 patients with AD by relying on recent CSF and clinical criteria for AD. Patient files were checked for psychopathology, neuropsychological test performance, autoimmune indicators, CSF, and MRI results.ResultsOur patient groups did not differ in their psychopathology, autoimmune indicators, or MRI profile. The progression of cognitive dysfunction [as measured by the difference in Mini-Mental State Examination (MMSE) scores since disease onset, and the yearly progression rate (MMSE loss/per year)] did not vary significantly between groups. Total tau protein was significantly higher in AD patients than NABD patients revealing no signs of Alzheimer’s disease pathology in their CSF (p < 0.05). Total tau protein levels in CSF correlated with cognitive decline since disease onset (r = 0.38, p < 0.05) and yearly progression rates (r = 0.56, p < 0.005) in all patients.DiscussionOur results suggest that the progression of cognitive dysfunction as defined by MMSE does not seem to be an appropriate biomarker for distinguishing NABD from AD. However, the total tau protein level in CSF might be a relevant molecular biomarker that can indicate disease pathology and/or progression in both known AD and NABD, which is often accompanied by axonal degeneration. Total tau protein may be an additional diagnostic tool with which to differentiate anti-neural-associated dementia from AD if further research confirms these proof-of-concept findings in larger patient cohorts.
BackgroundAnti-neural autoantibodies associated with psychiatric syndromes is an increasing phenomenon in psychiatry. Our investigation aimed to assess the frequency and type of neural autoantibodies associated with distinct psychiatric syndromes in a mixed cohort of psychiatric patients.MethodsWe recruited 167 patients retrospectively from the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen for this study. Clinical features including the assessment of psychopathology via the Manual for Assessment and Documentation of Psychopathology in Psychiatry (AMDP), neurological examination, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and electroencephalography (EEG) analysis were done in patients. Serum and or CSF anti- neural autoantibodies were measured in all patients for differential diagnostic reasons.ResultsWe divided patients in three different groups: (1) psychiatric patients with CSF and/or serum autoantibodies [PSYCH-AB+, n = 25 (14.9%)], (2) psychiatric patients with CSF autoantibodies [PSYCH-AB CSF+, n = 13 (7.8%)] and (3) those psychiatric patients without autoantibodies in serum and/or CSF [PSYCH-AB-, n = 131]. The prevalence of serum neural autoantibodies was 14.9% (PSYCH-AB+), whereas 7.2% had CSF autoantibodies (PSYCH-AB CSF+) in our psychiatric cohort. The most prevalent psychiatric diagnoses were neurocognitive disorders (61–67%) and mood disorders (25–36%) in the patients presenting neural autoantibodies (PSYCH-AB+ and PSYCH-AB CSF+). However, psychiatric diagnoses, neurological deficits, and laboratory results from CSF, EEG or MRI did not differ between the three groups. To evaluate the relevance of neural autoantibody findings, we applied recent criteria for possible, probable, or definitive autoimmune based psychiatric syndromes in an paradigmatic patient with delirium and in the PSYCH-AB+ cohort. Applying criteria for any autoimmune-based psychiatric syndromes, we detected a probable autoimmune-based psychiatric syndrome in 13 of 167 patients (7.8%) and a definitive autoimmune-based psychiatric syndrome in 11 of 167 patients (6.6%).ConclusionsNeural autoantibodies were detected mainly in patients presenting neurocognitive and mood disorders in our psychiatric cohort. The phenotypical appearance of psychiatric syndromes in conjunction with neural autoantibodies did not differ from those without neural autoantibodies. More research is therefore warranted to optimize biomarker research to help clinicians differentiate patients with potential neural autoantibodies when a rapid clinical response is required as in delirium states.
BackgroundAutoantibody-mediated psychiatric disorder is often difficult to diagnose as the clinical features of psychiatric disorder associated with neural autoantibodies are often similar. Thus, it is of major relevance to investigate whether psychopathology can differentiate between both disease entities as a biomarker and help us in searching for specific autoantibodies associated with psychiatric symptoms.MethodsWe enrolled 154 patients of the Department of Psychiatry and Psychotherapy of the University Medical Center Göttingen with psychopathology data and retrospectively evaluated their patient records using the classification systems AMDP (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie) and HiTOP (Hierarchical Taxonomy of Psychopathology).ResultsWe identified 35 psychiatric patients revealing autoantibodies in their serum and/or cerebrospinal fluid (CSF) and 119 with no autoantibodies. Relying on the AMDP system, many more psychiatric patients with serum autoantibodies (51%) had problems with orientation than those without autoantibodies (32%) (p < 0.05). Furthermore, fewer psychiatric patients with serum autoantibodies exhibited a blunted affect (11.4 vs. 32.8%, p < 0.01) and affective rigidity (20 vs. 45%, p < 0.01). In particular, psychiatric patients presenting CSF autoantibodies (indicating an autoimmune symptomatic basis) experience more loss of vitality (5%) than those without autoantibodies (0%) (p < 0.05). Another interesting finding is that according to the AMDP classification, a manic syndrome is much more frequent in autoantibody-positive (8.6%) than autoantibody-negative psychiatric patients (0.8%) (p < 0.05). Another aspect is the more frequent occurrence of attention and memory deficits in patients with autoantibodies against intracellular targets compared with targets on the membrane surface.ConclusionOur findings indicate that neural autoantibodies in psychiatric patients could indicate a phenotype more often characterized by a manic syndrome, orientation disturbances within the cognitive spectrum, and fewer affect disturbances characterized by less blunted affect and not as seriously impaired feelings of vitality compared to controls. The novelty of our approach is the extensive autoantibody tests for various psychiatric syndromes in combination with a profound psychometric measurement with two different scales.
BackgroundPsychiatric autoimmune encephalitis (pAE) is a growing field of interest in diagnosis and therapy in psychiatric hospitals and institutions. This study investigates the relevant extent to which there are potential biomarkers in cerebrospinal fluid (CSF) that can differentiate against a cohort with neurodegenerative disease.MethodsWe included in this study a total of 27 patients with possible and definite psychiatric autoimmune encephalitis and compared with a cohort with CSF-based AD (n = 27) different biomarkers in CSF such as lactate, cell count, % lymphocytes, % monocytes, total protein content, albumin, immunoglobulins G (IgG), M (IgM) and A (IgA), CSF/serum albumin ratio, CSF/serum IgG ratio, CSF/serum IgA ratio, intrathecal IgG synthesis, blood–brain barrier disruption, specific antibody synthesis for measles, rubella, herpes simplex virus, varicella zoster virus, Ebstein-Barr virus and cytomegalovirus, total tau protein (t-tau), phosphorylated tau protein 181 (p-tau181), amyloid beta 42 (Aß42), amyloid beta 40 (Aß40) and the amyloid beta 42/ amyloid beta 40 (Aß42/40) ratio.ResultsThe p-tau 181 was elevated above cut-off values in both possible pAE and AD. However, in definitive pAE, p-tau181 levels were not elevated. When elevated p-tau181 levels in possible AE were compared with those in AD, we found relevant differences, such as a relative increase in p-tau181 in AD patients. Elevated p-tau181 levels were detected in possible psychiatric AEs with IgLON5, glycine, recoverin, titin, and nonspecific neuropil antibodies in serum and IgLON5, titin, Yo, and nonspecific neuropil autoantibodies in CSF. In addition, we detected elevated levels of p-tau181 and IgLON5 autoantibodies in serum and CSF, and Yo autoantibodies in CSF in patients with definitive pAE. Interestingly, we observed a higher CSF/serum IgM ratio in possible and definitive pAE than in AD patients.ConclusionOur results suggest that neuroaxonal brain damage may occur in specific psychiatric AEs associated with IgLON5, glycine, recoverin, and titin autoantibodies. Further research should focus on the CSF/serum IgM ratio as an early marker of autoantibody production in pAE compared to AD as a potential biomarker for differential diagnosis.
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