Protein Profiling in Serum and Cerebrospinal Fluid Following Complex Surgery on the Thoracic Aorta Identifies Biological Markers of Neurologic Injury.

Surgery on the arch or descending aorta is associated with significant risk of neurological complications. As a consequence of intubation and sedation, early neurologic injury may remain unnoticed. Biomarkers to aid in the initial diagnostics could prove of great value as immediate intervention is critical. Twenty-three patients operated in the thoracic aorta with significant risk of perioperative neurological injury were included. Cerebrospinal fluid (CSF) and serum were obtained preoperatively and in the first and second postoperative days and assessed with a panel of 92 neurological-related proteins. Three patients suffered spinal cord injury (SCI), eight delirium, and nine hallucinations. There were markers in both serum and CSF that differed between the affected and non-affected patients (SCI; IL6, GFAP, CSPG4, delirium; TR4, EZH2, hallucinations; NF1). The study identifies markers in serum and CSF that reflect the occurrence of neurologic insults following aortic surgery, which may aid in the care of these patients.

Low mood, visual hallucinations, and falls - heralding the onset of rapidly progressive probable sporadic Creutzfeldt-Jakob disease in a 73-year old: a case report.

BACKGROUND: Creutzfeldt-Jakob disease is a rare and rapidly fatal neurodegenerative disease. Since clinicians may see only very few cases during their professional career, it is important to be familiar with the clinical presentation and progression, to perform appropriate investigations, and allow for quick diagnosis. CASE PRESENTATION: A 73-year-old British Caucasian woman presented with acute confusion of 2 weeks' duration on a background of low mood following a recent bereavement. Her symptoms included behavioral change, visual hallucinations, vertigo, and recent falls. She was mildly confused, with left-sided hyperreflexia, a wide-based gait, and intention tremor in her left upper limb. Initial blood tests, computed tomography, and magnetic resonance imaging of her brain showed no significant abnormality. Following admission, she had rapid cognitive decline and developed florid and progressive neurological signs; a diagnosis of prion disease was suspected. A lumbar puncture was performed; cerebrospinal fluid was positive for 14-3-3 protein, real-time quaking-induced conversion, and raised levels of s-100b proteins were detected. An electroencephalogram showed bilateral periodic triphasic waves on a slow background. The diagnosis of probable Creutzfeldt-Jakob disease was made. CONCLUSIONS: This case report highlights key features in the initial presentation and clinical development of a rare but invariably rapidly progressive and fatal disease. It emphasizes the importance of considering a unifying diagnosis for multifaceted clinical presentations. Although it is very rare, Creutzfeldt-Jakob disease should be considered a diagnosis for a mixed neuropsychiatric presentation, particularly with rapid progressive cognitive decline and development of neurological signs. However, to avoid overlooking early signal change on magnetic resonance imaging, it is important to take diffusion-weighted magnetic resonance imaging for all patients with neuropsychological symptoms. Importantly, early diagnosis also ensures the arrangement of suitable contamination control measures to minimize the risk of infection to health care professionals and other patients.

Cerebrospinal fluid α-synuclein and Lewy body-like symptoms in normal controls, mild cognitive impairment, and Alzheimer's disease.

BACKGROUND: Reduced cerebrospinal fluid (CSF) α-synuclein has been described in synucleinopathies, including dementia with Lewy bodies (DLB). Common symptoms of DLB include visual hallucinations and visuospatial and executive deficits. Co-occurrence of Lewy body pathology is common in Alzheimer's disease (AD) patients, but it is unknown if reduced CSF α-synuclein is associated with Lewy body-like symptomatology in AD. OBJECTIVE: Determine associations between CSF α-synuclein and Lewy body-like symptomatology. METHODS: We included 73 controls (NC), 121 mild cognitive impairment (MCI) patients, and 61 AD patients (median follow-up 3.5 years, range 0.6-7.8). We tested associations between baseline CSF α-synuclein and visual hallucinations and (longitudinal) cognition. Models were tested with and without co-varying for CSF total tau (T-tau), which is elevated in AD patients, and believed to reflect neurodegeneration. RESULTS: Hallucinations were reported in 20% of AD patients, 13% of MCI patients, and 8% of NC. In AD, low CSF α-synuclein was associated with hallucinations. When adjusting for CSF T-tau, low CSF α-synuclein was associated with accelerated decline of executive function (NC, MCI, and AD), memory (MCI and AD), and language (MCI). CONCLUSION: The associations of low CSF α-synuclein with hallucinations and poor executive function, which are hallmarks of DLB, indirectly suggest that this biomarker may reflect underlying synuclein pathology. The associations with memory and language in MCI and AD suggests either that reduced CSF α-synuclein also partly reflects global impaired neuronal/synaptic function, or that non-specific overall cognitive deterioration is accelerated in the presence of synuclein related pathology. The findings will require autopsy verification.

Cerebrospinal fluid homovanillic acid is correlated to psychotic features in neurological patients with delirium.

OBJECTIVE: The aim of this study was to determine if cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) are related to the clinical features of delirium in a group of patients with acute onset neurological illness. METHODS: Fifty-one patients with probable acute brain infection were classified as delirious and nondelirious according to Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) and Delirium Rating Scale (DRS). CSF HVA concentration was analyzed by high-performance liquid chromatography. RESULTS: Delirium was present in 60.8% of the total sample. HVA levels were not significantly different between delirious and nondelirious patients. Remarkably, patients with psychotic symptoms shown higher levels of CSF HVA as compared to nonpsychotic patient values. In addition, HVA levels were positively correlated to specific items of DRS such as delusions (r=0.463, P=.001), hallucinations (r=0.438, P=.001), cognitive dysfunction (r=0.286, P=.042) and fluctuation of symptoms (r=0.280, P=.046) in the total sample. Subanalyses excluding patients taking antipsychotic drugs revealed that HVA CSF levels were higher in those patients with delusions, and furthermore, the dopamine metabolite remained positively correlated to delusion subscale of DRS. CONCLUSIONS: Our results suggest that psychotic symptoms in delirious patients may be related to increased dopamine neurotransmission, as reflected by increased CSF HVA concentration, providing direct evidence to support the dopaminergic theory of psychosis.

Antiphospholipid antibodies in blood and cerebrospinal fluids of patients with psychosis.

Antiphospholipid antibodies (aPL) have been reported in the cerebrospinal fluids (CSF) of neurology patients but no CSF studies with psychiatric patients exist. We tested serum from 100 hospitalized psychotic patients having hallucinations and/or delusions for aPL. Patients with positive serum aPL findings were asked to submit CSF for aPL testing. Five CSF samples had aPL specificities not found in the patient's serum suggesting the possibility of intrathecal synthesis. Specificity and isotype discordance between CSF and blood aPL in these psychiatric patients implicates a central nervous system independent autoimmune process that may have an underlying association with the pathophysiology of their diseases.

CSF hypocretin-1 levels and clinical profiles in narcolepsy and idiopathic CNS hypersomnia in Norway.

OBJECTIVE: To evaluate the relationship between CSF hypocretin-1 levels and clinical profiles in narcolepsy and CNS hypersomnia in Norwegian patients. METHOD: CSF hypocretin-1 was measured by a sensitive radioimmunoassay in 47 patients with narcolepsy with cataplexy, 7 with narcolepsy without cataplexy, 10 with idiopathic CNS hypersomnia, and a control group. RESULTS: Low hypocretin-1 values were found in 72% of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy. Patients with low CSF hypocretin-1 levels reported more extensive muscular involvement during cataplectic attacks than patients with normal levels. Hypnagogic hallucinations and sleep paralysis occurred more frequently in patients with cataplexy than in the other patient groups, but with no correlation to hypocretin-1 levels. CONCLUSION: About three quarters of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy had low CSF hypocretin-1 values, and appear to form a distinct clinical entity. Narcolepsy without cataplexy could not be distinguished from idiopathic CNS hypersomnia by clinical symptoms or biochemical findings.

[Hashimoto encephalopathy. Analysis of four case reports]. / Encéphalopathie de Hashimoto. Analyse de quatre observations.

INTRODUCTION: Encephalopathy associated with Hashimoto's thyroiditis has been recognized for more than 30 years and is probably underestimated. EXEGESIS: We report four patients with Hashimoto's thyroiditis who presented neurological or psychiatric features. There were three women and one man, with a mean age of 68 years. Neurological presentations were various: seizures, psychotic episodes, altered consciousness, hallucinations without usual aetiological diseases (infectious, metabolic, neoplasic, vascular, etc.). Neurological investigations (EEG, brain CT, magnetic resonance imaging) were unspecific. In all cases, a moderately high CSF protein level without pleocytosis was found. Patients presented slight hypothyroidism with high titers of antithyroperoxidase antibodies. Despite hormone therapy replacement, neurological features persisted. Outcome was favorable under steroid therapy. CONCLUSION: Hashimoto's encephalopathy must be considered in the face of neuropsychiatric manifestations without obvious etiology. Pathogenic mechanisms are not clear but probably involve autoimmune cerebral vasculitis because of the efficacy of steroids.

Hallucinations in patients with major depression. Interactions between CSF monoaminergic and endorphinergic indices.

CSF levels of radioreceptorassayed endorphins Fraction I (EndFI, n = 92) and homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) (n = 118) were measured in patients with major depressive disorders according to Research Diagnostic Criteria (18% were psychotic; 11% hallucinated during the peak of the depressive episode). CSF measures (both "raw" variables and ranks) were uni- and multivariately correlated with both dichotomized and scored measures of hallucinations of any type. Hallucinations were statistically strongly associated with higher HVA levels, irrespective of prior medication with neuroleptics, and with the interactive product HVA X EndFI and the interactive ratio HVA/5-HIAA. Results suggest interactions between dopaminergic, serotonergic and endorphinergic neurotransmission being involved in the biochemical substrate of depressive hallucinatory episodes.