Classical Cerebrospinal Fluid Biomarkers in Dementia with Lewy Bodies.

The use and interpretation of diagnostic cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders, such as Dementia with Lewy bodies (DLB), represent a clinical challenge. According to the literature, the composition of CSF in DLB patients varies. Some patients present with reduced levels of amyloid, others with full Alzheimer Disease CSF profile (both reduced amyloid and increased phospho-tau) and some with a normal profile. Some patients may present with abnormal levels of a-synuclein. Continuous efforts will be required to establish useful CSF biomarkers for the early diagnosis of DLB. Given the heterogeneity of methods and results between studies, further validation is fundamental before conclusions can be drawn.

Telltale Signs of Idiopathic Intracranial Hypertension With Normal Opening Cerebrospinal Fluid Pressure.

Introduction: Idiopathic Intracranial Hypertension (IIH) with normal opening cerebrospinal fluid (CSF) pressure comprises a rare IIH variant. Case Report: We report the case of a non-obese Caucasian woman, who presented with asymmetrical papilledema, typical IIH-findings on optic nerve sonography and brain magnetic resonance imaging (MRI), and was diagnosed with IIH despite normal opening CSF pressure. Following treatment with acetazolamide, a complete remission of her symptoms was achieved, accompanied by significant improvement of the fundoscopy findings. Conclusion: Although normal opening CSF pressure in IIH patients is rare, clinicians should be aware of this IIH variant and promptly indicate IIH treatment in patients presenting with typical clinical symptoms and neuroimaging findings suggestive of IIH.

Guillain-Barré syndrome and fulminant encephalomyelitis following Ad26.COV2.S vaccination: double jeopardy.

This correspondence comments on a published article presenting a case of rhombencephalitis following SARS-CoV-2-vaccination with the mRNA vaccine BNT162b2 (Pfizer/BioNTech). We also present the case of a 47-year-old man who developed Guillain-Barré-syndrome and a fulminant encephalomyelitis 28 days after immunization with Ad26.COV2.S (Janssen/Johnson & Johnson). Based on the presented cases, we underscore the importance of clinical awareness for early recognition of overlapping neuroimmunological syndromes following vaccination against SARS-CoV-2. Additionally, we propose that that role of autoantibodies against angiotensin-converting enzyme 2 (ACE2) and the cell-surface receptor neuropilin-1, which mediate neurological manifestations of SARS-CoV-2, merit further investigation in patients presenting with neurological disorders following vaccination against SARS-CoV-2.

Cerebral Amyloid Angiopathy-Related Inflammation: A Single-Center Experience and a Literature Review.

Background: Limited data exist regarding the prevalence of clinical, neuroimaging, and genetic markers among patients diagnosed with Cerebral Amyloid Angiopathy−related inflammation (CAA-ri). We sought to determine these characteristics in patients diagnosed in our center and to summarize available literature published either as single-case reports or small case series (<5 patients). Methods: We reported our single-center experience of patients diagnosed with CAA-ri according to international criteria during a seven-year period (2015−2022), and we abstracted data from 90 previously published cases. Results: Seven patients (43% women, mean age 70 ± 13 years) were diagnosed with CAA-ri in our center. The most common symptom at presentation was focal neurological dysfunction (71%), and the most prevalent radiological finding was the presence of T2/FLAIR white matter hyperintensities (100%). All patients were treated with corticosteroids and had a favorable functional outcome. Among 90 previously published CAA-ri cases (51% women, mean age 70 ± 9 years), focal neurological dysfunction was the most common symptom (76%), followed by a cognitive decline (46%) and headache (34%). The most prevalent neuroimaging findings were cerebral microbleeds (85%), asymmetric T2/FLAIR white matter hyperintensities (81%), and gadolinium-enhancing T1-lesions (37%). Genetic testing for the Apolipoprotein-E gene was available in 27 cases; 59% carried the APOE ε4/ε4 genotype. The majority of the published CAA-ri cases (78%) received corticosteroid monotherapy, while 17 patients (19%) were treated with additional immunosuppressive treatment. Favorable functional outcome following treatment was documented in 70% of patients. Conclusion: Improving the vigilance of clinicians regarding the early recognition and accurate diagnosis of CAA-ri is crucial for swift therapy initiation, which may result in improved functional outcomes.

Plasma Phospho-Tau-181 as a Diagnostic Aid in Alzheimer's Disease.

Cerebrospinal fluid (CSF) biomarkers remain the gold standard for fluid-biomarker-based diagnosis of Alzheimer's disease (AD) during life. Plasma biomarkers avoid lumbar puncture and allow repeated sampling. Changes of plasma phospho-tau-181 in AD are of comparable magnitude and seem to parallel the changes in CSF, may occur in preclinical or predementia stages of the disease, and may differentiate AD from other causes of dementia with adequate accuracy. Plasma phospho-tau-181 may offer a useful alternative to CSF phospho-tau determination, but work still has to be done concerning the optimal method of determination with the highest combination of sensitivity and specificity and cost-effect parameters.

Optic disc drusen mimicking Idiopathic Intracranial Hypertension (IIH): rely on ultrasound.

Optic nerve ultrasound is an established routine supplementary diagnostic tool for idiopathic intracranial pressure but it can also be helpful in avoiding misdiagnoses. We describe a case of an obese 15- year-old girl with persistent headaches, fundoscopic findings suggesting papilledema, normal brain imaging who underwent two lumbar punctures with unremarkable cerebrospinal fluid findings before ultrasound revealed optic disc drusen as the cause of the optic disc elevation.

From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer's Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients.

Analysis of classical cerebrospinal fluid biomarkers, especially when incorporated in a classification/diagnostic system such as the AT(N), may offer a significant diagnostic tool allowing correct identification of Alzheimer's disease during life. We describe four patients with more or less atypical or mixed clinical presentation, in which the classical cerebrospinal fluid biomarkers amyloid peptide with 42 and 40 amino acids (Aß42 and Aß40, respectively), phospho-tau (τP-181) and total tau (τΤ) were measured. Despite the unusual clinical presentation, the biomarker profile was compatible with Alzheimer's disease in all four patients. The measurement of classical biomarkers in the cerebrospinal fluid may be a useful tool in identifying the biochemical fingerprints of Alzheimer's disease, especially currently, due to the recent approval of the first disease-modifying treatment, allowing not only typical but also atypical cases to be enrolled in trials of such treatments.

Glycemic variability of acute stroke patients and clinical outcomes: a continuous glucose monitoring study.

INTRODUCTION: Glycemic variability (GV) has been associated with worse prognosis in critically ill patients. We sought to evaluate the potential association between GV indices and clinical outcomes in acute stroke patients. METHODS: Consecutive diabetic and nondiabetic, acute ischemic or hemorrhagic stroke patients underwent regular, standard-of-care finger-prick measurements and continuous glucose monitoring (CGM) for up to 96 h. Thirteen GV indices were obtained from CGM data. Clinical outcomes during hospitalization and follow-up period (90 days) were recorded. Hypoglycemic episodes disclosed by CGM but missed by finger-prick measurements were also documented. RESULTS: A total of 62 acute stroke patients [48 ischemic and 14 hemorrhagic, median NIHSS score: 9 (IQR: 3-16) points, mean age: 65 ± 10 years, women: 47%, nondiabetic: 79%] were enrolled. GV expressed by higher mean absolute glucose (MAG) values was associated with a lower likelihood of neurological improvement during hospitalization before and after adjusting for potential confounders (OR: 0.135, 95% CI: 0.024-0.751, p = 0.022). There was no association of GV indices with 3-month clinical outcomes. During CGM recording, 32 hypoglycemic episodes were detected in 17 nondiabetic patients. None of these episodes were identified by the periodic blood glucose measurements and therefore they were not treated. CONCLUSIONS: Greater GV of acute stroke patients may be related to lower odds of neurological improvement during hospitalization. No association was disclosed between GV indices and 3-month clinical outcomes.

True Restriction in Diffusion-Weighted Imaging in a Mistreated Patient With Phenylketonuria.

INTRODUCTION: Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism and causes neurological manifestations because of excessive accumulation of phenylalanine (PHE). It can also affect adult patients who discontinue their treatment, even if they had been under adequate metabolic control during childhood. For that reason, it is recommended that PKU treatment should be continued throughout life and target PHE levels for adult patients should range between 120 and 600 µmol/L. CASE REPORT: The authors present an adult patient with PKU who discontinued treatment and developed cognitive dysfunction because of high blood levels of PHE. Brain magnetic resonance imaging (MRI) of the patient was characteristic for PKU, presenting periventricular and callosal white matter hyperintensities in T2 and fluid-attenuated inversion recovery sequences, which were additionally associated with true restriction in diffusion-weighted imaging sequence, a far less recognized PKU neuroimaging feature. DISCUSSION: Cognitive dysfunction and psychiatric disorders can be present in adult patients with PKU who discontinue treatment and have poor PHE metabolic control. The presence of white matter hyperintensities in T2 and fluid-attenuated inversion recovery MRI-sequences is a well-described neuroimaging feature of PKU, but diffusion-weighted imaging sequence may also be reliable in detecting brain lesions in patients with PKU. PKU lesions should be considered in the differential diagnosis of true diffusion restriction in brain MRI of patients with PKU history or those who might have escaped newborn screening diagnosis but present neurocognitive dysfunction. Appropriate treatment for the management of PKU should be initiated for the reversal of the clinical and neuroimaging findings.