Abstract Background Plasma neurofilament light chain (NfL) levels reflect large calibre myelinated axonal loss; and has been proposed as a blood‐based biomarker for neurodegeneration in dementia and parkinsonian disorders. Recent studies have suggested an association between increased plasma NfL levels and worse global cognition in Parkinson’s Disease (PD) patients. However, its relationship with specific cognitive domains remain unclear. This study thus aims to investigate the association between plasma NfL and cognitive domains in early PD. Method Plasma NfL was measured using Quanterix’s Single Molecule Array (Simoa) technology in a total of 197 subjects (175 early PD patients and 22 healthy controls). Cognitive function was assessed using a standard battery of neuropsychological tests. This included the Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) as tests of global cognition, as well as two tests for each of five relevant cognitive domains, namely episodic memory, language, working memory, visuospatial, and executive function. Result PD patients had higher plasma NfL levels (mean=16.3 pg/ml, SD=8.59) compared to healthy controls (mean=12.2 pg/ml, SD = 4.18) ( p= .023). Amongst PD patients, increased NfL levels associated significantly with worse global cognition scores (MMSE: b=‐1.11 p =.009; MoCA: b=‐1.27, p =.026). In particular, higher levels of plasma NfL significantly correlated with poorer episodic memory (b=‐.541, p =.003) and executive function scores (b=‐.427, p =.002). No significant associations were found between plasma NfL and cognitive measures in healthy controls. Conclusion Higher plasma NfL levels were found in PD patients compared to healthy controls and associated significantly with poorer global cognitive function in PD. Interestingly, higher NfL levels correlated with worse episodic memory and executive function. These results implicate plasma NfL’s role as a potential biomarker for cognition in PD. Further studies are required to validate these findings.
We screened 662 subjects comprising 462 essential tremor (ET) subjects (285 sporadic, 125 with family history, and 52 probands from well‐characterized ET pedigrees) and 200 controls and identified pathogenic NOTCH2NLC GGC repeat expansions in 4 sporadic ET patients. Two patients were followed up for >1 decade; one with 90 repeats remained an ET phenotype that did not evolve after 40 years, whereas another patient with 107 repeats developed motor symptoms and cognitive impairment after 8 to 10 years. Neuroimaging in this patient revealed severe leukoencephalopathy; diffusion‐weighted imaging hyperintensity in the corticomedullary junction and skin biopsy revealed intranuclear inclusions suggestive of intranuclear inclusion body disease (NIID). No GGC repeats of >60 units were detected in familial ET cases and controls, although 4 ET patients carried 47 to 53 “intermediate” repeats. NOTCH2NLC GGC repeat expansions can be associated with sporadic ET. Carriers presenting with a pure ET phenotype may or may not convert to NIID up to 4 decades after initial tremor onset. ANN NEUROL 2020;88:614–618
Marginal zone lymphoma (MZL) is an indolent lymphoma that rarely involves the central nervous system (CNS). Clonal B-cell lymphomatosis of marginal zone origin (CBL-MZ) is a premalignant condition referring to the presence of clonal B cells in the peripheral blood without evidence of organomegaly, lymphadenopathy or other features of established lymphoma, which may uncommonly progress to MZL, and as such does not require treatment beyond active surveillance. A 54-year-old male with previously diagnosed CBL-MZ presented with multiple recurrent subcortical ischaemic strokes. There was no evidence of progression to overt MZL or secondary transformation on repeated evaluation. His strokes proved refractory to antithrombotic therapy and anticoagulation. The absence of significant cardiovascular risk factors led to an extensive evaluation which excluded secondary causes such as cardioembolism, prothrombotic state or systemic vasculitis. Eventually, he was found to have lymphomatous involvement of the cerebrospinal fluid. The recurrent ischaemic strokes were attributed to a cerebral small vessel vasculopathy from neoplastic meningitis, which prompted the initiation of chemotherapy, leading to a remarkable cessation of stroke recurrence. This case highlights the importance of considering CNS involvement even in indolent or premalignant lymphomas when these patients present with "cryptogenic" recurrent strokes that appear refractory to standard secondary stroke prevention therapy. We also describe the approach to recurrent ischaemic stroke, the importance of imaging to determine the stroke mechanism, and the approach to small vessel cerebral arteriopathies.
Objective Following the outbreak of coronavirus 2019 (COVID-19), there is strong evidence of neurological involvement in these patients. We aimed to determine the clinical characteristics of neurological manifestations in COVID-19.
Progressive supranuclear palsy (PSP) with predominant cerebellar ataxia (PSP-C) is a rare phenotype of PSP. The clinical and radiological features of this disorder remain poorly characterized. Through a retrospective case series, we aim to characterize the clinical and radiological features of PSP-C. Four patients with PSP-C were identified: patients who presented with prominent cerebellar dysfunction that disappeared with the progression of the disease. Supranuclear gaze palsy occurred at a mean of 2.0 ± 2.3 years after the onset of ataxia. Mild cerebellar volume loss and midbrain atrophy were detected on brain imaging, which are supportive of a diagnosis of PSP. Videos are presented illustrating the co-existence of cerebellar signs and supranuclear gaze palsy and the disappearance of cerebellar signs with disease progression. Better recognition and the development of validated diagnostic criteria would aid in the antemortem recognition of this rare condition.
This paper introduces an integrated fiber physical unclonable function (PUF) verification system based on a semiconductor laser source at substantially lower complexity and cost than existing alternatives. A source sub-section consisting of a linear frequency-swept semiconductor laser is used in combination with an optical frequency domain reflectometry (OFDR)/LiDAR-based measurement sub-section in order to conduct fiber identification via measurement of the unique Rayleigh reflection pattern of a section of optical fiber. When using these Rayleigh reflection patterns as PUFs, this technique results in a maximum equal error rate (EER) of 0.15% for a 5-cm section of optical fiber and an EER of less than 1% for a 4-cm section. These results demonstrate that the system can serve as a robust method fiber identification for device and communication verification applications.
An elderly Singaporean male with no travel history was hospitalized for fever and altered mental status. Blood cultures grew Enterococcus faecalis, and given a preceding history of steroid use and peripheral eosinophilia, Strongyloides hyperinfection was suspected. Stool specimens were positive for Strongyloides stercoralis larvae over four days, and larvae were also isolated in an early morning nasogastric aspirate specimen prior to initiation of ivermectin. A cerebrospinal fluid examination was consistent with partially treated bacterial meningitis and ventriculitis was demonstrated on neuroimaging. In view of a persistent fever, a further imaging evaluation was performed, which demonstrated bilateral pneumonia as well as the unusual finding of gas-forming emphysematous spondylodiscitis and left psoas abscesses. Despite the early suspicion of Strongyloides hyperinfection, commencement of appropriate antibiotics and anti-helminthics, microbiological clearance of bacteremia as well as clearance of S. stercoralis from the stool, the patient still succumbed to infection and passed away 11 days after admission.
Olfactory dysfunction is a robust and early sign for Parkinson's disease (PD). Previous studies have revealed its association with dementia and related neural changes in PD. Yet, how olfactory dysfunction affects white matter (WM) microstructure in newly diagnosed and untreated PD remains unclear. Here we comprehensively examined WM features using unbiased whole-brain analyses. 88 newly diagnosed PD patients without dementia (70 with hyposmia and 18 without hyposmia) and 33 healthy controls underwent clinical assessment and diffusion tensor imaging (DTI) scanning. Tract-based special statistics (TBSS), graph-theoretic methods and network-based statistics (NBS) were used to compare regional and network-related WM features between groups. TBSS analysis did not show any differences in fractional anisotropy and mean diffusivity between groups. Compared with controls, PD patients without hyposmia showed a significant decrease in global efficiency, whilst PD patients with hyposmia exhibited significantly reduced global and local efficiency and additionally a disrupted connection between the right medial orbitofrontal cortex and left rectus and had poorer frontal-related cognitive functioning. These results demonstrate that hyposmia-related WM changes in early PD only occur at the network level. The confined disconnectivity between the bilateral olfactory circuitry may serve as a biomarker for olfactory dysfunction in early PD.
Abstract Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder associated with GGC repeats of >60 to 500 copies in the 5′‐untranslated region of NOTCH2NLC . The clinical and genetic characterization of NIID outside of East Asia remains unknown. We identified twelve patients who underwent genetic testing using long‐read sequencing or repeat primed polymerase chain reaction. All were positive for a GGC repeat expansion; the median repeat length was 107 (range 92‐138). Ten were Chinese and two of Malay ethnicity. Age at onset ranged from 50 to 69 years. Eight (66.7%) patients had dementia, while four (33.3%) patients were oligosymptomatic, without typical NIID symptoms of dementia, Parkinsonism, or muscle weakness. GGA interruptions within the GGC expansion were present in four patients; the number of GGA interruptions was highest (6.71%) in the patient with the earliest age at onset (50 years). Median plasma neurofilament light level was 47.3 pg/mL in seven patients (range 26‐380 pg/mL). The highest level (380 pg/mL) was found in one patient who experienced an encephalitic episode. Overall, we describe a cohort of genetically confirmed NIID patients from Southeast Asia and provide further information that the presence of GGA interruptions within GGC repeat expansions may serve as a potential genetic modifier in NIID.
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