COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital
We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74  years (38–97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, sev en (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients d...
Source: Brain - April 15, 2021 Category: Neurology Source Type: research

Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy
In conclusion, we identified variants in theLIG3 gene that result in a mitochondrial disease characterized by predominant gut dysmotility, encephalopathy, and neuromuscular abnormalities. (Source: Brain)
Source: Brain - April 15, 2021 Category: Neurology Source Type: research

Photo-oxygenation by a biocompatible catalyst reduces amyloid- β levels in Alzheimer’s disease mice
In this study, we demonstrate that photo-oxygenation facilitates the clearance of aggregated amyloid- β from the brains of living Alzheimer’s disease model mice, and enhances the microglial degradation of amyloid-β peptide. These results suggest that photo-oxygenation may represent a novel anti-amyloid-β strategy in Alzheimer’s disease, which is compatible with immunotherapy. (Source: Brain)
Source: Brain - April 14, 2021 Category: Neurology Source Type: research

Erratum to: Gamma subunit of complement component 8 is a neuroinflammation inhibitor
Jong-Heon Kim, Ruqayya Afridi, Jin Han, Hyun-Gug Jung, Seung-Chan Kim, Eun Mi Hwang, Hyun Soo Shim, Hoon Ryu, Youngshik Choe, Hyang-Sook Hoe and Kyoungho Suk. Gamma subunit of complement component 8 is a neuroinflammation inhibitor.Brain. 2021;144:528 –552. doi:10.1093/brain/awaa425 (Source: Brain)
Source: Brain - April 14, 2021 Category: Neurology Source Type: research

Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder
AbstractIsolated REM sleep behaviour disorder (RBD) is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological α-synuclein in peripheral tissues of patients with isolated RBD may identify those progressing to Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testing preve ntive therapies. Real-time quaking-induced conversion (RT-QuIC) provided evidence of α-synuclein seeding activity in CSF and olfactory mucosa of patients with α-synucleinopathies. The aim of this study was to explore RT-QuIC detection of α-synuclein aggreg...
Source: Brain - April 14, 2021 Category: Neurology Source Type: research

De novo purine biosynthesis is a major driver of chemoresistance in glioblastoma
AbstractGlioblastoma is a primary brain cancer with a near 100% recurrence rate. Upon recurrence, the tumour is resistant to all conventional therapies, and because of this, 5-year survival is dismal. One of the major drivers of this high recurrence rate is the ability of glioblastoma cells to adapt to complex changes within the tumour microenvironment. To elucidate this adaptation's molecular mechanisms, specifically during temozolomide chemotherapy, we used chromatin immunoprecipitation followed by sequencing and gene expression analysis. We identified a molecular circuit in which the expression of ciliary protein ADP-ri...
Source: Brain - April 14, 2021 Category: Neurology Source Type: research

Classification of neurological diseases using multi-dimensional CSF analysis
AbstractAlthough CSF analysis routinely enables the diagnosis of neurological diseases, it is mainly used for the gross distinction between infectious, autoimmune inflammatory, and degenerative disorders of the CNS. To investigate, whether a multi-dimensional cellular blood and CSF characterization can support the diagnosis of clinically similar neurological diseases, we analysed 546 patients with autoimmune neuroinflammatory, degenerative, or vascular conditions in a cross-sectional retrospective study. By combining feature selection with dimensionality reduction and machine learning approaches we identified pan-disease p...
Source: Brain - April 13, 2021 Category: Neurology Source Type: research

Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis
In this study, we identified 10 new cases and reviewed 16 previously reported patients, investigating clinical features, IgG subclasses, human leucocyte antigen and CSF proteomic profiles. Patients with anti-AK5 limbic encephalitis were mostly male (20/26, 76.9%) with a median age of 66  years (range 48–94). The predominant symptom was severe episodic amnesia in all patients, and this was frequently associated with depression (17/25, 68.0%). Weight loss, asthenia and anorexia were also highly characteristic, being present in 11/25 (44.0%) patients. Although epilepsy was always lacking at disease onset, seizures develop...
Source: Brain - April 12, 2021 Category: Neurology Source Type: research

Uncovering the prevalence and neural substrates of anhedonia in frontotemporal dementia
AbstractMuch of human behaviour is motivated by the drive to experience pleasure. The capacity to envisage pleasurable outcomes and to engage in goal-directed behaviour to secure these outcomes depends upon the integrity of frontostriatal circuits in the brain. Anhedonia refers to the diminished ability to experience, and to pursue, pleasurable outcomes, and represents a prominent motivational disturbance in neuropsychiatric disorders. Despite increasing evidence of motivational disturbances in frontotemporal dementia (FTD), no study to date has explored the hedonic experience in these syndromes. Here, we present the first...
Source: Brain - April 12, 2021 Category: Neurology Source Type: research

Prevalence and severity of neurovascular compression in hemifacial spasm patients
AbstractHemifacial spasm is typically caused by vascular compression of the proximal intracranial facial nerve. Although the prevalence of neurovascular compression has been investigated in a cohort of patients with classical trigeminal neuralgia, the prevalence and severity of neurovascular compression has not been well characterized in patients with hemifacial spasm. We aimed to investigate whether presence and severity of neurovascular compression are correlated to the symptomatic side in patients with hemifacial spasm. All patients in our study were evaluated by a physician who specializes in the management of cranial ...
Source: Brain - April 11, 2021 Category: Neurology Source Type: research

Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state
AbstractDeposits of different abnormal forms of tau in neurons and astrocytes represent key anatomo-pathological features of tauopathies. Although tau protein is highly enriched in neurons and poorly expressed by astrocytes, the origin of astrocytic tau is still elusive. Here, we used innovative gene transfer tools to model tauopathies in adult mouse brains and to investigate the origin of astrocytic tau. We showed in our adeno-associated virus (AAV)-based models and in Thy-Tau22 transgenic mice that astrocytic tau pathology can emerge secondarily to neuronal pathology. By designing anin vivo reporter system, we further de...
Source: Brain - April 11, 2021 Category: Neurology Source Type: research

Functional cognitive disorder: dementia ’s blind spot
We welcome the article by Ball and colleagues on functional cognitive disorder (FCD), since it draws attention to a common and important clinical presentation.1 We agree with the authors that distinguishing cognitive symptoms that have a psychological basis from those that have an organic basis is particularly important in the area of dementia diagnosis. We nevertheless have concerns about some of the key messages in the article. (Source: Brain)
Source: Brain - April 10, 2021 Category: Neurology Source Type: research

Reply: The etymology of ‘neurology’, redux: early use of the term by Jean Riolan the Younger (1610)
It is axiomatic that those who claim priority for dates and details on behalf of specific individuals celebrated in the history of medicine (and other disciplines) give hostages to fortune on the accuracy of who first said ‘what’ and ‘when’. Dr Janssen points out that the Parisian anatomist, Jean Riolan the Younger (1580–1657), used the word ‘neurology’ before Thomas Willis (1621–75).1 We stand corrected. As an aside, unlike Riolan, Willis preferred Greek typography when using the word ‘νευρολογία’, accurately reflecting the derivation of the compound word. In the passages to which Dr Janssen ...
Source: Brain - April 10, 2021 Category: Neurology Source Type: research

The etymology of ‘neurology’, redux: early use of the term by Jean Riolan the Younger (1610)
(Source: Brain)
Source: Brain - April 10, 2021 Category: Neurology Source Type: research

Two heterozygous progranulin mutations in progressive supranuclear palsy
(Source: Brain)
Source: Brain - April 9, 2021 Category: Neurology Source Type: research