Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson’s disease.

Compound heterozygous mutations in the neuraminidase 1 gene in type 1 sialidosis: A case report and review of literature

BACKGROUND Type 1 sialidosis,also known as cherry-red spot-myoclonus syndrome,is a rare autosomal recessive lysosomal storage disorder presenting in the second decade of life.The most common symptoms are myoclonus,ataxia and seizure.It is rarely encountered in the Chinese mainland.CASE SUMMARY A 22-year-old male presented with complaints of progressive myoclonus,ataxia and slurred speech,without visual symptoms;the presenting symptoms began at the age of 15-year-old.Whole exome sequencing revealed two pathogenic heterozygous missense variants[c.239C>T(p.P80L)and c.544A>G(p.S182G)in the neuraminidase 1(NEU1)gene],both of which have been identified previously in Asian patients with type 1 sialidosis.All three patients identified in China's Mainland come from three unrelated families,but all three show the NEU1 mutations p.S182G and p.P80L pathogenic variants.Increasing sialidase activity through chaperones is a promising therapeutic target in sialidosis.CONCLUSION Through retrospective analysis and summarizing the clinical and genetic characteristics of type 1 sialidosis,we hope to raise awareness of lysosomal storage disorders among clinicians and minimize the delay in diagnosis.

A multiple-tissue-specific magnetic resonance imaging model for diagnosing Parkinson’s disease: a brain radiomics study

Brain radiomics can reflect the characteristics of brain pathophysiology.However,the value of T1-weighted images,quantitative susceptibility mapping,and R2*mapping in the diagnosis of Parkinson’s disease(PD)was underestimated in previous studies.In this prospective study to establish a model for PD diagnosis based on brain imaging information,we collected high-resolution T1-weighted images,R2*mapping,and quantitative susceptibility imaging data from 171 patients with PD and 179 healthy controls recruited from August 2014 to August 2019.According to the inclusion time,123 PD patients and 121 healthy controls were assigned to train the diagnostic model,while the remaining 106 subjects were assigned to the external validation dataset.We extracted 1408 radiomics features,and then used data-driven feature selection to identify informative features that were significant for discriminating patients with PD from normal controls on the training dataset.The informative features so identified were then used to construct a diagnostic model for PD.The constructed model contained 36 informative radiomics features,mainly representing abnormal subcortical iron distribution(especially in the substantia nigra),structural disorganization(e.g.,in the inferior temporal,paracentral,precuneus,insula,and precentral gyri),and texture misalignment in the subcortical nuclei(e.g.,caudate,globus pallidus,and thalamus).The predictive accuracy of the established model was 81.1±8.0%in the training dataset.On the external validation dataset,the established model showed predictive accuracy of 78.5±2.1%.In the tests of identifying early and drug-naïve PD patients from healthy controls,the accuracies of the model constructed on the same 36 informative features were 80.3±7.1%and 79.1±6.5%,respectively,while the accuracies were 80.4±6.3%and 82.9±5.8%for diagnosing middle-to-late PD and those receiving drug management,respectively.The accuracies for predicting tremor-dominant and non-tremor-dominant PD were 79.8±6.9%and 79.1±6.5%,respectively.In conclusion,the multiple-tissue-specific brain radiomics model constructed from magnetic resonance imaging has the ability to discriminate PD and exhibits the advantages for improving PD diagnosis.

Andersen-Tawil syndrome associated with myopathy

Dear editor,Andersen-Tawil syndrome(ATS)is a rare cause of periodic paralysis.The inheritance pattern of ATS is autosomal dominant.It is characterized by periodic paralysis,arrhythmias,and distinctive appearances.[1]ATS has been linked to mutations in the KCNJ2 gene that causes defective inward-rectifi er potassium channel Kir2.1,[2]which plays an important role in stabilizing resting membrane potential in both skeletal and cardiac muscles.[3]There are few reports[4,5]concerning ATS in the Chinese population.The potentially reversible muscular weakness and potentially life-threatening ventricular arrhythmia require early diagnosis.In this report,we presented one case of ATS who had the symptoms of persistent bilateral proximal limb weakness and mildly elevated creatinine kinase.This patient was initially diagnosed with myopathy.Periodic paralysis,dysmorphic feature,and heterozygous mutation of R218Q in KCNJ2 led us to the diagnosis of ATS.

Treatment of extracranial internal carotid artery dissecting aneurysm with SUPERA stent implantation:Two case reports

BACKGROUND There is no standard endovascular treatment for extracranial internal carotid artery dissecting aneurysms.In the past,stent-graft isolation and stent-assisted coil embolization were commonly used for wide-necked and fusiform aneurysms.Here,we present two cases of extracranial internal carotid artery dissecting aneurysms treated successfully using the SUPERA stent.CASE SUMMARY Case 1 was a 57-year-old male patient with sudden right limb weakness and vague speech and diagnosed with cerebral infarction in February 2019.Cervical computed tomographic angiography(CTA)revealed left internal carotid artery dissection with stenosis.CTA at 2 mo showed an eccentric wide-necked dissecting aneurysm(5 mm×5 mm×12 mm,10-mm neck)that was enlarged at 4 mo(7 mm×6 mm×12 mm,11-mm neck).The patient underwent SUPERA stent implantation.His condition was stable in July 2020.Case 2 was a 57-year-old man who suddenly felt dizzy and developed unsteady walking in November 2019.Cervical CTA suggested right internal carotid artery dissecting aneurysm(11 mm×9 mm×31 mm)complicated with severe lumen stenosis(95%).The patient underwent SUPERA stent implantation.The patient had no residual symptoms and was stable in December 2020.CONCLUSION SUPERA stent implantation might achieve good results in treating wide-necked or long fusiform internal carotid artery dissecting aneurysms.

Unilateral Isolated Basal Vein Thrombosis Associated with Deep Cerebral Venous Infarction

To the Editor： In the literature, there are few reports about unilateral isolated basal vein thrombosis. Owler et al.reported the first case with imaging evidence in 2004.

Soluble N-terminal fragment of mutant Huntingtin protein impairs mitochondrial axonal transport in cultured hippocampal neurons

Huntington＇s disease （HD） is an autosomal dominant, progressive, neurodegenerative disorder caused by an unstable expansion of CAG repeats （〉35 repeats） within exon 1 of the interesting transcript 15 （IT15） gene. This gene encodes a protein called Huntingtin （Htt）, and mutation of the gene results in a polyglutamine （polyQ） near the N-terminus of Htt. The N-terminal fragments of mutant Htt （mHtt）, which tend to aggregate, are sufficient to cause HD. Whether these aggregates are causal or protective for HD remains hotly debated. Dysfunctional mitochondrial axonal transport is associated with HD. It remains unknown whether the soluble or aggregated form of mHtt is the primary cause of the impaired mitochondrial axonal transport in HD pathology. Here, we investigated the impact of soluble and aggregated N-terminal fragments of mHtt on mitochondrial axonal transport in cultured hippocampal neurons. We found that the N-terminal fragment of mHtt formed aggregates in almost half of the transfected neurons. Overexpression of the N-terminal fragment of mHtt decreased the velocity of mitochondrial axonal transport and mitochondrial mobility in neurons regardless of whether aggregates were formed. However, the impairment of mitochondrial axonal transport in neurons expressing the soluble and aggregated N-terminal fragments of mHtt did not differ. Our findings indicate that both the soluble and aggregated N-terminal fragments of mHtt impair mitochondrial axonal transport in cultured hippocampal neurons. We predict that dysfunction of mitochondrial axonal transport is an early-stage event in the progression of HD, even before mHtt aggregates are formed.

Genetic profile of Chinese patients with Charcot-Marie-Tooth disease

To the Editor:Charcot-Marie-Tooth disease(CMT)encompasses a genetically heterogeneous group of inherited neuropathies,characterized by progressive distal muscle weakness and atrophy,sensory deficits,impaired tendon reflexes,and foot deformities.[1]To date,more than 80 causative genes have been identified in CMT patients,associated with either autosomal dominant or recessive inheritance,or X-linked transmission.The traditional classification of CMT was based on peripheral neuropathy type,as determined by nerve conduction velocity.As more causative genes were identified and the overlap of neuropathy phenotypes became apparent,the traditional classification system proved unwieldy and inadequate.Moreover,CMT needs to be distinguished from several entities including systemic disorders with neuropathy and other types of hereditary neuropathy.In clinical practice,overlap of phenotypes can present a major challenge in reaching the correct diagnosis.This study aimed to investigate the genetic profile in a cohort of Chinese CMT patients and evaluate the role of genetic testing in the diagnosis and subtyping of CMT.