GGC repeat expansions in NOTCH2NLC cause uN2CpolyG cerebral amyloid angiopathy.

The expansion of GGC repeats within NOTCH2NLC leads to the translation of the uN2CpolyG protein, the primary pathogenic factor in neuronal intranuclear inclusion disease (NIID). This study aims to explore the deposition of uN2CpolyG as an amyloid in the vessel wall, leading to uN2CpolyG cerebral amyloid angiopathy (CAA)-related cerebral microbleeds (CMBs). A total of 97 patients with genetically confirmed NIID were enrolled in this study. We analyzed the presence of CMBs using susceptibility-weighted imaging sequences and compared general clinical information, cerebrovascular risk factors, stroke history, antiplatelet medication use, and MRI features between NIID patients with and without CMBs. We further performed hematoxylin and eosin (H&E), Perl's, Congo red, and Thioflavin S staining, ubiquitin, p62 and uN2CpolyG immunostaining on brain tissue obtained from four NIID patients. A total of 354 CMBs were detected among 41 patients with NIID, with nearly half located in the deep brain, one-third in the lobes, and approximately 20% in the infratentorial area. No significant differences in cerebrovascular disease risk factors or history of antiplatelet drug use were observed between patients with and without CMBs. However, patients with CMBs suffered a higher incidence of previous ischemic and hemorrhagic stroke events. This group also had a higher incidence of recent subcortical infarcts and a higher proportion of white matter lesions in the external capsule and temporal pole. Conversely, patients without CMBs showed higher detection of high signals at the corticomedullary junction on diffusion-weighted imaging and more pronounced brain atrophy. H&E staining showed blood vessel leakage and hemosiderin-laden macrophage clusters, and Prussian blue staining revealed brain tissue iron deposition. CMBs occurred more frequently in small vessels lacking intranuclear inclusions, and extensive degeneration of endothelial cells and smooth muscle fibres was observed mainly in vessels lacking inclusions. Congo red-positive amyloid deposition was observed in the cerebral vessels of NIID patients, with disordered filamentous fibres appearing under an electron microscope. Additionally, the co-localization of Thioflavin S-labeled amyloid and uN2CpolyG protein in the cerebral vascular walls of NIID patients further suggested that uN2CpolyG is the main pathogenic protein in this form of amyloid angiopathy. In conclusion, we reviewed patients with GGC repeat expansion of NOTCH2NLC from a novel perspective, providing initial clinical, neuroimaging, and pathological evidence suggesting that uN2CpolyG may contribute to a distinct type of CAA.

Utility of labial salivary gland biopsy in the histological diagnosis of neuronal intranuclear inclusion disease.

BACKGROUND AND PURPOSE: Neuronal intranuclear inclusion disease (NIID) poses a diagnostic challenge because of its diverse clinical manifestations. Detection of intranuclear inclusions remains the primary diagnostic criterion for NIID. Skin biopsies have traditionally been used, but concerns exist regarding postoperative complications and scarring. We sought to investigate the diagnostic utility of labial salivary gland biopsy, a less invasive alternative. METHODS: This study included a total of 19 patients and 11 asymptomatic carriers who underwent labial gland biopsies, while 10 patients opted for skin biopsies. All these individuals were confirmed to have pathogenic GGC repeat expansions in the NOTCH2NLC gene. The control group comprised 20 individuals matched for age and sex, all with nonpathogenic GGC repeat expansions, and their labial gland tissue was sourced from oral surgery specimens. RESULTS: Labial gland biopsies proved to be a highly effective diagnostic method in detecting eosinophilic intranuclear inclusions in NIID patients. The inclusions showed positive staining for p62 and ubiquitin, confirming their pathological significance. The presence of uN2CpolyG protein in the labial gland tissue further supported the diagnosis. Importantly, all patients who underwent lip gland biopsy experienced fast wound healing without any noticeable scarring. In contrast, skin biopsies led to varying degrees of scarring and one instance of a localized infection. CONCLUSION: Labial salivary gland biopsy emerged as a minimally invasive, efficient diagnostic method for NIID, with rapid healing and excellent sensitivity.

Detection and prediction of freezing of gait with wearable sensors in Parkinson's disease.

Freezing of gait (FoG) is one of the most distressing symptoms of Parkinson's Disease (PD), commonly occurring in patients at middle and late stages of the disease. Automatic and accurate FoG detection and prediction have emerged as a promising tool for long-term monitoring of PD and implementation of gait assistance systems. This paper reviews the recent development of FoG detection and prediction using wearable sensors, with attention on identifying knowledge gaps that need to be filled in future research. This review searched the PubMed and Web of Science databases to collect studies that detect or predict FoG with wearable sensors. After screening, 89 of 270 articles were included. The data description, extracted features, detection/prediction methods, and classification performance were extracted from the articles. As the number of papers of this area is increasing, the performance has been steadily improved. However, small datasets and inconsistent evaluation processes still hinder the application of FoG detection and prediction with wearable sensors in clinical practice.

Causal Associations between Tea Consumption and Rapid Eye Movement Sleep Behavior Disorder: A Mendelian Randomization Study.

INTRODUCTION: Previous studies have shown that tea consumption may have a protective effect against neurodegenerative diseases. However, the exact causal relationship between tea consumption and the precursor stages of certain neurodegenerative diseases, namely, REM sleep behavior disorder (RBD), remains unclear. To evaluate the causal association between tea consumption and RBD, we employed a Mendelian randomization study. METHODS: We identified genetic instrumental variables that are significantly associated with tea consumption through genome-wide association studies (GWAS) in European populations. Bidirectional two-sample Mendelian randomization was utilized to determine the causal relationship between tea consumption and RBD, while sensitivity analyses were further employed to evaluate the robustness of the results. The multivariate Mendelian randomization method was used to assess the influence of relevant confounding factors on the results. RESULTS: In the MR analysis using the inverse-variance weighting method, a significant causal relationship between tea consumption and RBD was observed (OR = 0.046, 95% CI: 0.004-0.563, p = 0.016). The consistency of findings across maximum likelihood, MR Pleiotropy RESidual Sum and Outlier, and multivariate MR after adjusting for potential confounding further supports this causal association. Sensitivity analyses revealed no evidence of heterogeneity or pleiotropy. CONCLUSIONS: The findings of our study demonstrate a robust causal association between tea consumption and RBD, indicating that tea consumption may serve as a protective factor against the development of RBD.

Corneal nerve fibre loss as a marker to identify the impact of diabetes on Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease (PD) suffer from serious quality of life problems. Diabetes has been demonstrated as an independent risk element for PD, aggravating its severity and accelerating its progression. There are currently no suitable biomarkers to reveal the impact of diabetes on PD. The purpose of our research was to study the impact of diabetes on PD using corneal confocal microscopy (CCM), a non-invasive and objective test. METHODS: Fourteen PD patients with diabetes (PD-DM), 60 PD patients without diabetes (PD-NDM), and 30 healthy controls (HC) were included in the study. The clinical symptoms of patients with PD were assessed using the Unified Parkinson's Disease Rating Scale-3 (UPDRS-3) and the Parkinson's Disease Autonomic Symptom Prognosis Scale (SCOPA-AUT). Participants underwent CCM to quantify the corneal nerve fibres. RESULTS: Corneal nerve fibre density (CNFD) and corneal nerve fibre length (CNFL) in patients with PD were lower than HC. Furthermore, CNFD in PD-DM was lower than in PD-NDM (P < 0.01). We also assessed the relationship between CCM parameters and clinical scores. CNFL and Hamilton anxiety (HAMA) have a negative correlation (r = -0.261, P = 0.032), but this study did not observe a significant correlation between CCM parameters and SCOPA-AUT. Additionally, CNFD could distinguish PD-DM from PD-NDM, achieving an area under the curve of 75.06% (95% CI, 61.76%-88.36%). CONCLUSIONS: The CCM could be served as an objective and sensitive biomarker to investigate the impact of diabetes in PD.

Relationship between increased serum neurofilament light chain and glial fibrillary acidic protein levels with non-motor symptoms in patients with Parkinson's disease.

BACKGROUND: This study set out to investigate the relationship between serum neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and various non-motor symptoms (NMSs) in patients with Parkinson's disease (PD). METHODS: The study included 37 healthy controls (HCs) and 51 PD patients. Clinical assessments of PD symptoms were conducted for all PD patients. The NMSS was utilised to evaluate the NMS burden (NMSB) in individuals. Based on the severity of NMSB, we further categorised the PD group into two subgroups: mild-moderate NMSB group and severe-very severe NMSB group. The amounts of NFL and GFAP in the serum were measured using an extremely sensitive single molecule array (Simoa) method. Statistical analyses were performed on the collected data using SPSS 26.0 and R (version 3.6.3). RESULTS: Serum GFAP and NFL levels in the PD group with severe-very severe NMSB were significantly higher than those in the mild-moderate NMSB group (GFAP: P < 0.007; NFL: P < 0.009). Serum NFL and GFAP levels had positive correlations with NMSS total scores (GFAP: r = 0.326, P = 0.020; NFL: r = 0.318, P = 0.023) and multiple subdomains. The relationship between the attention/memory domains of NMSS and NFL levels is significantly positive (r = 0.283, P = 0.044). Similarly, the mood/apathy domains of NMSS are also significantly positively correlated with GFAP levels (r = 0.441, P = 0.001). Patients with emotional problems or cognitive impairment had higher GFAP or NFL levels, respectively. Furthermore, it has been demonstrated that NMSs play a mediating role in the quality of life of patients with PD. Moreover, the combination of NFL and GFAP has proven to be more effective than using a single component in identifying PD patients with severe-very severe NMSB. CONCLUSIONS: The severity of NMSs in PD patients, particularly cognitive and emotional symptoms, was found to be associated with the levels of serum NFL and GFAP. This study marks the first attempt to examine the connection between NMSs of PD and the simultaneous identification of NFL and GFAP levels.

The relationship between serum neurofilament light chain and glial fibrillary acidic protein with the REM sleep behavior disorder subtype of Parkinson's disease.

Studies have shown that rapid eye movement (REM) sleep behavior disorder (RBD) is a subtype of Parkinson's disease (PD) characterized by severe cognitive impairment and rapid disease progression. However, reliable biological markers are lacking presently. Neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) have been widely studied as biomarkers of cognition impairment. This study aimed to find biomarkers for the RBD subtype of PD by investigating the possible relationship between serum NFL, GFAP levels, and the RBD subtype. A total of 109 PD patients and 37 healthy controls (HCs) were included, and their clinical characteristics were evaluated. PD patients were divided into two groups based on whether they had probable RBD or not. Serum NFL and GFAP levels were measured using the ultrasensitive single molecule array (Simoa) platform. The obtained data were statistically analyzed using SPSS 25.0 (IBM, Chicago, IL, USA). NFL and GFAP in the PD-RBD group were elevated compared with the PD-nRBD and control groups. Moreover, serum NFL and GFAP levels positively correlated with RBD. The combination of NFL and GFAP showed good performance in identifying PD-RBD patients from PD-nRBD. After considering potential confounding factors such as age, and disease duration, serum NFL and GFAP emerged as independent risk factors for RBD. Serum NFL and GFAP were related to RBD in PD patients. Concludingly, serum NFL and GFAP might serve as promising biomarkers for the RBD subtype of PD.

Upregulation of MDH1 acetylation by HDAC6 inhibition protects against oxidative stress-derived neuronal apoptosis following intracerebral hemorrhage.

Oxidative stress impairs functional recovery after intracerebral hemorrhage (ICH). Histone deacetylase 6 (HDAC6) plays an important role in the initiation of oxidative stress. However, the function of HDAC6 in ICH and the underlying mechanism of action remain elusive. We demonstrated here that HDAC6 knockout mice were resistant to oxidative stress following ICH, as assessed by the MDA and NADPH/NADP+ assays and ROS detection. HDAC6 deficiency also resulted in reduced neuronal apoptosis and lower expression levels of apoptosis-related proteins. Further mechanistic studies showed that HDAC6 bound to malate dehydrogenase 1 (MDH1) and mediated-MDH1 deacetylation on the lysine residues at position 121 and 298. MDH1 acetylation was inhibited in HT22 cells that were challenged with ICH-related damaging agents (Hemin, Hemoglobin, and Thrombin), but increased when HDAC6 was inhibited, suggesting an interplay between HDAC6 and MDH1. The acetylation-mimetic mutant, but not the acetylation-resistant mutant, of MDH1 protected neurons from oxidative injury. Furthermore, HDAC6 inhibition failed to alleviate brain damage after ICH when MDH1 was knockdown. Taken together, our study showed that HDAC6 inhibition protects against brain damage during ICH through MDH1 acetylation.

Current advances in neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a rare but probably underdiagnosed neurodegenerative disorder due to pathogenic GGC expansions in the NOTCH2NLC gene. In this review, we summarize recent developments in the inheritance features, pathogenesis, and histopathologic and radiologic features of NIID that subvert the previous perceptions of NIID. GGC repeat sizes determine the age of onset and clinical phenotypes of NIID patients. Anticipation may be absent in NIID but paternal bias is observed in NIID pedigrees. Eosinophilic intranuclear inclusions in skin tissues once considered pathological hallmarks of NIID can also present in other GGC repeat diseases. Diffusion-weighted imaging (DWI) hyperintensity along the corticomedullary junction once considered the imaging hallmark of NIID can frequently be absent in muscle weakness and parkinsonism phenotype of NIID. Besides, DWI abnormalities can appear years after the onset of predominant symptoms and may even disappear completely with disease progression. Moreover, continuous reports of NOTCH2NLC GGC expansions in patients with other neurodegenerative diseases lead to the proposal of a new concept of NOTCH2NLC-related GGC repeat expansion disorders (NRED). However, by reviewing the previous literature, we point out the limitations of these studies and provide evidence that these patients are actually suffering from neurodegenerative phenotypes of NIID.

Clinical Observation of Macular Superficial Capillary Plexus and Ganglion Cell Complex in Patients with Parkinson's Disease.

INTRODUCTION: We investigated macular superficial capillary plexus (SCP) density and the thicknesses of the ganglion cell complex (GCC) in patients with Parkinson's disease (PD) and correlated them. We also observed the correlations between SCP density and clinical parameters of PD patients. The retina might be a novel biomarker of PD and will be useful in the future for the early diagnosis of PD and detecting disease progression. METHODS: Seventy-four participants (38 patients with PD and 36 healthy controls) were recruited at the Affiliated Hospital of Xuzhou Medical University between January 2022 and June 2022 in this study. The macular SCP densities was measured by optical coherence tomography angiography (OCTA), and the GCC thickness was measured by optical coherence tomography (OCT). The parameters were compared between PD patients and healthy controls. The correlation between SCP and clinical parameters was tested. RESULTS: Compared with the control group, PD patients showed reduced SCP densities in all areas of the macular region (parafovea-temporal: t = 3.053, p = 0.003; parafovea-superior: t = 3.680, p = 0.001; parafovea-nasal: t = 4.643, p < 0.001; parafovea-inferior: t = 2.254, p = 0.027; perifovea-temporal: t = 3.798, p < 0.001; perifovea-superior: t = 3.014, p = 0.004; perifovea-nasal: t = 2.948, p = 0.004; perifovea-inferior: t = 3.337, p = 0.021). The average GCC thickness in the PD patients was significantly reduced (t = 2.365, p = 0.021). There were positive correlations between the average GCC thickness and the SCP densities in most of the areas of the macular regions in PD patients (parafovea-temporal: r = 0.325, p = 0.005; parafovea-superior: r = 0.295, p = 0.011; parafovea-nasal: r = 0.335, p = 0.003; perifovea-superior: r = 0.362, p = 0.002; perifovea-nasal: r = 0.290, p = 0.012; perifovea-inferior: r = 0.333, p = 0.004). We found significant correlations between SCP densities and Hoehn and Yahr (H and Y) scales, UPDRS III scores, and MMSE scores. No significant correlation was observed between SCP density and PD disease duration (all p > 0.05). CONCLUSIONS: We demonstrated that the macular SCP density was decreased, and the average GCC thickness was reduced in PD patients. The correlation between SCP density damage and GCC thinning also suggested that the retinal microvascular damage may be associated with retinal structural degeneration in PD patients. OCTA and OCT may be considered objective biomarkers for detecting microvascular impairment and neuronal damage in the early stages of PD in the future.

Functional MRI in Parkinson's disease with freezing of gait: a systematic review of the literature.

BACKGROUND: Freezing of gait (FOG), a common and disabling symptom of Parkinson's disease (PD), is characterized by an episodic inability to generate effective stepping. Functional MRI (fMRI) has been used to evaluate abnormal brain connectivity patterns at rest and brain activation patterns during specific tasks in patients with PD-FOG. This review has examined the existing functional neuroimaging literature in PD-FOG, including those with treatment. Summarizing these articles provides an opportunity for a better understanding of the underlying pathophysiology in PD-FOG. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a literature review of studies using fMRI to investigate the underlying pathophysiological mechanisms of PD-FOG. RESULTS: We initially identified 201 documents. After excluding the duplicates, reviews, and other irrelevant articles, 39 articles were finally identified, including 18 task-based fMRI studies and 21 resting-state fMRI studies. CONCLUSIONS: Studies using fMRI techniques to evaluate PD-FOG have found dysfunctional connectivity in widespread cortical and subcortical regions. Standardized imaging protocols and detailed subtypes of PD-FOG are furthered required to elucidate current findings.

NOD1/RIP2 signalling enhances the microglia-driven inflammatory response and undergoes crosstalk with inflammatory cytokines to exacerbate brain damage following intracerebral haemorrhage in mice.

BACKGROUND: Secondary brain damage caused by the innate immune response and subsequent proinflammatory factor production is a major factor contributing to the high mortality of intracerebral haemorrhage (ICH). Nucleotide-binding oligomerization domain 1 (NOD1)/receptor-interacting protein 2 (RIP2) signalling has been reported to participate in the innate immune response and inflammatory response. Therefore, we investigated the role of NOD1/RIP2 signalling in mice with collagenase-induced ICH and in cultured primary microglia challenged with hemin. METHODS: Adult male C57BL/6 mice were subjected to collagenase for induction of ICH model in vivo. Cultured primary microglia and BV2 microglial cells (microglial cell line) challenged with hemin aimed to simulate the ICH model in vitro. We first defined the expression of NOD1 and RIP2 in vivo and in vitro using an ICH model by western blotting. The effect of NOD1/RIP2 signalling on ICH-induced brain injury volume, neurological deficits, brain oedema, and microglial activation were assessed following intraventricular injection of either ML130 (a NOD1 inhibitor) or GSK583 (a RIP2 inhibitor). In addition, levels of JNK/P38 MAPK, IκBα, and inflammatory factors, including tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, and inducible nitric oxide synthase (iNOS) expression, were analysed in ICH-challenged brain and hemin-exposed cultured primary microglia by western blotting. Finally, we investigated whether the inflammatory factors could undergo crosstalk with NOD1 and RIP2. RESULTS: The levels of NOD1 and its adaptor RIP2 were significantly elevated in the brains of mice in response to ICH and in cultured primary microglia, BV2 cells challenged with hemin. Administration of either a NOD1 or RIP2 inhibitor in mice with ICH prevented microglial activation and neuroinflammation, followed by alleviation of ICH-induced brain damage. Interestingly, the inflammatory factors interleukin (IL)-1ß and tumour necrosis factor-α (TNF-α), which were enhanced by NOD1/RIP2 signalling, were found to contribute to the NOD1 and RIP2 upregulation in our study. CONCLUSION: NOD1/RIP2 signalling played an important role in the regulation of the inflammatory response during ICH. In addition, a vicious feedback cycle was observed between NOD1/RIP2 and IL-1ß/TNF-α, which could to some extent result in sustained brain damage during ICH. Hence, our study highlights NOD1/RIP2 signalling as a potential therapeutic target to protect the brain against secondary brain damage during ICH.

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice.

BACKGROUND: Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model. METHODS: Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl's and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention. RESULTS: Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction. CONCLUSION: Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.

An analysis of the clinical and imaging features of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).

Objective: To investigate the clinical features and imaging characteristics of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).Methods: Seventeen patients with MELAS diagnosed in the Affiliated Hospital of Xuzhou Medical University from July 2014 to August 2018 were enrolled in this study and their clinical manifestations, imaging and histopathological features were retrospectively analysed. We also discussed and summarised the related literature.Results: All of the 12 patients had seizures; stroke-like episodes in 12 cases; audio-visual impairment in 12 cases; headache in six cases; dysplasia in four cases; mental retardation in three cases; ataxia in two cases. On cranial magnetic resonance (MR) scans, the most common manifestations were in temporal-occipital-parietal lobe, cortical or subcortical areas as well as frontal lobe, thalamus, and basal ganglia showing long or equal T1 signals, long T2 signals, and hyperintense or iso-intense diffusion-weighted imaging (DWI) signals accompanied by ventricular enlargement and brain atrophy. MR spectroscopy showed that lactic acid peaks could be found in lesion sites, normal brain tissues, and cerebrospinal fluid. Muscle biopsy and genetic testing are the gold standard for diagnosing MELAS, muscle biopsy revealed COX-negative muscle fibres and SDH-stained red ragged fibres (RRF) under the sarcolemma. Mutations of mtDNA A3243G locus were common on gene testing. Improvement of mitochondrial function was observed after symptomatic and supportive treatment.Conclusion: MELAS should be considered for patients with epileptic seizures, headache, stroke-like episodes, extraocular palsy, cognitive decline and other clinical manifestations with the lesion located in the temporal-occipital-parietal lobe regardless of the distribution of blood vessels, and further examinations including muscle biopsy and gene testing should be performed to confirm the diagnosis.

Recent progress in neuronal intranuclear inclusion disease: a review of the literature.

OBJECTIVE: To summarize the current understanding of neuronal intranuclear inclusion disease (NIID) and improve the understanding of the physician about this condition. METHODS: We searched PubMed with keywords related to NIID and selected publications which seemed appropriate. We analyzed its clinical features, pathogenesis, evaluation methods, treatment options, and research prospectives. RESULTS: NIID is a degenerative condition which can affect multiple organ systems especially central nervous system. Its clinical features greatly vary, and making the exact diagnosis is often difficult. There are several genes which have been associated with this disorder. Some specific signs on diffusion-weighted-imaging (DWI) sequence of magnetic resonance (MR) imaging are characteristics to NIID. CONCLUSION: Intranuclear inclusions have been found in various nonneural cells of the body; therefore, the term systemic intranuclear inclusion disease is, perhaps, better suited to explain this disorder. There are several disorders which need to be ruled out before making the diagnosis, and neuroimaging and biopsy analysis should be combined to support the diagnosis.

Trousseau Syndrome Related Cerebral Infarction: Clinical Manifestations, Laboratory Findings and Radiological Features.

PURPOSE: We summarized the clinical manifestations, laboratory data, and brain MRI of patients with Trousseau syndrome related cerebral infarction and compared them to patients with other types of cerebral infarction. Through our present research, we hope to aid the neurologists in recognizing and diagnosing this syndrome. METHODS: A total of 31 patients at our institution were identified with cerebral infarction resulting from Trousseau syndrome. We have also selected the 180 patients who have suffered from cerebral infarction as control groups and these patients were distributed to large-artery atherosclerosis group; cardio-embolism group; small-artery occlusion group, according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The clinical data and neuroimage of these patients were collected. RESULTS: All our 31 cancer patients were confirmed by pathological biopsy to be adenocarcinomas and the most common cancers are gastric and lung cancers. Patients with Trousseau syndrome exhibited high serum carbohydrate antigen CEA, CA 125 and CA 199 levels. Compared to patients with other types of cerebral infarction, patients with Trousseau syndrome had an increased severity and worse prognosis. Besides, patients had the highest mean level of plasma D-dimer. We also found multiple lesions in multiple vascular territories was the most frequent type of DWI patterns in patients of Trousseau syndrome. CONCLUSIONS: Trousseau syndrome can progress rapidly and become life-threatening. For patients who developed unexplained cerebral infarction involving multiple arterial territories, with elevated plasma D-dimer and cancer antigens, Trousseau syndrome should always be considered.

A clinical analysis on 40 cases of spontaneous intracranial hypotension syndrome.

OBJECTIVE: To investigate clinical and imaging features of 40 patients with spontaneous intracranial hypotension (SIH). METHODS: 40 cases of spontaneous intracranial hypotension (SIH) diagnosed in our hospital from June 2013 to September 2017 were collected and retrospectively analyzed. RESULTS: In our study, the male to female ratio was 2:3. The average age of onset was 43.0 ± 15.0 years. There were 12 (30.0%) patients with clear incentives, mostly catching cold. The average length of hospital stay was 11.2 ± 6.3 days. All the patients showed orthostatic headaches, 62.5% patients with nausea or vomiting, 40.0% patients with neck stiffness, 17.5% patients with dizziness and vertigo, 10.0% patients with numbness and weakness of limbs, 5% patients with neck discomfort, and 2.5% patients with visual symptoms (visual impairment, photophobia, diplopia). 24 patients underwent CT scans which showed no abnormalities in 20 cases (83.3%), subdural fluid accumulation in 3 cases (12.5%), and subdural haematoma in 1 case (2.5%). Cranial contrast-enhanced MR scans showed diffuse pachymeningeal enhancement (95.83%, 23/24), signs of pituitary hyperaemia in 5 cases (20.8%), subdural fluid accumulation and subdural hematoma in 4 cases (16.7%), sagging of the brain in 3 cases (12.5%), and engorgement of venous structures in 1 case (4.1%). Six patients underwent plain and contrast-enhanced spinal MR scans which showed varying degrees of dural thickening and enhanced performance in all the patients. 92.5% (37/40) of patients had cerebrospinal fluid pressure <60 mmH2O on lumbar puncture. 97.5% of patients underwent conservative treatment with drugs and had a good outcome. CONCLUSION: Orthostatic headache and cranial MRI diffuse pachymeningeal enhancement are characteristic features of SIH. Cranial contrast-enhanced MR scan is recognized as the first and non-invasive investigation in the diagnosis of SIH. Most patients had cerebrospinal fluid pressure <60 mmH2O. The vast majority of patients improved with fluid replacement.

The aetiologies of unilateral oculomotor nerve palsy: a clinical analysis on 121 patients.

Background and purpose: To strengthen the understanding, increase the early diagnostic rate, and improve the outcome of unilateral oculomotor nerve palsy through the analysis of the 121 patients suffering from this disease in our hospital. Methods: A retrospective study was performed on the 121 patients with unilateral oculomotor nerve palsy diagnosed at the Affiliated Hospital of Xuzhou Medical University from October 2014 to October 2015. The clinical data, such as gender, age, aetiology, clinical features, laboratory tests, and six months follow up reports were analyzed. Results: The main causes identified in the 121 patients with unilateral oculomotor nerve palsy were intracranial aneurysm (29.8%), diabetic peripheral neuropathy (26.5%), painful ophthalmoplegia (9.9%), and other causes (33.9%). The results from the six month follow up showed that in all the patients, 53.7% were fully recovered, 38.0% improved, and 8.3% had no significant change in symptoms. The results also indicated that the patients with diabetic peripheral neuropathy had the best outcome with 71.9% full recovery rate, which was significantly higher than that in the patients with intracranial aneurysm (36.1%, p < .05), and idiopathic causes (44.5%, p < .05). Conclusions: Our data indicates that intracranial aneurysm is the leading cause of unilateral oculomotor nerve palsy, and that diabetic peripheral neuropathy has better outcome. Understanding the common causes and clinical features of unilateral oculomotor nerve paralysis is helpful for its early diagnosis and treatment.

The clinical and imaging features of hypertrophic pachymeningitis: a clinical analysis on 22 patients.

OBJECTIVE: To explore the clinical and imaging features of patients with hypertrophic cranial pachymeningitis (HCP). METHODS: A retrospective study was performed on 22 patients with HCP diagnosed at the Affiliated Hospital of Xuzhou Medical University from February 2014 to September 2017. RESULTS: A headache was present as an initial symptom in 18 patients. The headache was associated with the loss of vision (2 cases), facial pain (1 case), and unsteady walking (1 case). Other symptoms included cranial nerve dysfunction (15 cases), cerebellar ataxia (4 cases), and sinus thrombosis (3 cases). In the laboratory tests, 7 patients showed an increased number of white blood cells, higher levels of C-reaction protein (CRP), and erythrocyte sedimentation rate (ESR). An elevated level of immunoglobulin G4 (IgG4) and the presence of the anti-neutrophil cytoplasmic antibody (ANCA) were found in 3 and 2 patients respectively. There were 17 patients who had abnormalities in their cerebrospinal fluid (CSF) on lumbar puncture. On magnetic resonance imaging (MRI), a local or generalized thickening was observed in the cerebral falx, the tentorium of the cerebellum, the fronto-parietal lobe, the occipito-parietal lobe, and the dura of skull base. A dural biopsy obtained in one case showed a variety of inflammatory changes. An immunohistochemical analysis revealed the positivity of CD138, IgG, and IgG4 in some cells. All 22 patients had a good response to corticosteroids. CONCLUSION: HCP mainly leads to a headache and the paralysis of multiple cranial nerves. A biopsy and MRI are often required and serve as the basis for the diagnosis and effective therapy.