Facial onset sensory and motor neuronopathy (FOSMN syndrome): Cases series and systematic review.

OBJECTIVE: To provide new and comprehensive evidence for diagnosis and management of FOSMN syndrome. METHODS: We reviewed our database to identify patients with FOSMN syndrome. Online database including PubMed, EMBASE, and OVID were also searched for relevant cases. RESULTS: We identified a total of 71 cases, including 4 cases from our database and 67 ones from online searching. A predominance of male was observed [44 (62.0%)] with median onset age of 53 (range: 7-75) years old. The median (range) disease duration was 60 (3-552) months at the time of the visit. The initial symptoms could be sensory deficits in face (80.3%) or oral cavity (4.2%), bulbar paralysis (7.0%), dysosmia (1.4%), dysgeusia (4.2%), weakness or numbness of upper limbs (5.6%), or lower limbs (1.4%). Abnormal blink reflex was presented in 64 (90.1%) patients. CSF tests showed elevated protein level in 5 (7.0%) patients. Six (8.5%) patients had MND-related gene mutation. Five (7.0%) patients showed transient responsiveness to immunosuppressive therapy, then deteriorated relentlessly. Fourteen (19.7%) patients died, with an average survival time of around 4 years. Among them, five patients died of respiratory insufficiency. CONCLUSION: The age of onset, progress of disease course, and prognosis of FOSMN syndrome could be varied significantly. The prerequisites of diagnosis were progressive and asymmetric lower motor neuron dysfunction, with sensory dysfunction which usually showed in face at the onset. Immunosuppressive therapy could be tried in some patients with suspected inflammatory clues. In general, FOSMN syndrome tended to be motor neuron disease with sensory involvement.

Comparing characteristics and outcomes of in-hospital stroke and community-onset stroke.

BACKGROUND: In-hospital strokes account for 4-17% of all strokes and usually lead to urgent and severe conditions. However, features of in-hospital strokes have been scarcely reported in China, and the management systems of in-hospital strokes are unestablished. The study aims to analyze the characteristics of in-hospital strokes in comparison to community-onset strokes and provides evidence for the development of national in-patient stroke care systems. METHODS: We retrospectively analyzed consecutive patients with in-hospital strokes (IHS group) and community-onset strokes (COS group) hospitalized in our hospital between June 2012, and January 2022. Clinical characteristics, care measures, and outcomes were compared between the two groups. RESULTS: A total of 1162 patients (age 61 ± 16 and 65% male) were included, of whom 193 (16.6%) had an in-hospital stroke and 969 (83.4%) had community-onset stroke. Compared with COS group, patients in IHS group had higher NIHSS at onset (7.25 vs 5.96, P = 0.054), higher use of endovascular therapy (10.4% vs 2.0%, P < 0.001), and lower use of intravascular thrombolysis (1.6% vs 7.2%, P = 0.003). Also, in-hospital strokes were associated with lower rate of mRS0-2 at discharge (OR[95%CI] = 0.674[0.49, 0.926], P = 0.015) and increased in-hospital mobility (OR[95%CI] = 3.621[1.640, 7.996], P = 0.001), after adjusting for age, sex, and cardiovascular risk factors. CONCLUSION: Compared with community-onset strokes, the patients with in-hospital stroke had insufficient urgent treatment and poorer outcomes, reflecting the need for increased awareness of in-patient stroke, and strategies to streamline in-hospital acute stroke care.

Slow progression of amyotrophic lateral sclerosis in a Chinese patient carrying SOD1 p.S135T mutation.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Most patients die of respiratory failure within 3 years of onset. In this study, we reported a female Chinese ALS patient with SOD1 c.404G > C, p.S135T mutation. The missense mutation was identified as "Likely pathogenic" according to the ACMG/AMP 2015 guideline. The patient presented with weakness and atrophy of lower limbs with slow progression. We reviewed two other reports on patients with the same SOD1 p.S135T mutation. These patients had lower extremity onset, negative Babinski sign, slow disease progression, and prolonged survival. This report indicates that specific phenotype-genotype correlations of SOD1 p.S135T mutation in ALS.

Association between lipoprotein(a) concentration and the risk of stroke in the Chinese Han population: a retrospective case-control study.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a risk factor of coronary heart disease, however, its effects on stroke are less well-defined. METHODS: We performed a single-center, retrospective case-control study in 1,953 and 196 ischemic stroke and hemorrhagic stroke in-hospital patients, respectively. Controls were healthy individuals that were matched for sex and age (±5 years) for the ischemic (1:1 ratio) and hemorrhagic (1:2 ratio) stroke. Lp(a) concentration was measured using the latex agglutination turbidimetric method. Logarithmic transformation and quartile categorization were applied to adjust for the skewed distribution of Lp(a). Conditional logistic regression models were used to assess the association between Lp(a) and stroke risk. RESULTS: Median Lp(a) concentration was higher in stroke patients when compared with controls (12.2 vs. 8.60 mg/dL) and hemorrhagic strokes (14.40 vs. 13.40 mg/dL). The conditional multivariate analysis revealed a positive association between Lp(a) and ischemic stroke (OR =2.03, 2.36, and 2.03 for quartiles 2, 3 and 4, respectively, vs. quartile 1; P<0.001). In addition, elevated Lp(a) was also significantly associated with increased hemorrhagic stroke risk, after adjusted for potential covariates (OR =1.93, 3.24, and 2.19 for quartile 2, 3 and 4 respectively vs. quartile 1, P<0.05). The stratified analyses for ischemic and hemorrhagic stroke revealed significant association between elevated log-transformed Lp(a) and ischemic stroke in men. Furthermore, there was a trend towards a higher stroke risk for younger patients compared with older patients. CONCLUSIONS: Elevated serum Lp(a) is significantly positively correlated with ischemic and hemorrhagic stroke risk in the Chinese Han population, especially among men and younger patients.

Mutation analysis of KIF5A in Chinese amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is an age-related fatal neurodegenerative orphan disorder that is characterized by progressive injury of both the upper and lower motor neurons. Recently, loss-of-function mutations predominately disrupting the C-terminal amino acid sequence of KIF5A via aberrant exon 27 splicing have been reported in European ALS cohorts. However, the contributions of KIF5A mutations in Asian patients with ALS remain unclear. KIF5A sequences, including exons 26 and 27, were analyzed in a large Chinese ALS cohort comprising 33 unrelated familial ALS probands, 645 sporadic ALS (SALS) patients, 15 ALS patients presenting with concomitant frontotemporal dementia, 400 in-house controls, and 12,951 East Asian individuals from the Exome Aggregation Consortium and Genome Aggregation Database databases. As a result, the previously reported canonical splicing site mutation c.2993-1G>A was found in 1 SALS patient, while no mutations were detected in familial ALS case or ALS patients presenting with concomitant frontotemporal dementia. The frequency of KIF5A mutations accounts for 0.16% (1/645) of Chinese SALS patients, implying that it is an uncommon genetic determinant of ALS in Chinese patients.

Restless Legs Syndrome in Chinese Patients With Sporadic Amyotrophic Lateral Sclerosis.

Objective: To evaluate the frequency and clinical features of restless legs syndrome (RLS) in a group of Chinese patients with amyotrophic lateral sclerosis (ALS). Methods: 109 Patients included in this study fulfilled the revised El Escorial diagnostic criteria for clinically definite, probable and lab-supported probable ALS, and a group of 109 control subjects was matched for age and sex to the ALS group. Disease severity was assessed by the revised ALS functional rating scale (ALSFRS-R). The diagnosis of RLS was made according to the criteria of the International RLS Study Group. Other characteristics including sleep quality, excessive daytime sleepiness (EDS), REM sleep behavior disorder (RBD), depression and anxiety were also evaluated in ALS patients. Results: RLS was significantly more frequent in ALS patients than in control subjects (14.6 vs. 0.9%; P < 0.05). Compared to those without RLS, ALS patients with RLS reported a higher frequency of anxiety and EDS. ALS patients with RLS showed more severe legs dysfunction. EDS and legs function scores of the ALSFRS-R were independent factors significantly associated with RLS in ALS patients. Conclusions: Our findings suggest that Chinese ALS patients exhibit a high frequency of RLS symptoms and that these patients may benefit from recognition of the condition and optimized management of its symptoms. Moreover, ALS patients might cause circadian rhythms disturbance and our study further supports that ALS is a heterogeneous disorder involving multiple systems; further studies are needed to confirm these preliminary findings.

Excessive daytime sleepiness in Chinese patients with sporadic amyotrophic lateral sclerosis and its association with cognitive and behavioural impairments.

OBJECTIVE: To examine the frequency and clinical features of excessive daytime sleepiness (EDS) and its association with cognitive and behavioural impairments in patients with amyotrophic lateral sclerosis (ALS). METHODS: We conducted a cross-sectional investigation to explore the frequency and clinical features of EDS in a group of 121 Chinese patients with ALS compared with 121 age-matched and sex-matched healthy subjects. EDS was diagnosed using the Epworth Sleepiness Scale (ESS). Other characteristics of patients with ALS including sleep quality, REM sleep behaviour disorder (RBD), restless legs syndrome (RLS), cognition, behaviour, depression and anxiety were also evaluated. RESULTS: EDS was significantly more frequent in patients with ALS than in controls (26.4% vs 8.3%; p<0.05). Patients with ALS with EDS scored lower scores on the revised ALS Functional Rating Scale (ALSFRS-R), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and MMSE and MoCA delayed memory subitems and higher on the Frontal Behavioural Inventory (FBI) than patients with ALS without EDS. ESS scores correlated with global ALSFRS-R, FBI, MMSE and MoCA scores and MMSE and MoCA delayed memory scores. RLS and global ALSFRS-R scores were independently associated with EDS in patients with ALS. CONCLUSIONS: We identified a high frequency of EDS symptoms in Chinese patients with ALS, and these patients might have more serious physical, cognitive and frontal behaviour impairment. Patients with ALS might improve quality of life from the timely recognition and optimised management of EDS symptoms. Our results further suggest that ALS is a heterogeneous disease that might exhibit abnormal sleep-wake patterns.

Brain Structural and Perfusion Signature of Amyotrophic Lateral Sclerosis With Varying Levels of Cognitive Deficit.

OBJECTIVE: To characterize the patterns of brain atrophy and perfusion as measured by arterial spin labeling (ASL)-MRI, in amyotrophic lateral sclerosis (ALS) patients with varying levels of cognitive deficit, including ALS with frontotemporal dementia (FTD). METHODS: A total of 55 ALS patients and 20 healthy controls (HCs) were included, and all participants underwent neuropsychological assessments and MRI scans. According to their cognitive performance, ALS patients were further subclassified into ALS with normal cognition (ALS-Cn, n = 27), ALS with cognitive impairment (ALS-Ci, n = 17), and ALS-FTD (n = 11). Voxel-based comparisons of gray matter (GM) changes and cerebral blood flow (CBF) were conducted among the subgroups. RESULTS: The whole-brain comparisons of GM changes and CBF among ALS-Ci, ALS-Cn, and HCs were not significantly different. However, the ALS-FTD patients demonstrated a similar pattern of GM loss and hypoperfusion with more significant alterations in the left frontal and temporal lobe compared with the HCs, ALS-Cn, and ALS-Ci patients. Decreased CBF was found in many of the same brain areas wherein structural alterations occurred, although isolated GM loss and hypoperfusion were also observed. In addition, for both GM and CBF abnormalities, a similar pattern of changes was found in the comparisons of ALS-FTD vs. ALS-Ci, ALS-FTD vs. ALS-Cn, and ALS-FTD vs. HCs, with the differences being most significant between ALS-FTD and HCs. CONCLUSION: The cognitive status of ALS patients is associated with different patterns of GM changes and cerebral perfusion. ASL-MRI might be a useful tool with which to investigate the pathological burden of ALS and to disclose the early signature of possible cognitive impairment.

ANXA11 mutations prevail in Chinese ALS patients with and without cognitive dementia.

OBJECTIVE: To investigate the genetic contribution of ANXA11, a gene associated with amyotrophic lateral sclerosis (ALS), in Chinese ALS patients with and without cognitive dementia. METHODS: Sequencing all the coding exons of ANXA11 and intron-exon boundaries in 18 familial amyotrophic lateral sclerosis (FALS), 353 unrelated sporadic amyotrophic lateral sclerosis (SALS), and 12 Chinese patients with ALS-frontotemporal lobar dementia (ALS-FTD). The transcripts in peripheral blood generated from a splicing mutation were examined by reverse transcriptase PCR. RESULTS: We identified 6 nonsynonymous heterozygous mutations (5 novel and 1 recurrent), 1 splice site mutation, and 1 deletion of 10 amino acids (not accounted in the mutant frequency) in 11 unrelated patients, accounting for a mutant frequency of 5.6% (1/18) in FALS, 2.3% (8/353) in SALS, and 8.3% (1/12) in ALS-FTD. The deletion of 10 amino acids was detected in 1 clinically undetermined male with an ALS family history who had atrophy in hand muscles and myotonic discharges revealed by EMG. The novel p. P36R mutation was identified in 1 FALS index, 1 patient with SALS, and 1 ALS-FTD. The splicing mutation (c.174-2A>G) caused in-frame skipping of the entire exon 6. The rest missense mutations including p.D40G, p.V128M, p.S229R, p.R302C and p.G491R were found in 6 unrelated patients with SALS. CONCLUSIONS: The ANXA11 gene is one of the most frequently mutated genes in Chinese patients with SALS. A canonical splice site mutation leading to skipping of the entire exon 6 further supports the loss-of-function mechanism. In addition, the study findings further expand the ANXA11 phenotype, first highlighting its pathogenic role in ALS-FTD.

Genetic analysis of TIA1 gene in Chinese patients with amyotrophic lateral sclerosis.

Mutations in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1) was recently identified to be associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in non-Hispanic white populations. We sequenced the TIA1 exons 11-13 encoding LCD in a series of 588 Chinese ALS/ALS-FTD patients (Familial ALS = 29; Sporadic ALS = 546; ALS-FTD = 13) and 500 neurologically normal control subjects. We found a novel heterozygous missense mutation (c.973A>G, p.N325D) in a sporadic ALS patient, which suggests that TIA1 LCD mutations are not common in Chinese ALS/ALS-FTD.

Screening of GLE1 mutations in Chinese amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is a lethal neurological disease primarily involving the spinal cord, brainstem, and corticospinal tract. Recently, mutations in the GLE1 gene were reported in Caucasian ALS patients. To inquire whether Chinese ALS patients carried causal mutations in the gene, we screened all 16 coding exons of GLE1 with Sanger sequencing in a Han Chinese cohort of 250 ALS cases. No nonsynonymous coding variants were detected. Our results suggest that pathogenic variants in the GLE1 gene are rare in Chinese ALS patients.

Risk of left ventricular hypertrophy and diastolic and systolic dysfunction in Acromegaly: A meta-analysis.

OBJECTIVE: To perform a meta-analysis to evaluate the exact incidence of left ventricular hypertrophy, diastolic dysfunction and systolic dysfunction in patients with treatment-naïve acromegaly. METHODS: PubMed, EMBASE, Ovid MEDLINE, the Cochrane Library, Scopus, Science Citation Index Expand and PubMed Central were searched for eligible studies. Eligible data were extracted and evaluated using a fixed- or random-effects model. The Q test, I2 statistics for testing heterogeneity, the Newcastle-Ottawa Scale (NOS) for the retrospective appraisal of study quality, and Begg's test and Harbord's modified test for the evaluation of publication bias were used. RESULTS: Seven eligible studies were selected, and a total of 458 patients and 650 controls were included. Left ventricular hypertrophy was significantly more frequent in treatment-naïve acromegaly patients than in controls [odds ratio (OR) = 28.2, 95% confidence interval (CI) = 19.17-41.49] with a prevalence of 65.1%. Diastolic dysfunction was also common (50.5%) in acromegaly patients (OR = 15.62, 95% CI = 1.98-123.34). Moreover, 19.6% of patients presented abnormal systolic function with an OR of 13.1 (95% CI = 6.64-25.84). CONCLUSIONS: Patients with treatment-naïve acromegaly are at an increased risk of developing left ventricular hypertrophy, diastolic dysfunction and systolic dysfunction than the general population.

Radiotherapy and chemotherapy plus radiation in the treatment of patients with pure intracranial germinoma: A meta-analysis.

OBJECTIVE: To evaluate the efficiency of radiotherapy (RT) only and chemotherapy plus radiotherapy (CRT) strategy in the treatment of pure intracranial germinoma. METHODS: We searched PUBMED, EMBASE, Medline and Cochrane library up to May 2016 for studies that enrolled patients with pure intracranial germinoma receiving either RT only or CRT treatment as their first-line treatment. The meta-analysis was conducted on the overall survival rate (OS) and disease free survival (DFS) at 3years and 5years. The outcomes were pooled using a random-effect model. RESULTS: The final search included 15 studies with 310 patients. The pooled 3-year OS (97% vs. 94%, p=.000) and 3-year DFS (96% vs. 93%, p=0.043) of CRT group was significantly higher than that of RT only group. However, at 5years, the OS was 94% in RT only group and 92% in the combined group (p=0.29) . For DFS, the RT only group was higher than the combined group (94% vs.89%, p=.000). CONCLUSIONS: Both RT and CRT for intracranial pure germinoma gain satisfying outcomes, and the CRT strategy has a higher overall survival rate and disease free survival rate at 3years than RT regimen. At 5years in the postoperative period, the advantage of survival rates for CRT is eliminated or even reversed. For patients with pure intracranial germinoma, especially those with acute and severer condition and poorer prognosis, CRT strategy would be a better choice.

Cerebrovascular Safety of Sulfonylureas: The Role of KATP Channels in Neuroprotection and the Risk of Stroke in Patients With Type 2 Diabetes.

Sulfonylureas are ATP-sensitive potassium (KATP) channel blockers commonly used in the treatment of type 2 diabetes mellitus (T2DM). Activation of KATP channels plays a neuroprotective role in ischemia; thus, whether sulfonylureas affect the outcomes of stroke in patients with T2DM needs to be further studied. In our study, streptozotocin (STZ)-induced diabetic mice subjected to transient middle cerebral artery occlusion (MCAO) showed larger areas of brain damage and poorer behavioral outcomes. Blocking the KATP channel by tolbutamide increased neuronal injury induced by oxygen-glucose deprivation (OGD) in vitro and permanent MCAO (pMCAO) in vivo. Activating the KATP channel by diazoxide reduced the effects of both the OGD and pMCAO. Western blot analysis in STZ mouse brains indicated an early increase in protein levels of N-methyl-d-aspartate receptor 2B and postsynaptic density protein-95, followed by a decrease in phosphorylation of glycogen synthase kinase 3ß. Our systematic meta-analysis indicated that patients with T2DM treated with sulfonylureas had a higher odds ratio for stroke morbidity than those who received comparator drugs. Taken together, these results suggest that sulfonylurea treatment in patients with T2DM may inhibit the neuroprotective effects of KATP channels and increase the risk of stroke.

Pituicytoma Coexisting With Corticotroph Hyperplasia: Literature Review With One Case Report.

Pituicytoma is a rare, low-grade glial neoplasm that arises in the neurohypophysis or infundibulum and usually presents as pituitary gland enlargement. They are often misdiagnosed as pituitary adenomas. Causes have varied for high serum adrenocorticotropic hormone level reported in a few patients with pituicytoma.We report a rare case of pituicytoma accompanied by corticotroph hyperplasia-a challenging diagnosis guided by clinical presentations, radiological signs, and biopsy.We present a case of pituicytoma with corticotroph hyperplasia in a 46-year-old woman with typical Cushing syndrome. Magnetic resonance imaging revealed a lesion in the sellar area with equal T1 and T2 signals and marked homogeneous enhancement. We present detailed analysis of the patient's disease course and review pertinent literature. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary.The patient underwent a surgical exploration and tumor resection through a trans-sphenoidal approach. Pathologic results revealed pituicytoma and corticotroph hyperplasia. As adrenocorticotropic hormone and cortisol levels did not decrease to normal, the patient received radiotherapy and recovered uneventfully. No recurrence was found over 8 years of follow-up.Pituicytoma is a rare type of sellar tumor. Pituicytomas in patients with Cushing syndrome are rarer still. To our knowledge, this is the first report of Cushing syndrome caused by corticotroph hyperplasia in a pituicytoma patient.

The prognosis and clinicopathology of CXCR4 in gastric cancer patients: a meta-analysis.

The chemokine receptor 4 (CXCR4) has been widely investigated in diagnosis and prognosis of gastric cancer (GC). However, the impact of CXCR4 on GC patients remains controversial; Here, we conducted a meta-analysis to obtain the precise role of CXCR4 in GC prognosis and clinicopathology. Thirteen published studies with a total of 1,936 patients were included. Original data included the hazard ratio (HR) of overall survival (OS) and odds ratio (OR) in GC patients. We combined HR/OR with 95% confidence interval (CI) to estimate the hazard. In this study, OS was significantly related to CXCR4 expression, with the HR 2.63 (95% CI 1.69-4.09; p < 0.0001), and a significant correlation was also revealed between CXCR4 expression and stage (I + II, +) (OR 0.52, 95% CI 0.32-0.83; p = 0.007), depth of invasion (T1/T2, +) (OR 0.44, 95% CI 0.27-0.73; p = 0.001), lymph node metastasis (LN, +) (OR 2.30, 95% CI 1.57-3.36; p < 0.0001), as well as vascular invasion (vas.inv, +) (OR 0.72, 95% CI 0.53-0.98; p = 0.04). Heterogeneity was observed among the included studies with OS (I(2) = 51%), stage (I(2) = 78%), depth of invasion (I(2) = 74%), lymph node metastasis (I(2) = 64%), and histology differentiation (I(2) = 79%). No publication bias was observed. In conclusion, this meta-analysis showed CXCR4 expression indicates poor prognosis in GC patients with advanced stage or deep invasion in GC tissues, which also implied lymph node metastasis and vascular invasion. Thus, CXCR4 could help predict patient prognosis and guide clinical diagnosis and treatment.