Spatiotemporal Dynamics of Cerebral Vascular Permeability in Type 2 Diabetes-Related Cerebral Microangiopathy

AimsDiabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral vascular permeability (Ktrans) in the progression of type 2 diabetes mellitus (T2DM).MethodsKtrans was cross-sectionally measured in T2DM and non-diabetes groups with or without CSVD using dynamic contrast-enhanced MRI (DCE-MRI).ResultsIn all patients with T2DM, the Ktrans of white matter (WM) was increased, whereas the Ktrans of gray matter (GM) was increased only in T2DM with CSVD. The involvement of WM was earlier than GM and was before the CSVD features could be visualized on MRI. Among the commonly available four CSVD items of MRI, microbleeds were the most sensitive, indicating the increased permeability in all patients. Increased Ktrans in T2DM was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces, in contrast to patients without diabetes. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs.ConclusionsThis study highlights the early development of cerebral microangiopathy with increased BBB leakage in T2DM, before the CSVD features can be visualized on MRI. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.

A Study of the Protective Effect of Bushen Huoxue Prescription on Cerebral Microvascular Endothelia Based on Proteomics and Bioinformatics

Diabetic cognitive dysfunction is a serious complication of type 2 diabetes mellitus (T2DM), which can cause neurological and microvascular damage in the brain. At present, there is no effective treatment for this complication. Bushen Huoxue prescription (BSHX) is a newly formulated compound Chinese medicine containing 7 components. Previous research indicated that BSHX was neuroprotective against advanced glycosylation end product (AGE)-induced PC12 cell insult; however, the effect of BSHX on AGE-induced cerebral microvascular endothelia injury has not been studied. In the current research, we investigated the protective effects of BSHX on AGE-induced injury in bEnd.3 cells. Our findings revealed that BSHX could effectively protect bEnd.3 cells from apoptosis. Moreover, we analyzed the network regulation effect of BSHX on AGE-induced bEnd.3 cells injury at the proteomic level. The LC-MS/MS-based shotgun proteomics analysis showed BSHX negatively regulated multiple AGE-elicited proteins. Bioinformatics analysis revealed these differential proteins were involved in multiple processes, such as Foxo signaling pathway. Further molecular biology analysis confirmed that BSHX could downregulate the expression of FoxO1/3 protein and inhibit its nuclear transfer and inhibit the expression of downstream apoptotic protein Bim and the activation of caspase, so as to play a protective role in AGE-induced bEnd.3 injury. Taken together, these findings demonstrated the role of BSHX in the management of diabetic cerebral microangiopathy and provide some insights into the proteomics-guided pharmacological mechanism study of traditional Chinese Medicine.

Transient Global Amnesia (TGA): Younger Age and Absence of Cerebral Microangiopathy Are Potentially Predisposing Factors for TGA Recurrence

Background: Transient global amnesia (TGA) is defined by an acute memory disturbance of unclear etiology for a period of less than 24 h. TGA occurs as a single event in most cases. Prevalence rates of recurrent TGA vary widely from 5.4 to 27.1%. This retrospective study aimed to determine predictors for TGA recurrence.Methods: Cardiovascular risk profile and magnetic resonance imaging (MRI) of 340 hospitalized TGA patients between 2011 and 2020 were retrospectively analyzed. The median follow-up period amounted to 4.5 ± 2.7 years. Comparisons were made between TGA patients with and without subsequent recurrence.Results: TGA patients with subsequent recurrence were significantly younger (recurrent vs. single episode, 63.6 ± 8.6 years vs. 67.3 ± 10.5 years, p = 0.032) and showed a lower degree of cerebral microangiopathy compared to TGA patients without recurrence. The mean latency to recurrence was 3.0 years ± 2.1 years after the first episode. In a subgroup analysis, patients with at least five years of follow-up (N = 160, median follow-up period 7.0 ± 1.4 years) had a recurrence rate of 11.3%. A 24.5% risk of subsequent TGA recurrence in the following five years was determined for TGA patients up to 70 years of age without microangiopathic changes on MRI (Fazekas' score 0).Conclusion: Younger TGA patients without significant microangiopathy do have an increased recurrence risk. In turn, pre-existing cerebrovascular pathology, in the form of chronic hypertension and cerebral microangiopathy, seems to counteract TGA recurrence.

Spatiotemporal Dynamics of Cerebral Vascular Permeability in Type 2 Diabetes-Related Cerebral Microangiopathy

Objective Diabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral permeability (Ktrans) in the progression of diabetes-related CSVD. Methods Cerebral vascular permeability was crossectional measured in diabetic patients with or without CSVD, and non-diabetic patients with or without CSVD by using dynamic contrast-enhanced MRI (DCE-MRI). Results In all diabetic patients, the Ktrans of white matter (WM) was increased. However, the Ktrans of gray matter (GM) was only increased in those with CSVD. This suggested the earlier involvement of WM than GM and indicated the development of diabetes-related cerebral microangiopathy was prior to it could be visualized as features of CSVD on MRI. To broaden the application of cerebral permeability and overcome the limitations of DCE-MRI, the commonly available CSVD items of MRI were used to indicate the increase in Ktrans. Among all CSVD items, the presence of microbleeds was most correlated with the increased permeability in all patients. In contrast to non-diabetic patients, increased Ktrans in diabetes was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs. Conclusions This study highlights the early development of cerebral microangiopathy in diabetes and broadens the applicability of cerebral permeability. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.

Treatment of cognitive impairment in arterial hypertension

Cognitive impairment (CI) is one of the earliest and most frequent neurological disorders in patients with arterial hypertension. Arterial hypertension is a leading modifiable risk factor for stroke and cerebral microangiopathy, which underlies the development of non-stroke associated CI. Antihypertensive therapy plays an essential role in preventing the development and slowing the progression of CI by controlling blood pressure. The review discusses the use of memantine – a reversible inhibitor of NMDA receptors (akatinol memantine) – in vascular CI.

Management tactics in patients with chronic cerebral ischemia during COVID-19 pandemic

The article describes the current state of evidence of hypertension and diabetes mellitus roles in the pathophysiology of chronic cerebral ischemia (CCI). CCI is mediated by cerebral microangiopathy, which develops due to vascular remodeling, increased arterial stiffness, endothelial dysfunction, impaired cerebrovascular reactivity, and neuroinflammation. All those mechanisms lead to white matter lesions and cognitive impairment. Arteriolosclerosis is the primary morphological process that damages perforating arteries and arterioles. COVID-19 pandemic can modify CCI progression due to similar pathophysiology. In particular, COVID-19-associated coagulopathy can lead to silent lacunar infarctions and lacunar stroke development. Treatment features of patients with CCI during the COVID-19 pandemic are reviewed. It is concluded that special attention in this group of patients should be paid to primary and secondary cardiovascular prevention issues, an essential element of which is the use of dipyridamole since it has a pleiotropic effect.

Case Report: Clinical Features of Childhood Leukoencephalopathy With Cerebral Calcifications and Cysts Due to SNORD118 Variants

Background: Leukoencephalopathy with cerebral calcifications and cysts (LCC) is a rare autosomal recessive cerebral microangiopathy. Recently, biallelic variants in a non-protein-coding gene SNORD118 have been discovered to cause LCC.Case Presentation: We here report a genetically confirmed childhood case of LCC. The patient was a 4-year-and-1-month-old boy with focal seizures. The age at onset of his seizure was 10 days after birth. The seizures were well-controlled by antiepileptic treatment but reoccurred twice due to a head impact accident and a fever, respectively. He suffered from a self-limited esotropia and unsteady running gait during the seizure onset. He had the typical neuroimaging triad of multifocal intracranial calcifications, cysts, and leukoencephalopathy. Genetic analysis indicated that he carried compound heterozygous variants of n.*9C>T and n.3C>T in SNORD118, which were inherited from his parents.Conclusion: We report a childhood LCC case with compound heterozygous variants in SNORD118. To the best of our knowledge, the patient reported in our case had the youngest onset age of LCC with a determined genotype. The triad cerebral-imaging findings of calcifications, cysts, and leukoencephalopathy provide a crucial diagnostic basis. Moreover, the gene assessment, together with the clinical investigations, should be considered for the diagnosis of LCC.

Paediatric neurosurgical implications of a ribosomopathy: illustrative case and literature review

Ribosomopathies are rare, recently defined entities. One of these, Labrune syndrome, is recognisable radiologically by its distinctive triad of leukoencephalopathy, intracranial calcifications and cysts (LCC). These cysts may have neurosurgical implications at different ages because of their progressive expansion and local mass effect. The aetiology of LCC is related to a widespread cerebral microangiopathy and is due to a genetic mutation in SNORD118, responsible for stabilisation of the large ribosomal subunit during assembly.