Periventricular White Matter Research Articles

Efficacy and safety of different noninvasive ventilation strategies for postextubation respiratory support in Neonatal Respiratory Distress Syndrome: a systematic review and network meta-analysis

ObjectiveThe study aimed to compare the efficacy and safety of different noninvasive ventilation (NIV) modalities as primary respiratory support following extubation in Neonatal Respiratory Distress Syndrome (NRDS).MethodsA search was conducted in PubMed, Embase, Cochrane, Web of Science, China National Knowledge Network (CNKI), Wanfang database, VIP, and Chinese Biomedical Literature databases with a search time limit of April 2024 for the year of construction, and included randomized controlled clinical trials of different modes of noninvasive respiratory support after extubation in NRDS. The primary outcome indicators were the need for re-tracheal intubation within 72 h of extubation on noninvasive ventilatory support and carbon dioxide retention (PCO2) 24 h after extubation. Secondary outcome indicators included the incidence of bronchopulmonary dysplasia (BPD), nasal injury, pneumothorax, intraventricular hemorrhage (IVH) or periventricular white matter softening (PVL), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and mortality rate. A systematic review and network meta-analysis of the literature was performed by two investigators who screened, extracted, and evaluated the quality of the data. A systematic review and network meta-analysis were then performed using R software.ResultsA total of 23 studies involving 2,331 neonates were analyzed. These studies examined four noninvasive respiratory modalities: continuous positive airway pressure ventilation (NCPAP), noninvasive intermittent positive pressure ventilation (NIPPV), bi-level positive airway pressure ventilation (N-BiPAP), and noninvasive high-frequency oscillatory ventilation (NHFOV). Results indicated that NHFOV, NIPPV, and N-BiPAP were significantly more effective than NCPAP in reducing the risk of reintubation (all P < 0.05), with NHFOV being the most effective. For carbon dioxide clearance, NHFOV outperformed both NIPPV and NCPAP (P < 0.05). Regarding the reduction of bronchopulmonary dysplasia (BPD) incidence, NHFOV and NIPPV showed a significant advantage over NCPAP.ConclusionsThis network meta-analysis (NMA) suggested that NHFOV is the most effective mode of noninvasive respiratory support post-extubation, while NCPAP is the least effective. However, these findings should be interpreted with caution due to the limited number and quality of the studies included.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier (CRD42024544886).

RADT-42. DISSEMINATED TUMORAL AMYLOIDOSIS OF THE CRANIAL NERVES IN THE ABSENCE OF SYSTEMIC DISEASE: CASE REPORT

Abstract Tumoral amyloidosis, characterized by tumor-like deposits without systemic disease, is rare in the central nervous system. Most often located in the periventricular white matter, tumoral amyloidosis typically consist of immunoglobulin light chains (AL). While prior reports describe cases of tumoral amyloidosis isolated to the trigeminal nerve, we report herein a first known case of diffuse cranial nerve involvement. The patient is a 43-year-old man who presented with left trigeminal dysesthesias, which led to self-excoriation and erosion of the left naris. On exam, he had absent sensation in the V1-V3 distributions, left trochlear nerve palsy, and bilateral abducens nerve palsies. Imaging demonstrated significant thickening of the left trigeminal nerve and diffuse cisternal contrast enhancement of the other cranial nerves, including the oculomotor, abducens, facial, and glossopharyngeal nerves. Work-up began with a lumbar puncture that found elevated protein with otherwise benign results, including flow cytometry. He was therefore recommended to undergo open biopsy of the left trigeminal nerve and cavernous sinus. Pathology from this surgery demonstrated congo red- positive AL amyloid deposits. Following this pathologic diagnosis, he subsequently underwent a full workup for systemic amyloidosis including bone marrow biopsy, abdominal fat pad biopsy, and a PET CT scan. Biopsy of a long nodule was negative for amyloidosis. Systemic amyloid testing did not demonstrate non-CNS sites of amyloid deposition. Medical therapy with daratumumab, cyclophosphamide, bortezomib, and dexamethasone was started but then discontinued due to ineffectiveness. He underwent radiation treatment of 4500 cGy to the left cavernous sinus where the tumoral amyloidosis was most severe. He has had no further progression of his disease. Tumoral amyloidosis of the cranial nerves remains a rare and poorly-understood disease. Prior reports have described the disease isolated to the trigeminal nerve. This report raises attention to this diagnosis in cases of rare multi-nerve involvement and suggests that radiation may be a useful first-line treatment.

DNAR-13. LONG TERM FOLLOW-UP OF A LYNCH SYNDROME-ASSOCIATED GLIOBLASTOMA RESISTANT TO STANDARD-OF-CARE CHEMORADIATION

Abstract BACKGROUND Lynch syndrome is caused by pathogenic germline variants in the DNA mismatch repair (MMR) genes, predisposing individuals to malignancies, including glioblastoma (GBM). MMR-deficient tumors are resistant to monofunctional alkylators such as temozolomide but not to bifunctional alkylators such as the nitrosourea lomustine. Anti-programmed cell death protein 1 (PD1) immune checkpoint inhibitor (ICI) pembrolizumab represents another treatment option, which is approved by the United States Food and Drug Administration (FDA) for the treatment of mismatch repair deficient cancers. METHODS We present a patient with multifocal GBM and Lynch syndrome who experienced rapid progression following standard-of-care chemoradiation, followed by durable responses to lomustine and then to pembrolizumab. RESULTS A 58-year-old man with Lynch syndrome (MSH2 mutation) and prior history of colon cancer presented with seizures. Magnetic resonance imaging (MRI) brain identified right frontal and left parietal masses. Right frontal tumor was resected; pathology was consistent with GBM, IDH wildtype, MGMT-unmethylated. Both lesions were treated with radiation therapy (60 Gy, 30 fractions) with concurrent and adjuvant temozolomide. After two cycles of adjuvant temozolomide, his left parietal tumor progressed and was subtotally resected, followed by four cycles of lomustine (stopped due to myelotoxicity). He remained progression-free for 15 months. Surveillance MRI identified new enhancement involving the left frontal lobe, left periventricular white matter, and right internal auditory canal, concerning for leptomeningeal dissemination. MRI spine identified no additional lesions. Cerebrospinal fluid cytology was negative for tumor cells on two occasions. Patient was treated with pembrolizumab. He remains on treatment with stable disease four months after ICI initiation and 31 months after GBM diagnosis. CONCLUSIONS Patients with MMR-deficient GBM resist standard chemoradiation. Alternatives such as nitrosourea or ICI therapy may achieve durable responses. While data is insufficient to administer these agents as upfront therapy in this specific setting, both should be considered as options for recurrent disease.

Mechanism and significance of diffusion restriction followed by calcification in high-grade glioma treated with bevacizumab

In this study, we focused on calcification and diffusion restriction, which sometimes appear around the resection cavity or periventricular white matter in patients with high-grade glioma (HGG) treated with bevacizumab (BVZ), as candidate imaging biomarkers for BVZ treatment efficacy. We investigated the timing of the appearance of diffusion restriction and calcification using magnetic resonance imaging and computed tomography in 35 patients with newly diagnosed or recurrent HGG treated with BVZ. In 17 (48.6%) patients, calcification was identified around the resection cavity or periventricular white matter at a median of 12 months after the initiation of BVZ treatment. Patients with calcification had significantly longer progression-free survival (16 vs. 7 months; p = 0.0023) and overall survival (36 vs. 12 months; p = 0.0006) than those without calcification. Histopathological examination revealed the presence of scattered microcalcifications within areas of necrosis, which suggested dystrophic calcification induced by BVZ. Diffusion-restricted lesions that appeared in patients with calcification had significantly lower apparent diffusion coefficients than those in patients without calcifications, indicating the presence of treatment-related necrosis but not hypercellularity. In conclusion, the radiological finding of diffusion restriction followed by calcification could be a potential imaging biomarker for favorable clinical course in patients with HGG treated with BVZ.

Dopamine transporter availability based on white matter hyperintensity during early to mid-stage Parkinson's disease and multiple system atrophy: a case control study.

To evaluate the association of white matter hyperintensity (WMH) with dopamine transporter (DAT) availability in patients with early to mid-stage parkinson's disease (PD) and multiple system atrophy (MSA). The clinical and imaging data of 55 patients were collected, including 38 PD and 17 MSA patients and the clinical features of the two groups were compared. DAT specific binding ratio (SBR) were compared between severe and non-severe WMH groups, and between PD and MSA groups. The relationships of WMH with DAT availability and basic clinical characteristics were analyzed. Multiple linear regression analysis showed that age was the only significant variable showing correlation WMH. Age was the only clinical variable significantly correlated with WMH in PD patients (coefficient for periventricular white matter hyperintensity: 0.430, P = 0.007; coefficient for deep white matter hyperintensity: 0.381, P = 0.018). There was no significant correlation between WMH and SBRs and age in MSA patients. The SBR of the caudate nucleus and anterior putamen was significantly lower in the severe WMH group of patients than in the non-severe WMH group (P < 0.05). The values of the caudate nucleus, anterior putamen, and anterior putamen/posterior putamen were significantly lower in PD patients with than without severe WMH (P < 0.05), and the damage to the striatal DAT in MSA patients with severe WMH was similar to the non-severe patients (P>0.05). Patients with PD and a high WMH score had lower DAT availability. WMH affected the availability of DAT in patients with early to mid-stage PD compared to MSA.

White matter protection with insulin-like growth factor-1 after hypoxia-ischaemia in preterm foetal sheep.

Perinatal hypoxia-ischaemia in extremely preterm infants is associated with long-term neurodevelopmental impairment, for which there is no specific treatment. Insulin-like growth factor-1 can reduce acute brain injury, but its effects on chronic white matter injury after hypoxia-ischaemia are unclear. Preterm-equivalent foetal sheep (0.6 gestation) received either sham-asphyxia or asphyxia induced by umbilical cord occlusion for 30 min, and recovered for either 3 or 35 days after asphyxia. The 35 day recovery groups received either an intracerebroventricular infusion of insulin-like growth factor-1 (1 µg/24 h) or vehicle, from 3 to 14 days after asphyxia. Asphyxia was associated with ventricular enlargement, and loss of frontal and parietal white matter area (P < 0.05 versus sham-asphyxia). This was associated with reduced area fraction of myelin basic protein and numbers of oligodendrocyte transcription factor 2 and mature, anti-adenomatous polyposis coli-positive oligodendrocytes in periventricular white matter (P < 0.05), with persistent inflammation and caspase-3 activation (P < 0.05). Four of eight foetuses developed cystic lesions in temporal white matter. Prolonged infusion with insulin-like growth factor-1 restored frontal white matter area, improved numbers of oligodendrocyte transcription factor 2-positive and mature, anti-adenomatous polyposis coli-positive oligodendrocytes, with reduced astrogliosis and microgliosis after 35 days recovery (P < 0.05 versus asphyxia). One of four foetuses developed temporal cystic lesions. Functionally, insulin-like growth factor-1-treated foetuses had faster recovery of EEG power, but not spectral edge. Encouragingly, these findings show that delayed, prolonged, insulin-like growth factor-1 treatment can improve functional maturation of periventricular white matter after severe asphyxia in the very immature brain, at least in part by suppressing chronic neural inflammation.

Comparison of Syn T2-FLAIR and Syn DIR with conventional T2-FLAIR in displaying white matter hyperintensities in migraine patients.

Young migraine patients often present with white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). This study aimed to analyze whether synthetic (Syn) T2-FLAIR and Syn double inversion recovery (DIR) can reveal WMHs more clearly and sensitively than conventional T2-FLAIR. Conventional MRI and Syn MRI data from 50 young migraine patients were analyzed prospectively. WMHs in each anatomical region (periventricular, deep white matter, and juxtacortical) were recorded separately. The differences in the clarity of lesion boundaries and the number of lesions displayed in the three sequences in the same anatomical region were analyzed. A total of 80 (periventricular area, 15; deep white matter, 31; juxtacortical area, 34), 163 (17, 50, 96), and 134 (18, 42, 74) lesions were observed with conventional T2-FLAIR, Syn T2-FLAIR, and Syn DIR, respectively. Syn T2-FLAIR and Syn DIR can show lesions more clearly than conventional T2-FLAIR (all P < 0.001). There was no significant difference in the number of lesions observed in the periventricular white matter among the three sequences (P = 0.159, 0.083, 0.322). Syn T2-FLAIR and Syn DIR can detect more lesions in the deep white matter than conventional T2-FLAIR (P < 0.001, P = 0.006). Syn T2-FLAIR revealed more lesions in the juxtacortical white matter than Syn DIR and conventional T2-FLAIR imaging (all P < 0.001), and conventional T2-FLAIR revealed the fewest lesions (P < 0.001). Syn T2-FLAIR and Syn DIR sequences can clearly and sensitively detect WMHs, especially in deep and juxtacortical white matter areas.

Clinical characteristics of children with MT-TK gene m.8344A>G variation

Objective: To summarize the clinical characteristics of children carrying the m.8344A>G variant of MT-TK gene. Methods: A case series study was conducted to retrospectively collect data of 22 children with mitochondrial disease caused by MT-TK gene m.8344A>G variation who were treated at the Department of Neurology of Beijing Children's Hospital of Capital Medical University from January 2012 to January 2024. Their clinical data, laboratory tests, muscle pathology, genetic testing, and the follow-up results were analyzed. Pearson correlation analysis was used for correlation analysis. Results: Among the 22 children, there were 13 boys and 9 girls. The age of onset was 5.00 (2.75, 9.00) years. Fifteen children had myoclonic epilepsy with ragged-red fibers (MERRF), 3 had Leigh syndrome (LS), and 4 had LS-MERRF overlap syndrome (LS-MERRF). Myoclonus presented and worsened progressively in all 15 MERRF children, with 10 as the initial symptom and 5 developing progressively during the disease course. Myoclonus was predominantly focal, worsening with fine motor tasks or stress. Electroencephalogram monitoring in the 15 MERRF children revealed myoclonic seizures in 10 children, with 6 classified as myoclonic epilepsy, and 4 as subcortical myoclonus. Two children had generalized myoclonic seizures, and 1 each had absence seizures and generalized seizures. Twelve children had cerebellar ataxia, 10 children exhibited exercise intolerance, and 8 children had muscle weakness. Magnetic resonance imaging (MRI) revealed periventricular white matter involvement in 1 child and bilateral hippocampal involvement in 1 child, likely due to frequent seizures. All 3 children with LS exhibited developmental regressions, accompanied with 2 symptoms include cerebellar ataxia, muscle weakness, and dysphagia. The clinical manifestations of 4 LS-MERRF overlap children presented with combined features of MERRF and LS. Cranial MRI in the 7 LS and LS-MERRF children showed brainstem involvement (all affecting the midbrain) in 6 children and basal ganglia involvement in 4 children. Among the 22 children, 12 had m.8344A>G variant levels >90%, 3 had >80%-90%, 4 had >70%-80%, and 3 had >60%-70%. Higher variant level correlated with the LS phenotype and earlier onset age (r=0.47, -0.50; P=0.018 and 0.029, respectively). Sanger sequencing in 19 mothers revealed m.8344A>G variations in 18, with 4 showing exercise intolerance. Follow-up of 13 children on antimyoclonic treatment showed>75% reduction in seizures with levetiracetam monotherapy in 2 children, with combination therapy required in others. Most achieved >50% seizures reduction within 2 years, but the effectiveness declined with disease progression. Conclusions: The m.8344A>G variant is rare, with MERRF being the most common phenotype, while LS and LS-MERRF are less common. Children with higher ratio of the m.8344A>G variant are more likely to present LS phenotype. Myoclonus, primarily focal, is a key feature, with levetiracetam as the first-line treatment and benzodiazepines recommended for refractory cases.

Choroid Plexus Volume in Rural Chinese Older Adults: Distribution and Association With Cardiovascular Risk Factors and Cerebral Small Vessel Disease.

The choroid plexus (CP) is involved in neurodegenerative diseases. However, the association of CP with cardiovascular risk factors and cerebral small vessel disease in older adults remains unclear. This population-based study included 1263 participants (60 years and older) from the MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China) substudy (2018-2020), of which 111 individuals completed diffusion tensor imaging examination. CP volume was automatically segmented. White matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), cerebral microbleeds, and lacunes were assessed following the Standards for Reporting Vascular Changes on Neuroimaging 1. Peak width of skeletonized mean diffusivity and free water were derived from diffusion tensor imaging images. We used linear regression models to evaluate the association between CP volume and cardiovascular risk factors, WMH volumes, and diffusion tensor imaging metrics, and logistic regression models to examine the association between CP volume and EPVS, cerebral microbleeds, and lacunes. The CP volume increased with age (P<0.001). Men (β coefficient=0.47 [95% CI, 0.29-0.64]) and participants with diabetes (β coefficient=0.16 [95% CI, 0.01-0.31]) had larger CP volumes than women and individuals without diabetes, respectively (P<0.05). Greater CP volume was significantly associated with larger total and periventricular WMH volumes and moderate to severe EPVS in basal ganglia (P<0.05) but not with deep WMHs, EPVS in centrum semiovale, lacunes, or cerebral microbleeds. In the diffusion tensor imaging subsample, enlarged CP was significantly associated with higher peak width of skeletonized mean diffusivity and free water of periventricular and deep white matter (P<0.05). An enlarged CP is associated with larger global and periventricular WMH volume and higher likelihoods of EPVS in basal ganglia and impaired white matter integrity, suggesting that an enlarged CP may represent a precursor of cerebral small vessel disease.

Quantification of white matter hyperintensities in type 1 diabetes and its relation to neuropathy and clinical characteristics

AimsThe aims were to quantify periventricular and deep white matter hyperintensities (WMHs) in adults with type 1 diabetes with different neuropathic phenotypes and to correlate WMH measurements to explanatory factors in diabetes. MethodsWMH measurements were obtained from brain magnetic resonance imaging of 56 adults with type 1 diabetes in subgroups including painful diabetic peripheral neuropathy (DPN), painless DPN, without DPN and 20 healthy controls using Fazekas scale and automatic segmentation analysis. ResultsNo differences in Fazekas assessed WMHs were found (individuals with periventricular lesions: diabetes 66 % vs. controls 40 %,p = 0.063, deep lesions: diabetes 52 % vs. controls 50 %,p = 1.0). Using automatic detection, there were no significant differences in count of periventricular (p = 0.30) or deep (p = 0.31) WMHs. Higher periventricular lesion burden was present in diabetes compared with controls (0.21 % vs. 0.06 %,p = 0.048), which was associated with more severe DPN, increased age, decreased cognitive function, and reduced volumetric and metabolic brain measures (all p < 0.05). ConclusionsOur findings indicate increased burden of periventricular WMHs in diabetes which were associated to DPN severity and measures reflecting neurodegeneration. Deep WMHs, often considered as chronic ischemic, were not significantly different. Mechanisms reflecting neurodegeneration and accelerated brain aging could be an overlooked aspect of peripheral and central neuropathy.

Cerebrovascular pulsatility indicates preoperative subcortical cognitive impairment and an increased risk for postoperative delirium in elderly patients undergoing elective spine surgery.

Advances in spine surgery enable safe interventions in elderly patients, but perioperative neurocognitive disorders (pNCD), such as post-operative delirium (POD) and cognitive dysfunction (POCD), remain a serious concern. Pre-operative cognitive impairment is a major risk factor for pNCD. Comprehensive pre-operative cognitive assessments are not feasible in clinical practice, making effective screening methods desirable. This study investigates whether pre-operative cerebrovascular duplex sonography can assess subcortical (vascular) cognitive impairment and the risk for POD. This prospective single-center study recruited patients aged ≥60 years scheduled for elective spine surgery at a German university hospital. Patients underwent pre-operative assessments including cognitive abilities (CERAD test battery), structural MRI, and cerebrovascular duplex sonography. POD screening was conducted three times daily for at least 3 days. The primary hypothesis, that the mean pulsatility index (PI) of both internal carotid arteries (ICA) predicts POD risk, was tested using logistic regression. Secondary analyses examined the association between POD risk and ICA flow (time-averaged peak velocities, TAPV) and correlations with cognitive profiles and MRI characteristics. POD occurred in 22% of patients (n = 22/99) within three postoperative days. Patients with POD were significantly older (75.9 ± 5.4 vs. 70.0 ± 6.9 years, p < 0.01) but did not differ by gender (p = 0.51). ICA PI significantly predicted POD risk (OR = 5.46 [95%CI: 1.81-16.49], p = 0.003), which remained significant after adjustment for age and duration of surgery (ORadj = 6.38 [95% CI: 1.77-23.03], p = 0.005). TAPV did not inform the POD risk (p = 0.68). ICA PI Pre-operative cognitive scores were significantly associated with ICA PI (mean CERAD score: r = -0.32, p < 0.001). ICA PI was also significantly associated with total white matter lesion volume (τ = 0.19, p = 0.012) and periventricular white matter lesion volume (τ = 0.21, p = 0.007). This is the first study to demonstrate that cerebrovascular duplex sonography can assess the risk for POD in elderly spine surgery patients. Increased ICA PI may indicate subcortical impairment, larger white matter lesion load, and lower white matter volume, predisposing factors for POD. Pre-operative cerebrovascular duplex sonography of the ICA is widely available, easy-to-use, and efficient, offering a promising screening method for POD risk. Increased ICA PI could supplement established predictors like age to adjust surgical and peri-operative procedures to individual risk profiles.

No Short-Term Effect of Low-Dose Nicotine on Inflammation after Global Hypoxia in Newborn Piglets

Introduction: Perinatal asphyxia initiates cytokine release and complement activation with risk of brain damage. We assessed the effect of nicotine on innate immunity and hypothesized that nicotine infusion in a newborn piglet model of asphyxia would decrease the immune response and be neuroprotective. Methods: Newborn piglets (n = 41) were randomized to one of three groups after hypoxia: two groups receiving nicotine, (1) 18 µg/kg/h (n = 17), (2) 46 µg/kg/h (n = 15), and (3) control group receiving saline (n = 9). C3a, IL-6, TNF, and IL-10 were measured in plasma and IL-6 and IL-8 in microdialysis fluid from cerebral periventricular white matter, using immuno-assays. Results: Plasma C3a and IL-6 increased significantly from start to end hypoxia (mean 4.4 ± 0.55 to 5.6 ± 0.71 ng/mL and 1.66 ± 1.04 to 2.68 ± 0.71 pg/mL, respectively), while IL-10 and TNF increased significantly after 4 h (mean 1.4 ± 1.08 to 2.9 ± 1.87 and 3.3 ± 0.67 to 4.0 ± 0.58 pg/mL, respectively) (p < 0.001 for all). IL-6 increased significantly (p < 0.001) in microdialysis samples from end hypoxia to end experiment (mean 0.65 ± 0.88 to 2.78 ± 1.84 ng/mL). No significant differences were observed between the nicotine groups and the control group neither in plasma nor in microdialysis samples. Conclusion: Hypoxia leads to rapid release of cytokines in plasma and cerebral microdialysis fluid, and complement activation measured on C3a. However, low-dose nicotine administration did not affect the immune response.

Increased extracellular free water is related to white matter hyperintensity burden.

Extracellular free water (FW) has important roles in the occurrence and development of white matter hyperintensity (WMH). To explore the correlations between FW and WMH burden. A prospective analysis was conducted using magnetic resonance imaging (MRI) data from 126 individuals. WMH burden was determined based on WMH volumes and Fazekas scores from deep and periventricular white matter hyperintensity (DWMH and PWMH, respectively) in fluid-attenuated inversion recovery (FLAIR) images. FW values were taken from diffusion tensor imaging (DTI). Univariate analysis showed that FW values were correlated with WMH burden, including WMH volumes and DWMH and PWMH Fazekas scores (P < 0.05). After multivariate analysis, FW values were correlated with WMH volumes and DWMH and PWMH Fazekas scores when adjusted for age and hypertension (P < 0.05). Using MRI, increasing extracellular FW was related to WMH burden.

Brain glycogen build-up measured by magnetic resonance spectroscopy in classic infantile Pompe disease.

Classic infantile Pompe disease is caused by abnormal lysosomal glycogen accumulation in multiple tissues, including the brain due to a deficit in acid α-glucosidase. Although treatment with recombinant human acid α-glucosidase has dramatically improved survival, recombinant human acid α-glucosidase does not reach the brain, and surviving classic infantile Pompe patients develop progressive cognitive deficits and white matter lesions. We investigated the feasibility of measuring non-invasively glycogen build-up and other metabolic alterations in the brain of classic infantile Pompe patients. Four classic infantile patients (8-16 years old) and 4 age-matched healthy controls were scanned on a 7 T MRI scanner. We used T2-weighted MRI to assess the presence of white matter lesions as well as 1H magnetic resonance spectroscopy and magnetic resonance spectroscopy imaging to obtain the neurochemical profile and its spatial distribution, respectively. All patients had widespread white matter lesions on T2-weighted images. Magnetic resonance spectroscopy data from a single volume of interest positioned in the periventricular white matter showed a clear shift in the neurochemical profile, particularly a significant increase in glycogen (result of acid α-glucosidase deficiency) and decrease in N-acetyl-aspartate (marker of neuronal damage) in patients. Magnetic resonance spectroscopy imaging results were in line and showed a widespread accumulation of glycogen and a significant lower level of N-acetyl-aspartate in patients. Our results illustrate the unique potential of 1H magnetic resonance spectroscopy (imaging) to provide a non-invasive readout of the disease pathology in the brain. Further study will assess its potential to monitor disease progression and the correlation with cognitive decline.

Quantitative Evaluation of White Matter Injury by Cranial Ultrasound to Detect the Effects of Parenteral Nutrition in Preterm Babies: An Observational Study.

Nutrition in early life has an impact on white matter (WM) development in preterm-born babies. Quantitative analysis of pixel brightness intensity (PBI) on cranial ultrasound (CUS) scans has shown a great potential in the evaluation of periventricular WM echogenicity in preterm newborns. We aimed to investigate the employment of this technique to objectively verify the effects of parenteral nutrition (PN) on periventricular WM damage in preterm infants. Prospective observational study including newborns with gestational age at birth ≤32 weeks and/or birth weight ≤1500 g who underwent CUS examination at term-equivalent age. The echogenicity of parieto-occipital periventricular WM relative to that of homolateral choroid plexus (RECP) was calculated on parasagittal scans by means of quantitative analysis of PBI. Its relationship with nutrient intake through enteral and parenteral routes in the first postnatal week was evaluated. The study included 42 neonates for analysis. We demonstrated that energy and protein intake administered through the parenteral route positively correlated with both right and left RECP values (parenteral energy intake vs. right RECP: r = 0.413, p = 0.007; parenteral energy intake vs. left RECP: r = 0.422, p = 0.005; parenteral amino acid intake vs. right RECP: r = 0.438, p = 0.004; parenteral amino acid intake vs. left RECP: r = 0.446, p = 0.003). Multivariate linear regression analysis confirmed these findings. Quantitative assessment of PBI could be considered a simple, risk-free, and repeatable method to investigate the effects of PN on WM development in preterm neonates.

Role of diffusion tensor imaging in the evaluation of white matter integrity in idiopathic intracranial hypertension.

To determine whether idiopathic intracranial hypertension (IIH) may affect white matter integrity and optic pathways by using diffusion tensor imaging (DTI) and to correlate the DTI metrics with intracranial pressure (ICP). This study is a retrospective case-control study. A total of 42 patients who underwent lumbar puncture and those with elevated ICP, meeting the diagnostic criteria for IIH, were included in the study. All patients had supportive magnetic resonance imaging findings for the diagnosis of IIH. The headache control group comprised 36 patients who presented to the Neurology Department with infrequent episodic tension-type headache, had a normal neurologic examination, and had clinical and radiological findings suggestive of normal ICP. For each patient with IIH, clinical findings and ophthalmological measurements were recorded. The apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) values were calculated using a region of interest-based method in different white matter tracts and optic pathways and compared. A total of 42 patients diagnosed with IIH (three males, 39 females), with a mean (standard deviation [SD] age of 38.1 (8.9) years), and 36 headache controls (10 males, 26 females, mean [SD] age; 38.1 [9.4] years) were included in the study. The mean (SD) body mass index (BMI) of the patients with IIH was 25.2 (1.9) kg/m2, and the mean (SD) BMI of the headache controls was 23.3 (1.5) kg/m2 (p < 0.001). Decreased FA values and increased RD values in the cingulum were detected in patients with IIH compared to the headache controls (p = 0.003, Cohen's d = 0.681; p = 0.002 Cohen's d = -0.710). Decreased AD values in the left and right superior cerebellar peduncle and increased ADC values in the middle cerebellar peduncle were detected in patients with IIH compared to the headache controls (p < 0.001, Cohen's d = 0.961; p = 0.009, Cohen's d = 0.607; p = 0.015, Cohen's d = -0.564). Increased ADC and RD values and decreased FA values in optic nerve were detected in patients with IIH (p = 0.010, Cohen's d = -0.603; p = 0.004, Cohen's d = -0.676; p = 0.015 Cohen's d = 0.568). Apositive correlation was found between the cerebrospinal fluid pressure and ADC values of the left and right superior and left inferior longitudinal fasciculus, genu of the corpus callosum, and right optic radiation (r = 0.43, p = 0.005; r = 0.31, p = 0.044; r = 0.39, p = 0.010; r = 0.35, p = 0.024; r = 0,41, p = 0.007). There was a positive correlation between the retinal nerve fiber layer thickness and the ADC values of the optic nerve (r = 0.32, p = 0.039). Intracranial hypertension can be associated with deteriorated DTI values, which might be interpreted as a sign of impaired white matter microstructural integrity in many brain regions beyond the periventricular white matter. Pressure-induced edema and axonal degeneration may be the potential underlying mechanisms of this microstructural damage.

Multiple sclerosis and amyotrophic lateral sclerosis: is there an association or a red flag? A case report and literature review

BackgroundMultiple sclerosis (MS) is an inflammatory disease of the central nervous system that causes damage to the myelin and axons and is caused by genetic or environmental factors. Amyotrophic lateral sclerosis (ALS) is characterized by rapidly progressive degeneration of the motor neurons resulting in the presence of upper and lower motor-neuron signs and symptoms.Case presentationA 46-year-old female patient presented with symmetrical weakness of the lower limbs and numbness that developed over weeks. Magnetic resonance imaging (MRI) of the brain exhibited typical demyelination features, high signal abnormality involving the periventricular and subcortical white matter, and an oval-shaped lesion. The patient was diagnosed with MS based on the clinical presentation and radiological examination. However, there was rapid progression of the symptoms, involvement of bulbar dysfunction, and muscle atrophy. Furthermore, the patient did not respond to acute therapy and immunotherapy, which made the diagnosis of MS less likely or suggested that it could be associated with another diagnosis. Her neurophysiological test met the criteria of ALS, and she was started on riluzole.Literature reviewWe reviewed all articles from 1986 to 2023, and there were 32 reported cases describing the co-occurrence of ALS and MS in different populations. Our case is the 33rd, and to our knowledge, it is the only case reported in the Middle East and specifically in Saudi Arabia. The main proposed mechanism according to postmortem examinations is a combination of degenerative and inflammatory processes with a cascade of production of reactive oxygen species and nitric oxide, which lead to cell death and apoptosis during concomitant ALS with MS.ConclusionThe co-occurrence of ALS and MS is extremely rare, but it can be explained by pathogenesis related to neurodegeneration, inflammation, or genetic susceptibility. Rapid progressive motor and bulbar symptoms could be red-flag symptoms, extensive evaluation might be needed for these patients.

An Algorithmic Approach to MR Imaging of Hypomyelinating Leukodystrophies.

Hypomyelinating leukodystrophies (HLDs) are a heterogeneous group of white matter diseases characterized by permanent deficiency of myelin deposition in brain. MRI is instrumental in the diagnosis and recommending genetic analysis, and is especially useful as many patients have a considerable clinical overlap, with the primary presenting complains being global developmental delay with psychomotor regression. Hypomyelination is defined as deficient myelination on two successive MR scans, taken at least 6 months apart, one of which should have been obtained after 1 year of age. Due to subtle differences in MRI features, the need for a systematic imaging approach to diagnose and classify hypomyelinating disorders is reiterated. The presented article provides an explicit review of imaging features of a myriad of primary and secondary HLDs, using state of the art genetically proven MR cases. A systematic pattern-based approach using MR features and specific clinical clues is illustrated for a quick yet optimal diagnosis of common as well as rare hypomyelinating disorders. The major MR features helping to narrow the differential diagnosis include extent of involvement like diffuse or patchy hypomyelination with selective involvement or sparing of certain white matter structures like optic radiations, median lemniscus, posterior limb of internal capsule and periventricular white matter; cerebellar atrophy; brainstem, corpus callosal or basal ganglia involvement; T2 hypointense signal of the thalami; and presence of calcifications. The authors also discuss the genetic and pathophysiologic basis of HLDs and recent methods to quantify myelin in vivo using advanced neuroradiology tools. The proposed algorithmic approach provides an improved understanding of these rare yet important disorders, enhancing diagnostic precision and improving patient outcomes. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

PLEKHG1: New Potential Candidate Gene for Periventricular White Matter Abnormalities.

Hypoxic-ischemic brain damage presents a significant neurological challenge, often manifesting during the perinatal period. Specifically, periventricular leukomalacia (PVL) is emerging as a notable contributor to cerebral palsy and intellectual disabilities. It compromises cerebral microcirculation, resulting in insufficient oxygen or blood flow to the periventricular region of the brain. As widely documented, these pathological conditions can be caused by several factors encompassing preterm birth (4-5% of the total cases), as well single cotwin abortion and genetic variants such as those associated with GTPase pathways. Whole exome sequencing (WES) analysis identified a de novo causative variant within the pleckstrin homology domain-containing family G member 1 (PLEKHG1) gene in a patient presenting with PVL. The PLEKHG1 gene is ubiquitously expressed, showing high expression patterns in brain tissues. PLEKHG1 is part of a family of Rho guanine nucleotide exchange factors, and the protein is essential for cell division control protein 42 (CDC42) activation in the GTPase pathway. CDC42 is a key small GTPase of the Rho-subfamily, regulating various cellular functions such as cell morphology, migration, endocytosis, and cell cycle progression. The molecular mechanism involving PLEKHG1 and CDC42 has an intriguing role in the reorientation of cells in the vascular endothelium, thus suggesting that disruption responses to mechanical stress in endothelial cells may be involved in the formation of white matter lesions. Significantly, CDC42 association with white matter abnormalities is underscored by its MIM phenotype number. In contrast, although PLEKHG1 has been recently associated with patients showing white matter hyperintensities, it currently lacks a MIM phenotype number. Additionally, in silico analyses classified the identified variant as pathogenic. Although the patient was born prematurely and subsequently to dichorionic gestation, during which its cotwin died, we suggest that the variant described can strongly contribute to PVL. The aim of the current study is to establish a plausible association between the PLEKHG1 gene and PVL.

MRI-based quantification of cardiac-driven brain biomechanics for early detection of neurological disorders.

We present a pipeline to quantify biomechanical environment of the brain using solely MRI-derived data in order to elucidate the role of biomechanical factors in neurodegenerative disorders. Neurological disorders, like Alzheimer's and Parkinson's diseases, are associated with physical changes, including the accumulation of amyloid-β and tau proteins, damage to the cerebral vasculature, hypertension, atrophy of the cortical gray matter, and lesions of the periventricular white matter. Alterations in the external mechanical environment of cells can trigger pathological processes, and it is known that AD causes reduced stiffness in the brain tissue during degeneration. However, there appears to be a significant lag time between microscale changes and macroscale obstruction of neurological function in the brain. Here, we present a pipeline to quantify the whole brain biomechanical environment to bridge the gap in understanding how underlying brain changes affect macroscale brain biomechanics. This pipeline enables image-based quantification of subject-specific displacement field of the whole brain to subject-specific strain, strain rate, and stress across 133 labeled functional brain regions. We have focused our development efforts on utilizing solely MRI-derived data to facilitate clinical applicability of our approach and have emphasized automation in all aspects of our methods to reduce operator dependance. Our pipeline has the potential to improve early detection of neurological disorders and facilitate the identification of disease before widespread, irreversible damage has occurred.