Moinuddin, F. M.

Abstract Background Spinal cord injury (SCI) induces complex secondary pathophysiological cascades, including microvascular disruption, glial activation, and chronic neuroinflammation. These vascular changes are dynamic and spatially heterogeneous across acute, subacute, and chronic phases. However, limitations in in vivo imaging resolution have impeded precise, longitudinal evaluation of spinal microcirculation. Objective To quantify post-SCI alterations in spinal cord vessel density, flow speed, and morphology over time using ultrasound localization microscopy (ULM), and to correlate these changes with chronic astrocytic reactivity assessed by GFAP expression. Methods Eleven Sprague-Dawley rats underwent T9–T11 laminectomy; nine received a standardized 200 kdyn contusion using the Infinite Horizons Impactor and were assigned to acute (24h), subacute (7d), and chronic (21d) groups (n = 3/group), while two served as uninjured controls. ULM was performed using a Vevo 3100 high-frequency ultrasound system with a 40 MHz transducer following intravenous Definity® microbubble injection. Vessel density (VD) and flow speed (FS) were quantified at the lesion epicenter and adjacent rostral/caudal regions. Arterial and venous compartments were distinguished by flow direction. Histological sections were stained for glial fibrillary acidic protein (GFAP), and %Area was quantified across phases. One-way ANOVA and Tukey’s test evaluated between-group differences; Pearson correlation identified phase-specific relationships between vascular metrics and chronic GFAP expression. Results ULM provided super-resolved imaging of spinal microvasculature at 5–10 µm resolution. Venous VD significantly declined from 0.92 ± 0.18 (acute) to 0.42 ± 0.23 (subacute) and 0.11 ± 0.07 (chronic, p < 0.001), particularly in dorsal regions. Arterial VD remained stable across timepoints (p > 0.05), while FS demonstrated transient reductions in both arterial and venous systems during the subacute phase. Chronic venous FS partially recovered by Day 21. GFAP-positive area increased significantly in the chronic group (3.3 ± 0.87%) compared to acute (1.52 ± 0.42%) and subacute (1.40 ± 0.05%) (p < 0.05), indicating delayed astrocyte reactivity. Correlation analysis revealed significant inverse associations between chronic GFAP %Area and early ventral venous density (r = − 1.0, p < 0.05), as well as positive correlations with chronic ventral arterial FS (r = 1.0, p < 0.01), suggesting early microvascular deficits may predict long-term gliosis. Conclusion This study demonstrates the feasibility and power of ULM to quantify dynamic microvascular remodeling in SCI with unprecedented resolution. Venous rarefaction precedes chronic astrocytosis, while arterial flow speed partially recovers over time. These findings highlight key spatiotemporal biomarkers of injury progression and support the use of ULM as a noninvasive platform for monitoring SCI pathophysiology and guiding therapeutic timing.

Background: Intrasellar kissing carotid arteries are a rare variant in which bilateral internal carotid arteries run very near each other at their cavernous sinus portion. We encountered a woman with the pituitary gland mimicking a pituitary microadenoma because the pituitary gland was compressed bilaterally by intrasellar kissing carotid arteries. Case Description: A 61-year-old woman with a chronic headache underwent magnetic resonance imaging, which revealed a sellar mass measuring 10.2 mm in height, 8.2 mm in length, and 4.0 mm in width at the midintercarotid level. Blood levels of all pituitary and target-organ hormones were within normal range. The height and superior convex shape of the sellar mass suggested that it was a nonfunctioning microadenoma, which was monitored over the past 16 years. A recent three-dimensional reconstruction of magnetic resonance angiography clearly showed that the pituitary gland was squeezed upward, compressed bilaterally, and extended superiorly by intrasellar kissing carotid arteries. Conclusion: The pituitary gland can be squeezed upward by intrasellar kissing carotid arteries and mimic pituitary tumor.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder presenting a triad including dementia and ventricular enlargement. The mechanism causing excessive cerebrospinal fluid (CSF) accumulation in the ventricles in iNPH is poorly understood. We hypothesized that the age-related degradation of the spinal shock-absorbing system composed of a spinal dural sac (SDS) and surrounding soft tissue, preventing ventricular enlargement caused by wide CSF pulsation driven by heartbeats, may be involved in the ventricular enlargement observed in iNPH. Methods: Sixty-four patients with iNPH in their seventies who underwent a lumboperitoneal shunt and a control group of 79 people in the same age group who underwent brain check-ups were included in the study. We compared the sizes of the cervical and upper parts of the thoracic SDS using magnetic resonance imaging between the two groups. Results: The anterior-posterior distances of the dural sac at C5 were shorter in patients with iNPH of both sexes than those in the control group (P = 0.0008 in men and P = 0.0047 in women). The number of disc levels with disappeared CSF space surrounding the cervical cord was more in iNPH (P = 0.0176 and P = 0.0003). The midsagittal area of the upper part of the spinal sac, C2-Th4, was smaller in iNPH (P = 0.0057 and P = 0.0290). Conclusion: Narrowing of the cervical dural sac and midsagittal area in the upper part of the SDS in patients with iNPH may reflect the degradation of the shock-absorbing mechanism for CSF pressure pulsations, which may cause iNPH or at least aggravate iNPH by other unknown causes.

Background:We previously found the usefulness of dural sac shrinkage signs (DSSSs), which are the anterior shift of the spinal cord and dura mater behind the cord, detected by magnetic resonance imaging (MRI) at the thoracic level for the diagnosis of spontaneous intracranial hypotension (IH). This is a retrospective survey on the usefulness of DSSSs for the early detection of iatrogenic IH caused by overdrainage through a lumboperitoneal shunt (LPS) for patients with idiopathic normal pressure hydrocephalus (INPH).Methods:Forty-five INPH patients had an LPS using a pressure programmable valve equipped with an anti-siphon device.Results:Nine patients complained of orthostatic headache after the LPS, indicating IH due to overdrainage, which persisted for more than a week in three patients and 2–7days in six patients. The headache was transient/ nonorthostatic in ten patients and absent in 26 patients. The DSSSs and accompanying enlargement of the venous plexus were observed in all three patients with prolonged orthostatic headaches. Only the anterior shift of the dura mater was observed in 1 (4%) among 25 patients who had short-term orthostatic headache, transient/ nonorthostatic headache, or absent headache, and underwent spinal MRI. A patient with prolonged severe orthostatic headache with both DSSSs eventually developed intracranial subdural effusion and underwent tandem valve surgery, which provided a quick improvement of symptoms. The DSSSs on thoracic MRI also disappeared promptly.Conclusion:DSSSs may serve as objective signs for the diagnosis of IH due to overdrainage through an LPS for INPH.

Background: Anterior inferior cerebellar artery (AICA) aneurysms in the internal auditory canal (IAC) are rare. We have reported a case of dissecting AICA aneurysm in the IAC presenting initially with the eighth nerve palsy followed by the seventh nerve palsy without hemorrhage. Case Description: A 68-year-old woman presented with a sudden onset of vertigo accompanied by deafness and tinnitus on the right side that was preceded by intermittent right retroauricular pain 2 weeks before. Audiogram showed severe sensorineural hearing loss. Computed tomography and magnetic resonance imaging (MRI) indicated absence of prior subarachnoid hemorrhage. Magnetic resonance angiogram (MRA) suggested a tiny aneurysm at the fundus of the IAC accompanied with thinning of the lateral pontine segment of the AICA. Conservative treatment led to moderate improvement of the symptoms. However, the patient developed the right retroauricular pain again, followed by the right facial paralysis 5 months later but still without signs of hemorrhage on MRI. Digital subtraction angiogram showed dissecting aneurysm in the IAC. The patient was managed with oral steroids and direct intervention was avoided due to a risk of ischemia supposed by large area irrigated by the AICA. Follow-up MRA 18 months after the first presentation showed improvement in the narrowing of the AICA proximal to the aneurysm. The patient was functionally independent despite right-sided hearing loss and slight facial paresis. Conclusion: This report warns physicians that a dissecting AICA aneurysm without subarachnoid hemorrhage may cause eighth and seventh nerve palsy.

Neuroimmunology plays a critical role in our understanding of the pathophysiological processes that underlie a variety of diseases treated by neurosurgeons, including degenerative disc disease (DDD), glioblastoma (GBM), aneurysmal subarachnoid hemorrhage (aSAH), and others. Compared with traditional methods in neuroimmunology, which study one pathway or gene at a time, emerging multiomics methodologies allow for holistic interrogation of multiple immune-signaling pathways to test hypotheses and the effects of therapeutics at a systems level. In this review, the authors summarize key concepts for gathering and analyzing multiomics data so that neurosurgeons can contribute to the emerging field of systems neuroimmunology. Additionally, they describe 3 use cases, based on original research published by their group and others, that utilize transcriptomic, metabolomic, and proteomic analyses to study immune-signaling pathways in DDD, aSAH, and GBM. Through these use cases, techniques for performing machine learning and network-based analyses to generate new clinical insights from multiomics data are shared. The authors hope that neurosurgeons might use this review as a summary of common tools and principles in systems immunology to better engage in creating the immunotherapies of tomorrow.

Currently, large numbers of clinical trials are performed to investigate different forms of experimental therapy for patients suffering from chronic spinal cord injury (SCI). However, for the enrollment process, there are different views on how the time period between injury and interventions should be determined. Herein, we sought to evaluate the impact of time-to-enrollment in chronic SCI clinical trials. A data set comprising 957 clinical studies from clinicalTrials.gov was downloaded and analyzed focusing on the eligibility criteria for post-injury time-to-enrollment. We also aggregated individual patient data from nine clinical trials of regenerative interventions for chronic SCI selected by a systematic literature search from 1990 to 2018. Characteristics of the studies were assessed and compared by dividing into three groups based on time-to-enrollment (group 1 ≤ 12 months, group 2 = 12–23 months and group 3 ≥ 24 months). In ClinicalTrials.gov registry, 445 trials were identified for chronic SCI where 87% (385) were unrestricted in the maximum post-injury time for trial eligibility. From systematic literature search, nine studies and 156 patients (group 1 = 30, group 2 = 55 and group 3 = 71) were included. The range of time-to-enrollment was 0.5 to 321 months in those studies. We also observed various degrees of motor and sensory improvement in between three time-to-enrollment groups. Our results indicate that enrolling wide ranges of time-to-enrollment in a group may present imprecise outcomes. Clinical trial designs should consider appropriate post-injury time frames to evaluate therapeutic benefit.

Background: Giant perivascular spaces (PVSs) are very rare condition in the brain and can be associated with neurological symptoms. It often enlarges and causes obstructive hydrocephalus which requires surgical intervention. However, the growth velocity has never been investigated. Case Description: Here, we report a woman in her early eighties with giant PVSs eventually followed up 17 years. She presented with dizziness and mild headache for a week and her neurological examination showed no abnormality. Her brain magnetic resonance imaging (MRI) showed a multiple cystic lesion, 28 mm in maximum diameter as a whole, in the left mesencephalothalamic region. There were no solid part, rim enhancement, or perilesional intensity change suggesting edema or gliosis. Smaller PVSs were also seen in bilateral-hippocampi, basal ganglia, white matter, and left frontal operculum. Retrospectively, five MRI studies over 17 years were analyzed using a 3-D volumetric software and found a very slow growth of the lesion, from 6.54 ml to 9.83 ml indicating gain of 0.1752 ml (2.68%) per year. Conclusion: This is the first report verifying a gradual enlargement of giant PVSs in a natural course. The prospective 3-D volumetric analysis on PVSs may elucidate the true nature of these lesions.