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PloS One 2022This patient and public-involved systematic review originally focused on arachnoiditis, a supposedly rare "iatrogenic chronic meningitis" causing permanent neurologic... (Review)
Review
BACKGROUND & IMPORTANCE
This patient and public-involved systematic review originally focused on arachnoiditis, a supposedly rare "iatrogenic chronic meningitis" causing permanent neurologic damage and intractable pain. We sought to prove disease existence, causation, symptoms, and inform future directions. After 63 terms for the same pathology were found, the study was renamed Diseases of the Leptomeninges (DLMs). We present results that nullify traditional clinical thinking about DLMs, answer study questions, and create a unified path forward.
METHODS
The prospective PRISMA protocol is published at Arcsology.org. We used four platforms, 10 sources, extraction software, and critical review with ≥2 researchers at each phase. All human sources to 12/6/2020 were eligible for qualitative synthesis utilizing R. Weekly updates since cutoff strengthen conclusions.
RESULTS
Included were 887/14286 sources containing 12721 DLMs patients. Pathology involves the subarachnoid space (SAS) and pia. DLMs occurred in all countries as a contributor to the top 10 causes of disability-adjusted life years lost, with communicable diseases (CDs) predominating. In the USA, the ratio of CDs to iatrogenic causes is 2.4:1, contradicting arachnoiditis literature. Spinal fusion surgery comprised 54.7% of the iatrogenic category, with rhBMP-2 resulting in 2.4x more DLMs than no use (p<0.0001). Spinal injections and neuraxial anesthesia procedures cause 1.1%, and 0.2% permanent DLMs, respectively. Syringomyelia, hydrocephalus, and arachnoid cysts are complications caused by blocked CSF flow. CNS neuron death occurs due to insufficient arterial supply from compromised vasculature and nerves traversing the SAS. Contrast MRI is currently the diagnostic test of choice. Lack of radiologist recognition is problematic.
DISCUSSION & CONCLUSION
DLMs are common. The LM clinically functions as an organ with critical CNS-sustaining roles involving the SAS-pia structure, enclosed cells, lymphatics, and biologic pathways. Cases involve all specialties. Causes are numerous, symptoms predictable, and outcomes dependent on time to treatment and extent of residual SAS damage. An international disease classification and possible treatment trials are proposed.
Topics: Arachnoiditis; Biological Products; Humans; Iatrogenic Disease; Meningitis; Prospective Studies
PubMed: 36178925
DOI: 10.1371/journal.pone.0274634 -
Methods in Molecular Biology (Clifton,... 2020This chapter describes the microanatomy of the spinal cord that is relevant to intrathecal drug delivery started with covering of the spinal cord that are pierced to...
This chapter describes the microanatomy of the spinal cord that is relevant to intrathecal drug delivery started with covering of the spinal cord that are pierced to enter the intrathecal space. The dural sac is mostly constituted by the outer layer of dura and the inner layer called arachnoid membrane, which regulates diffusion of drugs into the intrathecal space. The pia matter surrounding the spinal cord is a permeable structure allowing the passage of drugs through intercellular spaces. The relationship between nerve roots, CSF, and subarachnoid catheters determines the passage of an intrathecal catheter which can cause damage to nerve roots and spinal cord. Multiple factors may be involved in the mechanisms of drug diffusion across the membranes of the spinal cord, as well as in their dilution with the CSF, which will lead to the final drug distribution and availability at nerve roots and the spinal cord.
Topics: Cerebrospinal Fluid; Diffusion; Drug Delivery Systems; Humans; Infusion Pumps, Implantable; Injections, Spinal; Spinal Cord; Spinal Nerve Roots; Subarachnoid Space
PubMed: 31435917
DOI: 10.1007/978-1-4939-9798-5_4 -
Journal of Magnetic Resonance Imaging :... Sep 2021
Topics: Arachnoiditis; Humans; Magnetic Resonance Imaging
PubMed: 33713514
DOI: 10.1002/jmri.27597 -
AJNR. American Journal of Neuroradiology Feb 2023Arachnoiditis ossificans is an uncommon end-stage appearance of chronic adhesive arachnoiditis. Imaging features of arachnoiditis ossificans are characteristic and...
Arachnoiditis ossificans is an uncommon end-stage appearance of chronic adhesive arachnoiditis. Imaging features of arachnoiditis ossificans are characteristic and should be diagnosed to avoid unnecessary intervention and guide prognosis and management. In this case series, we retrospectively analyzed CT and MR imaging of 41 patients to identify common patterns of intrathecal ossification and present the common etiologies. Thirty-two patients had a confirmed history of spinal instrumentation, 7 were discovered on imaging without prior surgical history, 1 had a history of ankylosing spondylitis, and 1 had trauma. The most frequent site of ossification was at the conus and cauda equina. Four patterns of ossification were identified, including central, nerve root encasing, weblike, and peripheral. Arachnoiditis ossificans is an important, likely under-recognized consideration in patients who present with back pain. Diagnosis can be made readily on CT; MR imaging diagnosis is also possible but may be challenging.
Topics: Humans; Retrospective Studies; Osteogenesis; Arachnoiditis; Tomography, X-Ray Computed; Magnetic Resonance Imaging
PubMed: 36635055
DOI: 10.3174/ajnr.A7764 -
Journal of Neurological Surgery. Part... Jan 2021The aim of this study was to analyze the demographics, clinical presentation, and surgical outcome of intracranial arachnoid cysts and to review the surgical options. (Observational Study)
Observational Study
OBJECTIVES
The aim of this study was to analyze the demographics, clinical presentation, and surgical outcome of intracranial arachnoid cysts and to review the surgical options.
METHODS
This is a retrospective observational study of 56 cases of symptomatic arachnoid cysts among all age groups treated between 2004 and 2020 at the Bombay Hospital, Mumbai. Endoscopic fenestration, microsurgical cyst excision, and shunt insertion were the interventions performed. Clinical presentation, cyst reduction post-intervention, and complications were studied. The follow-up period varied from 1 month to 16 years. Statistical analysis was done for 43 patients with a minimum of 3 years' follow-up.
RESULTS
In all, 75% of patients were <18 years of age. Of these, the majority were between the age of 1 and 10 years. There were 14 cases of temporal, 13 cases of retrocerebellar, 10 cases of quadrigeminal cistern, and 7 cases each of interhemispheric and suprasellar arachnoid cysts. The most common clinical presentation was headache and vomiting. Concomitant hydrocephalus was seen on imaging in 24 cases. Endoscopic fenestration of cyst was the most routinely performed procedure (35 cases). Four patients of endoscopic fenestration underwent a redo endoscopic procedure on follow-up. Post-operative reduction in cyst size was found to be significantly better after endoscopic fenestration ( < 0.05).
CONCLUSION
Though the best available treatment for arachnoid cysts remains controversial, surgery has been found to be beneficial in symptomatic cases. Endoscopic fenestration is considered the first-line surgical option and it may be followed by shunt, if necessary. Shunts may be preferred in very young children where there is associated hydrocephalus/macrocephaly.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Young Adult; Arachnoid Cysts; Hydrocephalus; Retrospective Studies; Subarachnoid Space; Treatment Outcome; Neuroendoscopy; Megalencephaly
PubMed: 33157563
DOI: 10.1055/s-0040-1718522 -
Journal of Obstetrics and Gynaecology :... Nov 2022Few studies on the prediction of skin to subarachnoid space depth (SSD) in African parturients undergoing caesarean delivery are available. We undertook a prospective... (Observational Study)
Observational Study
Few studies on the prediction of skin to subarachnoid space depth (SSD) in African parturients undergoing caesarean delivery are available. We undertook a prospective observational study of 402 parturients scheduled for elective caesarean delivery to determine simple and clinically applicable formulae for predicting skin to SSD. Additionally, the impact of patient characteristics and variables such as age, height, weight, body mass index (BMI), and body surface area on SSD was studied. We employed a Stepwise Multiple Linear Regression Model to predict SSD in normal weight, overweight, and obese parturients using previously described formulae and compared our derived SSDs to these previous formulae for concordance. (Craig, Abe, Stocker, Chong's modified, Prakash, Ma, Hazarika, Taman and Celik). Mean SSD was 6.62 ± 1.07 cm in the overall population. SSD in normal weight patients was (6.19 ± 0.92 cm), overweight (6.44 ± 0.92 cm) and obese (6.97 ± 1.17 cm). There was a correlation between SSD and BMI ( = 0.001). Formulae for predicting SSD in the overall population, normal weight, overweight and obese parturients were 4.34 + weight × 0.03, 4.43 + weight × 0.03, 4.54 + weight × 0.03 and 3.56 + weight × 0.03, respectively. We also found the Prakash formula to correlate best with our observed SSD. We concluded that SSD correlated well with weight in the overall parturient population and that Prakash's formula was the most accurate of the other previously described formulae in predicting SSD in this subset of African parturients.
Topics: Female; Humans; Pregnancy; Body Mass Index; Body Weight; Cesarean Section; Obesity; Overweight; Subarachnoid Space; Prospective Studies; Adult
PubMed: 36518050
DOI: 10.1080/01443615.2022.2151348 -
Fluids and Barriers of the CNS Nov 2022Today's availability of medical imaging and computational resources set the scene for high-fidelity computational modelling of brain biomechanics. The brain and its...
BACKGROUND
Today's availability of medical imaging and computational resources set the scene for high-fidelity computational modelling of brain biomechanics. The brain and its environment feature a dynamic and complex interplay between the tissue, blood, cerebrospinal fluid (CSF) and interstitial fluid (ISF). Here, we design a computational platform for modelling and simulation of intracranial dynamics, and assess the models' validity in terms of clinically relevant indicators of brain pulsatility. Focusing on the dynamic interaction between tissue motion and ISF/CSF flow, we treat the pulsatile cerebral blood flow as a prescribed input of the model.
METHODS
We develop finite element models of cardiac-induced fully coupled pulsatile CSF flow and tissue motion in the human brain environment. The three-dimensional model geometry is derived from magnetic resonance images (MRI) and features a high level of detail including the brain tissue, the ventricular system, and the cranial subarachnoid space (SAS). We model the brain parenchyma at the organ-scale as an elastic medium permeated by an extracellular fluid network and describe flow of CSF in the SAS and ventricles as viscous fluid movement. Representing vascular expansion during the cardiac cycle, a prescribed pulsatile net blood flow distributed over the brain parenchyma acts as the driver of motion. Additionally, we investigate the effect of model variations on a set of clinically relevant quantities of interest.
RESULTS
Our model predicts a complex interplay between the CSF-filled spaces and poroelastic parenchyma in terms of ICP, CSF flow, and parenchymal displacements. Variations in the ICP are dominated by their temporal amplitude, but with small spatial variations in both the CSF-filled spaces and the parenchyma. Induced by ICP differences, we find substantial ventricular and cranial-spinal CSF flow, some flow in the cranial SAS, and small pulsatile ISF velocities in the brain parenchyma. Moreover, the model predicts a funnel-shaped deformation of parenchymal tissue in dorsal direction at the beginning of the cardiac cycle.
CONCLUSIONS
Our model accurately depicts the complex interplay of ICP, CSF flow and brain tissue movement and is well-aligned with clinical observations. It offers a qualitative and quantitative platform for detailed investigation of coupled intracranial dynamics and interplay, both under physiological and pathophysiological conditions.
Topics: Humans; Cerebral Ventricles; Subarachnoid Space; Pulsatile Flow; Computer Simulation; Brain; Magnetic Resonance Imaging; Cerebrospinal Fluid
PubMed: 36320038
DOI: 10.1186/s12987-022-00376-2 -
British Journal of Neurosurgery Jun 2023Virchow Robin spaces are normally found pial-lined perivascular spaces traversing from subarachnoid space to the brain parenchyma. Giant dilated Virchow robin spaces...
Virchow Robin spaces are normally found pial-lined perivascular spaces traversing from subarachnoid space to the brain parenchyma. Giant dilated Virchow robin spaces (dVRS) are rare. They do not require any surgical intervention unless they are causing symptoms. Here we report a young boy with an incidentally detected giant dVRS in brainstem which was referred for surgery with an initial impression of glioma. Knowledge about such an entity is important to prevent mismanagement.
Topics: Humans; Male; Brain; Brain Stem; Dilatation, Pathologic; Glymphatic System; Magnetic Resonance Imaging; Subarachnoid Space
PubMed: 32909842
DOI: 10.1080/02688697.2020.1817854 -
Journal of Neurosurgery. Spine Feb 2021Surgical treatment for nonforaminal syringomyelia related to spinal arachnoiditis is still controversial. The authors sought to assess respective outcomes and rates of...
OBJECTIVE
Surgical treatment for nonforaminal syringomyelia related to spinal arachnoiditis is still controversial. The authors sought to assess respective outcomes and rates of reintervention for shunting and spinal cord untethering (arachnolysis) in spinal arachnoiditis with syringomyelia.
METHODS
This retrospective cohort study was conducted at a single reference center for syringomyelia. Patients undergoing arachnolysis and/or shunting interventions for nonforaminal syringomyelia were screened.
RESULTS
The study included 75 patients undergoing 130 interventions. Arachnolysis without shunting was performed in 48 patients, while 27 patients underwent shunting. The mean follow-up between the first surgery and the last outpatient visit was 65.0 months (range 12-379 months, median 53 months). At the last follow-up, the modified McCormick score was improved or stabilized in 83.4% of patients after arachnolysis versus 66.7% after shunting. Thirty-one (41.3%) patients underwent reintervention during follow-up, with a mean delay of 33.2 months. The rate of reintervention was 29.2% in the arachnolysis group versus 63.0% in the shunting group (chi-square = 8.1, p = 0.007). However, this difference was largely driven by the extension of the arachnoiditis: in patients with focal arachnoiditis (≤ 2 spinal segments), the reintervention rate was 21.6% for arachnolysis versus 57.1% for shunting; in patients with extensive arachnoiditis, it was 54.5% versus 65.0%, respectively. Survival analysis assessing the time to the first reintervention demonstrated a better outcome in both the arachnolysis (p = 0.03) and the focal arachnoiditis (p = 0.04) groups.
CONCLUSIONS
Arachnolysis led to fewer reinterventions than shunting in patients with nonforaminal syringomyelia. There was a high risk of reintervention for patients with extensive arachnopathies, irrespective of the surgical technique.
Topics: Adolescent; Adult; Aged; Arachnoiditis; Cerebrospinal Fluid Shunts; Humans; Male; Middle Aged; Neurosurgical Procedures; Retrospective Studies; Spinal Cord; Syringomyelia; Vascular Surgical Procedures; Young Adult
PubMed: 33545681
DOI: 10.3171/2020.8.SPINE20928 -
Journal of Neurochemistry Apr 2022The purpose of this study was to elucidate the absolute abundance of transporters, enzymes, receptors, and tight junction and marker proteins at human blood-arachnoid...
The purpose of this study was to elucidate the absolute abundance of transporters, enzymes, receptors, and tight junction and marker proteins at human blood-arachnoid barrier (BAB) and compare with those of dogs and pigs. Protein expression levels in plasma membrane fractions of brain leptomeninges were determined by quantitative targeted absolute proteomics. To realistically compare the absolute abundance of target molecules at the BAB among humans, dogs, and pigs, the unit was converted from fmol/μg-protein to pmol/cm -leptomeninges. Of a total of 70 proteins, 52 were detected. OAT1, OAT3, GLUT1, 4F2hc, EAAT1, EAAT2, MCT8, SMVT, CTL2, GFAP, Claudin-5, Na /K -ATPase, COMT, GSTP1, and CES1 were abundantly expressed at the human BAB (>1 pmol/cm ). The protein expression levels were within a 3-fold difference for 16 out of 33 proteins between humans and dogs and for 13 out of 28 proteins between humans and pigs. Both human-dog and human-pig differences in protein expression levels were within 3-fold for OAT1, OAT3, 4F2hc, xCT, OCT2, MDR1, BCRP, PEPT2, SYP, and MCT1. In contrast, OCT3, MCT4, and OATP1A2 were detected in humans but not in dogs or pigs. MRP3 was detected in dogs and pigs but not in humans. The absolute level of GLUT1 in humans was nearly the same as that in dogs but was 6.14-fold greater in pigs. No significant differences in the levels were observed between male and female dogs for nearly all molecules. These results should be helpful in understanding the physiological roles of BAB and cerebrospinal fluid pharmacokinetics in humans and their differences from dogs and pigs.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Animals; Arachnoid; Biomarkers; Blood-Brain Barrier; Dogs; Female; Glucose Transporter Type 1; Humans; Male; Membrane Transport Proteins; Neoplasm Proteins; Swine; Tight Junctions
PubMed: 35226354
DOI: 10.1111/jnc.15599