The leptomeninges as a critical organ for normal CNS development and function: First patient and public involved systematic review of arachnoiditis (chronic meningitis).

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.

Arachnoiditis Ossificans of the Lumbar Spine: A Rare Cause of Progressive Cauda Equina Syndrome.

Arachnoiditis ossificans of the spine is a rare entity defined as an ossification of the leptomeninges resulting in neurologic decline. We describe the case of a 42-year-old woman, without any obvious predisposing factor, who presented with a progressive cauda equina syndrome. The imaging findings on magnetic resonance imaging were confusing by showing an atypical intraspinal lesion extending from L1 to S1. The computed tomography scan was more specific by showing suggestive images of a huge arachnoiditis ossificans of the lumbar spine. The patient underwent a large lumbar laminectomy with an incomplete resection of the ossified arachnoid. The histologic study confirmed the bony nature of the lesion. This illustrative case highlights the importance of helical computed tomography scan with multiplanar reconstruction for the diagnosis of arachnoiditis ossificans.

Prolonged inflammation leads to ongoing damage after spinal cord injury.

The pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment remains limited. Emerging evidence indicates that post-SCI inflammation is severe but the role of reactive astrogliosis not well understood given its implication in ongoing inflammation as damaging or neuroprotective. We have completed an extensive systematic study with MRI, histopathology, proteomics and ELISA analyses designed to further define the severe protracted and damaging inflammation after SCI in a rat model. We have identified 3 distinct phases of SCI: acute (first 2 days), inflammatory (starting day 3) and resolution (>3 months) in 16 weeks follow up. Actively phagocytizing, CD68+/CD163- macrophages infiltrate myelin-rich necrotic areas converting them into cavities of injury (COI) when deep in the spinal cord. Alternatively, superficial SCI areas are infiltrated by granulomatous tissue, or arachnoiditis where glial cells are obliterated. In the COI, CD68+/CD163- macrophage numbers reach a maximum in the first 4 weeks and then decline. Myelin phagocytosis is present at 16 weeks indicating ongoing inflammatory damage. The COI and arachnoiditis are defined by a wall of progressively hypertrophied astrocytes. MR imaging indicates persistent spinal cord edema that is linked to the severity of inflammation. Microhemorrhages in the spinal cord around the lesion are eliminated, presumably by reactive astrocytes within the first week post-injury. Acutely increased levels of TNF-alpha, IL-1beta, IFN-gamma and other pro-inflammatory cytokines, chemokines and proteases decrease and anti-inflammatory cytokines increase in later phases. In this study we elucidated a number of fundamental mechanisms in pathogenesis of SCI and have demonstrated a close association between progressive astrogliosis and reduction in the severity of inflammation.

A Novel Technique Using Magnetic Resonance Imaging in the Supine and Prone Positions for Diagnosing Lumbar Adhesive Arachnoiditis: A Preliminary Study.

BACKGROUND: Lumbar adhesive arachnoiditis is a debilitating neuropathic condition and is difficult to diagnose owing to lack of definitive diagnostic criteria. By focusing on the intrathecal mobility of nerve roots, we assessed whether useful diagnostic criteria could be established using MRI. METHODS: Seventeen patients with a high risk for lumbar adhesive arachnoiditis and 18 no-risk patients with chronic low back pain and/or leg pain participated in this study. The patients underwent MRI in both the supine and prone positions. Eleven axial T2-weighted images between the L2 and L5/S levels were obtained, and the proportion of the low-intensity area in the dorsal half to the total low-intensity area in the dural sac was calculated for each axial view. RESULTS: At some lumbar levels, the low-intensity area in the dorsal half of the dural sac was relatively larger in patients with a high risk for lumbar adhesive arachnoiditis than in the no-risk patients. In the no-risk group, the proportion of the low-intensity area in the dorsal half in the supine position was significantly higher than that in the prone position at all lumbar levels. However, in the high-risk group, at some levels, the proportions were not significantly different in the dorsal half of the dural sac between the supine and prone positions. CONCLUSION: In patients with a known risk for lumbar adhesive arachnoiditis, nerve roots lose their potential to migrate in the dural sac in the gravitational force direction on MRI.

Spinal Arachnoiditis Ossificans: Report of Quadruple-Triggered Case.

BACKGROUND: Arachnoiditis ossificans (AO) is a rare condition often associated with previous spine surgery. Here we describe a unique case of a patient affected by ankylosing spondylitis (AS), presenting with progressive neurologic deterioration due to AO. We also review the literature on evaluation and management of patients suffering from AO. CASE DESCRIPTION: The 65-year-old patient had a history of previous spinal trauma and related thoracolumbar surgery. Magnetic resonance imaging revealed multiloculated intradural/extramedullary cysts on the posterior surface of the spinal cord at Th9-L1, with clustered nerve roots. Computed tomography, with 3-dimensional reconstruction, demonstrated a likely ossification of both the dura and arachnoid from Th9 to S1. Microsurgical debridement of scar tissue from previous surgery, drilling of posterior ossified plaques at Th11-Th12-L1, and marsupialization and drainage of arachnoid cysts at Th11-Th12 were performed. CONCLUSIONS: We submit that AS, spinal trauma, epidural hematoma, and related surgery may be synergistic and independent factors in the etiopathogenesis of AO. This should be considered in patients with AS and/or a history of spinal surgery who present neurologic worsening.

Arachnoiditis ossificans associated with syringomyelia: a case report.

The association of arachnoiditis ossificans with syringomyelia is a rare pathological entity. We present an unusual case who presented with progressive myelopathy caused by arachnoidits ossificans and syringomyelia. The pathophysiology and treatment strategy of this rare entity are still controversial.

Aracnoidits y quistes aracnoideos espinales múltiples. Revisión bibliográfica a propósito de un caso / ARACNOIDITIS AND MULTIPLE ARACNOID CYSTS : CASE REPORT AND REVISION OF THE LITERATURE

Los quistes aracnoideos son lesiones malformativas que contienen en su interior un líquido de características similares al líquido cefalorraquídeo. Constituyen alrededor del 1% de todos los procesos ocupantes de espacio a nivel intracraneal y, en menor número de casos pueden localizarse a nivel espinal. Presentamos una asociación de aracnoiditis espinal y posterior cavitación.

Arachnoid cysts are malformative lesions that contain a liquid with characteristics similar to cerebrospinal fluid. They constitute about 1% of all space-occupying processes at the intracranial level and, in a smaller number of cases, they can be located at the spinal level. We present an association of spinal arachnoiditis and posterior cavitation

Central Nervous System Tuberculosis.

Central nervous system tuberculosis (CNS-TB) takes three clinical forms: meningitis (TBM), intracranial tuberculoma, and spinal arachnoiditis. TBM predominates in the western world and presents as a subacute to chronic meningitis syndrome with a prodrome of malaise, fever, and headache progressing to altered mentation and focal neurologic signs, followed by stupor, coma, and death within five to eight weeks of onset. The CSF formula typically shows a lymphocytic pleocytosis, and low glucose and high protein concentrations. Diagnosis rests on serial samples of CSF for smear and culture, combined with CSF PCR. Brain CT and MRI aid in diagnosis, assessment for complications, and monitoring of the clinical course. In a patient with compatible clinical features, the combination of meningeal enhancement and any degree of hydrocephalus is strongly suggestive of TBM. Vasculitis leading to infarcts in the basal ganglia occurs commonly and is a major determinant of morbidity and mortality. Treatment is most effective when started in the early stages of disease, and should be initiated promptly on the basis of strong clinical suspicion without waiting for laboratory confirmation. The initial 4 drug regimen (isoniazid, rifampin, pyrazinamide, ethambutol) covers the possibility of infection with a resistant strain, maximizes antimicrobial impact, and reduces the likelihood of emerging resistance on therapy. Adjunctive corticosteroid therapy has been shown to reduce morbidity and mortality in all but late stage disease.

Longitudinal measurements of syrinx size in a rat model of posttraumatic syringomyelia.

OBJECTIVE Syringomyelia pathophysiology is commonly studied using rodent models. However, in vivo studies of posttraumatic syringomyelia have been limited by the size of animals and lack of reliable noninvasive evaluation techniques. Imaging the rat spinal cord is particularly challenging because the spinal cord diameter is approximately 1-3 mm, and pathological lesions within the spinal cord parenchyma are even smaller. The standard technique has been histological evaluation, but this has its limitations. The aim of the present study was to determine whether syrinx size could be reliably measured using a preclinical high-field MRI animal system in a rat model of posttraumatic syringomyelia. METHODS The authors used an existing rat model of posttraumatic syringomyelia, which was created using a controlled pneumatic compression device to produce the initial spinal cord injury, followed by a subarachnoid injection of kaolin to produce arachnoiditis. T2-weighted MRI was performed on each animal using a 9.4-T scanner at 7, 10, and 13 weeks after injury. Animals were killed and syrinx sizes were calculated from in vivo MRI and histological studies. RESULTS MRI measurements of syrinx volume and length were closely correlated to histological measurements across all time points (Pearson product moment correlation coefficient r = ± 0.93 and 0.79, respectively). CONCLUSIONS This study demonstrates that high-field T2-weighted MRI can be used to measure syrinx size, and data correlate well with syrinx size measured using histological methods. Preclinical MRI may be a valuable noninvasive technique for tracking syrinx formation and enlargement in animal models of syringomyelia.

Idiopathic opticochiasmatic arachnoiditis.

: A critical review of the literature indicates that idiopathic opticochiasmatic arachnoiditis, once considered an important consideration in patients with otherwise unexplained optic atrophy, is not a valid disease entity.

Familial adhesive arachnoiditis associated with syringomyelia.

Adhesive arachnoiditis is a rare condition, often complicated by syringomyelia. This pathologic entity is usually associated with prior spinal surgery, spinal inflammation or infection, and hemorrhage. The usual symptoms of arachnoiditis are pain, paresthesia, and weakness of the low extremities due to the nerve entrapment. A few cases have had no obvious etiology. Previous studies have reported one family with multiple cases of adhesive arachnoiditis. We report a second family of Belgian origin with multiple cases of arachnoiditis and secondary syringomyelia in the affected individuals.

[Flexible endoscopy in surgical treatment of spinal adhesive arachnoiditis and arachnoid cysts].

Thecaloscopy is less invasive exploration of spinal subarachnoid space with ultra-thin flexible endoscope and endoscopic fenestration of scars and adhesions. Thecalopscopy was used in Russian neurosurgery at the first time. Since 2009 we operated 32 patients with following diagnosis: 17--spinal adhesive arachnoiditis (8--local forms, 9--diffuse forms), 12--spinal arachnoid cysts (7--posstraumatic cysts, 5--idiopathic cysts), 3--extramedullary tumors (thecaloscopic videoassistance and biopsy). In all cases we realized exploration of subarachnoid space and pathologic lesion with endoscopic perforation of cyst or dissection of adhesions using special instrumentation. Mean follow-up in our group was 11.4 months. Neurological improvement (mean 1.4 by modified Frankel scale, 1.8 by Ashworth spasticity scale) was seen in 87% of patients operated for spinal arachnopathies. Temporary neurological deterioration (mild disturbances of deep sensitivity) was seen in 9% of patients and managed successfully with conservative treatment. 1 (3.1%) patient was operated 3 times because of relapse of adhesions. There were no serious intraoperative complications (e.g., serious bleeding, dura perforation etc). Postoperative complications included 1 CSF leakage and 1 postoperative neuralgic pain. Mean term of hospitalization was 7.6 days. According to our data, we suppose that thecaloscopy is efficient and safe method, and should be widely used for spinal arachnopaties, adhesive arachnoiditis and arachnoid cysts. Taking into account that adhesive spinal arachnoiditis is systemic process and spinal arachnoid cysts can be extended as well, thecaloscopy may be regarded as the most radical and less-invasive way of surgical treatment existing currently in neurosurgery.

Cauda equina syndrome after cesarean section.

This report describes a case of cauda equina syndrome possibly caused by arachnoiditis due to levobupivacaine after spinal-epidural anesthesia. A 39-yr-old woman delivered by cesarean section under a combined spinal-epidural anesthesia. After an uneventful procedure and surgery, she complained of weakness in her lower extremities, which increased in a few hours. Neurologic examination revealed severe weakness in both her lower extremities, perianal anesthesia, and absence of muscle stretch reflexes. She was unable to urinate. Magnetic resonance imaging performed immediately revealed entirely normal results; however, gadolinium-enhanced magnetic resonance imaging 10 days later revealed contrast enhancement in the cauda equina fibers concordant with arachnoiditis. The patient was included in an intense rehabilitation program with a diagnosis of cauda equina syndrome and recovered completely in 8 wks. Practitioners should be aware of neurologic complications of spinal-epidural anesthesia. Early detection and treatment of the complication are important to minimize the risk of adverse outcome.

[Fulminant adhesive arachnoiditis]. / Zlepne zapalenie pajeczynówki o piorunujacym przebiegu.

Adhesive arachnoiditis is a rare disease with insidious course. It causes damage of the spinal cord and nerve roots. The causes of adhesive arachnoiditis include earlier traumatic injury of the spinal cord, surgery, intrathecal administration of therapeutic substances (e.g. anaesthetics, chemotherapy) or contrast media, bleeding, and inflammation. It can also be idiopathic or iatrogenic. We present the case of a 42-year-old patient with fulminant adhesive arachnoiditis which was provoked by spinal surgery and caused severe neurological disability with profound, progressive, flaccid paraparesis and bladder dysfunction. The electromyography (EMG) showed serious damage of nerves of both lower limbs at the level of motor roots L2-S2 and damage of the motor neuron at the level of Th11-Th12 on the right side. Magnetic resonance imaging of the lumbosacral and thoracic part of the spinal cord demonstrated cystic liquid spaces in the lumen of the dural sac in the bottom part of the cervical spine and at the Th2-Th10 level, modelling the lateral and anterior surface of the cord. Because of the vast lesions, surgery could not be performed. Conservative treatment and rehabilitation brought only a small clinical improvement.

Severe adhesive arachnoiditis resulting in progressive paraplegia following obstetric spinal anaesthesia: a case report and review.

A 27-year-old woman developed severe adhesive arachnoiditis after an obstetric spinal anaesthetic with bupivacaine and fentanyl, complicated by back pain and headache. No other precipitating cause could be identified. She presented one week postpartum with communicating hydrocephalus and syringomyelia and underwent ventriculoperitoneal shunting and foramen magnum decompression. Two months later, she developed rapid, progressive paraplegia and sphincter dysfunction. Attempted treatments included exploratory laminectomy, external drainage of the syrinx and intravenous steroids, but these were unsuccessful and the patient remains significantly disabled 21 months later. We discuss the pathophysiology of adhesive arachnoiditis following central neuraxial anaesthesia and possible causative factors, including contamination of the injectate, intrathecal blood and local anaesthetic neurotoxicity, with reference to other published cases. In the absence of more conclusive data, practitioners of central neuraxial anaesthesia can only continue to ensure meticulous, aseptic, atraumatic technique and avoid all potential sources of contamination. It seems appropriate to discuss with patients the possibility of delayed, permanent neurological deficit while taking informed consent.

Reversible distension of the subarachnoid space around the optic nerves in a case of idiopathic hypertrophic pachymeningitis.

Idiopathic hypertrophic pachymeningitis (IHP) is a chronic inflammatory disease of unknown cause. We report a case of IHP with bilateral distended subarachnoid space (SAS) of the optic nerves and unilateral visual disturbance. We observed marked amelioration of magnetic resonance (MR) imaging findings after initiation of treatment with prednisolone. This radiological finding implicates optic nerve sheath involvement that affects cerebrospinal fluid (CSF) dynamics around the optic nerve.

The relationship between localized subarachnoid inflammation and parenchymal pathophysiology after spinal cord injury.

Subarachnoid inflammation following spinal cord injury (SCI) can lead to the formation of localized subarachnoid scarring and the development of post-traumatic syringomyelia (PTS). While PTS is a devastating complication of SCI, its relative rarity (occurring symptomatically in about 5% of clinical cases), and lack of fundamental physiological insights, have led us to examine an animal model of traumatic SCI with induced arachnoiditis. We hypothesized that arachnoiditis associated with SCI would potentiate early parenchymal pathophysiology. To test this theory, we examined early spatial pathophysiology in four groups: (1) sham (non-injured controls), (2) arachnoiditis (intrathecal injection of kaolin), (3) SCI (35-g clip contusion/compression injury), and (4) PTS (intrathecal kaolin+SCI). Overall, there was greater parenchymal inflammation and scarring in the PTS group relative to the SCI group. This was demonstrated by significant increases in cytokine (IL-1α and IL-1ß) and chemokine (MCP-1, GRO/KC, and MIP-1α) production, MPO activity, blood-spinal cord barrier (BSCB) permeability, and MMP-9 activity. However, parenchymal inflammatory mediator production (acute IL-1α and IL-1ß, subacute chemokines), BSCB permeability, and fibrous scarring in the PTS group were larger than the sum of the SCI group and arachnoiditis group combined, suggesting that arachnoiditis does indeed potentiate parenchymal pathophysiology. Accordingly, these findings suggest that the development of arachnoiditis associated with SCI can lead to an exacerbation of the parenchymal injury, potentially impacting the outcome of this devastating condition.

The presence of arachnoiditis affects the characteristics of CSF flow in the spinal subarachnoid space: a modelling study.

Syringomyelia is a neurological disorder characterised by high pressure fluid-filled cysts within the spinal cord. As syringomyelia is associated with abnormalities of the central nervous system that obstruct cerebrospinal fluid (CSF) flow, it is thought that changes in CSF dynamics play an important role in its pathogenesis. Using three-dimensional computational models of the spinal subarachnoid space (SAS), this study aims to determine SAS obstructions, such as arachnoiditis, change in CSF dynamics in the SAS. The geometry of the SAS was reconstructed from a series of MRI images. CSF is modelled as an incompressible Newtonian fluid with a dynamic viscosity of 1 mPa s. Three computational models simulated CSF flow in either the unobstructed SAS, or with the SAS obstructed by a porous region simulating dorsal or circumferential arachnoiditis. The permeability of this porous obstruction was varied for the model with dorsal arachnoiditis. The results show that arachnoiditis increases flow resistance in the SAS and this is accompanied by a modest increase in magnitude and/or shift in timing (with respect to the cardiac cycle) of the CSF pressure drop across the region of arachnoiditis. This study suggests that syrinx formation may be related to a change in temporal CSF pulse pressure dynamics.

Experimental syringohydromyelia induced by adhesive arachnoiditis in the rabbit: changes in the blood-spinal cord barrier, neuroinflammatory foci, and syrinx formation.

There are many histological examinations of syringohydromyelia in the literature. However, there has been very little experimental work on blood permeability in the spinal cord vessels and ultrastructural changes. We prepared an animal model of spinal adhesive arachnoiditis by injecting kaolin into the subarachnoid space at the eighth thoracic vertebra of rabbits. The animals were evaluated 4 months later. Of the 30 rabbits given kaolin injection into the cerebrospinal fluid, 23 showed complete circumferential obstruction. In the 7 animals with partial obstruction of the subarachnoid space, intramedullary changes were not observed. However, among the 23 animals showing complete obstruction of the subarachnoid space, dilatation of the central canal (hydromyelia) occurred in 21, and intramedullary syrinx (syringomyelia) was observed in 11. In animals with complete obstruction, fluorescence microscopy revealed intramedullary edema around the central canal, extending to the posterior columns. Electron microscopy of hydromyelia revealed a marked reduction of villi on the ependymal cells, separation of the ependymal cells, and cavitation of the subependymal layer. The dilated perivascular spaces indicate alterations of fluid exchange between the subarachnoid and extracellular spaces. Syringomyelia revealed that nerve fibers and nerve cells were exposed on the surface of the syrinx, and necrotic tissue was removed by macrophages to leave a syrinx. Both pathologies differ in their mechanism of development: hydromyelia is attributed to disturbed reflux of cerebrospinal fluid, while tissue necrosis due to disturbed intramedullary blood flow is considered to be involved in formation of the syrinx in syringomyelia.