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.

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.

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.

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.

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

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.

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.

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.

[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.

[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.

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.

Intrapleural migration of a spinal catheter in a patient with arachnoiditis and extensive epidural scarring after tethered cord release: a case report and review of literature.

OBJECTIVE: The objective of this study was to report a case of new onset refractory pain from intrapleural migration of a spinal catheter five months after the implantation of an intrathecal drug delivery system (IDDS). MATERIALS AND METHODS: A 57-year-old man had intractable pain because of multiple intradural spinal explorations for tethered cord release. His pain was effectively treated with intrathecal morphine via an IDDS. Five months after the implantation, the patient developed return of the original pain more than two weeks after intrapleural migration of the intrathecal catheter. RESULTS: The migration was documented by computed tomography, and repositioning of the catheter rendered the patient comfortable. The gradual onset of pain may have been due to decreasing delivery of drug to the cerebrospinal fluid as the catheter tip migrated further away from the dura. To our knowledge, this complication has not been reported in the literature. CONCLUSION: Physicians and nursing staff that place and manage an IDDS should be aware of this complication.

Arachnoiditis ossificans.

OBJECTIVE: Arachnoiditis ossificans is an uncommon clinical entity in which arachnoid ossification leads to clinical symptomatology. In this case report, we describe the case of a myelopathic patient with arachnoid ossifications, an arachnoid cyst, and syringomyelia coexisting with a herniated thoracic disc at the same levels. CASE DESCRIPTION: An 81-year-old woman presented with rapidly progressive leg weakness, dysesthetic pains, and urinary incontinence. RESULTS: The patient underwent thoracic laminectomy with costotransversectomy for resection of ossified arachnoid and re-establishment of cerebrospinal fluid pathways. CONCLUSION: Altered cerebrospinal fluid dynamics secondary to the obstruction in subarachnoid flow may predispose to the formation of an arachnoid cyst, and the cyst itself may be the proximate cause of the myelopathy.

Novel surgical management of spinal adhesive arachnoiditis by arachnoid microdissection and ventriculo-subarachnoid shunting.

Spinal cord tethering and cerebrospinal fluid (CSF) flow disturbance are two major features in the pathophysiology of spinal adhesive arachnoiditis. We hypothesized that insufficient CSF supply to the surgically untethered spinal cord may be one of the causes of the typical post-operative recurrent extensive lesion. We report a patient with extensive spinal adhesive arachnoiditis, who was successfully treated using a novel surgical technique consisting of two procedures. First, microdissection of the thickened adherent arachnoid was performed to resolve spinal cord tethering. Next, a ventriculo-subarachnoid shunt was placed to provide sufficient flow of CSF. Clinical improvement was sustained for at least 22 months after surgery. The present surgical procedure may improve clinical outcome in patients with longitudinally extensive spinal adhesive arachnoiditis.

Syringomyelia due to thoracic spinal stenosis with ossified ligamentum flavum--case report.

A 50-year-old male presented with back pain and numbness of the lower extremities persisting for 10 years. He had played volleyball for a long period until recently. He had no history of meningitis or traumatic injury. Magnetic resonance imaging revealed a syringomyelia located in the region from T8 to T9 without contrast enhancement or Chiari malformations. Computed tomography showed T9-10 spinal stenosis caused by the right enlarged ossified yellow ligament. Decompressive laminectomy was performed and the ossified ligament removed. Due to the finding of arachnoid thickening and adhesions during the intradural operation, shunting was also performed. Postoperatively, the neuroimaging and clinical findings improved. Syringomyelia is often associated with Chiari malformations, trauma, spinal tumor, hemorrhaging, and meningitis. We suggest that repeated minor mechanical damage caused by physical exercise in addition to long-standing compression of the spinal cord due to spinal spondylosis could induce severe arachnoid fibrotic change similar to adhesive arachnoiditis, which may be one of the main triggers of syringomyelia. Extradural decompressive surgery is considered to be the initial treatment for syringomyelia associated with spinal spondylosis.

Evaluation of tenoxicam on prevention of arachnoiditis in rat laminectomy model.

Post laminectomy arachnoiditis has been shown by experiments with rats and post operative radiological imaging in humans. The purpose of this experimental study was to determine the efficacy of tenoxicam in preventing arachnoiditis in rats. Twenty-four Wistar rats were divided into two groups, and L3 laminectomy was performed. In the tenoxicam group, 0.5 mg/kg tenoxicam was applied intraperitoneally. Normal saline was applied intraperitoneally in the control group. Later, the rats were killed at weeks 3 and 6, and the laminectomy sites were evaluated pathologically for arachnoiditis. The results showed that 6 weeks after surgery, the tenoxicam group showed lowest arachnoiditis grades. However, statistically significant difference was not found in arachnoiditis between the control group and the tenoxicam group. Based on these findings it is concluded that application of the tenoxicam after lumbar laminectomy did not effectively reduce arachnoiditis. Performing the most effective surgical technique without damage around tissue in a small surgical wound and having meticulous hemostasis in surgery seem to be the key for preventing arachnoiditis effectively.

Neurocysticercosis causing sudden death.

Neurocysticercosis causes significant morbidity due to neurologic manifestations including seizures. Sudden unexpected death in epilepsy (SUDEP) is responsible for mortality associated with seizure disorders. This case highlights death from neurocysticercosis and possible SUDEP in a nonendemic country.

Lumbar arachnoiditis and thecaloscopy: brief review and proposed treatment algorithm.

The term arachnoiditis describes the inflammation of the meninges and subarachnoid spaces. Lumbar arachnoiditis is characterized by obliterated nerve root sleeves and the adherence of nerve roots to each other in the proximity of the cauda equina, and may be secondary to infectious diseases or tumors, iatrogenic (subsequent to spinal surgery) or idiopathic. It is not very clearly defined epidemiologically or clinically, and various theories regarding its pathophysiology have been proposed; furthermore, its treatment is difficult because there is a lack of evidence-based diagnostic and therapeutic gold standards. Thecaloscopy has been recently described as a novel technique for retrograde transcutaneous neuroendoscopic inspection of the subarachnoid structures of the lumbar thecal sac; it has also been suggested for the treatment of lumbar arachnoiditis. We here review the most modern techniques for the treatment of this disease such as thecaloscopy and neurostimulation.

A new approach for observing cerebral cisterns and ventricles via a percutaneous lumbosacral route by using fine, flexible fiberscopes.

OBJECT: To establish a new method for the diagnosis of central nervous system diseases, the authors visualized the cerebral cisterns and ventricles via a percutaneous lumbosacral route by using newly developed fine, flexible fiberscopes. METHODS: Fine, flexible fiberscopes, 0.9 and 1.4 mm in diameter, were introduced up to the cerebral cisterns and ventricles through a percutaneous lumbosacral route in awake patients with chronic headache and/or neck pain or those undergoing spinal surgery and in whom MR imaging did not disclose any particular abnormalities in the brain. A lumbosacral subarachnoid puncture was made with a modified method of a continuous epidural block. RESULTS: In 25 of 31 patients tested, the cerebellomedullary and/or pontine/interpeduncular cisterns were easily and safely reached, and the brainstem structures were visualized. Advancement of the fiberscope beyond the spinal level was abandoned in 6 patients with adhesive spinal arachnoiditis, because the fiberscopes encountered resistance seemingly caused by arachnoid adhesions. Further advancement of the fiberscopes up to the fourth and third ventricles was successfully achieved in 2 patients. A number of arachnoid filaments were found in the cerebellomedullary cistern in 4 patients: 2 with chronic spinal arachnoiditis, 1 with a spinal arachnoid cyst, and 1 with posttraumatic pain syndrome. None of the patients reported pain or any major complication except a postspinal headache and light fever, which were encountered in 4 and 1 patient, respectively. CONCLUSIONS: The approach to the supraspinal structures via the lumbosacral route by using a fine, flexible fiberscope may provide a new, minimally invasive, and safe way to observe the cerebral cisterns and/or brainstem regions.

Cervicothoracic postarachnoiditic hydrosyringomyelia secondary to pedicular hook dislocation: case report.

BACKGROUND: Pedicular hook dislocation is a rare complication of spinal instrumentation. We report on the first case of hydrosyringomyelia secondary to intracanalar hook displacement after scoliosis surgery. CASE DESCRIPTION: A 15-year-old girl presented to our institution with a 7-month history of persistent neck and occipital pain as well as numbness of the lower extremities and previous dorsolumbar instrumentation with dorsal pedicular hooks and lumbar screws. Magnetic resonance imaging showed intramedullary cystic cavity from C5 to T7, isointense to cerebrospinal fluid (CSF) on T1- and T2-weighted images. Computed tomographic scan showed intracanalar displacement of the left hook. On admission, the patient presented with mild weakness of the lower extremities, hypalgesia below the level of T4, and urinary disturbance. The patient underwent surgical hook removal, T4 laminectomy, and midline dural opening: the arachnoid membrane was found to be thick and adhered to the dura and dorsolateral spinal cord. The arachnoid scarring was dissected, and the cord was untethered. A small posterior-median myelotomy was performed, and a syringosubarachnoid catheter was placed into the subarachnoid space to restore CSF flow. CONCLUSIONS: Late intracanalar displacement of spinal devices is an event that may complicate spinal instrumentation for scoliosis. This case highlights the importance of correct spinal device positioning and that of careful follow-up after instrumentation to detect complications early. We also discuss the pathogenetic pathway of the postarachnoiditic syringomyelia in this case.