Fig 1.
Diagram includes searches of databases, registers and other sources, and pre-clinical studies for leptomeningeal pathology review.
Fig 2.
Neurosurgeon Charles Burton’s operative pictures of different phases of pathology after Pantopaque myelogram and/or spine surgery.
(5) Each section contains an operative picture of his proposed 3 phases, followed by his illustration and description. The first section shows nerve inflammation of the cauda equina, which he termed “radiculitis” to differentiate this stage from “adhesive arachnoiditis” shown in the second panel. Burton proposed adhesive arachnoiditis as a middle phase with clearly visible nerve root clumping and early nerve atrophy. The final phase, often termed “empty thecal sac” appearance on MRI is characterized by nerve roots permanently adhered to the dura and covered with fibrotic tissue.
Table 1.
Global patient responses regarding arachnoiditis questions or associated complications.
Table 2.
Eligibility criteria, modifications, information sources, and different terms for same pathology.
Table 3.
Critical appraisal of sources.
These questions were used in our quality and bias tool.
Table 4.
Standard data elements were captured for all sources if present. Specialized baseline characteristics were charted on in the listed population, in addition to standardized elements.
Table 5.
This table contains all data charted for the study and used for synthesis, with references. Data are sorted into major category, then subcategory. (NOTE: The reference numbers are specific to this table and do not correspond to article reference numbers). The year span of papers within a subcategory is included to help the reader understand that changes in therapy over time may have occurred and as a gauge as to when LM damage from diseases were first identified.
Fig 3.
The bar-chart displays the distribution of publishing year for papers in this PSR stratified by N-OECD versus OECD.
In both regions the number of papers published has increased over time indicating that research in the area is intensifying. The scatter plot displays the number of subjects diagnosed with DLMs per paper over time. The increase in variation over time exhibits the change from mostly case reports to larger scale observational studies and randomized controlled trials.
Fig 4.
Visualizing the LM from macro to microscopic.
(A) shows a human autopsy specimen at the level of the cauda equina, demonstrating the arachnoid closely following the dura. The nerve roots are wrapped in the pia membrane.† (B) is a cross-section of a mouse spinal cord with surrounding meninges, demonstrating how many critical structures traverse the SAS.† (C) is a SEM of an arachnoid trabecula {b*} traversing from arachnoid barrier layer {a} to pia {c} showing the porous nature of the trabecula.† (D) The glymphatic schematic and BBB demonstrating the critical role of unimpaired CSF flow into the CNS from and back to the SAS.§ Pictures: † Courtesy of C. Cohen PhD, Curator of The Brain Museum, University of Buffalo NY, used with written permission. § Micrograph and illustration ©F. Fornai MD (31) used with written permission.
Table 6.
Characteristics of major categories by economic status (A), and use of “arachnoiditis” terminology in subcategories of DLMs (B): All sources were divided into major categories, then further divided into subcategories.
Part A shows numbers of papers, total patients, and numbers from N-OECD and OECD. Part B shows papers, sources, those who had diagnoses of DLMs (without the term “arachnoiditis”), and % of total population in the specific subcategory who had diagnoses of DLMs (inclusive of arachnoiditis). Of 887 sources, 2 had undeclared location of patients, removed from economic columns for clarity.
Table 7.
Calculated real world incidences of LMDs in selected diseases based on WHO and CDC incidences.
Δ Data is based on minimum incidences of DLMs noted in the PSR* or published X 2020 population numbers. The incidence of DLMs is far greater than the “rare disease” threshold of 1:200K or 39,500 annually in the US.
Table 8.
Common symptoms per area involved occur.
Symptoms were remarkable similar across the 3 areas presented (spine, base of brain, brain). Spine and CN DLMs produce the same types of symptoms but localized to the area involved during early phases. If available, response to CDs therapy is included.
Fig 5.
Proposed ICD11 Classification system for a new section named “Diseases of the meninges”.
The current version of ICD 11 does not contain a section for meningeal diseases, although there are scattered places where this complication appears as a complication of a specific disease. As many disease entities cause the same pathologic changes and symptoms, progress in quantifying LMDs, clinical course and outcomes, and eligibility for clinical trials will only be possible with consistent coding. We have proposed the hierarchical system below, with “grandchildren” being brain, brainstem, and spinal involvement of the LM. The example “generation 4 and 5” in green and purple would be repeated for each of the 3 main grandchildren. This proposal will be resubmitted to WHO, with all input welcome.
Table 9.
Possible treatment ideas for clinical trials from the PSR and subclinical studies.