Focal Chronic Meningitis With Lymphoid Follicle-Like Structures Associated With Cocaine-Induced Midline Destructive Lesion: A Case Report

To the Editor: Cocaine abuse has long been known to be associated with a variety of central nervous system (CNS) sequelae (1). A few case reports have shown secondary CNS involvement in the context of cocaine-induced midline destructive lesions (CIMDLs) (2, 3), a potential consequence of intranasal cocaine abuse. CIMDL is an autoimmune phenomenon affecting a minority of intranasal cocaine users (4, 5). It is associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) and nasal mucosa damage which often results in septal perforation and advanced destruction of midline structures (4, 5). Histologically, the nasal mucosa shows mixed inflammatory infiltrates, microabscesses in vascular walls, perivenulitis, leukocytoclastic vasculitis, and vascular microthrombotic changes (5). The most common differential diagnosis of CIMDL is Wegener’s granulomatosis/granulomatosis with polyangiitis (GPA). Features that differentiate these 2 entities in favor of CIMDL include more severe and extensive nasal involvement, the absence of systemic disease (4) and the presence of ANCA directed toward human neutrophil elastase (HNE) instead of ANCA targeting myeloperoxidase (MPO) (6). In the few cases in which CIMDL affects the CNS, it does so via extension of the nasal lesion contiguously through the skull. The histopathological features of CNS involvement in CIMDL have not been described in detail. Herein, we report the rare pattern of chronic meningitis with reactive meningeal lymphoid follicle-like structures in the context of CIMDL. A 52-year-old patient presented with sub-acute onset of cognitive dysfunction and personality changes coinciding with a year-long history of worsening bitemporal headaches. This occurred in the setting of 5 years of daily cocaine use, 1 g per day administered intranasally. He had ceased use of cocaine in the month prior to admission due to escalating symptoms. On admission, he demonstrated florid disinhibition, frontal executive dysfunction, disorientation, lack of insight, and an abnormal Montreal Cognitive Assessment (MoCA) score of 17/30. Imaging studies (computed tomography [CT] and magnetic resonance imaging [MRI]) of the head demonstrated bilateral frontal lobe edema with dural and leptomeningeal enhancement, and absent nasal septum, middle and inferior turbinates, and medial wall of the right maxillary sinus (Fig. 1). Erosion of the cribriform plate was noted, providing continuity between sinuses and the intracranial vault. A nasal biopsy was not performed. Unenhanced and contrast-enhanced CT head (A–C) and MRI brain pre- and post-gadolinium administration imaging studies. (A) Coronal image with bone window shows largely absent nasal septum, inferior and middle turbinates, and medial wall of the right maxillary sinus in keeping with osseocartilaginous necrosis secondary to cocaine abuse. (B) Magnified coronal image with bone window demonstrates erosion of the cribriform plate (solid arrows). (C) Axial contrast-enhanced image shows large areas of vasogenic edema in the frontal lobes with gyral swelling and mild mass effect on the lateral ventricles and leptomeningeal enhancement over the frontal lobes. (D) Axial T2-weighted image shows large areas of vasogenic edema in the frontal lobes with cortical involvement (solid arrow). (E) Axial and (F) coronal post-gadolinium T1 MPRAGE images show bilateral frontal dural and leptomeningeal thickening and enhancement with parenchymal enhancement seen within the area of involved brain parenchyma (open arrow). Initial differential diagnosis most principally included lymphoma and autoimmune/inflammatory conditions such as GPA, IgG4-related disease, and sarcoidosis. A broad diagnostic work-up (including extensive cerebrospinal fluid analysis with fungal cultures and virology, cytometry and cytology; paraneoplastic testing and whole-body positron emission tomography scan) was negative except for the presence of ANCA directed against proteinase 3 (ANCA-PR3), which raised the possibility of ANCA-vasculitis or cocaine-induced vasculopathy. ANCA-MPO was negative and ANCA-HNE was not tested. Clinical suspicion for GPA vasculitis was low given the lack of recurrent sinusitis, pulmonary and renal findings, and the patient’s limited sinus inflammation. Given the diagnostic uncertainty, a left frontal brain and meningeal biopsy was obtained. The leptomeninges were mildly fibrotic and diffusely infiltrated by lymphocytes, plasma cells, and macrophages, with interspersed reactive follicles (Fig. 2A, B). No granulomas or evidence of vasculitis was present. Immunohistochemical stains showed the reactive lymphoid follicles to have a benign dendritic follicular network (CD21, Fig. 2C) and follicle-associated B cells (CD20, Fig. 2D). Normal Bcl6, Bcl2, and CD10 staining patterns (not shown) excluded the possibility of a low-grade lymphoma. CD3 staining demonstrated small T cells associated with lymphoid follicles and diffusely infiltrating the leptomeninges (Fig. 2E). Anti-CD138 showed the presence of numerous infiltrating plasma cells without kappa/lambda restriction or increased IgG4/IgG ratio (Fig. 2F). Anti-CD68 highlighted macrophages infiltrating the meninges in a non-granulomatous pattern (not shown). Stains for microorganisms and 16S PCR test for bacterial RNA were negative. Brain tissue showed reactive gliosis and mild perivascular T-cell lymphocytic infiltrates in the superficial cortex, interpreted as reactive changes to the presence of leptomeningeal inflammation. There were also associated foci of cortical demyelination on myelin basic protein (MBP) and phosphorylated neurofilament (PNF) stains (Fig. 2G–I). MBP and PNF in the underlying white matter were unremarkable (not shown). During admission, the patient’s behavior stabilized on anti-psychotics and he was diagnosed with CIMDL. The patient ceased his use of cocaine with significant improvement including a repeat MoCA test score of 28/30 and significant improvement in the frontal lobe parenchymal signal abnormalities on follow-up imaging with only mild residual frontal meningeal thickening and contrast enhancement. Meningeal biopsy (H&E and immunohistochemical stains). Low-power (A) and high-power (B) hematoxylin and eosin stains highlight chronic dural inflammation with lymphoid follicle-like formations. (C) CD21, (D) CD20, (E) CD3, immunohistochemical stains show a reactive lymphoid follicle pattern. (F) IgG4 immunohistochemistry reveals no evidence of IgG4 disease. Phosphorylated neurofilament (G) and myelin basic protein ([MBP], H and I) immunohistochemical stains reveal focal areas of superficial cortical demyelination (H) compared to areas with more preserved myelination (I). Original magnifications: A, 40×; B, 400×; C–H, 200×; I, 100×. Our literature review found only 2 cases with detailed histopathological descriptions of CNS involvement in CIMDL. One patient presented with an encephalocele resulting from brain herniation through a CIMDL-induced bony defect. Microscopic evaluation of the resected brain tissue revealed necrosis, acute and chronic inflammation, gliosis and granulation tissue without evidence of vasculitis (2). The other patient developed CIMDL with contiguous extension into the cranial vault and brain resulting in a mass lesion (3). In this instance, a partial anterior frontal lobectomy revealed extensive meningeal and cortical lymphoplasmacytic infiltrate with perivascular accentuation and without reactive lymphoid follicles. Compared to previous histological descriptions of CIMDL affecting the CNS, our case showed the unique features of chronic meningitis with reactive lymphoid follicles. Most commonly, meningeal follicle-like structures are neoplastic follicles seen in setting of low-grade lymphomas (7), which was excluded in this case. Reactive meningeal lymphoid follicle-like formations are an infrequent histological finding, described so far almost exclusively in patients with multiple sclerosis (MS) (8) and they have, to our knowledge, not been reported in the context of cocaine abuse. Variable cortical demyelination has been shown to be specific for demyelinating disorders such as MS, acute disseminated encephalomyelitis, progressive multifocal leukoencephalopathy, and extrapontine myelinolysis, each with disease‐specific histopathological pattern of cortical myelin loss (9). Other conditions with meningeal inflammation such as infectious and neoplastic processes do not show this change (9). Why focal cortical demyelination and reactive meningeal lymphoid follicles were seen in our case is unclear. It is possible that the 2 processes may be related, although additional examples of non-MS cases with this meningeal inflammatory pattern are required to evaluate this hypothesis. Finally, levamisole is a common adulterant in cocaine and has previously been associated with a variety of serious complications including multifocal inflammatory leukoencephalopathy and ANCA-associated vasculitis (10). Brain pathology associated with levamisole toxicity is typified by a demyelinating inflammatory leukoencephalopathy predominantly affecting periventricular and subcortical white matter (11), which was not seen on either brain biopsy nor imaging studies in this case. We do not know whether the patient’s cocaine was adulterated with levamisole, and it is therefore difficult to speculate as to its possible contributory effects in this case. VH-R receives salary support from the Vancouver Coastal Health Research Institute through its Mentored Clinician Salary Award. The authors have no duality or conflicts of interest to declare.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.