Distinct features of ANCA-associated hypertrophic pachymeningitis compared to other etiologies: findings from a study of 74 patients.

OBJECTIVES: We aimed to characterize the clinical and radiological features, and outcomes, of a large cohort of hypertrophic pachymeningitis (HP) patients from a single center. METHODS: We conducted a retrospective study at a tertiary referral center, encompassing patients diagnosed with HP between 2003 and 2022. The diagnosis of HP relied on the identification of thickening of the dura mater via magnetic resonance imaging (MRI) of the brain or spine. RESULTS: We included 74 patients with a mean age of 43.6 ± 14.2 years, of whom 37 (50%) were male. Among them, 32 (43.2%) had an immune-mediated origin, including 21 with granulomatosis with polyangiitis (GPA) (predominantly PR3-ANCA positive), four with systemic lupus erythematosus, three with IgG4-related disease, three with idiopathic HP, and one with rheumatoid arthritis. Non-immune-mediated HP accounted for 45 cases (56.8%). Within this category, 21 (28.4%) were infectious cases, with 14 being Mycobacterium tuberculosis infection (TB-HP), and 21 (28.4%) were malignancy-associated HP. Clinical and MRI characteristics exhibited variations among the four etiological groups. Hypoglycorrhachia was primarily observed in infectious and malignancy-associated HP. Immune-mediated HP was associated with a peripheral pattern of contrast enhancement and the Eiffel-by-night sign. MRI features strongly indicative of TB-HP included leptomeningeal involvement, brain parenchymal lesions, and arterial stroke. MPO-ANCA GPA was associated with a higher prevalence of spinal HP. CONCLUSIONS: Within our cohort, GPA and Mycobacterium tuberculosis emerged as the predominant causes of HP. We identified significant disparities in clinical and radiological features among different etiologies, which could have implications for diagnosis.

Two cases of MPO-ANCA-positive hypertrophic pachymeningitis mimicking as intracranial infection.

Hypertrophic pachymeningitis (HP) is a rare disorder marked by thickening of the dura mater due to diverse etiologies. MPO-ANCA-positive HP represents a variant of AAV confined to the central nervous system, distinguished by the presence of serum MPO antibodies. Distinguishing HP triggered by MPO-ANCA from other causes can be challenging.In this study, we present two cases of MPO-ANCA-positive HP initially misdiagnosed as intracranial infections. Case 1 underwent surgery for chronic suppurative otitis media, with histopathological findings revealing inflammatory changes without definitive suppuration. He was presumed to have a secondary intracranial infection resulting from the surgery. However, his condition deteriorated despite two weeks of antibiotic and antiviral treatment. Case 2 presented with headache and was initially suspected of having intracranial Brucellosis given his serum Brucella positivity. Despite treatment for brucellosis, his symptoms persisted, and he developed visual and hearing impairments. Both patients were ultimately diagnosed with MPO-ANCA-positive HP, exhibiting serum MPO antibody positivity. Their symptoms showed improvement with glucocorticoid and immunosuppressive therapy.Based on these observations, we propose that MPO-ANCA-positive HP may initially present as intracranial infection. For HP patients presenting with headache, mastoiditis, otitis media, and visual loss, it is imperative to conduct ANCA antibody-related tests to enhance diagnostic precision.

Hypertrophic pachymeningitis of the internal auditory canal and cerebellopontine angle from a large recurrent attic cholesteatoma.

OBJECTIVES: To describe a rare complication of cholesteatoma. METHODS: Case report with literature review. RESULTS: We report a case of a 37-year-old male who presented for evaluation of otorrhea, headache, and progressive left sensorineural hearing loss. Clinical and radiologic evaluation demonstrated a large recurrent attic cholesteatoma with erosion into the lateral and superior semicircular canals, and diffuse enhancement of the internal auditory canal and cerebellopontine angle suggestive of hypertrophic pachymeningitis secondary to cholesteatoma. After treatment with a course of antibiotics and canal wall down mastoidectomy surgery for cholesteatoma exteriorization, he experienced improvement of his symptoms and resolution of hypertrophic pachymeningitis. CONCLUSION: Hypertrophic pachymeningitis is a rarely described complication of cholesteatoma. In the context of cholesteatoma, treatment with antibiotics and surgical removal or exteriorization of cholesteatoma are effective treatments for HP.

Non-infectious hypertrophic pachymeningitis associated with orbital inflammatory disease: a pooled analysis.

PURPOSE: To describe four cases of non-infectious hypertrophic pachymeningitis (HP)-associated with orbital inflammatory disease (OID). This study summarises the clinico-radiological features, outcomes, and management of HP-associated OID. METHODS: Retrospective case-series of patients with radiological evidence of HP and OID. Comprehensive literature review of all published English-language non-infectious causes of HP-associated OID. Reference lists were screened for inclusion of relevant articles. RESULTS: Thirty-seven cases of HP-associated OID (Mean age: 49.2 ± 17.4 years old; Male: 15) were identified, including four cases from our institution. Aetiologies included ANCA-associated vasculitis (12/37), non-specific/idiopathic (11/37), IgG4/multifocal fibrosclerosis (11/37), neurosarcoidosis (1/37), inflammatory myofibroblastic tumour (1/37), and giant cell arteritis (1/37). Orbital pain, headache, visual deterioration, and cranial nerve palsies were common clinical presentations. Both "focal" and "diffuse" HP were observed, with the most common sign of orbital involvement being an inflammatory orbital mass, typically with orbital apex involvement. Orbital myositis and dacryoadenitis were less common. The cavernous sinus was the most common site of extra-orbital inflammation. There was no single differentiating specific radiological feature between non-specific and specific forms of HP-associated OID. CONCLUSION: The clinico-radiological manifestations of HP-associated OID differ from those described in isolated HP or OID. There is no single specific radiological marker differentiating non-specific/idiopathic disease from secondary causes; however, the co-existence of HP in OID should prompt suspicion of an underlying cause. The disease may be refractory or resistant to initial treatment, although guidelines surrounding its management and the long-term prognosis remain to be determined.

Hypertrophic Pachymeningitis Development in Eosinophilic Granulomatosis with Polyangiitis at Relapse of Disease: A Case-Based Review.

Hypertrophic pachymeningitis (HP) presents with thickening of the dura mater in the cerebrum and spine, and its symptoms vary depending on the affected location. The association of HP with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been recognized, and most cases are complicated by granulomatosis with polyangiitis. We report the case of a 47-year-old man who presented with HP upon relapse of eosinophilic granulomatosis with polyangiitis (EGPA), with literature review. He presented with disturbance of consciousness, and magnetic resonance imaging (MRI) revealed thickening of the dura mater around the left parietal lobe. Although myeloperoxidase (MPO)-ANCA was positive on EGPA diagnosis, the elevation of MPO-ANCA was not documented at the onset of HP. Brain perfusion scintigraphy showed an increase in blood flow in the left parietal lobe and temporal lobe, and electroencephalogram (EEG) revealed slow waves in the left parietal lobe. He was treated with a high dose of corticosteroid and rituximab, and the slow waves on EEG and brain perfusion were normalized. Although the most frequent symptom of HP is headache, disturbance of consciousness can be the manifestation of HP, and inflammation of HP could affect the cerebral parenchyma, which can be documented as abnormal EEG and perfusion scintigraphy. Literature review revealed that most of the HP in EGPA developed when EGPA relapsed, and was observed in patients with MPO-ANCA positivity. HP develops without evidence of other clinical features of EGPA; therefore, adequate imaging, including contrast-enhanced MRI, is necessary. Rituximab may be effective for treating HP complicated with EGPA.

Otitis media with ANCA-associated vasculitis: A retrospective study of 30 patients.

OBJECTIVES: Otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is a new category of otitis media in which cases of otitis media due to ANCA-associated vasculitis (AAV) are classified, regardless of ANCA variant or ANCA serotype. We aimed to describe the clinical features and course of patients with OMAAV and identify factors associated with hearing outcomes. METHODS: We retrospectively analysed 30 patients with OMAAV, classified based on the criteria proposed by the Japan Otological Society in 2016. RESULTS: Single-positive myeloperoxidase-ANCA, single-positive proteinase 3-ANCA, double-positive ANCA, and double-negative ANCA were identified in 47%, 33%, 7%, and 13% of the patients, respectively. All patients subjected to audiometry showed hearing impairments, and 85% were affected bilaterally. Mixed- and sensorineural-type hearing impairments were identified in 80% and 20% of impaired ears, respectively. Hypertrophic pachymeningitis (HPM) was identified in 37% of the patients. Immunosuppressive therapy was administered to 93% of patients, and the median air conduction hearing levels at pre- and post-treatment were 66.1 dB and 43.4 dB, respectively, indicating significant hearing improvements. HPM and a long interval between disease onset and treatment initiation were significantly correlated with poor hearing prognosis. CONCLUSIONS: OMAAV develops under any type of ANCA-serology and typically causes mixed or sensorineural bilateral hearing loss. The early initiation of immunosuppressive therapy and the absence of HPM were associated with good hearing outcomes.

Hypertrophic pachymeningitis caused by Schizophyllum sp.: a novel case report.

BACKGROUND: The pathogenic fungus Schizophyllum sp. can cause allergic fungal rhinosinusitis and allergic bronchopulmonary mycosis in humans. Sinus and lung infections due to Schizophyllum sp. have been reported globally; however, no case of hypertrophic pachymeningitis due to this pathogen has been reported yet. Herein, we describe for the first time, a case of hypertrophic pachymeningitis due to Schizophyllum sp. CASE PRESENTATION: A 69-year-old woman visited the hospital with chief complaints of headache, right trigeminal neuralgia (third branch), ataxic gait, and deafness in the right ear. Magnetic resonance imaging revealed a tumor in the right sphenoidal sinus and thickening of the dura mater surrounding the right porus acusticus internus. Endoscopic sinus surgery and neuroendoscopic biopsy were performed to remove sinus lesions and intracranial lesions, respectively. Both pathological specimens showed findings indicative of filamentous fungi on Grocott's staining. DNA sequencing with the sinus specimen revealed Schizophyllum sp. as the causative pathogen, consistent with the diagnosis of fungal sinusitis and hypertrophic pachymeningitis. Intravenous liposomal amphotericin B was started, but owing to lack of improvement, the treatment was switched to intravenous voriconazole. We observed improvements in both radiological findings and symptoms. However, the symptoms exacerbated again when the trough level of voriconazole decreased. Upon increasing the voriconazole dose, a higher trough level was obtained and the symptoms improved. CONCLUSION: Our study suggests that when symptoms of central nervous system infection due to Schizophyllum sp. do not improve with liposomal amphotericin B, voriconazole can be administered at high trough levels to improve the symptoms.

Polycystic subdural hygroma associated with immunoglobulin G4-related intracranial hypertrophic pachymeningitis: a case report.

BACKGROUND: Recent studies have examined hypertrophic pachymeningitis as an IgG4-RD. However, there are no reports of immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis with polycystic subdural hygroma. CASE PRESENTATION: A 56-year-old man presented to the hospital with complaints of a persistent, pulsatile, occipital headache and general malaise. Magnetic resonance imaging of the brain revealed hypertrophic pachymeningitis with polycystic subdural hygroma and hematoma. Based on the dural biopsy findings and exclusion of other diseases, the patient was diagnosed with immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis. IgG4-related diseases may cause subdural hygroma more commonly than other diseases that cause hypertrophic pachymeningitis. CONCLUSIONS: This is the first case report discussing polycystic subdural hygroma and hematoma with IgG4-related hypertrophic pachymeningitis.

Hypertrophic chronic pachymeningitis associated with Epstein-Barr virus reactivation: a case report.

Hypertrophic pachymeningitis is a rare inflammatory condition characterized by the thickening of the dura mater. We describe a patient who presented with intractable headache and complex cranial nerve palsy. Hypertrophy of the frontal dura was accompanied by pleocytosis and detection of Epstein-Barr virus (EBV) by PCR in cerebrospinal fluid. Clinical symptoms gradually improved after acyclovir and corticosteroid treatment, whereas dural pathology remained unchanged on neuroimaging. This case points at an expansion of the spectrum of neurological manifestations for EBV.

SLE pachymeningitis and multiple cranial nerve palsies: a case report and review of the literature.

Hypertrophic pachymeningitis (HP) is a relatively uncommon disease associated with focal or diffuse thickening of the dura mater secondary to underlying chronic inflammation. The link between systemic lupus erythematosus (SLE) and hypertrophic pachymeningitis (HP) is extremely rare, with only six other cases reported in the literature. We, however, report the first case of SLE pachymeningitis presenting with multiple cranial nerve palsies. The patient showed good response to steroids and cyclophosphamide therapy. One should maintain a high index of suspicion to make the diagnosis in patients with SLE presenting with neurological dysfunction. Prompt therapy prevents long-term neurological sequelae.

Anti-NMDAR encephalitis with simultaneous hypertrophic pachymeningitis in a 68-year-old male: a rare case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most frequent types of autoimmune encephalitis. However, the instigating mechanisms are as yet not fully ascertained. Cardinal clinical manifestations of anti-NMDAR encephalitis include acute behavioural change, psychosis, and catatonia. As the level of diagnosis increases, encephalitis becomes more common, but there are never been published in patients with anti-NMDAR encephalitis and simultaneous hypertrophic pachymeningitis. CASE PRESENTATION: A sixty-eight-year-old man who presented with mental, behavioral abnormalities, unstable walking, headaches, and erratic hand movements. The neuropsychiatric symptoms and cerebrospinal fluid examination was consistent with the diagnosis criteria of anti-NMDAR encephalitis. Magnetic resonance imaging of the brain showed a thickening of dura mater localized at the left tentorium cerebelli, left cerebral hemisphere, and cerebral falx; the thickening dura mater was characterized by an intense contrast enhancement after the administration of gadolinium. High doses of intravenous methylprednisolone were administrated during his hospitalization. After 5 days, the patient's condition improved. CONCLUSIONS: We herein describe a rare case of a 68-year-old man with anti-NMDAR encephalitis presenting with concomitant hypertrophic pachymeningitis. We systematically expounded anti-NMDAR encephalitis and hypertrophic pachymeningitis, and made bold conjectures on the etiology and pathogenesis of these two diseases, hoping to stimulate new ideas from clinicians and basic medical researchers.

The clinical and imaging features of hypertrophic pachymeningitis: a clinical analysis on 22 patients.

OBJECTIVE: To explore the clinical and imaging features of patients with hypertrophic cranial pachymeningitis (HCP). METHODS: A retrospective study was performed on 22 patients with HCP diagnosed at the Affiliated Hospital of Xuzhou Medical University from February 2014 to September 2017. RESULTS: A headache was present as an initial symptom in 18 patients. The headache was associated with the loss of vision (2 cases), facial pain (1 case), and unsteady walking (1 case). Other symptoms included cranial nerve dysfunction (15 cases), cerebellar ataxia (4 cases), and sinus thrombosis (3 cases). In the laboratory tests, 7 patients showed an increased number of white blood cells, higher levels of C-reaction protein (CRP), and erythrocyte sedimentation rate (ESR). An elevated level of immunoglobulin G4 (IgG4) and the presence of the anti-neutrophil cytoplasmic antibody (ANCA) were found in 3 and 2 patients respectively. There were 17 patients who had abnormalities in their cerebrospinal fluid (CSF) on lumbar puncture. On magnetic resonance imaging (MRI), a local or generalized thickening was observed in the cerebral falx, the tentorium of the cerebellum, the fronto-parietal lobe, the occipito-parietal lobe, and the dura of skull base. A dural biopsy obtained in one case showed a variety of inflammatory changes. An immunohistochemical analysis revealed the positivity of CD138, IgG, and IgG4 in some cells. All 22 patients had a good response to corticosteroids. CONCLUSION: HCP mainly leads to a headache and the paralysis of multiple cranial nerves. A biopsy and MRI are often required and serve as the basis for the diagnosis and effective therapy.

Clinical features of hypertrophic pachymeningitis in a center survey.

BACKGROUND: Hypertrophic pachymeningitis (HP) is characterized by cranial and/or spinal thickening of the dura mater with or without associated inflammation. Neuroimaging studies reveal dura mater thickening and focal or diffuse contrast enhancement. It is described in association with trauma, infections, tumors, autoimmune/inflammatory diseases, and cerebrospinal fluid hypotension syndrome, with some cases remaining idiopathic. METHODS: A retrospective study was conducted with patients' identification through a key terms search within MRI reports in the period of July 2008 to September 2015. Clinical files, MRI, laboratory, and pathology data were reviewed. RESULTS: Fifty-three patients were identified and 20 were excluded because they did not meet the inclusion criteria. Of the 33 included, 19 were female, with a mean age at symptoms onset of 51.2 ± 17.6 years. The most common presenting symptoms were headache and cranial nerves palsy, followed by seizures, delirium, lumbar pain, cognitive decline, motor deficit, and language impairment. In 17 patients, a neoplastic etiology was identified; in eight, inflammatory/autoimmune; in six, infectious; and two were classified as idiopathic. Of the eight patients with inflammatory/autoimmune etiology, four had possible IgG4-related disease (IgG4-RD) and the remaining had granulomatosis with polyangiitis, sarcoidosis, rheumatoid arthritis, and Tolosa-Hunt syndrome. Treatment was directed according to the underlying etiology. DISCUSSION: In the described series, a female predominance was identified, with symptoms' onset in the 5th decade. Although headache was the most common symptom, clinical presentation was varied, emphasizing the role of MRI in HP diagnosis. The underlying etiologies were diverse, with only a few cases remaining idiopathic, also reflecting the contribution of the recently described IgG4-RD.

Large dural-based mass with bony hyperostosis in a 16-year-old male: IgG4-related disease mimicking lymphoplasmacyte-rich meningioma.

BACKGROUND: IgG4-related disease is an autoimmune process that presents with tumefactive lesions characterized by storiform fibrosis, a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, obliterative phlebitis, and often elevated serum IgG4 levels. Central nervous system IgG4-related disease is very rare and usually occurs in the form of hypertrophic pachymeningitis or hypophysitis. Presentation as a large solitary meningioma-like mass with overlying hyperostosis in a young adult has not been reported before. CASE SUMMARY: A 16-year-old male presented with focal seizures for 5 months. Imaging showed a large, extra-axial, and contrast-enhancing mass lesion in the left frontoparietal region with focal calvarial thickening. Histopathology revealed a fibrosclerotic lesion involving dura with a polymorphic infiltrate of plasma cells, mature lymphocytes, histiocytes, and occasional eosinophils. Immunohistochemical workup excluded the possibilities of meningioma, lymphoproliferative neoplasms, and histiocytic lesions. Majority of plasma cells were IgG4+ rendering a diagnosis of IgG4-related disease. Further serological and imaging workup did not reveal any evidence of systemic involvement. His serum IgG4 levels were normal. Considering a gross total resection of the lesion, no further treatment was given and the patient has been asymptomatic since. CONCLUSION: IgG4-related lesions of the CNS are under-recognized and accurate diagnosis, especially in those with isolated CNS disease and normal serum IgG4 levels, necessitates robust histopathological and laboratory workup to exclude mimics. They may occur as large dural masses with hyperostosis and differentiation from lymphoplasmacyte-rich meningiomas, in particular, can be challenging. While steroids are the mainstay of treatment in IgG4-related disease, surgical resection may be curative in solitary lesions presenting with compressive symptoms.

Idiopathic hypertrophic pachymeningitis mimicking hemicrania continua: An unusual clinical case.

Background Hemicrania continua (HC) is a primary headache syndrome characterized by a unilateral, moderate, continuous headache with exacerbations marked by migrainous and cranial autonomic symptoms. However, clinical phenotypes similar to primary HC may be subtended by several disorders. Case report We report the case of a 62-year-old man experiencing, over the previous year, a headache completely consistent with HC and its absolute responsiveness to indomethacin therapy. Later, the patient developed diplopia caused by sixth cranial nerve palsy ipsilateral to headache. In this frame, clinical, laboratory and neuroimaging characteristics supported the diagnosis of idiopathic hypertrophic pachymeningitis (IHP). Conclusions IHP is a rare fibrosing inflammatory disorder leading to a localized or diffuse dura mater thickening. IHP clinical manifestations are a progressively worsening headache and signs related to cranial nerves involvement and venous sinus thrombosis. Here, we report, for the first time, a HC phenotype subtended by IHP.

Headache Linked to Intracranial Hypertension and Hypertrophic Pachymeningitis as the Initial and Dominant Presentation of Granulomatosis With Polyangiitis. Case Report and Review of the Recent Literature.

OBJECTIVE: The objective of this article is to report a rare case of headache as the initial symptom of granulomatosis with polyangiitis (GPA) and to review the recent literature. BACKGROUND: Granulomatosis with polyangiitis is a rare, systemic, autoimmune disease of unknown etiology. GPA has a wide spectrum of clinical symptomatology, including involvement of the nervous system, even as the initial manifestation. Symptoms of the peripheral nervous system used to dominate the clinical symptomatology. However, recent reports are focusing increasingly in granulomatous lesions of the central nervous system, and especially on the increased frequency of patients with hypertrophic pachymeningitis (HP). We report the case of a patient with headache linked to intracranial hypertension and hypertrophic pachymeningitis as the initial and dominant presentation of GPA and we review the recent literature. METHODS: A 54-year-old male, without any related medical history developed a severe headache. In the following 2 months, he gradually developed hoarseness and diplopia at the left and lower fields of vision. A brain MRI revealed wide-spread fattening and meningeal enhancement over the left hemisphere and the left cerebellar hemisphere. An endoscopy of the pharynx revealed the presence of a tumor-like mass in the left half of the nasopharynx. A biopsy showed inflammation with presence of polykaryocyte Langhans giant cells. The laboratory testing revealed important albuminuria and microhematuria, positive c-ANCA and negative p-ANCA. A diagnosis of GPA was established. RESULTS: A steroid treatment was administered initially, which improved the headache drastically, followed by the administration of a combination of cyclophosphamide and corticosteroid, which led to a gradual resolve of the remaining symptomatology. A follow-up brain MRI showed a decrease in meningeal enhancement, whereas a second one, 2 years later, was completely normal. CONCLUSIONS: HP was considered an extremely rare manifestation of GPA. However, recent studies are reporting an increased frequency of HP and are distinguishing a granulomatous and a vasculitic phenotype, with different localization and relapse rates, that may eventually constitute a different clinical spectrum of GPA.

Rapidly progressive fatal idiopathic hypertrophic pachymeningitis with brainstem involvement in a child.

BACKGROUND: Hypertrophic pachymeningitis (HP) is a rare disorder characterized by diffuse thickening of the dura mater with resultant neurologic deficits. HP develops secondary to various conditions or idiopathically usually in adults but rarely in children. CASE REPORT: We describe a 3-year-old female child with idiopathic HP. Her HP involved the entire central nervous system with progression into the brainstem. The lesion responded poorly to pulsed steroids or any immunosuppressants. The brainstem lesion grew rapidly and formed various nodules that ultimately resulted in brain death. This is the first fatal case of HP in a child.

Anti-neutrophil cytoplasmic antibody-associated hypertrophic cranial pachymeningitis and otitis media: a review of literature.

BACKGROUND AND OBJECTIVE: It has been recognized that anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides may lead to hypertrophic pachymeningitis (HP) or intractable otitis media (OM). To our knowledge, few cases of coexistent ANCA-related HP and OM have been described previously. To increase awareness of this disease, we reviewed the literature describing patients with HP and intractable OM in a population with AAV to guide clinical decision making for otolaryngologists. METHODS:  PubMed was searched with the following terms: ANCA-associated vasculitis, otitis media, and hypertrophic pachymeningitis. Only patients with concomitant AAV, OM and HP were considered and included in this review. RESULTS: A total of 243 articles were reviewed, and of these, 6 met inclusion criteria. Headache, cranial polyneuropathy, and intractable OM with effusion or granulation were common. Serum MPO-ANCA positivity was most common in Asian patients. Almost all patients had dural mater thickening on gadolinium-enhanced magnetic resonance imaging of the brain. Corticosteroids plus an immunosuppressant was more effective and most patients had improved hearing after treatment, but approximately 50% of subjects had disease relapse. CONCLUSION: In this review, we summarized the current knowledge on the clinical features, diagnosis, treatment, and pathogenesis of this disease. We should carefully detect the potential cases of ANCA-related HP and OM in patients with intractable OM, HP, or AAV, and make the optimal treatment plan to avoid long-term neurological complications and irreversible hearing loss. Furthermore, due to an increased possibility of relapse, close follow-up, including a hearing test, ANCA titers, imaging examination, and detection of toxic and side effects of immunosuppressive therapy, are necessary.

Hypertrophic pachymeningitis as an important neurological complication of granulomatosis with polyangiitis.

Headache is a common symptom in patients with granulomatosis with polyangiitis (GPA) mainly due to chronic sinusitis or orbital disease. Meningeal involvement may thus remain unrecognized for a long time. This can lead to a significant delay in accurate diagnosis, serious local damage of the central nervous system and high relapse rates. New diagnostic techniques such as contrast MRI allow one to identify inflammation of the dura mater in the course of GPA more frequently. The objective of this article is to characterize hypertrophic pachymeningitis (HP) in patients with GPA and report diagnostic difficulties associated with this complication.

Increased BAFF and APRIL levels in the cerebrospinal fluid of patients with anti-neutrophil cytoplasmic antibody-related hypertrophic pachymeningitis.

Hypertrophic pachymeningitis (HP) is an inflammatory disorder involving intracranial or spinal thickened dura mater. It has been recognized that anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis may lead to HP; however, the immune-mediated pathogenesis of ANCA-related HP (ANCA-HP) remains elusive. In the present study, we analyzed B-cell activation factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) expression in the cerebrospinal fluid (CSF) and serum of patients with ANCA-HP, multiple sclerosis (MS), and non-inflammatory neurological disorders (NIND). BAFF and APRIL levels in the CSF were significantly higher in patients with ANCA-HP than in those with MS and NIND. In addition, a positive correlation between BAFF levels in the CSF and IgG-index was found in patients with ANCA-HP. On the other hand, no correlation was detected between CSF and serum levels of BAFF or APRIL. The results suggest that increased levels of BAFF and APRIL produced in the central nervous system may influence the development of ANCA-HP.