RARE DISEASE
Primary angiitis of the central nervous system
Primary angiitis of the central nervous system
Primary angiitis of the central nervous system
Synonyms: Isolated angiitis of the central nervous system, PACNS, PCNSV, Primary central nervous system vasculitis, Primary vasculitis of the central nervous system
Synonyms: Isolated angiitis of the central nervous system, PACNS, PCNSV, Primary central nervous system vasculitis, Primary vasculitis of the central nervous system
Synonyms: Isolated angiitis of the central nervous system, PACNS, PCNSV, Primary central nervous system vasculitis, Primary vasculitis of the central nervous system
Drug discovery
4
drugs
With orphan designations
Overview
Primary angiitis of the central nervous system (PACNS) is a rare idiopathic vasculitis affecting cerebral and spinal cord vessels, characterized by granulomatous, lymphocytic, or necrotizing inflammation. Clinical features include headache (53–83%), focal deficits (63–83%), cognitive impairment (40–55%), seizures (16–38%), and stroke-like symptoms [1][4][12]. Diagnosis hinges on neuroimaging (multiterritorial ischemic/hemorrhagic lesions [1]), angiography (stenoses [1][6]), CSF analysis (pleocytosis/protein elevation [6][12]), and biopsy confirmation after excluding mimics [5][6]. Untreated PACNS leads to progressive neurological deterioration with high morbidity and mortality.
Therapies
Categories: rare circulatory system diseases, rare genetic diseases, rare neurological diseases, rare systemic and rheumatological diseases
Research Papers
184 drug discovery papers about Primary angiitis of the central nervous system, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
184 drug discovery papers about Primary angiitis of the central nervous system, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-18 | Type I Interferonopathies in the Differential Diagnosis of Vasculitis: A Comprehensive Review.
Type I interferonopathies are a heterogeneous group of monogenic autoinflammatory disorders characterized by dysregulated type I interferon (IFN-I) signaling due to pathogenic variants that affect nucleic acid sensing, processing, or downstream signaling pathways. Mutations in genes including TREX1, RNASEH2A/B/C, SAMHD1, ADAR1, STING1 (TMEM173), PSMB8, COPA, and DNASE1L3 lead to persistent activation of innate immune pathways, particularly the cGAS-STING, MDA5, and Toll-like receptor pathways, with subsequent JAK-STAT signaling and sustained overexpression of interferon-stimulated genes. Chronic IFN-I activation promotes endothelial dysfunction, vascular inflammation, and tissue injury, providing a mechanistic link between interferonopathies and vasculitic disorders. Clinically, these conditions present with diverse manifestations, including chilblains, livedo reticularis, necrotizing cutaneous vasculopathy, panniculitis, interstitial lung disease, cerebral vasculopathy, and glomerulonephritis, often resembling autoimmune diseases such as primary central nervous system vasculitis, systemic lupus erythematosus (SLE), poliarteritis nodosa (PAN), immune complex vasculitis, and ANCA-associated vasculitis (AAV). A persistently elevated interferon gene signature represents a valuable diagnostic biomarker that distinguishes these disorders from most classical autoimmune vasculitides and facilitates early recognition. Timely genetic testing is essential to establish an accurate diagnosis, guide patient management, and avoid treatment delays. The present review summarizes the molecular mechanisms linking IFN-I dysregulation to endothelial injury and vasculitis, discusses the clinical spectrum and diagnostic challenges of monogenic interferonopathies, and highlights emerging targeted therapies, particularly Janus kinase inhibitors, that support precision medicine approaches for interferon-driven inflammatory diseases.
2026-08-06 | Primary Angiitis of the Central Nervous System: A Medical Mystery.
Primary angiitis of the central nervous system is an extremely rare diagnosis, with an incidence of 2.4 cases per 1,000,000 person-years. The exact cause of PACNS remains unknown, and typically cases present with a long prodrome. It is a diagnosis of exclusion, and various infectious, autoimmune, and malignant processes must be excluded prior to final diagnosis. Given the rarity of this condition, there is often a delay in diagnosis that can range from 6 to 23 months. It is imperative that all clinical providers be aware of this diagnosis when managing patients who present with insidious and non-specific neurological symptoms. We present a case of PACNS that responded well to a therapeutic regimen of high-dose steroids and cyclophosphamide.
2026-08-01 | NEW ONSET STATUS EPILEPTICUS AND MULTIFOCAL HAEMORRHAGE IN A YOUNG ADULT, A RARE CLINICAL PRESENTATION OF CNS VASCULITIS
Primary central nervous system vasculitis (PCNSV) is a rare inflammatory disorder affecting the blood vessels of the brain and spinal cord, without systemic involvement or underlying connective tissue disease. It usually presents with a wide range of nonspecific symptoms in the form of focal neurological deficits, new onset seizures, severe headaches, and cognitive impairment. Diagnosis is usually made when unexplained neurological deficits with either an angiogram or CNS biopsy shows features of vasculitis with other causes ruled out. Few cases are being reported every year thus making the diagnosis of PCNSV difficult in emergency department. The patient discussed here is a 29-year-old male who presents as status epilepticus to our emergency department. MRI brain reveals multiple subacute intraparenchymal haemorrhage with punctate micro haemorrhages. CSF analysis shows pleocytosis with mildly elevated protein levels. A diagnosis of primary CNS vasculitis was made and patient rapidly improved after receiving intravenous Methylprednisolone for 7 days.
2026-06-09 | MULTIPLE RECURRENT ISCHEMIC STROKES AS THE INITIAL MANIFESTATION OF PROBABLE PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM: A CARE-COMPLIANT CASE REPORT
report a 57-year-old previously healthy man presenting with multiple recurrent ischemic strokes over a short period despite adequate antiplatelet therapy. Conventional imaging was inconclusive. Advanced neuroimaging with vessel wall imaging demonstrated concentric arterial wall enhancement suggestive of vasculitis. Cerebrospinal fluid and extensive laboratory tests were unremarkable. Brain biopsy revealed inflammatory changes without definitive granulomatous vasculitis. The diagnosis of probable PACNS was established based on clinicoradiological correlation and exclusion of secondary causes. Intervention and outcome: The patient was treated with high-dose corticosteroids followed by cyclophosphamide, evolving with clinical improvement, radiological stabilization, and functional recovery. Conclusion: This case highlights the importance of considering PACNS in patients with recurrent unexplained strokes and underscores the role of advanced imaging and multidisciplinary evaluation.
2026-05-13 | Inside the Heterogeneity of Primary CNS Vasculitis: A Single-Center 40-Year Experience.
Primary CNS vasculitis (PCNSV) is a heterogeneous condition. This study examines a large cohort with long-term follow-up to identify potential disease subsets. We retrospectively analyzed 216 patients with PCNSV (Mayo Clinic, 1983-2023), using standardized diagnostic criteria, classifying by vessel size, histopathology, and outcomes. Subsets and predictors of functional and therapeutic outcomes were evaluated. Diagnosis was based on cerebral angiography in 142 patients and histologically confirmed in 74. Isolated small vessel involvement was positively associated with mass-lesion presentation (odds ratio [OR] 19.38, p = 0.02), meningeal-enhancing lesions (OR 39.10, p < 0.0001), elevated CSF protein (OR 4.04, p = 0.03), and β-amyloid vascular deposits (OR 23.43, p = 0.0001), but negatively with focal manifestations (OR 0.32, p = 0.04) and cerebral infarcts (OR 0.22, p = 0.003). Lymphocytic vasculitis was linked to younger age at diagnosis (p = 0.006), longer symptom-to-diagnosis interval (p = 0.05), more seizures (p = 0.04), and lower disability (p = 0.003) and mortality (p = 0.008). Necrotizing vasculitis was associated with intracranial hemorrhage (p = 0.008). Two or more relapses occurred in 12.7%, associated with histologic diagnosis (OR 3.15, p = 0.009) and inversely with gadolinium-enhanced lesions (OR 0.33, p = 0.01). Therapy response occurred in 82.9%, long-term remission in 23.6%. Cerebral infarcts, especially multiple, were associated with poor therapy response (OR 0.11, p = 0.03). Histologic diagnosis was inversely associated with long-term remission (OR 0.44, p = 0.03), whereas aspirin use was positively associated (OR 2.8, p = 0.002). A rapidly progressive course occurred in 13.4% of patients and was linked to increasing age (OR 1.34/10 years, p = 0.04), cognitive dysfunction (OR 5.59, p = 0.02), cerebral infarctions (OR 5.02, p = 0.004), and large vessel involvement (OR 3.51, p = 0.02). Gadolinium-enhanced lesions (OR 0.36, p = 0.04) and aspirin (OR 0.42, p = 0.08) were protective. Mortality (21.3%) was associated with older age (HR 1.42, p = 0.002), cognitive dysfunction (HR 3.93, p = 0.006), and cerebral infarctions (HR 1.94, p = 0.03). PCNSV heterogeneity, driven by vessel size and histology, affects presentation and outcomes; our findings offer insights to improve diagnosis and treatment.
antibodies
2026-09-13 | Telitacicept for primary angiitis of the central nervous system: A real-world retrospective study.
Primary central nervous system vasculitis (PACNS) is a rare inflammatory disease with limited treatment options. Telitacicept and high-resolution vessel wall imaging (HR-VWI) may offer new strategies for therapy and disease monitoring. To evaluate the clinical efficacy and safety of telitacicept in patients with PACNS and to explore the value of HR-VWI in assessing disease activity. A single-center retrospective study. Eight patients with PACNS who received telitacicept and completed HR-VWI follow-up were retrospectively enrolled. Neurological outcomes assessed by the modified Rankin Scale (mRS), HR-VWI vessel wall enhancement characteristics, and immunoglobulin and complement levels were compared at baseline and at 1, 3, 6, and 12 months after treatment. Relapse and adverse events were recorded during follow-up. Following telitacicept treatment, neurological outcomes progressively improved, with modified Rankin Scale (mRS) scores showing a gradual decline over time. At 12 months, all patients remained at a level of mild functional disability (mRS ≤ 2). HR-VWI demonstrated reduced vessel wall enhancement, shortened enhancement length, and decreased circumferential involvement of the affected vessels after treatment. In some patients, the degree of luminal stenosis improved or remained stable, with no evidence of progressive worsening. Immunological analyses showed a progressive decline in serum IgG and IgM levels, whereas IgA levels changed modestly. Complement C3 and C4 levels remained generally stable throughout treatment. Three patients experienced disease relapse, all occurring within 3 months after treatment initiation; however, the relapse frequency was lower than that observed before telitacicept therapy. One patient developed mild allergic cheilitis that resolved with symptomatic therapy. Telitacicept treatment was associated with improvements in neurological outcomes and reductions in HR-VWI inflammatory parameters in patients with PACNS. HR-VWI may provide valuable information for assessing disease activity and evaluating longitudinal vascular changes during follow-up.
2026-07-06 | [Successful treatment with rituximab in unilateral relapsing primary CNS vasculitis: a case report].
We report a case of unilateral relapsing primary CNS vasculitis (PCNSV) treated with Rituximab. A 52-year old man initially diagnosed as PCNSV by brain biopsy. He was treated with corticosteroids and no recurrence had been recognized for 4 years. However, after the reduction of corticosteroids to 9 mg, PCNSV recurred many times only in the right hemisphere. Mycophenolate mofetil and cyclophosphamide were not effective. We diagnosed this patient as unilateral relapsing PCNSV (UR-PCNSV), which is resistant to treatment and repeatedly relapses unilaterally. After rituximab was introduced, there was no clinical recurrence and abnormal lesions on head MRI improved. We emphasize that rituximab is a good candidate drug for treating the UR-PCNSV.
2026-05-05 | A Single-Center Study on Childhood Rare Vasculitides: Clinical and Outcome Analysis.
To evaluate rare childhood vasculitides using standardized clinical, laboratory, imaging, and outcome data. A retrospective cohort of 74 children with 8 rare vasculitides was assessed at a single center. Demographics, imaging, and disease activity (Pediatric Vasculitis Activity Score (PVAS)) and damage (Pediatric Vasculitis Damage Index) scores were recorded at diagnosis, 12 months, and last visit. Among 74 patients, 39 (52.7%) were girls. Median diagnosis age was 13.5 years. Subtype distribution was vascular Behçet syndrome 22 (29.7%), Takayasu arteritis (TA) 16 (21.6%), deficiency of adenosine deaminase 2 (DADA2) 14 (18.9%), polyarteritis nodosa 11 (14.9%), granulomatosis with polyangiitis (GPA) 6 (8.1%), primary angiitis of the central nervous system (PACNS) 3 (4.1%), eosinophilic GPA 1 (1.4%), and Cogan syndrome 1 (1.4%). The DADA2 had the longest diagnostic delay (median [IQR]: 20 [6-99.75] months), while PACNS had the youngest median age at onset (4.6 [3.07-7.95] years). Overall, 13.5% (n=10) were diagnosed before age 5, showing recurrent fever (60%, n=6) and anemia (50%, n=5), less skin/mucosal (40%, n=4), musculoskeletal (30%, n=3), cardiovascular (20%, n=2), and pulmonary involvement (20%, n=2), and higher PVAS (median 2.0, IQR 1.25-2.75). At 12 months, all had low disease activity. The TA had the longest corticosteroid use, highest damage, and slower remission. Overall remission was 91.9% (n=68/74), while GPA patients had more flares in the first year (median 1.0, IQR 0.25-1.75). Prognosis was favorable, but TA and monogenic vasculitides showed greater damage. In children <5 years, higher activity but good early response emphasize timely, individualized management.
2026-04-08 | Overview of Primary Angiitis of the Central Nervous System: Current Insights.
Primary angiitis of the central nervous system (PACNS), also known as primary central nervous system vasculitis, is a rare autoimmune condition characterized by exclusive involvement of the brain, spinal cord, and leptomeninges. With an estimated prevalence of 2.4 cases per million person-years in North America, PACNS represents one of the rarest vasculitides and continues to pose significant diagnostic and therapeutic challenges due to its heterogeneous clinical manifestations and lack of specific biomarkers. This critical review article provides a comprehensive overview of PACNS with emphasis on: (i) current understanding of pathophysiology and unique variations of clinical presentation, (ii) challenges and strategies in reaching a definitive diagnosis, and (iii) evaluation and comparison of pharmacological and neuromodulatory therapies currently available. Recent advances in understanding pathophysiology have identified elevated interleukin-17 in cerebrospinal fluid, distinct gene expression profiles including upregulation of TBC1D3C and TBC1D3L genes, and immune cell profiling showing increased intrathecal NK-cell and B-cell frequencies. Three histopathological subtypes have been characterized: granulomatous vasculitis (32-61%), lymphocytic vasculitis (24-79%), and necrotizing vasculitis (14-42%). Emerging biomarkers including neurofilament light chain, circulating endothelial cells, and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) show promise for diagnosis and disease monitoring. Advanced neuroimaging modalities, particularly high-resolution vessel wall magnetic resonance imaging and positron emission tomography, demonstrate utility in detecting vessel wall inflammation and guiding biopsy site selection. Treatment approaches include glucocorticoids combined with cyclophosphamide for induction therapy, with mycophenolate mofetil, rituximab, azathioprine, and methotrexate used for maintenance. TNF-α inhibitors have shown efficacy in refractory cases. Despite treatment, mortality ranges from 8-23%, and approximately 25% of patients experience severe disability. PACNS remains a diagnostically challenging condition requiring high clinical suspicion and comprehensive workup. Recent advances in understanding immunopathological mechanisms, identification of novel biomarkers, and development of advanced neuroimaging techniques offer promise for earlier diagnosis and more targeted therapeutic interventions. Brain biopsy remains the gold standard for diagnosis, though emerging non-invasive diagnostic modalities may reduce reliance on invasive procedures. Treatment strategies continue to evolve beyond traditional glucocorticoid and cyclophosphamide regimens, with biologics including rituximab and TNF-α inhibitors showing efficacy in refractory disease. Future multicenter collaborative studies are essential to validate emerging biomarkers, refine diagnostic criteria, establish evidence-based treatment protocols, and improve outcomes for this rare and heterogeneous disorder.
2026-03-02 | Primary Small Vessel Central Nervous System Vasculitis Presenting as a Parietotemporal Mass: A Case Report
Introduction: Primary central nervous system vasculitis (PCNSV) of small vessels is an exceedingly rare presentation of vasculitis. Diagnosis typically takes many months, requires multiple diagnostic modalities, and includes a positive biopsy in less than 50% of cases. We present a unique case of PCNSV that will help clinicians identify this rare disease. Clinical Findings: A man in his 60s presented with confusion and aphasia and was found to have a parietotemporal brain mass. The mass was heterogenous, with inflammatory, cystic, necrotic, and hemorrhagic components. Two separate brain biopsies underwent review at 3 institutions before the diagnosis was made. Clinical Course: The patient was initially treated with steroids, amphotericin B, and flucytosine due to concern for cryptococcus on initial biopsy. After a negative universal polymerase chain reaction and repeat biopsy, he was treated with prednisone, cyclophosphamide, and methotrexate without significant improvement. He died in hospice 4 months after initial presentation. Conclusions: Diagnosing PCNSV can be extremely difficult due to sampling error in biopsy tissue and a lack of systemic markers. We review PCNSV and its epidemiology, diagnosis, and treatment.
cell therapies
2025-09-14 | Autologous haematopoietic stem cell transplantation in non-MS neuroimmunological diseases.
Central and peripheral nervous system autoimmunity has varying pathomechanisms, mandating different treatment approaches. Whilst most patients respond to standard therapy (DMT), responses may be incomplete or non-sustained. Autologous haematopoietic stem cell transplantation (aHSCT) has been reported as an immune reconstitution in refractory neuroimmunological disease. Here, we evaluate the safety and efficacy of aHSCT in patients with non-MS neuroimmunological diseases, treated at St Vincent's Hospital, Sydney. Data from a single-centre, prospective, phase II clinical trial utilising aHSCT in cases of refractory neuroimmunological diseases (non-MS) comprised 12 patients treated at St Vincent's Hospital, Sydney between May 2013 and September 2021 (HREC Ref: HREC/10/SVH/135, ACTRN12613000339752). The primary outcome was safety, defined as Day-100 transplant-related-mortality (TRM). Secondary outcomes included efficacy as determined by remission, disability scores and quality of life metrics by disease subtype. 12 patients (4 systemic lupus erythematosus (SLE)/ central nervous system (CNS) vasculitis, 3 chronic inflammatory demyelinating polyneuropathy (CIDP), 2 stiff-person syndrome (SPS), 1 Behçet's Disease (BD), 1 opsoclonus-myoclonus-ataxia syndrome (OMAS), 1 neurosarcoidosis) underwent aHSCT. TRM was 0 % and adverse effects were consistent with expected toxicities from aHSCT. Five of 12 patients were relapse-free after aHSCT at median follow up of 36 months (range 12 - 60). Five patients remained off immunosuppressive therapy at last follow-up. Clinical evidence to support the use of aHSCT in treatment-refractory neuroimmunological diseases is scant. This study highlights the experience of the largest Australian autoimmune disease transplant unit over the last decade, shedding light on which neuroimmunological conditions beyond MS, may be more likely to benefit from aHSCT.
small molecules
2026-08-18 | Type I Interferonopathies in the Differential Diagnosis of Vasculitis: A Comprehensive Review.
Type I interferonopathies are a heterogeneous group of monogenic autoinflammatory disorders characterized by dysregulated type I interferon (IFN-I) signaling due to pathogenic variants that affect nucleic acid sensing, processing, or downstream signaling pathways. Mutations in genes including TREX1, RNASEH2A/B/C, SAMHD1, ADAR1, STING1 (TMEM173), PSMB8, COPA, and DNASE1L3 lead to persistent activation of innate immune pathways, particularly the cGAS-STING, MDA5, and Toll-like receptor pathways, with subsequent JAK-STAT signaling and sustained overexpression of interferon-stimulated genes. Chronic IFN-I activation promotes endothelial dysfunction, vascular inflammation, and tissue injury, providing a mechanistic link between interferonopathies and vasculitic disorders. Clinically, these conditions present with diverse manifestations, including chilblains, livedo reticularis, necrotizing cutaneous vasculopathy, panniculitis, interstitial lung disease, cerebral vasculopathy, and glomerulonephritis, often resembling autoimmune diseases such as primary central nervous system vasculitis, systemic lupus erythematosus (SLE), poliarteritis nodosa (PAN), immune complex vasculitis, and ANCA-associated vasculitis (AAV). A persistently elevated interferon gene signature represents a valuable diagnostic biomarker that distinguishes these disorders from most classical autoimmune vasculitides and facilitates early recognition. Timely genetic testing is essential to establish an accurate diagnosis, guide patient management, and avoid treatment delays. The present review summarizes the molecular mechanisms linking IFN-I dysregulation to endothelial injury and vasculitis, discusses the clinical spectrum and diagnostic challenges of monogenic interferonopathies, and highlights emerging targeted therapies, particularly Janus kinase inhibitors, that support precision medicine approaches for interferon-driven inflammatory diseases.
2026-08-06 | Primary Angiitis of the Central Nervous System: A Medical Mystery.
Primary angiitis of the central nervous system is an extremely rare diagnosis, with an incidence of 2.4 cases per 1,000,000 person-years. The exact cause of PACNS remains unknown, and typically cases present with a long prodrome. It is a diagnosis of exclusion, and various infectious, autoimmune, and malignant processes must be excluded prior to final diagnosis. Given the rarity of this condition, there is often a delay in diagnosis that can range from 6 to 23 months. It is imperative that all clinical providers be aware of this diagnosis when managing patients who present with insidious and non-specific neurological symptoms. We present a case of PACNS that responded well to a therapeutic regimen of high-dose steroids and cyclophosphamide.
2026-08-01 | NEW ONSET STATUS EPILEPTICUS AND MULTIFOCAL HAEMORRHAGE IN A YOUNG ADULT, A RARE CLINICAL PRESENTATION OF CNS VASCULITIS
Primary central nervous system vasculitis (PCNSV) is a rare inflammatory disorder affecting the blood vessels of the brain and spinal cord, without systemic involvement or underlying connective tissue disease. It usually presents with a wide range of nonspecific symptoms in the form of focal neurological deficits, new onset seizures, severe headaches, and cognitive impairment. Diagnosis is usually made when unexplained neurological deficits with either an angiogram or CNS biopsy shows features of vasculitis with other causes ruled out. Few cases are being reported every year thus making the diagnosis of PCNSV difficult in emergency department. The patient discussed here is a 29-year-old male who presents as status epilepticus to our emergency department. MRI brain reveals multiple subacute intraparenchymal haemorrhage with punctate micro haemorrhages. CSF analysis shows pleocytosis with mildly elevated protein levels. A diagnosis of primary CNS vasculitis was made and patient rapidly improved after receiving intravenous Methylprednisolone for 7 days.
2026-06-09 | MULTIPLE RECURRENT ISCHEMIC STROKES AS THE INITIAL MANIFESTATION OF PROBABLE PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM: A CARE-COMPLIANT CASE REPORT
report a 57-year-old previously healthy man presenting with multiple recurrent ischemic strokes over a short period despite adequate antiplatelet therapy. Conventional imaging was inconclusive. Advanced neuroimaging with vessel wall imaging demonstrated concentric arterial wall enhancement suggestive of vasculitis. Cerebrospinal fluid and extensive laboratory tests were unremarkable. Brain biopsy revealed inflammatory changes without definitive granulomatous vasculitis. The diagnosis of probable PACNS was established based on clinicoradiological correlation and exclusion of secondary causes. Intervention and outcome: The patient was treated with high-dose corticosteroids followed by cyclophosphamide, evolving with clinical improvement, radiological stabilization, and functional recovery. Conclusion: This case highlights the importance of considering PACNS in patients with recurrent unexplained strokes and underscores the role of advanced imaging and multidisciplinary evaluation.
2026-05-13 | Inside the Heterogeneity of Primary CNS Vasculitis: A Single-Center 40-Year Experience.
Primary CNS vasculitis (PCNSV) is a heterogeneous condition. This study examines a large cohort with long-term follow-up to identify potential disease subsets. We retrospectively analyzed 216 patients with PCNSV (Mayo Clinic, 1983-2023), using standardized diagnostic criteria, classifying by vessel size, histopathology, and outcomes. Subsets and predictors of functional and therapeutic outcomes were evaluated. Diagnosis was based on cerebral angiography in 142 patients and histologically confirmed in 74. Isolated small vessel involvement was positively associated with mass-lesion presentation (odds ratio [OR] 19.38, p = 0.02), meningeal-enhancing lesions (OR 39.10, p < 0.0001), elevated CSF protein (OR 4.04, p = 0.03), and β-amyloid vascular deposits (OR 23.43, p = 0.0001), but negatively with focal manifestations (OR 0.32, p = 0.04) and cerebral infarcts (OR 0.22, p = 0.003). Lymphocytic vasculitis was linked to younger age at diagnosis (p = 0.006), longer symptom-to-diagnosis interval (p = 0.05), more seizures (p = 0.04), and lower disability (p = 0.003) and mortality (p = 0.008). Necrotizing vasculitis was associated with intracranial hemorrhage (p = 0.008). Two or more relapses occurred in 12.7%, associated with histologic diagnosis (OR 3.15, p = 0.009) and inversely with gadolinium-enhanced lesions (OR 0.33, p = 0.01). Therapy response occurred in 82.9%, long-term remission in 23.6%. Cerebral infarcts, especially multiple, were associated with poor therapy response (OR 0.11, p = 0.03). Histologic diagnosis was inversely associated with long-term remission (OR 0.44, p = 0.03), whereas aspirin use was positively associated (OR 2.8, p = 0.002). A rapidly progressive course occurred in 13.4% of patients and was linked to increasing age (OR 1.34/10 years, p = 0.04), cognitive dysfunction (OR 5.59, p = 0.02), cerebral infarctions (OR 5.02, p = 0.004), and large vessel involvement (OR 3.51, p = 0.02). Gadolinium-enhanced lesions (OR 0.36, p = 0.04) and aspirin (OR 0.42, p = 0.08) were protective. Mortality (21.3%) was associated with older age (HR 1.42, p = 0.002), cognitive dysfunction (HR 3.93, p = 0.006), and cerebral infarctions (HR 1.94, p = 0.03). PCNSV heterogeneity, driven by vessel size and histology, affects presentation and outcomes; our findings offer insights to improve diagnosis and treatment.
antibodies
2026-09-13 | Telitacicept for primary angiitis of the central nervous system: A real-world retrospective study.
Primary central nervous system vasculitis (PACNS) is a rare inflammatory disease with limited treatment options. Telitacicept and high-resolution vessel wall imaging (HR-VWI) may offer new strategies for therapy and disease monitoring. To evaluate the clinical efficacy and safety of telitacicept in patients with PACNS and to explore the value of HR-VWI in assessing disease activity. A single-center retrospective study. Eight patients with PACNS who received telitacicept and completed HR-VWI follow-up were retrospectively enrolled. Neurological outcomes assessed by the modified Rankin Scale (mRS), HR-VWI vessel wall enhancement characteristics, and immunoglobulin and complement levels were compared at baseline and at 1, 3, 6, and 12 months after treatment. Relapse and adverse events were recorded during follow-up. Following telitacicept treatment, neurological outcomes progressively improved, with modified Rankin Scale (mRS) scores showing a gradual decline over time. At 12 months, all patients remained at a level of mild functional disability (mRS ≤ 2). HR-VWI demonstrated reduced vessel wall enhancement, shortened enhancement length, and decreased circumferential involvement of the affected vessels after treatment. In some patients, the degree of luminal stenosis improved or remained stable, with no evidence of progressive worsening. Immunological analyses showed a progressive decline in serum IgG and IgM levels, whereas IgA levels changed modestly. Complement C3 and C4 levels remained generally stable throughout treatment. Three patients experienced disease relapse, all occurring within 3 months after treatment initiation; however, the relapse frequency was lower than that observed before telitacicept therapy. One patient developed mild allergic cheilitis that resolved with symptomatic therapy. Telitacicept treatment was associated with improvements in neurological outcomes and reductions in HR-VWI inflammatory parameters in patients with PACNS. HR-VWI may provide valuable information for assessing disease activity and evaluating longitudinal vascular changes during follow-up.
2026-07-06 | [Successful treatment with rituximab in unilateral relapsing primary CNS vasculitis: a case report].
We report a case of unilateral relapsing primary CNS vasculitis (PCNSV) treated with Rituximab. A 52-year old man initially diagnosed as PCNSV by brain biopsy. He was treated with corticosteroids and no recurrence had been recognized for 4 years. However, after the reduction of corticosteroids to 9 mg, PCNSV recurred many times only in the right hemisphere. Mycophenolate mofetil and cyclophosphamide were not effective. We diagnosed this patient as unilateral relapsing PCNSV (UR-PCNSV), which is resistant to treatment and repeatedly relapses unilaterally. After rituximab was introduced, there was no clinical recurrence and abnormal lesions on head MRI improved. We emphasize that rituximab is a good candidate drug for treating the UR-PCNSV.
2026-05-05 | A Single-Center Study on Childhood Rare Vasculitides: Clinical and Outcome Analysis.
To evaluate rare childhood vasculitides using standardized clinical, laboratory, imaging, and outcome data. A retrospective cohort of 74 children with 8 rare vasculitides was assessed at a single center. Demographics, imaging, and disease activity (Pediatric Vasculitis Activity Score (PVAS)) and damage (Pediatric Vasculitis Damage Index) scores were recorded at diagnosis, 12 months, and last visit. Among 74 patients, 39 (52.7%) were girls. Median diagnosis age was 13.5 years. Subtype distribution was vascular Behçet syndrome 22 (29.7%), Takayasu arteritis (TA) 16 (21.6%), deficiency of adenosine deaminase 2 (DADA2) 14 (18.9%), polyarteritis nodosa 11 (14.9%), granulomatosis with polyangiitis (GPA) 6 (8.1%), primary angiitis of the central nervous system (PACNS) 3 (4.1%), eosinophilic GPA 1 (1.4%), and Cogan syndrome 1 (1.4%). The DADA2 had the longest diagnostic delay (median [IQR]: 20 [6-99.75] months), while PACNS had the youngest median age at onset (4.6 [3.07-7.95] years). Overall, 13.5% (n=10) were diagnosed before age 5, showing recurrent fever (60%, n=6) and anemia (50%, n=5), less skin/mucosal (40%, n=4), musculoskeletal (30%, n=3), cardiovascular (20%, n=2), and pulmonary involvement (20%, n=2), and higher PVAS (median 2.0, IQR 1.25-2.75). At 12 months, all had low disease activity. The TA had the longest corticosteroid use, highest damage, and slower remission. Overall remission was 91.9% (n=68/74), while GPA patients had more flares in the first year (median 1.0, IQR 0.25-1.75). Prognosis was favorable, but TA and monogenic vasculitides showed greater damage. In children <5 years, higher activity but good early response emphasize timely, individualized management.
2026-04-08 | Overview of Primary Angiitis of the Central Nervous System: Current Insights.
Primary angiitis of the central nervous system (PACNS), also known as primary central nervous system vasculitis, is a rare autoimmune condition characterized by exclusive involvement of the brain, spinal cord, and leptomeninges. With an estimated prevalence of 2.4 cases per million person-years in North America, PACNS represents one of the rarest vasculitides and continues to pose significant diagnostic and therapeutic challenges due to its heterogeneous clinical manifestations and lack of specific biomarkers. This critical review article provides a comprehensive overview of PACNS with emphasis on: (i) current understanding of pathophysiology and unique variations of clinical presentation, (ii) challenges and strategies in reaching a definitive diagnosis, and (iii) evaluation and comparison of pharmacological and neuromodulatory therapies currently available. Recent advances in understanding pathophysiology have identified elevated interleukin-17 in cerebrospinal fluid, distinct gene expression profiles including upregulation of TBC1D3C and TBC1D3L genes, and immune cell profiling showing increased intrathecal NK-cell and B-cell frequencies. Three histopathological subtypes have been characterized: granulomatous vasculitis (32-61%), lymphocytic vasculitis (24-79%), and necrotizing vasculitis (14-42%). Emerging biomarkers including neurofilament light chain, circulating endothelial cells, and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) show promise for diagnosis and disease monitoring. Advanced neuroimaging modalities, particularly high-resolution vessel wall magnetic resonance imaging and positron emission tomography, demonstrate utility in detecting vessel wall inflammation and guiding biopsy site selection. Treatment approaches include glucocorticoids combined with cyclophosphamide for induction therapy, with mycophenolate mofetil, rituximab, azathioprine, and methotrexate used for maintenance. TNF-α inhibitors have shown efficacy in refractory cases. Despite treatment, mortality ranges from 8-23%, and approximately 25% of patients experience severe disability. PACNS remains a diagnostically challenging condition requiring high clinical suspicion and comprehensive workup. Recent advances in understanding immunopathological mechanisms, identification of novel biomarkers, and development of advanced neuroimaging techniques offer promise for earlier diagnosis and more targeted therapeutic interventions. Brain biopsy remains the gold standard for diagnosis, though emerging non-invasive diagnostic modalities may reduce reliance on invasive procedures. Treatment strategies continue to evolve beyond traditional glucocorticoid and cyclophosphamide regimens, with biologics including rituximab and TNF-α inhibitors showing efficacy in refractory disease. Future multicenter collaborative studies are essential to validate emerging biomarkers, refine diagnostic criteria, establish evidence-based treatment protocols, and improve outcomes for this rare and heterogeneous disorder.
2026-03-02 | Primary Small Vessel Central Nervous System Vasculitis Presenting as a Parietotemporal Mass: A Case Report
Introduction: Primary central nervous system vasculitis (PCNSV) of small vessels is an exceedingly rare presentation of vasculitis. Diagnosis typically takes many months, requires multiple diagnostic modalities, and includes a positive biopsy in less than 50% of cases. We present a unique case of PCNSV that will help clinicians identify this rare disease. Clinical Findings: A man in his 60s presented with confusion and aphasia and was found to have a parietotemporal brain mass. The mass was heterogenous, with inflammatory, cystic, necrotic, and hemorrhagic components. Two separate brain biopsies underwent review at 3 institutions before the diagnosis was made. Clinical Course: The patient was initially treated with steroids, amphotericin B, and flucytosine due to concern for cryptococcus on initial biopsy. After a negative universal polymerase chain reaction and repeat biopsy, he was treated with prednisone, cyclophosphamide, and methotrexate without significant improvement. He died in hospice 4 months after initial presentation. Conclusions: Diagnosing PCNSV can be extremely difficult due to sampling error in biopsy tissue and a lack of systemic markers. We review PCNSV and its epidemiology, diagnosis, and treatment.
cell therapies
2025-09-14 | Autologous haematopoietic stem cell transplantation in non-MS neuroimmunological diseases.
Central and peripheral nervous system autoimmunity has varying pathomechanisms, mandating different treatment approaches. Whilst most patients respond to standard therapy (DMT), responses may be incomplete or non-sustained. Autologous haematopoietic stem cell transplantation (aHSCT) has been reported as an immune reconstitution in refractory neuroimmunological disease. Here, we evaluate the safety and efficacy of aHSCT in patients with non-MS neuroimmunological diseases, treated at St Vincent's Hospital, Sydney. Data from a single-centre, prospective, phase II clinical trial utilising aHSCT in cases of refractory neuroimmunological diseases (non-MS) comprised 12 patients treated at St Vincent's Hospital, Sydney between May 2013 and September 2021 (HREC Ref: HREC/10/SVH/135, ACTRN12613000339752). The primary outcome was safety, defined as Day-100 transplant-related-mortality (TRM). Secondary outcomes included efficacy as determined by remission, disability scores and quality of life metrics by disease subtype. 12 patients (4 systemic lupus erythematosus (SLE)/ central nervous system (CNS) vasculitis, 3 chronic inflammatory demyelinating polyneuropathy (CIDP), 2 stiff-person syndrome (SPS), 1 Behçet's Disease (BD), 1 opsoclonus-myoclonus-ataxia syndrome (OMAS), 1 neurosarcoidosis) underwent aHSCT. TRM was 0 % and adverse effects were consistent with expected toxicities from aHSCT. Five of 12 patients were relapse-free after aHSCT at median follow up of 36 months (range 12 - 60). Five patients remained off immunosuppressive therapy at last follow-up. Clinical evidence to support the use of aHSCT in treatment-refractory neuroimmunological diseases is scant. This study highlights the experience of the largest Australian autoimmune disease transplant unit over the last decade, shedding light on which neuroimmunological conditions beyond MS, may be more likely to benefit from aHSCT.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
4 orphan drug designations for Primary angiitis of the central nervous system, including 1 approved therapy.
4 orphan drug designations for Primary angiitis of the central nervous system, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Melatonin | — | FDA | — | WORPHMED Srl |
Mafosfamide | — | FDA | — | Baxter Healthcare Corporation |
Busulfan | — | FDA | SuperGen, Inc. | |
Cytarabine liposomal [DepoCyt] | — | FDA | Approved | Pacira Pharmaceuticals, Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.