Primary Angiitis of the Central Nervous System: Description of the First 52 Adult Patients Enrolled in the French COVAC’ Cohort

Hubert de Boysson¹, Mathieu Zuber², Olivier Naggara³, Jean-Philippe Neau⁴, Françoise Gray⁵, Marie-Germaine Bousser⁶, Isabelle Crassard⁶, Emmanuel Touze⁷, Pierre-Olivier Couraud⁸, Philippe Kerschen⁹, Catherine Oppenheim³, Olivier Detante¹⁰, Anthony Faivre¹¹, Nicolas Gaillard¹², Caroline Arquizan¹³, Boris Bienvenu¹⁴, Antoine Neel¹⁵, Loic Guillevin¹⁶, Christian Pagnoux¹⁷ and French Vasculitis Study Group and NeuroVascular Society¹⁸, ¹Division of Internal Medicine, Hôpital Cochin, University Paris Descartes, Paris, France, ²Department of Neurology, Groupe Hospitalier Saint-Joseph, Université Paris Descartes, Paris, France, ³Department of Neuroradiology, Hôpital Sainte-Anne, Paris, France, ⁴Department of Neurology, Centre Hospitalier Universitaire La Milétrie, Poitiers, France, ⁵Department of Pathology, APHP Hôpital Lariboisière, Université Paris Diderot, Paris, France, ⁶Department of Neurology, APHP Hôpital Lariboisière, Université Paris Diderot, Paris, France, ⁷Department of Neurology, Hôpital Sainte-Anne, Université Paris Descartes, Paris, France, ⁸Department of Cellular Biology, Institut Cochin, Paris, France, ⁹Department of Neurology, Centre Hospitalier Universitaire Henri Mondor, Créteil, France, ¹⁰Department of Neurology, Centre Hospitalier Universitaire de Grenoble, Grenoble, France, ¹¹Department of Neurology, Hôpital d'Instruction des Armées Saint-Anne, Toulon, France, ¹²Department of Neurology, Centre Hospitalier de Perpignan, Perpignan, France, ¹³Department of Neurology, Hôpital Gui de Chauliac, Université Montpellier, Montpellier, France, ¹⁴Division of Internal Medicine, Centre Hospitalier Régional Universitaire de Caen, Côte de Nacre, Caen, France, Caen, France, ¹⁵Department of Internal Medicine, Centre Hospitalier Universitaire de Nantes, Nantes, France, ¹⁶Internal Medicine, Division of Internal Medicine, Hôpital Cochin, University Paris Descartes, Paris, France, ¹⁷Rheumatology, Mount Sinai Hospital, Toronto, Canada, Toronto, ON, Canada, ¹⁸Paris, France

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: central nervous system involvement, Cerebrovascular disease, corticosteroids and vasculitis

Session Information

Title: Vasculitis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Primary angiitis of the central nervous system (PACNS) is rare and only 1 pediatric and 1 adult large cohorts including >30 PACNS patients have been published, both from North America. The French Vasculitis Study Group, in collaboration with the French NeuroVascular Society and Internal Medicine Society, initiated a multicenter cohort study to describe a new and large adult PACNS population.

Methods: Patients with PACNS, diagnosed recently or within the past 20 years, with follow-up >6 months after diagnosis (unless they died earlier) and negative diagnostic work-ups for alternative diagnoses or secondary CNS vasculitis, were eligible for inclusion. A multidisciplinary committee (internists, neuroradiologists, neurologists and pathologists) systematically analyzed all medical charts to validate patients’ diagnoses, characteristics and outcomes. Poor outcomes were defined as no disease control and/or PACNS relapse or death.

Results: Eighteen months after cohort initiation, 52 patients (30 M/22 F; median age at diagnosis, 43.5 [18–79] yr) from 21 French hospitals have been included. Thirty-one (60%) underwent brain biopsy, which showed vasculitis features in 19 (37% biopsy-proven PACNS). All 12 patients with normal or non-contributive biopsies and the remaining 21 without brain biopsies, had persistent (>6 months) conventional cerebral angiography suggesting PACNS (33 [63%] angiography-diagnosed PACNS). The most frequent initial manifestations were focal neurological deficits (83%), headaches (54%), cognitive impairment (35%), aphasia (35%) and/or seizures (33%). Compared to biopsy-proven PACNS, angiography-diagnosed PACNS patients had more frequent focal neurological deficits (p=0.004) and bilateral infarctions on MRI (p=0.04) but less frequent encephalitic manifestations, like seizures or cognitive disorders (p=0.003 and 0.04, respectively). Twenty-two (52%) of the 42 MRI with gadolinium injection showed enhanced-parenchymatous/meningeal (22/10) lesions. All but 1 patient received corticosteroids (CS) and 44 cyclophosphamide (CYC). At the time of this analysis (median follow-up, 35 [6–148] mo), 3 (6%) patients had died; 20 (51%) of the 49 survivors had poor outcomes (13 [27%] relapsed, 7 [13%] had no disease control) and 40 (77%) had some persistent neurological damage. Patients with gadolinium leptomeningeal enhancement responded promptly to therapy but relapsed more often (80%) than those without (14%; p<0.0001). Multivariable analysis retained only intraparenchymatous and meningeal gadolinium uptakes at diagnosis as independent predictors of poor prognosis or relapse (HR=2.45 [95% CI, 0.99–6.08] and 1.88 [95% CI, 0.80–4.46], respectively).

Conclusion: In this PACNS cohort, more than half the patients responded to CS–CYC and had good outcomes at 3 yr, but neurological damage was frequent. Leptomeningeal and intraparenchymatous enhancements on MRI were associated with a poorer outcome. Comparisons of the different ongoing cohorts should help identify subgroups with poorer outcomes.

Disclosure:

H. de Boysson,
None;

M. Zuber,
None;

O. Naggara,
None;

J. P. Neau,
None;

F. Gray,
None;

M. G. Bousser,
None;

I. Crassard,
None;

E. Touze,
None;

P. O. Couraud,
None;

P. Kerschen,
None;

C. Oppenheim,
None;

O. Detante,
None;

A. Faivre,
None;

N. Gaillard,
None;

C. Arquizan,
None;

B. Bienvenu,
None;

A. Neel,
None;

L. Guillevin,
None;

C. Pagnoux,
None;

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