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Central Nervous System Involvement in Hepatitis C Virus Cryoglobulinemia Vasculitis: A Multicenter Case-Control Study Using Magnetic Resonance Imaging and Neuropsychological Tests

MILVIA CASATO, DAVID SAADOUN, ANTONELLA MARCHETTI, NICOLAS LIMAL, CHRISTINE PICQ, PATRIZIA PANTANO, DAMIEN GALANAUD, ROSARIO CIANCI, PIERRE DUHAUT, JEAN CHARLES PIETTE, MASSIMO FIORILLI, and PATRICE CACOUB

ABSTRACT.

Objective. Involvement of the central nervous system (CNS) in patients with hepatitis C virus (HCV) mixed cryoglobulinemia (MC) is rare. The mechanism by which brain lesions are produced is unclear. We investigated these phenomena by clinical evaluation (neuropsychological tests) and cerebral magnetic resonance imaging (MRI) studies in patients with HCV-MC vasculitis.

Methods. This prospective study included 40 patients with MC vasculitis and chronic active HCV infection (HCV RNA+), 11 HCV controls without MC, and 36 healthy controls, matched for sex and age. A battery of 10 standardized neuropsychological tests was administered by one experienced neuropsychiatrist. All patients underwent cerebral MRI investigation.

Results. Twenty-four of the 27 (89%) evaluated patients with HCV-MC had a deficiency in one or more of the 10 cognitive domains examined. The most commonly involved domains were those of attention (70%), executive functions (44%), visual construction (37%), and visual spatial functions (33%). The number of impaired cognitive functions was significantly higher in patients with MC vasculitis than in HCV controls (2.18 ± 1.84 vs 0.87 ± 3.1; p < 0.05). MRI analysis showed that HCV-MC patients had a higher mean number of total (7.03 ± 9.9 vs 0.90 ± 1.81 and 2.03 ± 3.1; p < 0.05) and periventricular (2.4 ± 3.0 vs 0.38 ± 0.5 and 0.8 ± 1.4; p < 0.05) white matter high intensity signals than HCV controls and healthy controls, respectively.

Conclusion. The high frequency of impaired cognitive function and the extent of MRI brain abnormalities in patients with HCV-associated mixed cryoglobulinemia vasculitis strongly suggest specific inflammatory involvement of the CNS. (J Rheumatol 2005;32:484-8)

Key Indexing Terms:

HEPATITIS C VIRUS
EXTRAHEPATIC MANIFESTATIONS
COGNITIVE FUNCTION
MIXED CRYOGLOBULINEMIA
CENTRAL NERVOUS SYSTEM
NEUROPATHY, VASCULITIS
MAGNETIC RESONANCE IMAGING


From the Department of Clinical Medicine, Department of Neurological Sciences, and Department of Neuroradiology, First School of Medicine, University of Rome "La Sapienza," Rome, Italy; and Department of Internal Medicine, Department of Physical Medicine and Rehabilitation, and Department of Neuroradiology, Hôpital La Pitié-Salpêtrière, Paris, France.

Supported in part by grants to Dr. Fiorilli from the Italian Ministry for University and Scientific Research (Fondi di Ateneo) and from the Ministry of Health (Convenzione n. ICS 160.2/RF 00.119; 2001).

M. Casato, MD; R. Cianci, MD; M. Fiorilli, MD, Department of Clinical Medicine, University of Rome; D. Saadoun, MD; N. Limal, MD; P. Duhaut, MD; J-C. Piette, MD; P. Cacoub, MD, Department of Internal Medicine, Hôpital La Pitié-Salpêtrière; A. Marchetti, MD, Department of Neurological Sciences, University of Rome; C. Picq, Department of Physical Medicine and Rehabilitation, Hôpital La Pitié-Salpêtrière; P. Pantano, MD, Department of Neuroradiology, University of Rome; D. Galanaud, MD, Department of Neuroradiology, Hôpital La Pitié-Salpêtrière.

Address reprint requests to Prof. P. Cacoub, Department of Internal Medicine, Hôpital La Pitié-Salpêtrière, 83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France. E-mail: patrice.cacoub@psl.ap-hop-paris.fr

Submitted July 7, 2003; revision accepted October 29, 2004.




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