Newsgroup: it.sport.calcio
Titolo: Re: Side Effects


Central nervous system involvement in patients with HCV-related
cryoglobulinemia: review and a case report
D. Filippini, F. Colombo, S. Jann1 , R. Corneo2, B. Canesi
Divisione di Reumatologia, 1Divisione di Neurologia, 2Servizio 
Immuno-Trasfusionale
Ospedale Niguarda Cà Granda, Milano
SUMMARY
Introduction: Few well-documented cases of central nervous system 
involvement in patients with mixed cryoglobulinemia
and/or HCV infection have been reported. We can distinguish between acute or 
subacute diffuse and focal lesions (transient
ischemic attack-like syndromes and cerebrovascular accidents).
Methods: A search of two electronic databases (Medline and EMBASE) was 
conducted from the year of their inception
(1966 for Medline and 1988 for EMBASE) to September 2000. The search 
strategy employed entailed combining
these terms: Cryoglobulinemia, Central Nervous System, Hepatitis C, chronic 
hepatitis. Cryoglobulinemia and Central
Nervous System were also used as free test words. We analysed articles with 
case reports and the most frequent
articles on the references list.
Pathogenesis: The main pathophysiologic mechanism of cerebral involvement is 
ischemia (or rarely hemorrhage) due
to diffuse or segmental vasculitis of the small cerebral vessels. In these 
cases a brain MRI usually shows single or multiple
increased T2 signals. Furthermore an occasional occlusive vasculopathy 
without vasculitis was documented histologically.
In these patients ischemia could be started or enhanced by the engorgement 
of the microvasculature by
clumps of red cells and by aggregates of cryoglobulins. In the same patients 
vasculitis and hemoreological abnormalities
can affect the clinical picture of the cerebral involvement in mixed 
cryoglobulinemia. Finally, the detection
of HCV in the lesions induces a hypothesis that, in some cases, CNS 
involvement could be directly related to chronic
HCV infection, even in the absence of cryoglobulin production.
Case report: We describe a 63 year-old woman with acute severe 
encephalopathy. Laboratory evaluation revealed a
high positive test result for rheumatoid factor (3390 U/ml) and 
hypocomplementemia (C4 less than 1.67 mg/dl). Protein
immunofixation electrophoresis demonstrated 5% monoclonal proteins (IgM/k 
and IgG/k), 3% cryoglobulins were
present, HCV antibody and HCV-RNA (type 2a-2c) were positive. Cryoglobulins 
were never typed, because they disappeared
after plasma exchanges. Liver enzymes, renal function and findings on 
cerebrospinal fluid were normal. Cerebral
CT and MRI were also normal. Antinuclear antibodies, anti nDNA antibodies, 
antiphospholipid antibodies, lupus
anticoagulant, ANCA, Lyme disease serology, complete tests for thrombophilia 
were negative. Bone aspiration
was normal. The patient, in coma, was treated with two plasma exchanges. 
During the first treatment she recovered
consciousness. Prednisone (1 mg/Kg/day) and cyclophosphamide (400 mg iv for 
three days) were added. After a week
two plasma exchanges were performed again. Liver enzymes and rheumatoid 
factor were analyzed monthly for six
months and than every two months for another six month period up to the 
present. Liver enzymes were always normal,
rheumatoid factor was always at a lower level than the first evaluation (now 
it's 311 U/ml). At present she is taking
Prednisone 5 mg once a day, neurologic syntoms are absent and neurologic 
examination is normal.
Discussion: We can conclude that: central neurologic involvement may be the 
clinical presentation of HCV infection
and mixed cryoglobulinemia. HCV serologic tests and cryoglobulins should be 
considered in patient with encephalopathy
of non-obvious cause; plasma exchange is the treatment of choice in acute 
severe forms; in some patients
HCV could involve directly CNS, even in the absence of cryoglobulin 
production.

 Ospedale Niguarda Cr´ Granda, Milano
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