VASCULAR PARKINSONISM IN AN ELDERLY WOMAN WITH MIXED CRYOGLOBULINEMIA ASSOCIATED WITH HEPATITIS C INFECTION

Abstract

To the Editor: Central nervous system (CNS) involvement is rarely reported in patients infected with hepatitis C virus (HCV).1 Stroke, transient ischemia, lacunar infarction, or encephalopathic syndrome may occur. Mechanisms related to vasculitis induced by the mixed cryoglobulinemia frequently associated with HCV infection seem to generate neurological lesions.1, 2 Vascular parkinsonism (VP) is now recognized as a distinct clinicopathological entity,3, 4 especially in older people,5 although the validity of VP as a concept has been called into question since the original work of Critchley.6 VP accounts for 3% to 6% of all cases of parkinsonism in studies in which imaging or pathological analysis is used to support diagnosis.7 We report here a case of VP associated with mixed HCV-related cryoglobulinemia. An 83-year-old woman was hospitalized for rehabilitation after a gradual loss of autonomy related to gait problems, postural instability, and mild depression, all of which worsened after an episode of severe bronchopneumonia. Parkinson's disease had been diagnosed 6 years previously, but no improvement was observed on levodopa treatment. Four years after the onset of symptoms, the patient was admitted to a neurological facility. Magnetic resonance imaging showed microhypersignal for the basal ganglia (striatum, insula, thalamus), external capsule, periventricular white matter, and, to a lesser extent, geniculate bodies, cerebellar peduncles, and dentate nuclei. VP was diagnosed. The dose of levodopa was increased, but no real improvement followed. The patient had been diagnosed with chronic hepatitis C (Stage 6 of the Knodell classification based on liver biopsy) 10 years earlier. She had refused treatment and was reluctant to attend follow-up visits. One year before admission, biochemical markers (Fibrotest and Actitest) indicated severe fibrosis (A3-A4) and necroinflammatory activity (A3). Polymerase chain reaction tests showed that the patient was infected with HCV of genotype 1. The patient again refused treatment. She had a long history of hypertension more or less controlled by treatment. A consultant neurologist reexamined and found gait problems, postural instability with retropulsion, hypertonia involving all four limbs but most severe in the legs, and an absence of rest tremor. The neurologist reported generalized apraxia, no real cognitive impairment, and a Mini-Mental State Examination score of 29 of 30. She confirmed the diagnosis of VP. Cryoglobulinemia (type III) was detected. This is the first description of a case of VP associated with mixed HCV-related cryoglobulinemia. A causal effect is possible in this case. Disease of the small arteries and arterioles that penetrate the brain cortex and reach the underlying structures of the white and deep gray matter, such as the basal ganglia, are the primary cause of approximately one third of symptomatic strokes.8 Arteriolosclerosis probably affected these small vessels in our patient, who, like most patients with VP, had hypertension,3-5 but because few patients with hypertension develop parkinsonism, another determinant must also have been involved. We suspect that cryoglobulinemia may have played a role by increasing the burden on these small vessels affected by arteriolosclerosis. A previous study found9 that 40% of patients with VP had anticardiolipin antibodies (ACLA), which are associated with hypercoagulable states and stroke risk, but found no difference in vascular risk factors, such as hypertension, between ACLA-positive and -negative patients. Thus, as proposed in previous studies1, 3-5, 9 we suggest that a more-precise definition of the relationship between diseases of the small vessels in the brain and other conditions, such as HCV infection, is required. In particular, it would appear to be worthwhile to test patients with VP for HCV infection and cryoglobulinemia. Financial Disclosure: None. Author Contributions: All authors were involved in the analysis and interpretation of clinical data and the preparation of the manuscript. Sponsor's Role: None.