The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features.

BACKGROUND: Varicella zoster virus (VZV) vasculopathy produces stroke secondary to viral infection of cerebral arteries. Not all patients have rash before cerebral ischemia or stroke. Furthermore, other vasculitides produce similar clinical features and comparable imaging, angiographic, and CSF abnormalities. METHODS: We review our 23 published cases and 7 unpublished cases of VZV vasculopathy. All CSFs were tested for VZV DNA by PCR and anti-VZV IgG antibody and were positive for either or both. RESULTS: Among 30 patients, rash occurred in 19 (63%), CSF pleocytosis in 20 (67%), and imaging abnormalities in 29 (97%). Angiography in 23 patients revealed abnormalities in 16 (70%). Large and small arteries were involved in 15 (50%), small arteries in 11 (37%), and large arteries in only 4 (13%) of 30 patients. Average time from rash to neurologic symptoms and signs was 4.1 months, and from neurologic symptoms and signs to CSF virologic analysis was 4.2 months. CSF of 9 (30%) patients contained VZV DNA while 28 (93%) had anti-VZV IgG antibody in CSF; in each of these patients, reduced serum/CSF ratio of VZV IgG confirmed intrathecal synthesis. CONCLUSIONS: Rash or CSF pleocytosis is not required to diagnose varicella zoster virus (VZV) vasculopathy, whereas MRI/CT abnormalities are seen in almost all patients. Most patients had mixed large and small artery involvement. Detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). Determination of optimal antiviral treatment and benefit of concurrent steroid therapy awaits studies with larger case numbers.

The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy.

BACKGROUND: Factors that may obscure the diagnosis of varicella zoster virus (VZV) vasculopathy include the absence of rash before TIAs or stroke as well as similar clinical features and imaging, angiographic, and CSF abnormalities to those of other vasculopathies. Diagnosis relies on virologic confirmation that detects VZV DNA, anti-VZV IgG antibody, or both in the CSF. METHODS: We reviewed our current 14 cases of patients diagnosed with VZV vasculopathy based on combined clinical, imaging, angiographic, or CSF abnormalities. All CSFs must have been tested for VZV DNA by PCR and for anti-VZV IgG antibody by enzyme immunoassay and found to be positive for either or both. Of the 14 subjects, 8 had a history of recent zoster, whereas 6 had no history of zoster rash before developing vasculopathy. RESULTS: All 14 subjects (100%) had anti-VZV IgG antibody in their CSF, whereas only 4 (28%) had VZV DNA. The detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). CONCLUSIONS: In varicella zoster virus (VZV) vasculopathy, the diagnostic value of detecting anti-VZV IgG antibody in CSF is greater than that of detecting VZV DNA. Although a positive PCR for VZV DNA in CSF is helpful, a negative PCR does not exclude the diagnosis of VZV vasculopathy. Only when the CSF is negative for both VZV DNA and anti-VZV IgG antibody can the diagnosis of VZV vasculopathy be excluded.

Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid)

BACKGROUND: Topical tretinoin (retinoic acid) modifies fine wrinkles and certain other features of human skin damaged by exposure to the sun (photodamage), but histologic changes do not account for this improvement. In mice with photodamage induced by ultraviolet light, effacement of fine wrinkles by tretinoin is correlated with dermal collagen synthesis but not with histologic changes. We investigated whether collagen synthesis was reduced in photodamaged human skin and, if so, whether it could be restored by treatment with topical tretinoin. METHODS: Biopsies of photodamaged skin from the extensor aspect of the forearm and skin from the buttocks, which had been protected from the sun, were performed on 26 healthy subjects. In addition, 29 patients with photodamaged skin were treated for 10 to 12 months with a daily application of 0.1 percent tretinoin cream (15 patients) or vehicle cream (14 patients). Skin-biopsy specimens obtained at base line and after treatment were assessed immunohistologically for evidence of dermal collagen I formation (collagen synthesis). RESULTS: Collagen I formation was 56 percent less in the papillary dermis of photodamaged skin than in skin protected from the sun (P < 0.001) and was correlated with the clinical severity of photodamage (r = -0.58, P = 0.002). Treatment of photodamaged skin with tretinoin produced an 80 percent increase in collagen I formation, as compared with a 14 percent decrease in collagen formation with the use of vehicle alone (P = 0.006). CONCLUSIONS: The formation of collagen I is significantly decreased in photodamaged human skin, and this process is partly restored by treatment with tretinoin.

Development and multi-institutional implementation of coding and transmission standards for health outcomes data.

Health care delivery institutions and providers, employers, and government agencies throughout the U.S. are sharing information and pooling resources in an attempt to produce reliable measurements of health outcomes. The rapid rate of growth in the collection and pooling of health outcomes data has prompted the need for standardization. The work of health care organizations and consortiums pooling data would be greatly facilitated by widely accepted standards for the coding and transmitting of outcomes data. Moreover, standards allow for the inter-operation of data capture products, data analysis tools, and data pooling services developed by a variety of different vendors. The Health Outcomes Institute (HOI) and Henry Ford Health System (HFHS) have developed and maintain a database of health outcomes questions which provides a mechanism for uniquely coding data elements. HFHS and the American Medical Group Association (AMGA) have created a software tool to facilitate the conversion and transmission of health outcomes data elements in an American Society for Testing and Materials (ASTM)/Health Level Seven (HL7) format, which incorporates HOI question standards.