M. Longson

Specific neuro-radiological diagnosis of Herpes encephalitis in an animal model

SummaryThe potential of utilizing a radio-labelled derivative of the antiviral drug (E)-5-(2-iodovinyl)-2′-deoxyuridine (IVDU) for the specific, non-invasive, in vivo diagnosis of Herpes simplex virus encephalitis (HSVE) was investigated in a rat model of the disease. Following pharmacological disruption of the blood brain barrier radiolabelled IVDU was administered by intra-carotid injection. Brain radioactivity was compared between control and infected animals via gamma camera scintigraphy. After clearance of non-metabolized drug, markedly higher levels of activity were found in infected brain. Post-mortem studies of cryostat sections of brain examined by autoradiography and immunochemical staining showed the radioactivity selectively accumulated in areas of virus infection. These results indicate that radio-labelled derivatives of antiviral drugs may allow the specific neuro-radiological diagnosis of HSVE.

A rat model of herpes encephalitis with special reference to its potential for the development of diagnostic brain imaging

A rat model of herpes encephalitis using intraocular inoculation of herpes simplex virus strain SC16 was investigated. Virus distribution in the brain was examined by virus isolation and immunocytochemical staining using immuno-gold silver and peroxidase-anti-peroxidase. At 5 days post-infection virus was found in the thalamus, hypothalamus, septum, colliculus, geniculate bodies, the pons, trapezoidium and medulla oblongata, but less frequently, in the cerebellum and occipital lobes. Possible routes of spread of virus and the potential of this model in neuro-radiological scanning procedures are discussed.

Meningo-encephalitis caused by Coxsackievirus group B type 2. Diagnosis confirmed by measuring intrathecal antibody

We describe a case of meningo-encephalitis caused by Coxsackievirus group B type 2. Diagnosis was suggested by isolation of virus from faeces and high titres of serum antibody in which Coxsackie virus B2 specific IgM antibody was detected. Evidence of intrathecal production of antibody confirmed the diagnosis.

The treatment of herpes encephalitis

The advent of acyclovir has accentuated the problem of diagnosis and particularly the need for brain biopsy in patients with suspected herpes simplex encephalitis. U.S.A. and U.K. practices are contrasted and the current U.K. study of acyclovir in herpes simplex encephalitis is mentioned in which retrospective and relatively non-invasive methods of diagnosis are employed.

INFECTION OF THE VULVA AND CERVIX WITH A GENITAL STRAIN OF HERPES SIMPLEX VIRUS

UNNA (1883) quoted Rollet (1869) as the earliest to describe herpetic ulceration of the cervix as a cause of vaginal discharge. Slavin and Gavett (1946) first described cases of vulvo-vaginitis due to herpex simplex and confirmed by virus isolation. However, it was not until recently that cases of herpes simplex infection of the cervix confirmed by virus isolation were reported. Dooley, Jones and Pearson (1957), Stern and Longo (1963), Nigogosyan and Mills (1965) and Yen, Reagan and Rosenthal (1 965) described cases of herpes simplex cervicitis associated with acute vulvo-vaginitis that were confirmed by virus isolation. Another case not confirmed by virus isolation has been described by Diddle, Williamson and Gardner (1963). Cases of herpes simplex cervicitis may also occur during pregnancy. Yen et al. (1965) described two cases which caused generalized herpes simplex infection in three newborn infants. However, this complication may be prevented by performing elective Caesarean section in cases of pregnancy complicated by this disease. Stein and Siciliano (1966) described necrotidng herpes simplex infection of the cervix occurring in a twin pregnancy which terminated in premature labour. Since the infection had caused a rigid cervix Caesarean section was performed, and the infants remained unaffected. Josey et al. (1966) stated that Caesarean section would not prevent generalized herpes simplex infection from occurring in newborn infants once the membranes had ruptured, since the virus could migrate from the endocervix and infect the infant in utero. Yen et al. (1965) thought this mechanism could explain rare cases of intrauterine herpes simplex infection which had been thought to be transplacental in origin. Herpes simplex cervicitis has also been detected in women screened for cancer by means of cervical smears. Naib (1966), Naib, Nahmias and Josey (1966) and Josey et al. (1966) diagnosed cases of herpes simplex infection of the cervix by histological demonstration of multinucleate giant-cells containing typical inclusion bodies in cervical smears, some of which were confirmed by virus isolation. Naib et al. (1 966) found 62 of approximately 40,000 patients (016 per cent) screened in this way had cervical changes compatible with this infection. Twenty-two cases were investigated virologically and in 12 the virus was isolated. Other cases of herpes simplex cervicitis diagnosed by cytological studies and confirmed virologically have been described by Stern and Longo (1963), Yen et al. (1965), Nigogosyan and Mills (1965) and Stein and Siciliano (1966). Misinterpretation of virologically induced cytological changes in cervical smears, in particular giant-cell formation caused by herpes simplex infection, may result in incorrect diagnosis of carcinoma of the cervix (Varga and Browell, 1960; Stern and Longo, 1963). The presence of inclusion bodies helps to differentiate these from carcinoma cells or the atypical cells of cervical dysplasia, although erroneous diagnosis of carcinoma can also be made in the preinclusion phase of virus infection. Attention has recently been drawn to differences which appear to exist between strains of herpes simplex virus isolated from the genital tract or nearby areas in adults and strains isolated from areas in other parts of the body (Schneweis, 1962; Munk and Donner, 1963; Hutfield, 1967;

Herpetic infection in adults: Acute gingivostomatitis and associated traumatic herpes☆

Abstract Five cases of acute herpetic gingivostomatitis in adults with associated herpetic lesions of the fingers are reported. The distribution of the finger lesions and their time of onset suggest that they result from salivary contamination of sites of minor trauma. All patients were persistent nail- or cuticle-biters. Further evidence is presented for the increasing susceptibility of adults to primary infection with Herpesvirus hominis .

Effects of the anti-cancer agent etoposide on human herpesvirus 1 replication in vitro

The anti-human herpesvirus type 1 (herpes simplex virus 1; HSV1) activity of etoposide (VP-16-213, a semi-synthetic derivative of epipodophyllotoxin) was investigated in vitro. Etoposide (but not the proprietary solvent in which the compound is usually formulated) demonstrated a significant antiviral action, probably through an effect on virus replication. Etoposide, at 3 micrograms/ml, induced a 50% reduction of HSV1-plaque formation in Vero cells. These findings are considered in the context of the use of etoposide in an in vivo procedure for the diagnosis of herpes encephalitis through virus-specific scintigraphic brain imaging.