1989 - Diseases Which Mimic HSE

Subject
Diseases Which Mimic HSE 
 

Authors
Whitley RJ. Cobbs CG. Alford CA Jr. Soong SJ. Hirsch MS. Connor JD. Corey L. Hanley DF. Levin M. Powell DA.

Source
JAMA. 262(2):234-9, 1989 Jul 14.



Abstract 
A total of 432 patients underwent brain biopsy for presumptive herpes simplex encephalitis. Three patient groups were identified. The first group, 195 patients (45%), had herpes simplex encephalitis confirmed by the isolation of herpes simplex virus from brain tissue at biopsy (193 patients) or autopsy (2 patients). The second group, 95 patients (22%), had diseases that were identified but that were not caused by herpes simplex virus. Three subgroups were recognized: (1) 38 patients (9%) with treatable disease, (2) 40 patients (9%) with nontreatable but diagnosed viral infection, and (3) 17 patients (4%) with identified diseases neither of viral etiology nor treatable. The third group, 142 patients (33%), remained without a diagnosis. Clinical presentation of patients in the second group was similar to that of those with herpes simplex encephalitis and those without a diagnosis. Patients in the subgroup with nontreatable but diagnosed viral infections had the greatest likelihood of returning to normal.

1986 - Acyclovir Therapy of HSE

Subject
Acyclovir Therapy of HSE
 

Authors
Whitley RJ. Alford CA. Hirsch MS. Schooley RT. Luby JP. Aoki FY. Hanley D. Nahmias AJ. Soong SJ.

Source
New England Journal of Medicine. 314(3):144-9, 1986 Jan 16.

Abstract 
We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.

1982 - Prevention of Complications of Herpes Zoster

Subject
Prevention of Complications of Herpes Zoster
 

Authors
Whitley RJ. Soong SJ. Dolin R. Betts R. Linnemann C Jr. Alford CA Jr.

Source
New England Journal of Medicine. 307(16):971-5, 1982 Oct 14.

Abstract
We conducted a double-blind, placebo-controlled trial to assess the value of vidarabine therapy for the prevention of complications from herpes zoster in immunocompromised patients. Of 121 patients with localized herpes zoster of 72 hours duration or less, 63 received vidarabine and 58 received the placebo. Populations were matched for pertinent characteristics. Therapy accelerated cutaneous healing and decreased the rates of cutaneous dissemination (from 24 per cent [14 patients] to 8 per cent [5 patients]) (P = 0.014); and of zoster-related visceral complications (from 19 per cent [11 patients] to 5 per cent [3 patients]) (P = 0.015). therapy also decreased the total duration of post-herpetic neuralgia (P = 0.047). Patients with lymphoproliferative cancers and those 38 years of age or older were at greatest risk for complications and benefited most from therapy. There was no serious drug toxicity. We conclude that vidarabine therapy, when started within the first three days, is valuable for the reduction of complications related to herpes zoster.

1982 - Therapy of Chickenpox in Immune Compromised Children

Subject
Therapy of Chickenpox in Immune Compromised Children
 

Authors
Whitley R. Hilty M. Haynes R. Bryson Y. Connor JD. Soong SJ. Alford CA.
 

Source
Journal of Pediatrics. 101(1):125-31, 1982 Jul.

Abstract
In order to assess further the clinical usefulness of vidarabine therapy of chicken pox, a double-blind, placebo-controlled trial was performed in immunocompromised patients. Thirty-four patients entered the trial; 19 received vidarabine and 15 the placebo. All patients had disease less than or equal to 72 hours in duration and 23 had lymphoproliferative malignancies. Both patient populations were balanced for underlying disease, preceding chemotherapy, and duration of chicken pox. No patient received zoster immune globulin. Drug therapy accelerated cessation of new vesicle formation (P = 0.015) and decreased median daily lesion counts (P = 0.06 on days 2 and 3). Fever (greater than or equal to 37.8 degrees C orally) resolved more rapidly in the drug-treated group. By day five, 70% of drug-treated subjects were afebrile in contrast to 35% of placebo recipients (P = 0.066). One drug recipient developed mild pneumonitis during the study which resolved with therapy, whereas eight placebo recipients developed varicella-related complications which led to death in two patients (P less than 0.01). These results were achieved with minimal evidence of laboratory or clinical toxicity related to drug administration. The findings indicate that vidarabine has a good therapeutic index (efficacy/toxicity) for treatment of chicken pox in immunocompromised patients when given early in the course of the infection.

1982- Diagnosis of HSE

Subject
Diagnosis of HSE
 

Authors
Whitley RJ. Soong SJ. Linneman C Jr. Liu C. Pazin G. Alford CA.

Source
JAMA. 247(3):317-20, 1982 Jan 15.

Abstract
Continuing evaluations of antiviral agents for treatment of herpes simplex encephalitis (HSE) provided an opportunity to collect clinical data from 113 patients in whom the diagnosis was proved by viral isolation. Occurrence of HSE was in all ages and in both sexes and was nonseasonal. Characteristically, patients had behavioral changes, fever, confusion, speech disturbances, and, less frequently, seizures. The EEG was the most useful neurodiagnostic aid followed by technetium and computed axial tomographic scans. Employing a logistic regression model for variable selection, the diagnosis could be predicted by clinical findings and neurodiagnostic tests in 83% of the proved cases, but the evidence in 25% was falsely positive. There was evidence of localization by either clinical or neurodiagnostic assessment in all patients with proved disease. Among patients with negative findings for HSE, similar focal findings predominated in all but a few. The CSF and brain scans were normal in many patients with proved HSE. This extensive clinical experience in patients with diagnosis proved by viral isolation shows that diagnosis can be confirmed only by brain biopsy.

1981 - Therapy of HSE

Subject
Therapy of HSE


Authors
Whitley RJ. Soong SJ. Hirsch MS. Karchmer AW. Dolin R. Galasso G. Dunnick JK. Alford CA.

Source
New England Journal of Medicine. 304(6):313-8, 1981 Feb 5.

Abstract
To learn more about the treatment of herpes simplex encephalitis with vidarabine, we conducted an uncontrolled study of 132 patients referred to 22 hospitals because of suspected disease. All had a brain biopsy and were started on vidarabine, but only 75 were diagnosed by isolation of virus from a brain-biopsy specimen. Cumulative mortality in the latter group was 39 per cent at one year. Other than therapy, levels of consciousness and age were the major variables that influenced outcome. Of 23 patients under 30 years of age who were lethargic at the initiation of therapy, two died and 16 returned to normal. Of 26 patients over 30 years of age who were lethargic at the outset, nine died and 10 returned to normal. Semicoma and coma were associated with worse outcomes, especially in older patients. Our data suggest that outcome is improved with treatment; they provide more support for the use of brain biopsy to diagnose the infection and indicate a need for better therapy.

1980- Vira-A Therapy of Neonatal HSV

Subject
Vira-A Therapy of Neonatal HSV


Authors
Whitley RJ. Nahmias AJ. Soong SJ. Galasso GG.
Fleming CL. Alford CA.

Source
Pediatrics. 66(4):495-501, 1980 October

Abstract
Vidarabine (adenine arabinoside) was evaluated for treatment of neonatal herpes simplex virus infection in a randomized controlled study. Of 56 infected newborns, 13 had infection of skin, eye, or mouth only, 16 had localized brain disease (CNS), and 27 had disseminated disease. Both treatment and placebo groups were comparable by disease distribution and for major population characteristics. Because of the severity of CNS and disseminated disease, these groups were combined for mortality assessment. Mortality was significantly reduced in babies with CNS and disseminated disease from 74% to 38% with drug therapy, P = .014. Outcome in babies with disseminated disease alone, although improved, was poor. Death rate was reduced from 85% to 57% with therapy. Only 14% of drug and 8% of placebo recipients were assessed as normal at 1 year of age. Outcome was better with localized CNS disease; mortality was reduced from 50% to 10%. With treatment, 50% of infected newborns were normal and without only 17%. With skin, eye, or mouth infection death did not occur; however, severe sequelae occurred in 38% of placebo and minor sequelae in 25% of drug recipients. No evidence of acute toxicity was identified in this study. Thus, a beneficial effect of vidarabine therapy on neonatal herpes simplex infection is similar to that evident with therapy of herpes simplex encephalitis occurring in older individuals. Nevertheless, improvement in the mode of therapy or the development of more potent antiviral drugs is essential.