BRIEF REPORTS

Neonatal multiple focal clonic since day seven of life. She had been treated with Virus-2 several parenteral antibiotics including aminoglycosides and third generation M.T. Irani cephalosporins with -no significant im- A.R. Singh provement in cerebrospinal fluid (CSF) A.D. Udwadia parameters. On admission to our neona- R.H. Merchant tal nursery, the vital parameters were normal, no mucocutaneous vesicles Of the two virologically distinct were noted, there was mild types of Herpes simplex viruses i.e., types hepatosplenomegaly, fundoscopy re- 1 and 2, -2 [HSV-2] vealed no evidence of chorioretinitis. is the predominant cause of neonatal The multiple focal clonic seizures were , and is almost always acquired difficult to control despite full thera- from an infected maternal genital tract. peutic doses of intravenous pheno- Perinatally transmitted HSV-2 barbitone, phenytoin sodium and in the neonate may have either a local- diazepam. Systemic examination re- ized, disseminated or encephalitic pat- vealed a few crusted skin lesions on the tern of presentation. The encephalitic trunk. Nervous system examination re- from often remain undiagnosed as 40- vealed an increase in the tone of all the 60% of neonates with central nervous extremities and exaggerated deep system infection have no skin lesion at tendon reflexes. Maternal genital tract the time of clinical presentation(l). The showed no herpetic lesions. .V outcome of the disease is largely depen- A non-traumatic lumbar puncture dent on a prompt diagnosis, which is revealed xanthochromic CSF with 2 difficult to make and adequate treat- polymorphonuclear cells, 1155 red ment, which is expensive. We are re- blood cells/cu mm and 1150 mg/dl pro- porting the management of a neonate teins with a normal glucose level. Smear with HSV-2 encephalitis, which to our and culture were negative for bacteria. knowledge has not been documented A hemogram, liver function tests and earlier in Indian pediatric literature. coagulation profile were normal. In Case Report view of a hemorrhagic CSF report, A 21 day term vaginally delivered crusted skin lesions and no response to female neonate with a birth weight of adequate treatment for pyogenic menin- 2700 g was referred as a case of non- gitis, a diagnosis of HSV-2 encephalitis responsive pyogenic meningitis with was entertained. The first electroencephalogram From the Division of , Bai Jerbai (EEG) on admission showed an isoelec- Wadia Hospital for Children, Bombay. tric pattern (Fig. 1). HSV-2 specific se- Reprint requests: Dr. R.H. Merchant, Division of Neonatology, Bai Jerbai Wadia Hospital rum immune titres were as follows; (i) for Children, Parel, Bombay 400 012. HSV-2 IgM of neonate: 1.013 U/ml (pos- Received for publication: June 17, 1994; itive >0.229 U/ml); (ii) HSV-2 IgG of Accepted: August 18,1994 mother: 62.9 U/ml (positive >20 U/ml);

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and (Hi) IgM of mother: 0.249 U/ml Herpes simplex-2 is estimated to be be- (positive >0.208 U/ml). CSF HSV-2 tween 1:2000 to 1:5000 live births(l). immune titres were not available to us. Neonatal herpes infection is classified Radionuclide brain scan and cranial into three categories: (i) Infection local- ultrasonography were normal. Comput- ized to the skin, eye and/or mouth; (ii) ed tomography and magnetic resonance Encephalitis with/without localized imaging could not be performed. muco-cutaneous disease; and (iii) Dis- seminated infection with multiple organ The patient was treated with intrave- involvement including the CNS, lung, nous acyclovir 10 mg/kg/dose as an in- liver, adrenal, skin, eye and mouth. fusion over one hour, three times a day Each of these three presentations has an for 14 days and then maintained on oral almost equal incidence of between 30- acyclovir 30 mg/kg/day for 14 days(2). 35%(3). Localized CNS disease has a Clinically, the crusted lesions healed, mortality of 50%(l). multiple focal seizures ceased and the CSF abnormalities typically consist child accepted breast feeds; however, of xanthochromia, consistent with the the EEC continued to remain isoelectric release of blood into the subarachnoid (Fig. 2). CSF analysis at the end of three space secondary to the necrotizing na- weeks of treatment was normal. ture of the disease, RBCs ranging from 0-500/mm3, moderate pleocytosis(50- Discussion 200 WBCs/mm3), an elevation of pro- According to Western data, the inci- tein levels (60-200 mg/dl) with normal dence of newborn infection due to levels of glucose and cultures which are

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negative, for bacteria(4). This typical pic- ing Stuart medium(8). Facilities for virus ture was present in our case. isolation are not routinely available in The EEG in herpes encephalitis our country. Analysis of IgM spe- shows a diffuse slow wave background cific antibody response is the most rapid with periodic complexes, sharp and and suggested means of establishing the slow waves over the frontal and tempo- infection(9). This antibody appears two ral lobe indicative of the site of cerebral weeks following onset of infection and insult. These findings are only present in persists for 6-12 months. The rarity of 50% of cases(5). A low voltage, flat trac- HSV-2 infection in infants less then 6 ing or isoelectric pattern as seen in our months of age, makes finding of the IgM patient (Figs. 1 & 2), occurs in neonates antibody in this age group highly sug- with severe brain insult, due to hypoxia, gestive of perinatal infection. This diag- intra-ventricular hemorrhage, meningi- nostic facility is available only in a few tis, subdural hemorrhage and profound centres in our country. Newer tech- dysgenetic malformations. This pattern niques for rapid diagnosis of herpes sim- carries a poor prognosis(6,7). plex encephalitis include the nested The most definitive diagnosis of HSV polymerase chain reaction assay of infection entails recovery of the virus CSF(10). Characteristic though not from visible lesions or throat, stool, con- pathognomic features have been junctiva, urine and CSF. However, this described for neonatal herpes simplex requires the specimen to be frozen at virus encephalitis in brain imaging —70°C and shipped in dry ice or to be techniques. On computed tomography, transported in ambient temperatures us- the temporal lobes are most commonly

478 INDIAN VOLUME 32-APRIL 1995 involved, atrophy and periventricular nostic facilities available to us, and the high calcification may be seen. Magnetic mortality and morbidity associated with resonance imaging shows sulcal promi- delay in treatment of herpes encephalitis, nence and ventricular enlargement con- this recommendation is of particular sistent with brain atrophy. Intracerebral significance. calcifications are seen as foci of de- Acknowledgement creased signals and regions of infection We thank Dr. C. Rodriguez from the as increased signals in T2 weighted images(H). Immuno-serology Department, P.D. Hinduja National Hospital and Medical Research Currently the two effective anti-viral Centre for doing the HSV-2 IgG and igM drugs; (adenine arabinoside) tests in this case. and acyclovir (acyloguanosine) are REFERENCES available. Vidarabine was introduced 1. Whitley RJ. Herpes simplex virus in- earlier for the management of neonatal fection. In: Infectious in the herpes, with a significant reduction in Fetus and Newborn . Eds mortality(12). Acyclovir is a selective in- Remington JS, Klein JC. Philadelphia, hibitor of viral replication, has minimal W.B. Saunders Co, 1990, pp 282-305. side-effects, can be administered in rela- 2. Gutman LT, Wilfert CM, Epes S. tively small amounts over small time Herpes simplex virus encephalitis in periods and is the favored drug in treat- children; Analysis of CSF and ment at present. However, studies have progressive neurodevelopmental shown no significant differences in the deterioration. J Infect Dis 1986,154: final outcome with either drug(13). The 415-421. recommended dose of acyclovir is 10 3. Whitley RJ, Corey L, Arvin A. Chang- ing presentation of neonatal herpes mg/kg/q8h with each dose infused simplex virus infection. J Infect Dis over 1 hour and of Vidarabine is 15-30 1988,158:159. mg/kg/day given as an infusion over 4. Ackerman AD, Dean JM. Meningitis 12 hours. Both drugs are given for 10-14 and infectious encephalopathies. In: days(l). Controlled studies have shown Textbook of Pediatric Intensive Care. that antiviral therapy leads to an im- Baltimore, Ed. Rogers MC, Williams pressive reduction in mortality and and Wilkins, 1987, pp 919-923. morbidity. However, non administra- 5. Illis LS, Taylor FM. The electro tion of anti viral therapy or a delay in its encephalogram in herpes simplex institution is associated with a high encephalitis. Lancet 1982,1: 718-726. mortality and complications such as; 6. Lee SI. Electroencephalography in in- microcephaly, hyadranencephaly, pore- fantile and childhood epilepsy. In: Pe- ncephalic cysts, spasticity, chorio- diatric Epileptology-Classification and retinitis, blindness, learning disabilities Management of Seizures in the Child. and seizures(14). Low incidence of side- Eds. Dreifuss FE, London, 1983, pp 33- effects with acyclovir led to the recom- 36. mendation that in highly suggestive sit- 7. Elligson RJ. EEC's of premature and uations a specific diagnosis of herpetic full term newborns. In: Current infection before treatment is no longer Practice of Clinical Electroencepha- required(15). In view of limited diag- lography. Eds. Klass DW, Daly DD,

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New York, Raven Press, 1979, pp 149- 12. Whitley RJ, Nahmias AS, Soong SJ, 177. Galazzo CG, Fleming CL, Alford CA. 8. Rodin P, Hare MJ, Barwell CF, With- Vidarabine therapy in neonatal herpes ers MJ. Transport of herpes simplex simplex virus infection. Pediatrics virus in Stuart's medium. Br J Vener 1983,66:495-501. Dis 1971, 47:198-202. 13. Whitley RJ, Arvin A, Prober C, et al. A 9. Nahmias A, Dowdle W, Josey W. controlled trial comparing vidarabine Newborn with herpes virus with acyclovir in neonatal herpes sim- hominis types 1 and 2. J Pediatr 1969, plex virus infection. N Engl J Med 75:1194-1203. 1991,324:444-449. 10. Aurelius R, Johnson BO, Skoldenberg 14. Cole FS. Viral infections of the fetus B, Stanland A, Fergsen M. Rapid diag- and newborn. In: Schaffer and Averys- nosis of herpes simplex encephalitis Disease of the Newborn. Eds. Tauesch by nested polymerase reaction of CSF. HW, Ballard RA, Avery ME. Philadel- Lancet 1991, 337:189-192. phia, W.B. Saunders Co, 1991, pp 331- 11. Dublin AB, Mirten DF. Computed 349. tomography in the evaluation of herpes simplex encephalitis. Radio 15. Editorial. Herpes simplex encephalitis. logy 1977,125:133-138. Lancet 1986,1:535-536.

Complicated Anophthalmos of an unpaired Sphere and the lateral ventricles are represented by a single mid line cavity. Usually there is an asso- G.S. Bajwa ciated arhinencephaly-absence of olfac- K. Thapar tory bulbs and tracts, cleft lip and A.K. Dhawan microphthalmia or cyclopia. Affected A. Kapoor children rarely survive past infancy(l). Complete failure of development of the primary optic vesicle results in Holoprosencephaly is an early de- anophthalmos(2). Complicated anoph- velopmental defect of the brain in which thalmos is a syndrome comprising of there is a failure to form paired cerebral anophthalmos associated with craniofa- hemispheres. The cerebrum is made up cial malformation, harelip, polydactyly, cardiac malformations and mental retar- From the Departments of Ophthalmology and dation(3). We report a similar case. This Pediatrics, Government Medical College, condition is extremely rare. E.S.I. Hospital and Amritsar Medical Diagnostic Centre, Amritsar. Case Report Reprint requests: Dr. K. Thapar, 9-A, Krishna A 21-day-old infant was admitted Square Phase II, Near Shivala Bhaian, with facial abnormality, small eyes and Amritsar 143 001. inability to open the eyes. The baby was Received for publication: August 18,1992; 3rd in order delivered at term normally. Accepted: September 2,1994 There was a history of antenatal drug

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