Individual neurological complication caused by Herpes simplex viruses in neonates is well-known. We report neonatal Herpes encephalitis that caused multiple neurological complications in the same patient during acute phase of illness. Our patient differs from previously reported cases in the following ways: 1) Late onset neonatal presentation; 2) Development of multiple neurologic complications during acyclovir therapy; 3) Cesarean-section did not prevent perinatal transmission of Herpes simplex virus; and 4) Our patient’s acute hydrocephalus was managed conservatively and he had no reoccurrence of seizure, hydrocephalus, and no motor deficits. A high degree of suspicion, timely needed supportive medical and surgical care, and prompt initiation of intravenous acyclovir offer the best chance for neurological outcome in neonates with Herpes encephalitis.
Clinical signs associated with neonatal herpes simplex viral (HSV) infection are variable and its course tends to be rapidly progressive [
The individual neurological complications in isolation such as intracerebral or intraventricular hematoma, hydrocephalus, ischemic stroke, opsoclonus with and without myoclonus, Wallenberg’s lateral medullary syndrome, acute retinal necrosis, and uncal herniation have been reported in the past [
Authors report late onset neonatal Herpes encephalitis in a single patient who developed multiple neurological complications in acute phase of his illness. Authors provide evidence-based cases review of central nervous system (CNS) complications and outcome in neonates with Herpes encephalitis.
An 8-week-old boy was brought to a tertiary University Children’s Medical Center Emergency Department (ED) for continued fever (39˚C), poor feeding, and being “fussy” for the past five days. His birth history was complicated by early rupture of the membrane and cesarean section (C-section). He had multiple seizures without regaining consciousness. Emergency management of status epilepticus was initiated with intravenous (IV) lorazepam (0.14 mg/kg in two divided doses) and phenobarbital (20 mg/kg). The emergency medical interventions terminated the status. IV ampicillin, cefotaxime, and acyclovir (60 mg/kg/day) were started in the ED. Four days prior to admission, past medical history included inpatient medical care with empirical treatment for bacterial meningitis.
Examination in pediatric intensive care unit revealed a lethargic child with stable vitals. Head circumference was 39 centimeter (50th percentile) and anterior fontanel was open and soft. There were no mucocutaneous lesions. His pupils were equal and reactive to light. The eye movements were in full.
The routine blood tests, serum biochemistry, and coagulation profile, all were normal. Initial brain computerized tomography (CT) demonstrated a normal ventricular size and preservation of white matter-gray matter junction (
On day six, he developed chaotic eyes movements of varying amplitudes (opsoclonus) without facial movements (myoclonus). A stat follow-up brain CT scan revealed hydrocephalus, intraparenchymal and intraventricular hemorrhages. They were monitored clinically with the use of head ultrasound. His hydrocephalus was treated conservatively. A follow up brain CT, two 2 weeks after acyclovir therapy, is shown in
He completed a 21-day course of IV acyclovir therapy. He was discharged on phenobarbital. During the first two years of follow-up, his eye movements returned to normal. There was no reoccurrence of seizure, HSE, or hydrocephalus. He had no motor deficits.
Neonatal Herpes simplex encephalitis (HSE) is most commonly (70%) caused by HSV-2. By contrast, virtually all adults HSE are caused by HSV-1. The fetus acquires HSV-2 infection through shedding of the virus during vaginal delivery [
Like this case, an early diagnosis remains a significant problem. This may relate to the rarity of the condition. Non-specific CSF pleocytosis, the finding suggesting partially treated bacterial meningitis, and a false negative CSF PCR in the early course of the disease may delay the diagnosis [
The pathogenesis of multiple complications, intracerebral and intraventricular hemorrhage and communicating hydrocephalus may have been caused by a combined effect of an initial delay in diagnosis and intracerebral hemorrhage leading to intraventricular hemorrhage. Compromise in cerebro-vascular (arterial and venous circulation) would result in an impedance or inability to absorb CSF efficiently by arachnoid villi at the superior sagittal sinus. Such functional blockage has been reported to occur after intracranial hemorrhage.
Opsoclonus-myoclonus-syndrome is usually associated with diseases of the brainstem and cerebellum. This has been reported, but it is not limited to neuroblastoma, varicella-zoster, West Nile and Enteroviruses in adult and pediatric populations. This is thought to be a result of an autoimmune response directed against cross-reac- tive proteins of offending agents and neuronal cells. The cause of an isolated opsoclonus without myoclonus in our case remains speculative. Contrary to Krolczyk S et al. (2003), description of opsoclonus as a possible early sign of HSV-2 CNS infection, our patient opsoclonus developed during acyclovir therapy [
We performed PubMed online search for English literature for infants and neonatal herpes encephalitis. We used terms “Herpes simplex virus 1 and 2”, “Herpes Encephalitis”, “hydrocephalus”, “CNS complication”, neurological outcome in isolation or combination with either neonate or infant. Bibliography of the reports was searched for additional information.
The results of our search are shown in
Combined CNS complications occurred in 32/48 (67%) neonates. In HSV-1 group, 6 neonates (40%) and HSV-2 group, 26 (79%) had neurological complications. In HSV-1 group; 9 (64%) and in HSV-2 group; 7 (21%) had no neurologic sequelae. No deaths were reported in neonates with HSV-1. Two patients with hypertonicity were excluded in the graph. Neonates with no HSV typing done were excluded from the study.
Why our patient had good neurological outcome despite multiple complications? Probably, this relates to severity of the infection and maturity level of the brain, as our patient presented at age 8 weeks. The literature search revealed age ranges of neonatal Herpes encephalitis between births to a maximum of 26th days.
In conclusion, awareness of these complications together with previously reported entities will allow acting in timely manner. Acute hydrocephalus is a potentially life-threatening and a treatable surgical complication of
Clinical presentation | Antiviral initiation | HSV type | Acute CNS complication | Neurologic outcome [reference] | |
---|---|---|---|---|---|
At birth/boy | Mucocutaneous lesions | 4 days/yes | 2 | NA | Developmental delay, quadriplegia [ |
At birth/boy | Lethargy, mucocutaneous vesicles | 15 days/no | 2 | Necrotizing retinitis | Death-cause was not specified [ |
At birth/girl | Skin lesions and severe jitteriness | NA | 2 | Seizures, apnea, abnormal posture | Died-increased seizures, otherwise cause not specified [ |
At birth/boy | Generalized seizures, Lethargy, Full anterior fontanelle | NA | 2 | Large and tiny hemorrhages in cerebellar hemispheres | Died-supportive care discontinued due to poor prognosis [ |
2 hours/boy | Focal seizures and Apnea | 18 hours/yes | 2 | Encephalomalacia | Died; due to fulminant necrotizing enterocolitis [ |
2 days/boy | Lethargy, Apnea, and hypopnea | 4.5 hours/yes | 2 | NA | No sequelae [ |
7 days/girl | Clonic jerking of right side | 2 days/yes | 1 | Recurrent Obstructive hydrocephalus | Ventriculostomy needed three times [ |
9 days/girl | Vesicles on occipital and parietal scalp | <1 day/yes | 1 | None | No sequelae [ |
9 days/girl | Apnea, bradycardia, and encephalitis | <1 day/yes | 1 | Left parietal Encephalomalacia with hemorrhagic component | Seizures and significant developmental delay [ |
9 days/girl | Seizures | 4 days/yes | 2 | NA | Developmental delay and quadriplegia |
10 days/girl | Pustular rashes over the eyelid and encephalitis | <6 hours/yes | 2 | NA | No sequelae [ |
10 days/girl | Apnea, lethargy, encephalitis | 5 days/yes | 2 | Recurrent Herpes simplex virus encephalitis | Oromotor dysfunction, extensor posturing, and axial hypotonia [ |
13 days/girl | Generalized myoclonic seizures, lethargy | 7 days/yes | 2 | Cerebral malakoplakia | Death-secondary to chronic meningoencephalitis [ |
14 days/girl | Seizures, flaccid paralysis, left ptosis. | 2 days/yes | 2 | Spastic right hemiplegia, chorioretinitis, homonymous hemianopia | Microcephaly, multi-cystic encephalomalacia [ |
15 days/girl | Focal seizures, apneic episodes | 3 days/yes | 2 | Megacystic encephalomalacia, Cortical atrophy and Subdural effusions | Developmental delay, hypertonicity, and microcephaly [ |
15 days/girl | Seizures | <1 day/yes | 1 | NA | Developmental delay, quadriplegia [ |
16 days/girl | Lethargy, Facial diplegia, and Hypotonia | 1 day/yes | 2 | Hypotonia, and Hyperreflexia | Developmental delay, hypertonia, and hyperreflexia [ |
17 days/girl | Focal clonic upper limb seizures | 2 days/yes | 1 | Acute retinal necrosis | Poor vision in the left eye [ |
17 days/girl | Seizures and mucocutaneous lesions | 2 days/yes | 2 | NA | Developmental delay, and quadriplegia [ |
18 days/girl | Seizures | 2 days/yes | 2 | NA | Developmental delay, and quadriplegia [ |
---|---|---|---|---|---|
20 days/girl | Generalized seizures | 7 days/yes | 1 | Oro-glosso-pharyngeal paralysis | Epilepsy, opercular syndrome, and cerebral palsy [ |
20 days/girl | Seizures | 2 days/yes | 2 | NA | Developmental delay, Hemiparetic cerebral palsy [ |
23 days/girl | Generalized seizures | 5 days/yes | 2 | Severe bilateral Encephalomalacia, and chorioretinitis | Severe developmental delay and epilepsy [ |
26 days/girl | Lethargy and opsoclonus | 4 days/yes | 2 | Seizures | No sequelae [ |
1 - 15 days/NA | Lethargy, poor feeding, cutaneous lesions | 3 - 8 days/yes | 1 | Unknown | Eight neonates had no sequelae [ |
15 days/yes | 1 had canalicular and cornealscarring | ||||
1 - 15 days/NA | Lethargy, poor feeding, and cutaneous lesions | NA | 2 | Unknown | One neonate died due to encephalitis [ |
2 - 6 days/yes | Four neonates had no sequelae | ||||
0 - 10 days/yes | Ten neonates with neurologic sequelae are included in the bar graph |
NA, data not available. Foot note: our patient differs from previously reported cases in the following ways: 1) a late neonatal presentation; 2) a C-section did not prevent perinatal transmission; 3) Multiple CNS complications, opsoclonus, intraparenchymal and intraventricular hemorrhage, and acute hydrocephalus in the same patient. Additionally, our case required an emergent neurosurgical intervention. Two neonates, one neonate was diagnosed by positive serology testing [
Graph 1. Is showing neurologic outcome of neonates with combined herpes simplex encephalitis type 1 and 2. Combined CNS complications occurred in 32/48 (67%) neonates. In HSV-1 group, 6 neonates (40%) and HSV-2 group, 26 (79%) had neurologic complications. In HSV-1 group, 9 (64%) and in HSV-2 group; 7 (21%) had no neurologic sequelae. No deaths were reported in neonates with HSV-1. Two patients with hypertonicity were excluded in the graph. Neonates with no HSV typing done were excluded from the study.
Herpes encephalitis. These actions alone may not prevent the CNS complication. For this reason, primary prevention of perinatal transmission of herpes by considering an elective C-section remains important.
A high degree of suspicion, timely needed supportive medical and surgical care, and prompt initiation of intravenous acyclovir offer the best chance to improve morbidity and mortality of neonatal herpes encephalitis.
None.
Surya N. Gupta,Vikash S. Gupta,Nirali Borad, (2015) Late Onset Neonatal Herpes Encephalitis: A Case-Based CNS Complication and Neurological Outcome. Open Access Library Journal,02,1-7. doi: 10.4236/oalib.1101280
CNS: central nervous system;
CSF: cerebrospinal fluid;
CT: computerized tomography.