Does herpes simplex virus primarily affect the frontal lobes, establish latency in sensory ganglia causing recurrences, and do HIV infection or pregnancy guarantee vertical transmission of HSV to the newborn within the first two weeks?

HSV Neuroanatomy, Latency, and Vertical Transmission

HSV does NOT primarily affect the frontal lobes—it preferentially targets the temporal lobes and limbic system; the virus establishes latency in sensory ganglia (trigeminal for HSV-1, sacral for HSV-2), not "nerve gain"; and vertical transmission from mother to newborn is NOT guaranteed, with transmission risk ranging from 0-5% for recurrent infections to 30-50% for primary maternal infections.

Neuroanatomical Distribution of HSV Encephalitis

HSV encephalitis predominantly affects the temporal cortex and limbic system, not the frontal region. 1

• The characteristic pattern involves temporal lobe and limbic system involvement, which occurs through viral entry via the trigeminal nerve from oral cavity infections 1
• While the frontal lobes can be affected, this is secondary to the primary temporal-limbic distribution 2
• Brainstem involvement is rare (occurring in only 29% of cases as isolated brainstem disease) and represents an atypical presentation with significantly higher mortality (41%) 2
• The temporal-limbic predilection results from transneuronal spread after trigeminal nerve entry, particularly through the mandibular division that innervates the oral cavity 1

Viral Latency and Recurrence Mechanisms

HSV establishes latency in sensory ganglia—specifically the trigeminal ganglia for HSV-1 and sacral ganglia for HSV-2—where it remains in a non-replicating episomal form in neuronal nuclei. 3, 4

• HSV-1 resides latently in the trigeminal ganglia following primary orolabial infection 4
• HSV-2 establishes latency in the sacral ganglia after genital infection 3, 4
• Recurrences arise from viral reactivation triggered by various stresses, with frequency ranging from once every few years to several times per month 3
• The virus remains in a non-multiplying episomal form in neuronal nuclei during latency periods 3, 4
• Recurrent lesions typically appear at the same anatomical site as the primary infection 3

Recurrence Patterns by Viral Type

• HSV-2 recurs much more frequently in the genital area than HSV-1, which is critical for patient counseling 4
• Genital HSV-1 infections have a more benign natural history with fewer recurrences compared to genital HSV-2 4
• Most genital herpes cases (80-90%) progress subclinically but may become symptomatic at any time 3, 5, 4

Vertical Transmission Risk in Pregnancy

Vertical transmission of HSV from mother to newborn is NOT inevitable and depends critically on maternal antibody status and timing of infection. 3

Transmission Risk Stratification

• Primary maternal HSV infection at delivery carries 30-50% transmission risk 3
• Recurrent maternal infection (reactivation) carries only 0-5% transmission risk 3
• Neonatal HSV infection occurs at a rate of only 1 case per 2,000-5,000 deliveries overall 3

Risk Factors for Transmission

• Genital HSV shedding at the time of delivery significantly increases transmission risk 3
• Prolonged rupture of membranes (>6 hours) increases transmission risk through ascending infection from the cervix 3
• Invasive procedures during labor (such as fetal scalp monitoring) that disrupt fetal skin integrity increase risk 3
• Cesarean delivery substantially lowers transmission risk 3

HIV Coinfection Impact

• HIV-infected women, particularly those with low CD4+ counts, shed HSV from the vulva and cervix more commonly than HIV-uninfected women 3
• Among HIV-uninfected women, only 2-3% shed HSV on the day of delivery despite 25% having reactivation during the last month of pregnancy 3
• In HIV/HSV coinfected women, an estimated 10% have cervical HSV shedding on the day of delivery 3
• The majority of HSV shedding in HIV-infected women is asymptomatic 3

Neonatal HSV Clinical Manifestations

Neonatal HSV disease presents in three distinct patterns, typically appearing at 9-11 days of life, NOT within 1-2 weeks of healing. 3

Disease Categories

• Disseminated multiorgan disease (25% of neonatal cases): Usually appears at age 9-11 days, with encephalitis occurring in 60-75% of these infants 3
• Localized CNS disease (35% of neonatal cases): Presents around 10-11 days of life 3
• Skin, eyes, and mouth disease (40% of neonatal cases): Typically appears at 10-11 days, with vesicular rash present in approximately 80% 3

Important Clinical Pitfalls

• Vesicular rash is present in only approximately 60% of children with CNS or disseminated disease, making diagnosis challenging 3
• Even with treatment, neonates with skin lesions may have cutaneous recurrences during the first 6 months after treatment 3
• Infants remain at risk for neurologic sequelae despite treatment, with the most severe outcomes in those with CNS disease 3
• A limited percentage (2-6%) of infants with localized skin, eye, or mucus membrane disease may develop later neurologic sequelae after apparently successful treatment 3

Incubation Period

The incubation period for both HSV-1 and HSV-2 is typically 2-10 days, with extended periods up to 4 weeks documented. 3, 5, 4

• This standard range applies to both HSV-1 and HSV-2 infections, regardless of infection site (oral or genital) 5
• Individual immune status can significantly impact the incubation period, with immunocompromised patients potentially experiencing altered timelines 5
• The incubation period represents time between exposure and symptom onset, not time to serological conversion 5