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EMERGENCY:Fever + headache + confusion + personality change + seizure = possible herpes encephalitis —call040-46324365immediately — 24 hours, 7 days— 24/7

NEUROINFECTIOUS DISORDERS & COMPLICATIONS

Herpes Simplex Encephalitis in Hyderabad: The Race Against the Clock Where IV Acyclovir Is the Only Drug That Matters

Same-hour MRI brain (temporal lobe FLAIR/SWI), urgent CSF HSV PCR and lymphocytic pleocytosis assessment, EEG for PLEDs, and empirical IV acyclovir 10 mg/kg every 8 hours started before any test result returns — the KIMS HSE protocol at KIMS Neuroscience, Secunderabad, Hyderabad.

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HSE is the most common cause of fatal sporadic (non-epidemic) encephalitis globally, caused by HSV-1 reactivating from the trigeminal ganglion and spreading to the temporal lobes and orbitofrontal cortex via the olfactory pathway. Without treatment, mortality is approximately 70%; with early IV acyclovir, mortality drops to approximately 20–30%. The clinical signature: fever + headache + temporal lobe symptoms (personality change, bizarre behaviour, olfactory hallucinations of smells that are not there) + temporal lobe seizures. MRI shows bilateral asymmetric temporal lobe FLAIR/DWI signal change with haemorrhagic foci. EEG shows periodic lateralised epileptiform discharges (PLEDs) from the temporal lobe. CSF HSV PCR has sensitivity 96% specificity 99%, but can be negative in the first 24–48 hours. At KIMS: IV acyclovir 10mg/kg every 8 hours is started within 30 minutes of assessment in any HSE presentation — before MRI, before LP result, before PCR. The window between normal brain and destroyed temporal lobes is measured in hours, not days.

Acyclovir before test results — the non-negotiable: IV acyclovir 10mg/kg every 8 hours started within 30 minutes of assessment in ANY encephalitis presentation consistent with HSE. Not after MRI. Not after LP result. Not after PCR. Time = brain tissue. This is the most important clinical protocol on the site.
Olfactory hallucinations = HSE specific clue: Smelling things that are not there (burning rubber, chemicals, rotten food) from olfactory cortex destruction. Not all patients have this, but when present it points directly to temporal lobe and HSE. Specifically asked at KIMS in any encephalitis presentation.
PLEDs on EEG = temporal lobe signature: Periodic lateralised epileptiform discharges (PLEDs) arising from the temporal lobe on EEG. Highly characteristic of HSE. Also: temporal lobe FLAIR/DWI high signal on MRI, bilateral but asymmetric.
70% mortality without acyclovir: Without acyclovir: 70% mortality. With early acyclovir: 20–30% mortality. The difference is a single drug started in time. The antidote exists. The window closes. Call 040-46324365.
HSE relapse 5–26% at 1–3 months: After completing 14–21 days of acyclovir, 5–26% of patients relapse. Two mechanisms: true viral relapse (give more acyclovir) or immune-mediated post-infectious encephalitis (give steroids instead). Any neurological deterioration after completing acyclovir: urgent reassessment at KIMS.
Neonatal HSE — HSV-2, different drug dose: HSV-2 from maternal genital herpes during vaginal delivery. Acyclovir 20mg/kg every 8 hours (higher dose than adults) for 21 days IV, then oral suppression for 6 months to reduce neurological sequelae. Joint KIMS neurology + neonatology team.
If test returns negative: Negative CSF HSV PCR in first 24–48 hours does NOT exclude HSE. PCR can be negative early. If HSE remains clinically suspected: continue acyclovir + repeat CSF PCR at 3–7 days.

Fact	Details
Mechanism	HSV-1 reactivates from trigeminal ganglion · Spreads via olfactory pathway to temporal lobes + orbitofrontal cortex · Haemorrhagic necrosis of temporal lobe parenchyma
Clinical signature	Fever + headache + personality/behaviour change + olfactory hallucinations + temporal lobe seizures · Prodrome 1–7 days before neurological features
MRI	Bilateral asymmetric FLAIR/DWI high signal in temporal lobes + insula · Haemorrhagic foci on GRE/SWI · CT brain may be normal in first 48–72 hours
EEG	PLEDs in temporal lobe (periodic lateralised epileptiform discharges) · Characteristic of HSE · Identifies subclinical seizures
CSF	50–500 white cells (lymphocytes) · Raised protein · Red blood cells (haemorrhagic) · HSV PCR: 96% sensitivity, 99% specificity · Can be negative in first 24–48 hours
Treatment	IV acyclovir 10mg/kg every 8 hours · 21 days minimum for adults · Renal function + hydration monitored · Do NOT stop early even if improves rapidly
Relapse	5–26% at 1–3 months after completion · True viral: more acyclovir · Immune-mediated: steroids · All HSE patients followed up at 1, 3, 6 months after completing acyclovir

About This Condition

Herpes Simplex Encephalitis at a Glance

The essential facts that shape how HSE is recognised, triaged, and treated at KIMS — from the temporal-lobe targeting of HSV-1 and the dramatic mortality difference made by early acyclovir, through the distinctive clinical signature, to the KIMS protocol of empirical acyclovir before CSF PCR returns.

What it is

Herpes Simplex Encephalitis (HSE) is inflammation and destruction of the brain parenchyma caused by Herpes Simplex Virus type 1 (HSV-1). It is the most common cause of fatal sporadic (non-epidemic) encephalitis worldwide, responsible for approximately 10–20% of all viral encephalitis cases. HSV-1, the virus that causes cold sores, gains access to the brain from latent infection in the trigeminal ganglion, spreading retrogradely into the temporal lobes and orbitofrontal cortex — the areas of the brain responsible for memory, emotion, behaviour, and language.

Why it is the encephalitis that demands the most urgency

Without treatment, HSE has a mortality of approximately 70% and leaves most survivors with severe neurological disability. With IV acyclovir started early, mortality drops to approximately 20–30%, and a significant proportion of patients achieve good or complete recovery. The difference between a good outcome and death or permanent severe disability in HSE is measured in hours — specifically, how many hours between the first symptoms and the first acyclovir dose.

The clinical hallmarks

HSE has a distinctive clinical signature that KIMS recognises immediately: fever (always), headache (usually severe), temporal lobe symptoms (personality change, unusual behaviour, memory problems, hallucinations — particularly olfactory hallucinations of smells that are not there), and temporal lobe seizures (focal jerking, lip-smacking, eye deviation, followed by generalised seizures). This combination, in a previously well person, is HSE until proven otherwise.

The KIMS protocol

IV acyclovir 10 mg/kg every 8 hours is started empirically in ALL presentations of encephalitis at KIMS — before CSF PCR results are available. The CSF HSV PCR takes 24–48 hours. Starting acyclovir after receiving the result is 24–48 hours too late. Acyclovir is safe, and the cost of an unnecessary 14-day course is trivial compared to preventable death or severe disability.

Emergency

040-46324365

Appointment

040-44885000

About This Condition

The Disease That Destroys Memory in Days

A 45-year-old man in Hyderabad develops a fever on a Tuesday. By Thursday he is behaving very strangely — unable to recognise his wife, smelling things that are not there, saying things that do not make sense. On Friday morning his wife finds him having a generalised seizure. He is brought to KIMS.

The examination finds fever 38.9°C, GCS 13, mild neck stiffness, and aphasia (difficulty finding words). MRI brain at KIMS shows bilateral but asymmetric T2/FLAIR signal change in the temporal lobes and insula, with haemorrhagic foci on gradient echo sequences. The EEG shows periodic lateralised epileptiform discharges (PLEDs) arising from the right temporal lobe. CSF shows 120 white cells (predominantly lymphocytes), glucose 3.2 mmol/L (blood glucose 5.6), protein 1.1 g/L. CSF is sent for HSV PCR immediately.

IV acyclovir 10 mg/kg every 8 hours is started within 30 minutes of the LP. The KIMS team does not wait for the PCR result. The rationale is explicit and documented: the clinical picture, MRI, CSF, and EEG pattern are consistent with HSE. The cost of treating a patient without HSE with acyclovir for 14 days is negligible. The cost of withholding acyclovir from a patient with HSE for 24–48 hours while awaiting PCR is measured in destroyed brain tissue, permanent memory loss, and possible death.

The CSF PCR returns positive for HSV-1 at 36 hours. Acyclovir is continued for 21 days total. At discharge on day 25, the patient is awake and communicating but has a significant anterograde memory deficit — he cannot form new long-term memories. He remembers his wife and children, but cannot recall events that happened more than 20 minutes ago. With HSE, even when treatment succeeds in preventing death, the temporal lobes often sustain permanent damage. The earlier treatment is started, the less damage is sustained.

Suspect HSE? Call Now

Fever + confusion + personality change, or fever + olfactory hallucinations + seizure, is herpes simplex encephalitis until proven otherwise. KIMS Neuroscience starts IV acyclovir within 30 minutes of assessment in any presentation consistent with HSE — before MRI, LP, or PCR results return.

040-44885000Appointment line: 040-44885000

Disease Mechanism

Why HSV Targets the Temporal Lobes

HSV-1 encephalitis has a characteristic anatomical pattern. Understanding why the virus selectively attacks the temporal lobes explains the unique neurological and behavioural symptoms seen in this condition.

HSV-1 establishes latent infection in the trigeminal ganglion after primary infection, which may be asymptomatic or present as a cold sore. Reactivation usually produces recurrent cold sores.

But in a small proportion of people — for reasons not fully understood — HSV-1 travels retrogradely from the trigeminal ganglion into the brain via the olfactory bulb and trigeminal root, gaining direct access to the mesial temporal lobes and orbitofrontal cortex.

Temporal Lobe Involvement

Why temporal lobe damage produces classic HSV symptoms

The temporal lobes are responsible for memory formation through the hippocampus, language processing in the dominant temporal lobe, emotional regulation through the amygdala, and olfaction.

HSV destroys these structures, producing the characteristic clinical picture of memory loss, aphasia, behavioural change, olfactory hallucinations, and temporal lobe seizures.

Orbitofrontal Cortex

Personality and behavioural change in HSV encephalitis

The orbitofrontal cortex regulates social behaviour, impulse control, judgement, and decision-making.

Damage to this region produces personality change, disinhibition, emotional dysregulation, and inappropriate behaviour that is often initially mistaken for a primary psychiatric condition.

Recognising HSE

Clinical Features of Herpes Simplex Encephalitis

HSE has a distinctive clinical signature — a non-specific prodrome, then temporal-lobe personality change, olfactory hallucinations, focal temporal-lobe seizures with PLEDs on EEG, and aphasia and anterograde amnesia from hippocampal damage. Each is specifically asked about and acted on at KIMS.

Prodrome — the 1–7 days before the brain is clearly affected

Non-specific fever, headache, and malaise lasting 1–7 days before the neurological features become obvious. This prodromal period is the golden window — treatment during the prodrome, when the diagnosis is suspected clinically, produces the best outcomes. Unfortunately, the prodrome is non-specific and the diagnosis is rarely made at this stage.

Personality and behavioural change — the temporal lobe signature

Subtle at first: the patient seems “not themselves”, irritable, confused, or unusually quiet. Then more pronounced: agitation, bizarre behaviour, personality change, paranoia, or childlike regression. This behavioural change reflects damage to the orbitofrontal cortex and amygdala. It is often the feature that alerts the family that something is neurologically wrong.

Olfactory hallucinations — the specific clinical clue

Smelling odours that are not present — burning rubber, chemicals, rotten food. This occurs because HSV specifically damages the olfactory cortex in the temporal lobe. Not all patients report this, but when present it is a diagnostically valuable clue pointing directly to temporal lobe involvement and HSE. At KIMS, olfactory hallucinations are specifically asked about in any encephalitis presentation.

Temporal lobe seizures — the neurological emergency

Focal temporal lobe seizures: lip-smacking, chewing or swallowing movements, staring, automatisms (repetitive purposeless movements), memory flashbacks, or déjà vu, followed by post-ictal confusion. These may generalise to tonic-clonic seizures. Status epilepticus occurs in a significant proportion of HSE patients and requires emergency antiseizure medication. The EEG shows PLEDs (periodic lateralised epileptiform discharges) from the temporal lobe — a pattern highly characteristic of HSE.

Aphasia and memory loss — the residual deficits

Damage to the dominant temporal lobe produces aphasia — difficulty understanding or producing language. Damage to the hippocampus produces anterograde amnesia — inability to form new memories, while remote memories may be preserved. These deficits can persist after the acute encephalitis resolves and are the principal source of long-term disability in HSE survivors.

Diagnosis at KIMS

Diagnosis at KIMS — Same-Hour MRI, EEG, CSF HSV PCR, and Acyclovir Started Before Results Return

HSE diagnosis at KIMS combines same-hour MRI brain (temporal-lobe FLAIR/SWI), urgent EEG for PLEDs, lumbar puncture with CSF HSV PCR, and a non-negotiable rule that IV acyclovir is started before any of these results return.

MRI brain — the most important early investigation

MRI brain with gadolinium, specifically: FLAIR and T2 sequences showing high signal (oedema and inflammation) in the temporal lobes and insula, classically bilateral but asymmetric, sparing the basal ganglia (which helps distinguish HSE from JEV). DWI may show restricted diffusion in affected areas. GRE/SWI shows haemorrhagic changes (characteristic of HSE — the virus causes haemorrhagic necrosis). Gadolinium enhancement of the temporal lobe meninges and cortex. CT brain may be normal in the first 48–72 hours; MRI is far more sensitive. At KIMS, MRI is arranged within hours of presentation.

EEG — the temporal lobe electrical signature

EEG is arranged immediately at KIMS in any encephalitis presentation. Periodic lateralised epileptiform discharges (PLEDs) or lateralised rhythmic delta activity (LRDA) arising from the temporal lobe are characteristic of HSE. The EEG also identifies subclinical seizures requiring antiseizure medication. A normal EEG in the first 24 hours does not exclude HSE — EEG should be repeated if clinical suspicion persists.

CSF analysis — lymphocytic pleocytosis + HSV PCR

LP performed after CT has excluded contraindications. CSF typically shows: 50–500 white cells (predominantly lymphocytes; early in the illness there may be PMN predominance); raised protein (0.5–2 g/L); normal or mildly reduced glucose; red blood cells (due to the haemorrhagic nature of HSE — this is an important clue). HSV PCR (CSF): sensitivity approximately 96%, specificity approximately 99%. A negative HSV PCR in the first 24–48 hours of illness does not exclude HSE — the CSF PCR can be negative early. If HSE is clinically suspected and CSF PCR is negative, acyclovir is continued and CSF PCR is repeated at 3–7 days.

Acyclovir started BEFORE results — the KIMS non-negotiable

IV acyclovir 10 mg/kg every 8 hours (adjusted for renal function) is started at KIMS the moment HSE enters the differential diagnosis — not after the MRI, not after the LP result, not after the PCR. Acyclovir is safe. The CSF result takes 24–48 hours. Time is brain. This is the most important single clinical decision in HSE management and the one where delay most consistently produces preventable disability.

Treatment

Management at KIMS — IV Acyclovir, Seizure Control, Selective Steroids, and Post-HSE Neurorehabilitation

IV Acyclovir — Duration, Dose, and Stop Criteria

IV Acyclovir — Duration and Monitoring

Duration: 14 days minimum for immunocompetent adults; 21 days for immunocompromised patients and in severe HSE. Dose: 10 mg/kg every 8 hours IV (total 30 mg/kg/day), infused over 1 hour.

Renal function monitored every 2–3 days — acyclovir is nephrotoxic at inadequate hydration; good IV hydration (at least 1.5–2 litres IV fluid per day) prevents crystallisation in the renal tubules. The acyclovir course should not be shortened even if the patient improves rapidly — premature discontinuation is associated with relapse.

When to stop acyclovir: Acyclovir is stopped only when BOTH of the following criteria are met: (1) CSF HSV PCR is negative on a sample collected at least 14 days into treatment; AND (2) the patient has clinically improved and is neurologically stable. A positive HSV PCR persisting at 14 days requires extension of treatment.

Seizure Management

Seizure Management — Levetiracetam First, Status Pathway, 6–12 Months Maintenance

Levetiracetam IV 500–1,500mg twice daily is first-line for HSE-associated seizures at KIMS. IV lorazepam for acute seizure termination. Valproate IV for ongoing seizure control.

Status epilepticus managed per KIMS protocol (lorazepam → IV valproate or levetiracetam → phenobarbitone → intubation + midazolam infusion if refractory).

Anti-epileptic medication is continued for at least 6–12 months after HSE, as post-herpetic epilepsy is common.

Adjunctive Corticosteroids

Adjunctive Corticosteroids — Considered in Severe Cases

IV dexamethasone may be added in cases with severe cerebral oedema visible on MRI. Evidence is limited but clinical practice at specialist centres supports cautious use in life-threatening brain swelling.

Steroids do not replace acyclovir and are never given instead of acyclovir.

Neurorehabilitation

Neurorehabilitation After HSE

Memory rehabilitation (compensatory strategies, external memory aids), speech-language therapy for aphasia, neuropsychological assessment and cognitive rehabilitation, physiotherapy for any motor deficit, and epilepsy management are coordinated by the KIMS neurorehabilitation team.

Post-HSE memory impairment often improves over 6–12 months with active rehabilitation — the brain is plastic and compensatory reorganisation continues long after the acute illness. At KIMS, every HSE survivor is enrolled in a structured rehabilitation pathway.

Related Conditions

Herpes Simplex Encephalitis belongs to the family of infectious and post-infectious neurological disorders evaluated and managed at KIMS Neuroscience:

Encephalitis Meningitis Neurosyphilis Neuroinfectious Disorders & Complications (Master)

FAQs

Frequently Asked Questions

Absolutely yes — and if you are at KIMS, acyclovir will already have been started. This is one of the clearest situations in all of neurology where empirical treatment before diagnosis is the standard of care. The reasoning: if your husband has herpes encephalitis and acyclovir is not started while waiting 24–48 hours for CSF PCR results, substantial additional brain damage will occur during that window. If he does not have HSE and has been given acyclovir unnecessarily, the drug is safe and the course is finite. The potential harm of the wrong decision (not starting acyclovir) is catastrophic and irreversible. The potential harm of starting acyclovir when it turns out not to be needed is negligible. At KIMS, this protocol is followed without exception. Emergency: 040-46324365.

The memory loss you describe — inability to form new memories (anterograde amnesia) — is the most common and most distressing long-term consequence of herpes encephalitis. It results from damage to the hippocampus in the temporal lobes, which HSV specifically destroys. The degree of recovery depends on how much hippocampal tissue was destroyed and how quickly treatment was started. Recovery from post-HSE memory impairment follows a prolonged course of months to years. Significant improvement is possible, particularly in the first 12 months, as adjacent brain structures compensate and as the patient learns to use external memory strategies. Some patients achieve substantial functional recovery; others have lasting severe amnesia requiring permanent care. At KIMS, neuropsychological assessment is arranged 3–6 months after HSE to define the specific memory profile and guide rehabilitation. Call 040-44885000.

HSV-1, which causes cold sores, infects approximately 70–90% of adults worldwide, most during childhood through contact with saliva or skin. The initial (primary) infection is often completely asymptomatic — many people who carry HSV-1 have never noticed a cold sore. After primary infection, the virus travels to the trigeminal ganglion (a nerve cluster near the brain) where it remains latent (dormant) for life. In most people, periodic reactivation just causes cold sores. In rare cases — for reasons not fully understood — the virus reactivates and travels directly into the brain via the olfactory pathway, causing encephalitis. Having cold sores is not a prerequisite for HSE, and most people who have cold sores never develop HSE.

Yes — HSE relapse occurs in approximately 5–26% of patients, typically 1–3 months after completing the initial treatment course. Relapse can be either a recurrence of viral encephalitis (true relapse) or an immune-mediated post-infectious encephalitis triggered by the initial HSV infection (which responds to steroids rather than acyclovir). Signs of relapse: new or worsening neurological symptoms after initial improvement, new seizures, or psychiatric disturbance. At KIMS, HSE patients are followed up at 1, 3, and 6 months after completing acyclovir, and are advised to return immediately if any new neurological symptoms develop. A low threshold for repeating LP and MRI exists for any deterioration. Oral acyclovir maintenance (400–800mg twice daily) for 3–6 months after IV completion is sometimes considered in patients at higher relapse risk. Please call 040-44885000 if you notice any deterioration after discharge.

Yes — neonatal herpes encephalitis (caused by HSV-2, transmitted from mother to baby during vaginal delivery) is distinct from adult HSE. It is a devastating disease in newborns, causing fever, seizures, and brain damage within the first 2–3 weeks of life. Treatment is IV acyclovir 20 mg/kg every 8 hours for 21 days (a higher dose than in adults). Following the IV course, oral acyclovir suppression for 6 months significantly reduces neurological sequelae and is standard of care at KIMS. Neonatal HSE has a high mortality (approximately 30% even with treatment) and frequent severe neurological sequelae including epilepsy, developmental delay, and cerebral palsy. At KIMS, neonatal HSE is managed jointly by the neurology and neonatology teams. If you are concerned about a newborn with fever and seizures, call 040-46324365 immediately.

Call 040-46324365 right now. Do not wait. The symptoms you describe — fever + confusion + olfactory hallucinations (smelling things that are not there) — are the cardinal features of herpes simplex encephalitis, which destroys the temporal lobes within days without IV antiviral treatment. Olfactory hallucinations (the perception of smells that are not present) occur in HSE because the virus preferentially damages the olfactory and temporal lobe regions. She needs to be at KIMS within the next hour. Do not drive if you are distressed — call an ambulance. IV acyclovir at KIMS will be started within 30 minutes of assessment if the clinical picture supports HSE. The next few hours are the most important of this illness. Call 040-46324365 NOW.

Fever. Confusion. Smelling things that are not there. Personality change. A seizure. Herpes simplex encephalitis destroys the temporal lobes. The antidote is a single drug — IV acyclovir — which must be given now, not after test results.

At KIMS Neuroscience, Secunderabad, Hyderabad, acyclovir is started within 30 minutes of assessment in any presentation consistent with HSE. Emergency: 040-46324365.

040-44885000

International enquiries: info@kimsneurosciences.com