Herpes simplex encephalitis (HSE) is an infectious inflammation of the brain, caused, in adults and adolescents, by the herpes simplex virus type I. It leads to a multitude of neurological symptoms, that can either be generalized or focal.

The symptoms most typically related to HSE include fever, which is present in up to 90% of the patients and cephalalgia [1]. The full course of the clinical symptomatology tends to develop over a period of some days. Convulsions and psychiatric sequelae, such as psychotic incidences and behavioral pattern modifications are also common [1]. Patients may progress to a lethargy, confusion, and delirium. Profound neurological symptomatology also encompasses memory loss, speech impairment or aphasia, anosmia, limb weakness or even hemiparesis. Retinitis may also occur as a result of HSE and meningismus may be observed. The clinical picture in herpes simplex encephalitis infection is extremely broad and there is no pathognomonic clinical finding that can aid towards a precise diagnosis of the disorder [2]. Immunocompromised individuals tend to present with a less typical or less profound set of symptoms as compared to the immunocompetent population [3].

Neonatal herpes simplex encephalitis is usually a result of a herpes simplex type II infection and initial symptoms develop during the first two weeks after birth. The clinical picture includes seizures, loss of appetite, weakness, and lethargy, along with irritability and tremors. Lesions on the skin may also be observed.

• Fever

  Case 2 A 9-year-old male developed fever, headache, seizure and grossly abnormal behavior when he was 7 years old. He was diagnosed as probable Japanese encephalitis (JE) at that time. [neurologyindia.com]

  The clinical picture is often one of spontaneous and rapid developments of fever, headache, confusion, and seizures. Fever and abnormal mental status are the primary signs and symptoms of HSVE, occurring in >90% of patients. [hindawi.com]

  Rickettsial: Rocky Mountain spotted fever, endemic typhus, epidemic typhus, Q fever, human monocytic ehrlichiosis. Fungal: cryptococcosis, coccidiomycosis, histoplasmosis, North American blastomycosis, candidiasis. [patient.info]

  A 30-year-old man was admitted in PGIMER with the complaints of fever, altered sensorium and seizures. [ncbi.nlm.nih.gov]

  The classic symptoms of herpes encephalitis cases at the presentation are consciousness alteration, fever and epileptic seizures. Onset like isolated aphasia and hemiplegia without fever, mimicking stroke, is not a typical presentation. [scitechnol.com]

• Pain

  Orolabial herpes (Figure 1): edema and pain may lead to dysphagia. Genital herpes can be associated with extreme pain, edema, and dysuria. [infectiousdiseaseadvisor.com]

  The typical pain pattern of the virus is caused by increased excitability of central nociceptors in the spinal cord causing inflammation and disruption to the nerve cells, making them more sensitive to painful stimuli.3 VZV can also cause many different [ncbi.nlm.nih.gov]

  Patients may develop painful, severe visual impairment over a few days, or experience an insidious onset with mild visual symptoms such as floaters. [mja.com.au]

  By day three he was feeling much better, although complained of jaw pain, and it was noted that his jaw was not closing properly. His co-ordination was also still mildly impaired with bilateral arm drift on examination. [priory.com]

  Anti-viral or anti-bacterial medicines may be prescribed, along with other medications to relieve the symptoms, such as corticosteroids to reduce inflammation, anti-convulsants, and medications for pain relief. [brainfoundation.org.au]

• Malaise

  Adult: usually HSV-1 Transmission: see herpes simplex virus infections Infectivity: highly contagious References:[2] Pathophysiology Clinical features Prodromal phase Duration: few hours to days Nonspecific symptoms Fever Headache Nausea and vomiting Malaise [amboss.com]

  […] common, and most severe, in children (33% 50y) the classic triad of fever, headache and altered CAUSE HSV-1 encephalitis is more common in adults HSV-2 infection is more common in neonates CLINICAL FEATURES Classic presentation flu-like illness with malaise [lifeinthefastlane.com]

  […] children (33% <20y) and the elderly (50% >50y) the classic triad of fever, headache and altered CAUSE HSV-1 encephalitis is more common in adults HSV-2 infection is more common in neonates CLINICAL FEATURES Classic presentation flu-like illness with malaise [litfl.com]

  Infected patients develop prodromal symptoms, such as malaise, fever, headache, and nausea, followed by the acute or subacute onset of neurological symptoms, which can include lethargy, confusion, and delirium. [hindawi.com]

• High Fever

  An 11 months old girl patient has been brought to our clinic with the complaints of high fever and focal convulsions. Analysis of cerebrospinal fluid (CSF) revealed decreased glucose level and abundant red blood cells, despite it was not traumatic. [pesquisa.bvsalud.org]

  Call your doctor if your child has a high fever, especially if he or she also has a childhood illness (like measles, mumps, or chickenpox) or is recovering from one. [kidshealth.org]

  Symptoms may include a high fever and headache, accompanied by a stiff neck, vomiting, light sensitivity, and convulsions. Patients may also be drowsy, or confused, and difficult to rouse. In babies, there may be a bulge in the fontanelle. [brainfoundation.org.au]

  Any one who experiences a high fever, headache and disorientation should see a doctor, Whitley said: “We know there are other things that cause these symptoms, including some drugs. [nbcnews.com]

  Case 3 A 20-year-old female developed high fever, altered sensorium and seizures 2 days after delivery. She was treated as cortical venous thrombosis with heparin, since she also had coexisting severe deep vein thrombosis of the lower limbs. [neurologyindia.com]

• Anosmia

  Short term memory impairment (70%), anosmia (65%), and dysphasia (41%) were the most common signs. [jnnp.bmj.com]

  Profound neurological symptomatology also encompasses memory loss, speech impairment or aphasia, anosmia, limb weakness or even hemiparesis. Retinitis may also occur as a result of HSE and meningismus may be observed. [symptoma.com]

  After the initial symptoms appear, affected individuals may develop speech abnormalities such as a diminished ability to communicate by speech, writing, and/or signs (aphasia), absence of the sense of smell (anosmia), and memory loss. [rarediseases.org]

• Vomiting

  Abstract A 15-year-old girl was referred to our hospital due to fever, headache, and vomiting of 7 days duration and focal motor convulsion at the day of referral. [ncbi.nlm.nih.gov]

  A 2.5-year-old boy was brought to our emergency department with a 24-h history of fever, vomiting, dysphagia, and brief episodes of teeth-clenching. He was febrile (38.2°C), dysarthric, and drooling, with otherwise normal examination results. [jcm.asm.org]

• Nausea

  The manifestations of HSVE include low-grade pyrexia accompanied by severe headache, nausea, vomiting, and lethargy, followed by neurological features, which may include cognitive dysfunction (confusion, acute memory disturbances and disorientation), [orpha.net]

  […] both HSV-1 and HSV-2 Adult: usually HSV-1 Transmission: see herpes simplex virus infections Infectivity: highly contagious References:[2] Pathophysiology Clinical features Prodromal phase Duration: few hours to days Nonspecific symptoms Fever Headache Nausea [amboss.com]

• Loss of Appetite

  The clinical picture includes seizures, loss of appetite, weakness, and lethargy, along with irritability and tremors. Lesions on the skin may also be observed. [symptoma.com]

  She described a loss of appetite for 6 weeks but had no headache, fever, rash, pleuritic chest pain or shortness of breath suggestive of a lupus flare. Her initial visual acuity was 6/9 in her right eye and “hand movements” in her left eye. [mja.com.au]

  The patient had been previously well, although one week prior he had had flu-like symptoms, including loss of appetite and general myalgia, as well as a swelling on the right side of his neck which had resolved on its own. [casesjournal.biomedcentral.com]

  Patients with primary infection may have a prodrome, which can include symptoms, such as fever, malaise, loss of appetite, and localized pain and/or burning at the site the lesions will occur. [infectiousdiseaseadvisor.com]

• Blurred Vision

  One week following the last fraction of radiotherapy, he presented again with a 5-day history of progressive fatigue, intermittent fevers of up to 101°F, confusion, blurred vision and sharp right-sided headache. [karger.com]

• Diplopia

  Patient A 37-year-old woman was admitted to the hospital with fever, diplopia, left hemiparesis, sensory change in the face and limbs, personality changes, frontal dysexecutive syndrome, and a stiff neck. [jamanetwork.com]

• Skin Lesion

  Figure 1: Herpes skin lesion. [e-ijd.org]

  Skin lesions usually are not found in association with herpes simplex encephalitis. Herpes simplex encephalitis is caused by a virus known as herpes simplex virus (HSV). [rarediseases.org]

• Visual Hallucination

  Although rare, visual impairment can be associated with complex visual hallucinations indicative of Charles Bonnet syndrome. [ncbi.nlm.nih.gov]

  Motor agitation, disorientation, drowsiness, visual hallucinations, and aggressiveness were the most frequent symptoms. Other authors, such as Boyapati et al.13 also described such neuropsychological symptoms as psychosis and delirium. [elsevier.es]

  Delusions of misidentification of staff were present, as were visual hallucinations. [hindawi.com]

  The patient started experiencing a subjective slowing of mentation, visual hallucinations as well as auditory hallucinations. [jmedicalcasereports.com]

• Delusion

  Delusions of misidentification of staff were present, as were visual hallucinations. [hindawi.com]

  On October 14, he became suspicious, had delusion of persecution, and ran around. [dovepress.com]

  […] symptoms: memory impairment (n=31); speech disorders (n=18); cognitive impairment (n=15); disorientation (n=11); focal neurological signs (n=8); dysexecutive syndrome (n=3); disinhibition (n=2); perseveration (n=2); and hallucinations or aggressiveness or delusion [cambridge.org]

• Auditory Hallucination

  The patient started experiencing a subjective slowing of mentation, visual hallucinations as well as auditory hallucinations. [jmedicalcasereports.com]

• Gustatory Hallucination

  In addition, because of the involvement of the frontal and temporal lobes, patients often display bizarre behaviour, personality changes, anosmia, and gustatory hallucinations. [neuropathology-web.org]

• Seizure

  Clinical improvement was clear with prompt recovery and acute control of seizures. The only remaining deficits were mild memory and attention impairments. Seizures did not recur in the next 6 months. [ncbi.nlm.nih.gov]

  There was no seizure, headache or vomiting. The patient was in deep coma with Glasgow coma scale (GCS) of 5. [neurologyindia.com]

  A review of the literature showed that of 65 patients with ictal bradyarrhythmia, 36 had temporal seizures and 15 had frontotemporal seizures [ 13 ]. [casesjournal.biomedcentral.com]

• Headache

  His headache worsened day by day. A day before admission, he noticed involuntary jerks of his left arm with rapid progression to generalized tonic-clonic seizure for approximately 2 minutes. [journals.lww.com]

  On hospital day 3, she had a sudden onset of vomiting and severe headache. Brain CT showed frank temporal lobe hemorrhage. Despite aggressive medical treatment, she became increasingly drowsy. [ncbi.nlm.nih.gov]

  Case Report: A 27-year-old woman with no past medical history presented with altered mental state, headaches, and seizures. She had a nasal dermal filler injection for aesthetic purpose five weeks before her acute presentation. [ukm.pure.elsevier.com]

  […] other causes of headache, altered mental status and seizures such as brain tumors and delirium trmemns. [wikidoc.org]

  Patients with HSE typically present with a prodrome of headaches and fever, followed by sudden focal neurological deficits and altered mental status. [amboss.com]

• Meningism

  The coronal post-gadolinium T1-weighted image on the right shows abnormal meningeal thickening and enhancement, arrowheads. [svuhradiology.ie]

  Mollaret's meningitis Other names Benign recurrent lymphocytic meningitis Meninges of the central nervous system: dura mater, arachnoid, and pia mater. [en.wikipedia.org]

  Meningoencephalitis is an inflammatory process, most often due to viral infection, involving both the brain and meninges. [patient.info]

  Coma HSE may resemble bacterial meningitis, but the combination of altered mental status, seizures, and focal neurological deficits is more common for HSE! [amboss.com]

  There were no signs of meningeal irritation. Patient gradually become unconscious in the next few hours and pupils were constricted bilaterally with development of atonia in all four limbs and neck muscles. Doll's eye phenomenon was absent. [ncbi.nlm.nih.gov]

• Confusion

  These symptoms may include a stiff neck, altered reflexes, confusion, convulsions, and paralysis. [rarediseases.org]

  Most frequent symptoms at admission were fever, confusion, aphasia and seizures. Mortality rate was 11 %. 2 patients presented a clinical relapse. In conclusion, the most frequent neurological sequelae were aphasia and amnesia. [ncbi.nlm.nih.gov]

• Cognitive Impairment

  Despite profound cognitive impairment at their clinical nadir, both patients recovered fully. [ncbi.nlm.nih.gov]

The diagnosis of herpes simplex encephalitis requires a plethora of tests for confirmation. These include a medical history that is expected to be compatible with the main symptoms of the infection, a lumbar puncture to drain cerebrospinal fluid (CSF) for analysis, a CSF polymerase-chain-reaction test (PCR), a brain magnetic resonance imaging scan (MRI) and, possibly, a computed tomography scan (CT) of the brain or brain biopsy [4] [5].

CSF cytology

Cerebrospinal fluid analysis in a case of HSE is expected to display red blood cells and xanthochromia. Pleocytosis, with white blood cell levels of mononuclear type approximately at 10-500 per mL and augmented protein levels at 60-700 mg/dL are also exhibited in a typical analysis. Glucose may be slightly diminished. During the initial phase of the infection, CSF analysis may be normal in a considerable number of patients (app 10-15%) [6]. A viral HSV-II culture is solely possible in neonates.

Imaging modalities

Neuroimaging is widely used to detect brain inflammation in patients with a suspected HSE and, additionally, to differentiate between this disorder and other conditions that could result in the same symptomatology, such as a tumor. MRI scans are substantially preferred to CT scans with reference to the HSE diagnosis since the sensitivity of an MRI scan is superior [7].

PCR

A PCR test, carried out on the CSF sample, can directly detect viral load and greatly accelerate the diagnosis of HSE, both in adults and neonates. With the advent of PCR, the use of brain biopsy has diminished, since PCR constitutes a non-invasive, accurate tool for the detection of herpes simplex encephalitis, whose specificity and sensitivity amount to 98-100% and 94-98% respectively [8] [9].

• Cerebrospinal Fluid Abnormality

  A presumptive diagnosis of herpes simplex encephalitis was made in five patients with distinctive clinical findings and compatible cerebrospinal fluid abnormalities. [jamanetwork.com]

  fluid",[2] cerebrospinal fluid abnormalities may not be detectable for the entire time.[6] Diagnosis can be elusive, as Helbok et al. note: "in reality, many more weeks, even months pass by until the diagnosis is established. [en.wikipedia.org]

• Periodic Lateralized Epileptiform Discharges

  Watemberg and Morton (March 7 issue) describe a case of herpes simplex encephalitis in a 13-year-old boy and present the classic electroencephalographic finding of periodic lateralized epileptiform discharges. 1 Whereas it is gratifying to learn that [nejm.org]

  Electroencephalogram revealed periodic lateralized epileptiform discharges (PLEDS) in the left fronto-temporal lobes. [academic.oup.com]

  In addition, the patient had periodic lateralized epileptiform discharges on electroencephalogram, which supports the diagnosis of herpes encephalitis. [emedicine.medscape.com]

  Typical findings include diffuse slowing, focal temporal changes, periodic complexes, and periodic lateralizing epileptiform discharges (PLEDS). These latter findings are highly suggestive of HSE, in the proper clinical context. [casemed.case.edu]

• Hyponatremia

  Disorientation, hyponatremia and abnormalities in initial brain CT were identified as new prognostic factors. [ncbi.nlm.nih.gov]

  Introduction This report describes a patient with herpes simplex encephalitis who exhibited, during the acute stage of his illness, severe, transient hyponatremia with renal sodium loss presumably induced by inappropriate and excessive production of antidiuretic [jamanetwork.com]

  Laboratory values were only significant for hyponatremia with urine hyperosmolality consistent with syndrome of inappropriate antidiuretic hormone secretion. [karger.com]

  Other Names Learn More: HPO ID 80%-99% of people have these symptoms CSF lymphocytic pleiocytosis 0200149 EEG abnormality 0002353 30%-79% of people have these symptoms Fatigue Tired Tiredness [ more ] 0012378 Fever 0001945 Headache Headaches 0002315 Hyponatremia [rarediseases.info.nih.gov]

• Klüver-Bucy Syndrome

  We treated a patient with relapsing HSE of the contralateral temporal lobe, resulting in Klüver-Bucy syndrome, after a full-dose acyclovir treatment. [ncbi.nlm.nih.gov]

  Long term sequelae of HSE include neuropsychiatric and cognitive defects, including anterograde amnesia, dysnomia, Klüver-Bucy syndrome and epilepsy [8]. [raredisorders.imedpub.com]

  Kluver-Bucy syndrome, hypersexuality, and the law. Neurocase 2010;16:140-5. 12. Stewart JT. Carbamazepine treatment of a patient with Klüver-Bucy syndrome. J Clin Psychiatry 1985;46:496-7. 13. Jha S, Patel R. [cjhr.org]

  An autopsy case of probable herpes simplex encephalitis (HSE) showed the partial Klüver-Bucy syndrome from 1 to 7 months after the onset, which consists of strong oral tendencies, emotional changes and possible hypersexuality. [dict.cnki.net]

• Diffuse Encephalopathy

  Nonetheless, the clinical picture and ancillary diagnostic studies are compatible with a bilateral diffuse encephalopathy involving predominantly hippocampal and adjacent mesial temporal regions.Because of the predilection of herpes simplex encephalitis [jamanetwork.com]

[…] in diagnosis and treatment. [jnnp.bmj.com]

Relapsing herpes simplex encephalitis (HSE) rarely occurs after acyclovir treatment. We treated a patient with relapsing HSE of the contralateral temporal lobe, resulting in Klüver-Bucy syndrome, after a full-dose acyclovir treatment. [ncbi.nlm.nih.gov]

In these cases, it is often appropriate to restart treatment promptly. [encephalitis.info]

Favorable prognosis was observed in 73% of patients. [ncbi.nlm.nih.gov]

Prognosis Encephalitis causes high rates of illness and death. [ 1 ] The prognosis depends on the age of the patient and the underlying aetiology. [patient.info]

RESULTS: Of 251 cases of TL encephalitis, 43% had an infectious etiology compared with 16% with a noninfectious etiology. [ncbi.nlm.nih.gov]

Definition / general Herpes simplex (HSV) encephalitis is a severe necrotizing viral infection preferentially involving the medial temporal and frontal lobes of the brain Epidemiology Most commonly identified etiology of nonepidemic viral encephalitis [pathologyoutlines.com]

Therefore, HSE was not suspected to have a genetic etiology. [anr.fr]

Epidemiology References:[1] Epidemiological data refers to the US, unless otherwise specified. [amboss.com]

METHODS: Epidemiological study: we used the hospital medical and administrative discharge database to identify hospital stays, deaths and ICU admissions relating to HSE in 39 hospitals, from 2010 to 2013. [ncbi.nlm.nih.gov]

PMSI is becoming a useful and powerful epidemiologic tool [21–23]. [ccforum.biomedcentral.com]

In conclusion, this was the first epidemiological surveillance of herpes encephalitis in Cordoba. The findings contribute to understand the epidemiology of encephalitis and the clinical management of patients. [scielo.org.co]

Viral aetiology and clinico-epidemiological features of acute encephalitis syndrome in eastern India. Epidemiology and Infection 2014; 142: 2514–2512. 12. Ghannad, MS, et al. Herpes simplex virus encephalitis in Hamadan, Iran. [cambridge.org]

The postoperative viral pathophysiology remains a subject of debate. The rate of adverse outcome is high and early antiviral treatment seems to be a strong predictor of clinical outcome. [ncbi.nlm.nih.gov]

However its pathophysiology remains largely unknown and its poor prognosis is in contrast with the usually good tolerance of most clinical herpetic manifestations. [eurekaselect.com]

Etiology Pathogen: herpes simplex virus Neonates: both HSV-1 and HSV-2 Adult: usually HSV-1 Transmission: see herpes simplex virus infections Infectivity: highly contagious References:[2] Pathophysiology Clinical features Prodromal phase Duration: few [amboss.com]

Decompressive craniectomy prevented imminent brain herniation and a fatal outcome in both of these patients. [ncbi.nlm.nih.gov]

Can herpes meningoencephalitis be prevented? Avoiding herpes virus infections in the first place can help you prevent herpes meningoencephalitis. [hopkinsmedicine.org]

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8. Cinque P, Cleator GM, Weber T, et al. The role of laboratory investigation in the diagnosis and management of patients with suspected herpes simplex encephalitis: a consensus report. The EU Concerted Action on Virus Meningitis and Encephalitis. J Neurol Neurosurg Psychiatry. 1996 Oct; 61(4):339-45
9. Schloss L, Falk KI, Skoog E, et al. Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real-time PCR in patients with herpes simplex encephalitis. J Med Virol. 2009 Aug; 81(8):1432-7