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

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

• 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]

  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]

  […] year old gentleman who worked as an electrical engineer and part-time milkman presented to our acute admissions unit with a history of acute onset dizziness associated with fever and nausea, followed by seven days of headache, joint pains and general malaise [priory.com]

  […] in 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]

  […] 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]

• Plethora

  The diagnosis of herpes simplex encephalitis requires a plethora of tests for confirmation. [symptoma.com]

• Anosmia

  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]

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

  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]

• 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]

• 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]

• 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]

• 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]

• 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]

• Auditory Hallucination

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

• 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]

• Headache

  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]

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

• Meningism

  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]

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

  The meninges are the layers of thin tissue that cover your brain. If these tissues become infected, it’s called meningitis. When your brain becomes inflamed or infected, the problem is called encephalitis. [hopkinsmedicine.org]

• Confusion

  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]

  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. [symptoma.com]

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

• Cognitive Impairment

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

  In conclusion, this case of HSE had subacute course with a progressive cognitive impairment which is very atypical. [jmedsoc.org]

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 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]

  Periodic Lateralized Epileptiform Discharges (PLEDS) were present in EEG. Cranial MRI revealed hyperintensities in bilateral frontotemporal area, basal ganglia and brainstem. HSE was confirmed by polymerase chain reaction (PCR). [neurologyindia.com]

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

• PLED Bilaterally

  The EEG findings usually parallel the imaging abnormalities with focal slowing, periodic lateralized discharges (PLEDS), bilateral independent PLEDS (BiPLEDS) and occasionally NCSE [ 5 ]. [omicsonline.org]

• Kluver-Bucy Syndrome

  Keywords: Herpes simplex encephalitis, herpes simplex virus, Kluver-Bucy syndrome How to cite this article: Halder A, Mandal US, Halder S, Biswas A. Kluver-Bucy syndrome: A morbid consequences of post herpes simplex encephalitis. [cjhr.org]

  This patient had Kluver-Bucy Syndrome (hypermetamorphosis, hyperorality, hypersexuality and bulimia). We have observed 2 other similar cases-a consequence of untreated HSE. [neurologyindia.com]

  Other possible clinical features suggestive of HSV encephalitis include headache, urinary and faecal incontinence, and behavioural syndromes including loss of emotional control, hypomania, Kluver-Bucy syndrome, and psychosis. [hindawi.com]

  Behavioral observations were significant for hyperorality and hypersexuality suggesting Kluver-Bucy syndrome. [cureus.com]

  syndrome, 28 but we did not find this pattern in our patients. [jnnp.bmj.com]

• 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. [jamanetwork.com]

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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