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Herpes Simplex Encephalitis

Encephalitis Herpes

Herpes simplex encephalitis constitutes an uncommon infectious disease, leading to inflammation of the brain parenchyma, as a result of a herpes simplex virus type I (HSV-I) infection. Rarely, in neonates, the encephalitis is caused by herpes simplex virus type II (HSV-II).


Presentation

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]
  • She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction.[ncbi.nlm.nih.gov]
  • 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 15-mth-old female baby admitted with complaint of fever for 5 days and generalised tonic clonic seizure 10 hours before admission.[ncbi.nlm.nih.gov]
  • We report a 5-year-old girl who presented with fever, drooling, dysphagia, and anarthria. Moreover, voluntary facial movements were disturbed, but the emotional facial movements were completely normal.[ncbi.nlm.nih.gov]
Malingering
  • The patient also showed a typical testing pattern of insufficient effort and possible malingering, which was concerning as she was seeking disability compensation.[ncbi.nlm.nih.gov]
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]
  • Six days postoperatively she developed fever, vomiting and rapid decline in mental status. Brain MRI revealed enhancement of left insular cortex.[ncbi.nlm.nih.gov]
  • 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]
  • 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]
  • 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]
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]
Blepharospasm
  • Blepharospasm occurred in one patient. Five patients had CSF antibodies against NMDA receptor (NMDAR) and 3 against unknown neuronal cell surface proteins.[ncbi.nlm.nih.gov]
Visual Hallucination
  • Although rare, visual impairment can be associated with complex visual hallucinations indicative of Charles Bonnet syndrome.[ncbi.nlm.nih.gov]
  • Delusions of misidentification of staff were present, as were visual hallucinations.[hindawi.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]
  • Herpes simplex virus (HSV) is a common cause of viral encephalitis that can lead to refractory seizures.[ncbi.nlm.nih.gov]
  • The patient's clinical course improved with the resolution of seizures and EEG abnormalities.[ncbi.nlm.nih.gov]
  • Investigations confirmed the diagnosis of herpes simplex encephalitis (HSE) and she responded drastically to acyclovir along with complete control of seizures.[ncbi.nlm.nih.gov]
  • CONCLUSION: Seizure and behavioral abnormality are common features in HSE whereas focal reflex loss is commoner in JE. In a patient with acute encephalitis, thalamic lesion suggests JE and temporal lobe involvement HSE.[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]
  • 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 28 years old female presented with headache, fever, altered sensorium and right side weakness for one week. She was febrile and drowsy with right sided hemiplegia and papilledema.[ncbi.nlm.nih.gov]
  • The second patient, a 53-year-old woman was being treated for HSE; on day 8 after admission a temporal lobe hematoma with midline shift was disclosed due to persistent headache. Both patients survived but were left with sequelae.[ncbi.nlm.nih.gov]
  • […] other causes of headache, altered mental status and seizures such as brain tumors and delirium trmemns.[wikidoc.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]
  • On examination he was overtly confused, scoring 2 out of 10 on an abbreviated mental test score, and was found to be hyperreflexic throughout, with clonus in the lower limbs.[priory.com]
Amnesia
  • In conclusion, the most frequent neurological sequelae were aphasia and amnesia. Disorientation, hyponatremia and abnormalities in initial brain CT were identified as new prognostic factors.[ncbi.nlm.nih.gov]
  • Cognitively, the most common long-term sequela in HSE is anterograde amnesia ( 4 ): the impaired ability to form new episodic memories.[pubs.rsna.org]
  • Long term sequelae of HSE include neuropsychiatric and cognitive defects, including anterograde amnesia, dysnomia, Klüver-Bucy syndrome and epilepsy [ 8 ].[raredisorders.imedpub.com]
  • Severe anterograde and retrograde amnesia, naming deficits, perseverative behaviors and confabulations were observed on neuropsychological assessment. We discussed the concept of long term-working memory based on this evaluation.[ncbi.nlm.nih.gov]
  • There are without doubt more survivors, but many may suffer from permanent neurological and/or psychological deficits, for example amnesia (memory loss). Improvements are still needed to both speed diagnosis and improved treatment.[encephalitis.info]
Stupor
  • We report an unusual presentation of herpes simplex encephalitis, clinically as catatonic stupor and radiologically as isolated symmetrical cerebellar involvement affecting the posterior cerebellum.[ncbi.nlm.nih.gov]
  • Additional symptoms include drowsiness with general weakness (stupor), and confusion or disorientation.[rarediseases.org]
  • PROGNOSTIC FACTORS Development of stupor or coma before acyclovir was started (four of 29 good outcome, nine of 13 poor outcome, P Discussion Our study of the long term outcome after herpes simplex encephalitis differs from most of the other reports on[jnnp.bmj.com]

Workup

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].

Periodic Lateralized Epileptiform Discharges
  • 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]
  • 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]
  • Electroencephalography (EEG) revealed periodic lateralized epileptiform discharges (PLEDS). HSV-2 encephalitis was confirmed by a polymerase chain reaction (PCR) study in CSF.[atmph.org]
  • lateralizing epileptiform discharges from the temporal lobe. 8 For the patient in the present case, results of the CT, MRI, and EEG were all unremarkable.[jaoa.org]
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]
  • 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]

Treatment

  • 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]
  • Although the prognosis for people with HSV encephalitis can be improved by prompt treatment with aciclovir, there are often delays involved in the diagnosis and treatment of the disease.[ncbi.nlm.nih.gov]
  • We recommend early empirical treatment for any patient presenting with post-neurosurgical lymphocytic meningo-encephalitis, and prophylactic antiviral treatment for patients with a history of previous HSVE who will undergo a neurosurgical procedure.[ncbi.nlm.nih.gov]
  • In addition, while barbiturate coma has been studied for treatment of status epilepticus associated with infectious encephalitis, its use for treatment of encephalitis associated intractable intracranial hypertension has not been fully reported.[ncbi.nlm.nih.gov]
  • Treatment with acyclovir is highly effective in this disease. We report the case of a 27-year-old, immunocompetent woman with acyclovir-resistant herpes simplex encephalitis.[ncbi.nlm.nih.gov]

Prognosis

  • Prognosis was poor, with high short-term mortality and severe residual disability in survivors.[ncbi.nlm.nih.gov]
  • Early diagnosis and active treatment of herpes simplex encephalitis is essential for improving prognosis and saving lives.[ncbi.nlm.nih.gov]
  • It might be important as well, to personalize and elongate the treatment in terms of prognosis.[ncbi.nlm.nih.gov]
  • Favorable prognosis was observed in 73% of patients.[ncbi.nlm.nih.gov]
  • Although the prognosis for people with HSV encephalitis can be improved by prompt treatment with aciclovir, there are often delays involved in the diagnosis and treatment of the disease.[ncbi.nlm.nih.gov]

Etiology

  • RESULTS: Of 251 cases of TL encephalitis, 43% had an infectious etiology compared with 16% with a noninfectious etiology.[ncbi.nlm.nih.gov]
  • Infectious etiologies should be carefully investigated in the differential diagnosis of multicystic encephalopathy with mineralization, in particular if multinucleated giant cells are present.[ncbi.nlm.nih.gov]
  • The etiology of abnormal belching is not known. Currently, it is being subsumed under "functional gastroduodenal disorders."[ncbi.nlm.nih.gov]
  • These data identify AD partial TBK1 deficiency as a new genetic etiology of childhood HSE, indicating that TBK1 is essential for the TLR3- and IFN-dependent control of HSV-1 in the CNS.[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]

Epidemiology

  • 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]
  • Epidemiology References: [1] Epidemiological data refers to the US, unless otherwise specified.[amboss.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]
  • In this article, the author reviews the clinical features, pathogenesis, epidemiology, diagnosis, and management of herpes simplex encephalitis.[medlink.com]
  • Summary Epidemiology HSVE accounts for 20 % of encephalitis cases and its annual incidence is 1/250,000-1/500,000 in industrialized nations and is presumed to be the same across the globe.[orpha.net]
Sex distribution
Age distribution

Pathophysiology

  • 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]
  • Current understanding of the pathophysiology of post-herpes simplex virus encephalitis movement disorders proposes 2 possible mechanisms that may be responsible: reinfection with the resumption of viral replication, or a postinfectious, immune-mediated[ncbi.nlm.nih.gov]
  • We suspect that the pathophysiologic mechanisms by which HS virus infects neurons produce a higher likelihood of contracting anti-NMDA receptor antibody encephalitis.[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]

Prevention

  • Decompressive craniectomy prevented imminent brain herniation and a fatal outcome in both of these patients.[ncbi.nlm.nih.gov]
  • Herpes simplex encephalitis is a rare, but severe, cause of the anterior opercular syndrome that demands treatment as soon as possible in order to prevent high morbidity or mortality.[ncbi.nlm.nih.gov]
  • We stress on strict adherence to the standard precautions and preventive control measures.[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]
  • Lobectomy stopped the acute refractory seizures and can be considered a good approach to prevent later epilepsy, with only mild residual cognitive deficits.[ncbi.nlm.nih.gov]

References

Article

  1. Whitley RJ, Soong SJ, Linneman C Jr, et al. Herpes simplex encephalitis. Clinical Assessment. JAMA. 1982 Jan 15; 247(3):317-20.
  2. Whitley RJ, Cobbs CG, Alford CA Jr, et al. Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group. JAMA. 1989 Jul 14; 262(2):234-9.
  3. Tan IL, McArthur JC, Venkatesan A, Nath A. Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised. Neurology. 2012 Nov 20; 79(21):2125-32.
  4. Solomon T, Michael BD, Smith PE, et al. Management of suspected viral encephalitis in adults—Association of British Neurologists and British Infection Association National Guidelines. J Infect. 2012; 64: 347–373.
  5. Kneen R, Michael BD, Menson E, et al. Management of suspected viral encephalitis in children—Association of British Neurologists and British Paediatric Allergy, Immunology and Infection Group National Guidelines. J Infect. 2012; 64: 449–477.
  6. Mook-Kanamori B, van de Beek D, Wijdicks EF. Herpes simplex encephalitis with normal initial cerebrospinal fluid examination. J Am Geriatr Soc. 2009 Aug; 57(8):1514-5.
  7. Chow FC, Glaser CA, Sheriff H, et al. Use of Clinical and Neuroimaging Characteristics to Distinguish Temporal Lobe Herpes Simplex Encephalitis From Its Mimics. Clin Infect Dis. 2015 May 1; 60(9): 1377–1383.
  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

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Last updated: 2019-07-11 20:22