The hallmark of encephalitis, regardless of the cause, is the triad of a headache, vomiting, and fever and is seen in herpes zoster encephalitis as well. Altered consciousness is also a frequent finding, while seizures have been reported to occur in approximately 30-50% of cases [1]. Various neurological deficits may be present, including dementia [11]. Symptoms may be associated with the development of typical rash (shingles) and appear before the onset, during, or after, but numerous cases without an association between the two have been established. [4]. The onset may be either abrupt or gradual.

• Fever

  The hallmark of encephalitis, regardless of the cause, is the triad of a headache, vomiting, and fever and is seen in herpes zoster encephalitis as well. [symptoma.com]

  Clinical manifestations include rash, fever and altered mental status that can arise before, during or up to 6 months after the onset of skin lesions [ 2 ]. [academic.oup.com]

  Hayes Emerging infectious diseases 2009 Zika virus (ZIKV) is a flavivirus related to yellow fever, dengue, West Nile, and Japanese encephalitis viruses. In 2007 ZIKV… (More) [semanticscholar.org]

• Pain

  Sometimes there is pain without rash —herpes zoster "sine eruptione"—or rash without pain, most often in children. Pain and general symptoms subside gradually as the eruption disappears. [dermnetnz.org]

  Postherpetic pain may take several forms, including allodynia (nonpainful stimulus perceived as painful), hyperpathia (slightly painful stimulus perceived as very painful), and dysesthesia (abnormal sensation with no stimuli). 8 Women are at greater risk [aafp.org]

  Enlarged and painful lymph glands : Glands in the neck, under the arms, or in the groin can become enlarged or painful when you have an active herpes infection. [verywell.com]

  They may include: Pain, swelling, or redness where the shot was given Headache Feeling tired Muscle pain Shivering Fever Stomach pain or upset stomach Serious side effects from the shingles vaccine are very rare. [vaccines.gov]

  Pain medicine may also help with pain caused by shingles. Call your provider as soon as possible to discuss treatment options. Does past infection make a person immune? Usually. [health.ny.gov]

• Chills

  You may also feel: A tingling feeling in or under your skin Fever, chills, and headache An upset stomach The rash eventually turns into painful, red, fluid-filled blisters. They should begin to dry out and crust over within 7 to 10 days. [webmd.com]

  Symptoms of shingles include: A painful rash and blisters on 1 side of the face or body Fever Headache Chills Upset stomach Shingles can’t spread from person to person like chickenpox. [vaccines.gov]

  Other symptoms of shingles can include fever, headache, chills, and upset stomach. How soon do symptoms appear? The virus lies dormant in someone who has had chickenpox in the past. It can reactivate many years later. [health.ny.gov]

  Flu-like symptoms: The person may get a fever, headache, chills or upset stomach with the rash. The chest (thoracic), neck (cervical), forehead (ophthalmic) and lumbar or sacral sensory nerve supply regions are most commonly affected at all ages. [healthjade.net]

• High Fever

  Typical presentation includes the classical triad of a headache, vomiting and high fever that is often accompanied by altered consciousness, while seizures may be present as well. [symptoma.com]

  It causes cyclic outbreaks and nosocomial infections every 2-3 years, characterized by high fever, irritability, and seizures. There is no CSF pleiocytosis, and PCR is required for diagnosis. [neuropathology-web.org]

• Infectious Mononucleosis

  These include the Epstein-Barr virus, which commonly causes infectious mononucleosis, and the varicella-zoster virus, which commonly causes chickenpox and shingles. Enteroviruses. [mayoclinic.org]

  Baumgarten E et al. (1994) Life-threatening infectious mononucleosis: is it correlated with virus-induced T cell proliferation? Clin Infect Dis 19 : 152–156 61. [nature.com]

• Neck Pain

  Three days after the outbreak of the rash, he developed headache, neck pain, and fever, followed by confusion, memory impairment, and drowsiness with episodes of agitation and restlessness. [journals.lww.com]

• Eruptions

  Abstract Two elderly female patients developed symptoms and signs of encephalitis, coincident with a cutaneous zoster eruption ("shingles"). One recovered slowly with mild residual motor dysfunction, and the other died. [ncbi.nlm.nih.gov]

  Upon examination, the child was found to have a zosteriform radicular pattern of skin eruption corresponding to dermatomes C6, C7, and C8. The eruption was patchy, flat, nonblistering, and eczematous. [bcmj.org]

  It is followed by a vesicular eruption of the epithelium of the forehead, the nose, eyelids and sometimes the cornea. The vesicles rupture leaving haemorrhagic areas that heal in several weeks. [medical-dictionary.thefreedictionary.com]

  New lesions continue to erupt for several days within the distribution of the affected nerve, each blistering or becoming pustular then crusting over. [dermnetnz.org]

• Skin Rash

  The other 38-year-old patient developed neuroleukemia and VZV encephalitis without skin rash after completion of induction chemotherapy. In both patients the diagnosis was confirmed by polymerase chain reaction (PCR) for VZV DNA in serum and liquor. [em-consulte.com]

  Most recently, the entity of neurological complications of VZV reactivation, in absence of a skin rash has been recognized. [austinpublishinggroup.com]

  Shingles, also called herpes zoster or zoster, is a painful skin rash caused by the varicella-zoster virus, the same virus that causes chickenpox. After a person recovers from chickenpox, the virus remains inactive in the body. [health.ny.gov]

  A detailed physical examination, including full skin inspection to look for rash and meningeal signs, should be performed, whereas confirmation of herpes zoster encephalitis as the causative agent is made through CSF studies. [symptoma.com]

• Insect Bite

  For example: A history of recent foreign travel, contact with animals, insect bites, immune status and occupation may all give a clue to the infecting organism. Chickenpox encephalitis often has cerebellar involvement. [patient.info]

  Viruses enter the body via the respiratory tract (mumps, measles), gastrointestinal tract (enteroviruses), by inoculation from insect bites (arthropod-borne viruses), and from animal bites (rabies). Most viruses reach the CNS via the bloodstream. [neuropathology-web.org]

  There are several causes, including viral infection, autoimmune inflammation, bacterial infection, insect bites and others. When inflammation is caused by an infection in the brain, it's known as infectious encephalitis. [mayoclinic.org]

• Skin Disease

  Treatment of skin disease comprehensive therapeutic strategies. Saunders-Elsevier. 2010. pp. 340-42. (This book evaluates the evidence for treatments for many different diseases of the skin. [infectiousdiseaseadvisor.com]

• Confusion

  The main neu- suggest impaired visuoconstructive Florian Masuhr rological symptoms were confusion abilities, but statistical interpreta- Eva Schielke and somnolence as well as focal tion must be with caution owing to signs including hemihypaesthesia, [deepdyve.com]

  On the second day following intravenous acyclovir discontinuation confusion, cerebelar ataxia somnolescence and VZV encephalitis was diagnosed. [em-consulte.com]

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

  The patient was confused, but there were no focal deficits on neurologic examination. Figure 1: Photograph showing dermatomal maculopapular rash in the V1 distribution on the face of a 56-year-old woman. [cmaj.ca]

  Electroencephalography helps to identify nonconvulsive seizure activity in confused, obtunded or comatose patients [ 3 ]. Herpes zoster encephalitis is characterized by rash, fever and altered mental status. [academic.oup.com]

• Stroke

  […] deficits seen not only in prototypical neurodegenerative cognitive disorders (Alzheimer's disease, frontotemporal dementias, Huntington's disease, prionoses), but also in other common neurological disorders which may be complicated by cognitive impairment (stroke [books.google.com]

  Atypical stroke-like presentation of HSV encephalitis has been described as well and the clinicians should be aware that HSV encephalitis can mimic a stroke. [5] Pathophysiology [ edit ] HSE is thought to be caused by the transmission of virus from a [en.wikipedia.org]

  CT scan: Can help to rule out space-occupying lesions, strokes and basilar fractures of the skull and to detect CSF leaks to localise fracture sites. [patient.info]

• Encephalopathy

  The clinical appearance of an encephalopathy complicating herpes zoster may not be widely appreciated, particularly in view of the rare occurrence of such a complication. [annals.org]

  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]

  Herpes zoster encephalopathy or acyclovir neurotoxicity: a management dilemma Summary This is a case report of a 69-year-old morbidly obese woman who presented with mental status changes after she was treated with acyclovir for shingles. [casereports.bmj.com]

  After developing encephalopathy, tachypnea, and respiratory distress, the patient was admitted to the pediatric intensive care unit on day 13 and remained in the hospital for more than a month. [contagionlive.com]

• Rabies

  Since 2003, US Department of Agriculture's Wildlife Services has instituted a multistate oral rabies vaccination (ORV) program using bait containing vaccinia rabies glycoprotein recombinant virus vaccine. [pediatricneurologybriefs.com]

  PCR analysis of the CSF can be useful to diagnose several viral infections, including herpes simplex, Epstein-Barr, varicella-zoster, CMV, HIV, rabies and TB. FBC and film: leukocytosis. [patient.info]

  […] which cause cold sores (this is the most common cause of encephalitis) the varicella zoster virus, which causes chickenpox and shingles measles, mumps and rubella viruses viruses spread by animals, such as tick-borne encephalitis, Japanese encephalitis, rabies [nhs.uk]

  Rabies virus. Infection with the rabies virus, which is usually transmitted by a bite from an infected animal, causes a rapid progression to encephalitis once symptoms begin. Rabies is a rare cause of encephalitis in the United States. [mayoclinic.org]

• Neck Stiffness

  If you have viral meningitis, symptoms may include fever, light sensitivity, headache, and a stiff neck. [hopkinsmedicine.org]

  She later developed headache, photophobia, vertigo, diplopia and neck stiffness prompting admission to a local hospital. [austinpublishinggroup.com]

  Physical examination revealed no neck stiffness, meningism or focal signs. Blood tests showed hypoalbuminaemia and lymphopenia. [academic.oup.com]

The appearance of typical symptoms and a properly obtained patient history can easily point to CNS infection and in the setting of altered consciousness, encephalitis is most likely the diagnosis. A detailed physical examination, including full skin inspection to look for rash and meningeal signs, should be performed, whereas confirmation of herpes zoster encephalitis as the causative agent is made through CSF studies. A lumbar puncture should be performed in all patients with suspected CNS infection, followed by evaluation of protein, glucose and cellular content. Glucose levels are usually normal (distinguishing from bacterial pathogens, in which glucose levels are substantially decreased), proteins can be mildly elevated and an elevated opening pressure is often observed [1]. Microbiological investigations comprise serology for anti-VZV IgG and IgM antibodies, but PCR is the gold standard. If VZV DNA is identified through PCR, the diagnosis can be made firmly. Imaging studies may also be useful in the diagnostic workup, such as brain magnetic resonance imaging (MRI) [12].

There are no specific guidelines for treatment of herpes zoster encephalitis and therapy is given according to recommendations for herpes simplex encephalitis [12]. Hence, acyclovir is the first-line antiviral drug that belongs to the group of nucleoside analogs and is used as an intravenous infusion of 10 mg/kg over 1 hour q8h for 2-3 weeks, while pediatric doses reach 20 mg/kg [13]. The growing issue of antimicrobial resistance has included antiviral agents as well and studies conducted more than 20 years ago showed a resistance of VZV to acyclovir [14]. But for now, acyclovir proves to be the most effective drug for treating this condition. Supportive therapy consisting of adequate oxygenation, fever and blood pressure correction, as well as management of seizures is frequently necessary.

Mortality rates from herpes zoster encephalitis have drastically improved during the last few decades with the advent of antiviral therapy, but fatal outcomes may still be seen. Usually, 5-10% of cases end in death, but a significant number of patients (10-20%) develop neurological sequelae that may be long-term [1]. For these reasons, early initiation of treatment is detrimental in minimizing the risk of complications.

Varicella zoster virus (VZV) belongs to the groups of human herpes viruses and since its confirmation in the 1950s [6], much has been revealed in regard to its mechanism of disease and morphology. VZV is an enveloped, double-stranded DNA virus that binds to mucocutaneous and T cells in the human host, with the primary site of infection being the respiratory tract [2]. VZV is the cause of chickenpox (varicella) and after its resolution, the virus establishes a latent infection in the sensory ganglia and reactivates in some individuals to cause shingles (herpes zoster). In rare cases, however, encephalitis may develop and cause a life-threatening CNS infection, either during primary infection or during reactivation of the virus from sensory ganglia.

Humans are the only reservoir for VZV and the infection is spread from carrier hosts to seronegative individuals by either respiratory route or direct contact [7]. Moreover, approximately 90% of the population in developed countries are projected to have anti-VZV antibodies [2]. Studies estimate that complications of the CNS, mainly encephalitis, occur in approximately 1-2 per 10,000 cases of active VZV infection [1], with the most significant risk factor being underlying immunosuppression. HIV, in most cases, is the reason for weakened immune defenses, but hereditary T-cell diseases and organ transplantation are associated with herpes zoster encephalitis as well [8]. In addition to immunosuppression, older age is also shown to be a risk factor for complications of VZV infection [9]. Herpes zoster is an important cause of encephalitis and is projected as the causative agent of 5-15% of all encephalitis cases [10].

The pathogenesis of herpes zoster infections starts with a human-to-human transmission of the virus and initial replication in the nasopharynx, specifically the tonsils and the mucosal cells of upper respiratory tract [2]. Cell-to-cell replication eventually results in shedding into the circulation through hematogenous and lymphatic routes, followed by virus invasion of T cells for which they express high affinity and are able to evade cell-mediated killing. Usually, the virus travels inside T cells that reach the skin and causes varicella. Once the primary infection is established, the virus travels through the nervous system into the sensory ganglia, where it remains dormant for decades in most cases. Although immunosuppression is shown to be a potent factor for reactivation of the virus, immunocompetent patients have been observed, which assumes other factors in the mechanism of reactivation. Nevertheless, the virus is able to gain entry into the CNS and cause encephalitis during either episode.

Transfer of VZV to seronegative individuals can be achieved by avoiding contact with persons during active infection, as the virus is shed through respiratory routes, but also through the skin that is affected by a rash. However, a key step in prevention may be the widespread introduction of varicella vaccine. It is hypothesized that it should be added into the measles-mumps-rubella (MMR) combination and progress toward this effective immunization have been made in various countries over the world [5].

Encephalitis is one of the most severe complications of Varicella zoster virus (VZV) infection and is established to develop in approximately 1-2 cases per 10,000 VZV infections [1]. Together with herpes simplex viruses (HSV) 1 and 2, it belongs to the alphavirus family of human herpesviruses [2]. VZV is the causative agent of varicella (chicken pox), a primary infection by the viral pathogen, after which a latent infection in the sensory ganglia occurs [2]. Upon reactivation, which is most often seen in immunosuppression but in other pathogenic mechanisms as well, the virus causes herpes zoster (shingles), a typical skin rash along one specific dermatome, but in rare cases, a range of other manifestations may occur, one of them being encephalitis. Some reports, on the other hand, describe herpes zoster encephalitis in primary VZV infection [3], implying that this condition may develop in both primary infection and during reactivation. This form of encephalitis is most commonly seen in patients that have human immunodeficiency virus (HIV) infection and symptoms may appear before, during or after the appearance of rash [1]. However, some studies report that shingles may not be necessarily present [4]. Typical presentation includes the classical triad of a headache, vomiting and high fever that is often accompanied by altered consciousness, while seizures may be present as well. To make the diagnosis of herpes zoster encephalitis, a prompt lumbar puncture and subsequent cerebrospinal fluid (CSF) analysis is necessary. Evaluation of proteins, glucose and cellular content in the CSF, together with serology and polymerase chain reaction (PCR) testing for VZV DNA in CSF can confirm the diagnosis. Acyclovir is the mainstay of therapy in herpes zoster encephalitis and is often given empirically, before microbiological confirmation, in the attempt to achieve better outcomes. Mortality rates are substantially lower if proper therapy is initiated early on, but remain within the range of 5-10% [1]. Prevention strategies may significantly reduce the burden of herpes zoster encephalitis, primarily through the introduction of VZV vaccine in the current schedule [5].

Herpes zoster encephalitis is rare, but potentially fatal complication of varicella-zoster virus (VZV) infection. It represents an infection of the brain and the central nervous system and is established to occur in approximately 1-2 cases per 10,000 patients. VZV belongs to the group of human herpes viruses and is the principal cause of herpes zoster (commonly known as shingles) and varicella (chickenpox), but in rare cases, other types of infection may occur, such as encephalitis and pneumonia. Humans are the only known reservoir of this virus, which it is transmitted from person to person by either coughing or by direct contact of individuals during active infection. When the virus is transmitted, it initially replicates in the throat and lungs and subsequently disseminates through the body. In children, this event often leads to chickenpox and represents a primary infection by this viral pathogen. Once the infection resolves, the virus travels to the sensory ganglia and remains dormant for decades. For partly understood reasons, reactivation of the virus occurs, usually in older patients, and causes herpes zoster. Encephalitis may occur in primary infection or during herpes zoster, but many cases without a clear association between these events have been described, implying that some other factors play a role in its development. In addition to older age, immunosuppression seems to play a major role in predisposing individuals to infections caused by this virus. Human immunodeficiency virus (HIV) infection, hereditary immune system diseases, and organ transplantation are shown to be risk factors. Patients with herpes zoster encephalitis complain of the classical triad of symptoms seen in infections of the central nervous system - headache, vomiting, and fever. Altered consciousness and seizures may be reported as well. The diagnosis can be made by performing a lumbar puncture with subsequent evaluation of cerebrospinal fluid for viral DNA by a technique called polymerase chain reaction (PCR). In addition to PCR, detection of antibodies for VZV may also be an option. Treatment invariably includes administration of an antiviral agent, acyclovir, which markedly reduced mortality rates of this condition. Approximately 5-10% of patients do not survive this infection, however, which is why prompt administration of therapy can be life-saving. More importantly, an introduction of a VZV vaccine into regular programs is being implemented all over the world and may lead to a substantial decrease in the number of infections caused by this viral pathogen. Avoiding close contact with patients is also a recommended form of prevention, as individuals shed the virus through respiratory secretions during active stages of infection.

1. Gnann JW. Varicella-zoster virus: atypical presentations and unusual complications. J Infect Dis. 2002;186:S91-S98.
2. Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology. Seventh edition. Philadelphia: Elsevier/Saunders; 2013.
3. Häusler M, Schaade L, Kemény S, Schweizer K, Schoenmackers C, Ramaekers VT. Encephalitis related to primary varicella-zoster virus infection in immunocompetent children. J Neurol Sci. 2002;195(2):111-116.
4. De Broucker T, Mailles A, Chabrier S, Morand P, Stahl JP; steering committee and investigators group. Acute varicella zoster encephalitis without evidence of primary vasculopathy in a case-series of 20 patients. Clin Microbiol Infect. 2012;18(8):808-819.
5. Boccalini S, Bonanni P, Bechini A. Preparing to introduce the varicella vaccine into the Italian immunisation programme: Varicella-related hospitalizations in Tuscany, 2004-2012. Euro Surveill. 2016;21:14(16).
6. Elliott KJ. Other neurological complications of herpes zoster and their management. Ann Neurol. 1994;35:S57-S61.
7. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2015.
8. Sigaloff KC1, de Fijter CW. Herpes zoster-associated encephalitis in a patient undergoing CAPD: case report and literature review. Perit Dial Int. 2007;27(4):391-394.
9. Arvin A, Campadelli-Fiume G, Mocarski E, et al. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press; 2007.
10. Saxena A, Khiangte B, Tiewsoh I, Jajoo UN. Herpes zoster encephalitis presenting as multiple cerebral hemorrhages – a rare presentation: a case report. J Med Case Rep. 2013;7:155.
11. Bangen KJ, Delano-Wood L, Wierenga CE, Stricker NH, Hesselink JR, Bondi MW. Dementia following herpes zoster encephalitis. Clin Neuropsychol. 2010;24(7):1193–1203.
12. Steiner I, Budka H, Chaudhuri A, et al. Viral encephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol. 2005;12(5):331-343.
13. Gilbert DN, Chambers HF, Eliopoulos GN, Saag MS. The Sanford Guide to Antimicrobial Therapy 2015. 45th ed. Antimicrobial Therapy, Inc, Sperryville, VA; 2015.
14. Washio M, Hamada T, Goda H, Yoshimitsu T, Kajioka T, Koga H, Shogakiuchi Y, Fujishima M, Okayama M. Acyclovir-resistant herpes zoster encephalitis successfully treated with vidarabine: a case report. Fukuoka Igaku Zasshi. 1993;84(10):436-439.