sign in sign up
<<
Home , Polyradiculoneuropathy, Synkinesis, Varicella zoster virus, Viral encephalitis, Viral shedding, Wart

J Neurol (2001) 248:469–477 © Steinkopff Verlag 2001 ENS TEACHING REVIEW

Erich Schmutzhard Viral of the CNS with special emphasis on infections

Abstract Within the past decade method which has become the gold agent of facial palsy (Bell’s palsy) the management of acute HSV I standard of diagnosis of HSV I has been sought; only with the has been improved encephalitis, replacing diagnostic advent of PCR has this question dramatically by the advent of the uncertainties and, avoiding, in been answered. Although one sin- polymerase chain reaction (PCR), a particular, invasive brain biopsy. gle study indicates the superiority Early detection of HSV II in the of a combination of acyclovir plus neonate is mandatory; however, prednisone, this finding has to be prevention by Caesarean section confirmed by a large scale prospec- Received: 2 February 2001 and/or prenatal therapy of the tive randomised double blind Accepted: 8 February 2001 mother are for this the best option. study. Nevertheless, if other causes Very recently the causative agent for the clinical/neurological syn- of Mollaret’s has proved drome of peripheral facial palsy to be, at least in part, HSV I or II. have been excluded, a combination Prof. E. Schmutzhard So far prospective randomized therapy with acyclovir plus pred- Department of Neurology therapeutic trials are awaited for nisone seems to be indicated in a University Hospital Innsbruck the treatment of Mollaret’s menin- patient with Bell’s palsy. Anichstrasse 35 gitis using intravenous acyclovir or 6020 Innsbruck, Austria Key words Tel.: +43-51 25 04-38 53 the more modern oral forms of · Fax: +43-512504-4243 virostatics (, valaci- e-mail: [email protected] clovir). For decades the causative

caused by the family Herpesviridae detailling Introduction herpes simplex I encephalitis, neonatal with II,varicella zoster infection of Both DNA and RNA viruses are able to cause the central ,and it will offer new insights neurological ,including meningitis,encephalitis, into the role of Herpesviridae in Mollaret’s meningitis as meningovasculitis, , cranial , radiculitis well as idiopathic facial palsy (Bell’s palsy). and neuritis, potentially involving the entire range of neurological anatomical sites [26, 52, 64]. Table 1 lists the families, genera and main of Herpes simplex virus I encephalitis DNA viruses causing human neurological disease. Table 2 comprises the RNA viruses being of relevance in hu- Epidemiology man diseases. Thanks to recent developments in recognising cer- Herpes simplex virus I encephalitis (HSVE) is estimated tain viruses as the causative agents of neurological dis- to occur in approximately 2–4/1.000.000 individuals/ eases and because these are viral diseases that can be year, it is the most common sporadic fatal CNS viral in- JON 488 treated successfully by antiviral agents if recognised suf- fection in western countries and manifests throughout ficiently early, this review will mainly concentrate on the year in patients of all ages. There is a bimodal age 470

Tab. 1 DNA-Viruses Tab. 2 RNA-Viruses

Family Size Family Size Genus nm Genus nm Species, relevant in human medicine Species, relevant in human medicine

Poxviridae 200–300 150–300 Paramyxovirus Variola virus Human parainfluenza viruses 1 and 3 virus Rubulavirus Herpesviridae 120–200 virus Human parainfluenza viruses 2 and 4 Herpes simplex virus, type 1 Morbillivirus Herpes simplex virus, type 2 virus Pneumovirus Varicella-zoster virus Human respiratory syncytial virus 80–120 Human cytomegalovirus Influenzavirus viruses A, B, and C Epstein-Barr virus 70–85 Lyssavirus x 180 virus Human herpesvirus 7 Vesiculovirus Human herpesvirus 8 Vesicular virus Cercopithecine herpesvirus 80 x 1000 (B-Virus) Filovirus 70–90 virus Mastadenovirus Marburg virus Human adenovirus, types 1–49 Bunyaviridae 88 x 120 Papovaviridae 45–55 Bunyavirus Papillomavirus California encephalitis virus viruses La Crosse virus Polymavirus Jamestown Canyon virus Simian virus 40 Snowshoe hare virus JC virus Tahyna virus BK virus Inkoo virus 40–48 Cache Valley virus Orthohepadnavirus Tensaw virus Phlebovirus 18–26 virus Erythrovirus Nairovirus Human parvovirus B 19 Crimean-Congo hemorrhagic fever virus Hantavirus Hantaviruses distribution; more than 80% of cases develop in patients Arenaviridae 50–300 less than 20 or greater than 50 years of age. Both sexes Lymphocytic choriomeningitis virus are affected equally [26, 52, 64]. Lassa virus Junin virus Machupo virus Aetiology Guanarito virus Sabia virus HSVE develops when herpes simplex virus I infects Retroviridae 80–100 brain tissue in a lytic/necrotic manner [57]. Although (HTLV-BLV) both primary and recurrent HSV infections may lead to Human T- lymphotropic viruses I and II encephalitis, most HSVE cases in adults are due to reac- tivation of latent viruses [26, 52]. Primary HSVE occurs mostly in children. known sites of HSV I latency [52, 64]. However, viral Pathogen DNA has been found within other parts of the CNS in 34% of those dying of non neurological diseases, sug- Primary HSVE I infections are mainly gingivostomati- gesting that the brain itself may sometimes be a site of tis, rarely corneal or genital . The virus travels by HSV I latency [6]. Recurrent cutaneous herpetic dis- retrograde axonal transport to the neuronal cell body eases (in HSV I mostly herpes labials, also herpetic and establishes a latent infection that usually persists for keratitis) result when HSV I is reactivated from latency the life of the host. Trigeminal sensory ganglia are well- to a replicative stage.Many different events are known to 471

Tab. 2 contd. Clinical manifestation

Family Size It is accepted that HSV I encephalitis is one of the most Genus nm Species, relevant in human medicine severe human viral infections of the nervous system, al- though milder forms have been thought to occur. Table Lentivirus 3 lists the clinical found in patients Human viruses I and II with a condition suggestive of HSV I encephalitis, di- Spumavirus Human isolates (no known pathogens) vided into brain biopsy positive and brain biopsy nega- Coronaviridae 80–220 tive patient groups [52, 65]. Several human serotypes 60–80 Diagnosis Orthoreovirus Reoviruses 1–3 Since patients with HSV I encephalitis frequently show Coltivirus ongoing neurological deterioration and since alterna- Clorado tick fever virus tive diagnoses include a number of other treatable con- Group A an dB human rotoviruses ditions, an immediate diagnostic study is obligatory. Togaviridae 70 The dramatic urgency of this is underlined by the fact that the only predictor of outcome in HSV I encephalitis Eastern virus which can be influenced is the level of consciousness at Western equine encephalitis virus the time of initiation of therapy [52, 64]. The first diag- Venezuelan equine encephalitis virus Rubivirus nostic examination is MRI (without and with i. v. con- virus trast enhancement) mainly evaluating the temporobasal 45–60 and frontobasal regions [29]. If MRI is not available CT Flavivirus must be done immediately.After determining the safety St. Louis encephalitis virus virus of by imaging, CSF examination is the Murray Valley encephalitis virus immediate next diagnostic step.The CSF cell count,pro- Tick borne encephalitis viruses tein, glucose and a negative Gram stain provide rapid virus confirmation of an inflammatory process suggesting vi- Dengue viruses Pestivirus No human pathogens Genus unnamed Tab. 3 Comparision of clinical signs and symptoms in brain biopsy positive and virus negative HSV 1 encephalitis patients Picornaviridae 28–30 brain biopsy brain biopsy 1–3 positive patients negative patients Coxsackie viruses A (%) (%) 1–22, A 24, B 1–6 Human echoviruses 1–7, 9, 11–27, 29–33 Prehospital signs and symptoms Human 68–71 Alteration of consciousness 97 96 Cardiovirus CSF pleocytosis 97 87 Encephalomyocarditis virus Fever 90 78 Rhinovirus 81 77 Human rhinoviruses 1–100 Personality change 71 68 Hepatovirus 67 59 virus Vomiting 46 46 33 26 Memory loss 24 19 Clinical findings at presentatoin promote HSV I reactivation; none, however, has been Fever 92 81 Personality change 85 74 epidemiologically clearly linked to the development of Dysphasia 76 67 herpes simplex encephalitis. In most cases rami Autonomic dysfunction 80 58 meningeales of the trigeminal ganglia or trigeminal 40 40 respectively lead the way of reactivated HSV I, Hemiparesis 38 38 Seizures 38 47 causing temporo-polar, temporo-basal and/or fronto- Focal basal invasion of the brain [26, 52, 64]. In primary infec- Generalized tion or re-infection with HSV I, causing HSV I en- Both cephalitis, the olfactory route is usually the route of Cranial nerve defects 32 33 Visual field loss 14 12 invasion, leading to an initially frontobasally accentu- Papilledema 14 11 ated encephalitis. 472 ral encephalitis [42]. Cultures for bacterial, fungal, my- Management cobacterial and viral pathogens should be arranged, al- though is positive in less than 5% of pa- The management of the patient with suspected HSV I tients with HSV I encephalitis.The identification of HSV encephalitis parallels the diagnostic tests, immediate I DNA in the CSF of patients with HSV I encephalitis by antiviral being mandatory. Given the ap- polymerase chain reaction (PCR) is the diagnostic stan- propriate, suggestive clinical setting acyclovir (Zovi- dard technique, with a sensitivity of 98% and a speci- rax®) is promptly administered intravenously in a dose ficity of at least 94%. Results of the PCR can be available of 10–15 mg/kg bodyweight every 6–8 hours for a mini- within 6 to 8 hours.PCR has become the standard for di- mum of 10 (–14) days [26,52,64].Toxicity is usually mild agnosing HSV I encephalitis [6, 27, 51, 68]. Brain biopsy and not treatment-limiting; it includes thrombocytope- has been replaced by the PCR,the former carrying a risk nia, increased transaminases, creatinine, and BUN. In of 2–3% of serious morbidity [52, 64]. the rare case of acyclovir side effects or acyclovir re- sistance (15 mg/kg bw/day) or (230 mg/kg bw/day) can be given as antiviral alterna- tives [52, 64]. Table 4 shows the most important differential diagnoses Supportive measures in the management of a patient both treatable and non treatable, infectious and non in- with suspected HSV I encephalitis are extremely impor- fectious, diseases which can be mistaken for herpes en- tant, including early intubation for airway protection, cephalitis [65]. mechanical ventilation and, if necessary, mild hyper- ventilation to a pCO2 of 30–35mm Hg. If necessary os- modiuresis with 20% mannitol (0,25 g/kg i. v.) can be in- Tab. 4 Differential diagnosis of HSV I encephalitis stituted. The administration of is, even in the presence of seizures, in most cases not necessary, since Infections (treatable) patients undergoing intensive care therapy are treated /subdural empyema Bacterial with the appropriate, equally anticonvulsive sedation Listerial with (e. g.midazolam or lorazepam).If Fungal (ICP) continues to rise, evident ei- Mycoplasmal ther clinically (anisocoria, decortication- or decerebra- Cryptococcosis tion pattern etc.) or by neuroimaging,ICP monitoring is Rickettsiosis mandatory; occasionally decompressive craniectomy Mucormycosis can be life saving. Meningococcal meningitis Infections (nontreatable) Viral Complications and prognosis Togavirus infections St. Louis encephalitis After a full course of antiviral therapy, relapse of the in- Western equine encephalitis fection has been documented in a few cases. Ongoing Eastern equine encephalitis and deteriorating MRI findings have been reported, de- California encephalitis Other herpesviruses spite appropriate therapy [2, 38]. Epstein-Barr virus Although acyclovir therapy has led to a dramatically Others decreased mortality in HSV I encephalitis,it has resulted Echoviruses in survivors with varying degrees of neurological im- Influenza type A virus Mumpsvirus pairment. Both cognitive and behavioural disorders as Adenoviruses well as disorders are encountered [8, 23, 53]. Progressive multifocal leukencephalopathy (PML) Patient’s age and level of consciousness at the onset of Lymphocytic choriomeningitis treatment are the primary determinants of outcome; im- Subacute sclerosing panencephalitis (SSPE) Non-infectious causes proved survival is seen in patients younger than 30 years Vascular disease and with initial Glasgow coma score greater than 6 [52, Toxic 64]. Focal hyperperfusion of the involved brain regions Reye’s syndrome evidenced by SPECT scanning seems to be another in- Tumor dependent predictor of poor outcome in acute HSV I en- Subdural haematoma Systemic erythematosus cephalitis patients [28]. Adrenal Animal studies suggest a possible role of virion pro- teins for human [20]; their applicability in human medicine still awaits confirmation. 473

virus infection complications, since many uncomplicated varicella cases do not come to medical attention [10, 14]. Herpes simplex infection of the newborn is acquired in The CNS manifestations most frequently associated utero, intra partum or postnatally [4, 34, 60, 67]. The which are and encephalitis, most common time of of herpes simplex rare neurological complications include transverse virus II (HSV II) infection from mother to the fetus oc- myelitis, and Guillain-Barré-syn- curs intra partum when the infant comes into contact drome. Reye’s syndrome (encephalopathy with fatty with infected maternal genital secretions at delivery. infiltration and degeneration of the liver) is a known This accounts for more than 80% of cases of neonatal complication of varicella, but is now attributed to con- HSV II infection [54, 67]. comitant Salizylate therapy [10, 12, 32, 49, 55, 58]. Children with disseminated infection present to medical attention after 8 to 11 days of life. However, Neurological complications of herpes zoster signs of infections are usually present 4 to 5 days earlier. The principal organs involved in this disseminated HSV These can occurr during the acute eruption (e. g. seg- II infection are the liver,brain and adrenals.However,in- mental motor-,radiculitis leading to sensory and fection can involve the lungs, oesophagus, stomach, gas- motor radicular dysfunction) or appear weeks (even trointestinal tract, kidneys, heart, spleen and pancreas months) after the herpes zoster has resolved. [31]. The clinical signs and symptoms include irritabil- Neurological complications appear more frequently ity, seizures, respiratory distress, jaundice, in immunocompromised patients [54]; they are seen, diathesis and shock in addition to a characteristic vesic- however, also in immunocompetent individuals after ular exanthema,which is considered pathognomonic for even prolonged intervals of latency [11, 15]. The follow- neonatal HSV II infection [26,34,52,60].Mortality in the ing distinct clinical syndromes have been described [16, absence of therapy exceeds 80%, the survivors being 19, 39, 40, 43, 62, 63]: encephalitis, myelitis, multifocal usually severely handicapped.Encephalitis is a common leukoencephalitis, ophthalmic zoster with contralateral component of disseminated HSV II infection, occurring hemiparesis, brainstem vascular syndrome (locked in in about 60 to 70% of the infected newborns. It mani- syndrome) with herpes zoster in the upper cervical seg- fests as focal and/or generalised seizures, lethargy, irri- ments,cranial and peripheral nerve palsies,acute retinal tability, poor feeding, , temperature instability, , post herpetic . bulging fontanel and pyramidal tract signs [34, 60]. CSF Subclinical extension of viral into the cultures yield the virus in up to 40% [45]; the CSF shows CNS occurs commonly in acute herpes zoster which can a pleocytosis and a high protein content. EEG, CT or be visualized by magnetic resonance [22]. In CSF Vari- MRI are useful adjunctive diagnostic techniques in the cella zoster viral DNA can be detected by PCR in case of presence of CSF abnormalities. HSV II-DNA detection neurological disease [44, 56]. in CSF and serum is highly sensitive for the diagnosis of neonatal HSV infections but does not replace virus iso- Treatment lation and antigen detection in other locations [33]. Mortality rate is 50%; up to 50% of the surviving chil- Oral acyclovir therapy is optional in otherwise healthy dren have some degree of psychomotor retardation, of- children with varicella, but it should definitely be used ten associated with , hydrocephaly, poren- in adolescents and adults with varicella because of their cephalic cysts, spasticity, blindness, learning disabilities increased risk of more severe illness. In immunocom- etc. [26, 52]. promised individuals with varicella acyclovir therapy Mothers with active herpetic genital lesions should must be initiated as quickly as possible. deliver their children by Caesarean section if delivery is Few data exist to help address the question of antivi- within 4 hours of membrane rupture. Caesarean section ral therapy for neurological complications of varicella. is of unproven benefit if the membranes have been rup- The most frequently seen complication, the cerebellar tured for more than 4 hours. ataxia syndrome, is benign and self limiting and there is no evidence that antiviral therapy or therapy alters the natural course of this syndrome.Vari- Neurological manifestations of varicella zoster cella encephalitis is associated with a substantial degree infection of morbidity and – although there has been no ran- domised prospective trial – therapy with acyclovir in Neurological complications of varicella patients with varicella encephalitis is warranted. Ag- gressive supportive care and nursing are necessary for The incidence of CNS complications with varicella is re- critically ill children with varicella encephalitis. ported to be 1 to 3/10,000 cases, a figure that seems to Appropriate supportive care for patients with herpes overestimate the frequency of neurological varicella zoster includes: keeping the skin lesions clean and try- 474 ing to reduce the risk of bacterial superinfection and DNA has been detected in the CSF using PCR in patients generous analgesic therapy. with Mollaret’s meningitis. Even HSV II DNA has been Three oral antiviral drugs are in use for treatment of seen in the “classic”endothelial (Mollaret) cells [3,21,25, herpes zoster in the immunocompetent host: oral acy- 59, 70]. CSF from patients between episodes or from clovir (800 mg 5 times daily), valacyclovir (1000 mg 3 control patients without a recurrent meningitis syn- times daily) and famciclovir (500 mg 3 times daily). The drome did not have the viral DNA. The association of antiviral therapy reduces the duration of , Mollaret’s meningitis with HSV II has potential thera- limits the duration of new -formation, accelerates peutic importance, since acyclovir therapy might pre- the cutaneous healing and is superior to placebo in re- vent further recurrence. Further studies of this are ducing the duration of [62, 63]. needed. All these 3 drugs are safe and well tolerated for short term administration. Patients most likely to benefit from antiviral therapy of herpes zoster are those who Idiopathic peripheral facial nerve palsy (Bell’s palsy) present for medical attention within 72 hours after on- set of lesions and elderly patients who are at high risk for Epidemiology and Aetiology long term complications [52]. Herpes zoster ophthalmicus is a special situation in Although the biological basis of Bell’s palsy is so far not which antiviral therapy is clearly beneficial; it reduces completely clear [48], various studies report an associa- significantly the risk of ocular complications in such pa- tion of acute facial palsy with a variety of viruses in- tients and,possibly,also the risk of delayed contralateral cluding herpes simplex virus I, , hemiparesis (caused by granulomatous arteritis of the Epstein-Barr virus,cytomegalovirus,Coxsackie viruses, intracranial basal arteries, e. g. ACM). influenza viruses, poliomyelitis viruses and mumps Immunocompromised patients who develop herpes virus; furthermore bacteria, e. g. Mycoplasma pneumo- zoster are at significant risk for morbidity and mortality niae, Bartonella henselae, Borrelia burgdorferi spp. etc. related to disseminated infection. Intravenous acyclovir have been incriminated in the pathogenesis of Bell’s substantially reduces the risk for cutaneous and visceral palsy [7, 13, 24, 36, 50]. dissemination and is, therefore, currently the treatment However,most recent studies have shown that Herpes of choice [54, 55, 63]. simplex virus I may be the most likely candidate virus and by polymerase chain reaction (PCR) of endoneurial fluid Herpes simplex virus I has been identified Mollaret’s meningitis in more than three quarters of Bell’s palsy cases,whereas varicella zoster virus or Epstein-Barr virus have not Mollaret’s meningitis is a rare syndrome with recurrent been found therein [17, 35, 37, 41]. Reactivation of her- signs and symptoms of meningeal irritation, with fever, pes simplex virus I probably results in the initial facial accompanied by CSF pleocytosis without readily identi- weakness and the virus will become indetectable with fiable cause [9, 18]. The clinical criteria [52] are: recovery [17]. Histological studies of the facial nerve – recurrent attacks of fever, associated with signs and during the acute stage of Bell’s palsy,either at autopsy or symptoms of meningeal irritation during , have shown signs of oedema, perivascu- – the attacks last usually days and may be accompanied lar perineurial lymphocytic and infiltra- by generalized myalgia and are separated by symp- tion of the nerve, an increase in the axon: surface tom-free intervals lasting for weeks or months, ratio (thinning of myelin) and a decrease in the total fi- – during the attacks a CSF pleocytosis of a mixed type, bre count. including endothelial cells, leucocytes and lympho- The incidence of Bell’s palsy is 20 to 30/100,000 per- cytes is found. Endothelial cells (Mollaret cells) are sons/year. The rate increases with age up to the fourth rather typical but not pathognomonic, decade and then remains steady until the 8th decade – the disease remits spontaneously without residual when it again increases. Bell’s palsy is equally frequent signs, in man and women (ratio 46:54). The disease occurs on – approximately 5% of the patients will have transitory either side of the face and approximately 5% of patients neurological symptoms and signs in addition to will have a recurrent palsy affecting the same or oppo- meningeal irritation site side. Pregnancy, diabetes mellitus and arterial hy- – there may be an increased gamma globulin fraction pertension have all been associated with an increased in the CSF. incidence of Bell’s palsy [13, 46, 48]. Until recently an integral part of the clinical criteria was that no causative micro-organism could be found. Re- cently, a highly likely link with herpes simplex virus has been established. HSV II (in few instances also HSV I) 475

Signs and symptoms –trauma – Ramsay-Hunt-syndrome (varicella zoster virus in- Bell’s palsy usually has an acute onset, is unilateral and fection of the geniculate ganglion) there is no evidence of disease of the central nervous – neoplasms of the facial nerve system,ear or posterior fossa.Approximately 60% of pa- – infections of the middle ear or mastoid tients have a preceding viral illness. Numbness or pain – demyelinating disorders including acute inflamma- in front or behind the ear is present in about 50% of pa- tory demyelinating tients. Up to 90% have a decreased ipsilateral stapes- re- – space occupying lesion in the cerebello-pontine an- flex, approximately 25% have impaired taste perception gle (tumour, aneurysms, etc.) on direct questioning and 10% of patients suffer from – Lyme borreliosis loss or significant decrease of ipsilateral tearing or sub- – neurosarcoidosis mandibular salivary flow. – The clinical features of Bell’s palsy include the impair- –tuberculosis ment of the entire voluntary movement of facial and – Melkersson-Rosenthal-syndrome platysmal muscles; on attempting to close the eye,the ey- – diabetes mellitus. ball is diverted upward and inward (Bell’s phenomenon). The combination of acyclovir (500 mg four times daily) If the lesion is proximal to the geniculate ganglion there and prednisone has been shown in a single, small, dou- may be decreased tearing in the affected eye;if the chorda ble blinded, controlled study to be superior to pred- tympani is affected, salivation and taste in the anterior nisone alone. Metaanalysis of four randomised con- two thirds of the tongue is decreased. Every patient with trolled studies suggest only a marginal benefit of Bell’s palsy should be examined for masses in the head or steroids alone concerning eventual complete recovery. neck,signs of ear vesicles and facial twitching. Patients who had undergone a combination therapy of acyclovir with prednisone showed a more rapid im- Diagnosis provement in facial strength and less nerve degenera- tion. However, another study using similar outcome Electroneurography of the direct facial response and the measures found that single dose prednisone was more blink reflex are helpful in confirming the presence of a useful than acyclovir alone. Thus, although early use of peripheral facial neuropathy. Transcranial magnetic prednisone seems to be indicated, and the combination stimulation allows the study of the intracranial part of of acyclovir plus prednisone may prove superior to the facial nerve and has proved useful in differentiating prednisone or acyclovir alone, at this time further com- a “classical Bell’s palsy”from a mononeuritis cranialis as bination studies are warranted and urgently awaited [1, part of other diseases. The radiographic imaging in- 48, 50, 52]. cludes MRI with and without gadolinium or cerebral CT Eye care,eye lid surgery,facial rehabilition and surgi- (with and without i. v. contrast medium) of the brain cal decompression of the facial nerve as well as botu- stem, cerebello-pontine angle, temporal bone and skull linum toxin injections in symptomatic synkineses are base; both have not proved to be of prognostic value. A beyond the scope of this article to discuss. full blood count including differential count should help to detect , a blood glucose es- Prognosis and complications timation, erythrocyte sedimentation rate, perhaps also antinuclear antibody test, rheumatoid factor test, Lyme Full recovery occurs in up to 90% of patients; up to 10% , HIV titre and serum angiotensin converting may have recurrence of Bell’s palsy [13, 46]. Recovery is enzyme (for ) may be indicated in certain pa- usually complete by 4 to 6 months and is finished at the tients with Bell’s palsy. If by transcranial magnetic stim- most by 12 months. A facial motor potential amplitude ulation an intracranial affection is suspected,every such of less than 10% of normal is an indicator of poor prog- patient with an isolated facial palsy must undergo lum- nosis; however, even in this group up to 50 % of patients bar puncture in order to look for an acute inflammatory will have at least partial recovery. Other indicators of a demyelinating polyradiculoneuropathy, oligosympto- poor recovery include age over 60 years, untreated arte- matic polyneuritis cranialis, meningitis, meningeal car- rial hypertension, pains and abnormal electrogustome- cinomatosis and lymphoma, postinfectious or autoim- try at onset. mune disease [24, 36].

Differential diagnosis The differential diagnosis of acute facial weakness that may mimic Bell’s palsy is large and includes – as the most important – the following diagnoses [7, 46, 50]: 476

References

1. Adour KK, Ruboyianes JM,Von Doers- 15. Elliot KJ (1994) Other neurological 28. Launes J, Siren J,Valanne L,Salonen O, ten PG, Byl FM, Trent CS, Quesenberry complications of herpes zoster and Nikkinen P,Seppalainen AM, Liewen- CP,Hitchcock T (1996) Bell’s palsy their management. Ann Neurol dahl K (1997) Unilateral hyperfusion treatment with acyclovir and pred- 35:557–561 in brain-perfusion SPECT predicts nisone compared with prednisone 16. Friedman MS, MacDonald RD (1987) poor prognosis in acute encephalitis. alone: a double-blind, randomized, Herpes zoster opththalmicus with de- Neurology 48:1347–1351 controlled trial. Ann Otol Rhinol layed cerebral infarction and menin- 29. Leonard JR, Moran CJ, Cross DT,Wip- Laryngol 105:371–378 goencephalitis. Can J Neurol Sci pold FJ, Schlesinger Y,Storch GA 2. Asenbauer B, McEntagart M, King MD, 14:312–314 (2000). MR imaging of herpes simplex Gallagher P,Burke M, Farrell MA 17. Furuta Y,Fukuda S, Chida E, Takasu T, type 1 encephalitis in infants and (1998) Chronic active destructive her- Ohtani F,Inuyama Y,Nagashima K young children: a separate pattern of pes simplex encephalitis with recovery (1998) Reactivation of herpes simplex findings. Am J Roentgenol of viral DNA 12 years after disease on- virus type 1 in patients with Bell’s 174:1651–1655 set. Neuropediatrics 29:120–123 palsy. J Med Virol 54:162–166 30. Levin MJ, Murray M, Zerbe GO, White 3. Bachmeyer C, de la Blanchardiere A, 18. Galdi AP (1996) Benign recurrent CJ, Hayward AR (1994) Immune re- Lepercq J, et al. (1996) Recurring aseptic meningitis (Mollaret’s menin- sponses of elderly persons four years episodes of meningitis (Mollaret’s gitis): a case with increased circulating after receiving a live attenuated vari- meningitis) with one showing an asso- natural killer cells. Ann Neurol cella . J Infect Dis 170:522–526 ciation with herpes simplex virus type 20:359–361 31 Levinson RD, Reidy R, Chiu MT (1999) 2. J Infect 32:247–248 19. Garthy DS, Spalton DJ, Hykin PG after neonatal 4. Baker DA (1990) Herpes and preg- (1991) Acute retinal necrosis syn- herpes encephalitis. Br J Ophthalmol nancy: new management. Clin Obstet drome. Br J Opthalmol 75:292–297 83:123–124 Gynecol 33:253–257 20. Geiss BJ, Smith TJ, Leib DA, Morrison 32. Liu G, Urion DK (1992) Pre-eruptive 5. Balfour HH, Kelly JM, Suarez Cs, et al. LA (2000) Distruption of virion host varicella encephalitis and cerebellar (1990) Acyclovir treatment of varicella activity improves the immunogenicity ataxia. Pediatr Neurol 8:69–70 in otherwise healthy children. J Pediatr and protective capacity of a replica- 33. Malm G, Forsgren M (1999) Neonatal 116:633–639 tion-incompetent herpes simplex virus herpes simplex virus infections: HSV 6. Baringer JR, Pisani P (1994) Herpes type 1 vaccine strain. J Virol DNA in and serum. simplex virus in human ner- 74:11137–11144 Arch Dis Child Fetal Neonatal Ed vous system tissue analyzed by poly- 21. Gignoux L, Ryvling P,Najioullah F, 81:24–29 merase chain reaction. Ann Neurol Mauguiere F (1998) Recurrent Mol- 34. Malouf DJ, Oates RK (1995) Herpes 36:823–829 laret’s meningitis of herpetic origin. simplex virus infections in the 7. Bauer CA, Coker NJ (1996) Update on Presse Med 27:1470–1472 neonate. J Paediatr Child Health facial nerve disorders. Otolaryngol 22. Haanpaa M, Dastidar P,Weinberg A, 31:332–335 Clin North Am 29:445–454 LevinM, Miettenen A, Lapinlampi A, 35. Marra CM (1999) Bell’s palsy and 8. Borgo F,Sgaramella TM, Penello B, Laippala P,Nurmikko T (1998) CSF HSV-1 infection. Muscle Nerve L’Erario R, Tosso V (2000) A compo- and MRI findings in patients with 22:1476–1478 nential analysis of visual object recog- acute herpes zoster. Neurology 36. May M, Klein SR (1991) Differential di- nition deficits in patients with herpes 51:1405–1411 agnosis of facial nerve palsy. Otolaryn- simplex virus encephalitis. Brain Cogn 23. Hokkanen L, Launes J (2000) Cognitive gol Clin North Am 24:613–645 43:53–56 outcome in acute sporadic encephalitis 37. Mc Cormick DP,Spruance RB (2000) 9. Bruyn GW,Straathof LJ, Raymakers Neuropsychol Rev 10:151–167 Herpes simplex virus as a cause of GM (1962) Mollaret’s meningitis. Dif- 24. Imarhiagbe D, Prodinger W, Bell’s palsy. Rev Med Virol 10:285–289 ferential diagnosis and pitfalls. Neurol- Schmutzhard E (1993) Infektionser- 38. Meyding-Lamade UK, Lamade WR, ogy 12:745–753 reger als mögliche Ursache der idio- Wildemann DT, Sartor K, Hacke W. 10. Choo PW,Donahue JG, Manson JE, pathischen Facialisparese. Wr Klin (1999) Herpes simplex virus en- Plott R (1995) The epidemiology of Wschr 105:611–613 cephalitis: chronic progressive cerebral varicella and its complications. J Infect 25. Jensenius M, Myrvang B, Storvold G, magnetic resonance imaging abnor- Dis 172:706–712 Bucher A, Hellum KB, Brun AL (1998) malities in patients despite good clini- 11. Croen KD, Straus SE (1991) Varicella- Herpes simplex virus type 2 DNA de- cal recovery. Clin Inf Dis 28:148–150 zoster latency. Annu Rev Microbiol tected in cerebrospinal fluid of 9 pa- 39. Mizock BA, Bartt R, Agbemazdo B 45:265–282 tients with Mollaret’s meningitis. Acta (2000) Herpes zoster oticus with pon- 12. Dangood F,Engle E,Yessayan L, Sawer Neurol Scand 98:209–212 tine lesion: segmental brain-stem en- MH (1993) Pre-eruptive varicella cere- 26. Johnson RT (1998) Viral Infections of cephalitis. Clin Infect Dis 30:229–230 bellitis confirmed by PCR. Pediatr the Nervous System. 2nd ed. Lippincott- 40. Morgella S, Block GA, Price RW,Petito Neurol 9:491–493 Raven, Philadelphia, New York CK (1988) Varicella-zoster virus 13. Devriese PP,Schumacher T, Scheide A, 27. Lakeman FD, Whitley RJ, NIAID Col- leukoenzephalitis and cerebral vascu- et al. (1990) Incidence, prognosis and laborative Antiviral Study Group lopathy. Arch Pathol Lab Med recovery of Bell’s palsy. A survey of (1995) Diagnosis of herpes simplex en- 112:173–177 about 1000 patients (1974–1983). Clin cephalitis: application of polymerase 41. Murakami S, Mizobuchi M, Nakashiro Otolaryngol 15:15–27 chain reaction to cerebrospinal fluid Y,Doi T, Hato N,Yanagihara N (1996) 14. Donahue JG, Choo PW,Manson JE, from brain biopsied patients and cor- Bell’s palsy and herpes simplex virus: Plat R (1995) The incidence of herpes relation with disease. J Infect Dis identification of viral DNA in en- zoster. Arch Intern Med 155:1605–1609 171:857–863 doneurial fluid and muscle. Ann Intern Med 124:27–30 477

42. Nahimas AJ, Whitley RJ,Visintine AN, 52. Schmutzhard E (2000) Entzündliche 61. Troendle-Atkins J, Demmler GJ, Buf- Takei Y,Alford CA, NIAID Collabora- Erkrankungen des Nervensystems. fone GJ (1993) Rapid diagnosis of her- tive Antiviral Study Group (1982) Her- Thieme Verlag, Stuttgart pes simplex virus encephalitis by using pes simplex virus encephalitis: labora- 53. Sgaramella TM, Borgo F,Fenzo F, the polymerase chain reaction. J Pedi- tory evaluations and their diagnostic Garofalo P,Toso V (2000) Memory atr 123:376–380 significance. J Infect Dis 145:829–836 for/and execution of future intentions: 62. Watson CPN, Evand RJ, Walt VR, Bir- 43. Nau R, Lantsch M, Stiefel M, Polak T, evidence from patients with Herpes kett N (1988) Postherpetic neuralgia: Reiber H (1998) Varicella zoster virus- Simplex Encephalitis. Brain Cogn 208 cases. Pain 35:289–297 associated focal without her- 43:388–392 63. Weller TH (1992) Varicella and herpes pes zoster: recovery after treatment 54. Srugo I, Israela V,Wittek AE, et al. zoster: a perspective and overview. J with acyclovir. Neurology 51:914–915 (1993) Clinical manifestations of vari- Infect Dis 166:1–6 44. Puchhammer-Stöckl E, Popow-Kraupp cella zoster infections in human im- 64. Whitley RJ (1997) Herpes Simplex T, Heinz FX, Mandi CW,Kunz C. (1991) munodeficiency virus-infected chil- Virus. In: Scheld WM, Whitley RJ, Du- Detection of varicella-zoster virus dren. Am J Dis Child 147:742–745 rack DT (eds). Infections of the Cen- DNA by polymerase chain reaction in 55. Straus SE, Ostrove JM, Inchauspe G, tral Nervous System. Philadelphia, New the cerebrospinal fluid of patients suf- Felser JM, Freifeld A, Croen KD, York Lippincott-Raven, pp 73–89 fering from neurological complica- Sawyer MH (1988) Varicella-zoster 65. Whitley RJ, Cobbs CG, Alford CA, et al. tions associated with chickenpox or virus infections. Ann Intern Med (1989) Diseases which mimic herpes herpes zoster. J Clin Microbiol 108:221–237 simplex encephalitis: diagnosis, pre- 29:1513–1516 56. Straus SE, Reinhold W,Smith HA, sentation, and outcome. JAMA 45. Prober CG, Hensleigh PA, Boucher FD, Ruyechan WT, Henderson DK, Blaese 262:234–239 Yasukawa LL, Au DS, Arvin AM (1988) RM, Hay J (1984) Endonuclease analy- 66. Whitley RJ, Nahmias AJ (1985) Thera- Use of routine viral cultures at delivery sis of viral DNA from varicella and peutic challenges of neontatal herpes to identify neonates exposed to herpes subsequent zoster infection in the simplex virus infection. Scand J Infect simplex virus. N. Engl J Med same patient. N Engl J Med Dis 47:97–106 318:887–891 311:1362–1364 67. Whitley RJ, Nahmias AJ,Visintine AM, 46. Qui WW,Yin SS, Stucker FJ, et al. 57. Studahl M, Rosengren L, Gunter G, Fleming CL, Alford CA (1980) The nat- (1996) Time courses of Bell’s palsy. Hagber L (2000) Difference in patho- ural history of herpes simplex virus Arch Otolaryngol Head Neck Surg genesis between herpes simplex virus infection of mother and newborn. Pe- 122:967–972 type 1 encephalitis and tick-borne en- diatrics 66:489–494 47. Roob G, Fazekas F,Hartung HP (1999) cephalitis demonstrated by means of 68. Wildemann B, Ehrhart K, Storch-Ha- Peripheral facial palsy: etiology, diag- cerebrospinal fluid markers of glial genlocher B, Meyding-Lamade U, nosis and treatment. Eur Neurol 41:3–9 and neuronal destruction. J Neurol Steinworth S, Hacke W,Haas J (1997) 48. Roggenkamper P,Laskawi R, Damenz 247:636–642 Quantitation of herpes simplex virus W,et al (1994) Orbicular 58. Tagawa Y,Yuki N (2000) Bickerstaff’s type 1 DNA in cells of cerebrospinal after facial : treatment with brainstem encephalitis associated with fluid of patients with herpes simplex . Doc Ophthalmol . J Neurol 247:218–219 virus encephalitis. Neurology 86:395–402 59. Tang YW,Cleavinger PJ, Li H, Mitchell 48:1341–1346 49. Rosenfeld J, Taylor CL, Atlas SW (1993) PS, Smith TF,Persing DH (2000) 69. Willeit, Schmutzhard E (1991) Cervical Myelitis following chikenpox: a case Analysis of candidate-host immuno- Herpes zoster and delayed brainstem report. Neurology 43:1834–1836 genetic determinants in Herpes sim- infarction. Clin Neurol Neurosurg 50. Saito O, Aoyagi M, Tojima H, Koike Y plex virus-associated Mollaret’s 93:245–247 (1994) Diagnosis and treatment of meningitis. Clin Infect Dis 30:176–178 70. Yamoto LJ, Tedder DG, Ashley R, Levin Bell’s palsy associated with diabetes 60. Tookey P,Peckham CS (1996) Neonatal MJ (1991) Herpes simplex virus type I mellitus. Acta Otolaryngol (Stockh) herpes simplex virus infection in the DNA in cerebrospinal fluid of a patient 511:153–155 British Isles. Paediatr Perinat Epidemol with Mollaret’s meningiits. N Engl J 51. Sauerbrei A, Eichhorn U, Hottenrott G, 10:432–442 Med 325:1082–1085 Wutzler P (2000) Virological diagnosis of herpes simplex encephalitis. J Clin Virol 17: 31–36