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Mental nerve neuropathy as a result of primary herpes simplex virus infection in the oral cavity
Mental nerve neuropathy as a result of primary herpes simplex virus infection in the oral cavity A case report Yoshiaki Yura, DDS, PhD, Jun Kusaka, DDS, PhD, Rintaro Yamakawa, DDS, Takashi Bando, DDS, PhD, Hideo Yoshida, DDS, PhD, and Mitsunobu Sato, DDS, PhD, Tokushima, Japan TOKUSHIMA UNIVERSITY SCHOOL OF DENTISTRY
We describe a 25-year-old woman who had mental nerve neuropathy. The symptom was attributed to herpes simplex virus infection, which appeared as herpetic gingivostomatitis 4 days after the extraction of the lower third molar. This case suggests that herpes simplex virus can infect the inferior alveolar nerve through an extraction wound and can induce mental nerve neuropathy. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:306-9)
Gingivostomatitis by primary infection of herpes simplex virus (HSV) type 1 (HSV-1) is characterized by the development of fever, irritability, headache, pain on swallowing, and regional lymphoadenopathy. Vesicles of the oral mucosa rupture and form shallow, ragged, and extremely painful ulcers. In recurrent infection, the lesions are frequently preceded by a burning or tingling sensation, swelling, or slight soreness at the location in which the vesicles subsequently develop.1,2 However, HSV-1–induced anesthesia of the trigeminal nerve is not usually observed. Bell’s palsy is a sudden, isolated, peripheral facial paralysis caused by various known and sometimes unknown factors.3-5 The viral hypothesis for development of Bell’s palsy has been widely accepted because the condition can occur concomitantly with many viral infections.6-11 The theory suggests that axonal spread and multiplication of neurotropic virus results in inflammation, demyelination, and palsy.3,4 Indeed, HSV-1 US6 (gD) gene was demonstrated in facial nerve endoneural fluid and posterior auricular muscle from patients with Bell’s palsy, by using polymerase chain reaction in 11 of 14 patients with Bell’s palsy, but not in patients with the Ramsay Hunt syndrome or in other controls.12 An association between antibodies of HSV in patients of Bell’s palsy and elevated activity of the myelin-associated enzyme 2’3’-cyclic nucleotide 3’-phosphohydrolase suggests that facial nerve demyelination may play a pathogenic role in Bell’s palsy.13 Facial nerve paralysis associated with primary herpetic gingivostomatitis is also reported.14 These studies have shown that HSV is one of the most prevalent causes of facial nerve paralysis. In contrast, the Received for publication Nov 29, 1999; returned for revision Jan 1, 2000; accepted for publication Apr 7, 2000. Copyright © 2000 by Mosby, Inc. 1079-2104/2000/$12.00 + 0 7/13/108100 doi:10.1067/moe.2000.108100
306
possibility that HSV-1 could contribute to sensory nerve paralysis has not been examined extensively. The purpose of this article is to present a unique case in which a clinically, virologically, and serologically diagnosed primary herpetic gingivostomatitis was followed by mental nerve neuropathy. CASE REPORT A 25-year-old woman was seen with a complaint of a painless swelling of the gingiva around the lower molar of less than 1-week duration. On examination, the patient had a halfimpacted lower third molar. The surrounding gingiva was slightly erythematous. A periapical radiograph showed an area of decreased radiopacity on the mesial side of the left third molar, which was consistent with pericoronitis. The tooth was in the normal position, although the root apex was close to the mandibular canal (Fig 1, A). The patient had no significant medical history and no episode of herpetic gingivostomatitis or herpes labialis. The patient underwent extraction of the tooth under local anesthesia with lidocaine without any abnormal bleeding or pain during the procedure. She was given antibiotic (cefaclor, 500 mg, 3 times per day) and an anti-inflammatory drug (lysozyme chloride, 50 mg, 3 times per day) for 3 days. After cessation of the local anesthetic, all sensation along the distribution of the left inferior alveolar and mental nerves returned to normal. Two days later, there were no complications and a drain that was inserted into the extraction wound was removed. Three days after tooth extraction, the patient was found to be febrile. She visited her family physician and received medication. The next day, the patient felt irritation pain in the oral cavity and anesthesia in the left lower lip and mental skin area. When she came back to our hospital on the fourth day after the extraction, we found erythematous lesions involving the left retromolar mucous membranes, especially around the extraction wound and bilateral cervical gingiva of the upper and lower anterior teeth. Examination also showed anesthesia of the skin and mucosa over the distribution of the left mental nerve. Bilateral lymph nodes in the anterior triangle of the neck were enlarged, and pain was elicited by pressure. A radiograph showed the extraction socket of the third molar to be close to
Yura et al 307
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 90, Number 3
A
B
Fig 1. Panoramic radiograph of mandible before (A) and after (B) extraction of third molar.
the mandibular canal, but residual tooth or bone fragments were not observed (Fig 1, B). The oral findings were consistent with a possible primary infection of HSV, and a clinical diagnosis of herpetic gingivostomatitis with mental nerve neuropathy was made. The blood cell count and liver function tests were within the normal ranges. The serum complement fixation (CF) antibody against HSV was measured at SRL Laboratories (Tokyo, Japan). A series of doubling dilutions of the serum was performed, commencing at a dilution of 1:4, and the CF antibody titer was expressed by serum dilution. It was found that the CF antibody titer was at an undetectable level (<4 ). Viral isolation was performed in this laboratory. A sample was obtained from ulcerative lesions on the retromolar mucosa and was inoculated into monkey kidney Vero cell monolayers and incubated at 37°C. Twenty-four hours later, a cytopathic effect characteristic of HSV infection appeared throughout the monolayers. To identify the isolate, cell samples were harvested 24 hours after inoculation and were spread on polylysine–coated glass slides, fixed in cold acetone, and reacted with fluorescein isothiocyanate-conjugated monoclonal antibody against HSV-1 or HSV type 2 (HSV-2) (Syva Corporation, Palo Alto, Calif) for 30 minutes at 37°C. Only monoclonal antibody against HSV-1 reacted with the cell samples, so the isolate was confirmed to be HSV1. Three weeks later, a convalescent serum was tested; the CF antibody titer was found to be 1:64, indicating a significant rise (more than 4-fold) between acute and convalescent sera. These virologic and serologic findings supported the clinical diagnosis of primary herpetic gingivostomatitis. The patient was given acyclovir (200 mg, 5 times per day by mouth) for 5 days and vitamin B complex over 4 weeks. Treatment with acyclovir resulted in resolution of the HSV-related ulcers on the retromolar mucosa and gingiva of the anterior teeth in a week, but the effect of acyclovir on mental nerve neuropathy was marginal. The nerve symptom resolved gradually, and anesthesia was confined to the left lower lip 6 months later.
Two years later, the patient experienced a recurrent intraoral herpetic lesion in the left retromolar mucosa, and HSV-1 was again isolated from the lesion. The lesion resolved in 5 days without medication. During and after the recurrent episode, there were no changes in the symptom of the mental nerve.
DISCUSSION HSV-1 is an epitheliotropic and neurotropic virus. After the replication in the oral mucosal epithelia cells, HSV-1 invades the trigeminal nerve and moves through the axon to the ganglia. Reactivated virus in the ganglia also moves through the trigeminal nerve to the periphery, where recurrent lesion occurs.1,2,15,16 Several lines of evidence have implied that HSV infection can induce inflammatory response and demyelination of the facial nerve, followed by facial palsy.3,4,13,17 However, trigeminal nerve paralysis associated with HSV-1 infection seems to be very rare. Indeed, we have isolated infectious agents from 77 patients with herpetic gingivostomatitis or herpes labialis over 5 years; 30 isolates were subjected to immunofluorescent antibody staining, and all were found to be HSV-1. Anesthesia of the affected area has not been observed except for this case (data not shown). In this case, radiologic study showed that the extraction wound was close to the mandibular canal. One may suspect that the extraction procedure damaged the mandibular canal or a bacterial infection of the region resulted in mental nerve neuropathy. However, during the extraction, there was no abnormal bleeding, tooth root fracture, or bone fracture. The patient was given an antibiotic and anti-inflammatory drug after the operation. When the drain was removed from the extraction
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wound 2 days later, no symptoms suggested bacterial infection and neuropathy of the inferior alveolar and mental nerves. In fact, the patient stated that the anesthesia appeared on the fourth day after the extraction. Thus, it is not likely that extraction or bacterial infection was the direct cause of mental nerve anesthesia. Because she did not feel the anesthesia until the onset of the herpetic gingivostomatitis, HSV-1 infection seems to be the most likely cause of the neuropathy. In a recent study, recrudescent HSV infection mimicking primary herpetic gingivostomatitis in healthy children or young adults was reported.18 Intraoral ulcerations developed in these patients at both keratinized and nonkeratinized sites and had a mild pyrexia and cervical lymphoadenopathy. Each patient has experienced one such episode. A low level of HSV-specific IgG was detected at the onset of the illness and was increased significantly 10 to 15 days later. HSV-specific IgM became positive after resolution of the disease. Unfortunately, a viral culture was not attempted, and the type of HSV antibody was not determined. It is very difficult to exclude the possibility that the patient of this study had a robust recurrent infection but not a primary infection, because most symptoms in these conditions are identical. However, in this case, there was no history of herpetic gingivostomatitis or herpes labialis. The lesions were not confined to the lower molar region, but anterior gingiva was also involved and cervical lymphadenopathy was noted. The serum CF antibody titer in an acute phase was an undetectable level, but it showed a significant rise after resolution of the disease. Furthermore, HSV-1 was isolated from the oral lesions. Because 2% to 9% of healthy individuals have been shown to secrete reactivated HSV-1 in the saliva without any clinical disorders,19 virus isolation itself is not a direct evidence that the lesions are caused by HSV-1. However, it is conceivable that the amounts of the virus in asymptomatic shedding should be small, and greater amounts of virus would be released from acute oral lesions in primary infection as compared with recurrent intraoral lesions. In this study, most cells of the monolayers showed typical cytopathic effect of HSV within 24 hours after inoculation. This means that large amounts of virus are present in the swabbed sample and the isolate is responsible for the development of oral lesions. Taken together, we conclude that the diagnosis of this case is primary infection with HSV-1. There were no family members with episodes of HSV-1 infection. How the infectious agent was transmitted to the patient is unknown. A few reports suggest the association of HSV infection with continued paresthesia or anesthesia of sensory nerves. For example, herpetic whitlow caused by HSV-2 developed in a dental assistant at the time of her initial infection. She has subsequently experienced
9 recurrent infections with lesion spread, scarring, and persistent paresthesia.20 In an experimental study, it has been shown that herpetic infection of the dorsal root ganglion of rats produces paresthesia as a functional abnormality of the sensory neurons.21 This study provides a case with anesthesia of sensory nerve in relation to HSV-1 infection. The mechanism by which neuropathy occurred is unknown, but it may be explained as follows: after tooth extraction, HSV-1 replicated in the oral mucosa, and a number of infectious virus particles were released. Because the extraction wound was very close to the mandibular canal, a high dose of infectious virus could access to the inferior alveolar nerve and, as a consequence, a number of axons would be involved, leading to inflammation and demyelination of the nerve. Although we started acyclovir therapy from the early phase of infection, this treatment was only effective for the lesions on the oral mucosa and did not improve the symptom of the mental nerve. The effect of vitamin B administration for 1 month was marginal. This case suggests that HSV-1 can induce trigeminal nerve neuropathy. Primary HSV infection does not always accompany clinical signs and symptoms. In fact, most primary HSV infections are subclinical.1,2 It is possible that unknown mental nerve paralysis occurring after tooth extraction may be ascribed to secondary infection of the nerve by HSV-1. Although this article describes trigeminal nerve involvement after an episode of primary herpetic gingivostomatitis, it would be prudent to avoid surgical procedures with patients who have active recurrent intraoral herpes or recurrent labial lesions. REFERENCES 1. Whitley RJ. Herpes simplex viruses. In: Fields BN, Knipe DM, Howley PM, Chanock RM, Melnick JL, Monath TP, et al, editors. Fields virology. 3rd ed. Philadelphia: Lippincott-Ravin Press; 1996. p. 2297-342. 2. Scully C. Orofacial herpes simplex virus infections. Oral Surg Oral Med Oral Pathol 1989;68:701-10. 3. Adour KK, Byl FM, Hilsinger RL, Kahn ZM, Sheldon MI. The true nature of Bell’s palsy: analysis of 1000 consecutive patients. Laryngoscope 1978;88:787-801. 4. Morgan M, Nathwani D. Facial palsy and infection: the unfolding story. Clin Infec Dis 1992;14:263-71. 5. Kindstrand E. Lyme borreliosis and cranial neuropathy. J Neurol 1995;242:658-63. 6. Grose C, Feorino PM, Dye LA, Rand J. Bell’s palsy and infectious mononucleosis. Lancet 1973;2:231-2. 7. Traavik T, Storvold G, Sundsfjord A, Lund S, Mair IWS. Peripheral facial palsy and coincidental cytomegalovirus infection or re-activation. Scan J Infect Dis 1983;15:233-8. 8. Brown MM, Thompson A, Goh BT, Forster GE, Swash M. Bell’s palsy and HIV infection. J Neurol Neurosurg Psychiatry 1988;51:425-6. 9. Morgan M, Moffat M, Ritchie L, Collacott I, Brown T. Is Bell’s palsy a reactivation of varicella zoster virus? J Infect 1995;30:29-36. 10. Furuta Y, Fukuda S, Chida E, Takasu T, Ohtani F, Inuyama Y, et
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al. Reactivation of herpes simplex virus type 1 in patients with Bell’s palsy. J Med Virol 1998;54:162-6. Schulz P, Arbusow V, Strupp M, Dieterich M, Rauch E, Brandt T. Highly variable distribution of HSV-1-specific DNA in human geniculate, vestibular and spiral ganglia. Neurosci Lett 1998;252:139-42. Murakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell palsy and herpes simplex virus: identification of viral DNA in endoneurial fluid and muscle [see comments]. Ann Intern Med 1996;124:27-30. Honda H, Takahashi A. Virus-associated demyelination in the pathogenesis of Bell’s palsy. Intern Med 1992;31:1250-6. Nasatzky E, Katz J, Hassharon H. Bell’s palsy associated with herpes simplex gingivostomatitis: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:293-6. Baringer JR, Swoveland P. Recovery of herpes-simplex virus from human trigeminal ganglions. N Engl J Med 1973;288:648-50. Barnett EM, Evans GD, Sun N, Perlman S, Cassell MD. Anterograde tracing of trigeminal afferent pathways from the murine tooth pulp to cortex using herpes simplex virus type 1. J Neurosci 1995;15:2972-84. Vahlne A, Edstrom S, Hanner P, Andersen O, Svennerholm B,
Lycke E. Possible association of herpes simplex virus infection with demyelinating disease. Scand J Infect Dis Suppl 1985;47:1621. Christie SN, McCaughey C, Marley JJ, Coyle PV, Scott DA, Lamey P-J. Recrudescent herpes simplex infection mimicking primary herpetic gingivostomatitis. J Oral Pathol Med 1998;27:810. Scott DA, Coulter WA, Lamey P-J. Oral shedding of herpes simplex virus type 1: a review. J Oral Pathol Med 1997;26:441-7. Merchant VA, Molinari JA, Sabes WR. Herpetic whitlow: report of a case with multiple recurrences. Oral Surg Oral Med Oral Pathol 1983;55:568-71. Andoh T, Shiraki K, Kurokawa M, Kuraishi Y. Paresthesia induced by cutaneous infection with herpes simplex virus in rats. Neurosci Lett 1995;190:101-4.
11.
12.
13. 14. 15. 16.
17.
18.
19. 20. 21.
Reprint requests: Yoshiaki Yura, DDS, PhD Tokushima University School of Dentistry Second Department of Oral and Maxillofacial Surgery 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan [email protected]
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We describe a 25-year-old woman who had mental nerve neuropathy. The symptom was attributed to herpes simplex virus infection, which appeared as herpetic gingivostomatitis 4 days after the extraction of the lower third molar. This case suggests that herpes simplex virus can infect the inferior alveolar nerve through an extraction wound and can induce mental nerve neuropathy. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:306-9)
Gingivostomatitis by primary infection of herpes simplex virus (HSV) type 1 (HSV-1) is characterized by the development of fever, irritability, headache, pain on swallowing, and regional lymphoadenopathy. Vesicles of the oral mucosa rupture and form shallow, ragged, and extremely painful ulcers. In recurrent infection, the lesions are frequently preceded by a burning or tingling sensation, swelling, or slight soreness at the location in which the vesicles subsequently develop.1,2 However, HSV-1–induced anesthesia of the trigeminal nerve is not usually observed. Bell’s palsy is a sudden, isolated, peripheral facial paralysis caused by various known and sometimes unknown factors.3-5 The viral hypothesis for development of Bell’s palsy has been widely accepted because the condition can occur concomitantly with many viral infections.6-11 The theory suggests that axonal spread and multiplication of neurotropic virus results in inflammation, demyelination, and palsy.3,4 Indeed, HSV-1 US6 (gD) gene was demonstrated in facial nerve endoneural fluid and posterior auricular muscle from patients with Bell’s palsy, by using polymerase chain reaction in 11 of 14 patients with Bell’s palsy, but not in patients with the Ramsay Hunt syndrome or in other controls.12 An association between antibodies of HSV in patients of Bell’s palsy and elevated activity of the myelin-associated enzyme 2’3’-cyclic nucleotide 3’-phosphohydrolase suggests that facial nerve demyelination may play a pathogenic role in Bell’s palsy.13 Facial nerve paralysis associated with primary herpetic gingivostomatitis is also reported.14 These studies have shown that HSV is one of the most prevalent causes of facial nerve paralysis. In contrast, the Received for publication Nov 29, 1999; returned for revision Jan 1, 2000; accepted for publication Apr 7, 2000. Copyright © 2000 by Mosby, Inc. 1079-2104/2000/$12.00 + 0 7/13/108100 doi:10.1067/moe.2000.108100
306
possibility that HSV-1 could contribute to sensory nerve paralysis has not been examined extensively. The purpose of this article is to present a unique case in which a clinically, virologically, and serologically diagnosed primary herpetic gingivostomatitis was followed by mental nerve neuropathy. CASE REPORT A 25-year-old woman was seen with a complaint of a painless swelling of the gingiva around the lower molar of less than 1-week duration. On examination, the patient had a halfimpacted lower third molar. The surrounding gingiva was slightly erythematous. A periapical radiograph showed an area of decreased radiopacity on the mesial side of the left third molar, which was consistent with pericoronitis. The tooth was in the normal position, although the root apex was close to the mandibular canal (Fig 1, A). The patient had no significant medical history and no episode of herpetic gingivostomatitis or herpes labialis. The patient underwent extraction of the tooth under local anesthesia with lidocaine without any abnormal bleeding or pain during the procedure. She was given antibiotic (cefaclor, 500 mg, 3 times per day) and an anti-inflammatory drug (lysozyme chloride, 50 mg, 3 times per day) for 3 days. After cessation of the local anesthetic, all sensation along the distribution of the left inferior alveolar and mental nerves returned to normal. Two days later, there were no complications and a drain that was inserted into the extraction wound was removed. Three days after tooth extraction, the patient was found to be febrile. She visited her family physician and received medication. The next day, the patient felt irritation pain in the oral cavity and anesthesia in the left lower lip and mental skin area. When she came back to our hospital on the fourth day after the extraction, we found erythematous lesions involving the left retromolar mucous membranes, especially around the extraction wound and bilateral cervical gingiva of the upper and lower anterior teeth. Examination also showed anesthesia of the skin and mucosa over the distribution of the left mental nerve. Bilateral lymph nodes in the anterior triangle of the neck were enlarged, and pain was elicited by pressure. A radiograph showed the extraction socket of the third molar to be close to
Yura et al 307
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 90, Number 3
A
B
Fig 1. Panoramic radiograph of mandible before (A) and after (B) extraction of third molar.
the mandibular canal, but residual tooth or bone fragments were not observed (Fig 1, B). The oral findings were consistent with a possible primary infection of HSV, and a clinical diagnosis of herpetic gingivostomatitis with mental nerve neuropathy was made. The blood cell count and liver function tests were within the normal ranges. The serum complement fixation (CF) antibody against HSV was measured at SRL Laboratories (Tokyo, Japan). A series of doubling dilutions of the serum was performed, commencing at a dilution of 1:4, and the CF antibody titer was expressed by serum dilution. It was found that the CF antibody titer was at an undetectable level (<4 ). Viral isolation was performed in this laboratory. A sample was obtained from ulcerative lesions on the retromolar mucosa and was inoculated into monkey kidney Vero cell monolayers and incubated at 37°C. Twenty-four hours later, a cytopathic effect characteristic of HSV infection appeared throughout the monolayers. To identify the isolate, cell samples were harvested 24 hours after inoculation and were spread on polylysine–coated glass slides, fixed in cold acetone, and reacted with fluorescein isothiocyanate-conjugated monoclonal antibody against HSV-1 or HSV type 2 (HSV-2) (Syva Corporation, Palo Alto, Calif) for 30 minutes at 37°C. Only monoclonal antibody against HSV-1 reacted with the cell samples, so the isolate was confirmed to be HSV1. Three weeks later, a convalescent serum was tested; the CF antibody titer was found to be 1:64, indicating a significant rise (more than 4-fold) between acute and convalescent sera. These virologic and serologic findings supported the clinical diagnosis of primary herpetic gingivostomatitis. The patient was given acyclovir (200 mg, 5 times per day by mouth) for 5 days and vitamin B complex over 4 weeks. Treatment with acyclovir resulted in resolution of the HSV-related ulcers on the retromolar mucosa and gingiva of the anterior teeth in a week, but the effect of acyclovir on mental nerve neuropathy was marginal. The nerve symptom resolved gradually, and anesthesia was confined to the left lower lip 6 months later.
Two years later, the patient experienced a recurrent intraoral herpetic lesion in the left retromolar mucosa, and HSV-1 was again isolated from the lesion. The lesion resolved in 5 days without medication. During and after the recurrent episode, there were no changes in the symptom of the mental nerve.
DISCUSSION HSV-1 is an epitheliotropic and neurotropic virus. After the replication in the oral mucosal epithelia cells, HSV-1 invades the trigeminal nerve and moves through the axon to the ganglia. Reactivated virus in the ganglia also moves through the trigeminal nerve to the periphery, where recurrent lesion occurs.1,2,15,16 Several lines of evidence have implied that HSV infection can induce inflammatory response and demyelination of the facial nerve, followed by facial palsy.3,4,13,17 However, trigeminal nerve paralysis associated with HSV-1 infection seems to be very rare. Indeed, we have isolated infectious agents from 77 patients with herpetic gingivostomatitis or herpes labialis over 5 years; 30 isolates were subjected to immunofluorescent antibody staining, and all were found to be HSV-1. Anesthesia of the affected area has not been observed except for this case (data not shown). In this case, radiologic study showed that the extraction wound was close to the mandibular canal. One may suspect that the extraction procedure damaged the mandibular canal or a bacterial infection of the region resulted in mental nerve neuropathy. However, during the extraction, there was no abnormal bleeding, tooth root fracture, or bone fracture. The patient was given an antibiotic and anti-inflammatory drug after the operation. When the drain was removed from the extraction
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wound 2 days later, no symptoms suggested bacterial infection and neuropathy of the inferior alveolar and mental nerves. In fact, the patient stated that the anesthesia appeared on the fourth day after the extraction. Thus, it is not likely that extraction or bacterial infection was the direct cause of mental nerve anesthesia. Because she did not feel the anesthesia until the onset of the herpetic gingivostomatitis, HSV-1 infection seems to be the most likely cause of the neuropathy. In a recent study, recrudescent HSV infection mimicking primary herpetic gingivostomatitis in healthy children or young adults was reported.18 Intraoral ulcerations developed in these patients at both keratinized and nonkeratinized sites and had a mild pyrexia and cervical lymphoadenopathy. Each patient has experienced one such episode. A low level of HSV-specific IgG was detected at the onset of the illness and was increased significantly 10 to 15 days later. HSV-specific IgM became positive after resolution of the disease. Unfortunately, a viral culture was not attempted, and the type of HSV antibody was not determined. It is very difficult to exclude the possibility that the patient of this study had a robust recurrent infection but not a primary infection, because most symptoms in these conditions are identical. However, in this case, there was no history of herpetic gingivostomatitis or herpes labialis. The lesions were not confined to the lower molar region, but anterior gingiva was also involved and cervical lymphadenopathy was noted. The serum CF antibody titer in an acute phase was an undetectable level, but it showed a significant rise after resolution of the disease. Furthermore, HSV-1 was isolated from the oral lesions. Because 2% to 9% of healthy individuals have been shown to secrete reactivated HSV-1 in the saliva without any clinical disorders,19 virus isolation itself is not a direct evidence that the lesions are caused by HSV-1. However, it is conceivable that the amounts of the virus in asymptomatic shedding should be small, and greater amounts of virus would be released from acute oral lesions in primary infection as compared with recurrent intraoral lesions. In this study, most cells of the monolayers showed typical cytopathic effect of HSV within 24 hours after inoculation. This means that large amounts of virus are present in the swabbed sample and the isolate is responsible for the development of oral lesions. Taken together, we conclude that the diagnosis of this case is primary infection with HSV-1. There were no family members with episodes of HSV-1 infection. How the infectious agent was transmitted to the patient is unknown. A few reports suggest the association of HSV infection with continued paresthesia or anesthesia of sensory nerves. For example, herpetic whitlow caused by HSV-2 developed in a dental assistant at the time of her initial infection. She has subsequently experienced
9 recurrent infections with lesion spread, scarring, and persistent paresthesia.20 In an experimental study, it has been shown that herpetic infection of the dorsal root ganglion of rats produces paresthesia as a functional abnormality of the sensory neurons.21 This study provides a case with anesthesia of sensory nerve in relation to HSV-1 infection. The mechanism by which neuropathy occurred is unknown, but it may be explained as follows: after tooth extraction, HSV-1 replicated in the oral mucosa, and a number of infectious virus particles were released. Because the extraction wound was very close to the mandibular canal, a high dose of infectious virus could access to the inferior alveolar nerve and, as a consequence, a number of axons would be involved, leading to inflammation and demyelination of the nerve. Although we started acyclovir therapy from the early phase of infection, this treatment was only effective for the lesions on the oral mucosa and did not improve the symptom of the mental nerve. The effect of vitamin B administration for 1 month was marginal. This case suggests that HSV-1 can induce trigeminal nerve neuropathy. Primary HSV infection does not always accompany clinical signs and symptoms. In fact, most primary HSV infections are subclinical.1,2 It is possible that unknown mental nerve paralysis occurring after tooth extraction may be ascribed to secondary infection of the nerve by HSV-1. Although this article describes trigeminal nerve involvement after an episode of primary herpetic gingivostomatitis, it would be prudent to avoid surgical procedures with patients who have active recurrent intraoral herpes or recurrent labial lesions. REFERENCES 1. Whitley RJ. Herpes simplex viruses. In: Fields BN, Knipe DM, Howley PM, Chanock RM, Melnick JL, Monath TP, et al, editors. Fields virology. 3rd ed. Philadelphia: Lippincott-Ravin Press; 1996. p. 2297-342. 2. Scully C. Orofacial herpes simplex virus infections. Oral Surg Oral Med Oral Pathol 1989;68:701-10. 3. Adour KK, Byl FM, Hilsinger RL, Kahn ZM, Sheldon MI. The true nature of Bell’s palsy: analysis of 1000 consecutive patients. Laryngoscope 1978;88:787-801. 4. Morgan M, Nathwani D. Facial palsy and infection: the unfolding story. Clin Infec Dis 1992;14:263-71. 5. Kindstrand E. Lyme borreliosis and cranial neuropathy. J Neurol 1995;242:658-63. 6. Grose C, Feorino PM, Dye LA, Rand J. Bell’s palsy and infectious mononucleosis. Lancet 1973;2:231-2. 7. Traavik T, Storvold G, Sundsfjord A, Lund S, Mair IWS. Peripheral facial palsy and coincidental cytomegalovirus infection or re-activation. Scan J Infect Dis 1983;15:233-8. 8. Brown MM, Thompson A, Goh BT, Forster GE, Swash M. Bell’s palsy and HIV infection. J Neurol Neurosurg Psychiatry 1988;51:425-6. 9. Morgan M, Moffat M, Ritchie L, Collacott I, Brown T. Is Bell’s palsy a reactivation of varicella zoster virus? J Infect 1995;30:29-36. 10. Furuta Y, Fukuda S, Chida E, Takasu T, Ohtani F, Inuyama Y, et
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al. Reactivation of herpes simplex virus type 1 in patients with Bell’s palsy. J Med Virol 1998;54:162-6. Schulz P, Arbusow V, Strupp M, Dieterich M, Rauch E, Brandt T. Highly variable distribution of HSV-1-specific DNA in human geniculate, vestibular and spiral ganglia. Neurosci Lett 1998;252:139-42. Murakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell palsy and herpes simplex virus: identification of viral DNA in endoneurial fluid and muscle [see comments]. Ann Intern Med 1996;124:27-30. Honda H, Takahashi A. Virus-associated demyelination in the pathogenesis of Bell’s palsy. Intern Med 1992;31:1250-6. Nasatzky E, Katz J, Hassharon H. Bell’s palsy associated with herpes simplex gingivostomatitis: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:293-6. Baringer JR, Swoveland P. Recovery of herpes-simplex virus from human trigeminal ganglions. N Engl J Med 1973;288:648-50. Barnett EM, Evans GD, Sun N, Perlman S, Cassell MD. Anterograde tracing of trigeminal afferent pathways from the murine tooth pulp to cortex using herpes simplex virus type 1. J Neurosci 1995;15:2972-84. Vahlne A, Edstrom S, Hanner P, Andersen O, Svennerholm B,
Lycke E. Possible association of herpes simplex virus infection with demyelinating disease. Scand J Infect Dis Suppl 1985;47:1621. Christie SN, McCaughey C, Marley JJ, Coyle PV, Scott DA, Lamey P-J. Recrudescent herpes simplex infection mimicking primary herpetic gingivostomatitis. J Oral Pathol Med 1998;27:810. Scott DA, Coulter WA, Lamey P-J. Oral shedding of herpes simplex virus type 1: a review. J Oral Pathol Med 1997;26:441-7. Merchant VA, Molinari JA, Sabes WR. Herpetic whitlow: report of a case with multiple recurrences. Oral Surg Oral Med Oral Pathol 1983;55:568-71. Andoh T, Shiraki K, Kurokawa M, Kuraishi Y. Paresthesia induced by cutaneous infection with herpes simplex virus in rats. Neurosci Lett 1995;190:101-4.
11.
12.
13. 14. 15. 16.
17.
18.
19. 20. 21.
Reprint requests: Yoshiaki Yura, DDS, PhD Tokushima University School of Dentistry Second Department of Oral and Maxillofacial Surgery 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan [email protected]
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