Herpes simplex virus 1 and 2 infections affect up to 50 million people in the United States, with a natural history of recurrent viral shedding with or without recurrence of symptoms. Although many patients remain asymptomatic or with mild symptoms, a spectrum of rare but significant nervous system complications have been reported. Although urinary retention and constipation associated with genital herpesvirus infections is often attributed to painful genital ulcerations, herpesvirus-associated lumbosacral myeloradiculitis has been reported in adults. Here, we report an 18-year-old man with constipation, urinary retention, perineal paresthesias, and erectile dysfunction in the setting of a genital herpes infection. His workup was notable for a cerebrospinal fluid pleocytosis and MRI with enhancement of the cauda equina and nerve roots, all of which are consistent with sacral myeloradiculitis. The patient was treated with a 3-week course of intravenous acyclovir with complete resolution of symptoms. Pediatric practitioners should be aware of this complication of anogenital herpes simplex virus infection because appropriate diagnosis has implications for treatment delivery and duration.
Herpes simplex virus (HSV) is a common sexually transmitted infection with an estimated prevalence of HSV 1 of 53.9% and HSV 2 of 15.7%. In the 14 to 19-year-old subgroup, prevalence of HSV 1 and HSV 2 is estimated to be 30.1% and 1.2%, respectively.1 Infections are often asymptomatic or characterized by painful anogenital lesions.2 Although urinary retention associated with this condition is often attributed to dysuria secondary to painful lesions, HSV-associated neurogenic bladder dysfunction has also been reported. In sexually active adults, HSV-associated sacral radiculitis, which includes acute urinary retention and other sensory deficits, is a rare complication reported in the literature.3,4 In this report, we describe a case of constipation, urinary retention, and sensory deficit in a teenager with a genital HSV infection. We present this case to review the presentation and workup of a rare complication of anogenital HSV infection that has implications for treatment course and follow-up.
Case Report
An 18-year-old previously healthy man presented to the emergency department (ED) of our hospital with urinary retention and constipation beginning 3 weeks before presentation after unprotected receptive anal intercourse with a new partner. Several days after this sexual encounter, he developed rectal pain, difficulty urinating and difficulty defecating. He initially presented after 1 week of these symptoms to another ED and was diagnosed with anal fissures. Two weeks into symptoms, he was seen again in that ED for inability to urinate for 16 hours. Urinary catheterization produced ∼1 L of urine, and an abdominal computed tomography scan revealed a 4 to 5-mm nonobstructing stone in the lower pole of the left kidney without evidence of bladder outlet obstruction. He was unable to spontaneously void and was discharged on tamsulosin with a urinary catheter in place, with plan for follow-up with urology in 1 week. In the interim, he saw his primary pediatrician, who diagnosed him with genital HSV 2 infection by polymerase chain reaction (PCR) swab of 2 lesions on his scrotum and started him on oral acyclovir. On the day of final presentation, he was seen in the urology clinic as planned, where he reported persistent inability to urinate and no bowel movements for 1 week. His catheter was removed in clinic and he was unable to void, prompting replacement of his urinary catheter and referral to our ED for additional evaluation.
On review of systems, he described erectile dysfunction in the 3 weeks before admission, a marked change from his typical daily erections. He also endorsed numbness and “pins and needles” around his anus and inner thighs. He denied fever, weight loss, vomiting, gait instability, fatigue, abdominal pain, lymphadenopathy, or rashes apart from the 2 scrotal lesions noted earlier in his course.
His medical history was significant for irritable bowel syndrome with normal colonoscopy 4 years before this presentation. He reported a history of 5 male sexual partners, no female partners, and inconsistent condom use. He had no history of sexually transmitted infections and no personal history of HSV. He reported social alcohol use but denied drug use. He described feeling safe in his relationship and denied interpartner violence.
In the ED, he was well appearing and afebrile, with a heart rate of 80 beats per minute and mild elevation in blood pressure to 132/60 mm Hg. His examination was remarkable for a Tanner V circumcised man with a urinary catheter in place, 2 small circumscribed erythematous ulcers on the right scrotum, and external anal fissures at 12 o’clock and 6 o'clock without bleeding. Internal rectal examination was refused secondary to pain. His neurologic examination was significant for normal strength and sensation intact to light touch throughout, including in the perineal area. Anal wink was intact, although cremasteric reflex was absent bilaterally. Patellar and Achilles deep tendon reflexes were 2+ and symmetric. He had no oral ulcers or other skin findings. An abdominal radiograph revealed a large stool burden. The urology consultant agreed with admission for bowel cleanout and additional workup and had no emergent diagnostic or therapeutic recommendations.
He was admitted to general pediatrics for additional management. Neurology was consulted, and their examination revealed decreased pinprick sensation over the medial buttocks, underside of the scrotum, and posterior aspects of the bilateral legs extending down to mid-thigh. Laboratory workup revealed no leukocytosis or anemia, normal chemistry, no transaminitis, normal hemoglobin A1C, and no elevation of inflammatory markers. MRI with and without contrast of the spine revealed abnormal T2 prolongation, abnormal T1 postcontrast enhancement, and mild expansion within the distal spinal cord and conus as well as faint smooth enhancement within scattered cauda equine nerve roots without abnormal signal or enhancement elsewhere in the cord (Fig 1). Cerebrospinal fluid (CSF) studies revealed 208 white blood cells per mm3 with 92% lymphocyte predominance, protein of 79 mg/dL, glucose of 52 mg/dL, negative Gram-stain and culture results, and negative oligoclonal band results. HSV PCR results from the CSF were negative. HIV testing, rapid plasma reagin, urine gonorrhea, and Chlamydia nucleic acid amplification test results were negative, and hepatitis B and C serologies did not reveal evidence of acute infection. Given the positive HSV 2 test results at his primary care physician appointment, no additional viral testing was performed.
Coronal T1 postcontrast MRI revealed enhancement of the cauda equina in our patient with HSV sacral myelitis.
Coronal T1 postcontrast MRI revealed enhancement of the cauda equina in our patient with HSV sacral myelitis.
The patient was diagnosed with HSV sacral myeloradiculitis. The infectious disease team recommended at least a 2-week course of intravenous (IV) acyclovir based on his CSF pleocytosis, pretreated CSF HSV PCR, extent of his neurologic signs, MRI findings, and better bioavailability of IV acyclovir compared with enteral dosing. He had persistent urinary retention and was discharged with clean intermittent bladder catheterization and tamsulosin per urology recommendations. At the time of discharge, erectile dysfunction had resolved, and perineal sensation was improving. Constipation resolved on a regimen of polyethylene glycol and bisacodyl.
He completed the recommended course of IV antiviral agents as an outpatient; however, at initial follow-up, he still had persistence of some mild urinary retention and perineal paresthesia. Therefore, he completed an additional week of IV antiviral therapy. After completion of 3 weeks of IV acyclovir, he reported complete resolution of his presenting symptoms at his follow-up appointments with infectious diseases, adolescent medicine, and urology departments.
Discussion
The term “Elsberg syndrome,” initially reported in 1913,5 has been used to describe presentations of urinary retention, constipation, and sacral myeloradiculitis often of undetermined etiology and with or without CSF abnormalities and evidence of HSV infection. However, there exists a spectrum of peripheral and central neurologic system manifestations of anogenital HSV infection, ranging from isolated paresthesias in the lumbosacral distribution to more fulminant meningitis with associated urinary retention.6,7
Sacral myeloradiculitis, as described in our patient, is presumed to be a primary disorder of the peripheral nervous system with or without secondary central nervous system involvement and can occur with both current and remote HSV infections.7 Case reports of adults with this condition describe acute urinary retention associated with anogenital herpes with a spectrum of associated neurologic findings in the lumbosacral distribution, including constipation, erectile dysfunction, and paresthesias and neuropathic pain in the perineum, buttocks, and lower extremities. Physical examination may reveal perineal herpetic vesicles and ulcers, decreased sensation in the lumbosacral nerve distribution, loss of anal tone, decreased perineal reflexes, and decreased lower limb reflexes.8,9 Symptoms are often accompanied by CSF pleocytosis.3,8 Urodynamic studies reveal detrusor areflexia with an associated loss of bladder filling sensation.10 T2 weighted MRI images of the spine reveal enlargement and hyperintensity in the cauda equina or spinal cord with postcontrast enhancement.11,12
Similar syndromes related to anogenital HSV infections have been described, including case reports of acute urinary retention, CSF pleocytosis, positive HSV test results in the absence of other neurologic symptoms, neurologic deficits on examination, or herpetic rash.6 Meningitis-retention syndrome associated with HSV is a syndrome of acute urinary retention in the setting of meningitis and CSF pleocytosis without evidence of sacral myeloradiculitis.13
The pathophysiology of HSV-associated myeloradiculitis is thought to be related to the neurotropism of the virus with direct invasion of the sacral dorsal root ganglion in primary infections or reactivation of latent virus in the sacral root ganglion.14,15 Supporting this, HSV 2 has been cultured from sacral sensory ganglions from male cadavers.16 Axonal spread can then lead to spinal cord involvement.15 There is some evidence from animal models that the constipation seen in HSV-associated sacral radiculitis may be in part due to HSV involvement of the enteric nervous system with a resulting decrease in peristalsis.17 HSV 2 is implicated most commonly, followed by HSV 1 and varicella.15 In HSV meningitis-retention syndrome, given the lack of sacral cord involvement, the mechanism of lower urinary involvement remains unclear; hypotheses include meningeal irritation, inflammation of the upper motor neurons of the spinal cord, or development of postinfectious acute disseminated encephalomyelitis.7,13
In the existing case reports of HSV-associated sacral myeloradiculits, symptom resolution is reported as early as 10 to 14 days after symptom onset but can occur up to 8 weeks after onset and appears to be a self-limited condition.3,10,11,18 Patients are treated with bladder catheterization. Given that this is a rare complication of anogenital HSV infection, there is a lack of clinical trials to inform antiviral therapy, including decision to treat, dose, and duration in otherwise healthy individuals. However, most cases that present to care with neurologic findings are treated with acyclovir.11,18 Immunocompromised patients are at increased risk for complications, which can include ascending necrotizing myelopathy and permanent neurologic deficit.8,19 For severe HSV infections, which include central nervous system manifestations, the Centers for Disease Control and Prevention recommends 5 to 10 mg/kg of IV acyclovir every 8 hours for 2 to 7 days or until clinical improvement, followed by oral antiviral therapy to complete at least a 10-day course, with HSV encephalitis warranting 21 days of IV therapy.2
Conclusions
HSV myeloradiculitis is 1 manifestation of the rare nervous system complications of anogenital HSV infections. Pediatric practitioners should consider anogenital HSV infection in adolescent patients with acute urinary retention and neurologic deficits in the lumbrosacral nerve distribution.
Dr Whalen evaluated and treated the patient, researched the literature, and created the initial manuscript; Drs Mateo and Growdon evaluated and treated the patient; Dr Miller evaluated and treated the patient and conceptualized and assisted in the initial manuscript; and all authors revised and reviewed the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.
FUNDING: No external funding.
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