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Transient neurogenic bladder in genital herpes
Journal of Infection (1979) 1, 375-378
Transient neurogenic bladder in genital herpes Te-Wen Chang
Infectious Disease Service, New England Medical Center Hospital and Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111, U.S.A. Summary Transient retention of urine has been observed in seven cases of genital herpes. The presence of pain radiating down the back of thigh and calves indicating inflammed sacral ganglia was noted in all cases. There was a good response to a parasympathominetic drug in those with recurrent attacks. For those with primary herpes, catheterisation remained (he only effective therapeutic manoeuver.
Introduction
Retention of urine in patients with genital herpes infection has been well recognised only recently (Caplan, Kleeman and Berg, 1977). Its pathogenesis is not clearly understood. Except catheterisation, no efficient treatment has been developed. During the past five years, we have studied seven cases of genital herpes with urinary retention. The presence of symptoms and signs originating from infected sacral ganglia (ganglionitis) and the prompt response to parasympathomimetic drug in recurrent cases have led us to propose pathogenetic mechanism of this condition. Clinical features
A common feature with urinary retention was the presence of pain radiating to the buttocks, the back of the thighs and sometimes to the calves. Classified according to the onset of urinary retention in relation to genital herpes, transient neurogenic bladder fell into three categories: during the acute stage of primary genital herpes, post-herpetic, and recurrent cases. The first category was easily recognised because of the presence of diffuse ulcerative lesions at the time of urinary retention. The second and third categories, however, were often misdiagnosed as cystitis. Patients with postherpetic retention did not have active lesions and the retention was not complete. Catheterisation revealed 400-600 ml of residual urine. Urodynamic studies showed an areflexic bladder. A patient with recurrent attacks of urinary retention had been repeatedly treated with gantricin, ampicillin or tetracycline for'cystitis'. The retention preceded the appearance of vesicles 0163-4453/79/040375 + 04 $01.00/0
© 1979 The British Society for the Study of Infection
376
T - W . Chang
Table I Transient neurogenic bladder in genital herpes Age and Onset of urinary sex retention 22 F 27 F 21 F
Symptoms and signs*
Duration of retention
First week of primary genital herpes
Unable to void; abdominal distention and pain; or dysuria, frequency, difficulty in starting stream. Pain radiating down the back of thighs and calves.
6-8 days
23 F 24 F
3-4 weeks after the onset of primary genital herpes. Active lesions no longer present,
Frequency, urgency, difficulty in starting stream. Pain radiating down from the buttocks to the back of thighs and calves.
6-8 days
27 F
Primary and recurrent herpes for two years. First week of the primary, 1-2 days before the recurrent lesions,
The initial episode was characterised by abdominal distention and inability to void. The recurrent episodes were accompanied by hesitency, urgency, dysuria and difficulty in starting stream. Pain radiating down the back of thighs.
19 F
2-3 days in recurrent episodes.
*No objective sensory changes were detected except in one patient with posthherpetic neurogenic bladder, a diminished sensation to pain, temperature and touch was observed in areas with radiating pain. Although the clinical features in many cases suggested cystitis, urinalyses and urine cultures had been non-revealing.
by one to two days. Since urinalysis and cultures were not revealing, mechanical dilatation of the urethra had been attempted on two occasions on an assumption that urinary retention was caused by urethral obstruction. No improvement was noted. After the diagnosis of transient neurogenic bladder was made, marked relief of urinary symptoms following ingestion of three to four l 0 mg tablet of bethanichoi has been regularly observed. A summary of clinical features from seven virologically proved cases of genital herpes complicated by transient neurogenic bladder is shown in Table I.
Discussion Herpes simplex virus, although primarily causing mucocutaneous disease, has a strong affinity for nervous tissue. Experimental infection of the skin or eyes of animals shows that herpes virus migrates centripetally along the terminal nerve endings to reach sensory ganglia, causing ganglionitis, with virus replication demonstrated in the ganglia on the second day of infection, and persisting for a period of seven to eight days (Severin and White, 1968;
Neurogenic bladder in herpes genitatis
377
Stevens, Nesburn and Cook, 1972; Stevens and Cook, 1973; Cook, Baston and Stevens, 1974; Plummer, 1973). Thereafter, no virus can be recovered until the latent virus in the ganglia is activated by certain manoeuvers. After activation, the virus again replicates and presumably travels centrifugally along the sensory nerve to produce mucocutaneous disease. In man, similar changes probably also take place. Herpes virus has been recovered from the trigenimnal, sacral and superior cervical and vagus ganglia (Plummer, 1973; Bastian, Rabson, Yee and Tralka, 1972; Baringer and Swoveland, 1972; Baringer, 1974; Warrem, Brown, Wroblewska, Gilden, Koprowski and Subar-Sharpe, 1978). Clinical experience indicates a close association between mucocutaneous herpes and the changes in the peripheral sensory nervous system. In primary herpes, pain starts two to three days after onset of the skin lesions. In recurrent disease, it precedes or appears with the skin lesions (Chang, 1975). The progenital area is supplied by sensory nerves originating from the second to fourth sacral ganglia. These ganglia also send sensory nerve fibers to the skin of the lower back, the buttock, the posterior and inner thigh, the posterior leg and ankle, and the lateral sole. Herpes infection of the perineum may therefore be accompanied by pain radiating to these areas. This pain may involve the entire area or part of it, depending on the extent and severity of ganglionitis. Radiating pain in genital herpes has been referred to in the literature as a manifestation of~radiculitis ' . However, there is no basis, either clinical or experimental, to indicate that it originates from the nerve roots. All available evidence points clearly to the ganglia as the source of pain. Therefore, the term 'ganglionitis' is preferred. Innervation of the bladder comes from the autonomic nervous system. The parasympathetic, by stimulating the detrusor muscle and relaxing the sphinctor, empties the bladder of urine. Stimulation of the sympathetic causes the opposite effect--retention of urine. The integrity of the parasympathetic reflex arc is essential for normal emptying of the bladder. Impulses from bladder distention pass in parasympathetic afferents via spinal ganglia to the sacral region of the cord. The fibers from intercalary neurons emerge from the cord ($2 and 3) as the nervi erigentes which contain afferent fibers to the bladder wall. Disturbance of this reflex arc caused by herpetic infection of the sacral ganglia results in retention from unopposed sympathetic activity. Bethanechol hydrochloride (urecholine) is a parasympathomimetic (cholinergic) drug, a long acting muscarinic which is resistant to hydrolysis by either true or pseudocholinesterases. A 10 mg dose, to be repeated three times daily if necessary, gives prompt relief of urinary retention. In patients with recurrent genital herpes, the retention was usually relieved by three to four doses. In a patient with post-herpetic retention, repeated doses were necessary for a period of three to four days. Patients with primary diffuse genital herpes usually required an indwelling catheter for urinary retention because it was difficult to avoid pain caused by irritating urine.
378
T-W. Chang References
Baringer, J. R. (1974). Recovery of herpes simplex virus from human sacral ganglions. New England Journal of Medicine, 291,828. Baringer, J. R. and Swoveland, P. (1972). Recovery of herpes-simplex virus from human trigeminal ganglion. Science, 173, 306. Bastian, F. O., Rabson, A. S., Yee, C. L. and Tralka, T. S. (1972). Herpesvirus hominis: isolation from human trigeminal ganglion. Science, 178, 306. Caplan, L. R., Kleeman, F. J. and Berg, S. (1977). Urinary retention probably secondary to herpes gentialis. New England Journal of Medicine, 297, 920. Chang, T-W. (1975). Peripheral sensory neuropathy in herpes simplex. Dermatology Digest, 14, 17. Cook, M. I., Baston, V. B. and Stevens, J. G. (1974). Evidence of neurones harbor latent herpes simplex virus. Infection and Immunity, 9, 946. Plummer, G. (1973). Isolation of herpes virus from trigeminal ganglia of man, monkeys and cats. Journal of Infectious Diseases, 128, 345. Severin, M. J. and White, R. J. (1968). The neural transmission o f herpes simplex virus in mice. Light and electron microscopic findings. American Journal of Pathology, 53, 1009. Stevens, J. G. and Cook, M. L. (1973). Latent herpes simplex virus in sensory ganglia. Perspective Virology, 8, 171. Stevens, J. G., Nesburn, A. B. and Cook, M. L. (1972). Latent herpes simplex virus from trigeminal ganglia of rabbits with recurrent eye infection. Nature (New Biol.), 235, 216. Warrem, L. G., Brown, S. M., Wroblewska, Z., Gilden, D., Koprowski, H. and SubarSharpe, J. (1978). Isolation of latent herpes simplex virus from the superior cervical and vagus ganglions of human beings. New England Journal of Medicine, 298, 1068.
Transient neurogenic bladder in genital herpes Te-Wen Chang
Infectious Disease Service, New England Medical Center Hospital and Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111, U.S.A. Summary Transient retention of urine has been observed in seven cases of genital herpes. The presence of pain radiating down the back of thigh and calves indicating inflammed sacral ganglia was noted in all cases. There was a good response to a parasympathominetic drug in those with recurrent attacks. For those with primary herpes, catheterisation remained (he only effective therapeutic manoeuver.
Introduction
Retention of urine in patients with genital herpes infection has been well recognised only recently (Caplan, Kleeman and Berg, 1977). Its pathogenesis is not clearly understood. Except catheterisation, no efficient treatment has been developed. During the past five years, we have studied seven cases of genital herpes with urinary retention. The presence of symptoms and signs originating from infected sacral ganglia (ganglionitis) and the prompt response to parasympathomimetic drug in recurrent cases have led us to propose pathogenetic mechanism of this condition. Clinical features
A common feature with urinary retention was the presence of pain radiating to the buttocks, the back of the thighs and sometimes to the calves. Classified according to the onset of urinary retention in relation to genital herpes, transient neurogenic bladder fell into three categories: during the acute stage of primary genital herpes, post-herpetic, and recurrent cases. The first category was easily recognised because of the presence of diffuse ulcerative lesions at the time of urinary retention. The second and third categories, however, were often misdiagnosed as cystitis. Patients with postherpetic retention did not have active lesions and the retention was not complete. Catheterisation revealed 400-600 ml of residual urine. Urodynamic studies showed an areflexic bladder. A patient with recurrent attacks of urinary retention had been repeatedly treated with gantricin, ampicillin or tetracycline for'cystitis'. The retention preceded the appearance of vesicles 0163-4453/79/040375 + 04 $01.00/0
© 1979 The British Society for the Study of Infection
376
T - W . Chang
Table I Transient neurogenic bladder in genital herpes Age and Onset of urinary sex retention 22 F 27 F 21 F
Symptoms and signs*
Duration of retention
First week of primary genital herpes
Unable to void; abdominal distention and pain; or dysuria, frequency, difficulty in starting stream. Pain radiating down the back of thighs and calves.
6-8 days
23 F 24 F
3-4 weeks after the onset of primary genital herpes. Active lesions no longer present,
Frequency, urgency, difficulty in starting stream. Pain radiating down from the buttocks to the back of thighs and calves.
6-8 days
27 F
Primary and recurrent herpes for two years. First week of the primary, 1-2 days before the recurrent lesions,
The initial episode was characterised by abdominal distention and inability to void. The recurrent episodes were accompanied by hesitency, urgency, dysuria and difficulty in starting stream. Pain radiating down the back of thighs.
19 F
2-3 days in recurrent episodes.
*No objective sensory changes were detected except in one patient with posthherpetic neurogenic bladder, a diminished sensation to pain, temperature and touch was observed in areas with radiating pain. Although the clinical features in many cases suggested cystitis, urinalyses and urine cultures had been non-revealing.
by one to two days. Since urinalysis and cultures were not revealing, mechanical dilatation of the urethra had been attempted on two occasions on an assumption that urinary retention was caused by urethral obstruction. No improvement was noted. After the diagnosis of transient neurogenic bladder was made, marked relief of urinary symptoms following ingestion of three to four l 0 mg tablet of bethanichoi has been regularly observed. A summary of clinical features from seven virologically proved cases of genital herpes complicated by transient neurogenic bladder is shown in Table I.
Discussion Herpes simplex virus, although primarily causing mucocutaneous disease, has a strong affinity for nervous tissue. Experimental infection of the skin or eyes of animals shows that herpes virus migrates centripetally along the terminal nerve endings to reach sensory ganglia, causing ganglionitis, with virus replication demonstrated in the ganglia on the second day of infection, and persisting for a period of seven to eight days (Severin and White, 1968;
Neurogenic bladder in herpes genitatis
377
Stevens, Nesburn and Cook, 1972; Stevens and Cook, 1973; Cook, Baston and Stevens, 1974; Plummer, 1973). Thereafter, no virus can be recovered until the latent virus in the ganglia is activated by certain manoeuvers. After activation, the virus again replicates and presumably travels centrifugally along the sensory nerve to produce mucocutaneous disease. In man, similar changes probably also take place. Herpes virus has been recovered from the trigenimnal, sacral and superior cervical and vagus ganglia (Plummer, 1973; Bastian, Rabson, Yee and Tralka, 1972; Baringer and Swoveland, 1972; Baringer, 1974; Warrem, Brown, Wroblewska, Gilden, Koprowski and Subar-Sharpe, 1978). Clinical experience indicates a close association between mucocutaneous herpes and the changes in the peripheral sensory nervous system. In primary herpes, pain starts two to three days after onset of the skin lesions. In recurrent disease, it precedes or appears with the skin lesions (Chang, 1975). The progenital area is supplied by sensory nerves originating from the second to fourth sacral ganglia. These ganglia also send sensory nerve fibers to the skin of the lower back, the buttock, the posterior and inner thigh, the posterior leg and ankle, and the lateral sole. Herpes infection of the perineum may therefore be accompanied by pain radiating to these areas. This pain may involve the entire area or part of it, depending on the extent and severity of ganglionitis. Radiating pain in genital herpes has been referred to in the literature as a manifestation of~radiculitis ' . However, there is no basis, either clinical or experimental, to indicate that it originates from the nerve roots. All available evidence points clearly to the ganglia as the source of pain. Therefore, the term 'ganglionitis' is preferred. Innervation of the bladder comes from the autonomic nervous system. The parasympathetic, by stimulating the detrusor muscle and relaxing the sphinctor, empties the bladder of urine. Stimulation of the sympathetic causes the opposite effect--retention of urine. The integrity of the parasympathetic reflex arc is essential for normal emptying of the bladder. Impulses from bladder distention pass in parasympathetic afferents via spinal ganglia to the sacral region of the cord. The fibers from intercalary neurons emerge from the cord ($2 and 3) as the nervi erigentes which contain afferent fibers to the bladder wall. Disturbance of this reflex arc caused by herpetic infection of the sacral ganglia results in retention from unopposed sympathetic activity. Bethanechol hydrochloride (urecholine) is a parasympathomimetic (cholinergic) drug, a long acting muscarinic which is resistant to hydrolysis by either true or pseudocholinesterases. A 10 mg dose, to be repeated three times daily if necessary, gives prompt relief of urinary retention. In patients with recurrent genital herpes, the retention was usually relieved by three to four doses. In a patient with post-herpetic retention, repeated doses were necessary for a period of three to four days. Patients with primary diffuse genital herpes usually required an indwelling catheter for urinary retention because it was difficult to avoid pain caused by irritating urine.
378
T-W. Chang References
Baringer, J. R. (1974). Recovery of herpes simplex virus from human sacral ganglions. New England Journal of Medicine, 291,828. Baringer, J. R. and Swoveland, P. (1972). Recovery of herpes-simplex virus from human trigeminal ganglion. Science, 173, 306. Bastian, F. O., Rabson, A. S., Yee, C. L. and Tralka, T. S. (1972). Herpesvirus hominis: isolation from human trigeminal ganglion. Science, 178, 306. Caplan, L. R., Kleeman, F. J. and Berg, S. (1977). Urinary retention probably secondary to herpes gentialis. New England Journal of Medicine, 297, 920. Chang, T-W. (1975). Peripheral sensory neuropathy in herpes simplex. Dermatology Digest, 14, 17. Cook, M. I., Baston, V. B. and Stevens, J. G. (1974). Evidence of neurones harbor latent herpes simplex virus. Infection and Immunity, 9, 946. Plummer, G. (1973). Isolation of herpes virus from trigeminal ganglia of man, monkeys and cats. Journal of Infectious Diseases, 128, 345. Severin, M. J. and White, R. J. (1968). The neural transmission o f herpes simplex virus in mice. Light and electron microscopic findings. American Journal of Pathology, 53, 1009. Stevens, J. G. and Cook, M. L. (1973). Latent herpes simplex virus in sensory ganglia. Perspective Virology, 8, 171. Stevens, J. G., Nesburn, A. B. and Cook, M. L. (1972). Latent herpes simplex virus from trigeminal ganglia of rabbits with recurrent eye infection. Nature (New Biol.), 235, 216. Warrem, L. G., Brown, S. M., Wroblewska, Z., Gilden, D., Koprowski, H. and SubarSharpe, J. (1978). Isolation of latent herpes simplex virus from the superior cervical and vagus ganglions of human beings. New England Journal of Medicine, 298, 1068.