Micturitional disturbance in neuro-Behçet’s syndrome

Autonomic Neuroscience: Basic and Clinical 83 (2000) 86–89 www.elsevier.com / locate / autneu

Micturitional disturbance in neuro-Behc¸et’s syndrome a, a a a Ryuji Sakakibara *, Takamichi Hattori , Konan Boku , Tomoyuki Uchiyama , Tomonori Yamanishi b a

Department of Neurology, Chiba University School of Medicine, 1 -8 -1 Inohana Chuo-ku, Chiba 260 -8670 Japan b Department of Urology, Chiba University School of Medicine, 1 -8 -1 Inohana Chuo-ku, Chiba 260 -8670 Japan Received 1 December 1999; received in revised form 26 January 2000; accepted 26 January 2000

Abstract Background: Micturitional disturbance is known to occur in neuro-Behc¸et’s syndrome (NBS). However, its pathophysiology is uncertain and few data are available concerning urodynamic findings. We describe our findings on micturitional histories and urodynamic studies in patients with NBS. Methods: A history of urinary symptoms was obtained from nine patients with NBS [seven male, two female, aged 26 to 54 years; mean, 41 years]. Neurological and CT / MRI findings indicated that their lesions were located mainly in the cerebral cortex, basal ganglia, cerebellum, brainstem and the spinal cord. Symptomatic patients underwent urodynamic studies, including measurement of post-micturition residuals, urethral pressure profilometry and EMG cystometry. Results: Six of the nine patients (67%) had urinary symptoms that included diurnal urinary frequency in five, sensation of urgency in five, urge urinary incontinence in five, voiding difficulty in five and nocturnal urinary frequency in four. None had urinary retention. Urodynamic studies performed in six patients showed post-micturition residuals in five (50–180 ml), increased maximum urethral closure pressure in two, decrease in four and increase in one of bladder capacities, detrusor hyperreflexia in five, decreased bladder sensation in one, brisk bulbocavernosus reflex in four, detrusor-sphincter dyssynergia in two and neurogenic sphincter EMG in one. Conclusion: Our results indicate that micturitional disturbance is not rare in patients with NBS. Supranuclear pelvic nerve dysfunction seems to be mainly responsible for the disturbance.  2000 Elsevier Science B.V. All rights reserved. Keywords: Neuro-Behc¸et’s syndrome; Micturitional disturbance; Urodynamic study; Urinary incontinence

1. Introduction Behc¸et’s disease, first described by the Turkish dermatologist Hulusi Behc¸et (1937), (Behc¸et, 1937, 1940) occurs mostly in males of the ‘silk-road’ countries, including the Mediterranean, Middle East and Japan. It is a vasculitic disorder of obscure aetiology with multi-organ involvement. Clinical manifestations include recurrent aphthous ulcers of the oral mucosa, genital ulceration, ocular inflammatory lesions (uveitis), skin lesions, arthritis, intestinal ulcers and vascular lesions. It is also characterized by a positive skin pricking test and HLA-B51 typing. Inflammatory lesions in the lower urinary tract are not common, and include epididymitis in 6–19% and urethritis in 3%. (Kirkali et al., 1991; Cetinel et al., 1998) Of patients with Behc¸et’s disease, 5–15% also show neuroBehc¸et’s syndrome (NBS) (Inaba, 1989; Serdaroglu et al., *Corresponding author. Tel.: 181-43-226-2129; fax: 181-43-2262160. E-mail address: [email protected] (R. Sakakibara)

1989; Shakir et al., 1990; Farah et al., 1998), which includes dementia, psychiatric symptoms, cranial nerve palsy, cerebellar ataxia or pyramidal tract signs. Micturitional disturbance has been reported in 5–20% of patients with this disorder, but is considered to be a rare manifestation (Nakagawa et al., 1994; Cetinel et al., 1999). There are, however, patients with intractable urinary incontinence or voiding difficulty caused by NBS and their pathophysiology is still uncertain. The purpose of this paper is to describe the results of micturitional histories and urodynamic studies in nine patients with NBS.

2. Materials and methods We recruited nine patients with NBS in our Neurology outpatient clinic, and some of them were referred to our urodynamic laboratory for their urinary dysfunction, as described below. They were seven men and two women, aged between 26 and 54 years, with a mean age of 41 years (Table 1). All patients were diagnosed as having

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Table 1 Patients Patient

Age

Sex

Cortical abnormalities

Cranial nerve

Pseudobulbar palsy

Incoordination

Hyperreflexia

Babinski signs

Other signs

Brain CT, MRI

T.K.

26

M

2

2

1

1

1

2

Atrophy of the brainstem and the cerebellum

M.K.

29

F

1

2

2

35

M

Hypoalgesia of left tongue Nystagmus on right gaze

2

Y.Y.

Memory disturbance, behavioural abnormality Memory disturbance, psychiatric symptom Psychiatric symptom

1

1

1

2

Hypoalgesia of right side of the body Hypoalgesia of the body

Y.S.

40

M

2

1

1

1

1

Decreased deep sensation of the legs

S.K.

42

M

Memory disturbance, loss of volition, psychiatric symptom 2

2

2

2

1

1

H.Y.

45

M

Memory disturbance, euphoria

Anisocoria

1

1

1

2

Decreased superficial and deep sensation below T2 2

Abnormal intensity in the midbrain and pons Abnormal intensity in the basal ganglia, cerebral peduncle and pons Atrophy of the cerebrum and brainstem, ventricular enlargement Normal

H.S.

47

M

Psychiatric symptom

2

2

2

2

2

M.Y.

53

F

Loss of volition, left hemiparesis

2

2

1

1

1

Y.K.

54

M

2

2

2

2

1

2

NBS (International Study Group for Behcet’s disease, 1990) with recurrent uveitis, aphthous ulcers of the oral mucosa, genital ulceration as well as neuropsychiatric symptoms. Neurological findings included memory impairment, abnormal behaviour and psychiatric symptoms in seven, incoordination in six, hyperreflexia of the legs in six, Babinski sign in four and disturbed superficial sensation below the chest in two. None had apparent orthostatic hypotension. Nerve conduction studies showed mild neuropathy of the legs in two of the six patients studied. Brain CT and / or MRI was performed in all patients, showing atrophy and abnormal signal intensity in the brainstem in six, cerebral cortical atrophy and ventricular enlargement in three, abnormal signal intensity in the basal ganglia in two and cerebellar atrophy in one patient. Histories of micturitional symptoms were obtained from all patients; these were divided into filling and voiding. Filling-phase symptoms consisted of nocturnal or diurnal urinary frequency, sensation of urgency, urinary incontinence and enuresis. Voiding symptoms consisted of voiding difficulty (including urinary hesitation, prolongation, abdominal straining and sense of residual urine) and urinary retention. Urodynamic studies were performed in symptomatic patients, and consisted of measurement of postmicturition residuals, urethral pressure profilometry and EMG cystometry according to the criteria of the International Continence Society (Abrams et al., 1989). The normal range of urodynamic parameters were: residual urine volume under 30 ml; maximum urethral closure pressure of more than 41 cm H 2 O and less than 82 cm

Hypoalgesia of the perineal area Parkinsonism, decreased superficial and deep sensation Spastic paraparesis

Abnormal intensity in the basal ganglia and midbrain, ventricular enlargement Normal Abnormal intensity in the pontine basis, ventricular enlargement Normal

H 2 O; first sensation more than 100 ml but less than 300 ml and bladder capacity of more than 200 ml but less than 600 ml. Neurogenic sphincter motor unit potentials were defined as being of long duration if they were over 10 ms, polyphasic if they had over five phases and of high amplitude if they were over 600 mV. None of the male patients who underwent the urodynamic studies had apparent prostate hypertrophy on rectal examination and ultrasonography. No patient had an apparent urinary tract infection. None of them were taking drugs that would influence lower urinary tract function.

3. Results Six of the nine patients (67%) had micturitional symptoms (Table 2). The major symptoms were diurnal urinary frequency in five, sensation of urgency in five, urge urinary incontinence in five, voiding difficulty in five and nocturnal urinary frequency in four. None had urinary retention. The above micturitional symptoms appeared after the occurrence of the neurological symptoms, and deteriorated gradually along with other symptoms in each case. Urodynamic studies were performed for all six of the symptomatic patients (Table 2). Measurement of postmicturition residuals was performed on all patients and five of them (83%) had residual urine with a mean volume of 144 ml, ranging from 50 to 180 ml. Urethral pressure profilometry was performed on three patients. The maximum urethral closure pressure was increased in two

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Table 2 Urinary symptoms and urodynamic findings a Patient Age Sex Nocturnal Diurnal Urinary Urinary Enuresis Voiding Residual UPmax First Bladder Detrusor Low Unrelaxing Brisk Absent Neurogenic frequency frequency urgency incontinence difficulty urine (ml) (cm H 2 0) sensation capacity hyperreflexia compliance sphincter BCR AR sphincter EMG T.K.

26

M

2

1

1

Urge

1

1

M.K. Y.Y. Y.S. S.K. H.Y. H.S. M.Y. Y.K.

29 35 40 42 45 47 53 54

F M M M M M F M

2 2 1 1 2 1 2 1

2 1 1 1 2 1 2 2

2 1 1 1 2 2 2 1

2 Urge Urge Urge 2 2 2 Urge

2 1 1 1 2 2 2 1

2 2 1 1 2 1 2 1

a

200

.100↑

160 (ml)

160↓ (ml)

1

2

1

1

2

np

2 50 250

np np 94↑

70↓ 100 150

70↓ 300 160↓

1 1 1

2 2 2

2 2 np

1 1 np

2 2 np

np 2 np

90

NP

450↑

600↑

2

2

2

2

1

1

132

53

45↓

90↓

1

2

2

1

2

2

UPmax , maximum urethral closure pressure; BCR, bulbocavernosus reflex; AR, anal reflex; ↑, increased; ↓, decreased; np, not performed.

patients (T.K, S.K). Water cystometry was performed on all patients, and revealed detrusor hyperreflexia in five (83%) (T.K, Y.Y, Y.S, S.K, Y.K), i.e., a decrease in four with detrusor hyperreflexia and an increase in one (H.S) of first sensation and / or bladder capacity. None had a low compliance bladder. External sphincter electromyography was performed on five patients, and revealed a brisk bulbocavernosus reflex in four, an absent anal reflex in one (H.S) and an unrelaxing sphincter on voiding in two patients (T.K, Y.Y). Analysis of the motor unit potentials of the external sphincter was performed on three patients, and one patient (H.S) had enlarged neurogenic sphincter motor unit potentials.

4. Discussion Neuro-Behc¸et’s syndrome (NBS) is pathologically characterized by peri-venular inflammation and demyelination, involving the cerebral cortex, brainstem and the spinal cord (Inaba, 1989). Neurological and MRI findings in our patients also indicated that their lesions were located mainly in the cerebral cortex, basal ganglia, cerebellum, brainstem and the spinal cord. Micturitional disturbance has been reported in 5–20% of patients with this disorder, and is considered to be a rare manifestation (Nakagawa et al., 1994; Cetinel et al., 1999). The present study revealed, however, that six of nine patients (67%) had urinary symptoms. These symptoms seemed to appear and deteriorate gradually along with other symptoms and no apparent causes, such as prostate hypertrophy, were noted. As a result, we could attribute these symptoms to NBS. The major symptoms were diurnal urinary frequency in five, sensation of urgency in five, urge urinary incontinence in five, voiding difficulty in five and nocturnal urinary frequency in four, indicating that both filling and voiding disorders may occur in patients with NBS. All of the other three patients had neuropsychiatric manifestations that might prevent these patients from recognizing or being able to report their urinary symptoms, so that the actual

frequency of micturitional disturbance in NBS could be more common than that was reported. Urodynamic studies revealed that five patients (83%; all of those with urge urinary incontinence) had detrusor hyperreflexia. Previously, Nakagawa et al. (1994) also reported detrusor hyperreflexia in two patients with urinary frequency and incontinence, and Centinel et al. (1999) noted detrusor hyperreflexia in four of seven patients with urinary symptoms. These findings indicate that detrusor hyperreflexia is a major cause of the filling disorder in NBS. Detrusor hyperreflexia could be considered as a supranuclear type of pelvic nerve dysfunction, probably reflecting the lesions of the frontal cortex, basal ganglia or brainstem tegmentum (T.K, Y.Y, Y.S), and of the spinal cord (S.K, Y.K) in our patients with NBS (Sakakibara et al., 1993; Sakakibara et al., 1999). Maximum urethral closure pressure was increased in two of three patients studied. This may indicate a supranuclear type of hypogastric nerve dysfunction innervating the internal urethral sphincter, although increased pressure in a resting state should not directly reflect that in a voiding state. External sphincter EMG revealed an unrelaxing sphincter in two patients with voiding difficulty. Unrelaxing sphincter or detrusor-sphincter dyssynergia is a major cause of evacuating disorder (Siroky and Krane, 1982), probably reflecting a lesion of the basal ganglia (Y.Y) or the brainstem (T.K, Y.Y) in our patients with NBS (Sakakibara et al., 1993; Sakakibara et al., 1999). Centinel et al. found that four of seven patients with Behc¸et’s disease had a low compliance bladder. This finding is probably the result of a lesion of the sacral intermediolateral nucleus projecting pre-ganglionic pelvic nerve fibres, or may also be a result of bladder inflammation. The present study also showed a decreased bladder sensation (increased first sensation and bladder capacity), an absent anal reflex and a neurogenic sphincter EMG in a patient with hypoalgesia of the perineal area (H.S). These findings probably indicate the presence of a peripheral nerve lesion projecting to the lower urinary tract. Though not performed in our patients, Centinel et al.

R. Sakakibara et al. / Autonomic Neuroscience: Basic and Clinical 83 (2000) 86 – 89

(1998) biopsied lamina propria of the bladder in eight and detrusor muscle in three patients with Behc¸et’s disease, and found inflammation of the bladder wall and its vessels. The findings indicate that inflammation of the lower urinary tract may also contribute to the low compliance bladder and other urinary disturbances in NBS. Most of our patients had dementia, psychiatric symptoms, and also had a gait disorder due to ataxia, parkinsonism and spastic paraparesis. However, urinary incontinence in these patients was associated with mainly urge-type dysfunction and detrusor hyperreflexia. A third of the patients also had post-micturition residuals of over 100 ml. An approach to the care of urinary dysfunction in NBS patients may require a combination of behavioural therapy for functional incontinence due to dementia or gait disorder (Williams and Pannill, 1982; Sakakibara et al., 1993), a-adrenergic blocking agents (Petersen and Husted, 1993) or clean, intermittent self-catheterization for large residuals, and anti-cholinergic agents for urge urinary incontinence.

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