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The Influence of Skull Base Chordoma on Lower Urinary Tract Symptoms
Female Urology The Influence of Skull Base Chordoma on Lower Urinary Tract Symptoms R. Akhavan-Sigari, M. Abili, V. Rohde, and H. Tezval OBJECTIVE
METHODS
RESULTS
CONCLUSION
To provide the first insights into the potential role of skull base chordoma, which causes brainstem compression in and around Barrington’s nucleus and its effect on the micturition center. Chordoma is a rare malignant bone tumor that originates from the remnants of the embryonic notochord, which normally forms and dissolves during early fetal development. Although it is a slowly growing tumor, it displays local invasive growth. Urodynamic testing of 22 symptomatic patients was performed. All women and men with skull base chordoma treated in 2 hospitals in Germany between 1986 and 2007 were studied. Followup periods ranged from 6 months to 10 years. Lower urinary tract symptoms were documented in patients with acute brainstem compression because of local chordoma growth. Of 74 patients treated, 22 (7 women, 15 men) with a median age of 37 years were evaluated with voiding diaries and computer urodynamic investigation. Urodynamic testing of 22 symptomatic patients revealed detrusor overactivity in 55%, low compliance bladder in 14%, detrusorsphincter dyssynergia in 45%, and uninhibited sphincter relaxation in 27%. Despite the description of incomplete emptying and urgency, 4 patients had normal urodynamic findings (18%). Brain magnetic resonance images of the lesions of the symptomatic patients were obtained to determine the side of lesions. The dorsolateral pons, including pontine reticular nucleus and the reticular formation and the locus coeruleus, seems to be mainly responsible for lower urinary tract symptoms in our patients with skull base chordoma and brainstem compression. UROLOGY 83: 756e761, 2014. 2014 Elsevier Inc.
T
here are a number of reasons for voiding dysfunction associated with stroke,1 multiple sclerosis, Alzheimer’s disease, multiple system atrophy, traumatic brain lesion, brain tumors, normal pressure hydrocephalus, Parkinson’s disease, and other cerebral disorders.2,3 Their incidence has not been fully evaluated and probably underestimated. Previous reports showed urinary dysfunction in 25% of frontal lobe tumors4 and in 22% of infarctions of anterior cerebral artery territory.5 Indeed, local brain lesions seem to cause urinary dysfunction in about 20%-50% of all patients with tumor and cerebrovascular accident.6 Lesions of the dorsolateral pons involving pontine reticular nucleus and reticular formations, located in the ventromedial or lateral areas of the pontine micturition center (PMC)7,8 and the locus coeruleus, are mainly responsible for the micturitional disturbance in patients with brainstem lesion.9,10 R. Akhavan-Sigari and M. Abili contributed equally. Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Neurosurgery, University Medical Center G€ottingen, GeorgAugust-University G€ottingen, Germany; the Department of Neurosurgery, Mashhad University of Medical Sciences, Mashhad, Iran; and the Department of Urology, Hannover Medical School, Hannover, Germany Reprint requests: R. Akhavan-Sigari, M.D., Department of Neurosurgery, University Medical Center G€ottingen, Georg-August-University G€ottingen, Robert-Koch-Strasse 40, 37075 G€ottingen, Germany. E-mail: [email protected] or reza.akhavan-sigari@ med.uni-goettingen.de Submitted: October 23, 2013, accepted (with revisions): December 13, 2013
756
ª 2014 Elsevier Inc. All Rights Reserved
Extra-axial tumors, such as skull base chordoma with expansion and brainstem compression, are likely to cause conditions of critical illness, such as disturbances of consciousness, ataxia, and convulsions. To the best of our knowledge, there have been no previous urodynamic studies of urinary symptoms in brainstem chordoma. With a view toward determining whether skull base chordoma with tumor expansion and compression of the pons and possibly PMC are connected with urinary disturbances, this study reports the results of micturitional histories, urodynamic studies, and magnetic resonance images (MRI) showing the location of the PMC in patients with brainstem compressing skull base chordoma. In our study, micturitional disturbance could not be found in patients with tumor expansion to the midbrain but was found in 75% of patients with pons and 20% with medullary compression. However, the accurate location of the lesion could not be determined.
METHODS Seventy-four chordoma patients were treated at the Neurosurgical Departments of the Nordstadt Hospital in Hannover and the Hannover Medical School, Germany, between 1986 and 2007. The patients (32 women and 42 men) ranged in age from 16 to 88 years (median, 58). Twenty-four patients experienced recurrence and subsequent resection. All patients underwent 0090-4295/14/$36.00 http://dx.doi.org/10.1016/j.urology.2013.12.018
UROLOGY 83 (4), 2014
Table 1. Results of urodynamic testing Residual Urine (mL)
UPmax (cm H2O)
FDV (mL)
MDV (mL)
Detrusor Hyperreflexia
DSD
USR
Low Compliance
Age, y
Sex
Diagnosis/Expansion
Latency*
Urinary Symptoms at the Time of Urodynamic
20
M
1d
Incomplete emptying, urgency
30
110
30
530
þ
18 55
M F
Chordoma R-midbrain/rostral pontine Chordoma pontine, tegmentum Chordoma midbrain, pontine
1d 3 mo
np np
57 np
55 312
600 480
þ
þ
þ
þ
53 25 55 28
M F M M
Chordoma Chordoma Chordoma Chordoma
2 mo 2d 1 mo 3d
55 0 85 np
36 27 52 15
110 58 35 214
278 268 63 350
þ þ þ
þ þ þ
39
M
5d
90
33
110
268
þ
þ
32 17
M F
1 mo 2d
Frequency, intermittency Incomplete emptying, urgency
65 0
64 45
58 320
430 586
þ
32
M
Frequency, intermittency
140
61
120
345
þ
þ
28 51 25 36 47 38 11 22 70 52 48
M M F M M F F M M M F
Chordoma midbrain, lat. medullary Chordoma pons Chordoma R-midbrain/rostral pontine Chordoma/midbrain and tegmentum Chordoma pontine basis Chordoma midbrain, pons Chordoma pons, tegmentum Chordoma mons, midbrain Chordoma rostral pontine Chordoma lat. medullary Chordoma pons, midbrain Chordoma tegmentum Chondrosarcoma midbrain Chordoma pons, lat medullary Chordoma med. medullary
Incomplete emptying, urgency Nocturia, incontinence, frequency, intermittency Pollakiuria, nocturia Frequency, intermittency Nocturia, urgency. Noctuna, frequency, intermittency Frequency, intermittency
Retension Urgency, Nocturia Frequency, intermittency Pollakiuria Retension Nocturia, pollakiuria Nocturia, urgency Incomplete emptying, urgency Retention Retention Retention
250 405 0 np 30 55 75 200 110 70 60
18 29 18 87 58 39 86 18 37 35 65
89 93 40 25 103 180 200 175 158 230 60
325 267 390 580 220 380 530 560 248 510 325
þ þ þ þ þ þ
þ þ þ þ þ
þ þ þ
þ
lat. medullary pons, medulla rostral pontine pons, medulla
4d 2d 5d 4d 3d 2 mo 6d 1d 2d 5y 3 mo 2 mo
DSD, detruor sphincter dyssynergia; FDV, first desire to void; MDV, maximum desire to void; Np, not performed; UPmax, maximum urethral closure pressure; USR, uninhibited sphincter relaxation. * Latency of urodynamic tests after the occurrence of the neurologic deficits.
757
Figure 1. Magnetic resonance imaging of a patient with enhancing, diffusely infiltrative tumor classified as a skull base chordoma. (A) Sagittal T1-weighted image after gadolinium infusion demonstrates an enlarged, heterogeneously enhancing tumor within the pons. (B) Axial T1-weighted image after gadolinium infusion.
Table 2. Patients with micturitional disturbances Age Micturitional Symptoms According to IPSS Questionnaires Urinary retention/incomplete emptying Weak stream/straining Nocturnal urinary frequency Frequency/intermittency Urinary urgency
Gender
50-70 (N ¼ 18)
50 (N ¼ 33)
Male (N ¼ 28)
Female (N ¼ 23)
51/74
69%
5 3 6 8 8
11 11 16 13 7
12 8 18 17 9
4 6 4 4 6
16 14 22 21 15
22% 19% 30% 28% 20%
IPSS, International Prostate Symptom Score.
brain MRI, and we excluded patients with status lacunaris, a condition occurring in cerebral arteriosclerosis, in which there are numerous small areas of degeneration in the brain known to cause micturitional disturbance11. All treated chordoma patients with adequate documentation for our study, that is, 51 of 74, were included. The International Prostate Symptom Score (IPSS) was used in the assessment of lower urinary tract symptoms (LUTS) in our patients with symptoms of voiding dysfunction. Twenty-two of the 51 patients described voiding difficulties and were given the IPSS questionnaire. These patients underwent urodynamic testing from 1 day (at the earliest possible time) after diagnosis, that is, preoperatively, and up to a maximum of 2 years after the operation of the skull base chordoma (Table 1). Urodynamics consisted of measuring residual urine, urethral pressure profilometry, and water cystometry as described previously.12 The sites of lesions are shown in Figure 1A, B.
RESULTS Owing to neurologic deficits such as low level of consciousness, dizziness, and gait disturbance, 51 patients had indwelling urinary catheters during the first week of hospitalization. We observed our patients for periods ranging from 6 months to 10 years. Voiding complaints included incomplete emptying, urgency, frequency, intermittency, staining, and nocturia. Urinary symptoms began within 3 months after onset of the neurologic symptoms, namely the signs of raised intracranial pressure (deterioration in the level of consciousness, headache, 758
pupillary dysfunction, vomiting, possible papilledema, and so forth). Increased intracranial pressure was mainly because of the occlusive hydrocephalus caused by the skull base chordoma compressing the midbrain and cerebral aqueduct. Fifty-one patients (69%) had urinary complaints (Table 2). Their major symptoms were frequency and intermittency (21 patients, 28%), nocturia (22 patients, 30%), followed by urinary retention (16 patients, 22%). All patients with tumor recurrence and urinary retention became unable to urinate 6 months from the onset. Voiding problems, especially nocturia, frequency, and intermittency, seemed to be present in all patients with skull base chordoma, especially in those with the expansion of the lesion to the dorsal medulla and tegmentum. Furthermore, urinary symptoms such as those mentioned previously seemed to be more common in patients with incoordination than in those without incoordination and also in patients with sensory disturbance and with abnormal eye movements. Urinary complaints were noted almost equally in patients with or without hemiparesis. In contrast, most of the patients without urinary complaints had lesions of the pontine basis and the lateral medulla. MRI images of our patients have revealed that the chordoma expansion of the patients with severe urinary symptoms was located mostly in the region of the dorsolateral pons, including the pontine reticular nucleus, the reticular formation nucleus, and the locus coeruleus (Fig. 2). UROLOGY 83 (4), 2014
Figure 2. Brainstem nuclei of selected autonomic nervous system. Midbrain periaqueductal gray matter (PAG) surrounds the mesencephalic aqueduct that contains a micturition center; this receives ascending projections from the sacral cord and sends axons to the pontine micturition center (PMC), which is located in the dorsal area of the pons. Medial and lateral parabrachial nuclei located in the rostral cerebellar peduncle fibers in the pons. The nuclei relay visceral information from the solitary tract nucleus and spinal cord to the hypothalamus, contralateral thalamus, and limbic system. (Color version available online.)
Results of Urodynamic Studies Of the 22 patients who described voiding problems and had been given the IPSS questionnaire, all had urinary problems at urodynamic testing. These included frequency and intermittency in 7, nocturia in 7, urinary retention in 5 (4 men and 1 woman), urgency in 3, incontinence in 1, and pollakiuria in 3 (Table 1). These symptoms continued together with the occurrence of the neurologic symptoms. Measurement of residual urine was performed on 15 patients, of which 13 (87%) had residual urine of 55-405 mL, with an average of 128 mL. Water cystometry was performed on all patients, and the bladder volume at first desire UROLOGY 83 (4), 2014
to void and/or maximum desire to void was decreased in 17 (77%) and increased in 7 (32%) patients. Detrusor overactivity was noted in 12 (55%), low-compliance bladder in 3 (14%), detrusor-sphincter dyssynergia in 10 (45%), and uninhibited sphincter relaxation in 6 patients (27%). Four of 22 patients stated having incomplete emptying and urgency, but the urodynamic studies revealed normal findings.
COMMENT That a posterior fossa tumor can cause voiding dysfunction has long been known.13 However, little attention 759
has been paid to this because compression on the brainstem commonly causes a serious neurologic state characterized by disturbed consciousness or respiratory arrest. Our study reveals that 51 of 74 patients (69%) with skull base chordoma and brainstem compression had urinary problems. Urinary symptoms appear with the occurrence of acute brainstem compression because of the expansion of the skull base chordoma and could be regarded as neurogenical origin. The major symptoms were voiding difficulty in 7 patients (32%) and nocturia in 7 (32%), urinary retention in 5 (23%), and urinary incontinence in 1 (5%). The incidence of urinary difficulties in our patients, therefore, seems quite high. Previously, studies14 have stated that voiding difficulty could be a sign of posterior fossa tumors. In 1960, Ueki15 described 152 cases of posterior fossa tumors and found urinary incontinence in 3 (1.9%) and voiding difficulty in 46 (30%). Voiding difficulty was also noted by Betts16 and Baillieux17 in a patient with midbrain-rostral pontine tumor. Our study indicates that urinary symptoms such as urine storage and voiding dysfunction may also be common in patients with space-occupying lesions in the skull base tumors. Voiding dysfunctions in our patients seemed to be more common in chordoma with expansion to the dorsolateral pons, pontine reticular nucleus, reticular formation, and the locus coeruleus. Responsible Sites of Urinary Dysfunction Previous reports have indicated the significance of the pontine lesions within the brainstem with regard to micturitional disturbance.9,15,18 Ueki15 found voiding difficulty in 77.3% of patients with pons lesions, 66.7% with fourth ventricle lesions, 40.9% with lesions in the midline of cerebellum, 24.2% with cerebellar hemisphere lesions, and 9.1% with cerebellopontine angle in posterior fossa tumors. Urinary retention was also found in 71% of 17 children with pontine glioma by Renier et al.19 In a study by Sakakibara et al,1 of 30 clinically diagnosed brainstem infarctions, micturitional symptoms occurred in none with lesions in the midbrain but in 35% of patients with lesions in the pons and in 18% with medulla lesions. Urinary disturbance has also been reported in patients with acute infarction in the right lateral medulla who had voiding difficulty as an initial manifestation. Urodynamic study showed detrusor areflexia on voiding, and the voiding difficulty completely disappeared 2 weeks after the stroke onset.20 It has long been known in experimental animals that destruction of brain areas above the pons (supracollicular or intercollicular decerebration) did not impair micturition; however, infracollicular decerebration or transection of the neuraxis at any point caudal to the pons immediately abated micturition.21 These findings in laboratory animals seem to correspond to the aforementioned findings in human cases. LUTS may be associated with various neurologic signs, which could be attributable to the lesions near or adjacent to the micturitional area within the brainstem. The present study reveals 760
that LUTS seems common in patients with hemiparesis, sensory disturbance, abnormal eye movement, and incoordination (symptomatic of brainstem lesions), although there was no statistical significance. Similar to findings in the research by Sakakibara et al,9 the aforementioned findings seem to indicate that LUTS is associated with neurologic signs mainly seen in the dorsolateral brainstem. MRI showed that the responsible sites of the lesions appear to be located in the dorsolateral pons, including the pontine reticular nucleus and the reticular formation, adjacent to the medial parabrachial nucleus and the locus coeruleus. Urodynamic Findings and the Mechanism of Urinary Dysfunction Urodynamics carried out in 22 patients revealed a variety of findings, including detrusor overactivity in 12 patients (55%), low-compliance bladder in 3 (14%), detrusorsphincter dyssynergia in 10 (45%), and uninhibited sphincter relaxation in 6 patients (27%). The other 4 patients had normal findings. There are only a few urodynamic studies previously described of patients with brainstem lesions,9,22 and their findings are similar, with detrusor overactivity in lateral medullary lesions. Betts et al16 and Manente et al23 each described patients with midbrain-rostral pontine tumors detected using MRI with persistent detrusor areflexia. A transient hypocontractile bladder was described by Sakakibara et al24 with herpetic encephalitis localized at the pontine tegmentum with MRI. Detrusor areflexia in these various cases could be regarded as the “shock phase”, although some of the detrusor areflexias were more persistent.9 Detailed follow-up was available in 17 of 22 patients postoperatively. After some follow-up periods and repeated urodynamic studies, detrusor overactivity had completely disappeared in 11 patients (64.7%) within 3 years. Five patients (29.4%) with low-compliance bladder and urinary retention became able to urinate after a follow-up period of 6 months. Finally, detrusor-sphincter dyssynergia and uninhibited sphincter relaxation were still observed after a period of 5 years in 6 patients (35.2%).
CONCLUSION On the basis of our study, we suggest that skull base chordomas invading the dorsolateral pons, pontine reticular nucleus, reticular formation, and the locus coeruleus (PMC) are mainly responsible for the micturitional disturbance in patients with brainstem lesion. References 1. Sakakibara R, Hattori T, Tojo M, et al. Micturitional disturbance in patients with brainstem infarction. J Auton Nerv Syst. 1995;50: 362-363. 2. Zhang H, Reitz A, Kollias S, et al. An fMRI study of the role of suprapontine brain structures in the voluntary voiding control induced by pelvic floor contraction. NeuroImage. 2005;24:174-180. 3. Verne GN, Himes NC, Robinson ME, et al. Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome. Pain. 2003;103:99-110.
UROLOGY 83 (4), 2014
4. Fowler CJ, Griffiths DJ. A decade of functional brain imaging applied to bladder control. Neurourol Urodyn. 2010;29:49-55. 5. Kang SY, Kim JS. Anterior cerebral artery infarction stroke mechanism and clinical-imaging study in 100 patients. Neurology. 2008; 70:2386-2393. 6. de Groat WC. A neurologic basis for the overactive bladder. Urology. Dec 1997;50(Suppl):36-52; discussion 53-56. 7. Griffiths D, Holstege G, Dalm E, Wall HD. Control and coordination of bladder and urethral function in the brainstem of the cat. Neurourol Urodyn. 1990;9:63-82. 8. Nishizawa O, Sugaya K. Cat and dog: higher center of micturition. Neurourol Urodyn. 1994;13:169-179. 9. Sakakibara R, Hattori T, Yasuda K, Yamanishi T. Micturitional disturbance and the pontine tegmental lesion: urodynamic and MRI analyses of vascular cases. J Neurol Sci. 1996;141:105-110. 10. de Groat WC. Central neural control of the lower urinary tract. Ciba Found Symp. 1990;151:27-44; discussion 44-56. 11. Feder M, Heller L, Tadmor R, et al. Urinary continence after stroke: association with cystometric profile and computerised tomography findings. Eur Neurol. 1987;27:101-105. 12. Abrams P, Cardozo L, Fall M, et al; Standardisation SubCommittee of the International Continence Society. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003;61:37-49. 13. Holman E. Difficult urination associated with intracranial tumors of the posterior fossa: A physiologic and clinical study. Arch Neurol Psychiatry. 1926;15:371-380.
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14. Cuccurullo S, ed. Cancer Rehabilitation. New York, NY: Demo Medical Publishing; 2004. Available at: http://www.ncbi.nlm.nih. gov/books/NBK27276/. Accessed September 3, 2013. 15. Ueki K. Disturbances of micturition observed in some patients with brain tumor. Neurol Med Chir (Tokyo). 1960:25-33. 16. Betts CD, Kapoor R, Fowler CJ. Pontine pathology and voiding dysfunction. Br J Urol. 1992;70:100-102. 17. Baillieux H, Smet HJD, Lesage G, et al. Neurobehavioral alterations in an adolescent following posterior fossa tumor resection. Cerebellum. 2006;5:289-295. 18. Iwasaki H, Koyama Y, Tanaka Y, et al. Modulation by desmopressin of neuronal activity in brainstem micturition center. Urology. 2004; 63:994-998. 19. Renier W, Gabreëls F, Conen M. Evaluation of diagnosis and NonSurgical Therapy in 24 children with a pontine tumour. Neuropediatrics. 1979;10:446. 20. Lee KB, Jang IM, Roh H, et al. Transient urinary retention in acute right lateral medullary infarction. Neurologist. 2008;14:312-315. 21. Blok BF. Central pathways controlling micturition and urinary continence. Urology. 2002;59(Suppl 1):13-17. 22. Nathan PW, Smith MC. The centrifugal pathway for micturition within the spinal cord. J Neurol Neurosurg Psychiatry. 1958;21:177-189. 23. Manente G, Melchionda D, Uncini A. Urinary retention in bilateral pontine tumour: evidence for a pontine micturition centre in humans. J Neurol Neurosurg Psychiatry. 1996;61:528-529. 24. Sakakibara R, Hattori T, Fukutake T, et al. Micturitional disturbance in herpetic brainstem encephalitis; contribution of the pontine micturition centre. J Neurol Neurosurg Psychiatry. 1998;64:269-272.
761
METHODS
RESULTS
CONCLUSION
To provide the first insights into the potential role of skull base chordoma, which causes brainstem compression in and around Barrington’s nucleus and its effect on the micturition center. Chordoma is a rare malignant bone tumor that originates from the remnants of the embryonic notochord, which normally forms and dissolves during early fetal development. Although it is a slowly growing tumor, it displays local invasive growth. Urodynamic testing of 22 symptomatic patients was performed. All women and men with skull base chordoma treated in 2 hospitals in Germany between 1986 and 2007 were studied. Followup periods ranged from 6 months to 10 years. Lower urinary tract symptoms were documented in patients with acute brainstem compression because of local chordoma growth. Of 74 patients treated, 22 (7 women, 15 men) with a median age of 37 years were evaluated with voiding diaries and computer urodynamic investigation. Urodynamic testing of 22 symptomatic patients revealed detrusor overactivity in 55%, low compliance bladder in 14%, detrusorsphincter dyssynergia in 45%, and uninhibited sphincter relaxation in 27%. Despite the description of incomplete emptying and urgency, 4 patients had normal urodynamic findings (18%). Brain magnetic resonance images of the lesions of the symptomatic patients were obtained to determine the side of lesions. The dorsolateral pons, including pontine reticular nucleus and the reticular formation and the locus coeruleus, seems to be mainly responsible for lower urinary tract symptoms in our patients with skull base chordoma and brainstem compression. UROLOGY 83: 756e761, 2014. 2014 Elsevier Inc.
T
here are a number of reasons for voiding dysfunction associated with stroke,1 multiple sclerosis, Alzheimer’s disease, multiple system atrophy, traumatic brain lesion, brain tumors, normal pressure hydrocephalus, Parkinson’s disease, and other cerebral disorders.2,3 Their incidence has not been fully evaluated and probably underestimated. Previous reports showed urinary dysfunction in 25% of frontal lobe tumors4 and in 22% of infarctions of anterior cerebral artery territory.5 Indeed, local brain lesions seem to cause urinary dysfunction in about 20%-50% of all patients with tumor and cerebrovascular accident.6 Lesions of the dorsolateral pons involving pontine reticular nucleus and reticular formations, located in the ventromedial or lateral areas of the pontine micturition center (PMC)7,8 and the locus coeruleus, are mainly responsible for the micturitional disturbance in patients with brainstem lesion.9,10 R. Akhavan-Sigari and M. Abili contributed equally. Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Neurosurgery, University Medical Center G€ottingen, GeorgAugust-University G€ottingen, Germany; the Department of Neurosurgery, Mashhad University of Medical Sciences, Mashhad, Iran; and the Department of Urology, Hannover Medical School, Hannover, Germany Reprint requests: R. Akhavan-Sigari, M.D., Department of Neurosurgery, University Medical Center G€ottingen, Georg-August-University G€ottingen, Robert-Koch-Strasse 40, 37075 G€ottingen, Germany. E-mail: [email protected] or reza.akhavan-sigari@ med.uni-goettingen.de Submitted: October 23, 2013, accepted (with revisions): December 13, 2013
756
ª 2014 Elsevier Inc. All Rights Reserved
Extra-axial tumors, such as skull base chordoma with expansion and brainstem compression, are likely to cause conditions of critical illness, such as disturbances of consciousness, ataxia, and convulsions. To the best of our knowledge, there have been no previous urodynamic studies of urinary symptoms in brainstem chordoma. With a view toward determining whether skull base chordoma with tumor expansion and compression of the pons and possibly PMC are connected with urinary disturbances, this study reports the results of micturitional histories, urodynamic studies, and magnetic resonance images (MRI) showing the location of the PMC in patients with brainstem compressing skull base chordoma. In our study, micturitional disturbance could not be found in patients with tumor expansion to the midbrain but was found in 75% of patients with pons and 20% with medullary compression. However, the accurate location of the lesion could not be determined.
METHODS Seventy-four chordoma patients were treated at the Neurosurgical Departments of the Nordstadt Hospital in Hannover and the Hannover Medical School, Germany, between 1986 and 2007. The patients (32 women and 42 men) ranged in age from 16 to 88 years (median, 58). Twenty-four patients experienced recurrence and subsequent resection. All patients underwent 0090-4295/14/$36.00 http://dx.doi.org/10.1016/j.urology.2013.12.018
UROLOGY 83 (4), 2014
Table 1. Results of urodynamic testing Residual Urine (mL)
UPmax (cm H2O)
FDV (mL)
MDV (mL)
Detrusor Hyperreflexia
DSD
USR
Low Compliance
Age, y
Sex
Diagnosis/Expansion
Latency*
Urinary Symptoms at the Time of Urodynamic
20
M
1d
Incomplete emptying, urgency
30
110
30
530
þ
18 55
M F
Chordoma R-midbrain/rostral pontine Chordoma pontine, tegmentum Chordoma midbrain, pontine
1d 3 mo
np np
57 np
55 312
600 480
þ
þ
þ
þ
53 25 55 28
M F M M
Chordoma Chordoma Chordoma Chordoma
2 mo 2d 1 mo 3d
55 0 85 np
36 27 52 15
110 58 35 214
278 268 63 350
þ þ þ
þ þ þ
39
M
5d
90
33
110
268
þ
þ
32 17
M F
1 mo 2d
Frequency, intermittency Incomplete emptying, urgency
65 0
64 45
58 320
430 586
þ
32
M
Frequency, intermittency
140
61
120
345
þ
þ
28 51 25 36 47 38 11 22 70 52 48
M M F M M F F M M M F
Chordoma midbrain, lat. medullary Chordoma pons Chordoma R-midbrain/rostral pontine Chordoma/midbrain and tegmentum Chordoma pontine basis Chordoma midbrain, pons Chordoma pons, tegmentum Chordoma mons, midbrain Chordoma rostral pontine Chordoma lat. medullary Chordoma pons, midbrain Chordoma tegmentum Chondrosarcoma midbrain Chordoma pons, lat medullary Chordoma med. medullary
Incomplete emptying, urgency Nocturia, incontinence, frequency, intermittency Pollakiuria, nocturia Frequency, intermittency Nocturia, urgency. Noctuna, frequency, intermittency Frequency, intermittency
Retension Urgency, Nocturia Frequency, intermittency Pollakiuria Retension Nocturia, pollakiuria Nocturia, urgency Incomplete emptying, urgency Retention Retention Retention
250 405 0 np 30 55 75 200 110 70 60
18 29 18 87 58 39 86 18 37 35 65
89 93 40 25 103 180 200 175 158 230 60
325 267 390 580 220 380 530 560 248 510 325
þ þ þ þ þ þ
þ þ þ þ þ
þ þ þ
þ
lat. medullary pons, medulla rostral pontine pons, medulla
4d 2d 5d 4d 3d 2 mo 6d 1d 2d 5y 3 mo 2 mo
DSD, detruor sphincter dyssynergia; FDV, first desire to void; MDV, maximum desire to void; Np, not performed; UPmax, maximum urethral closure pressure; USR, uninhibited sphincter relaxation. * Latency of urodynamic tests after the occurrence of the neurologic deficits.
757
Figure 1. Magnetic resonance imaging of a patient with enhancing, diffusely infiltrative tumor classified as a skull base chordoma. (A) Sagittal T1-weighted image after gadolinium infusion demonstrates an enlarged, heterogeneously enhancing tumor within the pons. (B) Axial T1-weighted image after gadolinium infusion.
Table 2. Patients with micturitional disturbances Age Micturitional Symptoms According to IPSS Questionnaires Urinary retention/incomplete emptying Weak stream/straining Nocturnal urinary frequency Frequency/intermittency Urinary urgency
Gender
50-70 (N ¼ 18)
50 (N ¼ 33)
Male (N ¼ 28)
Female (N ¼ 23)
51/74
69%
5 3 6 8 8
11 11 16 13 7
12 8 18 17 9
4 6 4 4 6
16 14 22 21 15
22% 19% 30% 28% 20%
IPSS, International Prostate Symptom Score.
brain MRI, and we excluded patients with status lacunaris, a condition occurring in cerebral arteriosclerosis, in which there are numerous small areas of degeneration in the brain known to cause micturitional disturbance11. All treated chordoma patients with adequate documentation for our study, that is, 51 of 74, were included. The International Prostate Symptom Score (IPSS) was used in the assessment of lower urinary tract symptoms (LUTS) in our patients with symptoms of voiding dysfunction. Twenty-two of the 51 patients described voiding difficulties and were given the IPSS questionnaire. These patients underwent urodynamic testing from 1 day (at the earliest possible time) after diagnosis, that is, preoperatively, and up to a maximum of 2 years after the operation of the skull base chordoma (Table 1). Urodynamics consisted of measuring residual urine, urethral pressure profilometry, and water cystometry as described previously.12 The sites of lesions are shown in Figure 1A, B.
RESULTS Owing to neurologic deficits such as low level of consciousness, dizziness, and gait disturbance, 51 patients had indwelling urinary catheters during the first week of hospitalization. We observed our patients for periods ranging from 6 months to 10 years. Voiding complaints included incomplete emptying, urgency, frequency, intermittency, staining, and nocturia. Urinary symptoms began within 3 months after onset of the neurologic symptoms, namely the signs of raised intracranial pressure (deterioration in the level of consciousness, headache, 758
pupillary dysfunction, vomiting, possible papilledema, and so forth). Increased intracranial pressure was mainly because of the occlusive hydrocephalus caused by the skull base chordoma compressing the midbrain and cerebral aqueduct. Fifty-one patients (69%) had urinary complaints (Table 2). Their major symptoms were frequency and intermittency (21 patients, 28%), nocturia (22 patients, 30%), followed by urinary retention (16 patients, 22%). All patients with tumor recurrence and urinary retention became unable to urinate 6 months from the onset. Voiding problems, especially nocturia, frequency, and intermittency, seemed to be present in all patients with skull base chordoma, especially in those with the expansion of the lesion to the dorsal medulla and tegmentum. Furthermore, urinary symptoms such as those mentioned previously seemed to be more common in patients with incoordination than in those without incoordination and also in patients with sensory disturbance and with abnormal eye movements. Urinary complaints were noted almost equally in patients with or without hemiparesis. In contrast, most of the patients without urinary complaints had lesions of the pontine basis and the lateral medulla. MRI images of our patients have revealed that the chordoma expansion of the patients with severe urinary symptoms was located mostly in the region of the dorsolateral pons, including the pontine reticular nucleus, the reticular formation nucleus, and the locus coeruleus (Fig. 2). UROLOGY 83 (4), 2014
Figure 2. Brainstem nuclei of selected autonomic nervous system. Midbrain periaqueductal gray matter (PAG) surrounds the mesencephalic aqueduct that contains a micturition center; this receives ascending projections from the sacral cord and sends axons to the pontine micturition center (PMC), which is located in the dorsal area of the pons. Medial and lateral parabrachial nuclei located in the rostral cerebellar peduncle fibers in the pons. The nuclei relay visceral information from the solitary tract nucleus and spinal cord to the hypothalamus, contralateral thalamus, and limbic system. (Color version available online.)
Results of Urodynamic Studies Of the 22 patients who described voiding problems and had been given the IPSS questionnaire, all had urinary problems at urodynamic testing. These included frequency and intermittency in 7, nocturia in 7, urinary retention in 5 (4 men and 1 woman), urgency in 3, incontinence in 1, and pollakiuria in 3 (Table 1). These symptoms continued together with the occurrence of the neurologic symptoms. Measurement of residual urine was performed on 15 patients, of which 13 (87%) had residual urine of 55-405 mL, with an average of 128 mL. Water cystometry was performed on all patients, and the bladder volume at first desire UROLOGY 83 (4), 2014
to void and/or maximum desire to void was decreased in 17 (77%) and increased in 7 (32%) patients. Detrusor overactivity was noted in 12 (55%), low-compliance bladder in 3 (14%), detrusor-sphincter dyssynergia in 10 (45%), and uninhibited sphincter relaxation in 6 patients (27%). Four of 22 patients stated having incomplete emptying and urgency, but the urodynamic studies revealed normal findings.
COMMENT That a posterior fossa tumor can cause voiding dysfunction has long been known.13 However, little attention 759
has been paid to this because compression on the brainstem commonly causes a serious neurologic state characterized by disturbed consciousness or respiratory arrest. Our study reveals that 51 of 74 patients (69%) with skull base chordoma and brainstem compression had urinary problems. Urinary symptoms appear with the occurrence of acute brainstem compression because of the expansion of the skull base chordoma and could be regarded as neurogenical origin. The major symptoms were voiding difficulty in 7 patients (32%) and nocturia in 7 (32%), urinary retention in 5 (23%), and urinary incontinence in 1 (5%). The incidence of urinary difficulties in our patients, therefore, seems quite high. Previously, studies14 have stated that voiding difficulty could be a sign of posterior fossa tumors. In 1960, Ueki15 described 152 cases of posterior fossa tumors and found urinary incontinence in 3 (1.9%) and voiding difficulty in 46 (30%). Voiding difficulty was also noted by Betts16 and Baillieux17 in a patient with midbrain-rostral pontine tumor. Our study indicates that urinary symptoms such as urine storage and voiding dysfunction may also be common in patients with space-occupying lesions in the skull base tumors. Voiding dysfunctions in our patients seemed to be more common in chordoma with expansion to the dorsolateral pons, pontine reticular nucleus, reticular formation, and the locus coeruleus. Responsible Sites of Urinary Dysfunction Previous reports have indicated the significance of the pontine lesions within the brainstem with regard to micturitional disturbance.9,15,18 Ueki15 found voiding difficulty in 77.3% of patients with pons lesions, 66.7% with fourth ventricle lesions, 40.9% with lesions in the midline of cerebellum, 24.2% with cerebellar hemisphere lesions, and 9.1% with cerebellopontine angle in posterior fossa tumors. Urinary retention was also found in 71% of 17 children with pontine glioma by Renier et al.19 In a study by Sakakibara et al,1 of 30 clinically diagnosed brainstem infarctions, micturitional symptoms occurred in none with lesions in the midbrain but in 35% of patients with lesions in the pons and in 18% with medulla lesions. Urinary disturbance has also been reported in patients with acute infarction in the right lateral medulla who had voiding difficulty as an initial manifestation. Urodynamic study showed detrusor areflexia on voiding, and the voiding difficulty completely disappeared 2 weeks after the stroke onset.20 It has long been known in experimental animals that destruction of brain areas above the pons (supracollicular or intercollicular decerebration) did not impair micturition; however, infracollicular decerebration or transection of the neuraxis at any point caudal to the pons immediately abated micturition.21 These findings in laboratory animals seem to correspond to the aforementioned findings in human cases. LUTS may be associated with various neurologic signs, which could be attributable to the lesions near or adjacent to the micturitional area within the brainstem. The present study reveals 760
that LUTS seems common in patients with hemiparesis, sensory disturbance, abnormal eye movement, and incoordination (symptomatic of brainstem lesions), although there was no statistical significance. Similar to findings in the research by Sakakibara et al,9 the aforementioned findings seem to indicate that LUTS is associated with neurologic signs mainly seen in the dorsolateral brainstem. MRI showed that the responsible sites of the lesions appear to be located in the dorsolateral pons, including the pontine reticular nucleus and the reticular formation, adjacent to the medial parabrachial nucleus and the locus coeruleus. Urodynamic Findings and the Mechanism of Urinary Dysfunction Urodynamics carried out in 22 patients revealed a variety of findings, including detrusor overactivity in 12 patients (55%), low-compliance bladder in 3 (14%), detrusorsphincter dyssynergia in 10 (45%), and uninhibited sphincter relaxation in 6 patients (27%). The other 4 patients had normal findings. There are only a few urodynamic studies previously described of patients with brainstem lesions,9,22 and their findings are similar, with detrusor overactivity in lateral medullary lesions. Betts et al16 and Manente et al23 each described patients with midbrain-rostral pontine tumors detected using MRI with persistent detrusor areflexia. A transient hypocontractile bladder was described by Sakakibara et al24 with herpetic encephalitis localized at the pontine tegmentum with MRI. Detrusor areflexia in these various cases could be regarded as the “shock phase”, although some of the detrusor areflexias were more persistent.9 Detailed follow-up was available in 17 of 22 patients postoperatively. After some follow-up periods and repeated urodynamic studies, detrusor overactivity had completely disappeared in 11 patients (64.7%) within 3 years. Five patients (29.4%) with low-compliance bladder and urinary retention became able to urinate after a follow-up period of 6 months. Finally, detrusor-sphincter dyssynergia and uninhibited sphincter relaxation were still observed after a period of 5 years in 6 patients (35.2%).
CONCLUSION On the basis of our study, we suggest that skull base chordomas invading the dorsolateral pons, pontine reticular nucleus, reticular formation, and the locus coeruleus (PMC) are mainly responsible for the micturitional disturbance in patients with brainstem lesion. References 1. Sakakibara R, Hattori T, Tojo M, et al. Micturitional disturbance in patients with brainstem infarction. J Auton Nerv Syst. 1995;50: 362-363. 2. Zhang H, Reitz A, Kollias S, et al. An fMRI study of the role of suprapontine brain structures in the voluntary voiding control induced by pelvic floor contraction. NeuroImage. 2005;24:174-180. 3. Verne GN, Himes NC, Robinson ME, et al. Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome. Pain. 2003;103:99-110.
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4. Fowler CJ, Griffiths DJ. A decade of functional brain imaging applied to bladder control. Neurourol Urodyn. 2010;29:49-55. 5. Kang SY, Kim JS. Anterior cerebral artery infarction stroke mechanism and clinical-imaging study in 100 patients. Neurology. 2008; 70:2386-2393. 6. de Groat WC. A neurologic basis for the overactive bladder. Urology. Dec 1997;50(Suppl):36-52; discussion 53-56. 7. Griffiths D, Holstege G, Dalm E, Wall HD. Control and coordination of bladder and urethral function in the brainstem of the cat. Neurourol Urodyn. 1990;9:63-82. 8. Nishizawa O, Sugaya K. Cat and dog: higher center of micturition. Neurourol Urodyn. 1994;13:169-179. 9. Sakakibara R, Hattori T, Yasuda K, Yamanishi T. Micturitional disturbance and the pontine tegmental lesion: urodynamic and MRI analyses of vascular cases. J Neurol Sci. 1996;141:105-110. 10. de Groat WC. Central neural control of the lower urinary tract. Ciba Found Symp. 1990;151:27-44; discussion 44-56. 11. Feder M, Heller L, Tadmor R, et al. Urinary continence after stroke: association with cystometric profile and computerised tomography findings. Eur Neurol. 1987;27:101-105. 12. Abrams P, Cardozo L, Fall M, et al; Standardisation SubCommittee of the International Continence Society. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003;61:37-49. 13. Holman E. Difficult urination associated with intracranial tumors of the posterior fossa: A physiologic and clinical study. Arch Neurol Psychiatry. 1926;15:371-380.
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14. Cuccurullo S, ed. Cancer Rehabilitation. New York, NY: Demo Medical Publishing; 2004. Available at: http://www.ncbi.nlm.nih. gov/books/NBK27276/. Accessed September 3, 2013. 15. Ueki K. Disturbances of micturition observed in some patients with brain tumor. Neurol Med Chir (Tokyo). 1960:25-33. 16. Betts CD, Kapoor R, Fowler CJ. Pontine pathology and voiding dysfunction. Br J Urol. 1992;70:100-102. 17. Baillieux H, Smet HJD, Lesage G, et al. Neurobehavioral alterations in an adolescent following posterior fossa tumor resection. Cerebellum. 2006;5:289-295. 18. Iwasaki H, Koyama Y, Tanaka Y, et al. Modulation by desmopressin of neuronal activity in brainstem micturition center. Urology. 2004; 63:994-998. 19. Renier W, Gabreëls F, Conen M. Evaluation of diagnosis and NonSurgical Therapy in 24 children with a pontine tumour. Neuropediatrics. 1979;10:446. 20. Lee KB, Jang IM, Roh H, et al. Transient urinary retention in acute right lateral medullary infarction. Neurologist. 2008;14:312-315. 21. Blok BF. Central pathways controlling micturition and urinary continence. Urology. 2002;59(Suppl 1):13-17. 22. Nathan PW, Smith MC. The centrifugal pathway for micturition within the spinal cord. J Neurol Neurosurg Psychiatry. 1958;21:177-189. 23. Manente G, Melchionda D, Uncini A. Urinary retention in bilateral pontine tumour: evidence for a pontine micturition centre in humans. J Neurol Neurosurg Psychiatry. 1996;61:528-529. 24. Sakakibara R, Hattori T, Fukutake T, et al. Micturitional disturbance in herpetic brainstem encephalitis; contribution of the pontine micturition centre. J Neurol Neurosurg Psychiatry. 1998;64:269-272.
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