J Neurooncol (2007) 84:8589 DOI 10.

1007/s11060-007-9345-z

CLINICAL STUDYPATIENT STUDIES

Intramedullary spinal cord metastases: a single-institution experience

Sung Sook Lee Min Kyoung Kim Sun Jin Sym Sang Wee Kim Woo Kun Kim Sung-Bae Kim Jin-Hee Ahn

Received: 16 November 2006 / Accepted: 26 January 2007 / Published online: 20 February 2007 Springer Science+Business Media B.V. 2007

Abstract Background Intramedullary spinal cord metastasis (ISCM) is the rarest type of CNS involvement of systemic malignant tumors. The aim of this retrospective study is to evaluate the clinical features, treatment and natural course of patients with ISCM in a single institution of Korea. Methods We reviewed the medical records of all patients diagnosed with secondary malignant neoplasms involving the spinal cord at the Asan Medical Center between January 1995 and August 2006. Patients were diagnosed with ISCM if they had pathologically established malignancies originating outside the central nervous system (CNS), neurologic symptoms suggestive of spinal cord dysfunction, and either abnormal spinal MRI ndings suggestive of ISCM or surgical or postmortem conrmation of ISCM. We excluded patients in whom ISCM was suspected because of known cancer and myelopathy, but with normal neuroimaging results. Results All 12 ISCMs arised from breast cancer (six patients) and lung cancer (three small cell lung cancer, three non-small cell lung cancer). Eight lesions were in the thoracic cord, one in the cervical cord, and three in both. In 11 patients, brain metastasis were combined with the development of ISCM. Initial symptoms included various paresthesias, sensory loss, and leg weakness. The duration of symptoms before diagnosis

ranged from 2 days to 8 months (median, 7 days). Despite radiotherapy, neurologic status usually deteriorated rapidly, within a period of days to weeks. Median survival after ISCM diagnosis was 3.9 months (range 0.818.4 months) for all patients (breast cancer 5.5 months vs. lung cancer 1.0 month). Conclusion Our ndings indicate that ISCM is a very rare type of CNS involvement and represents a dismal nding of systemic malignancy. ISCM patients arising from breast cancer appeared to fare better than those with lung cancer. Keywords Intramedullary spinal cord metastases (ISCM) Breast cancer Lung cancer Prognosis

Introduction Intramedullary spinal cord metastasis (ISCM) is a rare condition, representing 8.5% of central nervous system (CNS) metastases. It affects 0.10.4% of all cancer patients and comprises 13% of all intramedullary spinal cord neoplasms [1, 2]. Close to 50% of all ISCMs arise from primary lung cancer, with small cell carcinoma being the most common, with the remainder originating from primary cancers of the breast, colon, and kidney, and from melanomas and lymphomas [3]. Symptoms at presentation are usually pain and/or weakness. Neurologic status deteriorates rapidly, within a period of days to weeks, with progression to a cord hemisection syndrome (Brown-Sequard) or full cord transection occurring in approximately half of the patients. Pain is usually followed by sensory level and sphincter disturbance. ISCMs arise mainly by the arterial route, although direct invasion through the

S. S. Lee M. K. Kim S. J. Sym S. W. Kim W. K. Kim S.-B. Kim J.-H. Ahn (&) Division of Oncology, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736, Korea e-mail: drjiny@amc.seoul.kr

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spinal roots or leptomeninges can also occur, and retrograde spread through the Batson plexus during the Valsava maneuver has also been suggested. The thoracic region of the cord is the most common site of involvement. CSF cytological results are usually negative and myelography may fail to show the ISCM [46]. More accurate diagnostic procedures, such as highresolution magnetic resonance imaging (MRI), are likely to increase the detection of ISCM in living patients [7]. Early diagnosis and prompt treatment have been recognized as important in improving the survival of cancer patients. Although there have been a few sporadic reports and retrospective reviews of ISCM, there are no available data about the development of ISCM in Orientals. We therefore assessed the clinical features, therapy and natural course of Korean patients with ISCM in a single institution.

Results Patient characteristics Of the 12 patients, four were men (33.3%) and eight were women, with a median age of 59 years (range 3277 years). In our series, all ISCMs were arised from breast cancer (six patients) and lung cancer (three small cell lung cancer (SCLC), three non-small cell lung cancer (NSCLC)). Entire neuraxis imaging was performed on all patients. Eight lesions were in the thoracic cord, one in the cervical cord, and three in both (Fig. 1). ISCM was detected at a median of 11.9 months (range, 0 ~ 91.2) after diagnosis of primary cancer. The duration of symptoms related to ISCM before diagnosis ranged from 2 days to 8 months (median, 7 days). Two patients had symptoms for more than 3 months before diagnosis. The initial symptoms included sensory alteration (ve patients, 42%), lower extremity weakness (three patients, 25%), urinary incontinence (two patients, 17%), and paraplegia/ paralysis (four patients, 33%). Among ve patients showing sensory alteration, two patients also complained of back pain. Involvement of other CNS sites was common. Among 12 patients, both brain metastasis and ISCM were diagnosed simultaneously in seven patients, ISCM occurred after the development of brain metastasis in three patients, and ISCM occurred before the development of brain metastasis in one patient. The other one NSCLC patient did not exam brain imaging study. Leptomeningeal involvement was suspicious in only one patient by spinal MRI, but cancer cells were not detected in CSF (cerebrospinal uid) analysis. Although CSF examination was performed in three other patients, cancer cells were not observed in

Materials and methods We retrospectively reviewed the medical records of all patients diagnosed with secondary malignant neoplasms, or bone marrow malignancy involving the spinal cord at the Asan Medical Center between January 1995 and August 2006. Patients were diagnosed with ISCM if, and only if, they had pathologically established malignancies originating outside the CNS, neurologic symptoms suggestive of spinal cord dysfunction, and either abnormal spinal MRI ndings suggestive of ISCM or surgical or postmortem conrmation of ISCM [3]. We excluded patients suspected of having ISCM because of known cancer and myelopathy, but whose neuroimaging results were normal. Neuroimaging studies consisted of spinal MRI, performed with sagittal views using T1-weighted, fast spindensity, and T2-weighted imaging with axial views at areas of interest. We assessed sites of primary neoplasms, intervals from the original diagnosis of cancer to the onset of neurologic symptoms, presenting neurologic signs and symptoms, time course from initial neurologic symptoms to development of a complete neurologic decit, outcomes after medical or surgical interventions and intervals until death. Overall survival was dened as the time from the date of intramedullary spinal cord metastases to the date of death or last follow-up. The probability of overall survival was calculated according to the Kaplan-Meier method and the difference in survival was compared by the log-rank test.

Fig. 1 (A) Shows the cervical lesions indicating enhancement at the C6 level compatible with ISCM on the contrast-enhancing T1-weighted image. (B) T2-weighted MRI view in the same patient indicating multiple enhancing intramedullary metastases at C6, T7 ~ 9

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all cases. Instead, CSF examinations of all four patients showed abnormally elevated protein level. Treatment and outcome The patient characteristics and clinical course of each of the 12 patients are shown in Table 1. Eleven of the ISCM patients (91%) received fractionated external beam radiotherapy (RT), with total doses from 20003000 cGy (median 3000 cGy), and the remaining one patient, however, refused treatment. Because paraplegia supervened in above half of the patients at diagnosis, motor function was not recovered by local radiation therapy to involved spinal cord. Two patients experienced transient improved motor function after treatment. However, in all patients, neurologic status deteriorated rapidly within a period of days to weeks, with progression to a cord hemisection syndrome or full cord transection. For all 12 patients with ISCM, the median overall survival after ISCM diagnosis was 3.9 months (range 0.818.4 months, Fig. 2). Patients with ISCM arising from breast cancer showed a more favorable clinical course than those with lung cancer (median survival, 5.5 months vs. 1.0 month).

Discussion ISCM is a rare complication of cancer that causes serious diagnostic and therapeutic problems. Although this complication have been studied by MRI more frequently in the clinical context to improve the survival of cancer patients, only a few small case reports have been published. In the literature, lung cancer especially SCLC accounts for a majority of cases, with

breast cancer, melanoma, lymphoma, renal cell carcinoma, and other common culprits [8, 9]. In our data, a retrospective review identied six breast cancer patients and six lung cancer patients with clinical symptoms of myelopathy and abnormal neuroimaging ndings consistent with ISCM [3]. Our study corroborates previous epidemiologic data regarding ISCM based on combinations of previously reported small case series. Patients with ISCM also have diseases at other levels of the CNS. A majority of patients with ISCM are known to have brain metastases and systemic metastasis at the time of diagnosis [10]. Indeed, in 83% of our patients, both brain metastasis and ISCM were diagnosed simultaneously or ISCM occurred either before or after the development of brain metastasis. Since several patients had asymptomatic brain metastasis, brain imaging should be considered for all patients with ISCM. In our data, cytologically identiable tumor was not seen in CSF analysis, but CSF analysis was abnormal in all patients who performed CSF examination, showing abnormally elevated protein level. Grem et al reported that a protein level greater than 50 mg/dl was observed in 95% of patients and cancer cells are only seen in 18% of CSF analysis [11]. Although one previous report suggested that onequarter of ISCM patients had concomitant leptominingeal carcinomatosis, CSF analysis does not provide specic diagnostic information regarding ISCM [8]. The greater the neurologic decit, the worse the chance of recovering lost function. Thus, grading spinal cord function prior to treatment can be regarded as a type of prognostic evaluation, using a scale for grading functional loss [12]. It is reported that patients usually present with rapidly progressive myelopathy over several weeks, but it may occur more slowly [5, 6, 1318].

Table 1 Treatment modality and outcomes

Patient Sex Age Primary Interval from No. (yr) primary diagnosis to brain metastasis (mon) 1 2 3 4 5 6 7 8 9 10 11 12 F F F F F F M M F F M M 57 50 49 62 32 59 61 63 65 32 77 73 Breast 62.2 Breast 51.3 Breast 83.5 Breast 86.9 Breast 7.2 Breast 11.0 SCLC 0.0 SCLC 13.1 SCLC 10.1 NSCLC 6.8 NSCLC 0.2 NSCLC NA

Interval from Treatment primary to ISCM diagnosis to ISCM (mon) 59.1 51.3 83.5 91.2 10.4 11.9 9.5 13.9 10.1 7.9 0.2 0.0

Overall survival after ISCM diagnosis (mon) (Death) (Death) (Death) (Survival) (Death) (Survival) (Death) (Death) (Death) (Death) (Death) (Death)

Abbreviations: SCLC, small cell lung cancer; NSCLC, non-small cell lung cancer; NA, not assessable; RT, radiotherapy

RT + steroid 3.9 RT + steroid 5.5 RT + steroid 9.0 RT + steroid 5.1 RT + steroid 3.9 RT + steroid 4.9 RT + steroid 2.1 RT + steroid 1.0 RT + steroid 8.8 RT + steroid 0.8 RT + steroid 1.0 Refuse 18.4

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OS after ISCM diagnosis

.8

.6

Median OS 3.9 months (range, 0.8-18.4 months)

.4

.2 0.0 0 5 10 15 20

elsewhere showing that ISCM patients arising from breast cancer tend to do better than other types of cancer [3]. In summary, our ndings indicate that ISCM represents a dismal nding of systemic malignancy, with short median survival after diagnosis. However, ISCM patients arising from breast cancer appeared to fare better than those with lung cancer. Early suspicion of ISCM and treatment before the development of paralysis is required to improve neurologic decit and survival of patients diagnosed as ISCM.

Time (months)

Fig. 2 Overall survival after ISCM diagnosis

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We found that the initial symptoms included various paresthesias, sensory loss, and leg weakness, lasting 2 days to 8 months (median, 7 days) before diagnosis. Although two patients showed a transient neurologic improvement after local radiotherapy, their motor function became worse eventually. In all patients, neurologic status deteriorated and they could not walk and became bedridden. Optimal treatment after diagnosis remains controversial. Since there have been no prospective clinical trials on the treatment of ISCM, treatment recommendations are based on anecdotal experiences described in retrospective reports. External beam radiation with concomitant corticosteroids has been the most effective method of treating ISCM before the development of paraplegia [3, 4, 7, 14, 19]. This treatment modality has been known to relieve the progression of neurologic symptoms and decrease pain. In our data, only a few patients were diagnosed as ISCM before the development of paralysis, and most patients showed poor response to local radiation treatment. Stereotactic radiosurgery has been shown to be effective in primary vascular tumors of the spinal cord, but there is not sufcient information supporting its use in ISCM. Currently, aggressive surgery for ISCM has been considered in selected ISCM patients, especially those presenting with previously undiagnosed or limited primary tumors, since surgery may improve the length and quality of survival [20, 21]. As with other CNS metastasis, patients with ISCM have a very short life expectancy, with a median survival of 3 to 4 months from the time of diagnosis [3, 6]. In our study, median survival of all patients was only 3.9 months (range 0.818.4 months). Patients with lung cancer showed worse prognosis than those with breast cancer (median survival, 1.0 month vs. 5.5 months). Theses ndings are comparable to those reported

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