Secondary Signal Change and an Apparent Diffusion Coefficient Decrease of the Substantia Nigra After Striatal Infarction
Background and Purpose—Diffusion-weighted imaging can depict secondary signal change of the substantia nigra of patients with ipsilateral striatal infarction via a decrease in the apparent diffusion coefficient (ADC). Clinical predictors of this phenomenon remain unclear.
Methods—We assessed 98 stroke patients with acute ischemic lesions in the hemilateral basal ganglia, external capsule, or internal capsule. The ADC values of the bilateral substantia nigra obtained from a follow-up MRI, various clinical factors, and patients’ outcome were analyzed. Nineteen patients who underwent a follow-up MRI within 3 days were excluded from analysis because none of them demonstrated a significant ADC change of substantia nigra.
Results—Of 79 patients, 21 (26.6%) revealed a decreased ADC in the substantia nigra. Ischemic lesions in the globus pallidus (odds ratio 12.90) and the presence of emboligenic diseases (odds ratio 6.95) were independent predictors for an ADC decrease in the substantia nigra. The clinical outcome 3 months after stroke onset was not different between patients with an ADC decrease and patients without.
Conclusions—A reduction of ADC in the substantia nigra after acute striatal infarction was more frequently observed when the globus pallidus was affected or when the patient had emboligenic diseases, however, did not necessarily relate to the patient’s clinical outcome.
Secondary signal change (SSC) of the substantia nigra (SN) after ipsilateral striatal infarction, detected by MRI, is one of the most well-known remote effects after focal brain damage.1–4 Diffusion-weighted imaging is capable of depicting this SSC as a hyperintense signal with a decreased apparent diffusion coefficient (ADC) more sensitively and earlier than other techniques.5–8
SSC of the SN is not always observed in patients with striatal infarction, and clinical predictors for this phenomenon have not yet been resolved. In previous reports, some clinical factors were suspected to have a relationship with the SSC of the SN.7,8 However, there have been no large-scale studies performed capable of elucidating the relationship between these factors and the SSC of the SN by analyses, including multivariate analysis. Additionally, the prognosis of patients who presented with SSC of the SN is unclear.4
The purpose of this study is to investigate the clinical characteristics and outcome of acute stroke patients who reveal an ADC decrease of the SN.
We prospectively collected consecutive stroke patients with acute ischemic lesions in the hemilateral basal ganglia on diffusion-weighted imaging performed at admission and who underwent follow-up MRI within 3 weeks.7,8 The basal ganglia included caudate head, putamen, globus pallidus, external capsule, and internal capsule. We excluded patients with any brainstem lesions or bilateral basal ganglia lesions. A total of 168 patients fulfilled the inclusion criteria, and 70 patients whose complete assessment by MRI was not obtained were excluded: pacemaker implantation (n=2), old lesions on the basal ganglia (n=7), no follow-up MRI (n=39), and a motion artifact or other technical issues (n=22). An informed consent was obtained from all of them or their family members.
We used a 1.5 T unit MRI system. In evaluation of secondary degeneration of the SN, we used an absolute ADC value on an ADC mapping image. A region of interest was manually drawn in the SN, at the level of the superior colliculus in all subjects (Figure).9 We defined the normal ADC range of the SN from analysis of images of control subjects. We calculated the ADC ratio of the SN (ADC contralateral to the symptom side/ADC ipsilateral to the symptom side) in each subject. When the ADC ratio is <−2 SD (<0.78), the patient was regarded as having a significant decrease of ADC of the SN.
We preliminarily investigated the relationship between the time interval from the onset of stroke to the MRI and the change of the ADC of the SN. Of 98 patients, none of the 19 patients who underwent follow-up MRI within 3 days of onset demonstrated a significantly decreased ADC ratio of <0.78. Therefore, we decided to analyze the ADC of the SN on MRI performed 3 days from onset. In 4 patients who underwent MRI twice 3 days after onset, we used a lower ADC ratio.
We divided the patients into 2 groups: those with a decreased ADC of the SN and those without a decreased ADC. The clinical factors were compared between the 2 groups. Additionally, we investigated the patients’ outcome in each group: the ΔNIHSS (National Institutes of Health Stroke Scale [NIHSS] score day 10−NIHSS score on day 0), functional outcome on discharge, and 3 months after onset (by a mailed questionnaire).
The Mann–Whitney U test, the χ2 test, or Fisher exact test was used for univariate analysis. Then, we performed logistic regression analysis with the step-up procedure. P values <0.05 were considered significant.
Of 79 patients, 21 (26.6%) showed a decreased ADC of the SN. On univariate analysis, the recanalization of the MCA, emboligenic diseases, globus pallidus lesions, and caudate nucleus lesions were most frequently observed in patients with an ADC decrease of the SN (Table 1). Based on logistic regression analysis, globus pallidus lesions and the presence of emboligenic diseases were independent predictors of an ADC decrease of the SN (Table 2). These results did not change after adjustment by NIHSS score on admission or ischemic lesion volume.
No statistically significant difference was observed between median NIHSS score at day 10 in patients with an ADC decrease of the SN and in those without (15 versus 11; P=0.23). However, median ΔNIHSS scores indicated a preferable trend to patients with an ADC decrease of the SN (−3 versus −1; P=0.06). The modified Rankin Scale score (5 versus 5; P=0.49) and Barthel index (5 versus 20; P=0.23) on discharge, and the modified Rankin Scale score 3 months were not different between the 2 groups (5 versus 4; P=0.10).
In this study, we provided 3 major findings about the ADC values of the SN after acute ipsilateral striatal infarction. First, globus pallidus lesions and the embolic mechanism have an independent relationship with an ADC decrease of the SN. Second, an ADC decrease of the SN begins 3 days after the index stroke. Third, an ADC decrease of the SN was not related to the patients’ clinical outcome.
The relationship between the globus pallidus ischemic lesions and the ADC decrease of the SN was an intriguing finding. Putaminal lesions did not reveal an independent relationship, unlike a previous report using T2-weighted imaging.2 In human beings, unlike in rats,10 the GABAergic inhibitory pathway from the neostriatum, including the caudate head and putamen, mainly projects into the pars reticulata, whereas the pathway from the paleostriatum, including the globus pallidus, projects into the pars compacta.11 Therefore, the relationship between the globus pallidus lesions and an ADC decrease of the SN in our study was consistent with previous reports that the neuropathologic changes in the SN mainly occurs in the pars compacta.1,2,12
The presence of emboligenic diseases was related to an ADC decrease of the SN in the study, which confirmed the validity of our hypothesis that sudden, destructive damage to the striatum may be related to SSC of the SN.7,8
In this study, we could not find any patients who presented a significant ADC decrease of SN within 3 days after stroke onset. Because the MRI results were not assessed on any successive days in this observational study, we cannot conclude that an ADC decrease of the SN begins approximately at 4 days.
An ADC decrease of the SN was not related to the short-term and long-term clinical outcomes. Because striatal lesions do not cause any severe neurologic deficits, clinical symptoms of the participants were presumably attributed to cortical or other subcortical lesions, including those of the pyramidal tract.
- Received August 2, 2012.
- Revision received September 27, 2012.
- Accepted October 1, 2012.
- © 2012 American Heart Association, Inc.
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