Progressive motor deficits in lacunar infarction

Methods.

The patients studied in this retrospective evaluation were drawn from a population of 222 consecutive patients with supratentorial lacunes in the internal capsule or the corona radiata who were admitted between April 1, 1989, and March 31, 1995, to St. Mary’s Hospital, Kurume, Japan. Lacunar infarction was defined as an acute focal neurologic deficit that lasted more than 24 hours, consistent with one of the following five classic lacunar syndromes3,4: pure motor hemiparesis, pure sensory stroke, ataxic hemiparesis, dysarthria–clumsy hand syndrome, and sensorimotor stroke. All patients had small (≤1.5 cm in diameter) infarcts in the basal ganglia or deep white matter as demonstrated on brain CT and MRI. Of these patients, 84 who had been admitted more than 24 hours after becoming aware of their stroke symptoms, 29 who had a previous history of stroke, and 16 who had no motor deficits were excluded from the study. One patient who had complete paralysis on admission was also excluded. Thus, the study group comprised 92 patients (47 men, 45 women) with a mean age of 69.4 ± 10.9 (SD) years.

Each patient was examined daily by the same neurologist, and based on documented changes in motor deficits, the patients were classified into two groups: those with progressive lacunar infarction and those with stable infarction. Motor deficits were assessed according to the Hemispheric Stroke Scale.5 Although the original scale grades arm and leg strength on an 8-point scale, it is difficult to differentiate grades 1 (positive drift of arm or leg), 2 (mild weakness), and 3 (moderate weakness). Therefore, we graded arm and leg strength on a 6-point scale: grade 0, normal; 2, weakness against resistance; 4, moves against gravity but no resistance; 5, motion without gravity only; 6, trace movement only; and 7, no movement. The upper and lower extremities of the affected side were scored separately, and the sum of the two motor deficit scores was used for evaluation (14 points equivalent to hemiplegia). Lacunar infarction was considered to be progressive if the sum of the two scores increased between admission and the day after admission by ≥1 point. We did not consider changes in sensory disturbance, because sensory disturbances are more difficult to assess quantitatively.

The two groups were compared regarding clinical profile obtained on admission; changes in blood pressure, hematocrit, and blood glucose levels after admission; radiologic findings; and functional status noted at discharge. The following factors were considered in the clinical profile: time of arrival at the hospital after awareness of stroke symptoms, age, gender, history of hypertension (defined as past use of antihypertensive agents or blood pressure recordings before stroke onset with systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥95 mm Hg), history of diabetes mellitus (use of insulin or oral hypoglycemic agents, fasting blood glucose ≥140 mg/dL, or random blood glucose ≥200 mg/dL), history of hypercholesterolemia (use of antilipotropic agents, or total cholesterol on admission ≥220 mg/dL), type of lacunar syndrome, severity of motor deficits, and blood pressure and hematocrit levels on admission. As for radiologic findings, the two groups were compared regarding the presence of a focal hypodense lesion consistent with the neurologic findings on admission CT, the site and size of the infarct, and the incidence of coexisting silent ischemic lesions. CT was performed with a Shimadzu (Kyoto, Japan) SCT-3000T scanner (340 × 340 matrix) or a General Electric (WI) CT HiSpeed Advantage scanner (512 × 512 matrix) with a slice thickness of 10 mm. We evaluated the size of the infarct and the incidence of coexisting silent ischemic lesions using MRI (Siemens [Erlangen, Germany] Magnetom H15, 1.5 T, with a slice thickness of 5 mm) performed 12.8 ± 8.4 days (range, 3 to 33 days) after stroke onset. Infarct size was evaluated at the maximal diameter by means of precontrast axial T2-weighted scan. All lesions more than 5 mm in diameter with low intensity in T1-weighted images and high intensity in T2-weighted images, except for the lesion responsible for the symptoms, were defined as silent ischemic lesions. The condition of the middle cerebral artery trunk from which the perforating artery responsible for the symptom departed was also evaluated using MR angiography performed at the same time as MRI. Functional status at discharge was assessed by the Barthel index.6

Results.

Clinical characteristics of progressive lacunar infarction.

Of the 92 patients, 25 had progressive infarction and 67 were classified into the stable infarction group. In the progressive infarction group, 18 patients (72%) were administered glycerol and 16 (64%) were administered low–molecular-weight dextran. In the stable infarction group, 39 patients (58%) were administered glycerol and 43 (64%) were administered low–molecular-weight dextran. No patients in either group were administered aspirin, ticlopidine, or heparin as their initial treatment. There were no significant differences regarding the initial treatment.

Among patients with progressive infarction, 22 showed deterioration in both arm and leg strength. In 3 patients, deterioration was restricted to arm strength. The number of days to maximal motor deficits ranged from 2 to 6, whereas the severity of maximal motor deficits differed according to the number of days. That is, the incidence of severe motor deficits increased when motor deficits progressed beyond the second hospital day (p < 0.05, chi-square test, figure 1).

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Figure 1. Number of days to maximal motor deficits in the progressive group. The incidence of severe motor deficits increased significantly when motor deficits progressed beyond the second hospital day. Moderate motor deficits indicate that the sum of the motor deficit scores of the upper and lower extremities was between 5 and 9 points. Severe motor deficits indicate that the sum was ≥10 points. There were no patients whose maximal motor deficits were mild (the sum was ≤4 points).

Functional status at discharge.

In patients without progression, functional status at discharge was good in most. On the other hand, in patients with progression, functional status was varied. Statistically, functional status at discharge was worse in the progressive group than in the stable group (median Barthel index for the progressive group was 45 versus the stable group, which was 100; p < 0.001, Mann-Whitney U test) and the incidence of poor functional status (Barthel index < 60) was significantly higher in patients with progression than in those without (p < 0.001, chi-square test; figure 2).

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Figure 2. Functional status at discharge. The incidence of poor functional status (Barthel index < 60; ▪) was significantly higher and good functional status (Barthel index ≥ 60; □) was significantly lower in patients with progression than in those without (p < 0.001, chi-square test).

Discussion.

Some patients with lacunar infarction show progression of their neurologic deficits. According to the Harvard Cooperative Stroke Registry,7 62% of lacunar infarctions progress or fluctuate. Stroke studies have demonstrated that progression of neurologic deficits is associated with increased mortality and more severe functional disabilities.8-10 Whether progression of neurologic deficits has the same implication in lacunar infarcts has been unclear.

The terms progressing stroke, stroke-in-progression, or stroke-in-evolution have various definitions. In the current study we evaluated patients who were admitted to the hospital within 24 hours of onset, and we defined progression as motor deficits that deteriorated after admission, meaning that there was worsening of their clinical findings even after medical care began.11 Furthermore, because a previous report suggested that the mechanism involved in progression is different between those patients who deteriorate early after onset and those who deteriorate later,12 we focused on progression between admission and the day after admission. According to this definition, it may be possible that some patients with progression of motor deficits were mistakenly classified into the stable infarction group due to the fact that the patient had been admitted to the hospital late after onset of the symptoms and the evaluator could not confirm progression in the early stages. Although we could not exclude this possibility completely, in the current study, time to presentation did not differ between the two groups. Furthermore, as for four patients who complained of progression of motor deficits before admission in the stable infarction group, we evaluated neurologic symptoms repeatedly and confirmed that motor deficits had not progressed after admission, which was in contrast to the patients in the progressive group, in whom motor deficits progressed even after medical care had begun, with progression continuing beyond the first hospital day. Considering these facts, the possibility of having made a mistake when classifying patients into the two groups would be very low. Based on this definition, the incidence of patients with progression was 27%. Because published studies have not followed uniform criteria, it is difficult to compare our findings with those of previous studies. However, previous studies1,2,7,13,14 have demonstrated that neurologic deficits progressed after admission in as many as 8 to 62% of patients. These results confirm that we should regard progressive lacunar infarction as important when treating these patients.

Progression of motor deficits after admission was strongly related to poor functional outcome, which means that it is imperative to identify those factors that have the capacity to predict progression and to make a maximal effort to prevent progression of motor deficits as soon as possible. Results of the current study suggest that diabetes mellitus and severity of motor deficit on admission are both associated with progression of motor deficits. Because there have been no previous reports suggesting the relation of these factors to progressive lacunar infarction, we should be cautious as to the significance of these factors for progression of motor deficits. However, it may be said that diabetes mellitus and severity of motor deficits on admission are factors that deserve to be examined when predicting progression of motor deficits after admission.

From the viewpoint of therapy, it is essential to clarify the mechanism of progression. In the current study, the size of the infarct, but not the site, was associated with progression of motor deficits. In general, the lack of collateral for the perforating arteries results in an infarct that spreads distally from the point of occlusion through the entire territory of the affected vessel and occlusion at the proximal portion of a perforating artery, or the ostium of a perforating artery where it departs from the parent major cerebral artery may yield a large infarct. Considering these points, the occluded portion of the responsible perforating artery may be one of the factors that regulate the duration of progression of motor deficits. That is, occlusion at the proximal portion of a perforating artery produces a large ischemic area, and a large ischemic area requires much time to complete an infarct, which may then be clinically recognized as progression. The more severe motor deficits on admission among patients with progression may reflect an ischemic area that is larger than that in patients without progression. A previous report15 suggesting an association between diabetes mellitus, which was demonstrated to be related to progression of motor deficits in the current study, and atherosclerosis at the proximal portion of a perforating artery may also, in a sense, support this hypothesis.

Recently, Castillo et al.16 demonstrated that early neurologic progression of acute ischemic stroke is associated with high concentrations of glutamate in the blood and CSF. Because an earlier report showed that glutamate was released in high concentrations in the penumbral cortex,17 the findings of Castillo et al.16 seem to suggest that the penumbral zone plays an important role in the progression of neurologic deficits and that a change from ischemic penumbra to a complete infarct is associated with progression. From this point of view, a deterioration in cerebral blood flow, which is a major cause of the change from ischemic penumbra to an infarct, may be associated with progression of motor deficits. Among various factors that influence cerebral blood flow, a fall in blood pressure or elevation of hematocrit levels often causes a decrease in cerebral blood flow. In our study, however, there were no differences regarding blood pressure or hematocrit levels on and after admission between patients with progression and those without. Based on a previous report13 that stated that anticoagulant therapy had been effective in preventing progression of motor deficits in minor ischemic stroke, local factors such as the formation of thrombus at the stenotic arteries may cause a deterioration in cerebral blood flow, which then contributes to the change.18 Another report19 showing that a thrombotic tendency was enhanced in diabetic patients suggests the importance of local factors in the progression of motor deficits in diabetic patients.

In addition to these factors, brain edema, which was demonstrated to be severe in the hyperglycemic state,20 may also play an important role in the progression of motor deficits.18 Taking account of the fact that there are discrepancies in the various reports regarding the efficacy of anticoagulant therapy in treating progressive lacunar infarction,13,14 it would seem that various factors combine to cause progression of motor deficits. To clarify fully the mechanism of the progression of motor deficits, however, additional studies are essential.