MTX-related acute leukoencephalopathy
Six (18.75%) of the 32 patients developed MTX-related acute
leukoencephalopathy. The details of the six patients are presented in
Table 1. The manifestation of acute leukoencephalopathy was so mild that
only one patient (No. 1) suffered from alalia. Two patients (No.3, 4)
were asymptomatic, and three (No.2, 5, 6) had fatigue that was not paid
attention to until the diagnosis of leukoencephalopathy. Five patients
(No.2, 3, 4, 5, 6) were diagnosed with leukoencephalopathy during
routine MRI after 6, 4, 4, 4, 6 cycles of chemotherapy, respectively.
For patient No.1, tumor cells were present in the CSF after one cycle of
chemotherapy. MTX (12.5 mg) was injected intravenously once a week for
the antitumor purpose. Three single doses were administered to this
patient totally during the interval between two cycles of chemotherapy.
As the patient developed alalia soon, she could not continue her next
cycle of chemotherapy. Brain MRI and brain vessel MRI were performed
thereafter. Brain MRI revealed multiple lesions in the bilateral
cerebellar hemispheres, thalamus, basal ganglia region, lateral
ventricle, radial coronal, center semicovale, bilateral frontoparietal
temporal lobe and right occipital lobe. T1 weighted imaging (T1W1)
revealed slightly low signal (Figs. 1A), T2 weighted imaging (T2WI)
showed high signal (Figs. 1B), while flair image presented slightly high
signal with blurred boundary (Figs. 1B). Diffusion weighted imaging
(DWI) suggested limited diffusion of some lesions (Figs. 1D and 1E), and
enhanced MTI suggested mild enhancement of some white matter lesions
(Figs. 1F). There was no obvious abnormality on brain vessel MRI (Figs.
1G and 1h). Oligoclonal band (OCB) analysis found the presence of
immunoglobulin G (IgGs) in her CSF. Leukoencephalopathy was diagnosed,
and she was treated with intravenous methyl prednisolone at 2 mg/kg
three times daily (which reduced over a 2-week period), oxygen support,
and human blood albumin injection.
Her condition was stable at the last follow-up.
In patient 2, screening MRI after the 6th cycle of
chemotherapy revealed several infiltrative lesions that involved the
bilateral frontal, parietal, temporal lobes, right cerebellar hemisphere
and left pontile. T1WI showed slightly low signal (Figs. 2A and 2D),
T2WI displayed high signal (Figs. 2B and 2E), while flair image revealed
slightly high signal (Figs. 2C and 2F). The largest size of the lesion
was about 1.5 cm, which was located in the right cerebellar hemisphere.
Magnetic resonance spectroscopy (MRS) revealed Cho/NAA=1.78 of the
lesion in the right cerebellar hemisphere, while Cho/NAA=0.97 of the
lesion around the left lateral ventricle. This finding led to the
differential diagnosis of tumefactive demyelinating lesions and MB
recurrence. Cerebral blood flow (CBF) was measured, but no abnormal
signal was observed during CBF subsequently. Leukoencephalopathy was
diagnosed thereafter. Therefore, dexamethasone at 10 mg/d and oxygen
support were given at a local hospital. A month later, the abnormal
signal in white matter area was slightly improved compared with before
(Figs. 3A, 3B and 3C). But the lesions in the cerebellar hemisphere
increased to 2.5 cm with contrast enhancement (Figs. 3D, 3E and 3F). MRS
revealed Cho+Cr/NAA=5.3 of this lesion. Besides, CBF revealed multiple
cerebral hyperperfusion lesions as well. Relapsed disease was
considered. The patient died two weeks later.
For patients No.3, 4, 5, 6, the findings were similar to those of
patient 1. All of these cases were alive with severe neurological
symptoms.
None of the patients in control group developed acute
leukoencephalopathy. With the exception of acute leukoencephalopathy,
there was no difference in the high-grade toxicity rate (grade ≥ 3)
between the two groups.