The patient, a 69-year-old man, was found walking more slowly and unsteady than before by his family. Within 5 days, the symptoms rapidly worsened so that he could not walk at all, and was wheelchair-dependent. At the same time, he developed symptoms of slurred speech, dysphagia, and urinary incontinence. The consciousness of the patient progressively worsened, being as the state of somnolence. Meanwhile, the orientations of time, space and place all decreased. The patient previously had hypertension and atherosclerosis, and left subclavian artery stent implantation. After repeated confirmation, no previous history of vaccination was found, neither the history of prodromal infection such as diarrhea, fever and cough before onset.
After admission, the physical examination was implemented. The patient's general vital signs were relatively stable and was wheeled into the ward. He was drowsiness and had poor orientation, with the Glasgow score of 7 points (2+3+2). Language comprehension was adequate, but significant dysarthria was present. Bilateral eye movements were less flexible but no nystagmus was seen. The pupils were round and equal bilaterally, and sensible to light reflexes. The right nasolabial fold was shallow and the frontal pattern was symmetrical. Tendon reflexes were brisk in limbs, and ankle clonus, Babinski sign as well as Chaddock sign were all positive. Due to the lack of cooperation, the sensory system, motor system and other cranial nerves examinations were not credible. Brain MRI showed multiple small patchy lesions, which were hypointense on T1-weighted imaging sequencing, hyperintense on T2-weighted imaging sequencing, slightly hyperintense on diffusion weighted imaging (DWI) sequencing, in bilateral corona radiata, bilateral internal and external capsules, genu of the corpus callosum, left side of the midline of the pons and the left cerebellar hemisphere, and mild ring enhancement was seen in some of the lesions after contrast injection (Figure 1). The patient had no significant intracranial space occupying, and spinal cord MRI was normal. Video electroencephalogram (EEG) suggested slow background wave rate with predominance of 6-8 Hz waves.
Lumbar puncture was performed on admission day 2. Cerebrospinal fluid (CSF) was clear and transparent in appearance, with initial pressure 225 mmH2O, end pressure 120 mmH2O, total cells 6/mm3 with mononuclear cells 2/mm3, total protein 0.53 g/L, and normal glucose and chloride levels. CSF bacterial, fungal, viral and other etiological examination showed no abnormalities. Serum and CSF were negative for anti-aquaporin 4 antibodies (anti-AQP4 abs), anti-myelin oligodendrocyte glycoprotein antibodies (anti-MOG abs), anti-glial fibrillary acidic protein antibodies (anti-GFAP abs), paraneoplastic antibodies and autoimmune encephalitis antibodies. However, oligoclonal band was positive in the CSF with type II, which was different from blood, and IgG index and IgG synthesis rate were elevated (Table1). CSF flow cytometry suggested an increased number of activated T lymphocytes (Table1). At the same time, peripheral blood lymphocytes flow cytometry also showed abnormality in the subsets of lymphocytes, with a predominance of T helper/induced lymphocytes. Although the percentage of cytotoxic lymphocytes was within the normal range, the percentage of the cells that exerted effects was significantly higher (Table 2). The autoimmune antibody profiles such as thyroid antibodies, antinuclear antibodies were all negative.
Table 1
CSF changes before and after treatment
|
Before Treatment
|
After Treatment
|
Appearance
|
transparent
|
transparent
|
White blood cell
|
2/mm^3
|
1/mm^3
|
Monocytes
|
2/mm^3
|
1/mm^3
|
Glucose (2.5-4.5mmol/L)
|
3.51 mmol/L
|
3.03 mmol/L
|
Protein (0.15-0.45g/L)
|
0.53 g/L
|
0.26 g/L
|
Pressure (80-180mmHg)
|
220mmHg
|
120mmHg
|
Oligoclonal bands
|
Type II
|
None
|
IgG Index (<0.85)
|
1.33
|
1.39
|
IgG Synthesize (<7mg/24h)
|
12.62mg/24h
|
7.21mg/24h
|
Table 2
Lymphocyte subgroup in serum before and after treatment
|
Initial presentation
|
7 days after treatment
|
27 days after treatmengt
|
T cells count (723-2737/µL)
|
3273.46
|
197.54
|
1234.49
|
T cells proportion (50-82%)
|
84.43%
|
60.56%
|
75.41%
|
T helper cells proportion (24-54%)
|
66.80%
|
41.70%
|
61.90%
|
Cytotoxic T cells proportion (14-41%)
|
29.10%
|
18.91%
|
18.90%
|
CD4/CD8 ratio (0.7-3.1%)
|
2.30%
|
2.20%
|
1.74%
|
NK cells count (84-724/µL)
|
185.59
|
32.282
|
135.14
|
NK cells proportion (6-38%)
|
12.47%
|
9.91%
|
8.29%
|
B cells count (80-616/µL)
|
194.16
|
94.04
|
247.55
|
B cells proportion (5-21%)
|
16.54%
|
28.87%
|
15.19%
|
Plasma cells proportion (0.1-4.8%)
|
1.00%
|
0.50%
|
1.30%
|
Because of the rapid progressive deterioration of the patient's consciousness, we administered intravenous methylprednisolone to the patient on day 3 of admission. We started treatment at a dose of 1000 mg, and on day 2 of corticosteroids, intravenous immune globulin (IVIG) 0.4 g / kg / day for 5 days was also added. On the 3rd day of treatment, the patient's consciousness was significantly improved, cooperating with the question and answer, and Glassgow score was 14 points (4+5+5), but neck rigidity and pyramidal signs were still present. After the 1000 mg methylprednisolone was maintained for 5 days, we sequentially tapered the dosage to 500 mg for 3 days and 240mg for 3 days. After that we adjusted the treatment regimen to oral prednisolone acetate 48mg once a day, which was reduced to 24mg after 5 days and maintained this dose for 1 month. After 20 days of hospitalization, the patient's vital signs leveled off, the state of consciousness returned to normal, tendon reflexes of both lower limbs returned to normal but remaining left Babinski sign positive. After 1 month, he was extubated gastric and urinary tube, and was discharged uneventfully. Review of the cranial MRI showed that the lesion was more reduced in size than before, and the signal intensity was markedly reduced (Figure 2). EEG was repeated, showing that background rate was slow, predominating at 7-9 Hz, right occipital and posterior temporal 7-9 Hz waves were less frequent than left, and a little bit more 𝛳waves.
A repeated lumbar puncture suggested that CSF pressure of 120mmH2O and a cell count of 1 / mm3 all as mononuclear cells. CSF total protein was 0.26 g/L, which was reduced to the normal range. The oligoclonal band in CSF returned to negative, and the IgG index and intrathecal synthesis rate were significantly decreased than before. Lymphocyte subsets in the peripheral blood showed that 7 days after the corticosteroids treatment, T lymphocyte counts (including regulatory T cells and cytotoxic T lymphocytes) and NK cell counts decreased significantly, suggesting a marked immunosuppressive effect of the drug. After 27 days of treatment, T lymphocytes and NK cell counts returned to the normal range, and B lymphocytes counts were also elevated compared to those before. Notably, the percentage of T helper / induced lymphocytes in the T lymphocyte subclass decreased, whereas the proportion of cytotoxic T lymphocytes increased. The CD4 + / CD8 + T lymphocyte ratio decreased compared to before, and the proportion of memory B cells and plasma cells increased in the B lymphocyte subclass, although all were within the normal range. Lymphocyte subsets in CSF and peripheral blood before and after treatment are compared in Table 1. and Table 2.
The patient was followed up half a year later, and symptoms did not recur, limb muscle strength further recovered, independent walking could be achieved without assistance, and cortical function returned to normal. Reexamination of the brain MRI showed that the lesions were further reduced in size and the signal intensity was markedly reduced (Figure 3).