A 57-year-old female patient was admitted to our hospital due to “nausea and vomiting for more than 4 months, numbness of limbs for more than 3 days, and blurred vision for 1 day.” Four months before admission, the patient developed nausea, hiccups, and vomiting without obvious inducement, and experienced unintentional weight loss. Her gastrointestinal endoscopy results were unremarkable, and her symptoms healed spontaneously without treatment. One month before admission, the patient began to experience numbness, itching, and tingling on the top of the head, as well as walking instability. She gradually developed numbness in her left upper limb and the inferior surface of the left anterior superior iliac spine, which continued without relief. Twenty days before admission, the patient developed bilateral facial numbness, and she was treated with drugs, such as pregabalin and mecobalamin, yet her symptoms did not improve. Three days before admission, the patient developed numbness and weakness in all four extremities. Two days later, her weakness worsened, accompanied by an unsteady gait, blurred vision, and occasional diplopia. During the course of the disease, the patient had no other presentations, such as dizziness, dysphagia, dyspnea, or dysphoria, and she denied history of chronic diseases, such as diabetes and rheumatic immune diseases.
On admission, physical examination of the nervous system revealed the following abnormalities: slight decrease in calculation ability and recent memory loss; reduced binocular visual acuity, diplopia, and horizontal coarse nystagmus in both eyes; spasmodic hypertonia of lower limbs; reduced (grade 4) muscle strength of lower limbs and distal end of upper limbs; segmental attenuation-disappearance of bilateral acupuncture sensation (from left thyroid cartilage to subclavian fossa, left upper limb, left anterior superior iliac spine below; from right mandibular angle to sternum); abdominal reflexes disappeared, limb tendon reflexes were hyperactive (+++), and clonus was present in bilateral ankles; bilateral finger-nose test and heel-knee-tibia test were inaccurate, and Romberg test was positive; Rossolimo sign was positive on the right side (+), Babinski sign and Chaddock sign were positive on both sides (+), and skin scratch sign was positive.
Auxiliary examinations showed positive antinuclear antibodies (ANAs): karyotype 1 (nucleolar type) with titer of 1:1000, karyotype 2 (cytoplasmic granular type) with titer of 1:100, anti-mitochondrial M2 antibodies were weakly positive, and anti-Ro-52 antibodies were positive. Lumbar puncture showed lower intracranial pressure (70 mmH2O) and abnormal cerebrospinal fluid (CSF) results (nuclear cells: 92×106/L, mononuclear cells: 89×106/L, multinucleated cells: 3×106/L; protein: 0.60 g/L, immunoglobulins G (IgG): 51.110 mg/L, IgM: 2.170 mg/L and IgA: 7.680 mg/L; positive for anti-sulfatide IgG antibodies and anti-AQP4 antibodies). In addition, she tested positive for anti-sulfatide IgG antibodies, anti-GD1a IgG antibodies, anti-GD3 IgM antibodies, and anti-AQP4 antibodies in her serum samples. More type III oligoclonal bands were seen in the CSF sample compared with the serum sample. Other examinations were almost normal. Three days after admission, neuroelectrophysiological examination demonstrated longer latency of the compound muscle action potential (CMAP), reduced occurrence rate of the F wave with prolonged latency, decreased sensory conduction velocity (SCV), and reduced sensory nerve action potential (SNAP) amplitude in the right wrist distribution of the median nerve; reduced CMAP and SNAP amplitudes, reduced occurrence rate of F wave with prolonged latency, decreased SCV and motor nerve conduction velocity (MCV) in the right ulnar nerve, presence of conduction block in the right common peroneal nerve and the tibial nerve, and decreased SCV in the right superficial peroneal nerve and the sural nerve (Table 1). One day later, spinal magnetic resonance imaging (MRI) revealed slight swelling with abnormal signals from medulla oblongata to spinal cord C3 (Fig. 1A and B), which were worsened at reexamination 33 days later (Fig. 1C and D). Results of other tests such as parotid gland ultrasound, Schirmer test, and tear film breaking time were all negative.
Table 1
Neuroelectrophysiological examination of right extremities
Nerve
|
Stimulation
site
|
Recording
site
|
Amplitude
|
Latency (ms)
|
Conduction
velocity (m/s)
|
F wave
(ms)
|
Motor
|
Median
|
Wrist
|
APB
|
8.35
|
4.45
|
-
|
32.4
|
|
Elbow
|
APB
|
7.71
|
8.70
|
54.10
|
-
|
|
Axilla
|
APB
|
5.51
|
11.1
|
60.40
|
-
|
Ulnar
|
Wrist
|
ADQ
|
2.92
|
3.30
|
-
|
37.3
|
|
Below elbow
|
ADQ
|
1.80
|
7.25
|
48.1
|
-
|
|
Above elbow
|
ADQ
|
1.96
|
10.10
|
34.5
|
-
|
|
Axilla
|
ADQ
|
1.38
|
12.00
|
52.6
|
-
|
Peroneal
|
Ankle
|
EDB
|
7.39
|
3.45
|
-
|
46.6
|
|
Below fibular
|
EDB
|
6.37
|
10.30
|
44.90
|
-
|
|
Above fibular
|
EDB
|
3.38
|
12.40
|
51.50
|
-
|
Tibial
|
Ankle
|
AHB
|
8.43
|
3.60
|
-
|
54
|
|
Popliteal fossa
|
AHB
|
3.35
|
11.9
|
49.4
|
-
|
Sensory
|
Median
|
Wrist
|
Second
finger
|
2.84
|
3.67
|
43.60
|
-
|
Ulnar
|
Wrist
|
Fifth finger
|
1.74
|
3.47
|
43.30
|
-
|
Sural
|
Calf
|
Lateral malleolus
|
5.70
|
3.37
|
37.10
|
-
|
Peroneal
|
Lateral leg
|
Foot
|
3.55
|
3.57
|
36.40
|
-
|
Amplitudes are measured in millivolt (mV, motor) and in microvolt (µV, sensory). APB, abductor pollicis brevis; ADQ, abductor digiti quinti; EDB, extensor digitorum brevis; AHB, adductor halluces brevis. |
Based on all examination results, the patient was diagnosed as NMOSD coexisting with undifferentiated connective tissue disease and peripheral neuropathy. Her limb numbness and blurred vision were slightly improved after treatment with intravenous methylprednisolone (first dose of 1000 mg/d and then gradually reduced) and gamma globulin shock therapy (for 5 consecutive days). During treatment, the patient presented with type II respiratory failure, and invasive ventilation was used to assist ventilation. Sixteen days after admission, reexamination showed that AQP4 titers of serum and CSF were unchanged as compared with admission (titer of 1:32). Hormonotherapy was continued and a high dose of plasma exchange (2000 ml) was performed every other day for 5 times. The patient's respiratory condition was gradually improved and invasive ventilator assisted ventilation was no longer required. Oxygen inhalation in the tracheal intubation tube could maintain normal oxygen saturation, and the tracheal intubation was discontinued 3 days later. After two doses of intravenous rituximab (first dose: 100 mg and second dose: 500 mg), the patient discharged from our hospital with a better health condition. At discharge, her limb numbness and blurred vision were improved, and she could walk with assistance (muscle strength of limbs was grade 5). She complained of spastic pain in her limbs, and slight horizontal nystagmus was still visible in both eyes during physical examination.