A 27 years old man presented to the neurology clinic with severe pain and weakness in the right upper limb.
The complaint started abruptly about a year and a half ago when he noticed right eyelid droop, miosis of the right pupil, and lack of right forehead sweating, all of which were compatible with Horner’s syndrome. A month later, he complained of severe pain and weakness in the right shoulder that progressed over three weeks to include the entire right upper limb. He was then admitted to the neurologic department in our hospital for evaluation.
On admission, his vital signs were within normal limits (BP: 125/80 mmHg, HR: 88/min, RR: 18/min, Temp: 37C, Sat: 98%). Physical examination was notable for right eye ptosis and miosis. The upper right limb examination revealed absent reflexes, atrophy (most prominent in the intrinsic hand muscles), flaccid paralysis (zero muscle strength in all proximal and distal muscle groups due to the Medical Research Council scale for assessing muscle strength), decreased pinprick and light touch sensation in the flexor face of the forearm and the dorsum of the hand. The rest of the neurological examination was normal.
Electrodiagnostic (EDX) testing showed a severe demyelinating lesion with complete blockade of the motor fibers of the medial cord (to a lesser extent in the posterior and lateral cords), disruption of sensory potentials confirms plexus damage, excluding preganglionic C8-T1 radicular damage.
CT scan imaging with contrast for the brain, neck, chest, and abdomen was negative for adenopathy or tumors. MRI of the brain and cervical spine and a carotid artery doppler ultrasound were normal. MRI of the brachial plexus showed marked thickening of the roots, trunks, and cords of the right brachial plexus that enhanced with gadolinium injection and atrophic changes in the infrascapular and infraspinatus muscles (high signal and relative decrease in their size). The radiographic findings were consistent with cervical plexopathy (Figure 1)
Laboratory study revealed normal CBC, electrolytes, Vit B12, ANA, ANCA, CRP (0.1 mg/dl), ESR (5 mm/h), and serum protein electrophoresis (table 1). CSF studies showed normal opening pressure (18 cmH2O), WBC: 4/mm3, RBCs: 6/mm3, Total protein: 53 mg/dL, glucose: 84 mg/dL (serum glucose: 161 mg/dL) (table 2). Cytology, herpes zoster polymerase chain reaction (PCR), and paraneoplastic panel were all negative.
He was diagnosed with idiopathic inflammatory plexopathy (Parsonage-Turner syndrome), for which a prednisone taper was started, but without improvement.
One year later, he developed progressive difficulty with swallowing, hoarseness, excessive salivation, palpitations, and dizziness when standing up. He also complained of pain and weakness in his lower limbs, lack of appetite, and weight loss of about 20 kg over the last year.
Examination showed: stable vital signs, the same findings as the previous examination (complete right Horner’s syndrome and complete right brachial plexus paralysis), and a new absence of bilateral patellar reflex, with preservation of the Achilles reflex.
A repeat MRI of the brain was unremarkable. A cervical MRI showed a 7x5 mm gadolinium-enhancing nodule in the anterior aspect of the spinal cord at the C3 level (Figure 2)
Electrodiagnostic testing (NSC/EMG) was repeated. It revealed moderate to severe axonal neuropathy in all studied nerves, suggesting a nerve biopsy if necessary.
Table 1: Laboratory tests in serum.
WBC
|
Neutrophils
|
Lymphocytes
|
RBCs
|
Hematocrit
|
Hemoglobin
|
13.8 K/uL
|
83.7%
|
7.8%
|
3.7 m/UL
|
36%
|
11.8 g/dl
|
MCV
|
Platelets
|
ESR
|
Glucose
|
Urea
|
Cr
|
97 fl
|
306 c/uL
|
10 mm/h
|
151 mg/dL
|
43 mg/dL
|
0.6 mg/dL
|
C3
|
C4
|
Anti SSA (Ro)
|
Anti SSB (La)
|
C-ANCA
|
P-ANCA
|
116
(normal: 86-182 mg/dL)
|
49
(normal: 17-51 mg/dL)
|
Neg
|
Neg
|
Neg
|
Neg
|
CU
|
RF
|
ANA
|
Anti-dsDNA
|
anti-AQP4
|
Anti-MOG antibodies
|
68
(normal: 60-160 ug/dl)
|
5.6
(normal: 0-24 IU/ml)
|
Neg
|
Neg
|
Neg
|
Neg
|
IgG
|
IgA
|
IgM
|
TSH
|
FT4
|
HBA1C
|
788
(normal: 700-1600 mg/d)
|
243
(normal: 70-400 mg/dl)
|
254
(normal: 40-230 mg/dL)
|
0.371
(normal: 0.27-4.2 micrU/ml)
|
1.56
(normal: 0.93-1.7 ng/dL)
|
5.1%
|
HIV Ag/Ab
|
B12
|
VitD
|
COVID19 PCR
|
Anti gangliosides antibodies
|
|
Neg
|
1455
(normal: 197-771 pg/mL)
|
30 ng/mL
|
Neg
|
Normal
|
|
Table 2: Cerebrospinal fluid studies.
Appearance
|
WBC
|
RBCs
|
Total protein
|
Glucose
|
Clear
|
2/mm3
|
5/mm3
|
48 mg/dL
|
72 mg/dL
|
Serum glucose
|
Cytology
|
IgG index
|
ACE
|
|
173 mg/dL
|
negative for atypical cells
|
0.46 (normal: 0.3-0.6)
|
0.2 (normal: up to 4)
|
|
A CXR for chest, echocardiogram, ECG, urine examination, VEP, neck, axillary and groin ultrasound, pulmonary function tests, CT scan for the whole body were performed and all of which were within normal. The right sural nerve was biopsied, showing mild perineural fibrosis and no evidence of malignancy.
Given the above findings, whole-body FDG-PET imaging was performed and showed right side cervical vertebral ganglia at the level of second and third vertebrae, three vertically located foci of moderate metabolic activity, mediastinal ganglia of moderately metabolically active tissue, poor metabolic activity in the right side of the nasopharynx without obvious thickening. No metabolically active lesions were seen in the remainder of the study (Figure 3).
The patient was then referred to neurosurgery, and a surgical biopsy of the lesion was taken at a C1-C2 level and showed intermediate-sized atypical lymphocytic infiltration. Fibrosis and focal perivascular lymphocytes are present. CD20 marker is positive for the infiltrative atypical lymphocytes. CD30 marker is positive for a few small lymphocytes in the background. Final diagnosis: Diffuse large B-cell non-Hodgkin’s lymphoma involving spinal and adjacent tissues.
Once the diagnosis and the staging were completed, he was treated with the DeAngelis protocol which consists of 19 weeks of therapy, involves chemotherapy and radiotherapy. It involves a combination of MTX, intrathecal MTX, vincristine, procarbazine, dexamethasone, high-dose cytarabine, and whole brachial plexus radiotherapy, to which the tumor responded well.