Mrs. G.S., a 45-year-old lady, presented with 3 month history of throbbing, continuous
bilateral headaches. She developed double vision and drooping of left eyelid 15 days
after the headache and went on to have numbness on left side of face, facial asymmetry,
intermittent spinning sensation and imbalance. There were no constitutional features.
She did not have neck stiffness, pallor, lymphadenopathy, rash or sternal tenderness.
Cranial nerve examination showed left third, fifth, sixth nerves and bilateral seventh
nerve deficits. Vision, optic fundus and rest of the cranial nerves were normal. Motor
and sensory examination of limbs was normal and there were no long tract signs. Review
of other systems was unremarkable.
Complete blood count (CBC), biochemistry and blood sugars were normal. Erythrocyte
sedimentation rate (ESR) was 10 mm at 1 hour. Cranial nerves were studied using T1,
T2, FLAIR, CISS, DWI, ADC map, SWI and contrast enhanced T1 weighted MRI sequences
which showed thickening of cisternal segments of left third [Figure 1a and b], left
fifth, [Figure 1c] and right seventh to eighth cranial nerve complex [Figure 1d].
The nerves were isointense on T1, T2 and FLAIR sequences and the affected nerves did
not show restricted diffusion. On gadolinium enhanced study the thickened nerves showed
uniform enhancement. There was neither parenchymal lesion nor any meningeal enhancement.
Cerebro spinal fluid (CSF) examination showed 52 cells/mm3 with 70% lymphocytes and
30% neutrophills. CSF sugar was 83 mg%, against simultaneous blood sugar of 123 mg%
and protein was mildly elevated to 63 mg%. No malignant or atypical cells could be
detected. Bacterial, acid fast bacillus (AFB) and fungal cultures were negative.
Figure 1
(a) Axial T1 weighted image showing thickened isointense Cisternal portion of left
occulomotor nerve (b) Contrast- enhanced axial T1 weighted image with fat suppression
showing homogenously enhancing cisternal portion of left occulomotor nerve (c) Contrast-
enhanced axial T1 weighted image with fat suppression showing thickened, homogenously
enhancing, cisternal portion of left trigeminal nerve. (d) Contrast-enhanced axial
T1 weighted image with fat suppression showing thickened and enhancing right facial
and vestibulocochlear nerve complex
Various possible causes of polyneuritis cranialis, such as immunological diseases,
(Sarcoidosis, chronic inflammatory demyelinating polyneuropathy or CIDP), both malignant
(Lymphoma, Carcinomatous) and infectious (tuberculosis, fungal, HIV) were considered
and patient was further investigated. Serum angiotensin-converting enzyme (ACE) level
was 8 units/L (normal 8-52 units/L) and calcium was 9.1 mg%. Antinuclear antibody
test (ANA) and ANA blot test was negative. Human immunodeficiency virus (HIV), hepatitis
B antigen (HBsAg), veneral disease research laboratory (VDRL) and hepatitis C virus
(HCV) serological tests were also negative. A computed tomography (CT) scan of paranasal
sinuses, skull base, chest, abdomen and pelvis with contrast was normal.
At this stage, the patient developed dysphagia, decreased hearing, tinnitus and worsening
of bifacial weakness. Her CSF was studied again on two occasions to look for malignant
cells, wherein 15 cc samples were taken each time and immediately centrifuged for
analysis. Both the samples were negative for malignant cells. Positron emission tomography-CT
(PET-CT) also was normal. She was empirically started on injection methyl prednisolone
1 g for 5 days with partial response, followed by oral prednisolone. Antitubercular
therapy was also used. Her headaches subsided completely. Her condition was assumed
to be immune mediated and injectable Cyclophosphamide was added. The initial response
to immunosuppression proved short lasting and she had to be readmitted with dysphagia,
right third nerve palsy, hearing loss in both ears and right arm pain. Repeat imaging
showed newfound involvement of right 3rd nerve which was thickened, enhancing and
also showed restricted diffusion with corresponding low signals on ADC. [Figure 2a–c].
This finding favored lymphoma. Right anterior cervical rootlet was thickened.
Figure 2
(a) Contrast- enhanced axial T1 weighted image with fat suppression showing thickened
and enhancing cisternal portions of bilateral occulomotor nerves (b) Axial DWI (diffusion
weighted image) showing restricted diffusion with increased signal intensity in both
occulomotor nerves as they are exiting from midbrain. (c) Axial ADC (Apparent diffusion
coefficient) map MRI image showing decreased signal intensity in both occulomotor
nerves as they are exiting from midbrain. (d) H&E section (40×) of biopsy from left
5th nerve lesion showing tumor comprising of highly pleomorphic large round cells
s/o high grade Non Hodgkin's lymphoma. Tumor cells have Hyperchromatic nuclei with
scant to moderate eosinophilic cytoplasm
In pursuit of a tissue diagnosis, the patient underwent left fifth nerve fascicular
biopsy which was suggestive of high grade non Hodgkin's lymphoma. [Figure 2d] Immunophenotyping
showed CD20 and Bcl-2 positivity and the tissue was negative for CD10 and CD3.
Discussion
Multiple cranial neuropathies have diverse etiologies.[1] Hypertrophy of the cranial
nerves on the MRI can be an important clue to the differential diagnosis. In particular,
the preferential affection of cisternal segment can help narrow down the etiologies.
MR enhancement and thickening of cisternal portions of the cranial nerves denotes
diseases like intrinsic tumors of the nerves, infiltrative malignancies, inflammatory
and infectious diseases [Table 1].[2
3
4
5
6
7
8] As can be seen from Table 1, when the nerves are significantly thickened, neoplasms
(Primary/metastatic) dominate the etiologies followed by conditions like sarcoidosis,
CIDP, and at times chronic infections like syphilis, schistosomiasis, chronic meningitis.
Table 1
Cranial neuropathies affecting cisternal portion of cranial nerves and Imaging characteristics
In the present case the nerve thickening was due to lymphomatous infiltration. As
such, primary CNS lymphomas (PCNSL) account for only 1-5% of all brain tumors.[9]
Our patient is further unusual in that she developed isolated hypertrophic cranial
neuropathies without parenchymal or meningeal lesions or any systemic involvement.
This is extremely uncommon in PCNSL as patients usually present with single or multiple
periventricular homogenously enhancing lesions.[10] The second MRI study favored lymphoma
by showing some degree of restricted diffusion and lower ADC values. Diffusion restriction
of lesions on DWI sequences with corresponding lower ADC values, if present, has been
shown to be associated with lymphoma more consistently than other inflammatory lesions,
tumors and metastatic lesions, but tissue diagnosis is mandatory.[10]
In conclusion, Lymphoma can mimic inflammatory/infectious diseases and an occasional
case of multiple cranial neuropathies showing thickened and enhancing cisternal segments
of the cranial nerves may be in fact, a case of PCNSL even in the absence of more
typical parenchymal/meningeal lesions and early tissue diagnosis should be considered.