Sir,

Malignant lymphomas are primary neoplasms of lymphoid tissue derived from lymphocytes and occur as solid tumours usually within lymph nodes and less often in extranodal lymphoid tissues such as the tonsil, gastrointestinal tract, and spleen. Most of the patients with non-Hodgkin's lymphomas present with superficial lymph node enlargement, with or without systemic symptoms. Presentation with purely central nervous system symptoms in the absence of other systemic signs is extremely rare and to our knowledge there are only three previous reports of patients with lymphoma presenting with nystagmus.1, 2, 3 We therefore report a further case in a patient who initially presented with nystagmus and ataxia and was subsequently diagnosed with non-Hodgkin's lymphoma.

Case report

A 60-year-old male was referred to the ophthalmology department with a 6-month history of an intermittent vertical diplopia and oscillopsia. The diplopia usually occurred during close work and usually lasted several seconds. He had no history of vertigo, nausea, or vomiting, although he was noted to have an unsteady gait. He was otherwise fit and well with no past medical or ophthalmic history of note. He was not taking any drug medication. His visual acuities were 6/6 in each eye and orthoptic examination revealed full extraocular movements and convergence to 10 cm. There was a small amplitude gaze evoked nystagmus of moderate frequency. The nystagmus was conjugated with a mixed horizontal and rotatory movement. The fast component of the horizontal nystagmus was in the direction of gaze. The rotatory component was clockwise on left gaze and counter clockwise on right gaze. The vertical and horizontal saccades were felt to be hypometric but smooth pursuits and convergence were thought to be normal by two independent and experienced observers. The prism cover test revealed an exophoria of 4 Δ (near) and an esophoria of 1–2 Δ (distance). Prism fusion range was 2 Δ base in to 2 Δ base out (near), and 2 Δ base in to 6 Δ base out (distance).

Other than a possible left-sided sensory-neural hearing loss, lower cranial nerve function was normal. Tone, power, and reflexes were normal in all four limbs. Coordination of the upper limbs was normal but ataxia was present on tandem walking and he had a positive Romberg's test. The remainder of his ophthalmic examination was normal. In view of his neurological signs, he was referred to the neurology department for further investigations.

MRI scan revealed thickening of the fifth, seventh, and eighth cranial nerves with enhancement after contrast, the appearance of which was thought to be consistent with an inflammatory disorder. The brain parenchyma, ventricular system, and cerebellopontine angles were clear. CSF examination showed a raised white count of 18 mm3 with an associated raised protein of 1.62 g/l and a normal glucose of 3.4 mmol/l. In addition, a polyclonal increase in CSF gamma globulin was noted. Mycobacterial cultures were negative. Routine blood investigations were normal although the adjusted serum calcium was slightly high at 2.61 mmol/l. B12, folate, and thyroid function tests were normal. Rheumatoid factor, antinuclear antibody, anti-neutrophil cytoplasmic antibody, VDRL, and treponemal enzyme immunoassay were all negative and his chest X-ray was normal. The diagnosis at this stage was unclear but neurosarcoidosis was thought to be the most likely possibility. He was therefore commenced on oral prednisolone, and although his symptoms improved gradually over a period of several months, he was still bothered by intermittent diplopia and oscillopsia.

Eleven months after his initial presentation, he developed myocardial type chest pain. He was found to be anaemic, thrombocytopaenic, neutropaenic, and the LDH was significantly elevated. A bone marrow biopsy was undertaken and this revealed a malignant infiltrate of lymphoid origin giving a diagnosis of a diffuse large B-cell lymphoma (stage IVB). A CT scan of the chest, abdomen, and pelvis revealed no evidence of bulk disease. A repeat MRI scan at this stage with gadolinum revealed no focal enhancement and no evidence of significant enhancement in relation to the seventh and eighth cranial nerves.

The patient was given a 3 weekly course of chemotherapy with R-CHOP (cyclophosphamide, hydroxodaunorubicin, vincristine(oncovin) and prednisolone) with CNS prophylaxis over a 6-month period. His oscillopsia, diplopia, gaze evoked nystagmus, and ataxia improved dramatically within 3 months. His prism fusion range improved to 8 Δ base in to 14 Δ base out (near) and 4 Δ base in to 10 Δ base out (distance). A repeat bone marrow trephine biopsy undertaken 6 months later revealed no evidence of residual lymphoma and he has remained asymptomatic.

Comment

Torsional nystagmus can result from peripheral vestibular imbalance or direct labyrinthine destruction; however, a pure torsional nystagmus almost never occurs with peripheral vestibular disease, as this would require the selective involvement of the vertical semicircular canals in both ears.4, 5 This imbalance in the vestibular tone can also cause a gait ataxia. It is extremely rare for lymphoma to present in this manner, and although this patient did have a prolonged period of investigation before a final diagnosis was reached, we believe that his initial presentation with nystagmus was due to lymphoma. We postulate that the infiltration of the eighth cranial nerves with lymphoma resulted in a disturbed vestibular tone from the semicircular canals, and consequently, the mixed horizontal and rotatory nystagmus, and the gait ataxia. The initial partial remission of his neuroophthalmological signs and the resolution of cranial nerve infiltration on the repeat MRI scan after steroid therapy are consistent with the diagnosis of lymphoma. This is further supported by the significant improvement following his chemotherapy. The intermittent diplopia was felt to be due to the patient's poor fusional range. The patient's fusional range and diplopia improved with the treatment of the lymphoma and orthoptic exercises. This case highlights the importance of appropriate referral and thorough neurological investigation in such patients particularly as appropriate management can lead to resolution of disabling visual symptoms.