| Description |
This patient is the index case of the Anti-Ri antibody, published in Annals of Neurology in 1988 (4). The Anti-Ri antibody is recognized to be a paraneoplastic marker in patients with breast and gynecological malignancies (10). The history of this case is particularly important because she was initially misdiagnosed as a case of acute labyrinthitis. In 1986, at age 56, she presented with the acute onset of dizziness, nausea and her eyes "going out of focus". Her symptoms began one month prior to admission, when she awoke one morning with a vague feeling of nausea and motion sickness. Because the symptoms were similar to those she had experienced during an episode of dizziness six years previously, her doctor attributed them to labyrinthitis. Five days later, she had difficulty focusing her eyes. When she attempted to read the newspaper the print appeared blurred and "moving in all directions". (oscillopsia). The next day she saw her ophthalmologist who commented on the presence of "marked nystagmus" . She complained of severe persistent dizziness with eyes open and closed and felt that the environment was spinning around her. She was admitted to the Infirmary at Massachusetts Institute of Technology Diagnosis: Acute labyrinthitis Four days later, she was unable to sit up in bed without falling over or stand. She was transferred and admitted to the Massachusetts General Hospital (MGH). Neurological examination showed: A constellation of cerebellar signs: •Titubation •Marked trunkal ataxia sitting and standing •Gait ataxia •Full horizontal eye movements disturbed by continuous bursts of rapid back-to-back saccades in all directions characteristic of opsoclonus. •Clockwise rotary nystagmus OU on gaze left •Right beating horizontal nystagmus OU on gaze right •Full vertical eye movements without nystagmus •Smooth pursuit eye movements when tested between attacks of opsoclonus to a slow moving target Motor system and sensory system intact. Reflexes 1+ throughout with flexor plantar responses. Coordination normal in the limbs. Diagnosis: Paraneoplastic Cerebellar Syndrome with Opsoclonus Investigations: The patient underwent intensive investigations to search for a primary occult neoplasm -- breast, ovary or lung. Lumbar puncture under fluoroscopy: Cerebrospinal fluid (CSF) protein 70 mg/dl Glucose 73 mg% RBC 0/cubic mm, WBC 8/cubic mm, 93% lymphocytes Cytology negative IgG 6.4 Albumin 4.1 and multiple oligoclonal bands. Chest x-ray: A tiny nodular density in the right middle lobe adjacent to the major fissure which was thought to represent a granuloma. A neoplasm could not be ruled out. (Figure 1) Bone Scan: Normal. Abdominal and Pelvic CT: normal. Brain MRI: Four MRI studies were done during her admission. The initial study in July 1986, and a study in October 1986 showed a lesion at the level of the tectum and inferior colliculus bilaterally, more obvious on the right. (Figure 2) This lesion was not seen in two MRI studies done in September, 1986, suggesting a transient waxing and waning of an inflammatory process. Mammogram: Mammography was delayed because of the patient's inability to stand for the examination due to severe vertigo. It revealed a small suspicious lesion in the upper outer quadrant of the right breast. Breast biopsy under fluoroscopy performed. (Figure 3) Pathology: Intraductal adenocarcinoma of the breast. (Figures 4-6). Surgery: The patient chose to have a segmental mastectomy followed by radiation. 5/9 lymph nodes were positive for CA. Chemotherapy was recommended. Paraneoplastic Markers: At the time the patient was in the MGH, the American Academy of Neurology met in Boston. I took the opportunity to meet Dr. Jerome Posner (for the first time) following his talk on Paraneoplastic Syndromes and Marker Antibodies. I asked Dr. Posner if he would be willing to study my patient and he agreed to do so. We sent tumor tissue, CSF and serum samples to him at the Sloan Kettering Cancer Center for assay for anti-Purkinje cell antibodies and other markers. Anti-Ri antibody: Dr. Posner discovered a new antibody. A highly specific anti-CNS nuclear neuronal antibody in the serum in a dilution of 1:800 and in the CSF in a dilution of 1:50. This observation was very significant. The antibody was named anti-Ri (Ri being the first two initials of the patient's last name) (Figures7-9). The Anti-Ri antibody is well recognized now to be a marker for occult malignancy of the breast and gynecological tumors. Plasmapheresis: The presence of anti-CNS neuronal antibodies in this patient raised the possibility that treatment with plasmapheresis might be beneficial. She was, however, turned down for this therapy. Chemotherapy and Radiation: In October 1986 she received a chemotherapeutic cocktail of Cytoxin, Adriamycin and 5 FUs weekly for a period of six months followed by local radiation therapy. Medications: The patient's vertigo, opsoclonus, titubation, trunkal ataxia and anxiety were variable throughout her hospital course. Multiple combinations of medications were tried to relieve vertigo and the most effective were Baclofen and Meclizine. She received Xanax for anxiety. Prednisone (20 mg p.o., t.i.d.) and Ranitidine were prescribed and taken for a period of six to eight weeks. Progress: Over the next two months she slowly improved and on completion of her chemotherapy she reported that she was "back in the land of the living", able to walk with a cane, climb one flight of stairs, go riding in a car out for lunch and generally doing much better. Visual blurring was less marked and she was able to read. She was considerably encouraged and cheerful at that time even though she was still experiencing occasional bursts of opsoclonus. Full recovery is excellent in these cases because the immune-mediated process affects the brainstem sparing the cerebellar Purkinje cells. Follow-up: By January 1987, she had made a complete recovery. She then remained well until 1993 when she was diagnosed with cancer of the bladder. She again made a complete recovery. I continued to follow this patient on an annual basis until Sept 2002 when she transferred her care to the University of Massachusetts to be close to her home. See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/92 |
