| Description |
This case was presented to the Clinical Eye Movement Society at the American Neurological Association Meeting in October 2009. The patient is a 65 year old woman who was in good health until seven weeks prior to admission. On June 22/09 on the return flight from her daughter's wedding in Oregon she began to feel "dizziness" which she characterized as an "inability to sense herself in space". This progressed insidiously over the course of hours and became intense enough to cause difficulty in standing and an inability to walk unassisted off the plane on arrival. Fully upright she felt as though "there is a sensation of backwards motion, with someone trying to push me off my heels". She also reported difficulty with short term memory, intermittent blurring of vision, and "eyes bobbing up and down", a prominent feature that "caused quite a stir among physicians". She had no impairment in her speech, or swallowing, no motor or sensory changes, and no hearing loss, tinnitus or headache. On return home, she consulted an ENT specialist on Cape Cod who diagnosed an inner ear problem and prescribed meclizine. Her PCP diagnosed vestibular neuritis and prescribed a short course of prednisone. Her symptoms progressed and she was admitted to the Massachusetts General Hospital. Past Medical History: Hypertension Family History: Hypertension in both parents and both were alcoholics Social History: Retired but working in the family business Smoked 1 to 2 packs per day for 25 years, quit 4 years ago. Alcohol: At least 2 glasses of wine per night for many years, occasionally "the better part of a bottle of wine on weekends". Symptomatic Inquiry: Weight loss of ten pounds in the last three months Appetite good No GI symptoms Neurological Examination: Alert, appropriately interactive, normal affect Orientation: Oriented to person, states' MEEI' for place and ‘Cambridge' for City Oriented to 2009 but states ‘June' for month (August) Attention: WORLD backwards without error Speech: fluent Followed simple and complex commands Repetition, naming, comprehension intact Memory: 3/3 at registration and 0/3 at 5 minutes. Normal fund of knowledge Calculations: intact Praxis: normal Cranial Nerves: Normal apart from ocular motility Motor System: 5/5 throughout 2+ symmetric reflexes Plantar responses flexor Sensory System: Impaired vibration sense in the toes All other modalities normal Coordination: No titubation Prominent trunkal ataxia Ataxic gait with a tendency to fall backwards sitting Neuro-ophthalmological Examination: Complained of marked oscillopsia and difficulty reading. Visual acuity: J5 with difficulty Confrontation fields, pupil reflexes and fundoscopy normal. Ocular Motility: Upbeat nystagmus fixing on a far target Lid nystagmus Square wave jerks (saccadic intrusions) Full horizontal and vertical eye movements. Normal convergence Upbeat nystagmus suppressed on convergence No nystagmus supine Horizontal and vertical saccadic dysmetria Saccadic pursuit in all directions Horizontal optokinetic response impaired Vestibular-ocular reflex appeared preserved. Blood Studies showed: WBC 12.1th/cmm (4.5-11.0) Polys 94% Neuts 11.34 th/cmm (1.8-7.7) Brain MRI without Gadolinium: Non-specific white matter foci representing chronic small vessel ischemic change. Brain MRI thin slices through the brainstem/cerebellum showed stable scattered T2/FLAIR hyperintensities in the periventricular and deep white matter that are non-specific. A demyelinating process cannot be fully excluded. Head and Neck MRA with 3D-reformatting: Normal studies CT scan of the chest with intravenous contrast: Normal study Bone scan: Skeletal degenerative changes No suspicious lytic or blastic lesions Lumbar Puncture: Cerebrospinal fluid protein 69 mg/dl (elevated) Sugar 60 mg/dl WBC 7 97% lymphs 3% monos Elevated IgG 22.5 mg/dl (0-8.0) CSF albumin 33.2 mg/dl (normal) Paraneoplastic Markers: Serum was sent to the Mayo Clinic for a paraneoplastic panel of antibodies including anti-Ma1, anti-Ma2, anti-Ri, anti-Yo, anti-Hu, anti-Zic4 anti-CV2. Result: Anti-Hu antibody positive - Titre 1:15,360 Transabdominal and transvaginal ultrasound: Heterogenous, thickened endometrial stripe measuring 17 mm Endometrial tissue biopsy negative. CT of abdomen and pelvis with intravenous contrast: Solid appearing 3.8 x 2.9 x 3.5 cm well defined heterogeneous mass (measuring 80 Hounsfield units post contrast) arising from the tail of the pancreas. (Figure 1) Core biopsies of the pancreatic mass were performed using CT guidance. Both normal pancreatic tissue and tumor were obtained (Figure 2A-E). The tumor cells are small, round, uniform cells in a single cell pattern without gland formation or mucin production, findings consistent with an endocrine neoplasm. (A) Immunohistochemical stains for endocrine (chromogranin (B) and synaptophysin (C)) and exocrine (trypsin (D)) differentiation confirm the diagnosis of an endocrine neoplasm. Distal Pancreatectomy/Pathology The excised distal pancreas revealed a 3.2 x 3.2 x 2.5 cm. well circumscribed, mottled tan-red heterogenous tumor mass with grossly clear resection margins (Figure 2E). Histology confirmed the diagnosis of an endocrine neoplasm. An immunohistochemical marker for proliferation (ki-67) highlighted a weak proliferation index (2%) and a marker for lymphatic endothelial cells (D2-40) did not reveal lymphatic invasion, however, malignant behavior was demonstrated by metastasis to a regional lymph node (1 of 23 nodes positive for tumor). As such this neoplasm is thus classified as a well-differentiated endocrine carcinoma. (Courtesy of Martha Bishop Pitman, M.D.) Hospital Course: The patient was treated with intravenous methylpredisolone (1,000 mg/day for five days), cyclophosphamide, one dose intravenously 1100 mg (600 mg/m2 ) followed by oral 75 mg daily (1mg/kg/day), and a course of intravenous immunoglobulin (0.5g/kg/day for five days). During the initial two months in hospital, she had progressive decline in cognitive function and memory and increasing gait ataxia, becoming wheelchair bound and unable to converse intelligibly. However, six weeks post-surgery, she started to improve cognitively, becoming more attentive, conversational and oriented, developing some insight into her illness. However, she still needed assistance to walk and her upbeat nystagmus persisted; at this point her eye movements were recorded. The recordings were made by R. John Leigh, M.D. et al Daroff-Dell'Osso Laboratory, Veterans Affairs Medical Center: Case Western Reserve University, Cleveland. A representative record of her nystagmus during far viewing and during near viewing is shown in Figure 3A-D. Paraneoplastic upbeat nystagmus suppressed by convergence and absent in the supine position is consistent with a channelopathy affecting the central otolith pathway. After the eye movement recordings, she started on memantine 10 mg/day increasing to 2 tablets/day and was seen several weeks later, on February 24, 2010. Her nystagmus persisted unchanged, suppressing with near viewing and abolished when supine. Her cognition was mildly improved. At this visit, a Brain FDG PET Scan (5.0 mCi of F-18 FDG injected) was done. The acquired tomographic images were evaluated independently and co-registered with images from two comparison MRI examinations for interpretation. The study showed: 1.Marked hypometabolism in the right and left rectus gyri, corresponding to focal volume loss that appears to have slightly progressed in the interval between the head MRI examinations of 8/13/2009 and 8/27/2009. This PET finding is of uncertain clinical significance, although the association of volume loss during a period when the patient was acutely symptomatic from her paraneoplastic syndrome suggests a possible correlation. 2.Mild hypometabolism in the left frontal lobe (outside of the gyrus rectus and oribitofrontal gyri) and in the left temporal lobe, of uncertain clinical significance, and not definitively suggestive of a specific neurodegenerative process. 3.There is otherwise essentially normal cortical metabolic activity in the right temporal lobe, the right and left parietal lobes, the right and left occipital lobes and in the deep gray matter nuclei and in the cerebellum. See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/357 |
