Patrick R Wood, MD Fellow, Rheumatology University of Colorado

Transcription

1 Patrick R Wood, MD Fellow, Rheumatology University of Colorado

2 Discuss an unusual case of CNS calcification encountered on an academic VA rheumatology service Summarize bilateral striatopallidodentate calcification as a clinical entity for the practicing rheumatologist Review the known literature on calcific brain disease in SLE, in particular Management, followup, and next steps

3 46F with a distant history of muscle weakness, fatigue, CK , then Gottrons/rash, diagnosed with dermatomyositis. No calcific disease. Treated with steroids, then developed a saddle PE- >+DRVVT/lupus anticoagulant, diagnosed with SLE/DM overlap with secondary APLS (+dsdna, Sm, RNP, low complements, lymphopenia). No CNS manifestations-including cerebritis, psychosis, seizures, strokes. Placed on MMF->Myfortic+HCQ, anticoagulation, stable for a decade or so. Self-tapered off IS and lost to rheum f/u for ~2 years.

4 Progressive anxiety issues *months-years with pcp. Re-presents to PCP with complaints of vague, progressive/chronic word finding difficulty, vague neuropsychiatric symptoms with?le movement problems (chorea). No headaches, focal numbness, weakness, fevers, lethargy, or other acute neurologic complaints. No rash, arthritis, or other previous SLE symptoms.

5 Exam: Normal vital signs, no distress. No rashes or arthritis. Alert, no nuchal rigidity, photophobia, or oral ulcers. Very subtle expressive aphasia and lower extremity chorea. MRI:

6 marked, large-burden striatopallidodentate calcinosis, raising question of Fahr s disease...

7

8

9 PTH, VitD, phos, calcium all normal No criteria by LP, history, or imaging for CNS SLE. Vague FH dementia/neurologic problems

10 Neurocognitive psychology and neurology evaluations: subtle neuropsych deficits, massive brain calcifications and chorea c/w Fahr s disease Restarted HCQ, warfarin/asa 81; eventually restarted Myfortic but no pulse steroids, CYC, etc for active CNS lupus +serologic improvement with HCQ, Myfortic, but no improvement in CNS symptoms Improvement in some symptoms with levodopa and cog/occupational therapy.

11 Fahr s disease, or bilateral symmetric striatopallidodentate calcification is radiographically described as bulky calcification of deep matter structures of the basal ganglia, deep white matter, and cerebellar structures, described as far back as the mid 1800s, with various other names through the 20 th century Rare: ~100 cases in the literature Pathology: calcium, trace aluminum, arsenic, cobalt, copper, and other deposition in capillaries, arterioles, small veins and perivascular space, with associated neural degeneration and gliosis.

12 Most common presenting features: parkinsonism, chorea, tremor, and progressive cognitive/speech impairment, psychiatric features. Diagnosis: based on MRI/CT Seen in association with CO poisoning, various viral insults (HBV, HIV), developmental disorders in addition to primary disease in sporadic, familial, and autosomal dominant syndrome linked to a single chromosomal locus. DDx=secondary calcium metabolism disorders (hypoparathyroidism, pseudohypoparathyroidism) (Manyam)

13 CT and MRI calcific disease has been described in SLE since at least 1985 (Nordstrom, et al) Typically seen in context of other major CNS SLE manifestations: cerebritis, multiple strokes, etc. (Raymond; Chang) Antiphopholipid antibodies, anti-glial fibrilary acidic protein, and chronic vascular injury implicated but presumed genetic predisposition (Canas; Stuart) Recent somewhat similar case reports describe dramatic primary calcification without major CNS lupus or neuropsych manifestations (Martinovic- Kaliterna)

14 This case describes Fahrs disease manifestations without typical CNS SLE, Poorly understood entity though clearly described in SLE, treatment implications poorly defined. No prior description in relation to dermatomyositis overlap as in this case. Generally accepted treatment is palliative for parkinsonian symptoms (probably?). Further understanding of primary brain calcification disorders in general and prognostic/treatment implications in SLE.

15 Drs. Jason Kolfenbach, Sterling West, Robert Janson (UC Denver/VA Denver Rheumatology) RWCS Fellow Program

16 Manyam BA. What is and what is not Fahr s disease. Parkinsonism and Related Disorders 11 (2005) Chang RS, Chun-Yin WL, Ho SL. Bilateral Striatopallidodentate Calcinosis associated with Systemic Lupus Erythematosus: case report and review of literature. Journal of the Neurological Sciences 358 (2015) Martinovic-Kaliterna, et al. Massive Cerebral Calcifications ( Fahrs Disease ) in a Patient with Systemic Lupus Erythematosis and No Major Neuropsychological Abnormalities. IMAJ Vol 15, Oct Raymond, et al. Brain calcification in patients with cerebral lupus. Lupus (1996) 5, Nordstrom DM, West SG, Andersen PA. Basal ganglia calcifications in central nervous system lupus erythematosus. Arthritis Rheum 1985; 28: Stuart BM et al. Cerebral calcifications in a patient with systemic lupus erythematosus and a monoclonal IgG reactive with glial fibrillary acidic protein. Br J Rheumatol 1998 Dec: 37 (12): Canas CA et al. Multiple brain calcifications in a patient with systemic lupus erythematosus. Clin. Rheumatol Dec: 27 Suppl 2: S63-5.