From dizziness to severe ataxia and dysarthria: New cases of anti-Ca/ARHGAP26 autoantibody-associated cerebellar ataxia suggest a broad clinical spectrum.

In 2010, a novel anti-neuronal autoantibody, termed anti-Ca, was described in a patient with subacute cerebellar ataxia, and Rho GTPase-activating protein 26 (ARHGAP26) was identified as the target antigen. Recently, three additional cases of anti-Ca-positive cerebellar ataxia have been published. In addition to ataxia, cognitive decline and depression have been observed in some patients. Here, we report two new cases of anti-Ca-associated autoimmune cerebellar ataxia. Patient 1 presented with dizziness and acute yet mild limb and gait ataxia. Symptoms stabilized with long-term oral corticosteroid therapy but transiently worsened when steroids were tapered. Interestingly, both initial occurrence and worsening of the patient's neurological symptoms after steroid withdrawal were accompanied by spontaneous cutaneous hematomas. Patient 2 initially presented with an increased startle response and myoclonic jerks, and subsequently developed severe limb and gait ataxia, dysarthria, oculomotor disturbances, head and voice tremor, dysphagia, cognitive symptoms and depression. Steroid treatment was started five years after disease onset. The symptoms then responded only poorly to corticosteroids. At most recent follow-up, 19 years after disease onset, the patient was wheelchair-bound. These cases extend the clinical spectrum associated with anti-ARHGAP26 autoimmunity and suggest that early treatment may be important in patients with this rare syndrome.

Release of zirconia nanoparticles at the metal stem-bone cement interface in implant loosening of total hip replacements.

In a previous failure analysis performed on femoral components of cemented total hip replacements, we determined high volumes of abraded bone cement. Here, we describe the topography of the polished surface of polymethyl methacrylate (PMMA) bone cement containing zirconia radiopacifier, analyzed by scanning electron microscopy and vertical scanning interferometry. Zirconia spikes protruded about 300nm from the PMMA matrix, with pits of former crystal deposition measuring about 400nm in depth. We deduced that the characteristically mulberry-shaped agglomerates of zirconia crystals are ground and truncated into flat surfaces and finally torn out of the PMMA matrix. Additionally, evaluation of in vitro PMMA-on-PMMA articulation confirmed that crystal agglomerations of zirconia were exposed to grain pullout, fatigue, and abrasion. In great quantities, micron-sized PMMA wear and zirconia nanoparticles accumulate in the cement-bone interface and capsular tissues, thereby contributing to osteolysis. Dissemination of nanoparticles to distant lymph nodes and organs of storage has been reported. As sufficient information is lacking, foreign body reactions to accumulated nanosized zirconia in places of long-term storage should be investigated. STATEMENT OF SIGNIFICANCE: The production of wear particles of PMMA bone cement in the interface to joint replacement devices, presents a local challenge. The presence of zirconia particles results in frustrated digestion attempts by macrophages, liberation of inflammatory mediators, and necrosis leading to aseptic inflammation and osteolyses. Attempts to minimize wear of articulating joints reduced the attention to the deterioration of cement cuffs. We therefore investigated polished surfaces of retrieved cuffs to demonstrate their morphology and to measure surface roughness. Industrially admixed agglomerates of the radiopacifier are abraded to micron and nano-meter sized particles. The dissemination of zirconia particles in the reticulo-endothelial system to storage organs is a possible burden. Research to replace the actual contrast media by non-particulate material deserves more attention.