Successful Autologous Hematopoietic Stem Cell Transplant in Glycine Receptor Antibody-Positive Stiff Person Syndrome: A Case Report

BACKGROUND AND OBJECTIVES: To describe a case of glycine receptor (GlyR) antibody-positive stiff person syndrome (SPS) treated with autologous hematopoietic stem cell transplant (aHSCT). METHODS: This was a multicenter collaboration for the treatment of a single patient who underwent aHSCT as part of a clinical trial (NCT00716066). To objectively assess the response to transplantation, several clinical outcome measures were evaluated pretransplant and up to 18 months post-transplant, including modified Rankin Score (mRS), stiffness index, Hauser Ambulation Score (HAS), hypersensitivity index, timed 25-foot walk, and Montreal Cognitive Assessment. RESULTS: After transplant, the patient achieved sustained clinical improvement evidenced across various clinical scales, including mRS, stiffness index, HAS, and 25-foot walk time. DISCUSSION: aHSCT represents a promising treatment option for SPS, including for GlyR-positive patients. In addition, this case represents the need to validate and standardize best clinical outcome measures for patients with SPS. CLASSIFICATION OF EVIDENCE: Class IV; this is a single observational study without controls.

Update in Autoimmune Movement Disorders: Newly Described Antigen Targets in Autoimmune and Paraneoplastic Cerebellar Ataxia.

Movement disorders are a common feature of many antibody-associated neurological disorders. In fact, cerebellar ataxia is one of the most common manifestations of autoimmune neurological diseases. Some of the first autoantibodies identified against antigen targets include anti-neuronal nuclear antibody type 1 (ANNA-1 or anti-Hu) and Purkinje cell cytoplasmic antibody (PCA-1) also known as anti-Yo have been identified in paraneoplastic cerebellar degeneration. Historically these antibodies have been associated with an underlying malignancy; however, recently discovered antibodies can occur in the absence of cancer as well, resulting in the clinical syndrome of autoimmune cerebellar ataxia. The pace of discovery of new antibodies associated with autoimmune or paraneoplastic cerebellar ataxia has increased rapidly over the last few years, and pathogenesis and potential treatment options remains to be explored. Here we will review the literature on recently discovered antibodies associated with autoimmune and paraneoplastic cerebellar ataxia including adaptor protein-3B2 (AP3B2); inositol 1,4,5-trisphophate receptor type 1 (ITPR1); tripartite motif-containing (TRIM) proteins 9, 67, and 46; neurochondrin; neuronal intermediate filament light chain (NIF); septin 5; metabotropic glutamate receptor 2 (mGluR2); seizure-related 6 homolog like 2 (SEZ6L2) and homer-3 antibodies. We will review their clinical characteristics, imaging and CSF findings and treatment response. In addition, we will discuss two clinical case examples of autoimmune cerebellar ataxia.

Evaluation and Management of Spinal Subarachnoid Hemorrhage in a Patient with Lupus Vasculitis.

BACKGROUND Isolated spinal artery subarachnoid hemorrhage is a rare occurrence in the general population, but occurs more commonly as one of many neurologic sequela of systemic lupus erythematosus (SLE). The etiology of a neurologic deficit in an SLE patient is often multifactorial. Comorbid conditions, such as antiphospholipid antibody syndrome, predispose to stroke. Other diagnoses, including transverse myelitis, may also be attributed to local inflammation. CASE REPORT A 37-year-old woman with SLE and antiphospholipid antibody syndrome experienced severe back pain followed by sudden paralysis and sensory loss below the T2 level. She remained alert and oriented on examination, with neurologic exam positive for diminished strength in the arms and with total loss of sensation and strength in the legs. Diagnostic workup was limited due to a contrast allergy and severe lupus nephritis; however, initial imaging showed increased cervical-thoracic spinal cord signal and concern for acute blood in the subarachnoid space. No neurosurgical intervention occurred, and the patient was treated with high-dose steroids and plasmapheresis for a possible transverse myelitis and non-aneurysmal subarachnoid hemorrhage. The patient received further neurologic and rheumatologic workup and remained neurologically stable, with improvement in proximal arm strength on physical exam. CONCLUSIONS We highlight the diagnostic challenges in treating a patient with SLE with acute paralysis and sensory loss. In this case, aggressive early treatment of the patient's myelitis and myelopathy were successful in leading to mild neurological improvement.

Treatment of brain metastases.

Brain metastases are associated with substantial morbidity and mortality. Key prognostic classification systems for brain metastases are reviewed. The role of surgery, particularly for single brain metastases, is discussed. This is followed by an overview of radiation, both whole brain and focal, in the treatment of brain metastases. Finally, we review examples of important concepts regarding the role of systemic therapy in the treatment of brain metastases.