Comorbidity was common between MD and VM, and their symptoms overlapped. More specific diagnostic criteria are needed to differentiate these diseases and address their coexistence. CSD co-occurred with VM but was rarely seen with MD.

IMPORTANCE Recognizing the presenting and immunopathological features of Kelch-like protein-11 immunoglobulin G seropositive (KLHL11 IgG+) patients may aid in early diagnosis and management.OBJECTIVE To describe expanding neurologic phenotype, cancer associations, outcomes, and immunopathologic features of KLHL11 encephalitis. DESIGN, SETTING, AND PARTICIPANTSThis retrospective tertiary care center study, conducted from October 15, 1998, to November 1, 2019, prospectively identified 31 KLHL11 IgG+ cases in the neuroimmunology laboratory. Eight were identified by retrospective testing of patients with rhomboencephalitis (confirmed by tissue-based-immunofluorescence and transfected-cell-based assays). MAIN OUTCOMES AND MEASURESOutcome variables included modified Rankin score and gait aid use.RESULTS All 39 KLHL11 IgG+ patients were men (median age, 46 years; range, 28-73 years). Initial clinical presentations were ataxia (n = 32; 82%), diplopia (n = 22; 56%), vertigo (n = 21; 54%), hearing loss (n = 15; 39%), tinnitus (n = 14; 36%), dysarthria (n = 11; 28%), and seizures (n = 9; 23%). Atypical neurologic presentations included neuropsychiatric dysfunction, myeloneuropathy, and cervical amyotrophy. Hearing loss or tinnitus preceded other neurologic deficits by 1 to 8 months in 10 patients (26%). Among patients screened for malignancy (n = 36), testicular germ-cell tumors (n = 23; 64%) or testicular microlithiasis and fibrosis concerning for regressed germ cell tumor (n = 7; 19%) were found in 83% of the patients (n = 30). In 2 patients, lymph node biopsy diagnosed metastatic lung adenocarcinoma in one and chronic lymphocytic leukemia in the other. Initial brain magnetic resonance imaging revealed T2 hyperintensities in the temporal lobe (n = 12), cerebellum (n = 9), brainstem (n = 3), or diencephalon (n = 3). Among KLHL11 IgG+ patients who underwent HLA class I and class II genotyping (n = 10), most were found to have HLA-DQB1*02:01 (n = 7; 70%) and HLA-DRB1*03:01 (n = 6; 60%) associations. A biopsied gadolinium-enhancing temporal lobe lesion demonstrated T cell-predominant inflammation and nonnecrotizing granulomas. Cerebellar biopsy (patient with chronic ataxia) and 2 autopsied brains demonstrated Purkinje neuronal loss and Bergmann gliosis, supporting early active inflammation and later extensive neuronal loss. Compared with nonautoimmune control peripheral blood mononuclear cells, cluster of differentiation (CD) 8+ and CD4+ T cells were significantly activated when patient peripheral blood mononuclear cells were cultured with KLHL11 protein. Most patients (58%) benefitted from immunotherapy and/or cancer treatment (neurological disability stabilized [n = 10] or improved [n = 9]). Kaplan-Meier curve demonstrated significantly higher probability of wheelchair dependence among patients without detectable testicular cancer. Long-term outcomes in KLHL11-IgG+ patients were similar to Ma2 encephalitis. IgG is a biomarker of testicular germ-cell tumor and paraneoplastic neurologic syndrome, often refractory to treatm...

Background: In 2017, the Movement Disorders Society put forward new clinical criteria for the diagnosis of PSP recognizing diverse PSP phenotypes. Objectives: In this study, we compare the sensitivity and specificity of the new criteria to the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy (NINDS-SPSP) criteria at different time points. Methods: Patients with clinical parkinsonism, clinical and/or neuropathological diagnosis of PSP were identified from the Society for Progressive Supranuclear Palsy (SPSP) brain bank. All patients had neuropathologic diagnoses and detailed clinical examination performed by a neurologist at one of the three Mayo Clinic sites located in Florida, Arizona and Minnesota. Clinical symptoms and signs were abstracted retrospectively in a blinded fashion and used to determine whether or not patients met either diagnostic criterion. Patients were divided into early and late disease stage groups using a 3-year cut off. Results: A total of 129 patients were included of which 66 (51%) had PSP pathology. The remainder had other neurodegenerative diseases. The overall sensitivity of the Movement Disorders Society criteria was 87.9% compared to 45.5% for National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria, whereas the specificity of the Movement Disorders Society criteria probable PSP criteria was 85.7% and 90.5% for National Institutes of Neurological Disease criteria. Individual patients were noted to have features of multiple PSP phenotypes. Conclusion: The Movement Disorders Society criteria recognize several phenotypes of PSP and hence have a higher sensitivity than the previous criteria.

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