Paraneoplastic cochleovestibulopathy: clinical presentations, oncological and serological associations.

OBJECTIVE: Cochleovestibulopathy is a distinguishable paraneoplastic phenotype. In this study, we evaluate clinical presentation, serological/cancer associations and outcomes of paraneoplastic cochleovestibulopathy. METHODS: Retrospective chart review of patients with hearing impairment and/or vestibulopathy who underwent serological evaluations for paraneoplastic antibodies between January 2007 and February 2021 was performed. RESULTS: Twenty-six patients were identified (men, n=23; median age, 45 years, range: 28-70). Biomarkers detected included: KLHL11-IgG| |(n=20,| |77% (coexisting LUZP4-IgG, n=8)),| ||ANNA1-IgG| | |(n=3,| |12%),| |amphiphysin-IgG|| |(n=2,| |8%)| |and| |LUZP4-IgG|| |(n=1,| |4%). Most common neoplastic association was |testicular|/|extra-testicular| |seminoma| | (n=13,| |50%).|| Hearing| impairment (bilateral, 62%) was |present| |in| |all| |patients.| |Fifteen patients (58%) had cochleovestibular dysfunction as their initial presentation before rhombencephalitis/encephalomyelitis manifestations (hearing loss, four; acute vertigo, eight; both, three). |Brain| |MRI| |demonstrated| |internal| |auditory| |canal| |enhancement| |in| |four |patients.| Audiometry commonly revealed severe-profound bilateral sensorineural hearing loss. Most patients |had| a refractory course |despite| |immunotherapy| |and/or| |cancer| |treatment|. CONCLUSION: Cochleovestibulopathy commonly presents with rapidly progressive bilateral hearing loss and/or acute vertigo. However, in some patients, these symptoms present along with or following brainstem/cerebellar manifestations. KLHL11-IgG and seminoma are the most common serological and cancer associations, respectively. Recognition of this phenotype may aid in earlier diagnosis of paraneoplastic autoimmunity and associated cancer.

Paraneoplastic Progressive Downbeat Nystagmus, Ataxia and Sensorineural Hearing Loss due to the ANTI-Kelch-11 Protein Antibody.

ABSTRACT: A 45-year-old man with a history of testicular seminoma treated 8 years earlier presented with chronic progressive truncal and limb ataxia, progressive sensorineural hearing loss, and episodic vertigo. Eye movement and neuro-otology examinations showed localizing abnormalities to the bilateral cerebellar flocculus, vermis, and bilateral cerebellar hemispheres. Audiometric testing showed bilateral symmetric sensorineural hearing loss. There was a normal MRI of the brain. Cerebrospinal fluid (CSF) showed modest lymphocytic pleocytosis, and there was an elevated serum choriogonadotrophic hormone. An abdominal CT scan showed a solitary, large retroperitoneal lymph node, and histopathologic examination of the node biopsy showed granulomatous inflammation without microorganisms; eventually, immunohistochemical markers confirmed the diagnosis of metastatic seminoma. Although normal neuroimaging and inflammatory CSF reaction suggested a paraneoplastic etiology, the initial paraneoplastic antibody testing was negative. Subsequent investigation identified a positive kelch-11 protein antibody, thus confirming the paraneoplastic connection between the metastatic seminoma and the subacute neurologic-cochleovestibular syndrome.

Sensitivity and Specificity of Diagnostic Criteria for Progressive Supranuclear Palsy.

BACKGROUND: In 2017, the International Parkinson and Movement Disorder Society put forward new clinical criteria for the diagnosis of PSP, recognizing diverse PSP phenotypes. In this study, we compared the sensitivity and specificity of the new criteria with the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria at different times. METHODS: Patients with clinical parkinsonism, clinical and/or neuropathological diagnosis of PSP, were identified from the Society for Progressive Supranuclear Palsy brain bank. All patients had neuropathologic diagnoses and detailed clinical examination performed by a neurologist at 1 of the 3 Mayo Clinic sites, in Florida, Arizona, and Minnesota. Clinical symptoms and signs were abstracted retrospectively in a blinded fashion and used to determine whether patients met either diagnostic criterion. Patients were divided into early and late disease stage groups using a 3-year cutoff. RESULTS: A total of 129 patients were included, of whom 66 had PSP pathology (51%). The remainder had other neurodegenerative diseases. The overall sensitivity of the International Parkinson and Movement Disorder Society criteria was 87.9%, compared with 45.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria, whereas the specificity of the International Parkinson and Movement Disorder Society probable PSP criteria was 85.7%, compared with 90.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy. Individual patients were noted to have features of multiple PSP phenotypes. CONCLUSION: The International Parkinson and Movement Disorder Society criteria recognize several phenotypes of progressive supranuclear palsy and hence have higher sensitivity than the previous criteria. © 2019 International Parkinson and Movement Disorder Society.

Approach to the Examination and Classification of Nystagmus.

BACKGROUND AND PURPOSE: Physical therapists caring for patients with neurologic or vestibular disorders must routinely examine and characterize nystagmus and other oscillatory eye movements. Often, the diagnosis hinges on proper interpretation of the nystagmus pattern. This requires understanding the terminology surrounding the numerous attributes and influencing factors of nystagmus, a systematic approach to the examination, and a classification structure that guides practitioners to the specific nystagmus type and subsequent evaluation and management. SUMMARY OF KEY POINTS: Nystagmus is an involuntary, rapid, rhythmic, oscillatory eye movement with at least 1 slow phase. Jerk nystagmus has a slow phase and a fast phase. Pendular nystagmus has only slow phases. Nystagmus is distinguished from other types of oscillatory eye movements, such as saccadic intrusions or oscillations. Characterizing nystagmus requires clearly describing its trajectory. This includes choosing a reference frame to describe the axes or planes and direction of eye movements. Several attributes are used to describe nystagmus: binocularity, conjugacy, velocity, waveform, frequency, amplitude, intensity, temporal profile, and age at first appearance. Several factors may influence nystagmus, including gaze position, visual fixation, vergence, and a variety of provocative maneuvers. Classification of nystagmus may be organized by physiologic or pathologic nystagmus versus other nystagmus-like movements. Pathologic nystagmus may be spontaneous, gaze-evoked, or triggered by provocative maneuvers. The combination of attributes allows differentiation between the many peripheral and central forms. RECOMMENDATIONS FOR CLINICAL PRACTICE: Therapists should carefully examine and characterize the trajectory and other attributes and influencing factors of nystagmus to accurately classify it and arrive at the correct diagnosis.

Vestibular migraine and persistent postural perceptual dizziness.

Dizziness is a common symptom among patients in primary care, general neurology, and headache clinic practices. Vestibular migraine is conceptualized as a condition of recurrent attacks of vestibular symptoms attributed to migraine. It is now considered the most common cause of spontaneous episodic vertigo. Persistent postural-perceptual dizziness (PPPD) has more recently been defined based on four previous clinical entities as a syndrome of chronic daily dizziness, unsteadiness, or nonspinning vertigo that fluctuates and is exacerbated by postural, motion, or visual factors. Although PPPD is more often precipitated by other conditions causing vertigo, unsteadiness, or dizziness, it is discussed at length in this chapter because vestibular migraine is among the most common triggers for development of PPPD. Pathophysiology of each is incompletely understood, and with lack of biomarkers, the diagnosis of each rests on consensus-derived, symptom-based criteria. Areas of uncertainty exist regarding some overlapping symptoms that may create potential diagnostic confusion between the conditions. This chapter provides a comprehensive review of the current state of vestibular migraine and PPPD, including diagnostic and management guidance for when they occur separately, together, or along with other common comorbidities.

Clinical and serological insights into paraneoplastic brachial amyotrophic diplegia.

BACKGROUND: Brachial amyotrophic diplegia (BAD) is typically linked to a neurodegenerative etiology such as amyotrophic lateral sclerosis (ALS). Clinical and serological characterizations of paraneoplastic neurologic syndromes resembling BAD are limited. METHODS: A retrospective chart review of patients with BAD-like presentations was conducted. Clinical/paraclinical features of paraneoplastic BAD and neurodegenerative BAD cases were compared. RESULTS: Between 2017 and 2023, 13 cases of BAD were identified, of these 10 were neurodegenerative BAD (ALS variant), and 3 cases associated with paraneoplastic autoimmunity. An additional paraneoplastic BAD case diagnosed in 2005 was included. LUZP4-IgG was detected in all four paraneoplastic cases, with coexisting KLHL11-IgG in three cases and ANNA1 (anti-Hu)-IgG in one case. Out of the four paraneoplastic cases, two patients had seminoma, while the remaining two had limited cancer investigation. Three patients exhibited bi-brachial weakness as the initial symptom before the onset of brainstem symptoms or seizures. Compared to BAD patients with a neurodegenerative etiology, a higher proportion of paraneoplastic cases had ataxia (75% vs 0%, p = 0.011). Other clinical features only detected in the paraneoplastic BAD group were vertigo (n = 2), hearing loss (n = 2) and ophthalmoplegia (n = 2). Electrodiagnostic studies in these patients revealed cervical myotome involvement, supportive of motor neuronopathy. All paraneoplastic cases but none of the neurodegenerative BAD cases exhibited inflammatory cerebrospinal fluid (CSF) findings (lymphocytic pleocytosis and/or supernumerary oligoclonal bands; p = 0.067). Despite the administration of immunotherapy and/or cancer treatment, none of the paraneoplastic patients reported clinical improvement. DISCUSSION: BAD or bi-brachial neurogenic weakness is a rare phenotypic presentation associated with paraneoplastic autoimmunity. Co-existing features of brainstem dysfunction or cerebellar ataxia should prompt further paraneoplastic evaluation. Common serological and cancer associations among these cases include LUZP4-IgG and KLHL11-IgG, along with testicular germ cell tumors, respectively.

Outcomes and Patient Experience in Individuals With Longstanding Dizziness.

PURPOSE: This study aimed to describe the relationship between changes in pre and post self-perceived dizziness handicap, scores on the patient health questionnaire, and perceptions of patient's value of being evaluated and managed by a multidisciplinary team. METHOD: Seventy-eight patients completed the Dizziness Handicap Inventory (DHI) and Patient Health Questionnaire-Fourth Edition (PHQ-4) questionnaires post multidisciplinary clinical consultations and testing for the chief complaints of dizziness, unsteadiness, vertigo, or balance problems. The diagnoses of each patient were recorded from the clinical reports of each specialty consultation and were classified as structural, functional, or psychiatric. They were contacted by phone at least 6 months after their visit to obtain feedback regarding their symptoms and overall patient experience. RESULTS: The change in DHI total score did not differ significantly by diagnosis (p = .56), indicating that patients experienced an improvement in DHI total score regardless of diagnosis. PHQ-4 anxiety scores worsened by a mean of 0.7 points for those with structural diagnoses (p = .04), improved by a mean of 0.7 points for psychiatric diagnoses (p = .16), and improved by a mean of 0.3 points for functional diagnoses (p = .39). Only seven patients would not recommend the team to a family or friend; these patients tended to report worsening DHI total scores (p = .27) compared to the significant improvement in DHI total scores for patients who would make such a recommendation (p < .001). Similarly, only 13 patients did not feel the information they received had a positive impact; these patients tended to report worsening DHI total scores (p = .18) compared to the significant improvement in DHI total scores for patients who did feel the information had a positive impact (p < .001). DISCUSSION: The assessment and management of patients with chronic dizziness is challenging due to symptoms arising from multiple etiologies. Our finding of a vast difference between high satisfaction and relatively unchanged dizziness handicap suggests that there is value in seeing a multidisciplinary team where consultations are unhurried, care is coordinated, and expectations regarding treatment can be managed.

Gray matter correlates of behavioral severity in progressive supranuclear palsy.

BACKGROUND: Behavioral changes occur in progressive supranuclear palsy. This study aimed to identify the anatomic correlate of behavioral severity in progressive supranuclear palsy. METHODS: We performed standardized tests of behavioral severity (Frontal Behavioral Inventory), cognitive severity (Mini-Mental State Examination), motor severity (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III), and a 3.0-T volumetric head magnetic resonance imaging scan in 18 prospectively recruited subjects meeting National Institute of Neurological Diseases and Stroke-Society of Progressive Supranuclear Palsy criteria for probable progressive supranuclear palsy. Atlas-based parcellation was utilized to obtain regional gray matter volumes of frontal, temporal, and parietal lobe, and caudate and putamen, and voxel-based morphometry was used to assess voxel-level gray matter loss. We performed correlation analyses between total Frontal Behavioral Inventory score and gray matter volume, as well as assessed gray matter volume across three groups defined according to behavioral severity (mild, moderate, and severe) based on total Frontal Behavioral Inventory score. RESULTS: Specific behaviors, with the exception of apathy that occurred in 83% of the subjects, were relatively infrequent. There was no association between Frontal Behavioral Inventory and cognitive or motor severity. Regions of the frontal lobe, particularly, the lateral posterior frontal cortex, significantly correlated with the total Frontal Behavioral Inventory score when using both regional volume and voxel-level analyses. The groupwise analyses also supported these findings. The presence of apathy correlated with atrophy of the putamen. DISCUSSION: Behavioral severity in progressive supranuclear palsy appears to be associated with volume loss of frontostriatal regions, in particular, lateral posterior frontal lobe and putamen.

Episodic Spontaneous Dizziness.

PURPOSE OF REVIEW: Conditions causing recurrent spontaneous episodes of dizziness or vertigo span several medical specialties, making it challenging for clinicians to gain confidence in evaluating and managing the spectrum of episodic vestibular disorders. Patients are often asymptomatic and have normal examinations at the time of evaluation. Thus, diagnosis depends heavily on eliciting key features from the history. Overreliance on symptom quality descriptions commonly leads to misdiagnosis. The goal of this article is to provide the reader with a straightforward approach to the diagnosis and management of conditions that cause episodic spontaneous dizziness. RECENT FINDINGS: Consensus diagnostic criteria have been established for vestibular migraine, Ménière disease, vestibular paroxysmia, and hemodynamic orthostatic dizziness/vertigo. Vertigo has been recognized as a common symptom in vertebrobasilar ischemia, cardiogenic dizziness, and orthostatic hypotension. Treatment recommendations for vestibular migraine still lack high-quality evidence, but controlled trials are occurring. SUMMARY: The evaluation should start with a detailed description of the episodes from the patient and any observers. Rather than focusing first on whether the symptom quality is most consistent with vertigo, dizziness, lightheadedness, or unsteadiness, the clinician should clarify the timing (episode frequency and duration), possible triggers or circumstances (eg, position changes, upright posture), and accompanying symptoms. History should identify any auditory symptoms, migraine features, posterior circulation ischemic symptoms, vascular risk factors, clues for anxiety, and potentially relevant medications. Carefully selected testing can help secure the diagnosis, but excessive and indiscriminate testing can lead to more confusion. Treatments for these conditions are vastly different, so an accurate diagnosis is critical.

Agreement between the Skull Vibration-Induced Nystagmus Test and Semicircular Canal and Otolith Asymmetry.

BACKGROUND: How significant asymmetries in otolith organ function in the presence of symmetrical and asymmetrical semicircular canal function influence skull vibration-induced nystagmus testing (SVINT) has not been well described. PURPOSE: The aim of the study is to examine the agreement between SVINT and caloric testing, ocular vestibular-evoked myogenic potentials (oVEMP), and cervical vestibular-evoked myogenic potentials (cVEMP) for detecting asymmetric vestibular function. RESEARCH DESIGN: This is a retrospective study of patients presenting with the chief complaint of vertigo, dizziness, or imbalance. STUDY SAMPLE: A total of 812 patients were studied with a median age at testing of 59 years (interquartile range 46-70; range 18-93) and included 475 (59%) women. INTERVENTION: Either the monothermal warm caloric test or alternate binaural bithermal caloric test, oVEMP, and cVEMP tests were administered to all patients. All patients underwent the SVINT prior to vestibular laboratory testing. DATA COLLECTION AND ANALYSIS: Agreement between tests categorized as normal versus abnormal was summarized using percent concordance (PC). Sensitivity and specificity values were calculated for SVINT compared with other tests of vestibular function. RESULTS: There was higher agreement between ipsilateral and contralateral SVINT with the caloric test (PC = 80% and 81%, respectively) compared with oVEMP (PC = 63% and 64%, respectively) and cVEMP (PC = 76% and 78%, respectively). Ipsilateral and contralateral SVINT showed higher sensitivity for the caloric test (sensitivity = 47% and 36%, respectively) compared with oVEMP (sensitivity = 26% and 21%, respectively), or cVEMP (sensitivity = 33% vs. 27%, respectively). Specificity of SVINT was high (>80%) for all assessments of vestibular function. CONCLUSION: The presence of SVIN is a useful indicator of the asymmetry of vestibular function between the two ears when making judgments about semicircular canal asymmetry but is less sensitive to asymmetries in otolith organ function.

Approaching Acute Vertigo With Diplopia: A Rare Skew Deviation in Vestibular Neuritis.

Evaluating the patient with acute constant vertigo or diplopia can be a daunting task for clinicians, who recognize that such symptoms can be the manifestation of potentially devastating disorders like stroke but may be uncomfortable eliciting and interpreting the key symptoms and subtle signs that distinguish dangerous from benign causes. We present a novel and highly instructive case of a patient with acute vertigo and binocular diplopia from a large skew deviation due to vestibular neuritis. As the case unfolds, text and video commentary guide the clinician through the important elements of the history, bedside examination, and laboratory evaluation necessary for accurate diagnosis in the acute vestibular syndrome. We demonstrate how to interpret nystagmus and properly perform the head impulse test and test of skew deviation and discuss the pitfalls of overreliance on imaging when evaluating patients with acute vertigo.

Expanded Clinical Phenotype, Oncological Associations, and Immunopathologic Insights of Paraneoplastic Kelch-like Protein-11 Encephalitis.

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 Participants: This 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 Measures: Outcome 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. Conclusions and Relevance: Kelch-like protein-11 IgG is a biomarker of testicular germ-cell tumor and paraneoplastic neurologic syndrome, often refractory to treatment. Described expanded neurologic phenotype and paraclinical findings may aid in its early diagnosis and treatment.

Classification of vestibular signs and examination techniques: Nystagmus and nystagmus-like movements.

This paper presents a classification and definitions for types of nystagmus and other oscillatory eye movements relevant to evaluation of patients with vestibular and neurological disorders, formulated by the Classification Committee of the Bárány Society, to facilitate identification and communication for research and clinical care. Terminology surrounding the numerous attributes and influencing factors necessary to characterize nystagmus are outlined and defined. The classification first organizes the complex nomenclature of nystagmus around phenomenology, while also considering knowledge of anatomy, pathophysiology, and etiology. Nystagmus is distinguished from various other nystagmus-like movements including saccadic intrusions and oscillations.View accompanying videos at http://www.jvr-web.org/ICVD.html.

Timing of milestone competency acquisition in neurology residency: What by when?

OBJECTIVE: To determine the stage of training at which neurology residents should achieve individual elements of the Accreditation Council for Graduate Medical Education neurology Milestones and to examine the relationship between perceived importance of Milestones and the stage by which they should be achieved. METHODS: A modified Delphi technique was used to establish consensus postgraduate year (PGY) expectations for neurology Milestone competencies across 3 geographically and administratively distinct Mayo Clinic neurology residency programs. Timing expectations were examined for relationships to perceived importance of the individual Milestones and effects of participant characteristics. RESULTS: PGY expectations for neurology Milestone elements ranged from PGY 1.3 to PGY 4.1. Extent of rater educational seniority had no effect on PGY competency expectations. There was a moderate inverse relationship between perceived importance of the Milestone element and the PGY by which it should be achieved (r s = -0.74, p < 0.0001). CONCLUSIONS AND RELEVANCE: Expectations for neurology Milestone competency acquisition can be measured and may help inform individual program design, educational expectations, and future Milestone design.

Rare Occurrence of an Intraocular Choroidal Solitary Fibrous Tumor/Hemangiopericytoma.

PURPOSE: Tumors previously diagnosed as solitary fibrous tumors (SFT) and hemangiopericytomas (HPC) are characterized by the NAB2-STAT6 fusion gene, leading to nuclear STAT6 expression, and are now considered part of one SFT/HPC tumor entity by the 2016 World Health Organization Classification of Tumors of the Central Nervous System. We present the first primary choroidal SFT/HPC with the diagnosis confirmed by STAT6 expression. PROCEDURES: A 51-year-old man underwent enucleation for a choroidal mass, which revealed a spindle cell neoplasm involving the optic nerve, without extrascleral extension. Immunohistochemical stains for S-100, melan-A, tyrosinase, and HMB45 were all negative; however, detection of monosomy 3 by FISH favored a choroidal spindle cell melanoma. Four years later, he presented with hepatic metastases of a spindle cell tumor, and a year later with an epithelioid malignancy involving the calvarium. RESULTS: The calvarial tumor showed nuclear STAT6 immunoreactivity, supporting the diagnosis of SFT/HPC. Retrospectively, the choroidal and hepatic masses were also found to demonstrate nuclear STAT6 expression, supporting the diagnosis of a primary choroidal SFT/HPC with metachronous metastases to the liver and calvarium. CONCLUSIONS: This case highlights the significance of considering SFT/HPC in the diagnosis of intraocular spindle cell tumors and the importance of STAT6 immunohistochemistry in the evaluation of such tumors.

Anti-GAD antibody cerebellar ataxia mimicking Creutzfeldt-Jakob disease.

In a patient with a rapidly progressive neurological condition with ataxia and cognitive complaints, Creutzfeldt-Jakob disease (CJD) is often high in the differential, particularly when there is an elevated CSF 14-3-3 protein level. We present a case of anti-glutamic acid decarboxylase antibody (anti-GAD65) positive cerebellar ataxia associated with cognitive complaints and elevated CSF 14-3-3 protein.

Progressive supranuclear palsy: progression and survival.

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder characterized by postural instability and falls, vertical supranuclear gaze palsy, parkinsonism with poor levodopa response, pseudobulbar palsy, and frontal release signs. The natural history of the disease has been previously described. However, the time frame of appearance of clinical milestones and how these symptoms may relate to survival in PSP are unknown. The primary objective was to determine the prevalence of symptoms at different stages of PSP and to estimate the time of appearance of clinical symptoms characteristic of the disease. Second, we determined the association between clinical symptoms and survival. We prospectively studied 35 PSP patients during assessments scheduled every 6 months for up to 2 years. We estimated symptoms prevalence and the association between symptoms and survival. The median age of onset was 65.9 years (IQR 60.6-70.0), and the median time from onset to first assessment was 3.0 years (IQR 2.4-3.9). The most commonly reported symptoms at baseline were: motor (100%) followed by cognitive/behavioral (89%), systemic and bulbar (80%), and sleep disturbances (60%). Slowness of movement, falls, neck stiffness and difficulty looking up/down had high prevalence from baseline, while balance and gait impairment were less common at baseline but increased in prevalence over time. The presence of sleep disturbances, and possibly hallucinations, was associated with increased death risk. Improved recognition of the clinical spectrum and milestones of PSP advances knowledge of the disease, helps earlier diagnosis, and allows prognostic predictions.

Solitary Metastasis to the Facial/Vestibulocochlear Nerve Complex: Case Report and Review of the Literature.

BACKGROUND: Distant metastasis of mucinous adenocarcinoma from the gastrointestinal tract, ovaries, pancreas, lungs, breast, or urogenital system is a well-described entity. Mucinous adenocarcinomas from different primary sites are histologically identical with gland cells producing a copious amount of mucin. This report describes a very rare solitary metastasis of a mucinous adenocarcinoma of unknown origin to the facial/vestibulocochlear nerve complex in the cerebellopontine angle. CASE DESCRIPTION: A 71-year-old woman presented with several month history of progressive neurological decline and a negative extensive workup performed elsewhere. She presented to our institution with complete left facial weakness, left-sided deafness, gait unsteadiness, headache and anorexia. A repeat magnetic resonance imaging scan of the head revealed a cystic, enhancing abnormality involving the left cerebellopontine angle and internal auditory canal. A left retrosigmoid craniotomy was performed and the lesion was completely resected. The final pathology was a mucinous adenocarcinoma of indeterminate origin. Postoperatively, the patient continued with her preoperative deficits and subsequently died of her systemic disease 6 weeks after discharge. CONCLUSIONS: The facial/vestibulocochlear nerve complex is an unusual location for metastatic disease in the central nervous system. Clinicians should consider metastatic tumor as the possible etiology of an unusual appearing mass in this location causing profound neurological deficits. The prognosis after metastatic mucinous adenocarcinoma to the cranial nerves in the cerebellopontine angle may be poor.

Responses to and Outcomes of Treatment of Autoimmune Cerebellar Ataxia in Adults.

IMPORTANCE: Classic Purkinje cell cytoplasmic antibody type 1 (PCA-1, or anti-Yo) paraneoplastic cerebellar ataxia has a poor prognosis, yet little has been published otherwise regarding treatment responses and outcomes among patients with autoimmune cerebellar ataxia. OBJECTIVES: To investigate treatment responses and outcomes in adults with autoimmune cerebellar ataxia. DESIGN, SETTING, AND PARTICIPANTS: A cohort study conducted at Mayo Clinic, Rochester, Minnesota, included 118 patients who had ataxia, were 18 years or older, were seropositive for at least 1 neural autoantibody, had received at least 1 immunotherapy or cancer therapy, and had neurologist-reported outcomes documented from January 1, 1989, through December 31, 2013. Data were collected from May 14, 2013, through August 9, 2014, and analyzed from August 9, 2014, through April 27, 2015. Responses to immunotherapy (corticosteroids, intravenous immunoglobulin, plasma exchange, and immunosuppressants) and ambulatory outcomes were compared between different subgroups. Subgroups were classified as paraneoplastic vs nonparaneoplastic disorders; neuronal nuclear and/or cytoplasmic (NNC) antibody positivity vs plasma membrane protein (PMP) antibody positivity; and glutamic acid decarboxylase 65-kDa isoform (GAD65) antibody positivity vs PMP antibody positivity. MAIN OUTCOMES AND MEASURES: Response to therapy and ambulatory ability, with univariate logistic regression and Kaplan-Meier analyses. RESULTS: Inclusion criteria were met by 118 patients. Median age at onset of neurologic symptoms was 58 (range, 27-83) years, and 87 patients (73.7%) were women. Median duration from symptom onset to last follow-up was 25 (range, 2-223) months. Sixty-three patients had paraneoplastic and 55 patients had nonparaneoplastic ataxic disorders. Eighty-one patients were seropositive for NNC antibodies (most commonly PCA-1 [anti-Yo], antineuronal nuclear antibody type 1 [anti-Hu], and GAD65 antibody); 22 patients, for neural PMP receptor or ion channel antibodies (most commonly targeting P/Q- or N-type voltage-gated calcium channels); and 15 patients, for antibodies from both categories. Neurologic improvements occurred in 54 patients (with a robust change in ambulatory ability in 22) attributable to immunotherapy; univariate regression analysis revealed that improvements were significantly more common among patients with nonparaneoplastic disorders (P = .03) and those with exclusively PMP antibodies (P = .02). Kaplan-Meier analyses revealed that progression to wheelchair dependence occurred significantly faster among patients with NNC antibody positivity only (P = .02), although those with GAD65 autoimmunity progressed to wheelchair dependence at a rate similar to those with PMP autoimmunity (P = .92). CONCLUSIONS AND RELEVANCE: Although autoimmune ataxia is usually severe, treatment responses can be gratifying, particularly in patients with nonparaneoplastic disorders and in those harboring autoantibodies directed against GAD65 or neural PMPs.