Scott D.Z. Eggers

Auditory and vestibular symptoms and chronic subjective dizziness in patients with Ménière's disease, vestibular migraine, and Ménière's disease with concomitant vestibular migraine

Objective To compare presentations of Ménière’s disease (MD), vestibular migraine (VM), and Ménière’s disease plus vestibular migraine (MDVM), with and without comorbid chronic subjective dizziness (CSD). Study Design Retrospective review with diagnosis confirmed by consensus conference of investigators using published criteria for MD, VM, and CSD. Setting Ambulatory, tertiary dizziness clinic. Patients Approximately 147 consecutive patients with diagnoses of MD, VM, or MDVM, with/without comorbid CSD. Interventions Diagnostic consultation. Main Outcome Measures Similarities and differences between diagnostic groups in demographics; symptoms; and results of neurotologic, audiometric, and vestibular laboratory assessments. Results Seventy-six patients had MD, 55 MD alone. Ninety-two patients had VM, 71 VM alone. Twenty-one patients had MDVM, representing about one-quarter of those diagnosed with MD or VM. Clinical features thought to differentiate VM from MD were found in all groups. Twenty-seven patients with VM (38%) had ear complaints (subjective hearing loss, aural pressure, and tinnitus) during episodes of vestibular symptoms and headache, including 10 (37%) with unilateral symptoms. Conversely, 27 patients with MD alone (49%) had headaches with migraine features that did not meet full IHS diagnostic criteria, migrainous symptoms (photophobia, headache with vomiting), or first-degree relative with migraine. Including MDVM patients, 59% (45/76) of all patients with MD had migrainous features. Thirty-two patients had CSD; most (29; 91%) were in the VM group. Conclusion 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.

Clinical Correlates of White Matter Tract Degeneration in Progressive Supranuclear Palsy

OBJECTIVES To use diffusion tensor imaging to assess white matter tract degeneration in progressive supranuclear palsy (PSP) and to investigate correlates between tract integrity and clinical measures. DESIGN Case-control study. SETTING Tertiary care medical center. PATIENTS/PARTICIPANTS Twenty patients with probable PSP and 20 age- and sex-matched healthy controls were enrolled. All patients with PSP underwent standardized clinical testing, including the Frontal Behavioral Inventory and Frontal Assessment Battery to assess behavioral change, the PSP Rating Scale to measure disease severity, the Movement Disorder Society-sponsored revision of the Unified Parkinsons Disease Rating Scale (parts II and III) to measure motor function, and the PSP Saccadic Impairment Scale to measure eye movement abnormalities. METHODS Fractional anisotropy and mean diffusivity were measured using region of interest analysis and tract-based spatial statistics. RESULTS Compared with controls, abnormal diffusivity was observed predominantly in the superior cerebellar peduncles, body of the corpus callosum, inferior longitudinal fasciculus, and superior longitudinal fasciculus in patients with PSP. Fractional anisotropy values in the superior cerebellar peduncles correlated with disease severity (r = -0.59, P = .006), inferior longitudinal fasciculus correlated with motor function (r = -0.51, P = .02), and superior longitudinal fasciculus correlated with severity of saccadic impairments (r = -0.45, P = .047). CONCLUSIONS The results of this study demonstrate that PSP is associated with degeneration of the brainstem, association, and commissural fibers and that this degeneration likely plays an important role in clinical dysfunction.

Paraneoplastic and Metastatic Neurologic Complications of Merkel Cell Carcinoma

Merkel cell carcinoma is a rare primary cutaneous neuroendocrine tumor that is locally aggressive and frequently accompanied by distant metastases. Neurologic complications of Merkel cell carcinoma are rare. We describe a 69-year-old man who presented with Lambert-Eaton myasthenic syndrome and was found to have Merkel cell carcinoma. The paraneoplastic syndrome improved with initial treatment of the malignancy. He subsequently developed a solitary brain metastasis and died of leptomeningeal carcinomatosis.

Acute intermittent porphyria presenting as a diffuse encephalopathy.

Although acute intermittent porphyria presents with dramatic neurological findings, the diagnosis is difficult. An 18‐year‐old woman had a clinical picture of porphyric encephalopathy. Magnetic resonance (MR) imaging demonstrated multiple large contrast‐enhancing subcortical white matter lesions, which regressed with glucose and hematin infusions. Diffusion‐weighted MR imaging was normal, and MR spectroscopy excluded acute demyelination or tissue necrosis. MR findings of acute intermittent porphyria can differ from those in posterior reversible encephalopathy syndrome by virtue of intense contrast enhancement. Because diffusion‐weighted MR imaging and spectroscopy were normal, the lesions are likely caused by reversible vasogenic edema and transient breakdown of the blood–brain barrier. Ann Neurol 2005;57:581–584

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 Parkinsons 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.

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.

Investigation of the Coherence of Definite and Probable Vestibular Migraine as Distinct Clinical Entities

Objectives: To investigate the following: 1) associations between vestibular symptoms and migraine in a well-characterized cohort of tertiary neurotology patients, 2) effects of comorbidity on clinical presentations, and 3) validity of proposed definitions of definite (dVM) and probable vestibular migraine (pVM). Study Design: Retrospective chart review. Setting: Tertiary neurotology center. Patients: All 228 subjects with headache were selected from a larger investigation of 410 patients with vestibular symptoms who underwent comprehensive medical, surgical, and behavioral neurotologic consultations. Subjects had at least one of 4 diagnoses: dVM/pVM, Ménières disease, benign paroxysmal positional vertigo, or chronic subjective dizziness. Interventions: Subjects were divided into migraine (n = 164) and nonmigraine headache (n = 64) groups by International Headache Society criteria, then subdivided by those with vestibular symptoms related or unrelated to headache. Subjects meeting proposed criteria for dVM (n = 46) and pVM (n = 42) were identified. Statistical analyses investigated discriminating features and cohesiveness in each group, with or without comorbidity. Main Outcome Measures: Characteristics of dVM and pVM. Results: Migraine, particularly migraine with aura, was more often related to vestibular symptoms than nonmigrainous headache. dVM and pVM groups did not differ in demographics, clinical histories, examinations, or vestibular testing. Numerous differences existed between dVM/pVM subjects with and without comorbid Ménières disease, benign paroxysmal positional vertigo, or chronic subjective dizziness. The pVM group contained 4 subtypes. Conclusion: These results support an association between vestibular symptoms and migraine but not proposed distinctions between dVM and pVM. pVM does not appear to be a coherent diagnostic entity. Comorbid conditions are important causes of vestibular symptoms in patients with migraine.

Neuroimaging comparison of primary progressive apraxia of speech and progressive supranuclear palsy

Primary progressive apraxia of speech, a motor speech disorder of planning and programming, is a tauopathy that has overlapping histological features with progressive supranuclear palsy. We aimed to compare, for the first time, atrophy patterns, as well as white matter tract degeneration, between these two syndromes.

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.

Progressive multifocal leukoencephalopathy in a patient treated with etanercept

Introduction:Recently, increased attention has been paid to the association of progressive multifocal leukoencephalopathy (PML) with the use of immunomodulatory medications for autoimmune diseases. Case Report:A 23-year-old Native American woman with a history of systemic lupus erythematosus and erosive polyarthritis treated with prednisone and etanercept presented with focal weakness, hemiataxia, diplopia, and dysarthria. Brain magnetic resonance imaging demonstrated progressive, T2 signal hyperintensities within the brainstem and cerebellar white matter without mass effect or gadolinium enhancement. Cerebrospinal fluid showed elevated protein and JC virus polymerase chain reaction positive with 28,600 copies/ml diagnostic of PML. Conclusions:The development of PML in this patient treated with etanercept and prednisone highlights the increased risk for opportunistic infection with JC virus in patients with autoimmune diseases on immunosuppressive therapies.