Cerebrospinal fluid immunoglobulins in primary progressive multiple sclerosis are pathogenic.

Multiple sclerosis is clinically characterized by relapses and remissions (relapsing-remitting multiple sclerosis) that over time may evolve to a progressive course (secondary progressive multiple sclerosis) or as having a progressive course from disease onset (primary progressive multiple sclerosis). At present, it is not definitively known whether these clinical entities constitute a single pathological disease or whether these manifestations represent two distinct disease entities sharing inflammatory demyelination as a pathological feature. Here we show using a novel mouse model that CSF of primary progressive multiple sclerosis patients is unique in its capacity to induce motor disability and spinal cord pathology including demyelination, impaired remyelination, reactive astrogliosis and axonal damage. Notably, removal of immunoglobulin G from primary progressive multiple sclerosis CSF via filtration or immunodepletion attenuates its pathogenic capacity. Furthermore, injection of recombinant antibodies derived from primary progressive multiple sclerosis CSF recapitulates the pathology. Our findings suggest that the clinical and pathological features of primary progressive multiple sclerosis are antibody-mediated and pathogenically distinct from relapsing-remitting and secondary progressive multiple sclerosis. Our study has potentially important implications for the development of specific therapies for patients with primary progressive multiple sclerosis.

Usability and Acceptability of Two Smartphone Apps for Smoking Cessation Among Young Adults With Serious Mental Illness: Mixed Methods Study.

BACKGROUND: Young adults with serious mental illness (SMI) have higher smoking rates and lower cessation rates than young adults without SMI. Scalable interventions such as smartphone apps with evidence-based content (eg, the National Cancer Institute's [NCI's] QuitGuide and quitSTART) could increase access to potentially appealing and effective treatment for this group but have yet to be tested in this population. OBJECTIVE: The goal of this user-centered design study is to determine the user experience (including usability and acceptability) of 2 widely available apps developed by the NCI-QuitGuide and quitSTART-among young adult tobacco users with SMI. METHODS: We conducted usability and acceptability testing of QuitGuide and quitSTART among participants with SMI aged between 18 and 35 years who were stable in community mental health treatment between 2019 and 2020. Participants were randomly assigned to use QuitGuide or quitSTART on their smartphones. App usability was evaluated at baseline and following a 2-week field test of independent use via a video-recorded task completion protocol. Using a mixed method approach, we triangulated 4 data sources: nonparticipant observation, open-ended interviews, structured interviews (including the System Usability Scale [SUS]), and backend app use data obtained from the NCI. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed using thematic analysis. RESULTS: Participants were 17 smokers who were not interested in quitting, with a mean age of 29 (SD 4) years; 41% (n=7) presented with psychotic disorders. Participants smoked an average of 15 (SD 7) cigarettes per day. The mean SUS scores for QuitGuide were similar at visits one and two (mean 64, SD 18 and mean 66, SD 18, respectively). The mean SUS scores for quitSTART numerically increased from visit one (mean 55, SD 20) to visit two (mean 64, SD 16). Acceptability scores followed the same pattern. Observed task completion rates were at least 75% (7/9 for QuitGuide, 6/8 for quitSTART) for both apps at both visits for all but 2 tasks. During the 13-day trial period, QuitGuide and quitSTART users interacted with their assigned app on an average of 4.6 (SD 2.8) days versus 10.8 (SD 3.5) days, for a mean total of 5.6 (SD 3.8) interactions versus 41 (SD 26) interactions, and responded to a median of 1 notification (range 0-8) versus 18.5 notifications (range 0-37), respectively. Qualitative comments indicated moderate to high satisfaction overall but also included concerns about the accuracy of the apps' feedback. CONCLUSIONS: Both QuitGuide and quitSTART had acceptable levels of usability and mixed levels of acceptability among young adults with SMI. The higher level of engagement with quitSTART suggests that quitSTART may be a favorable tool for young adult smokers with SMI. However, clinical support or coaching may be needed to overcome initial usability issues.

Perceptions of Mobile Apps for Smoking Cessation Among Young People in Community Mental Health Care: Qualitative Study.

BACKGROUND: Young adults with serious mental illness are over twice as likely to have tobacco use disorder than those in the general population and are less likely to utilize proven treatment methods during quit attempts. However, little research has evaluated the efficacy of interventions for this group. Smartphone apps may be an underutilized tool for tobacco use disorder among young adults with serious mental illness. OBJECTIVE: The aim of this study was to explore attitudes toward smoking cessation apps and preferences regarding app design in young adult smokers with serious mental illness. METHODS: Five focus groups involving 25- to 35-year-old adults with serious mental illness receiving treatment at a community mental health center were conducted between May 2019 and August 2019. Three researchers independently coded transcripts and identified themes using thematic analysis. RESULTS: Participants (n=22) were individuals who smoke daily: 10 (46%) self-identified as female, 18 (82%) self-identified as White, and 9 (41%) had psychotic disorders. Key themes that emerged included a general interest in using health apps; a desire for apps to provide ongoing motivation during a quit attempt via social support, progress tracking, and rewards; a desire for apps to provide distraction from smoking; concerns about app effectiveness due to a lack of external accountability; and concerns that apps could trigger cravings or smoking behavior by mentioning cigarettes or the act of smoking. CONCLUSIONS: Apps have the potential to support smoking cessation or reduction efforts among young adults with serious mental illness. However, they may require tailoring, optimization, and clinical support to effectively promote cessation in this population.

Acute Posterior Multifocal Placoid Pigment Epitheliopathy Complicated by Fatal Cerebral Vasculitis.

A 21-year-old man experienced unilateral vision loss associated with multiple atrophic chorioretinal lesions. He was treated for a presumptive diagnosis of acute retinal necrosis, but his vision did not improve with antiviral therapy. Over the course of several weeks, his symptoms progressed to involve both eyes. The fellow eye showed characteristic yellow-white placoid lesions, prompting treatment with oral corticosteroids for acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Despite high-dose therapy with prednisone 80 mg daily, the patient developed the acute onset of mental status changes within the next several days. Neuroimaging revealed multifocal large-vessel strokes associated with cerebral edema; these infarcts led to herniation and death. Postmortem histopathologic examination confirmed granulomatous inflammation in both ocular and cerebral vasculatures. Together with findings from multimodal imaging obtained throughout this patient's clinical course, our findings support the notion that granulomatous choroiditis is the mechanism of the ocular lesions seen in APMPPE. This granulomatous inflammation can also affect cerebral vessels, leading to strokes.

Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings.

Importance: Biomarker testing for asymptomatic, preclinical Alzheimer disease (AD) is invasive and expensive. Optical coherence tomographic angiography (OCTA) is a noninvasive technique that allows analysis of retinal and microvascular anatomy, which is altered in early-stage AD. Objective: To determine whether OCTA can detect early retinal alterations in cognitively normal study participants with preclinical AD diagnosed by criterion standard biomarker testing. Design, Setting, and Participants: This case-control study included 32 participants recruited from the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St Louis, St Louis, Missouri. Results of extensive neuropsychometric testing determined that all participants were cognitively normal. Participants underwent positron emission tomography and/or cerebral spinal fluid testing to determine biomarker status. Individuals with prior ophthalmic disease, media opacity, diabetes, or uncontrolled hypertension were excluded. Data were collected from July 1, 2016, through September 30, 2017, and analyzed from July 30, 2016, through December 31, 2017. Main Outcomes and Measures: Automated measurements of retinal nerve fiber layer thickness, ganglion cell layer thickness, inner and outer foveal thickness, vascular density, macular volume, and foveal avascular zone were collected using an OCTA system from both eyes of all participants. Separate model III analyses of covariance were used to analyze individual data outcome. Results: Fifty-eight eyes from 30 participants (53% female; mean [SD] age, 74.5 [5.6] years; age range, 62-92 years) were included in the analysis. One participant was African American and 29 were white. Fourteen participants had biomarkers positive for AD and thus a diagnosis of preclinical AD (mean [SD] age, 73.5 [4.7] years); 16 without biomarkers served as a control group (mean [SD] age, 75.4 [6.6] years). The foveal avascular zone was increased in the biomarker-positive group compared with controls (mean [SD], 0.364 [0.095] vs 0.275 [0.060] mm2; P = .002). Mean (SD) inner foveal thickness was decreased in the biomarker-positive group (66.0 [9.9] vs 75.4 [10.6] µm; P = .03). Conclusions and Relevance: This study suggests that cognitively healthy individuals with preclinical AD have retinal microvascular abnormalities in addition to architectural alterations and that these changes occur at earlier stages of AD than has previously been demonstrated. Longitudinal studies in larger cohorts are needed to determine whether this finding has value in identifying preclinical AD.

HINTS in the Acute Vestibular Syndrome: Pearls and Pitfalls.

The acute vestibular syndrome (AVS) is characterized by the rapid onset of vertigo, nausea/vomiting, nystagmus, unsteady gait, and head motion intolerance lasting more than 24 hours. We present 4 patients with AVS to illustrate the pearls and pitfalls of the Head Impulse, Nystagmus, Test of Skew (HINTS) examination.

Incidence and Causes of Overdiagnosis of Optic Neuritis.

Importance: Diagnostic error is an important source of medical error. Overdiagnosis of optic neuritis may prompt unnecessary and costly diagnostic tests, procedures, and treatments. Objective: To assess the incidence of and characterize factors contributing to overdiagnosis of acute optic neuritis. Design, Setting, and Participants: In this retrospective clinic-based cross-sectional study of new patient encounters, 122 patients referred for acute optic neuritis at a university-based Midwestern neuro-ophthalmology clinic between January 2014 and October 2016 were studied. Data were analyzed from September 2016 to July 2017. Interventions: Definite diagnosis was determined by neuro-ophthalmologists. For patients with alterative diagnoses, the Diagnosis Error Evaluation and Research taxonomy tool was applied to categorize the type of diagnostic error. Main Outcomes and Measures: The primary outcome was the primary type of diagnostic error in patients erroneously diagnosed as having optic neuritis. Secondary outcomes included final diagnosis and interventions undergone prior to referral. Results: A total of 122 patients were referred with acute optic neuritis during the study period; 88 (72.1%) were female, and the mean (SD) age was 42.6 (14.0) years. Of these, 49 patients (40.2%; 95% CI, 31.4-49.4) were confirmed to have optic neuritis, and 73 (59.8%; 95% CI, 50.6-68.6) had an alternative diagnosis. The most common alternative diagnoses were headache and eye pain, functional visual loss, and other optic neuropathies, particularly nonarteritic anterior ischemic optic neuropathy. The most common diagnostic error was eliciting or interpreting critical elements of history, which occurred in 24 of 73 patients (33%) with alternative diagnoses. Other common errors included errors weighing or considering alternative diagnoses (23 patients [32%]), errors weighing or interpreting physical examination findings (15 patients [21%]), and misinterpreting diagnostic test results (11 patients [15%]). In patients with alterative diagnoses, 12 (16%) had normal magnetic resonance imaging findings preceding the referral, 12 (16%) had received a lumbar puncture, and 8 (11%) had received unnecessary treatment with intravenous steroids. Conclusions and Relevance: These data suggest that nearly 60% (95% CI, 50.6-68.6) of patients referred for optic neuritis have an alternative diagnosis, with the most common errors being overreliance on a single item of history and failure to consider alternative diagnoses. Understanding pitfalls leading to overdiagnosis of optic neuritis may improve clinicians' diagnostic process.

A Middle-aged Man With Progressive Ophthalmoparesis, Ataxia, and Spastic Paraparesis.

A 50-year old man presented for evaluation of progressive gait ataxia with a superimposed spastic paraparesis. During his clinic visit, he was also observed to have slow and limited eye movements. In this article, we discuss the clinical approach to this triad of symptoms and guide the reader to discover the patient's ultimate genetic diagnosis.

Vertebrobasilar Dolichoectasia Causing An Optic Tract Syndrome.

Vertebrobasilar dolichoectasia (VBD) is characterized by significant dilation, elongation, and tortuosity of the vertebrobasilar system. We present a unique case of VBD, confirmed by neuroimaging studies, showing vascular compression of the right optic tract and lower cranial nerves leading to an incongruous left homonymous inferior quadrantanopia and glossopharyngeal neuralgia.

Skew Deviation and Partial Ocular Tilt Reaction Due to Intratympanic Gentamicin Injection, with Review of the Literature.

Skew deviation is a rare side effect of intratympanic gentamicin injection for intractable Meniere's disease. When the skew deviation is accompanied by pathologic head tilt and ocular torsion, the result is an ocular tilt reaction (OTR). The authors report the case of a 56-year-old man with refractory Meniere's disease who developed binocular vertical diplopia following intratympanic gentamicin injection and was found to have skew deviation and a partial ocular tilt reaction. The authors also review the reported cases of skew deviation following intratympanic gentamicin and confirm this phenomenon, which has only rarely been reported in the literature.

A Young Man With Progressive Vision and Hearing Loss.

A 37-year-old man with a history of progressive bilateral sensorineural hearing loss presented to a neuro-ophthalmology clinic with an acute left homonymous hemianopsia. In this article, we discuss the clinical approach and differential diagnosis of progressive combined vision and hearing loss and guide the reader to discover the patient's ultimate diagnosis.

A Young Woman With Blurred Vision and Distal Paresthesias.

A 29-year-old woman presented with blurred vision and distal paresthesias. Her initial evaluation revealed severe bilateral optic disc edema with distal lower-extremity sensory and motor deficits and electrodiagnostic evidence of a length-dependent mixed demyelinating and axonal polyneuropathy. The results of routine diagnostic testing, including laboratory tests, magnetic resonance imaging, and lumbar puncture, were nondiagnostic. A targeted biopsy was ultimately required for diagnosis. In this article, we discuss the differential diagnosis and outline the clinical evaluation indicated for a patient presenting with demyelinating polyneuropathy and concurrent papilledema.

Isolated Ocular Motor Nerve Palsies.

An isolated ocular motor nerve palsy is defined as dysfunction of a single ocular motor nerve (oculomotor, trochlear, or abducens) with no associated or localizing neurologic signs or symptoms. When occurring in patients aged 50 or older, the most common cause is microvascular ischemia, but serious etiologies such as aneurysm, malignancy, and giant cell arteritis should always be considered. In this article, the authors review the clinical approach, anatomy, and differential diagnosis of each isolated ocular motor nerve palsy and discuss the clinical characteristics, pathophysiology, and treatment of microvascular ischemia.

Ocular Neuromyotonia Associated with Chronic Inflammatory Demyelinating Polyneuropathy.

Ocular neuromyotonia (ONM) is a neuro-ophthalmic disorder characterized by episodic diplopia caused by contraction of one or more ocular muscles due to spontaneous excitation of the respective ocular motor nerve. We report a patient whose ocular neuromyotonia arose in the setting of a subacute demyelinating polyneuropathy consistent with chronic inflammatory demyelinating polyneuropathy (CIDP) and subsequently resolved following the initiation of intravenous immunoglobulin (IVIg) for her neuropathy. Our patient provides additional evidence towards the role of demyelination and ephaptic neurotransmission in ocular neuromyotonia and also represents the first reported case of ocular neuromyotonia associated with a systemic neurological condition.

Disparities in deep brain stimulation surgery among insured elders with Parkinson disease.

OBJECTIVE: To identify sociodemographic, clinical, and physician/practice factors associated with deep brain stimulation (DBS). DBS is a proven surgical therapy for Parkinson disease (PD), but is recommended only for patients with excellent health, results in significant out-of-pocket costs, and requires substantial physician involvement. METHODS: Retrospective cohort study of more than 657,000 Medicare beneficiaries with PD. Multivariable logistic regression models examined the association between demographic, clinical, socioeconomic status (SES), and physician/practice factors, and DBS therapy. RESULTS: There were significant disparities in the use of DBS therapy among Medicare beneficiaries with PD. The greatest disparities were associated with race: black (adjusted odds ratio [AOR] 0.20, 95% confidence interval [CI] 0.16-0.25) and Asian (AOR 0.55, 95% CI 0.44-0.70) beneficiaries were considerably less likely to receive DBS than white beneficiaries. Women (AOR 0.79, 95% CI 0.75-0.83) also had lower odds of receiving DBS compared with men. Eighteen percent of procedures were performed on patients with PD who had cognitive impairment/dementia, a reported contraindication to DBS. Beneficiaries treated in minority-serving PD practices were less likely to receive DBS, regardless of individual race (AOR 0.76, 95% CI 0.66-0.87). Even after adjustment for demographic and clinical covariates, high neighborhood SES was associated with 1.4-fold higher odds of receiving DBS (AOR 1.42, 95% CI 1.33-1.53). CONCLUSIONS: Among elderly Medicare beneficiaries with PD, race, sex, and neighborhood SES are strong independent predictors of DBS receipt. Racial disparities are amplified when adjusting for physician/clinic characteristics. Future investigations of the demographic differences in clinical need/usefulness of DBS, ease of DBS attainment, and actual/opportunity DBS costs are needed to inform policies to reduce DBS disparities and improve PD quality of care.

Neurologist-associated reduction in PD-related hospitalizations and health care expenditures.

OBJECTIVE: To investigate the impact of neurologist care on Parkinson disease (PD)-related hospitalizations. Recent data indicate that neurologist treatment in PD may be associated with improved survival, yet is underutilized. Factors contributing to this improved survival remain unknown, but may be due in part to optimal disease treatment or avoidance of disease-related complications. METHODS: This was a retrospective cohort study of Medicare beneficiaries diagnosed with PD in 2002 and still living in 2006. Hospitalization for PD-related (neurodegenerative disease, psychosis, depression, urinary tract infection, and traumatic injury) and general medical (hypertension, diabetes, congestive heart failure, angina, and gastrointestinal obstruction) illnesses was compared by PD treating physician specialty using Cox proportional hazard models, adjusting for confounders. Secondary analyses included PD-related rehospitalization and cost stratified by frequency of neurologist care. RESULTS: We identified 24,929 eligible incident PD cases; 13,489 had neurologist care. There were 9,112 PD-related hospitalizations, and these occurred and recurred less often among neurologist-treated patients. Neurologist PD care was associated with lower adjusted odds of both initial and repeat hospitalization for psychosis (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.59-0.86), urinary tract infection (HR 0.74, 0.63-0.87), and traumatic injury (HR 0.56, 0.40-0.78). PD-related outcomes improved with frequency of neurologist care in a stepwise manner. Odds of general illness hospitalization or hospitalization did not differ by neurologist involvement. CONCLUSIONS: Regular neurologist care in PD is specifically associated with lower risk of hospitalization and rehospitalization for several PD-related illnesses. This may reflect an improved ability of neurologists to prevent, recognize, or treat PD complications.