Relevance of antinuclear antibody in diagnosis and characteristics of multiple sclerosis.

BACKGROUND: Criteria for multiple sclerosis (MS) diagnosis rely upon clinical and paraclinical data that are supportive of MS in the absence of a better explanation. Patients referred for consideration of a MS diagnosis often undergo an extensive serologic workup including antinuclear antibody (ANA) testing, even when an individual already meets diagnostic criteria for MS. It is unclear whether ANA serostatus is associated with clinical outcomes in MS. The present study aims to determine if ANA seropositivity in those referred with concern for MS differs in those who meet 2017 revised McDonald criteria compared to those who did not receive a diagnosis of MS. Associations between ANA seropositivity and clinical or radiological phenotype of MS patients are also explored. METHODS: The cohort included people at least 18 years old, referred to our tertiary care MS center with concern for MS (regardless of prior diagnosis) who had an ANA test with known titer completed within one year of first evaluation. Electronic health record (EHR) charts were manually reviewed, and MRIs underwent blinded review by a radiologist with training in neuroradiology. Diagnosis of MS was determined by a neuroimmunologist and was based on 2017 revised McDonald Criteria. Results are reported as odds ratios from multivariable logistic regression analyses adjusted for age, sex at birth, race, smoking history, personal history of comorbid autoimmune conditions, and family history of autoimmunity. Within the MS cohort, similar analytical models were performed to assess association between ANA and clinical and radiological characteristics. RESULTS: A final cohort of 258 patients was analyzed (out of 542 referrals): 106 nonMS and 152 with MS. There was no association between MS (vs. nonMS) diagnosis and ANA status (ANA positive n = 74) in the multivariable models (OR 1.5, 95 % CI 0.82, 2.72, p = 0.20). Among those with MS, there was no association of ANA seropositivity with the odds of atypical brain MRI features, number of cardinal MRI areas involved, location of MRI lesions, or of having an atypical presentation of first demyelinating event. Black race (OR 2.8, 95 % CI 1.27, 6.26, p = 0.01) and family history of autoimmunity (OR 2.1, 95 % CI 1.09, 3.98, p = 0.03) were independently associated with increased odds of ANA positivity. Within the MS cohort analysis, progressive MS (PMS; vs relapsing-remitting MS), a covariate in the model, appeared to be at higher odds of being ANA positive (OR 3.6, 95 % CI 1.03, 13.05, p = 0.046) but only when assessing mean area of cardinal MS locations. CONCLUSIONS: While ANA testing does not appear to be useful in distinguishing MS from non-MS, it remains less clear as to whether it may be associated with differences in the clinical course of MS (relapsing-remitting vs progressive). Future studies should aim to systematically evaluate whether those who are ANA positive are more likely, in well-designed and representative prospective cohorts, to be diagnosed with or develop progressive MS. Whether a positive ANA early in MS is associated with increased risk over time of developing or diagnosing another systemic autoimmune disease would also be of interest.

Recognition, Description, and Variability of Spasticity in Individuals With Multiple Sclerosis and Potential Barriers to Clinician-Patient Dialogue: Results From SEEN-MSS, a Large-Scale, Self-Reported Survey.

BACKGROUND: The experience with spasticity varies among individuals with multiple sclerosis and spasticity (MSS), as they may not recognize it as spasticity or have the language to describe their symptoms. This can lead to potential delays in diagnosis and treatment. METHODS: Symptoms and Emotions Exploration Needed in Multiple Sclerosis Spasticity was an online survey completed by 1177 individuals with MSS in 2021. It sought to capture symptoms of spasticity, variability of symptoms, specific spasticity triggers, and how conversations with physicians were initiated. RESULTS: The mean age of the cohort was 56.8 years and it was 78% women. Prior to spasticity onset, 65% of respondents felt minimally prepared or unprepared for possibly developing spasticity and were unaware that spasticity manifests as part of MS. Eighty percent experienced spasticity daily, which was variable in severity and duration. Spasticity was triggered by a range of factors and 90% of those surveyed were unable to predict when it would occur or its severity. Day-to-day variability of spasticity prevented 65% of respondents from doing things they wished to do. Sixty percent were confused by their symptoms, not recognizing them as spasticity. Although 91% reported experiencing muscle spasms, only 69% used "muscle spasms" to describe their symptoms. Other descriptors included "muscle tightness," "stiffness," "cramping," and "pain." After recognizing spasticity, 78% proactively initiated discussions with their physicians, 52% wished they had done so sooner, and 42% delayed the conversation by up to or more than a year. CONCLUSIONS: Results emphasize the variable nature of spasticity and the lack of a common language to describe symptoms, underscoring the importance of education, earlier recognition, and customized treatments tailored to the severity and duration of spasticity symptoms.

Progressive Encephalomyelopathy in an Older Man: A Case Report From the National Multiple Sclerosis Society Case Conference Proceedings.

We present a case of subacute onset progressive encephalomyelopathy in a 77-year-old man with symmetric lateral column signal abnormalities on spinal MRI. We discuss the differential and presumptive final diagnosis along with a review of the postulated disease immunopathogenesis.

Relapsing White Matter Disease and Subclinical Optic Neuropathy: From the National Multiple Sclerosis Society Case Conference Proceedings

A 16-year-old adolescent boy presented with recurrent episodes of weakness and numbness. Brain MRI demonstrated subcortical, juxtacortical, and periventricular white matter T2 hyperintensities with gadolinium enhancement. CSF was positive for oligoclonal bands that were not present in serum. Despite treatment with steroids, IV immunoglobulins, plasmapheresis, and rituximab, he continued to have episodes of weakness and numbness and new areas of T2 hyperintensity on imaging. Neuro-ophthalmologic examination revealed a subclinical optic neuropathy with predominant involvement of the papillomacular bundle. Genetic evaluation and brain biopsy led to an unexpected diagnosis.

A 42-Year-Old Woman With Rapidly Expanding White Matter Lesions: From the National Multiple Sclerosis Society Case Conference Proceedings.

A 42-year-old woman and active cocaine user complained of subacutely worsening blurred vision and imbalance. Examination of the brain MRI showed rapidly expanding white matter lesions. Brain biopsy was consistent with inflammatory demyelination. Given an unusual presentation and a history of cocaine use, a broad differential diagnosis was considered including neurologic toxidromes.

Teenager With Recurrent Ataxia, Ophthalmoplegia, and Encephalopathy Associated With Demyelination: From the National Multiple Sclerosis Society Case Conference Proceedings

A 15-year-old adolescent boy developed subacute ataxia, encephalopathy, ophthalmoplegia, and dysarthria following a sore throat. An MRI examination revealed multifocal enhancing and nonenhancing supratentorial white matter and symmetric brainstem lesions. After 2 additional presentations with worsening symptoms and lesion accumulation, he was ultimately successfully treated with rituximab for his condition.

Insights for Healthcare Providers on Shared Decision-Making in Multiple Sclerosis: A Narrative Review.

Shared decision-making (SDM) between the patient and their healthcare provider (HCP) in developing treatment plans is increasingly recognized as central to improving treatment adherence and, ultimately, patient outcomes. In multiple sclerosis (MS), SDM is particularly crucial for optimizing treatment in a landscape that has grown more complex with the availability of newer, high-efficacy MS therapies. However, little direct evidence on the effectiveness of SDM is available to guide practice. Multiple factors, including patient age, ethnic background, perceptions, invisible MS symptoms, and psychological comorbidities can influence a patient's willingness and ability to participate in SDM. HCPs need to appreciate these factors and ask the right questions to break down obstacles to SDM. The HCP has a responsibility to help patients feel adequately informed and comfortable in having an active role in their care. This review identifies potential barriers to SDM and provides a strategy for HCPs to overcome these obstacles through patient (and caregiver) discussions to ensure optimal patient satisfaction with treatment and thus the best possible outcomes for their patients.

Expanding clinical profiles and prognostic markers in stiff person syndrome spectrum disorders.

OBJECTIVE: To describe the clinical features of a cohort of individuals with stiff person syndrome spectrum disorders (SPSD) and identify potential early predictors of future disability. BACKGROUND: There is a need to better understand the full spectrum of clinical and paraclinical features and long-term impact of SPSD. DESIGN/METHODS: Observational study from 1997 to 2022 at Johns Hopkins. Clinical phenotypes included classic SPS, partial SPS (limb or trunk limited), SPS-plus (classic features plus cerebellar/brainstem involvement), and progressive encephalomyelitis with rigidity and myoclonus (PERM). Outcome measures were modified Rankin scale (mRS) and use of assistive device for ambulation. Multivariate logistic regression was used to assess significant predictors of outcomes. RESULTS: Cohort included 227 individuals with SPSD with mean follow-up of 10 years; 154 classic, 48 SPS-plus, 16 PERM, and 9 partial. Mean age at symptom onset was 42.9 ± 14.1 years, majority were white (69.2%) and female (75.8%). Median time to diagnosis was 36.2 months (longest for SPS-plus and PERM) and 61.2% were initially misdiagnosed. Most had systemic co-morbidities and required assistive devices for ambulation. Female sex (OR 2.08; CI 1.06-4.11) and initial brainstem/cerebellar involvement (OR 4.41; CI 1.63-14.33) predicted worse outcome by mRS. Older age at symptom onset (OR 1.04; CI 1.01-1.06), female sex (OR 1.99; CI 1.01-4.01), Black race (OR 4.14; CI 1.79-10.63), and initial brainstem/cerebellar involvement (OR 2.44; CI 1.04-7.19) predicted worse outcome by use of assistive device. Early implementation of immunotherapy was associated with better outcomes by either mRS (OR 0.45; CI 0.22-0.92) or use of assistive device (OR 0.79; CI 0.66-0.94). CONCLUSIONS: We present the expanding phenotypic variability of this rare spectrum of disorders and highlight potential predictors of future disability.

Tuberculous Meningitis or Neurosarcoidosis-a Diagnostic Quandary. From the National Multiple Sclerosis Society Case Conference Proceedings

Distinguishing granulomatous diseases remains diagnostically challenging. Clinical phenotypes and neuroimaging findings resemble many infectious and noninfectious disorders. We describe a Hispanic/Latino man diagnosed with tuberculous meningitis who deteriorated neurologically after treatments. Additional workup revealed a pathology more consistent with neurosarcoidosis. Care access delays and social circumstances likely complicated his diagnosis.

Prevalence of non-neurological autoantibodies and related comorbidities in stiff person spectrum disorders.

Background: Stiff Person Syndrome Spectrum Disorders (SPSD) are a group of rare neurological disorders that can present alongside other autoimmune conditions. However, not much is known about the breadth of non-neurological autoantibodies seen in SPSD nor the observed prevalence of co-existing autoimmune comorbidities and their impact on SPSD. Objective: This study aimed to investigate the prevalence of non-neurological autoantibodies and associated conditions in a large cohort of people with SPSD. Methods: A retrospective review of 205 patients with suspected/definitive SPSD seen at Johns Hopkins Hospital from 1997 to 2023 was performed as part of an ongoing, observational study. Relevant demographics, clinical data (e.g., SPSD phenotypes, comorbid conditions, and dates of diagnoses), and laboratory values were collected from electronic medical records. Lab values were excluded if completed within 6 months of receiving intravenous immunoglobin treatment. Summary statistics were performed and assessment for any associations between autoimmune comorbidities and disease burden (modified Rankin score [mRS] and ambulation status) was performed. Results: The majority of participants had classic SPS (66%), followed by SPS-plus (18%) and PERM (6%) with less than 5% each of the remaining phenotypes and suspected SPS. The average age at symptom onset in this cohort was 44.1 ± 14.5 years (mean ± standard deviation). The majority of the cohort was white (66%) and female patients (75%). The mean mRS was 2.5, and over 70% required assistive devices for ambulation. The most commonly identified non-neurological autoantibodies were anti-nuclear (ANA) (31%), thyroperoxidase (30%), thyroglobulin (20%), and anti-parietal cell (18%) autoantibodies. The most common comorbid autoimmune conditions were autoimmune thyroiditis (38%), insulin-dependent diabetes mellitus (26%), and pernicious anemia (10%). Having more autoimmune comorbidities was weakly associated with higher mRS and a greater need for ambulatory assistance. Conclusion: The results of this study will hopefully help promote awareness of which autoantibody and medical comorbidity clinicians should be aware of and monitor people with SPSD. Further research is needed to identify if poorly controlled non-neurological autoimmune disorders contribute to disease burden in SPSD and/or if the timing of being diagnosed with one of these conditions plays a role in future disability.

The many faces of gastrointestinal dysfunction in stiff person syndrome spectrum disorders.

Introduction: The effect of stiff person syndrome spectrum disorders (SPSD) on the gastrointestinal tract (GIT) is unknown. This case series aims to characterize the prevalence and types of GI dysfunction in individuals with SPSD. Methods: A retrospective chart review included individuals diagnosed with SPSD with descriptors of GI symptoms in their medical records. SPSD phenotypes, type of motility test performed, and dysmotility pattern (upper, lower, or diffuse) were assessed. Descriptive statistics and univariate chi-square analyses were utilized. Results: Of 240 individuals with SPSD, 32% reported GI symptoms, most were female (83.1%), and white (74%), with a median age at time of GI symptom onset of 50 ± 13 years. Most common symptoms reported were dysphagia (45%), constipation (40%), and nausea/vomiting (23%). Most individuals had classic SPS (47%) followed by SPS-plus (29%) and 82.9% were positive for serum antiGAD65 antibodies. Of 36 patients that underwent at least one GI motility test, 26 had evidence of upper, lower, or diffuse GI dysmotility (44.4%, 17%, and 4%, respectively). The group who did not undergo testing had a higher proportion of patients with DM. Discussion: There is a high prevalence of GI symptoms and transit abnormalities in patients with SPSD. Future prospective, longitudinal studies are warranted to further assess GI symptoms in the context of SPSD and to determine if individuals with GI symptoms differ in prognosis or treatment response from those without GI symptoms. In the meantime, there should be a low threshold for motility testing in patients with SPSD.

No Evidence of Disease Activity (NEDA) as a Clinical Assessment Tool for Multiple Sclerosis: Clinician and Patient Perspectives [Narrative Review].

The emergence of high-efficacy therapies for multiple sclerosis (MS), which target inflammation more effectively than traditional disease-modifying therapies, has led to a shift in MS management towards achieving the outcome assessment known as no evidence of disease activity (NEDA). The most common NEDA definition, termed NEDA-3, is a composite of three related measures of disease activity: no clinical relapses, no disability progression, and no radiological activity. NEDA has been frequently used as a composite endpoint in clinical trials, but there is growing interest in its use as an assessment tool to help patients and healthcare professionals navigate treatment decisions in the clinic. Raising awareness about NEDA may therefore help patients and clinicians make more informed decisions around MS management and improve overall MS care. This review aims to explore the potential utility of NEDA as a clinical decision-making tool and treatment target by summarizing the literature on its current use in the context of the expanding treatment landscape. We identify current challenges to the use of NEDA in clinical practice and detail the proposed amendments, such as the inclusion of alternative outcomes and biomarkers, to broaden the clinical information captured by NEDA. These themes are further illustrated with the real-life perspectives and experiences of our two patient authors with MS. This review is intended to be an educational resource to support discussions between clinicians and patients on this evolving approach to MS-specialized care.

Recent progress in multiple sclerosis (MS) has led to the development of new treatments, known as high-efficacy therapies. Compared with previous treatments, high-efficacy therapies are better at managing visible inflammation of the central nervous system, a main cause of worsening symptoms early on in people living with MS. Treatment with high-efficacy therapies means many people with MS may achieve better outcomes than previously possible. One such outcome is the set of criteria known as no evidence of disease activity (NEDA). Achieving NEDA-3, the most commonly used NEDA criteria, means that people exhibit no clinical relapses, no worsening of physical symptoms, and no visible disease activity on a magnetic resonance imaging scan. Researchers have studied NEDA as an outcome in MS clinical trials, but it may be useful in clinical practice as a tool for doctors to measure a person's disease progression and response to treatment. This could help to inform important decisions around treatment selection and improve overall care for people with MS. This review explores the available information about NEDA to understand its potential to support clinical decision-making and patient evaluations. We discuss the barriers to NEDA being used in clinical practice and the ways the criteria may change to capture a broader range of clinical information from the patient. These topics are presented alongside the real-life perspectives and experiences of our two patient authors with MS. This review is meant to be an educational resource to assist conversations about NEDA between clinicians and patients in everyday clinical practice.

A 28-Year-Old Woman With Left-Sided Weakness and Atypical MRI Lesions: From the National Multiple Sclerosis Society Case Conference Proceedings.

A 28-year-old woman presented with subacute relapsing left-sided weakness. MRI demonstrated both enhancing C3-C6 and nonenhancing T2-T4 lesions. Initial provisional diagnosis was inflammatory/autoimmune. Her left-sided weakness progressed despite immunosuppressive therapies. We reassessed our original suspected diagnosis because of an atypical clinicoradiologic course, leading to biopsy and a definitive diagnosis.

HACA3: A unified approach for multi-site MR image harmonization.

The lack of standardization and consistency of acquisition is a prominent issue in magnetic resonance (MR) imaging. This often causes undesired contrast variations in the acquired images due to differences in hardware and acquisition parameters. In recent years, image synthesis-based MR harmonization with disentanglement has been proposed to compensate for the undesired contrast variations. The general idea is to disentangle anatomy and contrast information from MR images to achieve cross-site harmonization. Despite the success of existing methods, we argue that major improvements can be made from three aspects. First, most existing methods are built upon the assumption that multi-contrast MR images of the same subject share the same anatomy. This assumption is questionable, since different MR contrasts are specialized to highlight different anatomical features. Second, these methods often require a fixed set of MR contrasts for training (e.g., both T1-weighted and T2-weighted images), limiting their applicability. Lastly, existing methods are generally sensitive to imaging artifacts. In this paper, we present Harmonization with Attention-based Contrast, Anatomy, and Artifact Awareness (HACA3), a novel approach to address these three issues. HACA3 incorporates an anatomy fusion module that accounts for the inherent anatomical differences between MR contrasts. Furthermore, HACA3 can be trained and applied to any combination of MR contrasts and is robust to imaging artifacts. HACA3 is developed and evaluated on diverse MR datasets acquired from 21 sites with varying field strengths, scanner platforms, and acquisition protocols. Experiments show that HACA3 achieves state-of-the-art harmonization performance under multiple image quality metrics. We also demonstrate the versatility and potential clinical impact of HACA3 on downstream tasks including white matter lesion segmentation for people with multiple sclerosis and longitudinal volumetric analyses for normal aging subjects. Code is available at https://github.com/lianruizuo/haca3.

Stiff Person Spectrum Disorders-An Update and Outlook on Clinical, Pathophysiological and Treatment Perspectives.

Stiff person spectrum disorders (SPSD) are paradigm autoimmune movement disorders characterized by stiffness, spasms and hyperekplexia. Though rare, SPSD represent a not-to-miss diagnosis because of the associated disease burden and treatment implications. After decades as an enigmatic orphan disease, major advances in our understanding of the evolving spectrum of diseases have been made along with the identification of multiple associated autoantibodies. However, the most important recent developments relate to the recognition of a wider affection, beyond the classic core motor symptoms, and to further insights into immunomodulatory and symptomatic therapies. In this review, we summarize the recent literature on the clinical and paraclinical spectrum, current pathophysiological understanding, as well as current and possibly future therapeutic strategies.

Therapeutic plasma exchange in the management of stiff person syndrome spectrum disorders: a case series and review of the literature.

Background: Stiff person syndrome spectrum disorders (SPSD) are a rare group of disabling neuroimmunological disorders. SPSD often requires immune therapies, especially in the setting of inadequate response to symptomatic treatments. The safety and efficacy of therapeutic plasma exchange (TPE) in SPSD remains uncertain. Objectives: To describe the safety, tolerability, and efficacy of TPE in patients with SPSD. Design: A retrospective observational study. Methods: A retrospective review of SPSD patients seen at Johns Hopkins Hospital (JHH) from 1997 to 2021 was performed. Patient demographics/history, examination/diagnostic findings, treatment response, and TPE-related complications were recorded. Assessment for any associations between clinical characteristics, including age, sex, clinical phenotype, and time on immunotherapy, and response to TPE 3 months after treatment was performed. A subgroup of 18 patients treated with TPE at JHH and 6 patients treated with TPE at outside institutions were evaluated for any change in usage of symptomatic medications 3 months after the TPE treatment. Literature review of SPSD and TPE was also conducted. Results: Thirty-nine SPSD patients were treated with TPE (21 at JHH and 18 at outside institutions); median age 48 years, 77% female, median modified Rankin Scale 3; mean initial anti-GAD65 antibody titer was 23,508 U/mL. Twenty-four patients (62%) had classic SPS, 10 (26%) had SPS-plus, 2 (5%) had progressive encephalomyelitis with rigidity and myoclonus, and 3 (8%) had pure cerebellar ataxia. All patients were on symptomatic treatments, 30 (77%) previously received IVIg, and 3 (8%) previously received rituximab. Four patients (10%) had a TPE-related adverse event. One developed asymptomatic hypotension, another had both line thrombosis and infection, and two had non-life-threatening bleeding events. Twenty-three (59%) patients reported improvement in symptoms after TPE. Of the subgroup of 24 patients evaluated for any change in usage of symptomatic medications 3 months after the TPE treatment, 14 (58%) required fewer GABAergic symptomatic medications. Literature review identified 57 additional patients with SPSD; 43 (75%) reported temporary improvement after TPE. Conclusion: The majority of patients treated with TPE had improvement. Moreover, most patients evaluated for any change in usage of symptomatic medications after the TPE treatment no longer required as much symptomatic medications months after TPE. TPE appears safe and well-tolerated in SPSD. Further studies are needed to assess the long-term efficacy of TPE in SPSD and identify which patients may benefit the most from TPE.

Differential diagnosis of suspected multiple sclerosis: an updated consensus approach.

Accurate diagnosis of multiple sclerosis requires careful attention to its differential diagnosis-many disorders can mimic the clinical manifestations and paraclinical findings of this disease. A collaborative effort, organised by The International Advisory Committee on Clinical Trials in Multiple Sclerosis in 2008, provided diagnostic approaches to multiple sclerosis and identified clinical and paraclinical findings (so-called red flags) suggestive of alternative diagnoses. Since then, knowledge of disorders in the differential diagnosis of multiple sclerosis has expanded substantially. For example, CNS inflammatory disorders that present with syndromes overlapping with multiple sclerosis can increasingly be distinguished from multiple sclerosis with the aid of specific clinical, MRI, and laboratory findings; studies of people misdiagnosed with multiple sclerosis have also provided insights into clinical presentations for which extra caution is warranted. Considering these data, an update to the recommended diagnostic approaches to common clinical presentations and key clinical and paraclinical red flags is warranted to inform the contemporary clinical evaluation of patients with suspected multiple sclerosis.

A Phase 1b, Open-Label Study to Evaluate the Safety and Tolerability of the Putative Remyelinating Agent, Liothyronine, in Individuals with MS.

Thyroid hormones are essential during developmental myelination and may play a direct role in remyelination and repair in the adult central nervous system by promoting the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes. Since tri-iodothyronine (T3) is believed to mediate the majority of important thyroid hormone actions, liothyronine (synthetic T3) has the potential to induce reparative mechanisms and limit neurodegeneration in multiple sclerosis (MS). We completed a phase 1b clinical trial to determine the safety and tolerability of ascending doses of liothyronine in individuals with relapsing and progressive MS. A total of 20 people with MS were enrolled in this single-center trial of oral liothyronine. Eighteen participants completed the 24-week study. Our study cohort included mostly women (11/20), majority relapsing MS (12/20), mean age of 46, and baseline median EDSS of 3.5. Liothyronine was tolerated well without treatment-related severe/serious adverse events or evidence of disease activation/clinical deterioration. The most common adverse events included gastrointestinal distress and abnormal thyroid function tests. No clinical thyrotoxicosis occurred. Importantly, we did not observe a negative impact on secondary clinical outcome measures. The CSF proteomic changes suggest a biological effect of T3 treatment within the CNS. We noted changes primarily in proteins associated with immune cell function and angiogenesis. Liothyronine appeared safe and was well tolerated in people with MS. A larger clinical trial will help assess whether liothyronine can promote oligodendrogenesis and enhance remyelination in vivo, limit axonal degeneration, or improve function.

Assessment of anti-GAD65-associated cerebellar ataxia with 18F-FDG cerebellar uptake: ROC analysis.

OBJECTIVE: Anti-glutamic acid decarboxylase 65 (anti-GAD65)-associated neurological disorders include two major phenotypes, namely Stiff person syndrome (SPS) and cerebellar ataxia (CA). Considering the potential for better outcomes with prompt immunotherapy, early detection of CA is crucial. Hence, a non-invasive imaging biomarker to detect CA with high specificity is desired. Herein, we evaluated brain 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) PET in detecting CA based on cerebellar uptake using receiver operating characteristic (ROC) analysis and five-fold cross-validation. METHODS: This study was based on STARD 2015 guidelines: thirty patients with anti-GAD65-associated neurological disorders, 11 of whom with CA were studied. Five test sets were created after patients were randomly sorted and divided into 5 equal folds. Each iteration included 24 patients for ROC analysis and 6 patients reserved for testing. The Z scores of left cerebellum, vermis, right cerebellum, and the average of the three regions were used in ROC analysis to determine areas with significant area under the curve (AUC). The cut-off values with high specificity were determined among the 24 patients in each iteration and tested against the reserved 6 patients. RESULTS: Left cerebellum and average of the three regions showed significant AUC above 0.5 in all iterations with left cerebellum being the highest AUC in 4 iterations. Testing the cut-off values of the left cerebellum against the reserved 6 patients in each iteration showed 100% specificity with sensitivities ranging from 0 to 75%. CONCLUSIONS: Cerebellar 18F-FDG PET uptake can differentiate CA phenotypes from patients with SPS with high specificity.

Respiratory symptoms are common in stiff person syndrome spectrum disorders and are associated with number of body regions involved.

BACKGROUND AND PURPOSE: Stiff person syndrome (SPS) spectrum disorders (SPSSD) cause spasms and rigidity throughout different body regions and can be associated with apnea and acute respiratory failure. There are limited data on the prevalence and predictors of respiratory symptoms with spasms (RSwS) in SPSSD. We sought to characterize the spirometry patterns and the frequency and predictors of RSwS in a large SPSSD cohort. METHODS: Participants were recruited from the Johns Hopkins SPS Center between 1997 and 2021, as part of an ongoing, longitudinal observational study. Medical records were reviewed to assess demographics and clinical characteristics. Data were analyzed using descriptive statistics and multivariable logistic regression models. RESULTS: One-hundred ninety-nine participants (mean age = 53.4 ± 13.6 years, median time to diagnosis = 36 [IQR 66] months, 74.9% women, 69.8% White, 62.8% classic SPS phenotype) were included in final analyses; 35.2% of participants reported RSwS, of whom 24.3% underwent spirometry as part of routine clinical care. Obstructive (23.5%) and restrictive (23.5%) patterns were most commonly observed in those with SPSSD. An increasing number of body regions involved predicted the presence of RSwS (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.50-2.53); those with ≥5 body regions involved (vs. ≤4) had higher odds (OR = 6.19, 95% CI = 2.81-13.62) of experiencing RSwS in adjusted models. Two patients died from SPSSD-associated respiratory compromise. CONCLUSIONS: RSwS are common in SPSSD and may be predicted by an increasing number of body regions involved by SPSSD. Close clinical monitoring and having a low threshold to obtain spirometry should be considered in people with SPSSD.