Small fiber neuropathy associated with ANCA positivity: a case series and brief literature review.

INTRODUCTION: Small fiber neuropathy [SFN] is a common peripheral neurologic disorder with a vast array of implicated etiologies. It has previously been proposed that some forms of immune-mediated small fiber neuropathy are driven by vasculitis, though antinuclear cytoplasmic antibodies [ANCA] antibodies have not commonly been reported in association with SFN, thus far. We present this case series to discuss the observation of a possible novel association between ANCA and SFN. METHODS: This is a retrospective case series of 6 patients with SFN and ANCA positivity, with and without systemic manifestations. Patients included were diagnosed with SFN by skin biopsy or autonomic function testing and were seropositive for ANCA by ELISA. RESULTS: Six patients are outlined, including 4 females and 2 males. Antigen specific antibodies were MPO alone in 4 cases, PR3 alone in 1 case and both MPO and PR3 in 1 case. Systemic vasculitis was noted in 2 patients. Five patients received immunosuppression. Three patients experienced partial improvement, while symptoms stabilized in 3 patients. DISCUSSION: This is the first series of patients with suspected immune-mediated SFN and ANCA antibody positivity, raising the possibility of ANCA mediated isolated SFN. This is in contradistinction to the more typical ANCA-mediated peripheral neuropathy manifestations of mononeuropathy multiplex or axonal sensorimotor neuropathy. We cannot unequivocally prove ANCA-associated vasculitis [AAV] causality in these cases; however, the stabilization in SFN symptomatology and associated improvement in ANCA antibody titer, after AAV treatment, may be indicative of an association.

Fluorescein Angiography Findings in Susac Syndrome: A Multicenter Retrospective Case Series.

BACKGROUND: Susac syndrome is a vasculopathy, resulting in the classic triad of branch retinal artery occlusion (BRAO), inner ear ischemia, and brain ischemia. In this retrospective chart review, we characterize fluorescein angiography (FA) findings and other ancillary studies in Susac syndrome, including the appearance of persistent disease activity and the occurrence of new subclinical disease on FA. METHODS: This multicenter, retrospective case series was institutional review board-approved and included patients with the complete triad of Susac syndrome evaluated with FA, contrasted MRI of the brain, and audiometry from 2010 to 2020. The medical records were reviewed for these ancillary tests, along with demographics, symptoms, visual acuity, visual field defects, and findings on fundoscopy. Clinical relapse was defined as any objective evidence of disease activity during the follow-up period after initial induction of clinical quiescence. The main outcome measure was the sensitivity of ancillary testing, including FA, MRI, and audiometry, to detect relapse. RESULTS: Twenty of the 31 (64%) patients had the complete triad of brain, retinal, and vestibulocochlear involvement from Susac syndrome and were included. Median age at diagnosis was 43.5 years (range 21-63), and 14 (70%) were women. Hearing loss occurred in 20 (100%), encephalopathy in 13 (65%), vertigo in 15 (75%), and headaches in 19 (95%) throughout the course of follow-up. Median visual acuity at both onset and final visit was 20/20 in both eyes. Seventeen (85%) had BRAO at baseline, and 10 (50%) experienced subsequent BRAO during follow-up. FA revealed nonspecific leakage from previous arteriolar damage in 20 (100%), including in patients who were otherwise in remission. Of the 11 episodes of disease activity in which all testing modalities were performed, visual field testing/fundoscopy was abnormal in 4 (36.4%), MRI brain in 2 (18.2%), audiogram in 8 (72.7%), and FA in 9 (81.8%). CONCLUSIONS: New leakage on FA is the most sensitive marker of active disease. Persistent leakage represents previous damage, whereas new areas of leakage suggest ongoing disease activity that requires consideration of modifying immunosuppressive therapy.

Contrasting Cases of HIV Vasculopathy Associated Fusiform Aneurysms.

Background: Human Immunodeficiency Virus (HIV) vasculopathy encompasses the development of aneurysms, stenosis and vessel occlusions. Intracranial fusiform aneurysms in Human Immunodeficiency Virus (HIV) were originally described in children; however, HIV-associated aneurysms are increasingly recognized in adults. Purpose: We present two cases to highlight the spectrum of severity and outline instructive clinical courses. Results: Case one is a 52-year-old woman with HIV, Acquired Immunodeficiency Syndrome (AIDS)-defining progressive multifocal leukoencephalopathy (PML) and an 18 years course of cerebral aneurysms, aneurysm thrombosis and the development of right middle cerebral artery (MCA) moyamoya pattern collaterals. Case two is a 55-year-old man with AIDS-defining cerebral toxoplasmosis, complicated by IRIS and anterior and posterior circulation fusiform aneurysm formation. Conclusions: The combination of both fusiform abnormalities and Moyamoya, discussed in our first case has not been previously described. In comparison, our second case actually demonstrated improvement in vasculopathy after nine-months of antiretroviral therapy (ART) adherence.

Lessons Learned in Outpatient Physical Therapy for Motor Functional Neurological Disorder.

BACKGROUND AND PURPOSE: Motor functional neurological disorder is a prevalent and costly condition at the intersection of neurology and psychiatry that is diagnosed using positive "rule-in" signs. Physical therapy is a first-line treatment and consensus recommendations exist to guide clinical care. Nonetheless, optimal outpatient treatment of adults with functional motor symptoms requires an expanded physical therapy tool kit to effectively guide care. SUMMARY OF KEY POINTS: In this article, lessons learned from a physical therapist practicing in a multidisciplinary and interdisciplinary outpatient functional neurological disorder clinic are highlighted. In doing so, we discuss how use of the biopsychosocial model and neuroscience constructs can inform physical therapy interventions. The importance of team-based care and the delivery of physical therapy through video telehealth services are also outlined. RECOMMENDATIONS FOR CLINICAL PRACTICE: Use of the biopsychosocial formulation to triage clinical challenges and guide longitudinal care, coupled with application of neuroscience to aid intervention selection, allows for patient-centered physical therapy treatment across the spectrum of functional motor symptoms.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A400 ).

Ischemic stroke in neurosarcoidosis: A retrospective cohort analysis.

BACKGROUND: Cerebrovascular disease is rarely reported in neurosarcoidosis and constitutes one of its least well-described forms, though recognition for it has grown in the last decade with recent studies estimating a higher frequency of occurrence than previously known. METHODS: Patients with ischemic stroke were included if the mechanism was directly attributable to sarcoidosis of the CNS. Patients were excluded if an alternative stroke etiology was of equal or higher likelihood than CNS sarcoidosis. RESULTS: Neurologic disease was the initial presenting manifestation of sarcoidosis in 8/11 (72.7%), and ischemic stroke was an inaugural manifestation of sarcoidosis in 4/11 (36.4%). Small vessel disease was the predominant ischemia subtype (10/11, 90.9%) with pontine perforating vessels (6/11, 54.5%) and lenticulostriate arteries (3/11, 27.3%) being the vasculature most often affected. Vessels with a more rostral supratentorial distribution were uncommonly affected. Common neuroinflammatory accompaniments included leptomeningitis (10/11, 90.9%) and cranial nerve disease (3/11, 27.3%). Recurrent strokes occurred in 8/11 (72.7%), and recurrent neuroinflammation occurred in 7/11 (63.6%). Antiplatelet drugs were used in 6/11 (54.5%) patients. Most (10/11, 90.9%) required at least two lines of immunosuppression to achieve inflammatory disease remission in this context; infliximab was the most successfully employed immunosuppressant (7/8 treatment courses, 87.5%). Recurrent strokes occurred in 8/11 (72.7%) patients, and a second inflammatory attack occurred in 7/11 (63.6%) patients. The presenting median modified Rankin Scale score of 4.0 improved to 2.0 over a median period of follow-up of 52.0 months. CONCLUSION: Ischemic strokes in neurosarcoidosis occur in a caudal-to-rostral distribution, tend to affect small caliber blood vessels that lack collateral blood flow, and typically associate with inflammatory leptomeningeal disease. The risk for relapse in the forms of stroke or neuroinflammation are high in this neurosarcoidosis phenotype.

Autoimmune and Paraneoplastic Chorea: A Review of the Literature.

Autoimmune chorea syndromes represent a vast array of paraneoplastic, parainfectious and idiopathic disorders. It is increasingly apparent that familiarity with these disorders is critically important, as they may be treatable or may be part of a syndrome requiring further work-up and monitoring. These disorders are mediated by an aberrant immunologic attack with resultant neuronal dysfunction, manifesting as chorea. These conditions are typically accompanied by other neurologic or systemic manifestations. In this review we outline the clinical features, epidemiologic factors, and delineate the specific antibodies associated with each of these autoimmune mediated disorders. We highlight up to date information regarding this heterogeneous group of disorders, including a discussion of parainfectious Sydenham's chorea; paraneoplastic syndromes associated with CRMP-5 (collapsin response mediated protein-5/CV2) and ANNA-1 (antineuronal nuclear antibody / Hu) antibodies, in addition to neuronal antibody-associated disorders including anti-NMDAR, LGI1 (leucine-rich glioma inactivated-1) and CASPR2 (contactin associated protein-2). We discuss the more recently described entities of IgLON5, which has evidence of both immunologic and degenerative pathophysiology, in addition to PDE-10A antibody-associated chorea. We also outline chorea secondary to systemic diseases including Systemic Lupus Erythematosus (SLE) and Primary Antiphospholipid Syndrome (PAPS). We provide a framework for diagnosis and treatment.

Adalimumab for CNS sarcoidosis: single-center experience and literature review.

BACKGROUND: Tumor necrosis factor (TNF) alpha is critical in the development of granulomas and multiple recent reports have highlighted the role of infliximab, an infused TNF alpha inhibitor, in the treatment of neurosarcoidosis. As a self-injected TNF alpha inhibitor, adalimumab has certain advantages over infused medications, including greater patient freedom and autonomy. Experience with adalimumab is not well reported in the literature. OBJECTIVE: To report clinical experience with adalimumab in the treatment of central nervous system (CNS) sarcoidosis by combining observations in our center with those that have been reported in the literature. METHODS: Patients were identified from the Mass General Brigham Research Patient Data Registry and in the literature by searching PubMed. Patients with CNS manifestations of sarcoidosis treated with adalimumab were included for retrospective review and analyzed for baseline characteristics, treatment indications, outcomes, and adverse effects. RESULTS: Adalimumab was commonly started after failure of or intolerance to infliximab and methotrexate. Of those with adequate follow-up, 5/10 ultimately improved, remission was maintained in 3/10, and 2/10 with active disease remained stable without further worsening. One patient suffered a relapse, likely multifactorial in etiology, but has remained relapse free on adalimumab for 10 months subsequently. Three patients ultimately discontinued adalimumab. CONCLUSIONS: Preliminary evidence suggests that adalimumab may be a reasonable therapeutic option for patients with neurosarcoidosis affecting the CNS, including those with medically refractory disease.

Treatment of psychosis in Parkinson's disease and dementia with Lewy Bodies: A review.

There is a considerable overlap between Parkinson's Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB). They present a challenge therapeutically, with regard to morbidity and mortality risk. In particular, symptoms of psychosis in these conditions augur a considerably increased burden. To date, there has been a myriad of prospective, retrospective and case studies examining the use of neuroleptics in the treatment of psychotic symptoms in PDD/DLB. Clozapine has the most robust evidence base however its use is limited by agranulocytosis risk and the associated need for frequent blood count monitoring. Quetiapine is more readily used, however, it has a more equivocal evidence base, in terms of efficacy. Other neuroleptics have thus far demonstrated mixed results with increased risk of extrapyramidal worsening. In addition to the atypical agents, the introduction of pimavanserin has provided another treatment option for Parkinson's Disease Psychosis (PDP), decreasing concern for deterioration in motor function. We await further research to confidently demonstrate its efficacy and safety in DLB psychosis. Cholinesterase inhibitors likely have a limited role in treating milder psychosis symptomatology in DLB and perhaps PDD. After review of the current literature for antipsychotic therapy in both PDD and DLB, we provide a logical framework for addressing psychotic symptoms in each condition.

Laser-induced fluorescence imaging and spectroscopy of GFP transgenic plants.

Green fluorescent protein (GFP) and other fluorescent protein bioreporters can be used to monitor transgenes in plants. GFP is a valuable marker for transgene presence and expression, but remote sensing instrumentation for stand-off detection has lagged behind fluorescent protein marker biotechnology. However, both biology and photonics are needed for the monitoring technology to be fully realized. In this paper, we describe laser-induced fluorescence imaging and laser-induced fluorescence spectroscopy of GFP-transgenic plants in ambient light towards the application of remote sensing of transgenic plants producing GFP.