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OBJECTIVE: To explore the clinical progression of the brain-/body-first categories within Lewy body disease (LBD): Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD dementia. METHODS: We used of the Rochester Epidemiology Project to establish a population-based cohort of clinically diagnosed LBD. We used two definitions for differentiating between brain- and body-first LBD: a previously hypothesized body-first presentation in patients with rapid eye movement sleep behavior onset before motor symptoms onset; and an expanded definition of body-first LBD when a patient had at least 2 premotor symptoms between constipation, erectile dysfunction, rapid eye movement sleep behavior, anosmia, or neurogenic bladder. RESULTS: Brain-first patients were more likely to be diagnosed with PD (RR = 1.43, p = 0.003), whereas body-first patients were more likely to be diagnosed with DLB (RR = 3.15, p < 0.001). Under the expanded definition, there was no difference in LBD diagnosis between brain-first and body-first patients (PD: RR = 1.03, p = 0.10; DLB: RR = 0.88, p = 0.58) There were no patterns between brain- or body-first presentation, PD dementia under either definition (original: p = 0.09, expanded: p = 0.97), and no significant difference in motor symptoms between brain-first and body-first. INTERPRETATION: Our findings do not support the dichotomous classification of body-first and brain-first LBD with the currently proposed definition. Biological exposures resulting in PD and DLB are unlikely to converge on a binary classification of top-down or bottom-up synuclein pathology. ANN NEUROL 2024;96:551-559.
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Doença por Corpos de Lewy , Doença de Parkinson , Humanos , Masculino , Idoso , Feminino , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Estudos de Coortes , Encéfalo/patologia , Encéfalo/fisiopatologia , Progressão da Doença , Transtorno do Comportamento do Sono REM/etiologia , Transtorno do Comportamento do Sono REM/epidemiologiaRESUMO
Risk of sudden death in multiple system atrophy (MSA) is greatest during sleep with unknown mechanisms. We compared nocturnal pulse event frequency in 46 MSA patients and age-/sex-matched controls undergoing overnight pulse oximetry. Nocturnal oxyhemoglobin desaturation indices and pulse event indices (PEIs) were recorded, and relationships between pulse oximetry variables and survival were analyzed. MSA patients had lower PEI (3.1 ± 5.3 vs. 12.8 ± 10.8, p < 0.001) despite greater hypoxic burden and similar frequency of respiratory events. Nocturnal pulse events were not associated with severity of daytime autonomic failure. Two MSA patients had suspected sudden death, both with severely reduced PEI. MSA patients have fewer nocturnal pulse events compared with controls, despite similar respiratory event frequency, suggesting abnormal cardiac responses to sleep-disordered breathing. Whether this contributes to sudden death in MSA requires further study. ANN NEUROL 2023;93:205-212.
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Atrofia de Múltiplos Sistemas , Síndromes da Apneia do Sono , Humanos , Sono/fisiologia , Síndromes da Apneia do Sono/complicações , Oximetria , Morte SúbitaRESUMO
PURPOSE: Prior studies reported evidence of autonomic involvement in motor neuron disease and suggested more severe dysfunction in upper motor neuron predominant syndromes. Hence, we sought to characterize autonomic impairment in primary lateral sclerosis. METHODS: Neurological evaluations, thermoregulatory sweat tests, and autonomic reflex screens were analyzed retrospectively in 34 primary lateral sclerosis patients (28 definite and 6 probable). Patients with other potential causes of autonomic failure and patients with autonomic testing results compromised by artifact were excluded. RESULTS: A total of 17 patients reported autonomic symptoms. Orthostatic lightheadedness was most frequent (8 patients), followed by bladder (7), bowel (5), and erectile dysfunction (3). The autonomic reflex screens of 33 patients were reviewed; 20 patients had abnormal studies. The thermoregulatory sweat tests of 19 patients were reviewed; 11 patients had abnormal studies. Composite Autonomic Severity Score was calculated for 33 patients and found abnormal in 20/33 patients (60.6%): 15/20 patients (75%) had mild impairment, and 5/20 patients (25%) had moderate impairment. The frequencies of testing abnormalities were: sudomotor 18/20 (90%), cardiovagal 9/20 (45%), and adrenergic 6/20 (30%). Sweat loss pattern analysis showed global, regional, and mixed patterns to be more common than length-dependent and distal patterns. CONCLUSION: We found evidence of frequent autonomic dysfunction in primary lateral sclerosis, which is generally of modest severity akin to prior reports for amyotrophic lateral sclerosis, but more commonly in a pattern consistent with preganglionic/ganglionic localization. This suggests that primary lateral sclerosis, as with amyotrophic lateral sclerosis, is a multisystem disease that affects the autonomic nervous system.
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BACKGROUND: Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. OBJECTIVE: Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. METHODS: We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. DISCUSSION: The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.
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Síndrome das Pernas Inquietas , Estimulação da Medula Espinal , Humanos , Qualidade de Vida , Síndrome das Pernas Inquietas/tratamento farmacológico , Síndrome das Pernas Inquietas/etiologiaRESUMO
OBJECTIVE: Advanced Parkinson's Disease (PD) is associated with Parkinson's Disease gait impairment (PDg), which increases the risk for falls and is often treatment-refractory. Subthalamic nucleus (STN) and globus pallidus pars interna (GPi) deep brain stimulation (DBS) often fails to improve axial symptoms like PDg. Spinal cord stimulation (SCS) has been suggested to improve PDg. SCS may benefit PDg by disrupting pathologic beta-oscillations and hypersynchrony in cortico-striatal-thalamic circuits to override excessive inhibition of brainstem locomotor regions. SCS may potentially improve locomotion by acting at any of these levels, either alone or in combination. METHODS: We conducted a comprehensive literature search and scoping review, identifying 106 patients in whom SCS was evaluated for PDg. RESULTS: Among the identified patients, 63% carried a pain diagnosis. Overall, the most common stimulation location was thoracic (78%), most commonly T9-T10. Burst (sub-perception) was the most common stimulation modality (59%). Prior treatment with DBS was used in 25%. Motor outcomes were assessed by the Unified Parkinson Disease Rating Scale (UPDRS) III-motor, UPDRS, the Timed Up and Go (TUG), and/or 10-/20-meter walking tests.Among these patients, 95 (90%) had PDg amelioration and improved motor outcomes. CONCLUSIONS: Despite small sample sizes, patient heterogeneity, and unblinded evaluations complicating interpretations of efficacy and safety, SCS may be beneficial for at least a subset of PDg. Further research is required to clarify the role of SCS for PDg and the patients most suitable to benefit from this intervention.
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Estimulação Encefálica Profunda , Doença de Parkinson , Estimulação da Medula Espinal , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Resultado do Tratamento , MarchaRESUMO
PURPOSE: To provide a brief and focused review on peripheral neuroimmune interactions and their implications for some clinical disorders. METHODS: Narrative review of the literature including of English-language articles published between 1985 and 2021 using PubMed and MEDLINE. RESULTS: Many studies on experimental models and in vitro indicate that there are close interactions between the neural and immune systems. Processes from sensory afferents and autonomic efferents co-localize with immune cells and interact at discrete anatomical sites forming neuroimmune units. These neuroimmune interactions are bidirectional and mediated by a wide range of soluble factors including neuropeptides, classical neurotransmitters, cytokines, and other molecules that mediate complex cross-talk among nerves and immune cells. Small-diameter sensory afferents express a wide range of receptors that respond directly to tissue damage or pathogen signals and to chemokines, cytokines, or other molecules released from immune cells. Reciprocally, immune cells respond to neurotransmitters released from nociceptive and autonomic fibers. Neuroimmune interactions operate both at peripheral tissues and at the level of the central nervous system. Both centrally and peripherally, glial cells have a major active role in this bidirectional communication. CONCLUSIONS: Peripheral neuroimmune interactions are complex and importantly contribute to the pathophysiology of several disorders, including skin, respiratory, and intestinal inflammatory disorders typically associated with pain and altered barrier function. These interactions may be relevant for persistence of symptoms in disorders associated with intense immune activation.
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Sistema Imunitário , Neuroimunomodulação , Sistema Nervoso Central , Citocinas , PeleRESUMO
PURPOSE: Post-COVID-19 syndrome is a poorly understood aspect of the current pandemic, with clinical features that overlap with symptoms of autonomic/small fiber dysfunction. An early systematic analysis of autonomic dysfunction following COVID-19 is lacking and may provide initial insights into the spectrum of this condition. METHODS: We conducted a retrospective review of all patients with confirmed history of COVID-19 infection referred for autonomic testing for symptoms concerning for para-/postinfectious autonomic dysfunction at Mayo Clinic Rochester or Jacksonville between March 2020 and January 2021. RESULTS: We identified 27 patients fulfilling the search criteria. Symptoms developed between 0 and 122 days following the acute infection and included lightheadedness (93%), orthostatic headache (22%), syncope (11%), hyperhidrosis (11%), and burning pain (11%). Sudomotor function was abnormal in 36%, cardiovagal function in 27%, and cardiovascular adrenergic function in 7%. The most common clinical scenario was orthostatic symptoms without tachycardia or hypotension (41%); 22% of patients fulfilled the criteria for postural tachycardia syndrome (POTS), and 11% had borderline findings to support orthostatic intolerance. One patient each was diagnosed with autoimmune autonomic ganglionopathy, inappropriate sinus tachycardia, vasodepressor syncope, cough/vasovagal syncope, exacerbation of preexisting orthostatic hypotension, exacerbation of sensory and autonomic neuropathy, and exacerbation of small fiber neuropathy. CONCLUSION: Abnormalities on autonomic testing were seen in the majority of patients but were mild in most cases. The most common finding was orthostatic intolerance, often without objective hemodynamic abnormalities on testing. Unmasking/exacerbation of preexisting conditions was seen. The temporal association between infection and autonomic symptoms implies a causal relationship, which however cannot be proven by this study.
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Doenças do Sistema Nervoso Autônomo/etiologia , COVID-19/complicações , Adulto , Idoso , Disreflexia Autonômica/etiologia , Fibras Autônomas Pós-Ganglionares/patologia , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Tontura , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Intolerância Ortostática/diagnóstico , Síndrome da Taquicardia Postural Ortostática/etiologia , Estudos Retrospectivos , Síndrome de Shy-Drager/etiologia , Adulto Jovem , Síndrome de COVID-19 Pós-AgudaRESUMO
Accurate antemortem diagnosis of parkinsonism is primarily based on clinical evaluation with limited biomarkers. We evaluated the diagnostic utility of quantitative rapid eye movement (REM) sleep without atonia analysis in the submentalis and anterior tibialis muscles in parkinsonian patients (53 synucleinopathy, 24 tauopathy). Receiver operating characteristic curves determined REM sleep without atonia cutoffs distinguishing synucleinopathies from tauopathies. Elevated submentalis muscle activity was highly sensitive (70-77%) and specific (95-100%) in distinguishing synucleinopathy from tauopathy. In contrast, anterior tibialis synucleinopathy discrimination was poor. Our results suggest that elevated submentalis REM sleep without atonia appears to be a potentially useful biomarker for presumed synucleinopathy etiologies in parkinsonism. ANN NEUROL 2019;86:969-974.
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Músculos Faciais/fisiologia , Sono REM/fisiologia , Sinucleinopatias/diagnóstico , Sinucleinopatias/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disorder from α-synuclein aggregation. in vitro studies suggest vitamin B12 may interrupt α-synuclein-mediated neurodegeneration. The objective of this study was to determine whether serum vitamin B12 level at MSA diagnosis is associated with survival. METHODS: One hundred eighty-two MSA patients evaluated at Mayo Clinic with vitamin B12 testing were studied. We determined the risk of death in relationship to serum vitamin B12 levels at MSA diagnosis, adjusting for predictors of poor survival. RESULTS: Predictors of shorter survival included vitamin B12 < 367 ng/L (HR, 1.8; 95% CI, 1.3-2.7), falls within 3 years of MSA diagnosis (HR, 1.6; 95% CI, 1.1-2.3), bladder symptoms (HR, 1.6; 95% CI, 1.0-2.6), urinary catheter requirement (HR, 1.7; 95% CI, 1.0-2.8), male sex (HR, 1.4; 95% CI, 1.0-2.0), and MSA-P subtype (HR, 1.5; 95% CI, 1.0-2.0). CONCLUSIONS: Low vitamin B12 levels are associated with shorter survival in MSA. Additional studies to explore this observation and assess the potential role of vitamin B12 as a modifiable survival factor are needed. © 2020 International Parkinson and Movement Disorder Society.
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Atrofia de Múltiplos Sistemas , Humanos , Masculino , Atrofia de Múltiplos Sistemas/diagnóstico , Vitamina B 12 , alfa-SinucleínaRESUMO
INTRODUCTION: Human papillomavirus (HPV) vaccination has been anecdotally connected to the development of dysautonomia, chronic fatigue, complex regional pain syndrome and postural tachycardia syndrome. OBJECTIVES: To critically evaluate a potential connection between HPV vaccination and the above-noted conditions. METHODS: We reviewed the literature containing the biology of the virus, pathophysiology of infection, epidemiology of associated cancers, indications of HPV vaccination, safety surveillance data and published reports linking HPV vaccination to autonomic disorders. RESULTS: At this time, the American Autonomic Society finds that there are no data to support a causal relationship between HPV vaccination and CRPS, chronic fatigue, and postural tachycardia syndrome to other forms of dysautonomia. CONCLUSION: Certain conditions are prevalent in the same populations that are vaccinated with the HPV vaccine (peri-pubertal males and females). This association, however, is an insufficient proof of causality.
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Doenças do Sistema Nervoso Autônomo/epidemiologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Sociedades Médicas/tendências , Doenças do Sistema Nervoso Autônomo/induzido quimicamente , Doenças do Sistema Nervoso Autônomo/diagnóstico , Síndrome de Fadiga Crônica/induzido quimicamente , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/epidemiologia , Humanos , Vacinas contra Papillomavirus/efeitos adversos , Síndrome da Taquicardia Postural Ortostática/induzido quimicamente , Síndrome da Taquicardia Postural Ortostática/diagnóstico , Síndrome da Taquicardia Postural Ortostática/epidemiologia , Disautonomias Primárias/induzido quimicamente , Disautonomias Primárias/diagnóstico , Disautonomias Primárias/epidemiologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Lipomatosis of nerve (LN) is a peripheral nerve disorder characterized by fibroadipose proliferation within the epineurium. It has been associated with nerve-territory overgrowth affecting soft tissue and/or bony structures. We sought to understand if there is an anatomical relationship associated with nerve-territory overgrowth. METHODS: A review of the literature and our institutional LN cases was performed to determine the prevalence of nerve-territory overgrowth. Only cases with sufficient clinical and/or imaging data were selected. The cases were then subdivided into two groups and analyzed: (1) motor (mixed) nerve and (2) predominant sensory nerve, based on the anatomical location of the LN lesion. Subgroup analysis was performed on median nerves affected by LN, for a more homogenous population. RESULTS: We identified 329 LN cases with sufficient information for analysis. Motor (mixed) nerve group (M) consisted of 287 cases (155 with overgrowth and 132 without overgrowth). Sensory nerve group (S) revealed group of 42 cases (4 cases with overgrowth and 38 without overgrowth). Statistical analysis comparing overgrowth status in the M and S nerve groups showed a statistically significant difference in overgrowth, favoring the M group for overgrowth (p < 0.0001). The analysis of median nerve group consisted of 225 cases in the M group (106 with overgrowth and 119 without overgrowth) and 20 cases in the S group (3 with overgrowth and 17 cases without overgrowth). A statistically significant difference in nerve-territory overgrowth status was present in the M vs. the S group, again favoring the M group for overgrowth. (p = 0.0083). Cases from our institution included 44 cases for this analysis. Forty-two cases in the M group (28 with overgrowth and 14 without overgrowth) and 2 cases in the S group (all 2 without overgrowth). CONCLUSION: We believe the association of LN and nerve-territory overgrowth might be explained by involvement of mixed motor nerves; however, the exact underlying mechanism is not known.
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Lipomatose/patologia , Nervo Mediano/patologia , Doenças do Sistema Nervoso Periférico/patologia , Feminino , Humanos , Lipomatose/epidemiologia , Masculino , Neurônios Motores/patologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Prevalência , Células Receptoras Sensoriais/patologiaRESUMO
The locus coeruleus (LC) contains norepinephrine (NE)-synthesizing neurons that send diffuse projections throughout the central nervous system. The LC-NE system has a major role in arousal, attention and stress responses. In the brain, NE may also contribute to long-term synaptic plasticity, pain modulation, motor control, energy homeostasis and control of local blood flow. The LC is severely affected in neurodegenerative disorders including Parkinson disease (PD). Involvement of the noradrenergic neurons of the LC precedes that of dopaminergic neurons of the substantia nigra pars compacta and has been increasingly recognized as a potential major contributor to cognitive manifestations in early PD, particularly impaired attention. Abnormal noradrenergic signaling may also potentially contribute to motor manifestations of the disease.This makes the LC-NE system a major contributor to the pathobiology and potential target for therapy of PD.
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Locus Cerúleo/patologia , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Humanos , Locus Cerúleo/diagnóstico por imagem , Locus Cerúleo/fisiopatologia , Norepinefrina/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologiaRESUMO
The synucleinopathies-Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure-result from distinct patterns of abnormal α-synuclein aggregation throughout the nervous system. Autonomic dysfunction in these disorders results from variable involvement of the central and peripheral autonomic networks. The major pathologic hallmark of Parkinson's disease and dementia with Lewy bodies is Lewy bodies and Lewy neurites; of multiple system atrophy, oligodendroglial cytoplasmic inclusions; and of pure autonomic failure, peripheral neuronal cytoplasmic inclusions. Clinical manifestations include orthostatic hypotension, thermoregulatory dysfunction, gastrointestinal dysmotility, and urogenital dysfunction with neurogenic bladder and sexual dysfunction. Strong evidence supports isolated idiopathic rapid eye movement sleep disorder as a significant risk factor for the eventual development of synucleinopathies with autonomic and/or motor involvement. In contrast, some neurologically normal elderly individuals have Lewy-related pathology. Future work may reveal protective or vulnerability factors that allow some patients to harbor Lewy pathology without overt autonomic dysfunction. © 2018 International Parkinson and Movement Disorder Society.
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Doenças do Sistema Nervoso Autônomo , Neuropatologia , Doença de Parkinson/complicações , Sinucleínas/metabolismo , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/metabolismo , Doenças do Sistema Nervoso Autônomo/patologia , HumanosRESUMO
BACKGROUND: There is growing interest in white matter (WM) imaging with positron emission tomography (PET). OBJECTIVES: We studied the association of cognitive function in late multiple sclerosis (MS) with cortical and WM Pittsburgh compound-B PET (PiB-PET) binding. METHODS: In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS (12 underwent PiB-PET). Controls were age and sex matched (5:1). We used automated or semi-automated processing for quantitative image analyses and conditional logistic regression for group differences. RESULTS: MS patients had lower memory ( p = 0.03) and language ( p = 0.02) performance; smaller thalamic volumes ( p = 0.003); and thinner temporal ( p = 0.001) and frontal ( p = 0.045) cortices on magnetic resonance imaging (MRI) than controls. There was no difference in global cortical PiB standardized uptake value ratios between MS and controls ( p = 0.35). PiB uptake was lower in areas of WM hyperintensities compared to normal-appearing white matter (NAWM) in MS ( p = 0.0002). Reduced PiB uptake in both the areas of WM hyperintensities ( r = 0.65; p = 0.02) and NAWM ( r = 0.69; p = 0.01) was associated with decreased visuospatial performance in MS. CONCLUSION: PiB uptake in the cortex in late MS is not different from normal age-matched controls. PiB uptake in the WM in late MS may be a marker of the large network structures' integrity such as those involved in visuospatial performance.
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Envelhecimento , Encéfalo/diagnóstico por imagem , Cognição , Esclerose Múltipla/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Idoso , Compostos de Anilina , Encéfalo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Esclerose Múltipla/psicologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tiazóis , Substância Branca/patologiaRESUMO
INTRODUCTION: Autosomal dominant haploinsufficiency of GATA2 causes monocytopenia and natural killer cell lymphopenia, resulting in predisposition to mycobacterial, fungal, and viral infections. METHODS: Herein we report on the clinical, serologic, electrophysiologic, and pathologic evaluations of a 29-year-old woman with GATA2 haploinsufficiency and active Epstein-Barr virus (EBV) infection complicated by subacute painful neuropathy. RESULTS: Nerve conduction and electromyography studies showed predominantly demyelinating sensorimotor polyradiculoneuropathy. Lumbar spine MRI showed thickening and enhancement of the cauda equina nerve roots. Serum and cerebrospinal fluid anti-IgG and IgM EBV capsid and nucleic acid antibodies were positive. Sural nerve biopsy showed microvasculitis and an increased frequency of fibers with segmental demyelination. Intravenous immunoglobulin and steroids improved the patient's neuropathy. CONCLUSION: GATA2 mutation-related immunodeficiency may predispose to EBV-associated subacute demyelinating polyradiculoneuropathy by both viral susceptibility and immune dysregulation. In patients who present in this manner, immunodeficiency syndromes should be considered when lymphomatous infiltration is excluded. Immunotherapy can be helpful. Muscle Nerve 57: 150-156, 2018.
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Infecções por Vírus Epstein-Barr/complicações , Fator de Transcrição GATA2/genética , Haploinsuficiência/genética , Polirradiculoneuropatia/complicações , Polirradiculoneuropatia/genética , Adulto , Anticorpos Anti-Idiotípicos , Doenças Autoimunes do Sistema Nervoso/patologia , Biópsia , Eletromiografia , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Feminino , Humanos , Síndromes de Imunodeficiência , Imageamento por Ressonância Magnética , Condução Nervosa , Exame Neurológico , Polirradiculoneuropatia/diagnóstico por imagem , Nervo Sural/patologiaAssuntos
Arritmias Cardíacas , Infarto , Humanos , Bloqueio Cardíaco , Bulbo , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: The objective of this study was to characterize the degree, pattern, lesion site, and temporal evolution of sudomotor dysfunction in multiple system atrophy (MSA) and to evaluate differences by parkinsonian (MSA-parkinsonism) and cerebellar (MSA-cerebellar) subtypes. METHODS: All cases of MSA evaluated at Mayo Clinic Rochester between 2005 and 2010 with postganglionic sudomotor testing and thermoregulatory sweat test were reviewed. Pattern and lesion site (preganglionic, postganglionic, or mixed) were determined based on thermoregulatory sweat test and postganglionic sudomotor testing. RESULTS: The majority of the 232 patients were MSA-parkinsonism (145, 63%). Initial postganglionic sudomotor testing was abnormal in 59%, whereas thermoregulatory sweat test was abnormal in 95% of all patients. MSA-parkinsonism patients were more likely to have an abnormal thermoregulatory sweat test compared with MSA-cerebellar (98% versus 90%, P = 0.006) and had a higher mean percentage of anhidrosis (57%) compared with MSA-cerebellar (48%; P = 0.033). Common anhidrosis patterns were regional (38%) and global (35%). The site of the lesion was preganglionic in 47% and mixed (preganglionic and postganglionic) in 41%. The increase in anhidrosis per year was 6.2% based on 70 repeat thermoregulatory sweat tests performed on 29 patients. The frequency of postganglionic sudomotor abnormalities increased over time. CONCLUSIONS: Our findings suggest: (1) sudomotor dysfunction is almost invariably present in MSA and even more common and severe in MSA-parkinsonism than MSA-cerebellar; (2) a preganglionic pattern of sweat loss is common in MSA; however, pre- and postganglionic abnormalities may coexist; and (3) the increasing frequency of postganglionic sudomotor dysfunction over time suggests involvement of postganglionic fibers or sweat glands later in the disease course. © 2016 International Parkinson and Movement Disorder Society.
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Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças Cerebelares/complicações , Hipo-Hidrose/diagnóstico , Hipo-Hidrose/etiologia , Atrofia de Múltiplos Sistemas/complicações , Transtornos Parkinsonianos/complicações , Idoso , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Feminino , Humanos , Hipo-Hidrose/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Fluoxetine is a selective serotonin reuptake inhibitor and long-lived open channel blocker of the acetylcholine receptor, often used in the treatment of slow-channel congenital myasthenic syndromes (CMS). METHODS: We report a 42-year-old woman who had a history of episodic limb weakness that worsened after initiation of fluoxetine for treatment of depression. Genetic testing for CMS revealed a homozygous pathogenic mutation in the rapsyn (RAPSN) gene (p.Asn88Lys). Electrodiagnostic testing was performed before and 1 month after discontinuation of fluoxetine. RESULTS: The 2 Hz repetitive nerve stimulation of the fibular and spinal accessory nerves showed a baseline decrement of 36% and 14%, respectively. One month after discontinuing fluoxetine, the spinal accessory nerve decrement was no longer present, and the decrement in the fibular nerve was improved at 17%. CONCLUSIONS: This case demonstrates worsening of both clinical and electrophysiologic findings in a patient with CMS secondary to a RAPSN mutation treated with fluoxetine. Muscle Nerve 55: 131-135, 2017.
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Antidepressivos de Segunda Geração/efeitos adversos , Fluoxetina/efeitos adversos , Proteínas Musculares/genética , Mutação/genética , Síndromes Miastênicas Congênitas/induzido quimicamente , Síndromes Miastênicas Congênitas/genética , Adulto , Feminino , Humanos , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/fisiopatologiaRESUMO
BACKGROUND: Accumulation of α-synuclein in multiple system atrophy (MSA) affects medullary autonomic and respiratory control areas, including the rostral ventrolateral medulla and raphe nuclei. Relative neuronal vulnerability and its relationship to α-synuclein accumulation in these areas are unknown. The aim of this study was to determine the extent of loss of adrenergic neurons in the rostral ventrolateral medulla and serotonergic neurons in the ventrolateral medulla and raphe nuclei and its relationship with α-synuclein accumulation. METHODS: Medullary sections from 7 MSA and 6 control subjects were processed for tyrosine hydroxylase, tryptophan hydroxylase, and α-synuclein immunoreactivity. Neuronal counts were performed stereologically, whereas α-synuclein burden in oligodendrocytes and neurons was quantified using object detection density (area/mm2). RESULTS: All MSA cases had orthostatic hypotension; 5 had laryngeal stridor. There was marked neuronal loss in the rostral ventrolateral medulla and medullary raphe in all cases. Most severely affected were tyrosine hydroxylase ventrolateral medulla (C1) neurons (83% reduction), followed by tryptophan hydroxylase neurons in the ventrolateral medulla (70%), raphe obscurus (56%), pallidus (57%), and magnus (47%). α-Synuclein accumulation occurred predominantly as glial cytoplasmic inclusions with rare α-synuclein accumulation occurring within the remaining neurons. Density of α-synuclein did not correlate with neuronal loss in any of the areas analyzed, and there was no correlation between α-synuclein density and disease duration for any regions of interest. CONCLUSIONS: These findings indicate that in MSA adrenergic neurons are more susceptible than serotonergic neurons in the medulla. Further, loss of medullary monoaminergic neurons may progress independently from α-synuclein accumulation in MSA. © 2016 International Parkinson and Movement Disorder Society.
Assuntos
Neurônios Adrenérgicos/patologia , Bulbo , Atrofia de Múltiplos Sistemas , Neurônios Serotoninérgicos/patologia , alfa-Sinucleína/metabolismo , Idoso , Feminino , Humanos , Hipotensão Ortostática/fisiopatologia , Doenças da Laringe/fisiopatologia , Masculino , Bulbo/metabolismo , Bulbo/patologia , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/metabolismo , Atrofia de Múltiplos Sistemas/patologia , Atrofia de Múltiplos Sistemas/fisiopatologia , Núcleos da Rafe/metabolismo , Núcleos da Rafe/patologia , Sons Respiratórios/fisiopatologiaRESUMO
Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients with multiple system atrophy, including a patient with visual hallucinations. Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was associated with cognitive impairment (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho ≥ 0.6) in pathologic glial and neuronal lesion burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system atrophy.