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OBJECTIVE: To evaluate the use and tolerability of noninvasive positive pressure ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS) early in their disease by comparing active NIV and sham NIV in patients not yet eligible for NIV use as recommended by practice guidelines. METHODS: This was a single-center, prospective, double-blind, randomized, placebo (sham)-controlled pilot trial. Patients with ALS were randomized to receive either sham NIV or active NIV and underwent active surveillance approximately every 3 months until they reached a forced vital capacity (FVC) <50% or required NIV for clinical symptom management. RESULTS: In total, 54 participants were randomized. The mean NIV use was 2.0 hours (95% confidence interval [CI] 1.1-3.0) per day in the sham NIV treatment group and 3.3 hours (CI 2.0-4.6) per day in the active NIV group, which did not differ by treatment group (p = 0.347). The majority of sham NIV participants (88%) and active NIV participants (73%) reported only mild or no problem with NIV use. Difference of change in FVC through the treatment period by group (0.44 per month) favored active NIV (p = 0.049). Survival and changes in maximal inspiratory or expiratory pressure did not differ between treatment groups. CONCLUSIONS: The efficacy of early NIV in ALS should be tested in randomized, placebo-controlled trials. The trial is registered on clinicaltrials.gov (NCT00580593). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with ALS, adherence with NIV and sham NIV are similar.
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Esclerosis Amiotrófica Lateral/terapia , Ventilación no Invasiva/métodos , Método Doble Ciego , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To determine if decline in corpus callosum (CC) white matter integrity in patients with amyotrophic lateral sclerosis (ALS) is localized to motor-related areas. MATERIALS AND METHODS: Twenty-one ALS patients and 21 controls participated. Diffusion tensor images (DTI) were acquired using 3 Tesla (T) MRI. Tract-based spatial statistics were used to examine whole-brain white matter damage. A segmentation schema was used to define CC volumes-of-interest (VOI). Fractional anisotropy (FA) and radial- and axial-diffusivity (RD, AD) were extracted from VOIs and compared between groups. DTI measurements in motor-related Area III were tested for correlation with symptoms and disease duration. RESULTS: Extracted FA values from CC VOIs were reduced in ALS patients (P≤0.0001), particularly in Areas II and III (P≤0.01). Reduced FA in Area III correlated with disease symptomology (P≤0.05) and duration (P≤0.02). Between-group whole-brain comparisons (P≤0.05, corrected) showed reduced FA and increased RD throughout white matter regions including the CC, corona radiata, and internal capsule. AD was increased in the left corona radiata and internal and external capsules. CONCLUSION: FA in motor-related regions of the CC is more affected than other CC areas in ALS patients. Microstructural pathology of transcallosal fiber tracts may represent a future component of an imaging biomarker for ALS.
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Esclerosis Amiotrófica Lateral/patología , Cuerpo Calloso/patología , Imagen de Difusión Tensora/métodos , Fibras Nerviosas Mielínicas/patología , Anciano , Esclerosis Amiotrófica Lateral/diagnóstico , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: To determine if a brain-computer interface (BCI) could be used as a plug-and-play input device to operate commercial assistive technology (AT), and to quantify the performance impact of such operation. METHOD: Using a hardware device designed in our lab, participants (11 with amyotrophic lateral sclerosis, 22 controls) were asked to operate two devices using a BCI. Results were compared to traditional BCI operation by the same users. Performance was assessed using both accuracy and BCI utility, a throughput metric. 95% confidence bounds on performance differences were developed using a linear mixed model. RESULTS: The observed differences in accuracy and throughput were small and not statistically significant. The confidence bounds indicate that if there is a performance impact of using a BCI to control an AT device, the impact could easily be overcome by the benefits of the AT device itself. CONCLUSIONS: BCI control of AT devices is possible, and the performance difference appears to be very small. BCI designers are encouraged to incorporate standard outputs into their design to enable future users to interface with familiar AT devices. IMPLICATIONS FOR REHABILITATION: Brain-computer interface (BCI) control of assistive technology (AT) devices is possible. The performance impact of such control is low when BCIs are commercially available, AT providers can use a BCI as an input device to existing AT devices already in use by their clients.
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Esclerosis Amiotrófica Lateral/rehabilitación , Interfaces Cerebro-Computador , Personas con Discapacidad/rehabilitación , Dispositivos de Autoayuda , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION: We present a Jordanian man with the typical LGMD 2L phenotype of early, asymmetric quadriceps weakness and subsequent biceps brachii weakness. METHODS: Case report. RESULTS: Muscle biopsies document a progressive dystrophic pattern unrelated to known sarcolemmal defects associated with muscular dystrophy. Genetic testing revealed novel, heterozygote Anoctamin 5 gene mutations. CONCLUSIONS: This case report expands the known mutations resulting in LGMD 2L and supports the assertion that Anoctamin 5 mutations are more prevalent than previously recognized.
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Canales de Cloruro/genética , Debilidad Muscular/genética , Distrofia Muscular de Cinturas/genética , Adulto , Anoctaminas , Humanos , Masculino , Debilidad Muscular/patología , Músculo Esquelético/patología , Distrofia Muscular de Cinturas/patología , MutaciónRESUMEN
Respiratory complications are a common cause of morbidity and mortality in amyotrophic lateral sclerosis (ALS). Treatment of respiratory insufficiency with noninvasive ventilation (NIV) improves ALS patients' quality of life and survival. Evidence-based practice guidelines for the management of ALS patients recommend treatment of respiratory insufficiency with NIV as well as consideration of insufflation/exsufflation to improve clearance of airway secretions. Despite these recommendations respiratory therapies remain underused. In this review we provide a practical guide for the clinician to prescribe and manage respiratory therapies for the patient with ALS.
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Esclerosis Amiotrófica Lateral/terapia , Insuficiencia Respiratoria/terapia , Terapia Respiratoria/métodos , Esclerosis Amiotrófica Lateral/complicaciones , Medicina Basada en la Evidencia , Humanos , Insuficiencia Respiratoria/etiología , Terapia Respiratoria/efectos adversosRESUMEN
Brain-computer interfaces (BCI) are designed to enable individuals with severe motor impairments such as amyotrophic lateral sclerosis (ALS) to communicate and control their environment. A focus group was conducted with individuals with ALS (n=8) and their caregivers (n=9) to determine the barriers to and mediators of BCI acceptance in this population. Two key categories emerged: personal factors and relational factors. Personal factors, which included physical, physiological and psychological concerns, were less important to participants than relational factors, which included corporeal, technological and social relations with the BCI. The importance of these relational factors was analysed with respect to published literature on actor-network theory (ANT) and disability, and concepts of voicelessness and personhood. Future directions for BCI research are recommended based on the emergent focus group themes. PRACTITIONER SUMMARY: This manuscript explores human factor issues involved in designing and evaluating brain-computer interface (BCI) systems for users with severe motor disabilities. Using participatory research paradigms and qualitative methods, this work draws attention to personal and relational factors that act as barriers to, or mediators of, user acceptance of this technology.
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Encéfalo , Equipos de Comunicación para Personas con Discapacidad , Conocimientos, Actitudes y Práctica en Salud , Interfaz Usuario-Computador , Esclerosis Amiotrófica Lateral , Femenino , Grupos Focales , Humanos , MasculinoRESUMEN
Cognitive impairment (CI) in amyotrophic lateral sclerosis (ALS) may present a serious barrier to a patient's wellbeing and significantly decrease quality of life. Although reports of CI in ALS without frank dementia are becoming quite common, questions remain regarding the specific cognitive domains affected, as well as how other psychological and medical factors may impact cognitive functioning in these patients. Additionally, the influence of depressive symptoms on disease processes is not known. We aimed to address these questions by completing extensive neuropsychological tests with 22 patients with ALS and 17 healthy volunteers. A subgroup of these patients also completed questionnaires to measure depressive and vegetative symptoms. We tested for overall cognitive differences between groups, the influence of physical (e.g., bulbar and limb), vegetative (e.g., fatigue), and depressive symptoms on cognitive performance, and the relationship between depressive symptoms and disease severity in ALS. Overall, patients performed more poorly than healthy controls (HCs), most notably on tests of executive functioning and learning and memory. Results suggest that true cognitive performance differences exist between patients with ALS and HCs, as these differences were not changed by the presence of vegetative or depressive symptoms. There was no effect of limb or bulbar symptoms on cognitive functioning. Also, patients were not any more depressed than HCs, however increased depressive scores correlated with faster disease progression and decreased limb function. Collectively, it is suggested that translational advances in psychological intervention for those with CI and depression become emphasized in future research.
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Universal design principles advocate inclusion of end users in every design stage, including research and development. Brain-computer interfaces (BCIs) have long been described as potential tools to enable people with amyotrophic lateral sclerosis (ALS) to operate technology without moving. Therefore the objective of the current study is to determine the opinions and priorities of people with ALS regarding BCI design. This information will guide BCIs in development to meet end-user needs. A telephone survey was undertaken of 61 people with ALS from the University of Michigan's Motor Neuron Disease Clinic. With regard to BCI design, participants prioritized accuracy of command identification of at least 90% (satisfying 84% of respondents), speed of operation comparable to at least 15-19 letters per minute (satisfying 72%), and accidental exits from a standby mode not more than once every 2-4 h (satisfying 84%). While 84% of respondents would accept using an electrode cap, 72% were willing to undergo outpatient surgery and 41% to undergo surgery with a short hospital stay in order to obtain a BCI. In conclusion, people with ALS expressed a strong interest in obtaining BCIs, but current BCIs do not yet provide desired BCI performance.
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Esclerosis Amiotrófica Lateral/psicología , Esclerosis Amiotrófica Lateral/rehabilitación , Equipos de Comunicación para Personas con Discapacidad/estadística & datos numéricos , Satisfacción del Paciente , Interfaz Usuario-Computador , Anciano , Equipos de Comunicación para Personas con Discapacidad/psicología , Recolección de Datos/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción/fisiologíaRESUMEN
INTRODUCTION: Assistive devices are prescribed for amyotrophic lateral sclerosis (ALS) patients with motor deficits, but little is known about their perceived benefit. Therefore, we assessed ALS patients' satisfaction with commonly prescribed devices. METHODS: A telephone survey of 63 ALS patients from a single multidisciplinary clinic was conducted to assess the frequency of use, perceived usefulness, and satisfaction with 33 assistive devices. RESULTS: Of those assistive technologies used "often or always" by ≥ 20% of respondents, arm rails by the toilet, elevated toilet seat, shower seat, shower bars, and slip-on shoes were ranked very highly for both usefulness and satisfaction. The ankle brace for ambulation, transfer board, speaker phone, and electronic seating controls were also ranked highly. The button hook, dressing stick, and long-handled reaching tool received low ratings for both usefulness and satisfaction. CONCLUSIONS: ALS patients reported high usefulness and satisfaction levels with all bathroom adaptive devices and certain low-technology devices.
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Actividades Cotidianas/psicología , Esclerosis Amiotrófica Lateral/psicología , Esclerosis Amiotrófica Lateral/terapia , Satisfacción del Paciente , Autoinforme , Dispositivos de Autoayuda/psicología , Anciano , Estudios Transversales , Femenino , Encuestas Epidemiológicas/métodos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Denervation of oropharyngeal muscles in obstructive sleep apnea (OSA) has been suggested by needle electromyography (EMG) and muscle biopsy, but little is known about oropharyngeal nerve conduction abnormalities in OSA. We sought to compare hypoglossal nerve conduction studies in patients with and without OSA. Unilateral hypoglossal nerve conduction studies were performed on 20 subjects with OSA and 20 age-matched controls using standard techniques. Median age was 48 years in OSA subjects and 47 years in controls. Hypoglossal compound muscle action potential (CMAP) amplitudes were significantly reduced (P = 0.01, Wilcoxon signed-rank test), but prolongation of latencies in OSA subjects did not reach significance in comparison to those of controls. Among a subgroup of subjects without polyneuropathy (15 pairs), reduced amplitudes in OSA subjects retained borderline significance (P = 0.05). Hypoglossal nerve conduction abnormalities may distinguish patients with OSA from controls. These abnormalities could potentially contribute to, or arise from, OSA.
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Nervio Hipogloso/fisiopatología , Conducción Nerviosa/fisiología , Apnea Obstructiva del Sueño/fisiopatología , Potenciales de Acción/fisiología , Adolescente , Adulto , Electromiografía , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Estudios ProspectivosRESUMEN
BACKGROUND: Obstructive sleep apnea (OSA) is a common condition with substantial health consequences. A recent randomized trial found that playing the didgeridoo improved both subjective and objective sleep measures. We undertook a cross-sectional survey of professional orchestra players to test the hypothesis that playing a wind instrument would be associated with a lower risk of OSA. METHODS: An anonymous internet-based survey of professional orchestra members assessed risk of sleep apnea using the Berlin questionnaire. Multivariable logistic regression was used to test the association between playing a wind instrument and having a high risk score on the Berlin questionnaire, both unadjusted and adjusted for age, body mass index, and gender. RESULTS: A total of 1,111 orchestra members responded, including 369 (33%) wind instrument players. Wind players were more often male and had a higher body mass index than non-wind players. Of all musicians, 348 (31%) had a high risk of sleep apnea. Wind players were more likely than non-wind players to be at high risk in unadjusted analysis (Odds ratio=1.47, 95% CI 1.13, 1.91), though this association was not significant in adjusted analysis (Odds ratio=1.12 (0.82, 1.54)). CONCLUSION: Playing a wind instrument was not associated with a lower risk of OSA.
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Música , Ocupaciones/estadística & datos numéricos , Síndromes de la Apnea del Sueño/etiología , Factores de Edad , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores Sexuales , Encuestas y CuestionariosRESUMEN
BACKGROUND AND PURPOSE: While sensitive to internal carotid artery (ICA) occlusion, carotid ultrasound can produce false-positive results. CT angiography (CTA) has a high specificity for ICA occlusion and is safer and cheaper than catheter angiography, although less accurate. We determined the cost-effectiveness of CTA versus catheter angiography for confirming an ICA occlusion first suggested by carotid ultrasound. METHODS: A Markov decision-analytic model was constructed to estimate the cost-effectiveness of CTA compared with catheter angiography in a hypothetical cohort of symptomatic patients with a screening examination consistent with an ICA occlusion. Costs in 2004 dollars were estimated from Medicare reimbursement. Effectiveness was measured in quality-adjusted life years. RESULTS: The 2-year cost in the CTA scenario was $9,178, and for catheter angiography, $11,531, consistent with a $2,353 cost-savings per person for CTA. CTA resulted in accrual of 1.83 quality-adjusted life years while catheter angiography resulted in 1.82 quality-adjusted life years. CTA was less costly and marginally more effective than catheter angiography. In sensitivity analyses, when CTA sensitivity and specificity were allowed to vary across a plausible range, CTA remained cost-effective. CONCLUSIONS: After screening examination has suggested an ICA occlusion, confirmatory testing with CTA provides similar effectiveness to catheter angiography and is less costly.
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Arteria Carótida Interna/diagnóstico por imagen , Estenosis Carotídea/economía , Cateterismo Periférico/economía , Angiografía Cerebral/economía , Tomografía Computarizada por Rayos X/economía , Arteria Carótida Interna/cirugía , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/mortalidad , Estenosis Carotídea/cirugía , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/economía , Infarto Cerebral/mortalidad , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Endarterectomía Carotidea , Mortalidad Hospitalaria , Hospitalización/economía , Humanos , Cadenas de Markov , Riesgo , Sensibilidad y EspecificidadRESUMEN
Little is known about the complications of needle electromyography (EMG) performed on anticoagulated patients, and no guidelines exist regarding its performance. We conducted an anonymous survey of academic EMG laboratories in the U.S. to understand current practices and complications with regard to anticoagulated patients and those receiving antiplatelet medications. Forty-seven (78%) of 60 EMG laboratories responded to the survey. Four laboratories (9%) reported at least one hemorrhagic complication requiring medical or surgical intervention in an anticoagulated patient, whereas none reported a hemorrhagic complication in patients receiving antiplatelet medications. Ten (21%) reported willingness to evaluate cranial, paraspinal, and all limb muscles in anticoagulated patients. This survey suggests that hemorrhagic complications from needle EMG of anticoagulated patients are rare. It also suggests that needle EMG of patients receiving antiplatelet therapy is not associated with increased reports of hemorrhagic complications.
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Electromiografía/efectos adversos , Encuestas de Atención de la Salud , Hemorragia/etiología , Neurología/estadística & datos numéricos , Enfermedades Neuromusculares/diagnóstico , Centros Médicos Académicos/normas , Centros Médicos Académicos/estadística & datos numéricos , Anticoagulantes/uso terapéutico , Electromiografía/normas , Electromiografía/estadística & datos numéricos , Humanos , Laboratorios de Hospital/normas , Laboratorios de Hospital/estadística & datos numéricos , Agujas , Neurología/normas , Inhibidores de Agregación Plaquetaria/uso terapéutico , Guías de Práctica Clínica como Asunto , Encuestas y CuestionariosRESUMEN
Non-invasive positive pressure ventilation (NIV) treatment of advanced respiratory insufficiency prolongs survival in ALS. To investigate the critical question of whether earlier initiation of NIV might provide additional benefit, a randomized trial with an appropriate placebo is needed. This study evaluated sub-therapeutic (sham) continuous positive airway pressure as a potential placebo. In a single-blind design, 40 ALS patients with forced vital capacity>50% were randomized to receive 30 seconds (s) of either active NIV, with 8 cm H2O inspiratory and 4 cm H2O expiratory pressure, or sham NIV with<1 cm of H2O continuous positive airway pressure at the mask. A questionnaire was then used to assess whether subjects thought that they had received a "real" or "pretend" treatment trial. The subjects' median age was 60.5 years, and 38% were female. Twelve of 20 subjects (60%) who received active NIV and 7 (35%) of the 20 subjects who received sham thought that they had tried the active treatment (p = 0.11). Only 8 (20%) of all subjects were confident about their determination that they had received "real" or "pretend" NIV. Thus, sub-therapeutic (sham) continuous positive airway pressure is a promising placebo control for NIV trials in ALS.
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Esclerosis Amiotrófica Lateral/terapia , Respiración Artificial , Anciano , Esclerosis Amiotrófica Lateral/fisiopatología , Presión de las Vías Aéreas Positiva Contínua , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Intercambio Gaseoso Pulmonar , Proyectos de Investigación , Capacidad VitalRESUMEN
The absence of data guiding optimal titration of noninvasive positive pressure ventilation (NIPPV) over time in ALS patients may contribute to the under-prescribing of NIPPV. We conducted a retrospective, single-center, chart review assessment of NIPPV pressure settings used for symptomatic treatment of ALS patients to determine NIPPV adjustments, and to compare survival between those who were tolerant and intolerant to NIPPV. All subjects were started on nocturnal NIPPV at 8 and 3 cm H2O inspiratory and expiratory pressure, respectively. Of the 18 tolerant subjects identified, 4 (22%) had no NIPPV pressure changes before death; 8 (44%), 1 change; 4 (22%), 2 changes; 1 (6%), 3 changes; and 1 (6%), 5 changes. Most pressure changes occurred during the first year of NIPPV initiation. The maximum pressure needed for comfort by any patient in this study was 19/5 cm H2O, while 4 (22%) found the original 8/3 cm H2O settings to be sufficient until death. Subjects in the tolerant group had better survival, when adjusting for age and site of symptom onset (bulbar versus limb), with a hazard ratio of 0.23 [95% confidence interval: 0.10, 0.54]. The current data suggest that ALS patients who are tolerant to NIPPV typically need at least one upward change in pressure settings. Tolerance to relatively low NIPPV inspiratory pressures is associated with improved survival.
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Esclerosis Amiotrófica Lateral/terapia , Respiración con Presión Positiva , Anciano , Esclerosis Amiotrófica Lateral/mortalidad , Esclerosis Amiotrófica Lateral/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Optimal timing of noninvasive positive pressure ventilation (NIPPV) initiation in patients with amyotrophic lateral sclerosis (ALS) is unknown, but NIPPV appears to benefit ALS patients who are symptomatic from pulmonary insufficiency. This has prompted research proposals of earlier NIPPV initiation in the ALS disease course in an attempt to further improve ALS patient quality of life and perhaps survival. We therefore used a cost-utility analysis to determine a priori what magnitude of health-related quality of life (HRQL) improvement early NIPPV initiation would need to achieve to be cost-effective in a future clinical trial. METHODS: Using a Markov decision analytic model we calculated the benefit in health-state utility that NIPPV initiated at ALS diagnosis must achieve to be cost-effective. The primary outcome was the percent utility gained through NIPPV in relation to two common willingness-to-pay thresholds: 50,000 dollars and 100,000 dollars per quality-adjusted life year (QALY). RESULTS: Our results indicate that if NIPPV begun at the time of diagnosis improves ALS patient HRQL as little as 13.5%, it would be a cost-effective treatment. Tolerance of NIPPV (assuming a 20% improvement in HRQL) would only need to exceed 18% in our model for treatment to remain cost-effective using a conservative willingness-to-pay threshold of 50,000 dollars per QALY. CONCLUSION: If early use of NIPPV in ALS patients is shown to improve HRQL in future studies, it is likely to be a cost-effective treatment. Clinical trials of NIPPV begun at the time of ALS diagnosis are therefore warranted from a cost-effectiveness standpoint.
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Esclerosis Amiotrófica Lateral/terapia , Actitud Frente a la Salud , Respiración con Presión Positiva/economía , Años de Vida Ajustados por Calidad de Vida , Insuficiencia Respiratoria/terapia , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/economía , Análisis Costo-Beneficio/estadística & datos numéricos , Árboles de Decisión , Tabla de Aranceles , Gastos en Salud , Humanos , Cadenas de Markov , Medicare , Modelos Econométricos , Calidad de Vida , Insuficiencia Respiratoria/etiología , Estados UnidosRESUMEN
BACKGROUND: Brain magnetic resonance imaging (MRI) findings during acute cerebellar ataxia in cases of postinfectious cerebellitis are frequently normal. This has resulted in the use of other imaging modalities, such as single-photon emission computed tomography, to aid diagnosis. OBJECTIVE: To illustrate the chronologic occurrence of cerebellar ataxia, abnormal findings on MRI, and cerebral spinal fluid pleocytosis in an adult case of postinfectious cerebellitis. METHODS: Case report. RESULTS: A patient with a 6-week history of occipital headaches and only mild tandem gait difficulty had abnormal MRI findings that were consistent with cerebellar inflammation. As cerebellar ataxia progressed in parallel with cerebral spinal fluid pleocytosis, MRI findings indicative of cerebellar inflammation resolved, while single-photon emission computed tomography showed cerebellar hyperperfusion. Recovery of neurologic function was accompanied by clearing of the pleocytosis and residual MRI-detected cerebellar atrophy. CONCLUSION: This case demonstrates that transient abnormalities can be detected by MRI before clinical manifestations of cerebellitis appear, while hyperperfusion detected by single-photon emission computed tomography is prolonged.