Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases / Atrofia multisistémica: características clínicas, anatomopatológicas y evolución de una serie de casos

Background and objective: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. Material and methods: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. Results: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. Conclusion: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.(AU)

Antecedentes y objetivo: La atrofia multisistémica es un trastorno neurodegenerativo raro y letal que se caracteriza por una disfunción autonómica en asociación con parkinsonismo o signos cerebelosos. La marca anatomopatológica es la presencia de agregados de α-sinucleína en los oligodendrocitos, que forman inclusiones citoplasmáticas gliales. Desde un punto de vista clínico, puede ser difícil de distinguir de otros parkinsonismos o ataxias, particularmente en las primeras etapas de la enfermedad. En esta serie de casos, nuestro objetivo es describir en detalle las características de los pacientes con atrofia multisistémica. Material y métodos: Se resumen los datos objetidos de la puntuación de la Escala de calificación unificada de la atrofia multisistémica (UMSARS), imágenes estructurales y funcionales y las pruebas autonómicas cardiovasculares realizadas desde las primeras etapas de la enfermedad. Resultados: La escala UMSAR demostró ser útil para hacer un seguimiento: el examen longitudinal esencial fue para estratificar el riesgo de peor evolución. El diagnóstico neuropatológico mostró un solapamiento entre los subtipos parkinsoniano y cerebeloso, con algunas peculiaridades que podrían ayudar a distinguir los subtipos. Conclusión: Una mejor descripción de las características de la atrofia multisistémica en casos confirmados mediante neuropatología podría ayudar a aumentar la sensibilidad del diagnóstico.(AU)

Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms. METHODS: The study included 87 patients with post-COVID condition, 50 patients with ME/CFS, and 50 healthy controls (HC). The hemodynamic autonomic function was evaluated using the deep breathing technique, Valsalva maneuver, and Tilt test. The presence of autonomic and sensory small fiber neuropathy (SFN) was assessed with the Sudoscan and with heat and cold evoked potentials, respectively. Finally, a complete neuropsychological evaluation was performed. The objective of this study was to analyze and compare the autonomic and neuropathic symptoms in post-COVID condition with ME/CFS, and HC, as well as, analyze the relationship of these symptoms with cognition and fatigue. RESULTS: Statistically significant differences were found between groups in heart rate using the Kruskal-Wallis test (H), with ME/CFS group presenting the highest (H = 18.3; p ≤ .001). The Postural Orthostatic Tachycardia Syndrome (POTS), and pathological values in palms on the Sudoscan were found in 31% and 34% of ME/CFS, and 13.8% and 19.5% of post-COVID patients, respectively. Concerning evoked potentials, statistically significant differences were found in response latency to heat stimuli between groups (H = 23.6; p ≤ .01). Latency was highest in ME/CFS, and lowest in HC. Regarding cognition, lower parasympathetic activation was associated with worse cognitive performance. CONCLUSIONS: Both syndromes were characterized by inappropriate tachycardia at rest, with a high percentage of patients with POTS. The prolonged latencies for heat stimuli suggested damage to unmyelinated fibers. The higher proportion of patients with pathological results for upper extremities on the Sudoscan suggested a non-length-dependent SFN.

Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases.

BACKGROUND AND OBJECTIVE: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. MATERIAL AND METHODS: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. RESULTS: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. CONCLUSION: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.

Usefulness of thermography in the diagnosis and classification of complex regional pain syndrome.

INTRODUCTION: We propose a protocol for study of complex regional pain syndrome (CRPS) based on a battery of quantitative measures (skin thermography, electrochemical skin conductance and sensory thresholds) and apply such protocol to 5 representative cases of CRPS. PATIENTS AND METHODS: 5 CPRS cases (2 women/3 men) that met the Budapest criteria for the diagnosis of CRPS. RESULTS: All patients showed spontaneous pain and allodynia. Two cases correspond to a stage I, in both the resting basal temperature was increased in the affected limb. Three cases reflect more advanced stages with a decrease in resting temperature and a delay in the recovery of the temperature when compared to contralateral limb. DISCUSSION: These non-invasive quantitative functional tests not only improve the diagnostic accuracy of CRPS but also, they help us to stratify and understand the pathological processes of the disease.

Usefulness of thermography in the diagnosis and classification of complex regional pain syndrome / Utilidad de la termografía en el diagnóstico y clasificación del síndrome de dolor regional complejo

Introduction: We propose a protocol for study of complex regional pain syndrome (CRPS) basedon a battery of quantitative measures (skin thermography, electrochemical skin conductanceand sensory thresholds) and apply such protocol to 5 representative cases of CRPS.Patients and methods: 5 CPRS cases (2 women/3 men) that met the Budapest criteria for thediagnosis of CRPS. Results: All patients showed spontaneous pain and allodynia. Two cases correspond to a stageI, in both the resting basal temperature was increased in the affected limb. Three cases reflectmore advanced stages with a decrease in resting temperature and a delay in the recovery ofthe temperature when compared to contralateral limb.Discussion: These non-invasive quantitative functional tests not only improve the diagnosticaccuracy of CRPS but also, they help us to stratify and understand the pathological processesof the disease.(AU)

Introducción: Proponemos un protocolo para el estudio del síndrome de dolor regionalcomplejo (SDRC) basado en una batería de medidas cuantitativas (termografía cutánea, con-ductancia electroquímica cutánea y umbrales sensoriales en la prueba sensorial cuantitativa[QST]) y aplicamos dicho protocolo a cinco casos representativos de SDRC. Pacientes y métodos: Se presentan cinco casos de SDRC (dos mujeres/tres hombres) quecumplieron con los criterios de Budapest para el diagnóstico de SDRC. Resultados: Todos los pacientes presentaron dolor espontáneo y alodinia. Dos casos correspon-den a un estadio I, en ambos, la temperatura basal de reposo se incrementó en el miembroafectado. Tres casos muestran estadios más avanzados con disminución de la temperatura dereposo y retraso en la recuperación de la temperatura, en comparación con la extremidadcontralateral, que reflejan fases más avanzadas de la enfermedad. Discusión: Estas pruebas funcionales cuantitativas no invasivas no solo mejoran la precisióndiagnóstica del SDRC sino que también nos ayudan a estratificar las diferentes fases y compren-der los procesos patológicos de la enfermedad.(AU)

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor? OBJECTIVE: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition. METHODS: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated. RESULTS: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue. CONCLUSIONS: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases.

BACKGROUND AND OBJECTIVE: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. MATERIAL AND METHODS: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. RESULTS: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. CONCLUSION: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.

Usefulness of thermography in the diagnosis and classification of complex regional pain syndrome.

INTRODUCTION: We propose a protocol for study of complex regional pain syndrome (CRPS) based on a battery of quantitative measures (skin thermography, electrochemical skin conductance and sensory thresholds) and apply such protocol to 5 representative cases of CRPS. PATIENTS AND METHODS: 5 CPRS cases (2 women/3 men) that met the Budapest criteria for the diagnosis of CRPS. RESULTS: All patients showed spontaneous pain and allodynia. Two cases correspond to a stage I, in both the resting basal temperature was increased in the affected limb. Three cases reflect more advanced stages with a decrease in resting temperature and a delay in the recovery of the temperature when compared to contralateral limb. DISCUSSION: These non-invasive quantitative functional tests not only improve the diagnostic accuracy of CRPS but also, they help us to stratify and understand the pathological processes of the disease.

Impacto de la estimulación subtalámica a largo plazo sobre la situación cognitiva de los pacientes con enfermedad de Parkinson avanzada / Long-term impact of subthalamic stimulation on cognitive function in patients with advanced Parkinson's disease

OBJETIVO: El objetivo es evaluar los efectos de la estimulación cerebral profunda del núcleo subtalámico bilateral (STN-DBS) sobre el estado cognitivo de los pacientes con enfermedad de Parkinson 5 años después de la cirugía. Materiales y métodos: En este estudio prospectivo se incluyeron 50 pacientes con enfermedad de Parkinson (62,5% hombres, edad media 62,2 ± 8,2 años y duración de la enfermedad 14,1 ± 6,3 años) sometidos a STN-DBS. Todos los pacientes fueron evaluados preoperatoriamente y un año después de la cirugía, y 40 pacientes fueron seguidos hasta 5 años. En cada visita se realizaron las siguientes evaluaciones neuropsicológicas: Mini-Mental State Examination, Mattis Dementia Rating Scale (MDRS), test de secuencias números-letras de WAIS III-LN, Prueba de dibujo de reloj, Prueba de aprendizaje verbal auditivo Rey, la Prueba de retención visual de Benton, la Prueba de juicio de orientación de línea de Benton, la fluidez verbal fonética y semántica, la Prueba Stroop y la Escala de clasificación de depresión de Montgomery-Asberg. RESULTADOS: Anualmente se observaron reducciones en la puntación de Mini-Mental State Examination (-0,89%), Prueba del dibujo de reloj (-2,61%) y MDRS (-1,72%), fueron más marcados tanto para la fluidez verbal fonética (-13,28%) como semántica (-12,40%). Para la Prueba de aprendizaje verbal auditivo Rey observamos un deterioro en la capacidad de recuerdo diferido (-10,12%) un año después de la cirugía. A los 5 años la mayor parte del deterioro se produjo en la fluidez verbal, con reducciones adicionales de 16,10% y 16,60% para la fluidez verbal semántica y fonética, respectivamente. Se observó un empeoramiento más moderado del recuerdo inmediato (-16,87%), WAIS III-LN (-16,67%) y de la prueba de orientación lineal de Benton (-11,56%). Discusión: La STN-DBS no condujo a deterioro cognitivo global a los 5 años de la cirugía. Hubo un deterioro significativo en la función verbal desde el primer año de la cirugía. El deterioro de la capacidad de aprendizaje y de las funciones visuoespaciales podría atribuirse al propio proceso degenerativo de la enfermedad

OBJECTIVE: The aim of this study was to evaluate the effects of deep brain stimulation of the subthalamic nucleus (DBS-SN) on cognitive function in patients with Parkinson's disease (PD) 5 years after surgery. MATERIAL AND METHODS: We conducted a prospective study including 50 patients with PD who underwent DBS-SN (62.5% were men; mean age of 62.2 ± 8.2 years; mean progression time of 14.1 ± 6.3 years). All patients were assessed before the procedure and at one year after surgery; 40 patients were further followed up until the 5-year mark. Follow-up assessments included the following neuropsychological tests: Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), letter-number sequencing of the WAIS-III (WAIS-III-LN), clock-drawing test, Rey auditory verbal learning test (RAVLT), Benton Visual Retention Test (BVRT), Judgment of Line Orientation (JLO) test, FAS Phonemic Verbal Fluency Test, Stroop test, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Patients were found to score lower on the MMSE (-0.89%), clock-drawing test (-2.61%), MDRS (-1.72%), and especially phonemic (-13.28%) and sematic verbal fluency tests (-12.40%) at one year after surgery. Delayed recall on the RAVLT worsened one year after the procedure (-10.12%). At 5 years, impairment affected mainly verbal fluency; scores decreased an additional 16.10% and 16.60% in semantic and phonemic verbal fluency, respectively. Moderate decreases were observed in immediate recall (-16.87%), WAIS-III-LN (-16.67%), and JLO test (-11.56%). Discussion: In our sample, DBS-SN did not result in global cognitive impairment 5 years after surgery. Verbal function was found to be significantly impaired one year after the procedure. Impaired learning and visuospatial function may be attributed to degeneration associated with PD

Long-term impact of subthalamic stimulation on cognitive function in patients with advanced Parkinson's disease. / Impacto de la estimulación subtalámica a largo plazo sobre la situación cognitiva de los pacientes con enfermedad de Parkinson avanzada.

OBJECTIVE: The aim of this study was to evaluate the effects of deep brain stimulation of the subthalamic nucleus (DBS-SN) on cognitive function in patients with Parkinson's disease (PD) 5 years after surgery. MATERIAL AND METHODS: We conducted a prospective study including 50 patients with PD who underwent DBS-SN (62.5% were men; mean age of 62.2±8.2 years; mean progression time of 14.1±6.3 years). All patients were assessed before the procedure and at one year after surgery; 40 patients were further followed up until the 5-year mark. Follow-up assessments included the following neuropsychological tests: Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), letter-number sequencing of the WAIS-III (WAIS-III-LN), clock-drawing test, Rey auditory verbal learning test (RAVLT), Benton Visual Retention Test (BVRT), Judgment of Line Orientation (JLO) test, FAS Phonemic Verbal Fluency Test, Stroop test, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Patients were found to score lower on the MMSE (-0.89%), clock-drawing test (-2.61%), MDRS (-1.72%), and especially phonemic (-13.28%) and sematic verbal fluency tests (-12.40%) at one year after surgery. Delayed recall on the RAVLT worsened one year after the procedure (-10.12%). At 5 years, impairment affected mainly verbal fluency; scores decreased an additional 16.10% and 16.60% in semantic and phonemic verbal fluency, respectively. Moderate decreases were observed in immediate recall (-16.87%), WAIS-III-LN (-16.67%), and JLO test (-11.56%). DISCUSSION: In our sample, DBS-SN did not result in global cognitive impairment 5 years after surgery. Verbal function was found to be significantly impaired one year after the procedure. Impaired learning and visuospatial function may be attributed to degeneration associated with PD.

Vagus nerve stimulation therapy for treatment-resistant epilepsy: a 15-year experience at a single institution.

OBJECTIVE: Treatment-resistant epilepsy (TRE) occurs in 20-30% of patients. The goal of this study is to assess the efficacy and safety of vagus nerve stimulation (VNS) in this group of patients, including adult and pediatric populations and several off-label indications. METHODS: This is a retrospective review of 59 consecutive patients in whom 60 VNS devices were implanted at a single institution during a 15-year period. Patients were evaluated in the Multidisciplinary Epilepsy Committee and complete presurgical workup was performed. The series included indications not approved by the FDA, such as children under 12 years of age, pregnancy and right-sided VNS. Performing the procedure on an out-patient basis was recently adopted, minimizing hospital length of stay. RESULTS: There were 42 adults and 17 children (14 under 12 years of age) and the mean age at implantation was 26 years. Duration of VNS therapy ranged from 6 months to 9 years. For the entire cohort, the mean percentage seizure reduction was 31.37%. Twenty patients (34.48%) were considered responders (seizure reduction ≥50%); 7 patients (12.06%) had seizure reduction of ≥75% and 2 patients had seizure control of ≥90% (3.4%). The patient in whom right-sided VNS was implanted achieved the same reduction in seizure burden and the patient who became pregnant could reduce antiepileptic drugs dosage, without complications. Side-effects were mild and there were no permanent nerve injuries. One patient died in the follow-up due to psychiatric disorders previously known. CONCLUSIONS: VNS is a safe and effective palliative treatment for TRE patients. There are an increasing number of indications and further randomized trials would potentially expand the number of patients who may benefit from it. A multidisciplinary team is crucial for a complete preoperative evaluation and selection of the optimal candidates for the treatment.

Cardiocirculatory manifestations in Parkinson's disease patients without orthostatic hypotension.

The objective of this study was to characterize cardiac sympathetic denervation in Parkinson's disease (PD) patients without neurogenic orthostatic hypotension (NOH), both in terms of hemodynamics and in its relation with vascular denervation. We studied 20 PD patients without NOH. We analyzed the heart rate and blood pressure variability during various physical maneuvers. The following parameters were calculated: expiratory-inspiratory ratio, stroke volume, cardiac output, cardiac index, left ventricular ejection time, left ventricular work index, thoracic fluid content, total peripheral resistance and baroreflex sensitivity (BRS). We also measured direct and spectral derivatives of cardiac (cardiovagal) parasympathetic function. Myocardial I-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed and early and late heart/mediastinum uptake ratios were analyzed. We observed that the late heart/mediastinum uptake ratio was 1.33±0.21. This parameter was correlated with years since diagnosis (correlation coefficient:-0.485; P=0.05), Unified Parkinson's Disease Rating Scale (UPDRS) III score (cc:-0.564; P=0.02) and pressure recovery time in the Valsalva maneuver (cc: 0.61; P<0.001). At rest, it was correlated with BRS (cc:0.75; P=0.003) and low-frequency diastolic blood pressure (LFDBP; cc: 0.58;P=0.017). We found no correlations with any of the cardiography impedance variables. In linear regression models, the variable that best correlated with MIBG results was LFDBP. Our results support that in absence of NOH the degree of denervation of the heart does not produce any effect on its inotropic function. Moreover, BRS and LFDBP can be used as an indirect measure of cardiac sympathetic denervation at rest.