RESUMO
BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a disabling neuropathy that occurs in intensive care unit (ICU) subjects. It was hypothesized that a low serum level or deficiency of 25(OH)D might be associated with CIPNM. The aim of the present study was to ascertain the 25(OH)D serum level in subjects with CIPNM. METHOD: Consecutive ICU patients admitted to neuro-rehabilitation were prospectively enrolled. At admission, vitamin D serum levels were measured and EMG examination was performed to ascertain those with CIPNM. 25(OH)D was stratified as sufficient (≥30 ng/mL) insufficient (20-29.9 ng/mL), and deficient (<20 ng/mL). RESULTS: Eighty-four patients (31 F, 53 M; mean age 51.7±12.6) were identified and 63 (21 F, 42 M) enrolled. CIPNM was detected in 38 (9 F, 29 M) patients. A deficient mean serum level of vitamin D was observed in the whole population: 18.1 ± 9.2 ng/mL. No difference of vitamin D serum levels was detected in subjects with and without CIPNM: 17.5 ± 8.4 and 19.0 ± 10.5 ng/mL (p=0.58), respectively. CONCLUSION: Almost all subjects showed Vitamin D deficiency. No difference was detected between those with and without CIPNM. The condition might represent a secondary phenomenon resulting from the inflammatory process as well as from conditions that could interfere with vitamin D metabolism.
Assuntos
Calcifediol/sangue , Estado Terminal , Unidades de Terapia Intensiva/tendências , Doenças Musculares/sangue , Polineuropatias/sangue , Deficiência de Vitamina D/sangue , Adulto , Idoso , Estado Terminal/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculares/diagnóstico , Doenças Musculares/epidemiologia , Polineuropatias/diagnóstico , Polineuropatias/epidemiologia , Estudos Prospectivos , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/epidemiologiaRESUMO
Familial cerebral cavernous malformation (FCCM) is an autosomal dominant vascular disorder caused by heterozygous deleterious variants in KRIT1, CCM2 or PDCD10. In a previous study, we presented the clinical and molecular findings in 140 FCCM individuals. In the present work, we report supporting information on (a) applied diagnostic workflow; (b) clinical significance of molecular findings according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology recommendations; (c) standardization of molecular and clinical data according to the Human Phenotype Ontology; (d) preliminary genotype-phenotype correlations on a subgroup of patients by considering sex, age at diagnosis, neurological symptoms, and number and anatomical site(s) of vascular anomalies; (e) datasets submitted to the Leiden Open Variation Database. An overview of the changes of our diagnostic approach before and after the transition to next-generation sequencing is also reported. This work presents the full procedure that we apply for molecular testing, data interpretation and storing in public databases in FCCM.
Assuntos
Interpretação Estatística de Dados , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Fluxo de Trabalho , Alelos , Biologia Computacional/métodos , Bases de Dados Genéticas , Feminino , Estudos de Associação Genética/métodos , Genótipo , Humanos , Masculino , Técnicas de Diagnóstico Molecular , FenótipoRESUMO
We report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis. Participants were treated with hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed. All participants displayed stability of clinical and laboratory outcomes, as well as lesion load and brain activity (MRI), compared with the study entry. Longitudinal metabolomics and lipidomics of biological fluids identified time- and dose-dependent responses with increased levels of acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of AEs and the stability of functional and structural outcomes are reassuring and represent a milestone for the safe translation of stem cells into regenerative medicines.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Células-Tronco Neurais , Humanos , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla/terapia , Transplante AutólogoRESUMO
Patients with COVID-19 may develop a range of neurological disorders. We report here 4 COVID-19 subjects with intensive care unit-acquired weakness and their functional outcome. In addition, a scoping review of COVID-19 literature was performed to investigate this issue. Of the post-COVID-19 patients admitted to our Neuro-Rehabilitation Unit, 4 (3 males, 1 female; mean age 59.2 ± 8.62 years) had intensive care unit-acquired weakness, diagnosed with electromyography. Muscle strength and functional evaluation were performed on all patients with Medical Research Council, Disability Rating Scale and Functional Independence Measure, respectively, at admission, discharge and 6-month follow-up after discharge. Electromyography revealed that 3 subjects had critical illness polyneuropathy and 1 had critical illness polyneuropathy/critical illness myopathy. At follow-up, the 3 subjects with critical illness polyneuropathy reached full recovery. The patient with critical illness polyneuropathy/critical illness myopathy showed moderate disability requiring bilateral ankle foot-orthosis and support for ambulation. The scoping review retrieved 11 studies of COVID-19 patients with intensive care unit-acquired weakness, concerning a total of 80 patients: 23 with critical illness myopathy (7 probable), 21 with critical illness polyneuropathy (8 possible), 15 with critical illness polyneuropathy and myopathy (CIPNM) and 21 with intensive care unit-acquired weakness. Of 35 patients who survived, only 3 (8.5%) reached full recovery. All 3 had critical illness myopathy, but 2 of these had a diagnosis of probable critical illness myopathy. Intensive care unit-acquired weakness commonly occurred in subjects with COVID-19. Recovery was variable and a low percentage reached full recovery. However, the heterogeneity of studies did not allow definitive conclusions to be drawn.
Assuntos
COVID-19 , Doenças Musculares , Polineuropatias , Idoso , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Polineuropatias/etiologiaRESUMO
Background: The COVID-19 disease can affect subjects suffering from myasthenia gravis (MG) and worsen its clinical course, leading to intensive care unit (ICU) admission. Critically ill subjects can develop a neuromuscular complication called ICU-acquired weakness (ICUAW). This disorder has also been detected in ICU subjects with COVID-19, but the association between MG and ICUAW has never been described in critically ill patients. We describe the case and functional outcome of a COVID-19 patient suffering from MG who developed critical illness polyneuropathy (CIP). Case Presentation: A 66-year-old man with a history of hypertension and ocular MG had COVID-19 and required ICU admission. The patient underwent mechanical ventilation and tracheotomy and was treated with remdesivir and corticosteroids. Fifteen days after admission, he complained of tetraparesis without the ocular involvement that remained unchanged despite the increase in anticholinesterase therapy. The length of stay (LOS) in ICU was 35 days. On day 2 of admission, the patient underwent a frontal muscle jitter study that confirmed the MG, and electroneurography (ENG) and electromyography (EMG) that showed overlapping ICUAW with electrophysiological signs characteristic of CIP. The cerebrospinal fluid (CSF) showed normal pressure, cell count, and protein levels (<45 mg/dl) without albumin-cytologic disassociation. The CSF/serum glucose ratio was normal. The CSF culture for possible organisms, laboratory tests for autoimmune disorders, the panel of antiganglioside antibodies, and the paraneoplastic syndrome were negative. Strength and functional outcomes were tested with the MRC scale, the DRS, Barthel scale, and the Functional Independence Measure (FIM) at admission, discharge, and follow-up. Muscular strength improved progressively, and the MRC scale sum-score was 50 at discharge. Anticholinesterase therapy with pyridostigmine at a dosage of 30 mg 3 times daily, which the patient was taking before COVID-19, was resumed. His motor abilities recovered, and functional evaluations showed full recovery at follow-up. Conclusion: In the described subject, the coexistence of both neuromuscular disorders did not affect the clinical course and recovery, but the question remains about generalization to all patients with MG. The rehabilitation interventions might have facilitated the outcome.