Monocyte exposure to mitochondrial Danger Associated Molecular Patterns (DAMPs), including mitochondrial DNA (mtDNA), induces a transient state in which these cells are refractory to further ...endotoxin stimulation. In this context, IRAK-M up-regulation and impaired p65 activity were observed. This phenomenon, termed endotoxin tolerance (ET), is characterized by decreased production of cytokines in response to the pro-inflammatory stimulus. We also show that monocytes isolated from patients with myocardial infarction (MI) exhibited high levels of circulating mtDNA, which correlated with ET status. Moreover, a significant incidence of infection was observed in those patients with a strong tolerant phenotype. The present data extend our current understanding of the implications of endotoxin tolerance. Furthermore, our data suggest that the levels of mitochondrial antigens in plasma, such as plasma mtDNA, should be useful as a marker of increased risk of susceptibility to nosocomial infections in MI and in other pathologies involving tissue damage.
Eye‐of‐the‐Tiger Sign with an Unexpected Pathological Diagnosis Natera‐Villalba, Elena; Martínez‐Castrillo, Juan Carlos; López‐Sendón Moreno, José Luis ...
Movement disorders clinical practice (Hoboken, N.J.),
January 2022, Letnik:
9, Številka:
1
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
Background
Clinical diagnosis of atypical parkinsonisms may be challenging. The eye‐of‐the‐tiger sign on brain MRI, typical of neurodegeneration with brain iron accumulation, has been ...anecdotally observed in cases clinically diagnosed as atypical parkinsonisms.
Objectives
To show how clinical syndromes and even neuroimaging sometimes may lead the neurologist to a misunderstanding, just as to emphasize the important role of pathology to establish the final diagnosis in these cases.
Methods
Clinico‐pathological case.
Results
A 67‐year‐old‐woman presented with progressive painful stiffness and allodynia in her left arm. On examination, she presented parkinsonism without tremor with greater involvement of left limbs. She developed dystonia, with myoclonic tremor and hypoesthesia involving her left arm, as well as an impairment of balance with falls, a significant axial involvement with disabling rigidity, supranuclear gaze abnormalities, facial dystonia, dysphonia, severe dysphagia, and anarthria. There was no response to levodopa. Syndromic diagnosis and findings on neuroimaging are discussed. Afterwards, the underlying pathology is revealed.
Conclusions
We present the first case of neuropathologically confirmed multiple system atrophy with the eye‐of‐the‐tiger sign on brain MRI. The presence of supranuclear vertical gaze palsy further complicated a correct clinical diagnosis. A pathological postmortem study remains essential to establish a definite diagnosis in atypical parkinsonisms.
Drug-induced parkinsonism (DIP) and tardive dyskinesia (TD) are iatrogenic consequences of antidopaminergic drugs. Both are particularly prevalent among the elderly and those with dementia. However, ...despite their prevalence, these disorders are often overlooked. Both entities share risk factors, physiopathological mechanisms and, to some degree, therapeutic approaches. Withdrawing the causal agent, reducing the dose or switching to a less potent antidopaminergic drug should be the first therapeutic options. Here we review both entities and emerging therapies including the recently approved drugs deutetrabenazine and valbenazine. We discuss relevant aspects for clinical practice such as new diagnostic techniques and the latest advances in the understanding of DIP and TD.
Urinary symptoms are common, disabling and generally unresponsive to treatment in Parkinson´s disease (PD). Safinamide is approved as an add-on therapy to levodopa to improve fluctuations.
...Retrospective analysis of electronic records of nondemented PD patients seen consecutively in a Movement Disorders Unit (November 2018-February 2019). All were assessed with Scale for Outcomes in Parkinson's disease for Autonomic Symptoms-Urinary subscale (SCOPA-AUT-U) by the attending neurologist, and a month afterwards by an independent researcher blinded to treatment and clinical records in a routine clinical practice setting. Clinical variables were compared among patients who were prescribed safinamide (SA+) for the treatment of motor fluctuations and those with different treatment regimes (SA-).
From 169 patients screened initially, 54 were excluded due to severe incontinence, absence of urinary symptoms or previous safinamide treatment. Thirty-five patients were included in SA+ and 79 in SA-. Both groups were comparable in terms of clinical variables, except in basal urinary symptoms, with more severity in the SA+ group. In the follow-up assessment, total SCOPA-AUT-U, as well as urgency, incontinence, frequency and nocturia subscales improved significantly in the SA+ group, while the SA- group remained unchanged.
Safinamide could be helpful in the improvement of urinary symptoms in PD.
Botulinum toxin type A is one of the most useful treatments of sialorrhea in neurological disorders. Evidence for the use of incobotulinumtoxin A (inco-A) in the treatment of sialorrhea is limited. ...Thirty-six patients with sialorrhea were treated with infiltrations of inco-A into both parotid glands. The severity of sialorrhea was evaluated by the Drooling Severity Scale (DSS), and the Drooling Frequency Scale (DFS). Patients' perceptions of clinical benefit were recorded via the Patient Global Impression of Improvement (PGI-I) scale. Following treatment, there was a significant difference in both the DFS and the DSS (
< 0.001). Clinical benefits on the basis of the PGI-I were present in up to 90% of patients.
KCNJ10
encodes the inward-rectifying potassium channel (Kir4.1) that is expressed in the brain, inner ear, and kidney. Loss-of-function mutations in
KCNJ10
gene cause a complex syndrome consisting of ...epilepsy, ataxia, intellectual disability, sensorineural deafness, and tubulopathy (EAST/SeSAME syndrome). Patients with EAST/SeSAME syndrome display renal salt wasting and electrolyte imbalance that resemble the clinical features of impaired distal tubular salt transport in Gitelman’s syndrome. A key distinguishing feature between these two conditions is the additional neurological (extrarenal) manifestations found in EAST/SeSAME syndrome. Recent reports have further expanded the clinical and mutational spectrum of
KCNJ10
-related disorders including non-syndromic early-onset cerebellar ataxia. Here, we describe a kindred of three affected siblings with early-onset ataxia, deafness, and progressive spasticity without other prominent clinical features. By using targeted next-generation sequencing, we have identified two novel missense variants, c.488G>A (p.G163D) and c.512G>A (p.R171Q), in the
KCNJ10
gene that, in compound heterozygosis, cause this distinctive EAST/SeSAME phenotype in our family. Electrophysiological characterization of these two variants confirmed their pathogenicity. When expressed in CHO cells, the R171Q mutation resulted in 50% reduction of currents compared to wild-type KCNJ10 and G163D showed a complete loss of function. Co-expression of G163D and R171Q had a more pronounced effect on currents and membrane potential than R171Q alone but less severe than single expression of G163D. Moreover, the effect of the mutations seemed less pronounced in the presence of Kir5.1 (encoded by
KCNJ16
), with whom the renal Kir4.1 channels form heteromers. This partial functional rescue by co-expression with Kir5.1 might explain the lack of renal symptoms in the patients. This report illustrates that a spectrum of disorders with distinct clinical symptoms may result from mutations in different parts of
KCNJ10
, a gene initially associated only with the EAST/SeSAME syndrome.
Potential explanations may include reduction of STEMI due to physical inactivity, reluctance of patients for seeking medical assistance due to the possibility of SARS-CoV-2 contamination, attribution ...of symptoms to COVID-19 infection, health system failures and diagnostic errors in attending patients with chest pain, delay in diagnosis losing the benefit of early coronary reperfusion, increased use of thrombolysis, and cardiac death before medical attendance. Mean age was not statistically different in both periods (63.4 ± 13.4 before, and 65.1 ± 13.1 during pandemic, p = 0.3769). ...the reduction in the number of patients with STEMI attended in tertiary hospitals only was found in men. ...men have higher treatment-seeking threshold than women, some studies having pointed towards men's sense of stoicism and self-reliance. Because of these reasons, COVID-19 pandemic might have impacted clearly on STEMI treatment only in male patients, and counterbalanced the classical advantage of more typical symptoms in male gender.
Patients with coronary total occlusions are at especially high risk for restenosis and new revascularizations. Sirolimus-eluting stents dramatically improved the clinical outcome of this subset of ...patients in randomized trials, but other drug-eluting stents, mainly the everolimus-eluting stent (currently the most frequently used stent), have not yet been evaluated in patients with coronary total occlusions. The objective was to compare the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent in patients with coronary total occlusions.
A total of 207 patients with coronary total occlusions and estimated time since occlusion >2 weeks were randomized to everolimus- or sirolimus-eluting stent. The primary end point was in-stent late loss at 9-month angiographic follow-up (noninferiority trial). Clinical follow-up was performed at 1 and 12 months. In-stent late loss at 9 months was 0.29±0.60 versus 0.13±0.69 mm in patients allocated to sirolimus- and everolimus-eluting stent, respectively. The observed difference in in-stent late loss between both groups was -0.16 mm (95% confidence interval, 0.04 to -0.36 mm; P for noninferiority <0.01). The rate of binary angiographic restenosis was 10.8% and 9.1% in patients allocated to sirolimus- and everolimus-eluting stent, respectively (P=0.709), whereas the rate of vessel reocclusion was 3.2% and 1.1%, respectively (P=0.339). At 12 months, the rate of major adverse events was 15.9% versus 11.1% with sirolimus- and everolimus-eluting stent, respectively (P=0.335), and probable or definitive stent thrombosis occurred in 3.0% and 0.0% of patients, respectively (P=0.075).
In patients with coronary total occlusions, everolimus-eluting stent is as effective as sirolimus-eluting stent.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00793221.
ABSTRACT Primary percutaneous coronary intervention (pPCI) is the best modality of reperfusion in ST segment elevation in acute myocardial infarction (STEMI). Its application requires networked ...assistance systems whose implementation requires significant organizational and logistical changes. In comparison with other scenarios of urgent action, a series of aspects are specific to the pPCI programs. They require immediate, clearly pre-established strategies, carried out by highly skilled professionals who attend to a high volume of highly complex patients. The lack of homogeneity in the creation and development of reperfusion programs in Spain has led to great differences in their implementation. If the pPCI programs are not carried out under adequate conditions, their sustainability can be complex. The present document, agreed between different scientific societies, aims to analyze the current situation in Spain of the network care programs for STEMI, identify their limitations and deficiencies, assess their vulnerability and establish a series of recommendations to ensure their sustainability.
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