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.
Substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is frequent in Parkinson's disease (PD), while lenticular nucleus hyperechogenicity (LN+) and 3rd ventricle enlargement (3V+) ...are typical of Atypical Parkinsonisms (AP). However, there are no studies assessing the diagnostic yield of all TCS biomarkers in the three AP (progressive supranuclear palsy, PSP, multiple system atrophy, MSA, corticobasal degeneration, CBD). Previous references lack homogeneous criteria and data are incomprehensive.
Analysis of TCS performed in routine clinical practice in AP and PD patients from two tertiary hospitals. Expert recommendations were strictly followed. Previous literature was critically analysed.
155 AP (98 PSP, 40 MSA, 14 CBD), 254 PD, 145 control subjects were included. We confirmed good sensitivity for SN+ in PD (80%), but specificity was lower than reported (61%). LN+ and 3V + had moderate sensitivity for AP and PSP diagnosis respectively (65%, 63%), but specificity was higher than reported (87%, 91%). We confirmed high specificity and positive predictive value of the combination SN/LN (98%, 93% AP; 83%, 86% PD). The combinations of two or three echofeatures, previously unreported, showed high specificity but lower sensitivity (SN/3V: 75% sensitivity, 87% specificity PD; 42% sensitivity, 98% specificity PSP) (SN + LN+: 79% sensitivity, 86% specificity CBD) (SN/3V/LN: 67% sensitivity, 89% specificity PD; 29% sensitivity, 99% specificity PSP; 41% sensitivity, 95% specificity MSA; 57% sensitivity 91% specificity CBD).
We present a large comprehensive study of TCS, confirming its usefulness and certain limitations in AP diagnosis. Adherence to consensus criteria is critical to implement TCS for clinical and research purposes.
•Real clinical practice TCS study of the largest sample of atypical parkinsonism and PD to date.•Diagnostic reliability of combinations of SN, 3V, LN was assessed for the first time.•Previous literature was systematically analysed and potential pitfalls criticised.•SN had higher sensitivity but lower specificity for PD diagnosis than previously reported.•Combinations of 2/3 echofeatures reached high specificity for AP diagnosis (>90%).
ABSTRACT
Aims: Lacosamide (LCM) is a well‐tolerated and increasingly used second‐generation AED, and side effects such as atrial fibrillation are rare and poorly characterized. Supported by a ...literature review, we share our experience of the management of the first reported case of cardioembolic cerebral infarcts in the context of de novo atrial fibrillation, which appeared following a 200‐mg intravenous infusion of LCM for the treatment of non‐convulsive status epilepticus.
Methods: Case report and literature review using search items including “atrial fibrillation OR atrial flutter AND LCM” in the thesaurus of Medline.
Results: We found three cases of atrial fibrillation/atrial flutter secondary to LCM, one following a 200‐mg intravenous infusion. In one patient, previous risk factors for atrial fibrillation were reported and another was started on warfarin; all required suspension of LCM for cessation of atrial fibrillation. Previous risk factors for atrial fibrillation in our patient were older age, male gender, obesity, hypertension, valvular disease, first‐degree atrioventricular block and left anterior fascicle block. Atrial fibrillation appeared at the end of the infusion and ceased after a loading dose of amiodarone and suspension of LCM. Apixaban was initiated indefinitely five days later, and MRI showed four acute silent infarctions.
Conclusions: The appearance of atrial fibrillation has severe therapeutic and clinical implications and the use of LCM might be reconsidered within a context of increased predisposition to developing atrial fibrillation. If atrial fibrillation appears, the drug should be discontinued and anticoagulation should be considered according to embolic risk. Further investigation is needed in order to better categorize the risk profile of lacosamide regarding atrial fibrillation.
•Motor fluctuations and dyskinesia remains a challenging problem in PD.•Safinamide is effective in fluctuating PD patients without increasing dyskinesia.•Glutamatergic modulation with safinamide ...seems to increase with higher doses.•Increasing safinamide >100 mg improved motor control without dyskinesia worsening.•Safinamide >100 mg may be considered when off time and dyskinesia coexist.
INTRODUCTIONAn increased incidence of stroke in HIV-infected patients has already been reported, suggesting that HIV infection may be a cerebrovascular risk factor. The objective of this study was to ...assess temporal trends in the proportion of HIV infection among patients with stroke in Spain. METHODSData were obtained from the minimum basic dataset (MBDS) of all patients hospitalized in Spain between 1997 and 2012 with a primary or secondary diagnosis of stroke. The annual proportion of HIV infection and time trends (stratifying by type of stroke and HIV stage) were calculated, and predictors of HIV infection and the social and economic impact of HIV-infected (HIV+) and non-infected (HIV-) patients were analyzed. RESULTSOf 857,371 patients hospitalized with an incident stroke, 2134 (0.25%) had HIV infection. A 2.5% year-on-year increase (OR 1.025, 95% CI 1.015-1.036, p<0.0001) of the proportion of HIV-infected patients was observed due to an increase in the asymptomatic stage of the infection (per year OR 1.077, 95% CI 1.057-1.097, p<0.0001), as the proportion of patients with AIDS remained stable. Factors independently associated with HIV infection and stroke were active smoking, stimulating drugs and hepatitis C virus (HCV) infection. A higher mortality rate, longer hospital stay and a higher cost per hospitalized patient was observed among HIV+ patients. CONCLUSIONSFrom 1997 to 2012, there was an increase in the proportion of HIV infection among patients hospitalized with stroke irrespective of the classical vascular risk factors, reinforcing the role of HIV infection as a cerebrovascular risk factor.
The role of immunosuppression among coronavirus disease 2019 (COVID‐19) patients has not been elucidated and management may be challenging. This observational study included confirmed COVID‐19 ...patients. The primary endpoint was the development of moderate–severe acute respiratory distress syndrome (ARDS). Time to moderate–severe ARDS, the need for mechanical or noninvasive ventilation (MV/NIV), death, and a composite of death or MV/NIV were secondary endpoints. Of 138 patients included, 27 (19.6%) were immunosuppressed (IS) and 95 (68.8%) were male, with a median (IQR) age of 68 (54–78) years. A significantly lower proportion of IS patients (25.9%) compared to non‐IS patients (52.3%) developed moderate–severe ARDS, in both unadjusted (0.32; 95% CI, 0.13–0.83; p = .017) and adjusted (aOR, 0.25; 95% CI, 0.08–0.80; p = .019) analyses. After stratifying by pathologies, only IS patients with autoimmune diseases remained significant (aOR 0.25; 95% CI, 0.07–0.98; p = .046). Nonsignificant trends toward a longer time to moderate or severe ARDS, a lower need for MV/NIV, and a lower risk of death or MV/NIV were detected among IS. In our cohort of COVID‐19 patients, nonsevere immunosuppression was associated with a lower risk of moderate–severe ARDS, especially among AD. This suggests a potential protective effect from a hypothesized hyper‐inflammatory response.
Highlights • HHV-7 was associated with central nervous system infection in an adult HIV-positive patient. • Neurologic disease occurred despite the patient having a normal blood CD4 count. • ...Foscarnet may be effective therapy for treating HHV-7 associated central nervous system infection.
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