Extent of pulmonary thromboembolic disease in patients with COVID-19 on CT: relationship with pulmonary parenchymal disease.

AIM: To report the severity and extent of pulmonary thromboembolic disease (PTD) in COVID-19 patients undergoing computed tomography pulmonary angiography (CTPA) in a tertiary centre. MATERIALS AND METHODS: This is a retrospective analysis of COVID-19 patients undergoing CTPA over a period of 27 days. The presence, extent, and severity of PTD were documented. Two observers scored the pattern and extent of lung parenchymal disease including potential fibrotic features, as well as lymph node enlargement and pleural effusions. Consensus was achieved via a third observer. Interobserver agreement was assessed using kappa statistics. Student's t-test, chi-squared, and Mann-Whitney U-tests were used to compare imaging features between PTD and non-PTD sub-groups. RESULTS: During the study period, 100 patients with confirmed COVID-19 underwent CTPA imaging. Ninety-three studies were analysed, excluding indeterminate CTPA examinations. Overall incidence of PTD was 41/93 (44%) with 28/93 patients showing small vessel PTD (30%). D-dimer was elevated in 90/93 (96.8%) cases. A high Wells' score did not differentiate between PTD and non-PTD groups (p=0.801). The interobserver agreement was fair (kappa=0.659) for parenchymal patterns and excellent (kappa=0.816) for severity. Thirty-four of the 93 cases (36.6%) had lymph node enlargement; 29/34 (85.3%) showed no additional source of infection. Sixteen of the 93 (17.2%) cases had potential fibrotic features. CONCLUSION: There is a high incidence of PTD in COVID-19 patients undergoing CTPA and lack of a risk stratification tool. The present data indicates a higher suspicion of PTD is needed in severe COVID-19 patients. The concomitant presence of possible fibrotic features on CT indicates the need for follow-up.

Severe acute respiratory syndrome-Coronavirus-2 infection: A review of the clinical-pathological correlations of Coronavirus disease-19 in children.

The coronavirus disease-19 (COVID-19) has become a global pandemic of acute respiratory disease in just less than a year by the middle of 2020. This disease caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has resulted in significant mortality especially among the older age population and those with health co-morbidities. In contrast, children are relatively spared of this potentially ravaging disease that culminates in the acute respiratory distress syndrome, multi-organ failure and death. SARS-CoV-2 infection induces exuberant release of pro-inflammatory mediators, causing a "cytokine storm" and hypercoagulable states that underlie these complications. The SARS-CoV-2 infection median incubation is 5.1 days, with most developing symptoms by 11.5 days. It is highly infectious, spreading via the horizontal mode of transmission, but there is yet very limited evidence of vertical transmission to the newborn infant occurring either transplacentally or through breastfeeding. This said, various immune factors during childhood may modulate the expression of COVID-19, with the multisystem inflammatory syndrome in children (MIS-C) at the severe end of the disease spectrum. This article gives an overview of the SARS-CoV-2 infection, clinical presentation and laboratory tests of COVID-19 and correlating with the current understanding of the pathological basis of this disease in the paediatric population.

All in the blink of an eye: new insight into cerebellar and brainstem function in DYT1 and DYT6 dystonia.

BACKGROUND AND PURPOSE: Traditionally dystonia has been considered a disorder of basal ganglia dysfunction. However, recent research has advocated a more complex neuroanatomical network. In particular, there is increasing interest in the pathophysiological role of the cerebellum. Patients with cervical and focal hand dystonia have impaired cerebellar associative learning using the paradigm eyeblink conditioning. This is perhaps the most direct evidence to date that the cerebellum is implicated in patients. METHODS: Eleven patients with DYT1 dystonia and five patients with DYT6 dystonia were examined and rates of eyeblink conditioning were compared with age-matched controls. A marker of brainstem excitability, the blink reflex recovery, was also studied in the same groups. RESULTS: Patients with DYT1 and DYT6 dystonia have a normal ability to acquire conditioned responses. Blink reflex recovery was enhanced in DYT1 but this effect was not seen in DYT6. CONCLUSIONS: If the cerebellum is an important driver in DYT1 and DYT6 dystonia our data suggest that there is specific cerebellar dysfunction such that the circuits essential for conditioning function normally. Our data are contrary to observations in focal dystonia and suggest that the cerebellum may have a distinct role in different subsets of dystonia. Evidence of enhanced blink reflex recovery in all patients with dystonia was not found and recent studies calling for the blink recovery reflex to be used as a diagnostic test for dystonic tremor may require further corroboration.

Cerebellum-dependent associative learning deficits in primary dystonia are normalized by rTMS and practice.

Eyeblink classical conditioning (EBCC) is a cerebellum-dependent paradigm of associative motor learning, and abnormal EBCC is a neurophysiological indicator of cerebellar dysfunction. We have previously demonstrated impaired EBCC in patients with primary dystonia, but it remains uncertain if this represents actual cerebellar pathology or reflects a functional cerebellar disruption. We examined this further by: (1) studying acquisition and retention of EBCC in a second session in eight patients with cervical dystonia (CD) who had a first session 7-10 days earlier; and (2) by investigating the potential of continuous theta burst stimulation (cTBS) over the right cerebellar hemisphere to modify a first-ever EBCC session in 11 patients with CD. EBCC data of eight healthy controls previously studied were used for additional between-group comparisons. We observed an improvement of EBCC in a second session in patients with CD, which is in contrast to patients with proven cerebellar pathology who do not show further improvement of EBCC in additional sessions. We also found that cerebellar cTBS paradoxically normalized EBCC in patients with CD, while we previously showed that it disrupts EBCC in healthy volunteers. Combined, these two experiments are in keeping with a functional and reversible disruption of the cerebellum in dystonia, a phenomenon that is probably secondary to either cerebellar compensation or to cerebellar recruitment in the abnormal sensorimotor network.

Neurophysiological evidence for cerebellar dysfunction in primary focal dystonia.

Recent studies have suggested that there may be functional and structural changes in the cerebellum of patients with adult onset primary focal dystonia. The aim of this study was to establish whether there is any neurophysiological indicator of abnormal cerebellar function, using the classic eyeblink conditioning paradigm. This paradigm at short intervals is dependent on the olivo-cerebellar circuit and does not require cerebral and basal ganglia structures. Eyeblink conditioning was performed by pairing an auditory tone with a supraorbital nerve stimulus with a delay interval of 400 ms in 12 patients with primary focal dystonia (seven cervical dystonias, five focal hand dystonias) and eight healthy controls. Healthy controls produced more conditioned eyeblink responses than patients with focal dystonia, indicating an abnormality of associative learning in this patient population. This study provides neurophysiological evidence for functional changes in the olivo-cerebellar pathway of patients with primary focal dystonia. Further work needs to be done to determine if these changes are primary, secondary or epiphenomenal to the disease.

Differing effects of intracortical circuits on plasticity.

Practice of a motor task leads to an increase in amplitude of motor-evoked potentials (MEP) in the exercised muscle. This is termed practice-dependent plasticity, and is abolished by the NMDA antagonist dextromethorphan and the GABA(A) agonist lorazepam. Here, we sought to determine whether specific subtypes of GABA(A) circuits are responsible for this effect by comparing the action of the non-selective agonist, lorazepam with that of the selective GABA(A)-alpha(1) receptor agonist, zolpidem. In seven healthy subjects, transcranial magnetic stimulation (TMS) was used to quantify changes in amplitude of MEP after practice of a ballistic motor task. In addition we measured how the same drugs affected MEP amplitudes and the excitability of a number of cortical inhibitory circuits [short-interval intracortical inhibition (SICI), short-interval afferent inhibition (SAI) and long-interval intracortical inhibition]. This allowed us to explore correlations between drugs effects in measures of cortical excitability and practice-dependent plasticity of MEP amplitudes. As previously reported, lorazepam increased SICI and decreased SAI, while zolpidem only decreased SAI. The new findings were that practice-dependent plasticity of MEPs was impaired by lorazepam but not zolpidem, and that this was negatively correlated with lorazepam-induced changes in SICI but not SAI. This suggests that the intracortical circuits involved in SICI (and not neurons expressing GABA(A)-alpha(1) receptor subunits that are implicated in SAI) may be involved in controlling the amount of practice-dependent MEP plasticity.

Pattern-specific role of the current orientation used to deliver Theta Burst Stimulation.

OBJECTIVE: To evaluate the role of current direction on the after-effects of Theta Burst Stimulation (TBS) delivered with a biphasic Magstim 200(2) stimulator. METHODS: Inhibitory (cTBS) and excitatory TBS (iTBS) were delivered over the motor cortex of healthy individuals using reversed and standard current orientations (initial current in the antero-posterior direction) at 80% and 100% of their respective active motor thresholds (AMT). The after-effects on the MEP amplitude were measured for 25 min. The effects of the most effective reversed cTBS paradigm on intracortical inhibition (SICI) and facilitation (ICF) were also tested. RESULTS: Reversing the current direction reduced AMT by 26%+/-2%. Compared to standard cTBS, reversed cTBS induced stronger and longer-lasting inhibition of corticospinal excitability when delivered at 100% AMTrev. SICI was reduced after cTBS100%revAMT while ICF was unchanged. The after-effects of reversed iTBS were quite variable regardless of the intensity. CONCLUSIONS: cTBS applied with antero-posterior current is more effective in suppressing subsequent MEPs than conventionally orientated cTBS when the absolute stimulation intensity is similar. On the contrary, posterior current orientation reduces the efficacy of iTBS. SIGNIFICANCE: The current direction may affect the power of inhibitory and excitatory TBS in opposite ways; this should be considered in order to optimise the after-effects of biphasic RTMS.

Bad design, bad practices, bad bugs: frustrations in controlling an outbreak of Elizabethkingia meningoseptica in intensive care units.

BACKGROUND: Elizabethkingia meningoseptica is a nosocomial-adapted Gram-negative bacillus intrinsically resistant to antibiotics commonly used in the intensive care setting. An outbreak investigation commenced when five patients developed E. meningoseptica infection in two intensive care units (ICUs). METHODS: Analysis of laboratory data, case reviews, ICU workflows and extensive environmental sampling were undertaken. Molecular typing was performed using repetitive element palindromic polymerase chain reaction. Follow-up studies after interventions included environmental monitoring and a survey of staff compliance with interventions. FINDINGS: Laboratory data revealed increasing incidence of E. meningoseptica colonization or infection in ICU patients compared with preceding years. E. meningoseptica was cultured from 44% (35/79) of taps, but not from other sources. Hand hygiene sinks were used for disposal of patient secretions and rinsing re-usable patient care items. Sinks misused in this way were contaminated more often than sinks that were not misused (odds ratio 4.38, 95% confidence interval 1.68-11.39; P = 0.004). Molecular typing revealed that patient isolates had identical patterns to several isolates from hand hygiene taps. An urgent education programme was instituted to change these practices. Taps were cleaned systematically and aerators were changed. A temporary reduction in case numbers was achieved. Recolonization of taps was demonstrated on follow-up environmental screening, and cases recurred after two months. A survey revealed that 77.3% (163/213) of nursing staff still misused sinks due to time constraints or other problems adhering to the interventions. CONCLUSION: Introduction of non-sanctioned practices due to suboptimal unit design may have unintentional consequences for ICU patients. Room design and staff workflows must be optimized for patient safety as lapses in procedure can inadvertently put patients at risk.

The blink reflex recovery cycle differs between essential and presumed psychogenic blepharospasm.

BACKGROUND: Psychogenic blepharospasm is difficult to distinguish clinically from benign essential blepharospasm (BEB). The blink reflex recovery cycle measures the excitability of human brainstem interneurons and is abnormal in BEB. We wished to study the blink reflex recovery cycle in patients with atypical (presumed psychogenic) blepharospasm (AB). METHODS: This was a prospective data collection study investigating the R2 blink reflex recovery cycle at interstimulus intervals (ISI) of 200, 300, 500, 1,000, and 3,000 msec in 10 patients with BEB, 9 patients with AB, and 9 healthy controls. All patients had spasm of the orbicularis oculi muscles. To compare individual patients, an R2 recovery index was calculated as average of the recovery values at ISIs of 200, 300, and 500 msec, with the upper limit of normal defined as mean (control group) + 2 SD. RESULTS: The R2 recovery cycle was significantly disinhibited in patients with BEB, whereas patients with AB did not differ from controls on a group level. The upper limit of normal for the R2 recovery index was 61%. The R2 index was abnormal in 9 out of 10 patients with BEB and in none of the patients with AB. CONCLUSIONS: A normal blink reflex recovery cycle indicates normal brainstem interneuron excitability. Assessment of the R2 recovery cycle may provide a useful diagnostic tool to distinguish patients with psychogenic blepharospasm from BEB and is worthy of further study.

Intracortical circuits modulate transcallosal inhibition in humans.

Previous results using paired-pulse transcranial magnetic stimulation (TMS) have suggested that the excitability of transcallosal (TC) connections between the hand areas of the two motor cortices is modulated by intracortical inhibitory circuits in the same way as corticospinal tract (CTS) projections to spinal motoneurons. Here we describe two further similarities in TC and CTS control using (1) an I-wave facilitation protocol and (2) preconditioning with rTMS. In experiment 1, excitability of TC pathways was measured using interhemispheric inhibition (IHI) and the ipsilateral silent period (iSP), whilst excitability of CTS pathways was measured by recording the EMG response evoked in the first dorsal interosseous muscle contralateral to the conditioning stimulus (cMEP). The intensity of the conditioning stimulus was first adjusted to threshold for evoking IHI and iSP, then pairs of conditioning stimuli were applied randomly at interstimulus intervals (ISIs) from 1.3 to 4.3 ms. IHI and iSP were facilitated at ISI=1.5 ms and 3.0 ms, respectively, as was the MEP evoked by the conditioning stimuli in the contralateral hand. We suggest that TC projections receive I-wave-like facilitation similar to that seen in CTS projections. In experiment 2, short interval inhibition of the iSP (SICIiSP), and short interval intracortical inhibition of the cMEP (SICIcMEP) were examined before and after 600 pulses of 5 Hz rTMS at 90% resting motor threshold. Both SICIiSP and SICIcMEP were reduced, as was the iSP; the cMEP was unchanged. This shows that the population of inhibitory interneurons that control TC neurons respond in the same way to 5 Hz rTMS as those that control CTS neurons. Taken together, the data from the two experiments suggest that the layer III and layer V pyramidal neurons that give rise to TC and CTS pathways, respectively, are controlled by neuronal circuitry with similar properties.