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.

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.

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.

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.

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.

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.

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.