Post-activation depression from primary afferent depolarization (PAD) produces extensor H-reflex suppression following flexor afferent conditioning.

Suppression of the extensor H-reflex by flexor afferent conditioning is thought to be produced by a long-lasting inhibition of extensor Ia afferent terminals via GABAA receptor-activated primary afferent depolarization (PAD). Given the recent finding that PAD does not produce presynaptic inhibition of Ia afferent terminals, we examined in 28 participants if H-reflex suppression is instead mediated by post-activation depression of the extensor Ia afferents triggered by PAD-evoked spikes and/or by a long-lasting inhibition of the extensor motoneurons. A brief conditioning vibration of the flexor tendon suppressed both the extensor soleus H-reflex and the tonic discharge of soleus motor units out to 150 ms following the vibration, suggesting that part of the H-reflex suppression during this period was mediated by postsynaptic inhibition of the extensor motoneurons. When activating the flexor afferents electrically to produce conditioning, the soleus H-reflex was also suppressed but only when a short-latency reflex was evoked in the soleus muscle by the conditioning input itself. In mice, a similar short-latency reflex was evoked when optogenetic or afferent activation of GABAergic (GAD2+ ) neurons produced a large enough PAD to evoke orthodromic spikes in the test Ia afferents, causing post-activation depression of subsequent monosynaptic EPSPs. The long duration of this post-activation depression and related H-reflex suppression (seconds) was similar to rate-dependent depression that is also due to post-activation depression. We conclude that extensor H-reflex inhibition by brief flexor afferent conditioning is produced by both post-activation depression of extensor Ia afferents and long-lasting inhibition of extensor motoneurons, rather than from PAD inhibiting Ia afferent terminals. KEY POINTS: Suppression of extensor H-reflexes by flexor afferent conditioning was thought to be mediated by GABAA receptor-mediated primary afferent depolarization (PAD) shunting action potentials in the Ia afferent terminal. In line with recent findings that PAD has a facilitatory role in Ia afferent conduction, we show here that when large enough, PAD can evoke orthodromic spikes that travel to the Ia afferent terminal to evoke EPSPs in the motoneuron. These PAD-evoked spikes also produce post-activation depression of Ia afferent terminals and may mediate the short- and long-lasting suppression of extensor H-reflexes in response to flexor afferent conditioning. Our findings highlight that we must re-examine how changes in the activation of GABAergic interneurons and PAD following nervous system injury or disease affects the regulation of Ia afferent transmission to spinal neurons and ultimately motor dysfunction in these disorders.

GABA facilitates spike propagation through branch points of sensory axons in the spinal cord.

Movement and posture depend on sensory feedback that is regulated by specialized GABAergic neurons (GAD2+) that form axo-axonic contacts onto myelinated proprioceptive sensory axons and are thought to be inhibitory. However, we report here that activating GAD2+ neurons directly with optogenetics or indirectly by cutaneous stimulation actually facilitates sensory feedback to motor neurons in rodents and humans. GABAA receptors located at or near nodes of Ranvier of sensory axons cause this facilitation by preventing spike propagation failure at the many axon branch points, which is otherwise common without GABA. In contrast, GABAA receptors are generally lacking from axon terminals and so cannot inhibit transmitter release onto motor neurons, unlike GABAB receptors that cause presynaptic inhibition. GABAergic innervation near nodes and branch points allows individual branches to function autonomously, with GAD2+ neurons regulating which branches conduct, adding a computational layer to the neuronal networks generating movement and likely generalizing to other central nervous system axons.

Successful Percutaneous Balloon Dilatation of Supravalvular Aortic Membrane.

Supravalvular aortic stenosis is the least common type of left ventricular outflow tract obstruction. Primary balloon dilatation of membranous supravalvular aortic stenosis was performed in a 10-year-old male child with a remarkable reduction in systolic pressure gradient. Balloon dilatation is a feasible treatment modality for membranous supravalvular aortic stenosis. It provides good immediate results and sustained relief of stenosis.

Large Right Ventricle Thrombus in Uhl's Anomaly: A Rare Presentation of Extremely Rare Disease.

Uhl's anomaly is an extremely rare congenital cardiac malformation and is characterized by the partial or complete absence of right ventricular myocardium. The absence of myocardium may be the result of primary non-development of myocytes or a form of selective apoptosis. It is mainly sporadic although some familial occurrences have been reported. Congestive cardiac failure is the most common mode of presentation. Associated congenital cardiac malformations are also reported. We report a case of a 17-year-old male who presented with symptoms and signs of right heart failure, during evaluation found to have large right ventricle free wall thrombus.

Locomotor-related V3 interneurons initiate and coordinate muscles spasms after spinal cord injury.

Spinal cord injury leads to a devastating loss of motor function and yet is accompanied by a paradoxical emergence of muscle spasms, which often involve complex muscle activation patterns across multiple joints, reciprocal muscle timing, and rhythmic clonus. We investigated the hypothesis that spasms are a manifestation of partially recovered function in spinal central pattern-generating (CPG) circuits that normally coordinate complex postural and locomotor functions. We focused on the commissural propriospinal V3 neurons that coordinate interlimb movements during locomotion and examined mice with a chronic spinal transection. When the V3 neurons were optogenetically activated with a light pulse, a complex coordinated pattern of motoneuron activity was evoked with reciprocal, crossed, and intersegmental activity. In these same mice, brief sensory stimulation evoked spasms with a complex pattern of activity very similar to that evoked by light, and the timing of these spasms was readily reset by activation of V3 neurons. Given that V3 neurons receive abundant sensory input, these results suggest that sensory activation of V3 neurons is alone sufficient to generate spasms. Indeed, when we silenced V3 neurons optogenetically, sensory evoked spasms were inhibited. Also, inhibiting general CPG activity by blocking N-methyl-d-aspartate (NMDA) receptors inhibited V3 evoked activity and associated spasms, whereas NMDA application did the opposite. Furthermore, overwhelming the V3 neurons with repeated optogenetic stimulation inhibited subsequent sensory evoked spasms, both in vivo and in vitro. Taken together, these results demonstrate that spasms are generated in part by sensory activation of V3 neurons and associated CPG circuits. NEW & NOTEWORTHY We investigated whether locomotor-related excitatory interneurons (V3) play a role in coordinating muscle spasm activity after spinal cord injury (SCI). Unexpectedly, we found that these neurons not only coordinate reciprocal motor activity but are critical for initiating spasms, as well. More generally, these results suggest that V3 neurons are important in initiating and coordinating motor output after SCI and thus provide a promising target for restoring residual motor function.

Intravascular Ultrasound-Guided Management of Proximal Left Anterior Descending Artery Aneurysm With Covered Stent - A Case Report.

Coronary artery aneurysm is defined as the localized dilatation of a coronary artery segment more than 1.5 times the size of adjacent normal segments. The aneurysms of the coronary arteries are rare. Coronary aneurysms can be congenital or acquired. The majority are atherosclerotic in origin. The primary complication is myocardial ischemia or infarction, sudden cardiac death with rupture being rare. Some aneurysms are diagnosed incidentally in arteries other than the culprit artery. Treatment options include medical management with anticoagulation, percutaneous intervention with covered stents or surgery. We report a case of 67-year-old male who presented with acute coronary syndrome. Coronary angiogram showed a moderate size aneurysm of the proximal left anterior descending artery. This aneurysm was successfully managed percutaneously with a covered stent.

Extrasynaptic α5GABAA receptors on proprioceptive afferents produce a tonic depolarization that modulates sodium channel function in the rat spinal cord.

Activation of GABAA receptors on sensory axons produces a primary afferent depolarization (PAD) that modulates sensory transmission in the spinal cord. While axoaxonic synaptic contacts of GABAergic interneurons onto afferent terminals have been extensively studied, less is known about the function of extrasynaptic GABA receptors on afferents. Thus, we examined extrasynaptic α5GABAA receptors on low-threshold proprioceptive (group Ia) and cutaneous afferents. Afferents were impaled with intracellular electrodes and filled with neurobiotin in the sacrocaudal spinal cord of rats. Confocal microscopy was used to reconstruct the afferents and locate immunolabelled α5GABAA receptors. In all afferents α5GABAA receptors were found throughout the extensive central axon arbors. They were most densely located at branch points near sodium channel nodes, including in the dorsal horn. Unexpectedly, proprioceptive afferent terminals on motoneurons had a relative lack of α5GABAA receptors. When recording intracellularly from these afferents, blocking α5GABAA receptors (with L655708, gabazine, or bicuculline) hyperpolarized the afferents, as did blocking neuronal activity with tetrodotoxin, indicating a tonic GABA tone and tonic PAD. This tonic PAD was increased by repeatedly stimulating the dorsal root at low rates and remained elevated for many seconds after the stimulation. It is puzzling that tonic PAD arises from α5GABAA receptors located far from the afferent terminal where they can have relatively little effect on terminal presynaptic inhibition. However, consistent with the nodal location of α5GABAA receptors, we find tonic PAD helps produce sodium spikes that propagate antidromically out the dorsal roots, and we suggest that it may well be involved in assisting spike transmission in general. NEW & NOTEWORTHY GABAergic neurons are well known to form synaptic contacts on proprioceptive afferent terminals innervating motoneurons and to cause presynaptic inhibition. However, the particular GABA receptors involved are unknown. Here, we examined the distribution of extrasynaptic α5GABAA receptors on proprioceptive Ia afferents. Unexpectedly, these receptors were found preferentially near nodal sodium channels throughout the afferent and were largely absent from afferent terminals. These receptors produced a tonic afferent depolarization that modulated sodium spikes, consistent with their location.

"Superdominant" Left Anterior Descending Artery Continuing as Posterior Descending Artery: Extremely Rare Coronary Artery Anomaly.

The posterior descending artery (PDA) supplying the posterior one-third of the inter-ventricular septum usually arises from the right coronary artery (RCA) or the left circumflex artery (LCX). PDA arising from the left anterior descending artery (LAD) is an extremely rare anomaly. Here we report a rare type of left dominant circulation in which a large LAD is continuing as PDA after winding round the apex in the presence of a diminutive RCA. Such a large LAD continuing as PDA is referred as "hyperdominant" or "superdominant". A 32-year-old male chronic smoker presented with acute onset retrosternal pain of 4 h duration with profuse sweating in primary health center with electrocardiography (ECG) changes in inferior leads and was thrombolysed with intravenous streptokinase 15 lacs IU over one hour and was referred to our center for further management and coronary intervention. Coronary angiogram revealed PDA as a continuation of the LAD beyond the crux and a non-dominant right coronary as well as LCX. The LAD had plaque in mid-LAD course. Intravascular ultrasound study (IVUS) showed insignificant plaque in mid-LAD (30%). Hence, we decided to keep him on medical therapy only.

Congenital Absence of the Left Circumflex Artery With Super-Dominant Right Coronary Artery: Extremely Rare Coronary Anomaly.

Among the congenital anomalies of the coronary arteries, absent left circumflex artery (LCX) defect is extremely rare. Only a few cases have been reported in the literature. We report a case of a 48-year-old female who presented with a 4-month history of exertional chest pain with positive stress (treadmill) test. Conventional coronary angiogram showed a normal left anterior descending, absent LCX and a super-dominant right coronary artery (RCA) with prominent branches. Aortography also failed to show a separate ostium for the left circumflex artery. Multi-detector computed tomographic coronary angiography was performed to confirm the diagnosis of congenital absence of the LCX. It is a benign incidental finding, however some patients present with angina-like symptoms often resulting in detection of this rare anatomy on coronary angiography. Precise morphological and functional evaluation of the anomalous coronary artery is important for selecting the best treatment modality and better prognosis.

A rare cause of anuria in a case of pre-B acute lymphoblastic leukaemia.

Renal failure in cases of acute lymphoblastic leukaemia during induction is mainly because of sepsis and tumour lysis syndrome. This 18-year-old man had sudden onset anuria with increase in creatine. At this time, patient did not have any overt signs or laboratory features suggestive of sepsis. Imaging studies documented bilateral hydronephrosis. Ureteroscopy was done, and it showed presence of soft tissue mass obstructing the ureter. On the the left side, it was noted in its middle part and on the right, at the ureteropelvic junction. The mass on the left side was removed under ureteroscopic guidance and was sent for histopathology examination. It was confirmed to be fungal ball on histopathology examination. Though rare, even in immunocompromised patients, bilateral fungal ball should be considered in differential diagnosis in cases of acute leukaemia with sudden onset anuria. We share our experience in managing this case for which there are no clear guidelines.

Paraquat Poisoning: A Case Report.

Paraquat is commonly used herbicide by farmers in North West Rajasthan. Despite its easy availability, poisoning of its not common. Fatal dose of paraquat is so small that >10 ml poison can damage lungs permanently. Diagnosis is often difficult without proper history, absence of specific clinical feature and lack of diagnostic test. Inhalation exposures represent one of the most important routes of poisoning. We are reporting a case of inhaled paraquat poisoning with complication of irreversible acute kidney, liver and lung injury.