Asymmetric Distributions of Achromatic Bipolar Cells in the Mouse Retina

In the retina, evolutionary changes can be traced in the topography of photoreceptors. The shape of the visual streak depends on the height of the animal and its habitat, namely, woods, prairies, or mountains. Also, the distribution of distinct wavelength-sensitive cones is unique to each animal. For example, UV and green cones reside in the ventral and dorsal regions in the mouse retina, respectively, whereas in the rat retina these cones are homogeneously distributed. In contrast with the abundant investigation on the distribution of photoreceptors and the third-order neurons, the distribution of bipolar cells has not been well understood. We utilized two enhanced green fluorescent protein (EGFP) mouse lines, Lhx4-EGFP (Lhx4) and 6030405A18Rik-EGFP (Rik), to examine the topographic distributions of bipolar cells in the retina. First, we characterized their GFP-expressing cells using type-specific markers. We found that GFP was expressed by type 2, type 3a, and type 6 bipolar cells in the Rik mice and by type 3b, type 4, and type 5 bipolar cells in the Lhx4 mice. All these types are achromatic. Then, we examined the distributions of bipolar cells in the four cardinal directions and three different eccentricities of the retinal tissue. In the Rik mice, GFP-expressing bipolar cells were more highly observed in the nasal region than those in the temporal retina. The number of GFP cells was not different along with the ventral-dorsal axis. In contrast, in the Lhx4 mice, GFP-expressing cells occurred at a higher density in the ventral region than in the dorsal retina. However, no difference was observed along the nasal-temporal axis. Furthermore, we examined which type of bipolar cells contributed to the asymmetric distributions in the Rik mice. We found that type 3a bipolar cells occurred at a higher density in the temporal region, whereas type 6 bipolar cells were denser in the nasal region. The asymmetricity of these bipolar cells shaped the uneven distribution of the GFP cells in the Rik mice. In conclusion, we found that a subset of achromatic bipolar cells is asymmetrically distributed in the mouse retina, suggesting their unique roles in achromatic visual processing.

Late-Onset Ictal Asystole and Falls Related to Severe Coronary Artery Stenosis: A Case Report

Introduction: Ictal asystole (IA) is a rare, underestimated, and life-threatening cause of transient loss of consciousness and fall. Current treatment options for seizures associated with IA usually include cardiac pacemaker implantation. We report, for the first time, a case of IA that is related to coronary stenosis, which was resolved after coronary angioplasty.Case Presentation: A 73-year-old man had a 2-year history of focal seizures with impaired awareness. Three months before our observation, he started to have sudden falls resulting in injury on several occasions. General and neurological examinations, as well as brain MRI, were unremarkable. Interictal electroencephalography (EEG) showed bitemporal spiking. Ictal video-polygraphy revealed a diffuse electrodecrement, followed by a buildup of rhythmic 4–6 Hz sharp activity, which was more evident in the left temporal region. After the seizure onset, the ECG showed sinus bradycardia, followed by sinus arrest that was associated with the patient's fall from the standing position. Afterwards, sinus rhythm returned spontaneously. A diagnosis of IA was made. A comprehensive cardiologic evaluation revealed a sub-occlusive stenosis of the left anterior descending artery. Successful coronary angioplasty resolved IA, levetiracetam was added, and no seizure or fall has occurred in the following 20 months. Moreover, he underwent a 7-day Holter ECG monitoring, and no asystole was depicted.Conclusion: The present case was unique as it shows the potential association between IA and coronary stenosis, also suggesting a possible therapeutic role for coronary angioplasty. It also highlights the importance of carefully investigating epilepsy patients with falls, especially in the elderly, since IA-related falls can be easily misdiagnosed in older age. Thus, if IA is identified, a deeper cardiac evaluation should be considered. As seen in our patient, non-invasive diagnostic examination including routine, prolonged, and exercise ECG, as well as echocardiogram, were readily available and were informative in diagnosing cardiac abnormalities that are amenable to specific treatment.

Cranial Fasciitis in Children: Expanding the Spectrum of USP6-Associated Clonal Transient Neoplasms

Background: Cranial fasciitis (CF) is a benign (myo)fibroblastic proliferation of children. Typical presentation consists of a rapidly growing solitary mass on the temporal or parietal cranium in the first 2 years of age. CF is characterized by a rapid growth followed by a relative slowdown and even growth arrest. The finding of somatic USP6 gene rearrangements demonstrating clonality in CF together with its clinical behavior places it in the category of diseases recently termed “transient neoplasia.” Methods: Histological, immunohistochemical, and molecular findings of 18 patients with CF were retrospectively studied. Results: The tumor typically presented as a painless rapidly enlarging mass in the temporal region. Sixty-six percent of the cases harbored USP6 gene rearrangement. Nine patients were treated with gross total resection (GTR) and 9 with subtotal tumor resection (STR). Two patients treated with GTR had recurrence. Five patients treated with STR had progression-free disease for at least 10 months after surgery and in four patients the tumor regressed spontaneously a median 16 months after surgery. Conclusions: In this largest series to date, we reported the clinicopathological, immunohistochemical, and molecular findings of 18 pediatric cases of CF with emphasis on the clinical growth pattern of these tumors.

Repercussion of cAMP and EPAC in Memory and Signaling

It is well recognized that cyclic adenosine monophosphate (cAMP) signaling within neurons plays a key role in the foundation of long-term memories. Memory storage is the process that demands the movement of signals, neural plasticity, and the molecules which can transfer the signals from the sensory neuron to the dorsal root ganglion (DRG) neurons and later into the temporal region of the brain. The discovery of cAMP in 1958 as the second messenger also had a role in memory formation and other neural aspects. Further, in 1998 the scientists found that cAMP does not just activate protein kinase A (PKA) but also exchange protein directly activated by cAMP (Epac) which has an active role to play in hyperalgesia, memory, and signaling. The cAMP has three targets, hyperpolarization-activated cyclic nucleotide modulated (HCN) channels, protein kinase A (PKA), and exchange protein activated by cAMP (Epac). Different research has exposed that both PKA and HCN channels are significant for long-term memory creation. Epac is a cAMP-dependent guanine nucleotide exchange factor for the small G proteins including Rap1. However, slight information is there about the role of Epac in this process. The effects of cAMP are predominantly imparted by activating protein kinase A (PKA) and the more newly discovered exchange proteins are directly activated by cAMP 1 and 2 (EPAC1 and EPAC2). This review provides an insight regarding the function and role of both of these secondary messengers in memory and nerve signaling.

Secondary Trigeminal Neuralgia: a Case Report and Literature Review of Red Flags

Introduction: Trigeminal neuralgia (TN) is characterized by recurrent paroxysmal brief episodes of electric shock-like pain along the trigeminal nerve distribution. Based on the underlying cause, current classification systems have classified TN into idiopathic, classical, and secondary TN. This manuscript presents a case report of a patient seen in the clinic with features of trigeminal neuralgia secondary to an intracranial lesion. Case description: A 39-year-old female presented to the clinic with a 15-month history of severe, intermittent, short-lasting episodes of pain affecting the left lower teeth, jaw, nose, and temporal region. The patient reported familiar shock-like pain during the physical examination when the skin of the left ala of the nose was lightly touched. The rest of the clinical examination was non-significant. The magnetic resonance imaging of the brain showed an approximately 20 mm wide lesion at the level of the cerebellopontine angle. After subsequent tests, the lesion was diagnosed as meningioma, and the patient was treated with stereotactic radiation therapy. Practical Implications: In up to 10 % of TN cases, the underlying cause can be due to a brain tumor. Although persistent pain, sensory or motor nerve dysfunction, gait disturbances, and other neurological signs may concurrently exist, raising a red flag for intracranial pathology, patients often present with pain alone as the heralding symptom of a brain tumor. Due to this, it is imperative that all patients suspected of having TN undergo an MRI of the brain as part of the diagnostic work-up.

Perceptual uncertainty alternates top-down and bottom-up fronto-temporal network signaling during response inhibition

Response inhibition is a primary executive control function that allows the withholding of inappropriate responses, and requires appropriate perception of the external environment to achieve a behavioral goal. It remains unclear, however, how response inhibition is achieved when goal-relevant information involves perceptual uncertainty. Twenty-six human participants of both sexes performed a go/no-go task where visually presented random-dot motion stimuli involved perceptual uncertainties. The right inferior frontal cortex (rIFC) was involved in response inhibition, and the middle temporal (MT) region showed greater activity when dot motions involved less uncertainty. A neocortical temporal region in the superior temporal sulcus (STS) specifically showed greater activity during response inhibition in more perceptually certain trials. In this STS region, activity was greater when response inhibition was successful than when it failed. Directional effective connectivity analysis revealed that in more coherent trials, the MT and STS regions showed enhanced connectivity to the rIFC, whereas in less coherent trials, the signal direction was reversed. These results suggest that a reversible fronto-temporal functional network guides response inhibition under perceptual uncertainty, and in this network, perceptual information in the MT is converted to control information in the rIFC via STS, enabling achievement of response inhibition.

Distribution of Corneal Geometric Landmarks and Relationship Between Their Distances and Biomechanical Parameters in the Development of Keratoconus

Purpose: To analyze the changes in coordinates and distances among three typical geometric landmarks of the cornea, namely, the thinnest point (TP), maximum curvature (Kmax), and corneal apex (AP) during the development of keratoconus, and explore the potential relationship between these changes and the abnormalities of corneal biomechanics.Methods: Normal eyes (n = 127), clinical keratoconic eyes (CKC, n = 290), and the eyes of forme fruste keratoconus (FFKC, n = 85) were included; among them, the CKC group was classified into four grades based on the Topographic Keratoconus Classification (TKC) provided by Pentacam. A total of 38 Corvis ST output parameters and three distance parameters of three typical landmarks (DKmax-AP, DTP-AP, and DKmax-TP) based on Pentacam were included. The differences of parameters among the abovementioned six groups (Normal, FFKC, and CKC stage I to CKC stage IV) were analyzed. Spearman’s rank correlation test was performed to choose several dynamic corneal response (DCR) parameters that could best reflect the changes of corneal biomechanical characteristics during the progression of the disease, and the Pearson’s or Spearman’s correlation test was conducted to determine the association between the three distances and the selected DCR parameters in each grade. In addition, by flipping the X coordinate of the left eye on the vertical axis to reflect the direction of the right eye, the coordinates of TP and Kmax in different developmental grades were highlighted.Results: From CKC stage II, the three geometric landmark distances commenced to correlate with the corneal DCR parameters (CBI, SPA1, IR, DA Ratio 2, ARTh, MIR, Radius, Pachy, and DA Ratio 1), which could better represent the changes of biomechanical properties from normal cornea to keratoconus. From normal cornea to CKC stage IV, the coordinates of Kmax were gradually tended to the inferior temporal region from dispersion, while TP was always concentrated in the inferior temporal region. Although DKmax-AP, DKmax-TP, and DTP-AP all showed a gradual decreasing trend with the progress of the disease, the first two did not change significantly, and only DTP-AP significantly approached AP in the later stage of disease development. In addition, from the FFKC group, the corresponding values of DKmax-TP in each disease development group were smaller than DKmax-AP.Conclusions: In the later stage of keratoconus, the relationship between the three typical landmark distance parameters and DCR parameters is stronger, and even the weakening of corneal biomechanical properties may be accompanied by the merger of typical landmark positions.

Differing Associations between Optic Nerve Head Strains and Visual Field Loss in Normal- and High-Tension Glaucoma Subjects

Purpose: To study the associations between optic nerve head (ONH) strains under intraocular pressure (IOP) elevation with retinal sensitivity in glaucoma subjects. Design: Clinic based cross-sectional study. Participants: 229 subjects with primary open angle glaucoma (subdivided into 115 high tension glaucoma (HTG) subjects and 114 normal tension glaucoma (NTG) subjects). Methods: For one eye of each subject, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 33 mmHg) achieved through ophthalmodynamometry. A 3-dimensional (3D) strain-mapping algorithm was applied to quantify IOP-induced ONH tissue strain (i.e. deformation) in each ONH. Strains in the pre-lamina tissue (PLT) and the retina, the choroid, the sclera and the lamina cribrosa (LC) were associated (using linear regression) with measures of retinal sensitivity from the 24-2 Humphrey visual field test (Carl Zeiss Meditec, Dublin, CA, USA). This was done globally, then locally according to the regionalization scheme of Garway-Heath et al. Main Outcome Measures: Associations between ONH strains and values of retinal sensitivity from visual field testing. Results: For HTG subjects, we found that (1) there were significant negative linear associations between ONH strains and retinal sensitivity (p<0.001) (on average, a 1% increase in ONH strains corresponded to a decrease in retinal sensitivity of 1.1 dB), (2) high strain regions co-localized with anatomically-mapped regions of high visual field loss, (3) the strongest negative associations were observed in the superior region and in the PLT. In contrast, for NTG subjects, no significant associations between strains and retinal sensitivity were observed except in the supero-temporal region of the LC. Conclusion: We found significant negative associations between IOP-induced ONH strains and retinal sensitivity in a relatively large glaucoma cohort. Specifically, HTG subjects who experienced higher ONH strains were more likely to exhibit lower retinal sensitivities. Interestingly, this trend was in general less pronounced in NTG subjects, which could suggest a distinct pathophysiology between the two glaucoma subtypes.

Superficial temporal artery pseudoaneurysm as cause of refractory headache

Case presentation: A 36-year-old male presented with moderate, progressive headache, in the left temporal region, irradiating to the ipsilateral frontal region, with several months of evolution, refractory to analgesic medication, including opioids. He reported a closed traumatic brain injury (TBI) 5 years before in a motorcycle collision with an automobile, without a helmet. At the physical examination, it was possible to verify a pulsatile mass measuring 1.5 cm in diameter, with fremitus, in the left temporal region. The magnetic resonance imaging scan presented a round lesion, encapsulated, on the course of the superficial temporal artery (STA). The digital subtraction angiography confirmed the diagnosis of STA pseudoaneurysm. A surgical resection of the aneurysm was performed, leading to the complete resolution of the headache. Discussion: The STA pseudoaneurysm is a rare condition, representing less than 1% of aneurysms, usually presenting as a late complication of TBI. The majority of cases are asymptomatic, although focal symptoms and even bleeding may occur. The presentation with a chronic refractory headache is exceptional. Its treatment is indicated for local symptom resolution, aesthetic purposes, and rupture prevention, done by clipping and resection of the pseudoaneurysm. Conclusion: Even though unusual, the awareness of this condition is important for the etiological diagnosis of a persistent temporal headache in a patient with a history of TBI.

The relationship between head shape, head musculature and bite force in caecilians (Amphibia: Gymnophiona)

Caecilians are enigmatic limbless amphibians that, with a few exceptions all have an at least partly burrowing lifestyle. Although it has been suggested that caecilian evolution resulted in sturdy and compact skulls as an adaptation to their head-first burrowing habits, no relationship between skull shape and burrowing performance has been demonstrated to date. However, the unique dual jaw-closing mechanism and the osteological variability of their temporal region suggest a potential relationship between skull shape and feeding mechanics. Here, we explored the relationships between skull shape, head musculature, and in vivo bite forces. Although there is a correlation between bite force and external head shape, no relationship between bite force and skull shape could be detected. Whereas our data suggest that muscles are the principal drivers of variation in bite force, the shape of the skull is constrained by factors other than demands for bite force generation. However, a strong covariation between the cranium and mandible exists. Moreover, both cranium and mandible shape covary with jaw muscle architecture. Caecilians show a gradient between species with a long retroarticular process associated with a large and pennate-fibered m. interhyoideus posterior and species with a short process but long and parallel-fibered jaw adductors. Our results demonstrate the complexity of the relationship between form and function of this jaw system. Further studies that focus on factors such as gape distance or jaw velocity will be needed in order to fully understand the evolution of feeding mechanics in caecilians.