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In this cross-sectional study, we investigate the presence of Severe Acute Respiratory Syndrome Coronavirus 2 Ribonucleic Acid (SARS-CoV-2 RNA) in the tears of hospitalized COVID-19 patients. After laboratory confirmation of SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) analysis, tear samples from both eyes of each patient were collected using conjunctival swab for RT-PCR. Detailed demographic profile, systemic and ocular symptoms, comorbidities, clinical, ancillary, and ocular manifestations were evaluated. Of the 83 patients enrolled in the study, 7 (8.43%) had SARS-CoV-2 RNA detected in the tear samples. Neutrophils’ count, C-reactive protein, and D-dimer were higher in patients with SARS-CoV-2 detected in tears than in patients without virus in ocular surface samples. One patient with SARS-CoV-2 in tears showed mild ocular eyelid edema, hyperemia, and chemosis. No relevant ocular manifestations were detected in the other patients. Although the levels of viral RNA on ocular surface samples were low for most patients (5/7), with positivity only for gene N and CT higher than 30, two patients were positive for all viral targets tested ( N, E, and RpRd), with viral load near 1 × 105 ePFU/mL, indicating that the ocular transmission of SARS-CoV-2 is a possibility that needs to be considered, especially in the hospital environment. Further studies need to be conducted to demonstrate whether infective viral particles could be isolated from tears.

Aim To use an animal model of migraine to test whether migraine headache might arise from a brainstem-trigeminal nucleus pathway. Methods We measured evoked and spontaneous activity of second-order trigeminovascular neurons in rats to test whether the activity of these neurons increased following the induction of cortical spreading depression or the imposition of light flash – two potential migraine triggers, or headache provokers. We then tested whether drugs that could activate, or inactivate, neurons of the nucleus raphe magnus or the periaqueductal gray matter, would affect any such increases selectively for the dura mater. Results Injection of sodium glutamate (a neuronal excitant) into these two nuclei selectively inhibited the responses of trigeminovascular second-order neurons to dura mater, but not to facial skin, stimulation. Injection of lignocaine (a local anaesthetic) into these nuclei selectively potentiated the responses of these neurons to dura, but not to facial skin, stimulation. Furthermore, injections into either nucleus of glutamate inhibited the increase in the ongoing discharge rate of these neurons produced by cortical spreading depression and light flash. Conclusions These results provide indirect evidence that trigeminovascular nociception may be tightly controlled by these two nuclei, whereas cutaneous trigeminal sensation may be less so. These nuclei may be relays of one possible brainstem-trigeminal pathway that could mediate migraine headache. Modification of neuronal activity in these two nuclei produced by migraine (headache) triggers may lie behind the pain of a migraine attack, at least in some cases.

Background Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory central nervous system disorder, typically presenting with subacute symptoms referable to brainstem and cerebellar pathology. This is the first report of CLIPPERS presenting with a painful trigeminal neuropathy. Case report We report an unusual case of CLIPPERS presenting with facial pain and sensory symptoms, in the absence of other brainstem or cerebellar signs. Perivascular enhancement of peri-pontine structures on neuroimaging, lymphocytic infiltrate on histopathology and rapid clinical and radiological responsiveness to glucocorticosteroids were key to diagnosis. Extensive investigations excluded various differential aetiologies. Conclusion The pathogenesis of CLIPPERS is poorly understood, and the diagnostic criteria are yet to be validated. In this case, facial pain was not associated with other brainstem or cerebellar signs, broadening current understanding of how CLIPPERS may present. This has clinical implications in guiding future investigations for patients presenting with painful trigeminal neuropathy.

Aim We carried out experiments in cats to determine the thalamo-cortical projection sites of trigeminovascular sensory neurons. Methods 1) We stimulated the middle meningeal artery (MMA) with C-fibre intensity electrical shocks and made field potential recordings over the somatosensory cortical surface. 2) We then recorded neurons in the ventroposteromedial (VPM) nucleus of the thalamus in search of neurons which could be activated from the skin, MMA and superior sagittal sinus. 3) Finally, we attempted to antidromically activate the neurons found in stage 2 by stimulating the responsive cortical areas revealed in stage 1. Results VPM neurons received trigeminovascular input, input from the V1 facial skin and could also be activated by electrical stimulation of the somatosensory cortex. VPM neurons activated from the cortex responded with short and invariant latencies (6.7 ± 7.7 msec mean and SD). They could follow high rates of stimulation and sometimes showed collision with orthodromic action potentials. Conclusions We conclude that somatosensory (SI) cortical stimulation excites trigeminovascular VPM neurons antidromically. In consequence, these VPM neurons project to the somatosensory cortex. These findings may help to explain the ability of migraineurs with headache in the trigeminal distribution to localise their pain to a particular region in this distribution.

Available treatment for chronic tic disorders (CTD) focuses on the reduction of tics but often does not directly address the psychosocial impairment associated with tics. There is empirical support for a new psychosocial intervention to reduce tics and their related impairment, but this treatment has not yet been applied to adults with CTD. With this in mind, the authors report on the case of “Jim,” a 22-year-old male with significantly impairing tic symptoms. Following 10 sessions of weekly cognitive-behaviorally oriented therapy combining habit reversal training, distress tolerance, cognitive restructuring, and problem solving, Jim exhibited marked improvement in tic severity as illustrated by a decrease in his score on the total tic score of the Yale Global Tic Severity Scale from 16 at baseline to 8 at posttreatment. Therapeutic gains were maintained at 4-month follow-up. This case study provides preliminary support for the use of a psychosocial intervention for addressing coping with CTD in young adults.

Objectives: It can be difficult to distinguish vestibular migraine (VM) from Menière’s disease (MD) in its early stages. Using vestibular-evoked myogenic potentials (VEMPs), we sought to identify test parameters that would help discriminate between these two vestibular disorders. Methods: We first recorded ocular and cervical VEMPs (oVEMP/cVEMP) to air-conducted clicks and bone-conducted vibration in 30 control participants, 30 participants with clinically definite VM and 30 participants with clinically probable VM. Results were compared with a group of 60 MD patients from a previous study. oVEMPs and cVEMPs were then recorded at octave frequencies of 250 Hz to 2000 Hz in 20 controls and 20 participants each with clinically definite VM and MD. Inter-aural amplitude asymmetry ratios and amplitude frequency ratios were compared between groups. Results: For click, tendon-hammer-tap and minishaker-tap VEMPs, there were no significant differences in reflex amplitudes or symmetry between controls, definite VM and probable VM. Compared with MD patients, participants with VM had significantly fewer reflex abnormalities for click-cVEMP, click-oVEMPs and minitap-cVEMPs. The ratio of cVEMP amplitude generated by tone bursts at a frequency of 0.5 kHz to that generated by 1 kHz was significantly lower for MD affected ears than for VM or controls ears. cVEMP asymmetry ratios for 0.5 kHz tone bursts were significantly higher for MD than VM. Conclusions: The 0.5/1 kHz frequency ratio, 0.5 kHz asymmetry ratio and caloric test combined, separated MD from VM with a sensitivity of 90.0% and specificity of 70.0%.

Aim: To use an animal model to test whether migraine pain arises peripherally or centrally. Methods: We monitored the spontaneous and evoked activity of second-order trigeminovascular neurons in rats to test whether traffic increased following a potential migraine trigger (cortical spreading depression, CSD) and by what mechanism any such change was mediated. Results: Neurons ( n = 33) responded to stimulation of the dura mater and facial skin with A-δ latencies. They were spontaneously active with a discharge rate of 6.1 ± 6.4 discharges s−1. Injection of 10 µg lignocaine into the trigeminal ganglion produced a fully reversible reduction of the spontaneous discharge rate of neurons. Neuronal discharge rate returned to normal by 90 min. Lignocaine reduced the evoked responses of neurons to dural stimulation to 37% and to facial skin stimulation to 53% of control. Induction of CSD by cortical injection of KCl increased the spontaneous discharge rate of neurons from 2.9 to 16.3 discharges s−1 at 20 min post CSD. Injection of 10 µg lignocaine into the trigeminal ganglion at this time failed to arrest or reverse this increase. Injection of lignocaine prior to the initiation of CSD failed to prevent the subsequent development of CSD-induced increases in discharge rates. Conclusions: These results suggest that there is a continuous baseline traffic in primary trigeminovascular fibres and that CSD does not act to increase this traffic by a peripheral action alone − rather, it must produce some of its effect by a mechanism intrinsic to the central nervous system. Thus the pain of migraine may not always be the result of peripheral sensory stimulation, but may also arise by a central mechanism.

We tested the idea that migraine triggers cause cortical activation, which disinhibits craniovascular sensation through the nucleus raphe magnus (NRM) and thus produces the headache of migraine. Stimulation of the dura mater and facial skin activated neurons in the NRM and the trigeminal nucleus. Stimulation of the NRM caused suppression of responses of trigeminal neurons to electrical and mechanical stimulation of the dura mater, but not of the skin. This suppression was antagonized by the iontophoretic application of the 5-HT1B/1D receptor antagonist GR127935 to trigeminal neurons. Migraine trigger factors were simulated by cortical spreading depression (CSD) and light flash. Activity of neurons in the NRM was inhibited by these stimuli. Multiple waves of CSD antagonized the inhibitory effect of NRM stimulation on responses of trigeminal neurons to dural mechanical stimulation but not to skin mechanical stimulation. The cortico-NRM-trigeminal neuraxis might provide a target for a more universally effective migraine prophylactic treatment.

Intravenous infusions of serotonin (5-hydroxtryptamine creatinine sulphate, 5HT, 50-300 μg/kg/min) in cats reversibly inhibited the responses of cervical spinal cord neurons to electrical stimulation of the superior sagittal sinus. Inhibition developed over 20-30 min and resolved over the same time course, suggesting a dependence on accumulation of 5HT in the central nervous system. Inhibition was suppressed by prior intravenous injection of the 5HT antagonists methysergide (1 mg/kg) and methiothepin (1 mg/ kg). Infusions of 5HT (50 μg/kg/min) caused a rise in whole blood levels of 5HT by a factor of 1.5 of control values. 5HT levels in platelet-free plasma rose by a factor of 50. Levels of 5HT and 5 hydroxyindole acetic acid released into the cerebrospinal fluid rose significantly. The results suggest that earlier clinical observations that 5HT infusions can ameliorate the pain of migraine may not have been due to cranial vasoconstriction alone, but could have involved a central action of 5HT.

Primary angiitis of the central nervous system is a rare idiopathic vasculitis affecting small- and medium-sized vessels, isolated to the brain, leptomeninges and spinal cord. We report a case of biopsy-proven primary angiitis of the central nervous system, displaying some atypical features. This case highlights several key diagnostic and management issues of the disorder as well as its potential heterogeneity.

In recent years, much progress has been made in pharmacotherapy for pediatric obsessive-compulsive disorder (OCD) and chronic tic disorders (CTDs). What were previously considered relatively intractable conditions now have an array of efficacious medicinal (and psychosocial) interventions available at clinicians' disposal, including selective serotonin reuptake inhibitors, atypical antipsychotics, and alpha-2 agonists. The purpose of this review is to discuss the evidence base for pharmacotherapy with pediatric OCD and CTDs with regard to efficacy, tolerability, and safety, and to put this evidence in the context of clinical management in integrated behavioral healthcare. While there is no single panacea for these disorders, there are a variety of medications that provide considerable relief for children with these disabling conditions.