Rimegepant for the treatment of migraine.

Migraine is a common form of primary headache, affecting up to 1 in every 6 Americans. The pathophysiology is an intricate interplay of genetic factors and environmental influence and is still being elucidated in ongoing studies. The trigeminovascular system is now known to have a significant role in the initiation of migraines, including the release of pain mediators such as CGRP and substance P. Traditional treatment of migraine is usually divided into acute and preventive treatment. Acute therapy includes non-specific therapy, such as NSAIDs and other analgesics, which may provide relief in mild to moderate migraines. 5-HT1 agonists may provide relief in severe migraine, but are not universally effective and carry a significant side-effect profile with frequent redosing requirement. Prophylactic therapy may reduce the occurrence of acute migraine attacks in selected patients, but does not completely eliminate it. More recently, CGRP antagonism has been studied and shown to be effective in both abortion and prevention of migraine. Novel medications, targeting CGRP, divide into CGRP antibodies and receptor antagonists (gepants). Rimegepant, a second-generation gepant, has shown efficacy in several clinical trials in treating acute migraine. Ongoing trials are also evaluating its role in migraine prophylaxis, and results are promising. It is also generally safer for use than existing options, does not appear to increase the chance of developing chronic migraines, and carries a very tolerable side effects profile. It is a part of a growing arsenal in migraine treatment, and may present the silver bullet for treatment of this disease.

Automated nystagmus detection: Accuracy of slow-phase and quick-phase algorithms to determine the presence of nystagmus.

PURPOSE: To verify the accuracy of automated nystagmus detection algorithms. METHOD: Video-oculography (VOG) plots were analyzed from consecutive patients with dizziness presenting to a neurology clinic. Data were recorded for 30 s in upright position with fixation block. For automated nystagmus detection, slow-phase algorithm parameters included mean and median slow-phase velocity (SPV), and slow-phase duration ratio. Quick-phase algorithm parameters included saccadic difference and saccadic ratio. For verification, two independent blinded assessors reviewed VOG traces and videos and coded presence or absence of nystagmus. Assessor consensus was used as reference standard. Accuracy of slow-phase and quick-phase algorithm parameters were compared, and ROC analysis was performed. RESULTS: Among 524 analyzed VOG traces, 99 were verified as nystagmus present and 425 were verified as nystagmus absent. Prevalence of nystagmus in the sample population was 18.9%. In ROC analysis, areas under the curve of individual algorithm parameters were 0.791-0.896. With optimal thresholds for determining presence or absence of nystagmus, algorithm sensitivity (70.7-87.9%), specificity (71.8-84.0%), and negative predictive value (91.7-96.4%) were ideal, but positive predictive value (38.8-53.4%) was not ideal. Combining algorithm parameters using logistic regression models mildly improved detection accuracy. CONCLUSION: Both slow-phase and fast-phase algorithms were accurate for detecting nystagmus. Due to low positive predictive value, the utility of independent automated nystagmus detection systems is limited in clinical settings with low prevalence of nystagmus. Combining parameters using logistic regression models appears to improve detection accuracy, indicating that machine learning may potentially optimize the accuracy of future automated nystagmus detection systems.

Opicapone, a Novel Catechol-O-methyl Transferase Inhibitor, for Treatment of Parkinson's Disease "Off" Episodes.

Parkinson's Disease (PD) is a common neurodegenerative disorder and the leading cause of disability. It causes significant morbidity and disability through a plethora of symptoms, including movement disorders, sleep disturbances, and cognitive and psychiatric symptoms. The traditional pathogenesis theory of PD involves the loss of dopaminergic neurons in the substantia nigra (SN). Classically, treatment is pursued with an assortment of medications that are directed at overcoming this deficiency with levodopa being central to most treatment plans. Patients taking levodopa tend to experience "off episodes" with decreasing medication levels, causing large fluctuations in their symptoms. These off episodes are disturbing and a source of morbidity for these patients. Opicapone is a novel, peripherally acting Catechol-O-methyl transferase (COMT) inhibitor that is used as adjunctive therapy to carbidopa/levodopa for treatment and prevention of "off episodes." It has been approved for use as an adjunct to levodopa since 2016 in Europe and has recently (April 2020) gained FDA approval for use in the USA. By inhibiting COMT, opicapone slows levodopa metabolism and increases its availability. Several clinical studies demonstrated significant improvement in treatment efficacy and reduction in duration of "off episodes." The main side effect demonstrated was dyskinesia, mostly with the 100mg dose, which is higher than the approved, effective dose of 50mg. Post-marketing surveillance and analysis are required to further elucidate its safety profile and contribute to patient selection. This paper reviews the seminal and latest evidence in the treatment of PD "off episodes" with the novel drug Opicapone, including efficacy, safety, and clinical indications.

Suvorexant in the Treatment of Difficulty Falling and Staying Asleep (Insomnia).

Purpose of Review: Insomnia affects more than 10% of the population and causes significant discomfort and disability. Suvorexant is an orexin receptor antagonist that specifically targets the wake-sleep cycle. This review summarizes recent and seminal evidence in the biological and physiological evidence of insomnia, the mechanism of action of suvorexant in treating insomnia, and clinical evidence regarding its use. Recent Findings: There is no single clear diagnosis for insomnia, and thus prevalence is not entirely clear, but it is estimated to affect 10%-30% of the adult population. Comorbidities include obesity, diabetes, and various psychiatric conditions, and insomnia likely has a contributing role in these conditions. Insomnia, by definition, impacts sleep quality and also wakefulness, including academic success and work efficiency. Insomnia is likely related to genetic susceptibility and a triggering event, leading to hyper-arousal states and functional brain disturbances. This leads to hyperactivity of the hypothalamic-pituitary-adrenal axis, over-secretion of corticotropin-releasing factor, and aberrancy in neurotransmitter release. Though several pharmacological options exist for the treatment of insomnia, there is equivocal data regarding their efficacy or limits to their use due to side effects and contraindications. Suvorexant is a novel dual orexin receptor antagonist, which is shown to improve sleep by reducing arousals. Unlike classical therapeutics, suvorexant does not alter the sleep profile; it prolongs the time spent in each sleep state. Though it may cause some somnolence, it is milder than reported with other drugs. Summary: Multiple clinical studies support the use of suvorexant in insomnia. In primary insomnia, suvorexant is effective (over placebo), as measured by polysomnography and reported by patients, in both attaining and maintaining sleep. Similar, albeit to a smaller degree, results were found in secondary insomnia. Suvorexant carries two significant advantages over existing therapies; it has a much better safety profile in approved doses, and it preserves natural sleep architecture, thus promoting more restful sleep and recovery. Unfortunately, data exists mostly for suvorexant versus placebo, and head-to-head trials with common hypnotics are needed to assess the true efficacy of suvorexant over the alternatives. And while tolerance is less likely to develop, close monitoring of post-marketing data is required to evaluate for long term adverse events and efficacy.

Opicapone for the Treatment of Parkinson's Disease "Off" Episodes: Pharmacology and Clinical Considerations.

Parkinson's disease (PD) is a common neurodegenerative disorder. It is also the fastest-growing neurodegenerative disorder and has more than doubled between 1990 and 2016. Parkinson's disease causes significant morbidity and disability from motor dysfunction, sleep disturbances, and cognitive and psychiatric symptoms. This paper reviews recent evidence in the treatment of PD "off" episodes with the novel drug opicapone, including its efficacy, safety, and clinical indications. Opicapone is a novel, peripherally acting catechol-O-methyl transferase (COMT) inhibitor used as adjunctive therapy to carbidopa/levodopa for treatment and prevention of "off" episodes. It has been approved for use as an adjunct to levodopa since 2016 in Europe and has recently (April 2020) gained FDA approval for use in the USA. By inhibiting COMT, opicapone slows levodopa metabolism and increases its availability. Several clinical studies demonstrated significant improvement in treatment efficacy and reduction in the duration of "off" episodes The main side effect demonstrated was dyskinesia, mostly with the 100 mg dose, which is higher than the approved, effective dose of 50 mg.

Subjective visual vertical imprecision during lateral head tilt in patients with chronic dizziness.

Most prior studies of the subjective visual vertical (SVV) focus on inaccuracy of subjects' SVV responses with the head in an upright position. Here we investigated SVV imprecision during lateral head tilt in patients with chronic dizziness compared to healthy controls. Forty-five dizzy patients and 45 healthy controls underwent SVV testing wearing virtual reality (VR) goggles, sitting upright (0°) and during head tilt in the roll plane (± 30°). Ten trials were completed in each of three static head positions. The SVV inaccuracy and SVV imprecision were analyzed and compared between groups, along with systematic errors during head tilt, i.e., A-effect and E-effect (E-effect is a typical SVV response during head tilts of ± 30°). The SVV imprecision was found to be affected by head position (upright/right head tilt/left head tilt, p < 0.001) and underlying dizziness (dizzy patients/healthy controls, p = 0.005). The SVV imprecision during left head tilt was greater in dizzy patients compared to healthy controls (p = 0.04). With right head tilt, there was a trend towards greater SVV imprecision in dizzy patients (p = 0.08). Dizzy patients were more likely to have bilateral (6.7%) or unilateral (22.2%) A-effect during lateral head tilt than healthy controls (bilateral (0%) or unilateral (6.7%) A-effect, p < 0.01). Greater SVV imprecision in chronically dizzy patients during head tilts may be attributable to increased noise of vestibular sensory afferents or disturbances of multisensory integration. Our findings suggest that SVV imprecision may be a useful clinical parameter of underlying dizziness measurable with bedside SVV testing in VR.

Test-retest reliability of subjective visual vertical measurements with lateral head tilt in virtual reality goggles.

OBJECTIVE: The objective is to investigate the test-retest reliability of subjective visual vertical (SVV) in the upright position and with lateral head tilts through a computerized SVV measuring system using virtual reality (VR) goggles. MATERIALS AND METHODS: Thirty healthy controls underwent SVV test in upright position, with the head tilted to the right 30°, and with the head tilted to the left 30°. Subjects wore SVV VR goggles, which contained a gyroscope for monitoring the angle of head tilt. Each subject completed 10 adjustments in each head position. The mean value of SVV deviations and SVV imprecision (the intra-individual variability of SVV deviations from the 10 adjustments) were recorded and compared across different head positions. The participants then repeated the same SVV protocol at least 1 week later. The test-retest reliability of SVV deviation and SVV imprecision were analyzed. RESULTS: The SVV deviation (mean ± standard deviation) was 0.22° ± 1.56° in upright position, -9.64° ± 5.91° in right head tilt, and 7.20° ± 6.36° in left head tilt. The test-retest reliability of SVV deviation was excellent in upright position (intra-class correlation coefficient [ICC] = 0.77, P < 0.001), right head tilt (ICC = 0.83, P < 0.001) and left head tilt (ICC = 0.84, P < 0.001). The SVV values from the 10 adjustments made during right and left head tilts were less precise than when measured at upright (P < 0.001). The test-retest reliability of SVV imprecision was poor at upright (ICC = 0.21, P = 0.26) but fair-to-good in right head tilt (ICC = 0.72, P < 0.001) and left head tilt (ICC = 0.44, P = 0.04). CONCLUSION: The test-retest reliability of SVV deviation during lateral head tilts via VR goggles is excellent, which supports further research into the diagnostic value of head-tilt SVV in various vestibular disorders. In addition, the degree of SVV imprecision during head tilt has fair-to-good test-retest reliability, which suggests SVV imprecision may have clinical applicability.

Monomethyl Fumarate (MMF, Bafiertam) for the Treatment of Relapsing Forms of Multiple Sclerosis (MS).

Multiple sclerosis (MS) is a prevalent neurologic autoimmune disorder affecting two million people worldwide. Symptoms include gait abnormalities, perception and sensory losses, cranial nerve pathologies, pain, cognitive dysfunction, and emotional aberrancies. Traditional therapy includes corticosteroids for the suppression of relapses and injectable interferons. Recently, several modern therapies-including antibody therapy and oral agents-were approved as disease-modifying agents. Monomethyl fumarate (MMF, Bafiertam) is a recent addition to the arsenal available in the fight against MS and appears to be well-tolerated, safe, and effective. In this paper, we review the evidence available regarding the use of monomethyl fumarate (Bafiertam) in the treatment of relapsing-remitting MS.

Istradefylline to Treat Patients with Parkinson's Disease Experiencing "Off" Episodes: A Comprehensive Review.

Parkinson's disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and disability. PD is caused by a loss of dopaminergic, cholinergic, serotonergic, and noradrenergic neurons in the central nervous system (CNS), and peripherally; the syndromic parkinsonism symptoms of movement disorder, gait disorder, rigidity and tremor are mostly driven by the loss of these neurons in the basal ganglia. Unfortunately, a significant proportion of patients taking levodopa, the standard of care treatment for PD, will begin to experience a decrease in effectiveness at varying times. These periods, referred to as "off episodes", are characterized by increased symptoms and have a detrimental effect on quality of life and disability. Istradefylline, a novel adenosine A2A receptor antagonist, is indicated as a treatment addition to levodopa/carbidopa in patients experiencing "off episodes". It promotes dopaminergic activity by antagonizing adenosine in the basal ganglia. This review will discuss istradefylline as a treatment for PD patients with off episodes.

Cannabis and cannabidiol (CBD) for the treatment of fibromyalgia.

Fibromyalgia is a complex disease process that is as prevalent as it is poorly understood. Research into the pathophysiology is ongoing, and findings will likely assist in identifying new therapeutic options to augment those in existence today that are still insufficient for the care of a large population of patients. Recent evidence describes the use of cannabinoids in the treatment of fibromyalgia. This study provides a systematic, thorough review of the evidence alongside a review of the seminal data regarding the pathophysiology, diagnosis, and current treatment options. Fibromyalgia is characterized by widespread chronic pain, fatigue, and depressive episodes without an organic diagnosis, which may be prevalent in up to 10% of the population and carries a significant cost in healthcare utilization, morbidity, a reduced quality of life, and productivity. It is frequently associated with psychiatric comorbidities. The diagnosis is clinical and usually prolonged, and diagnostic criteria continue to evolve. Some therapies have been previously described, including neuropathic medications, milnacipran, and antidepressants. Despite some level of efficacy, only physical exercise has strong evidence to support it. Cannabis has been used historically to treat different pain conditions since ancient times. Recent advances allowed for the isolation of the active substances in cannabis and the production of cannabinoid products that are nearly devoid of psychoactive influence and provide pain relief and alleviation of other symptoms. Many of these, as well as cannabis itself, are approved for use in chronic pain conditions. Evidence supporting cannabis in chronic pain conditions is plentiful; however, in fibromyalgia, they are mostly limited. Only a handful of randomized trials exists, and their objectivity has been questioned. However, many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. Evidence supporting the use of cannabis in chronic pain and specifically in fibromyalgia is being gathered as the use of cannabis increases with current global trends. While the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia. Cannabis use is not without risks, including psychiatric, cognitive, and developmental as well as the risks of addiction. As such, clinical judgment is warranted to weigh these risks and prescribe to patients who are more likely to benefit from this treatment. Further research is required to define appropriate patient selection and treatment regimens.

Lasmiditan for the Treatment of Migraines With or Without Aura in Adults.

Migraines are a common form of primary headache, affecting women more than men (17.4% and 5.7% of US population, respectively, a total of 12%) that carry significant morbidity and disability, as well as a hefty healthcare price tag. They are most prevalent in women of reproductive ages and are estimated to be the 6th disease in order of causing global burden. They are estimated to cause 45.1 million years lived with disability, or 2.9% of global years lost to disability. Migraine treatment divides into acute, abortive treatment for relief of an ongoing migraine attack, and prophylactic therapy to reduce the occurrence of migraines, specifically for patients suffering from chronic and frequent episodic migraines. Traditional abortive treatment usually begins with NSAID and non-specific analgesics that are effective in curbing mild to moderate attacks. 5HT1-agonists, such as triptans, are often used for second-line and for severe attacks. Triptans are generally better tolerated in the longterm than NSAIDs and other analgesics, though they carry a significant side-effect profile and are contraindicated in large parts of the population. Prophylactic therapy is usually reserved for patients with frequent recurrence owing to medication side effects and overall poor adherence to the medication schedule. Importantly, medication overuse may actually lead to the development of chronic migraines from previously episodic attacks. Recent research has shed more light on the pathophysiology of migraine and the role of CGRP in the trigeminovascular system. Recent pharmacological advances were made in developing more specific drugs based on this knowledge, including CGRP neutralizing antibodies, receptor antagonists, and the development of ditans. These novel drugs are highly specific to peripheral and central 5-HT1F receptors and effective in the treatment of acute migraine attacks. Binding these receptors reduces the production of CGRP and Glutamate, two important ligands in the nociceptive stimulus involved with the generation and propagation of migraines. Several large clinical studies showed Lasmiditan to be effective in the treatment of acute migraine attacks. Importantly, due to its receptor specificity, it lacks the vasoconstriction that is associated with triptans and is thus safer is larger parts of the population, specifically in patients with cardiac and vascular disease. Though more research is required, specifically with aftermarket surveillance to elucidate rare potential side effects, Lasmiditan is a targeted anti-migraine drug that is both safe and effective, and carries an overall superior therapeutic profile to its predecessors. It joins the array of medications that target CGRP signaling, such as gepants and CGRP-antibodies, to establish a new line of care for this common disabling condition.

The bucket test differentiates patients with MRI confirmed brainstem/cerebellar lesions from patients having migraine and dizziness alone.

BACKGROUND: Amongst the most challenging diagnostic dilemmas managing patients with vestibular symptoms (i.e. vertigo, nausea, imbalance) is differentiating dangerous central vestibular disorders from benign causes. Migraine has long been recognized as one of the most common causes of vestibular symptoms, but the clinical hallmarks of vestibular migraine are notoriously inconsistent and thus the diagnosis is difficult to confirm. Here we conducted a prospective study investigating the sensitivity and specificity of combining standard vestibular and neurological examinations to determine how well central vestibular disorders (CVD) were distinguishable from vestibular migraine (VM). METHOD: Twenty-seven symptomatic patients diagnosed with CVD and 36 symptomatic patients with VM underwent brain imaging and clinical assessments including; 1) SVV bucket test, 2) ABCD2, 3) headache/vertigo history, 4) presence of focal neurological signs, 5) nystagmus, and 6) clinical head impulse testing. RESULTS: Mean absolute SVV deviations measured by bucket testing in CVD and VM were 4.8 ± 4.1° and 0.7 ± 1.0°, respectively. The abnormal rate of SVV deviations (> 2.3°) in CVD was significantly higher than VM (p < 0.001). Using the bucket test alone to differentiate CVD from VM, sensitivity was 74.1%, specificity 91.7%, positive likelihood ratio (LR+) 8.9, and negative likelihood ratio (LR-) 0.3. However, when we combined the SVV results with the clinical exam assessing gaze stability (nystagmus) with an abnormal focal neurological exam, the sensitivity (92.6%) and specificity (88.9%) were optimized (LR+ (8.3), LR- (0.08)). CONCLUSION: The SVV bucket test is a useful clinical test to distinguish CVD from VM, particularly when interpreted along with the results of a focal neurological exam and clinical exam for nystagmus.

No handedness effect on spatial orientation or ocular counter-roll during lateral head tilts.

Although vestibular inputs are bilaterally represented within the cerebral hemispheres, the higher level vestibular functions exhibit hemispheric asymmetries. Previous studies have suggested that such asymmetries are associated with handedness. Here, we studied the impact of handedness (i.e., hemispheric lateralization) on spatial orientation using a subjective visual vertical (SVV) task. We tested 22 right-handed and 22 left-handed subjects in upright position, during prolonged lateral head tilts of 20° (~15 min), and after the head returned to upright position. The corresponding changes in torsional eye position were measured simultaneously using video-oculography. During lateral head tilts, both right- and left-handers had initial SVV biases in the opposite direction of the head tilt (right-handers: left tilt 3.0 ± 1.3°, right tilt -4.7 ± 1.5°; left-handers: left tilt 3.4 ± 1.1°, right tilt -4.1 ± 1.0°). The SVV subsequently drifted in the direction of the head tilt, and there was an aftereffect in the same direction when the head was brought back upright. The ocular torsion initially changed in the opposite direction of the head tilt (right-handers: left tilt 3.8 ± 0.4°, right tilt -3.8 ± 0.4°; left-handers: left tilt 4.2 ± 0.5°, right tilt -4.5 ± 0.5°), and there were also drift and aftereffect in the same direction as the head tilt. The changes in upright perception and ocular torsion did not differ between right- and left-handers. These findings show no functional laterality, neither in the higher level neural mechanisms that maintain spatial orientation, nor in the lower level mechanisms that generate the ocular torsion response during lateral head tilt.

Placebos in the era of open-label trials: An update for clinicians.

Placebos have been used extensively by vast numbers of physicians, in a majority of clinical trials. Placebo effects involve behavioural, psychological and genetic factors and have been subject to ethical controversies stemming from the use of deception in treating patients. The patient-physician encounter, endogenous pharmacological pathways, personality traits and genetic diversity have all been reported to be key players in placebo responses. In the last decade, a new methodological paradigm of placebo research has emerged, using open-label placebos to investigate their effects which showed promising results for various common medical conditions. In this review, we will summarize the current body of evidence on placebos in clinical practice, with a view to open-label placebo trials in particular. It is our view that future larger-scale randomized blinded open placebo trials will benefit physicians and improve patient outcomes.

Errors of Upright Perception in Patients With Vestibular Migraine.

Patients with vestibular migraine (VM) often report dizziness with changes in the head or body position. Such symptoms raise the possibility of dysfunction in neural mechanisms underlying spatial orientation in these patients. Here we addressed this issue by investigating the effect of static head tilts on errors of upright perception in a group of 27 VM patients in comparison with a group of 27 healthy controls. Perception of upright was measured in a dark room using a subjective visual vertical (SVV) paradigm at three head tilt positions (upright, ±20°). VM patients were also surveyed about the quality of their dizziness and spatial symptoms during daily activities. In the upright head position, SVV errors were within the normal range for VM patients and healthy controls (within 2° from true vertical). During the static head tilts of 20° to the right, VM patients showed larger SVV errors consistent with overestimation of the tilt magnitude (i.e., as if they felt further tilted toward the right side) (VM: -3.21° ± 0.93 vs. Control: 0.52° ± 0.70; p = 0.002). During the head tilt to the left, SVV errors in VM patients did not differ significantly from controls (VM: 0.77° ± 1.05 vs. Control: -0.04° ± 0.68; p = 0.52). There was no significant difference in SVV precision between the VM patients and healthy controls at any head tilt position. Consistent with the direction of the SVV errors in VM patients, they largely reported spatial symptoms toward the right side. These findings suggest an abnormal sensory integration for spatial orientation in vestibular migraine, related to daily dizziness in these patients.

Exploring the Role of Temporoparietal Cortex in Upright Perception and the Link With Torsional Eye Position.

Upright perception is a key aspect of orientation constancy, as we maintain a stable perception of the world despite continuous movements of our eyes, head, and body. Torsional position of the eyes can impact perception of upright by changing orientation of the images on the retina relative to gravity. Here, we investigated the role of temporoparietal cortex in upright perception with respect to ocular torsion, by means of the inhibitory effect of continuous theta burst transcranial magnetic stimulation (TMS). We used a subjective visual vertical (SVV) paradigm to track changes in upright perception, and a custom video method to track ocular torsion simultaneously. Twelve participants were tested during a lateral head tilt of 20° to the left. TMS at the posterior aspect of the supramarginal gyrus (SMGp) resulted in an average SVV shift in the opposite direction of the head tilt compared to a sham stimulation (1.8°). Ocular torsion following TMS at SMGp showed no significant change compared to the sham stimulation (-0.1°). Thus, changes in upright perception at SMGp were dissociated from ocular torsion. This finding suggests that perception of upright at SMGp is primarily related to sensory processing for spatial orientation, as opposed to subcortical regions that have direct influence on ocular torsion.

Sudden Hearing Loss with Vertigo Portends Greater Stroke Risk Than Sudden Hearing Loss or Vertigo Alone.

BACKGROUND: Because it is unknown whether sudden hearing loss (SHL) in acute vertigo is a "benign" sign (reflecting ear disease) or a "dangerous" sign (reflecting stroke), we sought to compare long-term stroke risk among patients with (1) "SHL with vertigo," (2) "SHL alone," and (3) "vertigo alone" using a large national health-care database. METHODS: Patients with first-incident SHL (International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] 388.2) or vertigo (ICD-9-CM 386.x, 780.4) were identified from the National Health Insurance Research Database of Taiwan (2002-2009). We defined SHL with vertigo as a vertigo-related diagnosis ±30 days from the index SHL event. SHL without a temporally proximate vertigo diagnosis was considered SHL alone. The vertigo-alone group had no SHL diagnosis. All the patients were followed up until stroke, death, withdrawal from the database, or current end of the database (December 31, 2012) for a minimum period of 3 years. The hazards of stroke were compared across groups. RESULTS: We studied 218,656 patients (678 SHL with vertigo, 1998 with SHL alone, and 215,980 with vertigo alone). Stroke rates at study end were 5.5% (SHL with vertigo), 3.0% (SHL alone), and 3.9% (vertigo alone). Stroke hazards were higher in SHL with vertigo than in SHL alone (hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.28-2.91) and in vertigo alone (HR, 1.63; 95% CI, 1.18-2.25). Defining a narrower window between SHL and vertigo (±3 days) increased the hazards. CONCLUSIONS: The combination of SHL plus vertigo in close temporal proximity is associated with increased subsequent stroke risk over SHL alone and vertigo alone. This suggests that SHL in patients with vertigo is not necessarily a benign peripheral vestibular sign.

Perception of Upright: Multisensory Convergence and the Role of Temporo-Parietal Cortex.

We inherently maintain a stable perception of the world despite frequent changes in the head, eye, and body positions. Such "orientation constancy" is a prerequisite for coherent spatial perception and sensorimotor planning. As a multimodal sensory reference, perception of upright represents neural processes that subserve orientation constancy through integration of sensory information encoding the eye, head, and body positions. Although perception of upright is distinct from perception of body orientation, they share similar neural substrates within the cerebral cortical networks involved in perception of spatial orientation. These cortical networks, mainly within the temporo-parietal junction, are crucial for multisensory processing and integration that generate sensory reference frames for coherent perception of self-position and extrapersonal space transformations. In this review, we focus on these neural mechanisms and discuss (i) neurobehavioral aspects of orientation constancy, (ii) sensory models that address the neurophysiology underlying perception of upright, and (iii) the current evidence for the role of cerebral cortex in perception of upright and orientation constancy, including findings from the neurological disorders that affect cortical function.

The video ocular counter-roll (vOCR): a clinical test to detect loss of otolith-ocular function.

CONCLUSION: vOCR can detect loss of otolith-ocular function without specifying the side of vestibular loss. Since vOCR is measured with a simple head tilt maneuver, it can be potentially used as a bedside clinical test in combination with video head impulse test. OBJECTIVE: Video-oculography (VOG) goggles are being integrated into the bedside assessment of patients with vestibular disorders. Lacking, however, is a method to evaluate otolith function. This study validated a VOG test for loss of otolith function. METHODS: VOG was used to measure ocular counter-roll (vOCR) in 12 healthy controls, 14 patients with unilateral vestibular loss (UVL), and six patients with bilateral vestibular loss (BVL) with a static lateral head tilt of 30°. The results were compared with vestibular evoked myogenic potentials (VEMP), a widely-used laboratory test of otolith function. RESULTS: The average vOCR for healthy controls (4.6°) was significantly different from UVL (2.7°) and BVL (1.6°) patients (p < 0.0001). The vOCR and VEMP measurements were correlated across subjects, especially the click and tap oVEMPs (click oVEMP R = 0.45, tap oVEMP R = 0.51; p < 0.0003). The receiver operator characteristic (ROC) analysis showed that vOCR and VEMPs detected loss of otolith function equally well. The best threshold for vOCR to detect vestibular loss was at 3°. The vOCR values from the side of vestibular loss and the healthy side were not different in UVL patients (2.53° vs 2.8°; p = 0.59).