Gravity-Dependent Modulation of Downbeat Nystagmus and Subjective Visual Vertical in the Roll Plane.

Downbeat nystagmus (DBN) is the most common form of acquired central vestibular nystagmus. Gravity perception in patients with DBN has previously been investigated by means of subjective visual straight ahead (SVA) and subjective visual vertical (SVV) in the pitch and roll planes only during whole-body tilts. To our knowledge, the effect of head tilt in the roll plane on the SVV and on DBN has not yet been systematically studied in patients. In this study, we investigated static and dynamic graviceptive function in the roll-plane in patients with DBN (patients) and healthy-controls (controls) by assessment of the Subjective Visual Vertical (SVV) and the modulation of slow-phase-velocity (SPV) of DBN. SPV of DBN and SVV were tested at different head-on trunk-tilt positions in the roll-plane (0°,30° clockwise (cw) and 30° counterclockwise (ccw)) in 26 patients suffering from DBN and 13 controls. In patients, SPV of DBN did not show significant modulations at different head-tilt angles in the roll-plane. SVV ratings did not differ significantly between DBN patients vs. controls, however patients with DBN exhibited a higher variability in mean SVV estimates than controls. Our results show that the DBN does not exhibit any modulation in the roll-plane, in contrast to the pitch-plane. Furthermore, patients with DBN show a higher uncertainty in the perception of verticality in the roll-plane in form of a higher variability of responses.

Signatures of migraine aura in high-density-EEG.

OBJECTIVE: Cortical spreading depolarization is highly conserved among the species. It is easily detectable in direct cortical surface recordings and has been recorded in the cortex of humans with severe neurological disease. It is considered the pathophysiological correlate of human migraine aura, but direct electrophysiological evidence is still missing. As signatures of cortical spreading depolarization have been recognized in scalp EEG, we investigated typical spontaneous migraine aura, using full band high-density EEG (HD-EEG). METHODS: In this prospective study, patients with migraine with aura were investigated during spontaneous migraine aura and interictally. Time compressed HD-EEG were analyzed for the presence of cortical spreading depolarization characterized by (a) slow potential changes below 0.05 Hz, (b) suppression of faster activity from 0.5 Hz - 45 Hz (c) spreading of these changes to neighboring regions during the aura phase. Further, topographical changes in alpha-power spectral density (8-14 Hz) during aura were analyzed. RESULTS: In total, 26 HD-EEGs were recorded in patients with migraine with aura, thereof 10 HD-EEGs during aura. Eight HD-EEGs were recorded in the same subject. During aura, no slow potentials were recorded, but alpha-power was significantly decreased in parieto-occipito-temporal location on the hemisphere contralateral to visual aura, lasting into the headache phase. Interictal alpha-power in patients with migraine with aura did not differ significantly from age- and sex-matched healthy controls. CONCLUSIONS: Unequivocal signatures of spreading depolarization were not recorded with EEG on the intact scalp in migraine. The decrease in alpha-power contralateral to predominant visual symptoms is consistent with focal depression of spontaneous brain activity as a consequence of cortical spreading depolarization but is not specific thereof. SIGNIFICANCE: Cortical spreading depolarization is relevant in migraine, other paroxysmal neurological disorders and neurointensive care.

Cognitive Performance After Facial Botulinum Toxin Treatment in a Cohort of Neurologic Patients: An Exploratory Study.

OBJECTIVE: To investigate higher cognitive functions after mimicry changes after facial botulinum toxin (BTX) injections, we tested verbal and nonverbal reasoning in patients with blepharospasm or hemifacial spasm before and after their long-term botulinum toxin treatment. DESIGN: Explorative, nonrandomized, clinical trial. SETTING: Patients receiving ambulatory care and control participants from the general community. PARTICIPANTS: Volunteer sample (N=84) of patients (n=21) with blepharospasm or hemifacial spasm who received facial BTX injections. Control participants included patients (n=30) with cervical dystonia who received cervical BTX injections and individuals without neurological disorders (n=33). INTERVENTIONS: The 2 groups receiving injections were tested before and 3 weeks after their treatment. The group without neurological disorders received no injections. MAIN OUTCOME MEASURES: Verbal and nonverbal reasoning scores. RESULTS: The key unexpected finding was that patients who received facial BTX injections perform significantly worse in nonverbal reasoning tasks, when compared with those who did not receive injections (P=.022). There was no significant difference in the baseline reasoning scores and at follow-up for verbal reasoning between the 3 groups. There was no correlation between toxin dose and reasoning scores (verbal: P=.132; nonverbal: P=.294). CONCLUSIONS: Because of potential confounders, the results do not yet allow any conclusion on causality. Further research is needed to confirm our findings.

Hyposmia Is Associated with Reduced Cognitive Function in COVID-19: First Preliminary Results.

BACKGROUND: Hyposmia is frequently reported as an initial symptom in coronavirus disease 2019 (COVID-19). OBJECTIVE: As hyposmia accompanies cognitive impairment in several neurological disorders, we aimed to study whether hyposmia represents a clinical biomarker for both neurological involvement and cognitive impairment in mild CO-VID-19. We aimed to study whether olfactory dysfunction (OD) represents a clinical biomarker for both neurological involvement and cognitive impairment in mild COVID-19. METHODS: Formal olfactory testing using the Sniffin'Sticks® Screening test, neuropsychological assessment using the Montreal Cognitive Assessment (MoCA), and detailed neurological examination were performed in 7 COVID-19 patients with mild disease course and no history of olfactory or cognitive impairment, and 7 controls matched for age, sex, and education. Controls were initially admitted to a dedicated COVID-19 screening ward but tested negative by real-time PCR. RESULTS: The number of correctly identified odors was significantly lower in COVID-19 than in controls (6 ± 3, vs. 10 ± 1 p = 0.028, r = 0.58). Total MoCA score was significantly lower in COVID-19 patients than in controls (20 ± 5 vs. 26 ± 3, p = 0.042, r = 0.54). Cognitive performance indicated by MoCA was associated with number of correctly identified odors in COVID-19 patients and controls (COVID-19: p = 0.018, 95% CI = 9-19; controls: p = 0.18, r = 0.63, 95% CI = 13-18.5 r = 0.64). DISCUSSION/CONCLUSION: OD is associated with cognitive impairment in controls and mild COVID-19. OD may represent a potentially useful clinical biomarker for subtle and even subclinical neurological involvement in severe acute respiratory distress syndrome coronavirus-2 infection.

Assessment of Static Graviceptive Perception in the Roll-Plane using the Subjective Visual Vertical Paradigm.

Vestibular disorders are among the most common syndromes in medicine. In recent years, new vestibular diagnostic systems have been introduced that allow the examination of all semicircular canals in the clinical setting. Assessment methods of the otolithic system, which is responsible for the perception of linear acceleration and perception of gravity, are far less in clinical use. There are several experimental approaches for measuring the perception of gravity. The most frequently used method is the determination of the subjective visual vertical. This is usually measured with the head in an upright position. We present here an assessment method for testing otolith function in the roll plane. The subjective visual vertical is measured in the head upright position as well as with head inclination of ± 15° and ± 30° in the roll plane. This extended functional paradigm is an easy-to-perform clinical test of otolith function and ensures increased information content for the detection of impaired graviceptive perception.

A novel nonsense autosomal dominant mutation in the GLRA1 gene causing hyperekplexia.

We present a family with two members affected by hyperekplexia and two unaffected members. All exons in the glycine receptor alpha 1 subunit gene (GLRA1) were sequenced in all four family members. Our index patient harbored a novel nonsense mutation (p.Trp314*; rs867618642) in the transmembrane domain three of the GLRA1 and a novel missense variant in the NH2-terminal part (p.Val67Met; rs142888296). After development of tolerance for the effective treatment with clobazam a drug holiday led to a sustained restoration of the treatment response.

7-Tesla MRI demonstrates absence of structural lesions in patients with vestibular paroxysmia.

Vestibular parxoysmia (VP) is a rare vestibular disorder. A neurovascular cross-compression (NVCC) between the vestibulochochlear nerve and an artery seems to be responsible for short attacks of vertigo in this entity. An NVCC can be seen in up to every fourth subject. The significance of these findings is not clear, as not all subjects suffer from symptoms. The aim of the present study was to assess possible structural lesions of the vestibulocochlear nerve by means of high field magnetic resonance imaging (MRI), and whether high field MRI may help to differentiate symptomatic from asymptomatic subjects. 7 Tesla MRI was performed in six patients with VP and confirmed NVCC seen on 1.5 and 3.0 MRI. No structural abnormalities were detected in any of the patients in 7 Tesla MRI. These findings imply that high field MRI does not help to differentiate between symptomatic and asymptomatic NVCC and that the symptoms of VP are not caused by structural nerve lesions. This supports the hypothesis that the nystagmus associated with VP has to be conceived pathophysiologically as an excitatory vestibular phenomenon, being not related to vestibular hypofunction. 7 Tesla MRI outperforms conventional MRI in image resolution and may be useful in vestibular disorders.

Neuromagnetic cortical activation during initiation of optokinetic nystagmus: an MEG pilot study.

PURPOSE: To investigate the spatiotemporal evolution of cortical activation during the initiation of optokinetic nystagmus using magnetoencephalography. BACKGROUND: Previous imaging studies of optokinetic nystagmus in humans using positron emission tomography and functional magnetic resonance imaging discovered activation of a large set of cortical and subcortical structures during steady-state optokinetic stimulation, but did not provide information on the temporal dynamics of the initial response. Imaging studies have shown that cortical areas responsible for vision in occipital and temporo-occipital areas are involved, i.e. cortical areas control optokinetic stimulation in humans. Magnetoencephalography provides measures that reflect neural ensemble activity in the millisecond time scale, allowing the identification of early cortical components of visuomotor integration. DESIGN/METHODS: We studied neuromagnetic cortical responses during the initiation of optokinetic nystagmus in 6 right-handed healthy subjects. Neuromagnetic activity was recorded with a whole-head magnetoencephalograph, consisting of 143 planar gradiometers. RESULTS: The mean (±SD) latency between stimulus onset and initiation of optokinetic nystagmus was 177.7 ± 59 ms. Initiation of optokinetic nystagmus evoked an early component in the primary visual cortex starting at 40-90 ms prior to the onset of the slow phase of nystagmus. Almost simultaneously an overlapping second component occurred bilaterally in the temporo-occipital area (visual motion areas), pronounced in the right hemisphere, starting at 10-60 ms prior to the slow-phase onset. Both components showed long-duration activity lasting for up to 100 ms after slow-phase onset. CONCLUSIONS: Our findings suggest that the initiation of optokinetic nystagmus induces early cortical activation in the occipital cortex and almost simultaneously bilaterally in the temporo-occipital cortex. These cortical regions might represent essential areas for the monitoring of retinal slip.

Facial pain, scotomas and hemihypaesthesia as presenting symptoms of type A aortic dissection in a patient with migraine with aura.

We report the case of a 31-year-old man with a history of migraine with aura who was admitted to our emergency department because of a sudden onset of severe bilateral facial pain radiating bilaterally into the medial cervical region after defecation. The pain was accompanied by scotomas in the right visual field and hypaesthesia in both upper limbs. Imaging of the aorta and supra-aortic vessels revealed a type A aortic dissection. Subsequently, the patient received an aortic valve replacement and an aortic tube graft. After the surgery he experienced recurring visual disturbances with a sudden onset mimicking his migraine aura. Due to a new onset of atrial fibrillation, he was put on oral anticoagulants. At follow-up after 10 months he still reported episodic and mostly isolated visual auras with a gradual onset.

Clopidogrel-induced platelet inhibition cannot be detected by the platelet function analyzer-100 system in stroke patients.

The administration of an adenosine diphosphate (ADP) receptor antagonist, such as clopidogrel, is recommended for recurrent stroke patients under aspirin treatment. However, up to 25% of vascular patients have an inadequate response to clopidogrel treatment, which could be associated with increased reinfarction rates. This study investigated whether the platelet function analyzer (PFA-100) system represents an appropriate tool for monitoring clopidogrel's antiplatelet effects in stroke patients. Sixteen stroke patients on clopidogrel therapy (75 mg/day) were included in a prospective analyst-blinded, cross-sectional study. Platelet function was assayed by collagen/epinephrine (CEPI)- and collagen/ADP (CADP)-induced closure times (CTs) using the PFA-100 system. von Willebrand factor antigen (vWF-Ag) levels were measured by enzyme immunoassay. CEPI-CT and CADP-CT values averaged 160 +/- 15 seconds and 102 +/- 10 seconds, respectively, and were in the normal range. vWF-Ag concentrations averaged 153 +/- 17% and correlated inversely with CTs (r = .71; P < .002 for CEPI-CT, r = .54; P < .04 for CADP-CT). Our data indicate that the current PFA-100 cartridges are not sufficiently sensitive to detect clopidogrel-induced platelet inhibition in stroke patients.