Prevention of benign paroxysmal positional vertigo with vitamin D supplementation: A randomized trial.

OBJECTIVE: To assess the effect of vitamin D and calcium supplementation in preventing recurrences of benign paroxysmal positional vertigo (BPPV). METHODS: We performed an investigator-initiated, blinded-outcome assessor, parallel, multicenter, randomized controlled trial in 8 hospitals between December 2013 and May 2017. Patients with confirmed BPPV were randomly assigned to the intervention (n = 518) or the observation (n = 532) group after successful treatment with canalith repositioning maneuvers. The primary outcome was the annual recurrence rate (ARR). Patients in the intervention group had taken vitamin D 400 IU and 500 mg of calcium carbonate twice a day for 1 year when serum vitamin D level was lower than 20 ng/mL. Patients in the observation group were assigned to follow-ups without further vitamin D evaluation or supplementation. RESULTS: The intervention group showed a reduction in the ARR (0.83 [95% confidence interval (CI), 0.74-0.92] vs 1.10 [95% CI, 1.00-1.19] recurrences per 1 person-year) with an incidence rate ratio of 0.76 (95% CI, 0.66-0.87, p < 0.001) and an absolute rate ratio of -0.27 (-0.40 to -0.14) from intention-to-treat analysis. The number needed to treat was 3.70 (95% CI, 2.50-7.14). The proportion of patients with recurrence was also lower in the intervention than in the observation group (37.8 vs 46.7%, p = 0.005). CONCLUSIONS: Supplementation of vitamin D and calcium may be considered in patients with frequent attacks of BPPV, especially when serum vitamin D is subnormal. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with BPPV, vitamin D and calcium supplementation reduces recurrences of BPPV.

Acquired Ocular Motor Nerve Palsy in Neurology Clinics: A Prospective Multicenter Study.

BACKGROUND AND PURPOSE: This study aimed to determine the patterns and etiologies of acquired ocular motor nerve palsy (OMNP) diagnosed in neurology clinics. We also investigated the clinical features that may predict the causes other than microvascular ischemia in isolated OMNP. METHODS: We performed a prospective multicenter study that had recruited 298 patients with acquired OMNP from the neurology clinics of referral-based 9 university hospitals in Korea. We finally selected 235 patients with isolated OMNP and divided them into older (age ≥50 years, n=188) and younger (age <50 years, n=47) groups. We investigated the underlying etiologies of acquired OMNP. We also estimated the frequency of microvascular ischemia and other causes in isolated OMNP, and sought to determine the clinical features that can predict the causes other than microvascular ischemia. RESULTS: Abducens nerve palsy was the most common (40%) of the acquired OMNPs, followed by oculomotor nerve palsy (27%), trochlear nerve palsy (23%), and multiple OMNPs (10%). The etiologies included microvascular ischemia (47%), inflammatory (21%), stroke (5%), trauma (5%), neoplasm (3%), and others (2%), with the cause not being determined in 13% of the patients. Microvascular ischemia was the most common cause (83%) in patients aged ≥50 years with isolated OMNP, followed by inflammation (6%), stroke (6%), neoplasm (3%), and aneurysm (1%). Microvascular ischemia was more common in the older than the younger group (83% vs. 49%, p<0.001). The intensity of headache was the only risk factor for causes other than microvascular ischemia in isolated OMNP. CONCLUSIONS: Vascular and inflammatory disorders are the most common causes of acquired OMNP diagnosed in neurology clinics. Microvascular ischemia was the predominant cause of isolated OMNP. Severe headache indicates causes other than microvascular ischemia in isolated OMNP.

Development of the clinical assessment scale in autoimmune encephalitis.

OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92). INTERPRETATION: CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352-358.

Switch to Semont maneuver is no better than repetition of Epley maneuver in treating refractory BPPV.

The objectives of this study is to compare the efficacy between repetition of Epley maneuver and switch to alternate Semont maneuver in treating posterior canal benign paroxysmal positional vertigo (PC-BPPV) that does not respond to the initial Epley maneuver. In the nationwide, seven dizziness clinics of Korea, 506 consecutive patients (303 women, age range 22-87, mean age ± SD = 64 ± 12, median = 61) with idiopathic PC-BPPV were initially treated with a single Epley maneuver. Of those, 144 (28.5%) patients, who did not respond to the therapy, were randomized to the repetition of Epley maneuver (n = 70) or switch to Semont maneuver (n = 74). The therapeutic efficacy was determined within 1 h by a blinded examiner after the trial of each second maneuver. The efficacy did not differ between the repetition of Epley maneuver and switch to Semont maneuver groups (38.6 vs. 27.0%, p = 0.14, Chi-square test). However, the patients with a long duration (p < 0.001, linear regression) and latency (p = 0.01) of the positional nystagmus during Dix-Hallpike maneuver showed a higher rate of the initial and second treatment failures. Either Epley or Semont maneuver may be applied as a second treatment to the patients with PC-BPPV refractory to the initial Epley maneuver. This study provides Class I evidence that repeated Epley and switch to Semont maneuver shows a similar efficacy in treating PC-BPPV that does not respond to the initial Epley maneuver. CLINICAL TRIAL REGISTRATION: NCT01822002.

Intermittent Theta Slowings in Contralateral Side of Weakness after Sleep Deprivation on Spot EEG in Sporadic Hemiplegic Migraine.

Hemiplegic migraine (HM) is an uncommon type of migraine which is classified into sporadic and familial subtype. The noticed electroencephalogram (EEG) findings during HM attack are diffuse slowing contralateral to the weakened limb, but are usually normal in asymptomatic states. A 52-year-old woman who suffered from headache accompanying right arm weakness and aphasic symptoms admitted to our hospital. She underwent total five times of EEG including 2 times before admission. Only the last EEG exam after 24 hours of sleep deprivation (SD) showed intermittent slowing and higher amplitude of positive occipital sharp transients (POSTs) on the left parieto-occipital area. Here, we report a case with HM who revealed abnormal EEG findings after SD, which was not observed in the routine EEG study without SD.

Persistent otolith dysfunction even after successful repositioning in benign paroxysmal positional vertigo.

To evaluate utricular and saccular function during the acute and resolved phases of BPPV, ocular and cervical vestibular evoked myogenic potentials (VEMPs) were studied in 112 patients with BPPV and 50 normal controls in a referral-based University Hospital. Ocular (oVEMPs) and cervical VEMPs (cVEMPs) were induced using air-conducted sound (1000Hz tone burst, 100dB normal hearing level) at the time of initial diagnosis and 2 months after successful repositioning in patients with BPPV, and the results were compared with those of the controls. Abnormalities of cVEMPs and oVEMPs in patients with BPPV were prevalent and significantly higher compare to the healthy control group (p<0.01 in each VEMP by chi-square test). In the patient group, difference between the proportions of abnormal responses of cVEMP and oVEMP was not significant in both affected (p=0.37, chi-squared test) and non-affected (p=1.00) ears. The abnormalities were more likely reduced or absent responses rather than delayed ones; reduced or absent responses are 17.6% in cVEMPs (p=0.04, chi-square) and 21.6% in oVEMPs (p<0.01). The non-affected ear in the BPPV group also showed significantly higher abnormalities of cVEMP and oVEMP when compared to the control group. The follow-up VEMPs after repositioning maneuvers were not significantly different compared to the initial values from both stimulated affected and non-affected ears. Although most patients had unilateral BPPV, bilateral otolithic dysfunction was often shown by persistently reduced or absent cervical and ocular VEMPs, suggesting that BPPV may be caused by significant bilateral damage to the otolith organs.

Clinical classification and neuro-vestibular evaluation in chronic dizziness.

OBJECTIVE: This study attempts to clarify the clinical characteristics of chronic dizziness and its relationships with specific vestibular, oculomotor, autonomic and psychiatric dysfunctions. METHODS: 73 Patients with idiopathic chronic dizziness were recruited and classified based on history taking and clinical examination into the following four clinical subgroups; vestibular migraine (VM), dysautonomia, psychogenic, and unspecified groups. They were also evaluated using oculomotor, otolithic and autonomic function tests, and psychologic investigation. RESULTS: Patients in the VM group showed a high proportion of abnormality on smooth pursuit and otolithic function testing compared to the other groups. The dysautonomia group revealed significant abnormalities in sympathetic and cardiovagal autonomic function, while the psychogenic group had a high frequency of abnormality in sympathetic autonomic testing and in Beck's anxiety inventory scale. The unspecified group showed abnormalities on saccade, smooth pursuit and autonomic function testing. CONCLUSIONS: Clinical classification of patients with chronic dizziness was relevant and they showed a correlation with disease-specific abnormal results in oculomotor, otolithic, autonomic function and psychology testing. SIGNIFICANCE: Appropriate diagnostic investigation based on precise clinical diagnosis of chronic dizziness reduces the need for extensive laboratory testing, neuroimaging, and other low-yield tests.

Topology of brainstem lesions associated with subjective visual vertical tilt.

OBJECTIVE: We aimed to determine the topology of anatomical pathways for verticality perception in the brainstem. METHODS: We measured the subjective visual vertical (SVV) in 82 patients with acute unilateral infarction of the brainstem alone. The topology of the brainstem lesions responsible for pathologic SVV tilt were determined using MRI-based voxel-wise lesion-behavior mapping, from which probabilistic lesion maps were constructed. RESULTS: Fifty percent of patients (41/82) with acute unilateral brainstem infarcts had abnormal SVV tilt, of which 76% (31/41) had ipsiversive tilt and 24% (10/41) had contraversive tilt. Patients with contraversive SVV tilt exhibited overlapping lesions of the rostral medial vestibular nucleus, medial longitudinal fasciculus, rostral interstitial medial longitudinal fasciculus, and interstitial nucleus of Cajal. In contrast, patients with ipsiversive SVV tilt and oculomotor disturbances exhibited lesions of the medial and inferior vestibular nuclei in the caudal medulla, while those with isolated vertical perceptual changes had injury to the medial side of the medial lemniscus. CONCLUSIONS: Our findings provide evidence of a pathway transmitting ipsiversive otolithic signals that bypass the oculomotor system at the medial side of the medial lemniscus, called the ipsilateral vestibulothalamic tract.

Homonymous Visual Field Loss without Structural Lesion on Magnetic Resonance Imaging: Documented with Positron Emission Tomography and Diffusion Tensor Imaging.

The authors describe a 35-year-old man suffering from homonymous hemianopia after head trauma 4 years before but with negative magnetic resonance imaging (MRI) findings. Brain fluorine-18 fluorodeoxyglucose positron emission tomography (18FDG-PET) showed hypometabolism at the unilateral occipital lobe and crossed cerebellar hemisphere, and diffusion tensor imaging (DTI) revealed that the ipsilateral optic radiations were completely interrupted. The crossed cerebellar diaschisis (CCD) observed in the chronic stage of brain damage was caused by cerebellar suppression of the cerebral blood flow due to an involvement of the corticopontocerebellar tract. PET and DTI provide objective means for determining the relationship of functional deficits to head trauma, even in cases where the injury was sustained years prior to the evaluation.

Geotropic central paroxysmal positional nystagmus in a patient with human immunodeficiency virus encephalopathy.

Central vestibular lesions may cause paroxysmal positional nystagmus (PPN) or paroxysmal positional vertigo as a result of lesions involving the brainstem dorsolateral to the fourth ventricle or the cerebellar nodulus/uvular region. PPN usually presents as persistent downbeating nystagmus during head hanging or as apogeotropic horizontal nystagmus during head turning in the supine position. Geotropic PPN during head turning in the supine position has not been previously reported. We report such a case in a patient with HIV encephalopathy.

Cervical and ocular vestibular-evoked myogenic potentials in vestibular neuritis: comparison between air- and bone-conducted stimulation.

To clarify the changes of cervical (cVEMP) and ocular (oVEMP) vestibular evoked myogenic potentials induced by air-conducted sound (ACS) and bone-conducted vibration (BCV) in patients with vestibular neuritis (VN), patients with VN (n = 30) and normal controls (n = 45) underwent recording of cVEMP and oVEMP in response to ACS (1,000 Hz, 5 ms, tone bursts) and BCV (500 Hz, short tone burst). Patients with VN showed a high proportion of oVEMP abnormalities in response to both ACS (80.0 %) and BCV at the forehead (Fz, 73.3 %) or the mastoid (76.7 %). In contrast, cVEMPs were mostly normal with both ACS and BCV in the patients. The dissociations in the abnormalities of cVEMP and oVEMP induced by ACS and BCV at the mastoids and at the forehead in patients with VN suggest that oVEMP reflects functions of the superior vestibular nerve and most likely the utricular function. The results of our study suggest that oVEMP induced by either ACS or BCV appears to depend on integrity of the superior vestibular nerve, possibly due to the utricular afferents travelling in it. In contrast, cVEMP elicited by either ACS or BCV may reflect function of the saccular afferents running in the inferior vestibular nerve.

The MpkB MAP kinase plays a role in post-karyogamy processes as well as in hyphal anastomosis during sexual development in Aspergillus nidulans.

Two genes encoding MAP kinase homologs, designated as mpkB and mpkC, were isolated from Aspergillus nidulans by PCR with degenerate primers. Deletion and over-expression mutants of mpkC showed no detectable phenotypes under any external stress tested. Deletion of mpkB caused pleiotropic phenotypes including a failure in forming cleistothecia under any induction conditions for sexual development, increased Hülle cell production, slow hyphal growth and aberrant conidiophore morphology. Over-expression of mpkB led to increased cleistothecium production. While the transcripts of mpkB and mpkC were constitutively synthesized through the entire life cycle, their size and amount differed with developmental stages. An outcross test using fluorescent protein reporters showed that the mpkB deletion mutant could not form heterokaryons with wild type. Protoplast fusion experiments showed that the fusant of the mpkB mutant with wild type could undergo normal sexual development. However, heterokaryotic mycelia that were produced from a fusant between two mpkB deletion mutants could not form cleistothecia, although they did appear to form diploid nuclei. These results suggest that the MpkB MAP kinase is required for some post-karyogamy process as well as at the hyphal anastomosis stage to accomplish sexual development successfully.

Identification of maturation and protein synthesis related proteins from porcine oocytes during in vitro maturation.

BACKGROUND: In vitro maturation (IVM) of mammalian oocytes is divided into the GV (germinal vesicle stage), MI (metaphase I stage) and MII (metaphase II stage) stages, and only fully mature oocytes have acquired the ability to be fertilized and initiate zygotic development. These observations have been mostly based on morphological evaluations, but the molecular events governing these processes are not fully understood.The aim of the present study was to better understand the processes involved in the molecular regulation of IVM using 2-DE analysis followed by mass spectrometry to identify proteins that are differentially expressed during oocyte IVM. RESULT: A total of 16 up-regulated and 12 down-regulated proteins were identified. To investigate the IVM process, we specifically focused on the proteins that were up-regulated during the MII stage when compared with the GV stage, which included PRDX 2, GST, SPSY, myomegalin, PED4D, PRKAB 1, and DTNA. These up-regulated proteins were functionally involved in redox regulation and the cAMP-dependent pathway, which are essential for the intracellular signaling involved in oocyte maturation. Interestingly, the PDE4D and its partner, myomegalin, during the MII stage was consistently confirmed up-regulation by western blot analyses. CONCLUSION: These results could be used to better understand some aspects of the molecular mechanisms underlying porcine oocyte maturation. This study identified some regulatory proteins that may have important roles in the molecular events involved in porcine oocyte maturation, particularly with respect to the regulation of oocyte meiotic resumption, MII arrest and oocyte activation. In addition, this study may have beneficial applications not only to basic science with respect to the improvement of oocyte culture conditions but also to mammalian reproductive biotechnology with potential implications.

Role of plasminogen activator inhibitor-2 (PAI-2) in keratinocyte differentiation.

BACKGROUND: Plasminogen activator inhibitor-2 (PAI-2) is an enzyme inhibitor which is involved in various biological processes including cell differentiation, tissue regrowth and regeneration. Although PAI-2 has been originally isolated as an extracellular inhibitor of urokinase plasminogen activator (uPA), recent studies indicate that PAI-2 has other intracellular effects in keratinocyte, such as the component of cornified envelope. OBJECTIVE: The aim of this study is to investigate the expression and functional role of PAI-2 during the keratinocyte differentiation. METHODS: We transduced keratinocytes with adenovirus harboring the expression cassette for PAI-2, then examined the effect on keratinocytes differentiation. RESULTS: When cultured epidermal keratinocytes were treated with 1.2 mM calcium, PAI-2 expression was increased time-dependently at both mRNA and protein levels. The calcium-induced PAI-2 expression was abolished by treatment with p38 MAPK inhibitor, while overexpression of MKK6 led to the increase of PAI-2 expression. When PAI-2 was overexpressed by adenoviral transduction, the expression of keratinocyte differentiation markers such as involucrin, keratin 10 and loricrin was markedly increased. Concomitantly, overexpression of PAI-2 resulted in the retardation of cell growth, with the increase of Rb and p53. CONCLUSION: These results suggest that PAI-2 has a role for promoting the differentiation of epidermal keratinocytes.

Recurrent Streptococcus Pneumoniae Meningoencephalitis in a Patient With a Transethmoidal eningoencephalocele.

We report a case of recurrent Streptococcus Pneumoniae meningoencephalitis with a transethmoidal meningoencephalocele (TEME) but without cerebrospinal fluid (CSF) leakage.A 35-year-old man was admitted with S. pneumoniae meningitis. He had suffered from four episodes of recurrent pneumococcal meningitis during the previous 4 years. A computed tomography scan of the paranasal sinus showed the TEME protruding through a bony defect of the right frontal base. However, the patient did not have symptoms that could be attributable to CSF leakage, and radioisotope cisternography did not identify a leak. Brain magnetic resonance imaging revealed cortical lesions overlying the TEME, and electroencephalography revealed epileptiform discharges in frontal regions. Appropriate antibiotics therapy without steroids was given to improve his condition.The presented case suggests that even in the absence of clinically demonstrable CSF leakage, an occult skullbase defect and its associated meningoencephalocele should be considered in patients with recurrent bacterial meningitis.