Ocular motor and vestibular dysfunction in central nervous system lymphoma.

BACKGROUND AND PURPOSE: Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma. METHODS: A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed. RESULTS: Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain. CONCLUSIONS: This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.

Bioupgrading of the aqueous phase of pyrolysis oil from lignocellulosic biomass: a platform for renewable chemicals and fuels from the whole fraction of biomass.

Pyrolysis, a thermal decomposition without oxygen, is a promising technology for transportable liquids from whole fractions of lignocellulosic biomass. However, due to the hydrophilic products of pyrolysis, the liquid oils have undesirable physicochemical characteristics, thus requiring an additional upgrading process. Biological upgrading methods could address the drawbacks of pyrolysis by utilizing various hydrophilic compounds as carbon sources under mild conditions with low carbon footprints. Versatile chemicals, such as lipids, ethanol, and organic acids, could be produced through microbial assimilation of anhydrous sugars, organic acids, aldehydes, and phenolics in the hydrophilic fractions. The presence of various toxic compounds and the complex composition of the aqueous phase are the main challenges. In this review, the potential of bioconversion routes for upgrading the aqueous phase of pyrolysis oil is investigated with critical challenges and perspectives.

Chrysanthemum boreale Makino Inhibits Oxidative Stress-Induced Neuronal Damage in Human Neuroblastoma SH-SY5Y Cells by Suppressing MAPK-Regulated Apoptosis.

Oxidative stress has been demonstrated to play a pivotal role in the pathological processes of many neurodegenerative diseases. In the present study, we demonstrated that Chrysanthemum boreale Makino extract (CBME) suppresses oxidative stress-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and elucidated the underlying molecular mechanism. Our observations revealed that CBME effectively protected neuronal cells against H2O2-induced cell death by preventing caspase-3 activation, Bax upregulation, Bcl-2 downregulation, activation of three mitogen-activated protein kinases (MAPKs), cAMP response element-binding protein (CREB) and NF-κB phosphorylation, and iNOS induction. These results provide evidence that CBME has remarkable neuroprotective properties in SH-SY5Y cells against oxidative damage, suggesting that the complementary or even alternative role of CBME in preventing and treating neurodegenerative diseases is worth further studies.

Erratum: Isolated Vestibular Syndrome With "Double-Panda" Sign in CNS Lymphoma.

This corrects the article on p. 111 in vol. 18, PMID: 35021288.

Custom-made artificial eyes using 3D printing for dogs: A preliminary study.

Various incurable eye diseases in companion animals often result in phthisis bulbi and eye removal surgery. Currently, the evisceration method using silicone balls is useful in animals; however, it is not available to those with impaired cornea or severe ocular atrophy. Moreover, ocular implant and prostheses are not widely used because of the diversity in animal size and eye shape, and high manufacturing cost. Here, we produced low-cost and customized artificial eyes, including implant and prosthesis, using computer-aided design and three-dimensional (3D) printing technique. For 3D modeling, the size of the artificial eyes was optimized using B-mode ultrasonography. The design was exported to STL files, and then printed using polycaprolactone (PCL) for prosthesis and mixture of PCL and hydroxyapatite (HA) for ocular implant. The 3D printed artificial eyes could be produced in less than one and half hour. The prosthesis was painted using oil colors and biocompatible resin. Two types of eye removal surgery, including evisceration and enucleation, were performed using two beagle dogs, as a preliminary study. After the surgery, the dogs were clinically evaluated for 6 months and then histopathological evaluation of the implant was done. Ocular implant was biocompatible and host tissue ingrowth was induced after in vivo application. The custom-made prosthesis was cosmetically excellent. Although long-term clinical follow-up might be required, the use of 3D printed-customized artificial eyes may be beneficial for animals that need personalized artificial eye surgery.

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.

Genotype and Phenotype Spectrum of FRMD7-Associated Infantile Nystagmus Syndrome.

Purpose: We investigate the genotype and phenotype spectrum of FRMD7-associated infantile nystagmus syndrome in Korean probands. Methods: A total of 37 patients with infantile nystagmus syndrome were recruited prospectively for genetic analysis. We performed polymerase chain reaction (PCR)-based direct sequencing and haplotype analysis for FRMD7. Detailed ophthalmic examinations and eye movement recordings were compared between FRMD7 and non-FRMD7 groups. Results: In 13 (35%) of 37 patients, five different mutations of FRMD7 were detected: start codon mutation c.1A>G, splice site mutation c.162+6T>C, and three missense mutations (c.575A>C, c.722A>G, and c.875T>C). The latter mutation was identified in seven unrelated patients, and always was accompanied with two single nucleotide polymorphisms of exon 12 (rs6637934, rs5977623). Compared to non-FRMD7 groups, a cup-to-disc ratio was significantly decreased in FRMD7 groups (P < 0.001), and a disc-macula distance to disc diameter ratio markedly increased in the FRMD7 group (P = 0.015). Most patients in the FRMD7 group had at least two types of the nystagmus waveforms, and the most common type was unidirectional jerk nystagmus (75%), such as pure jerk and jerk with extended foveation, followed by pendular (25%), bidirectional jerk (19%), and dual jerk (6%) nystagmus. No significant differences were observed between FRMD7 and non-FRMD7 groups in terms of the nystagmus waveform, presence of periodic alternating nystagmus, and mean foveation time. Conclusions: We identified five FRMD7 mutations in 35% of our infantile nystagmus syndrome cohort, expanding its mutational spectrum. The missense mutation c.875T>C may be a common mutation arisen from the founder effect in Korea. Optic nerve dysplasia associated with FRMD7 mutations suggests that the abnormal development of afferent visual systems may affect neural circuitry within the oculomotor system.

Highly stable gold nanoparticles green-synthesized by upcycling cartilage waste extract from yellow-nose skate (Dipturus chilensis) and evaluation of its cytotoxicity, haemocompatibility and antioxidant activity.

Skate (Dipturus chilensis) cartilage extract was utilized as a green reducing agent for the synthesis of spherical gold nanoparticles with an average size of 16.7 ± 0.2 nm. The gold nanoparticle solution showed a surface plasmon resonance at 543 nm with a wine-red colour. A strong X-ray diffraction pattern and clear lattice structure in high-resolution transmission electron microscopy indicated a face-centred cubic structure of the gold nanoparticles. The gold nanoparticles retained excellent colloidal stability. Gold nanoparticles showed strong antioxidant activity in terms of 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. In vitro cytotoxicity was observed for seven cancer cells assessed by the water-soluble tetrazolium assay. Among the seven cancer cells, the highest cytotoxicity was observed for MDA-MB-231 (human breast adenocarcinoma cell) followed by HeLa (human epithelial cervix adenocarcinoma cell) and lastly by HT-29 (human colorectal adenocarcinoma cell). Furthermore, gold nanoparticles showed excellent haemocompatibility, indicating the possibility of their use as a future nanomedicine. These results strongly suggest that gold nanoparticles green-synthesized by upcycling skate cartilage waste extract will be valuable carriers or vehicles for the delivery of drugs or bioactive molecules, such as anti-cancer agents, for the treatment of cancers.

Chasing dizzy chimera: Diagnosis of combined peripheral and central vestibulopathy.

Diagnosis of combined peripheral and central vestibulopathy remains a challenge since the findings from peripheral vestibular involvements may overshadow those from central vestibular disorders or vice versa. The aim of this study was to enhance detection of these intriguing disorders by characterizing the clinical features and underlying etiologies. We had recruited 55 patients with combined peripheral and central vestibulopathy at the Dizziness Clinic of Seoul National University Bundang Hospital from 2003 to 2013. Peripheral vestibular involvement was determined by decreased caloric responses in either ear, and central vestibulopathy was diagnosed with obvious central vestibular signs or the lesions documented on MRIs to involve the central vestibular structures. Combined peripheral and central vestibulopathy could be classified into four types according to the patterns of vestibular presentation. Infarctions were the most common cause of acute unilateral cases while cerebellopontine angle tumors were mostly found in chronic unilateral ones. Wernicke encephalopathy and degenerative disorders were common in acute and chronic bilateral disorders. Twenty five (45.5%) patients showed only vestibular findings with or without auditory involvements, but association with gaze-evoked nystagmus, impaired smooth pursuit or central types of head shaking nystagmus indicated a central vestibular involvement in most of them (23/25, 92.0%). Given the requirements for urgent treatments and potentially grave prognosis of combined vestibulopathy, central signs should be sought even in patients with clinical or laboratory features of peripheral vestibulopathy. Scrutinized bedside evaluation, however, secured the diagnosis in almost all the patients with combined vestibulopathy.

Paraneoplastic downbeat nystagmus associated with cerebellar hypermetabolism especially in the nodulus.

A 52-year-old man with vertigo and imbalance for two weeks showed spontaneous downbeat (DBN), horizontal gaze-evoked, and positional apogeotropic nystagmus along with severe limb and truncal ataxia. Gadolinium-enhanced brain MRI was normal, but whole body and brain 2-deoxy-2-[F18]fluoro-d-glucose-positron emission tomography revealed hypermetabolism in the right lower lobe of the lung and the cerebellum, especially in the nodulus. The lesion in the lung was confirmed as mixed cell carcinoma. Paraneoplastic DBN may be associated with cerebellar hypermetabolism, especially in the nodulus.

Combined peripheral and central vestibulopathy.

Diagnosis of central vestibulopathy remains a challenge when it is associated with peripheral vestibular dysfunction because neurotological findings from peripheral vestibulopathy may overshadow those from central vestibular involvements. To define the characteristics of disorders involving both peripheral and central vestibular structures, we classified the combined vestibulopathies into four types according to their vestibular manifestations, and describe a typical case in each subtype. Infarction involving the territory of anterior inferior cerebellar artery is the most common cause of acute unilateral cases, whereas tumors involving the cerebellopontine angle should be of prime suspicion in patients with chronic unilateral ones. Wernicke encephalopathy was most common in patients with acute bilateral combined vestibulopathy while degenerative disorders should be considered in chronic bilateral ones. Since the head impulse test (HIT) is mostly positive in combined vestibulopathy, signs of central vestibular dysfunction other than negative HIT should be sought carefully even in patients with obvious clinical or laboratory features of peripheral vestibulopathy.