Acute Cerebellar Ataxia Induced by Nivolumab.

A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment.

Downbeat nystagmus due to ranitidine in a pediatric patient.

BACKGROUND: Ranitidine has not been considered as a potential cause of ocular movement conditions. However, it is known that the vestibular nucleus complex, that has a key role in gaze control and vestibule-ocular reflexes, receives hypothalamic histaminergic innervations. Some studies reported the effect of ranitidine blocking the excitatory responses of vestibular nuclei neurons to histamine. CASE REPORT: We report the first case of a downbeat nystagmus secondary to ranitidine in an infant. A 3-month-old female developed a downbeat gaze after starting treatment with ranitidine for a pediatric gastroesophageal reflux disease. Microbiological test were negative and neuroblastoma evaluation was normal. CONCLUSION: As ranitidine is widely prescribed in the pediatric population, clinicians should be aware of its potential to cause ocular movements disorders.

Differential physiological and behavioral cues observed in individuals smoking botanical marijuana versus synthetic cannabinoid drugs.

CONTEXT: Synthetic cannabinoid use has increased in many states, and medicinal and/or recreational marijuana use has been legalized in some states. These changes present challenges to law enforcement drug recognition experts (DREs) who determine whether drivers are impaired by synthetic cannabinoids or marijuana, as well as to clinical toxicologists who care for patients with complications from synthetic cannabinoids and marijuana. Our goal was to compare what effects synthetic cannabinoids and marijuana had on performance and behavior, including driving impairment, by reviewing records generated by law enforcement DREs who evaluated motorists arrested for impaired driving. METHODS: Data were from a retrospective, convenience sample of de-identified arrest reports from impaired drivers suspected of using synthetic cannabinoids (n = 100) or marijuana (n = 33). Inclusion criteria were arrested drivers who admitted to using either synthetic cannabinoids or marijuana, or who possessed either synthetic cannabinoids or marijuana; who also had a DRE evaluation at the scene; and whose blood screens were negative for alcohol and other drugs. Exclusion criteria were impaired drivers arrested with other intoxicants found in their drug or alcohol blood screens. Blood samples were analyzed for 20 popular synthetic cannabinoids by using liquid chromatography-tandem mass spectrometry. Delta-9-tetrahydrocannabinol (THC) and THC-COOH were quantified by gas chromatography-mass spectrometry. Statistical significance was determined by using Fisher's exact test or Student's t-test, where appropriate, to compare the frequency of characteristics of those in the synthetic cannabinoid group versus those in the marijuana group. RESULTS: 16 synthetic cannabinoid and 25 marijuana records met selection criteria; the drivers of these records were arrested for moving violations. Median age for the synthetic cannabinoid group (n = 16, 15 males) was 20 years (IQR 19-23 years). Median age for the marijuana group (n = 25, 21 males) was 20 years (IQR 19-24 years) (p = 0.46). In the synthetic cannabinoid group, 94% (15/16) admitted to using synthetic cannabinoids. In the marijuana group, 96% (24/25) admitted to using marijuana. Blood was available for testing in 96% (24/25) of the marijuana group; 21 of these 24 had quantitative levels of THC (mean + SD = 10.7 + 5 ng/mL) and THC-COOH (mean + SD = 57.8 + 3 ng/mL). Blood was available for testing in 63% (10/16) of the synthetic cannabinoid group, with 80% (8/10) of these positive for synthetic cannabinoids. Those in the synthetic cannabinoid group were more frequently confused (7/16 [44%] vs. 0/25 [0%], p ≤ 0.003) and disoriented (5/16 [31%] vs. 0/25 [0%], p ≤ 0.003), and more frequently had incoherent, slurred speech (10/16 [63%] vs. 3/25 [12%], p = 0.0014) and horizontal gaze nystagmus (8/16 [50%] vs. 3/25 [12%], p = 0.01) than those in the marijuana group. CONCLUSION: Drivers under the influence of synthetic cannabinoids were more frequently impaired with confusion, disorientation, and incoherent, slurred speech than drivers under the influence of marijuana in this population evaluated by DREs.

Toxicology observation: nystagmus after marijuana use.

Traditional teaching has held that horizontal-gaze nystagmus is a sign of intoxication by sedatives such as alcohol but not marijuana. This is a case report of an adult male who presents with 3 days of visual disturbance and dizziness following marijuana use. The exam was notable for gaze-evoked nystagmus and ataxia. Lab testing was normal except that urine drug screening was positive for marijuana only. Imaging included computed tomography (CT) and magnetic resonance imaging (MRI) scans of the head. Prior studies showing a negative association of nystagmus with marijuana are reviewed. This case is presented as a possible exception to the generalisation that marijuana is not associated with nystagmus.

Vértigo con nistagmo vertical por administración de morfina intratecal y reversión con naloxona / Vertigo and vertical nystagmus associated with intrathecal morphine administration and resolution by naloxone

La anestesia regional combinada es utilizada frecuentemente como herramienta para el tratamiento del dolor postoperatorio. Los efectos secundarios de los opioides utilizados por esta vía son similares a los que se presentan luego de la administración sistémica. La aparición de vértigo con nistagmo vertical es un efecto adverso muy pocas veces descripto con el uso de morfina por vía intratecal, epidural o endovenosa. Comunicamos el caso de un paciente que presentó esta complicación en el postoperatorio de una nefrectomía parcial, luego de la administración de morfina intratecal, con resolución completa mediante el uso de naloxona endovenosa.

Combined regional anesthesia is frequently used as a tool for management of postoperative pain. The profile of side effects of the opioids used via this route is similar to those occurring after systemic administration. The onset of vertigo with vertical nystagmus is an adverse effect rarely described after the use of intrathecal, epidural or intravenous morphine. We report the case of a patient who presented this complication in the postoperative period of a partial nephrectomy, after the administration of intrathecal morphine, with complete resolution by intravenous naloxone.

Nicotine-induced nystagmus correlates with midpontine activation.

The pathomechanism of nicotine-induced nystagmus (NIN) is unknown. The aim of this study was to delineate brain structures that are involved in NIN generation. Eight healthy volunteers inhaled nicotine in darkness during a functional magnetic resonance imaging (fMRI) experiment; eye movements were registered using video-oculography. NIN correlated with blood oxygen level-dependent (BOLD) activity levels in a midpontine site in the posterior basis pontis. NIN-induced midpontine activation may correspond to activation of the dorsomedial pontine nuclei and the nucleus reticularis tegmenti pontis, structures known to participate in the generation of multidirectional saccades and smooth pursuit eye movements.

Central anticholinergic syndrome: a case report.

Postoperative central anticholinergic syndrome (CAS) is caused by anticholinergic medications that cross the blood-brain barrier. Medications with central anticholinergic effects block muscarinic cholinergic receptors, resulting in a wide array of symptoms. Symptoms may range from coma to a highly agitated state. CAS may be underdiagnosed because of its varying presentation and lack of awareness. Differential diagnosis for the patient presenting with abnormal neurological signs and symptoms should include CAS after the exclusion of other potential causes. This case report details the occurrence of CAS in a patient in her 20's. A review of CAS including causes, signs and symptoms, incidence, differential diagnosis, and treatment is discussed.

Lateral medullary syndrome in a woman after ovulation induction.

Although atherothrombotic complications due to ovulation induction are well known in the literature, there is no previous report specifically on the presentation of a lateral medullary infarction. Recently, we have encountered a 36 years old woman with primary infertility having acute vertiginous attack after ovulation induction. Audiovestibular test battery revealed bilateral normal hearing, bilateral gaze nystagmus, rebound nystagmus beating toward the right side, loss of visual suppression with augmentation of caloric nystagmus in light on the left side, and delayed vestibular evoked myogenic potentials on the left side, which was subsequently confirmed as lateral medullary syndrome by MRI scan. In this patient, polycystic ovary syndrome plus high levels of follicle stimulating hormone (FSH) and estrogen, together with S protein deficiency may precipitate the occurrence of lateral medullary infarct after ovulation induction. Thus, in vitro fertilization treatment protocol has been terminated.

Benign paroxysmal positional nystagmus in hospitalized subjects receiving ototoxic medications.

OBJECTIVE: To investigate the occurrence of benign paroxysmal positional nystagmus in subjects undergoing treatment with potentially ototoxic medications. STUDY DESIGN: Prospective and retrospective record reviews. SETTING: Tertiary referral neurotology clinic; clinical research and technology center. SUBJECTS: Ninety-nine hospitalized subjects undergoing treatment of infectious disease or carcinoma with potentially ototoxic medications. INTERVENTIONS: Records review, tests of vestibular function. MAIN OUTCOME MEASURE: Results of Hallpike positional tests for benign paroxysmal positional nystagmus (electro-oculography). RESULTS: Forty-one (41%) of 99 subjects were female and 58 (59%) were male. Age range was 15 to 73 years (mean, 47 years). Forty-nine (50%) of 99 subjects had an unequivocally positive Hallpike test for benign paroxysmal positional nystagmus in one or both ears. The occurrence of benign paroxysmal positional nystagmus in the Hallpike-positive population was distributed equally across age decades. Of the 49 subjects with benign paroxysmal positional nystagmus, 22 (44%) were female and 27 (56%) were male. CONCLUSIONS: Benign paroxysmal positional nystagmus is the most common cause of vertigo in the general population, including subjects receiving ototoxic drugs. Complaints of vertigo in subjects receiving ototoxic drugs therefore may or may not indicate onset of ototoxicity. Occurrence of benign paroxysmal positional nystagmus in subjects receiving ototoxic drugs was independent of gender or age. The high occurrence rate of benign paroxysmal positional nystagmus in subjects receiving potentially ototoxic medications is consistent with the observation that benign paroxysmal positional nystagmus occurs in combination with many pathologic conditions. Benign paroxysmal positional nystagmus presenting in subjects receiving ototoxic drugs may complicate the clinical identification of ototoxicity and obfuscate clinical decision-making processes.

Temporal changes of cFos-like protein expression in medial vestibular nuclei following arsanilate-induced unilateral labyrinthectomy in rats.

The compensation of spontaneous nystagmus and head deviation following chemical unilateral labyrinthectomy (UL) induced by arsanilate was delayed compared with surgical UL. Surgical UL produced two phases of significant asymmetry of cFos-like (cFL) protein expression between the bilateral medial vestibular nuclei, with more expression in the contralateral medial vestibular nuclei to the injured side than in the ipsilateral medial vestibular nuclei 2 h after UL; the pattern reversed after 6 h and expression disappeared after 72 h. Chemical UL produced three phases of asymmetric expression, with more cFL protein expression in the contralateral medial vestibular nuclei than in the ipsilateral medial vestibular nuclei 6 h after UL and a reversed pattern after 12 h. Asymmetric expression 72 h after UL followed increased expression in the contralateral medial vestibular nuclei. These results suggest that the course of vestibular compensation and the temporal expression of cFL protein in the medial vestibular nuclei following UL differed between surgical and chemical labyrinthectomy.

Transtympanic tetrodotoxin alters the VOR and Fos labeling in the vestibular complex.

The sodium channel blocker tetrodotoxin (TTX) is an effective tool for blockade of action potentials. Unilateral transtympanic administration of 3 mM TTX produced behavioral symptoms similar to those following unilateral peripheral vestibular ablation. Complete resolution of visible symptoms occurred between 48 and 72 h post-TTX. Eye-coil recordings indicated a spontaneous nystagmus and a decrease in the VOR in TTX-treated animals. Neuronal activity in the central vestibular complex (VC), as monitored with Fos immunocytochemistry, revealed an asymmetric pattern of Fos labeling in the medial, inferior and superior vestibular nuclei and the prepositus hypoglossal nucleus. Although the spatio-temporal pattern of Fos labeling was consistent and reproducible at each time-point, changes were noted among time-points. Transient blockade with TTX may be useful for studying the central vestibular response to recurrent or episodic vestibular disruption in the intact system.

[Vestibular and oculomotor changes in subjects treated with cisplatin]. / Alteraciones vestibulares y del sistema oculomotor en sujetos tratados con cisplatino.

Cisplatin is an agent used in the treatment of distinct oncologic diseases. We present the electrooculographic (EOG) findings of 6 patients which were seen at our Department under the diagnosis of chronic toxicity for cisplatin and associated vestibular alterations. Mean of age was 45 years. Three subjects were female (50%). The most frequent pathologic finding was ataxic pursuit tracking (100%). Additionally, spontaneous nystagmus, alterations in positional test, and vestibulo-ocular reflex suppression were also found. These results are discussed and the main literature concerning this matter is reviewed.

Smoking and balance: correlation of nicotine-induced nystagmus and postural body sway.

Unaccustomed smoking may elicit transient nystagmus, dizziness, unsteadiness, and nausea. Infrared videonystagmography and posturography were performed simultaneously to study the differential effects of nicotine on the association of ocular motor and postural disturbances in 25 non- or occasional smokers. Sixteen showed nicotine-induced nystagmus (NIN) of various directions (mainly horizontal or upbeat) which was associated with a significant increase in postural sway after smoking a cigarette (total sway path (SP) before smoking 2.22 +/- 0.82 m/min (mean +/- s.d.), 1 min after smoking 3.83 +/- 1.41 m/min; p < 0.0004, ANOVA); nine showed neither effect. There was a high correlation between the intensity of the nystagmus (measured as peak slow phase velocity) and the increase in total SP (correlation coefficient 0.78) as well as the time courses of both. Visual fixation of an LED integrated in the mask not only caused a suppression of NIN but also a decrease in body sway. Transient ocular motor and postural effects are compatible with simultaneous nicotine-induced effects on the vestibulo-ocular and vestibulo-spinal functions.

Adverse effects associated with the intrathecal administration of ziconotide.

The omega-conopeptide, ziconotide, is an N-type calcium-channel blocker that has been shown to produce antinociception in animals using formalin and hot-plate tests. Initial reports of intrathecal administration of ziconotide in cancer and AIDS patients whose pain was unrelieved with opioids demonstrated analgesic efficacy. Although adverse effects were reported, these appeared to be easily managed through dose reduction or symptomatic treatment. This clinical report describes the experiences of three patients with serious adverse effects associated with intrathecal ziconotide.

Cyclosporine-induced optic neuropathy, ophthalmoplegia, and nystagmus in a patient with Crohn disease.

PURPOSE: To report the cyclosporine-induced complications of optic neuropathy, partial external ophthalmoplegia, and other neurologic abnormalities. METHODS: Case report. A 22-year-old man with severe active Crohn disease developed bilateral optic neuropathy, nystagmus, external ophthalmoplegia, and ataxia on the fifth day of cyclosporine A (CyA) parenteral therapy. RESULTS: Cyclosporine therapy was discontinued as soon as toxic clinical manifestations appeared. Cyclosporine blood level detected then was 1,290 ng/ml (therapeutic level: 150 to 300 ng/ml). Partial external ophthalmoplegia improved dramatically; however, the patient's optic neuropathy progressed to optic atrophy, leaving the patient visually impaired. Various possible mechanisms for cyclosporine-induced neurotoxicity are discussed. CONCLUSION: It is important to closely monitor neuro-ophthalmologic and neurologic signs of patients treated with cyclosporine.