Intravenous methadone causes acute toxic and delayed inflammatory encephalopathy with persistent neurocognitive impairments.

BACKGROUND: The mu-opioid agonist methadone is administered orally and used in opioid detoxification and in the treatment of moderate-to-severe pain. Acute oral methadone-use and -abuse have been associated with inflammatory and toxic central nervous system (CNS) damage in some cases and cognitive deficits can develop in long-term methadone users. In contrast, reports of intravenous methadone adverse effects are rare. CASE PRESENTATION: Here, we report a patient who developed acute bilateral hearing loss, ataxia and paraparesis subsequently to intravenous methadone-abuse. While the patient gradually recovered from these deficits, widespread magnetic resonance imaging changes progressed and delayed-onset encephalopathy with signs of cortical dysfunction persisted. This was associated with changes in the composition of monocyte and natural killer cell subsets in the cerebrospinal fluid. CONCLUSION: This case suggests a potential bi-phasic primary toxic and secondary inflammatory CNS damage induced by intravenous methadone.

Bilateral sensorineural hearing loss induced by regorafenib.

WHAT IS KNOWN AND OBJECTIVE: Regorafenib is a novel multi-targeted tyrosine kinase inhibitor approved for use in refractory metastatic colorectal cancer, advanced gastrointestinal stromal tumours and hepatocellular carcinoma. We report a case of bilateral sensorineural hearing loss caused by regorafenib. CASE SUMMARY: A 48-year-old woman was diagnosed with colon cancer that had metastasized to the liver, ureter and left ovary. She was initially treated with oral regorafenib at the lowest recommended dosage of 80 mg/d for 2 weeks, at which point the dose was increased to 120 mg/d. On the second day after the regorafenib dosage increase (ie, 15 days after starting regorafenib), she suddenly developed a bilateral hearing loss. Regorafenib was discontinued immediately, and the patient was treated with a course of intravenous steroids. Five weeks later, her bilateral hearing had subjective partial improvement. WHAT IS NEW AND CONCLUSION: This is the first report of bilateral sensorineural hearing loss induced by regorafenib.

Bilateral hearing loss after dichloromethane poisoning: a case report.

Dichloromethane is a widely used organic solvent. Occupational exposure to dichloromethane is frequent and can result in both acute and chronic toxicity, affecting mostly the central nervous system, directly or through its metabolite, carbon monoxide. The effects of dichloromethane on the peripheral nervous system are debated. Here we report the case of a 37-year-old woman who was accidentally exposed to dichloromethane. In the days following the incident she experienced bilateral hypoacusis. Hearing loss regressed after 25 days treatment with hyperbaric oxygen. This is the first report of sudden hearing loss after acute exposure to dichloromethane, suggesting a possible toxic effect of this solvent on the auditory system.

[Plasmodium falciparum and Salmonella Typhi co-infection: a case report]. / Plasmodium falciparum ve Salmonella Typhi koenfeksiyonu: Bir olgu sunumu.

Malaria and salmonella infections are endemic especially in developing countries, however malaria and salmonella co-infection is a rare entity with high mortality. The basic mechanism in developing salmonella co-infection is the impaired mobilization of granulocytes through heme and heme oxygenase which are released from haemoglobin due to the breakdown of erythrocytes during malaria infection. Thus, a malaria infected person becomes more susceptible to develop infection with Salmonella spp. In this report a case with Plasmodium falciparum and Salmonella Typhi co-infection was presented. A 23-year-old male patient was admitted to hospital with the complaints of diarrhea, nausea, vomiting, abdominal pain, fatigue and fever. Laboratory findings yielded decreased number of platelets and increased ALT, AST and CRP levels. Since he had a history of working in Pakistan, malaria infection was considered in differential diagnosis, and the diagnosis was confirmed by the detection of P.falciparum trophozoites in the thick and thin blood smears. As he came from a region with chloroquine-resistant Plasmodium, quinine (3 x 650 mg) and doxycycline (2 x 100 mg/day) were started for the treatment. No erythrocytes, parasite eggs or fungal elements were seen at the stool microscopy of the patient who had diarrhoea during admission. No pathogenic microorganism growth was detected in his stool culture. The patient's blood cultures were also taken in febrile periods starting from the time of his hospitalization. A bacterial growth was observed in his blood cultures, and the isolate was identified as S. Typhi. Thus, the patient was diagnosed with P.falciparum and Salmonella Typhi coinfection. Ceftriaxone (1 x 2 g/day, 14 days) was added to the therapy according to the results of antibiotic susceptibility test. With the combined therapy (quinine, doxycycline, ceftriaxone) the fever was taken under control, his general condition improved and laboratory findings turned to normal values. However, on the fifth day of his anti-malaria therapy sudden bilateral hearing loss developed due to quinine use. Thus, the treatment was replaced with an artemisinin-based (arthemeter/lumefantrine) combination therapy. No adverse effects were detected due to artemisinin-based therapy, and the patient completely recovered. In conclusion, if a patient is diagnosed with malaria, he/she should be closely monitored in terms of having co-infections and appropriate diagnostic methods including blood cultures taken in febrile episodes should be performed.

Methadone-induced bilateral severe sensorineural hearing loss.

Methadone, a long-acting opiate agonist, and naltrexone, an opiate receptor antagonist, are both commonly used to treat patients with morphine and heroin addiction. We present a rare case of methadone-induced persistent bilateral sensorineural hearing loss (SNHL) after chronic naltrexone use and review opioid-induced hearing loss in the literature. Methadone-induced hearing loss has been described previously described in the literature with all reported cases recovering functional hearing. This is the first description of persistent bilateral severe SNHL following methadone ingestion. We propose opiate receptor sensitization from prolonged naltrexone use as a predisposing factor for methadone-induced irreversible cochlear injury.

Hearing loss associated with xylene exposure in a laboratory worker.

BACKGROUND: Xylene is an organic solvent, widely used in histology laboratories and other occupational settings. Research in animals has demonstrated that xylene induces outer hair cell damage. Evidence regarding the effects of xylene in humans is only available from studies investigating workers exposed to mixtures of solvents containing xylene. These data indicate that mixtures of solvents containing xylene may induce hearing loss and central auditory dysfunction. PURPOSE: To comprehensively evaluate the peripheral and central auditory system of a histology laboratory worker exposed to xylene, who had presented with bilateral mild sensorineural hearing loss at an initial assessment. RESEARCH DESIGN: A case report of a male histology laboratory worker who has been exposed to xylene for over 20 yr. RESULTS: A diagnosis of bilateral mild sensorineural hearing loss of cochlear origin was made on the basis of otological, neuroimaging, and audiological examinations. Results indicating the absence of transient-evoked otoacoustic emissions, and auditory brainstem responses as expected for a mild cochlear hearing loss, were obtained. CONCLUSIONS: The observed bilateral mild sensorineural hearing loss was considered to have been induced by xylene exposure, due to the absence of any other etiological factors related to the onset of hearing loss. The results found in this patient are in agreement with animal data indicating xylene-induced ototoxicity. Xylene-exposed individuals should be audiologically monitored on a regular basis.

Downbeat Nystagmus and Bilateral Sudden Hearing Loss by Suicidal Aspirin Intoxication.

Ototoxic side effects such as sensorineural hearing loss and tinnitus can be caused by acute salicylate intoxication. Bilateral symmetric sensori- neural hearing loss involving all tested frequencies is a typical pattern of hearing loss in acute salicylate intoxication, which usually resolves within 2 or 3 days without any specific treatment for ototoxicity. Herein, we report a case of suicidal aspirin intoxication resulting in sudden bilateral hearing loss and vertigo. The patient exhibited spontaneous downbeat nystagmus, and the mechanism underlying this characteristic nystagmus is discussed.

Sudden bilateral sensorineural hearing loss following polysubstance narcotic overdose.

BACKGROUND: Auditory disorders associated with substance abuse are rare. Hearing loss secondary to heroin and hydrocodone abuse has been described variously as not always responsive to steroid management, as not always reversible, and in some cases, as nonresponsive profound sensorineural hearing loss requiring cochlear implantation. We present a case of a teenager with sudden-onset moderate to severe bilateral sensorineural hearing loss after documented polysubstance "binging." The hearing loss improved substantially after high-dose steroid and vasoactive therapy. PURPOSE: The purpose of this report is to describe the hearing disorder of a patient who had awakened with a bilateral severe hearing loss following a night of recreational drug abuse. RESEARCH DESIGN: Case report and review of the literature. DATA COLLECTION AND ANALYSIS: The subject of this report is an 18-yr-old patient with a history of substance abuse. Data collected were magnetic resonance /computed tomography brain imaging; metabolic, infectious disease, and autoimmune evaluation; and extensive audiologic evaluation, including pure-tone and speech audiometry, immittance measures, distortion-product otoacoustic emissions, and auditory brainstem response testing. Serial audiograms were collected for 10 mo following the onset of symptoms. RESULTS: Two days of polysubstance abuse (heroin, benzodiazepine, alcohol, and crack [smoked cocaine]) resulted in moderately severe sensorineural hearing loss bilaterally. The loss responded to a 1 mo course of high-dose prednisone and a 10 mo course of pentoxifylline. Hearing sensitivity subsequently improved, leaving only residual high-frequency sensorineural hearing loss. CONCLUSIONS: This case report highlights the importance of "recreational" drug abuse in the evaluation of sudden hearing loss. Potential etiologies include altered pharmacokinetics, vascular spasm/ischemia, encephalopathy, acute intralabyrinthine hemorrhage, and genetic polymorphisms of drug-metabolizing enzymes.

Bilateral Sensorineural Hearing Loss Associated With Nivolumab Therapy for Stage IV Malignant Melanoma.

OBJECTIVES: Present the case of a 67-year-old male with stage IV malignant melanoma who presented with uveitis and sensorineural hearing loss (SNHL) while on nivolumab and review the literature for likely etiologies. METHODS: A retrospective case review was conducted. The current literature was accessed to inquire about possible pathologic mechanisms and treatment options. RESULTS: A 67-year-old male with stage IV malignant melanoma was treated with nivolumab. During therapy, the patient presented with bilateral uveitis, vertigo, and bilateral moderate sloping to moderate-severe SNHL. After 4 cycles of nivolumab, restaging scans showed no evidence of disease. Nivolumab was discontinued. The patient was placed on a 3-week course of systemic high dose steroids and topical steroid eye drops. Both his uveitis and SNHL resolved after treatment. Nivolumab enhances the antitumor activity of T cells by inhibiting the programed death-1 receptor. While nivolumab has shown great promise in the treatment of many types of cancers, it has also been associated with many autoimmune side effects. We propose the etiology of this 67-year-old male's SNHL and uveitis are the result of an autoimmune process secondary to an augmented T cell response induced by nivolumab. CONCLUSION: While immunotherapeutic agents such as nivolumab have shown great promise in the treatment of cancer, one should maintain an awareness and caution of autoimmune side effects such as uveitis and SNHL.

Sudden bilateral sensorineural hearing loss as an unusual consequence of accidental ingestion of potassium hydroxide.

OBJECTIVE: To discuss the possible etiopathogenetic mechanism of inner ear damage induced by the ingestion of potassium hydroxide (KOH). CLINICAL PRESENTATION AND INTERVENTION: We report the case of a 37-year-old patient with sudden bilateral sensorineural hearing loss after accidental ingestion of a KOH solution. The first ear, nose and throat examination disclosed only mild edema of the upper airways. He was treated in the intensive care unit and prescribed high-dose steroids, proton pump inhibitors and sucralfate for 2 weeks. Unfortunately, there was no recovery of the hearing loss, and no audiogram changes were noticed after 12 months of follow-up. CONCLUSION: After exploring the possible etiopathogenetic mechanism involved, the authors believe that in this case, a transient severe hemodynamic imbalance can actually be considered to be the most reliable explanation for the inner ear damage and subsequent onset of permanent bilateral sensorineural hearing loss.

Case of neuromyelitis optica: bilateral sensorineural hearing loss and transverse myelopathy following intrathecal chemotherapy.

Neurotoxicity from intrathecally administered chemotherapeutic drugs is frequent, particularly with some agents like methotrexate, which are more prone to developing adverse effects. Myelopathy ranks among the most frequently reported neurological entities; with the diagnosis being straightforward, after ruling out infectious, metabolic, autoimmune or paraneoplastic causes. Scarcity of cases precludes evidence-based recommendations for the management of these complications. The most common therapeutic approach consists of the suspension of chemotherapy, exclusion of infectious and neoplastic causes, with prompt administration of high-dose steroids. We report a 21-year-old patient with acute lymphoblastic leukaemia, who developed acute transverse myelitis and bilateral sensorineural hearing loss, after five rounds of intrathecal methotrexate and cytarabine. Although neurotoxicity from both agents has been documented, this combination has not been previously reported.

Etiology of Childhood Bilateral Sensorineural Hearing Loss in Shandong Province, China.

Objectives The purpose of this study is to ascertain the etiology of bilateral sensorineural hearing loss (SNHL) in children aged ≤ 18 years living in Shandong province. Method Data were taken from a cross-sectional study, which was conducted between 2015 and 2017. The study included children aged ≤ 18 years, recruited from special schools for children with hearing loss and from hearing rehabilitation centers in Shandong province of China. Children were screened for bilateral SNHL through audiological testing. Clinical examination, genetic testing, and structured interviews were conducted for those children who were identified as having hearing loss to identify the potential cause. Results The etiology of bilateral SNHL in our sample was genetic in 874 (39.3%), acquired in 650 (29.3%), and unknown in 697 (31.4%) children. Among children with acquired SNHL, the cause was maternal viral infection in 75 (11.5%); perinatal factors in 238 (36.6%); meningitis, measles, and mumps in 146 (22.5%); and ototoxic exposure in 117 (18%) children. Among the children with genetic SNHL, only 44 (4.9%) were identified as having syndromic hearing loss, and the remainder (95.1%) were classified as nonsyndromic hearing loss. Conclusion The findings indicated that nearly 30% of bilateral SNHL in Shandong province could be preventable through immunization, early prenatal diagnosis, proper treatment of infections, and avoidance of prescription of ototoxic drugs. This finding emphasizes the need for programs aimed at improving the health services at primary and secondary levels of health care, which will in turn prevent childhood hearing loss.

[Hearing assessment of children treated with Cisplatin]. / Ocena sluchu u dzieci leczonych cisplatyna.

THE AIM OF THE STUDY: Cisplatin's effect on the inner ear in children and compare results of the tonal audiometry and the oto-acousitic emission audiometry. MATERIAL AND METHODS: Audiological examinations were conducted on 33 children who had been treated with Cisplatin. Normal hearing prior to the cytostatic therapy would qualify a child for inclusion in the examinations. Cisplatin was administered via intravenous infusion in dosages of 15 mg/m2 to 20 mg/m2 on five successive days of each month or 50-75 mg/m2 every 3 weeks. The patients were divided into groups according to ratio of the cumulative dosage per 1 m2 of the body area. Hearing was assessed with tonal and impendence audiometry as well as oto-acousitic emission audiometry--DPOAE. RESULTS: The tonal audiometry helped detect hearing damage in 12 out of the 33 children participating in the examination, with unilateral loss found in 2 and bilateral loss encountered in 10 children. Hearing threshold shifts ranged between 10 and 40 dB in frequencies above 2000 Hz. The largest hearing threshold shift was registered for the region of 6000-8000 Hz. Tonal audiometry and oto-acoustic emission audiometry result consistency was encountered in 11 children from the study group. CONCLUSIONS: No effect of the cytostatic dose level on the degree of hearing loss could be demonstrated in the examined group of children. The sensitivity of the oto-acoustic emission and of the tonal audiometry to detect and monitor hypacusis were found to be comparable.

Cochlear Implantation after Bromate Intoxication-Induced Bilateral Deafness: A Case Report.

Hearing loss is a common consequence of the strong acidosis induced by bromate poisoning. Partial hearing recovery has been achieved through medical or rehabilitative therapy but reports of surgical otology treatment for this condition are rare. We report the case of a 48-year-old female patient who underwent cochlear implantation after bromate intoxication had induced bilateral deafness. In cases with life-threatening renal damage, the diagnosis of hearing loss is sometimes delayed, but in our case, hearing impairment was unavoidable despite early detection of symptoms and early disruption of the use of diuretics that could cause hearing damage. Hearing loss 12 hours after bromate ingestion was successfully reversed through cochlear implantation (CI) six months after completing acute phase treatment, including dialysis for acute kidney injury. The benefit of CI for deafness by bromate intoxication is highlighted by this case.

Left-right asymmetry in hearing loss following cisplatin therapy in children--the left ear is slightly but significantly more affected.

OBJECTIVES: Bilateral symmetric high frequency hearing loss is regarded as one of the main characteristics of cisplatin-induced ototoxicity. Hair-cell damage because of cisplatin is discussed as the leading cause of hearing loss. Our observations in long-term audiological follow-up of children treated with cisplatin did not always show the anticipated symmetry of hearing loss. DESIGN: Pure-tone audiograms of 55 (34 m, 21 f) children receiving chemotherapy with cisplatin at Muenster university hospital were analyzed. We compared pure tone hearing thresholds, transient evoked otoacoustic emissions levels and distortion product otoacoustic emissions levels before and after chemotherapy with cisplatin. RESULTS: After therapy, the 55 children showed slightly higher average hearing levels in the range 2000 to 8000 Hz in the left ear. The side difference was significant at 4000, 6000, and 8000 Hz. In girls, the effect was less pronounced than in boys. CONCLUSIONS: This result, on the one hand, indicates that the auditory system is already responding asymetrically at the cochlear level, on the other hand it underscores the need for further research into the pathophysiology of platinum ototoxicity. There are parallels with stronger effects to the left ear in oiseinduced hearing loss as described in literature. Special attention should be given to possible supracochlear pathways of damage. Clinicians should consider that cisplatin associated hearing loss is not necessarily symmetric.

Sudden bilateral sensorineural hearing loss following speedballing.

BACKGROUND: Hearing loss is an infrequently-reported consequence of recreational drug abuse. Although there are sporadic reports of hearing loss from heroin and cocaine ingested separately, there are no reports of hearing loss resulting from the combination of both drugs ingested simultaneously in the form of speedballing. PURPOSE: The purpose of this report is to document a case of bilateral sensorineural hearing loss associated with an episode of speedballing. RESEARCH DESIGN: Case Report. DATA COLLECTION AND ANALYSIS: The subject of this report was a 40-year-old man with a 20-year history of substance abuse. Data collected included a case history, pure tone audiometry, tympanometry and acoustic reflexes, and transient evoked otoacoustic emissions. RESULTS: The audiologic evaluation indicated a mild to moderate, relatively flat, bilateral sensorineural hearing loss that was worse in the right ear. CONCLUSIONS: A bilateral sensorineural hearing loss involving both cochlear and neural pathology may be a rare complication of cocaine, heroin, or the combination of the two drugs.

Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss is associated with the 12S rRNA C1494T mutation in three Han Chinese pedigrees.

We report here the clinical, genetic and molecular characterization of three Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic bilateral hearing loss. Clinical evaluation revealed the wide range of severity, age-at-onset and audiometric configuration of hearing impairment in matrilineal relatives in these families. The penetrances of hearing loss in these pedigrees were 28%, 20%, and 15%, with an average of 21%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss in these seven pedigrees were 21%, 13% and 8%, with an average of 14%. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the presence of the deafness-associated 12S rRNA C1494T mutation, in addition to distinct sets of mtDNA polymorphism belonging to Eastern Asian haplogroups F1a1, F1a1 and D5a2, respectively. This suggested that the C1494T mutation occurred sporadically and multiplied through evolution of the mtDNA. The absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in their mtDNA suggests that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the C1494T mutation in those Chinese families. In addition, the lack of significant mutation in the GJB2 gene ruled out the possible involvement of GJB2 in the phenotypic expression of the C1494T mutation in those affected subjects. However, aminoglycosides and other nuclear modifier genes play a modifying role in the phenotypic manifestation of the C1494T mutation in these Chinese families.

Very low penetrance of hearing loss in seven Han Chinese pedigrees carrying the deafness-associated 12S rRNA A1555G mutation.

Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here the clinical, genetic and molecular characterizations of seven Han Chinese pedigrees with aminoglycoside-induced and nonsyndromic bilateral hearing loss. Clinical evaluation revealed the variable phenotype of hearing impairment including severity, age-at-onset and audiometric configuration in these subjects. The penetrance of hearing loss in these pedigrees ranged from 3% to 29%, with an average of 13.6%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss in these seven pedigrees varied from 0% to 17%, with an average of 5.3%. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the presence of the deafness-associated 12S rRNA A1555G mutation, in addition to distinct sets of mtDNA polymorphism belonging to East Asian haplogroups B4, D4, D5 and F1, respectively. This suggested that the A1555G mutation occurred sporadically and multiplied through evolution of the mtDNA in China. Despite the presence of several evolutionary conservative variants in protein-encoding genes, there was the absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in these seven Chinese families. These suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the A1555G mutation in those Chinese families with very low penetrance of hearing loss. However, aminoglycosides appear to be a major modifier factor for the phenotypic manifestation of the A1555G mutation in these Chinese families.

The protective effect of intratympanic dexamethasone on cisplatin-induced ototoxicity in guinea pigs.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection as a protection agent against cisplatin-induced ototoxicity. STUDY DESIGN AND SETTING: The four groups of guinea pigs were injected as follows: 1) cisplatin, 2) intratympanic dexamethasone, 3) cisplatin following intratympanic dexamethasone, and 4) cisplatin after intratympanic saline. Before and 3 days following injections, the ototoxic effect was measured with distortion product otoacoustic emissions (DPOAEs). RESULTS: The DPOAEs amplitudes and signal-to-noise ratio (SNR) values at 1 to 6 kHz frequencies for group 1 animals after injections significantly decreased over those before injections (P < 0.05). In group 2, there were no significant differences in DPOAE amplitude and SNR values between before and after intratympanic dexamethasone injections (P > 0.05). Considering group 3, there were also no significant differences in DPOAEs amplitudes and SNR values before and after of dexamethasone and cisplatin injections (P > 0.05). CONCLUSIONS: Intratympanic dexamethasone injection did not cause any ototoxic effect; in contrast, it might have a significant protective effect after cisplatin injection.