An Italian case series' description of thiamine responsive megaloblastic anemia syndrome: importance of early diagnosis and treatment.

BACKGROUND: Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations. CASES PRESENTATION: Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed. CONCLUSIONS: Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease.

A Case Report of Riboflavin Treatment and Cochlear Implants in a 4-Year-Old Girl with Progressive Hearing Loss and Delayed Speech Development: Brown-Vialetto-Van Laere Syndrome.

BACKGROUND Brown-Vialetto-Van Laere (BVVL) syndrome is a rare autosomal recessive disorder caused by mutations in intestinal riboflavin transporter genes, resulting in a motor neuron disorder of childhood, which can be associated with sensorineural deafness. This report describes a 4-year-old Polish girl with progressive hearing loss and delayed speech development diagnosed with Brown-Vialetto-Van Laere syndrome who was treated with riboflavin (vitamin B2) and cochlear implants. CASE REPORT The case report concerns a girl from Poland who, at the age of 2 years 10 months, developed progressive atypical neurological symptoms of unknown etiology: ataxia of the upper and lower limbs, gait abnormalities, generalized muscle weakness, visual and hearing problems, and regression of speech development. A karyotype study (whole-exome sequencing) revealed alterations within SLC52A2, leading to the diagnosis of Brown-Vialetto-Van Laere syndrome and initiation of high-dose riboflavin treatment. As a 4-year-old child, she presented to the Institute of Physiology and Pathology of Hearing - World Hearing Center in Poland with progressive hearing loss and speech regression. Hearing tests revealed bilateral profound sensorineural hearing loss with auditory neuropathy. Surgical treatment was applied in the form of bilateral cochlear implantation. CONCLUSIONS This report shows the importance of genetic testing in infants who present with atypical symptoms or signs. In this case, the diagnosis of Brown-Vialetto-Van Laere syndrome resulted in timely correction of the genetic riboflavin (vitamin B2) deficiency and improved hearing following the use of cochlear implants.

SUCLA2 Arg407Trp mutation can cause a nonprogressive movement disorder - deafness syndrome.

SUCLA2 is a component of mitochondrial succinate-CoA ligase and nucleotide diphosphokinase activities. Its absence results in Krebs cycle failure, mitochondrial DNA depletion, and a childhood-fatal encephalomyopathy. We describe a purely neurologic allelic form of the disease consisting of deafness, putamenal hyperintensity on MRI and a myoclonic-dystonic movement disorder unchanging from childhood into, so far, the late fourth decade. We show that succinate supplementation circumvents the Krebs cycle block, but does not correct the neurologic disease. Our patients' Arg407Trp mutation has been reported in children with (yet) no MRI abnormalities. It remains possible that early succinate supplementation could impact the disease.

Structural changes in the inner ear over time studied in the experimentally deafened guinea pig.

Today a cochlear implant (CI) may significantly restore auditory function, even for people with a profound hearing loss. Because the efficacy of a CI is believed to depend mainly on the remaining population of spiral ganglion neurons (SGNs), it is important to understand the timeline of the degenerative process of the auditory neurons following deafness. Guinea pigs were transtympanically deafened with neomycin, verified by recording auditory brainstem responses (ABRs), and then sacrificed at different time points. Loss of SGNs as well as changes in cell body and nuclear volume were estimated. To study the effect of delayed treatment, a group of animals that had been deaf for 12 weeks was implanted with a stimulus electrode mimicking a CI, after which they received a 4-week treatment with glial cell-derived neurotrophic factor (GDNF). The electrical responsiveness of the SGNs was measured by recording electrically evoked ABRs. There was a rapid degeneration during the first 7 weeks, shown as a significant reduction of the SGN population. The degenerative process then slowed, and there was no difference in the amount of remaining neurons between weeks 7 and 18. © 2016 The Authors Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

[Clinical analysis of Ginkgo biloba injection combined with traditional therapy in treatment of explosive deafness].

OBJECTIVE: To investigate the clinical efficacy of Ginkgo biloba injection combined with traditional therapy in the treatment of explosive deafness. METHODS: Fifty-six (98 ears) participants who were all coal miners were selected. These patients were diagnosed with explosive deafness. and admitted to the otolaryngology department of our hospital from May 2010 to October 2013. They were.equally divided into control group and treatment group according to the therapeutic method. The patients in the control group only received traditional therapy, such as hyperbaric oxygen, while the patients in the treatment group were given Ginkgo biloba injection in addition to the therapy for the control group. The improvement in hearing was recorded and compared between the two groups. RESULTS: The rate of improvement in tinnitus symptom in the treatment group was 78.0% (32/41), significantly higher than that in the control group (55.6%, 25/45) (χ2=4.857, P<0.05); compared with the treatment group (93.5%, 43/46), the control group had a significant lower overall response rate at 76.9% (40/52) (χ2=5.160, P<0.05). CONCLUSION: Compared with traditional therapy alone, combined ginkgo biloba extract injection and traditional therapy can significantly improve tinnitus symptom and overall response rate in the treatment of explosive deafness in coal miners, which suggests that the combination therapy is worthy of clinical application.

Effect of hypoglycemic anti-deafness capsules in diabetic patients with deafness and toxicological assessment in rats.

OBJECTIVE: Through experiment on animals and clinical trials to explore the safety and efficacy of hypoglycemic anti-deafness capsules on diabetic patients with deafness. METHODS: Total 296 patients with non-insulin dependent diabetes mellitus (NIDDM) were randomly divided into two groups. A treatment group of 164 patients (208 ears) was treated with hypoglycemic anti-deafness capsules based on TCM syndrome differentiation. A control group of 132 patients (184 ears) was treated with glibenclamide and conventional drug treatment for deafness. The following were observed: hearing, fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2hPG), 24 h urine glucose (24hUG), improvement of main symptoms, platelet function, and changes in superoxide dismutase (SOD) and lipid peroxide (LPO) levels. In animal studies, Kunming mice, weighing 18-22 g were used. Half of the mice were males and half were females. Wistar rats, weighing 80-120 g were used. Half of the rats were males and half were females. Male Wistar rats, weighing 200-220 g, were also used. Their acute and chronic toxicity was studied. RESULTS: The hearing improvement was 56.7% in the treatment group and 26.6% in the control group. FPG, 2hPG, and 24hUG were improved significantly (P < 0.05, P < 0.01, P < 0.01, respectively) in the treatment group and 2hPG and 24hUG improved significantly in the control group (P < 0.05, P < 0.05). The improvement in 2hPG and 24hUG in the treatment group was significantly greater than that in the control group P < 0.01).There was no significant difference in FPG between the two groups (P < 0.05). Main symptoms in the treatment group were significantly more improved than those in the control group (P < 0.05, P < 0.01). In the treatment group, platelet adhesion and aggregation, SOD, and LPO were all significantly improved from before treatment (P < 0.05, P < 0.01). However, in the control group, except LOP (P < 0.05), there were no significant differences from before treatment to after (P < 0.05). In animal studies, no obvious acute or long-term toxicity was observed from capsule administration. CONCLUSION: Through experiment on animals and clinical trials, we can found that hypoglycemic anti-deafness capsules could decrease blood glucose and serum triglycerides of alloxan-induced diabetic rats. This herbal capsule is effective for safely treating diabetic patients with deafness.

The proteomic research of the cure of experimental diabetes deafness by granules of eliminating phlegm and removing blood stasis.

OBJECTIVE: Observing the expression changes of serum proteome in model rats after intervention of the Granules of Eliminating Phlegm and Removing Blood Stasis ((see text) also known as GEPRB), screening outand identifying the differentially expressed proteins by mass spectrometry and bioinformatics analysis, discussing the molecular mechanism of control the Diabetes deafness by GEPRB. METHODS: By use of proteomics technology, the serum protein serum proteome of the control group, model control group, Duxil and each observation group were observed for 2-DE gel pattern matching, and the difference in the relative content of 2 times was chosen for the differentially expressed proteins. Identification of differentially expressed proteins by MALDI-TOF MS/MS, the authors further analysis the phosphorylation, subcellular localization, interaction, direct regulation, and transmembrane of the differences proteins by the way of bioinformatics analysis. Sixty SPF level SD rats elected in diabetic rats model group (abbreviated as DM group) were be randomly divided into 5 groups based on random number sheet, namely model control group, positive drug control group (Du-ke-xi group) and Mai-tong-fang high, medium and low dose group respectively. In addition, set of normal control group. 10 rats in each group. RESULTS: By Coomassie brilliant blue staining, identified 51 differential protein spots dug from 2-D gel by mass spectrometry, successfully identified 13 non-redundant proteins. Most of the identified proteins were secreted protein and belong to different protein families. There were about 12 proteins have the transmembrane region from the authors' result, ten of them were plasma membrane proteins. CONCLUSION: It's suggesting that 13 differential proteins is most likely the protein response to GEPRB in vivo, these proteins may play key role for the treatment of GEPRB to Diabetes deafness. The two highly differentially expressed proteins Apolipoprotein E (apoE) and C3 may be a potential drug target of GEPRB.

The NGF point-injection for treatment of the sound-perceiving nerve deafness and tinnitus in 68 cases.

OBJECTIVE: To observe the therapeutic effects of the point-injection with nerve growth factor (NGF) for the sound-perceiving nerve deafness and tinnitus. METHODS: The 140 cases in this series were randomly divided into a treatment group of 68 cases treated by NGF injection at the points of Yifeng (TE 17) and Wangu (GB 12), and a control group of 72 cases orally taking Xibiling and adenosine triphosphate (ATP) and intramuscular injection with VB1 and VB12. RESULTS: The total effective rate was 78.6% in the treatment group and 31.8% in the control group, with significant difference between the two groups (P<0.05). CONCLUSION: For treating nervous deafness and tinnitus, NGF point-injection may show good therapeutic effects, but inversely proportional to the illness course, age and the extent of hypoacusis.

Anakinra improves sensory deafness in a Japanese patient with Muckle-Wells syndrome, possibly by inhibiting the cryopyrin inflammasome.

Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory syndrome. Patients with MWS have a mutation in CIAS1, the gene encoding cryopyrin, a component of the inflammasome that regulates the processing of interleukin-1beta (IL-1beta). In this report we describe an 8-year-old Japanese girl with MWS who had symptoms of periodic fever, urticarial rash, conjunctivitis, arthropathy, and sensory deafness. Laboratory analysis of the patient's serum showed abnormally high concentrations of C-reactive protein, serum amyloid A, and IL-1beta, and she had a heterozygous mutation in the CIAS1 gene, with C-to-T transversion at nucleotide position 778, encoding an arginine-to-tryptophan mutation at position 260 (R260W). Mononuclear cells (MNCs) isolated from the patient secreted large amounts of IL-1beta, without stimulation, and were highly sensitive to muramyldipeptide and lipopolysaccharide. After treatment with anakinra, laboratory results normalized, and clinical symptoms, including sensory deafness, disappeared, while MNCs appeared to remain activated. Thus, our case suggests that anakinra possibly affects the cryopyrin inflammasome and markedly improves the clinical and laboratory manifestations of MWS.

Intraoperative brainstem auditory evoked potential pattern and perioperative vasoactive treatment for hearing preservation in vestibular schwannoma surgery.

OBJECTIVE: In vestibular schwannoma surgery, four different intraoperative brainstem auditory evoked potential (BAEP) patterns (stable BAEP, abrupt loss, irreversible progressive loss, reversible loss) can be identified and correlated with postoperative hearing outcome. Patients with reversible loss significantly benefit from postoperative vasoactive treatment consisting of hydroxyethyl starch and nimodipine. The present study investigates the treatment effect in the remaining three BAEP patterns. METHODS: A retrospective analysis was performed in 92 patients operated on for vestibular schwannoma between 1997 and 2005. Between 1997 and 2001, only patients with reversible loss of BAEP received vasoactive medication. Subsequently, all patients operated on between 2001 and 2005 received a 10 day course of therapy, regardless of the BAEP pattern. Serial audiological examinations before, after surgery and after 1 year were performed in all patients. RESULTS: All 30 patients with reversible loss of BAEP received medication, and postoperative hearing preservation was documented in 21 patients. All 13 patients with stable waves showed hearing preservation, regardless of treatment. In all 24 patients with abrupt loss and in all 25 patients with irreversible progressive loss, postoperative anacusis was documented, regardless of treatment. CONCLUSION: In patients with reversible loss of BAEP, a disturbed microcirculation of the cochlear nerve seems to be the underlying pathophysiological factor. In patients with abrupt or irreversible progressive loss, additional mechanical injury of nerve fibres determines hearing outcome. The study provides evidence that for the purpose of hearing preservation, only patients with reversible loss of BAEP benefit from vasoactive treatment.

[Prognosis and treatment of sudden sensorineural hearing loss with total and severe all frequency hearing loss].

OBJECTIVE: To evaluate the treatment and prognosis of sudden sensorineural hearing loss (SSHL) with total and severe all frequency hearing loss. METHODS: Sixty-two patients diagnosed as SSHL (0.25, 0.5, 1, 2, 4 kHz pure tone average > or = 56 dB) were studied from January 2003 to October 2006, in which 18 of them were treated with Xueshuantong (Panax notoginseng saponins) while 19 of them treated with steroid and Xueshuantong, and 25 of them treated with steroid, DF-521 and Xueshuantong. RESULTS: The hearing improvement rate of the patients treated with Xueshuantong was 22.2% (4/18) while the patients treated with steroid and Xueshuantong was 57.9% (11/19) and the patients treated with steroid, DF-521 and Xueshuantong was 68.0% (17/25). The good improvement rate of the patients treated with Xueshuantong was 5.6% (1/18) while the patients treated with steroid and Xueshuantong was 36.8% (7/19) and the patients treated with steroid, DF-521 and Xueshuantong was 60.0% (15/25). Over hearing improvement was significantly better in patients treated with steroid, defibrinogenation and Xueshuantong than in those treated with Xueshuantong only (P < 0.05). The patients of total hearing loss had a significantly higher vertigo rate and worse therapy effect. CONCLUSIONS: The combined therapy include high-dose corticosteroids and defibrinogenation therapy is effective for the patients with total deafness and severe all frequency hearing loss. The prognosis of patients with total hearing loss was poor.

Effects of nimodipine on salicylate ototoxicity.

The purpose of this study was to examine the effects of nimodipine on salicylate ototoxicity in guinea pigs. The compound action potential (CAP) was recorded at the round window, and the cochlear blood flow (CBF) was measured simultaneously from the lateral wall of the basal turn of the cochlea by laser Doppler flowmetry. After administration of salicylate (100 mg/kg), the CAP thresholds were significantly elevated, by 5 to 20 dB (p < .05), and the CBF was significantly decreased (p < .05). After administration of nimodipine (2 mg/kg), the CAP thresholds were unchanged, but the CBF had increased significantly (p < .05), while systemic blood pressure had decreased significantly (p < .05). Simultaneous administration of both salicylate (100 mg/kg) and nimodipine (2 mg/kg) resulted in significant elevation of the CAP thresholds (p < .05), while the CBF did not decrease. These results suggest that nimodipine prevents the decrease in CBF induced by salicylate, but that nimodipine does not prevent the deterioration in the CAP.

Does exogenous GM1 ganglioside enhance the effects of electrical stimulation in ameliorating degeneration after neonatal deafness?

This study examined the combined effects of administration of exogenous GM1 ganglioside and electrical stimulation on the cochlear nucleus (CN) of cats deafened neonatally by ototoxic drugs. Five normal hearing adult cats served as controls. Another 12 cats were deafened bilaterally by daily injections of neomycin sulfate (60 mg/kg) for 17-21 days after birth until auditory brainstem testing demonstrated profound hearing loss. Six of the deaf animals comprised the GM1 group, which received daily injections of GM1 ganglioside (30 mg/kg) for 28-38 days during the period after profound deafness was confirmed, and prior to receiving a cochlear implant. The non-GM1 group (n=6) received no treatment during this interim period. All the deafened animals underwent unilateral cochlear implantation at 6-9 weeks postnatal and received several months (mean duration, 32 weeks) of chronic electrical stimulation (4 h/day, 5 days/week). Stimulation was delivered by intracochlear bipolar electrodes, using electrical signals that were designed to be temporally challenging to the central auditory system. Results showed that in the neonatally deafened animals, both the GM1 and non-GM1 groups, the volume of the CN was markedly reduced (to 76% of normal), but there was no difference between the animals that received GM1 and those that did not. The cross sectional areas of spherical cell somata in both GM1 and non-GM1 groups also showed a highly significant reduction in size, to < or =75% of normal after neonatal deafening. Moreover, in both the GM1 and non-GM1 groups, the spherical cells in the CN ipsilateral to the implanted cochlea were significantly larger (6%) than cells in the control, unstimulated CN. Again, however, there was no significant difference between the GM1 group and the non-GM1 group in spherical cell size. These results contrast sharply with previous reports that exogenous GM1 prevents CN degeneration after neonatal conductive hearing loss and partially prevents spiral ganglion cell degeneration when administered immediately after ototoxic drug deafening in adult animals. Taken together, findings to date suggest that GM1 may be effective in preventing degeneration only if the GM1 is administered immediately at the time hearing loss occurs.

Treatment of 100 cases of nerve deafness with injectio radix salviae miltiorrhizae.

100 cases of nerve deafness were treated with Injectio Radix Salviae Miltiorrhizae by i.v. drip, and additional drugs that promoted blood circulation were used according to symptom differentiation. Results were 28 cases cured, 45 cases improved, and 27 cases failed, for a total effective rate of 73%.

[Clinical and experimental use of ATP in internal ear diseases]. / ATP-Anwendung bei Innenohrerkrankungen in der Klinik und im Experiment

Intra-arterial ATP infusions with glucose and hyaluronidase were successful in 267 patients suffering from various inner ear disturbances but particularly in sudden deafness. Good clinical results were noted not only in early-treated but also in later cases. Recently, we have also used ATP with hyperbaric oxygen, being successful in cases which were previously treated without improvement. Investigations in guinea-pigs, using artificial hypoxia as a model for human sudden deafness failed because the patterns are not the same. So long as an increase of ATP in the cochlear cells cannot be demonstrated after the i.a. infusions, only an unspecific mechanism can be held responsible for the undoubted clinical successes.