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Laron Syndrome (LS), (OMIM# 262500), a rare recessively inherited disease caused by deletions or mutations of the GH receptor, gene characterized by dwarfism with low or undetectable serum IGF-I in the presence of high serum GH. In addition to dwarfism, the IGF-I deficiency leads to metabolic abnormalities including aberrations in protein biosynthesis and homeostasis. The only available treatment for LS patients is (r)IGF-I administration. The present study was aimed to determine the plasma concentrations of specific amino acids and their metabolites in the blood of untreated and IGF-I-treated LS patients. The study involved a total of 10 LS patients (3 untreated and 7 treated), 2 heterozygote mothers and 3aged subjects. Forty healthy boys and girls served as controls. The analysis of amino acids and their metabolites was performed using the LC-MS/MS analysis and Waters Acc-Q Tag ultra-derivatization kit. Serum IGF-I levels were measured by a one-step sandwich chemiluminescence immunoassay. The results revealed that long-term IGF-I deficiency in LS patients led to abnormal changes in the plasma amino acids metabolism, such as low levels of plasma citrulline, sarcosine and taurine that increased upon IGF-I replacement. The plasma amino acid levels of the heterozygous family members resembled those of the untreated LS patients, whereas the pattern in the 2 double heterozygote sisters previously treated with IGF-I resembled that of the presently IGF-I-treated patients. In addition, plasma ɑ-amino adipic acid levels were elevated in both untreated and IGF-I-treated patients. In summary our data revealed that LS patients, a condition associated with congenital IGF-I deficiency, have an abnormal plasma amino acid metabolism that is partially restored by IGF-I treatment., Competing Interests: Declaration of Competing Interest Authors have nothing to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Megakaryocytes (MKs), the precursor cells for platelets, migrate from the endosteal niche of the bone marrow (BM) toward the vasculature, extending proplatelets into sinusoids, where circulating blood progressively fragments them into platelets. Nonmuscle myosin IIA (NMIIA) heavy chain gene (MYH9) mutations cause macrothrombocytopenia characterized by fewer platelets with larger sizes leading to clotting disorders termed myosin-9-related disorders (MYH9-RDs). MYH9-RD patient MKs have proplatelets with thicker and fewer branches that produce fewer and larger proplatelets, which is phenocopied in mouse Myh9-RD models. Defective proplatelet formation is considered to be the principal mechanism underlying the macrothrombocytopenia phenotype. However, MYH9-RD patient MKs may have other defects, as NMII interactions with actin filaments regulate physiological processes such as chemotaxis, cell migration, and adhesion. How MYH9-RD mutations affect MK migration and adhesion in BM or NMIIA activity and assembly prior to proplatelet production remain unanswered. NMIIA is the only NMII isoform expressed in mature MKs, permitting exploration of these questions without complicating effects of other NMII isoforms. Using mouse models of MYH9-RD (NMIIAR702C+/-GFP+/-, NMIIAD1424N+/-, and NMIIAE1841K+/-) and in vitro assays, we investigated MK distribution in BM, chemotaxis toward stromal-derived factor 1, NMIIA activity, and bipolar filament assembly. Results indicate that different MYH9-RD mutations suppressed MK migration in the BM without compromising bipolar filament formation but led to divergent adhesion phenotypes and NMIIA contractile activities depending on the mutation. We conclude that MYH9-RD mutations impair MK chemotaxis by multiple mechanisms to disrupt migration toward the vasculature, impairing proplatelet release and causing macrothrombocytopenia.

Objective: EAST syndrome comprises of epilepsy, ataxia, sensorineural deafness, and tubulopathy. It is caused by a mutation in KCNJ10 gene. Less than thirty cases have been reported in the literature with emphasis on genetic mutation and renal tubulopathy. In this article, our goal is to present a comprehensive description of epilepsy and its management. A literature review is also presented to consolidate and compare our findings with the previously reported cases., Methods: Retrospective chart review was done to collect patient data. Research clinic was organized to obtain missing data. Molecular genetic testing was done at the CGC Genetics Laboratory. Electroencephalogram (EEG) was done for all patients and interpreted by a pediatric epileptologist and brain MRI was reviewed by a pediatric neuroradiologist. Developmental assessment was done by a developmental pediatrician using Griffiths Mental Developmental Scale., Results: In patients with EAST syndrome, seizure is the first symptom occurring around 3-4 months of age. Most common seizure type was generalized tonic clonic (GTC). Usually, the seizures were brief lasting <3 min but few patients also presented with status epilepticus especially when the medication was weaned. Carbamazepine (CBZ) was found to be effective in most cases. Lamotrigine (LTG), valproic acid (VPA), and topiramate (TPM) were also found to be helpful. Routine EEGs were usually normal or showed non-specific findings. In few patients, EEG showed background slowing. Brain MRI revealed hyperintensity in the dentate nuclei in some patients, and quantitative volumetric analysis studies showed volume loss in different regions of the brain especially the cerebellum. All our five patients have the same homozygous c.170C>T (p.Thr57Ile) missense mutation in KCNJ10 gene., Conclusion: This article provides the readers with an understanding of the natural history of epilepsy in this syndrome to help in early recognition, avoid unnecessary investigations, and provide the best treatment for seizures. It also helps the physicians to share the prognosis of this rare syndrome with the parents., (Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Pediatric retinal detachments occur rarely, and thus may be easily missed. Without treatment, this condition leads to permanent vision loss. Patients with Stickler syndrome, an inherited disorder of collagen synthesis, are more likely to have retinal detachments than the general population., Case Report: We present a case of a 9-year-old boy who presented to the Emergency Department with blurry vision, and who was subsequently diagnosed with bilateral retinal detachments. The patient underwent successful operative intervention. He was eventually determined to have Stickler syndrome. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important for emergency physicians to recognize pediatric visual problems such as retinal detachment, as their presentations may be unusual, and delay of definitive care could result in lifelong visual impairment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Fabry disease (FD) is a lysosomal storage disorder (LSD) that involves the cochleovestibular system. Tinnitus and progressive sensorineural hearing loss are frequent complains. A stabilization of hearing function has been reported with enzyme replacement therapy (ERT). This study aims to characterize the inner ear involvement, identify factors associated to hearing loss and evaluate the effect of ERT on the hearing function of FD patients., Methods: We reviewed the clinical records of patients with confirmed diagnosis of FD followed in a Reference Centre on LSD in the North of Portugal., Results: We included a total of 122 patients with a mean age of 47.1 ± 17.6 years and 48.3% males. Hearing loss was reported by 26.2% of the patients and 23.0% mentioned tinnitus. Pure tone audiometry revealed sensorineural hearing loss in 36.9% of the cases. FD patients presented worse age-adjusted hearing thresholds in all analysed frequencies compared to the normal population (p = .001). Patients with hearing loss presented a significantly higher value of microalbuminuria (p = .001) and a higher frequency of acroparesthesias (p = .032). Patients presented a comparable hearing level one year after starting ERT (p = .384)., Conclusions: In FD, hearing loss is common and age-matched hearing thresholds by frequency are worse than in the general population. Hearing loss was associated to the presence of acroparesthesias and higher values of microalbuminuria. Hearing loss stabilized in patients under ERT. A careful cochleo-vestibular evaluation should be part of the clinical assessment of FD., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

There is a general consensus that many children and adults with dyslexia and/or specific language impairment display deficits in auditory processing. However, how these deficits are related to developmental disorders of language is uncertain, and at least four categories of model have been proposed: single distal cause models, risk factor models, association models, and consequence models. This study used children with mild to moderate sensorineural hearing loss (MMHL) to investigate the link between auditory processing deficits and language disorders. We examined the auditory processing and language skills of 46, 8-16year-old children with MMHL and 44 age-matched typically developing controls. Auditory processing abilities were assessed using child-friendly psychophysical techniques in order to obtain discrimination thresholds. Stimuli incorporated three different timescales (µs, ms, s) and three different levels of complexity (simple nonspeech tones, complex nonspeech sounds, speech sounds), and tasks required discrimination of frequency or amplitude cues. Language abilities were assessed using a battery of standardised assessments of phonological processing, reading, vocabulary, and grammar. We found evidence that three different auditory processing abilities showed different relationships with language: Deficits in a general auditory processing component were necessary but not sufficient for language difficulties, and were consistent with a risk factor model; Deficits in slow-rate amplitude modulation (envelope) detection were sufficient but not necessary for language difficulties, and were consistent with either a single distal cause or a consequence model; And deficits in the discrimination of a single speech contrast (/bɑ/ vs /dɑ/) were neither necessary nor sufficient for language difficulties, and were consistent with an association model. Our findings suggest that different auditory processing deficits may constitute distinct and independent routes to the development of language difficulties in children., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. It is the mildest form known to date of peroxisome biogenesis disorder caused by hypomorphic mutations of PEX1 and PEX6 genes. We report on a second Moroccan family with Heimler syndrome with early onset, severe visual impairment and important phenotypic overlap with Usher syndrome. The patient carried a novel homozygous missense variant c.3140T > C (p.Leu1047Pro) of PEX1 gene. As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with HS, patients with SNHL and retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the patterns and mechanisms of audiovestibular impairments associated with intracranial hypotension., Methods: We had consecutively recruited 16 patients with intracranial hypotension at the Neurology Center of Pusan National University Hospital for two years. Spontaneous, gaze-evoked, and positional nystagmus were recorded using 3D video-oculography in all patients, and the majority of them also had pure tone audiometry and bithermal caloric tests., Results: Of the 16 patients, five (31.3%) reported neuro-otological symptoms along with the orthostatic headache while laboratory evaluation demonstrated audiovestibular impairments in ten (62.5%). Oculographic analyses documented spontaneous and/or positional nystagmus in six patients (37.5%) including weak spontaneous vertical nystagmus with positional modulation (n=4) and pure positional nystagmus (n=2). One patient presented with recurrent spontaneous vertigo and tinnitus mimicking Meniere's disease, and showed unidirectional horizontal and torsional nystagmus with normal head impulse tests during the attacks. Bithermal caloric tests were normal in all nine patients tested. Audiometry showed unilateral (n=6) or bilateral (n=1) sensorineural hearing loss in seven (53.8%) of the 13 patients tested., Conclusions: Intracranial hypotension frequently induces audiovestibular impairments. In addition to endolymphatic hydrops and irritation of the vestibulocochlear nerve, compression or traction of the brainstem or cerebellum due to loss of CSF buoyancy may be considered as a mechanism of frequent spontaneous or positional vertical nystagmus in patients with intracranial hypotension., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Hereditary spastic paraplegia (HSP) includes a group of diseases characterized by progressive spastic weakness of the lower limbs (pure forms) with possible additional signs (complicated forms). The SPG10 form is due to alteration in the kinesin1A gene (KIF5A) that encodes the neuronal kinesin heavy chain, a protein required for the anterograde axonal transport. We performed clinical, neurophysiological and molecular studies in two siblings affected by AD-HSP complicated by deafness. The screening of the KIF5A gene revealed the novel mutation p.Leu259Gln in two affected siblings and in their father with a pure form of HSP., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: The Stickler syndromes are the most common causes of inherited and childhood retinal detachment; however, no consensus exists regarding the effectiveness of prophylactic intervention. We evaluate the long-term safety and efficacy of the Cambridge prophylactic cryotherapy protocol, a standardized retinal prophylactic treatment developed to prevent retinal detachment arising from giant retinal tears in type 1 Stickler syndrome., Design: Retrospective comparative case series., Participants: Four hundred eighty seven patients with type 1 Stickler syndrome., Methods: Time to retinal detachment was compared between patients who received bilateral prophylaxis and untreated controls, with and without individual patient matching. Patients receiving unilateral prophylaxis (after fellow eye retinal detachment) were similarly compared with an appropriate control subgroup. Individual patient matching ensured equal age and follow-up between groups and that an appropriate control (who had not suffered a retinal detachment before the age at which their individually matched treatment patient underwent prophylactic treatment) was selected. Matching was blinded to outcome events. Individual patient matching protocols purposely weighted bias against the effectiveness of treatment. All treatment side effects are reported., Main Outcome Measures: Time to retinal detachment and side effects occurring after prophylactic treatment., Results: The bilateral control group (n = 194) had a 7.4-fold increased risk of retinal detachment compared to the bilateral prophylaxis group (n = 229) (hazard ratio [HR], 7.40; 95% confidence interval [CI], 4.53-12.08; P<0.001); the matched bilateral control group (n = 165) had a 5.0-fold increased risk compared to the matched bilateral prophylaxis group (n = 165) (HR, 4.97; 95% CI, 2.82-8.78; P<0.001). The unilateral control group (n = 104) had a 10.3-fold increased risk of retinal detachment compared to the unilateral prophylaxis group (n = 64) (HR, 10.29; 95% CI, 4.96-21.36; P<0.001); the matched unilateral control group (n = 39) had a 8.4-fold increased risk compared to the matched unilateral prophylaxis group (n = 39) (HR, 8.36; 95% CI, 3.24-21.57; P<0.001). No significant long-term side effects occurred., Conclusions: In the largest global cohort of type 1 Stickler syndrome patients published, all analyses indicate that the Cambridge prophylactic cryotherapy protocol is safe and markedly reduces the risk of retinal detachment., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the use of swept-source optical coherence tomography (OCT) for measuring the area and degree of peripheral anterior synechia (PAS) involvement in patients with angle-closure glaucoma., Design: Cross-sectional study., Participants: Twenty-three eyes with PAS (detected by indentation gonioscopy) from 20 patients with angle-closure glaucoma (20 eyes had primary angle-closure glaucoma and 3 eyes had angle-closure glaucoma secondary to chronic anterior uveitis [n = 2] and Axenfeld-Rieger syndrome [n = 1])., Methods: The anterior chamber angles were evaluated with indentation gonioscopy and imaged by swept-source OCT (Casia OCT, Tomey, Nagoya, Japan) in room light and in the dark using the "angle analysis" protocol, which was composed of 128 radial B-scans each with 512 A-scans (16-mm scan length). The area and degree of PAS involvement were measured in each eye after manual detection of the scleral spur and the anterior irido-angle adhesion by 2 masked observers. The interobserver variability of the PAS measurements was calculated., Main Outcome Measures: The agreement of PAS assessment by gonioscopy and OCT, the area and the degree of PAS involvement, and the intraclass correlation coefficient (ICC) of interobserver PAS measurements., Results: The area of PAS (mean ± standard deviation) was 20.8 ± 16.9 mm(2) (range, 3.9-74.9 mm(2)), and the degree of PAS involvement was 186.5 ± 79.9 degrees (range, 42-314 degrees). There was no difference in the area of PAS (P = 0.90) and the degree of PAS involvement (P = 0.95) between images obtained in room light and in the dark. The interobserver ICCs were 0.99 (95% confidence interval [CI], 0.98-1.00) for the area of PAS and 0.99 (95% CI, 0.97-1.00) for the degree of PAS involvement. There was good agreement of PAS assessment between gonioscopy and OCT images (kappa = 0.79; 95% CI, 0.67-0.91)., Conclusions: Swept-source OCT allows visualization and reproducible measurements of the area and degree of PAS involvement, providing a new paradigm for evaluation of PAS progression and risk assessment for development of angle-closure glaucoma., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate cardiovascular risk factors and pre-clinical atherosclerosis in subjects affected by idiopathic sudden sensorineural hearing loss (ISSHL)., Methods: In this study, 29 ISSHL patients and 29 healthy controls were evaluated. All of the patients underwent a complete audiovestibular and clinical evaluation. Carotid intima-media thickness (C-IMT) and flow-mediated dilation (FMD) of the brachial artery were assessed as early markers of atherosclerosis., Results: Our results showed that FMD was significantly lower in the ISSHL patients than in the controls (5.6 ± 1.6% vs. 7.7 ± 3.7%, p < 0.01). Moreover, the total cholesterol and low density lipoprotein cholesterol were significantly higher in the ISSHL patients than in the controls (p < 0.05). The two groups did not differ with regards to C-IMT and other cardiovascular risk factors. Vestibular involvement was shown to be associated with lower FMD values (4.1 ± 1.7% vs. 5.8 ± 1.5%, p < 0.05). No relationship was found between C-IMT and vestibular involvement. Finally, multiple logistic regression highlighted the finding that only FMD values seemed to predispose individuals to developing ISSHL (p = 0.03, OR: 1.4)., Conclusions: ISSHL seemed to be associated with vascular endothelial dysfunction and an increased cardiovascular risk, which supports the hypothesis of a vascular aetiology for this disease., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disease characterized by sensorineural hearing loss and multiple cranial nerve palsies, usually involving the VIIth and IXth to XIIth cranial nerves. We describe the clinical and pathological features of a 33-year-old woman with BVVLS. The patient developed progressive exertional dyspnea, with clinical and laboratory findings of right-sided heart failure and pulmonary hypertension. She developed status epilepticus in the setting of cardiac deterioration and respiratory infection, and died of cardiogenic and septic shock. Autopsy disclosed bilateral neuronal loss and gliosis in the inferior colliculi, locus coeruleus and facial and vestibular nuclei. Cor pulmonale is a complication of hypoventilation-induced hypoxia and hypercapnia and had not yet been reported in BVVLS., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Galactosemia and congenital Rogers syndrome or thiamine-responsive megaloblastic anemia are 2 rare inherited metabolic diseases. The combination of the 2 diseases has never been reported in the literature. We describe the case of an infant followed for congenital galactosemia since the age of 8 days, with thiamine-responsive megaloblastic anemia diagnosed at the age of 10 months. Galactosemia's symptoms occur in the first 2 weeks of life with severe liver disease. Total eviction of the galactose allows complete regression and prevention of early symptoms but does not prevent late complications. Rogers syndrome associates megaloblastic anemia, deafness, and diabetes mellitus that begin in childhood. Supplementation with thiamine allows regression of anemia and prevents the onset of diabetes at least until adolescence., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Neurofilament (NF) is one of the major cytoskeleton proteins of neurons. We investigated the concentrations of the heavy subunit of NF (NF-H) in cerebrospinal fluid (CSF) as biomarkers of neuronal injury in bacterial meningitis. Concentrations of NF-H in CSF of 26 children with bacterial meningitis and in 16 control subjects were measured by ELISA. The CSF NF-H levels were elevated in 22 of the 26 children (85%) with bacterial meningitis. The peak CSF NF-H level occurred at a median period of 10.5 days after onset of illness (range, 1 to 35 days). The peak CSF NF-H levels of the patients with neurological sequelae (n=4) were significantly higher than those without sequelae (n=22) (7.06 vs. 2.46 ng/mL as median, p=0.048). There was no significant difference in CSF NF-H levels between patients with and without severe neurological sequelae up to day 14 of illness, but the CSF NF-H levels in patients with sequelae were significantly higher than in those without sequelae after day 14 of illness (2.04 vs. 1.19 ng/mL as median, p=0.024). We suggest that neuronal injury occurs in bacterial meningitis regardless of the presence or absence of neurological sequelae.

Gap junctions, which consist of connexins, are intercellular channels that mediate rapid intercellular communication. In the skin, connexins are involved in the regulation of epidermal growth and differentiation. GJB2 encodes connexin26, which is an important skin-expressed gap junction protein. Mutations in GJB2 cause a wide variety of unique disorders, but despite extensive research, their mechanisms of action are poorly understood. The identification of novel diseases caused by mutations in GJB2 may help to illuminate the genotype-phenotype correlation and elucidate the function of different regions of the protein. Here, we report the first account of a family with a GJB2 missense mutation in the second extracellular domain (p.Ser183Phe) that causes skin abnormalities in addition to sensorineural hearing loss. Using fluorescent connexin26-EGFP fusion proteins, we showed that the mutation induces a partial protein transport defect that cannot be rescued by wild-type protein. Dye-transfer experiments using a parachute assay revealed channel functionality. Although p.Ser183Phe affects the second extracellular domain, mutations in the first extracellular domain also lead to focal palmoplantar keratoderma and likewise perturb protein transport in a dominant-negative manner. Therefore, we hypothesize that focal palmoplantar keratoderma in gap junction skin disease may be specifically associated with connexin trafficking defects as well as with mutations affecting its extracellular domains, thus broadening the spectrum of GJB2-associated diseases.

Alström syndrome is among the rarest genetic disorders described in the medical literature. It is characterized by retinal pigment degeneration, obesity, sensorineural deafness, non-insulin-dependent diabetes mellitus, progressive chronic nephropathy, cardiomyopathy, and hepatic dysfunction. Hepatic inflammation and fibrosis, which leads to cirrhosis, portal hypertension, and liver failure, is the final pathway of the hepatopathy in Alström syndrome. We report a case of Alström syndrome with particular emphasis on hepatic findings.

The clinical observation that multichannel intra-cochlear cochlear implants have a suppressive effect on tinnitus in profoundly deaf patients is supported by many published studies. Whilst there are problems with that literature, specifically in the way that tinnitus outcomes are reported, the finding of tinnitus benefit is consistent. New developments in this area include the use of functional imaging to investigate tinnitus suppression by cochlear implant stimulation and consideration of a reported worsening effect on tinnitus of binaural implantation. Following work on hearing aids, it is suggested that optimization of the benefit of monaural cochlear implantation on tinnitus in a tinnitus-specific electrode configuration might include the use of a low knee point compression algorithm and disabling directional microphone function: these strategies are potentially also of benefit in patients whose tinnitus results in sleep disturbance. Opportunities for stimulation strategies for tinnitus suppression that bypass speech processing are also identified.

Susac's syndrome is a vasospastic disease resulting from bilateral microangiopathy of the brain, cochlea and retina. It is characterized by encephalopathy, bilateral sensorineural fluctuating hearing loss and visual loss. It is very uncommon and usually affects women during young adulthood. Since all three symptoms of the triad may not be present, the clinical diagnosis is difficult. Therefore, neuroimaging, particularly magnetic resonance imaging, has an important role in establishing the diagnosis. In this case report, we present a young woman who had all the symptoms of Susac's syndrome. This is the first Susac's syndrome case reported in Turkey.

Specific reading disability (SRD) is now widely recognised as often being caused by phonological processing problems, affecting analysis of spoken as well as written language. According to one theoretical account, these phonological problems are due to low-level problems in auditory perception of dynamic acoustic cues. Evidence for this has come from studies showing poor discrimination of frequency-modulated from unmodulated tones. We measured frequency modulation detection limens (FMDLs) in 16 children with specific reading disability (SRD group), 16 children with mild to moderate hearing loss (SNH group) and 16 age-matched controls (CA group) aged 8-14. To obtain information about possible mechanisms used in frequency modulation detection, FMDLs were measured at modulation rates of 2 and 20 Hz, both in the absence and the presence of amplitude modulation, intended to force listeners to rely, if possible, upon phase-locking cues. Although both the SNH and SRD groups showed a trend for elevated FMDLs at both 2 and 20 Hz, these differences reached statistical significance for the SNH group alone. However, the SNH group had no evidence of literacy impairments. This study thus shows that impairments in perceiving dynamically modulated auditory stimuli do not necessarily lead to difficulty in learning to read.

We encountered a 10-year-old girl with fluctuating sensorineural hearing loss, episodic headache, and white matter stroke. Strenuous exercise, febrile illness, and general anesthesia all temporarily worsened hearing. Audiologic findings were asymmetric: left-sided retrocochlear dysfunction consistent with auditory neuropathy contrasted with cochlear hearing loss in the right ear. Platelets obtained during a headache-free period showed excessive responsiveness to collagen in vitro, while episodic elevations of thromboxane B(2) and thrombin-antithrombin III complex were noted in blood sampled during headache. Treatment of hyperaggregability of platelets with aspirin and antioxidant vitamins relieved headache, while adenosine triphosphate administration improved hearing thresholds. In this patient, hearing impairment and white matter strokes appeared to respectively related to impaired blood flow to the cochlea and white matter caused by platelet dysfunction triggered by physiologic stresses.

Background: In recent years there has been a significant increase in the diagnosis of sudden sensorineural hearing loss (SSHL) in western, countries with an incidence of 20 of 100,000 people affected every year. No clear causes for this disease have been found thus far, but cochlear ischemia has been hypothesized in patients in whom an infectious episode or acoustic neurinoma have been excluded., Objectives: The aim of this case-control study was to investigate a number of acquired and inherited thrombophilic risk factors [antithrombin, protein C and S; factor V (FV) Leiden, FII polymorphism; lupus anticoagulant (LA); anticardiolipin (aCL) antibodies; fasting homocysteine (Hcy); lipoprotein(a) (Lp(a)); plasminogen activator inhibitor-1 (PAI-1)] in addition to cardiovascular risk factors in patients with idiopathic SSHL (ISSHL)., Patients and Methods: We investigated 155 patients (67 male/88 female; age: 55 (range 19-79 years) with a diagnosis of ISSHL within 30 days from the onset of symptoms, and 155 controls (67 male/88 female; age 54 (range 19-78 years). Fasting Hcy levels were significantly higher in patients than in controls [11.6 (6.7-60) micromol/L vs. 8.7 (5.0-24) micromol/L] as well as PAI-1 levels [19 (2-95) mg/dL vs. 14.5 (4.0-87) mg/dL]. Lupus anticoagulant was present in 13 of 155 (8.4%) patients; 20 patients (12.9%) had positivity of aCL (four IgM and 16 IgG). In no patient was a deficiency of physiological clotting inhibitors antithrombin, protein C and protein S found. No significant differences between patients and controls were observed for Lp(a) plasma levels [111 (1-1146) mg/L vs. 103 (11-695) mg/L] and for the presence of FV Leiden (4.5% vs. 4.5%) and FII variant G20210A (3.8% vs. 3.2%)., Results and Conclusions: Independent risk factors for ISSHL at the multivariate analysis (adjusted for age, sex and the traditional cardiovascular risk factors) were the positivity of aCL: OR 5.6 (95% CI 2.0-15.3); cholesterol levels within the second and third tertiles (with respect to the first tertile): T2 = OR 4.8 (95% CI 1.9-12.6)/T3 = OR 19 (95% CI 7-50.1); PAI-1 and Hcy levels within the third tertile (with respect to the first tertile): OR 20 (95% CI 7.8-78) and OR 4.0 (95% CI 2.0-8.1), respectively. These preliminary data suggest that hypercholesterolemia, hyperhomocysteinemia, elevated PAI-1 levels and anticardiolipin antibodies are associated with ISSHL, so indirectly supporting the hypothesis of a vascular occlusion in the pathogenesis of the disease.

A 44-year-old man was admitted to our hospital because of congestive heart failure. He had various symptoms caused by insulin-dependent diabetes mellitus, sensorineural deafness, Wolff-Parkinson-White syndrome and cardiomyopathy associated with mitochondrial DNA point mutation A3243G. Echocardiography had showed symmetrical hypertrophy of the left ventricular wall and normal cardiac function (ejection fraction 55%) at age 32 years. However, echocardiography showed cardiac transformation, consisting of posterior wall thinning and significantly reduced cardiac function (ejection fraction 11%), at age 44 years. Electrocardiography showed lowered R-wave in the chest leads and QRS widening. Both lactic acid and pyruvate serum levels were increased. Mitochondrial respiratory enzyme analysis in gastrocnemius muscle tissue indicated a partial deficiency of rotenone-sensitive NADH cytochrome C reductase. He was discharged from our hospital, and medically treated with coenzyme Q10(30 mg/day). He had no progression of cardiomyopathy or congestive heart failure. However, he suddenly died of lactic acidosis at age 47 years.

Objective: To determine the severity of visual acuity impairment in patients, age 45 years or older, with either isolated or identifiable genetic subtypes of retinitis pigmentosa (RP) and Usher syndrome., Design: Multicenter, retrospective, cross-sectional analysis., Participants: Visual acuity data were obtained on 999 patients with different genetic subtypes of RP and Usher syndrome, age 45 years or older, from 4 major eye care centers in the United States., Intervention: The best-corrected visual acuity obtained on these patients from the eye with better vision on their most recent visit was used for the analysis., Main Outcome Measure: Best-corrected visual acuity was the main parameter analyzed for the study, and it was obtained with Snellen or Feinbloom low vision charts or with a B-VAT II monitor (Mentor)., Results: The final analyses were done on 982 patients (17 patients with a sector form of RP were analyzed separately). Of the 982 patients, 506 (52%) had a visual acuity of 20/40 or better, and 678 (69%) had a visual acuity of 20/70 or better in at least one eye. There were 243 (25%) patients who had a visual acuity of 20/200 or worse in both eyes. Five (0.5%) patients had no light perception in both eyes. The odds ratio for any patient having a visual acuity of 20/200 or worse in this population was 1.4 for each difference of 10 years of age. Similarly, the odds ratio of a patient having a visual acuity of 20/40 or better in at least one eye was 0.95 for a 10-year age difference., Conclusions: In this large population of patients with RP and Usher syndrome from four centers, it was rare for such patients to lose all vision in both eyes. One fourth of the patients had a visual acuity of 20/200 or worse in both eyes, and more than half of the population had a visual acuity of 20/40 or better in at least one eye. These data can be used to counsel such patients on the extent of potential visual acuity impairment from their disease.

Keratitis, ichthyosis and deafness are the dominant signs of KID syndrome. The lesions involving cornea, epidermis and internal ear are probably the result of a congenital ectodermal abnormality. Associated signs such as increased sensitivity to infections, and dermoskeleton dystrophies are also useful for the diagnosis. There are no specific biological signs. Most cases are sporadic but familial cases have been described with unclear mode of inheritance. Treatment is disappointing. Thus management mainly relies upon early detection of complications.

Comorbidity of sensorineural hearing deficits and both depressive states and dementia in late life provided the rationale for this investigation. Cognitively intact geriatric major depressives (n = 43) were assessed for depressive symptoms, cognitive performance, and delusions while symptomatic, and following treatment, when audiometry was performed. Late-onset depressed patients (LOD) had more hearing deficits compared to early-onset depressives (EOD). Age at onset of depression was found to have a significant effect on Pure-Tone Thresholds for 0.5-4.0 kHz and on Word Recognition in Noise in the better ear (0.001 < p < 0.031; ANCOVA). Criteria for neural deficit were met more frequently in LODs compared to EODs, although this was attributable to the older age of LOD. Additional investigations can contribute to our understanding of the relationship between forms of hearing loss and both the course of geriatric depression and its relationship to dementia.

Twenty-three members of a 96-member family exhibited an autosomal dominant disorder which has not previously been described. This disorder involves progressive optic atrophy, abnormal electroretinography without retinal pigment changes, and progressive sensorineural hearing loss usually evident in the first or second decade of life. In midlife, ptosis, ophthalmoplegia, dystaxia, and a nonspecific myopathy occur.

Autosomal dominant optic atrophy is an abiotrophy with an insidious onset in the first decade of life. The clinical features of 31 individuals in six pedigrees are detailed in this study. These data suggest that here is considerable intrafamilial and interfamilial expression of dysfunction. Moreover, asymmetry of the visual loss in not unusual. An unexpected result of this study is the previously unreported frequent association of a neural hearing loss with this disorder.