Suicidal ideation in people with tinnitus: a systematic review and meta-analysis.

OBJECTIVE: Tinnitus is associated with a variety of cognitive, psychosocial and psychiatric disorders, and may contribute to suicidality. However, the prevalence of suicidal ideation (SI) in tinnitus populations has not previously been systematically reviewed. METHOD: Medline, Embase and PsychInfo were searched in August 2020 to identify studies that assessed suicidal ideation in people aged 16 years and above with subjective tinnitus. RESULTS: Six cross-sectional studies were included, representing 7192 tinnitus sufferers across 4 countries. The pooled prevalence of suicidal ideation in tinnitus populations was 20.6 per cent (95 per cent confidence interval, 10.8-30.3 per cent; I2 = 88 per cent). Two studies included a control population, in which the prevalence of suicidal ideation was significantly lower. The quality of included studies was variable. CONCLUSION: It is not possible to arrive at any reasonable conclusion given the lack of quality studies, meaning the pooled prevalence should be interpreted very cautiously. Suicidal ideation may be more prevalent in tinnitus populations. Further large-scale epidemiological research investigating this relationship is needed, which may help psychiatric risk stratification.

Sediment Characterization at the Equatorial Mid-Atlantic Ridge From P-to-S Teleseismic Phase Conversions Recorded on the PI-LAB Experiment.

Accurate marine sediment characteristics, for example, thickness and seismic velocity, are important for constraining sedimentation rates with implications for climate variations and for seismic imaging of deeper structures using ocean bottom seismic deployments. We analyze P-to-S seismic phase conversions from the sediment-crust boundary recorded by the Passive Imaging of the Lithosphere-Asthenosphere Boundary (PI-LAB) experiment to infer the sediment thickness across the Mid-Atlantic Ridge covering 0- to 80-Myr-old seafloor. We find P d s-P delay times of 0.04-0.37 s, or 5- to 82-m thickness. Sediment thickness increases with age. Thickness agrees with global estimates for young (<15-20 Myr) seafloor but is thinner on older lithosphere. Our result may represent a lower limit on sediment thickness, given that several of our stations are on topographic highs. The sedimentation rate decrease observed from 5 to 1.2 mm/kyr at ∼10 Myr suggests a recent increase in productivity related to climate change, eolian dust fluxes, and/or biogenic marine activity.

Long-term trajectories of cognitive deficits in schizophrenia: A critical overview.

BACKGROUND: Cognitive disturbances are widely pronounced in schizophrenia and schizophrenia spectrum disorders. Whilst cognitive deficits are well established in the prodromal phase and are known to deteriorate at the onset of schizophrenia, there is a certain discrepancy of findings regarding the cognitive alterations over the course of the illness. METHODS: We bring together the results of the longitudinal studies identified through PubMed which have covered more than 3 years follow-up and to reflect on the potential factors, such as sample characteristics and stage of the illness which may contribute to the various trajectories of cognitive changes. RESULTS: A summary of recent findings comprising the changes of the cognitive functioning in schizophrenia patients along the longitudinal course of the illness is provided. The potential approaches for addressing cognition in the course of schizophrenia are discussed. CONCLUSIONS: Given the existing controversies on the course of cognitive changes in schizophrenia, differentiated approaches specifically focusing on the peculiarities of the clinical features and changes in specific cognitive domains could shed light on the trajectories of cognitive deficits in schizophrenia and spectrum disorders.

A User and Their Family's Perspective of The Use of a Low-Tech Vs A High-Tech AAC System.

This qualitative case study describes a 9-year-old child, diagnosed with homonymous hemianopia, left side weakness and seizures that has been followed by Access to Communication and Technology Unit in Malta for 5 years. The child previously used a communication book and now uses an iPad as a speech generating device. A semi-structured interview was utilised with the parent to explore preference for each AAC system and the reasons for it. The impact of each AAC system on the family and on the child's communication skills, and perceived barriers in the implementation of the AACs were also explored. The child's own experience using the AAC systems was also investigated using a structured interview format. Talking Mats was used to support the child's understanding of the questions and to explore her perspectives on the two AAC systems using Yes-No responses. The parent interview was analysed thematically and represented visually using a thematic network. This was compared with child responses. Four organising themes emerged including barriers, benefits, facilitators, and expectations. Specific barriers included self-funding in order to provide the child with the best fit high-tech AAC. Perceived benefits for both AAC systems were that it increased her communicative intent. The child's mother perceived access to increased vocabulary and capacity for sentence building, operational autonomy as well as voice output as a benefit of the SGD. The child's results indicated a preference for the high-tech AAC because she found it easier to navigate than the low-tech AAC.

An unusual cause of chest pain in a young man: bronchogenic cysts and their cardiac manifestations.

We report a case of a 24-year-old man who presented with chest pain and electrocardiographic evidence of myocardial ischaemia. An abnormal structure located behind the heart on the urgent transthoracic echocardiogram and a computed tomography scan of the mediastinum led to prompt surgery with eventual resection of the lesion. The histology revealed fragments of connective tissue covered by squamous epithelium and ciliated epithelium, consistent with a bronchogenic cyst. The case study is accompanied by a literature review of the pathogenesis, diagnosis and management of bronchogenic cysts and their association with cardiac symptoms.

Identifying and treating patients with suboptimal responses.

Multiple sclerosis (MS) is an immune-mediated neurologic disease in which acute inflammatory events early in the disease course contribute to subsequent neurologic disability. The early relapsing inflammatory phase is followed by a progressive degenerative phase in which the frequency of acute inflammatory attacks diminishes but progressive loss of neurologic function continues. Current immune therapies are most effective in suppressing the acute inflammatory events that characterize the earlier stages of disease. Optimal suppression of these inflammatory events is likely to have the best potential for delaying or preventing loss of axons and decline in neurologic function. In view of these considerations, and because MS is a heterogeneous disease and response to disease-modifying agents (DMA) varies across individuals, it is important to identify suboptimal responders as early as possible to allow therapeutic modification while the opportunity to avert future loss of function remains. At present, no criteria for identifying suboptimal responders have been validated. In January 2004, a group of neurologists from 16 MS centers in the United States met to develop a consensus on criteria for defining suboptimal response for use in compelling clinical situations and to prompt clinical studies to validate the efficacy of these criteria. Consensus criteria included relapse rates of either 1/year or unchanged from pretreatment rates, incomplete recovery from multiple attacks, evolution of polyregional neurologic involvement, recurrent brainstem or spinal cord lesions, and cumulative loss of neurologic function sufficient to disrupt daily activities. The panel then considered the use of mitoxantrone for patients with worsening MS and a suboptimal response to DMA therapy.

An open-label safety and drug interaction study of natalizumab (Antegren) in combination with interferon-beta (Avonex) in patients with multiple sclerosis.

In this open-label drug-interaction trial, we studied 38 patients with relapsing-remitting multiple sclerosis (MS) who received 3.0 or 6.0 mg/kg of natalizumab as a single intravenous (i.v.) infusion during stable treatment with intramuscular (i.m.) interferon beta-1a 30 microg (IFNbeta-1a; Avonex). To assess the pharmacokinetic (PK) interaction of natalizumab and IFNbeta-1a, serum concentration-time data for both agents were collected and analysed. Biologic response markers of IFNbeta-1a activity, beta2-microglobulin and neopterin, were also assessed to determine effects of natalizumab on IFNbeta-1a pharmacodynamics (PD). Further, safety and immunogenicity were evaluated. The combination of drug therapies was well tolerated. Although natalizumab serum concentrations (and corresponding PK exposure measures) appeared to be somewhat elevated in the presence of IFNbeta-1a, when compared to the same dose (6.0 mg/kg) administered alone in a concurrent comparator study, the differences were generally small and unlikely to be clinically relevant. In general, natalizumab had no apparent clinically relevant effects on the PK or PD properties of IFNbeta-1a. The presence of antibodies to IFNbeta-1a and natalizumab was relatively low. Overall, the study provided safety, immunogenicity, PK and PD data to support a combination strategy for the use of natalizumab and IFNbeta-1a in the treatment of patients with relapsing-remitting MS. A large clinical study is currently in progress to evaluate the efficacy and long-term safety of this combination drug therapy.

Presynaptic congenital myasthenic syndrome due to quantal release deficiency.

OBJECTIVE: To provide clinical, electrophysiologic, and ultrastructural findings in three patients with a presynaptic congenital myasthenic syndrome (CMS). BACKGROUND: Familial infantile myasthenia and paucity of synaptic vesicles are the only two fully characterized CMS. We are describing here three patients with another form of presynaptic CMS characterized by deficiency of the action potential-dependent release without reduction of the spontaneous release of neurotransmitter from the nerve terminal. METHODS: The authors performed electromyography and anconeus muscle biopsies that included intracellular recordings and electron microscopy of the neuromuscular junction in three patients with presynaptic CMS. They also sequenced part of the P/Q-calcium alpha(1)-subunit gene (CACNA1A) and the acetylcholine receptor subunit (AChR) genes in these patients. RESULTS: In these patients there were additional neurologic findings including nystagmus and ataxia. In all three patients the end-plate potential quantal content (m) was markedly reduced but neither the amplitudes nor the frequencies of miniature end-plate potentials were diminished. Ultrastructurally, postsynaptic end-plate folds, nerve terminal size, and synaptic vesicle number were normal but double-membrane-bound sacs containing synaptic vesicles were present in the nerve terminal of all three patients. The screening of reported pathogenic mutations in the CACNA1A and a mutational analysis of AChR subunit genes were negative. CONCLUSION: This form of CMS appears to result only from a deficiency of the quantal release of neurotransmitter that may be due to an abnormal calcium mechanism or impaired endocytosis and recycling of synaptic vesicles.

Autoantibodies in thymoma-associated myasthenia gravis with myositis or neuromyotonia.

BACKGROUND: About 50% of patients with thymoma have paraneoplastic myasthenia gravis (MG). Myositis and myocarditis or neuromyotonia (NMT) will also develop in some. Patients with thymoma-associated MG produce autoantibodies to a variety of neuromuscular antigens, particularly acetylcholine receptor (AChR), titin, skeletal muscle calcium release channel (ryanodine receptor [RyR]), and voltage-gated potassium channels (VGKC). OBJECTIVE: To examine whether neuromuscular autoantibodies in patients with thymoma correlate with specific clinical syndromes. METHODS: Serum and plasma samples from 19 patients with thymoma-associated MG, of whom 5 had myositis and 6 had NMT, underwent testing for antibodies to AChR, titin, RyR, and VGKC. RESULTS: Antibodies to AChR and titin were found in 19 and 17 patients, respectively. Antibodies to RyR correlated with the presence of myositis (P = .03); they were found in all 5 patients with myositis and in only 1 patient with NMT, but also in 4 of 8 patients with neither disease. Antibodies to VGKC were found in 4 patients with NMT, 1 of 3 patients undergoing testing for myositis, and 2 of 7 patients undergoing testing with neither comorbidity. Presence of RyR antibodies correlated with high levels of titin antibodies. CONCLUSIONS: The results appear to distinguish partially between 3 groups of patients with thymoma-associated MG: the first with RyR antibodies and myositis or myocarditis, the second with NMT without RyR antibodies, and the third without RyR antibodies, myositis, or NMT. Differences in the thymoma may underlie these pathologic associations.

High prevalence of anti-alpha-crystallin antibodies in multiple sclerosis: correlation with severity and activity of disease.

INTRODUCTION: The presence of T-cell reactivity to alphaB-crystallin in patients with multiple sclerosis (MS) has suggested that this small molecular weight heat shock protein (Hsp) may be an autoantigen in MS. MATERIAL AND METHODS: We have tested the serum of patients with clinically definite MS (n=30), other inflammatory neurological disease (n=22), non-inflammatory neurological disease (n=42) and healthy individuals (n=23) for systemic humoral responses to bovine alphaB-crystallin, to the homologous chaperone protein, alphaA-crystallin, and to another small Hsp, Hsp 27. RESULTS: Sixty-three percent of MS patients exhibited immunoreactivity to alpha-crystallin and this was present in all 4 of 4 non-ambulatory patients with MS. In contrast, serum concentrations in MS patients of antibodies to the small Hsp, Hsp27, and to myelin basic protein were negligible (P<0.001). Serum anti-alpha-crystallin immune responses were detected in significantly lower percentages of patients with other inflammatory neurological diseases (32%, P<0.025), and with non-inflammatory neurological diseases (12%, P<0.001). None of the healthy control individuals showed anti-alpha-crystallin reactivity. The concentration of anti-alpha-crystallin antibodies in patients with MS correlated with severe disease (P<0.05) and with active disease (P<0.025). CONCLUSION: Our observations support the notion that anti-alpha-crystallin autoimmune responses may contribute to pathogenicity in MS and may represent a mechanism of how recurrent attacks of MS develop subsequent to an isolated demyelinating episode.

Morvan's fibrillary chorea: a paraneoplastic manifestation of thymoma.

Morvan's fibrillary chorea is a rare disease characterised by symptoms which include neuromyotonia, cramping, weakness, pruritus, hyperhidrosis, insomnia, and delirium. The first case of Morvan's fibrillary chorea to be associated with clinical manifestations of myasthenia gravis with thymoma, psoriasis, and atopic dermatitis is reported. Muscle histopathology disclosed chronic denervation and myopathic changes and in vitro electrophysiology demonstrated both presynaptic and postsynaptic defects in neuromuscular transmission. Serum antibodies to acetylcholine receptors, titin, N-type calcium channels, and voltage gated potassium channels were detected. Plasmapheresis, thymectomy, and long term immunosuppression induced a dramatic resolution of symptoms. The association of thymoma with other autoimmune disorders and autoantibodies, and prolonged and sustained remission with chronic immunosuppression, place Morvan's fibrillary chorea on the range of neurological diseases arising as a paraneoplastic complication of cortical thymomas.