Continuous positive airway pressure treatment may negatively affect auditory maturation in preterm infants.

AIM: Nasal continuous positive airway pressure (CPAP) devices generate loud noise, which might harm auditory function and maturation. The function of auditory pathways can be examined by using brainstem auditory evoked potential (BAEP) and brainstem audiometry (BA) recordings. Our objective was to study whether CPAP treatment during the neonatal period is associated with abnormalities in BAEP and BA recordings. METHODS: Included in this retrospective study were preterm infants (birth weight ≤1500 g and/or gestational age ≤32 weeks) born between 2002 and 2006 with a comprehensive clinical background and follow-up data, including the duration of CPAP treatment (n = 162). BAEP and BA were recorded near the mean corrected age of one month. The following variables from BAEP and BA examinations were analysed: latencies of BAEP components I, III, V, interpeak intervals (IPI) I-V, I-III, III-V (ms), amplitude I and V (µV), amplitude ratio I/V and BA thresholds. RESULTS: In the adjusted analysis, a longer CPAP treatment leads to longer latencies of BAEP component III (p = 0.01) and V (p = 0.02) in the right ear. CONCLUSION: CPAP treatment may impair the auditory maturation and processing mediated via the dominant right ear. The hearing and neurodevelopment of the children who are treated with CPAP should be followed.

Developing a research diagnostic criteria for burning mouth syndrome: Results from an international Delphi process.

OBJECTIVE: To develop a beta version of a preliminary set of empirically derived research diagnostic criteria (RDC) for burning mouth syndrome (BMS) through expert consensus, which can then be taken into a test period before publication of a final RDC/BMS. DESIGN: A 6 round Delphi process with twelve experts in the field of BMS was used. The first round formed a focus group during which the purpose of the RDC and the definition of BMS was agreed upon, as well as the structure and contents. The remaining rounds were carried out virtually via email to achieve a consensus of the beta version of the RDC/BMS. RESULTS: The definition of BMS was agreed to be 'an intraoral burning or dysaesthetic sensation, recurring daily for more than 2 hours per day over more than 3 months, without evident causative lesions on clinical examination and investigation'. The RDC was based upon the already developed and validated RDC/TMD and formed three main parts: patient self-report; examination; and psychosocial self-report. A fourth additional part was also developed listing aspirational biomarkers which could be used as part of the BMS diagnosis where available, or to inform future research. CONCLUSION: This Delphi process has created a beta version of an RDC for use with BMS. This will allow future clinical research within BMS to be carried out to a higher standard, ensuring only patients with true BMS are included. Further validation studies will be required alongside refinement of the RDC as trialling progresses.

Validation of diagnostic methods for traumatic sensory neuropathy and neuropathic pain.

INTRODUCTION: We evaluated diagnostic value of sensory tests during recovery from iatrogenic sensory neuropathy using intraoperatively verified nerve injury with subjective symptoms as gold standard. METHODS: Inferior alveolar nerves were monitored neurophysiologically throughout mandibular osteotomy in 19 patients. Sensory disturbance was registered and sensation tested using clinical and quantitative sensory (QST) and neurophysiologic tests postoperatively at 1, 3, 6, and 12 months. Sensitivity, specificity, and predictive values were calculated for all tests. RESULTS: The sensitivity of clinical tests was at best 37%, with 100% specificity, but they lost diagnostic value at chronic stages. Best diagnostic accuracy (highest combination of sensitivity and specificity) at different time points was achieved by combining neurophysiologic and thermal QST or tactile and thermal QST. The single most accurate test was sensory neurography. CONCLUSIONS: Neurography or combinations of neurophysiologic and quantitative tests enables most reliable early and late diagnosis. Clinical sensory examination is inadequate for accurate diagnosis. Muscle Nerve 59:342-347, 2019.

Perinatal nutrition impacts on the functional development of the visual tract in infants.

BACKGROUND AND OBJECTIVE: We investigated the associations of maternal diet and serum fatty acids during pregnancy and in early infancy on infantile neurodevelopment. METHODS: Pattern-reversal visual evoked potentials (pVEP) as depictors of central nervous system maturation were recorded from 56 children when they were 2 years old. Maternal nutrient intakes were calculated from food diaries and fish consumption from questionnaires collected during pregnancy. Serum phospholipid fatty acids were determined by gas chromatography in late pregnancy and from infants at 1 month of age. RESULTS: The children of the women who consumed fish three or more times per week during the last trimester of pregnancy had a higher pVEP component P100 amplitude for 60' (mean 23.4, SD 8.1) and 30' (mean 20.4, SD 6.7) of arcminute check sizes compared to those who consumed fish 0-2 times per week (mean 15.0, SD 4.8, p = 0.023, adjusted for birth weight and gender p = 0.058 and mean 13.4, SD 2.0, respectively, p = 0.028, adjusted p = 0.072). Maternal and child serum phospholipid fatty acids correlated with child pVEP measurements. CONCLUSION: The results of this small-scale study suggest that fish consumption during pregnancy and perinatal serum fatty acid status may associate with neurodevelopment within visual system during infancy.

Nerve conduction study of the three supraclavicular nerve branches.

INTRODUCTION: We describe a new nerve conduction study technique with reference values for the 3 branches of the supraclavicular nerve (SCN) in young healthy subjects and application of it in 2 patients. METHODS: The recording electrode was placed on the posterior border of the sternocleidomastoid muscle, 6-7 cm from the sternoclavicular joint. SCN branches were stimulated below the clavicle, 2.5, 7, and 10.5 cm lateral to the sternoclavicular joint. RESULTS: Twenty healthy volunteers (10 men), 19-38 years, mean 25.9 years (SD 6.3), and 2 patients with SCN lesions were studied. The mean conduction velocities of the SCN branches were 70-78 m/s (SD 8-10 m/s), and amplitudes 3-4 µV (SD 0.9-2.0 µV). There were no side-to-side or gender differences. DISCUSSION: The 3 SCN branches could be studied in all subjects. We provide reference values for young subjects. This new method was useful in verifying SCN lesions in 2 patients. Muscle Nerve 58: 300-303, 2018.

Psychiatric (Axis I) and personality (Axis II) disorders and subjective psychiatric symptoms in chronic tinnitus.

OBJECTIVE: Chronic tinnitus has been associated with several psychiatric disorders. Only few studies have investigated these disorders using validated diagnostic interviews. The aims were to diagnose psychiatric and personality disorders with structured interviews, to assess self-rated psychiatric symptoms and elucidate temporal relations between psychiatric disorders and tinnitus. DESIGN: Current and lifetime DSM-IV diagnoses of axis-I (psychiatric disorders) and axis-II (personality disorders) were assessed using structured clinical interviews (SCID-I and -II). Current subjective psychiatric symptoms were evaluated via self-rating instruments: the Symptom Check List-90 (SCL-90), the Beck Depression Inventory, and the Dissociative Experiences Scale (DES). STUDY SAMPLE: 83 patients (mean age 51.7, 59% men) with chronic, disturbing tinnitus and a median Tinnitus Handicap Inventory score of 32. RESULTS: The rates of lifetime and current major depression were 26.5% and 2.4%. The lifetime rate of obsessive-compulsive personality disorder (type C) was 8.4%. None of the patients had cluster B personality disorder or psychotic symptoms. The SCL-90 subscales did not differ from the general population, and median DES score was low, 2.4. CONCLUSIONS: Tinnitus patients are prone to episodes of major depression and often also have obsessive-compulsive personality features. Psychiatric disorders seem to be comorbid or predisposing conditions rather than consequences of tinnitus. Clinical trial reference: ClinicalTrials.gov (ID NCT 01929837).

Burning mouth syndrome.

Objective To review the clinical entity of primary burning mouth syndrome (BMS), its pathophysiological mechanisms, accurate new diagnostic methods and evidence-based treatment options, and to describe novel lines for future research regarding aetiology, pathophysiology, and new therapeutic strategies. Description Primary BMS is a chronic neuropathic intraoral pain condition that despite typical symptoms lacks clear clinical signs of neuropathic involvement. With advanced diagnostic methods, such as quantitative sensory testing of small somatosensory and taste afferents, neurophysiological recordings of the trigeminal system, and peripheral nerve blocks, most BMS patients can be classified into the peripheral or central type of neuropathic pain. These two types differ regarding pathophysiological mechanisms, efficacy of available treatments, and psychiatric comorbidity. The two types may overlap in individual patients. BMS is most frequent in postmenopausal women, with general population prevalence of around 1%. Treatment of BMS is difficult; best evidence exists for efficacy of topical and systemic clonazepam. Hormonal substitution, dopaminergic medications, and therapeutic non-invasive neuromodulation may provide efficient mechanism-based treatments for BMS in the future. Conclusion We present a novel comprehensive hypothesis of primary BMS, gathering the hormonal, neuropathic, and genetic factors presumably required in the genesis of the condition. This will aid in future research on pathophysiology and risk factors of BMS, and boost treatment trials taking into account individual mechanism profiles and subgroup-clusters.

Electric field-navigated transcranial magnetic stimulation for chronic tinnitus: a randomized, placebo-controlled study.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) may alleviate tinnitus. We evaluated effects of electric field (E-field) navigated rTMS targeted according to tinnitus pitch. No controlled studies have investigated anatomically accurate E-field-rTMS for tinnitus. DESIGN: Effects of E-field-rTMS were evaluated in a prospective randomised placebo-controlled 6-month follow-up study on parallel groups. Patients received 10 sessions of 1 Hz rTMS or placebo targeted to the left auditory cortex corresponding to tonotopic representation of tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3 and 6 months. Primary outcome measures were visual analogue scores (VAS 0-100) for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap Inventory (THI). STUDY SAMPLE: Thirty-nine patients (mean age 50.3 years). RESULTS: The mean tinnitus intensity (F3 = 15.7, p < 0.0001), annoyance (F3 = 8.8, p = 0.0002), distress (F3 = 9.1, p = 0.0002) and THI scores (F4 = 13.8, p < 0.0001) decreased in both groups over time with non-significant differences between the groups. After active rTMS, 42% and 37% of the patients showed excellent response at 1 and 3 months against 15% and 10% in the placebo group (p = 0.082 and p = 0.065). CONCLUSIONS: Despite the significant effects of rTMS on tinnitus, differences between active and placebo groups remained non-significant, due to large placebo-effect and wide inter-individual variation.

Improved sensory recovery with a novel dual neurorrhaphy technique for breast reconstruction with free muscle sparing TRAM flap technique.

BACKGROUND: We describe a new dual neurorrhaphy method for a free abdominal-based flap and compare sensory recovery with this novel technique to that with conventional neurorrhaphy technique for breast reconstruction. METHODS: 70 breast cancer patients underwent muscle sparing innervated transversal rectus abdominis myocutaneous flap (neuro ms-TRAM) breast reconstruction with either a novel dual neurorrhaphy technique (N = 41) or single (N = 29) neurorrhaphy only. Dual neurorrhaphy was performed on both sides and single neurorrhaphy on one side of the flap, using the end-to-end or end-to-side technique. Two years postoperatively, quantitative sensory testing (QST) was performed for tactile, and thermal sensory modalities, and other tests included sharp-blunt, vibration, and two-point discrimination. Sensory modalities were scored either zero (abnormal) or one point (normal) at each test site against normal reference values (five sites for most tests). The total sensory scores (TSC) were calculated on the basis of the sums of the individual test scores, and all data are presented as the median (interquartile range, IQR). RESULTS: The median of TSC in the breast reconstruction with the dual neurorrhaphy was higher (15.3, IQR 11.8-19.4), than that with the single neurorrhaphy (11.5, IQR 9.1-17.4) (P = 0.037). Regarding the different sensory modalities, the dual technique especially enhanced the tactile (P = 0.005) and cool detection (P = 0.021) recovery compared to the single neurorrhaphy. CONCLUSIONS: Dual neurorrhaphy improved the sensory recovery of the reconstructed breast, and may therefore be recommended for clinical practice. © 2014 Wiley Periodicals, Inc. Microsurgery 37:21-28, 2017.

Electric field navigated transcranial magnetic stimulation for chronic tinnitus: A pilot study.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has shown potential in reducing tinnitus symptoms. We evaluated effects of electric field (E-field) navigated rTMS targeted neuroanatomically according to tinnitus pitch. DESIGN: In this open methodological pilot study, the patients received E-field navigated 1-Hz rTMS in daily treatment sessions to the left superior temporal gyrus, targeted according to tonotopic representation of their individual tinnitus pitch. Patients rated their tinnitus intensity and annoyance with a numeric rating scale (NRS) from 0 to 10 at the baseline and after each rTMS session. They also rated their global impression of change (scale - 3 to + 3) after the treatment. STUDY SAMPLE: Thirteen patients (mean age 53 years; 10 men, 3 women) with chronic, intractable tinnitus. RESULTS: The mean intensity was 7.1 (SD 1.8) at the baseline, decreasing to 4.5 (SD 2.2) after the rTMS (p < 0.0001). The mean annoyance 7.0 (SD 1.8) at the baseline decreased to 4.0 (SD 2.4) after the treatment (p < 0.0001). Intensity diminished at least 30% in 8/13 patients and annoyance in 9/13 patients. A total of 10/13 patients felt subjective benefit from the treatment. CONCLUSIONS: These preliminary observations suggest that E-field-rTMS may improve the current treatment options for intractable tinnitus.

[Phenotype and incidence of Creutzfeldt-Jakob disease in Finland in 1997-2013]. / Creutzfeldt-Jakobin taudin ilmiasu ja ilmaantuvuus Suomessa vuosina 1997-2013.

INTRODUCTION: The incidence of Creutzfeldt-Jakob disease (CJD) in Finland in 1974-1989 was reported to be 0.6/1 000 000. Our aim was to compare the current incidence of CJD in Finland with the earlier incidence and also study the diagnostics of the disease. METHODS: Register study of the Finnish CJD cases from 1997 to 2012 and the clinical data of CJD patients within the Hospital District of Southwest Finland from 2007 to 2013. RESULTS: There were 119 cases. The average yearly incidence was 1.36-1.44/1 000 000. CONCLUSIONS: Compared with the previous study, the incidence in Finland appears to have increased. The change is propably due to increased awareness and improved diagnostic methods.

The blink reflex and its modulation - Part 2: Pathophysiology and clinical utility.

The blink reflex (BR) is integrated at the brainstem; however, it is modulated by inputs from various structures such as the striatum, globus pallidus, substantia nigra, and nucleus raphe magnus but also from afferent input from the peripheral nervous system. Therefore, it provides information about the pathophysiology of numerous peripheral and central nervous system disorders. The BR is a valuable tool for studying the integrity of the trigemino-facial system, the relevant brainstem nuclei, and circuits. At the same time, some neurophysiological techniques applying the BR may indicate abnormalities involving structures rostral to the brainstem that modulate or control the BR circuits. This is a state-of-the-art review of the clinical application of BR modulation; physiology is reviewed in part 1. In this review, we aim to present the role of the BR and techniques related to its modulation in understanding pathophysiological mechanisms of motor control and pain disorders, in which these techniques are diagnostically helpful. Furthermore, some BR techniques may have a predictive value or serve as a basis for follow-up evaluation. BR testing may benefit in the diagnosis of hemifacial spasm, dystonia, functional movement disorders, migraine, orofacial pain, and psychiatric disorders. Although the abnormalities in the integrity of the BR pathway itself may provide information about trigeminal or facial nerve disorders, alterations in BR excitability are found in several disease conditions. BR excitability studies are suitable for understanding the common pathophysiological mechanisms behind various clinical entities, elucidating alterations in top-down inhibitory systems, and allowing for follow-up and quantitation of many neurological syndromes.

Returning from oblivion: imaging the neural core of consciousness.

One of the greatest challenges of modern neuroscience is to discover the neural mechanisms of consciousness and to explain how they produce the conscious state. We sought the underlying neural substrate of human consciousness by manipulating the level of consciousness in volunteers with anesthetic agents and visualizing the resultant changes in brain activity using regional cerebral blood flow imaging with positron emission tomography. Study design and methodology were chosen to dissociate the state-related changes in consciousness from the effects of the anesthetic drugs. We found the emergence of consciousness, as assessed with a motor response to a spoken command, to be associated with the activation of a core network involving subcortical and limbic regions that become functionally coupled with parts of frontal and inferior parietal cortices upon awakening from unconsciousness. The neural core of consciousness thus involves forebrain arousal acting to link motor intentions originating in posterior sensory integration regions with motor action control arising in more anterior brain regions. These findings reveal the clearest picture yet of the minimal neural correlates required for a conscious state to emerge.

A prospective, double-blind, pilot, randomized, controlled trial of an "embodied" virtual reality intervention for adults with low back pain.

ABSTRACT: Adults with chronic low back pain, disability, moderate-to-severe pain, and high fear of movement and reinjury were recruited into a trial of a novel, automated, digital therapeutics, virtual reality, psychological intervention for pain (DTxP). We conducted a 3-arm, prospective, double-blind, pilot, randomized, controlled trial comparing DTxP with a sham placebo comparator and an open-label standard care. Participants were enrolled for 6 to 8 weeks, after which, the standard care control arm were rerandomized to receive either the DTxP or sham placebo. Forty-two participants completed assessments at baseline, immediately posttreatment (6-8 weeks), 9-week, and 5-month follow-up. We found that participants in the DTxP group reported greater reductions in fear of movement and better global impression of change when compared with sham placebo and standard care post treatment. No other group differences were noted at posttreatment or follow-up. When compared with baseline, participants in the DTxP group reported lower disability at 5-month follow-up, lower pain interference and fear of movement post treatment and follow-up, and lower pain intensity at posttreatment. The sham placebo group also reported lower disability and fear of movement at 5-month follow-up compared with baseline. Standard care did not report any significant changes. There were a number of adverse events, with one participant reporting a serious adverse event in the sham placebo, which was not related to treatment. No substantial changes in medications were noted, and participants in the DTxP group reported positive gaming experiences.

Subjective sensory symptoms associated with axonal and demyelinating nerve injuries after mandibular sagittal split osteotomy.

PURPOSE: The effect of the type of nerve injury on subjective sensory disturbances and recovery has not been addressed in orthognathic surgery. Using neurophysiologic monitoring during 19 bilateral sagittal split osteotomy operations, we were able to classify intraoperative inferior alveolar nerve injuries as either axonal or demyelinating. This study aimed to analyze the quality and extent of the subjective sensations experienced by the patients after these 2 injury types at different time points up to 12 months. MATERIALS AND METHODS: Of the 36 injured nerves, 21 showed signs of demyelinating injury and 15 showed signs of axonal damage. The quality of subjective sensory symptoms was asked about at 2 weeks and 1, 3, 6, and 12 months postoperatively and classified into 4 categories: normal, negative, positive (including pain), and mixed sensations. In addition, the extent of the sensory alteration was determined by measuring the affected skin regions from symptom charts. RESULTS: The quantity, quality, and evolution of experienced subjective sensations differed between the injury types during follow-up: Subjective sensations normalized more rapidly after demyelinating-type injuries than after axonal-type injuries. Persistence of mixed sensation patterns at 3 months and appearance instead of disappearance of positive sensory phenomena after 3 months indicated axonal damage. Painful sensations at 1 month or later after surgery indicated axonal damage and predicted poor recovery and more long-term sequelae. CONCLUSIONS: Postoperative pain at 1 month and type of nerve injury are important prognostic factors for the persistence of subjective symptoms and development of neuropathic pain.

Successful suppression of musical hallucinations with low-frequency rTMS of the left temporo-parietal junction: A case report.

BACKGROUND: Inhibitory low frequency repetitive transcranial magnetic stimulation (rTMS) of the temporo-parietal area has been applied to treat both auditory verbal hallucinations as well as tinnitus. OBJECTIVE: We hypothesized that 1 Hz rTMS to the left temporoparietal junction (TPJ) may be beneficial in alleviating musical hallucinations (MH), another condition with auditory experiences in the absence of an external source. METHODS: Here we describe a patient with almost insufferable life-long MH with comorbid depression, who received inhibitory rTMS to the left TPJ as well as the right dorsolateral prefrontal cortex (DLPFC). RESULTS: The intrusiveness and frequency of her MH as well as her depressive symptoms alleviated quickly and substantially, and once-a-week maintenance therapy with rTMS seemed to preserve this amelioration. Future studies will hopefully reveal whether this is a viable treatment approach for other patients suffering from MH with or without comorbid depression.

No effects of mobile phone electromagnetic field on auditory brainstem response.

The present study investigated the possible effects of the electromagnetic field (EMF) emitted by an ordinary GSM mobile phone (902.4 MHz pulsed at 217 Hz) on brainstem auditory processing. Auditory brainstem responses (ABR) were recorded in 17 healthy young adults, without a mobile phone at baseline, and then with a mobile phone on the ear under EMF-off and EMF-on conditions. The amplitudes, latencies, and interwave intervals of the main ABR components (waves I, III, V) were compared among the three conditions. ABR waveforms showed no significant differences due to exposure, suggesting that short-term exposure to mobile phone EMF did not affect the transmission of sensory stimuli from the cochlea up to the midbrain along the auditory nerve and brainstem auditory pathways.

Non-invasive therapeutic brain stimulation for treatment of resistant focal epilepsy in a teenager.

AIMS: A 13-year-old boy with symptomatic focal epilepsy due to a right parietal dysembryoplastic neuroepithelial tumor (DNET) presented pre- and post-operatively fluctuating tinnitus and sensory symptoms which became persistent after incomplete tumor resection. He received low-frequency rTMS treatment and cathodal tDCS treatment. METHODS: Case report with clinical details and pictures from rTMS and tDCS stimulation targets. RESULTS: The patient became symptom free with an initial low-frequency rTMS treatment series targeted to the EEG-verified epileptic zone followed by maintenance therapy at the same region with cathodal tDCS at home. CONCLUSIONS: Both rTMS and tDCS could be more often used in adolescents when drug treatment and surgery do not cease focal epilepsy, here with fluctuating tinnitus.

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018).

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150-206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson's disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.