Clinical Features and Burden Scores in Japanese Pediatric Migraines With Brainstem Aura, Hemiplegic Migraine, and Retinal Migraine.

BACKGROUND: Migraines are a broad spectrum of disorders classified by the type of aura with some requiring attentive treatment. Vasoconstrictors, including triptans, should be avoided in the acute phase of migraines with brainstem aura, in hemiplegic migraine, and in retinal migraine. This study investigated the characteristics and burden of these migraines. METHODS: Medical charts of 278 Japanese pediatric patients with migraines were retrospectively reviewed. Migraine burden of migraines with brainstem aura, hemiplegic migraines, and retinal migraine was assessed using the Headache Impact Test-6™ (HIT-6) and the Pediatric Migraine Disability Assessment scale (PedMIDAS). RESULTS: Of 278 patients screened, 12 (4.3%) patients with migraines with brainstem aura (n = 5), hemiplegic migraines (n = 2), and retinal migraine (n = 5) were enrolled in the study. All patients had migraine with/without typical aura, whereas some patients had coexisting migraine with another type of headache (chronic tension-type headache in 3 patients, and 1 each with frequent episodic tension-type headache, headache owing to medication overuse, and chronic migraine). Migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients with coexisting headaches had higher HIT-6 or PedMIDAS scores, whereas migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients without coexisting headache did not show high HIT-6 or PedMIDAS scores. CONCLUSION: All migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients experienced migraine with or without typical aura, and some patients having other coexisting headaches also had high PedMIDAS and HIT-6 scores. PedMIDAS and HIT-6 should not be considered diagnostic indicators of migraines with brainstem aura, hemiplegic migraines, or retinal migraine. In clinical practice for headaches in children, careful history taking and proactive assessment of the aura are needed for accurate diagnosis of migraines with brainstem aura, hemiplegic migraines, and retinal migraine.

[Is the current level of investigation for vestibular schwannoma reasonable?] / Utredningsnivån av vestibulära schwannom måste bli rimlig - Nationella riktlinjer behövs.

The main aim of this study was to evaluate if the level of investigation with MRT or BRA (Brainstem Response Audiometry) is adequate in relation to the number of vestibular schwannomas (VS) found in a county like  Dalarna (277 000 inhabitants) in Sweden. The reason to investigate was asymmetrical sensorineural hearing loss (ASHL) defined as a one-sided hearing loss exceeding 10 dB compared to the contralateral side. Between 2007-2014 a total of 55 patients (incidence 2.5/100 000) were diagnosed with a VS in the county. The local ENT department found two thirds of these patients. In the year of 2010, MRT was advocated by SBU (Swedish Agency for Health Technology Assessment and Assessment of Social Services) as the primary step of investigation. During 2011-2014, 981 patients underwent MRT and 482 patients BRA, because of ASHL. Seventeen VS were found, meaning that 58 MRT and 29 BRA were conducted to find one VS. According to earlier studies, only one third of VS show growth tendency. Taking this into consideration, 174 (58 × 3) investigations with MRT will only diagnose approximately 1 patient with a growing VS. We therefore question today's level of investigation and ask for new uniform recommendations on how to investigate for VS in cases of ASHL.

[Brainstem auditory evoked potentials in neurophysiological assessment of brain stem dysfunction in patients with atherostenosis of vertebral arteries]. / Akusticheskie stvolovye vyzvannye potentsialy v neirofiziologicheskoi otsenke disfunktsii stvola mozga u patsientov s aterostenozom pozvonochnykh arterii.

AIM: To assess brain stem dysfunction in patients with hemodynamically significant stenosis of vertebral arteries (VA) using short latency brainstem auditory evoked potentials (BAEP). MATERIAL AND METHODS: The study group included 50 patients (mean age 64±6 years) with hemodynamically significant extracranial VA stenosis. RESULTS: Patients with hemodynamically significant extracranial VA stenosis had BAEP abnormalities including the elongation of interpeak intervals I-V and peak V latency as well as the reduction of peak I amplitude. After transluminal balloon angioplasty with stenting of VA stenoses, there was a shortening of peak V latency compared to the preoperative period that reflected the improvement of brain stem conductive functions. CONCLUSION: Atherostenosis of vertebral arteries is characterized by the signs of brain stem dysfunction, predominantly in the pontomesencephal brain stem. After transluminal balloon angioplasty with stenting of VA, the improvement of brain stem conductive functions was observed.

Assessment of Blink Reflex in Genetic Generalized Epilepsy Patients With Eyelid Myoclonia.

Eyelid myoclonia (EM) with or without absences are a rare type of generalized seizures associated with a variety of epilepsy syndromes with an unknown pathophysiology. The aim of this study was to investigate the possible contribution of the brainstem structures in this underrecognized special type of seizures. Sixteen consecutive patients with EM, diagnosed with genetic generalized epilepsy (GGE) according to International League Against Epilepsy 2010 criteria were included. Brainstem excitabilities were examined by blink reflex (BR) studies. The results of BR studies in GGE patients with EM were statistically compared with 2 control groups; namely age- and gender-matched healthy volunteers and juvenile myoclonic epilepsy (JME) patients without any absences and using similar antiepileptic drugs. There were no statistical differences between the thresholds of the BR studies and the BR recovery curves in terms of amplitudes and areas of healthy subjects, JME patients and GGE patients with EM. Our findings do not support a profound interictal hyperexcitability in the BR-related brainstem structures of the GGE patients with EM. It can be considered that EM may be associated with excitability changes of the occipital cortex and other cortical areas.

Assessment of excitability at the brainstem and cortex in primary headaches with allodynia.

PURPOSE: The aims were to assess the excitability of motor cortex and trigeminal structures in patients with primary headaches experiencing allodynia and to investigate the alterations in interictal allodynia and blink reflex excitability after repetitive transcranial magnetic stimulation (rTMS). METHODS: Patients with strictly lateralized primary headaches were included, and Allodynia Symptom Checklist was used to detect allodynia. Paired transcranial magnetic stimulation and blink reflex recovery studies were performed on both sides. Ten Hertz or sham rTMS was applied on the motor cortex in patients with interictal allodynia. Allodynic symptoms were registered quantitatively, and blink reflex study was repeated after these trials. RESULTS: Seventeen of 34 patients with headache described allodynia. Our findings showed bilateral hyperexcitability of cortical and trigeminal structures in the allodynic group. Interictal allodynia, detected in 13 allodynic patients, improved after rTMS as compared with sham stimulation, and this effect appeared to be more evident in the late period. CONCLUSIONS: Bilateral increases in the cortical and trigeminal excitability were shown in patients with allodynia, and rTMS was effective for reducing clinical allodynia. The authors suggest that allodynic condition of the patients should be taken into account in the planning and evaluation of electrophysiological studies, and rTMS may be considered as a treatment alternative for troublesome allodynia.

Unilateral pyramidotomy of the corticospinal tract in rats for assessment of neuroplasticity-inducing therapies.

The corticospinal tract (CST) can be completely severed unilaterally in the medullary pyramids of the rodent brainstem. The CST is a motor tract that has great importance for distal muscle control in humans and, to a lesser extent, in rodents. A unilateral cut of one pyramid results in loss of CST innervation of the spinal cord mainly on the contralateral side of the spinal cord leading to transient motor disability in the forelimbs and sustained loss of dexterity. Ipsilateral projections of the corticospinal tract are minor. We have refined our surgical method to increase the chances of lesion completeness. We describe postsurgical care. Deficits on the Montoya staircase pellet reaching test and the horizontal ladder test shown here are detected up to 8 weeks postinjury. Deficits on the cylinder rearing test are only detected transiently. Therefore, the cylinder test may only be suitable for detection of short term recovery. We show how, electrophysiologically and anatomically, one may assess lesions and plastic changes. We also describe how to analyse fibers from the uninjured CST sprouting across the midline into the deprived areas. It is challenging to obtain >90% complete lesions consistently due to the proximity to the basilar artery in the medulla oblongata and survival rates can be low. Alternative surgical approaches and behavioural testing are described in this protocol. The pyramidotomy model is a good tool for assessing neuroplasticity-inducing treatments, which increase sprouting of intact fibers after injury.

Bulbar and speech motor assessment in ALS: challenges and future directions.

Bulbar motor deterioration due to amyotrophic lateral sclerosis (ALS) leads to the eventual impairment of speech and swallowing functions. Despite these devastating consequences, no standardized diagnostic procedure for assessing bulbar dysfunction in ALS exists and adequate objective markers of bulbar deterioration have not been identified. In this paper, we consider objective measures of speech motor function, which show promise for forming the basis of a comprehensive, quantitative bulbar motor assessment in ALS. These measures are based on the assessment of four speech subsystems: respiratory, phonatory, articulatory, and resonatory. The goal of this research is to design a non-invasive, comprehensive bulbar motor assessment instrument intended for early detection, monitoring of disease progression, and clinical trial application. Preliminary data from an ongoing study of bulbar motor decline are presented, which demonstrate the potential clinical efficacy of the speech subsystem approach.

Prognostic indicators for long-term disability in multiple sclerosis patients.

BACKGROUND: Daily practice is still faced with uncertainty in predicting the long-term disability of multiple sclerosis (MS). Most information comes from northern hemisphere cohorts, but in South America this information is scarce, and race, genetic and environmental factors could play an important role in the heterogeneity observed in disease outcomes. METHODS: We evaluated 197 patients attending our MS Center gathering clinical and demographic information. Outcome measures analyzed were time from first clinical symptom to EDSS of 6, 7 and 8. For survival analysis we employed Cox regression models and the Kaplan-Meier method. RESULTS: Time to EDSS 6 was 25.83 years (95% CI 15.36-36.31), and 36.25 years (95% CI 20.72-51.78) for EDSS 7. Male sex was associated with a 4.63 and 4.69 fold increased risk to EDSS 6 and 7, respectively (p<0.001 and p=0.006). Motor and brainstem symptoms at onset were also associated with an 8.1 and 13.1 fold increased risk to EDSS 6, respectively (p=0.04 and p=0.01). The number of relapses in five and ten years of disease onset was associated with a slightly increased risk to EDSS 8 (1.28 and 1.19, respectively; p=0.032 and p=0.015). CONCLUSIONS: Male patients presenting with frequent relapses, especially those with motor and brainstem involvement, deserve close observation and should be cautiously monitored to early signs of treatment failure.

Outline of restorative neurology: definition, clinical practice, assessment, intervention.

Rather than focusing on the deficits and lost function caused by upper motor neuron lesions or disorders, it is more advantageous to elucidate, in each individual, the specific neural functions that remain available, and then, to build upon them by designing a treatment protocol to optimize their effectiveness and thus improve recovery. The practice of Restorative Neurology is based on detailed assessment of the individual patient, the use of neurophysiological methods to elucidate and characterize subclinical function and the application of interventions that modify neural activity to improve clinical function.

Safety and the violent person: guidelines for emergency services.

Emergency service providers (EMS), police, health-care providers, counselors, and other helping professionals are at times called upon to provide services to violent or potentially violent individuals. Providing these services safely can be enhanced with six general guidelines that can be implemented to reduce the risk of violence or contain what violence may have already erupted. Thinking about medical/ psychiatric illnesses, call log information, scene surveillance, old brain stem functioning, early warning signs of loss of control, and the theories of violence may provide strategies to enhance both the safety and quality ofservices provided in these difficult situations.

Hearing threshold assessment in young children with electrocochleography (EcochG) and auditory brainstem responses (ABR): experience at the University Hospital of Ferrara.

OBJECTIVE: Electrophysiological evaluation is a fundamental procedure for the diagnostic assessment of hearing loss during infancy; in these cases, information concerning threshold level and auditory perception is particularly useful to establish a correct hearing rehabilitation program (hearing aids and cochlear implants). Purpose of this study is to underline the role of auditory brainstem responses (ABR) and electrocochleography (EcochG) in the definition of hearing loss in a selected group of children, referred to the Audiology Department of the University Hospital of Ferrara, for a tertiary level audiological assessment. METHODS: A retrospective study of the paediatric patient database at the Audiology Department of the University Hospital of Ferrara has been performed. In a period between January 2000 and December 2007, a total of 272 paediatric cases have been identified (544 ears). An EM 12 Mercury apparatus has been used for the electrophysiological threshold identification (ABR and EcochG). Recordings were carried out under general anaesthesia, in a protected enviroment. RESULTS: In 19 of the 272 paediatric cases selected--38 ears (7%), the results of threshold evaluation through ABR were uncertain. The Ecochg recording resulted crucial for the final diagnosis in terms of definition of the hearing threshold level, and it was then possible to ensure the better hearing rehabilitation strategy. CONCLUSIONS: ABR has to be considered the first choice in hearing assessment strategy, either for screening or for diagnosis in newborns as well as in non-collaborating children; ECochG still may be considered a reliable diagnostic tool.

The proinflammatory environment in potential heart and lung donors: prevalence and impact of donor management and hormonal therapy.

BACKGROUND: Brain stem death can elicit a potentially manipulable cardiotoxic proinflammatory cytokine response. We investigated the prevalence of this response, the impact of donor management with tri-iodothyronine (T3) and methylprednisolone (MP) administration, and the relationship of biomarkers to organ function and transplant suitability. METHODS: In a prospective randomized double-blinded factorially designed study of T3 and MP therapy, we measured serum levels of interleukin-1 and -6 (IL-1 and IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein, and procalcitonin (PCT) levels in 79 potential heart or lung donors. Measurements were performed before and after 4 hr of algorithm-based donor management to optimize cardiorespiratory function and +/-hormone treatment. Donors were assigned to receive T3, MP, both drugs, or placebo. RESULTS: Initial IL-1 was elevated in 16% donors, IL-6 in 100%, TNF-alpha in 28%, CRP in 98%, and PCT in 87%. Overall biomarker concentrations did not change between initial and later measurements and neither T3 nor MP effected any change. Both PCT (P =0.02) and TNF-alpha (P =0.044) levels were higher in donor hearts with marginal hemodynamics at initial assessment. Higher PCT levels were related to worse cardiac index and right and left ventricular ejection fractions and a PCT level more than 2 ng x mL(-1) may attenuate any improvement in cardiac index gained by donor management. No differences were observed between initially marginal and nonmarginal donor lungs. A PCT level less than or equal to 2 ng x mL(-1) but not other biomarkers predicted transplant suitability following management. CONCLUSIONS: There is high prevalence of a proinflammatory environment in the organ donor that is not affected by tri-iodothyronine or MP therapy. High PCT and TNF-alpha levels are associated with donor heart dysfunction.

Self assessment exercises in Intensive Care Medicine.

Intensive Care Medicine (ICM) is no longer the exclusive preserve of anaesthetists as both emergency medicine and general medicine trainees now also train in this increasingly important speciality. This edition of the JRAMC self assessment question series serves to cover some of the current 'hot topics' in ICM and enables readers with experience of ICM to test their knowledge as well as educating junior trainees in relevant subjects that they may be unfamiliar with. Similarly, the Focus On .... series of papers elsewhere in this journal demonstrate the increasing importance of ICM in the deployed Field Hospital setting.

Comparison of auditory steady-state responses and auditory brainstem responses in audiometric assessment of adults with sensorineural hearing loss.

OBJECTIVE: Many of the medico-legal patients who claimed compensation may exaggerate hearing loss that varies in degree, nature, and laterality. The purpose of this study was to investigate whether Auditory Steady-State Response (ASSR) could be used to predict the hearing level of adults, and whether ASSR could become a better testing method than Auditory brainstem response (ABR) in audiometric assessment of adults with sensorineural hearing loss. METHODS: This was a prospective study, which was conducted in a tertiary referral hospital. From January to June 2007, 142 subjects (284 ears) with varying degrees of sensori-neural hearing impairment were included in this study. Four commonly used frequencies (500, 1000, 2000, 4000Hz) were evaluated. All subjects received pure-tone audiometry, multi-channel ASSR, and ABR tests for threshold measurement. The correlation of pure tone thresholds with ASSR and ABR thresholds were assessed. RESULTS: Between multi-channel ASSR and pure tone thresholds, a difference of less than 15dB was found in 71% while a difference of less than 25dB was found in 89% of patients. The correlation coefficient (r) of multi-channel ASSR and pure tone thresholds were 0.89, 0.95, 0.96, and 0.97 at 500, 1000, 2000, and 4000Hz, respectively. The strength of the relationship increased with increasing frequency. On the other hand, between ABR and pure-tone thresholds, a difference of less than 15dB was found in 31%; a difference of less than 25dB was found in 62% of patients. The r correlation value for ABR and pure tone thresholds was 0.83. CONCLUSION: ASSR is a more reliable test for the accurate prediction of auditory thresholds than ABR. It can be a powerful and convenient electro-physiologic examination tool for clinically assessing of adults with sensorineural hearing loss.

Assessment of regional GABA(A) receptor binding using 18F-fluoroflumazenil positron emission tomography in spastic type cerebral palsy.

Periventricular leukomalacia (PVL) due to hypoxic-ischemic insult to the immature brain, chorioamnionitis and maternal infection are the major etiological factors of spastic type cerebral palsy (CP). Despite advances in preventing and treating certain causes of CP, the number of patients has remained essentially unchanged and the pathophysiological mechanisms related to motor dysfunction remain poorly understood. In this study, statistical parametric mapping (SPM) analysis of cerebral gamma-aminobutyric acid (GABA) receptor PET imaging using [18F]-fluoroflumazenil showed increased GABA(A) receptor binding in the bilateral motor and visual cortices in spastic diplegia (SD) type CP patients (n = 20) compared with normal controls (n = 10). As GABA(A) receptor signaling modulates biological perception and production of movement, complex motor skills and use-dependent plasticity in the motor cortex, increased GABA(A) receptor binding in the motor cortex might play a important role in poor motor control. Decreased GABA(A) receptor binding was seen in the brain stem in SD CP patients, which appears to be related to spastic symptom.

Assessment of MRI abnormalities of the brainstem from patients with migraine and multiple sclerosis.

BACKGROUND: In patients with migraine, functional changes have been described in the red nucleus (RN), substantia nigra (SN) and periaqueductal gray matter (PAG). PURPOSE: To evaluate whether and at which frequency these structures are involved by MRI-detectable structural abnormalities in migraineurs and to investigate the pathogenic role of these abnormalities by assessing their frequency and extent in patients with multiple sclerosis (MS) and migraine. METHODS: On brain dual-echo scans obtained from 58 migraineurs (40 without and 18 with aura), 37 MS patients with migraine without aura and 42 MS patients without migraine, the presence of hyperintense lesions involving the brainstem structures was recorded. A test of heterogeneity between groups was used to compare the presence of lesions among patient groups. RESULTS: Lesions of RN, SN and PAG were found in all patient groups, with frequency from 57.5% to 86.5%. Significant between-group differences for all these regions were found. No difference was found between migraine patients with and without aura. Compared with MS patients without migraine, MS patients with migraine had more significant involvement of the SN (p=0.02) and RN (p<0.0001). Compared with migraine patients, MS patients with migraine had more significant involvement of the SN and PAG (p ranging from 0.009 to 0.02). CONCLUSIONS: T2-visible lesions in the brainstem are frequent in patients with migraine, but do not seem to be associated with the presence of aura. Demyelinating lesions in the RN, SN and PAG might be among the factors responsible for the presence of migraine in patients with MS.

Assessment of the maturity-related brainstem functions reveals the heterogeneous phenotypes and facilitates clinical management of Rett syndrome.

We have investigated whether brainstem assessment using the Neuro Scope could be used for objective and quantitative monitoring of early development and later progress in Rett syndrome. Brainstem features can be seen on bedside examination of Rett patients and are included in the International Scoring system. The following cardiovascular vital signs were recorded simultaneously in real-time: cardiac vagal tone (CVT), cardiac sensitivity to baroreflex (CSB), heart rate (HR), and mean arterial blood pressure (MAP) and respiratory vital signs: breathing rate and pattern, transcutaneous partial pressures of oxygen (pO(2)) and carbon dioxide (pCO(2)). We assessed the occipito-frontal head circumference (OFHC), height and body mass index (BMI). Results are from 72 patients with classical Rett syndrome studied at the Swedish National Rett Centre. Three cardiorespiratory phenotypes, designated Forceful, Feeble and Apneustic breathers were present in similar proportions in the Rett population but early development measured by OFHC and BMI differed. Height was not affected. Baseline levels of CVT and CSB also differed within the phenotypes indicating differences in parasympathetic activities. However, parasympathetic activity in the whole population was similar to that previously reported in Rett. Baseline levels of MAP and HR were similar across the phenotypes, consistent with previous reports of little effect of Rett disorder on baseline sympathetic tone. Adverse responses to opiate analgesics and hypocapnoeic attacks were unique to specific phenotypes. We recommend early characterisation of these phenotypes in the management of Rett syndrome. We conclude that classical Rett syndrome consists of heterogeneous clinical phenotypes with distinct cardiorespiratory states. Brainstem functions can be used to identify these and to monitor development and treatment, thereby facilitating clinical management.

The physiology and processing of pain: a review.

Despite the many advances in our understanding of the mechanisms underlying pain processing, pain continues to be a major healthcare problem in the United States. Each day, millions of Americans are affected by both acute and chronic pain conditions, costing in excess of $100 billion for treatment-related costs and lost work productivity. Thus, it is imperative that better treatment strategies be developed. One step toward improving pain management is through increased knowledge of pain physiology. Within the nervous system, there are several pathways that transmit information about pain from the periphery to the brain. There is also a network of pathways that carry modulatory signals from the brain and brainstem that alter the incoming flow of pain information. This article provides a review to the physiology and processing of pain.

Assessment of FIV-C infection of cats as a function of treatment with the protease inhibitor, TL-3.

BACKGROUND: The protease inhibitor, TL-3, demonstrated broad efficacy in vitro against FIV, HIV and SIV (simian immunodeficiency virus), and exhibited very strong protective effects on early neurologic alterations in the CNS of FIV-PPR infected cats. In this study, we analyzed TL-3 efficacy using a highly pathogenic FIV-C isolate, which causes a severe acute phase immunodeficiency syndrome, with high early mortality rates. RESULTS: Twenty cats were infected with uncloned FIV-C and half were treated with TL-3 while the other half were left untreated. Two uninfected cats were used as controls. The general health and the immunological and virological status of the animals was monitored for eight weeks following infection. All infected animals became viremic independent of TL-3 treatment and seven of 20 FIV-C infected animals developed severe immunodepletive disease in conjunction with significantly (p < or = 0.05) higher viral RNA loads as compared to asymptomatic animals. A marked and progressive increase in CD8+ T lymphocytes in animals surviving acute phase infection was noted, which was not evident in symptomatic animals (p < or = 0.05). Average viral loads were lower in TL-3 treated animals and of the 6 animals requiring euthanasia, four were from the untreated cohort. At eight weeks post infection, half of the TL-3 treated animals and only one of six untreated animals had viral loads below detection limits. Analysis of protease genes in TL-3 treated animals with higher than average viral loads revealed sequence variations relative to wild type protease. In particular, one mutant, D105G, imparted 5-fold resistance against TL-3 relative to wild type protease. CONCLUSIONS: The findings indicate that the protease inhibitor, TL-3, when administered orally as a monotherapy, did not prevent viremia in cats infected with high dose FIV-C. However, the modest lowering of viral loads with TL-3 treatment, the greater survival rate in symptomatic animals of the treated cohort, and the lower average viral load in TL-3 treated animals at eight weeks post infection is indicative of a therapeutic effect of the compound on virus infection.