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Functional Neurology[JOURNAL]

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Delayed auditory conduction in diabetes: is metformin-induced vitamin B12 deficiency responsible?

Khattar D, Khaliq F, Vaney N … +1 more , Madhu SV

Funct Neurol · 2016 · PMID 27358222 · Full text

The present study aims to evaluate the functional integrity of the auditory pathway in patients with diabetes taking metformin. A further aim is to assess its association with vitamin B12 deficiency induced by metformin.... The present study aims to evaluate the functional integrity of the auditory pathway in patients with diabetes taking metformin. A further aim is to assess its association with vitamin B12 deficiency induced by metformin. Thirty diabetics taking metformin and 30 age-matched non-diabetic controls were enrolled. Stimulus-related potentials and vitamin B12 levels were evaluated in all the subjects. The diabetics showed deficient vitamin B12 levels and delayed wave III latency and III-V interpeak latency in the right ear and delayed Na and Pa wave latencies in the left ear compared with the controls. The dose and duration of metformin showed no association with the stimulusrelated potentials. Therefore, although vitamin B12 levels were deficient and auditory conduction impairment was present in the diabetics on metformin, this impairment cannot be attributed to the vitamin B12 deficiency.

Antiepileptic drug use in a nursing home setting: a retrospective study in older adults.

Callegari C, Ielmini M, Bianchi L … +3 more , Lucano M, Bertù L, Vender S

Funct Neurol · 2016 · PMID 27358221 · Full text

The authors set out to examine qualitatively the use of antiepileptic drugs (AEDs) in a population of older adults in a nursing home setting, evaluating aspects such as specialist prescriptions and changes in dosage. Thi... The authors set out to examine qualitatively the use of antiepileptic drugs (AEDs) in a population of older adults in a nursing home setting, evaluating aspects such as specialist prescriptions and changes in dosage. This retrospective prevalence study was carried out in a state-funded nursing home that provides care and rehabilitation for elderly people. The first objective of the study was to determine the prevalence of AED use in this population. The second objective was to monitor AED dosage modifications during the fifteen-month study period, focusing on the safety and the tolerability of AEDs. In the period of time considered, 129 of 402 monitored patients received at least one anti-epileptic therapy. The prevalence of AED use was therefore 32%. Gabapentin was found to be the most commonly prescribed drug, with a frequency of 29%, and it was used mainly for anxiety disorders, psychosis, neuropathic pain and mood disorders.

Cerebral venous hemodynamic abnormalities in episodic and chronic migraine.

Petolicchio B, Viganò A, di Biase L … +5 more , Tatulli D, Toscano M, Vicenzini E, Passarelli F, Di Piero V

Funct Neurol · 2016 · PMID 27358220 · Full text

Alterations of cerebral venous drainage have been demonstrated in chronic migraine (CM), suggesting that cerebral venous hemodynamic abnormalities (CVHAs) play a role in this condition. The aim of the present study was t... Alterations of cerebral venous drainage have been demonstrated in chronic migraine (CM), suggesting that cerebral venous hemodynamic abnormalities (CVHAs) play a role in this condition. The aim of the present study was to look for a correlation between CM and CVHAs. We recruited 33 subjects suffering from CM with or without analgesic overuse, 29 episodic migraine (EM) patients with or without aura, and 21 healthy subjects as controls (HCs). CVHAs were evaluated by transcranial and extracranial echo-color Doppler evaluation of five venous hemodynamic parameters. CVHAs were significantly more frequent in the CM and EM patients than in the HCs. In the migraine patients, CVHAs were not correlated with clinical features. The significantly greater frequency of CVHAs observed in the migraineurs may reflect a possible relationship between migraine and these abnormalities. Prospective longitudinal studies are needed to investigate whether CVHAs have a role in the processes of migraine chronification.

Vestibular disorders following different types of head and neck trauma.

Kolev OI, Sergeeva M

Funct Neurol · 2016 · PMID 27358219 · Full text

This review focuses on the published literature on vestibular disorders following different types of head and neck trauma. Current knowledge of the different causes and underlying mechanisms of vestibular disorders, as w... This review focuses on the published literature on vestibular disorders following different types of head and neck trauma. Current knowledge of the different causes and underlying mechanisms of vestibular disorders, as well as the sites of organic damage, is presented. Non-organic mechanisms are also surveyed. The frequency of occurrence of vestibular symptoms, and of other accompanying subjective complaints, associated with different types of trauma is presented and related to the specific causes. Hypotheses about the pathogenesis of traumatic vestibular disorders are presented, and the knowledge derived from animal experiments is also discussed. We believe this to be a very important topic, since vestibular complaints in traumatic patients often remain undiagnosed or underestimated in clinical practice. This review article aims to suggest directions for additional research and to provide guidance to both the scientific and clinical practice communities.

Lower- and higher-level models of right hemisphere language. A selective survey.

Gainotti G

Funct Neurol · 2016 · PMID 27358218 · Full text

The models advanced to explain right hemisphere (RH) language function can be divided into two main types. According to the older (lower-level) models, RH language reflects the ontogenesis of conceptual and semantic-lexi... The models advanced to explain right hemisphere (RH) language function can be divided into two main types. According to the older (lower-level) models, RH language reflects the ontogenesis of conceptual and semantic-lexical development; the more recent models, on the other hand, suggest that the RH plays an important role in the use of higher-level language functions, such as metaphors, to convey complex, abstract concepts. The hypothesis that the RH may be preferentially involved in processing the semantic-lexical components of language was advanced by Zaidel in splitbrain patients and his model was confirmed by neuropsychological investigations, proving that right brain-damaged patients show selective semanticlexical disorders. The possible links between lower and higher levels of RH language are discussed, as is the hypothesis that the RH may have privileged access to the figurative aspects of novel metaphorical expressions, whereas conventionalization of metaphorical meaning could be a bilaterally-mediated process involving abstract semantic-lexical codes.

The cerebral venous system in migraine: the not so innocent bystander?

Tassorelli C

Funct Neurol · 2016 · PMID 27358217

Abstract loading — click title to view on PubMed.

Andrographis Paniculata shows anti-nociceptive effects in an animal model of sensory hypersensitivity associated with migraine.

Greco R, Siani F, Demartini C … +5 more , Zanaboni A, Nappi G, Davinelli S, Scapagnini G, Tassorelli C

Funct Neurol · 2016 · PMID 27027895 · Full text

Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we ev... Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we evaluated the anti-nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the hyperalgesia induced by NTG administration in the formalin test. We also analyzed mRNA expression of cytokines in specific brain areas after AP treatment. Male Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or vehicle injection. The data show that AP extract significantly reduced NTG-induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In addition, AP extract reduced IL-6 mRNA expression in the medulla and mesencephalon and also mRNA levels of TNFalpha in the mesencephalic region. These findings suggest that AP extract may be a potential therapeutic approach in the treatment of general pain, and possibly of migraine.

Does chronic exposure to mobile phones affect cognition?

Mohan M, Khaliq F, Panwar A … +1 more , Vaney N

Funct Neurol · 2016 · PMID 27027894 · Full text

Mobile phones form an integral part of our modern lifestyle. Following the drastic rise in mobile phone use in recent years, it has become important to study its potential public health impact. Amongst the various mobile... Mobile phones form an integral part of our modern lifestyle. Following the drastic rise in mobile phone use in recent years, it has become important to study its potential public health impact. Amongst the various mobile phone health hazards, the most alarming is the possible effect on the brain. The aim of the present study was to explore whether chronic exposure to mobile phones affects cognition. Ninety subjects aged 17-25 years with normal hearing were recruited for the study and divided into three groups according to their duration of mobile phone use. No significant differences in N100, P200, N200, P300 latencies or N2-P300 amplitude were observed. Our results suggest that chronic mobile phone exposure does not have detrimental effects on cognition.

Global fractional anisotropy and mean diffusivity together with segmented brain volumes assemble a predictive discriminant model for young and elderly healthy brains: a pilot study at 3T.

Garcia-Lazaro HG, Becerra-Laparra I, Cortez-Conradis D … +1 more , Roldan-Valadez E

Funct Neurol · 2016 · PMID 27027893 · Full text

Several parameters of brain integrity can be derived from diffusion tensor imaging. These include fractional anisotropy (FA) and mean diffusivity (MD). Combination of these variables using multivariate analysis might res... Several parameters of brain integrity can be derived from diffusion tensor imaging. These include fractional anisotropy (FA) and mean diffusivity (MD). Combination of these variables using multivariate analysis might result in a predictive model able to detect the structural changes of human brain aging. Our aim was to discriminate between young and older healthy brains by combining structural and volumetric variables from brain MRI: FA, MD, and white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) volumes. This was a cross-sectional study in 21 young (mean age, 25.71±3.04 years; range, 21-34 years) and 10 elderly (mean age, 70.20±4.02 years; range, 66-80 years) healthy volunteers. Multivariate discriminant analysis, with age as the dependent variable and WM, GM and CSF volumes, global FA and MD, and gender as the independent variables, was used to assemble a predictive model. The resulting model was able to differentiate between young and older brains: Wilks' λ = 0.235, χ² (6) = 37.603, p = .000001. Only global FA, WM volume and CSF volume significantly discriminated between groups. The total accuracy was 93.5%; the sensitivity, specificity and positive and negative predictive values were 91.30%, 100%, 100% and 80%, respectively. Global FA, WM volume and CSF volume are parameters that, when combined, reliably discriminate between young and older brains. A decrease in FA is the strongest predictor of membership of the older brain group, followed by an increase in WM and CSF volumes. Brain assessment using a predictive model might allow the follow-up of selected cases that deviate from normal aging.

Melatonin 4 mg as prophylactic therapy for primary headaches: a pilot study.

Bougea A, Spantideas N, Lyras V … +2 more , Avramidis T, Thomaidis T

Funct Neurol · 2016 · PMID 27027892 · Full text

There is growing evidence that headaches are connected to melatonin secretion. Our aim was to assess the potential effectiveness of melatonin for primary headache prevention. Forty-nine patients (37 with migraine and 12... There is growing evidence that headaches are connected to melatonin secretion. Our aim was to assess the potential effectiveness of melatonin for primary headache prevention. Forty-nine patients (37 with migraine and 12 with chronic tension-type headache, TTH) were prescribed oral melatonin, 4 mg, 30 minutes before bedtime for six months. Forty-one (83.6%) of the 49 patients completed the study, while eight dropped out for personal reasons. A statistically significant reduction in headache frequency was found between baseline and final follow-up after six months of treatment (p=0.033 for TTH patients and p<0.001 for migraineurs). The Headache Impact Test score was significantly reduced in both groups of headache patients (p=0.002 and p<0.001, respectively). At baseline, melatonin levels, measured both during a headache attack and a pain-free period, did not differ between patients with TTH and migraineurs (p=0.539 and p=0.693, respectively), and no statistically significant differences in Hamilton Depression Rating Scale scores were found between the two groups. This pilot study shows promising results, in terms of headache frequency reduction and daily quality of life improvement, in both groups.

Effects of treadmill training on cognitive and motor features of patients with mild to moderate Parkinson's disease: a pilot, single-blind, randomized controlled trial.

Picelli A, Varalta V, Melotti C … +7 more , Zatezalo V, Fonte C, Amato S, Saltuari L, Santamato A, Fiore P, Smania N

Funct Neurol · 2016 · PMID 27027891 · Full text

The aim of this pilot randomized controlled trial was to evaluate the effects of treadmill training on cognitive and motor performance in patients with Parkinson's disease (PD). Seventeen persons with mild to moderate PD... The aim of this pilot randomized controlled trial was to evaluate the effects of treadmill training on cognitive and motor performance in patients with Parkinson's disease (PD). Seventeen persons with mild to moderate PD were enrolled. Nine patients were allocated to the Intervention group and received twelve 45-minute sessions of treadmill training: one session a day, three days a week, for four consecutive weeks. Eight patients were allocated to the Control group; these patients did not undergo physical training but were required to have regular social interactions, following a specific lifestyle program. All the patients were evaluated at baseline and one month later. The primary outcome measures were the Frontal Assessment Battery-Italian version (FAB-it) and the 6-minute walking test (6MWT). At the one month evaluation significant differences were found between the groups in their performance on the FAB-it (p=0.005) and the 6MWT (p=0.018). Our findings support the hypothesis that treadmill training might effectively improve cognitive and motor features in patients with PD.

Disability may influence patient willingness to participate in decision making on first-line therapy in multiple sclerosis.

D'Amico E, Leone C, Patti F

Funct Neurol · 2016 · PMID 27027890 · Full text

Patient autonomy is a concept that implies variable degrees of patient participation in different aspects of health and healthcare, including the choice of therapy. This study, conducted in patients with multiple scleros... Patient autonomy is a concept that implies variable degrees of patient participation in different aspects of health and healthcare, including the choice of therapy. This study, conducted in patients with multiple sclerosis (MS), examined several factors in relation to the patient's role in the therapeutic decision-making process. One hundred newly diagnosed patients with MS attending their first ever specialist consultation at the MS center of Catania, Italy, were consecutively enrolled in a single-center, open, observational study. Clinical and demographic data were collected as part of this routine first consultation. Through administration of the Control Preferences Scale, we ascertained the patients' willingness to participate in the decision-making process on their first-line treatment, classifying them, on the basis of their attitude, as passive, collaborative or active. Of 100 patients with MS, 40 had a passive attitude, while 35 were willing to collaborate and 25 wanted to play an active role in the decision-making process. The patients showing an active attitude had a significantly higher Expanded Disability Status Scale score and a significantly higher number of relapses (p<0.5 for both) than those who showed other attitudes. Persons with MS prefer to know the benefits and risks related to the first-line treatment. Those with higher disability prefer to be active in the decision-making process.

Amyotrophic lateral sclerosis and environmental factors.

Bozzoni V, Pansarasa O, Diamanti L … +3 more , Nosari G, Cereda C, Ceroni M

Funct Neurol · 2016 · PMID 27027889 · Full text

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that affects central and peripheral motor neuron cells. Its etiology is unknown, although a relationship between genetic background and environmen... Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that affects central and peripheral motor neuron cells. Its etiology is unknown, although a relationship between genetic background and environmental factors may play a major role in triggering the neurodegeneration. In this review, we analyze the role of environmental factors in ALS: heavy metals, electromagnetic fields and electric shocks, pesticides, β-N-methylamino-L-alanine, physical activity and the controversial role of sports. The literature on the single issues is analyzed in an attempt to clarify, as clearly as possible, whether each risk factor significantly contributes to the disease pathogenesis. After summarizing conflicting observations and data, the authors provide a final synthetic statement.

Decision making in MS: factors affecting engagement in treatment choices.

Muhlert N

Funct Neurol · 2016 · PMID 27027888 · Full text

Abstract loading — click title to view on PubMed.

Functional magnetic resonance imaging in disorders of consciousness: preliminary results of an innovative analysis of brain connectivity.

De Pasquale F, Caravasso CF, Péran P … +4 more , Catani S, Tuovinen N, Sabatini U, Formisano R

Funct Neurol · 2015 · PMID 26910178 · Full text

The aim of this preliminary study was to present a new approach for connectivity analysis in patients with severe acquired brain injury (ABI) that overcomes some of the difficulties created by anatomical abnormalities du... The aim of this preliminary study was to present a new approach for connectivity analysis in patients with severe acquired brain injury (ABI) that overcomes some of the difficulties created by anatomical abnormalities due to the brain injury. Using a data-driven approach, resting-state structural MRI (sMRI) and functional MRI (fMRI) data from three severe ABI patients - two with disorders of consciousness (DOC) and one who had recovered consciousness (non-DOC) - were integrated and analyzed. Parameters extracted from the distribution of the connectivity values, such as mean, standard deviation and skeweness, were considered. The distribution parameters estimated seem to provide an accurate multivariate classification of the considered cases that can be summarized as follows: connectivity in the severe ABI patients with DOC was on average lower than in the severe ABI non-DOC patient and healthy subjects. The dispersion of connectivity values of the severe ABI patients, non-DOC and DOC, was comparable, however the shape of the distribution was different in the non-DOC patient. Eventually, seed-based connectivity maps of the default mode Functional magnetic resonance imaging in disorders of consciousness: preliminary results of an innovative analysis of brain connectivity network show a pattern of increasing disruption of this network from the healthy subjects to non-DOC and DOC patients. Consistent results are obtained using an ICA-based approach..

Intravenous methylprednisolone pulse therapy for children with epileptic encephalopathy.

Pera MC, Randazzo G, Masnada S … +4 more , Dontin SD, De Giorgis V, Balottin U, Veggiotti P

Funct Neurol · 2015 · PMID 26910177 · Full text

The aim of this retrospective study of children affected by epileptic encephalopathy was to evaluate seizure frequency, electroencephalographic pattern and neuropsychological status, before and after intravenous methylpr... The aim of this retrospective study of children affected by epileptic encephalopathy was to evaluate seizure frequency, electroencephalographic pattern and neuropsychological status, before and after intravenous methylprednisolone therapy. Eleven children with epileptic encephalopathy were administered one cycle of intravenous methylprednisolone (15-30 mg/kg/day for three consecutive days, once a month for four months) in addition to constant dosages of their regular antiepileptic drugs. The treatment resulted in statistically significant reductions of generalized slow spike-and-wave discharges (p<0.0028) and seizure frequency (p<0.013), which persisted even after methylprednisolone pulse therapy was stopped. A globally positive outcome was noted in 9/11 patients (81.8%). This methylprednisolone treatment regimen did not cause significant or persistent adverse effects. We suggest that children with epileptic encephalopathy without an underlying structural lesion could be the best candidates for intravenous methylprednisolone pulse therapy.

Why is nitric oxide important for our brain?

Džoljić E, Grbatinić I, Kostić V

Funct Neurol · 2015 · PMID 26910176 · Full text

The freely diffusible gaseous compound nitric oxide (NO) has been shown to be an important messenger in many organ systems throughout the body, and particularly in the central nervous system (CNS). The importance of NO a... The freely diffusible gaseous compound nitric oxide (NO) has been shown to be an important messenger in many organ systems throughout the body, and particularly in the central nervous system (CNS). The importance of NO as an intermediary in cell communication in the brain is highlighted by the fact that the excitatory amino acid glutamate, the most abundant CNS neurotransmitter, is an initiator of the reaction that forms NO. Because of its numerous physiological and pathophysiological roles, the impact of NO on clinical medicine is developing. NO can act as a "double-edged sword" and it has been demonstrated that clarification of the dual effect of NO might have implications for clinical medicine, and could lead to the emergence of therapeutic opportunities. Accordingly, NO was proclaimed "Mole cule of the Year" in 1992 by the journal Science, while discovery of the pathways and roles of NO was acknowledged with the Nobel Prize in 1998. Additionally, the ubiquity of NO in the CNS implies that drugs designed to modify the biological activity of NO may have distinct effects. Thus, further clinical applications of NO, of its analogs or of newly developed NOS inhibitors are forthcoming. The therapeutic challenge would be to succeed in manipulating the NO pathways selectively.

Acute effects of high-frequency microfocal vibratory stimulation on the H reflex of the soleus muscle. A double-blind study in healthy subjects.

Alfonsi E, Paone P, Tassorelli C … +9 more , De Icco R, Moglia A, Alvisi E, Marchetta L, Fresia M, Montini A, Calabrese M, Versiglia V, Sandrini G

Funct Neurol · 2015 · PMID 26727706 · Full text

This study in healthy subjects examined the effects of a system delivering focal microvibrations at high frequency (Equistasi®) on tonic vibration stimulus (TVS)-induced inhibition of the soleus muscle H reflex. Highfreq... This study in healthy subjects examined the effects of a system delivering focal microvibrations at high frequency (Equistasi®) on tonic vibration stimulus (TVS)-induced inhibition of the soleus muscle H reflex. Highfrequency microvibrations significantly increased the inhibitory effect of TVS on the H reflex for up to three minutes. Moreover, Equistasi® also significantly reduced alpha-motoneuron excitability, as indicated by the changes in the ratio between the maximumamplitude H reflex (Hmax reflex) and the maximumamplitude muscle response (Mmax response); this effect was due to reduction of the amplitude of the H reflex because the amplitude of muscle response remained unchanged. The present findings indicate that Equistasi® has a modulatory effect on proprioceptive reflex circuits. Therefore, Equistasi® might interfere with some mechanisms involved in both physiological and pathophysiological control of movement and of posture.

Measurement of urinary copper excretion after 48-h d-penicillamine cessation as a compliance assessment in Wilson's disease.

Dzieżyc K, Litwin T, Chabik G … +1 more , Członkowska A

Funct Neurol · 2015 · PMID 26727705 · Full text

Treatment of Wilson's disease (WD) with anti-copper agents is effective in most compliant patients. During long-term treatment with chelating agents, a two-day interruption of the treatment should result in normal urinar... Treatment of Wilson's disease (WD) with anti-copper agents is effective in most compliant patients. During long-term treatment with chelating agents, a two-day interruption of the treatment should result in normal urinary copper concentrations (<50 μg/dl). The aim of this study was to establish the usefulness of this method as a compliance assessment in these patients. We examined consecutive patients treated with d-penicillamine (DPA) undergoing routine follow-up studies at our center. We performed 24-h urinary copper excretion analysis 48 h after interruption of chelating therapy. Thirty-two patients were enrolled. After DPA cessation, normalization of copper excretion was observed in 91% of reportedly compliant patients. The specificity and sensitivity values of this test were 87% and 77%, respectively. Measurement of 24-h urinary copper excretion after a 48-h interruption of DPA therapy in patients with WD is a reliable method for confirming patients' compliance.

Cortical excitability changes over time in progressive multiple sclerosis.

Ayache SS, Créange A, Farhat WH … +5 more , Zouari HG, Lesage C, Palm U, Abdellaoui M, Lefaucheur JP

Funct Neurol · 2015 · PMID 26727704 · Full text

In 25 patients with progressive forms of multiple sclerosis (MS), motor cortex excitability was longitudinally studied over one year by means of transcranial magnetic stimulation (TMS). The following TMS parameters were... In 25 patients with progressive forms of multiple sclerosis (MS), motor cortex excitability was longitudinally studied over one year by means of transcranial magnetic stimulation (TMS). The following TMS parameters were considered: resting and active motor thresholds (MTs), input-output curve, short-interval intracortical inhibition (SICI), and intracortical facilitation. Clinical evaluation was based on the Expanded Disability Status Scale (EDSS). In the 16 patients not receiving disease-modifying drugs, the EDSS score worsened, resting MT increased, and SICI decreased. By contrast, no clinical for neurophysiological changes were found over time in the nine patients receiving immunomodulatory therapy. The natural course of progressive MS appears to be associated with a decline in cortical excitability of both pyramidal neurons and inhibitory circuits. This pilot study based on a small sample suggests that disease-modifying drugs may allow cortical excitability to remain stable, even in patients with progressive MS.
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