Odelya E. Pagovich MD Mary L. Vo MD Zijun Zhao BA Ioannis N. Petropoulos PhD Michelle Yuan BA Buntitar Lertsuwanroj MD Jessica Ciralsky MD Edward Lai MD Szilard Kiss MD Donald J. D'Amico MD Jason G. Mezey PhD Rayaz A. Malik PhD Ronald G. Crystal MD; Ann Neurol. Accepted Author Manuscript. First published: 07 October 2018, doi:10.1002/ana.25355
CCM demonstrated a significant reduction in nerve fiber density and length in FRDA compared to healthy controls. Importantly, CCM parameters correlated with genotype, SARA and FARS neurological scales, and linear regression modeling of CCM nerve parameters generated equations that predict the neurologic severity of FRDA.
Tuesday, October 9, 2018
Sunday, October 7, 2018
Mitochondrial Targeting in Neurodegeneration: A Heme Perspective
Veronica Fiorito, Deborah Chiabrando and Emanuela Tolosano; Pharmaceuticals 2018, 11(3), 87; doi:10.3390/ph11030087
Mitochondrial dysfunction has achieved an increasing interest in the field of neurodegeneration as a pathological hallmark for different disorders. The impact of mitochondria is related to a variety of mechanisms and several of them can co-exist in the same disease. The central role of mitochondria in neurodegenerative disorders has stimulated studies intended to implement therapeutic protocols based on the targeting of the distinct mitochondrial processes. The review summarizes the most relevant mechanisms by which mitochondria contribute to neurodegeneration, encompassing therapeutic approaches. Moreover, a new perspective is proposed based on the heme impact on neurodegeneration. The heme metabolism plays a central role in mitochondrial functions, and several evidences indicate that alterations of the heme metabolism are associated with neurodegenerative disorders. By reporting the body of knowledge on this topic, the review intends to stimulate future studies on the role of heme metabolism in neurodegeneration, envisioning innovative strategies in the struggle against neurodegenerative diseases.
Mitochondrial dysfunction has achieved an increasing interest in the field of neurodegeneration as a pathological hallmark for different disorders. The impact of mitochondria is related to a variety of mechanisms and several of them can co-exist in the same disease. The central role of mitochondria in neurodegenerative disorders has stimulated studies intended to implement therapeutic protocols based on the targeting of the distinct mitochondrial processes. The review summarizes the most relevant mechanisms by which mitochondria contribute to neurodegeneration, encompassing therapeutic approaches. Moreover, a new perspective is proposed based on the heme impact on neurodegeneration. The heme metabolism plays a central role in mitochondrial functions, and several evidences indicate that alterations of the heme metabolism are associated with neurodegenerative disorders. By reporting the body of knowledge on this topic, the review intends to stimulate future studies on the role of heme metabolism in neurodegeneration, envisioning innovative strategies in the struggle against neurodegenerative diseases.
Saturday, October 6, 2018
Automated functional upper limb evaluation of patients with Friedreich ataxia using serious games rehabilitation exercises
Bruno Bonnechère, Bart Jansen, Inès Haack, Lubos Omelina, Véronique Feipel, Serge Van Sint Jan and Massimo Pandolfo; Journal of NeuroEngineering and Rehabilitation 201815:87 doi.org/10.1186/s12984-018-0430-7
The use of new technologies in rehabilitation, including SG, is becoming increasingly important. In this study demonstrated that it is possible to combine rehabilitation exercises using SG and automated upper limb functional assessment in FRDA patients in wheelchairs. Future works are needed to determine if such kind of solution can be successfully integrated in the rehabilitation program and whether the kind of data presented in this paper can be used to predict disease progression.
The use of new technologies in rehabilitation, including SG, is becoming increasingly important. In this study demonstrated that it is possible to combine rehabilitation exercises using SG and automated upper limb functional assessment in FRDA patients in wheelchairs. Future works are needed to determine if such kind of solution can be successfully integrated in the rehabilitation program and whether the kind of data presented in this paper can be used to predict disease progression.
Thursday, October 4, 2018
Electrophysiological study of patients with spinocerebellar and Friedreich's ataxia
Blerim Myftiu, Mehmet Barış Baslo, Elif Kocasoy Orhan; Neurol Sci Neurophysiol 2018; 35: 138-144 DOI: 10.5152/NSN.2018.11239
Polyneuropathy is frequently detected in SCA and FRDA patients. The sensory nerves in lower extremities were predominantly involved; however motor dysfunction was also noted. MUNE can offer quantitative information on motor nerve fiber and motor neuron involvement. Nerve conduction studies and needle EMG demonstrate clinical or subclinical polyneuropathy in patients with SCA and FRDA ataxia. MUNE might present another parameter for peripheral involvement.
Polyneuropathy is frequently detected in SCA and FRDA patients. The sensory nerves in lower extremities were predominantly involved; however motor dysfunction was also noted. MUNE can offer quantitative information on motor nerve fiber and motor neuron involvement. Nerve conduction studies and needle EMG demonstrate clinical or subclinical polyneuropathy in patients with SCA and FRDA ataxia. MUNE might present another parameter for peripheral involvement.
Tuesday, October 2, 2018
Effects of a wearable proprioceptive stabilizer on kinematics and spatio-temporal gait parameters in young with genetic ataxias
A. Romano, M. Favetta, T. Schirinzi, G. Vasco, S. Summa, S. Minosse, E. Castelli, M. Petrarca; Gait & Posture , Volume 66 , S33 Doi:10.1016/j.gaitpost.2018.07.152
Genetic ataxias are a degenerative disease of cerebellum, brain stem, and spinal cord, in which gait and limb ataxia are key clinical features. Focal mechanical vibration was found effective in improve limb and gait ataxia in adults with hereditary ataxias. Equistasi® is a medical wearable device composed by nanotechnology fibers that transform body temperature into mechanical able to generate a variation of muscle length of max 0.002 mm. This is a preliminary study to evaluate the effect of Equistasi® focal mechanical vibration on kinematic and spatio-temporal parameters in three young patients with genetic ataxias through 3D gait analysis.
Genetic ataxias are a degenerative disease of cerebellum, brain stem, and spinal cord, in which gait and limb ataxia are key clinical features. Focal mechanical vibration was found effective in improve limb and gait ataxia in adults with hereditary ataxias. Equistasi® is a medical wearable device composed by nanotechnology fibers that transform body temperature into mechanical able to generate a variation of muscle length of max 0.002 mm. This is a preliminary study to evaluate the effect of Equistasi® focal mechanical vibration on kinematic and spatio-temporal parameters in three young patients with genetic ataxias through 3D gait analysis.
Monday, October 1, 2018
The importance of central auditory evaluation in Friedreich's ataxia
Zeigelboim BS, Teive HAG, Rosa MRD, Malisky JS, Fonseca VR, Marques JM, Liberalesso PB. Arq Neuropsiquiatr. 2018 Mar;76(3):170-176. doi: 10.1590/0004-282x20180008.
Objective To assess central auditory function in Friedreich's ataxia. Methods A cross-sectional, retrospective study was carried out. Thirty patients underwent the anamnesis, otorhinolaryngology examination, pure tone audiometry, acoustic immittance measures and brainstem auditory evoked potential (BAEP) assessments. Results The observed alterations were: 43.3% in the pure tone audiometry, bilateral in 36.7%; 56.6% in the BAEP test, bilateral in 50%; and 46.6% in the acoustic immittance test. There was a significant difference (p < 0.05) in the comparison between the tests performed. Conclusion In the audiological screening, there was a prevalence of the descending audiometric configuration at the frequency of 4kHz, and absence of the acoustic reflex at the same frequency. In the BAEP test, there was a prevalence of an increase of the latencies in waves I, III and V, and in the intervals of interpeaks I-III, I-V and III-V. In 13.3% of the patients, wave V was absent, and all waves were absent in 3.3% of patients.
Objective To assess central auditory function in Friedreich's ataxia. Methods A cross-sectional, retrospective study was carried out. Thirty patients underwent the anamnesis, otorhinolaryngology examination, pure tone audiometry, acoustic immittance measures and brainstem auditory evoked potential (BAEP) assessments. Results The observed alterations were: 43.3% in the pure tone audiometry, bilateral in 36.7%; 56.6% in the BAEP test, bilateral in 50%; and 46.6% in the acoustic immittance test. There was a significant difference (p < 0.05) in the comparison between the tests performed. Conclusion In the audiological screening, there was a prevalence of the descending audiometric configuration at the frequency of 4kHz, and absence of the acoustic reflex at the same frequency. In the BAEP test, there was a prevalence of an increase of the latencies in waves I, III and V, and in the intervals of interpeaks I-III, I-V and III-V. In 13.3% of the patients, wave V was absent, and all waves were absent in 3.3% of patients.
Friday, September 28, 2018
Functional and Structural Brain Damage in Friedreich's Ataxia
Vavla Marinela, Arrigoni Filippo, Nordio Andrea, De Luca Alberto, Pizzighello Silvia, Petacchi Elisa, Paparella Gabriella, D'Angelo Maria Grazia, Brighina Erika, Russo Emanuela, Fantin Marianna, Colombo Paola, Martinuzzi Andrea; Front. Neurol., 06 September 2018 doi.:10.3389/fneur.2018.00747
Our study demonstrates the extent of CNS brain damage in FRDA by using a composite protocol of clinical and multimodal neuroimaging tools as VBM, DTI and fMRI in a cross-sectional study. Our findings support the need for future longitudinal studies and highlights the possibility that MRI studies could provide valuable paraclinical biomarkers in FRDA.
In conclusion, our multimodal imaging study provided convergent results, with a strong involvement of the cerebellar cortex, cerebellar WM tracts, in particular SCPs and ICPs and a strong functional involvement of the anterior lobe of the cerebellum during the non-dominant hand motor task. These findings bring a new dimensional role of the cortical circuitry involved in FRDA.
Our study demonstrates the extent of CNS brain damage in FRDA by using a composite protocol of clinical and multimodal neuroimaging tools as VBM, DTI and fMRI in a cross-sectional study. Our findings support the need for future longitudinal studies and highlights the possibility that MRI studies could provide valuable paraclinical biomarkers in FRDA.
In conclusion, our multimodal imaging study provided convergent results, with a strong involvement of the cerebellar cortex, cerebellar WM tracts, in particular SCPs and ICPs and a strong functional involvement of the anterior lobe of the cerebellum during the non-dominant hand motor task. These findings bring a new dimensional role of the cortical circuitry involved in FRDA.
Thursday, September 27, 2018
Young couples from Paphos advised to get checked for rare disease before having kids
CyprusMail online, September 26th, 2018 Evie Andreou: Young couples, especially from Paphos, ought to get tested before deciding to have children to discover if they are at a high risk of having a child with the rare Ataxia disease, the Institute of Neurology and Genetics (CING) said on Tuesday.
n a written statement to mark International Ataxia Awareness Day – September 25 – CING said that in Cyprus high rates of patients have been identified in the Paphos district. Following a study in 2001-2002 it was found that about one in 12 people are carriers in the wider Paphos district. The frequency of carriers in European populations ranges between one in 50 to one in 100 people.
n a written statement to mark International Ataxia Awareness Day – September 25 – CING said that in Cyprus high rates of patients have been identified in the Paphos district. Following a study in 2001-2002 it was found that about one in 12 people are carriers in the wider Paphos district. The frequency of carriers in European populations ranges between one in 50 to one in 100 people.
Thursday, September 20, 2018
Chemical synthesis of lipophilic methylene blue analogues which increase mitochondrial biogenesis and frataxin levels.
Indrajit Bandyopadhyay, Sandipan Roy Chowdhury, Nishant P. Visavadiya, Sidney M. Hecht, Omar M. Khdour, Data in Brief, Volume 20, 2018,
Pages 1105-1114, doi:10.1016/j.dib.2018.08.156
As part of an ongoing program to develop potential therapeutic agents for the treatment of the neurodegenerative disease Friedreich׳s ataxia (FRDA), we have prepared a number of lipophilic methylene blue analogues. Some of these compounds significantly increase mitochondrial biogenesis and frataxin levels in cultured Friedreich’s ataxia cells . This data article describes the chemical synthesis and full physicochemical characterization of the new analogues.
Pages 1105-1114, doi:10.1016/j.dib.2018.08.156
As part of an ongoing program to develop potential therapeutic agents for the treatment of the neurodegenerative disease Friedreich׳s ataxia (FRDA), we have prepared a number of lipophilic methylene blue analogues. Some of these compounds significantly increase mitochondrial biogenesis and frataxin levels in cultured Friedreich’s ataxia cells . This data article describes the chemical synthesis and full physicochemical characterization of the new analogues.
Wednesday, September 19, 2018
Iron in Friedreich Ataxia: A Central Role in the Pathophysiology or an Epiphenomenon?
Alsina, D.; Purroy, R.; Ros, J.; Tamarit, J.; Pharmaceuticals 2018, 11, 89. doi:10.3390/ph11030089
Friedreich ataxia is a neurodegenerative disease with an autosomal recessive inheritance. In most patients, the disease is caused by the presence of trinucleotide GAA expansions in the first intron of the frataxin gene. These expansions cause the decreased expression of this mitochondrial protein. Many evidences indicate that frataxin deficiency causes the deregulation of cellular iron homeostasis. In this review, we will discuss several hypotheses proposed for frataxin function, their caveats, and how they could provide an explanation for the deregulation of iron homeostasis found in frataxin-deficient cells.
Friedreich ataxia is a neurodegenerative disease with an autosomal recessive inheritance. In most patients, the disease is caused by the presence of trinucleotide GAA expansions in the first intron of the frataxin gene. These expansions cause the decreased expression of this mitochondrial protein. Many evidences indicate that frataxin deficiency causes the deregulation of cellular iron homeostasis. In this review, we will discuss several hypotheses proposed for frataxin function, their caveats, and how they could provide an explanation for the deregulation of iron homeostasis found in frataxin-deficient cells.
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