|
1
|
Noioso CM, Bevilacqua L, Acerra GM, Valle PD, Serio M, Pecoraro A, Rienzo A, De Marca U, De Biasi G, Vinciguerra C, Piscosquito G, Toriello A, Tozza S, Barone P, Iovino A. The spectrum of anti-GQ1B antibody syndrome: beyond Miller Fisher syndrome and Bickerstaff brainstem encephalitis. Neurol Sci 2024; 45:5657-5669. [PMID: 38987510 DOI: 10.1007/s10072-024-07686-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 07/03/2024] [Indexed: 07/12/2024]
Abstract
INTRODUCTION Since the initial identification of Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE),significant milestones have been achieved in understanding these diseases.Discoveries of common serum antibodies (IgG anti-GQ1b), antecedent infections, neurophysiological data, andneuroimaging suggested a shared autoimmune pathogenetic mechanism rather than distinct pathogenesis, leadingto the hypothesis that both diseases are part of a unified syndrome, termed "Fisher-Bickerstaff syndrome". The subsequent identification of atypical anti-GQ1b-positive forms expanded the classification to a broader condition known as "Anti-GQ1b-Antibody syndrome". METHODS An exhaustive literature review was conducted, analyzing a substantial body of research spanning from the initialdescriptions of the syndrome's components to recent developments in diagnostic classification and researchperspectives. RESULTS Anti-GQ1b syndrome encompasses a continuous spectrum of conditions defined by a common serological profilewith varying degrees of peripheral (PNS) and central nervous system (CNS) involvement. MFS and BBE represent theopposite ends of this spectrum, with MFS primarily affecting the PNS and BBE predominantly involving the CNS.Recently identified atypical forms, such as acute ophthalmoparesis, acute ataxic neuropathy withoutophthalmoparesis, Guillain-Barré syndrome (GBS) with ophthalmoparesis, MFS-GBS and BBE-GBS overlap syndromes,have broadened this spectrum. CONCLUSION This work aims to provide an extensive, detailed, and updated overview of all aspects of the anti-GQ1b syndromewith the intention of serving as a stepping stone for further shaping thereof. Special attention was given to therecently identified atypical forms, underscoring their significance in redefining the boundaries of the syndrome.
Collapse
Affiliation(s)
- Ciro Maria Noioso
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy.
| | - Liliana Bevilacqua
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Gabriella Maria Acerra
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Paola Della Valle
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Marina Serio
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Agnese Pecoraro
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Annalisa Rienzo
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Umberto De Marca
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Giuseppe De Biasi
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Claudia Vinciguerra
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Giuseppe Piscosquito
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Antonella Toriello
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Stefano Tozza
- Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Naples, Italy
| | - Paolo Barone
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| | - Aniello Iovino
- Neurology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy
| |
Collapse
|
|
2
|
Bell T, Lindner M, Langdon A, Mullins PG, Christakou A. Regional Striatal Cholinergic Involvement in Human Behavioral Flexibility. J Neurosci 2019; 39:5740-5749. [PMID: 31109959 PMCID: PMC6636079 DOI: 10.1523/jneurosci.2110-18.2019] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 05/08/2019] [Accepted: 05/13/2019] [Indexed: 12/12/2022] Open
Abstract
Animal studies have shown that the striatal cholinergic system plays a role in behavioral flexibility but, until recently, this system could not be studied in humans due to a lack of appropriate noninvasive techniques. Using proton magnetic resonance spectroscopy, we recently showed that the concentration of dorsal striatal choline (an acetylcholine precursor) changes during reversal learning (a measure of behavioral flexibility) in humans. The aim of the present study was to examine whether regional average striatal choline was associated with reversal learning. A total of 22 participants (mean age = 25.2 years, range = 18-32 years, 13 female) reached learning criterion in a probabilistic learning task with a reversal component. We measured choline at rest in both the dorsal and ventral striatum using magnetic resonance spectroscopy. Task performance was described using a simple reinforcement learning model that dissociates the contributions of positive and negative prediction errors to learning. Average levels of choline in the dorsal striatum were associated with performance during reversal, but not during initial learning. Specifically, lower levels of choline in the dorsal striatum were associated with a lower number of perseverative trials. Moreover, choline levels explained interindividual variance in perseveration over and above that explained by learning from negative prediction errors. These findings suggest that the dorsal striatal cholinergic system plays an important role in behavioral flexibility, in line with evidence from the animal literature and our previous work in humans. Additionally, this work provides further support for the idea of measuring choline with magnetic resonance spectroscopy as a noninvasive way of studying human cholinergic neurochemistry.SIGNIFICANCE STATEMENT Behavioral flexibility is a crucial component of adaptation and survival. Evidence from the animal literature shows that the striatal cholinergic system is fundamental to reversal learning, a key paradigm for studying behavioral flexibility, but this system remains understudied in humans. Using proton magnetic resonance spectroscopy, we showed that choline levels at rest in the dorsal striatum are associated with performance specifically during reversal learning. These novel findings help to bridge the gap between animal and human studies by demonstrating the importance of cholinergic function in the dorsal striatum in human behavioral flexibility. Importantly, the methods described here cannot only be applied to furthering our understanding of healthy human neurochemistry, but also to extending our understanding of cholinergic disorders.
Collapse
Affiliation(s)
- Tiffany Bell
- School of Psychology and Clinical Language Sciences, and Centre for Integrative Neuroscience and Neurodynamics, University of Reading, Reading RG6 6AL, United Kingdom
| | - Michael Lindner
- School of Psychology and Clinical Language Sciences, and Centre for Integrative Neuroscience and Neurodynamics, University of Reading, Reading RG6 6AL, United Kingdom
| | - Angela Langdon
- Princeton Neuroscience Institute, Princeton University, New Jersey 08544, and
| | | | - Anastasia Christakou
- School of Psychology and Clinical Language Sciences, and Centre for Integrative Neuroscience and Neurodynamics, University of Reading, Reading RG6 6AL, United Kingdom,
| |
Collapse
|
|
3
|
Kadodwala VH, Hadjivassiliou M, Currie S, Skipper N, Hoggard N. Is 1H-MR spectroscopy useful as a diagnostic aid in MSA-C? CEREBELLUM & ATAXIAS 2019; 6:7. [PMID: 31321064 PMCID: PMC6612153 DOI: 10.1186/s40673-019-0099-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 04/26/2019] [Indexed: 02/08/2023]
Abstract
Background Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disease with a cerebellar subtype where ataxic symptoms predominate (MSA-C) associated with autonomic dysfunction and a grave prognosis. The purpose of this analysis was to identify if cerebellar volumetry and MR spectroscopy obtained as part of routine clinical work up of patients with sporadic ataxia differentiates patients with multiple system atrophy- cerebellar type (MSA-C) from those with sporadic adult-onset ataxia of unknown etiology (SAOA) who’s condition follows a more benign course. Methods Retrospective comparison was undertaken of 20 clinically probable or possible MSA-C patients, 20 age and sex matched patients with SAOA and 20 healthy control subjects. Single voxel 1H-MR spectroscopy of the cerebellar hemisphere and vermis and volumetric analysis of the cerebellum and brainstem were undertaken on baseline scans, comparing all groups. Results There was significant reduction in NAA/Cr levels in patients with MSA-C when compared to those with ISA (p = 0.005) and healthy controls (p < 0.001) in both the hemisphere and vermis. Brainstem volume was significantly reduced in MSA-C patients compared to SAOA patients (p < 0.001) and healthy controls (p < 0.001). There was no difference in cerebellar volume between MSA-C patients and SAOA patients. Conclusion This paper demonstrates that at presentation, MSA-C patients have a significant reduction of NAA/Cr in the cerebellum and significant decrease in brainstem volume when compared to SAOA and healthy controls. This is the first study to sucessfully show clinical utility of MR spectroscopy of the cerebellum for differentiating MSA-C from patients with SAOA. Electronic supplementary material The online version of this article (10.1186/s40673-019-0099-0) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Viren H Kadodwala
- Academic Unit of Radiology, C Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF UK
| | - Marios Hadjivassiliou
- Academic Unit of Radiology, C Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF UK
| | - Stuart Currie
- Academic Unit of Radiology, C Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF UK
| | - Nicholas Skipper
- Academic Unit of Radiology, C Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF UK
| | - Nigel Hoggard
- Academic Unit of Radiology, C Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF UK
| |
Collapse
|
|
4
|
Shanmugarajah PD, Hoggard N, Aeschlimann DP, Aeschlimann PC, Dennis GJ, Howell SJ, Reuber M, Grünewald RA, Hadjivassiliou M. Phenytoin-related ataxia in patients with epilepsy: clinical and radiological characteristics. Seizure 2018; 56:26-30. [PMID: 29427835 DOI: 10.1016/j.seizure.2018.01.019] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 01/22/2018] [Accepted: 01/29/2018] [Indexed: 10/18/2022] Open
Abstract
PURPOSE Phenytoin is an effective anticonvulsant for focal epilepsy. Its use can be associated with long-term adverse effects including cerebellar ataxia. Whilst phenytoin is toxic to Purkinje cells in vitro; the clinical and radiological phenotype and mechanism of cerebellar degeneration in vivo remain unclear. We describe the prevalence, clinical and radiological characteristics of phenytoin-related ataxia. METHODS Patients with epilepsy receiving treatment with phenytoin were recruited from the Epilepsy clinics at Royal Hallamshire Hospital, Sheffield, UK. Neurological examination was performed on all patients after recruitment. Patients were categorised into those with and without ataxia. We determined the severity of ataxia clinically (SARA score) and the pattern of cerebellar involvement by neuroimaging (MRI volumetry and MR spectroscopy). RESULTS Forty-seven patients were recruited. Median duration of epilepsy was 24 years, median duration of phenytoin treatment was 15 years and current median phenytoin daily dose was 325 mg. Fifty-five percent of patients complained of poor balance. Clinical evidence of ataxia was seen in 40% patients. Gait, stance and heel-shin slide were the predominant features of cerebellar dysfunction. MRI demonstrated structural, volumetric and functional deficits of the cerebellum. Only one patient with ataxia had phenytoin levels above the normal range. CONCLUSIONS Cerebellar ataxia is present in 40% of patients with epilepsy and chronic exposure to phenytoin. Patients on long-term phenytoin have reduced cerebellar volume even if they have no clinical evidence of ataxia. Evidence of structural deficits on imaging suggests a predilection for vermian involvement.
Collapse
Affiliation(s)
- Priya D Shanmugarajah
- Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK.
| | - Nigel Hoggard
- Academic Unit of Radiology, University of Sheffield, Sheffield, UK.
| | - Daniel P Aeschlimann
- Matrix Biology & Tissue Repair Research Unit, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University, Cardiff, UK.
| | - Pascale C Aeschlimann
- Matrix Biology & Tissue Repair Research Unit, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University, Cardiff, UK.
| | - Gary J Dennis
- Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK.
| | - Stephen J Howell
- Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK.
| | - Markus Reuber
- Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK.
| | - Richard A Grünewald
- Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK.
| | - Marios Hadjivassiliou
- Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK.
| |
Collapse
|
|
5
|
Zhang L, Li M, Sui R. Correlation between cerebellar metabolism and post-stroke depression in patients with ischemic stroke. Oncotarget 2017; 8:91711-91722. [PMID: 29207680 PMCID: PMC5710960 DOI: 10.18632/oncotarget.21063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 08/31/2017] [Indexed: 12/11/2022] Open
Abstract
The neurochemical changes that occur in the brain of patients with post-stroke depression (PSD) are not fully understood. This study aims to explore the correlation between cerebellar metabolism changes and PSD using proton magnetic resonance spectroscopy (1H-MRS). Participants were assigned to 3 groups: 60 patients with PSD (PSD group), 60 stroke patients without depression (NOPSD group), and 60 healthy volunteers (HEAL group). T1 WI, T2 WI, DWI and 1H-MRS examination were performed for patients at 14 days, 3 months after the stroke, respectively, and for healthy volunteers once when included in the study. Cho/Cr and Cho/NAA ratios in the cerebellar hemisphere contralateral to the lesion were higher in the PSD group than those in the HEAL and NOPSD groups on 14th day after the stroke (P < 0.05). In PSD group, Cho/Cr and Cho/NAA ratios in the cerebellar hemisphere contralateral to the lesion were positively correlated to the HAMD scale scores at both 14 days and 3 months after stroke (P < 0.05); Higher Cho/Cr and Cho/NAA ratios, and lower NAA/Cr ratio in the cerebellar hemisphere contralateral to the lesion were observed at 3 months after stroke compared to that at 14 days after stroke. Cerebellar damage may lead to PSD, and the degree of cerebellar damage may be associated with severity of PSD.
Collapse
Affiliation(s)
- Lei Zhang
- School of Nursing, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Muzi Li
- Department of Neurology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Rubo Sui
- Department of Neurology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China
| |
Collapse
|
|
6
|
Mormina E, Petracca M, Bommarito G, Piaggio N, Cocozza S, Inglese M. Cerebellum and neurodegenerative diseases: Beyond conventional magnetic resonance imaging. World J Radiol 2017; 9:371-388. [PMID: 29104740 PMCID: PMC5661166 DOI: 10.4329/wjr.v9.i10.371] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 07/18/2017] [Accepted: 08/02/2017] [Indexed: 02/06/2023] Open
Abstract
The cerebellum plays a key role in movement control and in cognition and cerebellar involvement is described in several neurodegenerative diseases. While conventional magnetic resonance imaging (MRI) is widely used for brain and cerebellar morphologic evaluation, advanced MRI techniques allow the investigation of cerebellar microstructural and functional characteristics. Volumetry, voxel-based morphometry, diffusion MRI based fiber tractography, resting state and task related functional MRI, perfusion, and proton MR spectroscopy are among the most common techniques applied to the study of cerebellum. In the present review, after providing a brief description of each technique’s advantages and limitations, we focus on their application to the study of cerebellar injury in major neurodegenerative diseases, such as multiple sclerosis, Parkinson’s and Alzheimer’s disease and hereditary ataxia. A brief introduction to the pathological substrate of cerebellar involvement is provided for each disease, followed by the review of MRI studies exploring structural and functional cerebellar abnormalities and by a discussion of the clinical relevance of MRI measures of cerebellar damage in terms of both clinical status and cognitive performance.
Collapse
Affiliation(s)
- Enricomaria Mormina
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
- Neuroradiology Unit, Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, 98100 Messina, Italy
| | - Maria Petracca
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
- Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80138 Naples, Italy
| | - Giulia Bommarito
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy
| | - Niccolò Piaggio
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy
- Department of Neuroradiology, San Martino Hospital, 16132 Genoa, Italy
| | - Sirio Cocozza
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
- Department of Advanced Biomedical Sciences, University of Naples Federico II, 80138 Naples, Italy
| | - Matilde Inglese
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy
| |
Collapse
|
|
7
|
Shanmugarajah PD, Hoggard N, Currie S, Aeschlimann DP, Aeschlimann PC, Gleeson DC, Karajeh M, Woodroofe N, Grünewald RA, Hadjivassiliou M. Alcohol-related cerebellar degeneration: not all down to toxicity? CEREBELLUM & ATAXIAS 2016; 3:17. [PMID: 27729985 PMCID: PMC5048453 DOI: 10.1186/s40673-016-0055-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 09/29/2016] [Indexed: 12/04/2022]
Abstract
Background Alcohol-related cerebellar degeneration is one of the commonest acquired forms of cerebellar ataxia. The exact pathogenic mechanisms by which alcohol leads to cerebellar damage remain unknown. Possible autoreactive immune mediated mechanisms have not been explored previously. In this study, we aim to investigate the potential role of alcohol-induced immune mediated cerebellar degeneration. Methods Patients with ataxia and a history of alcohol misuse were recruited from the Ataxia and Hepatology tertiary clinics at Sheffield Teaching Hospitals NHS Trust. We determined the pattern of cerebellar involvement both on clinical (SARA score) and imaging (MRI volumetry and MR spectroscopy) parameters. In addition, HLA genotyping, serological markers for gluten-related disorders and serological reactivity on rat cerebellar tissue using indirect immunohistochemistry were assessed. Results Thirty-eight patients were included in the study all of whom had ataxia. The gait (97 %), stance (89 %) and heel-shin slide (89 %) were the predominant SARA elements affected. MRI volumetric and spectroscopy techniques demonstrated significant structural, volumetric and functional deficits of the cerebellum with particular involvement of the cerebellar vermis. Circulating anti-gliadin antibodies were detected in 34 % patients vs. 12 % in healthy controls. Antibodies to transglutaminase 6 (TG6) were detected in 39 % of patients and 4 % of healthy control subjects. Using immunohistochemistry, Purkinje cell and/or granular layer reactivity was demonstrated in 71 % of patient sera. Conclusions Alcohol induced tissue injury to the CNS leading to cerebellar degeneration may also involve immune mediated mechanisms, including sensitisation to gluten. Electronic supplementary material The online version of this article (doi:10.1186/s40673-016-0055-1) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Priya D Shanmugarajah
- Academic Department of Neurosciences, Royal Hallamshire Hospital, and University of Sheffield, Sheffield, UK
| | - Nigel Hoggard
- Academic Unit of Radiology, University of Sheffield, Sheffield, UK
| | - Stuart Currie
- Academic Unit of Radiology, University of Sheffield, Sheffield, UK
| | - Daniel P Aeschlimann
- Matrix Biology & Tissue Repair Research Unit, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University, Cardiff, UK
| | - Pascale C Aeschlimann
- Matrix Biology & Tissue Repair Research Unit, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University, Cardiff, UK
| | - Dermot C Gleeson
- Academic Department of Hepatology, Royal Hallamshire Hospital, and University of Sheffield, Sheffield, UK
| | - Mohammed Karajeh
- Academic Department of Hepatology, Royal Hallamshire Hospital, and University of Sheffield, Sheffield, UK
| | - Nicola Woodroofe
- Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK
| | - Richard A Grünewald
- Academic Department of Neurosciences, Royal Hallamshire Hospital, and University of Sheffield, Sheffield, UK
| | - Marios Hadjivassiliou
- Academic Department of Neurosciences, Royal Hallamshire Hospital, and University of Sheffield, Sheffield, UK
| |
Collapse
|
|
8
|
Long Z, Dyke JP, Ma R, Huang CC, Louis ED, Dydak U. Reproducibility and effect of tissue composition on cerebellar γ-aminobutyric acid (GABA) MRS in an elderly population. NMR IN BIOMEDICINE 2015; 28:1315-23. [PMID: 26314380 PMCID: PMC4594865 DOI: 10.1002/nbm.3381] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2015] [Revised: 07/22/2015] [Accepted: 07/24/2015] [Indexed: 05/06/2023]
Abstract
MRS provides a valuable tool for the non-invasive detection of brain γ-aminobutyric acid (GABA) in vivo. GABAergic dysfunction has been observed in the aging cerebellum. The study of cerebellar GABA changes is of considerable interest in understanding certain age-related motor disorders. However, little is known about the reproducibility of GABA MRS in an aged population. Therefore, this study aimed to explore the feasibility and reproducibility of GABA MRS in the aged cerebellum at 3.0 T and to examine the effect of differing tissue composition on GABA measurements. MRI and (1)H MRS examinations were performed on 10 healthy elderly volunteers (mean age, 75.2 ± 6.5 years) using a 3.0-T Siemens Tim Trio scanner. Among them, five subjects were scanned twice to assess the short-term reproducibility. The MEGA-PRESS (Mescher-Garwood point-resolved spectroscopy) J-editing sequence was used for GABA detection in two volumes of interest (VOIs) in the left and right cerebellar dentate. MRS data processing and quantification were performed with LCModel 6.3-0L using two separate basis sets, generated from density matrix simulations using published values for chemical shifts and J couplings. Raw metabolite levels from LCModel outputs were corrected for cerebrospinal fluid contamination and relaxation. GABA-edited spectra yielded robust and stable GABA measurements with averaged intra-individual coefficients of variation for corrected GABA+ between 4.0 ± 2.8% and 13.4 ± 6.3%, and inter-individual coefficients of variation between 12.6% and 24.2%. In addition, there was a significant correlation between GABA+ obtained with the two LCModel basis sets. Overall, our results demonstrated the feasibility and reproducibility of cerebellar GABA-edited MRS at 3.0 T in an elderly population. This information might be helpful for studies using this technique to study GABA changes in normal or diseased aging brain, e.g. for power calculations and the interpretation of longitudinal observations.
Collapse
Affiliation(s)
- Zaiyang Long
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Jonathan P. Dyke
- Department of Radiology, Weill Cornell Medical College, New York, NY, USA
| | - Ruoyun Ma
- School of Health Sciences, Purdue University, West Lafayette, IN, USA
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Chaorui C. Huang
- Brain and Mind Research Institute, Weill Medical College of Cornell University, New York, NY, USA
| | - Elan D. Louis
- Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT, USA
- Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA
| | - Ulrike Dydak
- School of Health Sciences, Purdue University, West Lafayette, IN, USA
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA
- Correspondence to: U. Dydak, School of Health Sciences, Purdue University, West Lafayette, IN, 47907, USA.
| |
Collapse
|
|
9
|
Sandler RD, Hoggard N, Hadjivassiliou M. Miller-Fisher Syndrome: Is the ataxia central or peripheral? CEREBELLUM & ATAXIAS 2015; 2:3. [PMID: 26331046 PMCID: PMC4552373 DOI: 10.1186/s40673-015-0021-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 02/12/2015] [Indexed: 11/10/2022]
Abstract
A 50-year-old man presented with a brief history of slurred speech, unsteadiness, double vision and paraesthesia. He had been unwell for 12 days with campylobacter gastroenteritis. On examination, there was ophthalmoplegia, nystagmus, areflexia and lower limb and gait ataxia. Serological testing was positive for GQ1b antibody in keeping with the diagnosis of Miller Fisher Syndrome (MFS). He was treated with two courses of intravenous immunoglobulins and made a good recovery, only displaying mild gait ataxia when reviewed in clinic 2.5 months later. There has long been a debate as to whether the ataxia in MFS originates in the cerebellum or it is more peripheral. In this case, magnetic resonance spectroscopy (MRS) revealed a reduced NAA/Cr ratio in the cerebellar vermis and right cerebral hemisphere, suggestive of cerebellar dysfunction. The NAA/Cr normalised 2.5 months later reflecting the clinical recovery. The findings on MRS suggest that the cerebellum is involved in MFS.
Collapse
Affiliation(s)
- Robert D Sandler
- Academic Department of Neurosciences, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF UK
| | - Nigel Hoggard
- Academic Department of Neurosciences, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF UK
| | - Marios Hadjivassiliou
- Academic Department of Neurosciences, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF UK
| |
Collapse
|
|
10
|
Metabolic evidence for cerebral neurodegeneration in spinocerebellar ataxia type 1. THE CEREBELLUM 2014; 13:199-206. [PMID: 24085647 DOI: 10.1007/s12311-013-0527-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Autosomal-dominant spinocerebellar ataxia type 1 (SCA1) is an adult-onset progressive disorder with well-characterized neurodegeneration in the cerebellum and brainstem. The objective of this study is to evaluate neurochemical changes associated with neurodegeneration in cerebral tissue in SCA1 patients compared to age- and gender-matched healthy controls. Nine patients with genetically proven SCA1 and nine gender- and age-matched healthy controls were prospectively recruited from the ataxia clinic and received clinical examination. A 1.5 T single-voxel brain proton MR spectroscopy was performed for total N-acetyl aspartate (tNAA) in cerebellum, parietofrontal lobe white matter, sensory cortex, and visual cortex. In the patients, tNAA was severely decreased in the cerebellar voxel; however, in the voxels positioned in sensory cortex, parietofrontal lobe white matter and visual cortex tNAA was reduced in comparison to controls. In addition to the profoundly affected cerebellum, we also found evidence for cerebral neurodegeneration in parietal lobe white matter, sensory cortex, and visual cortex in SCA1 patients illustrating a multisystem neurodegenerative character of the disease.
Collapse
|
|
11
|
Deelchand DK, Adanyeguh IM, Emir UE, Nguyen TM, Valabregue R, Henry PG, Mochel F, Öz G. Two-site reproducibility of cerebellar and brainstem neurochemical profiles with short-echo, single-voxel MRS at 3T. Magn Reson Med 2014; 73:1718-25. [PMID: 24948590 DOI: 10.1002/mrm.25295] [Citation(s) in RCA: 93] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 04/08/2014] [Accepted: 04/25/2014] [Indexed: 12/25/2022]
Abstract
PURPOSE To determine whether neurochemical concentrations obtained at two MRI sites using clinical 3T scanners can be pooled when a highly optimized, nonvendor short-echo, single-voxel proton MRS pulse sequence is used in conjunction with identical calibration and quantification procedures. METHODS A modified semi-LASER sequence (TE = 28 ms) was used to acquire spectra from two brain regions (cerebellar vermis and pons) on two Siemens 3T scanners using the same B0 and B1 calibration protocols from two different cohorts of healthy volunteers (N = 24-33 per site) matched for age and body mass index. Spectra were quantified with LCModel using water scaling. RESULTS The spectral quality was very consistent between the two sites and allowed reliable quantification of at least 13 metabolites in the vermis and pons compared with 3-5 metabolites in prior multisite magnetic resonance spectroscopy trials using vendor-provided sequences. The neurochemical profiles were nearly identical at the two sites and showed the feasibility to detect interindividual differences in the healthy brain. CONCLUSION Highly reproducible neurochemical profiles can be obtained on different clinical 3T scanners at different sites, provided that the same, optimized acquisition and analysis techniques are used. This will allow pooling of multisite data in clinical studies, which is particularly critical for rare neurological diseases.
Collapse
Affiliation(s)
- Dinesh K Deelchand
- Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA
| | | | | | | | | | | | | | | |
Collapse
|
|
12
|
|
|
13
|
Currie S, Hoggard N, Clark MJR, Sanders DS, Wilkinson ID, Griffiths PD, Hadjivassiliou M. Alcohol induces sensitization to gluten in genetically susceptible individuals: a case control study. PLoS One 2013; 8:e77638. [PMID: 24204900 PMCID: PMC3817350 DOI: 10.1371/journal.pone.0077638] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Accepted: 09/12/2013] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND The mechanisms of cerebellar degeneration attributed to prolonged and excessive alcohol intake remain unclear. Additional or even alternative causes of cerebellar degeneration are often overlooked in suspected cases of alcohol-related ataxia. The objectives of this study were two fold: (1) to investigate the prevalence of gluten-related serological markers in patients with alcohol-related ataxia and; (2) to compare the pattern of brain involvement on magnetic resonance imaging between patients with alcohol and gluten ataxias. MATERIALS & METHODS Patients diagnosed with alcohol and gluten ataxias were identified from a retrospective review of patients attending a tertiary clinic. HLA genotype and serological markers of gluten-related disorders were recorded. Cerebellar volumetry, MR spectroscopy and voxel-based morphometric analyses were performed on patients and compared with matched control data. RESULTS Of 904 registered patients, 104 had alcohol ataxia and 159 had gluten ataxia. 61% of the alcohol ataxia group and 70% of the gluten ataxia group had HLA DQ2/DQ8 genotype compared to 30% in healthy local blood donors. 44% of patients with alcohol ataxia had antigliadin antibodies compared to 12% in the healthy local population and 10% in patients with genetically confirmed ataxias. None of the patients with alcohol ataxia and antigliadin antibodies had celiac disease compared to 40% in patients with gluten ataxia. The pattern of structural brain abnormality in patients with alcohol ataxia who had antigliadin antibodies differed from gluten ataxia and was identical to that of alcohol ataxia. CONCLUSIONS Alcohol related cerebellar degeneration may, in genetically susceptible individuals, induce sensitization to gluten. Such sensitization may result from a primary cerebellar insult, but a more systemic effect is also possible. The duration and amount of exposure to alcohol may not be the only factors responsible for the cerebellar insult.
Collapse
Affiliation(s)
- Stuart Currie
- Academic Unit of Radiology, University of Sheffield, Sheffield, United Kingdom
- * E-mail:
| | - Nigel Hoggard
- Academic Unit of Radiology, University of Sheffield, Sheffield, United Kingdom
| | - Matthew J. R. Clark
- Academic Unit of Radiology, University of Sheffield, Sheffield, United Kingdom
| | - David S. Sanders
- Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
| | - Iain D. Wilkinson
- Academic Unit of Radiology, University of Sheffield, Sheffield, United Kingdom
| | - Paul D. Griffiths
- Academic Unit of Radiology, University of Sheffield, Sheffield, United Kingdom
| | - Marios Hadjivassiliou
- Department of Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
| |
Collapse
|