Multiple Sclerosis: Arnold DL

Simon JH, Li D, Traboulsee A, Coyle PK, Arnold DL, Barkhof F, Frank JA, Grossman R, Paty DW, Radue EW, Wolinsky JS. · Department of Radiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. · AJNR Am J Neuroradiol. · Pubmed #16484429 links to  free full text

This publication has no abstract.

Arnold DL, Goodin DS. · No affiliation provided · Ann Neurol. · Pubmed #19334057 No free full text.

This publication has no abstract.

Giacomini PS, Arnold DL, Bar-Or A, Antel JP. · No affiliation provided · Arch Neurol. · Pubmed #19139295 No free full text.

This publication has no abstract.

Paty DW, Arnold DL. · No affiliation provided · N Engl J Med. · Pubmed #11796856 No free full text.

This publication has no abstract.

Giacomini PS, Arnold DL. · McConnell Brain Imaging Centre, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Quebec, Canada. · Curr Opin Neurol. · Pubmed #18451709 No free full text.

Abstract: PURPOSE OF REVIEW: To summarize recent developments using non-conventional MRI techniques to measure neuroprotection, repair and plasticity in multiple sclerosis. RECENT FINDINGS: Recent advances in our understanding of the pathogenesis of multiple sclerosis, particularly as it relates to the development of chronic disability, have led away from a 'lesion-centric' view of multiple sclerosis towards investigating neurodegeneration and pathology in normal appearing brain tissue. Advanced image processing techniques that measure atrophy globally and regionally also have provided insight into the putative mechanisms that contribute to neurodegeneration. In addition, novel quantitative imaging techniques that are more specific than conventional MRI for myelin and axonal pathology have been instrumental in revealing the dynamic nature of injury and repair of myelin and axons in lesions. Novel imaging techniques that are sensitive to the pathology of myelin and axons that happens in multiple sclerosis also provide a method by which we can measure neuroprotection and test the efficacy of putative therapeutic agents in multiple sclerosis. SUMMARY: Non-conventional MRI techniques have contributed to a greater understanding of the complex pathogenesis of neurodegenerative phenomena that occur in multiple sclerosis. The pathological specificity of these novel imaging methods enables the evaluation of the neuroprotective effects of novel therapeutic strategies.

De Stefano N, Filippi M, Miller D, Pouwels PJ, Rovira A, Gass A, Enzinger C, Matthews PM, Arnold DL. · Department of Neurological and Behavioral Sciences, University of Siena, Viale Bracci 2, 53100 Siena, Italy. · Neurology. · Pubmed #17998486 No free full text.

Abstract: Proton MR spectroscopy (MRS) allows noninvasive characterization of chemical-pathologic changes in the brain. In patients with multiple sclerosis (MS), proton MRS reveals chemical pathology in focal inflammatory lesions as well as in regions of the brain that are not associated with structural abnormalities on conventional MRI. In MS studies, it has been particularly useful as a method for the assessment of neurodegeneration based on decreases in the levels of the neuro-axonal marker compound, N-acetylaspartate. Also, MRS has provided evidence of chemical pathology and repair involving non-neuronal brain cells based on changes in metabolites, including choline, myo-inositol, glutamate, and GABA. Despite its greater pathologic specificity for axonal integrity compared to conventional MRI, MRS has been used only infrequently in clinical trials. This prompted us to review current MRS clinical applications in MS, discuss the potential and limitations of the technique, and suggest recommendations for the application of MRS to clinical trials.

Arnold DL. · Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada. · Neurology. · Pubmed #17548574 No free full text.

Abstract: MRI is used routinely in clinical practice and pharmaceutical trials to measure disease activity and assess the effects of treatment in multiple sclerosis. Conventional MRI techniques sensitively detect inflammation, demyelination, and tissue injury. Less conventional imaging modalities, such as magnetic resonance spectroscopy and magnetization transfer imaging, and advanced image processing to quantify structural changes can provide more specific and inherently quantitative markers of the pathologic processes underlying the accumulation of disease burden and the progression of clinical disability. Together, these techniques can assess both the anti-inflammatory and the neuroprotective effects of immunomodulatory therapies.

Arnold DL. · Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec, Canada. · J Neurol Sci. · Pubmed #17376485 No free full text.

Abstract: Evidence of focal white matter inflammation on MRI can be related to relapses and chronic disability. The strength of the relationship depends on the stage of the disease. The predictive value is stronger early in the course of MS, when the focal white matter lesions are more important in the pathogenesis of MS. As the disease progresses, the predictive value of white matter lesions weakens and measures related to other, more diffuse aspects of the disease strengthen. Thus, lesion activity on MRI can be helpful as a guide to therapy, particularly early in the disease. Appropriate MRI criteria for a suboptimal response to therapy are not clear and may depend on the therapy being evaluated. The fact that diffuse pathology tends to progress despite effective suppression of focal inflammation is a cause for concern and needs to be addressed with new approaches to therapy that are more effective against this aspect of the disease.

Tartaglia MC, Arnold DL. · Department of Neurology, University of Western Ontario, London, Canada. · Adv Neurol. · Pubmed #16400835 No free full text.

Abstract: Multiple sclerosis is now recognized as more than simply a disease of inflammation and demyelination in the brain and spinal cord. Conventional MRI has been established as the most important paraclinical tool in the diagnostic assessment of patients with suspected MS, and in the monitoring of treatment efficacy in clinical trials, at least in relapsing disease. Magnetization-transfer, diffusion-weighted MRI, 1H-MRS, and fMRI improve our ability to quantify the pathological changes in MS in vivo. Although we have gained some insight into the disease and are starting to uncover some of the structural and physiological substrates for the disability that develops in MS patients, we are far from understanding what causes MS and how to prevent its progression. Imaging can be used as a tool to better understand the pathophysiology of MS and ultimately improve on the treatment of MS.

Arnold DL, Chen J. · Montreal Neurological Institute, McGill University, Quebec, Canada. · Ernst Schering Res Found Workshop. · Pubmed #16315614 No free full text.

Abstract: Neuroprotection in MS needs to be considered in the context of several pathological processes: limitation of acute inflammatory injury to myelin and axons, remyelination, survival of demyelinated axons, and limitation of more diffuse, nonlesional pathology that affects myelin and axons. Advanced MRI techniques are capable of reporting on all of these different pathological features of MS and will be an important aspect of the assessment of neuroprotection strategies in MS, when these become available.

Arnold DL. · Montreal Neurological Institute and Dept. of Neurology and Neurosurgery, McGill University, 301 University St., Montreal, Quebec, Canada H3A 2B4. · J Neurol. · Pubmed #16254698 No free full text.

Abstract: Multiple sclerosis has long been recognized as a multifocal inflammatory demyelinating disease of the central nervous system. The fact that patients with multiple sclerosis can develop a secondary progressive phase of their disease which is resistant to anti-inflammatory therapies, together with the fact that brain atrophy can develop in patients with a relatively low volume of white matter lesions, has led to suggestions that multiple sclerosis may be a degenerative disease. However, primary degenerative disorders are not usually associated with recurrent episodes of inflammatory demyelination. Support for neurodegeneration in MS being associated with focal lesions comes from topographical mapping of the spatial relationship of axonal injury and tissue loss to lesions using advanced image analysis methods.

Caramanos Z, Narayanan S, Arnold DL. · Magnetic Resonance Spectroscopy Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. · Brain. · Pubmed #16230321 links to  free full text

Abstract: Meta-analysis was performed on the results of 75 comparisons from the 30 peer-reviewed publications that used proton magnetic resonance spectroscopy (1H-MRS) or spectroscopic imaging to (i) quantify the mean concentrations of total creatine (tCr, found in neurons, astrocytes and oligodendrocytes), and/or total N-acetyl groups (tNA, found only in neurons), in the lesional and/or non-lesional white matter (WM) and/or the grey matter (GM) of patients with multiple sclerosis (MS) and (ii) compare these values with those in the homologous tissues of normal controls (NC). For mean [tNA] values, there was (i) a large-effect-sized overall decrease in patients' lesional WM relative to NC WM (25 comparisons), (ii) a medium-effect-sized overall decrease in patients' non-lesional WM relative to NC WM (36 comparisons) and (iii) a medium-effect-sized overall decrease in patients' GM relative to NC GM (14 comparisons). Patients' mean [tNA] values were sometimes statistically normal but were never statistically increased. For mean [tCr] values, there was (i) no statistically significant overall change in the patients' lesional WM relative to NC WM (24 comparisons), although statistically significant increases and decreases were sometimes found, (ii) a medium-effect-sized overall increase in patients' non-lesional WM relative to NC WM (33 comparisons) and (iii) no statistically significant overall change in patients' GM relative to NC GM (12 comparisons), although a significant decrease was found in one comparison. Of 41 comparisons with statistically significant changes, 38 combined in a way that would probably result in decreased mean [tNA]/[tCr] ratios such that (i) 66% had statistically decreased mean [tNA] and statistically unchanged mean [tCr] values, (ii) 13% had statistically decreased mean [tNA] and statistically increased mean [tCr] values and (iii) 21% had statistically unchanged mean [tNA] values and statistically increased mean [tCr] values. Of the 25 comparisons that came from studies that also analysed [tNA]/[tCr] ratios, the direction of change in mean [tNA] values and mean [tNA]/[tCr] ratios was concordant in 84%. In comparisons that quantified both [tNA] and [tCr], there was a similar amount of variability in both measures in each of the different tissue types studied, both in patients and NCs. Together, these results suggest that within-voxel tNA/tCr ratios can be interpreted as valid and accurate surrogate measures of 'cerebral tissue integrity'-with decreased tNA/tCr ratios indicating some combination of neuroaxonal disturbance, oligodendroglial disturbance, and astrocytic proliferation. These results also suggest that, although within-voxel tNA/tCr ratios are not perfect indicators of [tNA] content, they do represent a practical compromise to acquiring surrogate measures of within-voxel neuroaxonal integrity.

Filippi M, Falini A, Arnold DL, Fazekas F, Gonen O, Simon JH, Dousset V, Savoiardo M, Wolinsky JS, Anonymous00084. · Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy. · J Magn Reson Imaging. · Pubmed #15906322 No free full text.

Abstract: On October 9-11, 2003, the third meeting of the White Matter Study Group of the International Society for Magnetic Resonance in Medicine was held in Venice, Italy. This article is the report of the meeting on how to use MRI in the diagnostic workup of multiple sclerosis (MS) and allied white matter disorders, and to define the nature and the extent of MS pathology in vivo. Both of these steps are central to the design of future treatment strategies aimed at limiting the functional consequences of the most disabling aspects of this disease.

Arnold DL, Matthews PM. · Montreal Neurological Institute, Montreal, Quebec, Canada. · Neurology. · Pubmed #11971123 No free full text.

Abstract: MRI techniques, including conventional T(2)-weighted and gadolinium (Gd)-enhanced T(1)-weighted images, have provided important insights into the pathophysiology of MS. Although the correlation of MRI measures with clinical disability and outcome continues to be investigated, MRI measures are routinely used both in clinical practice and in MS research. In addition to its use as a diagnostic tool, MRI is used as a surrogate marker to monitor disease progression and response to therapy. A variety of MRI measures are used in drug development studies and have aided our understanding of the potential benefits and possible mechanisms of action of drug therapies. Advances in MRI techniques may further elucidate the pathology of MS, thus providing opportunities for new treatment strategies.

Matthews PM, Arnold DL. · aDepartment of Clinical Neurology and Centre for Functional Magnetic Resonance Imaging, University of Oxford, Oxford, UK. · Curr Opin Neurol. · Pubmed #11371749 No free full text.

Abstract: Magnetic resonance imaging methods allow observation of pathological changes in vivo. Magnetic resonance-based studies have provided a number of important insights into the spatio-temporal evolution of the pathology of multiple sclerosis in vivo, particularly with respect to the relation between pathology and progression of disability. Magnetic resonance techniques have shown that this pathology is not restricted to the plaques that are evident at autopsy, but also involve the so-called normal-appearing white matter. Nonconventional magnetic resonance imaging strategies such as magnetization transfer imaging and spectroscopic imaging provide measures with higher pathological specificity for myelin and axonal injury. These and other advanced magnetic resonance techniques (such as the measurement of atrophy, lesion relaxation spectra, and lesion dynamics) are affording opportunities to use observations of patients to test biologically specific hypotheses. This should help us to better define new targets for drug therapy and to assess responses to new therapeutic agents.

Arnold DL, De Stefano N, Narayanan S, Matthews PM. · Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3A 2B4. · Neuroimaging Clin N Am. · Pubmed #11359725 No free full text.

Abstract: Axonal injury in multiple sclerosis (MS) is focal and diffuse, and is directly responsible for irreversible disability. Acute inflammatory events can be associated with reversible disability that may parallel reversible axonal injury. This in part accounts for the remission following relapses early in the disease. By the time there is clinical disability, substantial axonal injury already has occurred. This provides a strong rationale for the early limitation of inflammation and its consequences.

De Stefano N, Narayanan S, Mortilla M, Guidi L, Bartolozzi ML, Federico A, Arnold DL. · Neurometabolic Unit, Institute of Neurological Sciences, University of Siena, Italy. · Neurol Sci. · Pubmed #11205368 No free full text.

Abstract: Axonal damage in multiple sclerosis has become an important issue. This has been emphasized by recent in vivo proton magnetic resonance (MR) spectroscopy and in vitro pathology studies that have found axonal damage in both lesions and the surrounding normal-appearing white matter. In particular, proton MR spectroscopy, by monitoring levels of N-acetylaspartate (a putative marker of axonal integrity), has been particularly illuminating, as the extent of axonal injury associated with white matter inflammation and demyelination had not been well appreciated from classical pathology studies. Recent MR data demonstrate that cerebral axonal damage begins and contributes to disability from the earliest stages of the disease. This implies that the apparently primary role of axonal damage and loss in the pathogenesis of the disease should be given due importance, and argues for the early treatment of multiple sclerosis with agents directed not only against inflammation, but also towards axonal protection.

Stefano ND, Narayanan S, Matthews PM, Mortilla M, Dotti MT, Federico A, Arnold DL. · Neurometabolic Unit, Institute of Neurological Sciences, University of Siena, Italy. · J Neurovirol. · Pubmed #10871799 No free full text.

Abstract: Proton MR spectroscopy allows in vivo measurement of N-acetylaspartate in white matter, providing a biochemical index of axonal integrity. Several recent studies of patients with multiple sclerosis and other white matter disorders have shown both transient and sustained decreases in N-acetylaspartate in white matter lesions and in brain regions appearing normal on conventional MRI. These data have emphasised that a substantial amount of axonal damage or loss (presumably secondary to myelin pathology) is consistently present in most of these disorders. Recent post-mortem studies support these results. In contrast to changes seen with conventional MR imaging, decreases in N-acetylaspartate have shown a close correlation with changes in neurological status. This suggests that axonal damage may be more relevant than demyelination for determining chronic functional impairments in primary white matter diseases. Thus, serial measurement of brain N-acetylaspartate with proton MR spectroscopy can provide a reliable and clinically-relevant monitor of disease evolution. As pathological changes responsible for long-term morbidity are logically important targets for therapeutic agents, early treatment directed at axonal protection should be useful in these disorders.

Rudkin TM, Arnold DL. · University of Ottawa, Ontario, Canada. · Arch Neurol. · Pubmed #10448796 links to  free full text

Abstract: The use of magnetism in medicine has a long and colorful history since its legendary discovery in the Western world by the shepherd Magnes. More recent use of magnetism has centered on nuclear magnetic resonance. Magnetic resonance spectroscopy (MRS) provides chemical information on tissue metabolites. Both hydrogen 1 (1H) and phosphorus 31 resonances have been used to study brain tissue, but the magnetic resonance sensitivity for protons is far greater than it is for phosphorus. One of the most important contributions of 1H-MRS to clinical neurology is its ability to quantify neuronal loss and to demonstrate reversible neuronal damage. 1H-magnetic resonance spectroscopy has been found to be a useful research tool in elucidating the pathophysiology underlying certain diseases. This review focuses on the use of proton MRS to study various neurologic diseases, including epilepsy, multiple sclerosis, brain tumors, human immunodeficiency virus 1-associated neurologic disorders, as well as cerebrovascular, neurodegenerative, and metabolic diseases. It highlights the contributions of 1H-MRS to the diagnosis and the monitoring of these neurologic diseases that make it a useful adjunct in patient management.

Arnold DL. · MRS Unit, Montreal Neurological Institute, Quebec, Canada. · J Neuroimmunol. · Pubmed #10426355 No free full text.

Abstract: Recent observations made using magnetic resonance spectroscopy to measure the axonal marker N-acetylaspartate have emphasized the fact that substantial axonal damage occurs in multiple sclerosis, in addition to demyelination. The axonal damage is present both in lesions and normal appearing white matter, progresses over time, and correlates with clinical disability. These observations, together with observations demonstrating that adaptations of sodium channels can restore conduction in demyelinated axons, have led to the hypothesis that axonal damage may be responsible for a significant proportion of the chronic disability that accrues in MS.

Filippi M, Rocca MA, Arnold DL, Bakshi R, Barkhof F, De Stefano N, Fazekas F, Frohman E, Wolinsky JS. · Neuroimaging Research Unit, Department of Neurology Scientific Institute and University Ospedale San Raffaele, Milan, Italy. · Eur J Neurol. · Pubmed #16643308 No free full text.

Abstract: Magnetic resonance (MR)-based techniques are widely used for the assessment of patients with suspected and definite multiple sclerosis (MS). However, despite the publication of several position papers, which attempted to define the utility of MR techniques in the management of MS, their application in everyday clinical practice is still suboptimal. This is probably related, not only, to the fact that the majority of published guidelines focused on the optimization of MR technology in clinical trials, but also to the continuing development of modern, quantitative MR-based techniques, that have not as yet entered the clinical arena. The present report summarizes the conclusions of the 'EFNS Expert Panel of Neuroimaging of MS' on the application of conventional and non-conventional MR techniques to the clinical management of patients with MS. These guidelines are intended to assist in the use of conventional MRI for the diagnosis and longitudinal monitoring of patients with MS. In addition, they should provide a foundation for the development of more widespread but rational clinical applications of non-conventional MR-based techniques in studies of MS patients.

Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH, Anonymous00169. · Department of Neurology, University of California at San Francisco, San Francisco, CA 94143-0114, USA. · N Engl J Med. · Pubmed #18272891 links to  free full text

Abstract: BACKGROUND: There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis, and they may be a therapeutic target. Rituximab, a monoclonal antibody, selectively targets and depletes CD20+ B lymphocytes. METHODS: In a phase 2, double-blind, 48-week trial involving 104 patients with relapsing-remitting multiple sclerosis, we assigned 69 patients to receive 1000 mg of intravenous rituximab and 35 patients to receive placebo on days 1 and 15. The primary end point was the total count of gadolinium-enhancing lesions detected on magnetic resonance imaging scans of the brain at weeks 12, 16, 20, and 24. Clinical outcomes included safety, the proportion of patients who had relapses, and the annualized rate of relapse. RESULTS: As compared with patients who received placebo, patients who received rituximab had reduced counts of total gadolinium-enhancing lesions at weeks 12, 16, 20, and 24 (P<0.001) and of total new gadolinium-enhancing lesions over the same period (P<0.001); these results were sustained for 48 weeks (P<0.001). As compared with patients in the placebo group, the proportion of patients in the rituximab group with relapses was significantly reduced at week 24 (14.5% vs. 34.3%, P=0.02) and week 48 (20.3% vs. 40.0%, P=0.04). More patients in the rituximab group than in the placebo group had adverse events within 24 hours after the first infusion, most of which were mild-to-moderate events; after the second infusion, the numbers of events were similar in the two groups. CONCLUSIONS: A single course of rituximab reduced inflammatory brain lesions and clinical relapses for 48 weeks. This trial was not designed to assess long-term safety or to detect uncommon adverse events. The data provide evidence of B-cell involvement in the pathophysiology of relapsing-remitting multiple sclerosis. (ClinicalTrials.gov number, NCT00097188 [ClinicalTrials.gov].).

Chen JT, Collins DL, Atkins HL, Freedman MS, Arnold DL, Anonymous00222. · McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada. · Ann Neurol. · Pubmed #18257039 No free full text.

Abstract: OBJECTIVE: To assess demyelination and remyelination in vivo in acute gadolinium (Gd)-enhancing lesions of multiple sclerosis (MS). METHODS: We measured significant changes in magnetization transfer ratio (MTR) consistent with demyelination and remyelination of individual lesion voxels, as well as the mean normalized MTR over all lesion voxels during and after contrast enhancement, in MS patients participating in a 3-year Canadian trial assessing immunoablation and autologous stem cell transplantation for treatment of MS. RESULTS: The average mean normalized lesion MTR over all lesions exhibited partial recovery over 2 to 4 months after Gd enhancement. Voxel-based analysis demonstrated that approximately 70% of the initially enhancing lesion volume (GdLV) was left with stably low MTR over 39 months of evaluation. The percentage of the GdLV undergoing significant increases in MTR consistent with remyelination increased for approximately 7 months after enhancement and then stabilized at 21 %GdLV. Significant decreases in MTR consistent with demyelination were ongoing for approximately 33 months after enhancement, stabilizing at 9 %GdLV. The estimated error of these measurements, based on scan/rescan analysis, was less than 0.4 %GdLV. INTERPRETATION: We found significant changes in MTR consistent with demyelination and remyelination that followed different temporal evolutions and were ongoing in different lesion regions for at least 3 years after lesion formation.

Bar-Or A, Vollmer T, Antel J, Arnold DL, Bodner CA, Campagnolo D, Gianettoni J, Jalili F, Kachuck N, Lapierre Y, Niino M, Oger J, Price M, Rhodes S, Robinson WH, Shi FD, Utz PJ, Valone F, Weiner L, Steinman L, Garren H. · Montreal Neurological Institute, Montreal, Quebec, Canada. · Arch Neurol. · Pubmed #17698695 links to  free full text

Abstract: OBJECTIVE: To assess safety and immune modulation by BHT-3009, a tolerizing DNA vaccine encoding full-length human myelin basic protein, in patients with multiple sclerosis (MS). DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Subjects receiving placebo were crossed over into an active arm after treatment unblinding. SETTING: The trial was conducted at 4 academic institutions within North America. Patients Thirty patients with relapsing-remitting or secondary progressive MS who were not taking any other disease-modifying drugs were enrolled in the trial. Further, the patients were required to have either 1 to 5 gadolinium-enhancing lesions on screening brain magnetic resonance imaging (MRI), a relapse in the previous 2 years, or disease worsening in the previous 2 years. INTERVENTIONS: BHT-3009 was administered as intramuscular injections at weeks 1, 3, 5, and 9 after randomization into the trial, with or without 80 mg of daily oral atorvastatin calcium in combination. Three dose levels of BHT-3009 were tested (0.5 mg, 1.5 mg, and 3 mg). MAIN OUTCOME MEASURES: The primary outcome measures were safety and tolerability of BHT-3009. Secondary outcome measures included the number and volume of gadolinium-enhanced lesions on MRI, relapses, and analysis of antigen-specific immune responses. RESULTS: BHT-3009 was safe and well tolerated, provided favorable trends on brain MRI, and produced beneficial antigen-specific immune changes. These immune changes consisted of a marked decrease in proliferation of interferon-gamma-producing, myelin-reactive CD4+ T cells from peripheral blood and a reduction in titers of myelin-specific autoantibodies from cerebral spinal fluid as assessed by protein microarrays. We did not observe a substantial benefit of the atorvastatin combination compared with BHT-3009 alone. CONCLUSION: In patients with MS, BHT-3009 is safe and induces antigen-specific immune tolerance with concordant reduction of inflammatory lesions on brain MRI.

Dhib-Jalbut S, Arnold DL, Cleveland DW, Fisher M, Friedlander RM, Mouradian MM, Przedborski S, Trapp BD, Wyss-Coray T, Yong VW. · UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, and The Cleveland Clinic, OH, USA. · J Neuroimmunol. · Pubmed #16983747 No free full text.

Abstract: Multiple sclerosis is considered a disease of myelin destruction; Parkinson's disease (PD), one of dopaminergic neuron depletion; ALS, a disease of motor neuron death; and Alzheimer's, a disease of plaques and tangles. Although these disorders differ in important ways, they also have common pathogenic features, including inflammation, genetic mutations, inappropriate protein aggregates (e.g., Lewy bodies, amyloid plaques), and biochemical defects leading to apoptosis, such as oxidative stress and mitochondrial dysfunction. In most disorders, it remains uncertain whether inflammation and protein aggregation are neurotoxic or neuroprotective. Elucidating the mechanisms that orchestrate neuronal diseases should facilitate development of neuroprotective and neurorestorative strategies.