MRI markers to understand progression mechanisms by Maria A. Rocca
Neuroimaging Research Unit, Institute of Experimental
Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
MRI characteristics in Relapsing- Remitting versus Secondary- Progressive MS by Till Sprenger, Department of Neurology and Division of Neuroradiology University Hospital Basel, Switzerland
Can brain atrophy measurement help us in monitoring MS progression in routine...MS Trust
This presentation by Dana Horáková, Department of Neurology and Centre of Clinical Neuroscience at the Charles University in Prague, looks at why and how we should measure brain atrophy.
It was presented at the MS Trust Annual Conference in November 2014.
This document discusses Meige syndrome, which involves involuntary contractions of the muscles around the eyes (blepharospasm) and mouth (oromandibular dystonia). It can be primary or secondary to conditions like neuroleptic medication use or brain injuries. Pathophysiology may involve dopaminergic/cholinergic hyperactivity or decreased inhibitory neurons in the cortex. Diagnosis involves tests like EMGs and imaging to rule out other causes. Treatment options include anticholinergics, dopamine antagonists, Botox injections, and deep brain stimulation. Differential diagnoses include other movement disorders or neurological/psychiatric conditions.
icometrix offers imaging biomarkers for anatomical MRI or CT images as well as for functional, diffusion and perfusion MR images.
Medical imaging serves as an endpoint in an increasing number of clinical trials for neurological disorders to evaluate the effectiveness of novel therapeutic options and to better understand the pathophysiology. It is critical to obtain objective imaging measurements.Therefore, the use of
high-quality MRI data and quantitative MRI biomarkers is also recommended in the latest guidelines of the European Medicine Agency on clinical investigation of medicinal products for treatment of dementia, multiple sclerosis and other neurological disorders.
This document discusses Stiff Person Syndrome (SPS), a rare autoimmune neurological disorder. It provides information on the epidemiology, pathophysiology, clinical manifestations, diagnosis, variants, treatment and prognosis of SPS. SPS is often misdiagnosed or underdiagnosed and is characterized by painful muscle rigidity and spasms. It involves autoimmunity related to glutamic acid decarboxylase or other synaptic proteins. Treatment involves diazepam and other GABAergic drugs, which can provide relief from symptoms.
MRI Workshop
Dr. Ben Turner held an MRI workshop in November 2018. He discussed the principles of magnetic resonance imaging, different MRI techniques like T2 imaging and flair images, and how MRI is beneficial but also has drawbacks for monitoring multiple sclerosis. MRI is most useful for research, diagnosis, therapeutic innovation for drug trials, and monitoring therapies. New diagnostic criteria for multiple sclerosis were also presented, focusing on dissemination of lesions in space and time with no better explanation. Factors like lesion number and location provide prognostic information about progression.
The document summarizes proposed updates to MRI criteria for diagnosing multiple sclerosis (MS) by the MAGNIMS group in 2016. The updates aim to 1) expand the definition of dissemination in space to include more lesion locations, 2) revise lesion count requirements, and 3) remove the distinction between symptomatic and asymptomatic lesions. The changes also broaden the criteria's applicability to more age groups and ethnicities. Key revisions include requiring 3+ periventricular lesions instead of 1, considering lesions in the optic nerves, and applying the same dissemination standards to both relapsing-remitting and primary progressive MS. The updates are meant to improve sensitivity while maintaining specificity in MS diagnosis.
Grey matter and multiple sclerosis
GM damage in MS is common and widespread, especially in chronic MS.
GM atrophy correlated more strongly than WM atrophy with disability and cognitive impairment.
Cortical lesions have been difficult to visualize with conventional MRI, but due to newer imaging techniques (like DIR, PSIR and (Ultra) high-field MRI ) lesion detection improved.
MRI characteristics in Relapsing- Remitting versus Secondary- Progressive MS by Till Sprenger, Department of Neurology and Division of Neuroradiology University Hospital Basel, Switzerland
Can brain atrophy measurement help us in monitoring MS progression in routine...MS Trust
This presentation by Dana Horáková, Department of Neurology and Centre of Clinical Neuroscience at the Charles University in Prague, looks at why and how we should measure brain atrophy.
It was presented at the MS Trust Annual Conference in November 2014.
This document discusses Meige syndrome, which involves involuntary contractions of the muscles around the eyes (blepharospasm) and mouth (oromandibular dystonia). It can be primary or secondary to conditions like neuroleptic medication use or brain injuries. Pathophysiology may involve dopaminergic/cholinergic hyperactivity or decreased inhibitory neurons in the cortex. Diagnosis involves tests like EMGs and imaging to rule out other causes. Treatment options include anticholinergics, dopamine antagonists, Botox injections, and deep brain stimulation. Differential diagnoses include other movement disorders or neurological/psychiatric conditions.
icometrix offers imaging biomarkers for anatomical MRI or CT images as well as for functional, diffusion and perfusion MR images.
Medical imaging serves as an endpoint in an increasing number of clinical trials for neurological disorders to evaluate the effectiveness of novel therapeutic options and to better understand the pathophysiology. It is critical to obtain objective imaging measurements.Therefore, the use of
high-quality MRI data and quantitative MRI biomarkers is also recommended in the latest guidelines of the European Medicine Agency on clinical investigation of medicinal products for treatment of dementia, multiple sclerosis and other neurological disorders.
This document discusses Stiff Person Syndrome (SPS), a rare autoimmune neurological disorder. It provides information on the epidemiology, pathophysiology, clinical manifestations, diagnosis, variants, treatment and prognosis of SPS. SPS is often misdiagnosed or underdiagnosed and is characterized by painful muscle rigidity and spasms. It involves autoimmunity related to glutamic acid decarboxylase or other synaptic proteins. Treatment involves diazepam and other GABAergic drugs, which can provide relief from symptoms.
MRI Workshop
Dr. Ben Turner held an MRI workshop in November 2018. He discussed the principles of magnetic resonance imaging, different MRI techniques like T2 imaging and flair images, and how MRI is beneficial but also has drawbacks for monitoring multiple sclerosis. MRI is most useful for research, diagnosis, therapeutic innovation for drug trials, and monitoring therapies. New diagnostic criteria for multiple sclerosis were also presented, focusing on dissemination of lesions in space and time with no better explanation. Factors like lesion number and location provide prognostic information about progression.
The document summarizes proposed updates to MRI criteria for diagnosing multiple sclerosis (MS) by the MAGNIMS group in 2016. The updates aim to 1) expand the definition of dissemination in space to include more lesion locations, 2) revise lesion count requirements, and 3) remove the distinction between symptomatic and asymptomatic lesions. The changes also broaden the criteria's applicability to more age groups and ethnicities. Key revisions include requiring 3+ periventricular lesions instead of 1, considering lesions in the optic nerves, and applying the same dissemination standards to both relapsing-remitting and primary progressive MS. The updates are meant to improve sensitivity while maintaining specificity in MS diagnosis.
Grey matter and multiple sclerosis
GM damage in MS is common and widespread, especially in chronic MS.
GM atrophy correlated more strongly than WM atrophy with disability and cognitive impairment.
Cortical lesions have been difficult to visualize with conventional MRI, but due to newer imaging techniques (like DIR, PSIR and (Ultra) high-field MRI ) lesion detection improved.
Prediction of outcome of Multiple sclerosisAmr Hassan
Prediction of outcome of Multiple sclerosis
An understanding of the natural history of multiple sclerosis(MS) in a patient is important to begin proper treatment at the correct time, especially when there is a high risk for poor prognosis. Factors that predict unfavorable prognosis are a primary or secondary progressive course, older age at disease onset, short interval between first and second attacks, initial cerebellar or pyramidal symptoms, a large number of functional systems involved at onset, moderate to severe disability within the first 2 years, and the presence of typical plaques or greater lesion volume shown by magnetic resonance imaging results during the first 5 years. However, there are no established laboratory tests able to predict long-term prognosis.
The Role of DaT Scan in Diagnosing Parkinson Disease Ade Wijaya
1) The diagnosis of Parkinson's disease is traditionally based on clinical examination, however around 20% of cases are initially misdiagnosed.
2) DaT scan is used when it is uncertain if clinical parkinsonism reflects degeneration of dopaminergic neurons, to assist in diagnosis and treatment decisions.
3) DaTscan imaging helps distinguish between nigrostriatal dopaminergic degeneration and other causes of parkinsonism, improving diagnostic accuracy and informing medication management.
Dr Trevor Pickersgill - Diagnosing a RelapseMS Trust
1) Diagnosing relapses in multiple sclerosis (MS) patients can be complex, as relapses can mimic other conditions and symptoms are not always clearly MS-related.
2) It is important to properly diagnose relapses to determine the MS disease course, guide treatment decisions, and understand the patient's prognosis.
3) In addition to traditional relapses, atypical presentations must be considered, such as relapses related to MS treatments, infections, neurological conditions mimicking MS, and non-neurological or functional issues. A thorough examination is needed.
This document discusses treating multiple sclerosis (MS) to target no evident disease activity (NEDA).
It acknowledges the author's disclosures from pharmaceutical companies and grants. It then discusses how MS is progressive from onset and inflammation contributes to neurodegeneration. NEDA is defined as no relapses, disability progression, or MRI activity.
Finally, it summarizes evidence that immunotherapies can benefit those with progressive MS, including data from clinical trials showing patients with primary progressive MS experienced improved outcomes on fingolimod.
Multiple sclerosis (MS) is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged.This damage disrupts the ability of parts of the nervous system to communicate, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems
Neurological Implications of von-Hippel Lindau diseaseAde Wijaya
This document summarizes the neurological implications of von Hippel-Lindau disease. It is an autosomal dominant genetic disorder caused by mutations in the VHL tumor suppressor gene. Patients with VHL frequently develop benign tumors called hemangioblastomas in the brain and spinal cord. While these tumors are non-cancerous, they can cause neurological problems due to their location and mass effect. Younger patients and those with more tumors have worse outcomes and faster tumor progression. Regular screening and surgical removal of tumors can help prevent disability. However, hemangioblastomas remain the most common cause of morbidity and reduced life expectancy in patients with VHL disease.
This document discusses new and emerging drugs for progressive multiple sclerosis. It provides an overview of the current treatment landscape and explores potential reasons for past clinical trial failures. It also examines the underlying pathological mechanisms of progressive disease and proposes that trials may have targeted the wrong outcomes, patient populations, or stages of disease progression. Ongoing trials of drugs like ocrelizumab and natalizumab aim to address some of these challenges by exploring therapies in earlier progressive phases and assessing disability outcomes over longer periods of time.
Rare aetiology of encephalopathy, as presented in American College of Physicians (ACP) 3rd India Meet 2018 in Lucknow on September 1.
The poster was adjudged as the 'Best Clinical Vignette'.
This document discusses highly active multiple sclerosis (MS). It defines several subtypes of aggressive MS including malignant, fulminant, and highly active MS. Predictors of highly active MS are discussed from a 2016 study. The case vignette describes a 34-year-old male physician's MS course from 2006 to 2017, showing recurrent attacks and progression. The timing of therapy is key to preventing disability, with an emphasis on early treatment to preserve brain reserve. Treatment algorithms recommend escalating therapy for aggressive MS to effectively treat within a narrow therapeutic window.
Clinically isolated syndromes (CIS) refer to the first clinical episodes of neurological symptoms suggestive of multiple sclerosis. The document discusses CIS in three parts: definition and clinical features of CIS, risk factors for conversion from CIS to multiple sclerosis, and management of CIS. Regarding clinical features, optic neuritis, transverse myelitis, and brainstem syndromes are highlighted as common presentations of CIS. MRI abnormalities, younger age of onset, smoking, and vitamin D deficiency are identified as risk factors for progression to multiple sclerosis. The management section outlines acute treatment with corticosteroids, use of disease-modifying therapies based on MRI findings, and consideration of vitamin D supplementation.
This presentation by Gavin Giovannoni looks at the new treatment paradigm for MS. It includes: arguments for early treatment in multiple sclerosis, the effect of MS on quality of life and whether highly-effective treatments stabilise MS.
It was presented at the MS Trust Annual Conference in November 2013.
Neuroradiology in multiple sclerosis
MRI in diagnosis of MS
MRI in D.D. of MS
MRI in monitoring disease progression and response to DMT
New imaging techniques
Vagal Nerve stimulation
Vagus nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. It is used as an add-on treatment for certain types of intractable epilepsy and treatment-resistant depression. Frequent side effects include coughing and shortness of breath. Serious side effects may include trouble talking and cardiac arrest.
Spinal cord injury without radiographic abnormalities (SCIWORA)SanchitUppal5
- SCIWORA refers to spinal cord injury without radiographic abnormality. It commonly occurs in children and involves the cervical spine.
- MRI is now considered the gold standard for diagnosis as it can detect abnormalities not seen on plain radiographs or CT scans like edema, hemorrhage or cord transection.
- Treatment involves immobilization, IV steroids may help, and surgery is indicated if MRI shows instability, compression or worsening neurological status. Prognosis depends on initial neurological status and MRI findings, with most patients showing improvement but some facing permanent impairments.
A 3-year-old boy presented to the emergency department with new onset lower extremity weakness after falling from a high chair two days prior. On examination, he had decreased strength and sensation in both lower extremities. Cervical spine films and CT were normal. He received a diagnosis of spinal cord injury without radiographic abnormality (SCIWORA) and was admitted to the neurosurgery service for MRI and further evaluation.
This document discusses progressive multiple sclerosis (MS) and whether it is possible to prevent or slow its progression. It begins by acknowledging potential conflicts of interest from clinical trials and industry relationships. It then explains that relapsing and progressive MS are part of a continuum, with continuous tissue loss driving progression even during relapsing stages. While symptoms and deficits differ depending on tissue loss and brain reserve, MS remains a single disease. Later stages are determined more by neuroanatomy and length of affected nerve fibers. The document advocates considering progressive MS patients' expectations realistically and evaluating therapies based on proven efficacy in both relapsing and progressive MS as well as safety and convenience factors.
Management strategies in multiple sclerosisAmr Hassan
This document discusses key decision making points in the treatment of multiple sclerosis (MS). It begins with an overview of the diagnostic criteria for MS and algorithms for clinical follow up of patients with a first attack or those at risk of converting to clinically definite MS. It then covers factors to consider when choosing a first-line disease modifying therapy, including adherence, patient preferences, prognostic factors, disease activity, comorbidities, safety, tolerability, efficacy, and pregnancy plans. Specific MS comorbidities and pregnancy categories for various therapies are also summarized. The document concludes with discussions on definitions of suboptimal response, treatment algorithms, escalation versus induction strategies, and considerations for discontinuing disease modifying therapies.
1. Klaus Schmierer presents disclosures related to research funding and speaking engagements from various pharmaceutical companies involved in multiple sclerosis treatment.
2. He discusses two important lessons about MS treatment - that the disease is progressive from the start, and patients have a better chance of avoiding disability if treated early.
3. Selective immune reconstitution therapy (SIRT) and treatments like alemtuzumab and cladribine that deplete memory B cells have been shown to be highly effective at controlling disease activity, with alemtuzumab demonstrating similar efficacy to cladribine but with different adverse effect profiles.
This document summarizes the London experience with autologous hematopoietic stem cell transplantation (AHSCT) for multiple sclerosis (MS). It provides data on 54 patients who underwent AHSCT, with a median follow up time of 23 months. Complications included admissions to the intensive care unit and re-admissions post-transplant, with no treatment related deaths in this group. Outcomes included low rates of relapses, disability progression, and new MRI lesions post-transplant. The results were consistent with prior studies and support further investigation of AHSCT as a treatment for highly active relapsing MS and progressive MS with disease activity. Ongoing trials are exploring whether AHSCT may be superior to
The future: Presentation by Gavin GiovannoniMS Trust
This document summarizes information from a presentation on multiple sclerosis (MS). It begins with disclosures from the presenter regarding compensation received from pharmaceutical companies. It then provides images and diagrams on various topics related to MS, including: cortical lesions; brain atrophy across disease stages; remyelination pathways and targets like LINGO-1; and study designs testing potential neuroprotective and remyelinating agents. One study examines the drug phenytoin in acute optic neuritis to assess neuroprotection by measuring retinal nerve fiber layer thickness. In summary, the document reviews MS pathology and potential new therapeutic strategies targeting remyelination and neuroprotection that are being investigated in clinical trials.
Diagnosis of MS and related disorders in children - Cheryl HemingwayMS Trust
This document discusses the diagnosis of multiple sclerosis (MS) and related disorders in children. It begins by reviewing the spectrum of acquired demyelinating syndromes (ADS) and criteria for diagnosing pediatric MS. Through several case examples, it illustrates key features of ADS and differential diagnoses. It also discusses current challenges in diagnosis and new phenotypes associated with antibodies. The document emphasizes the importance of timely and accurate diagnosis to guide appropriate treatment in the potential window of therapeutic opportunity.
- Ocrelizumab (OCR) significantly reduced disability progression and disease activity in patients with primary progressive multiple sclerosis (PPMS) compared to placebo in the ORATORIO clinical trial.
- Evaluation of efficacy in subgroups of patients with and without T1 gadolinium-enhancing (Gd+) lesions at baseline was a key objective. OCR reduced disability progression and disease activity in both subgroups.
- Specifically, OCR reduced the risk of 12-week and 24-week confirmed disability progression by 24-25% in the overall population and in both subgroups. It also reduced the worsening of walking ability and brain lesion volume over 120 weeks compared to placebo.
Prediction of outcome of Multiple sclerosisAmr Hassan
Prediction of outcome of Multiple sclerosis
An understanding of the natural history of multiple sclerosis(MS) in a patient is important to begin proper treatment at the correct time, especially when there is a high risk for poor prognosis. Factors that predict unfavorable prognosis are a primary or secondary progressive course, older age at disease onset, short interval between first and second attacks, initial cerebellar or pyramidal symptoms, a large number of functional systems involved at onset, moderate to severe disability within the first 2 years, and the presence of typical plaques or greater lesion volume shown by magnetic resonance imaging results during the first 5 years. However, there are no established laboratory tests able to predict long-term prognosis.
The Role of DaT Scan in Diagnosing Parkinson Disease Ade Wijaya
1) The diagnosis of Parkinson's disease is traditionally based on clinical examination, however around 20% of cases are initially misdiagnosed.
2) DaT scan is used when it is uncertain if clinical parkinsonism reflects degeneration of dopaminergic neurons, to assist in diagnosis and treatment decisions.
3) DaTscan imaging helps distinguish between nigrostriatal dopaminergic degeneration and other causes of parkinsonism, improving diagnostic accuracy and informing medication management.
Dr Trevor Pickersgill - Diagnosing a RelapseMS Trust
1) Diagnosing relapses in multiple sclerosis (MS) patients can be complex, as relapses can mimic other conditions and symptoms are not always clearly MS-related.
2) It is important to properly diagnose relapses to determine the MS disease course, guide treatment decisions, and understand the patient's prognosis.
3) In addition to traditional relapses, atypical presentations must be considered, such as relapses related to MS treatments, infections, neurological conditions mimicking MS, and non-neurological or functional issues. A thorough examination is needed.
This document discusses treating multiple sclerosis (MS) to target no evident disease activity (NEDA).
It acknowledges the author's disclosures from pharmaceutical companies and grants. It then discusses how MS is progressive from onset and inflammation contributes to neurodegeneration. NEDA is defined as no relapses, disability progression, or MRI activity.
Finally, it summarizes evidence that immunotherapies can benefit those with progressive MS, including data from clinical trials showing patients with primary progressive MS experienced improved outcomes on fingolimod.
Multiple sclerosis (MS) is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged.This damage disrupts the ability of parts of the nervous system to communicate, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems
Neurological Implications of von-Hippel Lindau diseaseAde Wijaya
This document summarizes the neurological implications of von Hippel-Lindau disease. It is an autosomal dominant genetic disorder caused by mutations in the VHL tumor suppressor gene. Patients with VHL frequently develop benign tumors called hemangioblastomas in the brain and spinal cord. While these tumors are non-cancerous, they can cause neurological problems due to their location and mass effect. Younger patients and those with more tumors have worse outcomes and faster tumor progression. Regular screening and surgical removal of tumors can help prevent disability. However, hemangioblastomas remain the most common cause of morbidity and reduced life expectancy in patients with VHL disease.
This document discusses new and emerging drugs for progressive multiple sclerosis. It provides an overview of the current treatment landscape and explores potential reasons for past clinical trial failures. It also examines the underlying pathological mechanisms of progressive disease and proposes that trials may have targeted the wrong outcomes, patient populations, or stages of disease progression. Ongoing trials of drugs like ocrelizumab and natalizumab aim to address some of these challenges by exploring therapies in earlier progressive phases and assessing disability outcomes over longer periods of time.
Rare aetiology of encephalopathy, as presented in American College of Physicians (ACP) 3rd India Meet 2018 in Lucknow on September 1.
The poster was adjudged as the 'Best Clinical Vignette'.
This document discusses highly active multiple sclerosis (MS). It defines several subtypes of aggressive MS including malignant, fulminant, and highly active MS. Predictors of highly active MS are discussed from a 2016 study. The case vignette describes a 34-year-old male physician's MS course from 2006 to 2017, showing recurrent attacks and progression. The timing of therapy is key to preventing disability, with an emphasis on early treatment to preserve brain reserve. Treatment algorithms recommend escalating therapy for aggressive MS to effectively treat within a narrow therapeutic window.
Clinically isolated syndromes (CIS) refer to the first clinical episodes of neurological symptoms suggestive of multiple sclerosis. The document discusses CIS in three parts: definition and clinical features of CIS, risk factors for conversion from CIS to multiple sclerosis, and management of CIS. Regarding clinical features, optic neuritis, transverse myelitis, and brainstem syndromes are highlighted as common presentations of CIS. MRI abnormalities, younger age of onset, smoking, and vitamin D deficiency are identified as risk factors for progression to multiple sclerosis. The management section outlines acute treatment with corticosteroids, use of disease-modifying therapies based on MRI findings, and consideration of vitamin D supplementation.
This presentation by Gavin Giovannoni looks at the new treatment paradigm for MS. It includes: arguments for early treatment in multiple sclerosis, the effect of MS on quality of life and whether highly-effective treatments stabilise MS.
It was presented at the MS Trust Annual Conference in November 2013.
Neuroradiology in multiple sclerosis
MRI in diagnosis of MS
MRI in D.D. of MS
MRI in monitoring disease progression and response to DMT
New imaging techniques
Vagal Nerve stimulation
Vagus nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. It is used as an add-on treatment for certain types of intractable epilepsy and treatment-resistant depression. Frequent side effects include coughing and shortness of breath. Serious side effects may include trouble talking and cardiac arrest.
Spinal cord injury without radiographic abnormalities (SCIWORA)SanchitUppal5
- SCIWORA refers to spinal cord injury without radiographic abnormality. It commonly occurs in children and involves the cervical spine.
- MRI is now considered the gold standard for diagnosis as it can detect abnormalities not seen on plain radiographs or CT scans like edema, hemorrhage or cord transection.
- Treatment involves immobilization, IV steroids may help, and surgery is indicated if MRI shows instability, compression or worsening neurological status. Prognosis depends on initial neurological status and MRI findings, with most patients showing improvement but some facing permanent impairments.
A 3-year-old boy presented to the emergency department with new onset lower extremity weakness after falling from a high chair two days prior. On examination, he had decreased strength and sensation in both lower extremities. Cervical spine films and CT were normal. He received a diagnosis of spinal cord injury without radiographic abnormality (SCIWORA) and was admitted to the neurosurgery service for MRI and further evaluation.
This document discusses progressive multiple sclerosis (MS) and whether it is possible to prevent or slow its progression. It begins by acknowledging potential conflicts of interest from clinical trials and industry relationships. It then explains that relapsing and progressive MS are part of a continuum, with continuous tissue loss driving progression even during relapsing stages. While symptoms and deficits differ depending on tissue loss and brain reserve, MS remains a single disease. Later stages are determined more by neuroanatomy and length of affected nerve fibers. The document advocates considering progressive MS patients' expectations realistically and evaluating therapies based on proven efficacy in both relapsing and progressive MS as well as safety and convenience factors.
Management strategies in multiple sclerosisAmr Hassan
This document discusses key decision making points in the treatment of multiple sclerosis (MS). It begins with an overview of the diagnostic criteria for MS and algorithms for clinical follow up of patients with a first attack or those at risk of converting to clinically definite MS. It then covers factors to consider when choosing a first-line disease modifying therapy, including adherence, patient preferences, prognostic factors, disease activity, comorbidities, safety, tolerability, efficacy, and pregnancy plans. Specific MS comorbidities and pregnancy categories for various therapies are also summarized. The document concludes with discussions on definitions of suboptimal response, treatment algorithms, escalation versus induction strategies, and considerations for discontinuing disease modifying therapies.
1. Klaus Schmierer presents disclosures related to research funding and speaking engagements from various pharmaceutical companies involved in multiple sclerosis treatment.
2. He discusses two important lessons about MS treatment - that the disease is progressive from the start, and patients have a better chance of avoiding disability if treated early.
3. Selective immune reconstitution therapy (SIRT) and treatments like alemtuzumab and cladribine that deplete memory B cells have been shown to be highly effective at controlling disease activity, with alemtuzumab demonstrating similar efficacy to cladribine but with different adverse effect profiles.
This document summarizes the London experience with autologous hematopoietic stem cell transplantation (AHSCT) for multiple sclerosis (MS). It provides data on 54 patients who underwent AHSCT, with a median follow up time of 23 months. Complications included admissions to the intensive care unit and re-admissions post-transplant, with no treatment related deaths in this group. Outcomes included low rates of relapses, disability progression, and new MRI lesions post-transplant. The results were consistent with prior studies and support further investigation of AHSCT as a treatment for highly active relapsing MS and progressive MS with disease activity. Ongoing trials are exploring whether AHSCT may be superior to
The future: Presentation by Gavin GiovannoniMS Trust
This document summarizes information from a presentation on multiple sclerosis (MS). It begins with disclosures from the presenter regarding compensation received from pharmaceutical companies. It then provides images and diagrams on various topics related to MS, including: cortical lesions; brain atrophy across disease stages; remyelination pathways and targets like LINGO-1; and study designs testing potential neuroprotective and remyelinating agents. One study examines the drug phenytoin in acute optic neuritis to assess neuroprotection by measuring retinal nerve fiber layer thickness. In summary, the document reviews MS pathology and potential new therapeutic strategies targeting remyelination and neuroprotection that are being investigated in clinical trials.
Diagnosis of MS and related disorders in children - Cheryl HemingwayMS Trust
This document discusses the diagnosis of multiple sclerosis (MS) and related disorders in children. It begins by reviewing the spectrum of acquired demyelinating syndromes (ADS) and criteria for diagnosing pediatric MS. Through several case examples, it illustrates key features of ADS and differential diagnoses. It also discusses current challenges in diagnosis and new phenotypes associated with antibodies. The document emphasizes the importance of timely and accurate diagnosis to guide appropriate treatment in the potential window of therapeutic opportunity.
- Ocrelizumab (OCR) significantly reduced disability progression and disease activity in patients with primary progressive multiple sclerosis (PPMS) compared to placebo in the ORATORIO clinical trial.
- Evaluation of efficacy in subgroups of patients with and without T1 gadolinium-enhancing (Gd+) lesions at baseline was a key objective. OCR reduced disability progression and disease activity in both subgroups.
- Specifically, OCR reduced the risk of 12-week and 24-week confirmed disability progression by 24-25% in the overall population and in both subgroups. It also reduced the worsening of walking ability and brain lesion volume over 120 weeks compared to placebo.
1) A phase 3 clinical trial evaluated the efficacy of ocrelizumab in reducing disability progression in patients with primary progressive multiple sclerosis (PPMS) with and without T1 gadolinium-enhancing lesions at baseline.
2) Results showed that ocrelizumab reduced the risk of 12-week and 24-week confirmed disability progression by 24% and 25% respectively compared to placebo in the overall study population.
3) When analyzing subgroups based on presence of T1 lesions at baseline, ocrelizumab reduced risk of disability progression in both subgroups, though the results did not reach statistical significance in the subgroup with lesions at baseline.
This document discusses clinical trials and the drug development process. It begins with an overview of the stages of clinical trials from Phase 0 to Phase IV. It then covers topics like trial design, endpoints, biases, sample sizes, regulatory authorities, and cost-effectiveness. The failures and successes of translating pre-clinical findings to human studies are analyzed. Repurposing existing drugs and the challenges academic researchers face are also addressed.
This document provides an overview of multiple sclerosis (MS) models and the challenges of translating findings from animal models to clinical applications. It discusses key aspects of MS like pathogenesis, clinical courses, and neurodegeneration. Common MS models like experimental autoimmune encephalomyelitis (EAE) are described along with their limitations in mimicking the human disease. Issues like preclinical failure to translate findings and limitations of experimental design that can contribute to clinical trial failures are reviewed. Guidelines for improving experimental design and reporting are also mentioned.
Switching therapy in Multiple sclerosisDivya Shilpa
1) A 37-year-old housewife, Mrs. S.D., has relapsing-remitting multiple sclerosis. She has experienced breakthrough disease activity while on interferon beta therapy.
2) The document discusses criteria for evaluating clinically relevant disease activity and considerations for treatment adjustment, including relapse rate, disability progression, and MRI findings. It also reviews options for switching or adding therapy, such as increasing interferon beta dose or switching to glatiramer acetate, natalizumab, fingolimod, or other drugs.
3) The evidence on switching therapies suggests that some patients with suboptimal response to interferon beta may experience reduced relapse rates and disability progression after switching to glat
Sequencing of Disease Modifying Treatments in Multiple Sclerosis - Belinda We...MS Trust
1) There are two broad categories of disease modifying treatments (DMTs) for multiple sclerosis - drugs of moderate efficacy including beta interferons, glatiramer acetate, teriflunomide, and dimethyl fumarate, and drugs of high efficacy including alemtuzumab and natalizumab.
2) The prevailing practice is treatment escalation, starting with a first-line drug and changing treatments based on tolerability, safety, and efficacy. No relapses, disability progression, or MRI activity (NEDA) indicates treatment success.
3) There is no accepted treatment algorithm in the UK. Involving patients in decision making is important as the treatment landscape becomes more complex
Ideate, innovate! Co-creating with Social CustomersLithium
The document summarizes a webcast on using social media and ideation sites to engage customers in the product development process. It provides examples of how companies like National Instruments and Verizon have successfully launched ideation sites to gather customer input and implemented customer-suggested ideas. The benefits of co-creation are discussed, such as fueling innovation, validating ideas early, and engaging customers. Tips are provided on running a successful ideation site.
This document provides an overview of the Engineering 245 Lean LaunchPad course at Stanford. The summary is:
1. The course teaches students about entrepreneurship through customer development and building business models for scalable startups with the goal of growing to $100 million in revenue.
2. Students work in teams to develop and test hypotheses about problems, solutions, customers and business models over 8 weeks through customer interviews and iterative prototyping.
3. Grades are based on weekly presentations and a final presentation where students demonstrate what they learned through customer development about the viability of their startup idea.
This document summarizes research on correlating MRI findings with neuropathological features in multiple sclerosis (MS). Key points include:
- MRI techniques like MTR can detect myelin and axonal loss validated by histology. Non-lesional white matter shows more extensive pathology than just lesions.
- Cortical grey matter also shows demyelination, neuronal loss, and atrophy correlated with disability.
- Spinal cord pathology including diffuse axonal loss and myelin damage contributes to disability, not just atrophy.
- Validating MRI with post-mortem tissue is important for diagnosis, predicting disease progression, and understanding substrates of disability in MS.
PET scans use radioactive tracers and detectors to generate 3D images of metabolic processes in the body. They have various applications in neurology for diagnosing and monitoring conditions like dementia, epilepsy, movement disorders, and brain tumors. For example, PET can help differentiate Alzheimer's from other dementias based on patterns of hypometabolism in temporal and parietal lobes. It is also useful for localizing epileptic foci before epilepsy surgery. The document discusses the history, mechanisms, common tracers, and limitations of PET scanning as well as its role in evaluating specific neurological conditions and potential future applications.
Presentation1, new mri techniques in the diagnosis and monitoring of multiple...Abdellah Nazeer
This document discusses new MRI techniques for diagnosing and monitoring multiple sclerosis (MS). It recommends protocols for baseline and follow-up brain and spinal cord MRIs, including mandatory and optional sequences. Advanced techniques like double inversion recovery, diffusion tensor imaging, and MR spectroscopy are highlighted for improving detection of gray matter lesions and diffuse white matter damage compared to conventional MRI. The document concludes that while conventional MRI is important for MS, advanced techniques provide higher sensitivity and specificity for both lesions and normal-appearing brain tissue, furthering understanding of MS pathophysiology.
This document provides an overview of magnetic resonance imaging (MRI) of the brain, including basic principles, MRI sequences, interpretation, and clinical correlation. It discusses normal brain anatomy as seen on MRI and provides labeled images. Common MRI protocols for various neurological conditions such as brain tumors, stroke, and infections are outlined. The value of clinical history and MRI findings for diagnosis is emphasized. An interactive case discussion session is included to demonstrate clinical correlations.
Brief description of various neuroimaging modalities used in psychiatry which help in early detection, diagnosis and treatment of various neuropsychiatric disorders.
1) Clinical trials in progressive multiple sclerosis (MS) face many challenges due to heterogeneity of the condition and unclear pathological mechanisms.
2) Current trials are exploring therapies targeting inflammation, neuroprotection, and repair, with mixed results. Adaptive trial designs may help overcome challenges.
3) Future research priorities include better defining MS phenotypes, identifying pathological drivers of progression, and developing biomarkers to aid trial design and measure treatment response. Several promising therapies are now in late-stage clinical testing.
The document discusses various neuroimaging techniques used to study the brain, including their basic principles and psychiatric applications. It describes CT, MRI, MRS, fMRI, and SPECT, explaining what each measures, how they work, and what tissues appear as on the images. It provides examples of structural images and contrasts the advantages and disadvantages of the different modalities. It also outlines specific indications for neuroimaging in clinical practice and research into psychiatric disorders.
Neurology advanced mr imaging in epilepsy v laiJFIM
This document discusses advanced magnetic resonance (MR) imaging techniques for epilepsy. It provides an overview of various structural and functional imaging findings and concepts. The document outlines several etiologies of epilepsy that can be identified on imaging such as malformations of cortical development, mesial temporal sclerosis, tumors, and vascular or nonvascular insults. Advanced MR techniques discussed include high resolution structural imaging, susceptibility weighted imaging, and functional techniques like radionuclide imaging, T2 relaxometry, MR spectroscopy, diffusion tensor imaging, and arterial spin labeling that can help localize the epileptogenic lesion. The document also presents some of the author's preliminary work utilizing 3T MR imaging and quantitative volumetry to detect subtle lesions, improve detection
Emerging MRI and metabolic neuroimaging techniques in mild traumatic brain in...IntesarAldweri
Traumatic brain injury (TBI) is one of the leading causes of death worldwide, and mild traumatic brain injury (mTBI) is the most common traumatic injury.
This document summarizes a study evaluating the use of MRI and MRS in characterizing intracranial ring-enhancing lesions. 50 patients with ring-enhancing lesions detected on CT or MRI were evaluated using conventional MRI sequences, diffusion-weighted imaging, and MRS. The most common lesions observed were tuberculomas (44%), followed by primary brain tumors (22%) and neurocysticercosis (12%). MRS found choline peaks in most lesions (56%), with lipid peaks also common. MRI and MRS patterns helped differentiate between benign and malignant lesions, with MRS providing additional metabolic information to aid characterization though not enabling diagnosis on its own.
1) Brain metastases are the most common intracranial tumors in adults, developing in 10-30% of patients with cancer.
2) Primary tumors that commonly metastasize to the brain include lung cancer, breast cancer, kidney cancer, and colorectal cancer in adults and sarcomas, neuroblastoma, and germ cell tumors in children.
3) Treatment for brain metastases depends on the patient's health status, primary tumor type, and number/location of lesions, and may include corticosteroids, whole brain radiation, surgery, stereotactic radiosurgery, or a combination of these approaches tailored to the individual patient.
This document summarizes research on using SPECT (Single Photon Emission Computed Tomography) imaging to study brain function in patients with concussions, vertebrobasilar insufficiency, and other neurological disorders. SPECT can show brain abnormalities in patients with normal CT and MRI scans after minor head injuries. One study found that children with medial temporal hypoperfusion on early SPECT scans after minor head injuries were more likely to develop persistent post-concussion syndrome. Another study examined whether the drug Piracetam could improve cerebral perfusion as seen on SPECT scans in patients with post-concussion syndrome.
Optical Coherence Tomography in Multiple Sclerosisneurophq8
OCT is a non-invasive technology used in ophthalmology to assess retinal diseases and glaucoma. In recent years , OCT has been used to assess axonal loss and neurodegeneration in MS. This presentation will highlight the main uses of the OCT in MS and review of the literature.
Stereotactic Radiosurgery for Malignant CNS Tumors.pptxAsha Arjunan
- Stereotactic radiosurgery (SRS) uses focused radiation to treat brain tumors and metastases. Common indications include brain metastases, where SRS alone may be sufficient for 1-3 lesions.
- Randomized trials have shown SRS alone leads to less cognitive decline than SRS plus whole brain radiation for limited brain metastases. However, SRS alone is associated with higher local recurrence rates.
- For resected brain metastases, observation or postoperative SRS may be appropriate depending on factors like number/size of lesions and extracranial disease control. Whole brain radiation provides improved intracranial control but not overall survival.
- For high grade gliomas, maximum safe resection followed by chemor
Optic Neuritis and OCT in Multiple Sclerosis neurophq8
An overview of the update in optic neuritis and the utility of OCT in multiple sclerosis presented at the MS perceptorship in Dasman Institute in April 13 , 2017
Vestibular schwannomas, meningiomas, and epidermoid cysts are the most common tumors found in the cerebellopontine angle. They typically present with symptoms of cranial nerve dysfunction such as hearing loss, vertigo, and facial numbness. MRI is the gold standard for diagnosis and shows the location and size of the tumor. Treatment involves surgical resection while attempting to preserve cranial nerve function, with the goal of complete removal while minimizing complications.
Transcatheter Aortic Valve Replacement (TAVR) is a transformational and rapidly evolving treatment for the patients with aortic stenosis which require valve replacement surgery. Get more details at website.
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Brain MRI biomarkers for improved follow up of people with Multiple Sclerosis...Wim Van Hecke
MRI is increasingly used for the diagnosis and follow-up of people with Multiple Sclerosis (MS). However, there is a need for objective MRI biomarkers that can be used in clinical practice. This is now possible. By sending MRI data to a icometrix, reliable and objective reports of brain atrophy and lesion load can be obtained.
This document describes a study that used FreeSurfer software to obtain volumetric measurements of subcortical structures and cortical thickness measurements from MRI scans of patients with Alzheimer's disease, mild cognitive impairment, or frontotemporal dementia, as well as healthy control subjects. The study aimed to identify diagnostic markers for these neurodegenerative diseases but was unable to determine correlations between brain structures and specific diseases due to confidentiality constraints on disease diagnoses. Common errors during FreeSurfer processing were corrected before analysis of subcortical and cortical thickness results.
Similar to MRI markers to understand progression (20)
In Switzerland, Hippotherapy-K® is applied for central neurological disorders in the brain and spine. It is acknowledged and paid for by health insurances in the case of Multiple Sclerosis. Riding the horse loosens spasms in the legs and reduces coordination disorders while sitting. The movements and rhythm of the horse are optimally used.
Hippotherapy-K® („K“ stands for its Swiss founder, Ursula Künzle) is an acknowledged medical method in which the threedimensional gait of the horse is transferred to the patient. This trains the muscles that sustain the torso, stabilises the spine and supports balancing abilities. The joints of the pelvis and spine are mobilised in an optimal way.
Risk factors in Multiple Sclerosis: Detection and Treatment in Daily Life
Caroline Pot and Patrice Lalive
Unit of Neuroimmunology and Multi Sclerosis Geneva University Hospital
This document summarizes a presentation on quantifying exercise intensity during rehabilitation training for people with multiple sclerosis (PwMS). It defines sports therapy and discusses the benefits of exercise for PwMS. It then focuses on quantifying intensities for endurance and resistance training, discussing methods like maximum oxygen consumption, heart rate peaks, ratings of perceived exertion, and resistance training norms. Recommendations are given for endurance training intensities and a case study is presented. The document concludes that moderate training intensities are well tolerated and beneficial for improving quality of life and reducing fatigue in PwMS.
This document discusses multiple sclerosis (MS) and the role of exercise therapy. It contains the following key points:
1) MS is a chronic progressive disease despite disease-modifying drugs. Studies show disability worsening over time with the duration of the disease.
2) Early studies were skeptical about treating MS, but more recent evidence and reviews find moderate to strong evidence that exercise therapy can improve muscle power, exercise tolerance, mobility and mood in people with MS with no evidence of harmful effects.
3) Specific exercise therapy programs may be as effective as other exercise treatments in improving activities and participation for people with MS. Exercise training can result in improved fitness and quality of life.
4) Temporary increases
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfrightmanforbloodline
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Know the difference between Endodontics and Orthodontics.Gokuldas Hospital
Your smile is beautiful.
Let’s be honest. Maintaining that beautiful smile is not an easy task. It is more than brushing and flossing. Sometimes, you might encounter dental issues that need special dental care. These issues can range anywhere from misalignment of the jaw to pain in the root of teeth.
How to Control Your Asthma Tips by gokuldas hospital.Gokuldas Hospital
Respiratory issues like asthma are the most sensitive issue that is affecting millions worldwide. It hampers the daily activities leaving the body tired and breathless.
The key to a good grip on asthma is proper knowledge and management strategies. Understanding the patient-specific symptoms and carving out an effective treatment likewise is the best way to keep asthma under control.
low birth weight presentation. Low birth weight (LBW) infant is defined as the one whose birth weight is less than 2500g irrespective of their gestational age. Premature birth and low birth weight(LBW) is still a serious problem in newborn. Causing high morbidity and mortality rate worldwide. The nursing care provide to low birth weight babies is crucial in promoting their overall health and development. Through careful assessment, diagnosis,, planning, and evaluation plays a vital role in ensuring these vulnerable infants receive the specialize care they need. In India every third of the infant weight less than 2500g.
Birth period, socioeconomical status, nutritional and intrauterine environment are the factors influencing low birth weight
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
1. Neuroimaging Research Unit, Institute of Experimental
Neurology, Division of Neuroscience, San Raffaele Scientific
Institute, Vita-Salute San Raffaele University, Milan, Italy.
MRI MARKERS
TO UNDERSTAND PROGRESSION
MECHANISMS
Maria A. Rocca
3. SPMS
60 SPMS with monthly brain MRI for 4 months
32 (53%) had enhancing lesions at baseline
42 (70%) displayed one or more new enhancing lesions
at follow-up
14 (23%) showed no enhancing lesions either at baseline
or follow-up
Tubridyetal.,Neurology1998
Khaleelietal.,MultScler2010
PPMS
45 PPMS with brain and spinal cord MRI for 5
years
15 (33%) had enhancing lesion at baseline
12 (26%) had enhancing lesion at 5 year
26 (58%) had ≥1 enhancing lesion during the study
19 (42%) had no enhancing lesion during the study
MRI & Progressive MS
Brain WM lesions / Enhancement
4. Khaleeli et al., Ann Neurol 2008
101 PPMS followed up for 10 yrs
MRI & Progressive MS
Brain WM lesions / Prognosis
Mesarosetal.,JNeurol2008
RRMS
Sormani et al., Neurology 2009
• Similar slope of the relationship
between baseline T2LV and
EDSS in RRMS and SPMS
• Median yearly T2LV change:
0.27 mL in RRMS, and 0.30 mL
in SPMS (p=0.59)
T2 lesions
5. MRI & Progressive MS
Brain WM lesions / Distribution
Ceccarellietal.,NeuroImage2008
CIS RR SP PP
T2 lesion maps
Bodinietal.,JNNP2011
T2 lesion location vs disability worsening
T1 lesion maps
PPMS
PP vs RR: 29 vs 19% peak probability
DiPerrietal.,ArchNeurol2008
• Higher T1 lesion occurrence in the CC,
CST and other tracts adjacent to the lateral
ventricles in SPMS vs RRMS
Filli et al., MSJ 2012
6. Multiple hyperintense
lesions in the spinal cord
Rovaris et al., Brain 2001
Spinal cord / T2 lesions
MRI & Progressive MS
Number of cord lesions Number of damaged
cord segments
0.0
1.0
2.0
3.0
4.0
5.0
0.0
1.0
2.0
3.0
4.0
5.0
6.0
p = 0.03
0.0
30.0
60.0
90.0
Cord area [mm2]
Rovarisetal.,Brain2001
PPMSSPMSControls
8. Atrophy
MRI & Progressive MS
1 y FU: 963 untreated MS patients
De Stefano et al., Neurology 2010
p = 0.003
Dalton et al., Neurology 2006
CIS MS
(<1 year)
RRMS SPMS
n.s.
p=0.003
p=0.001
p=0.001
Ventricularvolumechange
21 CIS, 30 early relapse-onset,
41 RRMS, 23 SPMS
9. Atrophy
Fisher et al., Ann Neurol 2008
GM atrophy rates:
CIS→RRMS and RRMS stable > HC (p=0.05)
RRMS→SPMS and SPMS > HC (p= 0.005)
WM atrophy rates similar in all disease groups
MRI & Progressive MS
NGMV
NWMV
** p<0.001
* p<0.01
GM atrophy explains physical disability and
cognitive impairment better than WM volume
Roosendaal et al., MSJ 2011
** p<0.001
* p<0.01
11. Pulizzi et al., Arch Neurol 2007
CIS vs HC PPMS vs HC
1
2
3
4
5
t value
2
4
6
8
t value
MDFA
RRMS vs BMS
t value
t value
SPMS vs RRMS SPMS vs PPMS
Preziosa et al., Radiology 2011
MRI & Progressive MS
NAWM damage
p=0.003
p=0.01
-
p=0.004
RRMS BMS
SPMS PPMS
Tortorella et al., Neurology 2000
13. Kutzelnigg et al., Brain 2005
Focal demyelinated plaques in WM
Cortical demyelination
Demyelinated plaques in deep GM
MRI & Progressive MS
GM damage / Cortical lesions
Extensive subpial
demyelination of the
cerebellum in a
PPMS case
14. Baseline CL volume: B: -0.525, p <0.001
Baseline T2-WM-LV: B: -0.448, p <0.001
48 PPMS patients followed up
for 2 years
Calabrese et al., Neurology 2009
DIR and disease evolution
MRI & PROGRESSIVE MS
GM damage / Cortical lesionsMulti-slab 3D DIR
Geurtsetal.,
Radiology2005
vs. SE = +538%; vs. FLAIR = +152%
RRMS PPMS
Calabreseetal.,Neurology2010
Cohen-Adad et al.,
NeuroImage 2011
T2*-w / 7 T
15. Power to discriminate SPMS from BMS
Filippietal.,MSJ2012
MDFA
Age: OR 1.2, p =0.001
Baseline CL volume: OR 1.7, p <0.001
Baseline cerebellar cortical volume:
OR 0.2, p <0.001
334 relapse-onset MS patients, 5 years FU
Calabrese et al., Ann Neurol 2013
MRI & Progressive MS
GM damage / Cortical lesions
Baseline CL volume:
entire group: B=0.511; p<0.001
RRMS: B=0.512; p<0.001
SPMS: B=0.495; p<0.001
107 relapse-onset MS patients, 3-year FU
Calabrese et al., Ann Neurol 2010
16. Baseline GMF: OR 0.79, p=0.01
C index: 69%
73 relapse-onset MS patients followed up for 13 years
MRI & Progressive MS
Evolution to SPMS at 13 year FU:
Baseline T2 LV (OR=1.13, p=0.005)
Baseline GMF (OR=0.71, p=0.04)
C-index: 84%
Cognitive deterioration at 13 year FU:
Baseline average GM MTR (OR=0.87, p=0.03)
Baseline disease duration (OR=1.50, p=0.08)
C-index: 97%
Baseline GMF: OR 0.79 (CI 0.7–0.9)
Baseline EDSS: OR 2.88 (CI 1.9–4.36)
241 relapse-onset
MS patients followed up for 9 years
Lavorgna et al., MSJ 2013
“Diffuse” GM damage
Filippi et al., Neurology 2013
17. MRI & Progressive MS
“Regional” GM damage
SPMS vs RRMS
SPMS vs PPMS
Ceccarelli et al., NeuroImage 2008
Selective GM loss
19. C
MRI & Progressive MS
Spinal cord / Atrophy
CSAn vs EDSS: r=-0.49, p<0.0001 EDSS
CSAn
Differential effect among disease clinical phenotypes (p<0.001):
no association in CIS and BMS patients
association in RRMS (r=-0.30), SPMS (r=-0.34) and PPMS patients (r=-0.27)
Roccaetal.,Neurology2011
20. Roccaetal.,JNNP2013
BMS vs RRMS SPMS vs RRMS SPMS vs BMS SPMS vs PPMSPPMS vs HC
P A L R P A L R P A L R P A L R P A L R
T2 lesion
probability
RRMS BMS PPMS SPMSCIS
MRI & Progressive MS
Spinal cord damage
21. Average MD
[x10-3mm2s-1] (SD)
Mean FA
(SD)
Controls
1.203
(0.09)
0.42
(0.04)
PPMS
1.280
(0.10)
0.38
(0.05)
p
0.024
0.007
Agosta et al., Neurology 2005
MRI & Progressive MS
Spinal cord / Diffuse damage
Composite MR model vs EDSS:
Cord area + cord MTR peak height
(r=0.21, p=0.04)
Rovaris et al., Brain 2001
0
10
20
30
40
50
60
70
0 10 20 30 40 50 60 70 80
Controls
MTR [%]
Normalizedpixelcount
SPMS
PPMS
22. MRI & Progressive MS
Spinal cord damage
Baseline cross-sectional area and FA
vs EDSS at follow-up:
r = -0.40; p = 0.01
Agosta et al., Brain 2007
-10% -5% 0 +5% +10% +15% +20%
FA
MD
Cross-
sectional
area
RRMS
SPMS
PPMS
Overall
UCCA, T1LV, diffuse abnormalities and number of
involved segments were significant explanatory factors for
clinical disability (R2 = 0.564)
Lukas et al., Radiology 2013
24. CIS vs
non-disabled RRMS
SMC
Non-disabled vs mildly
disabled RRMS
SMC, SMA
Mildly disabled RRMS
vs SPMS
Thalamus
SII
SPMS vs
mildly disabled RRMS
Precuneus,
IPL, MFG
MFG, IPL
Precuneus,
CMA, MFG
Rocca et al., Lancet Neurol 2005
MRI & Progressive MS
CNS reorganization / Brain
25. SPMS (reduced activations)
L SMA
L putamen
R cerebellum
Rocca et al., Neurology 2010
BMS
L SMC vs T2 lesion volume:
r = 0.63, p < 0.001
Rocca et al., Neurology 2010
MRI & Progressive MS
CNS reorganization / Brain
STG
MFG
Insula
PPMS
Filippi et al., NeuroImage 2002
26. Correlations between DMN fluctuations and:
PASAT (r=0.42, p<0.001)
CC FA and JD (r ranging from 0.54 to 0.87, p<0.001)
Cingulum FA (r=0.83, p<0.001)
Roccaetal.,Neurology2010
DMN fluctuations in progressive MS patients
HC
PPMS
SPMS
MRI & Progressive MS
CNS reorganization / Brain
32. Neuroimaging Research Unit & WM
diseases group
Director: M. Filippi
DIVISION OF NEUROSCIENCE INSTITUTE OF EXPERIMENTAL NEUROLOGY
Scientific coordinator: M.A. Rocca
Department of Neurology
G. Comi, B. Colombo,
M. Comola, F. Esposito, V. Martinelli, F.
Martinelli Boneschi,
L. Moiola, G. Pavan, M. Rodegher
Department of Neuroradiology
A. Falini
MAGNIMS
Physicians: M. Absinta
A. Bisecco
G. Boffa
S. Cirillo
E. De Meo
G. Longoni
F. Mele
R. Messina
M.E. Morelli
L. Parisi
P. Preziosa
G. Riccitelli
Physicists:
M. Copetti
E. Pagani
P. Valsasina
Technicians:
L. Dall’Occhio
A. Meani
P. Misci
M. Petrolini
S. Sala
M. Sibilia
R. Vuotto
University of Belgrade
V.S. Kostic,
J. Drulovic, S. Mesaros
Gallarate Hospital, MS Centre
A. Ghezzi