Progressive multiple sclerosis (MS) can be primary progressive or secondary progressive and occurs on a spectrum with relapsing MS. Treatment approaches for progressive MS include immunomodulation, B-cell therapies like ocrelizumab which is approved for primary progressive MS, and neuroprotective agents. Monitoring for progression may involve markers like neurofilament light chain in serum and cerebrospinal fluid as well as optical coherence tomography and spinal cord MRI measures. Management of progressive MS also focuses on controlling medical comorbidities.
This document discusses electrodiagnostic criteria for Guillain-Barré syndrome (GBS) subtypes acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). It reviews the evolution of criteria sets over time, including those proposed by Asbury, Albers, Cornblath, Ho, Hadden, and others. Key findings include that early electrodiagnosis can be difficult, with reversible conduction failure in AMAN sometimes mimicking AIDP. Serial nerve conduction studies are important for distinguishing subtypes and determining prognosis, as features may change over time. The document also discusses pathological mechanisms and involvement of sensory fibers.
This document discusses non-5q spinal muscular atrophy (SMA). It begins by describing the upper motor neuron (UMN) and lower motor neuron (LMN) pathways. The majority of SMA cases are caused by mutations on chromosome 5q, but 4% are non-5q SMA. Non-5q SMA is clinically and genetically heterogeneous. Several causal genes have been identified for different subtypes. The document then describes the clinical features and inheritance patterns of several rare non-5q SMA subtypes. Advanced genetic testing techniques like next-generation sequencing have helped identify more causal genes but also increased heterogeneity. Management involves symptom management while future challenges include determining pathogenicity of variants and developing accurate models.
neuromyelitis optica spectrum disorder Dr. Musa AtarzadehMusa Atazadeh
1. The document discusses the diagnosis and diagnostic criteria for Neuromyelitis Optica Spectrum Disorder (NMOSD) according to the 2015 AAN criteria.
2. The diagnosis involves assessing for core clinical characteristics, compatible neuroimaging findings, and testing for AQP4-IgG antibodies.
3. Certain clinical presentations and neuroimaging patterns can raise red flags and suggest alternative diagnoses rather than NMOSD. Repeating AQP4-IgG testing over time or in the CSF may also be considered in some cases.
Primary central nervous system vasculitis (PACNS) is a rare disorder characterized by inflammation of blood vessels within the brain and spinal cord. It can be classified as granulomatous or atypical based on biopsy findings. Common symptoms include headache, seizures, strokes, and cognitive or neurological deficits. Diagnosis involves neuroimaging showing vessel inflammation or infarction, and ruling out other causes. Treatment is typically high-dose corticosteroids. Other CNS vasculitides can be secondary to infections like varicella zoster virus or systemic conditions like giant cell arteritis that affect larger vessels. Reversible cerebral vasoconstriction syndrome is a related disorder of reversible cerebral artery constriction causing similar symptoms.
This document provides an overview of neuromyelitis optica spectrum disorders (NMOSD). It discusses the epidemiology, clinical features, diagnostic criteria, investigations, neuroimaging findings, and treatments for NMOSD. Key points include that NMOSD predominantly affects the optic nerves and spinal cord, is strongly associated with antibodies against the aquaporin-4 protein, and treatments involve high-dose steroids, plasma exchange, or intravenous immunoglobulins for acute exacerbations. The diagnostic criteria were revised in 2015 to incorporate aquaporin-4 antibody testing and distinguish NMOSD from multiple sclerosis.
Aging is associated with cognitive decline, and older subjects can have demonstrable cognitive impairment without crossing the threshold for dementia.
This condition has been termed “mild cognitive impairment” (MCI), and these patients have an increased risk of developing dementia, especially Alzheimer disease (AD).
Studies conducted in referral clinics have shown that patients with MCI progress to AD at a rate of 10% to 15% per year, and 80% of these patients have converted to AD after approximately 6 years of follow-up.
The identification and classification of MCI can be a major challenge.
This document provides an overview of key concepts for visual analysis of EEG recordings, including:
1. Frequency, amplitude, distribution, symmetry, synchrony, reactivity, morphology, rhythmicity, and regulation are terms used to describe EEG activity.
2. Common normal brain rhythms include alpha, beta, and theta waves that have characteristic frequencies, distributions, and reactivity patterns.
3. Aging-related temporal slowing involving sporadic theta waves over the temporal regions is a normal variant seen in older adults.
This document discusses electrodiagnostic criteria for Guillain-Barré syndrome (GBS) subtypes acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). It reviews the evolution of criteria sets over time, including those proposed by Asbury, Albers, Cornblath, Ho, Hadden, and others. Key findings include that early electrodiagnosis can be difficult, with reversible conduction failure in AMAN sometimes mimicking AIDP. Serial nerve conduction studies are important for distinguishing subtypes and determining prognosis, as features may change over time. The document also discusses pathological mechanisms and involvement of sensory fibers.
This document discusses non-5q spinal muscular atrophy (SMA). It begins by describing the upper motor neuron (UMN) and lower motor neuron (LMN) pathways. The majority of SMA cases are caused by mutations on chromosome 5q, but 4% are non-5q SMA. Non-5q SMA is clinically and genetically heterogeneous. Several causal genes have been identified for different subtypes. The document then describes the clinical features and inheritance patterns of several rare non-5q SMA subtypes. Advanced genetic testing techniques like next-generation sequencing have helped identify more causal genes but also increased heterogeneity. Management involves symptom management while future challenges include determining pathogenicity of variants and developing accurate models.
neuromyelitis optica spectrum disorder Dr. Musa AtarzadehMusa Atazadeh
1. The document discusses the diagnosis and diagnostic criteria for Neuromyelitis Optica Spectrum Disorder (NMOSD) according to the 2015 AAN criteria.
2. The diagnosis involves assessing for core clinical characteristics, compatible neuroimaging findings, and testing for AQP4-IgG antibodies.
3. Certain clinical presentations and neuroimaging patterns can raise red flags and suggest alternative diagnoses rather than NMOSD. Repeating AQP4-IgG testing over time or in the CSF may also be considered in some cases.
Primary central nervous system vasculitis (PACNS) is a rare disorder characterized by inflammation of blood vessels within the brain and spinal cord. It can be classified as granulomatous or atypical based on biopsy findings. Common symptoms include headache, seizures, strokes, and cognitive or neurological deficits. Diagnosis involves neuroimaging showing vessel inflammation or infarction, and ruling out other causes. Treatment is typically high-dose corticosteroids. Other CNS vasculitides can be secondary to infections like varicella zoster virus or systemic conditions like giant cell arteritis that affect larger vessels. Reversible cerebral vasoconstriction syndrome is a related disorder of reversible cerebral artery constriction causing similar symptoms.
This document provides an overview of neuromyelitis optica spectrum disorders (NMOSD). It discusses the epidemiology, clinical features, diagnostic criteria, investigations, neuroimaging findings, and treatments for NMOSD. Key points include that NMOSD predominantly affects the optic nerves and spinal cord, is strongly associated with antibodies against the aquaporin-4 protein, and treatments involve high-dose steroids, plasma exchange, or intravenous immunoglobulins for acute exacerbations. The diagnostic criteria were revised in 2015 to incorporate aquaporin-4 antibody testing and distinguish NMOSD from multiple sclerosis.
Aging is associated with cognitive decline, and older subjects can have demonstrable cognitive impairment without crossing the threshold for dementia.
This condition has been termed “mild cognitive impairment” (MCI), and these patients have an increased risk of developing dementia, especially Alzheimer disease (AD).
Studies conducted in referral clinics have shown that patients with MCI progress to AD at a rate of 10% to 15% per year, and 80% of these patients have converted to AD after approximately 6 years of follow-up.
The identification and classification of MCI can be a major challenge.
This document provides an overview of key concepts for visual analysis of EEG recordings, including:
1. Frequency, amplitude, distribution, symmetry, synchrony, reactivity, morphology, rhythmicity, and regulation are terms used to describe EEG activity.
2. Common normal brain rhythms include alpha, beta, and theta waves that have characteristic frequencies, distributions, and reactivity patterns.
3. Aging-related temporal slowing involving sporadic theta waves over the temporal regions is a normal variant seen in older adults.
NeuroMyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory disorder of the central nervous system characterized by demyelination and damage of the optic nerves and spinal cord. It was previously considered a variant of multiple sclerosis but is now recognized as a distinct condition mediated by autoantibodies against aquaporin-4. NMOSD can present with optic neuritis causing vision loss or transverse myelitis with varying degrees of weakness and sensory loss. Brain involvement is also seen in around half of patients. The disease predominantly affects women and typically involves recurrent, severe attacks with varying recovery. Diagnosis involves identifying clinical features, MRI imaging, and serologic testing for aquaporin-4 antibodies.
Hereditary neuropathies are a diverse group of inherited conditions affecting the peripheral nervous system. They are frequently underdiagnosed due to their indolent onset over decades and lack of clear family history in some cases. Charcot-Marie-Tooth disease is the most common inherited neuropathy, with two main types - CMT1 characterized by demyelination and CMT2 characterized by axonal loss. CMT1 results from mutations affecting myelin protein zero or peripheral myelin protein 22 genes, causing demyelination and onion bulb formation. Accurate diagnosis relies on detailed family history, neurological examination, and electrodiagnostic testing to distinguish inherited from acquired neuropathies.
This document provides guidelines for the diagnosis and treatment of multiple sclerosis (MS). It discusses the different subtypes of MS, diagnostic criteria, disease mechanisms, epidemiology in India, clinical features of relapses, and guidelines for using disease-modifying therapies. Key recommendations include using McDonald criteria for diagnosis, treating relapsing forms of MS with approved disease-modifying drugs, monitoring patients on treatment, and considering ocrelizumab for primary progressive MS.
Anti-MOG Antibody-Associated Diseases - Prof. Ayman NassefTalal Thabet
In this slides deck, Prof. Ayman Nassef clarifies the role of Myelin Olidodendrocyte Glycoprotein (MOG) in demyelinating conditions, and explains how MOG-IgGs cause damage of myelin and axons and the impact of such damage on the disease.
This document provides diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP), including:
1) Clinical criteria for typical and atypical CIDP with inclusion/exclusion factors.
2) Definite, probable, and possible electrophysiological criteria involving compound muscle action potential tests.
3) Supportive diagnostic criteria including cerebrospinal fluid analysis, MRI findings, nerve conduction studies, and nerve biopsy results.
It also outlines inclusion/exclusion criteria and supportive criteria specifically for diagnosing pure sensory CIDP without motor involvement.
CIDP is a chronic acquired demyelinating neuropathy. It has two patterns - a continuous progressive course over months to years or a relapsing course with partial recovery between episodes. Diagnosis requires documentation of demyelination through electrodiagnostic testing, CSF analysis and sometimes nerve biopsy. Treatment includes corticosteroids, IVIG and plasmapheresis, which are effective in around 50-70% of patients. Corticosteroids are usually the first line treatment, starting with high dose prednisone and slowly tapering as response occurs.
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is a rare neurological disorder characterized by progressive weakness and impaired sensory function caused by damage to the peripheral nervous system. It has an incidence rate of 1-2 per 100,000 people and predominantly affects males over 50 years old. CIDP is diagnosed based on progressive muscle weakness, reduced reflexes, nerve conduction studies showing demyelination, elevated CSF protein, and nerve biopsy with signs of demyelination. Treatment involves intravenous immunoglobulin, plasma exchange, steroids, or other immunosuppressants, with around 50% of patients experiencing improvement with therapy.
Autoimmune encephalitis current conceptsNeurologyKota
1) Autoimmune encephalitis is a debilitating neurological disorder caused by inflammation of the brain. It develops subacutely over weeks and can affect individuals of all ages.
2) It has diverse clinical manifestations and immunological associations. Identification of neural autoantibodies has led to classification of different subtypes.
3) Prominent among these are anti-NMDAR encephalitis commonly seen in young women and children, autoimmune limbic encephalitis, and other syndromes associated with antibodies targeting neuronal cell-surface and intracellular antigens.
Multiple sclerosis and newer concept in management till 2014 maydrnikhilver
This document provides information about Multiple Sclerosis (MS), including what it is, possible causes, types, diagnosis, treatment and newer concepts in management. It defines MS as a chronic neurological disorder affecting the central nervous system, where myelin is destroyed in the brain and spinal cord. The exact cause is unknown but is believed to involve immunological, viral, environmental and genetic factors. Diagnosis involves clinical symptoms and tests like MRI, CSF examination and evoked potentials. Treatment includes managing acute attacks, reducing disease activity through medications, and symptom management. Newer oral medications and concepts in disease-modifying therapies are discussed.
1. The document discusses the approach to evaluating and diagnosing ataxia. It covers the history, examination, localization, and differential diagnosis of ataxia.
2. Key points include distinguishing cerebellar ataxia from sensory ataxia and vestibular dysfunction based on examination. The approach involves a detailed history and neurological exam followed by ancillary testing which may include imaging, genetics, and labs.
3. Common causes discussed are cerebellar, sensory, and vestibular system lesions. The differential diagnosis depends on features in the history such as onset, progression, family history, and associated findings on exam.
Neuro-Psychiatric aspect of Diabetes MellitusDr.Jeet Nadpara
- The document discusses the neuro-psychiatric aspects of diabetes mellitus, including the links between diabetes and conditions like depression. It notes that as early as the 17th century, diabetes was thought to be caused by sadness or emotional distress.
- Managing diabetes requires significant patient self-care and support systems, but psychiatric illnesses can interfere with self-management behaviors. Conditions like depression may also impact diabetes through neurohormonal changes.
- The document examines topics like cognitive effects of diabetes, links between diabetes and depression, eating disorders and diabetes, and the impacts on patients, families, and development.
This document defines and discusses critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and critical illness neuromyopathy (CINMP). It describes the history, introduction, muscles involved, pathologies, clinical features, diagnosis, prevention, and recovery for CIP and CIM. Key points include: CIP and CIM are acquired neuromuscular weaknesses that develop in ICU patients; CIP involves axonal polyneuropathy while CIM involves myopathy; both can prolong mechanical ventilation and recovery. Diagnosis involves assessing weakness, reflexes, and electrophysiology. Prevention focuses on limiting corticosteroids and paralysis while early rehabilitation aims to improve outcomes. Recovery is often prolonged and incomplete with potential
1) Recent advances in understanding the pathophysiology of motor neuron disease include insights into excitotoxicity, oxidative stress, mitochondrial defects, impaired axonal transport, protein aggregation, inflammation, and neurotrophic factor deficits.
2) Riluzole remains the only FDA-approved drug shown to modestly prolong survival for patients with ALS, though Edaravone may also provide benefits for certain subgroups. Experimental therapies targeting genes, antioxidants, neurotrophic factors, and other mechanisms are under investigation.
3) Making an accurate diagnosis involves evaluating the patient's history, physical exam, electrodiagnostic testing, imaging, and sometimes genetic or biomarker analysis to differentiate ALS from other conditions.
Dr. Shubham Garg discusses neuromyelitis optica (NMO), an autoimmune condition where antibodies attack aquaporin-4 in the central nervous system. NMO predominantly affects women and has a median age of onset of 32-41 years. Key clinical features include transverse myelitis, typically longitudinally extensive, and severe optic neuritis. Treatment involves high-dose steroids for acute attacks and immunosuppressants like azathioprine to reduce relapse rates. Prognosis is generally worse than multiple sclerosis due to risk of cumulative disability, though relapse rates can be lowered with appropriate treatment.
This is a case presentation of a 49-year-old male with uncontrolled type 2 diabetes and hypertension who presented with fever, swelling of the right side of his face, and loss of vision in his right eye. Imaging and biopsy revealed rhinocerebral mucormycosis involving the paranasal sinuses and multiple cranial nerves on the right side. A definitive diagnosis of mucormycosis requires a positive culture from a sterile site or histopathologic evidence of invasive fungal hyphae.
This document summarizes several demyelinating diseases of the central and peripheral nervous systems. It describes multiple sclerosis as the most common inflammatory demyelinating disease, affecting the brain and spinal cord, with classifications based on disease course. It also discusses central pontine myelinolysis, transverse myelitis, Guillain-Barre syndrome, and chronic inflammatory demyelinating polyneuropathy. For each, it provides details on characteristics, causes, clinical manifestations, diagnosis, and treatment.
Neurosarcoidosis is a rare condition where sarcoidosis affects the nervous system. It can be difficult to diagnose as it often presents with non-specific neurological symptoms. Diagnosis requires a combination of CSF analysis, MRI imaging showing characteristic abnormalities, and biopsy evidence of granulomas. A multidisciplinary team approach is needed to manage this complex condition.
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.
Targeting Progession: The Progressive MS AllianceMS Trust
Progressive MS is an unmet clinical need with limited treatment options. This document discusses defining progressive MS, exploring disease mechanisms and interventions, current clinical trials, and the need for an international initiative. It summarizes research showing inflammation, demyelination, gray matter involvement, and axonal loss contribute to progression. Clinical trials have targeted inflammation with limited success. Future trials aim to test neuroprotective agents, lifestyle factors, and remyelination/rehabilitation approaches. An international collaborative is needed to expedite therapies through target identification, preclinical models, clinical outcome measures, trial design, and engaging the research community. The goal is to accelerate development of effective treatments for disease modification and symptom management in progressive MS.
NeuroMyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory disorder of the central nervous system characterized by demyelination and damage of the optic nerves and spinal cord. It was previously considered a variant of multiple sclerosis but is now recognized as a distinct condition mediated by autoantibodies against aquaporin-4. NMOSD can present with optic neuritis causing vision loss or transverse myelitis with varying degrees of weakness and sensory loss. Brain involvement is also seen in around half of patients. The disease predominantly affects women and typically involves recurrent, severe attacks with varying recovery. Diagnosis involves identifying clinical features, MRI imaging, and serologic testing for aquaporin-4 antibodies.
Hereditary neuropathies are a diverse group of inherited conditions affecting the peripheral nervous system. They are frequently underdiagnosed due to their indolent onset over decades and lack of clear family history in some cases. Charcot-Marie-Tooth disease is the most common inherited neuropathy, with two main types - CMT1 characterized by demyelination and CMT2 characterized by axonal loss. CMT1 results from mutations affecting myelin protein zero or peripheral myelin protein 22 genes, causing demyelination and onion bulb formation. Accurate diagnosis relies on detailed family history, neurological examination, and electrodiagnostic testing to distinguish inherited from acquired neuropathies.
This document provides guidelines for the diagnosis and treatment of multiple sclerosis (MS). It discusses the different subtypes of MS, diagnostic criteria, disease mechanisms, epidemiology in India, clinical features of relapses, and guidelines for using disease-modifying therapies. Key recommendations include using McDonald criteria for diagnosis, treating relapsing forms of MS with approved disease-modifying drugs, monitoring patients on treatment, and considering ocrelizumab for primary progressive MS.
Anti-MOG Antibody-Associated Diseases - Prof. Ayman NassefTalal Thabet
In this slides deck, Prof. Ayman Nassef clarifies the role of Myelin Olidodendrocyte Glycoprotein (MOG) in demyelinating conditions, and explains how MOG-IgGs cause damage of myelin and axons and the impact of such damage on the disease.
This document provides diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP), including:
1) Clinical criteria for typical and atypical CIDP with inclusion/exclusion factors.
2) Definite, probable, and possible electrophysiological criteria involving compound muscle action potential tests.
3) Supportive diagnostic criteria including cerebrospinal fluid analysis, MRI findings, nerve conduction studies, and nerve biopsy results.
It also outlines inclusion/exclusion criteria and supportive criteria specifically for diagnosing pure sensory CIDP without motor involvement.
CIDP is a chronic acquired demyelinating neuropathy. It has two patterns - a continuous progressive course over months to years or a relapsing course with partial recovery between episodes. Diagnosis requires documentation of demyelination through electrodiagnostic testing, CSF analysis and sometimes nerve biopsy. Treatment includes corticosteroids, IVIG and plasmapheresis, which are effective in around 50-70% of patients. Corticosteroids are usually the first line treatment, starting with high dose prednisone and slowly tapering as response occurs.
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is a rare neurological disorder characterized by progressive weakness and impaired sensory function caused by damage to the peripheral nervous system. It has an incidence rate of 1-2 per 100,000 people and predominantly affects males over 50 years old. CIDP is diagnosed based on progressive muscle weakness, reduced reflexes, nerve conduction studies showing demyelination, elevated CSF protein, and nerve biopsy with signs of demyelination. Treatment involves intravenous immunoglobulin, plasma exchange, steroids, or other immunosuppressants, with around 50% of patients experiencing improvement with therapy.
Autoimmune encephalitis current conceptsNeurologyKota
1) Autoimmune encephalitis is a debilitating neurological disorder caused by inflammation of the brain. It develops subacutely over weeks and can affect individuals of all ages.
2) It has diverse clinical manifestations and immunological associations. Identification of neural autoantibodies has led to classification of different subtypes.
3) Prominent among these are anti-NMDAR encephalitis commonly seen in young women and children, autoimmune limbic encephalitis, and other syndromes associated with antibodies targeting neuronal cell-surface and intracellular antigens.
Multiple sclerosis and newer concept in management till 2014 maydrnikhilver
This document provides information about Multiple Sclerosis (MS), including what it is, possible causes, types, diagnosis, treatment and newer concepts in management. It defines MS as a chronic neurological disorder affecting the central nervous system, where myelin is destroyed in the brain and spinal cord. The exact cause is unknown but is believed to involve immunological, viral, environmental and genetic factors. Diagnosis involves clinical symptoms and tests like MRI, CSF examination and evoked potentials. Treatment includes managing acute attacks, reducing disease activity through medications, and symptom management. Newer oral medications and concepts in disease-modifying therapies are discussed.
1. The document discusses the approach to evaluating and diagnosing ataxia. It covers the history, examination, localization, and differential diagnosis of ataxia.
2. Key points include distinguishing cerebellar ataxia from sensory ataxia and vestibular dysfunction based on examination. The approach involves a detailed history and neurological exam followed by ancillary testing which may include imaging, genetics, and labs.
3. Common causes discussed are cerebellar, sensory, and vestibular system lesions. The differential diagnosis depends on features in the history such as onset, progression, family history, and associated findings on exam.
Neuro-Psychiatric aspect of Diabetes MellitusDr.Jeet Nadpara
- The document discusses the neuro-psychiatric aspects of diabetes mellitus, including the links between diabetes and conditions like depression. It notes that as early as the 17th century, diabetes was thought to be caused by sadness or emotional distress.
- Managing diabetes requires significant patient self-care and support systems, but psychiatric illnesses can interfere with self-management behaviors. Conditions like depression may also impact diabetes through neurohormonal changes.
- The document examines topics like cognitive effects of diabetes, links between diabetes and depression, eating disorders and diabetes, and the impacts on patients, families, and development.
This document defines and discusses critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and critical illness neuromyopathy (CINMP). It describes the history, introduction, muscles involved, pathologies, clinical features, diagnosis, prevention, and recovery for CIP and CIM. Key points include: CIP and CIM are acquired neuromuscular weaknesses that develop in ICU patients; CIP involves axonal polyneuropathy while CIM involves myopathy; both can prolong mechanical ventilation and recovery. Diagnosis involves assessing weakness, reflexes, and electrophysiology. Prevention focuses on limiting corticosteroids and paralysis while early rehabilitation aims to improve outcomes. Recovery is often prolonged and incomplete with potential
1) Recent advances in understanding the pathophysiology of motor neuron disease include insights into excitotoxicity, oxidative stress, mitochondrial defects, impaired axonal transport, protein aggregation, inflammation, and neurotrophic factor deficits.
2) Riluzole remains the only FDA-approved drug shown to modestly prolong survival for patients with ALS, though Edaravone may also provide benefits for certain subgroups. Experimental therapies targeting genes, antioxidants, neurotrophic factors, and other mechanisms are under investigation.
3) Making an accurate diagnosis involves evaluating the patient's history, physical exam, electrodiagnostic testing, imaging, and sometimes genetic or biomarker analysis to differentiate ALS from other conditions.
Dr. Shubham Garg discusses neuromyelitis optica (NMO), an autoimmune condition where antibodies attack aquaporin-4 in the central nervous system. NMO predominantly affects women and has a median age of onset of 32-41 years. Key clinical features include transverse myelitis, typically longitudinally extensive, and severe optic neuritis. Treatment involves high-dose steroids for acute attacks and immunosuppressants like azathioprine to reduce relapse rates. Prognosis is generally worse than multiple sclerosis due to risk of cumulative disability, though relapse rates can be lowered with appropriate treatment.
This is a case presentation of a 49-year-old male with uncontrolled type 2 diabetes and hypertension who presented with fever, swelling of the right side of his face, and loss of vision in his right eye. Imaging and biopsy revealed rhinocerebral mucormycosis involving the paranasal sinuses and multiple cranial nerves on the right side. A definitive diagnosis of mucormycosis requires a positive culture from a sterile site or histopathologic evidence of invasive fungal hyphae.
This document summarizes several demyelinating diseases of the central and peripheral nervous systems. It describes multiple sclerosis as the most common inflammatory demyelinating disease, affecting the brain and spinal cord, with classifications based on disease course. It also discusses central pontine myelinolysis, transverse myelitis, Guillain-Barre syndrome, and chronic inflammatory demyelinating polyneuropathy. For each, it provides details on characteristics, causes, clinical manifestations, diagnosis, and treatment.
Neurosarcoidosis is a rare condition where sarcoidosis affects the nervous system. It can be difficult to diagnose as it often presents with non-specific neurological symptoms. Diagnosis requires a combination of CSF analysis, MRI imaging showing characteristic abnormalities, and biopsy evidence of granulomas. A multidisciplinary team approach is needed to manage this complex condition.
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.
Targeting Progession: The Progressive MS AllianceMS Trust
Progressive MS is an unmet clinical need with limited treatment options. This document discusses defining progressive MS, exploring disease mechanisms and interventions, current clinical trials, and the need for an international initiative. It summarizes research showing inflammation, demyelination, gray matter involvement, and axonal loss contribute to progression. Clinical trials have targeted inflammation with limited success. Future trials aim to test neuroprotective agents, lifestyle factors, and remyelination/rehabilitation approaches. An international collaborative is needed to expedite therapies through target identification, preclinical models, clinical outcome measures, trial design, and engaging the research community. The goal is to accelerate development of effective treatments for disease modification and symptom management in progressive MS.
Primary progressive multiple sclerosis (PPMS) is characterized by progressive accumulation of disability from disease onset, with occasional plateaus or improvements. PPMS is diagnosed based on 1 year of progression plus MRI or CSF evidence of disseminated lesions. PPMS affects men and women equally and has an average later age of onset than relapsing-remitting MS. While several treatments have failed in PPMS or been ineffective, glatiramer acetate, rituximab, methotrexate, stem cell therapy, and low-dose naltrexone may be partially effective in subsets of patients. Future trials are exploring therapies such as fingolimod, natalizumab, ocrelizumab, and ib
This document provides an overview of the management of multiple sclerosis (MS). It describes MS as a chronic inflammatory demyelinating disease of the central nervous system that predominantly affects women aged 20-40. The main phenotypes discussed are relapsing-remitting MS, clinically isolated syndrome, secondary progressive MS, and primary progressive MS. Diagnosis involves dissemination of lesions in time and space based on clinical symptoms and MRI findings. Treatment aims to reduce relapse rates and disability progression through disease-modifying therapies like interferons, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate. Symptomatic treatments are also discussed.
1. This patient has aggressive relapsing-remitting multiple sclerosis (RRMS) based on more than 2 relapses in the past year and active lesions on MRI.
2. Treatment guidelines recommend natalizumab (Tysabri) or fingolimod (Gilenya) for aggressive RRMS, depending on JCV antibody status.
3. As this patient is JCV antibody negative, treatment with natalizumab is recommended due to its higher efficacy in reducing relapses and disability progression compared to other disease-modifying therapies.
- Early treatment initiation is most effective for MS, especially for those with recent disease activity or clinically isolated syndrome. A diagnosis of relapsing-remitting MS requires evidence of more than one inflammatory episode.
- Management of clinically isolated syndrome and early MS is complex, involving education, lifestyle management, and usually discussing disease-modifying therapy. Treatment selection involves considering the patient's risks and preferences.
- Common approaches to treatment include escalation therapy, starting with low-risk treatments, or an induction approach starting with an aggressive therapy. Recent evidence suggests avoiding delays in initiating or escalating treatment.
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.
This study investigated the ability of continuous EEG (cEEG) monitoring to predict seizures in patients with intracerebral hemorrhage (ICH). The study found that lateralized periodic discharges (LPDs) on cEEG were significantly associated with increased seizure occurrence. The majority of seizures occurred without clinical signs, indicating the value of cEEG monitoring. Location of hemorrhage, neurological exam, or hemorrhage size did not predict seizures. This validates the potential use of prophylactic anti-epileptic drugs in ICH patients with LPDs on cEEG to prevent seizures.
This document summarizes the presentation of a 38-year-old female teacher and mother of two who is experiencing partial response to treatment for major depressive disorder despite switching antidepressant medications. She reports ongoing symptoms of sadness, pessimistic thoughts, and excessive worry. The document notes some potential risks of atypical antipsychotic drugs, including metabolic changes and weight gain. It provides safety warnings for increased suicidal risk in younger patients and increased mortality risk in elderly patients with dementia-related psychosis. The document indicates that REXULTI is approved as an adjunctive therapy for adults with major depressive disorder.
This document discusses childhood multiple sclerosis (MS). It notes that pediatric MS is rare, with an incidence of 1.35-2.5 per 100,000 children. While the cause is unknown, genetic and environmental factors are thought to play a role. Clinically, children present similarly to adults but are more likely to have optic neuritis or brainstem symptoms. Diagnosis relies on the McDonald criteria and involves MRI and CSF analysis. Treatment focuses on disease-modifying therapies like interferon and glatiramer acetate to reduce relapse rates. Prognosis is generally better in pediatric MS compared to adult-onset MS.
1) Multiple sclerosis is an immune-mediated disease that causes inflammation and damage to the central nervous system, often resulting in disability. It primarily affects young and middle-aged adults.
2) Recent advances include more effective monoclonal antibody treatments like natalizumab that greatly reduce relapse rates, but also carry risks like progressive multifocal leukoencephalopathy.
3) New diagnostic criteria allow use of cortical lesions on MRI and certain biomarkers like neurofilament light chain levels provide additional insight into disease activity and progression.
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Jeremy Chow
Cardiologist, Electrophysiologist
Asian Heart & Vascular Centre
www.ahvc.com.sg
Trials in secondary progressive multiple sclerosis: design & efficiencyMS Trust
- The NHS reforms have established new structures including NHS England which commissions clinical services and is accountable for improving outcomes as outlined in the NHS Outcomes Framework.
- The framework includes overarching indicators related to preventing premature death, enhancing quality of life for people with long-term conditions, helping people recover from episodes of ill health or injury, and ensuring that people have a positive experience of care.
- The new system aims to improve quality, outcomes and experience of care but also faces challenges in coordinating services across new organizational boundaries and ensuring the needs of patients with long-term conditions like MS remain a priority.
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.
This document provides information about therapeutic options for spinal muscular atrophy (SMA). It first defines SMA as a genetic disorder that causes degeneration of motor neurons in the spinal cord, resulting in muscle weakness. It then discusses the four main types of SMA based on severity and age of onset. The causes and diagnosis of SMA are also outlined. The therapeutic options section summarizes gene replacement therapies like nusinersen and onasemnogene abeparovec, which aim to increase SMN protein levels. It also mentions the small molecule risdiplam and ongoing clinical trials evaluating these treatment approaches.
covering the topic of chronic immune mediated demyelinating neuropathies with a detailed focus on the typical form of chronic inflammatory demyelinating polyradiculoneuropathy (Typical CIDP).
This study conducted a prospective population-based cohort study and systematic review/meta-analysis to evaluate the risk of stroke in patients with asymptomatic carotid stenosis receiving medical therapy alone. The cohort study included patients found to have asymptomatic carotid stenosis between 2002-2017 who received contemporary medical management including antiplatelet/statin therapy and blood pressure control. The primary outcome was ipsilateral ischemic stroke. A systematic review/meta-analysis of previous studies on this topic was also performed to determine stroke risks with medical therapy alone and evaluate if routine carotid intervention is still warranted.
This document discusses the case of a 7-year-old girl presenting with progressive muscle weakness for 3 months. On examination, she has characteristic rashes including a violaceous rash on the eyelids, Gottron papules over the joints, and an erythematous rash on the chest. The most likely diagnosis is juvenile dermatomyositis. Diagnostic criteria include characteristic rashes and muscle inflammation. Treatment involves corticosteroids, methotrexate, and other immunosuppressants to control symptoms and prevent complications like aspiration pneumonia. The natural course varies, but about 1/3 of patients improve spontaneously, 1/3 have a chronic lingering course, and 1/3 may die from the
This document provides an overview of evaluating the etiology of seizures. It discusses the initial evaluation steps, including distinguishing epileptic from non-epileptic events. It reviews diagnostic investigations like imaging, EEG, and bloodwork. Common structural etiologies and epilepsy syndromes are described. The document emphasizes performing a thorough history, physical exam, and targeted workup to identify underlying causes and guide treatment and prognosis.
1. Hemiplegia is defined as weakness or paralysis of one side of the body caused by an upper motor neuron lesion above C5 in the pyramidal motor pathway.
2. Common causes of hemiplegia include vascular (85% ischemic, 15% hemorrhagic), tumors, head injuries, demyelinating diseases like multiple sclerosis, and metabolic disorders.
3. The clinical presentation depends on the cause and location of the lesion. Lesions in the internal capsule typically cause contralateral hemiplegia and hemisensory loss with facial and hypoglossal weakness on the same side.
This document provides an overview of how to examine the 12 cranial nerves. It describes how to test each nerve's motor, sensory and reflex functions. For example, it explains how to test the optic nerve by checking visual acuity, color perception and visual fields. It also provides details on potential abnormalities for each nerve, such as ptosis indicating issues with the 3rd cranial nerve. The overview aims to guide practitioners on systematically examining each cranial nerve.
This document discusses different types of muscle disease. It begins by describing the anatomy of skeletal muscle and defining muscle disease as any primary disease of the muscular system related to changes in the muscles. It then outlines six main types of muscle disease: muscular dystrophies, myotonic myopathies and disorders, inflammatory muscle diseases, myasthenic muscle diseases, metabolic myopathies, and endocranial myopathies. Within each type, several specific conditions are described in brief, including Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, and distal muscular dystrophy. The document provides details on clinical features, investigations, and treatment for some of the major muscular dyst
This document provides an overview of peripheral neuropathy. It defines peripheral neuropathy as inflammation or degeneration of peripheral nerves or cranial nerves leading to motor and/or sensory dysfunction. It then classifies peripheral neuropathies and discusses various causes including inherited, acquired, infectious, toxic and metabolic. Clinical features, investigations and management are described for different types of peripheral neuropathy such as diabetic neuropathy, Guillain-Barre syndrome and Charcot-Marie-Tooth disease. Key examination findings and the presentations of different neuropathies are highlighted.
This document provides an outline for taking a patient's history. It begins with sections on personal history, complaint, history of present illness, past history, family history, and diagnosis. Each section of the history of present illness examines a different body system, including motor, sensory, cranial nerves, speech, sphincters, and cognition. Questions are provided as examples to elicit relevant details from the patient for each system. The overall summary is an outline for obtaining a comprehensive medical history by systematically exploring each body system and area of the patient's health.
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Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
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Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
6. So Progressive and relapsing MS should be considered to occur on a spectrum rather than as different diseases,
and the understanding that these two forms share several common features in biology, clinical evolution, and
imaging findings is growing.
7. Long-term worsening is common in relapsing MS patients, is largely independent of relapse activity,
and is associated with accelerated brain atrophy. We propose the term silent progression to describe
the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing–
remitting MS.
19. Aggressive RRMS
• One or more of the following :
>>>EDSS > or = 6 within 5 years of MS onset.
>>>EDSS > or = 6 by age 40
>>> SPMS within 3 years of a relapsing onset course,
Menon et al ., 2013
28. Criteria for Diagnosis PPMS
• The 2017 revised McDonald diagnostic criteria for MS include specific criteria for primary
progressive MS:
including 1 year of disability progression (retrospectively or prospectively determined)
independent of relapses plus at least two of the following: one or more T2 lesions in
characteristic regions on brain MRI, two or more spinal cord MRI lesions, or the presence
of OCB.
Over 1 year + 2/3
1 MRI brain lesion
2 spinal cord lesions
OCB
29. Criteria for Diagnosis SPMS
• 3-6-month sustained worsening of at least 1 point.
• The magnitude of EDSS sustained worsening many times is defined on the baseline level of disability. Definitions have
included
>>> 1.5 points for baseline EDSS score of 0,
>>> 1 point sustained change for those with a baseline EDSS score of less than 6.0,
>>> 0.5 point for baseline EDSS score greater than 6.0.
- Pyramidal score > or =2
- No recent relapse
- EDSS > or = 4
• A 2015 study showed that requiring demonstration of sustained worsening for longer periods (12 to 24 months)
Remember
2-3-4-5-6
30.
31.
32. EDSS PLUS
EDSS +
-(timed 25-foot walk)
-(9-hole peg test): upper extremity function
[a test of manual dexterity in which the time to place nine pegs into a
3 x 3 array is recorded]
33. Multiple Sclerosis Functional
Composite (MSFC)
-(timed 25-foot walk)
-(9-peg hole test): upper extremity function
[a test of manual dexterity in which the time to place nine pegs into a
3 x 3 array is recorded]
-Cognitive function (Paced Auditory serial addition test)
37. Interpretation :
• a 20% change in the timed 25-foot walk
• a 20% change in the 9-hole peg test,
• a 4-point (10%) change in the Symbol Digit Modalities Test.
>>>>>>> indicates progession
38. CASE
A 38-year-old man presented for a second neurologic opinion with a 2-year
history of progressive left lower extremity weakness and difficulty controlling his
right hand. Worsening over the past 12 months was confirmed by his prior
neurologist.
Examination revealed left lower extremity weakness, with long tract signs, spasticity, and moderate right arm
dysmetria. MRI of his brain showed several T2 lesions, and two of the lesions demonstrated contrast
enhancement. MRI of his cervical spine showed nonenhancing discrete lesions at C4 and T1. CSF studies
showed positive oligoclonal bands with normal glucose, protein, and cell count.
40. • This patient meets diagnostic criteria for primary progressive multiple sclerosis
and would be an ideal candidate for ocrelizumab. In addition, he is male and
young and has enhancing lesions and positive oligoclonal bands, all suggesting
that he may respond favorably to treatment. Infectious complications, although
possible, are relatively less likely than in older patients with more advanced
disability given that he is otherwise healthy.
43. Markers for progression :
3- Conventional and advanced spinal cord MRI diffusion tensor imaging and
spectroscopy measures hold promise as potential biomarkers for progressive
multiple sclerosis.
● Brain lesions in progressive multiple sclerosis are indistinguishable from
those seen in relapsing multiple sclerosis; however, on average, patients with
primary progressive multiple sclerosis tend to have fewer brain T2 lesions
and fewer lesions with gadolinium enhancement.
48. Immunomodulation:
Early trials focused on older immunosuppressant medications,
including azathioprine, cyclosporine, mycophenolate mofetil, And
cyclophosphamide >>> -ve
49. B-cell therapies:
• Rituximab, a chimeric anti-CD20 monoclonal antibody, was the first B-cell therapy
studied in progressive MS; a placebo-controlled study in primary progressive MS
showed no benefit on the primary outcome of EDSS .
• However, subsequent subgroup analysis demonstrated possible benefit for younger
patients (≤51 years) with gadolinium-enhancing MRI lesions.
• ocrelizumab, a humanized anti-CD20 monoclonal antibody had FDA approval of for
primary progressive MS. It is important to note that 27% of patients in ORATORIO
trial>>> ocrelizumab arm had enhancing lesions at baseline, leading to speculation
that the use of a powerful anti-inflammatory in an enriched patient population
explains the positive results.
50. Neuroprotection:
• Several studies have been conducted examining the effects of putative
neuroprotectant medications in progressive MS, but no medications
have yet been approved .
• Simvastatin 80 mg >>>showed a 43% reduction in brain volume loss
compared with placebo in SPMS. (phase 3 trial).
• Ibudilast >>> a phosphodiesterase 2 inhibitor, was studied in 255
participants with primary progressive MS and secondary progressive
MS followed over 2 years. (plans for phase 3 trial )
51. Neuroprotection:
• High-dose biotin modestly improved EDSS scores in a placebo-controlled phase 3 study.
• The MS-SMART (Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial) study
compared the effects of riluzole, amiloride, and fluoxetine against placebo in patients with secondary
progressive MS in a large phase 2 clinical trial >>> -ve for all therapies.
• Several trials using remyelinating agents and cell-based therapies are under development.
• Finally, the management of progressive MS should also include control of medical comorbidities,
including hypertension, hyperlipidemia, diabetes mellitus, and vascular disease, and address issues
such as weight control and smoking .
• Supplementation of vitamin D, although not demonstrated to have an effect in progressive MS clinical
trials to date, should be considered with suspected or demonstrated low vitamin D levels.
52. Ocrelizumab (Ocrevus)
Dose Baseline
Monitoring
On therapy
Monitoring
Special
consideartion
SE Potentially serious
SE
the first anti-CD20 monoclonal antibody FDA approved to treat relapsing forms of MS and the
first of any disease-modifying therapy to gain approval for primary progressive MS.
53.
54. Siponimod (Mayzent)
Mechanism of Action:
siponimod binds the sphingosine-1-phosphate receptor, subtypes 1 and 5 .
It was approved by the FDA on March 27, 2019, for relapsing forms of MS, including clinically
isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. This
was based on the results of the EXPAND (Exploring the Efficacy and Safety of Siponimod in
Patients With Secondary Progressive Multiple Sclerosis) trial of patients with secondary
progressive MS.
55. Siponimod (mayzent)
Dose:
Patients with CYP2C9 genotypes *1/*1, *1/*2, or *2/*2(rapid
metabolizers)
Initiate with a 5-day titration
Maintenance dose (Day 6): 2 mg PO qDay
Use a starter pack for patients who will be titrated to the 2-
mg maintenance dosage
Do not use starter pack for patients who will be titrated to
the 1-mg maintenance dosage
Titration for the 2-mg/day maintenance dose
Day 1: 0.25 mg (1 x 0.25 mg) PO
Day 2: 0.25 mg (1 x 0.25 mg) PO
Day 3: 0.50 mg (2 x 0.25 mg) PO
Day 4: 0.75 mg (3 x 0.25 mg) PO
Day 5: 1.25 mg (5 x 0.25 mg) PO
Day 6 and thereafter: 2 mg (1 x 2 mg) PO qDay
• Patients with CYP2C9 genotypes *1/*3 or
*2/*3 (Slow metabolizers)
• Initiate with a 4-day titration
• Maintenance dose (Day 5): 1 mg PO qDay
• Do not use the starter pack for patients who
will be titrated to the 1-mg maintenance
dosage
• Titration for 1-mg/day maintenance dose
• Day 1: 0.25 mg (1 x 0.25 mg) PO
• Day 2: 0.25 mg (1 x 0.25 mg) PO
• Day 3 0.50 mg (2 x 0.25 mg) PO
• Day 4: 0.75 mg (3 x 0.25 mg) PO
• Day 5 and thereafter: 1 mg (4 x 0.25 mg) PO qDay
56. Siponimod (Mayzent)
Side effects :
-Bradyarrhythmia and AV conduction delays
-Macular edema
-Elevated transaminases
-Incidence of hypertension reported in clinical
trials in -patients treated with siponimod was
slightly higher than those treated with placebo
-PRES
-a decline in pulmonary function
-increased risk of basal cell carcinoma (BCC) with
long term use.
-Lymphopenia.
-infections : Herpes virus inf , PML, fatal
cryptococcal meningitis (CM)
57. Ozanimod (zeposia 0.92mg)
Mechanism of action :
Sphingosine 1-phosphate (S1P) receptor
modulator.
Binds with high affinity selectively to S1P
subtypes 1 (S1P1) and 5.
Indications :
Indicated for relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome,
relapsing-remitting disease, and active secondary progressive disease.
58. Ozanimod (zeposia)
Dose :
• Days 1-4: 0.23 mg PO qDay
• Days 5-7: 0.46 mg PO qDay
• Day 8 and thereafter: 0.92 mg PO qDay
Side Effects:
• Adverse Effects
• Upper respiratory tract infection (26%)
• Elevated hepatic transaminases (10%)
• Orthostatic hypotension (4%)
• Urinary tract infection (4%)
• Back pain (4%)
• Hypertension (4%)
• Upper abdominal pain (2%)
• <1% >>> Macular edema
• Bradycardia
59. Cladribine (Mavenclad)
• Mechanism of Action:
a purine analogue, is metabolized to its active form and concentrated
in lymphocytes and monocytes but not in other cells. Single-stranded
DNA breaks cannot be repaired, eventually resulting in cell death
>>>It is approved for relapsing-remitting disease and active secondary
progressive disease in those who have had an inadequate response to
or are unable to tolerate an alternate drug.
60. Cladribine (Mavenclad)
• Dose: 1.75 mg/kg per year
>>>Taken as 10 mg/d to 20 mg/d for 4 to 5
days in week 1 and week 5.
>>>The dose is repeated 1 year later.
>>>No treatment is given in years 3 and 4.
Oral tablets are 10 mg.
61. Cladribine (Mavenclad)
Important Adverse Effects :
• Lymphopenia
• Neutropenia
• Infections :
Varicella-zoster
Progressive multifocal leukoencephalopathy
Hepatitis B and C reactivation
Tuberculosis reactivation Malignancies
• Rash
• Alopecia
• Because of the risk of teratogenicity, both males and females should use effective
contraception for 6 months after the last dose of treatment.
• Cases of acute cardiac failure with myocarditis have been reported with cladribine.
62. Cladribine (Mavenclad)
• Laboratory tests and follow-up evaluations required during therapy with cladribine tablets
I. Prior to treatment initiation (first cycle):
• 1. CBC with differential: lymphocytes counts must be normal ≥ 1,000 cells/mm 3
• 2. Serum transaminases, bilirubin, blood urea nitrogen, creatinine
• 3. Screening for latent infections, in particular hepatitis B and C and tuberculosis (T-spot test). Initiation of cladribine should be delayed until the
infection is fully controlled
• 4.Testing for anti-VZV antibodies in patients without a history of chickenpox or without varicella zoster virus (VZV) vaccine. VZV vaccination of antibody-
negative patients should be considered prior to treatment initiation.
II. During the first and up to 6 months after the last (second) treatment cycle:
• 1. Complete blood count with differential: a) at 2 and 6 months of treatment initiation in each year of treatment.
• b) Before initiating cladribine in year 2, the lymphocyte counts should be at least 800 cells/mm3 . If necessary, the year 2 treatment cycle can be delayed
for up to 6 months to allow recovery of lymphocytes.
64. Rituximab (Mabthera)
• Mechanism of action:
a chimeric antibody against CD20 similar to ocrelizumab.
It has less antibody-dependent and more complement-dependent
cytotoxicity than ocrelizumab and a different binding site on the CD20 molecule. It is more highly immunogenic than
ocrelizumab.
Dose :
500 mg or 1000 mg IV every 6 months.
Precautions / Monitoring common SE
66. Home message
• Progressive MS is a heterogeneous disease both pathologically and clinically.
• Although distinguished as a separate entity, progressive MS likely occurs on a spectrum with relapsing disease.
• Clinical and imaging features vary between progressive and relapsing MS and may be used to classify the
disease based on the occurrence of progression and presence of clinical and MRI activity.
• The first approved disease-modifying therapy for primary progressive MS, ocrelizumab .
• a medication for active secondary progressive MS (siponimod) has also been approved
• the use of disease-modifying therapies will need to be individualized considering the expected benefits and
risks of each medication.