This document discusses neurological problems that can arise in patients with hematological neoplasms. It covers direct neoplastic involvement of the nervous system such as primary central nervous system lymphoma and leptomeningeal metastasis. It also discusses indirect manifestations like paraneoplastic cerebellar degeneration. Treatment involves an interdisciplinary approach between oncologists, neurologists, and other specialists. Diagnosis involves imaging, spinal fluid analysis, biopsies, and consideration of both direct tumor involvement and indirect paraneoplastic mechanisms.
Primary CNS lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma that affects the brain and spinal cord. It most commonly presents as a solitary mass in the deep brain structures in immunocompetent patients ages 45-65. On imaging, PCNSL typically enhances strongly and homogenously with MRI. A biopsy is required for definitive diagnosis as other conditions like glioblastoma can appear similar. Immunocompromised patients are at higher risk and may present with multiple enhancing lesions with necrosis.
Primary Central Nervous System Lymphoma Ade Wijaya
Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin's lymphoma that arises in the brain and spinal cord. It represents around 1% of brain tumors. Most cases are diffuse large B-cell lymphomas with very rapid growth. Presentations include cognitive decline, headaches, and seizures. Diagnosis involves brain imaging, spinal fluid analysis, and biopsy. Treatment typically involves high-dose methotrexate-based chemotherapy with or without whole brain radiation. Prognosis is generally poor despite treatment.
Primary central nervous system vasculitis (PACNS) is a rare disorder characterized by inflammation of blood vessels in the brain and spinal cord. It presents with non-specific symptoms like headache, cognitive impairment, and focal neurological deficits. Diagnosis involves neuroimaging showing multifocal lesions, angiography revealing vessel narrowing and dilation, and brain biopsy detecting immune cell infiltration of vessel walls. While the cause is unknown, infectious agents may trigger PACNS. Treatment involves immunosuppression but prognosis depends on disease severity and response to treatment.
This document discusses various types of central nervous system lymphomas. It begins by introducing CNS lymphomas and noting that 95% are diffuse large B-cell lymphomas. It then discusses primary CNS lymphoma, focusing on its etiology, pathology, clinical presentation, imaging features, and differential diagnosis. Several other specific types of CNS lymphomas are also summarized, including intravascular lymphoma, lymphomatosis cerebri, MALT lymphoma, lymphomatoid granulomatosis, and post-transplant lymphoproliferative disorder. Metastatic intracranial lymphoma is briefly covered at the end.
Primary CNS Vasculitis - diagnostic and therapeutic challengesDiana Girnita
1. This 38-year-old male presented with severe frontal headache, speech difficulties, weakness, and confusion. Imaging showed multiple small white matter lesions that progressed significantly over 4 days.
2. Cerebrospinal fluid analysis showed elevated white blood cells and protein with positive oligoclonal bands. Infectious and autoimmune workups were negative.
3. Brain biopsy showed early acute ischemic changes and a microscopic focus of acute infarction without evidence of vasculitis, inflammation, or other pathologies. This is consistent with a diagnosis of primary central nervous system vasculitis.
Leukemias and Neurological menifestationsNeurologyKota
This document discusses neurological manifestations of leukemia, focusing on acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). It provides details on:
- CNS involvement is more common in ALL than AML and presents with headaches, seizures, cranial nerve palsies, etc. Imaging like MRI and LP are used for diagnosis.
- Treatment involves risk-based CNS prophylaxis with intrathecal chemotherapy instead of radiation to prevent relapse. Outcomes have improved with prophylaxis.
- AML rarely involves the CNS but risks are higher in subsets like acute promyelocytic leukemia or those with specific mutations. Evaluation is recommended for neurological symptoms. Treatment involves intr
Stem cell therapy shows promise for treating various neurological disorders. There are two main types of stem cells - embryonic stem cells which are pluripotent, and adult stem cells which are multipotent. Stem cells may promote cell replacement in damaged organs through proliferation, migration, and differentiation. Challenges include optimal cell types and doses, monitoring transplanted cells, and ensuring safety. While stem cell therapy is being studied for conditions like Alzheimer's, Parkinson's, ALS, and stroke, more research is still needed to address current obstacles in translating laboratory findings to clinical applications.
Primary CNS lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma that affects the brain and spinal cord. It most commonly presents as a solitary mass in the deep brain structures in immunocompetent patients ages 45-65. On imaging, PCNSL typically enhances strongly and homogenously with MRI. A biopsy is required for definitive diagnosis as other conditions like glioblastoma can appear similar. Immunocompromised patients are at higher risk and may present with multiple enhancing lesions with necrosis.
Primary Central Nervous System Lymphoma Ade Wijaya
Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin's lymphoma that arises in the brain and spinal cord. It represents around 1% of brain tumors. Most cases are diffuse large B-cell lymphomas with very rapid growth. Presentations include cognitive decline, headaches, and seizures. Diagnosis involves brain imaging, spinal fluid analysis, and biopsy. Treatment typically involves high-dose methotrexate-based chemotherapy with or without whole brain radiation. Prognosis is generally poor despite treatment.
Primary central nervous system vasculitis (PACNS) is a rare disorder characterized by inflammation of blood vessels in the brain and spinal cord. It presents with non-specific symptoms like headache, cognitive impairment, and focal neurological deficits. Diagnosis involves neuroimaging showing multifocal lesions, angiography revealing vessel narrowing and dilation, and brain biopsy detecting immune cell infiltration of vessel walls. While the cause is unknown, infectious agents may trigger PACNS. Treatment involves immunosuppression but prognosis depends on disease severity and response to treatment.
This document discusses various types of central nervous system lymphomas. It begins by introducing CNS lymphomas and noting that 95% are diffuse large B-cell lymphomas. It then discusses primary CNS lymphoma, focusing on its etiology, pathology, clinical presentation, imaging features, and differential diagnosis. Several other specific types of CNS lymphomas are also summarized, including intravascular lymphoma, lymphomatosis cerebri, MALT lymphoma, lymphomatoid granulomatosis, and post-transplant lymphoproliferative disorder. Metastatic intracranial lymphoma is briefly covered at the end.
Primary CNS Vasculitis - diagnostic and therapeutic challengesDiana Girnita
1. This 38-year-old male presented with severe frontal headache, speech difficulties, weakness, and confusion. Imaging showed multiple small white matter lesions that progressed significantly over 4 days.
2. Cerebrospinal fluid analysis showed elevated white blood cells and protein with positive oligoclonal bands. Infectious and autoimmune workups were negative.
3. Brain biopsy showed early acute ischemic changes and a microscopic focus of acute infarction without evidence of vasculitis, inflammation, or other pathologies. This is consistent with a diagnosis of primary central nervous system vasculitis.
Leukemias and Neurological menifestationsNeurologyKota
This document discusses neurological manifestations of leukemia, focusing on acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). It provides details on:
- CNS involvement is more common in ALL than AML and presents with headaches, seizures, cranial nerve palsies, etc. Imaging like MRI and LP are used for diagnosis.
- Treatment involves risk-based CNS prophylaxis with intrathecal chemotherapy instead of radiation to prevent relapse. Outcomes have improved with prophylaxis.
- AML rarely involves the CNS but risks are higher in subsets like acute promyelocytic leukemia or those with specific mutations. Evaluation is recommended for neurological symptoms. Treatment involves intr
Stem cell therapy shows promise for treating various neurological disorders. There are two main types of stem cells - embryonic stem cells which are pluripotent, and adult stem cells which are multipotent. Stem cells may promote cell replacement in damaged organs through proliferation, migration, and differentiation. Challenges include optimal cell types and doses, monitoring transplanted cells, and ensuring safety. While stem cell therapy is being studied for conditions like Alzheimer's, Parkinson's, ALS, and stroke, more research is still needed to address current obstacles in translating laboratory findings to clinical applications.
CADASIL is caused by mutations in the NOTCH3 gene and is the most common monogenic form of cerebral small vessel disease. It is characterized clinically by recurrent strokes, cognitive decline, and mood disorders. Diagnosis involves identifying white matter changes, cerebral microbleeds, and NOTCH3 gene mutations on imaging and genetic testing. While there are currently no disease-modifying treatments, understanding the pathogenic mechanisms of CADASIL may help develop new therapeutic strategies.
The document describes a 35-year-old male who presented with seizures. Imaging showed a lesion in the right frontal lobe suspected to be an ischemic infarct. Further MRI revealed features suggestive of an anaplastic astrocytoma. The patient underwent surgery and the tumor was diagnosed as a low-grade oligodendroglioma. The patient is currently undergoing radiotherapy.
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.
The document discusses several types of central nervous system (CNS) tumors including gliomas, meningiomas, and pilocytic astrocytomas. Key points include:
- Gliomas are the most common CNS tumors in adults and children arising from glial cells. Astrocytomas including glioblastoma multiforme are the most common gliomas.
- Meningiomas arise from arachnoid granulation cells and are typically benign, slow growing tumors attached to the dura.
- Pilocytic astrocytomas are a type of low-grade glioma that predominantly affects children and presents as a cystic mass with a mural nodule, often
This document provides an overview of recent advances in the pathogenesis and management of Guillain-Barré syndrome (GBS). It discusses the variants of GBS (AIDP and AMAN), their pathogenesis involving molecular mimicry and antibody responses, clinical manifestations, diagnostic criteria and tests, treatment including immunotherapy options, prognostic indicators, and novel immunomodulatory approaches being studied.
This document discusses remyelinating therapies for multiple sclerosis (MS). It begins by explaining how MS results in demyelination and how remyelination can restore neuronal function. Several potential remyelinating therapies currently in preclinical or clinical trials are described, including clobetasol, opicinumab, guanabenz, and olesoxime. Biomarkers for measuring remyelination like diffusion tensor imaging, magnetization transfer imaging, and positron emission tomography are also summarized. The document concludes that while challenges remain, promising remyelinating strategies exist to provide benefit throughout the entire course of MS.
This document discusses demyelinating diseases that damage the white matter of the brain. It describes three major categories of leukoencephalopathies: genetic, acquired non-inflammatory, and acquired inflammatory. Genetic disorders include defects in lipid metabolism, cytoskeletal proteins, and myelin proteins. Acquired non-inflammatory disorders are toxic, metabolic, vascular or traumatic. Acquired inflammatory disorders include infectious diseases like HIV encephalitis and progressive multifocal leukoencephalopathy, as well as autoimmune diseases like multiple sclerosis. Multiple sclerosis involves inappropriate immune cell migration across the blood-brain barrier, leading to inflammation and damage to myelin, glia, axons and neurons.
Oligodendrocytes produce myelin sheaths around axons that insulate and speed up nerve conduction. Demyelinating disorders involve damage to existing myelin sheaths, while dysmyelinating disorders impair myelin formation. Common demyelinating conditions include multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica spectrum disorder. Diagnostic tools include neurological exam, MRI, and lumbar puncture. Differential diagnosis requires considering alternative causes such as infection, autoimmune disease, or metabolic derangement.
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.
Multiple Sclerosis (MS) is a disease of the central nervous system that affects women more than men and is more common in Caucasians. The typical age of onset is between 20-35 years for women and 35-45 years for men. MRI is an important tool in the diagnosis and monitoring of MS, with findings including lesions in the white matter, corpus callosum, and brainstem. Gadolinium enhancement on MRI indicates breakdown of the blood-brain barrier and active inflammation. While MRI lesion number and location provide some prognostic information, disability as measured by scales such as EDSS correlates poorly with MRI findings. MS pathology involves both acute inflammatory lesions and chronic lesions involving demyelination and axonal loss.
Abusive head trauma: SBU report and beyond Felice D'Arco
A short presentation summarising the main findings of the consensus paper on abusive head trauma, the controversies raised by the SBU report about triad and "shaken baby syndrome" and main criticisms moved against SBU report. A useful summary for radiologists and clinicians involved in child abuse.
Presented at the Pediatric Neuroradiology PanLondon Sunset Meeting July 2019
1) MRI is useful for diagnosing and monitoring multiple sclerosis (MS). Common MRI findings in MS include ovoid lesions perpendicular to ventricles that appear as high signal on T2-weighted and FLAIR images.
2) Different MS subtypes have distinct clinical patterns. Relapsing-remitting MS (RRMS) accounts for 58% of cases and is characterized by neurological symptoms lasting over 24 hours followed by complete or partial recovery with intervals of at least one month between relapses.
3) Optimal MRI protocols for evaluating MS include 3D FLAIR, DIR, and SWI sequences which can help detect cortical and subclinical lesions. Monitoring for contrast enhancing lesions on post-g
The document describes a 75-year-old housewife who is experiencing memory loss, repetition, and disrupted sleep, with a history of being active and social. A mini mental state exam score of 30/30 and normal blood tests are noted. The differential diagnosis mentioned includes dementia, depression, and age-related cognitive impairment.
A 27-year-old female teacher collapsed in her classroom and was witnessed having a generalized tonic-clonic seizure by her students. She was brought to the emergency department by paramedics accompanied by a colleague. Differential diagnoses discussed include idiopathic epilepsy, meningitis, brain tumor, and other potential causes. Further workup is suggested to determine the underlying etiology.
This document discusses Leber's hereditary optic neuropathy (LHON), a maternally inherited mitochondrial disease affecting vision. Key points include:
- LHON is caused by mutations in mitochondrial DNA and results in degeneration of retinal ganglion cells and optic nerve atrophy, leading to legal blindness.
- The most common mutations occur at positions 11778, 3460, and 14484 of mitochondrial DNA and decrease ATP production in retinal ganglion cells.
- LHON typically begins in young adults and males are more commonly affected, developing vision loss in 40% of cases compared to 10% for females.
- While mutations are necessary, additional genetic and environmental factors like smoking are thought to trigger
The document provides an overview of various cellular reactions, disease patterns, malformations, injuries, and degenerative conditions that can affect the central nervous system (CNS). It discusses the different cell types of the CNS, including neurons, glia and their roles. Common CNS disease patterns are described as degenerative, inflammatory, neoplastic and traumatic. Specific CNS diseases, injuries, infections, malformations and degenerative conditions are then outlined in detail with their characteristic clinical and pathological features.
This presentation is a comprehensive & updated presentation that delves deeply into Multiple Sclerosis. It is intended for healthcare professionals and features the Anatomy and Physiology, Common Etiology, a focused review of the disease Pathophysiology, Prevalence & Morbidity, Clinical Manifestations, Diagnostics, Classification & Prognosis, Treatment (Both current and experimental), Nutrition, and Psychosocial issues and resources available to patients. It is very rich in details, diagrams (on every slide), and interactive content when in slide presentation mode. The presentation has also hyperlinks to videos (3 D Patho) and controversial treatments. Finally, it concludes with a Case Study to highlight the clinical application.
Please note that you're welcome to use any slides as long as you reference my post when you do so to maintain the integrity of authorship
If interested in detailed answers, please email: aamirdash@yahoo.com
Thanks, Ahmad
The document discusses various topics related to neurology including:
1. Common neurological disorders such as headache, low back pain, and stroke.
2. Components of a neurological examination including signs, reflexes, and tests of sensory and motor function.
3. Diagnostic tools used in neurology such as CT, MRI, angiography, EEG, lumbar puncture, and PET.
4. Types of disturbances of consciousness including those caused by brainstem or cortical damage.
5. Criteria for determining brain death.
This document provides an overview of various demyelinating diseases of the central nervous system. It begins by defining demyelinating diseases as those involving disruption of myelin, which forms an insulating sheath around axons. It then classifies and describes several specific diseases, including acute disseminated encephalomyelitis (ADEM), inflammatory demyelinating pseudotumor, multiple sclerosis (MS), neuromyelitis optica, central pontine myelinolysis, HIV encephalopathy, progressive multifocal leukoencephalopathy (PML), and others. For each disease, it discusses clinical features, magnetic resonance imaging (MRI) findings, differential diagnoses, and pathology where relevant.
CADASIL is caused by mutations in the NOTCH3 gene and is the most common monogenic form of cerebral small vessel disease. It is characterized clinically by recurrent strokes, cognitive decline, and mood disorders. Diagnosis involves identifying white matter changes, cerebral microbleeds, and NOTCH3 gene mutations on imaging and genetic testing. While there are currently no disease-modifying treatments, understanding the pathogenic mechanisms of CADASIL may help develop new therapeutic strategies.
The document describes a 35-year-old male who presented with seizures. Imaging showed a lesion in the right frontal lobe suspected to be an ischemic infarct. Further MRI revealed features suggestive of an anaplastic astrocytoma. The patient underwent surgery and the tumor was diagnosed as a low-grade oligodendroglioma. The patient is currently undergoing radiotherapy.
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.
The document discusses several types of central nervous system (CNS) tumors including gliomas, meningiomas, and pilocytic astrocytomas. Key points include:
- Gliomas are the most common CNS tumors in adults and children arising from glial cells. Astrocytomas including glioblastoma multiforme are the most common gliomas.
- Meningiomas arise from arachnoid granulation cells and are typically benign, slow growing tumors attached to the dura.
- Pilocytic astrocytomas are a type of low-grade glioma that predominantly affects children and presents as a cystic mass with a mural nodule, often
This document provides an overview of recent advances in the pathogenesis and management of Guillain-Barré syndrome (GBS). It discusses the variants of GBS (AIDP and AMAN), their pathogenesis involving molecular mimicry and antibody responses, clinical manifestations, diagnostic criteria and tests, treatment including immunotherapy options, prognostic indicators, and novel immunomodulatory approaches being studied.
This document discusses remyelinating therapies for multiple sclerosis (MS). It begins by explaining how MS results in demyelination and how remyelination can restore neuronal function. Several potential remyelinating therapies currently in preclinical or clinical trials are described, including clobetasol, opicinumab, guanabenz, and olesoxime. Biomarkers for measuring remyelination like diffusion tensor imaging, magnetization transfer imaging, and positron emission tomography are also summarized. The document concludes that while challenges remain, promising remyelinating strategies exist to provide benefit throughout the entire course of MS.
This document discusses demyelinating diseases that damage the white matter of the brain. It describes three major categories of leukoencephalopathies: genetic, acquired non-inflammatory, and acquired inflammatory. Genetic disorders include defects in lipid metabolism, cytoskeletal proteins, and myelin proteins. Acquired non-inflammatory disorders are toxic, metabolic, vascular or traumatic. Acquired inflammatory disorders include infectious diseases like HIV encephalitis and progressive multifocal leukoencephalopathy, as well as autoimmune diseases like multiple sclerosis. Multiple sclerosis involves inappropriate immune cell migration across the blood-brain barrier, leading to inflammation and damage to myelin, glia, axons and neurons.
Oligodendrocytes produce myelin sheaths around axons that insulate and speed up nerve conduction. Demyelinating disorders involve damage to existing myelin sheaths, while dysmyelinating disorders impair myelin formation. Common demyelinating conditions include multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica spectrum disorder. Diagnostic tools include neurological exam, MRI, and lumbar puncture. Differential diagnosis requires considering alternative causes such as infection, autoimmune disease, or metabolic derangement.
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.
Multiple Sclerosis (MS) is a disease of the central nervous system that affects women more than men and is more common in Caucasians. The typical age of onset is between 20-35 years for women and 35-45 years for men. MRI is an important tool in the diagnosis and monitoring of MS, with findings including lesions in the white matter, corpus callosum, and brainstem. Gadolinium enhancement on MRI indicates breakdown of the blood-brain barrier and active inflammation. While MRI lesion number and location provide some prognostic information, disability as measured by scales such as EDSS correlates poorly with MRI findings. MS pathology involves both acute inflammatory lesions and chronic lesions involving demyelination and axonal loss.
Abusive head trauma: SBU report and beyond Felice D'Arco
A short presentation summarising the main findings of the consensus paper on abusive head trauma, the controversies raised by the SBU report about triad and "shaken baby syndrome" and main criticisms moved against SBU report. A useful summary for radiologists and clinicians involved in child abuse.
Presented at the Pediatric Neuroradiology PanLondon Sunset Meeting July 2019
1) MRI is useful for diagnosing and monitoring multiple sclerosis (MS). Common MRI findings in MS include ovoid lesions perpendicular to ventricles that appear as high signal on T2-weighted and FLAIR images.
2) Different MS subtypes have distinct clinical patterns. Relapsing-remitting MS (RRMS) accounts for 58% of cases and is characterized by neurological symptoms lasting over 24 hours followed by complete or partial recovery with intervals of at least one month between relapses.
3) Optimal MRI protocols for evaluating MS include 3D FLAIR, DIR, and SWI sequences which can help detect cortical and subclinical lesions. Monitoring for contrast enhancing lesions on post-g
The document describes a 75-year-old housewife who is experiencing memory loss, repetition, and disrupted sleep, with a history of being active and social. A mini mental state exam score of 30/30 and normal blood tests are noted. The differential diagnosis mentioned includes dementia, depression, and age-related cognitive impairment.
A 27-year-old female teacher collapsed in her classroom and was witnessed having a generalized tonic-clonic seizure by her students. She was brought to the emergency department by paramedics accompanied by a colleague. Differential diagnoses discussed include idiopathic epilepsy, meningitis, brain tumor, and other potential causes. Further workup is suggested to determine the underlying etiology.
This document discusses Leber's hereditary optic neuropathy (LHON), a maternally inherited mitochondrial disease affecting vision. Key points include:
- LHON is caused by mutations in mitochondrial DNA and results in degeneration of retinal ganglion cells and optic nerve atrophy, leading to legal blindness.
- The most common mutations occur at positions 11778, 3460, and 14484 of mitochondrial DNA and decrease ATP production in retinal ganglion cells.
- LHON typically begins in young adults and males are more commonly affected, developing vision loss in 40% of cases compared to 10% for females.
- While mutations are necessary, additional genetic and environmental factors like smoking are thought to trigger
The document provides an overview of various cellular reactions, disease patterns, malformations, injuries, and degenerative conditions that can affect the central nervous system (CNS). It discusses the different cell types of the CNS, including neurons, glia and their roles. Common CNS disease patterns are described as degenerative, inflammatory, neoplastic and traumatic. Specific CNS diseases, injuries, infections, malformations and degenerative conditions are then outlined in detail with their characteristic clinical and pathological features.
This presentation is a comprehensive & updated presentation that delves deeply into Multiple Sclerosis. It is intended for healthcare professionals and features the Anatomy and Physiology, Common Etiology, a focused review of the disease Pathophysiology, Prevalence & Morbidity, Clinical Manifestations, Diagnostics, Classification & Prognosis, Treatment (Both current and experimental), Nutrition, and Psychosocial issues and resources available to patients. It is very rich in details, diagrams (on every slide), and interactive content when in slide presentation mode. The presentation has also hyperlinks to videos (3 D Patho) and controversial treatments. Finally, it concludes with a Case Study to highlight the clinical application.
Please note that you're welcome to use any slides as long as you reference my post when you do so to maintain the integrity of authorship
If interested in detailed answers, please email: aamirdash@yahoo.com
Thanks, Ahmad
The document discusses various topics related to neurology including:
1. Common neurological disorders such as headache, low back pain, and stroke.
2. Components of a neurological examination including signs, reflexes, and tests of sensory and motor function.
3. Diagnostic tools used in neurology such as CT, MRI, angiography, EEG, lumbar puncture, and PET.
4. Types of disturbances of consciousness including those caused by brainstem or cortical damage.
5. Criteria for determining brain death.
This document provides an overview of various demyelinating diseases of the central nervous system. It begins by defining demyelinating diseases as those involving disruption of myelin, which forms an insulating sheath around axons. It then classifies and describes several specific diseases, including acute disseminated encephalomyelitis (ADEM), inflammatory demyelinating pseudotumor, multiple sclerosis (MS), neuromyelitis optica, central pontine myelinolysis, HIV encephalopathy, progressive multifocal leukoencephalopathy (PML), and others. For each disease, it discusses clinical features, magnetic resonance imaging (MRI) findings, differential diagnoses, and pathology where relevant.
The document discusses the importance of carefully considering alternative diagnoses to multiple sclerosis (MS) when evaluating patients. Common causes of MS misdiagnosis include nonspecific white matter abnormalities on brain MRI and vague neurological symptoms. Other disorders like neuromyelitis optica spectrum disorders, acute disseminated encephalomyelitis, and inherited disorders can mimic MS clinically and radiologically. A thorough evaluation of demographic, clinical, laboratory, and imaging factors is necessary to avoid misdiagnosis, as an MS diagnosis has significant implications for treatment.
This document discusses the diagnosis and treatment of primary central nervous system lymphoma (PCNSL). It begins by describing the typical clinical presentation of PCNSL, which most commonly involves focal neurological deficits, personality changes, and increased intracranial pressure. Magnetic resonance imaging is the preferred imaging modality, showing lesions that are often hypointense on T2-weighted imaging and demonstrate homogeneous enhancement with contrast. Stereotactic biopsy is the preferred method for diagnosis while avoiding gross tumor resection which has not shown survival benefits. The document goes on to discuss treatment approaches and challenges in managing this rare and aggressive malignancy of the central nervous system.
leptomeningeal metastases, leptomeningeal carcinomatosis, clinical features of leptomeningeal metastases, pathophysiology of leptomeningeal metastases, diagnosis of leptomeningeal metastases, CSF analysis, MRI findings in leptomeningeal metastases, treatment of leptomeningeal metastases,
leptomeningeal metastases, leptomeningeal carcinomatosis, clinical features of leptomeningeal metastases, pathophysiology of leptomeningeal metastases, diagnosis of leptomeningeal metastases, CSF analysis, MRI findings in leptomeningeal metastases, treatment of leptomeningeal metastases,
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
This document summarizes primary nervous system tumors in adults. It discusses that primary brain tumors arise from different central nervous system cells and account for about 2% of cancers. Meningiomas are the most common non-malignant tumors, while gliomas account for 75% of malignant brain tumors, over half being glioblastomas. Symptoms, diagnostic imaging techniques, treatment options including surgery, radiation therapy, chemotherapy are described. The management of primary brain tumors in adults and children of different age groups is summarized.
Brain Imaging in Patients with HIV Infection Ade Wijaya
This document summarizes the common brain infections seen in patients with HIV through their appearance on brain imaging such as CT and MRI scans. It describes the typical lesions, locations, and imaging characteristics of various conditions including toxoplasmosis, primary CNS lymphoma, HIV encephalopathy, CMV encephalitis, progressive multifocal leukoencephalopathy, tuberculosis, cryptococcosis, and neurosyphilis. Differential features between some conditions are also provided.
Structural neuroimaging plays an important role in the assessment and diagnosis of different types of dementia. For Alzheimer's disease, MRI typically shows atrophy of the medial temporal lobes including the hippocampus. Vascular dementia is characterized by multiple brain infarcts visible on CT or MRI. Frontotemporal dementia demonstrates frontal and temporal lobe atrophy that can be asymmetric. Dementia with Lewy bodies may show mild generalized atrophy on MRI with occipital hypometabolism on PET. Scales like the MTA scale are used to quantify hippocampal atrophy, while MRS can detect metabolic changes in dementia. Neuroimaging thus aids in distinguishing dementia subtypes and excluding other pathological conditions.
A 67-year-old male presented with headache, facial weakness, and limb weakness. Imaging showed lesions in the left thalamus, midbrain, pons, and cerebellum enhancing on MRI. Biopsy of the thalamic lesion found diffuse large B-cell lymphoma. Further testing found lymphoma in peri-renal soft tissue as well. This represents either secondary CNS lymphoma with systemic involvement or synchronous primary lesions, unusual for primary CNS lymphoma.
Neurosarcoidosis is a multisystem granulomatous disease of unknown etiology where noncaseating granulomas can affect multiple organs including the lungs, heart, skin and nervous system. It most commonly involves the lungs in 90% of cases. The central nervous system is involved in 5-16% of cases, with cranial neuropathies being the most frequent neurological manifestation. Diagnosis involves evidence of systemic sarcoidosis along with neurological symptoms, and can be supported by MRI, lumbar puncture and biopsy when possible. Corticosteroids are the main treatment to suppress inflammation and immune activity, and some severe or refractory cases may require additional immunosuppressants. Prognosis depends on location
Neurosarcoidosis is a multisystem granulomatous disease of unknown etiology where noncaseating granulomas can affect multiple organs including the lungs, heart, skin and nervous system. It most commonly involves the lungs in 90% of cases. The central nervous system is involved in 5-16% of cases, with cranial neuropathies, encephalitis, meningitis and mass lesions being common neurological manifestations. Treatment involves corticosteroids as the mainstay, with immunosuppressants also used in refractory cases. Prognosis depends on location and type of involvement, with 72% of neurological cases deteriorating within 18 months if not treated.
Disorder of reversible subcortical vasogenic brain oedema in patients with acute neurological symptoms (eg, seizures, encephalopathy, headache, and visual disturbances) in the setting of renal failure, blood pressure fluctuations, cytotoxic drugs, autoimmune disorders, and pre-eclampsia or eclampsia.
Also called as:
Reversible posterior cerebral edema syndrome
Posterior leukoencephalopathy syndrome
Hyperperfusion encephalopathy
Brain capillary leak syndrome
PRES is caused by endothelial injury related to abrupt blood pressure changes or direct effects of cytokines on the endothelium, which leads to breakdown of the blood– brain barrier and subsequent brain edema.
PRES is generally reversible, both radio graphically and clinically, and has a favourable prognosis.
Cerebral blood flow can be regulated by four major mechanisms:
Myogenic,
Neurogenic,
Metabolic, or
Endothelial.
These mechanisms ensure that cerebral blood flow (CBF) is maintained within a relatively normal range. NO—nitric oxide, ET1—endothelin 1
Normal pressure hydrocephalus (NPH) is a reversible cause of dementia characterized by the classic triad of dementia, gait disturbance, and urinary incontinence. It is caused by excess cerebrospinal fluid in the brain's ventricles without increased fluid pressure. NPH typically affects older adults and can be diagnosed using criteria including an evaluation of symptoms, imaging scans, and lumbar puncture results. Treatment involves CSF shunting procedures, which can significantly improve symptoms in around 60% of NPH patients. Prognosis is generally good with sustained improvement possible after surgery, though shunt complications do occur in around 38% of cases.
Clinical imaging and molecular biomarkers of drug resistant epilepsy.pptxPramod Krishnan
Clinical, imaging and molecular biomarkers in drug resistant epilepsy
1. Several clinical factors predict drug resistant epilepsy including early age of onset, frequent seizures, neurological deficits, and failure to respond to initial treatment.
2. Imaging biomarkers such as abnormalities on MRI, focal hypometabolism on PET, and changes in diffusion can help identify potential epileptogenic lesions.
3. Molecular biomarkers reflect underlying pathological processes like abnormal excitatory/inhibitory neurotransmission, neuroinflammation, and changes in gene and protein expression that may contribute to drug resistance. Combining biomarkers provides a more precise approach to managing drug resistant epilepsy.
1. A 36-year-old man presented with a mass in his right adrenal gland and was found to have a pheochromocytoma, retinal hemangioma, kidney cysts, and liver lesions.
2. He was diagnosed with Von Hippel-Lindau disease based on his family history and multiple tumors.
3. Autopsy found brainstem and spinal cord hemangioblastomas consistent with VHL disease and catecholamine toxicity as the cause of death. Genetic testing identified a mutation in the VHL gene confirming the diagnosis.
This document discusses stroke mimics and chameleons. It begins by introducing stroke mimics, which account for 20-25% of suspected stroke cases. Common mimics include seizures, hypoglycemia, sepsis, migraines, and tumors. Functional disorders and delirium can also mimic strokes. The document then discusses stroke chameleons, which imitate other diseases due to their gradual onset or non-specific symptoms. Examples given include vertigo, monoparesis, and delirium. Several case studies are presented to illustrate specific mimics and chameleons. The document emphasizes the importance of thorough clinical assessment to distinguish strokes from mimicking conditions.
Similar to LLA 2011 - C. Hess - Neurological problems in patients with haematological neoplasms (20)
1) The study examines how and why certain breast cancer cells metastasize to bone through a "seed pre-selection" process.
2) It finds that high Src activity (denoted by a "Src activity signature" or SRS) in primary tumors associates with bone metastasis.
3) In ER-/ERBB2- breast cancers, cytokines CXCL12 and IGF1 in the tumor microenvironment activate Src which promotes cell survival and bone metastasis. Long term exposure to these cytokines in vitro selects for breast cancer cells with higher Src activity and bone metastatic ability.
The document discusses renal cancer (kidney cancer) and advances in its treatment. It describes several targeted drugs that have improved outcomes for metastatic renal cell carcinoma (mRCC) compared to previous immunotherapy options. Drugs include tyrosine kinase inhibitors like sunitinib, sorafenib, pazopanib and axitinib as well as the mTOR inhibitor temsirolimus. Clinical trials have established these as standard first and second line options depending on a patient's risk level and prior treatment history. Ongoing research focuses on optimizing treatment sequencing and identifying biomarkers to guide more personalized therapy selection.
The document summarizes key information about prostate cancer including incidence, mortality rates, clinical stages, risk groups for localized prostate cancer, treatment options for advanced disease including hormone therapy and chemotherapy, and results from clinical trials of chemotherapy agents like docetaxel and cabazitaxel.
The document summarizes highlights from the 11-ICML Lugano conference in 2011, including:
1) Studies showing the impact of the tumor microenvironment in lymphoma prognosis and the predictive value of increased macrophages in Hodgkin's lymphoma biopsies.
2) High response rates to antiviral treatment in patients with indolent B-cell lymphoma associated with HCV infection.
3) A PET-based approach can effectively guide treatment for limited-stage diffuse large B-cell lymphoma.
4) R-CHOP induction followed by rituximab maintenance improves survival over R-FC induction for elderly patients with mantle cell lymphoma.
This document summarizes the management of urinary bladder cancer. It discusses staging, histopathologic types, and treatment options for non-muscle invasive and muscle invasive bladder cancer as well as metastatic disease. Standard first-line chemotherapy for metastatic bladder cancer includes gemcitabine and cisplatin or MVAC. Newer chemotherapy regimens and agents are also discussed.
The document discusses new drugs for the treatment of lymphomas. It outlines several monoclonal antibodies that target antigens on B-cells, including CD20, CD19, CD22 and CD37. Ofatumumab and GA-101 are new anti-CD20 monoclonal antibodies that exhibit enhanced binding and cell-killing properties compared to Rituximab. Inotuzumab Ozogamicin is an antibody-drug conjugate targeting CD22 that is internalized and releases a cytotoxic drug, showing promising activity in early clinical trials.
This document discusses treatment of diffuse large B-cell lymphoma (DLBCL). It notes that DLBCL is a heterogeneous disease with genetic subgroups that have different prognoses and responses to treatment. The addition of the antibody rituximab to chemotherapy improves outcomes for DLBCL compared to chemotherapy alone. Strategies discussed to improve outcomes include increasing chemotherapy dose intensity and the potential role of the drug bortezomib for the activated B-cell subtype.
This document discusses treatment of diffuse large B-cell lymphoma (DLBCL). It notes that DLBCL is a heterogeneous disease with genetic subgroups that have different prognoses and responses to treatment. The addition of the antibody rituximab to chemotherapy like CHOP has improved outcomes for DLBCL compared to chemotherapy alone in the post-rituximab era. Strategies to further improve outcomes include targeting specific genetic subgroups like the activated B-cell subtype using drugs like bortezomib that inhibit pathways like NF-kB.
The document discusses the current state of cancer vaccines, focusing on HPV vaccines. It outlines the types of vaccines as prophylactic, preventive, or therapeutic. HPV vaccines have proven highly effective as prophylactic vaccines in preventing cervical cancer. Clinical trials demonstrated up to 100% efficacy of the HPV vaccines Gardasil and Cervarix in preventing precancerous lesions. However, challenges remain regarding cross-protection against other HPV types, long-term duration of protection, and reducing production costs to increase global access.
- Ovarian cancer is the ninth most common cancer in women and the fifth leading cause of cancer death in women. Risk factors include age over 60, obesity, talcum powder use, fertility drugs, genetic predispositions like BRCA mutations.
- Surgical staging is essential for determining prognosis and appropriate treatment. For early stage disease adjuvant chemotherapy is recommended. Advanced stage disease is treated with cytoreductive surgery followed by platinum/taxane chemotherapy.
- Prognosis depends on stage and completeness of cytoreduction. Median survival is 39 months for optimal vs 17 months for suboptimal cytoreduction. Secondary surgery and chemotherapy may provide benefit for recurrence in some patients.
This document summarizes key information about ovarian cancer, including epidemiology, staging, treatment milestones, prognostic factors, and recent clinical trials. It notes that the median age of diagnosis is 63 years and discusses improvements in 5-year survival over time. New developments discussed include the role of surgery, chemotherapy regimens, targeted therapies like bevacizumab, and trials in recurrent settings.
Nearly 500,000 new cases of cervical cancer occur worldwide each year, with the majority in developing countries. Infection with HPV is responsible for virtually all cervical cancer cases. Screening includes Pap smears and HPV testing, while vaccination may prevent up to 70% of cases but is not widely available due to cost. Diagnosis is through biopsy and histopathological examination, while staging uses the FIGO system based on tumor size and spread. Treatment depends on stage but commonly includes surgery such as hysterectomy with or without radiation or chemotherapy.
- Cervical cancer is a major cause of cancer deaths worldwide, with over 500,000 new cases and 260,000 deaths estimated annually. Most deaths occur in developing countries where screening and prevention programs are lacking.
- Early detection through screening programs can make cervical cancer highly curable, but the majority of cases in developing nations are diagnosed at late stages when survival rates are low. Vaccination and screening can help prevent a large percentage of cervical cancer cases.
- Risk factors for cervical cancer include human papillomavirus infection and lack of access to healthcare. While HPV infection is necessary, most infections clear without causing cancer. Other factors like multiple pregnancies, smoking, and HIV infection can increase the risk.
The document summarizes the current state of metastatic breast cancer treatment. It discusses how survival rates have improved over time and metastatic breast cancer is now considered a chronic, treatable disease rather than an immediately terminal condition. Treatment involves systemic therapies like chemotherapy, endocrine therapy, targeted therapies, as well as radiation, surgery, and supportive care. Selection of optimal first-line systemic treatment depends on disease characteristics and patient factors. Ongoing research focuses on tailoring and sequencing treatments to overcome resistance and further extend patient survival and quality of life.
1) Breast cancer is heterogeneous with different subtypes defined by receptor status and gene expression profiles. The subtypes have different biological behaviors and clinical outcomes.
2) Accurate diagnosis requires biopsy (FNA or core) followed by receptor testing before treatment decisions. Surgery options include breast conserving therapy or mastectomy with/without reconstruction.
3) For early breast cancer, sentinel lymph node biopsy guides the need for further axillary lymph node dissection. Omission of further dissection may be adequate for sentinel node positive patients.
- The document discusses liver and hepatobiliary cancers, focusing on hepatocellular carcinoma (HCC). It covers the epidemiology, risk factors, screening and diagnosis of HCC as well as staging systems and treatment options.
- Risk factors for HCC include hepatitis B and C infection, alcohol consumption, and aflatoxin intake. Screening ultrasound and AFP tests are used for early diagnosis in high-risk patients. The BCLC staging system guides treatment which includes resection, transplantation, ablation, and embolization.
- For intermediate stage HCC, transarterial chemoembolization provides the best outcomes, with 70-80% of patients surviving 1 year and 50% surviving 3 years. However
The document discusses guidelines for screening, diagnosis, staging, adjuvant therapy, advanced disease treatment, and follow-up for colorectal cancer from both the ESMO and NCCN perspectives. It provides recommendations for screening the general and high-risk populations. It also outlines the diagnostic and staging workup, including endoscopy, biopsy, imaging, and surgical staging. Guidelines are presented for adjuvant therapy based on cancer stage. Recommendations are provided for managing both synchronous and metachronous metastatic disease, as well as rectal cancer treatment.
1) A trial found that adding bevacizumab to chemotherapy for stage III colon cancer extended disease-free survival compared to chemotherapy alone, delaying cancer relapse but not preventing it completely.
2) There was no overall survival benefit observed from adding bevacizumab, suggesting it delays but does not alter the underlying biology of the disease.
3) The interpretation is that relapses were delayed by bevacizumab treatment but then occurred at a steady rate later on, similar to the chemotherapy alone group.
This document provides an overview of squamous cell carcinoma of the head and neck (SCCHN), including its anatomical sites, incidence and mortality rates, risk factors, staging guidelines, and treatment approaches. It discusses the roles of surgery, radiation therapy, chemotherapy, concurrent chemoradiation, and targeted therapies like cetuximab in managing localized and advanced SCCHN. Concurrent chemoradiation is now standard for improving local control and organ preservation compared to radiation alone. The addition of cetuximab to radiation was shown to improve locoregional control and overall survival.
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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
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
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.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
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LLA 2011 - C. Hess - Neurological problems in patients with haematological neoplasms
1. ESO Course Leukaemia and Lymphoma 12-14 June 2011 Ascona, Switzerland Neurological problems in patients with haematological neoplasms C W Hess, Bern
11. Rx CT/MRI contrast enhancement in almost 100% (except following steroids!), enhancement may be homogenous – heterogeneous DD: malignant gliomas, metastases, sarcoidosis, and inflammatory disease (ADEM) Dg: • CSF: pleocytosis in 36%, cytology with lymphoma cells in 20% (Fischer L, 2006) • stereotactic biopsy if possible • histology: diffuse large B celllymphoma • looking for extra-cns involvement (staging): complete blood count CT thorax & abdomen, bone marrow biopsy; Eye slit lamp exam, LDH, HIV.
16. Rx CT/MRI contrast enhancement in almost 100% (except following steroids!), enhancement may be homogenous – heterogeneous DD: malignant gliomas, metastases, sarcoidosis, and inflammatory disease (ADEM) • responsive to steroids (melts away in >40%) BUT: steroids may obscure histology (-> aim at histological diagnosis before starting a “steroid trial”) • relapses are usually no longer steroid responsive Th: • Problem: BB-Barrier renders chemotherapy difficult • high dose(≥3 g/m2)MTX, WB Rx (<60 yrs), Autolog. Stem-Cell Transpl., intrathRituximab? …
34. long term memory ↓Histo-pathological Dg: diffuse large B cell NHL
35. Primary central nervous system lymphoma (PCNSL) Male, 79 y. gait difficulty, falls, and memory problems MRI: T1 without Gd Contrast T1 with Gd Contrast Histo-pathological Dg: diffuse large B cell NHL
36. Primary central nervous system lymphoma (PCNSL) Male, 79 y. gait difficulty, falls, and memory problems MRI: T2 T1 with Gd Contrast Histo-pathological Dg: diffuse large B cell NHL
37. Multifocal central nervous system lymphoma MRI T1 with Gd Contrast Female, 51 y. Headache, episodic fever, night sweat, nausea vomitus, fatigue Episodes of R sided weakness & dysarthria sometimes confusion lasting mins to 1h Clinical S & S: - alertness ↓ - fatigue - no focal deficits Histo-pathological Dg: diffuse large B cell NHL
38. Multifocal central nervous system lymphoma MRI T1 with Gd Contrast Female, 51 y. Headache, episodic fever, night sweat, nausea vomitus, fatigue Episodes of R sided weakness & dysarthria sometimes confusion lasting mmin to 1h Clinical S & S: - alertness ↓ - fatigue - no focal deficits Histo-pathological Dg: diffuse large B cell NHL Histo-pathological Dg: diffuse large B cell NHL
39. Direct neoplastic manifestation in the nervous system of haematological neoplasms: 2. Secondary (metastatic) nervous system involvement Most frequent direct neurologic complications of hematologic malignancies (Leptomeningeal M.) , (Leptomeningeal M.) , (Leptomeningeal M.) , (Leptomeningeal M.) , (Leptomeningeal M.) J.E.C. Bromberg, AAN April 2011
40. Direct neoplastic manifestation in the nervous system of haematological neoplasms: 2. Secondary (metastatic) nervous system involvement Frequency of Various Tumours of Origin Among Patients with Leptomeningeal Metastasis “CSF”(Meningeosisneoplastica) J Grewal, J P Duic, M Almaliah, S Kesari, E J Dropcho. Neurology MedLINK, updated 19. July 2010
41. A. Direct neoplastic manifestation in the nervous system of haematological neoplasms Secondary (metastatic) nervous system involvement 2.a. Leptomeningeal metastasis, “CSF” (meningeosislymphomatosa = lymphomatousmeningitis) Leukaemia (particularly ALL•)or NHL , rarely HD or plasma cell tumours - Clinical S & S: nausea, vomitus, headache (not obligatory), cranial nerve involv., cognitive problems, or radiating pain due to nerve root involvement - MRI often negative & usually without contrast enhancement! (>< carcinomas), (sometimes subarachnoid nodules, intradural nerve contrast enhancement) - CSF pressure often↑, lymphocytic pleocytosis, and/or increased protein (in 80%), and/or hypoglycorrhachia; cytology (+ immunophenotypingbyflowcytometry) (! perform lumbar puncture after MRI: -> i.c. hypotension -> dural enhancement! ) • ALL: often as CNS recurrence when adequate CNS prophylaxis was not given (standard prophylactic treatment: intrathecal MTX and/or Cytarabine) Problem: BB-Barrier renders chemotherapy difficult
42. Flow cytometric dot plots of cerebrospinal fluid specimens demonstrating lymphoma populations (immunophenotyping) Surface immunoglobulin-negative B-cell lymphoma Monoclonal B-cell population CD20– B-cell T-lymphoma Small population of monoclonal B cells with low cellularity Hedge U et al. Blood 2005;105:496-502 relative fluorescent intensity
43. Leptomeningeal metastasis(meningeosislymphomatosa) 3 yrsagotreatedforT-cell NHL incl. autologousstemcell transplantation MRI T1 with Gd Contrast VII & VIII New: Gait ataxia, memory problems, bilateral Abducens nerve paresis, right lid drooping, dysphagia
44. Leptomeningeal metastasis(meningeosislymphomatosa) 3 yrsagotreatedforT-cell NHL incl. autologousstemcell transplantation MRI T1 with Gd Contrast VI New: Gait ataxia, memory problems, bilateral Abducens nerve paresis, right lid drooping I,, dysphagia
45. A. Direct neoplastic manifestation in the nervous system of haematological neoplasms Secondary (metastatic) nervous system involvement 2.b. Systemic NHL infiltrating the CNS parenchyma (brain or spinal cord) Burkitt lymphoma and diffuse large B-cell lymphoma (HL: exceedingly rare) 3-24% of pts with systemic NHL develop a CNS localization, e.g. as CNS recurrence. In 20-25% of these CNS localization is present at beginning of disease (brain << CSF)
46. A. Direct neoplastic manifestation in the nervous system of haematological neoplasms Secondary (metastatic) nervous system involvement 2.c. Peripheral Nerve and Nerve Root Involvement „Neurolymphomatosis“ - NHL infiltrating cranial nerves, peripheral nerves, or nerve roots. - Clinical S & S: sensory loss, and/or focal weakness • asymmetric polyneuropathy or mononeuropathy or cranial neuropathy • severe pain (rarely painless) • sensory loss, and/or weakness • rapid evolution - CSF: Pleocytosis and/or protein↑ in 40-60%; malignant cells in 40% of pts. - Imaging: Gd-MRI (may be negative), PET-CT in 90% positive - Nerve biopsy may be necessary Problem: Blood-Nerve-Barrier (BNB) renders chemotherapy difficult
47. Peripheral Nerve and Nerve Root Involvement „Neurolymphomatosis“ R S1 nerve root Baehring JM et al. Neuro-Oncology 2003;5:104–115
48. Peripheral Nerve and Nerve Root Involvement „Neurolymphomatosis“ MRI T1 with Gd Contrast R Facial Nerve Baehring JM et al. Neuro-Oncology 2003;5:104–115
49. A. Direct neoplastic manifestation in the nervous system of haematological neoplasms secondary (metastatic) nervous system involvement 2.d. Epidural spinal cord (or caudaequina) compression - direct invasion of the spinal canal from a vertebral body or via the intervertebral foramina from paraspinal regions (extra-axial non-CNS location). - Multiple Myeloma (approximately 20% of cases) >> HL, NHL: caused by vertebral body collapse and impingement of bone on the spinal cord - Clinical S & S: back pain (progressive, worse when lying flat, and improved with walking), weakness, sensory loss, autonomic dysfunction (painless urinary retention, faecal incontinence, and impotence), and ataxia
50. A. Direct neoplastic manifestation in the nervous system of haematological neoplasms secondary (metastatic) nervous system involvement 2.d. Epidural spinal cord compression by Multiple Myeloma, HL, or NHL Outside of BB-Barrier: easily amenable to systemic treatment and chemosensitive & radiosensitive CAVE: Epidural NHL may co-exist with a leptomeningeal localization of lymphoma, which may be clinically silent.
51. A. Direct neoplastic manifestation in the nervous system of haematological neoplasms secondary (metastatic) nervous system involvement 2.d. Epidural spinal cord compression: Multiple Myeloma
52. A. Direct neoplastic manifestation in the nervous system of haematological neoplasms secondary (metastatic) nervous system involvement 2.d. Epidural spinal cord compression: Multiple Myeloma High power fieldshowingtypicalplasmacells T1 Low power viewshowing multiple plasmacells Infiltrativemass at level of T1 dorsal processvertebrae. F. Aziz, S. Doddi & S. Ghimire. The Internet Journal of Neurology2010;13
53. B. Indirect manifestation affecting the NS Paraneoplasticcerebellar degeneration (PCD) from HL HL is 3rd cause of PCD after lung Ca (anti-Hu AB) and ovarian Ca (anti-Yo AB) In HL it usually occurs after diagnosis or during long periods of remission (>< Ca) Pg: if HL not treated -> irreversible loss of Purkinje cells and atrophy of cerebellum Treatment aims at HL, otherwise no efficient treatment known (immunosuppression?) - Clinical S & S: Subacutedysarthria, nystagmus, truncal ataxia, and limb dysmetria 1.a. anti-Tr AB associated paraneoplastic cerebellar degeneration (PCD) Least severe form of PCD, may remit with treatment 1.b. anti-mGluR1 AB associated paraneoplastic cerebellar degeneration (PCD) Hodgkin Lymphoma Reed-Sternberg Cell
54. Paraffin sections of rat cerebellum (A) and Hodgkin lymphoma (B): incubated with biotinylated immunoglobulin G from an anti-Tr-positive serum and counterstained with haematoxylin. Reed-Sternberg cells Purkinijecell 20 µm 6 µm Bernal F et al. Neurology 2003;60;230-234
55.
56. Anti-NMDAR limbic encephalitis: coronal MRI FLAIR T1 with Gd Contrast Pellkofer HL et al. J NeurolNeurosurgPsychiatry 2010;81:1407-1408
57. Paraneoplastic limbic encephalitis MRI coronal SPECT mediastinal node enlargement arrow shows a Hodgkin’s-Reed-Stemberg cell with positive staining for CD30, magn. x600 Olmos D et al. Journal of Clinical Oncology2007;25:1802-1806
58. B. Indirect manifestation affecting the NS 2. Paraneoplasticlimbic encephalitis from HL: the “Ophelia syndrome” John William Waterhouse: Ophelia (1894) Carr I: Lancet 1982; 1:844-845
59. 2. Paraneoplasticlimbic encephalitis from HL: the “Ophelia syndrome” Tumors associated with paraneoplastic limbic encephalitis (all types): Ophelia Gultekin SH et al. Brain 2000;123:1481-494
60. B. Indirect manifestation affecting the NS 3. Paraneoplastic neuropathies from Lymphomas 3.a. Demyelinating polyneuritis: GBS (motor >> sensory) or CIDP from HL >> NHL 3.b. Chronic polyneuropathies: motor, sensory, autonomic from NHL >> HL 3.c. Autonomic dysfunction in NHL >> HL 3.d. Vasculitic neuropathy in HL & NHL: Axonal mononeuritis multiplex GBS = Guillain-Barré Syndrome: • acute inflammatory demyelinating polyneuritis (AIDP) • acute motor [sensory] axonal neuropathy (AMSAN / AMAN) Chronic variants of GBS: • chronic inflammatory demyelinating polyneuritis (CIDP) • mulitfocal motor neuropathy (MMN) • paraproteinaemic neuropathies: IgM(- anti-MAG, - CANOMAD: chronic ataxic neuropathy with ophthalmoplegia, M-protein, agglutination and disialosyl antibodies) IgG, IgA
61. Clinical presentations of neuropathies: Distribution distal symmetrical polyneuropathy usually predominantly sensory maybe painful proximal symmetrical polyneuropathy usually predominantly motor mononeuritis multiplex asymmetrical, multifocal mostly acute, often painful motor and/or sensory length dependent examples: proximal diabetic mono-n. plexus neuritis vasculitic neuropathies multifocal motor n. chronic inflammatory demyelinatingp. (CIDP) acute GBS diabetic, alcoholic, uraemic, toxic drug-induced, etc.
62. Axonal versus demyelinatingpolyneuropathy (ENMG) M normal Aetiology rule of thumb: Ae: toxic(dose-dependent) metabolic vasculitic „degenerative“ Ae: immune mediated inflammatory (GBS, CIDP) some genetic Ae: pressure palsy immune mediated inflammatory (MMN, …..) axonal demyelinating focal demyelinisation conduction block possible
63. Clinical presentations of neuropathies: Type of fibres involved Functions conveyed (signs) tendon reflexes position sense vibration sense autonomic peripheral ns - perspiration anhidrosis - postural hypotension - pain and warmth perception pain and cold perception diameter NCV Mechanorec. Sharp pain Slow pain (skin) Cold Warmth Mechanorec. Sharp pain Slow pain (skin) Cold Warmth
64. B. Indirect manifestation affecting the NS 4. Plasma cell disorders (dyscrasias) with dysimmune neuropathies 4.a. Benign monoclonal gammopathy MGUS: IgM-Gammopathy: demyelinating large fibre PNP (CIDP) - subtype with anti-MAG AB, slow progression, but relatively resistant to th. IgG-Gammopathy: axonal small (and medium) fibre PNP IgA-Gammopathy: rare 4.b. Primary systemic amyloidosis: axonal small fibre PNP with prominent autonomic features (other organs affected such as heart etc.) 4.c. Myeloma producing amyloid: Small fibre polyneuropathy PNP (axonal) Patients do not generally respond to treatment of the myeloma, but may respond to rituximab or stem cell transplantation. Pg: invasion of peripheral nerves by amyloid.
65. B. Indirect manifestation affecting the NS 4. Plasma cell disorders (dyscrasias) with dysimmune neuropathies 4.d. Osteolytic myeloma without amyloidosis: slowly progressive peripheral sensorimotor PNP, usually as late finding 4.e. Osteosclerotic myeloma: • Chronic sensorimotor inflammatory demyelinatingpolyneuropathyCIDP in 75% of patients. CSF protein↑ Pg: mostly IgG or IgM protein, usually with lambda light chains. PNP improves with treatment of the myeloma! special subtype: • POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Edema, M-protein, and Skin abnormalities). Pg role of vascularendothelial growth factor (VEGF)! - Waldenströmmacroglobulinaemia: demyelinating peripheral senorimotorpolyneuropathy CIDP in 10% of pts
66. D. Complications of treatment affecting the nervous system 1. Neurologic Complications of Radiotherapy (RT) 1.a. Post-radiation Dropped Head Syndrome (postactinicptosiscapitis) Weakness of neck extensor muscles causing an inability to extend the neck, from high-dose “mantle field” radiotherapy for HL. Typically no sensory deficit! Symptoms begin many years (> 20 years) after RT. Pg: combination of primary muscle damage and anterior horn/nerve root lesions? 1.b. Post-radiation Brachial Plexopathy Clinical S. & S.: Delayed progressive dysfunction (>1 year - up to 15 years): Paraesthesia (100%), hypaesthesia (75%), weakness (50%), pain (50%, delayed) Typical are fasciculations and myokymia (clinically and EMG) [>< tumour invasion] Pg: Hyalinization and obliteration of blood vessels causes ischaemia of nerve fibres EMG needle recording: myokymic discharge
67. D. Complications of treatment affecting the nervous system 1. Neurologic Complications of Radiotherapy (RT) 1.a. Post-radiation Dropped Head Syndrome (postactinicptosiscapitis) Weakness of neck extensor muscles causing an inability to extend the neck, from high-dose “mantle field” radiotherapy for HL. Typically no sensory deficit! Symptoms begin many years (> 20 years) after RT. Pg: combination of primary muscle damage and anterior horn/nerve root lesions? 1.b. Post-radiation Brachial Plexopathy Clinical S. & S.: Delayed progressive dysfunction (>1 year - up to 15 years): Paraesthesia (100%), hypaesthesia (75%), weakness (50%), pain (50%, delayed) Typical are fasciculations and myokymia (clinically and ENMG) [>< tumour invasion] Pg: Hyalinization and obliteration of blood vessels causes ischaemia of nerve fibres 1.c. Post-radiation carotid artery atherosclerosis (➔ stenosis, relatively frequent) with cerebrovascular complications (ischaemia)
68. D. Complications of treatment affecting the nervous system 2. Neurologic Complications of Chemotherapy 2.a. Drug induced Polyneuropathy (PNP) from Systemic Application - Vincristine: as most neurotoxicvinca alkaloid causes a large fibre sensori-motor (and later also -> small fibre) axonal PNP in most patients. Also: mononeuritis! - Clinical S. & S.: few weeks following initiation of therapy and progress for several weeks after drug discontinuance (coasting phenomenon) before reversible Early paraesthesias of fingertips -> toes, fine finger movements↓ -> glove and stocking sensory deficit, weakness of extensor muscles of feet Early loss of Achilles reflexes -> all deep tendon reflexes disappear eventually - Vinblastinemay cause a predominantly length-dependent small fiber sensory peripheral PNP - Cisplatincausis a length-dependent large fiber sensory peripheral PNP or ganglionopathy with a coasting phenomenon and only partial (if any) reversibility - Thalidomid causes a sensori-motor peripheral PNP, sometimes with a coasting phenomenon, and reversibility of weakness but only partial or often lacking reversibility of sensory deficits after cessation. For the development of PNP, the duration of exposure is more important than total cumulative dose - Cytarabine: sensory PNP - Bortezomid: “axonal, dose-dependentneuropathy“ ? [Filosto M et al 2007]
69.
70. Distal symmetrical sensory or sensorimotor PNP = length dependent • distal proximal* • legs > arms • sensory > motor plus symptoms: paraesthesias /dysaesthesias pain minus symptoms: numb feeling * toxic & metabolic PNP: involvement of the longest neurites earlier and more pronounced distal-symmetrical (= length dependent) PNP
71. • often also autonomic involvement • palmo-plantar anhidrosis • palmo-plantar hyperaemia (vasoparalysis due to damage to the peripheral sympathicus) Distal symmetrical sensory or sensorimotor PNP = length dependent • distal proximal • legs > arms • sensory > motor
73. D. Complications of treatment affecting the nervous system 2. Neurologic Complications of Chemotherapy 2.b. Drug induced Encephalitis or Encephalopathy / Myelopathy - Rituximab: JC-virus induced progressive multifocal leukoencephalopathy (PML) - Methotrexate (high dose): Reversible Encephalopathy in children - Cytarabine: Cerebellar Encephalopathy / Myelopathy 2.c. Cardiomyopathy producing cardiac emboli - Doxorubicin causes a cumulative, dose-dependent cardiomyopathy - Clinical S. & S.: transient ischemic attacks (TIA) or cerebral infarction 2.c. Intrathecal chemotherapy with methotrexate, cytarabine • CNS prophylaxis in the setting of NHL and leukaemia (ALL) • Therapy for meningeal metastasis (lymphomatous meningitis) - Chemical meningitis (methotrexate ≈ 10% risk; cytarabine ≈ 40% risk). Liposomal cytarabine is currently approved only for use in lymphomatous meningitis. - Transverse myelopathy - Delayed progressive leukoencephalopathy
75. The two prototypical Types of Peripheral Neuropathy: Large fibre polyneuropathy Acralparaesthesias of feet (fingertips) & hands (toes) Deficits in sensory discrimination and proprioception (vibration sense & position sense↓) -> Afferent dysmetria, ataxia Pinprick and temperature sensation spared Deep tendon reflexes diminished -> lost rather early Weakness, muscle wasting in sensori-motor PNP Small fibre polyneuropathy: Numbness in the feet and hands, burning and aching pains, burning feet Pinprick and temperature sensation are lost out of proportion to proprioception Deep tendon reflexes often relatively spared (abolished rather late during the course) Autonomic dysfunction: anhidrosis, palmo-plantar hyperaemia in advanced cases -> postural hypotension, diarrhea, impotence, and bladder dysfunction Later during the course of the disease -> Combination of the two!
81. Cerebral Symptoms Present Initially in 140 Patients with Leptomeningeal Metastasis (Meningeosisneoplastica) from Solid Tumors after: Posner JB. Neurologiccomplications of cancer. FA Davis, Philadelphia, 1995, p 102.
91. D. Complications of treatment affecting the nervous system 1. Neurologic Complications of Radiotherapy (RT) 1.d. Acute Brachial Plexitis (≈ Parsonage Turner Syndrome = Neuralgic amyotrophia) in HL Acute shoulder and arm pain followed by arm/hand sensory loss and weakness within days to weeks of starting RT; improvement occurs despite continued RT (may also occur without any RT in HD!) Pg: immune mediated, RT merely as “trigger” 1.e. Episodic Neurologic Dysfunction (TIAs?) [Feldmann 1986] Usually in HL following radiotherapy - Clinical S & S: Visual disturbances, language dysfunction, segmental motor, or segmental sensory defects. Pg: poorly understood Feldmann E, Posner JB. “Episodicneurologicdysfunction in patientswithHodgkin’sdisease,” ArchNeurology 1986;43:1227–1233
92. A.temporal development? speed of development context with possible trigger t B.distribution? distal - proximal symmetrical - asymmetrical legs – arms - head C.type of nerve fibres involved? sensory - motor – autonomic temperature-pain or position sense Clinical presentations of neuropathies t D.accompanying symptoms? pain, ataxia, cns symptoms
93. 2. Paraneoplasticlimbic encephalitis Diagnostic tests in paraneoplastic limbic encephalitis (all types): Gultekin SH et al. Brain 2000;123:1481-494
94. POEMS syndrome (= Crow-Fukase syndrome) Patient with solitarymyeloma with monoclonal gammopathy of IgG / λ type POE(E)MS = polyneuropathy, organomegaly, edema, endocrinopathy, M-protein, skin changes NORMAL control PATIENT dark, dusky violaceous skin (vasoparalysis)
95. POEMS syndrome (= Crow-Fukase syndrome) Patient with solitary myeloma with monoclonal gammopathy of IgG / λ type Sural nerve biopsy showing a severe axonal polyneuropathy -> arrows indicate Wallerian degeneration NORMAL control PATIENT 10 µm Methylene blue stain
96. B. Indirect manifestation affecting the NS 5. Primary Angiitis of the Central Nervous System (PACNS) in HL Granulomatousangiitis that affects small arteries of the leptomeninges, and parenchyma of the brain and spinal cord in the absence of systemic vasculitis - Clinical S & S: headache, encephalopathy, seizure, haemorrhage, and multifocal infarcts 6. Cerebrovascular Complications from Polycythaemiavera & Leukaemias (AML >> ALL) 6. a. Ischaemic complications - Diffuse encephalopathy with headaches, blurred vision, and confusion - Ischaemic events (TIA, stroke), deep venous thrombosis Pg: blood hyperviscosity↑ (sludge), leucostasis in severe leucocytoses 6.b. Intracerebral or subdural haemorrhage as a result of secondary thrombocytopenia Leucocyte counts > 100 x 109/l may cause sludging or leucostasis -> haemorrhage or cortical infarction Clinically this may present with focal deficits or diffuse encephalopathy.
97. C. CNS Infections due to neoplasm-induced immunosuppression Bacterial meningitis often occurs in the setting of myelo-suppression or neoplasm-related immunoglobulin deficiency Opportunistic infections particularly in T-cell–depleted patients, following stemcelltransplantation cryptococcal meningitis, aspergillosis, nocardia, toxoplasmosis Viral encephalitis in bortezomibtreatment(proteasomeinhibitor) herpes simplex virus, varicella-zoster virus, JC-virus (leading to progressive multifocal leukoencephalopathyPML)