Guest guest Posted December 19, 2006 Report Share Posted December 19, 2006 WHO IS EPILEPSY.COM/PROFESSIONALS DONATE ABOUT EPILEPSY & SEIZURES CO-EXISTING DISORDERS Brain Tumors Cardiac Disorders Cerebrovascular Disease Developmental Disorders Gastrointestinal & Liver Disease Head Trauma & Post-Traumatic Epilepsy Hematologic Disorders Infectious States & Seizures Inflammatory Disorders Metabolic Disorders Migraine & Epilepsy Pulmonary Disorders Renal Disorders Sleep Disorders Transplantation & Seizures SPECIALIZED POPULATIONS DIAGNOSIS & TREATMENT HALLWAY CONVERSATIONS CONFERENCE WEBCASTS CONTINUING MEDICAL EDUCATION RESOURCE LIBRARY Reporting from the First North American Regional Epilepsy Congress (AES & CLAE Annual Meetings) Pathways to Discovery in Epilepsy Research: Rethinking the Quest for Cures – Dan Lowenstein, MD presents the Judith Hoyer Lecture in Epilepsy Are Those with Epilepsy Excessive Caffeine Drinkers? Some Patients with Epilepsy Drive Against Doctors’ Orders Polyunsaturated Fats for Treatment of Refractory Epilepsy: Disappointing Results Are Newer Antiepileptic Drugs Being Used in the Elderly? Great selection and pricing on all sorts of products from all sorts of merchants and a chance to support your website and epilepsy research. Sarcoidosis Co-Existing Disorders > Inflammatory Disorders > Sarcoidosis Author: L Seiden and A Krumholz Sarcoidosis is a multisystem granulomatous disorder. Its precise etiology is unknown, but there is evidence that it is caused by heightened immune processes at the sites of disease activity.49 Sarcoidosis can be thought of as an inflammatory response to an unidentified foreign antigen.49-54 The central pathologic hallmark of sarcoidosis, the granuloma (see figure), consists of macrophages, macrophage-derived epithelioid cells, and multinucleated giant cells that secrete cytokines. Around this central core exist CD4 and CD8 lymphocytes, B lymphocytes, plasma cells, and fibroblasts. The lymphocytes are thought to be stimulated by antigen presentation by activated macrophages present at sites of inflammation.55-60 Left: Photomicrograph at 200 magnification of a brain showing an intraparenchymal noncaseating or non-necrotizing sarcoid granuloma. Right: Photomicrograph at 400 magnification of a sarcoid granuloma in the brain, demonstrating a multinucleated giant cell. In reaction to an antigen, monocytes and macrophages form granulomas. Ultimately, irreversible obliterative fibrosis can develop. Furthermore, small foci of ischemic necrosis can be found, probably because of vascular compromise due to perivascular inflammation. Importantly, these granulomas are not specific for sarcoidosis. Indistinguishable or nearly identical lesions occur in a variety of other conditions that must be excluded before a diagnosis of sarcoidosis can be made with certainty. Sarcoidosis usually presents between the ages of 20 and 40 years but it also occurs in children and older populations. Clinical manifestations appear similar in all age groups. Intrathoracic structures are most commonly affected, followed by lymph node, skin, and ocular disease: Frequency of organ involvement in sarcoidosis Manifestation Frequency (%) Intrathoracic 87 Hilar nodes 72 Lung parenchyma 46 Upper respiratory tract 6 Dermatologic — Skin 18 Erythema nodosum 15 Ocular 15 Lacrimal 3 Parotid 6 Splenomegaly 10 Peripheral lymphadenopathy 28 Bone 3 Cardiac 3 Hepatomegaly 10 Hypercalcemia 13 Neurologic 5 Hematologic Rare Endocrinologic Rare Gastrointestinal and genitourinary Rare Anatomic presence of the disease in any organ is possible and often occurs without overt clinical evidence of dysfunction. Sarcoidosis can present with constitutional symptoms and pulmonary or extrapulmonary manifestations, or it may be asymptomatic. It is estimated that 20-40% of patients are asymptomatic at presentation, with their disease being discovered by routine chest radiography.50 Neurologic Manifestations Neurologic symptoms are the presenting feature of sarcoidosis in one-half of individuals with neurosarcoidosis.42,43 One-third to one-half of neurosarcoidosis patients develop more than one neurologic manifestation of their disease: Clinical manifestation Approximate frequency (%) Cranial neuropathy 50-75 Facial palsy 25-50 Aseptic meningitis 10-20 Hydrocephalus 10 Parenchymal disease — Endocrinopathy 10-15 Mass lesion(s) 5-10 Encephalopathy/vasculopathy 5-10 Seizures 5-10 Neuropathy 5-10 Myopathy 10 Only rarely do patients with neurosarcoidosis have no evidence of disease in other organ systems, such as the lung.42,44-47,61,62 Systemic disease may not always be evident early in a patient's clinical course, however.Because of its varied manifestations, neurosarcoidosis is in the differential diagnosis of many unexplained neurologic syndromes. The diagnosis of sarcoidosis is most secure when based on pathology and when more than one organ system can be documented to be involved. Because tissue from the nervous system is difficult to secure for pathologic analysis and other tests are not diagnostic of neurosarcoidosis, however, the diagnosis must sometimes remain tentative.Palsy of the facial nerve (cranial nerve VII) is the single most frequent neurologic manifestation of sarcoidosis. It develops in 25-50% of all patients with neurosarcoidosis. Although usually unilateral, bilateral facial palsy also can occur, presenting with either simultaneous or sequential paralysis. More than half of all patients with facial palsy also have other forms of nervous system involvement. In general, the prognosis for the facial palsy is good, with more than 80% of patients having a good recovery of function.42,47 Hydrocephalus, affecting about 10% of neurosarcoidosis patients, is a potentially lethal complication. Patients with acute hydrocephalus may die suddenly from increased intracranial pressure, and even patients with chronic hydrocephalus have the potential to acutely decompensate. Patients with acute hydrocephalus characteristically present with headache, altered mentation or consciousness, and impaired gait. On examination, papilledema or other signs of raised intracranial pressure can be found. Acute decompensating hydrocephalus is a medical emergency that requires prompt diagnosis and treatment. Parenchymal brain disease is reported in about half of patients with neurosarcoidosis. It can present in several forms. The most common is hypothalamic dysfunction. This usually involves the neuroendocrinologic system or "vegetative functions." Neuroendocrinologic disease in sarcoidosis can also be secondary to pituitary disease. Any of the neuroendocrinologic systems can be affected by sarcoidosis.42 Potential endocrinologic manifestations of neurosarcoidosis include thyroid disorders, disorders of cortisol metabolism, and sexual dysfunction. An elevated serum prolactin level, found in 3-32% of patients with sarcoidosis, may be an indication of hypothalamic dysfunction. Hypothalamic disorders that affect vegetative functions vary considerably. A disorder of thirst is the most common hypothalamic disorder related to neurosarcoidosis and is attributed to a change in the hypothalamic "osmostat." More rarely, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can occur.43,63 These hypothalamic disorders can lead to severe hyponatremia, which can cause seizures. Neurosarcoidosis-induced disruptions of hypothalamic function also have been described as causing disorders of appetite, libido, temperature control, weight regulation, and sleep.43,63 Intraparenchymal mass lesions due to sarcoidosis may present as an isolated mass (see figure) or masses occurring in any cerebral area or multiple cerebral nodules. Subdural plaquelike masses may mimic meningiomas. Calcifications may also be seen. In the past, intraparenchymal mass lesions were considered rare, but CT and MRI have shown them to be more frequent than previously thought. This MRI (axial, T1 with gadolinium) shows a frontal intracerebral mass that was proven by biopsy to be neurosarcoidosis. The diffuse encephalopathy and vasculopathy associated with neurosarcoidosis are not well understood. Moreover, it is often difficult, both clinically and pathologically, to separate these entities clearly and they frequently coexist. For these reasons, they can be considered as a single overlapping entity, but one form or the other may predominate in an individual patient.42 Figure 3 shows an example of the MRI changes in a patient with neurosarcoid encephalopathy. This MRI (axial, T2-weighted) shows a large area of abnormality in the temporal lobe, which proved at biopsy to be sarcoidosis manifesting with a focal encephalopathy or vasculopathy. This patient presented with seizures. Seizures are an important manifestation of CNS parenchymal disease due to neurosarcoidosis, and their significance has recently been better understood.48 They have been reported in up to 20% of patients with neurosarcoidosis and may be focal or generalized. Seizures in neurosarcoidosis have been correlated with a poor prognosis. 64 The poor prognosis of neurosarcoidosis patients with seizures is due not to the seizures themselves but rather to the fact that seizures are an indicator for the presence of severe CNS parenchymal disease or hydrocephalus. This more severe pathology produces a higher risk for progressive or recurrent disease or death.48,64 Diagnosis of neurosarcoidosis Patients without documented systemic sarcoidosis When a patient without documented systemic sarcoidosis develops a clinical syndrome suggestive of neurosarcoidosis, confirming evidence for sarcoidosis should be sought in other organ systems. Such systemic disease can best be documented when a thorough, systematic evaluation based on the known natural history of sarcoidosis is undertaken (see first table above). Because sarcoidosis most frequently affects intrathoracic structures, followed by lymph node, skin, and ocular disease, histologic support for a diagnosis of sarcoidosis should be pursued in those areas, following leads obtained from the patient's clinical evaluation. Pulmonary involvement is so common in sarcoidosis that this should be the first organ system to consider when attempting to establish the presence of systemic sarcoidosis. Indeed, nearly 90% of patients with sarcoidosis are reported to show radiographic evidence of pulmonary involvement.65 Although an abnormal chest x-ray can be supportive evidence for the diagnosis of sarcoidosis, however, it is not necessarily specific or pathognomonic for sarcoidosis. Additional evidence to support pulmonary involvement can be obtained from pulmonary function testing, including diffusion capacity. When chest x-rays or pulmonary function studies suggest pulmonary involvement, a diagnosis of sarcoidosis is confirmed by obtaining histologic evidence of sarcoidosis with a transbronchial biopsy. To better define the extent of lung or lymph node involvement, chest CT imaging also can be useful. A diagnosis of sarcoidosis is most secure when it is based on histologic confirmation, but on average, 30% lack histologic confirmation, and the diagnosis is often based solely on clinical and radiologic findings.50Active sarcoidosis may cause an elevation in serum angiotensin-converting enzyme (SACE), which can then serve as a marker of the disease.51 Although it is the most specific laboratory test associated with sarcoidosis, SACE is not highly sensitive; just 50-60% of active sarcoidosis patients show abnormalities. Nor is it very specific; it is also often elevated in patients with other conditions, such as liver disease, diabetes mellitus, hyperthyroidism, systemic infection, malignancy, and Gaucher's disease.51,66 Patients with documented systemic sarcoidosis WHO IS EPILEPSY.COM/PROFESSIONALS DONATE ABOUT EPILEPSY & SEIZURES CO-EXISTING DISORDERS Brain Tumors Cardiac Disorders Cerebrovascular Disease Developmental Disorders Gastrointestinal & Liver Disease Head Trauma & Post-Traumatic Epilepsy Hematologic Disorders Infectious States & Seizures Inflammatory Disorders Metabolic Disorders Migraine & Epilepsy Pulmonary Disorders Renal Disorders Sleep Disorders Transplantation & Seizures SPECIALIZED POPULATIONS DIAGNOSIS & TREATMENT HALLWAY CONVERSATIONS CONFERENCE WEBCASTS CONTINUING MEDICAL EDUCATION RESOURCE LIBRARY Reporting from the First North American Regional Epilepsy Congress (AES & CLAE Annual Meetings) Pathways to Discovery in Epilepsy Research: Rethinking the Quest for Cures – Dan Lowenstein, MD presents the Judith Hoyer Lecture in Epilepsy Are Those with Epilepsy Excessive Caffeine Drinkers? Some Patients with Epilepsy Drive Against Doctors’ Orders Polyunsaturated Fats for Treatment of Refractory Epilepsy: Disappointing Results Are Newer Antiepileptic Drugs Being Used in the Elderly? Great selection and pricing on all sorts of products from all sorts of merchants and a chance to support your website and epilepsy research. Sarcoidosis Co-Existing Disorders > Inflammatory Disorders > Sarcoidosis Author: L Seiden and A Krumholz Sarcoidosis is a multisystem granulomatous disorder. Its precise etiology is unknown, but there is evidence that it is caused by heightened immune processes at the sites of disease activity.49 Sarcoidosis can be thought of as an inflammatory response to an unidentified foreign antigen.49-54 The central pathologic hallmark of sarcoidosis, the granuloma (see figure), consists of macrophages, macrophage-derived epithelioid cells, and multinucleated giant cells that secrete cytokines. Around this central core exist CD4 and CD8 lymphocytes, B lymphocytes, plasma cells, and fibroblasts. The lymphocytes are thought to be stimulated by antigen presentation by activated macrophages present at sites of inflammation.55-60 Left: Photomicrograph at 200 magnification of a brain showing an intraparenchymal noncaseating or non-necrotizing sarcoid granuloma. Right: Photomicrograph at 400 magnification of a sarcoid granuloma in the brain, demonstrating a multinucleated giant cell. In reaction to an antigen, monocytes and macrophages form granulomas. Ultimately, irreversible obliterative fibrosis can develop. Furthermore, small foci of ischemic necrosis can be found, probably because of vascular compromise due to perivascular inflammation. Importantly, these granulomas are not specific for sarcoidosis. Indistinguishable or nearly identical lesions occur in a variety of other conditions that must be excluded before a diagnosis of sarcoidosis can be made with certainty. Sarcoidosis usually presents between the ages of 20 and 40 years but it also occurs in children and older populations. Clinical manifestations appear similar in all age groups. Intrathoracic structures are most commonly affected, followed by lymph node, skin, and ocular disease: Frequency of organ involvement in sarcoidosis Manifestation Frequency (%) Intrathoracic 87 Hilar nodes 72 Lung parenchyma 46 Upper respiratory tract 6 Dermatologic — Skin 18 Erythema nodosum 15 Ocular 15 Lacrimal 3 Parotid 6 Splenomegaly 10 Peripheral lymphadenopathy 28 Bone 3 Cardiac 3 Hepatomegaly 10 Hypercalcemia 13 Neurologic 5 Hematologic Rare Endocrinologic Rare Gastrointestinal and genitourinary Rare Anatomic presence of the disease in any organ is possible and often occurs without overt clinical evidence of dysfunction. Sarcoidosis can present with constitutional symptoms and pulmonary or extrapulmonary manifestations, or it may be asymptomatic. It is estimated that 20-40% of patients are asymptomatic at presentation, with their disease being discovered by routine chest radiography.50 Neurologic Manifestations Neurologic symptoms are the presenting feature of sarcoidosis in one-half of individuals with neurosarcoidosis.42,43 One-third to one-half of neurosarcoidosis patients develop more than one neurologic manifestation of their disease: Clinical manifestation Approximate frequency (%) Cranial neuropathy 50-75 Facial palsy 25-50 Aseptic meningitis 10-20 Hydrocephalus 10 Parenchymal disease — Endocrinopathy 10-15 Mass lesion(s) 5-10 Encephalopathy/vasculopathy 5-10 Seizures 5-10 Neuropathy 5-10 Myopathy 10 Only rarely do patients with neurosarcoidosis have no evidence of disease in other organ systems, such as the lung.42,44-47,61,62 Systemic disease may not always be evident early in a patient's clinical course, however.Because of its varied manifestations, neurosarcoidosis is in the differential diagnosis of many unexplained neurologic syndromes. The diagnosis of sarcoidosis is most secure when based on pathology and when more than one organ system can be documented to be involved. Because tissue from the nervous system is difficult to secure for pathologic analysis and other tests are not diagnostic of neurosarcoidosis, however, the diagnosis must sometimes remain tentative.Palsy of the facial nerve (cranial nerve VII) is the single most frequent neurologic manifestation of sarcoidosis. It develops in 25-50% of all patients with neurosarcoidosis. Although usually unilateral, bilateral facial palsy also can occur, presenting with either simultaneous or sequential paralysis. More than half of all patients with facial palsy also have other forms of nervous system involvement. In general, the prognosis for the facial palsy is good, with more than 80% of patients having a good recovery of function.42,47 Hydrocephalus, affecting about 10% of neurosarcoidosis patients, is a potentially lethal complication. Patients with acute hydrocephalus may die suddenly from increased intracranial pressure, and even patients with chronic hydrocephalus have the potential to acutely decompensate. Patients with acute hydrocephalus characteristically present with headache, altered mentation or consciousness, and impaired gait. On examination, papilledema or other signs of raised intracranial pressure can be found. Acute decompensating hydrocephalus is a medical emergency that requires prompt diagnosis and treatment. Parenchymal brain disease is reported in about half of patients with neurosarcoidosis. It can present in several forms. The most common is hypothalamic dysfunction. This usually involves the neuroendocrinologic system or "vegetative functions." Neuroendocrinologic disease in sarcoidosis can also be secondary to pituitary disease. Any of the neuroendocrinologic systems can be affected by sarcoidosis.42 Potential endocrinologic manifestations of neurosarcoidosis include thyroid disorders, disorders of cortisol metabolism, and sexual dysfunction. An elevated serum prolactin level, found in 3-32% of patients with sarcoidosis, may be an indication of hypothalamic dysfunction. Hypothalamic disorders that affect vegetative functions vary considerably. A disorder of thirst is the most common hypothalamic disorder related to neurosarcoidosis and is attributed to a change in the hypothalamic "osmostat." More rarely, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can occur.43,63 These hypothalamic disorders can lead to severe hyponatremia, which can cause seizures. Neurosarcoidosis-induced disruptions of hypothalamic function also have been described as causing disorders of appetite, libido, temperature control, weight regulation, and sleep.43,63 Intraparenchymal mass lesions due to sarcoidosis may present as an isolated mass (see figure) or masses occurring in any cerebral area or multiple cerebral nodules. Subdural plaquelike masses may mimic meningiomas. Calcifications may also be seen. In the past, intraparenchymal mass lesions were considered rare, but CT and MRI have shown them to be more frequent than previously thought. This MRI (axial, T1 with gadolinium) shows a frontal intracerebral mass that was proven by biopsy to be neurosarcoidosis. The diffuse encephalopathy and vasculopathy associated with neurosarcoidosis are not well understood. Moreover, it is often difficult, both clinically and pathologically, to separate these entities clearly and they frequently coexist. For these reasons, they can be considered as a single overlapping entity, but one form or the other may predominate in an individual patient.42 Figure 3 shows an example of the MRI changes in a patient with neurosarcoid encephalopathy. This MRI (axial, T2-weighted) shows a large area of abnormality in the temporal lobe, which proved at biopsy to be sarcoidosis manifesting with a focal encephalopathy or vasculopathy. This patient presented with seizures. Seizures are an important manifestation of CNS parenchymal disease due to neurosarcoidosis, and their significance has recently been better understood.48 They have been reported in up to 20% of patients with neurosarcoidosis and may be focal or generalized. Seizures in neurosarcoidosis have been correlated with a poor prognosis. 64 The poor prognosis of neurosarcoidosis patients with seizures is due not to the seizures themselves but rather to the fact that seizures are an indicator for the presence of severe CNS parenchymal disease or hydrocephalus. This more severe pathology produces a higher risk for progressive or recurrent disease or death.48,64 Diagnosis of neurosarcoidosis Patients without documented systemic sarcoidosis When a patient without documented systemic sarcoidosis develops a clinical syndrome suggestive of neurosarcoidosis, confirming evidence for sarcoidosis should be sought in other organ systems. Such systemic disease can best be documented when a thorough, systematic evaluation based on the known natural history of sarcoidosis is undertaken (see first table above). Because sarcoidosis most frequently affects intrathoracic structures, followed by lymph node, skin, and ocular disease, histologic support for a diagnosis of sarcoidosis should be pursued in those areas, following leads obtained from the patient's clinical evaluation. Pulmonary involvement is so common in sarcoidosis that this should be the first organ system to consider when attempting to establish the presence of systemic sarcoidosis. Indeed, nearly 90% of patients with sarcoidosis are reported to show radiographic evidence of pulmonary involvement.65 Although an abnormal chest x-ray can be supportive evidence for the diagnosis of sarcoidosis, however, it is not necessarily specific or pathognomonic for sarcoidosis. Additional evidence to support pulmonary involvement can be obtained from pulmonary function testing, including diffusion capacity. When chest x-rays or pulmonary function studies suggest pulmonary involvement, a diagnosis of sarcoidosis is confirmed by obtaining histologic evidence of sarcoidosis with a transbronchial biopsy. To better define the extent of lung or lymph node involvement, chest CT imaging also can be useful. A diagnosis of sarcoidosis is most secure when it is based on histologic confirmation, but on average, 30% lack histologic confirmation, and the diagnosis is often based solely on clinical and radiologic findings.50Active sarcoidosis may cause an elevation in serum angiotensin-converting enzyme (SACE), which can then serve as a marker of the disease.51 Although it is the most specific laboratory test associated with sarcoidosis, SACE is not highly sensitive; just 50-60% of active sarcoidosis patients show abnormalities. Nor is it very specific; it is also often elevated in patients with other conditions, such as liver disease, diabetes mellitus, hyperthyroidism, systemic infection, malignancy, and Gaucher's disease.51,66 Patients with documented systemic sarcoidosis More to come in 2nd email. Quote Link to comment Share on other sites More sharing options...
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