This document discusses hereditary neuropathy, specifically Charcot-Marie-Tooth disease. It provides information on:
1) Charcot-Marie-Tooth disease is a group of disorders characterized by a chronic motor and sensory polyneuropathy caused by mutations that affect the structure and function of Schwann cells and peripheral neuron axons.
2) It has several clinical presentations and classifications based on inheritance, age of onset, electrodiagnostic features, and genetic testing. The most common types are autosomal dominant demyelinating CMT1 and axonal CMT2.
3) Management involves a multidisciplinary approach including physical therapy, orthotics, occupational therapy, and pain management, as there are currently
This document provides information on myelopathy and spinal cord lesions:
- Myelopathy describes any neurological deficit related to the spinal cord, and can cause quadriplegia, paraplegia, sensory deficits, and autonomic disturbances. It can be inflammatory (myelitis) or vascular in nature (vascular myelopathy).
- Cervical spondylotic myelopathy is the most common form of myelopathy. Lesions of the spinal cord can be compressive (intramedullary or extramedullary) or non-compressive.
- Different levels of spinal cord lesions present with distinct symptoms, such as sensory losses in specific dermatomes or weaknesses of particular muscles. Features help
This document provides an overview of congenital myopathies and congenital muscular dystrophies. It defines congenital myopathies as muscle disorders presenting in infancy with generalized muscle weakness and hypotonia. Several types of congenital myopathies are described based on their histopathological features, including nemaline myopathy, central core disease, centronuclear myopathy, and congenital fiber type disproportion. The clinical features, investigations, pathology, genetics, and management are discussed for each type. Congenital muscular dystrophies are also briefly introduced.
This document summarizes different types of Charcot-Marie-Tooth disease (CMT), a group of inherited neuropathies. It describes the main clinical features and genetic causes of the most common types: CMT1 (demyelinating), CMT2 (axonal), CMTX (X-linked), and CMT3 and CMT4 (severe childhood forms). The document provides details on onset, symptoms, electrodiagnostic findings, pathology, and genetic subtypes for each CMT classification.
This document provides details about myotonia, including its clinical presentation and underlying pathophysiology. It discusses:
1) Myotonia is defined as difficulty relaxing muscles after contraction and can affect different muscles to varying degrees. It is triggered by specific conditions and muscle groups.
2) Clinically, myotonia of the eyelids, tongue, hands, and legs can be observed and specific tests are described. Electromyography shows characteristic repetitive discharges.
3) The causes of myotonia include genetic channelopathies like myotonic dystrophy types 1 and 2, myotonia congenita, and periodic paralysis. Clinical features and genetic underpinnings are discussed for each condition.
Hereditary neuropathies are a diverse group of inherited conditions affecting the peripheral nervous system. They are frequently underdiagnosed due to their indolent onset over decades and lack of clear family history in some cases. Charcot-Marie-Tooth disease is the most common inherited neuropathy, with two main types - CMT1 characterized by demyelination and CMT2 characterized by axonal loss. CMT1 results from mutations affecting myelin protein zero or peripheral myelin protein 22 genes, causing demyelination and onion bulb formation. Accurate diagnosis relies on detailed family history, neurological examination, and electrodiagnostic testing to distinguish inherited from acquired neuropathies.
Neurosyphilis is an infection of the nervous system caused by the bacterium Treponema pallidum, which causes syphilis. It typically develops after many years of untreated syphilis. Symptoms vary depending on the areas affected but may include mental deterioration, paralysis, meningitis, tabes dorsalis resulting in girdle pain and joint damage, and ocular symptoms. Treatment involves intravenous penicillin, but neurosyphilis can still cause permanent damage. Nursing care focuses on maintaining patient health, safety, and independence through measures like seizure precautions, skin care, physiotherapy, and partner screening.
This document provides information on myelopathy and spinal cord lesions:
- Myelopathy describes any neurological deficit related to the spinal cord, and can cause quadriplegia, paraplegia, sensory deficits, and autonomic disturbances. It can be inflammatory (myelitis) or vascular in nature (vascular myelopathy).
- Cervical spondylotic myelopathy is the most common form of myelopathy. Lesions of the spinal cord can be compressive (intramedullary or extramedullary) or non-compressive.
- Different levels of spinal cord lesions present with distinct symptoms, such as sensory losses in specific dermatomes or weaknesses of particular muscles. Features help
This document provides an overview of congenital myopathies and congenital muscular dystrophies. It defines congenital myopathies as muscle disorders presenting in infancy with generalized muscle weakness and hypotonia. Several types of congenital myopathies are described based on their histopathological features, including nemaline myopathy, central core disease, centronuclear myopathy, and congenital fiber type disproportion. The clinical features, investigations, pathology, genetics, and management are discussed for each type. Congenital muscular dystrophies are also briefly introduced.
This document summarizes different types of Charcot-Marie-Tooth disease (CMT), a group of inherited neuropathies. It describes the main clinical features and genetic causes of the most common types: CMT1 (demyelinating), CMT2 (axonal), CMTX (X-linked), and CMT3 and CMT4 (severe childhood forms). The document provides details on onset, symptoms, electrodiagnostic findings, pathology, and genetic subtypes for each CMT classification.
This document provides details about myotonia, including its clinical presentation and underlying pathophysiology. It discusses:
1) Myotonia is defined as difficulty relaxing muscles after contraction and can affect different muscles to varying degrees. It is triggered by specific conditions and muscle groups.
2) Clinically, myotonia of the eyelids, tongue, hands, and legs can be observed and specific tests are described. Electromyography shows characteristic repetitive discharges.
3) The causes of myotonia include genetic channelopathies like myotonic dystrophy types 1 and 2, myotonia congenita, and periodic paralysis. Clinical features and genetic underpinnings are discussed for each condition.
Hereditary neuropathies are a diverse group of inherited conditions affecting the peripheral nervous system. They are frequently underdiagnosed due to their indolent onset over decades and lack of clear family history in some cases. Charcot-Marie-Tooth disease is the most common inherited neuropathy, with two main types - CMT1 characterized by demyelination and CMT2 characterized by axonal loss. CMT1 results from mutations affecting myelin protein zero or peripheral myelin protein 22 genes, causing demyelination and onion bulb formation. Accurate diagnosis relies on detailed family history, neurological examination, and electrodiagnostic testing to distinguish inherited from acquired neuropathies.
Neurosyphilis is an infection of the nervous system caused by the bacterium Treponema pallidum, which causes syphilis. It typically develops after many years of untreated syphilis. Symptoms vary depending on the areas affected but may include mental deterioration, paralysis, meningitis, tabes dorsalis resulting in girdle pain and joint damage, and ocular symptoms. Treatment involves intravenous penicillin, but neurosyphilis can still cause permanent damage. Nursing care focuses on maintaining patient health, safety, and independence through measures like seizure precautions, skin care, physiotherapy, and partner screening.
Absence seizures typically have two peaks in age of onset, between 5-8 years and near 12 years. Childhood absence epilepsy (CAE) accounts for 10-17% of childhood epilepsy cases and is characterized by brief seizures without aura or postictal period. Typical absence seizures involve eye blinking or movements lasting a few seconds accompanied by generalized spike-and-wave discharges on EEG. Treatment typically begins with ethosuximide, though valproate or lamotrigine may be used if generalized tonic-clonic seizures are also present. While often labeled benign, CAE has variable outcomes, with some studies finding generalized tonic-clonic seizures develop later in 40% of cases.
This document discusses sensory ataxia, including its causes, clinical presentation, and differential diagnosis. Sensory ataxia results from disorders of the cerebellum, vestibular system, or sensory pathways. It is characterized by incoordination without significant weakness. Key findings include impaired proprioception, positive Romberg's sign, pseudoathetosis, and loss of vibration or joint position sense. Causes include peripheral neuropathies, paraneoplastic disorders, infections like HIV, autoimmune conditions like Sjogren's syndrome, and medications like chemotherapy. Dorsal root ganglionopathies commonly underlie sensory ataxia and can be assessed through nerve conduction studies and lumbar puncture. Distinguishing sensory
Duchenne Muscular Dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin gene leading to progressive muscle weakness. It mainly affects boys and symptoms start between ages 2-3. Affected children become wheelchair bound by age 12 and have life-threatening heart, respiratory, and orthopedic complications if not properly managed. Management involves monitoring for cardiomyopathy, respiratory support, orthopedic care, corticosteroids which can prolong ambulation, and future therapies like gene therapy aim to treat the underlying genetic cause.
The document discusses cerebellar ataxia and provides an outline for a lecture on the topic. It begins with definitions of ataxia and discusses the challenges in diagnosing cerebellar ataxia. It then presents a clinical scenario of a patient and outlines the topics to be covered in the lecture, including anatomy and physiology of the cerebellum, diagnostic approaches, classifications of ataxias, hereditary and acquired ataxias, treatment options, and conclusions.
Hereditary motor and sensory neuropathyHazel Panabe
Hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease, is the most common inherited neuromuscular disorder. It is characterized by slowly progressive distal weakness and muscle atrophy in the legs and later in the hands. There are two major types - one with slow nerve conduction velocities associated with demyelinating neuropathy, and one with relatively normal nerve conduction velocities associated with axonal degeneration. Most families demonstrate autosomal dominant inheritance with a 50% chance of offspring being affected if a parent has the disease.
This document provides an overview of the approach to evaluating and diagnosing ataxia. It begins with definitions of ataxia and discusses tests to differentiate various systems that can cause ataxia-mimicking symptoms. It then covers approaches to evaluating cerebellar ataxia, including assessing mode of onset, progression, focal vs symmetric involvement, and localizing the lesion. Common etiologies of acquired, inherited, autosomal dominant and recessive ataxias are summarized. The document provides a step-wise algorithm for evaluating and categorizing ataxia.
This document provides information on spinal muscular atrophy (SMA), including its genetics, epidemiology, classification, clinical features, diagnosis, management, and clinical trials of potential treatments. SMA is caused by a loss of motor neurons in the spinal cord due to a defect in the SMN1 gene and results in progressive muscle weakness. It is classified into five types based on age of onset and severity. Current management involves a multidisciplinary approach including nutritional and respiratory support as well as pharmacological treatments such as nusinersen, onasemnogene abeparvovec, and risdiplam which are being investigated in clinical trials as potential disease-modifying therapies.
Chiari malformations are a group of hindbrain abnormalities involving the rhombencephalon and cerebrospinal fluid junction. There are four main types of Chiari malformations described. Chiari type I involves tonsillar herniation below the foramen magnum without brainstem herniation. Chiari type II involves herniation of the brainstem, cerebellar vermis, and fourth ventricle and is associated with myelomeningocele. Chiari type III is an occipital encephalocele with similar anomalies to type II. Chiari type IV involves cerebellar hypoplasia without herniation. Clinical features of Chiari I can include headache, numbness, and
Floppy infant syndrome is characterized by reduced muscle tone and weakness in infants. It is caused by a variety of central nervous system and neuromuscular disorders. Causes can be divided into central/CNS issues ("floppy strong") or peripheral issues involving motor neurons, neuromuscular junction, or muscle disease ("floppy weak"). Evaluation involves examining family history, assessing signs and symptoms, and testing for conditions like metabolic myopathies, spinal muscular atrophy, or myasthenia gravis. Management depends on the underlying cause but may include respiratory support, treating infections, and specialist referrals. Prognosis varies greatly depending on the specific condition causing floppiness.
Charcot-Marie-Tooth disease (CMT) is a group of inherited neurological disorders that damage the peripheral nerves, causing muscle weakness, loss of sensation in the feet and hands, and deformities. CMT is caused by genetic mutations that affect the myelin sheath or axons in the nerves. There are several types of CMT including CMT1, CMT2, CMT4 and CMTX, which are distinguished by their genetic causes and symptoms. Currently there is no cure for CMT but treatment focuses on managing symptoms through physical therapy, bracing, and surgery. Researchers are investigating potential new treatments to help prevent disability and progression of the disease.
Neuromyelitis optica (NMO), also known as Devic's disease, is an inflammatory disorder characterized by demyelination of the optic nerve and spinal cord. It is associated with antibodies against aquaporin-4 (AQP4-IgG). The disease predominantly affects women and typically presents with episodes of optic neuritis and transverse myelitis. MRI often shows long extensive lesions of the spinal cord. Treatment involves high-dose steroids for acute attacks and immunosuppressants like mycophenolate mofetil or rituximab to prevent relapses. Distinguishing NMO from multiple sclerosis is important for treatment, as some therapies effective for MS may worsen NMO.
EEG variants, are always to be recognized while interpreting the EEG one must be aware of these. Major and most common EEG is variants are discussed in the stated presentation.
Syed Irshad Murtaza.
This document discusses adult-onset spinal muscular atrophy (SMA), which can be caused by two main genetic disorders - SMA secondary to SMN1 gene mutations and spinal and bulbar muscular atrophy (SBMA, also known as Kennedy disease). SMA secondary to SMN1 mutations can present in adulthood as Type 4 SMA, characterized by remaining ambulant without respiratory assistance. SBMA is an X-linked disorder caused by a CAG repeat expansion in the androgen receptor gene, with onset typically in the second to seventh decade and slowly progressive weakness.
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by progressive supranuclear ophthalmoplegia, gait disturbance, postural instability, and cognitive and behavioral changes. It is caused by tau protein deposits in the brain and is the most common form of atypical parkinsonism. There is no cure for PSP and treatment aims to manage symptoms, though investigational therapies targeting tau are being explored. The prognosis is poor, with most patients becoming dependent within 3-4 years and median survival of 6-12 years after diagnosis.
Tuberous sclerosis complex (TSC) is a genetic disorder characterized by benign tumors that develop in many organs, including the brain, eyes, heart, lungs, kidneys and skin. It is caused by mutations in either the TSC1 or TSC2 gene. Major features seen on imaging include cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas. These lesions appear at specific locations and with characteristic appearances on CT and MRI scans that are useful for diagnosis. Treatment may involve medication or surgery depending on the impact of the lesions.
Peripheral neuropathy refers to damage to peripheral nerves. There are three main types: mononeuropathy affecting a single nerve, mononeuritis multiplex affecting multiple nerves asymmetrically, and polyneuropathy affecting multiple nerves concurrently and symmetrically. Polyneuropathy can be classified as axonopathy, myelinopathy, or neuronopathy depending on whether the axons, myelin sheaths, or neurons are affected. Symptoms and signs include both negative symptoms like numbness and weakness as well as positive symptoms like tingling and pain. Evaluation involves taking a history and examining for patterns of onset, progression, fluctuations, and other systemic diseases. Diagnosis involves nerve conduction studies and sometimes nerve biopsies. Treatment focuses
This document provides an overview of ataxia, including its causes, symptoms, classifications, and treatments. It begins with definitions of ataxia and descriptions of common symptoms like gait instability and limb incoordination. It then covers various types and classifications of ataxia including cerebellar, sensory, cortical, myopathic, and others. Specific genetic causes of inherited ataxia are also outlined. The document emphasizes the importance of determining the mode of onset, progression, focal vs. symmetric involvement, and localization of lesions in evaluating ataxia. Treatments aim to address reversible causes or structural lesions surgically with other supportive measures.
Myotonic dystrophy is a genetic multisystemic disease characterized by muscle wasting, myotonia, cataracts and heart defects. There are two main types: DM1 caused by CTG repeats on chromosome 19, and DM2 caused by CCTG repeats on chromosome 21. Symptoms range from mild myotonia to severe congenital weakness. Diagnosis involves muscle biopsy, EMG, ECG and MRI. While there is no cure, treatment focuses on symptom relief using medications, physical therapy and surgery.
1. Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a progressive neurodegenerative disease that affects upper and lower motor neurons.
2. The disease causes muscle weakness, disability, and eventually death, with annual incidence rates of 1-3 cases per 100,000 people.
3. While ALS is typically a sporadic disease, about 10% of cases are familial or genetic. The disease progresses relentlessly over time, typically beginning in the limbs or bulbar region and spreading to other areas.
Neuroblastoma is the most common solid extracranial tumor in children. It arises from neural crest cells and can occur anywhere sympathetic nerves develop. The disease ranges from low to high risk based on factors like age, tumor stage and biology. Diagnosis involves imaging like CT, MRI and MIBG scans along with biopsy. Treatment depends on risk group and may include surgery, chemotherapy, radiation and stem cell transplant. Complete surgical resection offers the best outcome for localized disease.
Los días 11 y 12 de diciembre de 2014, la Fundación Ramón Areces celebró el Simposio Internacional 'Neuropatías periféricas hereditarias. Desde la biología a la terapéutica' en colaboración con CIBERER-ISCIII y el Centro de Investigación Príncipe Felipe. El tipo más común de estas patologías es la enfermedad de Charcot-Marie-Tooth, un trastorno neuromuscular hereditario con una prevalencia estimada de 17-40 afectados por 100.000 habitantes. Durante estos dos días, investigadores mostraron sus avances en la mejora del diagnóstico y el tratamiento y, por ende, de la aproximación clínica y la calidad de vida de las personas afectadas por estas patologías.
Absence seizures typically have two peaks in age of onset, between 5-8 years and near 12 years. Childhood absence epilepsy (CAE) accounts for 10-17% of childhood epilepsy cases and is characterized by brief seizures without aura or postictal period. Typical absence seizures involve eye blinking or movements lasting a few seconds accompanied by generalized spike-and-wave discharges on EEG. Treatment typically begins with ethosuximide, though valproate or lamotrigine may be used if generalized tonic-clonic seizures are also present. While often labeled benign, CAE has variable outcomes, with some studies finding generalized tonic-clonic seizures develop later in 40% of cases.
This document discusses sensory ataxia, including its causes, clinical presentation, and differential diagnosis. Sensory ataxia results from disorders of the cerebellum, vestibular system, or sensory pathways. It is characterized by incoordination without significant weakness. Key findings include impaired proprioception, positive Romberg's sign, pseudoathetosis, and loss of vibration or joint position sense. Causes include peripheral neuropathies, paraneoplastic disorders, infections like HIV, autoimmune conditions like Sjogren's syndrome, and medications like chemotherapy. Dorsal root ganglionopathies commonly underlie sensory ataxia and can be assessed through nerve conduction studies and lumbar puncture. Distinguishing sensory
Duchenne Muscular Dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin gene leading to progressive muscle weakness. It mainly affects boys and symptoms start between ages 2-3. Affected children become wheelchair bound by age 12 and have life-threatening heart, respiratory, and orthopedic complications if not properly managed. Management involves monitoring for cardiomyopathy, respiratory support, orthopedic care, corticosteroids which can prolong ambulation, and future therapies like gene therapy aim to treat the underlying genetic cause.
The document discusses cerebellar ataxia and provides an outline for a lecture on the topic. It begins with definitions of ataxia and discusses the challenges in diagnosing cerebellar ataxia. It then presents a clinical scenario of a patient and outlines the topics to be covered in the lecture, including anatomy and physiology of the cerebellum, diagnostic approaches, classifications of ataxias, hereditary and acquired ataxias, treatment options, and conclusions.
Hereditary motor and sensory neuropathyHazel Panabe
Hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease, is the most common inherited neuromuscular disorder. It is characterized by slowly progressive distal weakness and muscle atrophy in the legs and later in the hands. There are two major types - one with slow nerve conduction velocities associated with demyelinating neuropathy, and one with relatively normal nerve conduction velocities associated with axonal degeneration. Most families demonstrate autosomal dominant inheritance with a 50% chance of offspring being affected if a parent has the disease.
This document provides an overview of the approach to evaluating and diagnosing ataxia. It begins with definitions of ataxia and discusses tests to differentiate various systems that can cause ataxia-mimicking symptoms. It then covers approaches to evaluating cerebellar ataxia, including assessing mode of onset, progression, focal vs symmetric involvement, and localizing the lesion. Common etiologies of acquired, inherited, autosomal dominant and recessive ataxias are summarized. The document provides a step-wise algorithm for evaluating and categorizing ataxia.
This document provides information on spinal muscular atrophy (SMA), including its genetics, epidemiology, classification, clinical features, diagnosis, management, and clinical trials of potential treatments. SMA is caused by a loss of motor neurons in the spinal cord due to a defect in the SMN1 gene and results in progressive muscle weakness. It is classified into five types based on age of onset and severity. Current management involves a multidisciplinary approach including nutritional and respiratory support as well as pharmacological treatments such as nusinersen, onasemnogene abeparvovec, and risdiplam which are being investigated in clinical trials as potential disease-modifying therapies.
Chiari malformations are a group of hindbrain abnormalities involving the rhombencephalon and cerebrospinal fluid junction. There are four main types of Chiari malformations described. Chiari type I involves tonsillar herniation below the foramen magnum without brainstem herniation. Chiari type II involves herniation of the brainstem, cerebellar vermis, and fourth ventricle and is associated with myelomeningocele. Chiari type III is an occipital encephalocele with similar anomalies to type II. Chiari type IV involves cerebellar hypoplasia without herniation. Clinical features of Chiari I can include headache, numbness, and
Floppy infant syndrome is characterized by reduced muscle tone and weakness in infants. It is caused by a variety of central nervous system and neuromuscular disorders. Causes can be divided into central/CNS issues ("floppy strong") or peripheral issues involving motor neurons, neuromuscular junction, or muscle disease ("floppy weak"). Evaluation involves examining family history, assessing signs and symptoms, and testing for conditions like metabolic myopathies, spinal muscular atrophy, or myasthenia gravis. Management depends on the underlying cause but may include respiratory support, treating infections, and specialist referrals. Prognosis varies greatly depending on the specific condition causing floppiness.
Charcot-Marie-Tooth disease (CMT) is a group of inherited neurological disorders that damage the peripheral nerves, causing muscle weakness, loss of sensation in the feet and hands, and deformities. CMT is caused by genetic mutations that affect the myelin sheath or axons in the nerves. There are several types of CMT including CMT1, CMT2, CMT4 and CMTX, which are distinguished by their genetic causes and symptoms. Currently there is no cure for CMT but treatment focuses on managing symptoms through physical therapy, bracing, and surgery. Researchers are investigating potential new treatments to help prevent disability and progression of the disease.
Neuromyelitis optica (NMO), also known as Devic's disease, is an inflammatory disorder characterized by demyelination of the optic nerve and spinal cord. It is associated with antibodies against aquaporin-4 (AQP4-IgG). The disease predominantly affects women and typically presents with episodes of optic neuritis and transverse myelitis. MRI often shows long extensive lesions of the spinal cord. Treatment involves high-dose steroids for acute attacks and immunosuppressants like mycophenolate mofetil or rituximab to prevent relapses. Distinguishing NMO from multiple sclerosis is important for treatment, as some therapies effective for MS may worsen NMO.
EEG variants, are always to be recognized while interpreting the EEG one must be aware of these. Major and most common EEG is variants are discussed in the stated presentation.
Syed Irshad Murtaza.
This document discusses adult-onset spinal muscular atrophy (SMA), which can be caused by two main genetic disorders - SMA secondary to SMN1 gene mutations and spinal and bulbar muscular atrophy (SBMA, also known as Kennedy disease). SMA secondary to SMN1 mutations can present in adulthood as Type 4 SMA, characterized by remaining ambulant without respiratory assistance. SBMA is an X-linked disorder caused by a CAG repeat expansion in the androgen receptor gene, with onset typically in the second to seventh decade and slowly progressive weakness.
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by progressive supranuclear ophthalmoplegia, gait disturbance, postural instability, and cognitive and behavioral changes. It is caused by tau protein deposits in the brain and is the most common form of atypical parkinsonism. There is no cure for PSP and treatment aims to manage symptoms, though investigational therapies targeting tau are being explored. The prognosis is poor, with most patients becoming dependent within 3-4 years and median survival of 6-12 years after diagnosis.
Tuberous sclerosis complex (TSC) is a genetic disorder characterized by benign tumors that develop in many organs, including the brain, eyes, heart, lungs, kidneys and skin. It is caused by mutations in either the TSC1 or TSC2 gene. Major features seen on imaging include cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas. These lesions appear at specific locations and with characteristic appearances on CT and MRI scans that are useful for diagnosis. Treatment may involve medication or surgery depending on the impact of the lesions.
Peripheral neuropathy refers to damage to peripheral nerves. There are three main types: mononeuropathy affecting a single nerve, mononeuritis multiplex affecting multiple nerves asymmetrically, and polyneuropathy affecting multiple nerves concurrently and symmetrically. Polyneuropathy can be classified as axonopathy, myelinopathy, or neuronopathy depending on whether the axons, myelin sheaths, or neurons are affected. Symptoms and signs include both negative symptoms like numbness and weakness as well as positive symptoms like tingling and pain. Evaluation involves taking a history and examining for patterns of onset, progression, fluctuations, and other systemic diseases. Diagnosis involves nerve conduction studies and sometimes nerve biopsies. Treatment focuses
This document provides an overview of ataxia, including its causes, symptoms, classifications, and treatments. It begins with definitions of ataxia and descriptions of common symptoms like gait instability and limb incoordination. It then covers various types and classifications of ataxia including cerebellar, sensory, cortical, myopathic, and others. Specific genetic causes of inherited ataxia are also outlined. The document emphasizes the importance of determining the mode of onset, progression, focal vs. symmetric involvement, and localization of lesions in evaluating ataxia. Treatments aim to address reversible causes or structural lesions surgically with other supportive measures.
Myotonic dystrophy is a genetic multisystemic disease characterized by muscle wasting, myotonia, cataracts and heart defects. There are two main types: DM1 caused by CTG repeats on chromosome 19, and DM2 caused by CCTG repeats on chromosome 21. Symptoms range from mild myotonia to severe congenital weakness. Diagnosis involves muscle biopsy, EMG, ECG and MRI. While there is no cure, treatment focuses on symptom relief using medications, physical therapy and surgery.
1. Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a progressive neurodegenerative disease that affects upper and lower motor neurons.
2. The disease causes muscle weakness, disability, and eventually death, with annual incidence rates of 1-3 cases per 100,000 people.
3. While ALS is typically a sporadic disease, about 10% of cases are familial or genetic. The disease progresses relentlessly over time, typically beginning in the limbs or bulbar region and spreading to other areas.
Neuroblastoma is the most common solid extracranial tumor in children. It arises from neural crest cells and can occur anywhere sympathetic nerves develop. The disease ranges from low to high risk based on factors like age, tumor stage and biology. Diagnosis involves imaging like CT, MRI and MIBG scans along with biopsy. Treatment depends on risk group and may include surgery, chemotherapy, radiation and stem cell transplant. Complete surgical resection offers the best outcome for localized disease.
Los días 11 y 12 de diciembre de 2014, la Fundación Ramón Areces celebró el Simposio Internacional 'Neuropatías periféricas hereditarias. Desde la biología a la terapéutica' en colaboración con CIBERER-ISCIII y el Centro de Investigación Príncipe Felipe. El tipo más común de estas patologías es la enfermedad de Charcot-Marie-Tooth, un trastorno neuromuscular hereditario con una prevalencia estimada de 17-40 afectados por 100.000 habitantes. Durante estos dos días, investigadores mostraron sus avances en la mejora del diagnóstico y el tratamiento y, por ende, de la aproximación clínica y la calidad de vida de las personas afectadas por estas patologías.
This document discusses Charcot-Marie-Tooth disease (CMT) and other genetic polyneuropathies. It covers the classification, genetics, clinical presentation, electrophysiology, diagnosis, and management of various types of CMT and hereditary sensory and autonomic neuropathies (HSAN). The majority of CMT cases are caused by mutations in the PMP22, MFN2, MPZ, or GJB1 genes. CMT is diagnosed through nerve conduction studies and genetic testing. Current management focuses on physical therapy, bracing, and orthopedic interventions to maintain function. HSAN affects sensory and autonomic nerves and is caused by mutations in various genes depending on the subtype.
Los días 11 y 12 de diciembre de 2014, la Fundación Ramón Areces celebró el Simposio Internacional 'Neuropatías periféricas hereditarias. Desde la biología a la terapéutica' en colaboración con CIBERER-ISCIII y el Centro de Investigación Príncipe Felipe. El tipo más común de estas patologías es la enfermedad de Charcot-Marie-Tooth, un trastorno neuromuscular hereditario con una prevalencia estimada de 17-40 afectados por 100.000 habitantes. Durante estos dos días, investigadores mostraron sus avances en la mejora del diagnóstico y el tratamiento y, por ende, de la aproximación clínica y la calidad de vida de las personas afectadas por estas patologías.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common chronic inflammatory neuropathy. CIDP is diagnosed according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria
https://www.youtube.com/watch?v=AYEhL1LdONY
Mfn2 hereditary motor and sensory neuropathysajjad46
This document summarizes information about the MFN2 gene and protein. It describes that MFN2 is located on chromosome 1p36.22 and encodes a 757 amino acid protein involved in mitochondrial fusion. Mutations in MFN2 can cause Charcot-Marie-Tooth disease type 2A, an inherited motor and sensory neuropathy. Symptoms include distal limb muscle weakness and atrophy. The document outlines the structure, functions, clinical significance, diagnosis, and treatment of conditions related to MFN2 mutations.
Presentation of Genomic Analysis of Non-NF2 Meningiomas Reveals Mutations in ...Kadir Sümerkent
This study analyzed the genomic profiles of 300 non-NF2 meningiomas and identified mutations in TRAF7, KLF4, AKT1, and SMO genes in addition to NF2 mutations. These mutations were mutually exclusive and defined distinct meningioma subtypes. Meningiomas with NF2 mutations were located in the cerebral hemispheres, while non-NF2 tumors originated from the skull base. Genomic analyses also revealed differences in chromosomal instability, gene expression, and histone modification between NF2 and non-NF2 subtypes. Identifying these genomic characteristics may help predict tumor behavior and inform targeted therapy approaches.
Paraneoplastic disorders of the peripheral nervous systemElectrodx Inr
Manifestaciones diversas en sistema nervioso periférico con relación a proceso oncológicos o su tratamiento, síndromes paraneoplásicos. Banderas rojas y alertas sobre su detección.
Plasmacytoma is a rare plasma cell neoplasm that can present as a solitary bone plasmacytoma (SBP) or extramedullary plasmacytoma (EMP). SBP most commonly involves the axial skeleton and presents with bone pain. EMP typically involves the upper aerodigestive tract and presents with symptoms related to site of involvement. Diagnosis involves biopsy and ruling out multiple myeloma. Radiotherapy is the primary treatment for both SBP and EMP and provides high rates of local control. Prognosis is generally good but some patients may progress to multiple myeloma.
Myasthenia Gravis is an autoimmune disorder of the neuromuscular junction where antibodies block neuromuscular transmission, reducing acetylcholine receptors. Clinical features include weakness of the eye muscles, face, neck, and limb muscles that worsens with activity and improves with rest. Diagnosis involves fatigue testing, pharmacological testing with edrophonium, electrical studies showing decremental responses, and serological testing for antibodies. Treatment includes anticholinesterases, steroids, immunosuppressants, IVIG, and plasmapheresis. Thymectomy may be considered for some patients.
1) Multiple sclerosis is an immune-mediated disease that causes inflammation and damage to the central nervous system, often resulting in disability. It primarily affects young and middle-aged adults.
2) Recent advances include more effective monoclonal antibody treatments like natalizumab that greatly reduce relapse rates, but also carry risks like progressive multifocal leukoencephalopathy.
3) New diagnostic criteria allow use of cortical lesions on MRI and certain biomarkers like neurofilament light chain levels provide additional insight into disease activity and progression.
This document discusses several neuromuscular disorders including spinal muscular atrophy (SMA), Charcot-Marie-Tooth disease, Guillain-Barré syndrome, myasthenia gravis, and transient neonatal myasthenia. SMA is caused by homozygous deletions of the SMN1 gene and presents as progressive muscle weakness. Charcot-Marie-Tooth disease is the most common inherited neuropathy and causes a steppage gait and muscle atrophy. Guillain-Barré syndrome is an acute autoimmune neuropathy that causes ascending paralysis. Myasthenia gravis is caused by antibodies against acetylcholine receptors and presents with fluctuating muscle weakness that worsens with activity. Transient
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2. THE BIOLOGY OF INHERITED PERIPHERAL
NEUROPATHIES
A common feature of the majority of genes mutated in CMT
is the role they play in maintaining the structure or function of the two
main cellular components of the peripheral nervous system, Schwann
cells and the axons of peripheral neurons.
3. Charcot-Marie-Tooth disease (CMT)
Charcot-Marie-Tooth (CMT) hereditary neuropathy
‘ a group of disorders characterized by a chronic motor and
sensory polyneuropathy, also known as hereditary motor and
sensory neuropathy (HMSN)’.
4. Clinical Presentation
prevalence-between 1 in 1213 to 1 in 2500.
Three common phenotype:
1)The typical phenotype - slowly progressive symmetric distal leg weakness with
sensory loss, usually beginning in the first to third decade and progressing to footdrop
and hand weakness .
O/E distal weakness and sensory loss, DTR -globally suppressed or absent.
At most, these patients require ankle-foot orthoses for ambulation.
5. 2) earlier onset of symptoms with delayed walking (after age 15 months or more), toe
walking, or clumsiness in childhood.
Patients with this phenotype progress to above-the-knee bracing, walkers, or
wheelchairs for ambulation.
3)adult onset (around 40 years) with variable subsequent progression.
Clinical Presentation
6. Classification of Charcot-Marie-Tooth
disease foot deformity.
A, First stage: flexible cavus foot, reducible.
B, Second stage: equinus and pronation of first ray (the
column of bones and joints forming the medial border of the
forefoot), possible reducible clawing of great toe.
C, Third stage: equinus of whole forefoot, varus of the heel,
irreducible clawing of great toe, no osseous structural
abnormalities.
D, Fourth stage: structural osseous changes, irreducible
clawing of toes, possible tarsal movements.
E-G, Fifth stage: firmly fixed deformity, pronounced osseous
changes, irreducible clawing of toes with subluxation or
luxation of metatarsophalangeal joints.
7. Classification:(based on electrodiagnostic
features and inheritance pattern).
1. autosomal dominant and a demyelinating - CMT type 1
2.autosomal dominant and an axonal - CMT type 2
3. autosomal recessive , regardless of the electrodiagnostic features-
CMT type 4 .
4. X-linked - CMT type X (CMTX).
8.
9.
10. Electrophysiology:
NCV- important tools to establish the presence of polyneuropathy, extent of
damage, and demyelinating versus axonal physiology.
Demyelinating forms of CMT are diagnosed based on uniformly slowed conduction
velocities of 38 meters per second or less in the upper extremities, without evidence
of conduction block or temporal dispersion (the latter two are features associated with acquired
demyelinating neuropathies).
Diagnosis of axonal forms is based on relatively normal velocities but prominently
reduced sensory nerve action potential (SNAP) amplitudes, reduced CMAP
amplitudes, or both.
11. Electrophysiology
In hereditary neuropathy, the electrophysiological changes are often already notably pronounced in early
adulthood.
CMT disorders can be classified into the following forms, according to the pattern of the damage/injury
1) Demyelinating:
injury to the myelin sheath; CMT1, motor nerve conduction velocity of the nerves in the arm <38 m/s
2)Axonal:
primary injury to the axon; CMT2, motor nerve conduction velocity of the nerves in the arm>38 m/s
3)Intermediate:
mixed forms of injury; motor nerve conduction velocity of the nerves in the arm 25–45 m/s.
12. Further diagnostic evaluation
Young age at manifestation and a positive familial history should give rise to the
suspicion of a hereditary neuropathy,
but thorough diagnostic evaluation is still required to rule out metabolic, nutritive-
toxic, infectious, and inflammatory or autoimmunological causes.
( CSF, ESR, Sr.creatinine, HbA1c, , ANA, ANCA, and vitamin B12,immunofixation
and protein electrophoresis , Nerve sonography- thickening of the nerves , MRI of
the muscle - distal muscular atrophy )
13. Nerve biopsy
The indication for a nerve biopsy (sural nerve) should be discussed
especially if non-hereditary neuropathies are considered as a
potentially treatable differential diagnosis.
These include inflammations such as vasculitis and perineuritis as well
as atypical cases of neuritis (chronic inflammatory demyelinating or
axonal neuropathy, CIDP or CIAP), a lymphoma affecting the nerves,
and amyloid neuropathy.
14. Genetics of Charcot-Marie-Tooth
Disease
>90% of patients with CMT -mutation in the PMP22, MFN2, MPZ, or GJB1gene.
Most cases of CMT- autosomal dominant.
Apprx 80% to 90% of cases of autosomal dominant CMT1 areCMT1A, which is due to
duplication of the PMP22 gene on chromosome 17p11.2, expressed in Schwann cells
One percent to nine percent are due to a PMP22 deletion, which causes hereditary
neuropathy with liability to pressure palsies (HNPP), presenting with recurrent
pressure palsies.
15. Genetics of Charcot-Marie-Tooth Disease
Of the autosomal dominant CMT1 cases, 10% are due to CMT1B, caused by
mutations in the MPZ gene, which results in deleterious overexpression of the major
myelin structural protein
CMT1X is caused by a mutation on the X chromosome in the GJB1 gene, also known
as the connexin 32 gene.
CMT2A accounts for 20% to 30% of all causes of CMT2 due to mutations in the
MFN2 gene.
The same CMT gene mutation can present in any of these three ways, demonstrating
the marked phenotypic variability of a single genotype
16.
17. An Approach to Diagnosis and
Genetic Testing
Obtaining a detailed three generation family pedigree- one of the most
important steps in establishing a possible diagnosis in CMT.
Patients should specifically be asked about early deaths in the extended family,
consanguinity, and family members with walking problems without a clear diagnosis.
More specific diagnosis provides the patient with the most accurate
inheritance and risk information, which is important in making reproductive
decisions.
Different mutations progress at different rates and are associated with
18.
19.
20. PROS & CONS of each genetic testing
Single Gene
Sequencing
(Traditional
genetic
testing)
PMP22, MPZ, GJB1,
MFN2, LITAF, EGR2,
RAB7, GARS, FEFL,
HSPB1, HSPB8,
GDAP1, SH3TC2,
PRX, FIG4, DNM2,
YARS, FGD4,
NDRG1, TRPV4,
MTMR2, SBF2, etc.
Good
historical
database to
track variants
of uncertain
significance;
Quick turn
around time
If testing for more than
one gene, can get
expensive.
If it is easy to
narrow down the
most likely type of
CMT to one to three
genes based on
clinical presentation
and family history.
TEST GENE PROS CONS BEST USE
21. Microarray Testing
(AKA array CGH,
aCGH)
PMP22 duplication/d
eletion
Cheap and
quick
Can only be used to
determine if someone has
CMT1A or HNPP. Can pick
up incidental findings if
there are duplications or
deletions in other parts of
the genome.
If someone has
classical signs of
CMT1A or HNPP, it is
the cheapest way to
determine if the
duplication or
deletion is present.
TEST GENE PROS CONS BEST USE
22. TEST GENE PROS CONS BEST USE
Next Generation
Sequencing
AARS , ATL1; DNM2; DNMT1;
DYNC1H1; EGR2; FGD4; GARS;
GDAP1; GJB1; GLA; HSPB1;
HSPB8; KIF1B; LITAF; LMNA;
LRSAM1; MED25; MFN2; MPZ;
MTMR2; NDRG1; NEFL; PMP22;
PRX; RAB7A; SBF2; SCN9A;
SH3TC2; SPTLC2; TRPV4; TTR;
YARS
Cheap
Many of the genes are only peripherally
associated with CMT – just known to
cause peripheral neuropathy.
Sequencing more genes can lead to
more variants and not necessarily a
clear result. Deletions and duplications
not picked up as well as in traditional
testing or CGH. Turn around time can
be lengthy.
Unusual presentation of CMT.
23. Key messages
Patients with an AD or sporadic demyelinating neuropathy should be tested using
the PMP22 duplication test.
Genetic testing for demyelinating Charcot-Marie-Tooth disease is recommended in
therapy refractory CIDP.
To find further explanations for hereditary neuropathies, a multitude of genes will
have to be considered because of genetic heterogeneity.
Next generation sequencing (NGS) is an effective testing method for peripheral
neuropathies and should be used early on in the stepwise diagnostic evaluation.
Integrating the results of NGS into the overall clinical picture requires close
collaboration between clinicians, neuropathologists, and human geneticists.
24. Management
Currently no disease-modifying treatment exists for CMT.
Current patient management can be optimized with a multidisciplinary
approach to care.
An annual evaluation by a neurologist, physiatrist, or both can assess the
patient’s function and continuing needs.
Physical therapy plays a major role in gait retraining, maintaining core muscle
strength, energy conservation, and use of serial casting and night splinting to
improve range of motion.
Occupational therapy can improve hand range of motion and provide tools to
improve activities of daily living, such as buttoning clothing, opening bottles,
and using eating utensils.
25. Management
An orthotist may provide ankle-foot orthoses to improve gait and
energy conservation, prevent falls, and reduce long-term damage to
knee and hip joints.
Orthopedic interventions, such as tendon lengthening and tendon
transfer, can help maintain long-term function, and guidelines are
currently being developed to direct proper timing of interventions to
optimize outcomes.
Pain management for genetic neuropathies follows the same principles
as for other chronic neuropathies, including encouragement of
movement and activity, maintenance of a healthy body mass index, and
avoidance of narcotics for long-term pain control
26.
27. Agents/Circumstances to Avoid
Obesity is to be avoided because it makes walking more difficult.
Medications that are toxic or potentially toxic to persons with CMT
comprise a spectrum of risk ranging from definitehigh risk to negligible
risk.
28.
29. HEREDITARY SENSORY AND
AUTONOMIC NEUROPATHIES
The primary hereditary sensory and autonomic neuropathies (HSANs) predominantly
affect myelinated and unmyelinated sensory nerves but also have motor nerve
involvement.
Classification of Hereditary Sensory and Autonomic Neuropathies
1.HSAN I with autosomal dominant inheritance (the most common form, but genetically
heterogeneous),
2.HSAN II (autosomal recessive inheritance, early onset),
3.HSAN III (familial dysautonomia, also known as Riley-Day syndrome, with AR
inheritance)
4. HSAN IV and
30. Genetics of Hereditary Sensory and
Autonomic Neuropathies
HSAN I - mutations in SPTLC1, SPTLC2, ATL1,DNMT1,
and ATL3 genes.
HSAN II - mutations in the WNK1 gene .
HSAN III -by mutations in the IKBKAP gene and is limited
to children of Ashkenazi Jewish descent.
HSAN IV and HSAN V- NTRK1 gene & NGF gene.
31. Clinical Presentation
HSAN I - sensory loss and neuropathic pain, sometimes with foot ulceration,while mean age
of presentation is in the mid-twenties & Autonomic and motor involvement can be variable.
Some patients also have sensorineural deafness and dementia. Pes cavus and absent
reflexes can be seen on examination.
HSAN II, involving both large and small nerve fibers, presents with loss of pain, temperature,
pressure, and touch sensation. It is associated with self-mutilation of fingers and toes and
can come to initial medical attention because of recurrent infections.
HSAN III presents with sympathetic autonomic dysfunction, including orthostatic
hypotension, excessive salivation, gastrointestinal dysmotility, bladder dysfunction,
decreased or absent tearing, absent fungiform tongue papillae, pupillary dilatation,
hypohidrosis, and episodic hyperhidrosis. Episodes of dysautonomic crises can be triggered
by physical and emotional stress.
32. Patients with HSAN IV present in infancy with mild to moderate
developmental delay; profound insensitivity to pain; and self-
mutilation of digits, face, and mouth regions.
HSAN IV differs from HSAN III by preservation of tearing and
tongue papillae.
Almost 20% of patients with HSAN die from hyperpyrexia
before the age of 3
Clinical Presentation
33. Electrophysiology
Nerve conduction studies in HSAN are highly variable, reflecting the
genetic heterogeneity.
HSAN I- axonal sensory more than motor neuropathy; however, motor
nerve conduction slowing into the demyelinating range can be seen.
HSAN II - axonal neuropathy with absent sensory responses.
HSAN III, similar to HSAN I, is associated with sensory more than
motor involvement.
HSAN IV and HSAN V, which predominantly affect small myelinated and
unmyelinated nerve fibers, typically show normal nerve conduction
studies.
34. Diagnosis and Management
Prominent sensory and autonomic manifestations should raise concern for the diagnosis of
HSAN. The diagnosis of HSAN I secondary to SPTLC1 mutations should be considered in
patients with a motor and sensory neuropathy, even in the presence of demyelinating
features, particularly if the patient has marked sensory involvement and a family history .
Dietary supplementation with oral L-serine in SPTLC1-mutant mice reduced the
sphingolipid metabolites and improved motor and sensory performance. However, despite
these promising studies, no specific treatment exists for HSAN.
Chronic sores and infections can lead to osteomyelitis and eventual amputation.
Management requires protection of the extremities, shoes that fit properly, orthotics for
footdrop, treatment of callus formation, proper dressing of wounds to promote healing, and
avoidance of trauma to the hands and feet.
Similarly,supportive care and symptomatic therapies are the mainstay of HSAN III
management.
35. POLYNEUROPATHIES ASSOCIATED WITH
GENETIC DISORDERS THAT HAVE SYSTEMIC
NEUROLOGIC MANIFESTATIONS
Many systemic disorders caused by genetic mutations have
a coexisting neuropathy.
Often the neuropathy is overshadowed by the systemic
manifestations of the disease.
An overview of selected disorders having CMT-like features
and specific treatment options are described in the following
sections
39. The classic picture of advanced polyneuropathy with distal wasting and
weakness, absent tendon reflexes, and glove and stocking sensory loss
should be easy to recognise.
-acute symmetrical peripheral neuropathy
-chronic symmetrical peripheral neuropathy
-multiple mononeuropathy
Peripheral neuropathy
40. 1.Acute symmetrical peripheral
neuropathy
commonest cause is Guillain Barré syndrome-Common early
symptoms are distal paraesthesiae and proximal or distal weakness
occurring one to two weeks after a respiratory or gastrointestinal
infection
42. 2.Multiple mononeuropathy
Acute multiple mononeuropathy is also a neurological emergency
because commonest cause is vasculitis
If multiple mono neuropathy develops in a patient with an established
connective tissue disorder ( RA, SLE ) it is reasonable to conclude
that vasculitis is the cause.
Steroids are the main treatment, with cyclophosphamide being
added depending on the severity and general medical condition.
Sometimes peripheral neuropathy is the presenting or sole feature of
vasculitis. In this case, vasculitis can be diagnosed only by nerve
43. 3.Chronic symmetrical peripheral
neuropathy
Most peripheral neuropathies are chronic and usually develop over severa
months.
Any history of a general medical disorder could be relevant.
Patients should always be asked about alcohol consumption, toxin
exposure (insecticides, solvents), and drugs.
They should also have a full examination, including breasts and genitalia,
to exclude underlying carcinoma.
The commonest causes of neuropathy can be identified from the history,
examination, and simple investigations
45. Chronic inflammatory demyelinating
polyradiculo neuropathy
commonest form of acquired demyelinating neuropathy and
affects about 2 per 100 000 of the population.
predominantly motor, and a proximal as well as distal
pattern of weakness; the condition may be relapsing and
remitting.
diagnosed by exclusion of the other causes and from
neurophysiological testing, which shows multifocal
abnormalities with partial conduction block.
It is thought to be an autoimmune disease because of the
46. Chronic axonal neuropathy
Axonal polyneuropathy can be sensory or sensory and motor.
Loss of pain and temperature sensation and spontaneous neuropathic pain, described as burning or pricking, can
be prominent symptoms of axonal neuropathy. They are due to degeneration of thinly myelinated and unmyelinated
nerve fibres. Occasionally small fibre neuropathy occurs without the thicker myelinated nerve fibres being affected
and the nerve conduction test results remain normal. The diagnosis in such cases usually relies on the clinical
symptoms and signs alone.
After exhaustive investigation no clear cause is found in about 25% of patients. Such chronic idiopathic axonal
neuropathy usually occurs in elderly people and is often indolent, predominantly sensory, and length dependent.
Proof of the diagnosis would require skin biopsy or enumeration of unmyelinated nerve fibres in electron
micrographs of a nerve biopsy specimen.
Chronic axonal neuropathy occurs in patients with many multisystem hereditary disorders
Patients can be reassured that, although their condition may progress, it will usually do so only slowly and is
unlikely to become seriously disabling.
47. Nodopathies or channelopathies
it is recognized that some toxic, immune mediated, and hereditary disorders target proteins
and ion channels in the nodal region.
The best example is the acute motor axonal neuropathy (AMAN) variant of the GBS which
characterized by rapid decline of CMAP, suggesting motor axon loss. The rapid resolution of
clinical and nerve conduction study changes, however, is not compatible with expected
recovery from that mechanism of injury. Conduction block produced by impaired ion channel function
unassociated with anatomic myelin or axonal injuryprovides a more likely explanation for the rapidly reversible conduction
failure seen in this disorder.
Like demyelination, nodopathies are not necessarily limited to disrupted conduction and may
be associated with subsequent axon loss. Impairment of sodium-calcium pump function is
hypothesized to lead to intracellular calcium accumulation contributing to eventual axonal
degeneration.
48. Nodopathies
Acute motor axonal variant of Guillain-Barre´ syndrome
Guillain-Barre´ syndrome with autoantibodies associated with nodal antigens
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with autoantibodies to nodal
antigens
Miller Fisher syndrome
Multifocal motor neuropathy (MMN)
Marine toxins (saxitoxin, ciguatoxin, tetrodotoxin)
Drugs with ion channel blocking properties (phenytoin)
Possibly critical illness polyneuropathy
Possibly ischemic monomelic neuropathy
Possibly thiamine deficiency
49. Classification:
Neuropathies that appear to originate in motor or sensory cell bodies are
referred to as neuronopathies. These disorders have clinical and
electrodiagnostic features that suggest axonal degeneration.
Sensory neuronopathies are presumed to result from selective damage
to dorsal root ganglia.
Motor neuronopathies (motor neuron diseases) preferentially target
anterior horn cells as a result of a select group of infectious, hereditary,
and degenerative conditions
52. Causes of multiple mononeuropathy
Vasculitis
Primary systemic vasculitis:
Polyarteritis nodosa
ChurgStrauss syndrome
Systemic vasculitis associated with
connective tissue diseases:
Rheumatoid arthritis
Sjögren's syndrome
Vasculitis confined to peripheral
nerves
Other causes
Sarcoidosis
Lymphoma
Carcinoma
Amyloid
Multiple compression
palsies
Associated with metabolic or toxic
neuropathy
Hereditary neuropathy with liability to
53. Summary points:
Peripheral neuropathy can be into divided into acute and chronic forms,
symmetrical polyneuropathy, and multiple mononeuropathy
Acute neuropathies are diagnostic emergencies
Neuropathy due to diabetes mellitus and alcohol misuse can be diagnosed in
primary care
Neurophysiological tests distinguish axonal from demyelinating neuropathies
Demyelinating neuropathies are commonly inflammatory and treatable
Axonal neuropathies have multiple causes
Generic management includes foot care, ankle supports, and treatment of
neuropathic pain