This document provides information about therapeutic options for spinal muscular atrophy (SMA). It first defines SMA as a genetic disorder that causes degeneration of motor neurons in the spinal cord, resulting in muscle weakness. It then discusses the four main types of SMA based on severity and age of onset. The causes and diagnosis of SMA are also outlined. The therapeutic options section summarizes gene replacement therapies like nusinersen and onasemnogene abeparovec, which aim to increase SMN protein levels. It also mentions the small molecule risdiplam and ongoing clinical trials evaluating these treatment approaches.
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 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.
This document discusses spinal muscular atrophy (SMA). It defines SMA as a genetic motor neuron disease caused by degeneration of motor neurons in the spinal cord and select brainstem nuclei. SMA is classified into types based on age of onset and severity, from Type 1 being the most severe to Type 4 being the mildest. Type 1 SMA presents in infants and leads to death usually by age 2. Type 2 presents between ages 6-18 months and patients can sit but not stand or walk. Type 3 presents after 18 months and patients can walk but have difficulty with motor skills. Nutritional support and respiratory aids are important for treatment.
This document discusses spinal muscular atrophy (SMA), including its causes, types, signs and symptoms, diagnosis, and treatment. SMA is caused by a mutation in the SMN1 gene that results in a lack of survival motor neuron protein and the degeneration of alpha motor neurons in the spinal cord. It is classified into five types based on age of onset and severity. There is currently no cure for SMA, but treatment focuses on managing symptoms through rehabilitation, assistive devices, ventilation support, and gene therapy research shows promise for slowing disease progression.
1. Spinal muscular atrophy (SMA) is caused by degeneration of motor neurons in the spinal cord and brainstem due to a defect in the SMN1 gene resulting in low levels of the SMN protein.
2. SMA is classified into five types based on age of onset and severity of symptoms - from very severe Type 1 to milder adult-onset Type 4.
3. Diagnosis involves family history, physical exam, genetic testing, and other tests like EMG; there is currently no cure but supportive care can help manage symptoms.
This document summarizes Spinal Muscular Atrophy (SMA). SMA is an autosomal recessive disorder caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, characterized by progressive weakness of body muscles. It is classified into 4 types based on age of onset, from severe Type 1 in infants to adult-onset Type 4. Diagnosis involves genetic testing, electrophysiology, and muscle biopsy. While there is no cure, treatment focuses on supportive care, ventilation, wheelchairs, and clinical trials of medications like Riluzole.
This document provides information about acute disseminated encephalomyelitis (ADEM). It defines ADEM as a demyelinating disease of the central nervous system that typically presents as a monophasic disorder with encephalopathy and multifocal neurological symptoms. The document discusses the pathogenesis, clinical features, diagnosis, differential diagnosis and treatment of ADEM. It states that ADEM is usually treated initially with high-dose intravenous corticosteroids over 3-5 days.
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 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.
This document discusses spinal muscular atrophy (SMA). It defines SMA as a genetic motor neuron disease caused by degeneration of motor neurons in the spinal cord and select brainstem nuclei. SMA is classified into types based on age of onset and severity, from Type 1 being the most severe to Type 4 being the mildest. Type 1 SMA presents in infants and leads to death usually by age 2. Type 2 presents between ages 6-18 months and patients can sit but not stand or walk. Type 3 presents after 18 months and patients can walk but have difficulty with motor skills. Nutritional support and respiratory aids are important for treatment.
This document discusses spinal muscular atrophy (SMA), including its causes, types, signs and symptoms, diagnosis, and treatment. SMA is caused by a mutation in the SMN1 gene that results in a lack of survival motor neuron protein and the degeneration of alpha motor neurons in the spinal cord. It is classified into five types based on age of onset and severity. There is currently no cure for SMA, but treatment focuses on managing symptoms through rehabilitation, assistive devices, ventilation support, and gene therapy research shows promise for slowing disease progression.
1. Spinal muscular atrophy (SMA) is caused by degeneration of motor neurons in the spinal cord and brainstem due to a defect in the SMN1 gene resulting in low levels of the SMN protein.
2. SMA is classified into five types based on age of onset and severity of symptoms - from very severe Type 1 to milder adult-onset Type 4.
3. Diagnosis involves family history, physical exam, genetic testing, and other tests like EMG; there is currently no cure but supportive care can help manage symptoms.
This document summarizes Spinal Muscular Atrophy (SMA). SMA is an autosomal recessive disorder caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, characterized by progressive weakness of body muscles. It is classified into 4 types based on age of onset, from severe Type 1 in infants to adult-onset Type 4. Diagnosis involves genetic testing, electrophysiology, and muscle biopsy. While there is no cure, treatment focuses on supportive care, ventilation, wheelchairs, and clinical trials of medications like Riluzole.
This document provides information about acute disseminated encephalomyelitis (ADEM). It defines ADEM as a demyelinating disease of the central nervous system that typically presents as a monophasic disorder with encephalopathy and multifocal neurological symptoms. The document discusses the pathogenesis, clinical features, diagnosis, differential diagnosis and treatment of ADEM. It states that ADEM is usually treated initially with high-dose intravenous corticosteroids over 3-5 days.
This document discusses the anatomy, imaging, classification, and treatment of various cervical vertebral anomalies. It begins with an overview of the normal anatomy of the atlantoaxial joint and landmarks seen on imaging. It then discusses various congenital and acquired bony and soft tissue anomalies that can occur in this region, including platybasia, basilar invagination, occipitalization of the atlas, and atlantoaxial dislocation. Imaging criteria and classifications for these conditions are provided. Common associated findings like Chiari malformation and syringomyelia are also mentioned. The document concludes with sections on clinical presentation and evaluation of these cervical vertebral anomalies.
Spinal muscular atrophy (SMA) is a genetic neuromuscular disease that affects motor neurons in the spinal cord, leading to progressive muscle weakness. It has varying severity depending on the number of SMN2 genes. SMA is classified into 4 types based on age of onset and highest physical milestone achieved. Management is supportive and focuses on nutrition, pulmonary health, scoliosis, contractures and hip dislocation. The disease has no cure and treatment aims to prolong survival and maximize quality of life through multidisciplinary care.
Recent advances and evaluation in muscular dystrophiesNeurologyKota
The document summarizes recent advances in the treatment of muscular dystrophy. Key points include:
1) Gene therapy and exon skipping techniques show promise in reversing primary defects by restoring dystrophin expression, though challenges remain with delivery and immune response.
2) Protein and cell-based therapies also aim to replace missing proteins or boost regeneration, though stable long-term delivery is difficult.
3) Combination therapies targeting both primary and secondary defects may be most effective, as the disease impacts multiple cellular processes.
4) The drug eteplirsen utilizes exon skipping to successfully increase dystrophin levels and walking ability in Duchenne patients.
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.
This document provides an overview of syringomyelia, including its pathogenesis, pathology, classification, clinical features, and natural history. Syringomyelia is a condition characterized by fluid-filled cavities within the spinal cord. It most commonly affects the cervical and thoracic regions. Clinical features include pain and sensory loss. The natural history varies, but symptoms typically progress slowly over years, with some patients experiencing stabilization or spontaneous resolution in rare cases.
This document discusses various types of myopathies (disorders affecting muscle). It defines myopathies and distinguishes them from other causes of muscle weakness. It then describes different categories of myopathies including inflammatory myopathies (such as polymyositis and dermatomyositis), muscular dystrophies (such as Duchenne, Becker, limb-girdle, facioscapulohumeral), congenital myopathies, metabolic myopathies, and others. For each type, it discusses inheritance, clinical features, diagnostic criteria, and treatment when available.
1) Repetitive nerve stimulation (RNS) studies can help diagnose neuromuscular junction disorders like myasthenia gravis and Lambert-Eaton myasthenic syndrome.
2) RNS measures changes in muscle action potentials in response to repetitive nerve stimulation and looks for signs of decrement or incremental response.
3) A post-synaptic disorder like myasthenia gravis will show a decrement greater than 10% following exercise due to fatigue at the neuromuscular junction, while a pre-synaptic disorder like LEMS may show an incremental response.
spinal muscular atrophy sma by alleliehalengleng28
Spinal muscular atrophy (SMA) is a genetic disorder that attacks motor neurons, causing muscle weakness and wasting. It is caused by a deficiency of the SMN protein due to mutations in the SMN1 gene. There are several types of SMA classified by age of onset and highest physical milestone achieved. Treatment focuses on maintaining function, mobility, nutrition, and respiratory health to maximize quality of life. While there is no cure, ongoing research into new drugs and therapies provides hope for modifying the course of the disease.
The craniovertebral junction (CVJ) refers collectively to the occiput, atlas, axis, and supporting ligaments. It is a transition zone between the mobile cranium and spinal column, enclosing the soft tissue structures of the cervicomedullary junction. The CVJ has important implications for embryology, anatomy, classification of anomalies, investigations, and clinical management. Anomalies can involve bony, soft tissue, arterial, and neural structures in this region. A variety of imaging modalities like X-rays, CT, MRI are used to classify and characterize CVJ anomalies.
This document summarizes the medical history and examination findings of a 16-year-old male patient presenting with occipital headache, neck pain, loss of pain and temperature sensation in the left upper limb, and laxity of the left shoulder joint. Examination revealed loss of sensation from C3 to T2 on the left side and absent biceps and supinator reflexes on the left. MRI showed Arnold-Chiari malformation type 1 with syringomyelia involving the cervical and thoracic spinal cord. The patient was diagnosed with syringomyelia related to Arnold-Chiari malformation.
Post polio syndrome is characterized by new muscle weakness, fatigue, and pain in polio survivors decades after their initial bout of polio. It is believed to be caused by overwork of motor neurons that survived the initial poliovirus infection but were left vulnerable. As time passes, these neurons fatigue and can no longer sufficiently innervate muscles. Treatment focuses on managing new symptoms, preserving function through exercise and assistive devices, and addressing pain. Physiotherapy plays a key role through energy conservation techniques, strengthening, and physical modalities like heat.
Syringomyelia is a condition where a cyst, called a syrinx, develops in the spinal cord. It most commonly affects the lower cervical spine. It is often associated with abnormalities of the skull or spinal column. The majority of cases are linked to Chiari malformation type 1, where the cerebellar tonsils are displaced into the spinal canal. Symptoms vary depending on the location of the syrinx but can include pain, loss of sensation, muscle weakness or atrophy, and autonomic dysfunction. Diagnosis is made using imaging like MRI. Treatment involves surgery to decompress pressure on the spinal cord like laminectomy with the goal of resolving the syrinx.
Klippel-Feil syndrome is a congenital condition where two or more cervical vertebrae are fused. It is caused by mutations in genes GDF6 and GDF3 which regulate bone growth. People with Klippel-Feil syndrome have a short neck, limited neck movement, and sometimes scoliosis. Diagnosis involves x-rays and MRIs showing fused vertebrae. Treatment focuses on pain management through medications, physical therapy, and sometimes surgery to correct spinal abnormalities.
Duchenne muscular dystrophy is a genetic disorder caused by mutations in the dystrophin gene located on the X chromosome. It is characterized by progressive muscle weakness starting in early childhood. Clinical features include difficulty walking, cardiac complications like dilated cardiomyopathy, respiratory issues like sleep apnea and hypoventilation, intellectual disabilities in 30% of patients, and orthopedic problems like fractures and scoliosis. Diagnosis involves elevated creatine kinase levels, muscle biopsy, and genetic testing. Management focuses on cardiac, respiratory, orthopedic care as well as corticosteroid therapy to prolong ambulation and improve lung function. Emerging treatments include gene therapy using viral vectors and exon skipping to restore dystrophin production.
The basal ganglia are brain nuclei that coordinate movement and cognitive functions. Deep brain stimulation (DBS) involves surgically implanting electrodes into the basal ganglia to deliver electrical stimulation for treating movement and neuropsychiatric disorders like Parkinson's disease. DBS was introduced in the 1990s and works by inhibiting or activating target areas in the basal ganglia to disrupt pathological oscillations. Common targets for stimulation include the subthalamic nucleus and globus pallidus. DBS improves motor symptoms in Parkinson's patients and allows for reductions in medication. Potential risks include infection, bleeding in the brain, and device-related complications.
Tabes dorsalis is a progressive degeneration of nerve cells and fibers in the spinal cord that carry sensory information to the brain, caused by untreated syphilis. It is characterized by sensory deficits, loss of coordination, and diminished reflexes. The disease progresses through preataxic, ataxic, and paralysis stages. Clinical features include loss of sensation, Argyll Robertson pupils, dementia, hypotonicity, loss of coordination, and trophic ulcers. Treatment involves antibiotics, steroids, pain medications, exercises, and splinting to manage symptoms.
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.
What is Muscular Dystrophy?
Types of Muscular Dystrophy
What is Duchenne muscular dystrophy (DMD), pathophysiology, clinical presentation, Gowers sign, DMD and Becker's muscular dystrophy and functional grades
Dwi Putro Widodo has extensive medical training and experience in neurology. He obtained degrees in general medicine and pediatric specialties. Additionally, he has a Master's in clinical neuroscience and has worked in neurology departments. His background qualifies him as an expert in the neurology field, specifically in areas like the neuromuscular system, spinal muscular atrophy, and potential treatments.
1) Human growth hormone (HGH) treatment increased survival motor neuron (SMN) protein levels in human neuronal cells in a dose-dependent manner by activating the STAT5 signaling pathway.
2) Systemic administration of HGH to spinal muscular atrophy (SMA) mouse models induced higher levels of SMN protein in the brain and spinal cord.
3) HGH treatment improved disease phenotypes and increased survival in two severe SMA mouse models, confirming that activating the STAT5 pathway may be a promising therapeutic strategy for SMA.
This document discusses the anatomy, imaging, classification, and treatment of various cervical vertebral anomalies. It begins with an overview of the normal anatomy of the atlantoaxial joint and landmarks seen on imaging. It then discusses various congenital and acquired bony and soft tissue anomalies that can occur in this region, including platybasia, basilar invagination, occipitalization of the atlas, and atlantoaxial dislocation. Imaging criteria and classifications for these conditions are provided. Common associated findings like Chiari malformation and syringomyelia are also mentioned. The document concludes with sections on clinical presentation and evaluation of these cervical vertebral anomalies.
Spinal muscular atrophy (SMA) is a genetic neuromuscular disease that affects motor neurons in the spinal cord, leading to progressive muscle weakness. It has varying severity depending on the number of SMN2 genes. SMA is classified into 4 types based on age of onset and highest physical milestone achieved. Management is supportive and focuses on nutrition, pulmonary health, scoliosis, contractures and hip dislocation. The disease has no cure and treatment aims to prolong survival and maximize quality of life through multidisciplinary care.
Recent advances and evaluation in muscular dystrophiesNeurologyKota
The document summarizes recent advances in the treatment of muscular dystrophy. Key points include:
1) Gene therapy and exon skipping techniques show promise in reversing primary defects by restoring dystrophin expression, though challenges remain with delivery and immune response.
2) Protein and cell-based therapies also aim to replace missing proteins or boost regeneration, though stable long-term delivery is difficult.
3) Combination therapies targeting both primary and secondary defects may be most effective, as the disease impacts multiple cellular processes.
4) The drug eteplirsen utilizes exon skipping to successfully increase dystrophin levels and walking ability in Duchenne patients.
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.
This document provides an overview of syringomyelia, including its pathogenesis, pathology, classification, clinical features, and natural history. Syringomyelia is a condition characterized by fluid-filled cavities within the spinal cord. It most commonly affects the cervical and thoracic regions. Clinical features include pain and sensory loss. The natural history varies, but symptoms typically progress slowly over years, with some patients experiencing stabilization or spontaneous resolution in rare cases.
This document discusses various types of myopathies (disorders affecting muscle). It defines myopathies and distinguishes them from other causes of muscle weakness. It then describes different categories of myopathies including inflammatory myopathies (such as polymyositis and dermatomyositis), muscular dystrophies (such as Duchenne, Becker, limb-girdle, facioscapulohumeral), congenital myopathies, metabolic myopathies, and others. For each type, it discusses inheritance, clinical features, diagnostic criteria, and treatment when available.
1) Repetitive nerve stimulation (RNS) studies can help diagnose neuromuscular junction disorders like myasthenia gravis and Lambert-Eaton myasthenic syndrome.
2) RNS measures changes in muscle action potentials in response to repetitive nerve stimulation and looks for signs of decrement or incremental response.
3) A post-synaptic disorder like myasthenia gravis will show a decrement greater than 10% following exercise due to fatigue at the neuromuscular junction, while a pre-synaptic disorder like LEMS may show an incremental response.
spinal muscular atrophy sma by alleliehalengleng28
Spinal muscular atrophy (SMA) is a genetic disorder that attacks motor neurons, causing muscle weakness and wasting. It is caused by a deficiency of the SMN protein due to mutations in the SMN1 gene. There are several types of SMA classified by age of onset and highest physical milestone achieved. Treatment focuses on maintaining function, mobility, nutrition, and respiratory health to maximize quality of life. While there is no cure, ongoing research into new drugs and therapies provides hope for modifying the course of the disease.
The craniovertebral junction (CVJ) refers collectively to the occiput, atlas, axis, and supporting ligaments. It is a transition zone between the mobile cranium and spinal column, enclosing the soft tissue structures of the cervicomedullary junction. The CVJ has important implications for embryology, anatomy, classification of anomalies, investigations, and clinical management. Anomalies can involve bony, soft tissue, arterial, and neural structures in this region. A variety of imaging modalities like X-rays, CT, MRI are used to classify and characterize CVJ anomalies.
This document summarizes the medical history and examination findings of a 16-year-old male patient presenting with occipital headache, neck pain, loss of pain and temperature sensation in the left upper limb, and laxity of the left shoulder joint. Examination revealed loss of sensation from C3 to T2 on the left side and absent biceps and supinator reflexes on the left. MRI showed Arnold-Chiari malformation type 1 with syringomyelia involving the cervical and thoracic spinal cord. The patient was diagnosed with syringomyelia related to Arnold-Chiari malformation.
Post polio syndrome is characterized by new muscle weakness, fatigue, and pain in polio survivors decades after their initial bout of polio. It is believed to be caused by overwork of motor neurons that survived the initial poliovirus infection but were left vulnerable. As time passes, these neurons fatigue and can no longer sufficiently innervate muscles. Treatment focuses on managing new symptoms, preserving function through exercise and assistive devices, and addressing pain. Physiotherapy plays a key role through energy conservation techniques, strengthening, and physical modalities like heat.
Syringomyelia is a condition where a cyst, called a syrinx, develops in the spinal cord. It most commonly affects the lower cervical spine. It is often associated with abnormalities of the skull or spinal column. The majority of cases are linked to Chiari malformation type 1, where the cerebellar tonsils are displaced into the spinal canal. Symptoms vary depending on the location of the syrinx but can include pain, loss of sensation, muscle weakness or atrophy, and autonomic dysfunction. Diagnosis is made using imaging like MRI. Treatment involves surgery to decompress pressure on the spinal cord like laminectomy with the goal of resolving the syrinx.
Klippel-Feil syndrome is a congenital condition where two or more cervical vertebrae are fused. It is caused by mutations in genes GDF6 and GDF3 which regulate bone growth. People with Klippel-Feil syndrome have a short neck, limited neck movement, and sometimes scoliosis. Diagnosis involves x-rays and MRIs showing fused vertebrae. Treatment focuses on pain management through medications, physical therapy, and sometimes surgery to correct spinal abnormalities.
Duchenne muscular dystrophy is a genetic disorder caused by mutations in the dystrophin gene located on the X chromosome. It is characterized by progressive muscle weakness starting in early childhood. Clinical features include difficulty walking, cardiac complications like dilated cardiomyopathy, respiratory issues like sleep apnea and hypoventilation, intellectual disabilities in 30% of patients, and orthopedic problems like fractures and scoliosis. Diagnosis involves elevated creatine kinase levels, muscle biopsy, and genetic testing. Management focuses on cardiac, respiratory, orthopedic care as well as corticosteroid therapy to prolong ambulation and improve lung function. Emerging treatments include gene therapy using viral vectors and exon skipping to restore dystrophin production.
The basal ganglia are brain nuclei that coordinate movement and cognitive functions. Deep brain stimulation (DBS) involves surgically implanting electrodes into the basal ganglia to deliver electrical stimulation for treating movement and neuropsychiatric disorders like Parkinson's disease. DBS was introduced in the 1990s and works by inhibiting or activating target areas in the basal ganglia to disrupt pathological oscillations. Common targets for stimulation include the subthalamic nucleus and globus pallidus. DBS improves motor symptoms in Parkinson's patients and allows for reductions in medication. Potential risks include infection, bleeding in the brain, and device-related complications.
Tabes dorsalis is a progressive degeneration of nerve cells and fibers in the spinal cord that carry sensory information to the brain, caused by untreated syphilis. It is characterized by sensory deficits, loss of coordination, and diminished reflexes. The disease progresses through preataxic, ataxic, and paralysis stages. Clinical features include loss of sensation, Argyll Robertson pupils, dementia, hypotonicity, loss of coordination, and trophic ulcers. Treatment involves antibiotics, steroids, pain medications, exercises, and splinting to manage symptoms.
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.
What is Muscular Dystrophy?
Types of Muscular Dystrophy
What is Duchenne muscular dystrophy (DMD), pathophysiology, clinical presentation, Gowers sign, DMD and Becker's muscular dystrophy and functional grades
Dwi Putro Widodo has extensive medical training and experience in neurology. He obtained degrees in general medicine and pediatric specialties. Additionally, he has a Master's in clinical neuroscience and has worked in neurology departments. His background qualifies him as an expert in the neurology field, specifically in areas like the neuromuscular system, spinal muscular atrophy, and potential treatments.
1) Human growth hormone (HGH) treatment increased survival motor neuron (SMN) protein levels in human neuronal cells in a dose-dependent manner by activating the STAT5 signaling pathway.
2) Systemic administration of HGH to spinal muscular atrophy (SMA) mouse models induced higher levels of SMN protein in the brain and spinal cord.
3) HGH treatment improved disease phenotypes and increased survival in two severe SMA mouse models, confirming that activating the STAT5 pathway may be a promising therapeutic strategy for SMA.
A Review on Spinal Muscular Atrophy Clinical Classification, Etiology, Diagno...ijtsrd
Spinal muscular atrophy SMA is an inherited, progressive neuromuscular disease that can cause weakness, degeneration of anterior horn cells, and muscle atrophy. It was first discovered in infants by physicians Guido Werdnig and Johan Hoffmann. SMA is mainly caused due to the mutation of the survival motor neuron 1 SMN1 . Based on phenotype it is classified into four grades of severity as SMA I, SMA II, SMA III and, SMA IV. SMA is diagnosed by Molecular genetic testing such as Multiplex Ligation Dependent Probe Amplification MLPA and real time polymerase chain reaction PCR laboratory examination includes creatine kinase dosage and electrophysiological tests such as electromyography EMG , and nerve conduction studies. Various drugs used for the treatment of SMA are Nusinersen, Risdiplam, Zolgensma, Reldesemtiv, and Combination therapy. Spinal muscular atrophy SMA Foundation and Pharmacy and therapeutic Committee PTC , have been conducting many clinical trials for a potential SMA treatment. Deborah Rose | Subhashini. A | Dr. K. C. Arul Prakasam | Aarthy. P | D. N. Ashritha "A Review on Spinal Muscular Atrophy: Clinical Classification, Etiology, Diagnosis and Treatment" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-6 , October 2021, URL: https://www.ijtsrd.com/papers/ijtsrd47658.pdf Paper URL : https://www.ijtsrd.com/pharmacy/other/47658/a-review-on-spinal-muscular-atrophy-clinical-classification-etiology-diagnosis-and-treatment/deborah-rose
Progressive multiple sclerosis (MS) can be primary progressive or secondary progressive and occurs on a spectrum with relapsing MS. Treatment approaches for progressive MS include immunomodulation, B-cell therapies like ocrelizumab which is approved for primary progressive MS, and neuroprotective agents. Monitoring for progression may involve markers like neurofilament light chain in serum and cerebrospinal fluid as well as optical coherence tomography and spinal cord MRI measures. Management of progressive MS also focuses on controlling medical comorbidities.
This document provides information on West syndrome, including its classification, clinical manifestations, treatment, and prognosis. West syndrome is a severe epilepsy syndrome in infants characterized by infantile spasms, abnormal EEG findings called hypsarrhythmia, and developmental regression. It is classified based on its etiology as symptomatic, cryptogenic, or idiopathic. First-line treatment options include ACTH, vigabatrin, and corticosteroids. Prognosis depends on the underlying etiology, with idiopathic cases generally having a better prognosis than symptomatic cases. Outcomes include cognitive impairments, cerebral palsy, and in some cases mortality.
Motor neuron disease (MND) refers to a group of conditions characterized by degeneration of lower and/or upper motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common form of MND, involving both upper and lower motor neurons. While Riluzole is the only FDA-approved treatment for ALS, other potential treatments discussed include ceftriaxone, tamoxifen, stem cell therapy, and supportive care approaches for symptoms such as spasticity, respiratory issues, and other complications.
Dr. Sharda Jain, Dr. Jyoti Agarwal, and Dr. Jyoti Bhaskar presented an interactive session on the medical management of dysfunctional uterine bleeding (DUB) in 2014. Ormeloxifene, a selective estrogen receptor modulator, was discussed as a non-steroidal treatment option for DUB that has shown efficacy in several pilot studies and randomized controlled trials. Ormeloxifene has advantages of a convenient dosing schedule and few side effects, and has been used to successfully treat over 700 patients with DUB. Feedback was encouraged from participants on experiences treating DUB.
Autoimmune Encephalitis is a particularly intimidating entity, as recognition of this disease can be delayed because diagnosis can involve ambiguous neurological symptoms, leading to detrimental long-term consequences. Auto-anti-bodies (NMDA,VGKC) can be found through serum lab tests, and magnetic resonance imaging can show inflammation, and spinal tap can reveal auto antibodies and other biomarkers in the cerebrospinal fluid that point to autoimmune encephalitis. Being that autoimmune encephalitis is a recently described diagnosis, there is still a tremendous amount of investigation to be done to discover the root causes of the disease, more anti-body essays need to be developed to discover all of the phenotypes, and the best most effective treatments need to be found to treat this mysterious disease.
This document discusses treatments for multiple sclerosis (MS), including medications and other therapies. It describes three main treatments: 1) Natalizumab, a monoclonal antibody that prevents immune cells from attacking the blood-brain barrier; 2) Interferon beta injections, which suppress inflammation but have side effects; 3) Adipose-derived stem cell therapy, which showed improvements in coordination, mobility, and energy for three MS patients. The conclusion notes that current MS treatment aims to reduce symptoms and slow progression, but that future research seeks a cure by preventing demyelination and repairing damage.
This randomized controlled trial assessed the efficacy and tolerability of pregabalin (75, 300, 600 mg/day) compared to placebo in treating pain from diabetic peripheral neuropathy. Patients receiving 300 and 600 mg/day of pregabalin showed significant improvements in pain scores and sleep interference compared to placebo. Improvements were seen as early as the first week and were sustained throughout the 5-week study. Pregabalin was well tolerated with few side effects, demonstrating its potential as an effective treatment for neuropathic pain associated with diabetes.
This study evaluated the effectiveness of microcurrent electrical stimulation using the Avazzia PRO-SPORTTM device to treat symptoms in children with post PANDAS episodes. Seven children received 10 treatment sessions over acupuncture points. Results showed the average intensity of symptoms decreased by 40.3% and average frequency of symptoms decreased by 34%. All children reported improvements and continued benefits when using the device during periods of stress. The study concluded microcurrent therapy safely and effectively improved PANDAS symptoms in children.
Enzyme replacement therapy in neurological disordersNeurologyKota
This document discusses enzyme replacement therapy (ERT) for lysosomal storage disorders. It provides details on ERT including its development, mechanisms, available products, dosing and costs. Challenges with ERT include limited blood-brain barrier penetration and immunogenicity. Alternative therapies discussed include substrate reduction therapy, pharmacological chaperones, and direct delivery of enzymes into the cerebrospinal fluid. ERT remains the standard treatment but has limitations for treating neurological manifestations of lysosomal storage disorders.
1) Recent advances in understanding the pathophysiology of motor neuron disease include insights into excitotoxicity, oxidative stress, mitochondrial defects, impaired axonal transport, protein aggregation, inflammation, and neurotrophic factor deficits.
2) Riluzole remains the only FDA-approved drug shown to modestly prolong survival for patients with ALS, though Edaravone may also provide benefits for certain subgroups. Experimental therapies targeting genes, antioxidants, neurotrophic factors, and other mechanisms are under investigation.
3) Making an accurate diagnosis involves evaluating the patient's history, physical exam, electrodiagnostic testing, imaging, and sometimes genetic or biomarker analysis to differentiate ALS from other conditions.
Ocrelizumab is a humanized monoclonal antibody that selectively targets CD20-positive B cells. Two phase III trials, OPERA I and OPERA II, compared ocrelizumab to interferon beta-1a in patients with relapsing-remitting multiple sclerosis. The studies found that ocrelizumab significantly reduced annualized relapse rates, disability progression, and MRI activity compared to interferon beta-1a over 96 weeks with an acceptable safety profile. Ocrelizumab was generally well-tolerated with a higher rate of infusion-related reactions but lower rates of serious adverse events and infections compared to interferon beta-1a. The trials provide support for the role of B
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This study evaluated the effectiveness and safety of PRO051, an antisense oligonucleotide, for the treatment of Duchenne muscular dystrophy (DMD). Twelve DMD patients received weekly subcutaneous injections of PRO051 for 5 weeks. Muscle biopsies taken 2 weeks after treatment showed restoration of the dystrophin protein in muscle fibers. PRO051 was found to be well tolerated with no serious safety issues. The antisense oligonucleotide masked exon 51 of the dystrophin gene, changing the splicing pattern and allowing production of a truncated but functional dystrophin protein, reducing the effects of DMD.
This document contains abstracts from multiple studies related to alemtuzumab treatment for relapsing-remitting multiple sclerosis (RRMS). Key findings from the studies include:
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This case presentation describes a 25-year-old male who presented with fever, body aches, and lymphocytosis. His symptoms began after trekking in an endemic area. Scrub typhus was suspected based on his symptoms and history. Diagnosis was confirmed with a positive IgM ELISA test for Orientia tsutsugamushi. Doxycycline is the treatment of choice for scrub typhus. Symptoms typically resolve within a week of doxycycline treatment. Prevention involves public education, rodent control, and chemoprophylaxis with antibiotics in endemic areas.
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1. Therapeutic options for Spinal Muscular
Atrophy
Presenter:-
Dr Monica Jain,
Professor & Head,
Department of Pharmacology,
SMS Medical College,Jaipur
3. What is Spinal Muscular Atrophy?
• Spinal muscular atrophy (SMA) is a rare autosomal recessive disease
that deteriorates NM functioning of the body by causing motor neurons
loss and associated muscle weakness.(when muscles get smaller).
• The disease was first described in the 1890s by Werdnig and by
Hoffmann.
• Spinal muscular atrophy (SMA) is characterized by degeneration of the
alpha motor neurons of the spinal cord anterior horn cells, leading to
progressive proximal muscle weakness & atrophy and in the most
severe types, paralysis.
4. • Spinal muscular atrophy linked to chromosome 5q (SMA) is a recessive,
progressive, neuromuscular disorder caused by bi-allelic mutations in
the SMN1 gene, resulting in motor neuron degeneration and variable
presentation in relation to onset and severity.
• SMA can affect a child's ability to crawl, walk, sit up, and control head
movements.
• Severe SMA can damage the muscles used for breathing and
swallowing.
5. There are four types of SMA on the basis of disease’s severity and age
when symptoms begin.
Types Age Characteristic Features
1.SMA-I
(Most severe)
(Werdnig-
Hoffmann
disease)
Up to 6 weeks Severe, progressive muscle weakness and flaccid or reduced
muscle tone (hypotonia) &Bulbar dysfunction includes poor
suck ability, reduced swallowing, and respiratory
failure,patient never sit and SMA-I is rapid motor neuron loss
result in death or permanent ventilator support in >90% of
patients.
2.SMA-II
(Moderate to
More Severe)
Intermediate
Between 7 to 18
months
Difficulties with sitting independently or failure to stand by 1
year of age and pseudohypertrophy of the gastrocnemius
muscle, musculoskeletal deformities, and respiratory failure
can occur and patient is live with ventilatory support.
3.SMA-III
(Mildest)
Kugelberg-
Welander disease
18 months to 35
years
Slowly progressive proximal weakness & most children can
stand and walk but have trouble with motor skills, such as
going up and down stairs and stand & walk during adulthood.
4.SMA-IV
(Very Less
Severe or Adult)
After 35 months Symptoms mimics to SMA –III but patients have a normal life
expectancy and walk unaided.
6. Causes of SMA?
• It is caused by a genetic defect in survival motor neuron(SMN)-1 gene
which encodes the SMN protein. (People have two SMN1 genes).
• SMA genes is located in the long arm of the chromosome 5, in the
5q13.2 region.
• A mutation in the SMN1 gene leads to a deficiency of a motor neuron
protein called SMN.
7. • As its name implies, this protein is responsible for gene expression
necessary for normal motor neuron function.
• A consequent decrease in the SMN protein leading to lower motor
neuron degeneration and progress into muscle atrophy and finally
muscle are paralyzed.
• In SMA,mainly respiratory and skeletal muscles are involved,so
patients are complaints difficulty in breathing and they unable to sit and
walk independently.
8. Incidence of SMA
• The incidence of SMA is 1 in 10,000 to 11,000 live births throughout
the worldwide and carrier frequency of 1/40 to 1/60,so it is rare
disease.
• As per orphan drug amendment (1983) act of USA, a rare disease
/condition is one affects less than 0.2 million people in the USA.
• Though these drugs may be life saving for some patients,they are
commercially difficult to obtain as a medicinal product.
• Rare disease criteria is differ from country to country.
9. How is SMA diagnosed?
• Genetic testing: This is the most common way to test for SMA.
Testing checks for a deletion or variation in the SMN1 gene.
• A muscle biopsy: Take a small sample of muscle to check under a
microscope.
11. I.Gene replacement therapy
1.Nusinersen:
In December 2016, the FDA approved nusinersen (Spinraza), the first
drug approved to treat children (including newborns) and adults with
SMA.
Nusinersen is an antisense oligonucleotide (ASO) designed to treat
SMA caused by mutations in chromosome 5q that lead to SMN protein
deficiency.
Using in vitro assays and studies in transgenic animal models of
SMA, nusinersen was shown to increase exon 7 inclusion in SMN2
messenger ribonucleic acid (mRNA) transcripts and production of
full-length SMN protein.
12. Pharmacology of Nusinersen
Mechanism of Action
An antisense oligonucleotide (ASO) designed to treat SMA caused by
mutations in chromosome 5q that lead to SMN protein deficiency.
Using in vitro assays and studies in transgenic animal models of
SMA, nusinersen was shown to increase exon 7 inclusion in SMN2
messenger ribonucleic acid (mRNA) transcripts and production of
full-length SMN protein.
Absorption
Through plasma levels relatively low, compared to trough CSF
concentration
Peak plasma time: 1.7-6 hrs
13. Distribution
CSF and peripheral tissues (eg, skeletal muscle, liver, kidney)
Metabolism
Metabolized via exonuclease (3’- and 5’)-mediated hydrolysis
Not a substrate for, or inhibitor, or inducer of CYP450 enzymes
Elimination
Half-life: 135-177 days (CSF); 63-87 days (plasma)
Excretion
Primary route of elimination is likely by urinary excretion; at 24 hr,
only 0.5% of the administered dose was recovered in the urine
14. Dosing
In Adults:
12 mg/5mL single dose vial intrathecally per administration
Initial: 4 loading doses; administer the first 3 doses at 14-day intervals
and the fourth dose 30 days after the third dose
Maintenance: One dose every 4 months
In Children:
12 mg intrathecally per administration
Initial: 4 loading doses; administer the first 3 doses at 14-day intervals
and the fourth dose 30 days after the third dose
Maintenance: One dose every 4 months
15. Clinical Trials:
• Nusinersen approval was based on the ENDEAR trial.
• After promising results for nusinersen in phase I and II trials in
children with SMA type II and III, two phase III, randomized, double-
blind, sham-procedure controlled studies were initiated consequently.
• ENDEAR (ClinicalTrials.gov identifier: NCT02193074, years 2014–
2016) assessed safety and clinical efficacy of nusinersen in 121 infants
with infantile-onset SMA and younger than seven months.
16. • In the interim analysis, infants treated with nusinersen had higher
improvement in the motor milestone categories of the Hammersmith
Infant Neurological Examination (HINE) than controls (41% vs. 0%, p <
0.001).
• Moreover, the nusinersen group demonstrated a prolonged time to death
(hard ratio for death 0.37; p = 0.004) or need for permanent ventilation
compared to controls and six out of 73 treated patients achieved
independent sitting over a one year treatment period.
17. • CHERISH (ClinicalTrials.gov identifier: NCT02292537, years 2014–
2017) involved 126 children with later-onset SMA.
• The median age at baseline was four years (two to nine years) in the
treated group and three years (two to seven years) in the controls.
• The ad interim results of the NURTURE open-label study
(ClinicalTrials.gov identifier: NCT02386553, started in 2017 and
ongoing).
18. 2.Onasemnogene Abeparovec-xioi:
• It is indicated for gene replacement therapy in children aged 2 years or
younger with spinal muscular atrophy (SMA) type 1 (also called
Werdnig-Hoffman disease) who have biallelic mutation in the survival
motor neuron 1 (SNM1) gene.
19. Pharmacology of Onasemnogene Abeparovec
Mechanism of Action
• Recombinant AAV9(adeno-associated virus)-based gene therapy
designed to deliver a copy of the gene encoding the human survival
motor neuron (SMN) protein.
Dosing(Pediatric)
• Suspension for IV infusion
• Provided in a kit containing 2 to 9 vials, as a combination of 2 vial fill
volumes (either 5.5 mL or 8.3 mL)
• All vials have a nominal concentration of 2 x 10^13 vector genomes
(vg) per mL
• Each vial contains an extractable volume of not less than either 5.5
mL or 8.3 mL
20. • ≥2 years: Safety and efficacy not established
• Administered as a one-time, single IV infusion through a venous catheter
• 1.1 x 10^14 vector genomes per kilogram (vg/kg) of body weight
Adverse Reactions:
• In >10% cases,Elevated aminotransferases (>ULN) (27.3%)
• In 1-10% case,Vomiting (6.8%)
21. Clinical Trials:-
• Approval was based on the ongoing phase 3 STR1VE trial and the
completed phase 1 START trial.
• Fifteen patients with SMA1 received a single dose of intravenous
adeno-associated virus serotype 9 carrying SMN complementary DNA
encoding the missing SMN protein.
• Out of the 12 patients who had received the high dose, 11 sat
unassisted, 9 rolled over, 11 fed orally, could speak and 2 walked
independently.
• Elevated serum aminotransferase levels occurred in 4 patients and
were attenuated by prednisolone.
22. • Interim data analysis from the ongoing phase 3 STR1VE trial described
21 of 22 (95%) patients were alive and event-free.
• The median age was 9.5 months, with 6 of 7 (86%) patients aged 0.5
months or older surviving event-free.
• Interim results also showed ongoing improvement of motor milestones
(eq. holding head erect, rolling over, sitting without support).
23. II.Small molecule
1.Risdiplem:
• It is indicated for spinal muscular atrophy, including types 1, 2, and 3,
in adults and children aged 2 months or older.
• It is a first drug which are given by orally.
• The drug was developed by Genentech, a member of the Roche
Group, in partnership with SMA Foundation and PTC Therapeutics.
• Evrysdi (risdiplam) is available as an oral solution with a maximum
dose of 5mg administered once daily, directly distributed to patients’
homes in the US by Accredo Health Group, a speciality pharmacy.
24. • The FDA approved Evrysdi (risdiplam) for the treatment of SMA in adults
and children aged two months and older in 7 August 2020.
Pharmacology of Risdiplam
Mechanism of Action:
• Survival of motor neuron 2 (SMN2) mRNA splicing modifier designed treat
mutations in chromosome 5q that lead to SMN protein deficiency
Absorption:
• Peak plasma time: 1-4 hr
• Steady-state reached: 7-14 days
Distribution:
• Protein bound: Predominantly bound to serum albumin, without any binding
to alpha-1 acid glycoprotein, with a free fraction of 11%
• Vd: 6.3 L/kg
25. Metabolism:
• Primarily metabolized by flavin monooxygenase 1 and 3 (FMO1 and
FMO3) and also by CYPs 1A1, 2J2, 3A4, and 3A7
• Parent drug was the major component found in plasma, accounting for
83% of drug-related material in circulation
Elimination:
• Half-life: ~50 hr
• Clearance: 2.1 L/h (14.9 kg patient)
Excretion: Feces 53% (14% unchanged); urine 28% (8% unchanged)
26. Dosing:
• Powder for oral solution-60mg/bottle
• In Spinal Muscular Atrophy-5 mg orally once a day for one year in
Adult.
• In Child ≥2 months:
1.Age ≥2 months to <2 years: 0.2 mg/kg PO qDay
2.Age ≥2 years and weight <20 kg: 0.25 mg/kg PO qDay
3.Age ≥2 years and weight ≥20 kg: 5 mg PO qDay
• Administer at approximately the same time each day after a meal
Adverse Effects:
• Mostly fever,diarrhea,Rashes but sometimes mouth and aphthous
ulcers,arthralgia & urinary tract infection.
27. Clinical Trials:
• Approval was supported by results from several phase 3 trials
(FIREFISH, SUNFISH, JEWELFISH, RAINBOWFISH).
• FIREFISH is an open-label, two-part pivotal clinical trial in infants
aged 2–7 months with Type 1 SMA. Results showed 41% (7/17) of
infants achieved ability to sit without support for at least 5 seconds and
90% (19/21) were alive without permanent ventilation at 12 months.
• After a minimum of 23 months of treatment and reaching an age of 28
months or older, 81% (17/21) of all patients were alive without
permanent ventilation.
• The SUNFISH study was a two-part, double-blind, placebo-controlled
pivotal clinical trial in children and young adults (aged 2–25 years) with
Type 2 or 3 SMA.
28. • A clinically meaningful and statistically significant improvement in
motor function among children and adults was observed as measured
by a change from baseline in the MFM-32 total score.
• Improved upper limb motor function compared to baseline, as
measured by the Revised Upper Limb Module (RULM), a secondary
independent motor function endpoint of the study, also showed
statistically significant improvement.
29. • JEWELFISH is an open-label exploratory trial in people with SMA
Type 1, 2 or 3, aged 6 months to 60 years who have been previously
treated with SMA therapy, gene therapy, or olesoxime.
• Recruitment is complete with 174 people enrolled.
• RAINBOWFISH is an open-label, single-arm, multicenter study,
investigating the efficacy, safety, pharmacokinetics, and
pharmacodynamics of risdiplam in babies (~n=25), from birth to 6
weeks of age (at first dose) with genetically diagnosed SMA who are
not yet presenting with symptoms.
• The study is currently recruiting.
30. III.Muscle enchancing therapy
1.Reldesemtiv:-
• It is a selective small-molecule troponin activator in fast skeletal
muscles.
• The rationale for its use in SMA stands on several lines of evidence.
• This molecule increases the affinity of troponin C to calcium, sensitizes
the sarcomere to calcium effects and reinforces contraction.
31. • Following a phase I study confirming its safety, a phase II, double-
blind, randomized, placebo-controlled trial (ClinicalTrials.gov
identifier: NCT02644668, years 2015–2018) on 70 patients with SMA
type II to IV examined its effect on functional and respiratory
performance.
• The results showed, in the higher dosage group, a trend towards an
increase from baseline in the six-minute walk test (6MWT) and of the
maximal expiratory pressure (MEP).
32. • Adverse events were similar between treated and placebo groups SRK-
015 is a monoclonal antibody, which selectively inhibits myostatin,
promoting muscle cells growth and differentiation and improving
muscle force in SMA mice .
• A phase I trial (ClinicalTrials.gov identifier: NCT02644777, years
2017–2018) confirmed its safety and tolerability.
• A phase II study (TOPAZ, ClinicalTrials.gov identifier: NCT03921528,
started in 2019 and ongoing), involved 58 SMA type II and SMA III
patients, aged two to 21 years. Patients have received treatment by
intravenous infusion every four weeks for one year. The six-month
interim results will be available by the end of 2020.
33. IV.Other therapy:-
• Medications such as valproic acid, phenylbutyrate, hydroxyurea, and
albuterol have been shown to increase SMN transcription in laboratory
studies, but clinical trials have not demonstrated significant
improvement in disease progression.
• The SMA CARNIVAL trials (parts 1 and 2) found valproic acid and L-
carnitine ineffective with regard to strength or functional improvement
at 6 months and 12 months in both ambulatory and non-ambulatory
children.
• Adverse effects were reported in 85% of patients.
34. • Gabapentin, riluzole, and olesoxime have been studied for their
suspected neuroprotective properties, without significant clinical
benefit noted.
• Treatment with creatine, phenylbutyrate, gabapentin, thyrotropin-
releasing hormone, and hydroxyurea have also proved ineffective.
35. References
• Werdnig G: Zwei frühinfantile hereditäre Fälle von progressive Muskelatrophie unter dem Bilde der Dystrophie, aber auf neurotischer
Grundlage [Two early infantile hereditary cases of progressive muscular atrophy simulating dystrophy, but on a neural basis; in
German]. Arch Psychiatr Nervenkr 1891, 22:437-480.
• Hoffmann J: U” ber chronische spinale Muskelatrophie im Kindesalter, auf familiärer Basis [On chronic spinal muscular atrophy in
childhood, with a familial basis; in German]. Dtsch Z Nervenheilkd 1893, 3:427-470
• Brzustowicz LM, Lehner T, Castilla LH, Penchaszadeh GK, Wilhelmsen KC, Daniels R, Davies KE, Leppert M, Ziter F, Wood D,
Dubowitz V, Zerres K, Hausmanowa-Petrusewicz I, Ott J, Munsat TL, Gilliam TC: Genetic mapping of chronic childhood-onset spinal
muscular atrophy to chromosome 5q11.2-13.3. Nature 1990, 344:540-41.
• Spinraza (nusinersen) [package insert]. Cambridge, MA: Biogen Inc. 2016 December.
• Chiriboga, C.A.; Swoboda, K.J.; Darras, B.T.; Iannaccone, S.T.; Montes, J.; De Vivo, D.C.; Norris, D.A.; Bennett, C.F.; Bishop, K.M.
Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology 2016, 86, 890–897.
• Finkel, R.S.; Chiriboga, C.A.; Vajsar, J.; Day, J.W.; Montes, J.; De Vivo, D.C.; Yamashita, M.; Rigo, F.; Hung, G.; Schneider, E.; et al.
Treatment of infantile-onset spinal muscular atrophy with nusinersen: A phase 2, open-label, dose-escalation study. Lancet Lond. Engl.
2016, 388, 3017–3026
• Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, et al. Single-Dose Gene-Replacement Therapy for Spinal
Muscular Atrophy. N Engl J Med. 2017 Nov 2. 377 (18):1713-1722.
• Al-Zaidy S, Pickard AS, Kotha K, Alfano LN, Lowes L, Paul G, et al. Health outcomes in spinal muscular atrophy type 1 following
AVXS-101 gene replacement therapy. Pediatr Pulmonol. 2019 Feb. 54 (2):179-185.
• Novartis. AveXis data reinforce effectiveness of Zolgensma in treating spinal muscular atrophy (SMA) Type 1. 2019 Apr 16.
36. • Servais L, Baranello G, Masson R, et al. FIREFISH Part 2: efficacy and safety of risdiplam (RG7916)
in infants with spinal muscular atrophy (SMA) (1302). Neurology. April 14, 2020;94
• Evrysdi (risdiplam) [package insert]. South San Francisco, CA: Genentech. August 2020.
• Hwee, D.T.; Kennedy, A.; Ryans, J.; Russell, A.J.; Jia, Z.; Hinken, A.C.; Morgans, D.J.; Malik, F.I.;
Jasper, J.R. Fast skeletal muscle troponin activator tirasemtiv increases muscle function and
performance in the B6SJL-SOD1G93AALS mouse model. PLoS ONE 2014, 9, e96921.
• Rudnicki, S.A.; Andrews, J.A.; Malik, F.I. CY 5021 A phase 2, double-blind, randomized, placebo-
controlled, multiple-dose study of reldesemtiv 2 ascending-dose cohorts of patients with Spinal
Muscular Atrophy (SMA). In Proceedings of the Cure SMA 2018, Dallas, TX, USA, 16 June 2018.
• Kissel JT, Scott CB, Reyna SP, Crawford TO, Simard LR, Krosschell KJ, et al. SMA CARNIVAL
TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory
children with spinal muscular atrophy. PLoS One. 2011. 6(7):e21296.
• Swoboda KJ, Scott CB, Crawford TO, Simard LR, Reyna SP, Krosschell KJ, et al. SMA CARNI-
VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in
spinal muscular atrophy. PLoS One. 2010 Aug 19. 5(8):e12140.
• Wadman RI, Bosboom WM, van der Pol WL, van den Berg LH, Wokke JH, Iannaccone ST, et al.
Drug treatment for spinal muscular atrophy types II and III. Cochrane Database Syst Rev. 2012 Apr
18. 4:CD006282.