Muscular Atrophy, Spinal
A group of disorders marked by progressive degeneration of motor neurons in the spinal cord resulting in weakness and muscular atrophy, usually without evidence of injury to the corticospinal tracts. Diseases in this category include Werdnig-Hoffmann disease and later onset SPINAL MUSCULAR ATROPHIES OF CHILDHOOD, most of which are hereditary. (Adams et al., Principles of Neurology, 6th ed, p1089)
Spinal Muscular Atrophies of Childhood
A group of recessively inherited diseases that feature progressive muscular atrophy and hypotonia. They are classified as type I (Werdnig-Hoffman disease), type II (intermediate form), and type III (Kugelberg-Welander disease). Type I is fatal in infancy, type II has a late infantile onset and is associated with survival into the second or third decade. Type III has its onset in childhood, and is slowly progressive. (J Med Genet 1996 Apr:33(4):281-3)
Survival of Motor Neuron 1 Protein
A SMN complex protein that is essential for the function of the SMN protein complex. In humans the protein is encoded by a single gene found near the inversion telomere of a large inverted region of CHROMOSOME 5. Mutations in the gene coding for survival of motor neuron 1 protein may result in SPINAL MUSCULAR ATROPHIES OF CHILDHOOD.
SMN Complex Proteins
A complex of proteins that assemble the SNRNP CORE PROTEINS into a core structure that surrounds a highly conserved RNA sequence found in SMALL NUCLEAR RNA. They are found localized in the GEMINI OF COILED BODIES and in the CYTOPLASM. The SMN complex is named after the Survival of Motor Neuron Complex Protein 1, which is a critical component of the complex.
Survival of Motor Neuron 2 Protein
A SMN complex protein that is closely-related to SURVIVAL OF MOTOR NEURON 1 PROTEIN. In humans, the protein is encoded by an often duplicated gene found near the inversion centromere of a large inverted region of CHROMOSOME 5.
Muscular Disorders, Atrophic
Disorders characterized by an abnormal reduction in muscle volume due to a decrease in the size or number of muscle fibers. Atrophy may result from diseases intrinsic to muscle tissue (e.g., MUSCULAR DYSTROPHY) or secondary to PERIPHERAL NERVOUS SYSTEM DISEASES that impair innervation to muscle tissue (e.g., MUSCULAR ATROPHY, SPINAL).
Bulbo-Spinal Atrophy, X-Linked
Spinal Cord Injuries
Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.).
Neuronal Apoptosis-Inhibitory Protein
An inhibitor of apoptosis protein that was initially identified during analysis of CHROMOSOME DELETIONS associated with SPINAL MUSCULAR ATROPHY. Naip contains a nucleotide binding oligomerization domain and a carboxy-terminal LEUCINE rich repeat.
Cyclic AMP Response Element-Binding Protein
Anterior Horn Cells
Spinal Cord Diseases
Atrophy of the optic disk which may be congenital or acquired. This condition indicates a deficiency in the number of nerve fibers which arise in the RETINA and converge to form the OPTIC DISK; OPTIC NERVE; OPTIC CHIASM; and optic tracts. GLAUCOMA; ISCHEMIA; inflammation, a chronic elevation of intracranial pressure, toxins, optic nerve compression, and inherited conditions (see OPTIC ATROPHIES, HEREDITARY) are relatively common causes of this condition.
Motor Neuron Disease
Diseases characterized by a selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In AMYOTROPHIC LATERAL SCLEROSIS there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes (see MUSCULAR ATROPHY, SPINAL) the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy (BULBAR PALSY, PROGRESSIVE), the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation. (Adams et al., Principles of Neurology, 6th ed, p1089)
Ribonucleoproteins, Small Nuclear
DEAD Box Protein 20
Chromosomes, Human, Pair 5
Spinal Nerve Roots
Paired bundles of NERVE FIBERS entering and leaving the SPINAL CORD at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots are efferent, comprising the axons of spinal motor and PREGANGLIONIC AUTONOMIC FIBERS.
Disease Models, Animal
A distinct subnuclear domain enriched in splicesomal snRNPs (RIBONUCLEOPROTEINS, SMALL NUCLEAR) and p80-coilin.
Multiple System Atrophy
A syndrome complex composed of three conditions which represent clinical variants of the same disease process: STRIATONIGRAL DEGENERATION; SHY-DRAGER SYNDROME; and the sporadic form of OLIVOPONTOCEREBELLAR ATROPHIES. Clinical features include autonomic, cerebellar, and basal ganglia dysfunction. Pathologic examination reveals atrophy of the basal ganglia, cerebellum, pons, and medulla, with prominent loss of autonomic neurons in the brain stem and spinal cord. (From Adams et al., Principles of Neurology, 6th ed, p1076; Baillieres Clin Neurol 1997 Apr;6(1):187-204; Med Clin North Am 1999 Mar;83(2):381-92)
Procedure in which an anesthetic is injected directly into the spinal cord.
snRNP Core Proteins
Spinal Cord Neoplasms
Benign and malignant neoplasms which occur within the substance of the spinal cord (intramedullary neoplasms) or in the space between the dura and spinal cord (intradural extramedullary neoplasms). The majority of intramedullary spinal tumors are primary CNS neoplasms including ASTROCYTOMA; EPENDYMOMA; and LIPOMA. Intramedullary neoplasms are often associated with SYRINGOMYELIA. The most frequent histologic types of intradural-extramedullary tumors are MENINGIOMA and NEUROFIBROMA.
The cavity within the SPINAL COLUMN through which the SPINAL CORD passes.
Spinal Cord Compression
Acute and chronic conditions characterized by external mechanical compression of the SPINAL CORD due to extramedullary neoplasm; EPIDURAL ABSCESS; SPINAL FRACTURES; bony deformities of the vertebral bodies; and other conditions. Clinical manifestations vary with the anatomic site of the lesion and may include localized pain, weakness, sensory loss, incontinence, and impotence.
Bulbar Palsy, Progressive
A motor neuron disease marked by progressive weakness of the muscles innervated by cranial nerves of the lower brain stem. Clinical manifestations include dysarthria, dysphagia, facial weakness, tongue weakness, and fasciculations of the tongue and facial muscles. The adult form of the disease is marked initially by bulbar weakness which progresses to involve motor neurons throughout the neuroaxis. Eventually this condition may become indistinguishable from AMYOTROPHIC LATERAL SCLEROSIS. Fazio-Londe syndrome is an inherited form of this illness which occurs in children and young adults. (Adams et al., Principles of Neurology, 6th ed, p1091; Brain 1992 Dec;115(Pt 6):1889-1900)
Narrowing of the spinal canal.
Operative immobilization or ankylosis of two or more vertebrae by fusion of the vertebral bodies with a short bone graft or often with diskectomy or laminectomy. (From Blauvelt & Nelson, A Manual of Orthopaedic Terminology, 5th ed, p236; Dorland, 28th ed)
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.
A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343)
A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251)
Magnetic Resonance Imaging
A group of inherited and sporadic disorders which share progressive ataxia in combination with atrophy of the CEREBELLUM; PONS; and inferior olivary nuclei. Additional clinical features may include MUSCLE RIGIDITY; NYSTAGMUS, PATHOLOGIC; RETINAL DEGENERATION; MUSCLE SPASTICITY; DEMENTIA; URINARY INCONTINENCE; and OPHTHALMOPLEGIA. The familial form has an earlier onset (second decade) and may feature spinal cord atrophy. The sporadic form tends to present in the fifth or sixth decade, and is considered a clinical subtype of MULTIPLE SYSTEM ATROPHY. (From Adams et al., Principles of Neurology, 6th ed, p1085)
Persistent flexure or contracture of a joint.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
Vocal Cord Paralysis
Congenital or acquired paralysis of one or both VOCAL CORDS. This condition is caused by defects in the CENTRAL NERVOUS SYSTEM, the VAGUS NERVE and branches of LARYNGEAL NERVES. Common symptoms are VOICE DISORDERS including HOARSENESS or APHONIA.
Progressive, autosomal recessive, diffuse atrophy of the choroid, pigment epithelium, and sensory retina that begins in childhood.
Trinucleotide Repeat Expansion
An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.
Neuromuscular Junction Diseases
Conditions characterized by impaired transmission of impulses at the NEUROMUSCULAR JUNCTION. This may result from disorders that affect receptor function, pre- or postsynaptic membrane function, or ACETYLCHOLINESTERASE activity. The majority of diseases in this category are associated with autoimmune, toxic, or inherited conditions.
Amyotrophic Lateral Sclerosis
A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94)
Spinal Cord Ischemia
Reduced blood flow to the spinal cord which is supplied by the anterior spinal artery and the paired posterior spinal arteries. This condition may be associated with ARTERIOSCLEROSIS, trauma, emboli, diseases of the aorta, and other disorders. Prolonged ischemia may lead to INFARCTION of spinal cord tissue.
Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.
Genes that influence the PHENOTYPE only in the homozygous state.
A form of MACULAR DEGENERATION also known as dry macular degeneration marked by occurrence of a well-defined progressive lesion or atrophy in the central part of the RETINA called the MACULA LUTEA. It is distinguishable from WET MACULAR DEGENERATION in that the latter involves neovascular exudates.
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
Intranuclear Inclusion Bodies
Circumscribed masses of foreign or metabolically inactive materials, within the CELL NUCLEUS. Some are VIRAL INCLUSION BODIES.
Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.
X-ray visualization of the spinal cord following injection of contrast medium into the spinal arachnoid space.
A generic term for any circumscribed mass of foreign (e.g., lead or viruses) or metabolically inactive materials (e.g., ceroid or MALLORY BODIES), within the cytoplasm or nucleus of a cell. Inclusion bodies are in cells infected with certain filtrable viruses, observed especially in nerve, epithelial, or endothelial cells. (Stedman, 25th ed)
Severe or complete loss of motor function in the lower extremities and lower portions of the trunk. This condition is most often associated with SPINAL CORD DISEASES, although BRAIN DISEASES; PERIPHERAL NERVOUS SYSTEM DISEASES; NEUROMUSCULAR DISEASES; and MUSCULAR DISEASES may also cause bilateral leg weakness.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations can often by visualized and take the form of a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of MOTOR NEURON DISEASE or PERIPHERAL NERVOUS SYSTEM DISEASES. (Adams et al., Principles of Neurology, 6th ed, p1294)
Myoclonic Epilepsies, Progressive
A heterogeneous group of primarily familial disorders characterized by myoclonic seizures, tonic-clonic seizures, ataxia, progressive intellectual deterioration, and neuronal degeneration. These include LAFORA DISEASE; MERRF SYNDROME; NEURONAL CEROID-LIPOFUSCINOSIS; sialidosis (see MUCOLIPIDOSES), and UNVERRICHT-LUNDBORG SYNDROME.
Organelles in which the splicing and excision reactions that remove introns from precursor messenger RNA molecules occur. One component of a spliceosome is five small nuclear RNA molecules (U1, U2, U4, U5, U6) that, working in conjunction with proteins, help to fold pieces of RNA into the right shapes and later splice them into the message.
An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered.
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
An appreciable lateral deviation in the normally straight vertical line of the spine. (Dorland, 27th ed)
A surgical procedure that entails removing all (laminectomy) or part (laminotomy) of selected vertebral lamina to relieve pressure on the SPINAL CORD and/or SPINAL NERVE ROOTS. Vertebral lamina is the thin flattened posterior wall of vertebral arch that forms the vertebral foramen through which pass the spinal cord and nerve roots.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.
A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
A syndrome characterized by new neuromuscular symptoms that occur at least 15 years after clinical stability has been attained in patients with a prior history of symptomatic poliomyelitis. Clinical features include new muscular weakness and atrophy of the limbs, bulbar innervated musculature, and muscles of respiration, combined with excessive fatigue, joint pain, and reduced stamina. The process is marked by slow progression and periods of stabilization. (From Ann NY Acad Sci 1995 May 25;753:68-80)
Hematoma, Epidural, Spinal
A rare epidural hematoma in the spinal epidural space, usually due to a vascular malformation (CENTRAL NERVOUS SYSTEM VASCULAR MALFORMATIONS) or TRAUMA. Spontaneous spinal epidural hematoma is a neurologic emergency due to a rapidly evolving compressive MYELOPATHY.
Hereditary Sensory and Motor Neuropathy
A group of slowly progressive inherited disorders affecting motor and sensory peripheral nerves. Subtypes include HMSNs I-VII. HMSN I and II both refer to CHARCOT-MARIE-TOOTH DISEASE. HMSN III refers to hypertrophic neuropathy of infancy. HMSN IV refers to REFSUM DISEASE. HMSN V refers to a condition marked by a hereditary motor and sensory neuropathy associated with spastic paraplegia (see SPASTIC PARAPLEGIA, HEREDITARY). HMSN VI refers to HMSN associated with an inherited optic atrophy (OPTIC ATROPHIES, HEREDITARY), and HMSN VII refers to HMSN associated with retinitis pigmentosa. (From Adams et al., Principles of Neurology, 6th ed, p1343)
Rotarod Performance Test
A performance test based on forced MOTOR ACTIVITY on a rotating rod, usually by a rodent. Parameters include the riding time (seconds) or endurance. Test is used to evaluate balance and coordination of the subjects, particular in experimental animal models for neurological disorders and drug effects.
Posterior Horn Cells
Neurons in the SPINAL CORD DORSAL HORN whose cell bodies and processes are confined entirely to the CENTRAL NERVOUS SYSTEM. They receive collateral or direct terminations of dorsal root fibers. They send their axons either directly to ANTERIOR HORN CELLS or to the WHITE MATTER ascending and descending longitudinal fibers.
Optic Atrophy, Autosomal Dominant
Dominant optic atrophy is a hereditary optic neuropathy causing decreased visual acuity, color vision deficits, a centrocecal scotoma, and optic nerve pallor (Hum. Genet. 1998; 102: 79-86). Mutations leading to this condition have been mapped to the OPA1 gene at chromosome 3q28-q29. OPA1 codes for a dynamin-related GTPase that localizes to mitochondria.
The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium.
A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the TIBIAL NERVE and the PERONEAL NERVE.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Muscle Fibers, Skeletal
Large, multinucleate single cells, either cylindrical or prismatic in shape, that form the basic unit of SKELETAL MUSCLE. They consist of MYOFIBRILS enclosed within and attached to the SARCOLEMMA. They are derived from the fusion of skeletal myoblasts (MYOBLASTS, SKELETAL) into a syncytium, followed by differentiation.
Region of the back including the LUMBAR VERTEBRAE, SACRUM, and nearby structures.
Age of Onset
VERTEBRAE in the region of the lower BACK below the THORACIC VERTEBRAE and above the SACRAL VERTEBRAE.
Gene Expression Regulation
Type III intermediate filament proteins that assemble into neurofilaments, the major cytoskeletal element in nerve axons and dendrites. They consist of three distinct polypeptides, the neurofilament triplet. Types I, II, and IV intermediate filament proteins form other cytoskeletal elements such as keratins and lamins. It appears that the metabolism of neurofilaments is disturbed in Alzheimer's disease, as indicated by the presence of neurofilament epitopes in the neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit of the neurofilament triplet in brains of Alzheimer's patients. (Can J Neurol Sci 1990 Aug;17(3):302)
A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.
Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.
Polymerase Chain Reaction
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Bulbous enlargement of the growing tip of nerve axons and dendrites. They are crucial to neuronal development because of their pathfinding ability and their role in synaptogenesis.
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
A class of closely related heterogeneous-nuclear ribonucleoproteins of approximately 34-40 kDa in size. Although they are generally found in the nucleoplasm, they also shuttle between the nucleus and the cytoplasm. Members of this class have been found to have a role in mRNA transport, telomere biogenesis and RNA SPLICING.
Muscle Strength Dynamometer
A device that measures MUSCLE STRENGTH during muscle contraction, such as gripping, pushing, and pulling. It is used to evaluate the health status of muscle in sports medicine or physical therapy.
Central Nervous System
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Spinal Cord Regeneration
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.