Where do the upper motor neurons originate? Where do they synapse?
They originate in the higher regions of the brain in the motor cortex. They synapse on lower motor neutrons.
What do disorders of Upper Motor Neurons lead to?
Spastiscity (continuous conraction), Overactive Tendon Reflexes, and Abnormal Plantar Extensory Reflex (Babinski Sign).
What do disorders of Lower Motor Neurons lead to?
Atrophy, decreased muscle tone, and loss of tendon reflex. The signs are weak, wasted, and twitching muscles.
Describe the typical activity in a normal muscle:
Muscle Fibers innervated by a single motor neuron are not adjacent to one another.
Describe the activity in diseased muscle as in with Myopathy:
In a diseased muscle the number of muscle fibers in a motor unit is reduced, some shrink and become nonfunctional.
Describe the activity of Reinnervated Muscle as in with Neuropathy:
This occurs when motor neurons are disease, the muscle fiber becomes denervated and atrophic. A surviving neuron can reinnervate a denervated muscle fiber.
What is used to Diagnose disease in myopathy, etc?
Electromyography tests to determine if damage is at muscle tissue, nerves, or the neuromuscular junction. An electromyogram measures the electrical activity of several neighboring motor units at rest and during contraction.
What are some of the findings of neurogenic and myopathic conditions with an Electromyography?
Distal limb weakness often indicate a neurogenic disorder. Proximl limb weakness often indicates a myopathy. Fibrillations are invisible twitches of muscle and they are due t spontaneous activity within single muscle fibers. Fasciculations are visible twitches of muscle that can be seen as flickers under skin. These are involuntary but synchronous contractions of all muscle fibers in a motor unit (seen in ALS).
What is ALS?
Amyotrophic Lateral Sclerosis aka Lou Gehrig Disease. This is mostly an adult-onset condition characterized by progressive degeneration of motor neurons. Amyotrophic: refers to atrophy of muscle, weakness and fasciculation. Lateral Sclerosis refers to the ahrdness felt when the pathologist examines the spinal cord in autopsy specimens. Most of the cases are sporadic.
What is seen histiologically in ALS? What are the pathological hallmarks of ALS?
The lateral sclerosis results from the proliferation of astrocytes and scarring of the lateral columns of spinal cord. There is degeneration and loss of motor neurons. There is Astrocytic Gliosis and intraneuronal inclusions are seen in degenerating neurons and glia. An MRI may show slight atrophy of motor cortex and wallerian degeneration of motor tracts. There is an increase in "FLAIR" and "T2 signal intensity" in the posterior limb of the internal capsule.
What are the clinical results of ALS?
Upper and Lower motor neuron signs are seen. If Lower only are seen, the condition is called Progressive Spinal Muscular Atrophy which leads to weakness, wasting, loss of reflexes, and fasciculation. If Upper are only seen then there are overactive tendon reflexes, Hoffmann's signs, clonus, and Babinski signs.
What types of mutations lead to the familial form of ALS and why?
SOD-1 mutations activate cell death pathways in familial amyotrophic lateral sclerosis. The mutation leads to glutamate excitotoxicity, disorganization of intermediate filaments, and abnormal protein aggregation.
Why does ALS lead to Dysarthria and Dysphagia?
Dysarthria (difficulty speaking) and Dysphagia (difficulty swallowing) are due to the lower part of the brainstaim neurons affecting the face, mouth, and throat.
What amino acids are seen to be higher than normal in ALS?
Glutamate due to the SOD-1 induced toxicity
What are the risk factors of ALS?
Age and male gender. Mechanical or electrical trauma, professional or environmental exposure to metals, herbicides or other toxic substance. Heavy Physical Activity such as with soccer players.
What is Riluzole?
An NMDA/glutamate receptor antagonist drug that is used to treat spasms and showed to slow the progression of ALS.
Most frequent and best understood of all muscular dystrophies. There is a progressive muscular atrophy that occurs only in boys. It is x-linked recessive and is caused by mutations in the Dystrophin Gene.
What are the clinical features of DMD?
Identified between 3rd and 6th years of age. There is evidence of the disease before beginning to walk. The kids exhibit the Gower Maneuver. These children are less active and are prone to fall. There is a calf pseudohypertrophy. Muscles of pelvic girdle, lumbosacral spine, and shoulders become weak and wasted.
What is characteristically elevated in the serum of a child with DMD?
Serum Creatine Kinase
What is Becker-Type Muscular Dystrophy?
Similar to Duchenne Type. This is an X linked disorder that is less problematic and occurs later in life. Patients will often walk well into adult life.
What does Dystrophin normally do?
Links internal cytoskeleton to the extracellular matrix. The amino terminal end binds to F-actin. Carboxyl terminal binds to dystrophin association complex. There is progressive fiber damage and membrane leakage.
What is given to improve muscle strength and function in boys?
Synthetic Glucocorticoid. Prolonged bed rest must be avoided.
What is Myotonic Dystrophy?
A slow progressive disease that is autosomal dominant. The effected gene is DMPK (myotonic dystrophy protein kinase). It manifests in the 3rd and 4th decade.
What are the presentations of Myotonic Dystrophy?
Muscle Stiffness with Myotonia and hair loss. Weakness of facial, sternocleidomastoi, ad distal limb muscles. There is no treatments available.
What is Myotonic Congenita?
Genetic mutation involving the chloride channel of muscles (CLCN-1 gene). Similar symptoms of muscle stiffness and hypertrophy. Stiffness is relieved by exercise and enhanced by cold. General myotonia without weakness is present from birth.
What is Limb Girdle Muscular Dystrophy?
Collection of congenital disorders that affect muscles around the shoulder girdle and hips. it affects both men and women. The onset is usually late first or second decade of life. There is severe disability with 20-30 years
What are the clinical presentations of Limb Girdle Muscular Dystrophy?
Muscle weakness affecting upper arms and legs. Patients have problems standing from sitting, raising arms. There is no mental function alteration. Pain is not present. There is weakness in the pelvis, hips, upper legs, shoulders, and a loss of muscle mass. There is facial muscle weakness with progression of disease. There are palpitations by abnormal heart rhythms and pseudohypertrophy of calves.
What is a unique contracture seen with Limb Girdle Muscular Dystrophy?
Achilles Tendon Contractures
What are the deficiencies in the different types of Limb Girdle Muscular Dystrophy?
Caplain, Dysferlin, Sarcoglycan, and Caveolin deficiencies. Note: Fitzgerald stated he would not expect us to know all of the different types
What are the treatments of LGMD?
None but gene therapy shows promise
Discuss Myasthenia Gravis:
An autoimmune disease in which there are antibodies against nicotinic AchR. There is fluctuating fatigability in which proximal > distal.
What treatments does Myasthenia Gravis respond to?
Acetylcholinesterase Inhibitors (Tensilon/Mestinon)
What is Eaton-Lambert Syndrome?
A particular Myasthenia Gravis in which patients get stronger then weaker in exercise. Patients with this can often develop a small cell lung cancer.
What is Guillain-Barre Syndrome?
The most frequent cause of generalized weakness. It is commonly preceded by an infectious illness. It has immune-mediated segmental demyelination followed by Wallerian degeneration.
What are the symptoms of Gullain-Barre Syndrome?
Symptoms include ascending symmetrical weekness with feeling sensory features, areflexia, and autonomic dysfunction. There is CSF with increased protein and normal cell count.
What is the treatment of GBS?
Respiratory support and immune modulating therapy. Approximately 95% of patients improve with 3/4 of them having a full neurological recovery. 35% will have permanent defects.
Discuss Multiple Sclerosis:
It is an autoimmune disease that is caused by an immune attack on myelin oligodendrocytes in white matter.
What are the symptoms of MS?
Weakness, Sensory Loss, Optic nerve Lesion, Ataxia, and Autonomic Problems.
What are the criteria and diagnostic principals of MS?
Criteria is 2 separate CNS lesions, objective physical findings and 2 separate attacks. MRI plaques in 95% of definite cases. There are oligoclonal bands in CSF in 90% of patients.
What are the supportive treatments for MS?
Steroids, INF 1a/1b, and Copoxone
What are the clinical findings in the patient in MS?
Reflexes are absent to reduced, Coordination trunk or extremity impaired along with gait. Nerve Conduction Velocity (axonal) is mild slowing without conduction block. Nerve Conducting Velocity (demyelinating) shows marked slowing, conduction block, and temporal dispersion.