Anterior horn cell disorders Lower motor neurons The LMNs are located in the brainstem and spinal cord The spinal LMNs are also known as anterior horn cell. Dorsal anterior horn cells innervate distal muscles, ventral located cells- proximal muscles, medially located neurons- truncal and axial muscles. Large spinal cord LMNs are called alpha neurons. Signs and Symptoms of Lower Motor Neuron Dysfunction Weakness: denervation as well as decreased number of functional LMN units reduces overall muscles strength. Muscle atrophy and Hyporeflexia Muscle hypotonicity and flaccidity Fasciculations Muscle cramps Motor Neuron Disease Incidence/100,000/year : Overall: 1.5 to 2 Age : 65 to 74 years Prevalence: 3 to 8 per 100,000 Risk increases with age up to 74 years Mortality Causes 1 in 700 deaths Rate: 1.9/100,000/year Male:Female 1.5:1 More male predominance in younger onset cases Clinical features Typical pattern: Upper + Lower motor neuron signs with normal sensation Onset & Patterns of weakness: Common features Asymmetric limb weakness : Upper > Lower extremity
Areas of weakness with some specificity for ALS Very proximal denervation 1. Paraspinous 2. Posterior neck Jaw weakness: Closure; Opening Voice 1. Nasal, slurred speech 2. Continuous emission of sound Poliomylitis Only a small proportion of people who are exposed to poliovirus develop either minor illness (gastroenteritis) or the major illness several days after the infection. Major illness resembles aseptic meningitis. Approximately 50% of patient progress to paralytic disease within 2-5 days. Paralytic phase: localized fasciculations, severe myalgia, hyperesthesia, and usually fulminant focal and asymmetrical paralysis. Leg muscle involvement is more frequent, than arm, respiratory, and bulbar muscles. Recovery may begin during fist week, but it estimated that 80% of recovery occurs in 6 months. Further improvement may continue over the ensuing 18-24 months. CSF: PN cells, protein is mild-to-moderately increased. Stool culture are positive nearly in 90% of patients by the 10 th day of illness Progressive Post Poliomyelitis Muscular Atrophy (PPMA) In the USA ~ 250k-640k people survived acute poliomyelitis during the last epidemics in the 1940s-1950s. The reported incidence of PPMA ranges from 0 to 64%
PPMA includes progressive LMN syndrome, and post polio syndrome or late effect of remote polio, chronic fatigue, orthopedic and musculoskeletal problems Benign Focal Amyotrophy/ Hirayama's disease Onset: Young adult; 15 to 25 years; Up to 40 years in India Epidemiology: more than 60% are man Male > Female: Up to 10:1 Usually sporadic Occasional familial occurrence Common in Eastern India The etiology is unknown. The number of large and small motor neurons is reduced. It may have some connection with segmental SMA. Weakness: Often confined to a single arm Distal involvement (97%): C7, C8 & T1 innervated muscles; Hand & Forearm Proximal > Distal: 10% Side: Right = Left Atrophy: "Oblique amyotrophy"; Sparing brachioradialis Tremor (80%): On finger extension Typical Hirayama syndrome Progression: Over 1 to 5 years; Occasionally as long as 8 years Static after progression phase: May persist for decades Disability: Mild or none in 73% Laboratory, EMG: Chronic denervation In affected limb(s) (100%) Opposite arm or lower extremities in some patients Signs of acute denervation in 45% NCS: Small CMAPs in affected limbs Sympathetic skin response: May be abnormal MRI? Some patients with inelastic dura: Spinal cord compression with neck flexion No major spinal anomalies T2 signal in anterior horns of gray matter Spinal cord atrophy: C6 & C7 Mild flexion-induced cord displacement Spinal muscular atrophy
SMA was described independently by Werdnig and Hoffmann in 1891 Werdnig described the condition as "neurogenic dystrophy" Hoffmann established the spinal nature of the disease Clinical features: Congenital SMA (5q) with arthrogryposis Severe hypotonia Movements: Absent; Respiratory failure at birth Cranial nerves: Facial diplegia; ± External ophthalmoplegia Contractures: Especially knees Course: Death < 30 days Pathology Loss of motor & sensory myelinated axons Motor neurons: Preserved, swollen Rule out X-linked SMA Werdnig-Hoffmann (Type 1) Onset Usually before 3 months Range 0 to 6 months Some with in utero decreased fetal movements Acute onset in occasional patient Weakness Diffuse; Proximal > Distal Severe Poor feeding Respiratory insufficiency: Paradoxical respirations Sparing of facial & oculomotor Hypotonia Fasciculations: Tongue Tendon reflexes: Reduced or absent Intellect: Normal; Alert faces Prognosis Respiratory failure Death: 50% by 7 months; 95% by 17 months Chronic course in 5% Pathology: Muscle
Large regions of grouped muscle fiber atrophy Most larger fibers are type I Kugelberg-Welander (Types II & III) Classification Type II: Intermediate Onset: Often < 18 months Never stand Life span 1. Often shortened 2. Death > 2 years Type III: Mild Onset: Often > 18 months Stand independently Life span 1. ± Shortened 2. Death in adulthood Laboratory Serum CK: Normal Electrophysiology EMG: Fibrillations; Large amplitude action potentials NCS: Small amplitude CMAPs; Mild slowing; Sensory normal Muscle biopsy Grouped atrophy Type I muscle fiber predominance Bulbo-Spinal Muscular Atrophy (Kennedy's Syndrome) Most common adult onset SMA General frequency: 1 in 50,000 SBMA especially common in western Finland Some regions in Japan Age: Mean 27 years; Range 15 to 60 years Early symptoms & signs: Adolescence Muscle discomfort: Cramps or Pain Fatigue: General; Chewing Gynecomastia: May be asymmetric
Weakness: Not common early; May be distal Symptoms at 30 years Lower > Upper limb weakness Occasionally cramps Progressive muscular atrophy Widespread Lower Motor Neuron Syndrome Weakness: Distribution Distal & Proximal: Either may be more prominent Asymmetric Often involves paraspinous & respiratory muscles Often spares bulbar musculature Spontaneous motor activity Cramps: Common in legs, at night Fasciculations No upper motor neuron signs Pain: Related to immobility Time course Progressive Similar to, more rapid, or slower than, typical ALS Muscle pathology: Grouped atrophy > Fiber type grouping No serum antibodies No conduction block No evidence for response to treatment Pathology: Loss of motor neurons in anterior horn of spinal cord Shrinkage of remaining motor neurons Thank You