Motor Neuron Diseases Flashcards
What is affected in Motor Neuron Diseases
-motor neurons, their motor axons, and secondarily the muscle fibers they innervated (the motor unit)
Werdnig-Hoffman
Infantile Spinal Muscular Atrophy -autosomal recessive -hypotonicity, hyporeflexia, fatal -tongue fasciculations -poor suck reflex -abdominal respirations Anterior Horn Cell Disease -difficulty breathing, swallowing , die early from respiratory failure, "frog-leg" posture
Wolfart-Kugelberg-Welander
-Juvenile Proximal Chronic Spinal Muscular Atrophy
-Autosomal recessive
-slowly progressive, fasciculations, proximal weakness, resembles myopathy
Anterior Horn Cell Disease
-atrophy of pectoralis & thigh muscles
Adult Onset Spinal Muscular Atrophy
-sproadic (some familial)
-Proximal, distal weakness
-hypotonicity, hyporeflexia
Anterior Horn Cell Disease
Werdnig-Hoffman Disease Tests
- EMG: signs of denervation and fasciculations
- Muscle Biopsy: group fiber atrophy
- Mutation: ‘survival motor neuron gene’ on chromosome 5q
Wolfart-Kugelberg-Welander Tests
- EMG & Biopsy: denervation changes
- Serum CK: normal
- Mutation: ‘survival motor neuron gene’ SNM1 is absent and the size of SMN2 determines if the patients have neonatal or juvenile form
- SMN2 is larger
Progressive Bulbar Palsy
Adult motor neuron disorders
- sproadic, fasciculations, Bulbar muscles weakness, rapidly progressive, tongue atrophy
- may develop ALS
Amyotrophic Lateral Sclerosis (ALS)
Adult motor neuron disorders
- mostly sporadic, some familial cases - 10%, hyperreflexia, spasticity
- muscle atrophy (fasciculations) , fasciculations, tongue atrophy, rapidly progressive (lethal)
- upper & lower motor neurons, bulbar weakness
- normal sensation
Presentation: difficulty swallowing & breathing
Late: biateral Babinski signs, hard to close mouth
Progressive Lateral Sclerosis
- sporadic, involves only upper motor neurons, spasticity
- hyperreflexia, more benign course
- little atrophy or signs of denervation
Progressive Spinal Muscular Atrophy
-mostly sporadic, progressive weakness, muscle atrophy, fasciculations, areflexia
Signs, Symptoms, & Labs of Motor Neuron Diseases
- Symmetrical or asymmetrical weakness
- Atrophy
- inc. or dec. reflexes dep. on corticospinal tract involvement (ALS)
- fasciculations
- normal sensation
- normal nerve conduction velocities
- denervation on EMG
- dec. # of motor units
- muscle biopsy shows atrophic fibers & fiber grouping
Cervical Spondylosis
- seen in MRI
- present: lower motor neuron signs in upper extremities secondary to nerve root compression & upper motor neuron signs in the lower extremities secondary to compression of spinal cord & corticospinal tracts
Kennedy’s Disease
- Bulbo-spinal muscular atrophy
- more benign than ALS, family history
- mutations of the androgen receptor on the x chromosome
- Phenotype: gyneocomastia & testicular atrophy, lower motor neuron syndrome (atrophy, fasciculations, signs of denervation in limbs & tongue, mild neuropathy)
- serum CPK elevated
- DNA testing diagnostic
Pathology of ALS
- degeneration of the corticospinal tracts (lack of myelin)
- Bunina body: dense granules inclusion in cell body cytoplasm (ubiquitin accumulations)
Etiology of ALS
-unknown, some familial cases (genetic)
Possible etiologies of ALS and other motor neuron diseases
Genetic Defects
- SOD gene mutations in chromosome 21 in AD familial ALS
- Juvenile ALS: chromosome 2q33 (also 9q34, 15q15, 8q21), and also ALS associated with mutation of 9q21, XP
- ALS associated with other diseases such as chromosome 17-linked fronto-temporal dementia (FTD)
- an expanded section of DNA on chromosome 9 in the gene C90RF72 is most common cause of familial ALS with or without FTD
- Excitotoxicity: evidence suggests an inc. of glutamate mediated excitotoxicity causing neuronal degeneration (secondary)
Treatment of ALS
- Glutamate antagonists (riluzole)
- Experimental: creatine & antioxidants such as carotene, coenzyme Q10, vitamins C & E could be of benefit, COX 2 inhibitors, nerve growth factors
- physical therapy
- symptomatic treatments such as anticholinergics for sialorrhea, stool softeners, antispastic drugs, botulinum toxin
- antidepressantts
- bracing
- gastrostomy
- respiratory assistance
Brachial plexus
- extends from spinal cord to distal aspect of axilla
- 6 divisions, behind clavicle
Sensory Domain
- the skin region innervated by the sensory nerve fibers contained with a nerve root
- Dermatome: sensory domain of a root
Muscle Domain
- the muscles innervated by the motor nerve fibers contained within a nerve root
- Myotome: motor domain of a root
What are the 2 most common causes of radiculopathies?
- Disk herniation & degeneration (>C6
-Spondylosis: C5 & C6> frequent
by age 60 yrs, 70% W and 85% M
after age 70 yrs, 93% W and 97% M - Lumbosacral radiculopathies
- >95% of HNPs affect either L5 or S1
Clinical features of Radiculopathies?
- Pain (hallmark): sharp, stabbing, hot; electric, radiating, aggravated by maneuvers that stretch the root (cervical: neck extension, neck rotation, Spurling’s maneuver)
- lower extremity (SLR used with L5 or S1 nerve root involvement is suspected and reverse SLR w/L4
- weakness & atrophy (motor nerve fibers, myotomal distrubution (muscle domain of root))
- Paresthesias & sensory loss: sensory nerve fibers, dermatomal distribution (sensory domain of a root)
- Muscle stretch reflexes (diminished or absent)
-Irritation = tingling
Spondylosis
> 50 yrs
- Cervical spondylosis: myeloradiculopathy (spinal canal stenosis)
- Lumbosacral spondylosis: neurogenic cladication (ambulation to LE pain & weakness), cauda equina syndrome
Radiculopathy: Fracture of Dislocation
-Trauma: major cause in young patients
minor cause amoung elderly
-Bone disease: osteoporosis; osteomalacia; Paget disease, Corticosteroid therapy, congenital anomalies
Radiculopathy: Infection
- fever
- immunosuppressed status
- IVDA
- Spinal surgery
- penetrating wound
Radiculopathy: Neoplasm
- history of cancer
- constitutional symptoms (weight loss)
- pain at rest
- neurologic deficit (cauda equina localization)
Evaluation of Radiculopathy
-H&P (most important):
Spinal cord compression: sensory level, anal tone, fecal or urinary incontinence, check cutaneous reflexes (abdominal; bulbocavernousus; anal wink; cremaster)
-Plain radiographs
-CT (+/- myelography)
-MRI: superior to CT for all spine conditions
multiplanar
greater contrast sensitivity (tumor & infection)
Noninvasive
Non-ionizing radiation
Gadolinium contrast (scar tissue vs. recurrent disk protrusion)
EDX Testing
- yields physiologic info
- complements MRI (anatomic changes, high false+)
- False + studies extremely uncommon
- assesses sensory & motor nerve fibers
- assesses muscle fibers
- identifies demyelination & axon loss
- localized the disorder
- generates ddx or the actual diagnosis
- determines severity
- determines prognosis
- dictates management & follow-up
Radiculopathy: Conservative Treatment
- most w/acute radiculopathies improve in 6 weeks
- bed rest 0-2 days
- physical therapy (heat, cold, ultrasound, massage, stretching, ergonomic education)
- Meds: NSAIDS, prednisone, benzodiazephines
- Nerve Block
Radiculopathy: Surgical Treatment
- Etiology (neoplastic process)
- spinal instability
- severe or progressive weakness
- spinal cord compression
- cauda equina syndrome
- sphincter or sexual dysfunction
- incapacitating neurogenic claudication
- intractable pain (ill-advised if isolated pain with negative imaging)
Plexopathies
-Brachial plexus elements
anterior primary rami, trunks, divisions, cords, terminal nerves
Polyneuropathy
- weakness symmetrically, distally
- stocking & glove pattern
- dec. reflexes
- slow nerve conduction velocities
- denervation & decreased # of motor units on EMG
- Muscle biopsy: atrophic fibers & fiber type grouping
Mononeuritis
(one nerve)
- weakness in nerve distribution
- slow nerve conduction velocities
- denervation & decreased # of motor units on EMG
- Muscle biopsy: atrophic fibers & fiber type grouping
Mononeuritis Multiplex
-several nerves
weakness in nerve distribution
-slow nerve conduction velocities
-denervation & decreased # of motor units on EMG
-Muscle biopsy: atrophic fibers & fiber type grouping
Demyelinating Neuropathy
- weakness: distal & proximal
- areflexia
- dec. vibration & position sense with little deficit of pain & temp sensations
- very slow NCV, conduction block with normal amplitude of nerve action potential
- prolonged distal latencies, F responses & H reflexes
Axonal Neuropathy
- mostly distal weakness with distal areflexia, glove & stocking sensory deficit to all modalities, trophic changes
- Nerve conduction is almost normal with reduced action potential amplitude, signs of denervation on EMG (uremia, toxins)
Wallerian Degeneration
-severe acute damaged to myelin & axons
trauma, vasculities
Charcot-Marie-Tooth Disease
- hereditary
- usually autosomal dominant
- usually demyelinating, rarely axonal
- high arched feet
- hammer toes
- check NCV in relatives
- some cases appear late
- Type 1 has deletions on the genes that express meylin protein PMP 22(1A) or protein 0 P0(1B)
Diabetic Neuropathies
- diffuse sensory motor neuropathy has metabolic origin (accumulation of sorbitol, deficiency of myoinositol)
- presens with burning of feet, then numbness & weakness
- improves with good control of diabetes
- mononeuritis, mononeuritis mulitplex & diabetic ophthalmoplegia are produced by infarct to nerves or plexus
- diabetics are more predisposed to entrapment neuropathies
Treatment of Diabetic Polyneuropathy
- good control of diabetes
- nerve growth factor
- sorbitol antagonist
- myoinositol & vitamin supplementation
- be aware of other conditions (CIDP)
Treatment of Mononeuropathy, mononeuropathy multiplex
-treatment is conservative, consider steroids if the disease is progressive
Guillain-Barre syndrome
-acute autoimmune, ascending paralysis accompanied by arreflexia & normal or mildly abnormal sensation with albuminocytological disassociation in the spinal fluid
Guillain-Barre syndrome: Clinical Findings
- progressive (symmetrical) paralysis over a period of one to three weeks
- acute inflammatory radiculoneuropathy
- ascending paralysis, facial weakness, respiratory insufficiency
- paresthesia but little evidence of sensory deficit
- areflexia, normal or almost normal sensation
Treatment of Guillian Barre Syndrome
- respiratory assistance if necessary
- includes plasmapheresis or gamma globulin infusions
- corticosteroids (NO benefit)
- physical therapy & emotional support
Chronic Inflammatory Neuropathy
- autoimmune inflammatory neuropathy that affects myelin sheath
- subacute to chronic weakness; symmetrical, distal & proximal
- no cranial nerve involvement
- areflexia
- marked deficit of positional & vibratory senses, little pain & temp deficit, elevated spinal fluid protein, slow NCV
- evidence of conduction block (vasculitic neuropathy sometimes produces conduction block, simulating demyelination)
- minimal denervation on EMG
- rarely can have CNS signs (central demyelination)
- could have relapsing course
- nerve biopsy: segmental demyelination, rarely, inflammation
- same patients have MUGS
- treat with corticosteroids, immunosuppressant, or gamma globulin
