Motor Neuron Lesions Notes

Anterior Horn Cell Disorders

  • Spinal Muscular Atrophy (SMA)
    • Mode of inheritance: Autosomal Recessive (AR)
    • Involves selective destruction of anterior horn cells.
    • Mutation of chromosome 5q 11.2-13.3 (“survival motor neuron 1”)
    • 5 Types:
      • SMA I
        • aka “Acute Werdnig Hoffman Disease” / “Acute Infantile SMA”
        • Onset: before 6 months
        • Lifespan: 2 years old (most severe form)
        • Unable to sit independently
      • SMA II
        • aka “Chronic Werdnig Hoffman Disease” / “Chronic Infantile SMA” / “Early-Onset SMA” / “Intermediate SMA”
        • Onset: 6-18 months
        • Lifespan: mid 20’s
        • Sits independently
        • No independent ambulation
        • Marked weakness and progressive decline in strength
        • Joint contractures
        • Severe progressive scoliosis
        • Restrictive lung disease
      • SMA III
        • aka “Kugelberg Welander” / “Chronic Juvenile SMA” / “Later-Onset SMA”
        • Onset: 5-15 years old
        • Lifespan: normal
        • Ambulation independently
        • Hand tremor
        • Tongue and limb fasciculations
        • Areflexia
      • SMA IV
        • aka “Adult-Onset SMA”
        • Onset: mid 30’s
        • Lifespan: normal
        • Either AR or AD
        • Same with SMA III but with slowly progressive proximal limb weakness and fasciculations
        • Hyporeflexia / areflexia
  • Spino-Bulbar Muscular Atrophy (SBMA)
    • aka “Kennedy Disease”
    • Not associated with SMN1 gene abnormalities
    • A hereditary adult-onset disease that causes preferential degeneration of LMN leads to weakness and atrophy of bulbar, facial, and limb muscles.
      • Mutation of Androgen Receptor gene
    • Mode of inheritance: X-linked recessive
    • Proximal or distal weakness
    • Wasting of facial, bulbar, and limb muscles
    • Sensory impairment
    • Endocrinologic disturbances:
      • Androgen resistance
      • Gynecomastia
      • Increased testosterone or progesterone
      • Decreased fertility
  • Poliomyelitis (“Heine-Medin Disease”)
    • “polio” = gray matter; “myelo” = spinal cord; “itis” = inflammation
    • Disease of the anterior horn neurons of the spinal cord and brainstem
    • Caused by poliovirus
    • Types of Poliovirus:
      • Type I (Brunhilde) – most common (MC)
      • Type II (Lansing) – rarest
      • Type III (Leon) – most paralytic
    • Mode of transmission: oral-fecal route
    • Types of Poliomyelitis:
      • Abortive
        • Flu-like symptoms (fever, headache, nausea or vomiting, sore throat, constipation, and abdominal pain)
        • No progression
      • Non-paralytic
        • Stiffness in the neck and along the spine
      • Paralytic
        • Most severe form of polio
        • Combined symptoms of abortive and non-paralytic
        • Subtypes:
          • Spinal Paralytic Polio
            • Virus attacks anterior horn cells in the lumbar region of the spinal cord
            • LE more affected than UE (LE > UE)
            • Asymmetric manifestation
            • Proximal more affected than distal (proximal > distal)
          • Bulbar Paralytic Polio
            • Virus attacks cranial nerves (CN 5, 9, 10, 11) in the brainstem
          • Spinobulbar Paralytic Polio
            • Mixed spinal and bulbar polio
    • Prevention (vaccines):
      • Salk (intramuscular) – inactivated polio vaccine
      • Sabin (oral) – live attenuated polio virus
  • Post-Polio Syndrome
    • Criteria for Diagnosis:
      • Confirmed history of paralytic polio
      • Partial or complete recovery of at least 15 years
      • Onset of progressive and persistent new muscle weakness
      • Persistent symptoms for 1 year
      • Exclusion of other conditions (neurologic/medical/orthopedic)

Peripheral Nerve Disorders

  • Guillain-Barré Syndrome (GBS)
    • aka “Landry’s Paralysis”
    • Progressive, symmetrical weakness of the limbs
      • With hyporeflexia/areflexia
      • With or without sensory abnormalities
    • Hallmark: bilateral ascending paralysis
    • Idiopathic
      • May be caused by infectious agents:
        • Campylobacter jejuni – MC
        • Cytomegalovirus (CMV)
        • Epstein-Barr virus (EBV)
        • Mycoplasma pneumoniae
        • Haemophilus influenza
    • GBS Subtypes:
      • Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)
        • MC type of GBS
        • Common in Europe and North America
        • Symmetrical weakness of all limbs
        • Hyporeflexia / areflexia
        • Mild sensory symptoms
        • Respiratory involvement
        • CN7 palsy (facial paralysis)
      • Axonal Forms
        • Rare
        • Common in Asia and South America
        • (+) axonal degeneration (myelin sheath not affected)
        • Subtypes:
          • Acute Motor Axonal Neuropathy (AMAN)
          • Acute Motor and Sensory Axonal Neuropathy (AMSAN)
        • Signs and Symptoms:
          • Variable sensory symptoms
          • Reflexes can be normal or increased (hyperreflexia)
          • Symmetrical weakness
          • Respiratory involvement
      • Miller Fisher
        • Symmetrical descending paralysis
        • Triad:
          • Ophthalmoplegia
          • Areflexia
          • Ataxia
        • Caused by infectious agents:
          • (MC)
          • Epstein-Barr virus
          • Mycoplasma pneumoniae
          • Haemophilus influenza
    • Criteria for Diagnosis of GBS:
      • Areflexia
      • Progressive weakness of both arms and legs
      • Lumbar puncture
        • (+) albuminocytologic dissociation
        • Elevated CSF protein with normal WBC count
      • Electrodiagnostic testing
        • Decreased NCV (nerve conduction velocity)
    • Poor Prognosis, if:
      • Male
      • Advanced age
      • Axonal involvement (i.e., Axonal Forms)
      • Diarrhea
      • Cytomegalovirus
    • Causes of Death:
      • Pulmonary embolism – MC
      • Cardiac arrhythmia
    • Management:
      • Plasma exchange
      • Intravenous immunoglobulins (IVIG)

Infectious Neuropathies

  • Leprosy (“Hansen’s Disease”)
    • Caused by mycobacterium leprae
    • Clinical Presentations:
      • Tuberculoid Form
        • Causes single/multiple well-circumscribed cutaneous lesions
        • Increased WBC levels kill the bacilli and causes nerve destruction:
          • Ulnar n. – MC
          • Median n.
          • Common peroneal n.
          • Facial n. (CN 7)
          • Superficial radial n.
          • Digital n.
          • Posterior auricular n.
          • Sural n.
      • Lepromatous Form
        • (+) macules
        • Direct nerve invasion of the bacillus causes nerve destruction
      • Borderline
        • Between lepromatous and tuberculoid
    • Management:
      • Dapsone – may cause progressive motor neuropathy if too much
  • Lyme’s Disease
    • A tick-borne disorder caused by spirochete borrelia burgdoferi
    • Management: IV ceftriaxone
    • 3 Stages:
      • Early Infection
        • (+) local erythematous lesion (“erythema migrans”)
      • Disseminated Infection
        • Facial nerve palsy (CN 7)
        • (+) radiculoneuritis that progresses to plexopathy (LE > UE)
      • Late-stage Infection
        • Distal symmetric neuropathy
        • Paresthesia + sensory loss

Diabetic Neuropathies

  • One of the most common causes of neuropathies
  • Types:
    • Symmetric
      • Chronic Sensorimotor Distal Polyneuropathy (MC)
      • LE > UE
      • Vibration and proprioception loss
      • Decreased Achilles reflex
      • Affected: Sural n.
    • Asymmetric
      • e.g., proximal motor neuropathy
      • (+) severe pain
      • Muscle atrophy of quads, adductors (longus, magnus, brevis), and iliopsoas
      • Affected: femoral n. and saphenous n. (distal continuation of femoral n.)
    • Focal
      • Mononeuropathies
      • Affected:
        • Cranial nerves: 3, 6, 7
        • Peripheral nerves: median n. (MC), ulnar n., peroneal n.

Toxic Neuropathies

  • Chronic Alcohol Abuse
    • Can cause midline cerebellar degeneration known as “Wernicke’s Syndrome”
    • Triad:
      • Ataxia
      • Dementia
      • Ophthalmoplegia
  • Lead Toxicity
    • Motor > sensory
    • MC affected: radial n.
    • Signs and Symptoms:
      • Atrophy of hand and foot intrinsic muscles
      • Wrist drop

Charcot-Marie-Tooth Disease

  • aka “HMSN” (Hereditary Motor Sensory Neuropathy) / “Peroneal Muscular Atrophy”
  • Autosomal Dominant (AD)
    • Mutation of 17p
  • Signs and Symptoms:
    • Steppage gait
    • Foot slap during heel strike
    • Pes cavus – due to affectation of peroneals (evertors), so stronger inversion
    • (+) inverted champagne sign
    • Claw hand
  • Types:
    • I. Hypertrophic Type
      • Characterized slow conduction velocity and segmental demyelination (spared axons)
      • Hallmark: (+) onion bulb appearance
        • Due to remyelination and demyelination
      • MC type
    • II. Axonal Type: axonal degeneration (with Wallerian degeneration)
    • III. Dejerine Sottas: early-onset with severe demyelination
      • Most severe type
    • IV. Refsum’s Disease
    • V. Spinocerebellar Ataxia
    • VI. with Optic Neuritis
    • VII. with Retinitis Pigmentosa

Neuromuscular Junction Disorders

  • Myasthenia Gravis
    • Post-synaptic disorder
    • Autoimmune disorder
    • Etiology: idiopathic
    • Pathophysiology: destruction of the nicotinic post-synaptic receptors for acetylcholine
    • Associated with thymoma
    • Female > Male
    • Signs and Symptoms:
      • Ptosis
      • Ophthalmoplegia (CN 3, 4, 6)
      • Diplopia
      • Proximal > distal
      • Heat sensitivity
      • Cervical extensor weakness
      • Respiratory failure
      • Decrementing muscle performance (due to ACh receptor defect)
    • Diagnostic test:
      • Tensilon Test – aka Edrophonium Test / Enlon Test
        • Administration of edrophonium chloride (an anti-acetylcholinesterase) which inhibits acetylcholinesterase
    • Pharmacologic management: Neostigmine, Pyridostigmine, Physostigmine
  • Lambert Eaton Myasthenic Syndrome (LEMS)
    • Presynaptic disorder
    • Autoimmune disorder
    • Etiology: idiopathic
    • Pathophysiology: antibodies block the calcium channels resulting in decreased acetylcholine
    • Associated with lung cancer (small cell / oat cell carcinoma)
    • Male > Female
    • Signs and Symptoms:
      • Autonomic nerve dysfunctions
      • Proximal > distal
      • Incrementing muscle response
    • Pharmacologic management: Guanidine
  • Botulism
    • Presynaptic disorder
    • Etiology: Claustridium Botulinum Toxin (from canned goods)
    • Pathophysiology: total nerve blockage
    • Signs and Symptoms:
      • Autonomic nerve dysfunctions
      • Generalized muscle weakness
      • Oculobulbar muscle weakness
        • Ophthalmoplegia (CN 3, 4, 6)
    • Pharmacologic management: Heptavalent botulinum anti-toxin

Amyotrophic Lateral Sclerosis

  • aka “Lou Gehrig’s Disease” / “Charcot’s Disease” / “Sporadic ALS”
  • Rapidly progressive neurodegenerative disease
  • Characterized by weakness, spasticity, and muscle atrophy with subsequent respiratory compromise leading to death
  • Etiology: idiopathic
  • Pathophysiology: excitotoxicity secondary to excessive glutamate activity
  • Male > Female
  • 40-60 years old
  • Pharmacologic management: Riluzole
  • Variants of ALS:
    • Sporadic ALS
      • MC
      • Idiopathic
      • Onset: 40-60 years old
    • Familial ALS
      • Associated with copper zinc superoxide dismutase (SOD1) gene
      • Onset: decade younger than sporadic ALS (30-50 years old)
    • Juvenile ALS
      • Onset: before 25 years old
      • Types:
        • ALS 5
          • AR (autosomal recessive)
          • mutation of 15q
        • ALS 2
          • AR (autosomal recessive)
          • mutation of 2q 33
        • ALS 4
          • AD (autosomal dominant)
          • mutation of 9q 34 (“Senataxin gene”)
  • Diagnostic Criteria: El Escorial Criteria
    • Anatomic Regions
      • Bulbar – face
      • Cervical – UE
      • Thoracic – abdominals
      • Lumbar – LE
    • Diagnostic Categories
      • Clinically Definite ALS: UMN and LMN signs in 3-4 regions
      • Clinically Probable ALS: UMN and LMN signs in 2 regions
      • Clinically Possible ALS: UMN and LMN signs in 1 region OR UMN signs in at least 2 regions
  • Clinical Manifestations:
    • UMN Signs:
      • Spasticity
      • Hyperreflexia
      • Pathological reflex
      • Pseudobulbar affect
      • Spastic dysarthria
    • LMN Signs:
      • Hypotonia
      • Hyporeflexia
      • Fasciculations
      • Cramps
      • Flaccid dysarthria
      • Muscle atrophy (cadaveric hand)