Anterior Horn Cell Diseases

Question 1

Spinal muscular atrophy

Answer 1

• Group of recessive disorders resulting in apoptosis of lower motor neurons
• Patients typically present during infancy or early childhood with progressive weakness, hypotonia, muscle atrophy, hyporeflexia/areflexia, and varying degrees of bulbar weakness.
• Diagnosis: Genetic testing
• Treatment: Supportive care.
  
  • Disease modifying:
    
    • Nusinersen (Causes differential splicing of SMA2 gene, causing translation to effectively produce the SMA1 gene product)
    • Onasemnogene abeparvovec (Recombinant virus that delivers a complete, healthy copy of SMA1)

Question 2

Poliomyelitis

Answer 2

• Caused by poliovirus, an enterovirus
  
  • Fecal-oral transmission
  • Incubation time 7-14 days
• Poliomyelitis is preceded by abortive poliomyelitis
  
  • GI upset, fever, nausea, sore throat, myalgias, headache for 1-3 days
• Nonparalytic poliomyelitis aka aseptic polio meningitis
  
  • Begins several days following abortive poliomyelitis
  • Fever, malaise, headache, nausea, back pain, neck pain, myalgia
  • Neck muscle weakness, but no frank paralysis
• Paralytic poliomyelitis
  
  • Begins 2-3 days following nonparalytic poliomyelitis
  • Asymmetric, flaccid paralysis that worsens over hours to days
  • Most commonly affects leg muscles, but may affect any muscle. Paralysis is more severe in proximal muscles.
  • Ascending paralysis eventually leads to respiratory paralysis
  • LMN signs are typically present

Question 3

Poliomyelitis and SMA as anterior horn diseases

Answer 3

Polio and SMA are the two main causes of isolated anterior horn cell pathology

And dinstinguishing them is often easy!

SMA will only occur in infants and very young children, without a prodrome.

Polio can occur in anyone unvaccinated, and will have a flu-like prodrome

Question 4

Diagnosis and treatment of polio and poliomyelitis

Answer 4

• Diagnosis:
  
  • CSF PCR (best test)
    
    • CSF will show high protein with pleocytosis (neutrophilic if early, lymphocytic if late), but normal glucose levels
  • Oral swab PCR
  • Fecal PCR
• Treatment:
  
  • Supportive care
  • Mechanical ventilation usually required if there is progression to poliomyelitis

Question 5

Post-polio syndrome

Answer 5

• Most frequent complication observed following poliovirus infection (up to 40% of survivors)
• Occurs decades after polio infection
• Manifests with progressive muscle weakness and pain, even in areas that were not affected by the initial infection

Question 6

Stiff person syndrome

Answer 6

• Caused by anti-GAD antibodies (glutamic acid decarboxylase, an enzyme in GABA synthesis) or other antibodies against GABAminergic neurons
• Reduced levels of GABA leads to loss of CNS inhibition and increasing muscle stiffness
• Associated with other autoimmune diseases, particularly type 1 diabetes mellitus. It may also be a paraneoplastic phenomenon.
• Diagnosis: EMG-CNS shows continuous motor activity that is reduced in response to diazepam. CSF shows oligoclonal bands. Definitive diagnosis is detection of anti-GAD antibodies or anti-amphiphysin antibodies
  
  • Most paraneoplastic SPS is GAD negative, and this is where anti-amphiphysin is primarily seen
• Treatment: Symptomatic treatment with benzodiazepines (diazepam, clonazepam) and muscle relaxants (baclofen). Immune modulation with IVIG, plasmapharesis, or rituximab. If suspected paraneoplastic, look for and resect the tumor to cure.

Question 7

SMA is a pure ___ disorder

Answer 7

SMA is a pure motor neuron disorder

Question 8

Pattern of motor neuron involvement in SMA

Answer 8

• Lower spinal motor neurons
• Bulbar motor neurons except oculomotor nerves

Question 9

Four types of SMA

Answer 9

• Type 1: Early infantile onset, most severe
• Type 2 and 3: Late infancy, less severe
• Type 4: Adult onset, less severe

Question 10

Diagnosing SMA

Answer 10

Just go straight to genetic testing.

They are mostly point mutations and cheap to screen for.

No need for muscle biopsy or EMG-NCS

Question 11

Categorization of infantile hypotonia

Answer 11

• Cerebral: Generally seen with other cortical and subcortical findings (altered awareness, epileptic seizures, subcortical myoclonus)
• Spinal
• Peripheral: Motor neuron disorders (like SMA), congenital neuropathies/myopathies, neurometabolic conditions (usually mitochondrial)
• Combined

Question 12

__ are a classic and often tested sign of SMA

Answer 12

Tongue fasciculations are a classic and often tested sign of SMA

Question 13

Essential pathology of SMA type 1

Answer 13

As part of normal neurodevelopment, we start with an excess of motor neurons which then trim themselves down by apoptosis

In SMA, this process never stops until all motor neurons are dead

Question 14

___ is highly suggestive of a cortical etiology for hypotonia in a newborn

Answer 14

Epilepsy is highly suggestive of a cortical etiology for hypotonia in a newborn

Think of it as a ‘cortical’ sign, even though it does not help you localize.

myoclonus and altered sensorium are also highly suggestive of a cortical etiology.

Question 15

An awake, attentive infant with significant weakness and hypotonia likely has a __ process

Answer 15

An awake, attentive infant with significant weakness and hypotonia likely has a peripheral process