Tag Archives: pathway

Amyotrophic Lateral Sclerosis (ALS) & the corticospinal tract

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corticospinal_tract

Amyotrophic Lateral Sclerosis (ALS) is a degenerative disease of the motor neurons in the brain and spinal cord. It progressively affects all the muscles in the body but there is no known cause and no treatment. Only about 5-10% of cases are inherited while the rest are sporadic.

The neurons ALS affects are primarily the upper motor neurons. These are the ones that originate in the brain and travel down the spinal cord. These neurons then synapse with the lower motor neurons in the ventral horn, and it is the lower motor neurons that go directly to the muscles.

In ALS there are both upper motor neuron and lower motor neuron symptoms. As the neurons die, a constellation of symptoms including numbness, weakness and paralysis emerge. Eventually the paralysis progresses leading to inability to speak, swallow and breath. There is no cure for ALS and treatments only help with the symptoms, they do not slow the progression of the disease.

So you may have seen a lot of ice bucket challenges over the last few weeks but please support this cause as it is a horrible disease that up until now had almost no recognition or support. So please donate to The ALS Association (alas.org).

And in case you get tired or jaded seeing your social media full of these videos, watch this one of my father doing it. He’s not an emotional guy, but he has lost more than his fair share of friends to this disease.

donate to help fund ALS research and support from Ali & Mike on Vimeo.

Lateral Spinothalamic Pathway

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The Lateral Spinothalamic Pathway is an ascending spinal tract, carrying sensory information to the brain. It is typically depicted as a chain of three neurons: first-, second-, and third-order neurons.

This pathway mediates sensation of pain and temperature.

The first-order neurons in the pathway are located in the dorsal root ganglia at all spinal levels. Their axons ascend the tract of Lissauer, and synapse with second-order neurons.

The second-order neurons are located in the dorsal horn, and their axons immediately decussate via the ventral white commissure. These axons ascend the lateral funiculus and project to the ventral posterolateral (VPL) nucleus of the thalamus.

Some collaterals are sent to areas involved in arousal, namely the midbrain reticular formation, and the intralaminar nuclei of the thalamus (which then project to the caudatoputamen, and frontal and parietal cortex).

The third-order VPL neurons send axons through the posterior limb of the internal capsule to the somatosensory cortex (areas 3, 1, 2).

Lesions to the Lateral Spinothalamic Pathway

Spinal cord lesions affecting the Lateral Spinothalamic pathway result in contralateral sensory deficits below the lesion, because the pathway immediately decussates at the second-order neuron level.

Ventral Spinothalamic Pathway

There is also a Ventral Spinothalamic Pathway, that carries crude touch sensation. It is organized very similarly to the Lateral Spinothalamic pathway; however, it is less clinically-emphasized since the Dorsal Column Medial Lemniscus pathway is more important for touch sensation. If the Ventral Spinothalamic pathway is lesioned, touch sensation will only be minimally affected, as long as the dorsal column remains intact.

Basal Ganglia (fill in the blanks)

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The basal ganglia are a group of nuclei in the brain stem and are associated with voluntary motor control, procedural learning and emotions.

I’ve decided to go back to the good old days and have one where you can fill in the blanks.

the answers:

Dorsal Column Medial Lemniscus Pathway

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Guest post!

The Medial Lemniscus-Dorsal Column pathway is an ascending spinal tract, carrying sensory information to the brain. It is typically depicted as a chain of three neurons: first-, second-, and third-order neurons.

This pathway mediates:

  • Conscious proprioception (most clinically relevant)
  • Sensation of tactile discrimination
  • Vibration sense
  • Form recognition

First order neurons

The first-order neurons in the pathway are located in the dorsal root ganglia at all spinal levels, giving rise to the fasciculus gracilis tract in the lower extremity and the fasciculus cuneatus tract in the upper extremity. The axons comprising these funiculi ascend ipsilaterally to the medulla, where they synapse with the second-order neurons.

Second order neurons

The second-order neurons are located in the cadual medulla, and their cell bodies form the gracile and cuneate nuclei. Their axons, referred to as internal arcuate fibers, decussate to form the medial lemniscus, which ascends the contralateral brainstem to project to the ventral posterolateral (VPL) nucleus of the thalamus.

Third order neurons

The third-order VPL neurons send axons through the posterior limb of the internal capsule to the somatosensory cortex (areas 3, 1, 2)

Spinal cord lesions affecting the dorsal column (e.g., vitamin B12 neuropathy, tabes dorsalis) result in ipsilateral sensory deficits below the lesion, because the pathway does not decussate until it is at the level of the medulla.

Dopamine Pathways in the Brain (and schizophrenia)

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There are 4 main dopamine pathways in the brain:

  1. Nigro-Striatal: substantial nigra to basal ganglia, involved in movement (what gets affected to cause EPS: tardive dyskinesia, akatisia)
  2. Meso-Limbic: VTA to nucleus accumbens, “reward” pathway (causes the positive symptoms of schizophrenia)
  3. Meso-Cortical: VTA to cortex, motivation and emotional response (thought to cause the negative symptoms of schizophrenia)
  4. Tubulo-Infundibular: hypothalamus to posterior pituitary (hypoprolactinemia in untreated individuals, but D2 blockade with antipsychotics can cause a hyperprolactenemia)

 

Antipsychotic medication can be divided into 2 classes

  1. Typical/First Generation
  2. Atypical/Second Generation

Typicals are characterized by strong D2 antagonism in the mess-limbic and meso-cortical pathways. This can also lead to significant extrapyramidal symptoms (EPS). They also have strong CYP-450 metabolism (which means lots of interactions with other drugs and grapefruits).

  • High-potency typicals: only slightly anticholinergic & minimally sedating but have more weight gain and a higher risk of EPS
  • Low-potency typicals: more quite sedating and more anticholinergic (bradycardia, GI upset) but have a lower risk of EPS

Atypicals have less risk for EPS, but carry a higher risk for metabolic side-effects and weight gain. While they bind to D2 receptors (like typicals), atypicals have higher affinity for serotonin (5HT) receptors.

Clozapine is a little different from the other atypicals in that is has been shown to have a shorter half-life, which is thought to be why it doesn’t produce as many EPS. However it has the very specific (and serious) risk of agranulocytosis.

Periaquaductal grey pain modulation pathway

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The periaquaductal grey pathway is the descending pathway that helps modulate pain. There are so many double/triple/quadruple negatives in this pathway it makes the head spin. Who knew that the activation of the inhibitory interneuron would inhibit the other inhibitory interneuron, releasing inhibition of another neuron only to inhibit pain?