Cerebrovascular accident

Clinicians differentiate deficits due to lesions of lower motor neurons (brainstem and spinal cord neurons innervating skeletal muscle) from those due to lesions of upper motor neurons, that refers not only to the corticospinal and corticobulbar neurons of the pyramidal tract, though also to cortical cells which drive reticulospinal (i.e., medial pathway) neurons. Therefore, upper motor neuron lesions generate much more severe deficits than those due to lesions of corticobulbar or corticospinal neurons alone. Strokes are the main cause of upper motor neuron lesions.

The most common cerebrovascular accident (CVA, stroke) is caused by a thromboembolism disturbing the branch of the middle cerebral artery which supplies the internal capsule. Infarction of the internal capsule generates a syndrome that does not resemble experimental lesions of the lateral motor pathways as the internal capsule also holds corticoreticular axons that drive lateral and medial reticulospinal tracts. Afterward an initial period of flaccid paralysis and lack of reflexes on the side reverse the lesion two main deficits are seen:

- Hemiparesis. Muscle weakness on one side which is greatest in arm extensors and leg flexors, as arm flexors are stronger than extensors and in the legs the reverse is true. When the corticobulbar fibers are affected, then voluntary facial movements are compromised. Whenever the weakness is too severe that paralysis answers the term hemiplegia is used. Weakness takes place as the loss of descending excitation means fewer motor units are recruited.

- Spasticity. An increase in muscle tone is seen in the stronger limb muscles. It is caused by improved excitability of the stretch reflex, mainly the phasic component, as attempts at quick muscle stretch are met with much greater resistance than slow stretch. Forceful efforts to stretch a muscle are met with great resistance (caused by the stretch reflex), that fails suddenly due to firing of high threshold muscle (i.e., non-spindle) afferents.

Spasticity in part outcomes from the loss of presynaptic inhibition on Ia terminals. Generally, presynaptic inhibition is brought about by the action of the reticulospinal tracts on GABA-ergic Ia presynaptic inhibitory interneurons. GABA released from such interneurons acts on GABA_B and GABA_A receptors on the Ia terminals. GABA_B receptors are the metabotropic receptors and when stimulated act through Gi proteins to increase the K⁺ conductance. The resultant hyperpolarization decreases Ca²⁺ influx into the primary afferent terminal, therefore curtailing the discharge of glutamate onto the motor neurons. In spasticity, the descending reticulospinal input is lost. This lead to failure of presynaptic inhibition and therefore hyperexcitability of the stretch reflex.
Baclofen is an agonist at GABA_B receptors and is used orally and intrathecally in the treatment of spasticity. As benzodiazepines (example, diazepam) are agonists at the GABA_A receptors included in presynaptic inhibition, they can also be used in spasticity.