A 3-year-old girl is brought to the office due to leg stiffness. Her mother reports that the patient is a clumsy walker and requires assistance to ambulate. The patient was born preterm and has delayed developmental skills. Physical examination shows increased knee and ankle reflexes and clonus at the ankles bilaterally. Muscle tone of the upper extremities and neck is also mildly increased. MRI of the brain reveals periventricular leukomalacia suggestive of cerebral palsy. An oral medication is prescribed that reduces the extremity stiffness. Which of the following CNS drug effects most likely resulted in this patient's improvement?

Question

A 3-year-old girl is brought to the office due to leg stiffness.  Her mother reports that the patient is a clumsy walker and requires assistance to ambulate.  The patient was born preterm and has delayed developmental skills.  Physical examination shows increased knee and ankle reflexes and clonus at the ankles bilaterally.  Muscle tone of the upper extremities and neck is also mildly increased.  MRI of the brain reveals periventricular leukomalacia suggestive of cerebral palsy.  An oral medication is prescribed that reduces the extremity stiffness.  Which of the following CNS drug effects most likely resulted in this patient's improvement?

Quizplus · Accepted Answer

11ec160b_3c1c_94c1_9249_112e334ad165_MD0001_00 This patient has cerebral palsy, a heterogeneous condition characterized by permanent, nonprogressive motor dysfunction caused by damage to the developing brain. Certain subtypes (eg, spastic cerebral palsy) often manifest as delayed gross motor milestones and spasticity (eg, hypertonia, hyperreflexia). Spastic cerebral palsy may be caused by white matter necrosis (seen in this patient as periventricular leukomalacia), which leads to a loss of descending inhibitory control from the upper motor neurons. This results in muscle overactivity, leading to increased tone and hyperreflexia. Enhancement of CNS inhibitory neurotransmitter activity can improve spasticity. GABA is the primary inhibitory neurotransmitter in the CNS and acts on two different receptors: GABA A receptor mediates a fast response to GABA because it is an ion-gated chloride channel. Activation of this receptor leads to rapid muscle relaxation and sedation. Its activity is enhanced by benzodiazepines, which can be used to treat spasticity. GABA B receptor mediates a slower response to GABA because it is mediated by a G protein-coupled receptor that opens potassium channels. It is agonized by baclofen, which can also be used to treat spasticity. (Choice A) Glutamate is the primary excitatory CNS neurotransmitter; therefore, activation of NMDA glutamate receptors would result in increased excitation and lead to further increases in muscle tone. (Choices C and E) Dopamine is a modulatory (rather than primarily excitatory or inhibitory) neurotransmitter that affects motor control. In patients with Parkinson disease who have a relative deficiency of dopamine in the substantia nigra, medications that increase dopaminergic activity (eg, levodopa) can improve muscle rigidity. In some patients, a relative excess of acetylcholine compared to dopamine has been implicated in the tremor or rigidity associated with Parkinson disease or drug-induced parkinsonism. In these patients, anticholinergic medications (eg, trihexyphenidyl) are sometimes used. (Choice D) Glycine is an inhibitory neurotransmitter found primarily in the spinal cord rather than in the brain. Blockade of glycine receptors (eg, strychnine poisoning) leads to increased muscle contraction. Educational objective: Cerebral palsy results in spasticity (eg, hypertonia, hyperreflexia) due to a loss of descending inhibitory control. Medications used to enhance the activity of GABA, the primary inhibitory neurotransmitter of the CNS, can improve spasticity.

A 3-Year-Old Girl Is Brought to the Office Due to Leg