On 2015 Dec 15, David Keller commented:

Trials of Parkinson disease treatments should report effects on dyskinesia along with improvements in "off" time

Patients with Parkinson disease (PD) can be described as being in one of the following 3 symptomatic states at any given time:

1) "Off" - the under-medicated state, when the patient feels the oppressive grip of bradykinesia, and tremors or dystonia may also worsen. Without treatment, the "off" state is the default pathological disease condition in PD.

2) "On, without dyskinesia" - the desired well-medicated near-normal state, when the patient is able to move with a minimum of bradykinesia, tremor or dyskinesia;

3) "On, with Dyskinesia" - the relatively over-medicated state, when the patient experiences disabling and tiring writhing movements.

Levodopa, dopamine agonists, and other PD medications which relieve "off"-state bradykinesia also tend to cause dyskinesias when their effects are excessive.

The current nomenclature in neurology lumps together the desired state of "on, without dyskinesia", with the uncomfortable and disabling state of "on, with dyskinesia". This imprecision causes confusing miscommunication, for the following reasons:

PD patients take medications with the goal of achieving a near-normal "on" state for the maximum amount of time per day. Dyskinesias and the "off" state can be disabling to PD patients to an equivalent degree, and both are detested and unpleasant. PD patients are not benefited by a medication which reduces "off" time if it increases "on" time with dyskinesia by an equal or greater amount.

The net increase in "on" time without dyskinesia is what benefits patients, and is what clinicians want to know concerning a new PD treatment.

Addendum: I have been posed the following question: if dyskinesia occurs in the over-medicated state, why can't the patient simply reduce the amount of medication, taking greater care not to exceed the amount required? The answer is that the "amount required" to emerge from the paralyzing grip of the off state can vary markedly from day to day. In advanced Parkinson disease, the therapeutic window can close completely - the patient is plunged into dyskinesia the moment he breaks free of the off state.

On 2015 Dec 15, David Keller commented:

Trials of Parkinson disease treatments should report effects on dyskinesia along with improvements in "off" time

Patients with Parkinson disease (PD) can be described as being in one of the following 3 symptomatic states at any given time:

1) "Off" - the under-medicated state, when the patient feels the oppressive grip of bradykinesia, and tremors or dystonia may also worsen. Without treatment, the "off" state is the default pathological disease condition in PD.

2) "On, without dyskinesia" - the desired well-medicated near-normal state, when the patient is able to move with a minimum of bradykinesia, tremor or dyskinesia;

3) "On, with Dyskinesia" - the relatively over-medicated state, when the patient experiences disabling and tiring writhing movements.

Levodopa, dopamine agonists, and other PD medications which relieve "off"-state bradykinesia also tend to cause dyskinesias when their effects are excessive.

The current nomenclature in neurology lumps together the desired state of "on, without dyskinesia", with the uncomfortable and disabling state of "on, with dyskinesia". This imprecision causes confusing miscommunication, for the following reasons:

PD patients take medications with the goal of achieving a near-normal "on" state for the maximum amount of time per day. Dyskinesias and the "off" state can be disabling to PD patients to an equivalent degree, and both are detested and unpleasant. PD patients are not benefited by a medication which reduces "off" time if it increases "on" time with dyskinesia by an equal or greater amount.

The net increase in "on" time without dyskinesia is what benefits patients, and is what clinicians want to know concerning a new PD treatment.

Addendum: I have been posed the following question: if dyskinesia occurs in the over-medicated state, why can't the patient simply reduce the amount of medication, taking greater care not to exceed the amount required? The answer is that the "amount required" to emerge from the paralyzing grip of the off state can vary markedly from day to day. In advanced Parkinson disease, the therapeutic window can close completely - the patient is plunged into dyskinesia the moment he breaks free of the off state.