Do you start an anti-seizure medication in a patient with a first unprovoked nocturnal seizure with a normal exam, imaging, and EEG; or wait until the second seizure?  

Not with the first seizure unless history suggests otherwise. Also, what is the age of the patient? For example, are benign epilepsy syndromes like rolandic epilepsy on your differential? If age does not fit, monitor the patient clinically. Repeat EEG after a few months with sleep recorded.

This is a loaded question, there is no one good answer as multiple factors have to be considered: age, comorbidities, seizure semiology, potential consequences (if no immediate treatment), patient's preferences, and anxiety level, etc. Taking a good history may reveal evidence of prior unrecognized ...

It depends on many things including age, the wishes of the patient, and whether the seizure was focal or generalized. I would definitely perform an ambulatory EEG to look for inter-ictal activity.

I agree with what is stated by many colleagues here...an age-old question. There are many factors to consider. In the end, we often give patients and families the choice, but I have a low threshold of treating with a low dose of a well-tolerated safe ASM. Beyond a routine EEG, a 3-day ambulatory...

A single nocturnal seizure has a high incidence of recurrence and by definition (ILAE > 60% risk of subsequent seizure) means the person has epilepsy. Guidelines suggest starting a medication. You can see it in UpToDate as well.

If it is TRULY a one-time seizure (not missed auras, myoclonus, etc.), the MRI is negative, the sleep-deprived EEG is negative, and the story is good, then I counsel the patient that there is no right answer. The long-term prognosis for waiting for a second seizure or starting a medication immediate...

I believe that the Italians addressed this in a study years ago where they identified a history of neurological injury, focal features to the exam, and positive findings in the EEG or imaging as contributing to the risk of additional seizures. Like Dr. @French, I believe it is a joint decision with ...

No.

I don't. They are asked not to drive for 6 months or do anything that can expose them to harm should they suddenly have a seizure, this is the toughest part to deal with. They are told that starting medication doesn't get them out of that state-based law. 

We all teach that the patient "gets one seizure" and yet as multiple doctors note above, this is not so easily conveyed to the patient, especially if the patient is told to refrain from driving, etc. "It depends".

A detailed neuro exam must be done for ankle clonus, babinski, and other reflex abnormalities or asymmetry. If it's a bus driver or a long haul trucker, I would do a 3-day ambulatory EEG and be sure that no amphetamines/cocaine or high caffeinated energy drinks were used to explain a single seizure....