The blurry line

The usual recommendations and institutional definitions nicely dichotomize the diagnosis of epilepsy for us. Two or more unprovoked seizures means epilepsy. The conceptual difficulty with the idea of provocation is more than disentangling processes which merely make an ictal state in the brain more favorable from those which set up long-term dynamical changes predisposing the brain to spontaneous seizures. It extends to the temporal. After what period of time following a provocation can we meaningfully infer that a seizure was provoked?

Consider a teen named Zed. Zed does a bunch of cocaine, stays up 3 nights in a row, and yet dutifully also takes his prescribed dexamfetamine, bupropion, and tramadol. Zed has two tonic-clonic seizures in a three-hour period. These are provoked.

Conversely, if Zed develops a pleomorphic xanthroastrocytoma and it affects the surrounding neural networks and he develops spontaneous seizures, this is epilepsy.

Suppose Zed skateboards and hits his head badly on a skate-park ramp. No helmet. He has no fracture but has a small frontal cerebral contusion. Three days later he has a seizure. Will he have more? What if he only had a concussion with loss of awareness of less than 10 s and no contusion? What if, in the latter scenario, he had a seizure at six days? Ten? Twenty?

Suppose Zed is prone to hypoglycemia. He has had three seizures ever and only in the setting of blood sugars of 20 mg/dL (about 1.1 mM). Otherwise he doesn’t have seizures.

Or Zed has seizures when binge-drinking and at no other time. If Zed remains abstinent from alcohol he doesn’t have seizures. Does he have epilepsy?

The gamut of causes

The most common etiology of epilepsy is Unknown. Which is to say 40% of cases have no definite cause.

Two-hit hypotheses have been put forward to explain, as in cancer, why some patients develop epilepsy and some do not.

The essential taxonomy of causes is acquired structural-vascular-inflammatory, inborn structural, primary genetic, and secondary genetic.

Anything which alters cortical tissue can alter brain dynamics and cortical connectivity. To the extent this sets up epileptic networks, epilepsy can result.

Acquired structural-vascular-inflammatory

Brain tumors, including metastases (breast, lung, and melanoma being commonest) as well as primary CNS tumors (both low-grade and high-grade). Other mass lesions such as dermal and epidermal cysts. Hybrid lesions such as hamartomas (incl cortical tubers) and DNETs.

Vascular malformations such as AVMs and cavernous hemangiomata.

Cortical infarction, venous sinus thrombosis, and intracranial hemorrhage and cerebral contusion.

Mechanical disruption as with penetrating head injury.

Intracranial infections such as HSV encephalitis, bacterial meningitis, trichinosis, cryptococcus.

Inflammatory diseases such as autoimmune epilepsy, Rasmussen’s encephalitis, vasculitides.