35 Medical Comorbidity in Epilepsy

Kimberly L. Pargeon and Sheryl R. Haut

Epilepsy Management Center, Einstein-Montefiore, Bronx, NY, USA
Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA

Many patients with epilepsy have comorbid medical conditions, which often complicate the treatment of seizures and affect quality of life. Disorders are comorbid if they occur in the same person more frequently than chance alone would suggest. Comorbid conditions in epilepsy occur in a number of forms: medical disorders that coexist with or increase the risk for epilepsy and are related to a common pathophysiology; conditions that arise as a direct result of epilepsy treatment; and conditions otherwise unrelated to epilepsy that complicate epilepsy treatment. These relationships can have important diagnostic and treatment considerations, and a broad familiarity is essential for anyone who cares for patients with epilepsy.

Conditions that coexist with epilepsy or increase epilepsy risk

Migraine headaches

The comorbidity of migraine and epilepsy presents both diagnostic dilemmas and treatment opportunities. Persons with either migraine or epilepsy appear to be more than twice as likely to also have the other disorder, and epilepsy and migraine share many similarities. Both are chronic disorders with episodic attacks, with a return to baseline between episodes. Both disorders are thought to be related, at least in part, to neuronal hyperexcitability, with some shared genetic influences. Similar triggers for migraine headaches and seizures include changes in stress levels and hormonal conditions, such as those that occur with menstruation. Considerable treatment overlap exists, possibly related to the shared pathophysiology, and antiepileptic drugs (AEDs) are often used for migraine prophylaxis, both with FDA approval (valproate sodium and topiramate) and off-label.

The sensory, motor, and cognitive characteristics of epilepsy and migraine may overlap and present diagnostic challenges, particularly if visual symptoms are present (Table 35.1). Furthermore, postictal headaches are frequently migrainous, and headache can occasionally be the sole or most predominant clinical manifestation of epileptic seizures. Seizures may also occur during or within an hour of migraine aura, in a condition that some have referred to as migralepsy. When a diagnostic dilemma arises, the EEG may be helpful in distinguishing migraine from seizure.

TIPS AND TRICKS

When using a single medication to treat comorbid disorders, be sure to dose appropriately for both disorders. For example, target dosing for topiramate in migraine is 50–100 mg daily, but the epilepsy dosing is sometimes higher, in the 50–400 mg range.

SCIENCE REVISITED

Familial hemiplegic migraine (FHM) is an autosomal dominant form of migraine characterized by hemiparesis during the migraine aura. Three major genetic loci involved in FHM are also associated with epilepsy: CACN1A, which codes for a neuronal P-/Q-type calcium channel and is associated with some focal epilepsies; ATP1A2, which codes for a Na/K ATPase and has been identified in families with benign familial infantile convulsions; and SCN1A, which codes for a sodium channel and is implicated in a wide spectrum of epileptic disorders from generalized epilepsy with febrile seizures + type 2 (GEFS + 2), a mild form of epilepsy, to the more severe myoclonic epilepsy of infancy (SMEI).

Stroke

Stroke has been well established as a risk factor for epilepsy, and it is one of the most common etiologies for new-onset seizures in the elderly. Seizures can occur in 6–15% of patients in the first 1–2 weeks immediately following a stroke. Factors that are associated with a higher risk of acute seizures include hemorrhagic stroke, subarachnoid hemorrhage, cortical localization, stroke recurrence, and larger infarcts with greater disability. Studies have been contradictory as to whether early or late initial seizures better predict development of chronic epilepsy.

Patients with epilepsy who are taking warfarin can be at risk for either embolic or hemorrhagic stroke due to drug interactions with certain AEDs, particularly agents interacting with hepatic cytochrome P450 enzymes. Drug interactions between warfarin and AEDs are described in detail in Chapter 13.

CAUTION!

Although acute seizures are not seen in the majority of stroke patients, clinicians should be mindful of this complication in a select group of patients, particularly those with large, cortically based infarcts and especially in patients with hemorrhagic infarcts.

Polycystic ovarian syndrome

There is an increased incidence of polycystic ovarian syndrome (PCOS) in epilepsy, affecting as many as 10–25% of women with epilepsy, with or without treatment with AEDs. PCOS has several key characteristics, including polycystic ovaries; disruption of normal menstruation, ranging from irregular cycle intervals to amenorrhea; and hyperandrogenism, which can clinically manifest as hirsutism, acne, and alopecia. The link between epilepsy, AED use, and PCOS remains controversial, particularly in relation to valproate sodium. The question often raised is whether valproate sodium directly causes PCOS or instead increases certain risk factors, such as excess weight or insulin resistance. Further, long-term treatment with valproate sodium may increase risk of developing aspects of PCOS such as hyperandrogenism but not overt disease. PCOS may contribute to the increased rate of infertility in women with epilepsy and is an important consideration when treating young women who have epilepsy.

Table 35.1. Distinguishing visual symptoms in seizure and migraine.

	Visual symptoms
	Migraine with aura, acephalgic migraine	Seizure
Color	Black and white (may be colored)	Colored
Positive symptoms	Linear or flash, zigzag	Circular, spherical
Localization	Begin at center, expand to hemianoptic field	Hemifield
Localization	Begin at center, expand to hemianoptic field	Same spatial localization each episode, may cross
Scotoma	Common, often follows positive visual symptoms	Uncommon
Scotoma	Common, often follows positive visual symptoms	“Postictal Todd’s” scotoma may occur

Conditions related to epilepsy treatment

Fractures and reduced bone density

Patients with epilepsy are at higher risk for fractures for multiple reasons, including seizure-related falls, imbalance of gait from medication side effects, and neurological deficits leading to decreased mobility. However, an important culprit appears to be bone loss that may be related to osteopenia or osteoporosis due to certain AEDs, particularly the enzyme-inducing agents (Chapters 12 and 19). Decreased bone mineral density may be caused by AEDs either by accelerated bone loss in adults or by poor bone accrual in children. It has been reported that the odds of a broken bone increase by 4–6% for every year of AED use; the risk for any fracture increases by 40% per decade, and the risk for seizure-related fractures increases by 60% per decade.

Currently, there are no official recommendations for timing and type of screening measures for bone health. For those at higher risk of fracture, routine and regular screening should include bone mineral density measurements with dual-energy X-ray absorptiometry (DEXA) as well as serum 25-OH-vitamin D. There are also limited data on appropriate calcium and vitamin D supplementation. The Institute of Medicine recently recommended a daily adult vitamin D intake of 600 international units (IU) with a maximum of 4000 IU (Table 35.2).

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