DISCUSSION
There are many etiologies that have been known to cause seizures. These include epilepsy, hemorrhagic stroke, cerebral hypoxia, metabolic derangement, thyroid disease, head trauma, CNS infection, vascular malformations, intoxication, poisoning and some of the rarer causes include brain tumors, hypertensive encephalopathy or PRES.6
Our patient had an extensive seizure work up during his hospital admissions. One of the most important tests to perform is VEEG as this provides insight as to the type of seizure a patient may be having and if there is underlying epilepsy.7,8 Continuous VEEG was performed on our patient during both admissions for seizures. Obtaining continuous VEEG monitoring or at least four separate VEEGs increases the chance of picking up underlying epileptic pathology by about 80-90%.9,10 Continuous VEEG in our patient never identified any wave-forms suggestive of epilepsy. Neuroimaging is another crucial component of the seizure work up. Typically brain magnetic resonance imaging (MRI) is preferred over CT scan as MRI has higher sensitivity for epileptogenic lesions as well as having superior soft tissue contrast for identifying any other possible underlying pathology, but CT scans are often sufficient enough to make an accurate diagnosis.7,11,12 Our patient had CT scans of the brain on both presentations but showed no abnormality suggesting the cause of his seizures. In this patient CT scans of the brain were preferred over MRI originally given the patient acuity as CT scans can be obtained quicker than an MRI and are often sufficient in identifying any potential causes of seizures.7,8,13 Typically seizure work up can be continued with outpatient MRI; however, in our case it was deferred as CT brain and VEEG were normal and an MRI was not going to change our treatment plan especially since the patient did not have any additional seizures once his blood pressure was controlled.
Additional work up of seizures includes blood work to evaluate metabolic and thyroid issues and ECG and lumbar puncture to rule out hypoxic cerebral injury from syncope and infectious processes respectively.7,14,15 Although there were some abnormalities in his lab results there was nothing evident as the cause of his seizures (Table 1). ECGs were done on our patient and were insignificant. Moreover, since there were no infectious signs or symptoms and blood cultures never showed any growth of organisms, a lumbar puncture was not indicated.
Given the extensive negative neurologic, hematologic, and infectious workup, seizures in our patient likely occurred due to hypertensive encephalopathy from increased intracranial pressure. The cerebral perfusion pressure (CPP) of the brain has a narrow and sensitive window that is easily affected by changes in systemic BP. Normally when there is an increase in systemic BP the cerebral vasculature vasoconstricts to maintain CPP in physiologic range. In sudden increases of systemic BP or uncontrolled hypertension CPP is not maintained and can lead to cerebral edema resulting in neurologic dysfunction manifesting as seizures.16,17 After our patient’s blood pressure was stabilized during admission, he did not have any additional seizures suggesting that the cause of his seizures was severely elevated blood pressures.
Acute or chronic kidney disease have been shown to cause hypertensive emergency and encephalopathy.4,5 80-85% of patients with chronic kidney disease (CKD) have hypertension.18Hypervolemia is due to decreased glomerular filtration rate (GFR), which results in sodium retention and extracellular fluid expansion.19 Furthermore, an overactive renin-angiotensin system due to renal ischemia can lead to increased angiotensin II and renin causing increased systemic BP, while uremia and decreased renal clearance can cause a neural reflex that increase levels of the vasoconstrictor endothelin.20 Some of the implicated renal diseases that can follow this physiology include acute glomerulonephritis, renal vascular disease, renal infarction, and renal failure. Anti-GBM disease is a rapidly progressive glomerulonephritis falling under this category.
Regarding treatment, initial management of this patient was aimed at controlling the seizure. Patients experiencing seizures without a history of epilepsy are typically treated with a single antiepileptic medication.21 Our patient received lorazepam to terminate the seizure and levetiracetam to prevent recurrence of seizures. Typically, anti-epileptic medications are not required for acute seizure management as seizures resolve on their own within a few minutes unless the patient is critically ill or has underlying metabolic derangements.22 Given that our patient was critically ill with renal disease and a dangerously elevated BP on presentation, levetiracetam was given to prevent further seizures, which has been shown to be more effective and have more long term benefits compared to other prophylactic seizure medications.16
Controlling BP in hypertensive emergency with hypertensive encephalopathy and ESRD varies by physician preference, although most of the treatments focus around IV antihypertensives for rapid control.23 Our patient’s BP was effectively treated at the first seizure admission with clonidine and his PTA medications (losartan, carvedilol, and minoxidil). On the second seizure admission he required a nitroglycerin drip which is commonly used in hypertensive emergency and was effective at controlling his BP.23We suspect the underlying cause of our patient’s hypertensive episodes to be the frequently resistant nature of hypertension in patients with ESRD in combination with anti-GBM disease. Although he was given anti-epileptic medications as well, the patient did not have any additional seizures after his BP was controlled. In addition, with BP medication compliance as an outpatient, there have been no further reports of additional seizures since his last admission.