Epilepsia Partialis Continua as Presenting Manifestation of AIDS

Abstract

Seizures, most commonly generalized tonic–clonic, are common in known human immune deficiency virus (HIV) sero-positive patients, and they usually have a focal lesion on brain imaging. However, it is very unusual to see a patient with no premorbid illness presenting with epilepsia partialis continua (EPC) and then being detected HIV seropositive with an Acquired Immune Deficiency Syndrome (AIDS)-defining illness. We report the case of a teenaged boy with no past significant history or known high-risk behavior who presented with recurrent focal seizures of 5 days’ duration, EPC, and encephalopathy. His electroencephalogram showed periodic lateralized epileptiform discharges (PLEDS), and magnetic resonance imaging (MRI) of the brain showed abnormal signal changes in the right parieto-occipital cortex and thalamus, both as yet unreported in cytomegalovirus (CMV) encephalitis, which was diagnosed by the cerebrospinal fluid (CSF) analysis.

Introduction

Seizures are a common occurrence in patients infected with HIV and the cause is usually a focal cerebral cortical lesion—the etiology being infective or neoplastic. ^{1 –4} However, seizures as a presenting manifestation of an HIV-related illness is rare, and even rarer is its presentation as epilepsia partialis continua. In this study, we report a case of a boy who presented with acute encephalopathy and EPC and was then detected to be HIV positive.

The Case

A previously healthy 14-year-old boy presented with recurrent focal seizures for 5 days and unresponsiveness for 1 day. He had left focal motor seizures, about 10 to 12 episodes per day initially, then increased in frequency to almost continuous twitching of the left half of the body. Two weeks prior to this, he had 2 episodes of generalized tonic–clonic seizures with an interval of 5 days, for which antiepileptic drugs were started. On examination, he was febrile, in altered sensorium—irritable and unable to follow commands. Neurologically, cranial nerves including both fundi were normal; the movement of his left upper and lower limbs was less, plantar reflexes were bilaterally extensor, and there were no signs of meningeal irritation. The EPC was refractory to phenytoin, levetiracetam, carbamazepine, phenobarbitone, and benzodiazepines. After 2 days, he became comatose and needed ventilatory support. Continuous electroencephalogram (EEG) monitoring demonstrated paroxysmal large amplitude slow waves occurring once in every 1.5 seconds approximately in predominantly right-sided centrotemporal leads—periodic lateralized epileptiform discharges (PLEDS; Figure 1).

Figure 1.

Electroencephalogram (EEG) of patient showing periodic lateralized epileptiform discharges (arrow).

Brain magnetic resonance imaging (MRI) showed hypointensities on T1-weighted (Figure 2A), hyperintensities on T2-weighted (Figure 2B and C), and fluid-attenuated inversion recovery (FLAIR) (Figure 2D) images in the right thalamus and parieto-occipital cortex, which were nonenhancing on contrast administration (Figure 2E and F). Cerebrospinal fluid (CSF) analysis revealed neutrophilic pleocytosis with 400 leukocytes, with protein of 112 mg/dL and glucose of 60 mg/dL. Serum ammonia and lactate were within normal range.

Figure 2.

Magnetic resonance imaging (MRI) brain of the patient.

He was started on intravenous Meropenem 2 gm every 8 hours, and intravenous Acyclovir 500 mg 8 hourly, as EEG showed PLEDS which are characteristically seen in herpes simplex encephalitis. However, polymerase chain reaction of CSF was negative for herpes simplex virus (HSV) and positive for CMV. CSF serology was negative for arboviruses, particularly Japanese B encephalitis virus. A serum enzyme-linked immunoassay for HIV-1 and HIV-2 was asked for in the light of above-mentioned investigations and it came out positive for HIV-1. This was later confirmed by Western blot test and his CD4+ Tcell count was 51 cells/mm³; he was started on antiretroviral therapy and acyclovir and changed to ganciclovir. Patient’s seizures reduced in frequency, but his sensorium did not improve and he expired within days.

Discussion

Studies have reported that seizures are the initial symptom in 4% (Sinha et al ² ) to 80% (Wong et al ³ ) of HIV-positive patients with new-onset seizures. Of the 100 HIV sero-positive individuals who were followed up in the study by Holtzman et al, ⁴ status epilepticus has also been reported in 12 of the 18 patients of new-onset seizures.

However, our case was unusual in several aspects. First, he had CMV meningoencephalitis presenting acutely as EPC. Usually, CMV encephalitis is of subacute onset, and there is progressive cognitive decline, multiple cranial nerve palsies, ataxia, and nystagmus in known HIV sero-positive patients. Pathologically, there is diffuse or ventriculoencephalitis. ⁵ Cerebrospinal fluid shows lymphocytic pleocytosis with raised proteins and, at times, low glucose. Our patient had neutrophil predominance in the CSF analysis—reported in cases with associated CMV radiculomyelopathy, ⁶ of which our patient did not have any clinical signs. Cytomegalovirus encephalitis occurs in severe immune deficiency, with CD4 counts lower than 50 cells/mm³ and prior or coexistent infection with CMV retinitis or gastroenteritis, which are more common than central nervous system infection. This patient had a CD4 count of 51 cells/mm³, but no evidence of CMV infection elsewhere during or before this episode.

Second, MRI brain of this patient showed abnormal signal changes in the right thalamus and parieto-occipital cortex which did not enhance on intravenous gadolinium. Such lesions are rare in CMV encephalitis in which imaging usually reveals ventricular prominence, enhancement in the periventricular subependymal lining along the lateral ventricles, septum pellucidum, corpus callosum and fornices due to ventriculitis, or diffuse or patchy increased signal intensities in white matter owing to demyelination. ^7,8 Ring-enhancing lesions with mass effect were proved by stereotactic biopsy to be due to CMV in 3 known HIV-positive patients reported by Moulignier et al, ⁹ but our patient’s lesions were not tumor like.

Various EEG changes have been described in HIV sero-positive patients including sharp waves, spikes, focal, and generalized slowing (Gabuzada et al ¹⁰ and Kellinghaus et al ¹¹ ). Periodic lateralized epileptiform discharges are most commonly seen in stroke or HSV encephalitis. Periodic lateralized epileptiform discharges on EEG in AIDS-associated CMV encephalitis as seen in our patient have never been reported, although PLEDS have been reported by others in HIV-positive patients.

Cury reported PLEDS over the right fronto-polar region in an HIV-positive patient, and his MRI revealed meningeal thickening in the same region along with other nonspecific findings. ¹² Ozkaya et al ¹³ described a patient who presented with aphasic status epilepticus and PLEDS on EEG, as the first presentation of AIDS-toxoplasma complex.

Ferrari et al ¹⁴ reported 2 patients with HIV type 1 infection who presented with new-onset EPC as an early manifestation of progressive multifocal leukoencephalopathy, with negative radiographic and electrophysiological findings for several weeks. Takagaki et al reported 2 patients of neurosyphilis who presented with encephalopathy, seizures and PLEDS on EEG, and one of them was HIV positive. ¹⁵ Also in the series by Sinha et al, the single patient (of the 99 HIV-positive patients) who presented with EPC did not have any lesion on MRI. ²

Conclusion

The combination of acute-onset EPC as the initial manifestation of AIDS-associated CMV encephalitis has never been reported. Although all the common causes must be investigated for when a patient presents with such unsual features, one must keep in mind rarer etiologies, and an immunocompromised state like HIV seropositivity must be ruled out.