Epilepsia partialis continua in a child with disseminated tuberculosis: a case report and review of literature

Introduction

Epilepsia partialis continua (EPC) belongs to the International League Against Epilepsy (ILAE) subclass of focal motor status epilepticus, characterized by stereotyped jerky movements of a single muscle or a group of muscles. These movements can extend to involve the entire limb and multiple parts of the hemibody. ¹ EPC can also present as somatosensory phenomena, such as aura continua. Most studies define EPC as lasting at least 60 min, with no more than a 10-s interval between jerks, and without affecting consciousness.^1,2 Therefore, EPC is distinct from typical epileptic seizures, which usually last only a few minutes.

In children, common causes of EPC include Rasmussen’s encephalitis, mitochondrial cytopathies such as Alpers disease, focal cortical dysplasia, trauma, stroke, infectious encephalitis, and inborn errors of metabolism. In adults, EPC may be more commonly associated with tumors, multiple sclerosis, progressive multifocal leukoencephalopathy, prion diseases, and nonketotic hyperglycemia. ¹ Very few cases of EPC caused by underlying central nervous system (CNS) tuberculosis have been reported, especially in children. Here, we describe a case of a child with disseminated tuberculosis who presented with EPC.

Case description

An 11-year-old female child presented with vague complaints of poor appetite, easy fatigability, and abdominal pain. She had been asymptomatic 3 months prior. There was no history of altered sensorium, irritability, neck stiffness, vomiting, or blurred vision. Subsequently, she developed weakness in her left upper and lower limbs, which improved over the next 5 days. However, the child began experiencing twitching movements on the left side, initially involving the fingers. These movements, initially lasting a few seconds, gradually increased in duration, affecting the left hand (Supplemental Video 1) as well as the left side of the face. The child remained conscious during these movements, which sometimes persisted even during sleep. There was no family history of similar conditions or exposure to tuberculosis and no past history of abnormal movements. Serum electrolytes were normal. Electroencephalography (EEG) revealed a normal background with sleep markers and spike-wave discharges arising from F8 T4 and C4 P4 in the right hemisphere (Figure 1). Differential diagnoses considered included Rasmussen’s encephalitis, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), Alpers disease, and channelopathy. The child was started on phenytoin and levetiracetam, but the twitching persisted. Arterial lactate levels were normal. Brain MRI revealed multiple T1 contrast-enhancing and T2 hyperintense lesions with a hypointense rim in the right parietal region (yellow arrows) with perilesional edema (black arrow), and magnetic resonance spectroscopy showed a lipid peak (white arrow), suggestive of tuberculomas with central liquefaction (Figure 2). The magnetic resonance (MR) angiogram was normal. Cerebrospinal fluid (CSF) analysis showed pleocytosis with elevated proteins and reduced glucose (WBC = 120 cells (0–5 Cells) 100% Lymphocytes, Protein 150 mg/dl (15–40 mg/dl), glucose 30 mg/dl (50–80 mg/dl)). The CSF GeneXpert showed rifampicin-sensitive Mycobacterium tuberculosis. Viral markers, including HIV and hepatitis, were negative. Ultrasound of the abdomen revealed mesenteric lymphadenopathy and dilated hypoechoic tubular structures in bilateral adnexa, suggesting the possibility of pyosalpinx. Contrast Enhanced Computerised tomography (CECT) abdomen confirmed the diagnosis of bilateral pyosalpinx along with mesenteric and retroperitoneal lymphadenopathy, with some of the nodes showing central necrosis. The child was started on a four-drug antitubercular regimen (intensive phase), including isoniazid (H = 10 mg/kg/day), rifampicin (R = 15 mg/kg/day), pyrazinamide (Z = 35 mg/kg/day), and ethambutol (E = 20 mg/kg/day) along with steroids (dexamethasone 0.15 mg/kg/dose four times daily). The seizures subsided within a week, and the child showed clinical improvement. At 4 weeks of follow-up, the steroids were tapered and discontinued over the next 4 weeks, and the child transitioned to the continuation phase of antitubercular treatment with isoniazid, rifampicin, and ethambutol for 10 months. Repeat EEG was normal (Figure 1(b)). She had started regaining her appetite with no abdominal pain.

OPEN IN VIEWER

Figure 1.

(a) EEG showing a normal background with sleep markers and spike and wave discharges (arrows) arising from multiple foci in the right hemisphere (F8 T4, C4 P4). (b) EEG on 4 weeks follow-up post-treatment shows resolution of interictal discharges with the normal background (Montage-average reference, sensitivity-70 µV/cm, high cut-70 Hz, low cut-1 Hz). EEG, electroencephalography.

OPEN IN VIEWER

Figure 2.

(a) Axial T2W brain MR image showing multiple lesions (yellow arrow) with a hypointense rim and central hyperintensity were observed in the right peri-Rolandic region. There is diffuse perilesional edema (black arrow). (b) Axial and (c) coronal T1W CE brain MR images showing multiple discrete (yellow arrow) and conglomerated (red arrow) ring-enhancing lesions. (d) MR spectrum showing a lipid peak at 1.3 ppm (arrow). These MRI features are characteristic of caseating tuberculoma with liquefaction. MR, magnetic resonance.

Discussion

A myriad of manifestations of tuberculosis can involve multiple organ systems, including the lungs, CNS, gastrointestinal tract, genitourinary tract, and lymph nodes. In the CNS, tuberculosis is the most devastating, leading to high mortality and morbidity. Children under 5 years of age who are not immunized with the BCG vaccine are especially prone to CNS tuberculosis. The pathology initially starts with the formation of Rich foci, which later leads to widespread CNS involvement. ³ Underlying HIV or immunodeficiency and delays in diagnosis and treatment initiation can further worsen the prognosis. The common CNS presentations include chronic meningitis with chronic fever, headache, vomiting, neck stiffness, altered sensorium, seizures, focal neurological deficits, tuberculomas, brain abscess, stroke, hydrocephalus, Pott’s spine, and optochiasmatic arachnoiditis. ⁴ Our case demonstrates an unusual presentation of EPC.

There are several types of EPC, namely, solitary episodes, chronic repetitive nonprogressive episodes, chronic persistent nonprogressive episodes, and chronic progressive episodes. ¹ EPC represents underlying damage to the cerebral cortex rather than a separate entity. The exact pathophysiology underlying EPC has yet to be discovered. Various inflammatory, infective, ischemic, traumatic, and metabolic events causing neocortical damage are thought to be causative in most cases.

In Rasmussen’s encephalitis, there are intractable focal seizures, EPC, and focal deficits with speech and cognitive decline. ⁵ Neuroimaging reveals progressive hemiatrophy. Hemimegalencephaly, focal cortical dysplasia, and Sturge-Weber syndrome represent some of the congenital cortical malformations present with EPC. Mitochondrial disorders such as Alpers, MELAS, MERRF, POLG, and Leigh syndrome are known to be associated with EPC. Thus, metabolic dysfunction can be a causative factor for EPC. ⁶ Stroke and trauma are acquired causes of cortical damage leading to EPC. Patients with autoimmune and paraneoplastic encephalitis, such as N-methyl-D-aspartate (NMDA) encephalitis and limbic encephalitis, usually present with behavioral changes, cognitive decline, encephalopathy, and abnormal movements. EPC may occur in these conditions due to inflammation and receptor internalization or disruption, leading to an excitatory-inhibitory imbalance. ⁷ CNS tubercular infection can lead to direct structural cortical damage via encephalitis or tuberculomas or indirectly via ischemia, vasculitis, metabolic disturbance, and inflammation, thus leading to EPC.

Treatment involves addressing the underlying etiology along with anti-seizure medications. For Rasmussen’s encephalitis, immunomodulation using methylprednisolone IV pulses, rituximab, Intravenous Immunoglobulin (IVIG), azathioprine, mycophenolate mofetil, etc., in the acute phase, followed by surgical methods such as hemispherectomy, is helpful. Surgical procedures are most valuable for treating focal structural malformations. In patients with autoimmune encephalitis, adequate immunomodulation early before the formation of epilepsy circuitry is of prime importance.

Despite being a minority, numerous reports have mentioned CNS tuberculosis as one of the causes of EPC in both adults and pediatric age groups.^{8 -11} Pandian et al., in their case series of 20 patients with EPC with a mean age of 18 years, found neurotuberculosis to be causative in four cases (two tubercular meningitis and two tuberculoma). ⁹ In a retrospective case series of 71 patients reported by Sinha et al., with a median age of 26 years, reported CNS tuberculosis in two cases (both tuberculomas). ¹⁰ Both these cases had a median duration of EPC of around 1.5 days only, while in our case, it lasted for a week. The outcome was good following treatment, as in our case. In an adult cohort of 17 patients who presented with EPC, the majority had a diabetic nonketotic hyperosmolar state as the underlying diagnosis. ¹² Autoimmune etiology still predominates in the pediatric age group. In a study of 51 children with EPC done by Kravljanac et al., only three had CNS tuberculosis. ¹¹ All three infants survived, and one of them was reported to have tuberculoma. One case of disseminated tuberculosis in a 54-year-old woman, complicated by hemophagocytic lymphohistiocytosis, presented with EPC with MRI showing tuberculoma in the left motor strip, resolving after therapy. ¹³ An 18-year-old adolescent girl with type 1 diabetes presented with EPC precipitated by a combination of both ketotic hyperglycemia and tubercular meningoencephalitis. ¹⁴ The imaging revealed a right frontal cortical laminar necrosis. ¹⁴ The EPC, which was drug refractory to just anti-seizure medication alone, responded when sugar levels were controlled along with the initiation of antitubercular therapy (ATT). ¹⁴ An immunocompromised adolescent on isoniazid prophylaxis who developed tubercular meningitis with vasculitis leading to EPC made an uneventful recovery with antitubercular therapy (ATT). ¹⁵ Contrary to our case, the adolescent was immunocompromised and developed right hippocampal gyrus, right putamen, and the head of the caudate nucleus infarctions with choreiform movements, EPC, and persistent weakness on the left side. Like in our case, the EPC responded soon after ATT. ¹⁵

Conclusion

Although few studies mention CNS tuberculosis causing EPC, the clinical profile, response to treatment, and outcomes have not been discussed in detail. The literature is even more sparse for pediatric patients. The common presentation of tuberculosis with EPC tends to have tuberculomas in neuroimaging in most cases. However, reports of cortical insult due to tubercular meningoencephalitis as well as vascular infarction are also available. Overall, the response of EPC seems to be good once ATT is initiated along with the anti-seizure medications, which is also demonstrated in our case. Future studies with more cases may help understand how EPC caused by tuberculosis might differ from that caused by other etiologies. Nonetheless, limited reports support that early suspicion, diagnosis, and treatment of the underlying etiology can be rewarding. Tuberculosis is common in developing countries, and it is one of the treatable causes of EPC that should be considered.

Supplemental Material