Refractory status epilepticus due to pneumococcal meningitis in an infant with congenital immunodeficiency.

Pneumococcal meningitis remains a life-threatening infection, with varied presentations. A 3 month-old-baby with pneumococcal meningitis presented with clusters of seizures evolving into refractory status epilepticus despite standard antibiotic and aggressive anticonvulsant therapy. Progressive illness despite antibiotic initially suggested possible antibiotic resistance and resulted in addition of another antibiotic. Nonresponse to standard treatment and previous history of abscess in the back of neck pointed to some underlying congenital immunodeficiency. Further evaluation showed a deficiency of complement factor C3. This case underlines the need to consider underlying immunodeficiency in cases of refractory status epilepticus due to bacterial meningitis. Gram-staining of cerebrospinal fluid sample showing plenty of Gram-positive bacteria and comparatively fewer pus cells is a clue regarding some underlying immunodeficiency.

Introduction

Pneumococcal meningitis is a life-threatening infection of the central nervous system with high rate of complications.[1] Despite antibiotic therapy and intensive supportive care, childhood pneumococcal meningitis remains a life-threatening disease, with highest morbidity and mortality rates among the various causes of bacterial meningitis. Nonresponse to standard treatment suggests either antibacterial resistance or underlying immunodeficiency.[2] We report a 3-month-old baby with refractory status epilepticus due to pneumococcal meningoencephalitis, with underlying congenital immunodeficiency.

Case Report

A 3-year-old male baby was admitted with a history of high-grade fever, excessive cry, and irritability for 3 days followed by one episode of generalized seizures. History revealed normal development and no significant illness except an abscess in the back of neck at 2 weeks of age. A provisional diagnosis of meningoencephalitis with symptomatic seizures was made and was started on ceftriaxone, fosphenytoin, and dexamethasone. After admission, he had 2 more episodes of the right focal seizures with secondary generalization followed by status epilepticus. He was started on intravenous valproate and midazolam infusion, intubated and put on ventilator support. The patient continued to deteriorate with persistent fever and multiple seizures even after 24 h. He also developed left lower motor neuron facial palsy on the day 2 without any ear discharge or any evidence of ear infection. Nonresponse to standard treatment suggested either antibacterial resistance or underlying immunodeficiency. The patient was also started on vancomycin. On investigations, he had anemia (hemoglobin 8 g/dL, platelet count 4.1 × 105 /L, white blood cell count 7.3 × 109 /L, polymorphs 63%, and erythrocyte sedimentation rate 22 in 1 h). Blood glucose, renal and liver function tests, serum calcium were normal. cerebrospinal fluid (CSF) study showed 35 cells, 90% polymorphs, elevated protein 308 mg/dL, sugar below 10g/dL. Gram-stain revealed plenty of lanceolate Gram-positive diplococci suggestive of pneumococci [Figure 1]. Neuroimaging showed multiple acute infarcts in bilateral periventricular white matter, left thalamus, and centrum semiovale. Meanwhile, culture reports were available, showing pneumococci sensitive to ceftriaxone, chloramphenicol, and ampicillin [Figure 2]. Workup for vasculitis and collagen vascular diseases were negative. Mantoux test, venereal disease research laboratory, and retroviral test were negative. Complement factor assay showed low level of C3 of 78 mg/dL (normal 90–180). The patient had a delayed and gradual recovery within next 6 days. On discharge, patient's sensorium was normal but left facial palsy persisted.

Figure 1

Gram-stain showing plenty of lanceolate Gram-positive diplococci and comparatively fewer pus cells

Figure 2

Culture plate showing pneumococci with typical carrom coin appearance

Discussion

Neuroinfection is a leading cause of status epilepticus.[3] The incidence of seizures and status epilepticus is much less common in bacterial compared to viral etiology. In our case, the clinical presentation as refractory status epilepticus and the nonresponse to standard antibacterial therapy were distinctly odd. Persistent fever and refractory seizures even after antibiotics and aggressive anticonvulsant therapy suggested either antibacterial resistance or underlying immunodeficiency.[4] Recently, there has been a dramatic increase, in the worldwide prevalence of penicillin-resistant Streptococcus pneumonia (PRSP).[5] Seven serotypes (6A, 6B, 9V, 14, 19A, 19F, and 23F) accounted for most PRSP, most frequent being serotype 19A.

Gram-staining of CSF sample showing plenty of Gram-positive lanceolate diplococci and comparatively fewer pus cells were a clue regarding some underlying immunodeficiency. Complement system plays a major role in host defense against many microbial pathogens; it appears most important in protection against encapsulated bacteria, such as Neisseria meningitidis and S. pneumonia.[6] Our patient had low levels of complement factor C3. Complement activation occurs via either the classical or the alternative pathway, which converge at the level of C3 and share a sequence of terminal components. The previous history of abscess in the back of neck pointed to recurrent bacterial infections. Recurrent infections with capsulated bacteria are common in complement factor deficiencies, but nonresponse to sensitive antibacterial and the occurrence of refractory status epilepticus are uncommon. This case underlines the need to consider underlying immunodeficiency in cases of refractory status epilepticus due to bacterial meningitis.

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Conflicts of interest

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