Pathophysiology of bacterial infection of the central nervous system and its putative role in the pathogenesis of behavioral changes

Invasion of the central nervous system (CNS) by microorganisms is a severe and frequently fatal event during the course of many infectious diseases. It may lead to deafness, blindness, cerebral palsy, hydrocephalus, cognitive impairment or permanent neurological dysfunction in survivors. Pathogens can cross the blood-brain barrier by transcellular migration, paracellular migration and in infected macrophages. Pathogens may breach the blood-brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors. This induces the activation of nuclear factor kappa B or mitogen-activated protein kinase pathways and subsequently induces leukocyte infiltration and proliferation and the expression of numerous proteins involved in inflammation and the immune response. Many brain cells can produce cytokines, chemokines and other pro-inflammatory molecules in response to bacteria stimuli; as a consequence, polymorphonuclear cells are attracted and activated, and release large amounts of superoxide anion and nitric oxide, leading to peroxynitrite formation and oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier breakdown, contributing to cellular injury during neuronal infection. Current evidence suggests that bacterial CNS infections can play a role in the etiopathogenesis of behavioral disorders by increasing pro-inflammatory cytokines and bacterial virulence factors. The aim of this review is to summarize the current knowledge of the relevant pathophysiologic steps in CNS infections.

Neurobrucellosis: a rare cause for spastic paraparesis

A 41 year old man presented to the outpatient department with a three month history of difficulty in walking. He also had a history of positive sensory symptoms in the form of pins and needle sensation mostly below the waist. His symptoms had been progressive and there was no significant family history. He demonstrated a spastic gait and could only walk with assistance and support. DTR were hypertonic and sensory deficit was observed below twelfth dorsal vertebra. Sphincter abnormalities were present. Plantars were extensor bilaterally. Cerebral and spinal MRI with contrast was unremarkable. Brucella antigen titers were significantly high. CSF report was consistent with neurobrucellosis. After detailed analysis of his history, clinical picture and investigations the diagnosis of neurobrucellosis was made. Combined antimicrobial therapy was started, his neurologic condition gradually improved and he was able to walk without help after three months of treatment. Hence this case showed that neurobrucellosis may present as acquired progressive spastic paraparesis and it should always be borne in mind in patients with spastic paraparesis.