Visceral hyperalgesia, intestinal dysfunction and unexplained irritability in neurological impaired children is a medical enigma for many healthcare professionals. The neuro-medical management can be challenging and difficult, due to poor understanding of the underlying aetiology and pathophysiology of the condition. Neuro-enteric axis has been proposed as emerging physiologic mechanism in the pathogenesis of many gastrointestinal diseases. The bidirectional connection between enteric and central nervous system may represent a direct relationship between neurological system and gut physiology. Insult to the brain indirectly contribute to the ongoing gut and brain axis sequalae. Microbiota has been an important modulator in the brain-gut axis. Irritability episodes in severe neurological impairment children has been commonly associated with pain originated from gastrointestinal pathology. Management of such condition requires a holistic approach to tackle multidimensional factors that has contributed to the ‘totality’ of the symptoms.