PATHOPHYSIOLOGY OF AUTONOMIC DYSREFLEXIA - LONG-TERM TREATMENT WITH TERAZOSIN IN ADULT AND PEDIATRIC SPINAL-CORD INJURY PATIENTS MANIFESTING RECURRENT DYSREFLEXIC EPISODES

Introduction: Spinal cord injury (SCI) results in disruption of synapt ic influences on the sympathetic preganglionic neurones. Remodelling o f spinal cord circuits rakes place in spinal neurones caudal to cord i njury. There is an increased vascular alpha-adrenoceptor responsivenes s, and peripheral afferent (bladder) stimulation in SCI subjects induc es a marked noradrenaline spillover below the level of spinal lesion. These neurophysiological changes possibly contribute to the developmen t of autonomic dysreflexia, a condition of sympathetic hyper-excitabil ity that develops after cervical, or upper dorsal cord injury with res ultant paroxysmal rise in arterial pressure, and provide the scientifi c basis for the use of terazosin, a once-a-day, selective alpha-one ad renergic blocking drug. Objectives: The use of terazosin, a long-actin g, alpha 1-selective blocking agent was investigated in SCI patients w ho developed recurrent symptoms of autonomic dysreflexia, eg headache, sweating flushing of the face together with an increase in the arteri al pressure. Design: An open, prospective study of the efficacy of ter azosin in controlling recurrent autonomic dysreflexia in traumatic tet raplegic/paraplegic patients manifesting clinical features of dysrefle xia in the absence of an acute precipitating cause such as a blocked c atheter. Setting: The initial assessment and treatment were carried ou t in the Spinal Injuries Centre. Subsequently, the patients were follo wed-up in the community. They were monitored by telephonic interviews, follow-up visits by the patients to the hospital, and home-visits by the staff of the spinal unit. Subjects: Eighteen adults with tetrapleg ia (female: 1, male: 17), three children with ventilator-dependent tet raplegia and three adult male patients with paraplegia who exhibited r ecurrent features of autonomic dysreflexia ill the absence of an acute predisposing factor for dysreflexia eg performance of an invasive pro cedure such as cystoscopy, digital evacuation of bowels, or acute urin ary retention, were enrolled in this study. Intervention: After discus sion with the patients and their carers, terazosin was prescribed with a starting dose of 1 mg in an adult and 0.5 mg in a child administere d nocte. The patients were observed for (1) drug-induced hypotension; (2) clinical symptoms due to side effects of terazosin; and (3) contin ued occurrence of dysreflexic symptoms. Step-wise increments of the do se of terazosin (1 mg in case of adults, and 0.5 mg in a child) was ca rried out at intervals of 3 - 4 days, if a patient continued to develo p dysreflexia but did not manifest any serious side effect. Outcome me asures: Complete subsidence of dysreflexic symptoms, or development of an adverse event necessitating termination of the terazosin therapy w as the clinical end point. Results: The dysreflexic symptoms subsided completely with the terazosin therapy in all the patients. The twenty- one adult patients required a dose varying from 1 - 10 mg, whereas the paediatric patients required only 1 - 2 mg of terazosin. The side eff ects of postural hypotension and drowsiness were transient, and mild. One tetraplegic patient developed persistent dizziness and therefore, the drug therapy was discontinued. Conclusion: In 21 adult and three p aediatric spinal cord injury patients manifesting recurrent episodes o f autonomic dysreflexia in the absence of an acute predisposing cause, the use of terazosin, a once-a-day, specific alpha-one blocker result ed in complete subsidence of the dysreflexic symptoms. However, one te traplegic patient required termination of terazosin therapy because of persistent dizziness.