Botulinum toxin in the treament of spasticity in HIV-infected children affected with progressive encephalopathy (2004)

HIV-associated progressive encephalopathy in vertically HIV-infected children may manifest early with a failure to attain or loss of developmental milestones, impaired brain growth or acquired progressive symmetric motor abnormalities [1]. The risk of developing progressive encephalopathy increases with the early age of infection and high viral loads [2,3]. Recent evidence suggests that highly active antiretroviral therapy (HAART) may halt or even partially reverse progressive encephalopathy, often leaving sequelae similar to those observed in static encephalopathies, including limb spasticity, usually with normal or mildly affected cognition [4]. Botulinum toxin type A (BT-A) injection has been proved to be a well-tolerated, safe and effective procedure in the treatment of children with cerebral palsy [5,6]. To our knowledge, no data regarding the use of BT-A in HIV-infected children has been reported to date. We report the cases of four vertically HIV-infected children in whom progressive encephalopathy developed severely during infancy and was the first AIDS-defining condition, leading to the diagnosis of HIV infection in their mothers. All of them showed good clinical and immunological responses to HAART. However, the sequelae from progressive encephalopathy included severe motor deficits in all cases, especially involving the lower limbs. The long-term treatment for the HIV-induced spasticity that affects these patients includes a physiotherapy programme, orthoses and sessions of BT-A (Dysport, Ipsen, Berks, UK or Botox, Allergan, Irvine, CA, USA) local injections every 4–6 months from the age of 3 years. An improvement in measures of gross motor function and functional mobility for daily living was observed in all cases, and our patients are now able to walk. No major side-effects have been observed to date. Clinical data and BT-A treatment characteristics are summarized in Table 1.Table 1: Clinical data and botulinum toxin type A treatment characteristics.BT-A is an exotoxin derived from Clostridium botulinum that is rapidly bound by the receptors in the presynaptic membranes of cholinergic motor neurones, preventing the discharge of acetylcholine and leading to a chemical denervation. The peak effect is usually noticed by 1–2 weeks after the injection, but the period of clinically useful relaxation lasts 12–16 weeks. Treatment-related adverse events are rare, mild and transient, local pain or weakening of the injected muscle being the most common, as once happened in one of our patients. The optimal timing for BT-A treatment in the lower extremity is between 2 and 5 years of age, the period of dynamic motor development, when there is the greatest chance to modify the natural course of the disease, reducing muscle contracture and the need for surgery. BT-A should always be used together with adjunctive treatments such as active motor training and orthotic treatment, in order to increase the injected muscle length and flexibility. Moreover, new motor skills will have to be achieved and retained at such early ages [5]. The pathogenic characteristics of HIV-related progressive encephalopathy spasticity are not different from those of more common causes of cerebral palsy. The patients we report have been treated according to our protocol for the treatment of spasticity in the paediatric population (dose, muscles injected, age at injection and interval between injections), which follows international recommendations [5] and has been applied to over 300 paediatric patients, with good functional results in most of them. It is remarkable that these four patients have shown an optimal clinical and immunological evolution after the initiation of HAART, with undetectable viral loads and normal CD4 T-cell counts over time. Whether BT-A treatment is also applicable to HIV-infected children with some degree of immunosuppression remains uncertain. In conclusion, BT-A seems to be effective as an adjunctive therapy in ameliorating progressive encephalopathy-related spasticity in HIV-infected children with good immunological status, and shows a good safety profile.