Hart, IK

Lozsadi, DA

Moore, AP

St George's Online Research Archive

Botulinum toxin A improves involuntary limbmovements in Rasmussen syndromeDora A. Lozsadi, DPhil, MRCP; Ian K. Hart, FRCP; andA. Peter Moore, FRCPRasmussen syndrome (RS) is a focal, progressive, cortical inflam-mation affecting one cerebral hemisphere that usually presentswith epilepsia partialis continua (EPC) that is resistant to antiepi-leptic drugs (AEDs). The encephalitis is often associated withipsilateral cerebral hemisphere and basal ganglia atrophy.1 Pa-tients can develop involuntary movements, including myoclonus,dystonia, and athetosis, usually in association with EPC.2 Theencephalitis is probably autoimmune mediated, although thepathogenesis of the atrophy is unknown.3 We report a man withestablished RS who developed EPC and painful dystonia thatimproved with botulinum toxin A (BTX-A).Case report. We described previously this 43-year-old, left-handed man.4 He sought treatment in 1989 for EPC followed byneurologic and cognitive deficits. The following therapies had nosustained effect: multiple AEDs, right corticectomy in 1990, infu-sions of sodium valproate or benzodiazepines into the corticectomycavity in 1994, and right frontoparietal subcortical transection in1995. Immunomodulatory therapy started in 1996, and his condi-tion improved, although he continued to have intermittent boutsof left upper limb myoclonic jerking.4He was stable until 2002 when he had several Klebsiella pneu-moniae bacteremias. Frequent complex partial seizures (CPSs)developed, and EPC returned with continuous myoclonic jerkingof the left upper limb and frequent, painful, dystonic, flexorspasms of the left fingers, wrist, and elbow, which sometimesspread to the shoulder. Although the CPS remitted with IV anti-biotics and increasing his AED regimen (topiramate, 800 mg/d;phenytoin, 425 mg/d; levetiracetam, 3 g/d; and vigabatrin, 2 g/d),his involuntary movements persisted. Clonazepam (20 mg/d), IVmidazolam boluses, and increasing prednisolone (1.5 mg/kg/d) andIV immunoglobulin (hIVIg; 2 g/kg fortnightly) doses had no effect.There was progressive atrophy of the remaining right cerebralhemisphere, caudate nucleus, and thalamus on serial brain MRIscans since 1993 (figure). However, there was no evidence of reac-tivation of brain inflammation on either the MRI scans or serialCSF analysis.We tried freehand injections of BTX-A (Dysport, Ipsen, UK;total dose, 1000 mouse units [MU]) into the most affected leftupper limb muscles (200 MU into biceps and flexor digitorumsuperficialis; 100 MU into trapezius, brachioradialis, triceps,flexor carpi radialis, and flexor digitorum profundus; and 50 MUinto flexor carpi ulnaris and the thenar muscles). Marked im-Figure. Progressive right basal ganglia and thalamic atrophy on serial MRI brain scans in a man with Rasmussen syn-drome. (A) MRI brain scan in 1993, 3 years after right central sulcus lesionectomy. There is extensive high T2-weightedsignal in the right hemisphere and normal basal ganglia and thalamus. (B) MRI brain scan in 1996 just before the startof immunomodulatory treatment. There is marked right hemisphere and basal ganglia atrophy. (C) MRI brain scan in2002 at the onset of left upper limb myoclonus and dystonia. Right hemisphere and basal ganglia atrophy hasprogressed.April (1 of 2) 2004 NEUROLOGY 62 1233provement of his involuntary movements began 1 week later. Hispainful spasms resolved over 2 weeks; the jerking became inter-mittent; and useful limb function returned. His dose of topiramatewas reduced to 400 mg/d; phenytoin was reduced to 350 mg/d;vigabatrin was reduced to 750 mg/d; and clonazepam was reducedto 2 mg/d. After 5 months, his involuntary movements reappeared.Additional BTX-A injections into the affected muscles (total dose,500 MU) reproduced the effects of the first treatment.Discussion. Repeated BTX-A injections were an effectivetreatment for our patient’s late-onset, limb dystonia and continu-ous myoclonic jerking. Changes in the ipsilateral basal ganglia inassociation with cerebral hemisphere abnormalities are commonin patients with RS and usually appear early in the course of thesyndrome. In one serial MRI study, eight of eight patients with RShad atrophy of the head of the caudate nucleus at 4 months afteronset of symptoms.1 In another patient, atrophy of the right cau-date, globus pallidus, and putamen and mild increased T2-weighted signal in the right striatum were the only MRI brainscan findings at presentation.5 However, no additional EPC-associated involuntary movements were described in any of thesepatients, and reports of hyperkinetic movements other than myoc-lonus are rare in EPC associated with RS.2 When these move-ments occur, they start typically at the onset or early in the courseof the syndrome.2 By contrast, our patient’s involuntary move-ments started 14 years after the clinical onset of RS when therewas established caudate atrophy. Human IVIg improved atheto-sis, dystonia, and EPC in one woman with RS, although the re-sponse was short lasting.2 Increasing the doses of prednisoloneand hIVIg had no effect on our patient’s involuntary movements.Our patient’s repeated response to BTX-A contrasts with thereports of its ineffectiveness in two patients with EPC and in twochildren with RS and EPC.6,7 These previous findings suggest thatuncomplicated EPC may be resistant to this therapy. However, itcan be difficult clinically to distinguish the recurrent, simple focalmotor seizures of EPC from the other hyperkinetic movements,especially myoclonus, occurring in patients with established RS.We propose that BTX-A can be a useful, long-term therapy forinvoluntary, hyperkinetic movements in RS and that it should beconsidered especially for those patients with late-onset, focalmovements that do not respond to conventional AED treatment orimmunotherapy.From the Walton Centre for Neurology and Neurosurgery (Drs. Lozsadi,Hart, and Moore) and University Department of Neurological Science (Drs.Hart and Moore), Liverpool, United Kingdom.Dr. Moore has received grants and personal compensation from Ipsen Ltd.,Maidenhead, UK, in excess of $10,000.Received September 17, 2003. Accepted in final form November 20, 2003.Address correspondence and reprint requests to Dr. Ian K. Hart, UniversityDepartment of Neurological Science, Lower Lane, Liverpool L7 9LJ, UK;e-mail: ian@kirkhart.freeserve.co.ukCopyright © 2004 by AAN Enterprises, Inc.References1. Granata T, Gobbi G, Spreafico R, et al. Rasmussen’s encephalitis: earlycharacteristics allow diagnosis. Neurology 2003;60:422–425.2. Frucht S. Dystonia, athetosis, and epilepsia partialis continua in a pa-tient with late-onset Rasmussen’s encephalitis. Mov Disord 2002;17:609–612.3. Levite M, Hart IK. Immunotherapy for epilepsy. Expert Rev Neurother2002;2:809–814.4. Leach JP, Chadwick DW, Miles JB, Hart IK. Improvement in adult-onset Rasmussen’s encephalitis with long-term immunomodulatory ther-apy. Neurology 1999;52:738–742.5. Koehn MA, Zupanc ML. Unusual presentation and MRI findings in Ras-mussen’s syndrome. Pediatr Neurol 1999;21:839–842.6. Tarsy D, Schachter SC. Botulinum toxin is not effective for epilepsypartialis continua. Mov Disord 1995;10:357–378.7. Jost WH, Kohl A. Botulinum toxin: evidence-based medicine criteria inrare indications. J Neurol 2001;248 (suppl 1):39–44.1234 NEUROLOGY 62 April (1 of 2) 2004

Botulinum toxin A improves involuntary limb movements in Rasmussen syndrome

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