CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Seizure 21 (2012) 147–150 Contents lists available at SciVerse ScienceDirect Seizure jou rnal homepage: www.elsevier.com/locate/yseiz Case report Extremely sustained startle-induced clonus: Non epileptic motor attacks mimicking clonic seizures in children with encephalopathy a a a a,b, Francesco Mari , Simone Gana , Francesca Piras , Renzo Guerrini * a Paediatric Neurology Unit and Laboratories, Paediatric Hospital A. Meyer – University of Florence, Florence, Italy b IRCCS Fondazione Stella Maris, Calambrone, Pisa, Italy A R T I C L E I N F O A B S T R A C T Article history: Clonus is a pathological motor pattern characterised by involuntary, rhythmic and brisk muscular Received 29 June 2011 contractions in response to peripheral stimuli producing muscle stretching. It indicates pathological Received in revised form 26 September 2011 involvement of the corticospinal tract and can be considered as a functional spastic movement disorder of Accepted 27 September 2011 variable clinical presentation and duration. We documented severe and prolonged episodes of startle- induced clonic attacks associated with severe apnoea, occurring in three infants with severe Keywords: encephalopathy. The clinical characteristics of such episodes are very similar to those of clonic epileptic Clonus seizures. Video-EEG recordings confirmed the non epileptic origin of the episodes. Previous anti-epileptic Startle-induced seizures drug treatment was unsuccessful but myorelaxing drugs produced a dramatic improvement. Clonic seizures Encephalopathy ß 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. 1. Introduction distress appeared, requiring intubation and ventilatory assistance. During his second day of life, frequent and prolonged paroxysmal Clonus is defined as a functional spastic movement disorder events characterised by startle-induced stiffness with apnoea 1 that indicates pathological involvement of the corticospinal tract. appeared. Brain MRI, performed on the 5th day of life, revealed It is characterised by involuntary, rhythmic (5–8 Hz) and brisk bilateral hyperintensity of basal ganglia, which was consistent muscular contractions in response to peripheral stimuli producing with early asphyxia. Interictal electroencephalogram (EEG) 2 muscle stretching. Clonus is usually seen after stroke, in multiple showed multifocal paroxysmal activity. A tentative diagnosis of sclerosis, as a consequence of brain and spinal cord injuries and startle-induced epilepsy was made and treatment with midazolam other CNS lesions leading to pyramidal system impairment. Its and phenobarbital was introduced, without benefit. In early spatial and temporal distribution are variable as it may involve just infancy, multiple per day, prolonged episodes of startle persisted, a restricted somatic area or be diffuse and persist for just a few progressing into rhythmic clonic jerks, with stiffness and apnoea. seconds to minutes. We documented prolonged episodes of Antiepileptic drugs produced no benefit. At the age of 7 months, startle-induced clonic attacks spreading to the whole body and the child was referred to our Unit. On physical examination, producing apnoea, in three infants with severe encephalopathy. microcephaly with severe global developmental delay, and spastic- The clinical characteristics of such episodes are clinically hypokinetic quadriplegia were apparent. Numerous clonic fits with indistinguishable from those of startle-induced clonic epileptic relevant apnoea were video-EEG recorded (see Video, Segment 1), seizures with which they had been misdiagnosed before their non which occurred with no concomitant EEG change (see Fig. 1A). epileptic pathophysiology was clarified. Holding the patient’s jerking limbs down reduced the duration of the attacks. Antiepileptic drug therapy was discontinued and myorelaxing treatment with clonazepam and oral baclofen was 2. Case reports started with dramatic improvement. Laboratory examinations (including routine blood and urine tests, and screening tests for Patient 1 is a 2 years old Chinese boy, who was born at term and metabolic defects) were normal. Mutation analysis of the alpha1 with unremarkable family history. Head circumference at birth subunit of inhibitory glycine receptor gene (GLRA1) resulted was normal. In the immediate postnatal period, respiratory negative. Brain MRI revealed severe diffuse cortical and subcortical atrophy sparing the brainstem and cerebellum (see Fig. 2A 1-2). Patient 2 is a 2 years old boy, who was born at term and with an * Corresponding author at: Paediatric Neurology Unit and Laboratories, unremarkable family history. Birth weight, height and head Children’s Hospital A. Meyer – University of Florence, Viale Pieraccini 24, 50139 circumference were appropriate for gestational age. At 1 month Firenze, Italy. Tel.: +39 0555662573; fax: +39 0555662329. E-mail address: [email protected] (R. Guerrini). of age, the patient was hospitalised for investigation of severe 1059-1311/$ – see front matter ß 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.seizure.2011.09.011 148 F. Mari et al. / Seizure 21 (2012) 147–150 Fig. 1. Ictal poligraphic recordings in Patients 1 and 2 (A and B, respectively): at (*), acoustic (A) and proprioceptive (B) stimuli were delivered causing startle-responses followed by rhythmic EMG bursts with no concomitant EEG changes. developmental delay and frequent episodes of sustained jerking. bilateral cataract. Brain MRI revealed cerebellar vermis hypoplasia Neurological examination revealed severe axial hypotonia, poor and bilateral hyperintensity of basal ganglia. He was discharged sucking, dysphagia (that later required the placing of percutaneous with a diagnosis of startle-induced seizures and encephalopathy of endoscopic gastrostomy, PEG), extremely brisk reflexes, and unknown etiology, and antiepileptic treatment with phenobarbital frequent, spontaneous or startle-induced, episodes of whole body and carbamazepine. No relevant effects on the frequency of the stiffness and clonic jerking. Screening tests for metabolic defects clinical episodes were noticed. resulted normal. EEG showed slow background activity and At the age of 12 months, the child was referred to our Unit. multifocal abnormalities. Ophthalmologic assessment evidenced Neurological examination revealed severe developmental delay, F. Mari et al. / Seizure 21 (2012) 147–150 149 Fig. 2. Coronal and axial T2 sequences on MR examination revealing severe diffuse brain atrophy in Patient 1 (A, 1-2), Patient 2 (B, 1-2) and Patient 3 (C, 1-2). spastic-hypokinetic quadriplegia and microcephaly. Frequent epi- intensity of attacks. A second brain MRI revealed severe diffuse sodes of low-threshold startle reaction, followed by stiffness, cortical and sub-cortical atrophy (see Fig. 2B 1-2). clonic jerks and apnoea were video-EEG recorded (see Video, Patient 3 is a 18 months old girl whose clinical history is only Segment 2 and Fig. 1B). Myorelaxing treatment with oral baclofen partially known. She was born at term after an apparently was introduced with remarkable reduction in the frequency and uncomplicated pregnancy. However, severe developmental delay 150 F. Mari et al. / Seizure 21 (2012) 147–150 was noticed since her first months of life. Severe spastic- tract. A large number of CNS lesions or disorders involving the 1 hypokinetic quadriplegia became apparent and brain MRI scan pyramidal system are known to be causative. The clinical pattern revealed massive cortical and subcortical atrophy, which was of clonus observed in our patients was remarkable for its long attributed to prenatal suffering (see Fig. 2C 1-2). Prolonged duration and somatic spreading, leading to severe apnoea, and was episodes of twitching and rhythmic clonic jerking appeared probably related to the massive cortical and subcortical atrophy. during the first months of life and were initially interpreted as Although clonus’ underlying mechanisms are not yet complete- clonic epileptic seizures. However, clinical observation and ly understood, an interaction between central mechanisms and 10,11 video-EEG recordings were consistent with startle-induced peripheral events has been proposed with, as main mecha- stiffness and clonic twitching of non epileptic origin. In nism, a strong facilitation of descending motor pathways from the 1 particular, we noticed that the episodes of jerking were brain to the spine. regularly precipitated by tapping and stretching and were In all three patients, the specific cause of the extremely severe terminated by interrupting the reverberating spinal reflex by brain atrophy remained unclear. It is possible that the extremely holding the patient’s jerking limbs down (see Video, Segment 3). frequent and prolonged apnoic episodes have contributed in The patient was lost from follow-up and no information on causing chronic post-anoxic damage superimposed to the origin- treatment was available. ary perinatal brain lesion. In all three cases, a written informed consent for publication of Our opinion is that the clinical manifestation we have described the videos has been obtained. is probably under-diagnosed and easily misdiagnosed as epileptic seizures. This report shows that careful video-EEG recordings are 3. Discussion required for a proper differential diagnosis of paroxysmal motor phenomena, particularly in children with severe brain damage