PAROXYSMAL MYOCLONUS DUE TO A SPINAL CORD TUMOR
Paroxysmal Kinesigenic Segmental Myoclonus Due to a Spinal Cord Glioma Manuel Marrufo, MD, Jeffrey Politsky, FRCP(C), Shyamal Mehta, MD, PhD,* John C. Morgan, MD, PhD, and Kapil D. Sethi, MD, FRCP Department of Neurology, Medical College of Georgia, Augusta, Georgia
Abstract: We report an 18-year-old man with paroxysmal jerking movements of the left arm since age 7 years. These were invariably precipitated by startle or sudden movements. He was subsequently diagnosed with a cervical cord anaplastic astrocytoma on MRI. We could not identify previous reports of paroxysmal myoclonus secondary to a spinal cord neoplasm. We have coined the term Paroxysmal Kinesigenic Segmental Myoclonus to describe this entity. © 2007 Movement Disorder Society Key words: paroxysmal; kinesigenic; myoclonus; spinal cord; glioma.
Myoclonus may result from lesions in multiple parts of the neuraxis including the cerebral cortex, subcortical areas, brainstem, spinal cord, and nerve roots.1 Typically myoclonus is stimulus sensitive, but not paroxysmal with the exception of cortical myoclonus. Paroxysmal dyskinesias are defined as sudden, episodic, involuntary movements that may be isolated or include a combination of dystonia, chorea, athetosis, or ballism.2 One common form is Paroxysmal Kinesigenic Dyskinesia (PKD). We report an 18-year-old man with paroxysmal jerking movements of his left arm since age 7 years, precipitated by movement or startle. These paroxysmal episodes did not respond to carbamazepine therapy. Investigations revealed a grade III anaplastic astrocytoma in his cervi-
This article includes supplementary video clips, available online at http://www.interscience.wiley.com/jpages/0885-3185/suppmat *Correspondence to: Dr. Shyamal Mehta, Department of Neurology, Medical College of Georgia, Augusta, GA 30912. E-mail:
[email protected] Received 24 November 2006; Revised 29 March 2007; Accepted 22 May 2007 Published online 27 June 2007 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.21635
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cal spinal cord that we believe, may be the cause of his paroxysmal kinesigenic myoclonus. CASE REPORT An 18-year-old left-handed man had episodes of involuntary jerky movements of his left arm since the age of 7 years. There was no family history of paroxysmal movement disorders. These movements were preceded on occasion by a tingling sensation of the ipsilateral shoulder. The movements involved the entire left arm, including the wrist, and typically lasted 20 –30 s (Video). He would have ⬃20 of these spells per day. Several months preceding the evaluation he noted abnormal movements in the right arm as well. These movements occurred independently of those on the left, and were more frequent but less intense. The movements on either side were precipitated exclusively by sudden movement, movement initiation, and startle (Video). He denied having weakness or any other symptoms between spells. Initially, no abnormalities were identified on neurological examination between spells. Several spells were witnessed on the left side. He had clonic jerking of the left shoulder and arm and rhythmic extension of left wrist that were brought on by startle and sudden movements. Hyperventilation did not bring out these spells. They lasted 20 –30 s and the patient stayed awake and alert during the spells (see Video). There was a period after the spell during which the movements could not be evoked by further stimuli. He was initially diagnosed with an atypical PKD for which he was prescribed carbamazepine. Laboratory investigations including an ionized calcium level were normal. He had poor response to carbamazepine, acetazolamide, and levodopa. A SPECT scan of the brain shortly after one of the spells was normal, as was the MRI of the brain with gadolinium. He was admitted to the video-EEG monitoring to determine if there was a cortical origin for these myoclonic-dystonic jerks. A physical examination showed mild atrophy of the left calf muscles and left biceps. He had slight weakness in the left upper extremity wrist extensors and deltoids at 4⫹/5. He had mildly spastic tone in his lower extremities. The patient had increased reflexes of the lower extremities with a crossed adductor reflex on the left. He had an extensor plantar response on the left as well. Multiple episodes of limb myoclonus were recorded during video-EEG, none of which were associated with epileptiform discharges during or after the brief runs of myoclonic jerks of either arm. Median and tibial somatosensory evoked potentials were performed. Tibial SSEP’s showed significantly lower amplitudes of the
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tibial waveforms on the left side. Median nerve SSEP’s were abnormal with absent N18 and N20 waveforms on the left. The findings were consistent with pathology in the efferent sensory pathways at the cervico-medullary region or higher. MRI of the cervical spine (Fig. 1) showed a large mass within the spinal cord extending from C3–C6, involving the posterior columns and extending towards the right side of the cord with minimal
FIG. 1. (A) T1-weighted MRI C-spine with gadolinium, (B) T2weighted MRI C-spine.
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contrast enhancement, favoring the diagnosis of an intramedullary neoplasm. A biopsy of the lesion revealed the neoplasm as an anaplastic astrocytoma (WHO grade III). He then received chemotherapy as well as radiotherapy. Four months later, he is still able to ambulate and run short distances and is receiving physical therapy. The frequency and intensity of the movements are essentially unchanged. DISCUSSION Paroxysmal dyskinesias are a heterogeneous group of disorders.2 A channelopathy may be the underlying pathophysiological mechanism linking these disorders. PKD is often inherited in an autosomal dominant fashion, but some cases are sporadic. The age of onset is 5–15 years in familial cases but varies in sporadic cases. The attacks are typically precipitated by startle or a sudden movement after a period of rest. There is a refractory period after an attack during which sudden movement may not provoke an attack. The attacks occur very frequently, up to 100 per day. The duration is short, usually a few seconds to a few minutes, although longlasting attacks may occur rarely.3 Patients may only have an abnormal sensation in the involved limbs, or the sensation may precede motor manifestation. Most patients have dystonia, but some have a combination of chorea and dystonia and rarely ballism. Although chorea, dystonia, and rarely ballism have been described in association with PKD, myoclonus is not a usual phenotype of PKD. The attacks may be limited to one side of the body or even one limb. In one review of 73 cases of PKD, 25 occurred on one side only, 12 occurred unilaterally on either side, 11 occurred unilaterally or bilaterally, and 22 were always bilateral.4 These patients respond well to anticonvulsants. Typical PKD has been well characterized.5 “Alarm bells” should go off if a patient has a late age of onset, prolonged attacks, or a lack of response to low dose of anticonvulsants. In our patient, the type of movement and the lack of response to carbamazepine constituted a “red flag.” In our patient, the lack of epileptiform activity on video EEG, and the presence of a physiologically disruptive lesion, as demonstrated by abnormal SSEP studies, support a cervical spinal cord origin of myoclonus. Spinal myoclonus is typically segmental and not kinesigenic. However, stimulus sensitive spinal myoclonus has been described.6 Pathophysiological mechanisms of spinal myoclonus have been widely studied and may involve dysfunction of inhibitory neurotransmitters (GABA/glycine) or ion channel dysfunction.7–9
ETIOLOGICAL HAND FACTORS IN FHDM: CASE STUDY In the patient we describe, the paroxysmal kinesigenic myoclonus was secondary to the slow growing spinal cord tumor present since early childhood. The recent appearance of the movements on the right side was probably due to an increase in the size of the tumor (transformation to Grade III). We speculate that the myoclonic dystonic jerks seen in our patient originated from the cervical spinal cord. These myoclonic jerks were initiated by movement. A segmental neuronal network depolarization, with or without failure of inhibitory glycine mediated synapses, could have been responsible for these types of movements.8,10 –12 The activation of myoclonic jerks can be segmental or multisegmental. They can be associated with spinal, subcortical, and cortical inhibitory–stimulatory mediated pathways.9 –11 In addition, a lack of epileptiform activity on video EEG and abnormal SSEP studies indicated a lesion in the cervical spinal cord. However, a secondary involvement of higher structures can not be ruled out. We propose the term Paroxysmal Kinesigenic Segmental Myoclonus (PKSM) for this unique entity. Spinal cord pathology should be considered in the differential diagnosis of an atypical PKD patient. LEGENDS TO VIDEO The patient has clonic jerking movements of the left shoulder and arm and rhythmic extension of left wrist brought on by startle (i.e., unexpected loud noise) and sudden movements. He remained alert during the episodes typically lasting 20 –30 s. REFERENCES 1. Fahn S, Marsden CD, Van Woert MH. Definition and classification of myoclonus. Adv Neurol 1986;43:1-5. 2. Sethi KD. Paroxysmal dyskinesias—the neurologist, May 2000, Vol. 6, pp. 177-185. 3. Demirkiran M, Jankovic J. Paroxysmal dyskinesias: clinical features and classification. Ann Neurol 1995;38:571-579. 4. Plant G. Focal paroxysmal kinesigenic choreoathetosis. J Neurol Neurosurg Psychiatry 1983;46:345-348. 5. Bruno MK, Hallett M, Gwinn-Hardy K, et al. Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria. Neurology 2004;63:2280-2287. 6. Davis SM, Murray NM, Diengdoh JV, Galea-Debono A, Kocen RS. Stimulus-sensitive spinal myoclonus. J Neurol Neurosurg Psychiatry 1981;44:884-888. 7. Serrao M, Cardinali P, Rossi P, et al. Spinal myoclonus with giant somatosensory evoked potentials and enhanced long-loop reflex: a case report. Funct Neurol 2004;19:203-206. 8. Simon ES. Involvement of glycine and GABA receptors in the pathogenesis of spinal myoclonus: in vitro studies in the isolated neonatal rodent spinal cord. Neurology 1995;45:1883-1892. 9. Graham BA, Schofield PR, Sah P, Margrie TW, Callister RJ. Distinct physiological mechanisms underlie altered glycinergic synaptic transmission in the murine mutants: spastic, spasmodic, and oscillator. J Neurosci 2006;26:4880-4890.
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10. Pablo M, Huang Y, Gilio F, et al. Abnormal cortical and spinal inhibition in paroxysmal kinesigenic dyskinesia. Brain 2005;128: 291-299. 11. Schulze-Bonhage A, Knot H, Ferbert A. Pure stimulus-sensitive truncal myoclonus of propriospinal origin. Mov Disord 1996;11: 87-89. 12. Bussel B, Roby-Brami A, Azouvi P, Biraben A, Yakovleff A, Held JP. Myoclonus in a patient with rhythmic segmental myoclonus. J Neurol Neurosurg Psychiatry 1996;61:641-644.
Etiological Musculo-Skeletal Factor in Focal Dystonia in a Musician’s Hand: A Case Study of the Right Hand of a Guitarist Joris N.A.L. Leijnse, PhD,1 and Mark Hallett, MD2 1
Laboratory for Clinical Biomechanics and Reconstructive Surgery of Hand and Upper Limb, Department of Mechanical Engineering, Speed School for Engineering & Price Institute for Surgical Research, Department of Surgery, University of Louisville, Louisville, Kentucky, USA; 2Human Motor Control Section, NINDS, National Institutes of Health, Bethesda, Maryland, USA
Abstract: A case study is presented in which a focal hand dystonia seems to have developed in the right hand of a classical guitarist as a result of a neuromuscular peripheral defect caused by trauma. The trauma was a near total perforation of the first web space by a splinter. Healing was uneventful without apparent functional complications. Two years later the patient noticed difficulties in extending the index in playing, for which he received various unsuccessful treatments during seven years. However, we found more severe dystonic symptoms (cocontractions) in the thumb than in the index during playing, which correlated with an undiagnosed insufficiency in the flexor pollicis brevis (FPB). This defect allowed proposing a biomechanical analysis of compensations for diminished thumb control in playing, which would explain the dysfunction in the index in playing as overcompensation for the thumb problem. If this analy-
This article includes supplementary video clips, available online at http://www.interscience.wiley.com/jpages/0885–3185/suppmat *Correspondence to: Dr. J.N.A.L. Leijnse, Assistant Professor of Research, Department of Mechanical Engineering, 200 Sackett Hall, University of Louisville, Louisville, KY 40292. E-mail:
[email protected] Received 29 August 2006; Revised 16 May 2007; Accepted 22 May 2007 Published online 20 July 2007 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.21636
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