~ We report a case of synchronous positive and negative myoclonus following pontine hemorrhage. Constant synchronous jerking of the eyes, tongue, face, mandible, larynx, pharynx, and diaphragms persisted during sleep. Jerking of limb muscles occurred during volitional activities, but not at rest. Inability to sustain glottic adduction during phonation contributed to severe dysarthria. Electromyography (EMG) revealed positive myoclonus of the branchial musculature with synchronous negative myoclonus in a generalized distribution. Treatment with trazodone reduced the ocular myoclonus but worsened the dysphagia. We suggest that a single neural rhythm generator may produce both positive and negative myoclonus. Key words: myoclonus dysarthria cerebral hemorrhage pathophysiology electromyography videofluoroscopy MUSCLE & NERVE 13~124-132 1991 SYNCHRONOUS POSITIVE AND NEGATIVE MYOCLONUS DUE TO PONTlNE HEMORRHAGE JEFFREY B. PALMER, MD, DONNA C. TIPPETT, MA, and JAMES S. WOLF, MD Myoclonus is defined as “sudden, brief, shock-like involuntary movements caused by muscular contractions (positive myoclonus) or inhibitions (negative myoclonus) arising from the central nervous system.lY6The movements may be single or multiple, rhythmic or arrhythmic, and may occur focally, segmentally, or in a generalized distribution. Palatal myoclonus is a syndrome characterized by rhythmic jerking of the soft palate due to involuntary muscular contractions (positive myoclonus). There may be synchronous contraction of other muscles, particularly those of the pharynx, larynx, From the Division of Rehabilitation Medicine and Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University (Dr. Palmer), Department of Speech-Language Pathology, The Good Samaritan Hospital (Ms. Tippett), and private practice of Neurology (Dr. Wolf), Baltimore, Maryland. Acknowledgments: We thank Keith Kuhlemeier, PhD for assisting with statistical analysis, Barbara Cox-Spahn for preparing the illustrations, and members of the Johns Hopkins University-Good Samaritan Hospital Rehabilitation Medicine Program for helping us evaluate and treat the patient. Mark Hallett, MD suggested using trazodone. Supported in part by awards from the NINCDS (NS01211) and the Johns Hopkins University School of Medicine (Clinician-Scientist Career Development Award). Presented in part at the annual joint meeting of the American Academy of Physica Medicine and Rehabilitation and American Congress of Rehabilitation Medicine, Seattle, 1988, and the annual meeting of the American Association of Electrodiagnostic Medicine, Washington, DC, 1989. Address reprint requests to Jeffrey B. Palmer, MD, Good Samaritan Professional Building, 5601 Loch Raven Boulevard. Room 303, Baltimore, MD 21239. Accepted for publication January 15, 1990 CCC 0148-639X/91/020124-09 $04 00 0 1991 John Wlley & Sons, Inc. 124 Positive a n d Negative Myoclonus eyes, face, and diaphragm. Palatal myoclonus persists during sleep and has a rate of 60-2001 min.’0”9 In this article, we report a case of palatal and extremity myoclonus with unusual features caused by pontine hemorrhage. Electromyography (EMG) showed synchronous positive and negative myoclonus, their timing and distribution, and the effects of volitional activities on these phenomena. Videofluoroscopy revealed the mechanism of the dysarthria. Treatment with trazodone led to an improvement in ocular myoclonus but a worsening of dysphagia. The physiology of negative myoclonus is poorly understood. Classifying involuntary movements due to muscular relaxation as myoclonus is controversial. The occurrence of this phenomenon in association with palatal myoclonus supports its classification as myoclonus. We will discuss implications for the pathophysiology of myoclonus. CASE REPORT A 23-year-old black woman lost consciousness suddenly on 9/9/85 while attending her mother’s funeral. Examination in the emergency room revealed bilateral decerebrate posturing with no purposeful responses. Ocular bobbing occurred spontaneously, but there were no lateral extraocular movements in response to caloric stimulation. Corneal and gag reflexes were absent, and there was facial diplegia. All 4 limbs were rigid, and clonus was noted at both knees and ankles. Plantar MUSCLE & NERVE February 1991 responses were extensor bilaterally. Mechanical ventilation was initiated via an endotracheal tube. Cranial computed tomography revealed a hemorrhage in the pons (Fig. 1). Angiography revealed normal vertebral and basilar arteries. Cocaine was detected on toxicology screen. EEG revealed nonreactive alpha with excessive slow-wave activity bilaterally. Wave V was absent on auditory brainstem responses. The N18 and P22 somatosensory evoked potentials were absent after stimulation of either median nerve, however the N9 and P13 responses were normal. There was slow improvement. Volitional vertical extraocular movements were reported on day 11 of hospitalization. During the third week, tracheostomy and feeding cervical esophagostomy were performed, and mechanical ventilation was discontinued. Volitional contraction of lower extremity muscles were reported on day 22. The patient was transferred to the Rehabilitation Medicine service on 12/12/85, several days after the tracheostomy was decannulated. She was dysarthric, quadriparetic, and grossly uncoordinated, with rhythmic involuntary jerking of the head, neck, face, palate, and eyes. Trismus was noted. EMG showed continuous involuntary motor unit (MU) activity of the right masseter. When the patient tried to open her mouth, MU activity increased in both masseters. She remained unable to propel her wheelchair or perform basic selfcare activities when discharged to home on 31251 86. The movement disorder was refractory to Valproic acid, Carbemazepine, and Desipramine. Feeding gastrostomy was performed on 411 1/86, and the esophagostomy was closed. The patient was readmitted on 3/21/88 for comprehensive reevaluation. Her many neurologic problems included quadriparesis, dysphagia, dysarthria, and neurogenic bowel and bladder. Ability to open the mouth and to swallow had improved. The patient could safely eat a wide variety of solid and liquid foods, limited only by her difficulties with mastication. The gastrostomy was used solely to supplement fluid intake. Mental status was normal. Ocular examination revealed neuropathic keratitis of the right eye, which necessitated tarsorrhaphy . Both eyes exhibited rapid, repetitive, involuntary, vertical and horizontal movements. Upward and downward gaze were preserved, but horizontal gaze was reduced. Visual acuity, visual fields, and fundoscopic examination were unremarkable. Synchronous with the downward eye movements were rapid, repetitive, involuntary jerking of the palate, tongue, larynx, mandible, left face, and head. These motions persisted during sleep. There was right facial palsy with quadriparesis involving the left side more than the right. FIGURE 1. CT scans with (A) and without (B)intravenous contrast enhancement show a hemorrhage in the pons. Positive and Negative Myoclonus MUSCLE & NERVE February 1991 125 All 4 extremties and the trunk were severely uncoordinated. Involuntary repetitive jerking occurred in the limbs during volitional activity, but not at rest. These involuntary limb movements were often synchronous with the repetitive jerking of head and neck structures. Muscle palpation revealed that the jerking of the limbs was due to involuntary relaxation of skeletal muscles during attempts to sustain contraction. Deep tendon reflexes were hyperactive in the left upper and both lower extremities. Plantar responses were flexor (down-going). A “crossed hemi-hypesthesia” was present, involving the left side of the body and right side of the face. The patient had poor sitting balance, and was unable to perform transfers or basic self-care activities. She was unable to stabilize the shoulder girdle to perform upper extremity activities. Language and cognitive abilities were intact. Verbal output was scmantically and syntactically correct. The patient responded appropriately during conversation and in response to specific instructions. Speech evaluation revealed a severe mixed dysarthria. Most striking were phonation breaks (inappropriate pauses in phonation) synchronized with the involuntary jerking. Vocal loudness and pitch fluctuated, resonance was hypernasal, and articulation was imprecise. Electro-oculography revealed continuous vertical and horizontal ocular jerking which increased upon closing the eyes (Fig. 2). EKG revealed sinus tachycardia of 120 beatslmin with no variation of R- R intervals, consistent with dysautonomia. EEG was normal. EEG-EMG correlations were studied by “back averaging” of EEG activity preceding c ( 1H E FIGURE 2. Ocular myoclonus. Electro-oculogram (EOG)showing vertical motion of the left eye under three different conditions: eyes open, gazing into the distance (top); gaze fixed in the primary position on an object 6 feet away (middle); and eyes closed (bottom). Ocular myoclonus persisted under various conditions; the amplitude of vertical motion increased when the eyes were closed. 126 Positive and Negative Myoclonus EMG bursts; no time-locked EEG discharges were present. After performing EMG and videofluoroscopic studies (to be described), a trial of clonazepam was started in 5/88. The dose was increased gradually to a maximum of 1.25 mglday in divided doses. Ocular and limb myoclonus improved slightly, but severe lethargy and dysphagia developed. Despite eliminating thin liquids from the diet, aspiration pneumonia occurred, and the drug was discontinued. The patient returned home on 6/19/88 after an uneventful recovery, and was readmitted to the hospital 7 months later for a trial of trazodone. On a dose of 100 mg every 8 hours, there was a reduction in ocular myoclonus, and the patient reported a subjective improvement in functional vision. The dysphagia was exacerbated, but the patient elected to continue trazodone because of the improvement in functional vision. N o respiratory sequelae have occurred during one year of treatment. METHODS EMG was performed on 4/8/ 88, 4/12/88, and 5/6/88 during sustained muscle contraction and at rest to define the distribution of myoclonus, differentiate positive from negative myoclonus, and assess the timing of myoclonus in various muscles. Surface electrode pairs were applied to the masseter, biceps brachii, triceps brachii, extensor carpi radialis, and quadriceps femoris muscles on the left, to the sternocleidomastoid muscle (SCM) on the right, and to the orbicularis oculi (OOculi) and tibialis anterior muscles on both sides. An additional pair of surface electrodes was applied to the suprahyoid muscles in the midline, recording from the anterior digastric and mylohyoid muscles of both sides via a single pair of electrodes. Needle electrodes were inserted into the tongue and left orbicularis oris (OOris) muscles. A maximum of 4 muscles were studied simultaneously; the suprahyoid muscles were included in every recording. Following 4 channel differential amplification with bandpass of 20 Hz to 10 kHz, signals were recorded on a strip chart at a paper speed of 5 cm/ sec. One recording session included simultaneous EKG. All recordings were made while the patient sat in her wheelchair. The patient was instructed either to relax and gaze into the distance or to perform volitional activities. These included holding the eyes closed, the mouth opened or closed, the elbow flexed or extended, the wrist extended, the knee extended, or the ankle dorsiflexed. Electromyography. MUSCLE & NERVE February 1991 The timing of myoclonus was analyzed by measuring a subset of the EMG strip chart recordings with a ruler. A muscle was excluded if the measurement points were unclear. The right OOculi muscle was excluded from all measurements because of the recent tarsorrhaphy. Cycles of myoclonus were defined as beginning at the onset of each EMG burst (positive myoclonus) in the suprahyoid muscles, and ending at the onset of the next cycle. Duration measurements were made for EMG bursts (positive myoclonus) and i