Post-hypoxic action (intention) myoclonus: a clinico-electroencephalographic study

Summary A patient with post-hypoxic action myoclonus classified as reticular reflex myoclonus was subjected to an electrophysiological investigation. The myoclonic movements involved mainly the legs but could also affect the whole body. Somatosensory evoked responses were not increased and electroencephalography (EEG) was normal when the patient was relaxed. Startle, self-paced movement or movement on command induced repetitive myoclonic jerks preceded and accompanied by repetitive small spikes in the EEG with phase reversal in the midline at the vertex or slightly posterior to it, regardless of the limb moved. The central spiking subsided considerably earlier than the myoclonic jerks as shown by polygraphic recordings. The EEG spikes were also provoked by mere imagination of movement and persisted in spite of a dramatic reduction of myoclonic activity after treatment with clonazepam. The observations suggest that the vertex spiking in post-hypoxic action myoclonus indicates synchronous cortical activation, but is not closely coupled with activation of the Betz cells of layer V where the pyramidal pathway originates.     

脑干起源肌阵挛模型的建立

目的 探讨建立在发生机制、发作行为、神经电生理学及药效学特征等方面均与临床脑干起源肌阵挛更为一致的实验动物模型.方法 以5-羟色胺(5-HT)的前体L-5-羟色胺酸(L-5-HTP)在健康幼年豚鼠脑桥背侧定点微量注射诱发肌阵挛(同步记录的脑电图暴发活动≤400 ms),观察肌阵挛发作潜伏期、达峰时间、最大发作频率、高峰持续时间和总持续时间等行为学特征.以多导电生理同步记录肌阵挛发作期脑电图、肌电图以及抽动逆向锁定的脑电叠加分析(JLA),论证及认定肌阵挛为脑干起源,并选择对控制肌阵挛具不同效力的丙戊酸(VPA)、氯硝西泮(CZP)和卡马西平(CBZ)等抗癫(癎)药物(AEDs),按达到半数有效浓度(EC_(50))的剂量预处理实验动物后,根据各自药效学特征择时诱导肌阵挛发作,观测抗癫(癎)药物预处理后肌阵挛发作行为及电生理学的变化特征.结果 (1)在一定剂量范围内,L-5-HTP在8只豚鼠脑桥背侧部微量注射,全部一次性诱发单纯性肌阵挛发作,诱发成功率100%.(2)行为学特征:脑桥起源肌阵挛发作表现为两侧或全身性肌阵挛,并显示对触摸、声音刺激的敏感性.(3)脑桥起源肌阵挛肌电暴发时程较长,达(208.75±81.42)ms,同步脑电图中,有散在不规则棘、尖波发放,但与肌电图活动不存在锁时关联.(4)脑桥起源肌阵挛发作中脑电图虽然时有散在棘、尖波发放,但经JLA叠加后无锁时关联的脑电图叠加波.(5)在一次性给药后达到EC_(50)浓度下,VPA和CZP使脑桥起源肌阵挛的最大发作频率[VPA组(28.13±3.79)次/min;CZP组(37.17±4.67)次/min]较对照组[(56.25±6.96)次/min]减少、高峰持续时间[VPA组(55.00±14.14)min;CZP组(50.00±11.73)min]和总持续时间[VPA组(124.17±40.04)min;CZP组(156.88±30.71)min]较对照组[高蜂持续时间(80.00±16.01)min;总持续时间(218.75±17.63)min]显著缩短(F=23.41～35.44,P＜0.01或P＜0.05),对肌阵挛的肌电图时程未有显著影响;CBZ使肌阵挛发作的高峰持续时间[(98.75±13.86)min]和总持续时间[(257.50±14.79)min]较对照组明显延长(P＜0.05、0.01).结论 本模型不仅保证了脑干肌阵挛纯起源,同时因使模型肌阵挛暴发时程显著缩短至400 ms以内,对触觉敏感和对CZP治疗显著有效等优点,较既往L-5-HTP全身注射造模更接近临床实际,从而成功获得在发作行为、神经电生理及药效学特性均与临床更趋一致的脑干起源肌阵挛模型.     

Post-hypoxic intention myoclonus treated with 5-hydroxytryptophan and an extracerebral decarboxylase inhibitor

Post-hypoxic intention myoclonus successfully treated by long-term administration of the combination of 5-hydroxytryptophan and carbidopa is described. Persistent euphoria and diarrhoea were essential side effects. Methysergide (12 mg/day) blocked the therapeutic effect, indicating a specific serotoninergic function of precursor loading with 5-hydroxytryptophan. Tryptophan (8 g/day) had no effect on the myoclonus suggesting a reduced tryptophan hydroxylase activity. Plasma concentrations of 5-hydroxytryptophan in the range of 10--30 micromoles per liter were obtained during maintenance therapy with 900 mg 5-hydroxytryptophan per day in combination with 150 mg carbidopa per day.     

Post-hypoxic myoclonus induces Fos expression in the reticular thalamic nucleus and neurons in the brainstem

Post-hypoxic myoclonus is a movement disorder characterized by brief, sudden involuntary muscle jerks. Although the mechanism underlying this disorder remains unclear, earlier pharmacological studies indicated that aberrant activity of specific neuronal circuitry in the central nervous system causes this disorder. In the present study, Fos protein, an immediate-early gene product, was used as a marker of neuronal activity to identify the brain nuclei possibly involved in post-hypoxic myoclonus. We found that Fos protein was immunologically detected in the reticular thalamic nucleus (RT), the medial longitudinal fasciculus (MLF) as well as in the locus coeruleus (LC) and the periventricular gray substance (PVG) in post-hypoxic rats that developed myoclonus in response to auditory stimuli. Fos was not detected in these nuclei from rats that underwent 4 min of cardiac arrest without myoclonus. Electrolytic lesions of the RT or MLF but not the LC/PVG significantly reduced auditory stimulated myoclonus in the post-hypoxic rats. The results suggest that neuronal activity in the RT and the MLF plays a contributing role in post-hypoxic myoclonus.     

Estrogen supplementation in the posthypoxic myoclonus rat model

The objective of the study was to investigate the effects of estrogen on severity and duration of myoclonus in the rat cardiac arrest model of posthypoxic myoclonus. Female sex hormones affect a variety of movement disorders and alter dopaminergic and serotonergic pharmacology. Although women represented three-fourths of patients from the original report of Lance and Adams and 80% of the largest published series, the impact of estrogens on myoclonus has never been studied. Twelve previously ovariectomized female rats underwent 8 minutes of mechanically induced cardiac arrest and were resuscitated according to a standardized protocol. On the same day, they were randomly assigned to subcutaneous treatment with a 21-day, 0.5-mg, 17 beta-estradiol or matching placebo pellet. Animals were tested daily with 7 sets of 45 auditory stimuli for 10 days, and myoclonus scores were obtained using a 5-point interval scale. Comparisons were based on two-sample Wilcoxon rank-sum tests. Estrogen treatment significantly enhanced myoclonus intensity and duration: mean peak myoclonus score, 210.2 +/- 18.0 versus 180 +/- 28.5 (p = 0.031); mean number of days above baseline, 9.2 +/- 0.4 versus 5.7 +/- 2.3 (p = 0.004); mean score on day 10, 90.7 +/- 38.7 versus 27.0 +/- 20.6 (p = 0.016). All estrogen-treated animals were above baseline on day 10 compared with none in the placebo group. Estrogen enhances and prolongs posthypoxic myoclonus, suggesting that female gender and estrogen status may play a pivotal role as a risk factor for human posthypoxic myoclonus.     

Neurophysiology of myoclonus and progressive myoclonus epilepsies

The high temporal resolution of neurophysiological recordings makes them particularly suited to faithfully describing the time course of rapid events such as myoclonus and to precisely measure its time relationship with other related activities. In progressive myoclonus epilepsies (PMEs) polygraphy with simultaneous EMG‐EEG recordings is a crucial tool for defining the characteristic of myoclonic jerks their topography over different muscles (namely antagonists), their time course and relationship with vigilance muscle activation and stimulations. Moreover on polygraphic recordings it is possible to detect EEG activities associated to myoclonic jerks and define their time relationship with myoclonus thus differentiating cortical types of myoclonus from subcorticallly generated ones. Tanks to the back averaging technique non obvious time‐locked EEG potentials can be detected on polygraphy, furthermore in stimulus sensitive myoclonus the analysis can include the potential evoked by the somatosensory stimulus (SEP). The polygraphic recording also gives information on muscle activity suppression occurring after jerk or as pure negative myoclonus. Besides the time domain analysis, techniques based on frequency analysis have been developed to evaluate EEG‐EMG coherence. The neurophysiological techniques provide investigators and clinicians with an invaluable information to define the type of myoclonus and its generating circuitry thus substantially contributing in the diagnosis and management of PMEs.     

Rhythmic skeletal myoclonus without palatal myoclonus]

We reported a case of 89-year-old woman showing rhythmic skeletal myoclonus mainly on the right upper limb. This myoclonus appeared five days after the cerebral infarction. It was seen constantly both at rest and in posture, and decreased during voluntary movement. When the patient was under emotional stress, it spread to the submandibular, neck and trunks of upper limb. During sleep, this movement completely disappeared. There was no myoclonus in palato-pharyngo-laryngo-oculo-diaphragmatic muscle group. In the examination of the surface electromyography, the movement was not reciprocal between extensor and flexor muscles, and its cycle was about 3.5 Hz. It was different from the intention tremor because it did not increase during the movement phase on the finger nose test. The examination of MRI revealed a small infarction including right dentate nucleus and right superior cerebellar peduncle, and from which an infarction of the superior cerebellar artery territory was considered. Only a few cases of rhythmic skeletal myoclonus without palatal myoclonus have been reported in the literature. All of these cases had small infarction of the same region as the above case. Their myoclonus began 5 to 15 days after the onset of cerebral infarction. These periods were markedly shorter than that of intention tremor and palatal myoclonus. This fact suggest that the rhythmic skeletal myoclonus has a different mechanism from that of the palatal myoclonus.     

Tardive myoclonus

We describe a 46-year-old, schizophrenic woman with late-onset myoclonus after treatment with antipsychotic drugs. The myoclonic jerking of the neck with synchronous contractions of the face persisted after all the antipsychotic drugs had been discontinued. Tardive myoclonus has not been documented previously.     

Opsoclonus myoclonus

Opsoclonus myoclonus is a rare autoimmune condition characterized by cerebellar degeneration. It occurs most often as a paraneoplastic syndrome when a cancer remote to the brain induces cerebellar dysfunction that is unrelated to metastases. Half of all cases occur in children with a neuroblastoma. Most adults with opsoclonus myoclonus have neoplastic, infectious, metabolic, or idiopathic etiologies. Signs of cerebellar dysfunction noted at presentation include opsoclonus, myoclonus and ataxia, hence the name "dancing eyes, dancing feet syndrome." Opsoclonus is characterized by rapid, involuntary eye movements that are dysrhythmic and uncoordinated.Neuronal damage is induced by antibodies usually related to the primary pathology. Treatment targets the etiology and also employs steroids, plasmapheresis, immunosuppressive agents, or other anti-inflammatory therapies. Children with opsoclonus myoclonus resulting from a neuroblastoma often retain neurological sequelae. Adult cases of opsoclonus myoclonus with idiopathic or infectious etiologies have a more favorable prognosis than those with neoplastic origins.     

Postanoxic myoclonus

Summary Postanoxic myoclonus was first accepted as being related to a dysfunction of the ventrolateral thalamic nucleus. Several stereotaxic studies have invalidated this hypothesis. The neurochemical approach, in particular the measure of 5-hydroxyindolacetic acid in the cerebrospinal fluid, has opened new theoretical and therapeutic possibilities involving serotoninergic pathways.A typical case is presented who improved markedly under a combined therapy with 5-hydroxytryptophan and a decarboxylase inhibitor. A review of the pathogenesis and therapeutic approach to postanoxic myoclonus is presented.

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Zusammenfassung Es wurde früher angenommen, daß der postanoxische Myoklonus durch eine Dysfunktion des ventro-lateralen thalamischen Nucleus bedingt ist. Diese Hypothese wurde durch verschiedene stereotaktische Studien in Frage gestellt. Neurochemische Untersuchungen, insbesondere die Messung von 5-Hydroxyindol-Essigsäure im Liquor öffnete den Weg zu neuen theoretischen und therapeutischen Möglichkeiten, Bahnen des serotoninergischen Systems zu beeinflussen.Ein typischer Fall wird vorgestellt, der unter einer Kombinationstherapie von 5-Hydroxytryptophan und einem Decarboxylase-Hemmer eine wesentliche Besserung zeigte. Die Pathogenese und therapeutische Möglichkeiten des postanoxischen Myoklonus werden diskutiert.

     

Spinal myoclonus

A case of rhythmic myoclonus affecting only the lower part of the body is described. This occurred as an acute self-limiting illness. The changes in the cerebrospinal fluid (CSF) suggested a viral infection. Clinical and electrophysiological findings indicated that the involuntary movements were arising at spinal level and were independent of suprasegmental influences. There are few previously reported cases of spinal myoclonus, all different in various respects from the present one, which is reminiscent of the results of experimental inoculation of virus into feline spinal cord.     

Olanzapine-associated myoclonus

Olanzapine is an atypical antipsychotic drug that infrequently has been reported to cause seizures and myoclonus despite a small proconvulsant risk. This is the first report of generalized myoclonus induced in a patient who had been maintained on low dose olanzapine for over seven years without any change in her dose. Olanzapine was discontinued, and the myoclonic jerks completely resolved within 48 h.