A case of cortical reflex positive-negative myoclonus--electrophysiological study

An 11-year-old girl who had the positive-negative myoclonus and the history of the generalized tonic clonic seizure was electrophysiologically studied. She had no siblings with either myoclonus or epilepsy, and her intellectual level was normal. She had no other neurological deficits including ataxia, pyramidal and extrapyramidal signs. Surface EMG showed a brief increase in the EMG activity followed by the silent period associated with positive and negative myoclonus during sustained wrist extension. Giant SEP and C reflex (38.6 ms) following electric stimulation of the median nerve at the wrist were obtained in the resting condition and the silent period (about 180 ms) following C reflex was obtained during voluntary contraction. Jerk-locked back averaging of the EEG time-locked to the onset of the myoclonic discharge recorded from the right biceps muscle showed a cortical spike at the left central region preceding the myoclonus onset by 12.6 ms. The latency of C reflex in this case was very short compared with that of previously reported cortical reflex myoclonus. The estimated cortical delay between the arrival of the somatosensory volley and the motor cortex discharge responsible for the C reflex was -1.0 ms and this value was shorter than that in patients with typical cortical reflex myoclonus (mean 3.7 +/- 1.1 ms). Conditioning stimuli (C) of the right median nerve at the wrist started to facilitate the amplitude of the motor evoked potential recorded from the right abductor pollicis brevis muscle after magnetic test stimuli (T) of the left motor cortex at 20 ms of the C-T interval. This C-T interval was shorter than that (24.6 +/- 1.6 ms) in patients with the typical cortical myoclonus. These electrophysiological findings suggested the shorter reflex pathway of the cortical reflex myoclonus in this case than in typical cortical reflex myoclonus. We speculated that the myoclonus was based upon the direct sensory projection from the thalamus to the motor cortex in this case.     

Pathophysiologies of dystonia and myoclonus--consideration from the standpoint of treatment

Pathophysiologies of disorders with dystonia or myoclonus were studied by evaluating the effects of treatment. Naturally, the main lesion of the dystonia responding to levodopa is in the nigrostriatal dopamine neuron. The target of stereotaxic operations is ventrolateral palladium for postural dystonia and the nucleus ventralis oralis posterior (Vop) thalamus for action dystonia. Torsion dystonia with lesion in the striatum and/or the pallidum causes axial torsion, it may be postural through the descending pathway and action through Vop. Stereotaxic operations on these pathways have shown to be effective. Focal dystonia is a reflection of abnormal co-activation of cortical motor neurons, occurring in a particular voluntary movement. Botulinus toxin injected into the affected muscle should be effective. Of myoclonus with epilepsy, cortical reflex myoclonus or cortical induced reticular myoclonus responds to valproic acid. However, no antiepileptic drugs are effective on those with primary brainstem lesion. Reticular reflex myoclonus due to asphyxia responds to ventralis intermedius thalamotomy. Idiopathic myoclonus associated with dystonia is particular because it responds to ventrolateral thalamotomy. Myoclonus except for idiopathic myoclonus with dystonia is associated with atonic NREM suggesting dysfunction of the dorsal raphe serotonergic neuron or the brainstem nucleus reticularis gigantocellularis, the causative neuron for experimental uremic myoclonus. Treatment for these neurons is necessary.     

Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival

We report the electrophysiologic findings of myoclonus in a patient with Huntington's disease (HD). This patient was studied postoperatively after a bilateral fetal cell transplant in his striatum. Incomplete transient improvement was seen in the myoclonus, followed by gradual deterioration. The myoclonus itself had a cortical correlate and was associated with an enlarged somatosensory evoked potential (SEP), consistent with the presence of cortical reflex myoclonus. An enlarged SEP has not been previously reported in myoclonus associated with HD. The postulated mechanisms for myoclonus, when it occurs in HD, have differed in the literature. The reason for the transient improvement of the myoclonus following transplantation is unclear, but this case raises the possibility that basal ganglia circuits may modulate cortical myoclonic activity.     

Development of a scoring system to assess disability in an Italian elderly population. Evaluation of a disability questionnaire

Patients with idiopathic and symptomatic restless legs syndrome (RLS) suffer from "dyskinesia while awake" or "daytime myoclonus" when at rest preceded by sensory symptoms. In order to characterise the RLS either as reflex movement or as voluntary movement we measured movement-related cortical potentials in 5 idiopathic and 8 uraemic RLS patients. Movements from both legs were polygraphically recorded concomitantly with cortical activity 2000 msec before to 500 msec after onset of EMG activity. These data were compared with a voluntary simulation of each patient's movement pattern and with 5 age-matched controls performing dorsiflexion of the right, left and both feet. Cortical activity preceding daytime myoclonus was absent in RLS patients whereas self-initiated leg movements in patients elicited onset times (1180-1380 msec) and amplitudes of Bereitschaftspotential (readiness potential) not significantly different from readiness potentials in control subjects (P > 0.05). Lack of movement-related potentials in myoclonus and/or dyskinesias during daytime in RLS patients is compatible with an involuntary mechanism of induction and points towards a subcortical or spinal origin of RLS.     

Familial cortical tremor, epilepsy, and mental retardation: a distinct clinical entity?

OBJECTIVE: To describe a European family with cortical tremor, epilepsy, and mental retardation, the pedigree of which indicates an autosomal dominant inheritance of the disease. DESIGN: Clinical, laboratory, neurophysiological, and neuroimaging data were studied. SETTING: Institute for research on mental retardation. PATIENTS: Two siblings (aged 25 and 28 years) and their 49-year-old mother had postural and action tremor, seizures, and mental retardation. Only tremor was present in the maternal grandmother (aged 68 years). The electroencephalogram showed diffuse spike-and-wave complexes and/or posterior spikes, and a photoparoxysmal response in the 4 subjects. The typical electrophysiologic features of cortical reflex myoclonus, such as giant somatosensory evoked potentials, enhancement of the C-reflex, and jerk-locked premyoclonus spikes, were found in all patients. CONCLUSION: This syndrome may represent a specific form of familial cortical tremor with a benign form of epilepsy and a new genetic model of cortical hyperexcitability inherited with an autosomal dominant mechanism.     

Geographic variation of secular trends of breast cancer mortality in Spain

Twenty-one patients with disabling spontaneous, reflex, or action myoclonus due to various causes, who had shown apparent clinical improvement on introduction of piracetam, entered a placebo-controlled double-blind crossover trial of piracetam (2.4-16.8 g daily). All but one patient had electrophysiological evidence of cortical myoclonus. Patients were randomly allocated to a 14-day course of piracetam followed by identical placebo, or placebo followed by piracetam. Nineteen patients received piracetam/placebo in addition to their routine antimyoclonic treatment (carbamazepine, clonazepam, phenytoin, primidone, sodium valproate, or tryptophan plus isocarboxazid, alone or in combination) and two received piracetam/placebo as monotherapy. All patients were rated at the end of each treatment phase using stimulus sensitivity, motor, writing, functional disability, global assessment, and visual analogue scales. Ten of the 21 patients had to be rescued from the placebo phase of the trial because of a severe and intolerable exacerbation of their myoclonus. No patients required rescue from the piracetam phase of the double-blind trial. When the 21 patients were considered together, there was a significant improvement in motor, writing, functional disability, global assessment, and visual analogue scores during treatment with piracetam compared with placebo. The total rating score also improved significantly with piracetam, by a median of 22%. Piracetam, usually in combination with other antimyoclonic drugs, is a useful treatment for myoclonus of cortical origin.     

Chronic herpes simplex encephalitis initially presenting with persistent myoclonus

A 59-year-old female patient with atypical chronic herpes simplex encephalitis was reported. Initial symptom was persistent myoclonus involving the trunk and limb muscles, and later lateral gaze palsy to the left side, cerebellar ataxia, consciousness disturbance and other brainstem symptoms including absence of corneal and gag reflex and vocal cord palsy developed. The patient was successfully treated with high dose of acyclovir. Electroencephalogram was normal in the initial stage but later showed diffuse slow waves. Although CT scan and MRI showed no abnormal finding in the cerebral cortex, brainstem lesion was observed on PD weighted image of MRI. Lumbar puncture yielded a clear cerebrospinal fluid, with slightly elevated protein, increased lymphocytes, and elevated titer of herpes simplex virus type I. The serological data, albumin ratio (10.3), antibody index (12.3) and antibody ratio (7.1) were consistent with herpes simplex encephalitis. Ten days' administration of acyclovir, 1,200 mg a day and repeated three times, was prominently effective for the myoclonus and consciousness disturbance. A diagnosis of chronic herpes simplex encephalitis initially presenting with brainstem encephalitis was made. Judging from the clinical and EEG findings, the brainstem lesion was initially thought to be a cause of myoclonus in this case. However, somatosensory evoked potential (SPE) of both upper and lower extremities revealed enlarged amplitude (giant SEP), and long loop reflex was enhanced (C-reflex) on the left. Giant SEP and C-reflex imply cerebral cortex as the origin of the myoclonus. Brainstem inflammatory lesion might have involved the ascending inhibitory system, thus disinhibiting the cortical sensorimotor area and causing cortical myoclonus.     

Cortical hyperexcitability in progressive myoclonus epilepsy: a study with transcranial magnetic stimulation

In progressive myoclonus epilepsy (PME), responses to afferent input are frequently abnormal. It is unclear whether the abnormality lies at the cortical, subcortical, or segmental level. To obtain evidence for an exaggerated effect on motor cortical excitability, we used peripheral nerve and transcranial magnetic stimulation in controls and subjects with idiopathic generalized epilepsy and PME. Mean threshold intensity was higher in those with idiopathic generalized epilepsy and PME than in controls, probably as a result of anticonvulsant treatment. A long-latency response to peripheral stimulation and an exaggerated facilitatory effect of peripheral stimulation on the motor evoked potential was present in subjects with PME. Latency differences between the late responses in the upper and lower limbs provided evidence against a segmental reflex and implicated rapidly conducting fibers in the spinal cord. Both the late response and the facilitatory effect had onset latencies consistent with a transcortical pathway, suggesting an exaggerated effect of afferent input on motor cortical excitability in PME.     

Grooming reflexes and Brown-Séquard epilepsy in cats with pontile lesions.

The literature on the relation between the scratch reflex and Brown-Séquard epilepsy in the guinea pig indicates that the scratch reflex is a stimulus-induced myoclonus that is the 1st component of a complete seizure. In the present experiment, with 26 male cats, Ss with pontile or frontal neocortical lesions exhibited the scratch reflex and other grooming reflexes. The grooming reflexes in Ss with pontile lesions developed over a period of a year or more into complete seizures that were similar to Brown-Séquard epilepsy. Cinematographic analyses revealed that the scratch reflex in Ss with pontile or frontal neocortical lesions had the same frequency and the same complex spatial and temporal pattern as normal scratching behavior. The myoclonus of the complete seizures was identified as the scratch reflex, representing a vigorous and long-lasting afterdischarge. Reconstructions of the pontile lesions indicated that the lateral and rostral portions of the paralemniscal tegmental fields were destroyed along with portions of the pontile gray and pyramidal tract. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prognostic value of myoclonus status in comatose survivors of cardiac arrest

Generalized myoclonus status is common in comatose patients after cardiac resuscitation, but its prognostic value is uncertain. We studied the clinical, radiologic, and pathologic findings in 107 consecutive patients who remained comatose after cardiac resuscitation. Myoclonus status was present in 40 patients (37%). Features more prevalent in patients with myoclonus status were burst suppression on electroencephalograms, cerebral edema or cerebral infarcts on computed tomography scans, and acute ischemic neuronal change in all cortical laminae. All patients with myoclonus status died. Of 67 patients without myoclonus, 20 awakened. We conclude that myoclonus status in postanoxic coma should be considered an agonal phenomenon that indicates devastating neocortical damage. Its presence in comatose patients after cardiac arrest must strongly influence the decision to withdraw life support.     

Psychosocial risk factors in near-fatal asthma and in asthma deaths

We report a patient with familial myoclonus showing an extremely benign clinical course. The patient was a 70-year-old woman, who first noticed shaking of hands at age of 25. The symptom did not worsen for more than 40 years. She visited our hospital at the age of 70 because of disturbance in chores because of worsening of her hand shaking in the past one year. A family history showed that 4 members had similar symptoms and that the two were afflicted with fits of loss of consciousness. On neurologic examination, rhythmic myoclonic jerks were noted in all the extremities, more in the upper limbs, both at rest and during action. Tandem gait was mildly disturbed. The remainings of neurologic examination were normal. SEP and jerk-locked back averaging provided evidence of cortical myoclonus. EEG showed multifocal polyspike discharges. Gene analysis for DRPLA, pyruvate and lactate levels in serum and the cerebrospinal fluid, serum amino acid levels, and CSF HVA and 5-HIAA levels were all normal. No brain atrophy was noted in cranial MRI. Myoclonus was markedly reduced after administration of clonazepam. The clinical features and electrophysiological data of our patient are consistent with the clinical diagnosis of familial essential myoclonus and epilepsy/benign adult familial myoclonic epilepsy.     

Brain chimeras for the study of an avian model of genetic epilepsy: structures involved in sound and light-induced seizures

The epileptic homozygotes of the Fayoumi strain of chickens (Fepi) are affected by photogenic reflex epilepsy with complete penetrance. Here we demonstrate that they are equally affected by audiogenic reflex epilepsy induced by intense sound stimulation. All the Fepi display sound-induced seizures from hatching to adulthood consisting of initial 'ictal arousal' and running fits usually followed by generalized clonico-tonic convulsions. A running fit is the preconvulsive motor symptom specifically induced by auditory stimulation while neck myoclonus is the preconvulsive motor symptom specifically induced by photic stimulation. The EEG interictal spikes and spike and waves are suppressed and replaced by a desynchronized trace during the seizures of both kinds. Viable neural chimeras were obtained by graft of embryonic brain vesicles from Fepi donors into normal chick embryos. Transfer of the complete audiogenic and photogenic phenotypes was obtained in chimeras resulting from embryonic substitution of both the prosencephalon and mesencephalon. The substitution of the prosencephalon alone resulted in transfer of interictal paroxysmal EEG activity accompanied by the sound and light-induced desynchronization and 'ictal arousal' with no motor seizures. Chimeras with embryonic substitution of the mesencephalon alone displayed running fits and convulsions induced by sound stimulation but only neck myoclonus following light stimulation. The conclusions are reached that: (i) the Fepi is a model of audiogenic and photogenic reflex epilepsy; (ii) in both types, the seizure initiator and the convulsion generator are localized in the brainstem, although reinforcement from telencephalic visual structures is needed to trigger photogenic generalized convulsions.     

Chaotic components in the high-frequency EEG of rabbit cortex during formation of a conditioned defensive reflex

The chaotic component of the high-frequency EEG of the rabbit cortex was studied during the development of a conditioned defensive reflex to nonrhythmic light stimulation with electric reinforcement applied to the animal's paw. Regular changes in the dynamic parameters of the chaotic component of the high-frequency EEG were demonstrated. Characteristic changes in the asymptotic evaluations of the correlational dimensionality of the attractor of the chaotic component (DCC) of the high-frequency EEG were detected in the cortical regions studied both during the action of the conditioned stimulus and in background conditions before presentation of combinations. These changes affected both the afferent and efferent cortical regions of the conditioned reflex arc, as well as regions not directly addressed by the conditioned or unconditioned stimuli. These results allow the dynamics of changes in the morphofunctional structures of the conditioned reflex to be seen at the cortical level during learning. Significant differences in the early and late stages of conditioned reflex formation were detected.     

Stretch reflex and servo action in a variety of human muscles

1. In the long flexor of the thumb the latency of the stretch reflex and of other manifestations of servo action is some 45 msec, roughly double the latency of a finger jerk. 2. Tendon jerks are feeble or absent in the long flexor of the thumb even in subjects with brisk long-latency stretch reflexes in this muscle. This, and other facts, suggests that the nervous mechanism of the tendon jerk is different from that of the stretch reflex. 3. A muscle that has feeble tendon jerks may show a late component in the response to a tendon tap, with a latency similar to that of the long-latency stretch reflex. 4. On the hypothesis that the excess latency of the stretch reflex over that of a tendon jerk is because the stretch reflex employs a cortical rather than a spinal arc, the excess would be expected to be larger in magnitude for the long flexor of the big toe and smaller for the jaw closing muscles. This is confirmed, 5. An alternative hypothesis that the long latency of stretch reflexes in thumb and toe is because they are excited by slow-conducting afferents is made improbable by the finding that stretch reflexes with an equal or greater excess latency are also found in proximal arm muscles. 6. The long-latency stretch reflex in proximal muscles was seen most distinctly in a healthy subject who happened to have feeble or absent tendon jerks. In ordinary subjects there is often a large, short-latency, presumably spinal component of the stretch reflex in proximal muscles; and short-latency responses to halt and release are also seen, The significance of this spinal latency servo action in proximal muscles remains to be explored. 7. The Discussion argues that the available data on conduction time to and from the cerebral cortex are compatible with the hypothesis that the long-latency component of the stretch reflex uses a transcortical reflex arc, and that none of the experiments described in the present paper are inimical to this view.     

GABA(A)-receptor subtypes: clinical efficacy and selectivity of benzodiazepine site ligands

Corticobasal degeneration (CBD) is a slowly progressive disorder characterized by an asymmetrical akinetic-rigid syndrome, supranuclear ophthalmoplegia, dystonia, often accompanied by involuntary movements, particularly myoclonus, and associated with lateralized cortical signs such as alien limb behavior and apraxia. Computerized tomography demonstrates asymmetrical frontoparietal cortical atrophy in the later stages of the illness. Neuropathological examination reveals neuronal loss, gliosis and swollen achromatic neurons within the frontal and temporal cortices, and the substantia nigra. We discuss here a unique phenomenon not described so far in three patients with clinical features of CBD, one with subsequent autopsy observations. When awake, they all showed a common behavior, their mouth opened constantly and immediately, when a tongue-depresser was approached in front of it by the examiner. In two of them, their mouth also opened when its corner was stroked by a tongue-depressor. They could not control these phenomena at all, even they were asked not to open their mouth. We would like to call these phenomena "forced mouth opening reactions" because they were uncontrollable voluntarily. They may be divided into two groups, i.e. visual and tactile "forced mouth opening reactions". In all the patients the neurological, neuro-imaging and neuropathological data showed that the frontal lobes were damaged. Additionally, they had some frontal lobe release signs such as forced grasping, forced groping, or alien limb sign. We would like to apply the mechanism for these release signs to the "forced mouth opening reactions". Thus, we speculate that the frontal lobe contains a higher motor control mechanism for normal mouth opening movement, and the "forced mouth opening reactions" result from impairment of this control.     

Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation

We studied the effects of low-frequency transcranial magnetic stimulation (TMS) on motor cortex excitability in humans. TMS at 0.1 Hz for 1 hour did not change cortical excitability. Stimulation at 0.9 Hz for 15 minutes (810 pulses), similar to the parameters used to induce long-term depression (LTD) in cortical slice preparations and in vivo animal studies, led to a mean decrease in motor evoked potential (MEP) amplitude of 19.5%. The decrease in cortical excitability lasted for at least 15 minutes after the end of the 0.9 Hz stimulation. The mechanism underlying this decrease in excitability may be similar to LTD. TMS-induced reduction of cortical excitability has potential clinical applications in diseases such as epilepsy and myoclonus. Spread of excitation, which may be a warning sign for seizures, occurred in one subject and was not accompanied by increased MEP amplitude, suggesting that spread of excitation and amplitude changes are different phenomena and also indicating the need for adequate monitoring even with stimulations at low frequencies.     

Clinical presentation and pharmacological therapy in corticobasal degeneration

BACKGROUND: To date, to our knowledge, there is no systematic presentation of treatment outcome in large series of patients clinically diagnosed as having corticobasal degeneration. OBJECTIVE: To evaluate the clinical presentation and treatment outcome of patients clinically diagnosed as having corticobasal degeneration. SUBJECTS: We gathered case patients seen in 8 major movement disorder clinics during the last 5 years who were diagnosed as having corticobasal ganglionic degeneration. METHODS: Using a chart review method, we recorded the clinical presentation, medications used, response to medications, and adverse effects. RESULTS: A total of 147 case patients were reviewed, 7 were autopsy proven. Parkinsonian features were present in all, other movement disorders in 89%, and higher cortical dysfunction in 93%. The most common parkinsonian sign was rigidity (92%), followed by bradykinesia (80%), gait disorder (80%), and tremor (55%). Other movement disorders were dystonia in 71% and myoclonus in 55%. Higher cortical dysfunction included dyspraxia (82%), alien limb (42%), cortical sensory loss (33%), and dementia (25%). Ninety-two percent of the case patients received dopaminergic drugs, which resulted in a beneficial effect for 24%. Parkinsonian signs were the elements improving the most and levodopa was the most effective drug. Benzodiazepines, primarily clonazepam, were administered to 47 case patients, which resulted in improvement of myoclonus in 23% and dystonia in 9%. The most frequent disabling adverse effects of drug trials in these case patients were somnolence (n = 24), gastrointestinal complaints (n = 23), confusion (n = 16), dizziness (n =12), hallucinations (n = 5), and dry mouth (n = 5). CONCLUSIONS: Pharmacological intervention was largely ineffective in the management of corticobasal degeneration, and new treatments are needed for ameliorating the symptoms of this syndrome.     

CETP and exchangeable apoproteins: common features in lipid binding activity

It was evaluated in the spinal cord-transected rats whether the urethrogenital (UG) reflex shows some of the features that are present during ejaculation in intact animals. It was found that the UG reflex was facilitated after its first elicitation: the latency of the reflex was shorter than the previous one and low intensity of stimulation was needed to produce the reflex. In addition, a change in the latency of the reflex was found that was correlated with the number of stimulation trials. The latency change showed a J-shaped curve that is similar to that found for the ejaculation latency in a copulatory series. An inhibition of the reflex appeared after several trials: the reflex could not be elicited after three continuous trials. The reflex could be elicited again if the intensity of stimulation was increased. The UG reflex also showed 'exhaustion': it could not be elicited, even with high intensities of stimulation, after 3 h of rest. All these findings were present when the UG reflex was elicited by applying pressure to the urethra or when it was evoked by the electrical stimulation to the pudendal nerve. According to these findings, it can be concluded that the UG reflex maintains some of the features that are found during ejaculation in intact animals. According to this view, it can be speculated that some of the mechanisms that control ejaculation in intact animals can be localized at a spinal level.     

The use and abuse of topical corticosteroids

An atypical case of "Foix-Chavany syndrome", is described. A definite diagnosis could be achieved through an electromyographic and reflessological investigation (jaw reflex, blink reflex, perioral reflex), when a poor clinical history was not helping towards a definite diagnostic conclusion. It is proposed that the diagnosis of "Foix-Chavany syndrome" should not be limited only to classical "facial diplegia of cortical origin" or to "facio-linguo-pharyngo-laryngo-masseter paralysis of cortico-subcortical origin". Considering the great clinical variability of a syndrome with a common anatomical substrate, it is proposed to use the eponym for all syndromes characterized by: 1) a motor deficit in the cephalic district with relative integrity of motor function of the limbs; 2) a dissociation between loss of voluntary motility and preservation of reflex and automatic motility.     

Bilateral central acetabular fracture dislocations secondary to sustained myoclonus

This case report presents a patient with bilateral central acetabular fracture dislocations secondary to sustained myoclonus treated with delayed bilateral total hip arthroplasty. This is an unusual mechanism of injury, but is similar to other uncontrolled muscular contractions, such as electroconvulsive therapy and seizures. Because of ongoing myoclonus, the patient initially was treated nonoperatively. The patient then successfully had staged bilateral total hip arthroplasty 15 months after injury. This case exemplifies that forceful, uncontrolled muscular contraction can cause bilateral symmetric fracture dislocations. In patients with a history of seizure or myoclonic contracture with subsequent pain or loss of function, radiographs are indicated and skeletal fracture or joint dislocation must be ruled out. Secondary reconstruction can be recommended when the patient is medically stable.