Periodic leg movements in sleep and periodic limb movement disorder: Prevalence, clinical significance and treatment

Objective: To test the hypothesis that periodic limb movements (PLMs) are related to spinal flexor reflexes (FRs), the authors compared the state-dependent changes in FR excitability in 10 patients with restless legs syndrome (RLS) and PLMs with those from matched controls. Background: PLM is a disorder of motor control during sleep, frequently occurring in RLS. Clinically, PLMs resemble spinal FRs. Methods: FRs were obtained by electrically stimulating the medial plantar nerve and recording from antagonist leg and thigh muscles bilaterally. Results: Compared with controls, patients had significantly increased spinal cord excitability, as indicated by lower threshold and greater spatial spread of the FR, which was more prominent during sleep. Multiple late responses were seen during sleep in all patients and in some controls at higher threshold. The most prominent of these responses had a very long duration and a latency range of 250 to 800 msec, and because of its close temporal relationship to the FR stimulus, the authors considered it was a late, high-threshold component of the FR (FR3). The authors also found a similarity between the pattern of muscle recruitment and spatial spread of late components of the FR and those of spontaneous PLMs. Conclusions: The results support the hypothesis that PLMs in RLS and FRs share common spinal mechanisms and suggest that PLMs may result from enhanced spinal cord excitability in RLS patients. Because dopaminergic mechanisms are involved in spinal FR control, the results are consistent with the current view that RLS is a disorder of dopaminergic function.

Periodic limb movements in sleep: state-dependent excitability of the spinal flexor reflex.

IntheLambert-Eaton myasthenic syndrome (LEMS), there isadecreased release ofacetylcholine quanta from thenerve terminal bynerve impulse. Recently, anautoimmune origin ofLEMSwasdocumented bypassive transfer ofits elec- trophysiologic features from mantomousewith IgG. Freeze-frac- ture electron microscopy ofLEMSneuromuscular junctions has revealed apaucity ofpresynaptic membrane active zones. Thus, theactive zones might bethetargets ofthepathogenic autoanti- bodies inLEMS.Totest this assumption, freeze-fracture electron microscopic studies weredone inmice injected with 10mgofIgG daily from each ofthree LEMSpatients andincontrol mice treated with normal human IgGornoIgG. IgGfrom patients 1and2im- paired neuromuscular transmission inmice, butIgGfrompatient 3failed todoso.After 52-69 days oftreatment, diaphragm or anterior tibial muscles wereremoved andcoded. Paired muscles fromcontrol miceandmicereceiving LEMSIgGwerestudied "blindly." Satisfactory freeze-fracture replicas of185presynaptic membrane P-faces wereanalyzed bystereometric methods. Inmice treated with LEMSIgGthat waspathogenic byelectrophysiologic criteria, there wasaselective depletion ofactive zones andactive- zone particles butnotofother membrane particles andthere was aconcomitant increase oflarge membrane particles aggregated into clusters. These findings provide additional evidence that the active zones facilitate quantal transmitter release bynerve im- pulse, lendiurther support totheassumption that theactive-zone particles areCa2+ channels, andestablish mediation ofthemem- brane lesions inLEMSbyIgG. Theclinical andelectrophysiologic

http://www.pnas.org/content/80/24/7636.full.pdf

Passive transfer ofLambert-Eaton myasthenic syndrome withIgG frommantomousedepletes thepresynaptic membrane active zones

Background: Although movement disorders that occur following a stroke have long been recognised in short series of patients, their frequency and clinical and imaging features have not been reported in large series of patients with stroke. 

Methods: We reviewed consecutive patients with involuntary abnormal movements (IAMs) following a stroke who were included in the Eugenio Espejo Hospital Stroke Registry and they were followed up for at least one year after the onset of the IAM. We determined the clinical features, topographical correlations, and pathophysiological implications of the IAMs. 

Results: Of 1500 patients with stroke 56 developed movement disorders up to one year after the stroke. Patients with chorea were older and the patients with dystonia were younger than the patients with other IAMs. In patients with isolated vascular lesions without IAMs, surface lesions prevailed but patients with deep vascular lesions showed a higher probability of developing abnormal movements. One year after onset of the IAMs, 12 patients (21.4%) completely improved their abnormal movements, 38 patients (67.8%) partially improved, four did not improve (7.1%), and two patients with chorea died. In the nested case–control analysis, the patients with IAMs displayed a higher frequency of deep lesions (63% v 33%; OR 3.38, 95% CI 1.64 to 6.99, p<0.001). Patients with deep haemorrhagic lesions showed a higher probability of developing IAMs (OR 4.8, 95% CI 0.8 to 36.6). 

Conclusions: Chorea is the commonest movement disorder following stroke and appears in older patients. Involuntary movements tend to persist despite the functional recovery of motor deficit. Deep vascular lesions are more frequent in patients with movement disorders.

https://jnnp.bmj.com/content/jnnp/75/11/1568.full.pdf

Post-stroke movement disorders: report of 56 patients

flow response to vibration in patients with blepharospasm. Neurology 1999;52:291–297. 38. Wichmann T, DeLong M. Functional and pathophysiological models of basal ganglia. Curr Opin Neurobiol 1996;6:751–758. 39. Eidelberg D, Moeller JR, Ishikawa T, et al. The metabolic topography of idiopathic torsion dystonia. Brain 1995;118: 1473–1484. 40. Dum RP, Strick PL. Premotor areas: nodal points for parallel efferent systems involved in the central control of movements. In: Humphrey DR, Freund HJ, eds. Motor control: concepts and issues. New York: Wiley, 1991:383—397. 41. Nakashima K, Rothwell JC, Thompson PD, et al. The blink reflex in patients with idiopathic torsion dystonia. Arch Neurol 1990;47:413—416. 42. Pauletti G, Berardelli A, Cruccu G, Agostino R, Manfredi M. Blink reflex and the masseter inhibitory reflex in patients with dystonia. Mov Disord 1993;8:495—500.

Functional MRI cerebral activation and deactivation during finger movement [7] (multiple letters)

Misdiagnosis in Fabry disease.

Twenty-six patients with syringomyelia were studied with polysomnography to determine the frequency of periodic limb movements (PLM) and its relationship to the presence of a Chiari anomaly, the severity of corticospinal tract involvement, and localization of the syrinx. Sixteen patients showed PLM in stages I and II of non-REM sleep and three PLM also while awake. There were no statistically significant differences in overall disability, corticospinal signs, presence of an associated Chiari anomaly, and disease duration between patients with and without PLM, although there was a trend for patients with PLM to have more severe disease. There was preservation of the lumbosacral enlargement of the spinal cord by the syrinx in all patients with PLM. The latency delay between lower and upper limb muscles was suggestive of conduction along propriospinal pathways. Syringomyelia may lead to an abnormal state of spinal hyperexcitability favoring the appearance of PLM. Detailed magnetic resonance image studies of patients with different localizations of the syrinx cavities may help to determine which tracts are involved in the production of PLM.

Periodic limb movements in syringomyelia and syringobulbia.

In order to search for early changes induced by the application of human immunoglobulin G (IgG) on motor nerve terminals, IgG from patients with amyotrophic lateral sclerosis (ALS) and control subjects was injected subcutaneously into the levator auris muscle of mice. A week or a month after the last injection, endplate potentials were recorded. No changes in quantal content of transmitter release were observed. In control and ALS IgG-treated muscles, neurotransmitter release remained sensitive to P/Q-type and insensitive to N-type voltage-sensitive calcium channel (VSCC) blockers as in untreated muscles. In contrast, IgG from 5 of 8 different ALS patients induced a significant reduction in quantal content of the evoked response after incubation with nitrendipine, indicating that a novel sensitivity to this calcium channel blocker appears in these motor nerve terminals. These results indicate that ALS IgG induces plastic changes at nerve terminals. The expression of transmitter release coupled to L-type VSCC indicate that ALS IgGs are capable of inducing plastic changes at the nerve terminals that may participate in the process leading to neuronal death.

Amyotrophic lateral sclerosis IgG-treated neuromuscular junctions develop sensitivity to L-type calcium channel blocker.

centration-of binding sites was reduced to 0.32 fmoVmg of wet tissue (figure, A). All electrophysiologic experiments were carried out in urethane-anesthetized animals so no clinical or electrographic seizures occurred in lithium-pilocarpine-treated or only-lithiumtreated animals. The paired-pulse inhibition versus interpulse interval curves are shown in the figure, B. The naive group differed from animals treated with lithium and pilocarpine; the lithium-treated group also differed from the lithium-pilocarpinetreated group. There was no significant difference between naive and lithium-treated groups. Discussion. There a re two primary conclusions of this study: (1) SE induced by lithium and pilocarpine results in the loss of high-affinity GABA binding site in the ra t forebrain, and (2) injection of a combination of lithium and pilocarpine results in reduction of GABA-mediated inhibition in the CA1 region of the hippocampus. We had previously demonstrated loss of GABA-mediated inhibition in the CA1 region of the hippocampus in other models of SE' similar to that observed in this study. The Kd values for muscimol binding in naive rat forebrain in our study was comparable with tha t reported by other workers4 and us' in t h e past , but there a r e no previous reports of the effect of SE on the GABA, receptors. Our study demonstrates that the number of GABA, receptors available for binding GABA are reduced during partial SE, suggesting that the mechanism for diminished GABA-mediated inhibition during SE is a reduction in the number of available GABA receptors. The biochemical basis of this loss of GABA receptor can be speculated. A posttranslational modification of the GABA, receptor protein may occur during SE to reduce the number of receptors available to bind GABA. Electrophysiologically, phosphorylation factors are needed for continued GABA receptor function.6 Loss of GABA receptors during prolonged SE is of significance, since several therapeutic measures are aimed at activating the GABA receptor. Benzodiazepines, phenobarbital, and pentobarbital bind to various sites in the GABA receptor complex and change its gating proper tie^.^ A diminution in the number of GABA receptors after prolonged SE would render these drugs less efficacious and would also explain why prolonged human SE is more difficult to treat than early SE. Since prolonged SE is associated with higher morbidity and mortality, these findings emphasize the need for emergent treatment of SE upon its recognition.

Ana Pardal

Papers

Misdiagnosis in Fabry disease.

Periodic limb movements in syringomyelia and syringobulbia.

Amyotrophic lateral sclerosis IgG-treated neuromuscular junctions develop sensitivity to L-type calcium channel blocker.

Sural neuropathy due to external pressure: Report of three cases

Focal myoclonus associated with posterior thalamic hematoma