Characterisation of the relationships between rhythmic masticatory muscle activities and limb movements in patients with sleep bruxism.

BACKGROUND: Most rhythmic masticatory muscle activities (RMMAs) have been shown to be accompanied with limb movements (LMs) in sleep bruxism (SB) patients during sleep. OBJECTIVES: To compare the relationships between RMMAs and LMs in SB patients and normal subjects. METHODS: Polysomnographic recordings were performed on eight SB patients and nine normal subjects and the frequencies and durations of RMMAs as well as LMs were determined. Linear regression and correlation analysis were performed to study the relationship between durations of RMMAs and LMs when RMMAs occurred with LMs. RESULTS: Most LMs in SB patients, but not in normal subjects, were accompanied with RMMAs. RMMAs in SB patients were more likely to be isolated, phasic or mixed, while RMMAs in normal subjects were more likely to be tonic. The frequencies of LMs, isolated RMMAs and RMMAs accompanied with LMs in SB patients were significantly higher than those in normal subjects. Furthermore, linear regression and correlation analysis showed that duration of RMMAs was significantly associated with that of LMs when RMMAs occurred with LMs. The duration of RMMAs, when accompanied with LMs, in SB patients was significantly longer than that in normal subjects. CONCLUSIONS: Close relationships between LMs and RMMAs exist in SB patients and normal subjects, and SB episodes may be part of cortical arousal responses and the increased cortical activities associated with SB episodes may not just be localised to the central nervous system (CNS) that controls jaw movements but may also include other parts of CNS that controls LMs.

Characterizing the Motor Skills in Children with Specific Language Impairment.

BACKGROUND/AIMS: Specific language impairment (SLI) is characterized by deficits in language ability. However, studies have also reported motor impairments in SLI. It has been proposed that the language and motor impairments in SLI share common origins. This exploratory study compared the gross, fine, oral, and speech motor skills of children with SLI and children with typical development (TD) to determine whether children with SLI would exhibit difficulties on particular motor tasks and to inform us about the underlying cognitive deficits in SLI. METHODS: A total of 13 children with SLI (aged 8-12 years) and 14 age-matched children with TD were administered the Movement Assessment Battery for Children - Second Edition and the Verbal Motor Production Assessment for Children to examine gross and fine motor skills and oral and speech motor skills, respectively. RESULTS: Children with SLI scored significantly lower on gross, fine, and speech motor tasks relative to children with TD. In particular, children with SLI found movements organized into sequences and movement modifications challenging. On oral motor tasks, however, children with SLI were comparable to children with TD. CONCLUSION: Impairment of the motor sequencing and adaptation processes may explain the performance of children with SLI on these tasks, which may be suggestive of a procedural memory deficit in SLI.

Richieri-Costa-Pereira syndrome: Expanding its phenotypic and genotypic spectrum.

Richieri-Costa-Pereira syndrome is a rare autosomal recessive acrofacial dysostosis that has been mainly described in Brazilian individuals. The cardinal features include Robin sequence, cleft mandible, laryngeal anomalies and limb defects. A biallelic expansion of a complex repeated motif in the 5' untranslated region of EIF4A3 has been shown to cause this syndrome, commonly with 15 or 16 repeats. The only patient with mild clinical findings harbored a 14-repeat expansion in 1 allele and a point mutation in the other allele. This proband is described here in more details, as well as is his affected sister, and 5 new individuals with Richieri-Costa-Pereira syndrome, including a patient from England, of African ancestry. This study has expanded the phenotype in this syndrome by the observation of microcephaly, better characterization of skeletal abnormalities, less severe phenotype with only mild facial dysmorphisms and limb anomalies, as well as the absence of cleft mandible, which is a hallmark of the syndrome. Although the most frequent mutation in this study was the recurrent 16-repeat expansion in EIF4A3, there was an overrepresentation of the 14-repeat expansion, with mild phenotypic expression, thus suggesting that the number of these motifs could play a role in phenotypic delineation.

A 24-month evaluation of a percutaneous osseointegrated limb-skin interface in an ovine amputation model.

Percutaneous osseointegrated (OI) prostheses directly connect an artificial limb to the residual appendicular skeleton via a permanently implanted endoprosthesis with a bridging connector that protrudes through the skin. The resulting stoma produces unique medical and biological challenges. Previously, a study using a large animal amputation model indicated that infection could be largely prevented, for at least a 12-month period, but the terminal epithelium continued to downgrow. The current study was undertaken to test the longer-term efficacy of this implant construct to maintain a stable skin-implant interface for 24 months. Using the previously successful amputation and implantation surgical procedure, a total of eight sheep were fitted with a percutaneous OI prosthesis. Two animals were removed from the study due to early complications. Of the remaining six sheep, one (16.7%) became infected at 15-months post-implantation and five remained infection-free for the intended 24 months. The histological data of the remaining animals further confirmed the grossly observable epithelial downgrowth. Albeit a receding interface, it was clear that all animals that survived to the end of the study had residual fibrous soft-tissue ingrowth into, and debris within, the exposed titanium porous-coated surface. Overall, the data demonstrated that the porous coated subdermal barrier offered initial protection against infection. However, the fibrous skin attachment was continuously lysed over time by the down-growing epithelium.

Are patients with limb and head tremor a clinically distinct subtype of essential tremor?

BACKGROUND: Essential tremor (ET) is the most common tremor disorder in adults. In addition to upper limbs, the tremor in ET may also involve head, jaw, voice, tongue, and trunk. Though head tremor (HT) is commonly present in patients with ET, large comparative studies of ET patients with HT (HT+) and without HT (HT-) are few. METHODS: To determine whether ET with HT is a distinct clinical subtype by comparing ET patients with and without HT, a chart review of 234 consecutive patients with ET attending the neurology clinics of the National Institute of Mental Health and Neurosciences, India, was done. A movement disorder specialist confirmed the diagnosis of ET in all patients using the National Institutes of Health collaborative genetic criteria. RESULTS: HT was present in 44.4% of the patients. Comparison between HT+ and HT- showed that the HT+ group patients: (1) were older, (2) had later onset of tremor, (3) had unimodal distribution of age at onset with a single peak in the fifth decade, (4) had more frequent voice tremor, and (5) were more likely to have mild cervical dystonia. HT was part of presenting symptoms in nearly two thirds of the ET patients and in the rest it was detected during clinical examination. CONCLUSIONS: Several demographic and clinical variables suggest that ET patients with HT have a distinct clinical phenotype.

Time-linked concurrence of sleep bruxism, periodic limb movements, and EEG arousals in sleep bruxers and healthy controls.

OBJECTIVE: Sleep bruxism (SB) and periodic limb movements during sleep (PLMS) may have a common underlying neurophysiologic mechanism, especially in relation to the occurrence of sleep-related electroencephalographic (EEG) arousals. To test this hypothesis, three research questions were assessed. First, it was assessed whether PLMS events occur more frequently in SB patients than in individuals without SB. Second, the question was put forward whether the combined presence of SB and PLMS events is more common than that of isolated SB or PLMS events in a group of SB patients. Third, as to further unravel the possible role of EEG arousals in the underlying neurophysiologic mechanism of SB and PLMS, it was assessed in a group of SB patients whether combined SB/PLMS events with associated EEG arousals are more common than those without associated EEG arousals. Positive answers to these questions could suggest a common neurophysiological basis for both movement disorders. MATERIALS AND METHODS: Seventeen SB patients and 11 healthy controls were polysomnographically studied. SB, PLMS, and EEG arousals were scored. An association was noted when the occurrence was within a 3-s association zone. RESULTS: The PLMS index was higher in SB patients than in healthy controls (P < 0.001). Within the group of SB patients, the combined SB/PLMS index was higher than the isolated SB index (P < 0.001) and the isolated PLMS index (P = 0.018). Similarly, the combined SB/PLMS index with EEG arousal was higher than the combined SB/PLMS index without EEG arousal in SB patients (P < 0.001). CONCLUSION: The results of this study indicate that SB, PLMS, and EEG arousals commonly concur during sleep in a time-linked manner. CLINICAL RELEVANCE: SB and PLMS probably have a common underlying neurophysiological mechanism.

Liposome-based vascular endothelial growth factor-165 transfection with skeletal myoblast for treatment of ischaemic limb disease.

The study aims to use cholesterol (Chol) + DOTAP liposome (CD liposome) based human vascular endothelial growth factor-165 (VEGF(165)) gene transfer into skeletal myoblasts (SkMs) for treatment of acute hind limb ischaemia in a rabbit model. The feasibility and efficacy of CD liposome mediated gene transfer with rabbit SkMs were characterized using plasmid carrying enhanced green fluorescent protein (pEGFP) and assessed by flow cytometry. After optimization, SkMs were transfected with CD lipoplexes carrying plasmid-VEGF(165) (CD-pVEGF(165)) and transplanted into rabbit ischaemic limb. Animals were randomized to receive intramuscular injection of Medium199 (M199; group 1), non-transfected SkM (group 2) or CD-pVEGF(165) transfected SkM (group 3). Flow cytometry revealed that up to 16% rabbit SkMs were successfully transfected with pEGFP. Based on the optimized transfection condition, transfected rabbit SkM expressed VEGF(165) up to day 18 with peak at day 2. SkMs were observed in all cell-transplanted groups, as visualized with 6-diamidino-2-phenylindole and bromodeoxyuridine. Angiographic blood vessel score revealed increased collateral vessel development in group 3 (39.7 +/- 2.0) compared with group 2 (21.6 +/- 1.1%, P < 0.001) and group 1 (16.9 +/- 1.1%, P < 0.001). Immunostaining for CD31 showed significantly increased capillary density in group 3 (14.88 +/- 0.9) compared with group 2 (8.5 +/- 0.49, P < 0.001) and group 1 (5.69 +/- 0.3, P < 0.001). Improved blood flow (ml/min./g) was achieved in animal group 3 (0.173 +/- 0.04) as compared with animal group 2 (0.122 +/- 0.016; P= 0.047) and group 1 (0.062 +/- 0.012; P < 0.001). In conclusion, CD liposome mediated VEGF(165) gene transfer with SkMs effectively induced neovascularization in the ischaemic hind limb and may serve as a safe and new therapeutic modality for the repair of acute ischaemic limb disease.

Companion of oral movements with limb movements in patients with sleep bruxism: preliminary findings.

BACKGROUND: Sleep bruxism (SB) patients show a higher incidence of leg movements than normal subjects. STUDY OBJECTIVES: The study aimed to characterize SB episodes and their relationships with limb movements (LMs). MATERIALS AND METHODS: Polysomnographic (PSG) recordings were performed on eight SB patients. The intervals between the onsets of adjacent SB episodes and LMs were determined and linear correlation analyses were used to estimate the relationship between the SB index and SB episodes in clusters. The Pearson χ2 and partitions of χ2 tests were used to analyze the differences in incidence of SB episodes and clusters in different sleep stages. RESULTS: A majority of SB episodes (85.05%) were found to be accompanied by LMs and among them, 70.52% SB episodes occurred with movements of both upper and lower limbs and most of LMs (70.54%) occurred before the onset of SB episodes. Most of SB episodes especially those accompanied by LMs occurred with microarousals or awakenings. Linear correlation analysis showed a positive correlation between the SB index and SB episodes in clusters (r2 = 0.7027, P = 0.0093). In addition, the percentage of SB episodes in clusters accompanied by LMs was significantly smaller than that of SB episodes not accompanied by LMs (χ2 test, P < 0.001) and the percentage of SB episodes in clusters during REM sleep was significantly smaller than that during NREM sleep (χ2 test, P < 0.0001). CONCLUSIONS: Most SB episodes might not be isolated events, but rather a part of a series of movements second to changes in arousal level.

Peripheral Stent Thrombosis Leading to Acute Limb Ischemia and Major Amputation: Incidence and Risk Factors in the Aortoiliac and Femoropopliteal Arteries.

PURPOSE: To report the real-world incidence and risk factors of stent thrombosis in the aortoiliac and femoropopliteal arteries in case of bare nitinol stent (BNS) or covered nitinol stent (CNS) placement from a single-centre retrospective audit. MATERIALS AND METHODS: Medical records of consecutive patients treated with peripheral stent placement for claudication or critical limb ischemia were audited for definite stent thrombosis defined as imaging confirmed stent thrombosis that presented as acute limb-threatening ischemia. Cases were stratified between aortoiliac and femoropopliteal anatomy. Cox regression analysis was employed to adjust for baseline clinical and procedural confounders and identify predictors of stent thrombosis and major limb loss. RESULTS: 256 patients (n = 277 limbs) were analysed over a 5-year period (2009-2014) including 117 aortoiliac stents (34 CNS; 12.8 ± 5.0 cm and 83 BNS; 7.8 ± 4.0 cm) and 160 femoropopliteal ones (60 CNS; 21.1 ± 11.0 cm and 100 BNS; 17.5 ± 11.9 cm). Median follow-up was 1 year. Overall stent thrombosis rate was 6.1% (17/277) after a median of 43 days (range 2-192 days) and affected almost exclusively the femoropopliteal segment (12/60 in the CNS cohort vs. 4/100 in the BNS; p = 0.001). Annualized stent thrombosis rates (per 100 person-years) were 12.5% in case of CNS and 1.4% in case of BNS (HR 6.3, 95% CI 2.4-17.9; p = 0.0002). Corresponding major amputations rates were 8.7 and 2.5%, respectively (HR 4.5, 95% CI 2.7-27.9; p = 0.0006). On multivariable analysis, critical leg ischemia and CNS placement were the only predictors of stent thrombosis. Diabetes, critical leg ischemia, femoropopliteal anatomy, long stents and CNS were independent predictors of major amputations. CONCLUSIONS: Placement of long femoropopliteal covered nitinol stents is associated with an increased incidence of acute stent thrombosis and ensuing major amputation. Risks are significantly lower in the aortoiliac vessels and with use of bare nitinol stents.

Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury.

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L(E397K), which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L(E397K) mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K). Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L(E397K) mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K) mice provide a model for determining the efficacy of novel therapies.

A comparison of two iatrogenic dyskinesias.

The authors compared the regions of motor involvement in levodopa-induced dyskinesia and neuroleptic-induced tardive dyskinesia. Significantly more patients with tardive dyskinesia than parkinsonian patients with levodopa-induced dyskinesia had lip and tongue movements. Patients with tardive dyskinesia had significantly higher mean AIMS scores in the orofacial region than parkinsonian patients with levodopa-induced dyskinesia. More patients with levodopa-induced dyskinesia than those with tardive dyskinesia demonstrated hyperkinesia in the lower extremities. Limb and truncal movements in levodopa-induced dyskinesia were worse in patients with more severe parkinsonism and correlated positively with the length of Parkinson's disease. These findings suggest that these dyskinesias may involve different pathophysiological mechanisms.

Periodic, aperiodic, and rhythmic motor disorders of sleep.

A variety of spontaneous movements can occur during sleep. Most are unassociated with identifiable CNS pathology and are presumed to be caused by sleep-related modulation of CNS motor control systems. Individual dyskinesias occurring during sleep can be characterized not only by their frequency, rhythmicity, and anatomic predilections, but also by the stage of sleep in which they characteristically occur. Wake-pattern movement disorders improve during sleep but, contrary to common belief, they do not entirely disappear. Instead, these disorders reemerge in attenuated form, often during nonrapid eye movement sleep. The identification and proper characterization of the various sleep-related dyskinesias are greatly aided by careful polysomnographic study.

Directed axonal growth towards axolotl limb blastemas in vitro.

Limb amputation in urodele amphibia is followed by formation of a blastema, which subsequently develops into a complete limb with normal pattern of innervation. In this study, we investigated the effects of axolotl limb blastemas on axonal growth in gels of collagen and extracellular matrix (matrigel). When peripheral nerves with attached dorsal root ganglia were cultured in collagen gels together with blastemas, axonal outgrowth was markedly increased compared with control preparations. Blastemas contain fibroblast growth factors, and may also contain neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, neurotrophin 3, neurotrophin 4, glial cell line-derived neurotrophic factor and hepatocyte growth factor/scatter factor, since these factors are expressed in developing limbs in other vertebrates. In collagen gels the neurotrophins and glial cell line-derived neurotrophic factor stimulated axonal growth, but outgrowing axons were shorter than in co-cultures with blastemas. The tyrosine kinase inhibitor K252a blocked the stimulatory effects of the neurotrophins on axonal growth but had relatively little effect on axonal growth in co-cultures with blastemas. In experiments in which peripheral nerves, with attached dorsal root ganglia, were cultured in matrigel, axons grew towards blastemas over distances of about 1mm. Directed axonal growth even occurred in these co-cultures after addition of high concentrations of all the above neurotrophic factors, suggesting that blastemas may release a different factor which stimulates axonal growth. The results indicate that during early stages of limb regeneration in amphibia, factor(s) are released which are capable of attracting the growth of peripheral nerves and may play an important role in the development of innervation of regenerated limbs. The identity of the factor(s) remains to be determined.

Rolandic arteriovenous malformations: improvement in limb function by IBC embolization.

Three patients with arteriovenous malformations in the rolandic region and significant limb deficit showed virtually complete functional recovery after awake operative embolization of most of the malformations using isobutyl-2 cyanoacrylate. Two of these patients, with functionally useless hands, had sustained the deficits months earlier as the result of a specific brain-damaging event: one as a result of surgery and the other as a result of a hemorrhage. Both of these showed significant return of function during the awake operative embolization procedure. The other patient had had progressive leg weakness over a 2 year period. The theory of steal phenomenon as an explanation for progressive neurologic deficits in association with large arteriovenous malformations must be extended to explain apparently stable deficits after some brain trauma (surgery or hemorrhage). These results suggest that some patients with arteriovenous malformations and without clinical deficits who are near a critical level of "near ischemia" may be thrown out of balance by an acute interceding event.

Repair of segmental load-bearing bone defect by autologous mesenchymal stem cells and plasma-derived fibrin impregnated ceramic block results in early recovery of limb function.

Calcium phosphate-based bone substitutes have not been used to repair load-bearing bone defects due to their weak mechanical property. In this study, we reevaluated the functional outcomes of combining ceramic block with osteogenic-induced mesenchymal stem cells and platelet-rich plasma (TEB) to repair critical-sized segmental tibial defect. Comparisons were made with fresh marrow-impregnated ceramic block (MIC) and partially demineralized allogeneic bone block (ALLO). Six New Zealand White female rabbits were used in each study group and three rabbits with no implants were used as negative controls. By Day 90, 4/6 rabbits in TEB group and 2/6 in ALLO and MIC groups resumed normal gait pattern. Union was achieved significantly faster in TEB group with a radiological score of 4.50 ± 0.78 versus ALLO (1.06 ± 0.32), MIC (1.28 ± 0.24), and negative controls (0). Histologically, TEB group scored the highest percentage of new bone (82% ± 5.1%) compared to ALLO (5% ± 2.5%) and MIC (26% ± 5.2%). Biomechanically, TEB-treated tibiae achieved the highest compressive strength (43.50 ± 12.72 MPa) compared to those treated with ALLO (15.15 ± 3.57 MPa) and MIC (23.28 ± 6.14 MPa). In conclusion, TEB can repair critical-sized segmental load-bearing bone defects and restore limb function.

Feasibility and dose discovery analysis of zoledronic acid with concurrent chemotherapy in the treatment of newly diagnosed metastatic osteosarcoma: a report from the Children's Oncology Group.

AIM: Patients with metastatic osteosarcoma (OS) have a poor outcome with conventional therapies. Zoledronic acid (ZA) is a third-generation bisphosphonate that reduces skeletal-related events in many adult cancers, and pre-clinical data suggest a possible benefit in OS. This study assessed the maximum tolerated dose (MTD) and the feasibility of ZA when combined with chemotherapy in patients with metastatic OS. PATIENTS AND METHODS: Patients with a histological diagnosis of OS were eligible if they were <40 years of age, had initially metastatic disease and met organ function requirements. Treatment combined surgery and a conventional chemotherapy regimen. ZA was given concurrent with chemotherapy for a total of eight doses over 36 weeks. Three dose levels of ZA were tested: 1.2 mg/m(2) [max 2 mg], 2.3 mg/m(2) [max 4 mg] and 3.5 mg/m(2) [max 6 mg]. The MTD was determined during induction. Six patients were to be treated at each dose level, with an additional six patients treated with the MTD to help assess post-induction feasibility. RESULTS: Twenty-four patients (median age 13.5 years [range, 7-22]; 16 females) were treated. Five patients experienced dose-limiting toxicities (DLTs) during induction, including three patients treated with 3.5 mg/m(2). DLTs included hypophosphatemia, hypokalemia, hyponatremia, mucositis, limb pain and limb oedema. There were no reports of excessive renal toxicity or osteonecrosis of the jaw. The MTD was defined as 2.3 mg/m(2) (max 4 mg). CONCLUSIONS: ZA can be safely combined with conventional chemotherapy with an MTD of 2.3 mg/m(2) (max 4 mg) for patients with metastatic osteosarcoma.

Erythromelalgia presenting with premature exfoliation of primary teeth: a diagnostic dilemma.

Erythromelalgia is an extremely rare neurovascular disorder, characterized by symptoms of red, hot, and painful extremities. There is considerable confusion regarding the etiology and pathogenesis of this condition, and the diagnosis is essentially a clinical one. This condition may occur in isolation or in association with other myeloproliferative disorders. Unfortunately, no therapy is effective consistently in managing the symptoms, although early diagnosis can aid in psychological counseling and minimizing the frequency and severity of the attacks. The purpose of this report was to describe the case of a child presenting with premature loss of primary teeth and the difficulties in determining the final diagnosis of erythromelalgia, which responded positively to low-grade aspirin therapy.

Unusual focal dyskinesias.

This chapter reviews focal dyskinesias that affect a restricted region of the body in isolation. Focal dyskinesias often affect body parts not commonly involved in isolation by movement disorders and are not readily classified into one of the major categories of movement disorders or peripheral nerve excitability syndromes. The clinical features and phenomenology of these "unusual focal dyskinesias" are discussed according to the region affected (ear, lip, chin, jaw, tongue, abdomen, and diaphragm (belly dancer's dyskinesias), back, scapula, and limbs). The phenomenology and origin of the unusual focal dyskinesias remain the subject of debate. Most are characterized by slow semirhythmic jerky movements at variable (usually slow) frequencies superimposed on sustained postures, consistent with dystonic movements. However, the body parts affected and pattern of occurrence (in repose rather than during action) are different to those usually seen in primary dystonia. Many of the unusual focal dyskinesias are associated with trauma and pain to the affected region, prompting the suggestion that the movements follow central sensorimotor reorganization occurring spontaneously or secondary to changes in the peripheral nervous system. In other cases, inconsistent signs and spontaneous recovery suggest a psychogenic origin.