Purpose
To investigate the safety, efficacy and effectiveness of botulinum toxin type-B (BTX-B) injections into the parotid glands to reduce drooling in Parkinson’s disease (PD) subjects.
Methods
A ...double-blind, randomised, placebo-controlled study enrolled 36 advanced phase PD subjects who complained of disabling drooling. Patients received either 4000U BTX-B or placebo. Anatomically guided injections were performed. Outcome measures were chosen to assess both the subjective feeling of improvement (i. e. the Drooling Severity and Frequency Scale, DSFS, visuo-analogic ratings of familial distress, VAS-FD, and social distress, VAS-SD) and objective saliva reduction (saliva production over five minutes was checked by weighing dental rolls). The Global Impression Score (GIS) was also applied, rating improvement from 0 to 3.
Results
One month after injections, BTX-B patients showed a meaningful improvement in almost all subjective outcomes. Two-way analysis of variance gave a significant time × treatment effect, F-value being 52.5 (p < 0.0001) for DS-FS, 23.2 (p < 0.0001) for VAS-FD, 29 (p < 0.0001) for VAS-SD, and 28.9 (p < 0.0001) for UPDRSADL drooling item score. All BTX-B subjects declared sialorrhea reduction of any kind (moderate for 44.4 % cases, and dramatic for 33.3 % subjects), at variance with 61.1 % controls who denied any benefit from treatment. (Chi-square = 22.9; p < 0.0001). When present, benefits lasted on average 19.2 ± 6.3 weeks in the BTX-B group compared to 6.7 ± 1.4 weeks in controls (T-value: 26.4; p < 0.0001).
Conclusions
BTXB represents a safe and efficacious tool for the management of PDrelated drooling, ensuring a longlasting waning of this disabling symptom.
Background: Patients with hyperhidrosis, a disorder characterized by increased sweat production, experience substantial functional and emotional problems. Botulinum toxin type A (BTX-A) has been ...shown to be useful in the treatment of hyperhidrosis; however, few studies have considered the effects of treatment on patients' quality of life (QOL).
Objectives: The objectives of this study were to assess QOL in patients with focal hyperhidrosis; to investigate whether the impairment in QOL in these patients is related to the type of hyperhidrosis or the number of sites involved; and to compare the changes in QOL and the response to BTX-A treatment in patients with axillary and palmar hyperhidrosis.
Methods: Patients with focal primary hyperhidrosis of the axillae, palms, and soles who had experienced decreased QOL and whose condition had not responded to conventional topical and physical therapies were included in this open-label study. Patients completed a self-administered Dermatology Life Quality Index (DLQI) questionnaire before and 2 weeks after treatment with BTX-A.
Results: All 41 patients had experienced a decrease in QOL as measured by the DLQI. The impairement in QOL was not dependent on the number or types of sites involved. Treatment with BTX-A led to improvement in QOL in all patients, with the median DLQI score decreasing (ie, improving) significantly from pretreatment level (
P < 0.001). The improvement in QOL and response to treatment were similar in patients with axillary and palmar hyperhidrosis.
Conclusions: Further studies with a longer follow-up period are needed to assess the long-term effects of BTX-A; however, preliminary data from the present study suggest that BTX-A improves QOL in patients with focal hyperhidrosis, independent of the presenting clinical picture.
To evaluate the efficacy of a combined treatment for spastic foot using selective injections of botulinum toxin (BTA) into the tibialis posterior muscle followed by ankle taping, and to compare it ...with current BTA treatment procedure.
Single-blind randomized control trial. Three-month follow-up after treatment.
Neurorehabilitation clinic.
Eighteen outpatients with equinovarus foot due to severe spasticity after stroke.
(1) Injection of 190 to 320 BTA U into several calf muscles (group A); (2) injection of 100 BTA U into the tibialis posterior muscle, followed by ankle-foot taping (group B).
Ankle range of motion (ROM), Ashworth scale, gait velocity, and step length.
Average Ashworth scores decreased 1 point in both groups, but the benefit appeared of shorter duration in group B. Changes in both foot position at rest and passive ankle ROM were observed in all patients, without treatment-related differences, except for gain in passive dorsiflexion that appeared higher in group A. Gait velocity and step length showed similar increases in both groups.
The combination of selective injections of low BTA doses with ankle-foot taping is as effective as the injection of the current doses for the reduction of foot inversion with positive effects on gait parameters.
The role of hypertension in the late onset of hemifacial spasm (HFS) is evaluated in a family, spanning four generations. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) ...revealed a variable anatomical relationship between nervous and vascular structures in the symptomatic cerebello-pontine angle. In one case, showing neurovascular conflict (NVC), microvascular surgical decompression was followed by clinical resolution of HFS. Neuroimaging suggesting NVC was found in all symptomatic patients of the last two generations and in three younger subjects not affected by HFS. As a determinant for the late development of clinical expression is reviewed the role of arterial hypertension, detected few years before HFS appearing in all symptomatic subjects. The distribution of NVC in several members of the same family suggests a genetic susceptibility towards vascular anomaly.
Although the botulinum toxin A (BTX-A) treatment has proved effective in spasticity management, no information is available with regard to the effects of repeated injections over time.
To evaluate ...the effects of BTX-A on moderate or severe upper limb spasticity, an exploratory investigation was performed on 28 stroke patients treated for 2 yr or longer and observed for 3 yr. Every 3 to 5 mo, each patient received BTX-A injections in upper limb muscles. The assessment, performed before and 1 mo after each injection for a median of 28 mo, included technical and functional objectives and the burden of care. The former were evaluated by using the modified Ashworth Scale for spasticity and the goniometric measurement of rest position and range of motion; functional objectives were evaluated by means of the Frenchay Arm Test and a patient/caregiver goals assessment scale.
BTX-A treatment was followed by an improvement in all technical outcome measures. Motor dexterity scores improved in only 8 of 28 patients, vs. daily living activities, which increased in all subjects. Although the average dosage injected per session did not change, intervals between injections became longer. No relationship between either spasticity onset or residual motoricity and response to treatment could be found.
This investigation is relevant clinically because repeated BTX-A injections show unchanging effectiveness in the management of focal spasticity after stroke.
The wide application of embolization in the treatment of aneurysms has created the need for an intraprocedural means to anticipate a poor outcome by monitoring hemodynamic changes in the brain.
...Transcranial Doppler sonography was used to monitor flow velocity in the middle cerebral artery (MCA) in 23 patients undergoing embolization with Guglielmi detachable coils (GDCs) of either incidental or symptomatic intracranial aneurysms. Sonographic values were recorded from the ipsilateral MCA at the beginning, middle, and end of the interventional procedure and 24 hours afterward.
No complications occurred in 15 patients. In these cases, sonography showed an average decrease in MCA flow velocity of 2.7% after GDC application, returning to baseline at the end of treatment and then increasing by about 17% 24 hours later. In four patients with vasospasm on posttreatment angiograms, MCA flow velocity increased to values higher than 120 cm/s after GDC application, returning to baseline after 24 hours. In four patients with ischemic complications (two transient ischemic attacks, one stroke, one vascular death), MCA flow velocity decreased more than 30% and did not return to preoperative values within 24 hours.
The application of transcranial Doppler sonographic monitoring during endovascular treatment may help to identify patients at risk for posttreatment cerebral ischemia.
Abstract
BACKGROUND
IVF for the treatment of infertility offers unique opportunities to observe human preimplantation development. Progress in time-lapse technology (TLT) and preimplantation genetic ...testing (PGT) has greatly expanded our knowledge of developmental patterns leading to a healthy pregnancy or developmental failure. These technologies have also revealed unsuspected plastic properties of the preimplantation embryo, at macromolecular, cellular and multicellular levels.
OBJECTIVE AND RATIONALE
This review focuses on the emerging concept of plasticity of the human embryo as revealed by recent evidence derived from TLT and PGT, calling for an updated and more precise redefinition of the boundaries between normal and abnormal development.
SEARCH METHODS
PubMed was used to search the MEDLINE database for peer-reviewed English-language original articles and reviews concerning human preimplantation development. Cross-searches were performed by adopting ‘fertilisation‘, ‘pronucleus’, ‘cleavage’, ‘multinucleation’, ‘compaction’, ‘embryo’, ‘preimplantation genetic testing’, ‘aneuploidy’, mosaicism’, ‘micromanipulation’, ‘time-lapse microscopy’ and ‘IVF/assisted reproduction’ as main terms. The most relevant publications, i.e. those concerning major phenomena occurring during normal and abnormal development—with a focus on the human species—were assessed and discussed critically.
OUTCOMES
Advances in TLT and PGT have revealed an astonishing plasticity and self-correction ability of the human preimplantation embryo in vitro. At fertilisation, an abnormal number of pronuclei do not always result in the formation of an aneuploid blastocyst. Animal studies and preliminary human observations indicate that combining of parental genomes may occur at the early cleavage stage, if not at fertilisation. Multinucleation occurs with much higher prevalence than previously thought and may be corrected at later cleavage stages. Irregular cleavage (multichotomous, direct, rapid and reverse cleavages) can generate chromosome segregation abnormalities that often lead to developmental arrest, but that sporadically may be confined to cells excluded from the blastocyst, and may sometimes result in viable pregnancy. Mitotic errors can generate mosaic blastocysts, but alternatively normal embryos may form from selective death or clonal depletion of aneuploid cells.
WIDER IMPLICATIONS
Deviations from developmental dogmas and the increasing evidence of plasticity of the human embryo challenge current embryological notions and suggest the need to write new rules governing cell cycle, cell determination and chromosome segregation during preimplantation development.
Abstract
BACKGROUND
Assisted reproduction technology offers the opportunity to observe the very early stages of human development. However, due to practical constraints, for decades morphological ...examination of embryo development has been undertaken at a few isolated time points at the stages of fertilisation (Day 1), cleavage (Day 2–3) and blastocyst (Day 5–6). Rather surprisingly, the morula stage (Day 3–4) has been so far neglected, despite its involvement in crucial cellular processes and developmental decisions.
OBJECTIVE AND RATIONALE
The objective of this review is to collate novel and unsuspected insights into developmental processes occurring during formation of the morula, highlighting the key importance of this stage for a better understanding of preimplantation development and an improvement of ART.
SEARCH METHODS
PubMed was used to search the MEDLINE database for peer-reviewed English-language original articles and reviews concerning the morula stage in mammals. Searches were performed by adopting ‘embryo’, ‘morula’, ‘compaction’, ‘cell fate’ and ‘IVF/assisted reproduction’ as main terms, in association with other keywords expressing concepts relevant to the subject (e.g. cell polarity). The most relevant publications, i.e. those concerning major phenomena occurring during formation of the morula in established experimental models and the human species, were assessed and discussed critically.
OUTCOMES
Novel live cell imaging technologies and cell biology studies have extended our understanding of morula formation as a key stage for the development of the blastocyst and determination of the inner cell mass (ICM) and the trophectoderm (TE). Cellular processes, such as dynamic formation of filopodia and cytoskeleton-mediated zippering cell-to-cell interactions, intervene to allow cell compaction (a geometrical requisite essential for development) and formation of the blastocoel, respectively. At the same time, differential orientation of cleavage planes, cell polarity and cortical tensile forces interact and cooperate to position blastomeres either internally or externally, thereby influencing their cellular fate. Recent time lapse microscopy (TLM) observations also suggest that in the human the process of compaction may represent an important checkpoint for embryo viability, through which chromosomally abnormal blastomeres are sensed and eliminated by the embryo.
WIDER IMPLICATIONS
In clinical embryology, the morula stage has been always perceived as a ‘black box’ in the continuum of preimplantation development. This has dictated its virtual exclusion from mainstream ART procedures. Recent findings described in this review indicate that the morula, and the associated process of compaction, as a crucial stage not only for the formation of the blastocyst, but also for the health of the conceptus. This understanding may open new avenues for innovative approaches to embryo manipulation, assessment and treatment.
The morula stage is a poorly understood developmental stage. In the morula, cell compaction can involve all or only some blastomeres, with largely unknown implications. Here, the prevalence, ...underlying morphokinetic mechanisms and possible consequences of partial compaction, were investigated.
Preimplantation genetic testing for aneuploidies (PGT-A) cycles of women whose embryos were observed by time-lapse technology were studied. PGT-A data, generated by array comparative genomic hybridization analysis and assessed in three age groups (≤34, 35–39 and ≥40 years), were obtained from trophectoderm biopsies after development to blastocyst stage.
Compaction occurred according to three modalities: (i) full compaction, with all blastomeres included (FCM); partial compaction (partially compacted morula PCM), with blastomeres (ii) excluded from the outset (excluded-PCM) or (iii) extruded after compaction (extruded-PCM). Partial compaction occurred more frequently than full compaction. Excluded-PCM displayed the slowest morphokinetics at most stages and were most often associated with abnormal cleavage. After compaction, embryo degeneration was more frequently associated with cell extrusion. In excluded-PCM, loss of ≥2 cells impacted blastocyst rate. In embryos of both younger and middle age groups, no statistical differences were observed in the rate of aneuploidy in relation to the three compaction groups, unlike what observed in ≥40 years women. Implantation rates after transfer of euploid blastocysts were not statistically different between the three groups.
Alternative modalities of incomplete compaction were detected. Such patterns are characterized by different morphokinetic behaviours overarching the entire preimplantation development, and by different developmental abilities.
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