•A classification and genetic basis for hypolipidemia disorders is provided.•We suggest guidance for the diagnosis and treatment of these disorders.•We discuss challenges encountered by patients with ...hypolipidemia disorders.•Topics for future research are highlighted.
The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is “to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders”. This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol and triglyceride, along with malabsorption of fat and fat-soluble vitamins are characteristic features of these diseases. We summarize the genetic basis of these disorders, provide guidance in their diagnosis and suggest treatment regimens including high dose fat-soluble vitamins as therapeutics. A section on preconception counseling and other special considerations pertaining to pregnancy is included. This information may be useful for patients, caregivers, physicians and insurance agencies involved in the management and support of affected individuals.
Background:
Although previous research has demonstrated that patients with posttraumatic migraine (PTM) after concussion report more symptoms and cognitive deficits after injury than do those without ...PTM, it is not known whether these effects persist beyond the first week of injury or whether PTM predicts recovery time.
Purpose:
To determine whether PTM during the first week after injury predicts (1) cognitive impairment and symptoms in the second week after injury and (2) overall recovery time.
Study Design:
Cohort study; Level of evidence, 2.
Methods:
Participants were 138 male high school football players with a mean age of 15.96 years (SD, 1.18 years; range, 13-19 years). They were classified into 3 groups: PTM (headache, nausea, and photosensitivity or phonosensitivity), headache (headache without the other PTM symptoms), or no headache (no headache or PTM symptoms). The Immediate Post-concussion Assessment and Cognitive Test (ImPACT) was used to assess cognitive performance and symptoms at baseline, postinjury days 1-7, and postinjury days 8-14. Recovery time data were collected from medical records.
Results:
The PTM group performed worse on verbal memory than did the headache group at 8-14 days after injury. The PTM group performed worse on visual memory, reaction time, and symptoms than did the other groups at 1-7 days and 8-14 days after injury. The PTM group was 7.3 times (95% confidence interval, 1.80-29.91) more likely to have protracted recovery (>20 days) than the no headache group and 2.6 times (95% confidence interval, 1.10-6.54) more likely than the headache group.
Conclusion:
Results suggest that PTM is associated with cognitive impairments and protracted recovery and that headache alone is not a good predictor of recovery.
BackgroundThrombolysis can significantly reduce the burden of stroke but the time window for safe and effective treatment is short. In patients travelling to hospital via ambulance, the sending of a ...‘prealert’ message can significantly improve the timeliness of treatment.ObjectiveExamine the prevalence of hospital prealerting, the extent to which prealert protocols are followed and what factors influence emergency medical services (EMS) staff's decision to send a prealert.MethodsCohort study of patients admitted to two acute stroke units in West Midlands (UK) hospitals using linked data from hospital and EMS records. A logistic regression model examined the association between prealert eligibility and whether a prealert message was sent. In semistructured interviews, EMS staff were asked about their experiences of patients with suspected stroke.ResultsOf the 539 patients eligible for this study, 271 (51%) were recruited. Of these, only 79 (29%) were eligible for prealerting according to criteria set out in local protocols but 143 (53%) were prealerted. Increasing number of Face, Arm, Speech Test symptoms (1 symptom, OR 6.14, 95% CI 2.06 to 18.30, p=0.001; 2 symptoms, OR 31.36, 95% CI 9.91 to 99.24, p<0.001; 3 symptoms, OR 75.84, 95% CI 24.68 to 233.03, p<0.001) and EMS contact within 5 h of symptom onset (OR 2.99, 95% CI 1.37 to 6.50 p=0.006) were key predictors of prealerting but eligibility for prealert as a whole was not (OR 1.92, 95% CI 0.85 to 4.34 p=0.12). In qualitative interviews, EMS staff displayed varying understanding of prealert protocols and described frustration when their interpretation of the prealert criteria was not shared by ED staff.ConclusionsUp to half of the patients presenting with suspected stroke in this study were prealerted by EMS staff, regardless of eligibility, resulting in disagreements with ED staff during handover. Aligning the expectations of EMS and ED staff, perhaps through simplified prealert protocols, could be considered to facilitate more appropriate use of hospital prealerting in acute stroke.
Functional areas located near or within brain gliomas prevent the complete resection of these tumors. It has recently been described that slow tumor invasion promotes neural reorganization, and even ...topographic plasticity, allowing a staged resection of those tumors. Thus, our aim was to promote plasticity by mimicking the tumor's capability to displace brain function. This proceeded through the production of a 'virtual lesion' in eloquent areas within a tumor using continuous high-frequency cortical electrical stimulation (cHFCS). An anaplastic astrocytoma located in Broca's area progressed in a patient whose lateralization of language to the side of the lesion was demonstrated with functional MRI. After partial tumor resection using awake cortical monitoring, we implanted a subdural grid over the eloquent cortex located within residual tumor. We then applied cHFCS for 25 days, using a frequency of 130 Hz and a pulse width of 1 ms. Stimulus intensity was set to the threshold wherein mild speech disturbance was evident without any other neurological effects. This treatment successfully achieved the displacement of speech functions, and a more radical resection of the tumor was possible in a second surgery. Critically, a reorganization of motor language areas was demonstrated both with functional MRI and cortical stimulation. Furthermore, motor language areas were also identified in the right hemisphere, where previously they were absent. The patient's speech fluency improved both after stimulation and resection. We therefore demonstrate the first evidence of induced topographic plasticity using cHFCS in eloquent areas within a tumor, which allowed for increased tumor removal. Our results open the possibility to induce plasticity before the resection of brain tumors near eloquent areas, in order to increase the extent of resection.
Abstract Background and aims With the debate over extent of lymphadenectomy in endometrial cancer, sentinel lymph node (SLN) mapping may provide a focused approach to evaluate the most relevant lymph ...nodes (LN) while minimizing the complications. We evaluated SLN mapping using filtered technetium99 , indocyanine green (ICG), and blue dye. Methods Prospective evaluation of 100 patients who underwent SLN mapping by using submucosal and deep stromal cervical injections of technetium99 , ICG, and blue dye as part of the staging for endometrial cancer. Results 286 SLNs were mapped (2.9 per patient) in 92% of patients. The bilateral detection rate was 76%. ICG had a significantly higher SLN detection rate than blue dye in both overall (87% vs 71%, respectively; p = 0.005) and bilateral (65% vs 43%, respectively; p = 0.002) detection, but similar SLN detection rates compared to technetium99 in both overall (87% vs 88%, respectively; p = 0.83) and bilateral (65% vs 71%, respectively; p = 0.36) detection. In eight cases, the SLN was in the para-aortic area and in 14 cases in the pre-sacral, hypogastric vein, or parametrial area. In nine cases, the SLN was positive for metastasis, and in seven cases the SLN was the only positive node. One SLN was falsely negative. No complications or anaphylactic reactions occurred. Conclusion Intra-operative SLN mapping using cervical injection is feasible in patients with endometrial cancer and yields adequate detection rates. It allows mapping of SLNs in areas (pre-sacral, hypogastric vein, parametrial) not routinely sampled. Given the poorer performance of blue dye, surgeons may omit its use if a combination of ICG and technetium99 is used.
Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC ...gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.
Myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions that are often responsive to alcohol. The dopamine D2 receptor gene (
DRD2) on ...chromosome 11q has been implicated in one family with this syndrome, and linkage to a 28-cM region on 7q has been reported in another. We performed genetic studies, using eight additional families with M-D, to assess these two loci. No evidence for linkage was found for 11q markers. However, all eight of these families showed linkage to chromosome 7 markers, with a combined multipoint LOD score of 11.71. Recombination events in the families define the disease gene within a 14-cM interval flanked by D7S2212 and D7S821. These data provide evidence for a major locus for M-D on chromosome 7q21.
Potential advantages of intramuscular botulinum toxin for the treatment of spasticity include the lack of sensory effects, ability to target specific muscle groups, ability to weaken muscles in a ...graded fashion and absence of caustic chemicals such as phenol. We describe the use of botulinum toxin for the treatment of severe lower extremity spasticity in two subjects with multiple sclerosis. Both subjects showed an improvement in spasticity, as measured by the modified Ashworth scale, and in functional status. Both subjects exhibited reductions in muscle tone not only in injected muscles, but also in noninjected muscles in the region. These more distant clinical effects have not been emphasized in previous studies after therapeutic injections of botulinum toxin. Further research is needed to clarify the cause and prevalence of these regional motor effects, as well as to further examine the safety and efficacy of botulinum toxin for spasticity treatment.
The aim of this study was to determine if changes in omega-3 polyunsaturated fatty acid status following tuna oil supplementation correlated with changes in scores of depression. A total of 95 ...volunteers receiving treatment for major depression were randomised to consume 8 × 1 g capsules per day of HiDHA (2 g DHA, 0.6 g EPA and 10 mg Vitamin E) or olive oil (placebo) for 16 weeks, whilst undergoing weekly counseling sessions by trained clinical psychologists using a standard empirically validated psychotherapy. Depression status was assessed using the 17 item Hamilton rating scale for depression and the Beck Depression Inventory by a psychodiagnostician who was blind to the treatment. Blood was taken at baseline and 16 weeks (
n
= 48) for measurement of erythrocyte fatty acids. With HiDHA supplementation, erythrocyte DHA content rose from 4.1 ± 0.2 to 7.9 ± 0.4 % (mean ± SEM,
p
< 0.001) of total fatty acids but did not change (4.0 ± 0.2 to 4.1 ± 0.2 %) in the olive oil group. The mean changes in scores of depression did not differ significantly between the two groups (−12.2 ± 2.1 for tuna oil and −14.4 ± 2.3 for olive oil). However, analysis of covariance showed that in the fish oil group there was a significant correlation (
r
= −0.51) between the change in erythrocyte DHA and the change in scores of depression (
p
< 0.05). Further study of the relationship between DHA and depression is warranted.
: Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer ...intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in two clinical studies of cardiac surgery patients, without new safety observations.
: The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety.
: The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.
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