Huntington disease-like 2: insight into neurodegeneration from an African disease.

Huntington disease (HD)-like 2 (HDL2) is a rare genetic disease caused by an expanded trinucleotide repeat in the JPH3 gene (encoding junctophilin 3) that shows remarkable clinical similarity to HD. To date, HDL2 has been reported only in patients with definite or probable African ancestry. A single haplotype background is shared by patients with HDL2 from different populations, supporting a common African origin for the expansion mutation. Nevertheless, outside South Africa, reports of patients with HDL2 in Africa are scarce, probably owing to limited clinical services across the continent. Systematic comparisons of HDL2 and HD have revealed closely overlapping motor, cognitive and psychiatric features and similar patterns of cerebral and striatal atrophy. The pathogenesis of HDL2 remains unclear but it is proposed to occur through several mechanisms, including loss of protein function and RNA and/or protein toxicity. This Review summarizes our current knowledge of this African-specific HD phenocopy and highlights key areas of overlap between HDL2 and HD. Given the aforementioned similarities in clinical phenotype and pathology, an improved understanding of HDL2 could provide novel insights into HD and other neurodegenerative and/or trinucleotide repeat expansion disorders.

Early Experience With Uniplanar Versus Biplanar Expandable Interbody Fusion Devices in Single-Level Minimally Invasive Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: To compare the early radiographic and clinical outcomes of expandable uniplanar versus biplanar interbody cages used for single-level minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: A retrospective review of 1-level MIS-TLIFs performed with uniplanar and biplanar polyetheretherketone cages was performed. Radiographic measurements were performed on radiographs taken preoperatively, at 6-week follow-up, and 1-year follow-up. Oswestry Disability Index (ODI) and visual analogue scale (VAS) for back and leg at 3-month and 1-year follow-up. RESULTS: A total of 93 patients (41 uniplanar, 52 biplanar) were included. Both cage types provided significant postoperative improvements in anterior disc height, posterior disc height, and segmental lordosis at 1 year. No significant differences in cage subsidence rates were found between uniplanar (21.9%) and biplanar devices (32.7%) at 6 weeks (odds ratio, 2.015; 95% confidence interval, 0.651-6.235; p = 0.249) with no additional instances of subsidence at 1 year. No significant differences in the magnitude of improvements based on ODI, VAS back, or VAS leg at 3-month or 1-year follow-up between groups and the proportion of patients achieving the minimal clinically important difference in ODI, VAS back, or VAS leg at 1 year were not statistically significantly different (p > 0.05). Finally, there were no significant differences in complication rates (p = 0.283), 90-day readmission rates (p = 1.00), revision surgical procedures (p = 0.423), or fusion rates at 1 year (p = 0.457) between groups. CONCLUSION: Biplanar and uniplanar expandable cages offer a safe and effective means of improving anterior disc height, posterior disc height, segmental lordosis, and patient-reported outcome measures at 1 year postoperatively. No significant differences in radiographic outcomes, subsidence rates, mean subsidence distance, 1-year patient-reported outcomes, and postoperative complications were noted between groups.

A comparison between the neurocognitive profile of Huntington Disease-Like 2 and Huntington Disease: Exploring the presence of double dissociations.

Huntington Disease Like-2 (HDL2) is a rare autosomal dominant genetic disease caused by a mutation in the JPH3 gene. HDL2 is the Huntington Disease (HD) phenocopy that has the greatest clinical resemblance to HD. Both are characterized by movement, psychiatric and cognitive dysfunction, which progress to dementia. The present study compared the neuropsychological profile of HDL2 with that of HD. Using a Single Case-Control Methodology in Neuropsychology, three HDL2 and seven matched HD patients were assessed with a comprehensive neuropsychological battery and compared to matched control samples, considering age, years of education, type of school (public/government) and language (all bi/multilingual). Potential double dissociations were explored by using Crawford, Garthwaite, and Wood's Inferential Methods for Comparing the Scores of Two Single-Cases in Case-Control Designs. Double dissociation between HDL2 and HD were identified in three tests, namely Letter Number Sequencing, Rey Auditory Learning Test Delayed and Recognition Trials. These dissociations possible are due to methodological limitations.

The Neuropsychiatry of Huntington Disease-Like 2: A Comparison with Huntington's Disease.

BACKGROUND: Huntington Disease-Like 2 (HDL2) is a rare autosomal dominant disorder caused by an abnormal CAG/CTG triplet repeat expansion on chromosome 16q24. The symptoms of progressive decline in motor, cognitive and psychiatric functioning are similar to those of Huntington's disease (HD). The psychiatric features of the HDL2 have been poorly characterized. OBJECTIVE: To describe the neuropsychiatric features of HDL2 and compare them with those of HD. METHODS: A blinded cross-sectional design was used to compare the behavioural component of the Unified Huntington's Disease Rating Scale (UHDRS) in participants with HDL2 (n = 15) and HD (n = 13) with African ancestry. RESULTS: HDL2 patients presented with psychiatric symptoms involving mood disturbances and behavioural changes that were not significantly different from those in the HD group. Duration of disease and motor performance correlated (p < 0.001) with the Functional Capacity score and the Independence score of the UHDRS. HD patients reported movement dysfunction as the first symptom more frequently than HDL2 Patients (p < 0.001). CONCLUSION: The psychiatric phenotype of HDL2 is similar to that of HD and linked to motor decline and disease duration. Psychiatric symptoms seem more severe for HDL2 patients in the early stages of the disease.

Temporal and structural genetic variation in reindeer (Rangifer tarandus) associated with the pastoral transition in Northwestern Siberia.

Just as the domestication of livestock is often cited as a key element in the Neolithic transition to settled, the emergence of large-scaled reindeer husbandry was a fundamental social transformation for the indigenous peoples of Arctic Eurasia. To better understand the history of reindeer domestication, and the genetic processes associated with the pastoral transition in the Eurasian Arctic, we analyzed archaeological and contemporary reindeer samples from Northwestern Siberia. The material represents Rangifer genealogies spanning from 15,000 years ago to the 18th century, as well as modern samples from the wild Taimyr population and from domestic herds managed by Nenetses. The wild and the domestic population are the largest populations of their kind in Northern Eurasia, and some Nenetses hold their domestic reindeer beside their wild cousins. Our analyses of 197 modern and 223 ancient mitochondrial DNA sequences revealed two genetic clusters, which are interpreted as representing the gene pools of contemporary domestic and past wild reindeer. Among a total of 137 different mitochondrial haplotypes identified in both the modern and archaeological samples, only 21 were detected in the modern domestic gene pool, while 11 of these were absent from the wild gene pool. The significant temporal genetic shift that we associate with the pastoral transition suggests that the emergence and spread of reindeer pastoralism in Northwestern Siberia originated with the translocation and subsequent selective breeding of a special type of animal from outside the region. The distinct and persistent domestic characteristics of the haplotype structure since the 18th century suggests little genetic exchange since then. The absence of the typical domestic clade in modern nearby wild populations suggests that the contemporary Nenets domestic breed feature an ancestry from outside its present main distribution, possibly from further South.

BMI Does Not Affect Complications or Patient Reported Outcomes After Lumbar Decompression Surgery.

STUDY DESIGN: This is a retrospective comparative review. OBJECTIVE: The objective of this study was to identify the influence of body mass index (BMI) on postsurgical complications and patient reported outcomes measures (PROMs) following lumbar decompression surgery. SUMMARY OF BACKGROUND DATA: Current literature does not accurately identify the impact of BMI on postsurgical complications or outcomes. MATERIALS AND METHODS: Records from a single-center, academic hospital were used to identify patients undergoing 1 to 3-level lumbar decompression surgery. Patients under 18 years of age, those undergoing surgery for infection, trauma, tumor, or revision, and those with <1-year follow-up were excluded. Patients were split into groups based on preoperative BMI: class I: BMI <25.0 kg/m; class II: BMI 25.0-29.9 kg/m; class III: BMI 30.0-34.9 kg/m; and class IV: BMI >35.0 kg/m. Absolute PROM scores, the recovery ratio and the percent of patients achieving minimum clinically important difference between groups were compared and a multiple linear regression analysis was performed. RESULTS: A total of 195 patients were included with 34 (17.4%) patients in group I, 80 (41.0%) in group II, 49 (25.1%) in group III, and 32 (16.5%) in group IV. Average age was 60.0 (58.0, 62.0) years and average follow-up was 13.0 (12.6, 13.4) months. All patients improved significantly within each group, except for class III and class IV patients, who did not demonstrate significant improvements in terms of Mental Component Score (MCS-12) scores (P=0.546 and 0.702, respectively). There were no significant differences between BMI groups for baseline or postoperative PROM values, recovery ratio, or the percent of patients reaching minimum clinically important difference. Multiple linear regression analysis revealed that BMI was not a significant predictor for change in outcomes for any measure. The 30-day readmission rate was 6.2% and overall revision rate at final follow-up was 5.1%, with no significant differences between groups. CONCLUSION: This study's results suggest that BMI may not significantly affect complications or patient outcomes at 1-year in those undergoing lumbar decompression surgery. LEVEL OF EVIDENCE: Level III.

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population.

The Impact of Multiple Comorbid Mental Health Disorders on Health-related Quality of Life Following ACDF.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: The goal was to determine whether comorbid depression and/or anxiety influence outcomes after anterior cervical discectomy and fusion (ACDF) for patients with degenerative cervical pathology. BACKGROUND DATA: The role preoperative mental health has on patient reported outcomes after ACDF surgery is not well understood. METHODS: Patients undergoing elective ACDF for degenerative cervical pathology were identified. Patients were grouped based on their preoperative mental health comorbidities, including patients with no history, depression, anxiety, and those with both depression and anxiety. All preoperative medical treatment for depression and/or anxiety was identified. Outcomes including Physical Component Score (PCS-12), Mental Component Score (MCS-12), Neck Disability Index (NDI), Visual Analogue Scale neck pain score (VAS Neck ), and Visual Analogue Scale arm pain score (VAS Arm) were compared between groups from baseline to postoperative measurements using multiple linear regression analysis-controlling for factors such as age, sex, and body mass index, etc. A P-value <0.05 was considered statistically significant. RESULTS: A total of 264 patients were included in the analysis, with an average age of 53 years and mean follow-up of 19.8 months (19.0-20.6). All patients with a diagnosis of depression or anxiety also reported medical treatment for the disease. The group with no depression or anxiety had significantly less baseline disability than the group with 2 mental health diagnoses, in MCS-12 (P=0.009), NDI (P<0.004), VAS Neck (P=0.003), and VAS Arm (P=0.001) scores. Linear regression analysis demonstrated that increasing occurrence of mental health disorders was not a significant predictor of change over time for any of the outcome measures included in the analysis. CONCLUSIONS: Despite more severe preoperative symptoms, patients with a preoperative mental health disorder(s) demonstrated significant improvement in postoperative outcomes after ACDF. No differences were identified in postoperative outcomes between each of the groups. LEVEL OF EVIDENCE: Level III.

A detailed description of the phenotypic spectrum of North Sea Progressive Myoclonus Epilepsy in a large cohort of seventeen patients.

INTRODUCTION: In 2011, a homozygous mutation in GOSR2 (c.430G > T; p. Gly144Trp) was reported as a novel cause of Progressive Myoclonus Epilepsy (PME) with early-onset ataxia. Interestingly, the ancestors of patients originate from countries bound to the North Sea, hence the condition was termed North Sea PME (NSPME). Until now, only 20 patients have been reported in literature. Here, we provide a detailed description of clinical and neurophysiological data of seventeen patients. METHODS: We collected clinical and neurophysiological data from the medical records of seventeen NSPME patients (5-46 years). In addition, we conducted an interview focused on factors influencing myoclonus severity. RESULTS: The core clinical features of NSPME are early-onset ataxia, myoclonus and seizures, with additionally areflexia and scoliosis. Factors such as fever, illness, heat, emotions, stress, noise and light (flashes) all exacerbated myoclonic jerks. Epilepsy severity ranged from the absence of or incidental clinical seizures to frequent daily seizures and status epilepticus. Some patients made use of a wheelchair during their first decade, whereas others still walked independently during their third decade. Neurophysiological features suggesting neuromuscular involvement in NSPME were variable, with findings ranging from indicative of sensory neuronopathy and anterior horn cell involvement to an isolated absent H-reflex. CONCLUSION: Although the sequence of symptoms is rather homogeneous, the severity of symptoms and rate of progression varied considerably among individual patients. Common triggers for myoclonus can be identified and myoclonus is difficult to treat; to what extent neuromuscular involvement contributes to the phenotype remains to be further elucidated.

Screening of the glucocerebrosidase (GBA) gene in South Africans of African ancestry with Parkinson's disease.

Sequence variants in glucocerebrosidase (GBA) are a major genetic risk factor for Parkinson's disease (PD), and display ethnic-dependent frequencies, for example, variants such as p.N370S and 84insGG are common in Ashkenazi Jewish patients. Notably, there are limited studies on black patients from the African continent; hence, we conducted a study on 30 South African black PD patients. All 11 exons of GBA were screened using a nested PCR approach to avoid pseudogene contamination. We identified previously described Gaucher's disease-associated variants, p.R120W in one patient [age at onset (AAO) of 35 years], and p.R131L in another patient (AAO 30 years) and in her affected sibling (AAO 45 years). In addition, we found 3 previously identified [p.K(-27)R, p.T36del, and p.Q497*] and 2 novel (p.F216L and p.G478R) variants. Screening of ethnic-matched controls for the novel variants revealed that the allele frequency of p.F216L was 9.9%, whereas p.G478R was not found in the controls. Studies such as these are important and necessary to reveal the genetic architecture underlying PD in the understudied patients of African ancestry.

Single case-control design for the study of the neuropsychological deficits and dissociations in Huntington's disease-like 2.

The Single-Case Methodology in Neuropsychology (Crawford & Howell, 1998) is a research design and robust inferential statistical method that facilitates the neuropsychological description of one case in terms of the differences between its profile and the performance of a carefully matched sample (Crawford & Garthwaite, 2012). The comparison is made by means of a t-test statistic that treats the normative sample as a sample and not as a population, with a particular effect-size associated with the size (n) of the sample. It is an ideal method for the neuropsychological investigation of rare diseases, such as Huntington's Disease Like-2 (HDL2), especially when the cases are embedded in contexts of great diversity. This paper presents a step by step guide to the implementation of this method in a series of demographically and clinically diverse group of patients. •The application of a Single-Case Methodology in Neuropsychology enables the characterisation of rare diseases while controlling for demographic and context-related variables.•The implementation Single-Case Methodology in Neuropsychology provides test norms for homogenous groups that can be used by practitioners in their clinical work.•The method was customised for the South African population by controlling variables of specific relevance, such as linguistic diversity and quality of education.

The neuropsychological deficits and dissociations in Huntington Disease-Like 2: A series of case-control studies.

OBJECTIVES: Huntington's Disease Like-2 (HDL2) is a rare autosomal dominant genetic disease caused by a mutation in the JPH3 gene. The Huntington's Disease (HD) phenocopy has the greatest clinical resemblance to HD, but its neurocognitive characterisation is poorly researched. This study reports on the neurocognitive profile of seven HDL2 patients including preserved functions, deficits and dissociations (classical and strong) and provides a general characterisation of the cognitive dysfunction of HDL2 in relation to the progression of the disease. METHODS: The neuropsychological performance of seven HDL2 patients were compared to one of four control groups, matched by age and level of education using a Single Case-Control design. All patients were polyglots and with public education (primary and secondary). Deficits, as well as classical and strong dissociations within each case profile, were identified by implementing Crawford and Howell's (1998) t-test and the Revised Standardized Difference Test (Crawford and Garthwaite, 2005), respectively. RESULTS: The HDL2 neurocognitive syndrome is heterogeneous with a variable rate of progression, with the psychomotor and dexterity domain consistently and severely impaired. CONCLUSION: HDL2 has a heterogeneous impact on cognitive functions from early stages in the disease, which evolve to dementia in a non-uniform manner, in keeping with preferential damage in the cerebrocortical-basal ganglia-thalamus-cerebrocortical circuit.

Does an Uninstrumented Level Increase the Rate of Revision Surgery in a Multilevel Posterior Cervical Decompression and Fusion?

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: The goal of this study is to determine if skipping a single level affects the revision rate for patients undergoing multilevel posterior cervical decompression and fusion (PCDF). SUMMARY OF BACKGROUND DATA: A multilevel PCDF is a common procedure for patients with cervical spondylotic myelopathy. With advanced pathology, it can be difficult to safely place screw instrumentation at every level increasing the risk of intraoperative and perioperative morbidity. It is unclear whether skipping a level during PCDF affects fusion and revision rates. PATIENTS AND METHODS: A cervical spine surgeries database at a single institution was used to identify patients who underwent ≥3 levels of PCDF. Inclusion criteria consisted of patients who had screws placed at every level or if they had a single level without screws bilaterally. Patients were excluded if the surgery was performed for tumor, trauma, or infection, and age below 18 years, or if there was <1 year of follow-up. RESULTS: A total of 157 patients met inclusion criteria, with 86 undergoing a PCDF with instrumentation at all levels and 71 that had a single uninstrumented level. Overall mean follow-up was 46.5±22.8 months. In patients with or without a skipped level, the revision rate was 25% and 26%, respectively (P<1.00). Univariate regression analysis demonstrated that proximal fixation level in the upper cervical region, having the fusion end at C7, prior surgery, and myelopathy were significant predictors of revision. Skipping a single level, however, was not predictive of revision. CONCLUSIONS: When performing a multilevel PCDF, there is no increase in the rate of revision surgery if a single level is uninstrumented. Conversely, other surgical factors, including the cranial and caudal levels, affect revision rates. In contrast to other reports, the C2 sagittal vertical axis did not affect reoperation rates. LEVEL OF EVIDENCE: Level IV.

Frequency of the LRRK2 G2019S mutation in South African patients with Parkinson's disease.

G2019S in LRRK2 is the most common mutation associated with Parkinson's disease (PD). Highest frequencies are in North African Arabic (30-41%) and Ashkenazi Jewish (6-30%) populations, mostly due to founder effects. Here, we investigated the frequency of G2019S in 647 unrelated South African PD patients from different ancestral origins. It was found in only 1.2% (8/647) of patients. Notably, none of the 91 individuals of African ancestry had G2019S. It was present in 1.9% (3/154) and 1% (5/493) of early- and late-onset cases, respectively. The frequency of G2019S exhibits ethnic-specific differences and warrants further study in sub-Saharan African populations.

Comparison of the Huntington's Disease like 2 and Huntington's Disease Clinical Phenotypes.

BACKGROUND: Huntington's disease like 2 (HDL2) is the most common Huntington's disease (HD) phenocopy in many countries and described as the phenocopy with the greatest resemblance to HD. The current clinical description of HDL2 is based on retrospective data. It is unknown whether HDL2 has clinical features that distinguish it from HD. OBJECTIVE: To describe the HDL2 phenotype and compare it to HD systematically. METHODS: A blinded cross-sectional design was used to compare the HDL2 (n = 15) and HD (n = 13) phenotypes. African ancestry participants underwent assessments, including the Unified Huntington's Disease Rating Scale (UHDRS). The UHDRS motor component was video recorded and evaluated by blinded experts and the inter-rater reliability calculated. RESULTS: Both groups were homogeneous in terms of demographics and disease characteristics. However, HDL2 patients presented three years earlier with more prominent dysarthria and dystonia. Raters could not distinguish between the two diseases with a high level of agreement. No significant differences in the TMS between HDL2 and HD were found. In both disorders, disease duration correlated with motor scores, with the exception of chorea. Psychiatric and cognitive scores were not significantly different between the groups. CONCLUSIONS: The HDL2 phenotype is similar to HD and is initially characterized by dementia, chorea, and oculomotor abnormalities, progressing to a rigid and bradykinetic state, suggesting the UHDRS is useful to monitor disease progression in HDL2. Although HDL2 patients scored higher on some UHDRS domains, this did not differentiate between the two diseases; it may however be emerging evidence of HDL2 having a more severe clinical phenotype.

Intraosseous Basivertebral Nerve Ablation for the Treatment of Chronic Low Back Pain: 2-Year Results From a Prospective Randomized Double-Blind Sham-Controlled Multicenter Study.

BACKGROUND: The purpose of the present study is to report the 2-year clinical outcomes for chronic low back pain (CLBP) patients treated with radiofrequency (RF) ablation of the basivertebral nerve (BVN) in a randomized controlled trial that previously reported 1-year follow up. METHODS: A total of 147 patients were treated with RF ablation of the BVN in a randomized controlled trial designed to demonstrate safety and efficacy as part of a Food and Drug Administration-Investigational Device Exemption trial. Evaluations, including patient self-assessments, physical and neurological examinations, and safety assessments, were performed at 2 and 6 weeks, and 3, 6, 12, 18, and 24 months postoperatively. Participants randomized to the sham control arm were allowed to cross to RF ablation at 12 months. Due to a high rate of crossover, RF ablation treated participants acted as their own control in a comparison to baseline for the 24-month outcomes. RESULTS: Clinical improvements in the Oswestry Disability Index (ODI), Visual Analog Scale (VAS), and the Medical Outcomes Trust Short-Form Health Survey Physical Component Summary were statistically significant compared to baseline at all follow-up time points through 2 years. The mean percent improvements in ODI and VAS compared to baseline at 2 years were 53.7 and 52.9%, respectively. Responder rates for ODI and VAS were also maintained through 2 years with patients showing clinically meaningful improvements in both: ODI ≥ 10-point improvement in 76.4% of patients and ODI ≥ 20-point improvement in 57.5%; VAS ≥ 1.5 cm improvement in 70.2% of patients. CONCLUSIONS: Patients treated with RF ablation of the BVN for CLBP exhibited sustained clinical benefits in ODI and VAS and maintained high responder rates at 2 years following treatment. Basivertebral nerve ablation appears to be a durable, minimally invasive treatment for the relief of CLBP.

Faecal biomarkers can distinguish specific mammalian species in modern and past environments.

Identifying the presence of animals based on faecal deposits in modern and ancient environments is of primary importance to archaeologists, ecologists, forensic scientists, and watershed managers, but it has proven difficult to distinguish faecal material to the species level. Until now, four 5ß-stanols have been deployed as faecal biomarkers to distinguish between omnivores and herbivores, but they cannot distinguish between species. Here we present a database of faecal signatures from ten omnivore and herbivore species based on eleven 5ß-stanol compounds, which enables us to distinguish for the first time the faecal signatures of a wide range of animals. We validated this fingerprinting method by testing it on modern and ancient soil samples containing known faecal inputs and successfully distinguished the signatures of different omnivores and herbivores.

Emerging differences between Huntington's disease-like 2 and Huntington's disease: A comparison using MRI brain volumetry.

Huntington's Disease-Like 2 (HDL2), caused by a CTG/CAG expansion in JPH3 on chromosome 16q24, is the most common Huntington's Disease (HD) phenocopy in populations with African ancestry. Qualitatively, brain MRIs of HDL2 patients have been indistinguishable from HD. To determine brain regions most affected in HDL2 a cross-sectional study using MRI brain volumetry was undertaken to compare the brains of nine HDL2, 11 HD and nine age matched control participants. Participants were ascertained from the region in South Africa with the world's highest HDL2 incidence. The HDL2 and HD patient groups showed no significant differences with respect to mean age at MRI, disease duration, abnormal triplet repeat length, or age at disease onset. Overall, intracerebral volumes were smaller in both affected groups compared to the control group. Comparing the HDL2 and HD groups across multiple covariates, cortical and subcortical volumes were similar with the exception that the HDL2 thalamic volumes were smaller. Consistent with other similarities between the two diseases, these results indicate a pattern of neurodegeneration in HDL2 that is remarkably similar to HD. However smaller thalamic volumes in HDL2 raises intriguing questions into the pathogenesis of both disorders, and how these volumetric differences relate to their respective phenotypes.

Utilization of Time-driven Activity-based Costing to Determine the True Cost of a Single or 2-level Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: This is a prospective case series. OBJECTIVE: To determine the actual cost of performing 1- or 2-level anterior cervical discectomy and fusion (ACDF) using actual patient data and the time-driven activity-based cost methodology. SUMMARY OF BACKGROUND DATA: As health care shifts to use value-based reimbursement, it is imperative to determine the true cost of surgical procedures. Time-driven activity-based costing determines the cost of care by determining the actual resources used in each step of the care cycle. MATERIALS AND METHODS: In total, 30 patients who underwent a 1- or 2-level ACDF by 3 surgeons at a specialty hospital were prospectively enrolled. To build an accurate process map, a research assistant accompanied the patient to every step in the care cycle including the preoperative visit, the preadmission testing, the surgery, and the postoperative visits for the first 90 days. All resources utilized and the time spent with every member of the care team was recorded. RESULTS: In total, 27 patients were analyzed. Eleven patients underwent a single-level ACDF and 16 underwent a 2-level fusion. The total cost for the episode of care was $29,299±$5048. The overwhelming cost driver was the hospital disposable costs ($13,920±$6325) which includes every item used during the hospital stay. Intraoperative personnel costs including fees for the surgeon, resident/fellow, anesthesia, nursing, surgical technician, neuromonitoring, radiology technician and orderlies, accounted for the second largest cost at $6066±$1540. The total cost excluding hospital overhead and disposables was $9071±$1939. CONCLUSIONS: Reimbursement for a bundle of care surrounding a 1- or 2-level ACDF should be no less than $29,299 to cover the true costs of the care for the entire care cycle. However, this cost may not include the true cost of all capital expenditures, and therefore may underestimate the cost.