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.

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.

A comparative retrospective exploration of the profiles of patients in South Africa diagnosed with epileptic and psychogenic non-epileptic seizures.

Psychogenic non-epileptic seizures (PNES) have a high prevalence globally but the accurate diagnosis of this condition still remains a challenge. This is particularly the case in countries where there is scarce expertise and insufficient affordable medical facilities to which patients have access. The rate of PNES diagnosis in epilepsy units is typically within the range of 20 to 30%. In the context of developing countries, this rate tends to be higher and increases demand on the existing scarce health care capacities. Although the profiling of patients with different seizure presentations is essential for informing appropriate treatment, to date there has been no comparative analysis of the profiles of patients with PNES and epilepsy in South Africa. The aim of the present study was to explore retrospectively the demographic and medication characteristics of these patients and to compare these characteristics to those reported in patient populations from other countries and regions. The total sample of 246 participants included 85 (35%) male and 161 (65%) female patients who were admitted to the Epilepsy Monitoring Unit (EMU) at Milpark Hospital, South Africa. Following the video-EEG monitoring assessment, 123 patients (50%) were diagnosed with PNES, and for 123 patients (50%) the diagnosis of epilepsy was confirmed. The results indicated that the demographic profiles of the groups of patients with epilepsy and PNES were similar with reference to age and self-ascribed ethnicity. In both groups, the majority of the patients were females, but proportionally their prevalence was higher in the PNES patient group than in the epilepsy patient group, which is compatible with the trends found in the PNES patient populations internationally. Pre-diagnostically, the type and the number of medications prescribed to patients with PNES and epilepsy were comparable. Subsequent to the diagnosis at the EMU, there was a significant reduction of overall medications in each group, but this reducton was more pronounced in the group with PNES. It is concluded that the rate of misdiagnosis of PNES in South Africa surpasses the rates reported for the patient populations in other countries and is one of the highest documented worldwide. Considering that post-diagnostically, there was reduction in central nervous system (CNS) medications as well as anti-epileptic drugs (AEDs) in both patients with epilepsy and those with PNES, it is likely that pre-diagnostically a significant proportion of all patients were over medicated. Compared to the epilepsy diagnosis, the PNES diagnosis resulted in a more substantial reduction of medication. These findings outline important dimensions of the diagnostic and medication treatment practices of epilepsy and PNES and point to the urgent need to improve these practices in South Africa and the African continent.

Antioxidant-Mediated Modulation of Protein Reactivity for 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopamine Metabolite.

3,4-Dihydroxyphenylacetaldehyde (DOPAL) is an endogenously produced toxic aldehyde. It is a bifunctional electrophile implicated in the loss of dopaminergic cells concomitant with Parkinson's disease and neurodegeneration. DOPAL is known to react with proteins and amino acids such as N-acetyl lysine (NAL); oxidation of the catechol moiety to the quinone of DOPAL increases this reactivity. Here, we demonstrate the ability of the antioxidants N-acetylcysteine, glutathione, and ascorbic acid to mitigate the reactivity of DOPAL with proteins and amino acids in a dose-dependent fashion. Conversely, Trolox did not lessen the observed reactivity with proteins. Interestingly, use of tricine, a buffer and reducing agent, in these systems also decreased the reactivity of DOPAL with amines, yielding tricine-derived free radical species. Modification of amines with aldehydes typically involves Schiff base chemistry; however, the observance of free radicals suggests that an oxidative step is involved in the reaction of DOPAL with lysine. Furthermore, while Schiff base formation is usually optimal at pH 5, the reaction rate of DOPAL with NAL is negligible at pH 5 and is enhanced under basic conditions (e.g., pH 9). Conditions of high pH are also favorable for catechol auto-oxidation, known to occur for DOPAL. The antioxidant-mediated protection demonstrated here suggests that oxidative stress may impart cellular vulnerability to protein modification by DOPAL. Therefore, depleted antioxidants and increased levels of lipid peroxidation products, known to prevent the detoxifying metabolism of DOPAL, may present a survival challenge to dopaminergic cells targeted in Parkinson's disease.

Radiographic variables that may predict clinical outcomes in cervical disk replacement surgery.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: To determine which, if any, radiographic parameters are predictive of clinical outcome after cervical disk replacement (CDR) surgery. SUMMARY OF BACKGROUND DATA: It is unclear whether radiographic parameters are predictive of outcome after CDR. METHODS: An analysis of the radiographic parameters and clinical outcomes of the CDR cohort of the Discover artificial cervical disk IDE trial was performed. Clinical outcome measures included Neck Disability Index (NDI), visual analog pain scale (neck, arm, and shoulder), and SF-36 physical component summary score scores, collected preoperatively and at regularly scheduled postoperative time periods. Patients with at least 1-year follow-up were included. The change in outcomes from baseline was determined at each follow-up interval. The following minimal clinically important difference (MCID) thresholds were applied: -7.5 for NDI, -25 for visual analog pain scale, and +4.1 for physical component summary score. Fifty-six radiographic variables were analyzed to identify factors that may be associated with a poor clinical outcome, defined as failure to achieve the MCID in NDI. RESULTS: A total of 243 patients underwent CDR at 304 levels (182 one level, 61 two level). One hundred seventy-one patients (89 female, 82 male; mean age, 44.2 y; range, 28-67 y) had at least 1-year follow-up. A preoperative disk height of <3.5 mm was associated with a 3.4 times greater risk of not achieving a MCID in NDI (P=0.018). Increasing the functional spinal unit angle by >3 degrees was associated with a 3.5 times greater risk of not achieving a MCID in NDI (P=0.016). There were 21/171 patients (25 levels) who did not achieve the NDI MCID threshold. All of these patients had at least1, and 16/21 of these patients had more than 1 abnormal radiographic finding. Seventy percent of treatment levels had severe or bridging heterotopic ossification at 3-years follow-up, the incidence of which increased linearly with time. CONCLUSIONS: Several radiographic variables are predictive of clinical outcomes, including decreased preoperative disk space height and excessive postoperative segmental lordosis.

Disc space preparation in transforaminal lumbar interbody fusion: a comparison of minimally invasive and open approaches.

BACKGROUND: Minimally invasive surgical (MIS) approaches to transforaminal lumbar interbody fusion (TLIF) have been developed as an alternative to the open approach. However, concerns remain regarding the adequacy of disc space preparation that can be achieved through a minimally invasive approach to TLIF. QUESTIONS/PURPOSES: The purpose of this cadaver study is to compare the adequacy of disc space preparation through MIS and open approaches to TLIF. Specifically we sought to compare the two approaches with respect to (1) the time required to perform a discectomy and the number of endplate violations; (2) the percentage of disc removed; and (3) the anatomic location where residual disc would remain after discectomy. METHODS: Forty lumbar levels (ie, L1-2 to L5-S1 in eight fresh cadaver specimens) were randomly assigned to open and MIS groups. Both surgeons were fellowship-trained spine surgeons proficient in the assigned approach used. Time required for discectomy, endplate violations, and percentage of disc removed by volume and mass were recorded for each level. A digital imaging software program (ImageJ; US National Institutes of Health, Bethesda, MD, USA) was used to measure the percent disc removed by area for the total disc and for each quadrant of the endplate. RESULTS: The open approach was associated with a shorter discectomy time (9 versus 12 minutes, p = 0.01) and fewer endplate violations (one versus three, p = 0.04) when compared with an MIS approach, percent disc removed by volume (80% versus 77%, p = 0.41), percent disc removed by mass (77% versus 75%, p = 0.55), and percent total disc removed by area (73% versus 71%, p = 0.63) between the open and MIS approaches, respectively. The posterior contralateral quadrant was associated with the lowest percent of disc removed compared with the other three quadrants in both open and MIS groups (50% and 60%, respectively). CONCLUSIONS: When performed by a surgeon experienced with MIS TLIF, MIS and open approaches are similar in regard to the adequacy of disc space preparation. The least amount of disc by percentage is removed from the posterior contralateral quadrant regardless of the approach; surgeons should pay particular attention to this anatomic location during the discectomy portion of the procedure to minimize the likelihood of pseudarthrosis.

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.

Emerging 'super ACOs' fill unique needs.

Hospitals and health systems exploring the idea of forming or joining a "Super ACO" should consider several key factors: Pace of change and partnership opportunities in their market. Market concentration and the organization's size relative to larger competitors. Whether the organization is financially strong enough to participate. How prepared the organization is for accountable care and population management. Whether the organization is equipped to care for new patient populations.

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.

Oxidation of 3,4-dihydroxyphenylacetaldehyde, a toxic dopaminergic metabolite, to a semiquinone radical and an ortho-quinone.

The oxidation and toxicity of dopamine is believed to contribute to the selective neurodegeneration associated with Parkinson disease. The formation of reactive radicals and quinones greatly contributes to dopaminergic toxicity through a variety of mechanisms. The physiological metabolism of dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL) via monoamine oxidase significantly increases its toxicity. To more adequately explain this enhanced toxicity, we hypothesized that DOPAL is capable of forming radical and quinone species upon oxidation. Here, two unique oxidation products of DOPAL are identified. Several different oxidation methods gave rise to a transient DOPAL semiquinone radical, which was characterized by electron paramagnetic resonance spectroscopy. NMR identified the second oxidation product of DOPAL as the ortho-quinone. Also, carbonyl hydration of DOPAL in aqueous media was evident via NMR. Interestingly, the DOPAL quinone exists exclusively in the hydrated form. Furthermore, the enzymatic and chemical oxidation of DOPAL greatly enhance protein cross-linking, whereas auto-oxidation results in the production of superoxide. Also, DOPAL was shown to be susceptible to oxidation by cyclooxygenase-2 (COX-2). The involvement of this physiologically relevant enzyme in both oxidative stress and Parkinson disease underscores the potential importance of DOPAL in the pathogenesis of this condition.

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.

Relative inhibitory potency of molinate and metabolites with aldehyde dehydrogenase 2: implications for the mechanism of enzyme inhibition.

Molinate is a thiocarbamate herbicide used as a pre-emergent in rice patty fields. It has two predominant sulfoxidation metabolites, molinate sulfoxide and molinate sulfone. Previous work demonstrated an in vivo decrease in liver aldehyde dehydrogenase (ALDH) activity in rats treated with molinate and motor function deficits in dogs dosed chronically with this compound. ALDH is an enzyme important in the catabolism of many neurotransmitters, such as dopamine. Inhibition of this enzyme may lead to the accumulation of endogenous neurotoxic metabolites such as 3,4-dihydroxyphenylacetaldehyde, a dopamine metabolite, which may account for the observed neurotoxicity. In this study, the relative reactivity of molinate and both of its sulfoxidation metabolites toward ALDH was investigated, as well as the mechanism of inhibition. The ALDH activity was monitored in two different model systems, human recombinant ALDH (hALDH2) and mouse striatal synaptosomes. Molinate sulfone was found to be the most potent ALDH inhibitor, as compared to molinate and molinate sulfoxide. The reactivity of these three compounds was also assessed, using N-acetyl Cys, model peptides, and hALDH2. It was determined that molinate sulfone is capable of covalently modifying Cys residues, including catalytic Cys302 of ALDH, accounting for the observed enzyme inhibition.

Defining "complications" in spine surgery: neurosurgery and orthopedic spine surgeons' survey.

STUDY DESIGN: Survey of neurosurgical and orthopedic spine surgeons. OBJECTIVE: To define the "complications of spinal surgery," we surveyed a large group of practicing spine surgeons to establish a preliminary definition of perioperative complications. SUMMARY OF BACKGROUND DATA: Although the risk of complications following spinal procedures plays an important role in determining the appropriateness of surgical intervention, there is little consensus among spine surgeons regarding the definition of complications in spine surgery. The relevance of medical complications is also not clearly defined. METHODS: We surveyed a cohort of practicing spine surgeons via email and a commercially maintained website. Surgeons were presented with various complication scenarios, and asked to assess the presence or absence of a complication, as well as complication severity, with responses limited to "major complication" and "minor complication/adverse event." RESULTS: The survey was sent to approximately 2000 practicing surgeons; complete responses were received from 229, giving a response rate of 11.4%. Orthopedic surgeons comprised the majority of respondents (73%); most surgeons reported being in practice for greater than 5 years (83%). Greater than 75% of surgeons agreed on complication presence or absence in 10 of 11 scenarios assessed (91%, P<0.05). Consensus (≥70% agreement, P<0.05) as to type of complication was found in 7 of 11 scenarios presented (64%). Events deemed major complications involved either severe medical adverse events with permanent sequela or events requiring return to the operating room. Surgeons consistently considered medical adverse events, whether or not directly related to surgery, relevant to complication assessment. CONCLUSIONS: We present a practical binary definition of complications in spine surgery based upon a survey of over 200 practicing spine surgeons. Further work is required in critically assessing spine surgery complications.

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.

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.

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.

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.