Analysis of human brain tissue derived from DBS surgery

Background: Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients. Postmortem samples usually represent the advanced disease stage of the patient. Furthermore, the postmortem interval can affect the transcriptomic and proteomic profiles. Therefore, fresh brain tissue samples from living patients represent a valuable resource of metabolically intact tissue. Implantation of deep brain stimulation (DBS) electrodes into the human brain is a neurosurgical treatment for, e.g., movement disorders. Here, we describe an improved approach to collecting brain tissues from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses. Methods: Samples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure to treat patients with Parkinson's disease, genetic dystonia and tremor. RNA sequencing was performed in tissues extracted from the recording microelectrodes and liquid chromatography-mass spectrometry (LC-MS) performed in tissues from guide tubes. To assess the performance of the current approach, the obtained datasets were compared with previously published datasets representing brain tissues. Results: Altogether, 32,034 RNA transcripts representing the unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients. By using LC-MS, we identified 734 unique proteins from 31 samples collected from 14 patients. The datasets are available in the BioStudies database (accession number S-BSST667). Our results indicate that surgical instruments used in DBS installation retain brain material sufficient for protein and gene expression studies. Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the protocol. Conclusions: The instruments used during routine DBS surgery are a useful source for obtaining fresh brain tissues from living patients. This approach overcomes the issues that arise from using postmortem tissues, such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain, and can be used for studying molecular aspects of DBS-treatable diseases.Peer reviewe

Deep brain stimulation in Parkinson’s disease and paediatric DBS service

Abstract Idiopathic Parkinson’s disease (PD) is globally the most common neurodegenerative movement disorder and it affects not only physical and cognition but also the activities of daily living and social life. Deep brain stimulation (DBS) is the neurosurgical treatment in advanced PD and it is the most common indication of DBS surgery. In PD, the most common target area of stimulation is the subthalamic nucleus (STN) in order to alleviate motor symptoms, e.g., rigidity, tremor and bradykinesia. After STN DBS, PD-medication, which includes levodopa, can be reduced. Thus, levodopa-induced involuntary hyperkinetic movements, i.e., dyskinesias are alleviated and the PD patient’s condition becomes more stable. Studies I-II were undertaken to evaluate the beneficial effects of bilateral STN DBS stimulation on PD patient’s motor symptoms and levodopa reduction 12 months after DBS surgery, when the DBS surgery was based on high-quality 3T MRI and the follow-up was conducted by the same DBS team. The results were compared with a previous study from OUH, which was presented by Tuomo Erola in his 2006 thesis. In Study II, the main interest was to study whether stimulation of the hyperdirective pathways between the lateral border of the STN and prefrontal cortex correlated with the motor outcome and levodopa reduction. The study implicated that diffusion tensor images (DTI) -based tractography can be applied in a clinically reasonable way for DBS targeting. The paediatric population is the smallest and the most fragile DBS patient group and the usual indication is severe hyperkinetic movement disorder, e.g., dystonia. Paediatric DBS surgery (pDBS) is not an everyday procedure and the pre- and postoperative preparations are as important as the surgery itself. For this reason practical instructions are required when starting a pDBS centre. This is the topic of Study III.Tiivistelmä Parkinsonin tauti on maailmanlaajuisesti yleisin aivoja rappeuttava liikehäiriösairaus. Se ei vaikuta ainoastaan ruumiillisesti ja tietotaidollisesti, vaan myös potilaan ja hänen läheisten koko arkielämään. Syväaivostimulaatio (engl. deep brain stimulation, DBS) on neurokirurginen hoitomuoto, jonka käytön yleisin peruste on edennyt Parkinsonin tauti. Tavallisimmin stimulaation kohdealueena käytetään aivojen näkökukkulan alapuolista hermosolukertymää (lat. subthalamic nucleus, STN). Tämän alueen stimulointi lievittää parkinsonintaudin liikehäiriöitä (jäykkyyttä, vapinaa ja liikkeiden hitautta). Stimulaation aloituksen jälkeen levodopalääkitystä päästään keventämään, jolloin lääkityksen haittavaikutukset lievittyvät ja potilaan voinnista tulee vakaampi. Tämän tutkimuksen I ja II osatyön aiheena oli arvioida parkinsonpotilaiden liikehäiriöoireiden ja levodopalääkityksen muutoksia 12 kuukauden seuranta-aikana STN DBS leikkauksen jälkeen. Leikkaustoimenpide perustui aivojen korkealaatuiseen korkeakenttämagneettikuvaukseen (3 tesla), ja leikkauksen jälkeinen yhden vuoden pituinen seuranta toteutettiin saman DBS-ryhmän toimesta. Tutkimustuloksia verrattiin Oulun yliopistossa vuonna 2006 julkaistuun Tuomo Erolan väitöskirjan tuloksiin. Lisäksi II osatyössä mielenkiinnon kohteena oli tutkia STN-ulkoreunan sekä otsalohkon etummaisen osan välisiä erityisen nopeita valkeanaivoaineen ratoja sekä sitä, onko ratojen eri osien stimuloinnilla vaikutusta potilaan liikehäiriön tai levodopalääkityksen muutokseen. Tutkimuksen III osatyössä käsiteltiin lasten DBS-hoitoa. Tämän ryhmän potilailla on yleensä vaikea liikehäiriö, kuten esimerkiksi lihasvääntötauti (dystonia), mikä tekee heistä erityisen hauraan potilasryhmän. Lapsipotilaiden DBS-hoito vaatii hyvän ennakkovalmistelun sekä leikkauksen hyvän jälkihoidon ja seurannan. Tämän vuoksi oli tarpeellista luoda ohjeistus lasten DBS-hoidolle

Starting a DBS service for children:it’s not the latitude but the attitude — establishment of the paediatric DBS centre in Northern Finland

Abstract Objective: Paediatric movement disorder patients can benefit from deep brain stimulation (DBS) treatment and it should be offered in a timely manner. In this paper we describe our experience establishing a DBS service for paediatric patients. Methods: We set out to establish a paediatric DBS (pDBS) procedure in Oulu University Hospital in northern Finland, where up to this point DBS treatment for movement disorders had been available for adult patients. Collaboration with experienced centres aided in the process. Results: A multidisciplinary team was assembled and a systematic protocol for patient evaluation and treatment was created, with attention to special features of the regional health care system. All of our first paediatric patients had very severe movement disorders, which is typical for a new DBS centre. The patients benefitted from pDBS treatment despite variable aetiologies of movement disorders, which included cerebral palsy and rare genetic disorders with variants in PDE10A, TPK1 and ARX. We also present our high-quality paediatric MR-imaging protocol with tractography. Conclusions: Establishment of a pDBS centre requires expertise in classification of paediatric movement disorders, longstanding experience in adult DBS and a committed multidisciplinary team. Besides high-quality imaging and a skilled neurosurgery team, careful patient selection, realistic treatment goals and experience in rehabilitation are imperative in pDBS treatment

Syväaivostimulaatio lasten ja nuorten dystonioiden hoidossa

Tiivistelmä Lasten liikehäiriöt ovat etiologialtaan ja taudinkuvaltaan heterogeeninen ryhmä. Vaikeissa häiriöissä vaste lääkehoitoon on usein vähäinen. Syväaivostimulaatio voi merkittävästi auttaa osaa potilaista. Hoitopäätös vaatii moniammatillisen työryhmän arvion liikehäiriön laadusta, neurofysiologiset tutkimukset ja korkealaatuisen kuvantamisen. Lapsia ja nuoria hoitavien yksiköiden on tärkeää verkostoitua kansallisesti ja kansainvälisesti.Abstract Movement disorders are disabling conditions that can cause abnormal posture, torsion, repetitive movement or tremor via the disruption of regulatory areas in the brain. Among paediatric patients, generalised dystonia is the most common primary movement disorder, and dyskinetic CP the most common secondary phenotype, both with limited or unsatisfactory traditional treatment options. The prevalence of dystonia is suggested to be higher than reported since it is not always easy to recognise. Deep brain stimulation (DBS) is an established treatment method for movement disorders in adults, and it has emerged as a significant option for children as well. Treatment seems to be more beneficial when initiated early, since the time spent with dystonia is inversely correlated with the effectiveness of treatment. DBS modifies the basal ganglia-thalamocortical pathways, resulting in alleviation of symptoms. The careful selection of patients and accurate location of the electrodes are important contributors to treatment success. The most prevalent adverse effects are infections or hardware failure; however, these complications are not more prevalent in DBS than in other surgical procedures. DBS is an effective treatment option for severe paediatric movement disorders and it should be offered in a timely manner to patients with severe symptoms

A comparison of indirect and direct targeted STN DBS in the treatment of Parkinson’s disease:surgical method and clinical outcome over 15-year timespan

Abstract Background: Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is used in advanced Parkinson’s disease (PD) for reducing motor fluctuations and the side effects of antiparkinsonian medication (APM). The development of neuroimaging has enabled the direct targeting of the STN. The aim of this study is to evaluate the outcome in patients with PD using STN DBS when changing from atlas-based indirect targeting method (iTM) to direct MRI-based targeting (dTM) assuming dTM is superior. Methods: Twenty-five consecutive PD patients underwent dTM STN DBS surgery from 2014 to 2017 with follow-up for 1 year. The neuroimaging, surgical method, outcome in Unified Parkinson’s Disease Rating Scale (UPDRS) scores, and reduction of APM are described and compared with the results of an earlier iTM STN DBS study. Results: Twelve months after a dTM STN DBS, significant improvement (p < 0.001) was seen in six out of seven parameters of UPDRS when patients had medication (medON) and stimulation (stimON). The activities of daily living (UPDRSII) and motor scores (UPDRSIII) improved by 41% and 62%, respectively. Dyskinesias and fluctuations were both reduced by 81%. In dTM STN DBS group, the levodopa equivalent dose (LED) and the total daily levodopa equivalent dose (LEDD) were significantly decreased by 62% and 55%, respectively, compared with the baseline (p < 0.001). Five patients (20%) were without levodopa medication 12 months after the operation. Conclusions: The development of surgical technique based on advanced neuroimaging has improved the outcome of PD STN DBS

Intracranial bullet removal using O-arm navigation guidance

Abstract Purpose: The purpose of this study is to report a new mini-invasive technique to remove an intracranial bullet in a child by using O-arm for intraoperative neuronavigation. Case report: A 14-year-old refugee boy had suffered a shooting injury 4 years earlier. O-arm imaging-assisted neuronavigation during craniotomy was performed in order to remove a bullet from the intracranial space in a paediatric patient. Conclusion: Navigation using O-arm is a feasible method in removing a foreign material in a child and gave an accurate location of the bullet in the adopted surgical operation position without significant imaging artefacts

Favourable long-term recovery after decompressive craniectomy:the Northern Finland experience with a predominantly adolescent patient cohort

Abstract Purpose: Decompressive craniectomy (DC) is an effective treatment of intracranial hypertension. Correspondingly, the procedure is increasingly utilised worldwide. The number of patients rendered vegetative following surgery has been a concern—a matter especially important in children, due to long anticipated lifetime. Here, we report the long-term outcomes of all paediatric DC patients from an 11-year period in a tertiary-level centre that geographically serves half of Finland. Methods: We identified all patients younger than 18 years who underwent DC in the Oulu University Hospital between the years 2009 and 2019. Outcomes and clinicoradiological variables were extracted from the patient records. Results: Mean yearly prevalence of brain injury requiring DC was 1.34/100 000 children—twenty-four patients underwent DC during the study period and 21 (88%) survived. The median age of the patients was 16.0 years, and the median preoperative GCS was 5.0 (IQR 5.0). Fifteen patients (63%) had made a good recovery (Extended Glasgow Outcome Scale ≥ 7). Of the surviving patients, two (9.5%) had not returned to school. After traumatic brain injury (n = 20), the Rotterdam CT score (mean 3.0, range 1 to 5) was not associated with mortality, poor recovery or inability to continue school (p = 0.13, p = 0.41, p = 0.43, respectively). Absent basal cisterns were associated with mortality (p = 0.005), but not with poor recovery if the patient survived DC (p = 0.81). Hydrocephalus was associated with poor recovery and inability to continue school (p = 0.01 and p = 0.03, respectively). Conclusion: Most of our patients made a favourable recovery and were able to continue school. No late mortality was observed. Thus, even in clinically and radiologically severely brain-injured children, decompressive craniectomy appears to yield favourable outcomes

Analysis of human brain tissue derived from DBS surgery

Abstract Background: Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients. Postmortem samples usually represent the advanced disease stage of the patient. Furthermore, the postmortem interval can affect the transcriptomic and proteomic profiles. Therefore, fresh brain tissue samples from living patients represent a valuable resource of metabolically intact tissue. Implantation of deep brain stimulation (DBS) electrodes into the human brain is a neurosurgical treatment for, e.g., movement disorders. Here, we describe an improved approach to collecting brain tissues from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses. Methods: Samples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure to treat patients with Parkinson’s disease, genetic dystonia and tremor. RNA sequencing was performed in tissues extracted from the recording microelectrodes and liquid chromatography-mass spectrometry (LC-MS) performed in tissues from guide tubes. To assess the performance of the current approach, the obtained datasets were compared with previously published datasets representing brain tissues. Results: Altogether, 32,034 RNA transcripts representing the unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients. By using LC-MS, we identified 734 unique proteins from 31 samples collected from 14 patients. The datasets are available in the BioStudies database (accession number S-BSST667). Our results indicate that surgical instruments used in DBS installation retain brain material sufficient for protein and gene expression studies. Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the protocol. Conclusions: The instruments used during routine DBS surgery are a useful source for obtaining fresh brain tissues from living patients. This approach overcomes the issues that arise from using postmortem tissues, such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain, and can be used for studying molecular aspects of DBS-treatable diseases