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

Serum HMGB1 in febrile seizures

The role of high-mobility group box 1 (HMGB1) in the pathogenesis of febrile seizures (FSs) is unclear. In our controlled follow-up study, we compared serum levels of HMGB1 (s-HMGB1) in the same individuals after the first FS, during febrile episodes without a FS, after recurrent FS, during healthy periods after FS, and between patients and controls. In all, 122 patients with FSs were included in the final analysis, including 18 with recurrent FSs with a complete follow-up protocol. We recruited 30 febrile children and 18 matched febrile children without seizures as controls. S-HMGB1 was lower in patients with recurrent FSs after the first FS than that in matched febrile control children (median 1.12 μg/L (0.14–2.95) vs 1.79 μg/L (0.33–47.90), P<0.04). We did not find any other differences in s-HMGB1 between the groups. S-HMGB1 did not differ in different types of FSs. We updated a meta-analysis of s-HMGB1 in patients with FSs and found that the differences were significant only in the studies conducted in East Asian populations. We conclude that S-HMGB1 does not seem to be a key factor in the pathogenesis of FSs but differences in HMGB1 concentrations could explain some of the ethnicity related susceptibility to FSs.Peer reviewe

Recurrent febrile seizures and serum cytokines : a controlled follow-up study

Background The role of cytokines in the pathogenesis of febrile seizures (FSs) is unclear, and information regarding cytokine production outside of FS episodes is scarce. Methods In our controlled follow-up study of patients with FSs, we compared the levels of 12 serum cytokines after the patients' first FSs, during febrile episodes without FSs, after recurrent FSs, during healthy periods after FSs, and between patients and controls. Results Two-hundred fifty-one patients with first FS participated in the study, of whom 17 (mean age 1.6 years, SD 0.7) with recurrent FSs completed the protocol as required by the sample size calculations. The mean IL-1RA level was higher after the first FSs (2580 pg/mL, SD 1516) than during febrile episodes without FSs (1336 pg/mL, SD 1364, P = 0.006) and healthy periods after FSs (474 pg/mL, SD 901, P = 0.001). IL-1RA levels were also higher during first (2580 pg/mL) and recurrent FSs (2666 pg/mL, SD 1747) in comparison with febrile controls (746 pg/mL, SD 551) (P < 0.001 and P = 0.001, respectively), but there was no difference in the IL-1RA between febrile episodes without FSs and febrile controls. Conclusions Patients with FSs produce stronger inflammatory reactions during febrile episodes with FSs compared with febrile episodes without FSs and febrile controls. Impact In patients with FSs, IL-1RA was higher following first FS than during febrile episodes without FSs and healthy periods after FSs. IL-1RA was higher in patients with FSs following first and recurrent FSs than in febrile controls. There was no significant difference in IL-1RA between febrile episodes of patients without FSs and febrile controls. Using IL-1RA as a surrogate marker of IL-1 axis activity, our results indicate that patients with FSs produced stronger inflammatory reactions during FS episodes but not during other febrile episodes or healthy periods after FSs. Cytokines may play a role in pathogenesis of FSs.Peer reviewe

Recurrent febrile seizures and serum cytokines:a controlled follow-up study

Abstract Background: The role of cytokines in the pathogenesis of febrile seizures (FSs) is unclear, and information regarding cytokine production outside of FS episodes is scarce. Methods: In our controlled follow-up study of patients with FSs, we compared the levels of 12 serum cytokines after the patients’ first FSs, during febrile episodes without FSs, after recurrent FSs, during healthy periods after FSs, and between patients and controls. Results: Two-hundred fifty-one patients with first FS participated in the study, of whom 17 (mean age 1.6 years, SD 0.7) with recurrent FSs completed the protocol as required by the sample size calculations. The mean IL-1RA level was higher after the first FSs (2580 pg/mL, SD 1516) than during febrile episodes without FSs (1336 pg/mL, SD 1364, P = 0.006) and healthy periods after FSs (474 pg/mL, SD 901, P = 0.001). IL-1RA levels were also higher during first (2580 pg/mL) and recurrent FSs (2666 pg/mL, SD 1747) in comparison with febrile controls (746 pg/mL, SD 551) (P &lt; 0.001 and P = 0.001, respectively), but there was no difference in the IL-1RA between febrile episodes without FSs and febrile controls. Conclusions: Patients with FSs produce stronger inflammatory reactions during febrile episodes with FSs compared with febrile episodes without FSs and febrile controls