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  • 1. Adams, David
    et al.
    Suhr, Ole
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Conceicao, Isabel
    Waddington-Cruz, Marcia
    Schmidt, Hartmut
    Buades, Juan
    Campistol, Josep
    Pouget, Jean
    Berk, John
    Coelho, Teresa
    Phase 2 open-label extension study of patisiran, an investigational RNAi therapeutic for the treatment of familial amyloid polyneuropathy2015Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, nr 11Artikkel i tidsskrift (Annet vitenskapelig)
  • 2.
    Bergenheim, Tommy A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL Institute of Neurology, London, UK.
    Selective peripheral denervation for cervical dystonia: long-term follow-up2015Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, nr 12, s. 1307-1313Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: 61 procedures with selective peripheral denervation for cervical dystonia were retrospectively analysed concerning surgical results, pain, quality of life (QoL) and recurrences.

    METHODS: The patients were assessed with the Tsui torticollis scale, Visual Analogue Scale (VAS) for pain and Fugl-Meyer scale for QoL. Evaluations were performed preoperatively, early postoperatively, at 6 months, then at a mean of 42 (13-165) months. All patients underwent electromyogram at baseline, which was repeated in cases who presented with recurrence of symptoms after surgery.

    RESULTS: Six months of follow-up was available for 55 (90%) of the procedures and late follow-up for 34 (56%). The mean score of the Tsui scale was 10 preoperatively. It improved to 4.5 (p<0.001) at 6 months, and 5.3 (p<0.001) at late follow-up. VAS for pain improved from 6.5 preoperatively to 4.2 (p<0.001) at 6 months and 4 (p<0.01) at late follow-up. The Fugl-Meyer score for QoL improved from 43.3 to 46.6 (p<0.05) at 6 months, and to 51.1 (p<0.05) at late follow-up. Major reinnervation and/or change in the dystonic pattern occurred following 29% of the procedures, and led in 26% of patients to reoperation with either additional denervation or pallidal stimulation.

    CONCLUSIONS: Selective peripheral denervation remains a surgical option in the treatment of cervical dystonia when conservative measures fail. Although the majority of patients experience a significant relief of symptoms, there is a substantial risk of reinnervation and/or change in the pattern of the cervical dystonia.

  • 3.
    Binzer, M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Andersen, P M
    Kullgren, Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Clinical characteristics of patients with motor disability due to conversion disorder: a prospective control group study.1997Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 63, nr 1, s. 83-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Previous studies have suggested associations between conversion and many different clinical characteristics. This study investigates these findings in a prospective design including a control group. METHODS: Thirty consecutive patients with a recent onset of motor disability due to a conversion disorder were compared with a control group of patients with corresponding motor symptoms due to a definite organic lesion. Both groups had a similar duration of symptoms and a comparable age and sex profile and were assessed on a prospective basis. Background information about previous somatic and psychiatric disease was collected and all patients were assessed by means of a structured clinical interview linked to the diagnostic system DSM III-R, the Hamilton rating depression scale, and a special life events inventory. RESULTS: The conversion group had a higher degree of psychopathology with 33% of the patients fulfilling the criteria for psychiatric syndromes according to DSM-III-R axis I, whereas 50% had axis II personality disorders compared with 10% and 17% respectively in the control group. Conversion patients also had significantly higher scores according to the Hamilton rating depression scale. Although patients with known neurological disease were not included in the conversion group, a concomitant somatic disorder was found in 33% of the patients and 50% complained of benign pain. The educational background in conversion patients was poor with only 13% having dropped out of high school compared with 67% in the control group. Self reported global assessment of functioning according to the axis V on DSM IV was significantly lower in conversion patients, who also registered significantly more negative life events before the onset of symptoms than controls. Logistic regression analysis showed that low education, presence of a personality disorder, and high Hamilton depression score were significantly associated with conversion disorder. CONCLUSION: The importance of several previously reported predisposing and precipitating factors in conversion disorder is confirmed. The results support the notion that conversion should be treated as a symptom rather than a diagnosis and that efforts should be made in diagnosing and treating possible underlying somatic and psychiatric conditions.

  • 4. Blain, C R V
    et al.
    Brunton, S
    Williams, V C
    Leemans, A
    Turner, M R
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Catani, M
    Stanton, B R
    Ganesalingham, J
    Jones, D K
    Williams, S C R
    Leigh, P N
    Simmons, A
    Differential corticospinal tract degeneration in homozygous 'D90A' SOD-1 ALS and sporadic ALS2011Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 82, nr 8, s. 843-849Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The homogeneous genotype and stereotyped phenotype of a unique familial form of amyotrophic lateral sclerosis (ALS) (patients homozygous for aspartate-to-alanine mutations in codon 90 (homD90A) superoxide dismutase 1) provides an ideal model for studying genotype/phenotype interactions and pathological features compared with heterogeneous apparently sporadic ALS. The authors aimed to use diffusion tensor tractography to quantify and compare changes in the intracerebral corticospinal tracts of patients with both forms of ALS, building on previous work using whole-brain voxelwise group analysis.

    METHOD: 21 sporadic ALS patients, seven homD90A patients and 20 healthy controls underwent 1.5&emsp14;T diffusion tensor MRI. Patients were assessed using 'upper motor neuron burden,' El Escorial and ALSFR-R scales. The intracranial corticospinal tract was assessed using diffusion tensor tractography measures of fractional anisotropy (FA), mean diffusivity, and radial and axial diffusivity obtained from its entire length.

    RESULTS: Corticospinal tract FA was reduced in sporadic ALS patients compared with both homD90A ALS patients and controls. The diffusion measures in sporadic ALS patients were consistent with anterograde (Wallerian) degeneration of the corticospinal tracts. In sporadic ALS, corticospinal tract FA was related to clinical measures. Despite a similar degree of clinical upper motor neuron dysfunction and disability in homD90A ALS patients compared with sporadic ALS, there were no abnormalities in corticospinal tract diffusion measures compared with controls.

    CONCLUSIONS: Diffusion tensor tractography has shown axonal degeneration within the intracerebral portion of the corticospinal tract in sporadic ALS patients, but not those with a homogeneous form of familial ALS. This suggests significant genotypic influences on the phenotype of ALS and may provide clues to slower progression of disease in homD90A patients.

  • 5.
    Blomstedt, Patric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stenmark Persson, Rasmus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Gun-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Fredricks, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Häggström, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Philipsson, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, UCL Institute of Neurology, London, UK.
    Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation2018Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 89, nr 7, s. 710-716Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Several open-label studies have shown good effect of deep brain stimulation (DBS) in the caudal zona incerta (cZi) on tremor, including parkinsonian tremor, and in some cases also a benefit on akinesia and axial symptoms. The aim of this study was to evaluate objectively the effect of cZi DBS in patients with Parkinson's disease (PD).

    Method: 25 patients with PD were randomised to either cZi DBS or best medical treatment. The primary outcomes were differences between the groups in the motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS-III) rated single-blindly at 6 months and differences in the Parkinson's Disease Questionnaire 39 items (PDQ-39). 19 patients, 10 in the medical arm and 9 in the DBS arm, fulfilled the study.

    Results: The DBS group had 41% better UPDRS-III scores off-medication on-stimulation compared with baseline, whereas the scores of the non-surgical patients off-medication were unchanged. In the on-medication condition, there were no differences between the groups, neither at baseline nor at 6 months. Subitems of the UPDRS-III showed a robust effect of cZi DBS on tremor. The PDQ-39 domains 'stigma' and 'ADL' improved only in the DBS group. The PDQ-39 summary index improved in both groups.

    Conclusion: This is the first randomised blinded evaluation of cZi DBS showing its efficacy on PD symptoms. The most striking effect was on tremor; however, the doses of dopaminergic medications could not be decreased. cZi DBS in PD may be an addition to existing established targets, enabling tailoring the surgery to the needs of the individual patient.

  • 6. Burman, Joachim
    et al.
    Iacobaeus, Ellen
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lycke, Jan
    Gunnarsson, Martin
    Nilsson, Petra
    Vrethem, Magnus
    Fredrikson, Sten
    Martin, Claes
    Sandstedt, Anna
    Uggla, Bertil
    Lenhoff, Stig
    Johansson, Jan-Erik
    Isaksson, Cecilia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Hägglund, Hans
    Carlson, Kristina
    Fagius, Jan
    Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience2014Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, nr 10, s. 1116-1121Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS. METHODS: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months. RESULTS: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%). CONCLUSIONS: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.

  • 7.
    Farahmand, Dan
    et al.
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wikkelsö, Carsten
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Tisell, Magnus
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Intracranial pressure in hydrocephalus: impact of shunt adjustments and body positions2015Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, nr 2, s. 222-228Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The association between intracranial pressure (ICP) and different shunt valve opening pressures in relation to body positions is fundamental for understanding the physiological function of the shunt.

    Objective To analyse the ICP and ICP wave amplitude (AMP) at different shunt settings and body positions in patients with hydrocephalus.

    Methods In this prospective study 15 patients with communicating hydrocephalus were implanted with a ligated adjustable ventriculoperitoneal shunt. They also received a portable intraparenchymatous ICP-monitoring device. Postoperative ICP and AMP were recorded with the patients in three different body positions (supine, sitting and walking) and with the shunt ligated and open at high, medium and low valve settings. In each patient 12 10 min segments were coded, blinded and analysed for mean ICP and mean AMP using an automated computer algorithm.

    Results Mean ICP and mean AMP were lower at all three valve settings compared with the ligated shunt state (p<0.001). Overall, when compared with the supine position, mean ICP was 11.5 +/- 1.1 (mean +/- SD) mm Hg lower when sitting and 10.5 +/- 1.1 mm Hg lower when walking (p<0.001). Mean ICP was overall 1.1 mm Hg higher (p=0.042) when walking compared with sitting. The maximal adjustability difference (highest vs lowest valve setting) was 4.4 mm Hg.

    Conclusions Changing from a supine to an upright position reduced ICP while AMP only increased at trend level. Lowering of the shunt valve opening pressure decreased ICP and AMP but the difference in mean ICP in vivo between the highest and lowest opening pressures was less than half that previously observed in vitro.

  • 8. Felbecker, Ansgar
    et al.
    Camu, William
    Valdmanis, Paul N
    Sperfeld, Anne-Dorte
    Waibel, Stefan
    Steinbach, Peter
    Rouleau, Guy A
    Ludolph, Albert C
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Four familial ALS pedigrees discordant for two SOD1 mutations: are all SOD1 mutations pathogenic?2010Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 81, nr 5, s. 572-577Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: 153 mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been claimed to be associated with amyotrophic lateral sclerosis (ALS) in familial and sporadic ALS in an autosomal dominant or autosomal recessive pattern with complete or reduced penetrance. The authors now report four ALS pedigrees from Finland, France, Germany and Sweden with either the D90A or E100K SOD1 mutations in some but not all affected members. After re-collecting DNA, the non-segregation of the SOD1 mutations with disease was confirmed by three independent laboratories using different PCR primers: while some of the affected patients carry SOD1 mutations, other affected family members have two wildtype/normal SOD1 genes. In addition, some unaffected members within the same families are carriers of SOD1 gene mutations. To exclude other known genetic causes, the authors ruled out mutations within the genes coding for VAPB, ANG, TDP43, FUS and DCTN1 in affected individuals in the four pedigrees.

    CONCLUSIONS: The authors find that the D90A and E100K SOD1 gene mutations found in some patients are not the exclusive cause of ALS in these pedigrees. Whether this is also the case for the other 151 SOD1 mutations reported in ALS pedigrees is unknown. The findings have consequences for genetic testing in clinical practice when diagnosing ALS and for genetic counselling in ALS. Some SOD1 mutations may be part of an oligo- or epigentic pattern of inheritance. Such a pattern of inheritance may model other oligo- or polygenetic traits responsible for other forms of ALS.

  • 9. Foltynie, T
    et al.
    Zrinzo, L
    Martinez-Torres, I
    Tripoliti, E
    Petersen, E
    Holl, E
    Aviles-Olmos, I
    Jahanshahi, M
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Limousin, P
    MRI-guided STN DBS in Parkinson's disease without microelectrode recording: efficacy and safety2011Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 82, nr 4, s. 358-363Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinson's disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology and Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording. Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6)&emsp14;mm. There were no haemorrhagic complications. At a median follow-up period of 12&emsp14;months, there was a mean improvement in the off-medication motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition, there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre-operatively, to 1.56 (SD 1.92) post-operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinson's disease Questionnaire 39 summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity.

  • 10.
    Forsberg, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Graffmo, Karin Sixtensdotter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Pakkenberg, Bente
    Weber, Markus
    Nielsen, Martin
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Munch Andersen, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS/FTD-associated genes2019Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, nr 8, s. 861-869Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: A hallmark of amyotrophic lateral sclerosis (ALS) caused by mutations in superoxide dismutase-1 (SOD1) are inclusions containing SOD1 in motor neurons. Here, we searched for SOD1-positive inclusions in 29 patients carrying ALS-linked mutations in six other genes.

    Methods: A panel of antibodies that specifically recognise misfolded SOD1 species were used for immunohistochemical investigations of autopsy tissue.

    Results: The 18 patients with hexanucleotide-repeat-expansions in C9orf72 had inclusions of misfolded wild type (WT) SOD1(WT) in spinal motor neurons. Similar inclusions were occasionally observed in medulla oblongata and in the motor cortex and frontal lobe. Patients with mutations in FUS, KIF5A, NEK1, ALSIN or VAPB, carried similar SOD1(WT) inclusions. Minute amounts of misSOD1(WT) inclusions were detected in 2 of 20 patients deceased from non-neurological causes and in 4 of 10 patients with other neurodegenerative diseases. Comparison was made with 17 patients with 9 different SOD1 mutations. Morphologically, the inclusions in patients with mutations in C9orf72HRE, FUS, KIF5A, NEK1, VAPB and ALSIN resembled inclusions in patients carrying the wildtype-like SOD1(D90A) mutation, whereas patients carrying unstable SOD1 mutations (A4V, V5M, D76Y, D83G, D101G, G114A, G127X, L144F) had larger skein-like SOD1-positive inclusions.

    Conclusions and relevance Abundant inclusions containing misfolded SOD1(WT) are found in spinal and cortical motor neurons in patients carrying mutations in six ALS-causing genes other than SOD1. This suggests that misfolding of SOD1(WT) can be part of a common downstream event that may be pathogenic. The new anti-SOD1 therapeutics in development may have applications for a broader range of patients.

  • 11.
    Fytagoridis, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Sandvik, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Åström, Mattias
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor2012Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, nr 3, s. 258-262Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose The ventral intermediate nucleus of thalamus is the standard target for deep brain stimulation (DBS) in essential tremor (ET). However, favourable data have recently highlighted the caudal zona incerta (cZi) as an alternative target. Reports concerning the long-term results are however lacking, and we have therefore evaluated the long-term effects in our patients with ET and cZi DBS.

    Methods 18 patients were evaluated using the Essential Tremor Rating Scale (ETRS) before and on-/off-stimulation at 1 and 3-5 years after surgery (mean 48.5±10.6 months). Two patients were operated on bilaterally but all electrodes were evaluated separately. The stimulation parameters were recorded and the stimulation strength calculated.

    Results A baseline total ETRS mean score of 46.0 decreased to 21.9 (52.4%) at the final evaluation. On the treated side, tremor of the upper extremity (item 5 or 6) improved from 6.1 to 0.5 (91.8%) and hand function (items 11-14) improved from 9.3 to 2.0 (78.0%). Activities of daily living improved by 65.8%. There was no increase in stimulation strength over time.

    Conclusion cZi DBS is a safe and effective treatment for the long term suppression of ET.

  • 12.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lindberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Impact of thalamic deep brain stimulation on disability and health-related quality of life in patients with essential tremor2002Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 72, nr 1, s. 47-52Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To evaluate the impact of thalamic deep brain stimulation (DBS) on disability and health-related quality of life in patients with essential tremor.

    METHODS: Twenty seven consecutive patients were evaluated prospectively, before surgery and at a mean of 12 months (range 6-26) after thalamic DBS. Assessment tools included the Fahn-Tolosa-Marìn tremor rating scale (TRS), activities of daily living (ADL) taxonomy, Nottingham health profile (NHP) and the visual analogue scale (VAS) for measuring impact of disease on life. Additional information on the side effects of, and expectations from surgery was obtained by interview.

    RESULTS: Thalamic DBS improved the ability of the patients in eating, drinking, writing, home maintenance, hobbies, and participation in society. Activities of daily life requiring bimanual skills were less improved. The emotional condition of the patients was positively affected and the negative impact of the disease on life as a whole, and on social life was decreased. Seventy per cent of the patients considered that the surgical treatment met their expectations.

    CONCLUSIONS: After thalamic DBS, health-related quality of life including disability in ADL and social life were improved in patients with essential tremor.

  • 13. Malm, J
    et al.
    Kristensen, B
    Ekstedt, J
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wester, P
    CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters.1991Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 54, nr 3, s. 252-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion.

  • 14. Menke, Ricarda A. L.
    et al.
    Proudfoot, Malcolm
    Wuu, Joanne
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Talbot, Kevin
    Benatar, Michael
    Turner, Martin R.
    Increased functional connectivity common to symptomatic amyotrophic lateral sclerosis and those at genetic risk2016Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 87, nr 6, s. 580-588Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To discern presymptomatic changes in brain structure or function using advanced MRI in carriers of mutations predisposing to amyotrophic lateral sclerosis (ALS).

    Methods T1-weighted, diffusion weighted and resting state functional MRI data were acquired at 3 T for 12 asymptomatic mutation carriers (psALS), 12 age-matched controls and affected patients with ALS. Cortical thickness analysis, voxel-based morphometry, volumetric and shape analyses of subcortical structures, tract-based spatial statistics of metrics derived from the diffusion tensor, and resting state functional connectivity (FC) analyses were performed.

    Results Grey matter cortical thickness and shape analysis revealed significant atrophy in patients with ALS (but not psALS) compared with controls in the right primary motor cortex and right caudate. Comparison of diffusion tensor metrics showed widespread fractional anisotropy and radial diffusivity differences in patients with ALS compared to controls and the psALS group, encompassing parts of the corpus callosum, corticospinal tracts and superior longitudinal fasciculus. While FC in the resting-state sensorimotor network was similar in psALS and controls, FC between the cerebellum and a network comprising the precuneus, cingulate & middle frontal lobe was significantly higher in psALS and affected ALS compared to controls.

    Conclusions Rather than structural brain changes, increased FC may be among the earliest detectable brain abnormalities in asymptomatic carriers of ALS-causing gene mutations. With replication and significant refinement, this technique has potential in the future assessment of neuroprotective strategies.

  • 15. Miltenberger-Miltenyi, Gabriel
    et al.
    Conceicao, Vasco A.
    Gromicho, Marta
    Pronto-Laborinho, Ana Catarina
    Pinto, Susana
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    de Carvalho, Mamede
    C9orf72 expansion is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis2019Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, nr 1, s. 118-120Artikkel i tidsskrift (Fagfellevurdert)
  • 16.
    Minde, Jan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Andersson, T
    Department of Clinical Neuroscience Section of Neurophysiology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden .
    Fulford, M
    Department of Internal Medicine, Gällivare Hospital, Gällivare, Sweden.
    Aguirre, M
    Department of Clinical Neuroscience Section of Neurophysiology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden .
    Nennesmo, I
    Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Remahl, I Nilsson
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Holmberg, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Toolanen, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Solders, G
    Department of Clinical Neuroscience Section of Neurophysiology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden .
    A novel NGFB point mutation: a phenotype study of heterozygous patients2009Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, nr 2, s. 188-195Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: A family with neurological findings similar to hereditary sensory and autonomic neuropathy type V having a point mutation in the nerve growth factor beta (NGFB) gene was recently described. The homozygous genotype gives disabling symptoms. The purpose of the present study was to evaluate the symptoms in heterozygous patients. METHODS: 26 patients heterozygous for the NGFB mutation (12 men, mean age 50 (13-90) years) were examined clinically and answered a health status questionnaire, including the Michigan Neuropathy Screening Instrument (MNSI). 28 relatives (15 men, mean age 44 (15-86) years) without the mutation served as controls in the clinical examination part. 23 of the heterozygotes were examined neurophysiologically and six heterozygous patients underwent a sural nerve biopsy. RESULTS: The heterozygous phenotype ranged from eight patients with Charcot arthropathy starting in adult age and associated with variable symptoms of neuropathy but without complete insensitivity to pain, anhidrosis or mental retardation, to 10 symptom free patients. There was no difference in MNSI between the young heterozygous cases (<55 years old) and the controls. Six of 23 heterozygous patients had impaired cutaneous thermal perception and 11 of 23 had signs of carpal tunnel syndrome. Sural nerve biopsies showed a moderate reduction of both small myelinated (Adelta) and unmyelinated (C) fibres. No apparent correlation of small fibre reduction to symptoms was found. CONCLUSIONS: The NGFB mutation in its heterozygous form results in a milder disease than in homozygotes, with a variable clinical picture, ranging from asymptomatic cases to those with Charcot arthropathy appearing in adult age. Particularly age, but perhaps lifestyle factors also, may influence the development of clinical polyneuropathy.

  • 17. Mueller, Kathrin
    et al.
    Brenner, David
    Weydt, Patrick
    Meyer, Thomas
    Grehl, Torsten
    Petri, Susanne
    Grosskreutz, Julian
    Schuster, Joachim
    Volk, Alexander E.
    Borck, Guntram
    Kubisch, Christian
    Klopstock, Thomas
    Zeller, Daniel
    Jablonka, Sibylle
    Sendtner, Michael
    Klebe, Stephan
    Knehr, Antje
    Guenther, Kornelia
    Weis, Joachim
    Claeys, Kristl G.
    Schrank, Berthold
    Sperfeld, Anne-Dorte
    Huebers, Annemarie
    Otto, Markus
    Dorst, Johannes
    Meitinger, Thomas
    Strom, Tim M.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Neurology, Ulm University, Ulm, Germany.
    Ludolph, Albert C.
    Weishaupt, Jochen H.
    Comprehensive analysis of the mutation spectrum in 301 German ALS families2018Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 89, nr 8, s. 817-827Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Recent advances in amyotrophic lateral sclerosis (ALS) genetics have revealed that mutations in any of more than 25 genes can cause ALS, mostly as an autosomal-dominant Mendelian trait. Detailed knowledge about the genetic architecture of ALS in a specific population will be important for genetic counselling but also for genotype-specific therapeutic interventions.

    Methods Here we combined fragment length analysis, repeat-primed PCR, Southern blotting, Sanger sequencing and whole exome sequencing to obtain a comprehensive profile of genetic variants in ALS disease genes in 301 German pedigrees with familial ALS. We report C9orf72 mutations as well as variants in consensus splice sites and non-synonymous variants in protein-coding regions of ALS genes. We furthermore estimate their pathogenicity by taking into account type and frequency of the respective variant as well as segregation within the families.

    Results 49% of our German ALS families carried a likely pathogenic variant in at least one of the earlier identified ALS genes. In 45% of the ALS families, likely pathogenic variants were detected in C9orf72, SOD1, FUS, TARDBP or TBK1, whereas the relative contribution of the other ALS genes in this familial ALS cohort was 4%. We identified several previously unreported rare variants and demonstrated the absence of likely pathogenic variants in some of the recently described ALS disease genes.

    Conclusions We here present a comprehensive genetic characterisation of German familial ALS. The present findings are of importance for genetic counselling in clinical practice, for molecular research and for the design of diagnostic gene panels or genotype-specific therapeutic interventions in Europe.

  • 18. Nuttin, Bart
    et al.
    Wu, Hemmings
    Mayberg, Helen
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. WSSFN Committee on Neurosurgery for Psychiatric Disorders.
    Gabriëls, Loes
    Galert, Thorsten
    Merkel, Reinhard
    Kubu, Cynthia
    Vilela-Filho, Osvaldo
    Matthews, Keith
    Taira, Takaomi
    Lozano, Andres M.
    Schechtmann, Gastón
    Doshi, Paresh
    Broggi, Giovanni
    Régis, Jean
    Alkhani, Ahmed
    Sun, Bomin
    Eljamel, Sam
    Schulder, Michael
    Kaplitt, Michael
    Eskandar, Emad
    Rezai, Ali
    Krauss, Joachim K.
    Hilven, Paulien
    Schuurman, Rick
    Ruiz, Pedro
    Chang, Jin Woo
    Cosyns, Paul
    Lipsman, Nir
    Voges, Juergen
    Cosgrove, Rees
    Li, Yongjie
    Schlaepfer, Thomas
    Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders2014Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, nr 9, s. 1003-1008Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background For patients with psychiatric illnesses remaining refractory to 'tandard' therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. Methods To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. Findings The proposed consensus document highlights that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered 'stablished' in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioural disorder, still remains at an investigational stage. Researchers are encouraged to design randomised controlled trials, based on scientific and data-driven rationales for disease and brain target selection. Experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient's capacity and autonomy, multifaceted preoperative as well as postoperative long-term follow-p evaluation, and reporting of effects and side effects for all patients. Interpretation This consensus document on ethical and scientific conduct of psychiatric surgery worldwide is designed to enhance patient safety.

  • 19. Oeckl, Patrick
    et al.
    Weydt, Patrick
    Steinacker, Petra
    Anderl-Straub, Sarah
    Nordin, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Volk, Alexander E.
    Diehl-Schmid, Janine
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Neurology, Ulm University hospital, Ulm, Germany.
    Kornhuber, Johannes
    Danek, Adrian
    Fassbender, Klaus
    Fliessbach, Klaus
    Jahn, Holger
    Lauer, Martin
    Mueller, Kathrin
    Knehr, Antje
    Prudlo, Johannes
    Schneider, Anja
    Thal, Dietmar R.
    Yilmazer-Hanke, Deniz
    Weishaupt, Jochen H.
    Ludolph, Albert C.
    Otto, Markus
    Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase2019Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, nr 1, s. 4-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers.

    Methods: The neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA.

    Results: CSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (-80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05).

    Conclusion: Our data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome.

  • 20.
    Olivecrona, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Rodling-Wahlström, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Naredi, Silvana
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    S-100B and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy2009Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, nr 11, s. 1241-1247Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To prospectively study S-100B and neuron specific enolase (NSE) levels in subjects treated for severe head injury (sTBI), and investigate the prognostic value of these biomarkers. METHODS: Subjects included in a prospective double blind randomised study for sTBI. Inclusion criteria: Glasgow Coma Score (GCS) 10 mm Hg and arrival <24 h after trauma. Subjects were treated with an intracranial pressure (ICP) targeted therapy. Blood samples for S-100B and NSE were drawn immediately after arrival and every 12 h for 5 days. Outcome was evaluated as Glasgow Outcome Scale (GOS) by independent staff at 3 and 12 months. RESULTS: 48 subjects, mean age 35.5 years, and median GCS 6 were included. The first blood sample was drawn at 15.6 (1.4) h after injury. Initial concentration of S-100B was 1.04 (0.21) microg/l and for NSE 18.94 (2.32) microg/l. The biomarkers were significantly higher in subjects with GCS 3 and in those who died compared with those with GCS 4-8 and GOS 2-5, respectively. Receiver operated characteristic curve analyses of the initial S-100B and NSE levels to GOS dichotomised as unfavourable (GOS 1-3) and favourable (GOS 4-5) showed a weak correlation: AUC 0.585 and 0.555, respectively. Using the dichotomisation dead (GOS 1)/alive (GOS 2-5), the AUC values were 0.687 and 0.734, respectively. Furthermore, a correlation was found between the biomarkers themselves and the biomarkers and ICP. CONCLUSION: At 3 and 12 months after trauma, no differences in prognostic values between the markers were apparent nor was there any clinical significant value of the markers as predictors of clinical outcome.

  • 21. Press, R.
    et al.
    Askmark, H.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Andersen, O.
    Axelson, H. W.
    Stroemberg, U.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Isaksson, C.
    Johansson, J-EJ.
    Haegglund, H.
    Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP2014Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, nr 6, s. 618-624Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months. Method Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients. Results The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis. Conclusions Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.

  • 22.
    Qvarlander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Lundkvist, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus2013Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, nr 7, s. 735-741Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: It is suggested that disturbed CSF dynamics are involved in the pathophysiology of idiopathic normal pressure hydrocephalus (INPH). The pulsatility curve describes the relationship between intracranial pressure (ICP) and the amplitude of cardiac related ICP pulsations. The position of baseline ICP on the curve provides information about the physiological state of the CSF dynamic system. The objective of the study was to investigate if shunt surgery modifies the pulsatility curve and the baseline position on the curve, and how this relates to gait improvement in INPH.

    Methods: 51 INPH patients were investigated with lumbar CSF dynamic investigations preoperatively and 5 months after shunt surgery. During the investigation, ICP was measured at baseline, and then a CSF sample was removed, resulting in pressure reduction. After this, ICP was regulated with an automated infusion protocol, with a maximum increase of 24 mm Hg above baseline. The pulsatility curve was thus determined in a wide range of ICP values. Gait improvement was defined as a gait speed increase >= 0.1 m/s.

    Results: The pulsatility curve was unaltered by shunting. Baseline ICP and amplitude were reduced (-3.0 +/- 2.9 mm Hg; -1.1 +/- 1.5 mm Hg; p < 0.05, n = 51). Amplitude reduction was larger for gait improvers (-1.2 +/- 1.6 mm Hg, n = 42) than non-improvers (-0.2 +/- 0.5 mm Hg, n = 9) (p < 0.05) although mean ICP reduction did not differ.

    Conclusions: The pulsatility curve was not modified by shunt surgery, while the baseline position was shifted along the curve. Observed differences between gait improvers and non-improvers support cardiac related ICP pulsations as a component of INPH pathophysiology.

  • 23. Schmidt, Hartmut
    et al.
    Adams, David
    Coelho, Teresa
    Conceicao, Isabel
    Waddington-Cruz, Marcia
    Buades, Juan
    Campistol, Josep
    Pouget, Jean
    Gollob, Jared
    Suhr, Ole
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Patisiran ph 2 open-label extension study in Familial Amyloidotic Polyneuropathy2016Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 87, nr 12Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: Familial Amyloid Polyneuropathy (FAP) is a progressive disease caused by deposition of transthyretin (TTR). Patisiran is an investigational, small interfering RNA (siRNA) inhibiting TTR. This abstract highlights patisiran's long-term safety. Methods: Phase 2 OLE study to evaluate patisiran's safety. Patisiran's effect on serum TTR levels, impact on neuropathy impairment scores and QOL were assessed. Results: 27 patients with FAP enrolled; median age 64 years. Patisiran was generally well tolerated out to 23-months. Five patients experienced SAEs (unrelated) including one discontinuation (gastroesophageal cancer); patient subsequently died. Flushing (25.9%) and infusion-related reactions (18.5%) were mild in severity; no discontinuations resulted. Approximately 80% sustained mean serum TTR lowering resulted with a mean nadir of up to 93% between doses. Among the 20 evaluable patients, neuropathy impairment scores were stable through 18-months; mean change in mNIS+7 and NIS of 1.7 and 4.2 points, respectively. This compares favorably to 17–26 point mNIS+7/NIS increase estimated at 18-months from prior FAP studies. Stabilization of QOL measures and improvement of distal thigh sweat gland nerve fiber density observed. Conclusion: Data demonstrates that 18-months of patisiran administration was generally well tolerated, resulted in sustained mean serum TTR lowering, supporting the hypothesis that TTR knockdown potentially halts neuropathy progression.

  • 24. Steinacker, Petra
    et al.
    Feneberg, Emily
    Weishaupt, Jochen
    Brettschneider, Johannes
    Tumani, Hayrettin
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    von Arnim, Christine A. F.
    Boehm, Sarah
    Kassubek, Jan
    Kubisch, Christian
    Lule, Dorothee
    Mueller, Hans-Peter
    Muche, Rainer
    Pinkhardt, Elmar
    Oeckl, Patrick
    Rosenbohm, Angela
    Anderl-Straub, Sarah
    Volk, Alexander E.
    Weydt, Patrick
    Ludolph, Albert C.
    Otto, Markus
    Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients2016Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 87, nr 1, s. 12-20Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Biomarkers for the diagnosis of motoneuron diseases (MND) are urgently needed to improve the diagnostic pathway, patient stratification and monitoring. The aim of this study was to validate candidate markers for MND in cerebrospinal fluid (CSF) and specify cut-offs based on large patient cohorts by especially considering patients who were seen under the initial differential diagnosis (MND mimics). Methods In a prospective study, we investigated CSF of 455 patients for neurofilament light chain (NfL), phosphorylated heavy chain (pNfH), tau protein (Tau) and phospho-tau protein (pTau). Analysed cohorts included patients with apparently sporadic and familial amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) (MND, n=253), MND mimics (n=85) and neurological control groups. Cut-off values were specified, and diagnostic performance and correlation with progression were analysed. Results Nfs were significantly higher in the MND group compared to the control groups, whereas Tau and pTau did not differ. At a cut-off level of 2200 pg/mL for NfL, a 77% diagnostic sensitivity (CI 71% to 82%), 85% specificity (CI 79% to 90%) and 87% positive predictive value (PPV) (CI 81% to 91%) were achieved. For pNfH, we calculated 83% sensitivity (CI 78% to 88%), 77% specificity (CI 71% to 83%) and 82% PPV (CI 77% to 86%) at 560 pg/mL. There were no significant differences between sporadic and genetic ALS or PLS. Nf levels were elevated at early disease stage, and correlated moderately with MND progression and duration. Conclusions Neurofilaments in CSF have a high relevance for the differential diagnosis of MNDs and should be included in the diagnostic work-up of patients. Their value as prognostic markers should be investigated further.

  • 25. Stephensen, H
    et al.
    Andersson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Tisell, M
    Wikkelsö, C
    Objective B wave analysis in 55 patients with non-communicating and communicating hydrocephalus2005Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 76, s. 965-970Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: B waves, slow and rhythmic oscillations in intracranial pressure (ICP), are claimed to be one of the best predictors of outcome after surgery for normal pressure hydrocephalus (NPH).

    Object: To determine the relation between the percentage of B waves and outcome in patients with hydrocephalus, and also the diurnal variation of B waves.

    Methods: ICP and patient behaviour were recorded overnight (17 to 26 hours) in 29 patients with non-communicating hydrocephalus and 26 with NPH. The B wave activity, measured with an amplitude threshold of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, and 5.0 mm Hg, was estimated as the percentage of total monitoring time (% B waves) using a computer algorithm, and correlated with postoperative outcome, defined as changes in 12 standardised symptoms and signs.

    Results: There was no linear correlation between improvement after surgery in the 55 patients and total % B waves, but a correlation was found between improvement and % B waves during sleep (r = 0.39, p = 0.04). The percentage of B waves was the same during sleep and wakefulness, and patients with NPH had the same proportion of B waves as the non-communicating patients.

    Conclusions: B waves are commonly observed in patients with both communicating and non-communicating hydrocephalus, but are only weakly related to the degree of postsurgical improvement.

  • 26. Synofzik, Matthis
    et al.
    Fernández-Santiago, Rubén
    Maetzler, Walter
    Schöls, Ludger
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    The human G93A SOD1 phenotype closely resembles sporadic amyotrophic lateral sclerosis2010Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 81, nr 7, s. 764-767Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Transgenic mouse models of human SOD1 mutations have opened up an area of intense investigation into the pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS). However, the human phenotype of the G93A SOD1 mutation-the most commonly studied mutation in rodent models-has remained essentially unknown. This complicates the interpretation and transfer of results from animal models. Here clinical, electrophysiological and genealogical data are presented from a large German pedigree with a G93A mutation in the SOD1 gene. This pedigree shows a highly homogenous phenotype which closely resembles the typical phenotype of sporadic ALS, thus implicating comparable disease pathology of G93A SOD1 ALS and sporadic ALS.

  • 27. Terént, A
    et al.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Farahmand, B
    Henriksson, K M
    Norrving, B
    Stegmayr, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wester, P-O
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Asberg, K H
    Asberg, S
    Stroke unit care revisited: who benefits the most? A cohort study of 105,043 patients in Riks-Stroke, the Swedish Stroke Register.2009Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, nr 8, s. 881-887Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Treatment at stroke units is superior to treatment at other types of wards. The objective of the present study is to determine the effect size of stroke unit care in subgroups of patients with stroke. This information might be useful in a formal priority setting. METHODS: All acute strokes reported to the Swedish Stroke Register from 2001 through 2005 were followed until January 2007. The subgroups were age (18-64, 65-74, 75-84, 85+ years and above), sex (male, female), stroke subtype (intracerebral haemorrhage, cerebral infarction and unspecified stroke) and level of consciousness (conscious, reduced, unconscious). Cox proportional hazards and logistic regression analyses were used to estimate the risk for death, institutional living or dependency. RESULTS: 105,043 patients were registered at 86 hospitals. 79,689 patients (76%) were treated in stroke units and 25,354 patients (24%) in other types of wards. Stroke unit care was associated with better long-term survival in all subgroups. The best relative effect was seen among the following subgroups: age 18-64 years (hazard ratio (HR) for death 0.53; 0.49 to 0.58), intracerebral haemorrhage (HR 0.61; 0.58 to 0.65) and unconsciousness (HR 0.70; 0.66 to 0.75). Stroke unit care was also associated with reduced risk for death or institutional living after 3 months. CONCLUSIONS: Stroke unit care was associated with better long-term survival in all subgroups, but younger patients, patients with intracerebral haemorrhage and patients who were unconscious had the best relative effect and may be given the highest priority to this form of care.

  • 28. van Es, Michael A
    et al.
    Dahlberg, Caroline
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Veldink, Jan Herman
    van den Berg, Leonard H
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Large-scale SOD1 mutation screening provides evidence for genetic heterogeneity in amyotrophic lateral sclerosis.2010Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 81, nr 5, s. 562-566Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To estimate the frequency of SOD1 mutations in a large referral cohort of familial amyotrophic lateral sclerosis (FALS) and sporadic amyotrophic lateral sclerosis (SALS) patients from The Netherlands and to compare this frequency with that of other developed countries. METHODS: A total of 451 sporadic and 55 FALS patients were screened for SOD1 mutations. The authors performed PCR amplification of all five coding exons of SOD1 followed by direct DNA sequencing using forward and reverse primers. RESULTS: One novel mutation (p.I99V) and a homozygous p.D90A mutation were identified in SALS patients. In a pedigree with Mendelian dominant FALS, one patient was found to be heterozygous for the p.D90A mutation. SOD1 mutation frequency was found to be significantly lower in The Netherlands compared with other countries with p=0.0004 for FALS (21.9% vs 2.5%) and p=0.005 for SALS (2.5% vs 0.44%). CONCLUSIONS: The authors demonstrate that SOD1 mutations are rare in The Netherlands in familial and SALS. This observation suggests that the genetic background of amyotrophic lateral sclerosis differs between different populations, countries and regions. This may have consequences for the interpretation of association studies and explain why replication of association studies has proven difficult in amyotrophic lateral sclerosis.

  • 29. Weber, M
    et al.
    Neuwirth, C
    Thierbach, J
    Schweikert, K
    Czaplinski, A
    Petersen, J
    Jung, HH
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Marklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersen, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    ALS patients with SOD1 mutations in Switzerland show very diverse phenotypes and extremely long survival2012Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, nr 3, s. 351-353Artikkel i tidsskrift (Fagfellevurdert)
  • 30.
    Ågren Wilsson, A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Roslin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, LO
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Bergenheim, AT
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Malm, J
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Intracerebral microdialysis and CSF hydrodynamics in idiopathic adult hydrocephalus syndrome2003Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 74, nr 2, s. 217-221Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In idiopathic adult hydrocephalus syndrome (IAHS), a pathophysiological model of "chronic ischaemia" caused by an arteriosclerotic process in association with a CSF hydrodynamic disturbance has been proposed. OBJECTIVE: To investigate whether CSF hydrodynamic manipulation has an impact on biochemical markers related to ischaemia, brain tissue oxygen tension (PtiO(2)), and intracranial pressure. METHODS: A microdialysis catheter, a PtiO(2) probe, and an intracerebral pressure catheter were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. A subcutaneous microdialysis probe was used as reference. Intracranial pressure and intracerebral PtiO(2) were recorded continuously. Samples were collected for analysis between 2 and 4 pm on day 1 (baseline) and at the same time on day 2, two to four hours after a lumbar CSF hydrodynamic manipulation. The concentrations of glucose, lactate, pyruvate, and glutamate on day 1 and 2 were compared. RESULTS: After CSF drainage, there was a significant rise in the intracerebral concentration of lactate and pyruvate. The lactate to pyruvate ratio was increased and remained unchanged after drainage. There was a trend towards a lowering of glucose and glutamate. Mean intracerebral PtiO(2) was higher on day 2 than on day 1 in six of eight patients. CONCLUSIONS: There is increased glucose metabolism after CSF drainage, as expected in a situation of postischaemic recovery. These new invasive techniques are promising tools in the future study of the pathophysiological processes in IAHS.

  • 31.
    Ågren-Wilsson, Aina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, L-O D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Brain energy metabolism and intracranial pressure in idiopathic adult hydrocephalus syndrome2005Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 76, nr 8, s. 1088-1093Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance. OBJECTIVE: To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter. METHODS: A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral Ptio2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate. RESULTS: When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (p < 0.05, Wilcoxon sign rank). There was no change in glutamate or the lactate to pyruvate ratio during ICP elevation. Ptio2 did not decrease during ICP elevation, but was significantly increased following CSF drainage. CONCLUSIONS: Raising intracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS.

1 - 31 of 31
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