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  • 1.
    Hägglund, Patricia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Sandström, Linda
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Karlsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Voice Tremor in Patients With Essential Tremor: Effects of Deep Brain Stimulation of Caudal Zona Incerta2016In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 30, no 2, p. 228-233Article in journal (Refereed)
    Abstract [en]

    Objectives. The present study aimed at evaluating the effect of deep brain stimulation (DBS) of the caudal zona incerta (cZi) on voice tremor in patients with essential tremor (ET). Study Design. This is a prospective nonrandomized design with consecutive patients.

    Methods. Twenty-six patients operated with cZi DBS were evaluated under two conditions: without stimulation (Stim OFF) and with stimulation (Stim ON). Voice tremor was assessed on the basis of recordings of sustained vowel productions using a four-point rating scale in a blinded and randomized procedure. Averaged values of multiple assessments for each stimulus were used in statistical testing. The group of patients with voice tremor in Stim OFF was analyzed separately from the group of patients without voice tremor.

    Results. Voice tremor was significantly reduced on stimulation compared with off for the subgroup with initial voice tremor. Voice tremor prevalence was found to be 50% (13 patients). Individual differences in voice tremor outcome were noticeable. Six of the patients with voice tremor at baseline improved substantially by cZi DBS treatment.

    Conclusions. On the group level, voice tremor in patients with ET was found to reduce when stimulating the cZi. Bilateral stimulation was indicated to be more effective in reducing voice tremor than unilateral stimulation. However, individual voice tremor outcomes suggest that not all patients benefit from cZi DBS. Severity of voice tremor at baseline may not be a good predictor of voice tremor outcome after cZi DBS. Patients should be informed before surgery regarding individual differences in response to DBS treatment.

  • 2.
    Sandström, Linda
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Impact of deep brain stimulation in the caudal zona incerta on voice tremor and speech in persons with essential tremor2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Objectives: Deep brain stimulation (DBS) is a symptomatic treatment for people with essential tremor (ET) who have unsatisfactory tremor relief with pharmacological treatment alone. A common symptom of ET is voice tremor, but only about 50% of patients with voice tremor get a satisfactory result with DBS. Moreover, stimulation-induced adverse effects on speech are often reported, especially with bilateral stimulation. In recent years, the caudal zona incerta (cZi) has been highlighted as a particularly efficient DBS-target for tremor; however, less is known about the effects of cZi-DBS on voice and speech. The aims of this thesis were to (i) describe how voice tremor and speech production are affected by habitual cZi-DBS optimized to treat the motor symptoms of ET, (ii) investigate how voice tremor and speech production are affected by unilateral cZi-stimulation at increasing amplitudes, with a particular focus on high-amplitude stimulation, and (iii) explore the extent to which patient characteristics and DBS related factors, such as electrode location and stimulation settings, influence the outcome.

    Methods: This thesis comprises two different study protocols. Study I was a retrospective study of 19 patients with ET and voice tremor, and DBS effects on voice tremor were evaluated from clinical assessments made at baseline and 1, 3, and 5 years after surgery, respectively. Studies II-V included 37 persons with ET, and DBS effects on voice tremor and speech production were evaluated off- and on habitual stimulation, as well as in an experimental protocol with unilateral stimulation at increasing amplitudes (up to a maximum of 4.5V). Voice tremor (study II, III) was assessed by two listeners using the Visual Sort and Rate (VISOR) method. Speech intelligibility (study IV) was estimated from orthographic transcriptions of nonsense sentences made by two speech-language pathology students. Speech function, including articulation and voice quality (study V) were analysed in 14 participants and assessed by two speech-language pathologists using VISOR. Voice and speech outcomes following the experimental stimulation condition were evaluated in relation to the location of the active electrode contacts.

    Results: Habitual cZi-DBS reduced voice tremor at all examinations and did not affect speech production on the group-level. By contrast, during unilateral high-amplitude stimulation, more negative effects on speech were noted, and the proportion of individuals with affected speech more than doubled at maximal amplitude stimulation compared with habitual cZi-DBS (40% compared to 17%). While most of these adverse effects were mild in general, a few participants exhibited more severe impairments of high-amplitude stimulation, especially on speech intelligibility and articulation. There were also cases in which high-amplitude stimulation worsened voice tremor or even induced the symptom. As for the contribution of electrode location, a deeper and more posterior stimulation origin were found to yield the most efficient voice tremor reduction, more medially located electrodes were associated with affected articulation, whereas deteriorated speech intelligibility was related to stimulation originating from a more superior location.

    Conclusions: cZi-DBS is relatively safe in the sense that adverse effects on speech production are rarely seen during stimulation with the clinical settings. Furthermore, voice tremor can be expected to improve, both short- and long- term, although not always to such an extent that the symptom is alleviated completely. However, by increasing the stimulation amplitude beyond the clinical setting, one increases the risk of inducing unwanted speech-related effects and worsen voice tremor. Thus, it appears as though the challenge in the postoperative management of the DBS treatment lies in maintaining the therapeutic effect while still keeping the stimulation amplitude at a low level. The combined results of this thesis indicate that the best outcome for voice and speech might be achieved by stimulating from the posterior-inferior-lateral part of the cZi.

  • 3.
    Sandström, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Karlsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Long-term effects of unilateral deep brain stimulation on voice tremor in patients with essential tremor2019In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 60, p. 70-75Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Voice tremor (VT) is a common symptom of Essential tremor (ET). Deep brain stimulation (DBS) is an established treatment for ET overall, however, its effect on VT is less clear. The aim of this study was to evaluate long-term effects of DBS on VT and to investigate how VT symptoms develop over time in patients with ET.

    METHODS: VT scores for the cohort of 81 ET patients that had undergone DBS surgery in the caudal zona incerta (cZi) were analyzed retrospectively. Thirty-four patients had preoperative VT and long-term evaluations were available for 19 patients. Longitudinal effects of cZi-DBS were investigated 1, 3 and 5 years postoperatively. VT progression was evaluated based on preoperative-, and off stimulation postoperative assessments.

    RESULTS: Unilateral cZi-DBS reduced average voice tremor by 58% at the 3-year follow-up and by 67% 5 years after surgery. Four patterns of VT development were identified among patients, and the effectiveness of cZi-DBS in alleviating voice tremor symptoms showed differing patterns for these subgroups.

    CONCLUSIONS: This retrospective analysis of a small cohort of patients suggests that cZi-DBS may reduce VT in the long-term for patients with ET overall, but the pattern of VT progression likely influences the effectiveness of the treatment. These results also suggest that unilateral cZi-DBS may be more efficacious when treating patients with mild to moderate VT. A prospective, blinded, controlled clinical trial in patients with ET is needed to determine developmental patterns of VT, and the safety and efficacy of cZi-DBS for the treatment of VT.

  • 4.
    Sandström, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Karlsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Voice Tremor Response to Deep Brain Stimulation in Relation to Electrode Location in the Posterior Subthalamic Area2019In: World Neurosurgery: X, ISSN 2590-1397, Vol. 3, p. 1-9, article id 100024Article in journal (Refereed)
    Abstract [en]

    Background: Deep brain stimulation of the motor thalamus or the posterior subthalamic area (PSA) shows promising results for patients with voice tremor, although only for about 50% of patients. There are indications that voice tremor requires more focused stimulation within the target area compared with hand tremor. The objective of the present study was to determine the most efficient location for reducing voice tremor within the PSA.

    Methods: Thirty-seven patients with essential tremor were evaluated off stimulation and in a set of experimental conditions with unilateral stimulation at increasing amplitude levels. Two listeners performed blinded assessments of voice tremor from recordings of sustained vowel productions.

    Results: Twenty-five patients (68%) had voice tremor. Unilateral stimulation reduced voice tremor for the majority of patients, and only 6 patients had poor outcomes. Contacts yielding efficient voice tremor reduction were deeper relative to the midcommissural point (MCP) and more posterior relative to the posterior tip of the subthalamic nucleus (pSTN) (z MCP = –3.1, y pSTN = –0.2) compared with poor contacts (z MCP = –0.7, y pSTN = 1.0). High-amplitude stimulation worsened voice tremor for 7 patients and induced voice tremor in 2 patients. Hand tremorimproved to a greater extent than voice tremor, and improvements could be seen throughout the target area.

    Conclusions: Our results indicate that efficient voice tremor reduction can be achieved by stimulating contacts located in the inferior part of the PSA, close or slightly posterior to the pSTN. We observed cases in which voice tremor was induced by high-amplitude stimulation.

  • 5.
    Sandström, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Hägglund, Patricia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Johansson, Louise
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Karlsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Speech intelligibility in Parkinson's disease patients with zona incerta deep brain stimulation2015In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 5, no 10, article id e00394Article in journal (Refereed)
    Abstract [en]

    Objectives

    To investigate the effects of l-dopa (Levodopa) and cZi-DBS (deep brain stimulation in caudal zona incerta) on spontaneous speech intelligibility in patients with PD (Parkinson's disease).

    Materials and Methods

    Spontaneous utterances were extracted from anechoic recordings from 11 patients with PD preoperatively (off and on l-dopa medication) and 6 and 12 months post bilateral cZi-DBS operation (off and on stimulation, with simultaneous l-dopa medication). Background noise with an amplitude corresponding to a clinical setting was added to the recordings. Intelligibility was assessed through a transcription task performed by 41 listeners in a randomized and blinded procedure.

    Results

    A group-level worsening in spontaneous speech intelligibility was observed on cZi stimulation compared to off 6 months postoperatively (8 adverse, 1 positive, 2 no change). Twelve months postoperatively, adverse effects of cZi-DBS were not frequently observed (2 positive, 3 adverse, 6 no change). l-dopa administered preoperatively as part of the evaluation for DBS operation provided the overall best treatment outcome (1 adverse, 4 positive, 6 no change).

    Conclusions

    cZi-DBS was shown to have smaller negative effects when evaluated from spontaneous speech compared to speech effects reported previously. The previously reported reduction in word-level intelligibility 12 months postoperatively was not transferred to spontaneous speech for most patients. Reduced intelligibility due to cZi stimulation was much more prominent 6 months postoperatively than at 12 months.

  • 6.
    Sandström, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Karlsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Unilateral Left Deep Brain Stimulation of the Caudal Zona Incerta Is Equally Effective on Voice Tremor as Bilateral Stimulation: Evidence from 7 Patients with Essential Tremor2018In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 96, no 3, p. 157-161Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Deep brain stimulation (DBS) is less effective on voice tremor than arm tremor, and it is generally assumed that successful voice tremor treatment requires bilateral DBS and possibly more precise thalamic stimulation. However, recent findings suggest that these assumptions should be reconsidered.

    OBJECTIVES: To evaluate whether unilateral DBS targeting the caudal zona incerta (cZi) may be sufficient to alleviate voice tremor in patients with essential tremor, or whether bilateral stimulation is needed.

    METHODS: Seven patients with voice tremor off stimulation were evaluated during bilateral stimulation using their clinical settings, and during unilateral left stimulation in iterations with increasing stimulation amplitude. Two expert listeners assessed voice tremor severity in all samples in a blinded procedure.

    RESULTS: Six patients had comparable or better effects with unilateral left stimulation compared to bilateral stimulation. For the seventh patient, unilateral DBS at a slightly higher amplitude achieved similar results as bilateral DBS. Overall, high-amplitude stimulation did not appear to be beneficial on voice tremor.

    CONCLUSIONS: Unilateral left and bilateral cZi-DBS had comparable effects on voice tremor in the investigated group of 7 patients. This finding suggests that the assumption that bilateral DBS is required to treat voice tremor may need to be reconsidered.

  • 7.
    Sandström, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy. Umeå University.
    Karlsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hartelius, Lena
    Göteborgs universitet, Neurovetenskap och fysiologi, Sektionen för hälsa och rehabilitering.
    The effects of deep brain stimulation on speech intelligibility in persons with essential tremorIn: Journal of Speech, Language and Hearing Research, ISSN 1092-4388, E-ISSN 1558-9102Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate how deep brain stimulation (DBS) of the caudal zona incerta (cZi) affects speech intelligibility in persons with essential tremor (ET).

    Method: Thirty-five participants were evaluated: off stimulation, on chronic stimulation optimized to alleviate tremor, and during unilateral stimulation at increasing amplitude levels. At each stimulation condition, the participants read 10 unique nonsense sentences from the Swedish Test of Intelligibility. Two listeners, blinded to stimulation condition, transcribed all recorded sentences orthographically in a randomised procedure. A mean speech intelligibility score for each patient and stimulation condition was computed, and comparisons were made between scores off- and on stimulation.

    Results: Chronic cZi-DBS had no significant effect on speech intelligibility, and there was no difference in outcome between bilateral and unilateral treatments. During unilateral stimulation at increasing amplitudes, nine participants demonstrated deteriorating speech intelligibility. These nine participants were on average older and had more superior contacts activated during the evaluation compared with the participants without deterioration.

    Conclusions: Chronic cZi-DBS, optimized for tremor suppression, does not generally affect speech intelligibility in persons with ET. Furthermore, speech intelligibility may be preserved in many individuals, even when stimulated at high amplitudes. Adverse effects of high-amplitude unilateral stimulation observed in this study were associated with stimulation originating from a more superior location, as well as with the participants’ age. These results, highlighting age and stimulation location as contributing to speech intelligibility outcomes were, however, based on a limited number of individuals experiencing adverse effects with high-amplitude stimulation and should, therefore, be interpreted with caution.

  • 8.
    Sandström, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy. Umeå University.
    Schalling, Ellika
    Karolinska Institutet, Klinisk vetenskap, Intervention och teknik, Logopedi.
    Karlsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Hartelius, Lena
    Göteborgs universitet, Neurovetenskap och fysiologi, Sektionen för hälsa och rehabilitering.
    Speech following DBS for essential tremor: Effects of chronic and high-amplitude stimulation in the posterior subthalamic area2020Conference paper (Other academic)
    Abstract [en]

    Deep brain stimulation (DBS) can be very effective in alleviating tremor, but adverse effects on speech are frequently reported, especially following bilateral DBS. Most of the existing literature on DBS and speech deals with the effects of DBS targeting the subthalamic nucleus or the ventral intermediate nucleus of the thalamus, which are the traditional targets for Parkinson’s disease and essential tremor, respectively. More recently, the posterior subthalamic area (PSA) has been highlighted as a particularly effective target for tremor; however, there are limited studies of PSA-DBS effects on speech.

    We report speech outcomes for 14 persons with essential tremor during chronic PSA-DBS and at unilateral high-amplitude PSA-stimulation.

    The objectives were to answer the following questions:

    • To what extent is speech function, and in particular articulation and voice, affected by chronic PSA-DBS?
    • How is speech affected by unilateral high-amplitude stimulation
    • Is bilateral chronic PSA-DBS worse for speech than unilateral PSA-stimulation?
  • 9.
    Sandström, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy. Umeå University.
    Schalling, Ellika
    Karolinska Institutet, Klinisk vetenskap, Intervention och teknik, Logopedi.
    Karlsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hartelius, Lena
    Göteborgs universitet, Neurovetenskap och fysiologi, Sektionen för hälsa och rehabilitering.
    Speech function following deep brain stimulation of the caudal zona incerta: effects of habitual and high-amplitude stimulationManuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: To investigate to what extent deep brain stimulation (DBS) of the caudal zona incerta (cZi) affects speech function in persons with essential tremor (ET).

    Method: fourteen participants with ET were evaluated: off stimulation (OFF), with habitual stimulation optimized to treat the motor symptoms of ET (ON), and during unilateral stimulation at increasing amplitudes. At each stimulation condition, the participants read three 16-word sentences designed to elicit a variety of articulatory movements. Two listeners made consensus ratings of overall speech function, articulation, and voice using a visual sort and rate method (VISOR). Rated function OFF and ON as well as during unilateral stimulation at the individual maximal amplitude level (MAX) was compared with Friedman nonparametric tests. The effects of bilateral and unilateral stimulation for the five participants treated with bilateral cZi-DBS were compared on a descriptive level.

    Results: Habitual cZi-DBS had no significant group-level effect on any of the investigated speech parameters. Articulation was adversely affected by MAX stimulation, and decreased articulation was associated with more medially located electrode contacts. Bilateral and unilateral stimulation were indicated to have similar effects on speech function.

    Conclusions: Habitual cZi-DBS did not have any systematic adverse effects on speech function, but response to stimulation was heterogeneous. Unilateral high-amplitude stimulation was found to have more consistent negative effects, particularly on articulation. Decreased articulatory function was associated with high-amplitude stimulation of medially located contacts, suggestive of cerebello-rubrospinal involvement. These results were, however, based on a limited number of individuals and should, therefore, be interpreted with caution.

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