Dysphagia in cervical dystonia patients receiving optimised botulinum toxin therapy: a single-center retrospective cohort study.

To explore the correlations of botulinum toxin (BT) therapy with dysphagia, we wanted to study a group of cervical dystonia (CD) patients with optimised BT therapy during a prolonged period of time to record their dysphagia frequency, severity and duration, to study potential risk factors and try to avoid it by BT application with ultrasound guidance. BT therapy of 75 CD patients (23 males, 52 females, age 60 ± 12 years, BT total dose 303.5 ± 101.5 uMU) was retrospectively analysed for 1 year. BT therapy was optimised prior to the observation period. Dysphagia was noticed by one fifth of the patients. In those patients, it only occurred in about one third of the injection series. It was never associated with a functional deficit and lasted several days to 2 weeks. It was not related to patient age or gender, BT total dose, BT dose in the sternocleidomastoid muscle, BT dose in the sternocleidomastoid and scalenii muscles, by BT therapy with bilateral sternocleidomastoid muscle injections or BT therapy with abobotulinumtoxinA. Ultrasound guidance was not able to prevent it. Further prospective studies will be necessary to study underlying dystonia associated swallowing abnormalities as a potentially predisposing factor.

IncobotulinumtoxinA for hypersalivation in patients with amyotrophic lateral sclerosis: an open-label single-centre study.

The objective of this study is to discover whether incobotulinumtoxinA (inco) can reduce relative hypersalivation in patients with amyotrophic lateral sclerosis (ALS). 14 patients with ALS (8 males and 6 females, age 55.4 ± 16.3 years) received ultrasound-guided injection of inco 100 MU in both parotid glands and inco 50 MU in both submandibular glands. Saliva production was gravimetrically measured with three cotton rolls placed in the mouth. Weight increase after 5 min was measured on an electronic scale. Subjective saliva production was registered with drooling frequency scale (DFS) and drooling severity scale (DSS). Saliva production was gravimetrically reduced at week 4 (p = 0.04), week 8 (p = 0.01) but not after week 12 after BT application. DFS was reduced at week 4 (p = 0.04), week 8 (p = 0.02), but not after week 12. DSS was reduced at week 4 (p = 0.03), week 8 (p = 0.04) and week 12 (p = 0.04). Patients in our study did not experience changes in their swallowing patterns or any other safety-relevant events. Inco is effective and well tolerated for saliva reduction in patients with ALS for 8-12 weeks.

Strategies to decrease injection site pain in botulinum toxin therapy.

Botulinum toxin is now used for numerous indications including dystonias, spasticity, cerebral palsy, hyperhidrosis, cosmetics and chronic migraine. It has to be injected into its target tissues thus causing injection site pain. We wanted to compare the efficacy of various analgesic interventions suggested for reduction of injection site pain. In 13 healthy controls, pain thresholds in the fingertips II and III bilaterally were determined by the Mechanical Pain Threshold Test and the Repetitive Pain Stimulation Test at baseline and under nitrous oxide/oxygen, ice spray, local anaesthetic cream and forearm ischaemia. All interventions studied produce statistically significant and robust elevations of the pain threshold in both tests. Nitrous oxide/oxygen had stronger effects than the other interventions, although this superiority was statistically significant only in the Repetitive Pain Stimulation Test and not against ice spray. Also considering duration, localisation and penetration depth of analgesic effects, hyperhidrosis treatment may benefit from nitrous oxide/oxygen, ice spray and local anaesthetic cream. In palmar hyperhidrosis, forearm ischaemia is possible and also reduces botulinum toxin washout. Cosmetic indications may also benefit from nitrous oxide/oxygen and local anaesthetic cream. For botulinum toxin therapy of spasticity, dystonia and tremor, only nitrous oxide/oxygen may offer intramuscular analgesic effect. Its systemic and prolonged effect is also an advantage in injections in several body parts. Future studies are necessary to test the influence of penetration depth and combinations of analgesic interventions.

Long-term treatment of chronic migraine with OnabotulinumtoxinA: efficacy, quality of life and tolerability in a real-life setting.

Botulinum toxin was shown to be effective in treatment of chronic migraine. We wanted to explore its efficacy and tolerability in chronic application under real-life conditions. For this, 27 consecutive patients (age 45.6 ± 10.8 years, 25 females, 2 males) received altogether 176 injection series (IS) with 189.7 ± 45.8MU onabotulinumtoxinA (Botox(®)) according to the PREEMPT scheme. During the study period altogether 6.5 ± 2.9 (min 4, max 13) IS were applied per patient (total treatment time of 73.1 ± 36.9 weeks). 96 % of the patients reported benefit. Monthly headache days were reduced from 18.9 ± 3.9 to 8.7 ± 4.5 (p < 0.001, -53.7 %), migraine days from 16.8 ± 4.9 to 7.4 ± 4.6 (p < 0.001, -55.1 %), autonomic days from 8.6 ± 7.5 to 2.7 ± 4.2 (p < 0.001, -71.9 %) and medication days from 14.2 ± 4.6 to 8.3 ± 4.2 (p < 0.001, -71.1 %). Health-related quality of life improved by 0.6-1.5 standard deviations (SD) (Short Form Health Survey), migraine-related quality of life by 1.4-2.0 SD (Migraine-Specific Quality of Life Questionnaire) and by 1.9 SD (Headache Impact Test), depression by 1.1 SD (Beck Depression Inventory). Subjective global clinical improvement was 2.6 ± 0.6 (Global Clinical Improvement Scale). All improvements were stable throughout the entire study period. Adverse effects were infrequent, mild and transient. Botulinum toxin provides highly effective and safe long-term treatment of chronic migraine.

Botulinum toxin therapy for hyperhidrosis: reduction of injection site pain by nitrous oxide/oxygen mixtures.

Injection site pain (ISP) reduces compliance of botulinum toxin (BT) therapy considerably. We wanted to study whether nitrous oxide/oxygen (NOO, Livopan(®), Linde Gas Therapeutics, Unterschleißheim, Germany) can reduce ISP in patients receiving intracutaneous BT injections for axillary or palmar hyperhidrosis (HH). The study followed an open-label design comparing intraindividually ISP in both axillae and/or both palms when NOO was applied or not during BT injections. BT efficacy was measured by the Hyperhidrosis Disease Severity Scale (HDSS) and by a 4-point Self-Assessment Scale. ISP was documented by a Visual Analogue Scale (VAS) and the Verbal Scale of Pain Intensity (VSPI), adverse effects by a Structuralised Interview (SI). Altogether 13 patients (age 34.1 ± 12.4 years, 9 females, 4 males) were studied. 11 BT treatments were for biaxillary and 3 for bipalmar HH. BT reduced biaxillary HH from HDSS 3.7 ± 0.5 to 1.0 ± 0 and bipalmar HH from 3.6 ± 0.6 to 1.0 ± 0. All patients reported ISP reduction by NOO. In axillary HH, NOO reduced ISP from 55.7 ± 12.7 to 12.8 ± 7.5 on the VAS (p < 0.05) and from 4.1 ± 0.3 to 0.7 ± 0.5 on the VSPI (p < 0.05), in bipalmar HH from 60.0 ± 10.0 to 13.3 ± 5.8 on the VAS (p < 0.05) and from 5.0 ± 0 to 1.3 ± 0.5 on the VSPI (p < 0.05). Adverse effects were not identified. NOO is a potent, non-sedative, quickly reversible and safe inhalative analgesic which reduces ISP considerably in patients receiving BT therapy for axillary and palmar HH thus substantially improving compliance of BT therapy.

Body Concept and Quality of Life in Patients with Idiopathic Dystonia.

Patients with dystonia experience unusual postures and disfigurement. The aim of the study was to examine changes in the body concept in relation to quality of life and severity of dystonia. Our cohort consisted of 20 patients with idiopathic dystonia resistant to medical therapy who were planned for pallidal deep brain stimulation. The results were compared to 25 healthy controls. The patients were assessed with Frankfurt Body Concept Scale, Short Form 36 (SF-36) Health Survey, Hamilton Depression Scale, Beck Depression Inventory, Social Phobia Inventory and Social Interaction Anxiety Scale. The disease severity was evaluated with Burke-Fahn-Marsden Dystonia Rating Scale and Toronto Western Spasmodic Torticollis Rating Scale. Patients with dystonia had a significantly impaired body concept in eight out of nine subscales in comparison to healthy controls. The differences were most pronounced for the subscales general health, body care, physical efficacy, sexuality and physical appearance (p < 0.001). Furthermore, all eight subscales of SF-36 exhibited significantly lower values in patients with dystonia compared to controls. We also found significant positive correlations between SF-36 and body concept subscales. Impairment of body concept was not associated with disease severity or levels of social anxiety symptoms. However, there was a significant association between self-rated depression and disease severity. Our patients suffered from increased depression and social anxiety symptoms except social interaction anxiety. We conclude that patients with dystonia have significant body concept impairment that interferes with quality of life in both physical and emotional domains. Future studies should focus on assessing these symptoms after adequate therapeutic management of motor symptoms.

Alexithymia Is Associated with Reduced Quality of Life and Increased Caregiver Burden in Parkinson's Disease.

Parkinson's disease (PD) is the second most frequent neurodegenerative disease of people who are beyond 50 years of age. People with PD (PwP) suffer from a large variety of motor and non-motor symptoms resulting in reduced health-related quality of life (HR-QoL). In the last two decades, alexithymia was identified as an additional non-motor symptom in PD. Alexithymia is defined as a cognitive affective disturbance resulting in difficulty to identify and distinguish feelings from bodily sensations of emotional arousal. In PD, the frequency of patients suffering of alexithymia is increased compared to healthy controls. The aim of the present study was to determine the relationship of alexithymia to HR-QoL of the PwP and caregiver burden of the corresponding caregiver. This cross-sectional questionnaire-based study used disease specific questionnaires for HR-QoL and caregiver burden. In total 119 PwP and their corresponding caregivers were included in the study. HR-QoL of the PwP correlated significantly with alexithymia (p < 0.001), especially the sub-components "identifying feelings" (p < 0.001) and "difficulties describing feelings" (p = 0.001). Caregiver burden also correlated significantly with PwP alexithymia (p < 0.001). However, caregiver burden was associated with sub-components "identifying feelings" (p < 0.008) and "external oriented thinking" (p < 0.004). These data support the importance of alexithymia as a non-motor symptom in PD.

Treatment expectations and patient-reported outcomes of nusinersen therapy in adult spinal muscular atrophy.

BACKGROUND: The antisense-oligonucleotide (ASO) nusinersen has recently been approved as the first genetically modifying therapy for 5q-associated spinal muscular atrophy (SMA) based on randomized sham-controlled trials in infants and children. The efficacy in adults with long disease history and advanced disease status is still widely unknown; the same applies to specific expectations of adult SMA patients and to what extent they are met and may impact outcome measures. METHODS: In a longitudinal monocentric study in adult patients with SMA types 2-4, the Stanford Expectations of Treatment Scale (SETS) was assessed prior to and during nusinersen treatment. Treatment outcome was evaluated using patient-reported outcomes (PROs) as well as objectively quantifiable motor outcome measures. RESULTS: Adult SMA patients had high expectations of nusinersen treatment effectiveness regarding increase in muscle strength and disease stabilization. Via PROs, 75% stated improvements in muscle strength, endurance and independence under therapy which was in line with slight improvements in quantifiable motor scores during a  ten month observation period. In contrast, patients only expressed few negative expectations which further decreased during therapy. CONCLUSIONS: This study showed mainly positive treatment expectations and PROs in patients undergoing nusinersen treatment along with measurable functional improvement in adult SMA patients. Moreover, treatment expectations did not significantly influence outcome measures.

Mindfulness and Psychological Flexibility are Inversely Associated with Caregiver Burden in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative movement disorder with progressive impairments in activities of daily living. With disease progression, people with PD (PwP) need more help and care from their spouses or professional caregivers. Identifying factors that help caregivers to cope with their burden is needed to frame future interventions for PwP caregivers. Mindfulness and psychological flexibility might be factors contributing to resilience against the burden of giving care. In this cross-sectional questionnaire-based study, 118 PwP and their respective primary caregivers were included. Caregivers reported moderate burden and only mild depressive symptoms. Mindfulness measured by the Mindfulness Attention and Awareness scale (p 0.003) and psychological flexibility measured by Acceptance and Actions Questionnaire II (p0.001) correlated negatively with caregiver burden. Data from this study indicate mindfulness and psychological flexibility are factors contributing to resilience against caregiver burden. Future interventions to reduce burden in PwP caregivers might be improved by the inclusion of mindfulness training programs.

Impaired Quality of Life and Need for Palliative Care in a German Cohort of Advanced Parkinson's Disease Patients.

BACKGROUND: Parkinson's disease (PD) is the second most frequent neurodegenerative disease of the elderly. Patients suffer from various motor and non-motor symptoms leading to reduced health-related quality of life (HRQOL) and an increased mortality. Their loss of autonomy due to dementia, psychosis, depression, motor impairments, falls, and swallowing deficits defines a phase when palliative care interventions might help to sustain or even improve quality of life. OBJECTIVE: The aim of this study was to investigate the current status of palliative care implementation and quality of life in a local cohort of advanced PD patients in order to frame and improve future care. METHODS: 76 geriatric patients with advanced idiopathic PD meeting the inclusion criteria for palliative care interventions were clinically evaluated by neurological examination using Movement Disorders Society Unified Parkinson's Disease Rating Scale, Barthel Index, Montreal Cognitive Assessment Test, and a structured interview concerning palliative care implementation. RESULTS: HRQOL is severely reduced in our cohort of geriatric advanced PD patients. We found motor deficits, impairment of activities of daily living, depression, and cognitive decline as most relevant factors determining decreased HRQOL. Only 2.6% of our patients reported present implementation of palliative care. By contrast, 72% of the patients indicated an unmet need for palliative care. CONCLUSION: Quality of life is dramatically affected in advanced PD patients. However, we found palliative care to be implemented extremely rare in their treatment concept. Therefore, geriatric patients suffering from advanced PD should be enrolled for palliative care to provide adequate and holistic treatment which may improve or sustain their quality of life.

Botulinum toxin in the management of chronic migraine: clinical evidence and experience.

Chronic migraine (CM) is a severely disabling neurological condition characterized by episodes of pulsating unilateral or bilateral headache. The United States Food and Drug Administration (FDA) approved onabotulinumtoxinA (Botox®) for the prophylactic treatment of CM in 2010. It has been shown that onabotulinumtoxinA is effective in the reduction of headache frequency and severity in patients with CM. Treatment is well tolerated by the patients. This review reports on the history of botulinum neurotoxin (BoNT) in CM and presents the current clinical evidence for the use of onabotulinumtoxinA in the treatment of CM.

Sensory Alterations in Patients with Isolated Idiopathic Dystonia: An Exploratory Quantitative Sensory Testing Analysis.

Abnormalities in the somatosensory system are increasingly being recognized in patients with dystonia. The aim of this study was to investigate whether sensory abnormalities are confined to the dystonic body segments or whether there is a wider involvement in patients with idiopathic dystonia. For this purpose, we recruited 20 patients, 8 had generalized, 5 had segmental dystonia with upper extremity involvement, and 7 had cervical dystonia. In total, there were 13 patients with upper extremity involvement. We used Quantitative Sensory Testing (QST) at the back of the hand in all patients and at the shoulder in patients with cervical dystonia. The main finding on the hand QST was impaired cold detection threshold (CDT), dynamic mechanical allodynia (DMA), and thermal sensory limen (TSL). The alterations were present on both hands, but more pronounced on the side more affected with dystonia. Patients with cervical dystonia showed a reduced CDT and hot detection threshold (HDT), enhanced TSL and DMA at the back of the hand, whereas the shoulder QST only revealed increased cold pain threshold and DMA. In summary, QST clearly shows distinct sensory abnormalities in patients with idiopathic dystonia, which may also manifest in body regions without evident dystonia. Further studies with larger groups of dystonia patients are needed to prove the consistency of these findings.

Human subthalamic nucleus - Automatic auditory change detection as a basis for action selection.

The subthalamic nucleus (STN) shapes motor behavior and is important for the initiation and termination of movements. Here we ask whether the STN takes aggregated sensory information into account, in order to exert this function. To this end, local field potentials (LFP) were recorded in eight patients suffering from Parkinson's disease and receiving deep-brain stimulation of the STN bilaterally. Bipolar recordings were obtained postoperatively from the externalized electrode leads. Patients were passively exposed to trains of auditory stimuli containing global deviants, local deviants or combined global/local deviants. The surface event-related potentials of the Parkinson's patients as well as those of 19 age-matched healthy controls were characterized by a mismatch negativity (MMN) that was most pronounced for the global/local double deviants and less prominent for the other deviant conditions. The left and right STN LFPs similarly were modulated by stimulus deviance starting at about 100ms post-stimulus onset. The MMN has been viewed as an index of an automatic auditory change detection system, more recently phrased in terms of predictive coding theory, which prepares the organism for attention shifts and for action. The LFP-data from the STN clearly demonstrate that the STN receives information on stimulus deviance, possibly as a means to bias the system to interrupt ongoing and to allow alternative actions.