Stürze bei Schwindel- und Gleichgewichtserkrankungen

Das Ziel der vorliegenden Dissertation war es, zunächst das krankheitsspezifische Sturzrisiko bei Schwindel- und Gleichgewichtsstörungen zu ermitteln und daraufhin die Gangstabilität als potentiellen Sturzrisikomarker in den Erkrankungsgruppen mit erhöhter Sturzgefährdung zu untersuchen. Parallel dazu wurde ein spezifisches Gangtraining für Patienten mit Morbus Parkinson, bei denen eine starke Disposition für Stürze bereits durch umfangreiche Forschungsarbeiten bekannt ist, entwickelt und evaluiert. Das Sturzrisiko zeigte sich bei Erkrankungen des Kleinhirns und der Basalganglien stark und bei peripheren Störungen, wie vestibulären Dysfunktionen und Polyneuropathie, moderat ausgeprägt. Dementsprechend waren diese Patienten auch von Angst vor Stürzen betroffen. Patienten mit funktionellen Schwindelbeschwerden berichteten ebenfalls unter Sturzbedenken zu leiden, obwohl das Sturzrisiko im Vergleich zur Kontrollgruppe nicht erhöht war. Bestimmte Gangabweichungen, insbesondere eine erhöhte Variabilität des Gangmusters, stellen Risikofaktoren für das Auftreten von Stürzen in der älteren Bevölkerung dar. Aus diesem Grund wurde eine Studienserie durchgeführt, innerhalb derer die Gangstabilität bei Patienten mit bilateraler Vestibulopathie, Polyneuropathie, Downbeat Nystagmus Syndrom und zerebellärer Ataxie quantifiziert wurde. Bei allen Krankheitsbildern war die Gangvariabilität bei langsamer Ganggeschwindigkeit gesteigert. Bei Patienten mit zerebellärer Ataxie zeigte sie sich zusätzlich bei schneller Ganggeschwindigkeit erhöht. Der Zusammenhang zwischen Gangvariabilität und Sturzhistorie wurde bis dato bei Patienten mit zerebellärer Ataxie überprüft. Eine gesteigerte Gangvariabilität bei langsamer Ganggeschwindigkeit ging mit einer hohen Sturzfrequenz einher, während eine erhöhte Gangvariabilität bei schneller Ganggeschwindigkeit mit einem hohen Ataxie-Schweregrad assoziiert war. Die Messung der Schritt- zu-Schritt-Fluktuation bei langsamem Gehen eignet sich daher für die Einschätzung des individuellen Sturzrisikos bei zerebellären Patienten. Basierend auf der aktuellen Studienlage zur Gangrehabilitation bei Morbus Parkinson wurde eine kombinierte Therapie aus Laufbandtraining und visuellen Schrittvorgaben entwickelt und in einer Pilotstudie mit 23 mittel- bis hochgradig betroffenen Patienten untersucht. Der Trainingserfolg zeigte sich vor allem durch ein verbessertes Ergebnis im Timed Up and Go Test. Dies bedeutet nicht nur eine Besserung der funktionellen Gehfähigkeit, sondern spricht gleichzeitig für eine Reduktion des individuellen Sturzrisikos

Stürze bei Schwindel- und Gleichgewichtserkrankungen

Das Ziel der vorliegenden Dissertation war es, zunächst das krankheitsspezifische Sturzrisiko bei Schwindel- und Gleichgewichtsstörungen zu ermitteln und daraufhin die Gangstabilität als potentiellen Sturzrisikomarker in den Erkrankungsgruppen mit erhöhter Sturzgefährdung zu untersuchen. Parallel dazu wurde ein spezifisches Gangtraining für Patienten mit Morbus Parkinson, bei denen eine starke Disposition für Stürze bereits durch umfangreiche Forschungsarbeiten bekannt ist, entwickelt und evaluiert. Das Sturzrisiko zeigte sich bei Erkrankungen des Kleinhirns und der Basalganglien stark und bei peripheren Störungen, wie vestibulären Dysfunktionen und Polyneuropathie, moderat ausgeprägt. Dementsprechend waren diese Patienten auch von Angst vor Stürzen betroffen. Patienten mit funktionellen Schwindelbeschwerden berichteten ebenfalls unter Sturzbedenken zu leiden, obwohl das Sturzrisiko im Vergleich zur Kontrollgruppe nicht erhöht war. Bestimmte Gangabweichungen, insbesondere eine erhöhte Variabilität des Gangmusters, stellen Risikofaktoren für das Auftreten von Stürzen in der älteren Bevölkerung dar. Aus diesem Grund wurde eine Studienserie durchgeführt, innerhalb derer die Gangstabilität bei Patienten mit bilateraler Vestibulopathie, Polyneuropathie, Downbeat Nystagmus Syndrom und zerebellärer Ataxie quantifiziert wurde. Bei allen Krankheitsbildern war die Gangvariabilität bei langsamer Ganggeschwindigkeit gesteigert. Bei Patienten mit zerebellärer Ataxie zeigte sie sich zusätzlich bei schneller Ganggeschwindigkeit erhöht. Der Zusammenhang zwischen Gangvariabilität und Sturzhistorie wurde bis dato bei Patienten mit zerebellärer Ataxie überprüft. Eine gesteigerte Gangvariabilität bei langsamer Ganggeschwindigkeit ging mit einer hohen Sturzfrequenz einher, während eine erhöhte Gangvariabilität bei schneller Ganggeschwindigkeit mit einem hohen Ataxie-Schweregrad assoziiert war. Die Messung der Schritt- zu-Schritt-Fluktuation bei langsamem Gehen eignet sich daher für die Einschätzung des individuellen Sturzrisikos bei zerebellären Patienten. Basierend auf der aktuellen Studienlage zur Gangrehabilitation bei Morbus Parkinson wurde eine kombinierte Therapie aus Laufbandtraining und visuellen Schrittvorgaben entwickelt und in einer Pilotstudie mit 23 mittel- bis hochgradig betroffenen Patienten untersucht. Der Trainingserfolg zeigte sich vor allem durch ein verbessertes Ergebnis im Timed Up and Go Test. Dies bedeutet nicht nur eine Besserung der funktionellen Gehfähigkeit, sondern spricht gleichzeitig für eine Reduktion des individuellen Sturzrisikos

Visual cues combined with treadmill training to improve gait performance in Parkinson's disease: a pilot randomized controlled trial

Objective: To evaluate the effects of visual cues combined with treadmill training on gait performance in patients with Parkinson's disease and to compare the strategy with pure treadmill training. Design: Pilot, exploratory, non-blinded, randomized controlled trial. Setting: University Hospital of Munich, Germany. Subjects: Twenty-three outpatients with Parkinson's disease (Hoehn and Yahr stage II-IV). Interventions: Patients received 12 training sessions within five weeks of either visual cues combined with treadmill training (n = 12) or pure treadmill training (n = 11). Main measures: Outcome measures were gait speed, stride length and cadence recorded on the treadmill. Functional tests included the Timed Up and Go Test, the Unified Parkinson's Disease Rating Scale and the Freezing of gait-questionnaire. Assessments were conducted at baseline, after the training period and at two months follow-up. Results: After the training period (n = 20), gait speed and stride length had increased in both groups (p <= 0.05). Patients receiving the combined training scored better in the Timed Up and Go Test compared with the patients receiving pure treadmill training (p <= 0.05). At two months follow-up (n = 13), patients who underwent the combined training sustained better results in gait speed and stride length (p <= 0.05) and sustained the improvement in the Timed Up and Go Test (p <= 0.05). Conclusions: This pilot study suggests that visual cues combined with treadmill training have more beneficial effects on gait than pure treadmill training in patients with a moderate stage of Parkinson's disease. A large-scale study with longer follow-up is required

The Gait Disorder in Downbeat Nystagmus Syndrome

Background: Downbeat nystagmus (DBN) is a common form of acquired fixation nystagmus with key symptoms of oscillopsia and gait disturbance. Gait disturbance could be a result of impaired visual feedback due to the involuntary ocular oscillations. Alternatively, a malfunction of cerebellar locomotor control might be involved, since DBN is considered a vestibulocerebellar disorder. Methods: Investigation of walking in 50 DBN patients (age 72 +/- 11 years, 23 females) and 50 healthy controls (HS) (age 70 +/- 11 years, 23 females) using a pressure sensitive carpet (GAITRite). The patient cohort comprised subjects with only ocular motor signs (DBN) and subjects with an additional limb ataxia (DBNCA). Gait investigation comprised different walking speeds and walking with eyes closed. Results: In DBN, gait velocity was reduced (p<0.001) with a reduced stride length (p<0.001),increased base of support (p<0.050),and increased double support (p<0.001). Walking with eyes closed led to significant gait changes in both HS and DBN. These changes were more pronounced in DBN patients (p<0.001). Speed-dependency of gait variability revealed significant differences between the subgroups of DBN and DBNCA (p<0.050). Conclusions: (I) Impaired visual control caused by involuntary ocular oscillations cannot sufficiently explain the gait disorder. (II) The gait of patients with DBN is impaired in a speed dependent manner. (III) Analysis of gait variability allows distinguishing DBN from DBNCA: Patients with pure DBN show a speed dependency of gait variability similar to that of patients with afferent vestibular deficits. In DBNCA, gait variability resembles the pattern found in cerebellar ataxia

Presynaptic α2δ subunits are key organizers of glutamatergic synapses

In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Moreover, α2δ-2 and α2δ-3 with mutated metal ion-dependent adhesion sites can fully rescue presynaptic synapsin expression but only partially calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. First, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Second, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density

Occupational injuries among children and adolescents in Cusco Province: a cross-sectional study

Background: Although the number of child laborers in Latin America is generally high, data on occupational hazards and injuries is insufficient. The objective of this study was therefore to determine the lifetime prevalence of and risk factors for occupational injuries among working students (10-17 years old) in Cusco Province. Methods: A cross-sectional study was conducted at five public night schools. 375 students (response 91.5%) completed an interview-based questionnaire on socio-demographics, work-related factors, and lifetime prevalence of occupational injuries. Multiple logistic regression analyses were performed to estimate risk factors for different types and causes of occupational injuries. Results: Falls (11%), car accidents (9%) and physical violence (3%) were common causes of injuries in this population. Severe injuries (fractures, luxation or amputations) were reported by 3% of the population. A high daily income (>= 20 PEN, similar to 15 USD) was a statistically significant predictor for injuries caused by falls [OR 2.8; 95% CI 1.2-6.5] and physical violence at work [12.1; 1.3-115.9] whereas children born in Cusco and those working in the service sector were at higher risk of injuries caused by car accidents [3.7; 1.5-9.3 and 4.2; 1.2-15.3]. Conclusions: Occupational accidents among child workers attending public night schools are common in Cusco with a lifetime prevalence of 3% for severe injuries. High income seems to convince child laborers to accept poor working conditions

Occupational injuries among children and adolescents in Cusco Province: A cross-sectional study

Although the number of child laborers in Latin America is generally high, data on occupational hazards and injuries is insufficient. The objective of this study was therefore to determine the lifetime prevalence of and risk factors for occupational injuries among working students (10-17 years old) in Cusco Province. Methods. A cross-sectional study was conducted at five public night schools. 375 students (response 91.5%) completed an interview-based questionnaire on socio-demographics, work-related factors, and lifetime prevalence of occupational injuries. Multiple logistic regression analyses were performed to estimate risk factors for different types and causes of occupational injuries. Results: Falls (11%), car accidents (9%) and physical violence (3%) were common causes of injuries in this population. Severe injuries (fractures, luxation or amputations) were reported by 3% of the population. A high daily income (?20 PEN, ?15 USD) was a statistically significant predictor for injuries caused by falls [OR 2.8; 95% CI 1.2-6.5] and physical violence at work [12.1; 1.3-115.9] whereas children born in Cusco and those working in the service sector were at higher risk of injuries caused by car accidents [3.7; 1.5-9.3 and 4.2; 1.2-15.3]. Conclusions: Occupational accidents among child workers attending public night schools are common in Cusco with a lifetime prevalence of 3% for severe injuries. High income seems to convince child laborers to accept poor working conditions. © 2014 Schlick et al.; licensee BioMed Central Ltd

Specific and individualized instructions improve the efficacy of booklet-based vestibular rehabilitation at home – a randomized controlled trial (RCT)

BACKGROUND: Vestibular rehabilitation therapy (VRT) is effective for most patients with dizziness and imbalance. Home exercise programs are widely used. It is unknown, however, how specific the instructions for exercises have to be. OBJECTIVE: To evaluate the effects of expert assessment and instructions in a booklet-based home VRT program for patients with chronic dizziness. METHODS: Randomized controlled study on 74 participants with disabling dizziness for >3 months. All study participants received a booklet-based VRT for training at home. Participants were prescribed 20 minutes of exercise, twice a day. The intervention group (n = 37) received specific instructions (expert physiotherapist). The control group (n = 37) practiced without specific instructions. Primary outcome was the total score of the Dizziness Handicap Inventory (DHI-G). All outcomes were assessed at baseline, after 4 weeks, and at follow up 4 weeks later. RESULTS: Both groups improved (DHI-G 43.94±18.89 at inclusion to 33.06±19.67 at follow-up in controls and 42.82±16.60 to 22.65±19.12 in the intervention group). The intervention group, however, improved more (p = 0.014). CONCLUSIONS: We show a significant effect of expert physiotherapy guidance in home-based VRT. This strengthens the role of the physiotherapist in VRT: Tailored, personalized instructions are needed to get the best effect of VRT

Panitumumab-associated encephalopathy after accidental intra-arterial application through dislocated Port-a-Cath device in the left ventricle

Acute central nervous system (CNS) toxicity and immune-related side effects are increasingly recognized with the use of monoclonal antibodies for cancer therapy. Here, we report a patient who developed of acute-onset encephalopathy and coma, which began shortly after administration of panitumumab for the treatment of metastatic colorectal cancer. Echocardiography revealed that the drug had been infused into the left cardiac ventricle via a dislocated central venous line. Diffusion-weighted magnetic resonance imaging disclosed multiple cortical hyperintensities, which were preferentially located in the frontal lobes. While the neurological condition improved within a few days, the patient died four weeks later. It seems likely that the administration of the antibody via the intra-arterial route contributed to the development of this condition. Toxic encephalopathy may be a hitherto unrecognized complication of panitumumab treatment and should be taken into consideration in patients developing CNS symptoms undergoing this therapy