Deep Brain Stimulation: When to Test Directional?

BACKGROUND Directional deep brain stimulation (DBS) allows for steering of the stimulation field, but extensive and time-consuming testing of all segmented contacts is necessary to identify the possible benefit of steering. It is therefore important to determine under which circumstances directional current steering is advantageous. METHODS Fifty two Parkinson's disease patients implanted in the STN with a directional DBS system underwent a standardized monopolar programming session 5 to 9 months after implantation. Individual contacts were tested for a potential advantage of directional stimulation. Results were used to build a prediction model for the selection of ring levels that would benefit from directional stimulation. RESULTS On average, there was no significant difference in therapeutic window between ring-level contact and best directional contact. However, according to our standardized protocol, 35% of the contacts and 66% of patients had a larger therapeutic window under directional stimulation compared to ring-mode. The segmented contacts warranting directional current steering could be predicted with a sensitivity of 79% and a specificity of 57%. CONCLUSION To reduce time required for DBS programming, we recommend additional directional contact testing initially only on ring-level contacts with a therapeutic window of less than 2.0 mA

Polymorphism in osteopontin-gene and quantification of the gene product in cerebrospinal fluid and serum of patients with Lewy body disease

Die Erkrankungen „Parkinson ohne Demenz“ (PDND), „Parkinson mit Demenz“ (PDD) und „Demenz mit Lewy-Körperchen“ (DLB) lassen sich aufgrund ihrer gemeinsamen klinischen und pathologischen Merkmale unter dem Begriff "Lewy-Körperchen-Erkrankungen (Lewy-body-diseases, LBD)" zusammenfassen. Die Ätiologie dieser Erkrankungen ist bis heute unbekannt, und viele pathogenetische Faktoren scheinen an der Entstehung der Erkrankung mitzuwirken. Unter anderem könnten dabei entzündliche Prozesse mit Mikroglia-Beteiligung eine wichtige Rolle spielen. Osteopontin (OPN), ein Zytokin und Matrixprotein, ist entscheidend in die pathophysiologischen Mechanismen von Autoimmunerkrankungen wie der Multiplen Sklerose und dem Systemischen Lupus Erythematodes involviert. Es könnte darüber hinaus an der Regulation von Mikrogliazellen beteiligt sein, was eine Brücke zwischen OPN und LBD schlägt. Es konnte bereits gezeigt werden, dass OPN in Liquor und Serum von Patienten mit M. Parkinson erhöht ist und das ein OPN-Mangel in einem Mausmodell neuroprotektive Effekt hatte. Die Frage welche Rolle OPN bei der Pathogenese von Lewy-Körperchen-Erkrankungen spielt, ist jedoch bislang wenig verstanden. In dieser Arbeit wurden deshalb die Liquor- und Serum-OPN-Spiegel von Lewy-Körperchen-Patienten und Kontrollen gemessen und die Genotypen zweier SNP-Varianten (T-66G, A1239C) im OPN-Gen bestimmt. Erstmals konnte eine Assoziation der genotypischen Varianten des SNP-66 mit dem Auftreten von Lewy-Körperchen-Erkrankungen nachgewiesen werden (p<0.05). Die bereits früher gezeigte Erhöhung der OPN-Spiegel in Serum (p=0.0064) und Liquor (p=0.0003) von LBD-Patienten konnte in der vorliegenden Arbeit bestätigt werden. Zusätzlich konnte gezeigt werden, dass genotypische Varianten des SNP-66 mit erhöhten Immunglobulin-G-Spiegeln im Liquor assoziiert sind (p<0.05). Diese Resultate weisen darauf hin, dass die Regulation von OPN eine primäre Rolle bei der Entstehung von LBD spielt, und das Potential von OPN als Marker für LBD weiter geprüft werden sollte.The diseases Parkinson without dementia (PDND), Parkinson with dementia (PDD) and dementia with Lewy-bodies (DLB) can be summarized under the term lewy body diseases (LBD), as they share clinical and pathological features. The aetiology of these diseases is not known until today, and many different pathogenetic factors appear to contribute to the development of these diseases including inflammatory processes of the microglia. Osteopontin (OPN), a cytokine and matrixprotein, is critically involved in the pathophysiology of autoimmune diseases like multiple sclerosis and systemic lupus erythematodes. Furthermore it could be involved in the regulation of microglia cells making a link between OPN and LBD. It has been shown that OPN is increased in cerebrospinal fluid (CSF), and serum of patients with Parkinson disease, and that OPN deficiency in a mouse model was neuroprotective. Which role OPN has in Lewy body disease is not well understood. Therefore we determined in our study CSF and serum OPN levels of patients with and wihtout Levy body disease, as well as the genotype of two SNP variations (T-66G, A1239C) in the OPN gene. For the first time an association between the genotype variation SNP-66 and the incidence of Lewy body disease could be demonstrated (p<0.05). The earlier shown increase of the OPN levels in serum (p=0.0064) and CSF (p=0.0003) of LBD patients was confirmed. Additionally we could show that the genotype variations of the SNP-66 are associated with increased IgG levels in CSF (p<0.05). These results point to a primary role of the regulation of OPN for the development of LBD. The potential role of OPN as a marker for LBD should be further tested

Untreated Classic Galactosemia – a rare cause of adult-onset progressive cerebellar ataxia: A case report.

Introduction: Identifying the underlying etiology of nonfamilial adult-onset progressive cerebellar ataxia is often challenging because neurologists must consider almost all nongenetic and genetic causes of ataxia. Case Presentation: A 39-year-old woman was hospitalized for progressive ataxia with pyramidal and cognitive dysfunction after a right arm shaking and coordination problem deteriorated progressively over 1.5 years. The patient's medical history included amenorrhea, cataracts, developmental delays, consanguinity of the parents, motor coordination issues, and diarrhea and vomiting in infancy. An important finding that enabled us to solve the diagnostic conundrum was the elevated CDT levels in the lack of alcohol-related symptoms, which also occur in untreated carbohydrate metabolism disorders, sometimes with ataxia as a leading symptom. The decreased erythrocyte galactose-1-phosphate uridyltransferase (GALT) enzyme activity and the elevated erythrocyte galactose-1-phosphate (Gal-1P) concentration led to the final diagnosis of galactosemia, a rare metabolic disorder. The patient's condition stayed stable with strict adherence to lactose-free and galactose-restricted diets, regular physiotherapy, and speech therapy, despite attempts to control the crippling tremor. Conclusion: This case highlights the importance of considering rare diseases based on unexplained clinical and laboratory findings. Newborn screening does not change the long-term complications of early-treated classical galactosemia. A small percentage of these patients develop ataxia tremor syndrome

Depression in blepharospasm: a question of facial feedback?

Depression is the most important nonmotor symptom in blepharospasm (BL). As facial expression influences emotional perception, summarized as the facial feedback hypothesis, we investigated if patients report fewer depressive symptoms if injections of botulinum neurotoxin (BoNT) include the "grief muscles" of the glabellar region, compared to treatment of orbicularis oculi muscles alone. Ninety BL patients were included, half of whom had BoNT treatment including the frown lines. While treatment pattern did not predict depressive symptoms overall, subgroup analysis revealed that in male BL patients, BoNT injections into the frown lines were associated with remarkably less depressive symptoms. We hypothesize that in BL patients presenting with dystonia of the eyebrow region, BoNT therapy should include frown line application whenever justified, to optimize nonmotor effects of BoNT denervation

Depression in blepharospasm: a question of facial feedback?

Depression is the most important nonmotor symptom in blepharospasm (BL). As facial expression influences emotional perception, summarized as the facial feedback hypothesis, we investigated if patients report fewer depressive symptoms if injections of botulinum neurotoxin (BoNT) include the "grief muscles" of the glabellar region, compared to treatment of orbicularis oculi muscles alone. Ninety BL patients were included, half of whom had BoNT treatment including the frown lines. While treatment pattern did not predict depressive symptoms overall, subgroup analysis revealed that in male BL patients, BoNT injections into the frown lines were associated with remarkably less depressive symptoms. We hypothesize that in BL patients presenting with dystonia of the eyebrow region, BoNT therapy should include frown line application whenever justified, to optimize nonmotor effects of BoNT denervation

No differences of butyrylcholinesterase protein activity and allele frequency in Lewy body diseases.

Butyrylcholinesterase (BChE) genotypes and protein (BuChE) activity, especially in combination with Apolipoprotein E4 (ApoE4), have been investigated as risk factors for developing Alzheimer disease (AD) and may be associated with the rate of progression of cognitive decline. Despite similar pathologic (e.g. amyloid deposition) and neurochemical (e.g. cholinergic deficits) aspects between AD and Lewy body diseases (LBD), scarce data is obtainable about BChE genotypes and BuChE activity in LBD. We measured BuChE activity levels in serum and cerebrospinal fluid (CSF) of 114 LBD subjects (59 of them were demented) and 31 elderly controls. We found higher CSF BuChE activity in males compared to females, and a negative correlation of serum BuChE activity with age and cognitive function. Demented LBD patients, non-demented LBD patients and controls did not differ significantly with regard to serum and CSF BuChE activity. Furthermore, BChE K variant and ApoE4 allele frequencies were determined. The BChE K variant was significantly associated with lower serum activity; the same trend was observable in CSF. The subgroups did not differ significantly with regard to BChE K/ApoE4 occurrence. These data confirm and extend previous results on the relationship between BChE gene and BuChE activity, and argue rather against a major impact of BuChE on LBD-associated pathologies

Stimulation of the globus pallidus internus in the treatment of Parkinson's disease: Long-term results of a monocentric cohort.

BACKGROUND Pallidal deep brain stimulation (DBS) has shown to be beneficial in patients with advanced levodopa-responsive Parkinson's disease (PD) in several short-term studies. However, reported long-term outcomes of pallidal DBS for PD are limited and contradictory. METHODS Eighteen consecutive PD patients were treated with unilateral or bilateral stimulation of the internal part of the globus pallidus (GPi). Assessments were carried out before and six months after neurosurgery, and annually thereafter for up to 16 years (mean follow-up time: 6 years). Primary outcomes included motor signs (Unified PD Rating Scale [UPDRS]-III), activities of daily living (ADL, UPDRS-II), and levodopa-induced motor complications (UPDRS-IV). RESULTS The results show that GPi stimulation improves levodopa-responsive PD motor signs (UPDRS-III), levodopa-induced motor complications (UPDRS-IV), and ADL (UPDRS-II) in advanced PD. Among motor signs, tremor showed the best response to pallidal stimulation. Levodopa-induced motor complications and tremor showed improvements for more than 10 years after neurosurgery. CONCLUSIONS The overall findings in our cohort demonstrate that pallidal stimulation is effective in reducing parkinsonian motor signs (UPDRS-III), particularly in the 'off'-medication state. Although the beneficial effects on bradykinesia, rigidity and ADL may be limited to 5-6 years, the follow up results indicate that the improvements of levodopa-induced motor complications (UPDRS-IV) and tremor can be sustained for more than 10 years