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OBJECTIVE: Trials for additional or alternative treatments for cervical dystonia (CD) are scarce since the introduction of botulinum neurotoxin (BoNT). We performed the first trial to investigate whether dystonic jerks/tremor in patients with CD respond to the selective serotonin reuptake inhibitor (SSRI) escitalopram. METHODS: In a randomised, double-blind, crossover trial, patients with CD received escitalopram and placebo for 6 weeks. Treatment with BoNT was continued, and scores on rating scales regarding dystonia, psychiatric symptoms and quality of life (QoL) were compared. Primary endpoint was the proportion of patients that improved at least one point on the Clinical Global Impression Scale for jerks/tremor scored by independent physicians with experience in movement disorders. RESULTS: Fifty-threepatients were included. In the escitalopram period, 14/49 patients (29%) improved on severity of jerks/tremor versus 11/48 patients (23%) in the placebo period (P=0.77). There were no significant differences between baseline and after treatment with escitalopram or placebo on severity of dystonia or jerks/tremor. Psychiatric symptoms and QoL improved significantly in both periods compared with baseline. There were no significant differences between treatment with escitalopram and placebo for dystonia, psychiatric or QoL rating scales. During treatment with escitalopram, patients experienced slightly more adverse events, but no serious adverse events occurred. CONCLUSION: In this innovative trial, no add-on effect of escitalopram for treatment of CD with jerks was found on motor or psychiatric symptoms. However, we also did not find a reason to withhold patients treatment with SSRIs for depression and anxiety, which are common in dystonia. TRIAL REGISTRATION NUMBER: NTR2178.

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Centralization of intravenous thrombolysis (IVT) for acute ischemic stroke in high-volume centers is believed to improve the door-to-needle times (DNT), but limited data support this assumption. We examined the association between DNT and IVT volume in a large Dutch province. We identified consecutive patients treated with IVT between January 2009 and 2013. Based on annualized IVT volume, hospitals were categorized as low-volume (≤ 24), medium-volume (25-49) or high-volume (≥ 50). In logistic regression analysis, low-volume hospitals were used as reference category. Of 17,332 stroke patients from 11 participating hospitals, 1962 received IVT (11.3 %). We excluded 140 patients because of unknown DNT (n = 86) or in-hospital stroke (n = 54). There were two low-volume (total 101 patients), five medium-volume (747 patients) and four high-volume hospitals (974 patients). Median DNT was shorter in high-volume hospitals (30 min) than in medium-volume (42 min, p < 0.001) and low-volume hospitals (38 min, p < 0.001). Patients admitted to high-volume hospitals had a higher chance of DNT < 30 min (adjusted OR 3.13, 95 % CI 1.70-5.75), lower risk of symptomatic intracerebral hemorrhage (adjusted OR 0.39, 95 % CI 0.16-0.92), and a lower mortality risk (adjusted OR 0.45, 95 % CI 0.21-1.01), compared to low-volume centers. There was no difference in DNT between low- and medium-volume hospitals. Onset-to-needle times (ONT) did not differ between the groups. Hospitals in this Dutch province generally achieved short DNTs. Despite this overall good performance, higher IVT volumes were associated with shorter DNTs and lower complication risks. The ONT was not associated with IVT volume.

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BACKGROUND: Studies of genetic association between TOR1A and adult-onset primary torsion dystonia have contradictory results. METHODS: The authors genotyped TOR1A single nucleotide polymorphisms rs1801968, rs2296793, rs1182 and rs3842225 in a cohort of clinically well characterized cervical dystonia patients (n=367) and constructed haplotypes. The authors systematically reviewed the published case-control TOR1A association studies in adult-onset primary torsion dystonia. RESULTS: In this Dutch cervical dystonia cohort, no significant association was found with TOR1A variants. In the meta-analysis (eight studies, 1332 adult-onset primary dystonia patients) no variant reached overall significance. However, in a selection of familial cases the functional variant p.Asp216His (rs1801968) was associated with increased dystonia risk (odds ratio 1.43; 95%CI 1.01-2.02). CONCLUSIONS: Meta-analysis does not show association with common variants in TOR1A in adult-onset primary dystonia, except for the functional variant rs1801968 in familial focal dystonia cases.

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Cervical dystonia, a late onset focal dystonia, has a complex genetic background. Multiple lines of evidence point to a role for aberrant dopamine levels in dystonia. We assessed whether common variation within genes that regulate brain dopamine levels and in key genes of the dopamine metabolic pathway, modulate the risk for cervical dystonia. DNA was collected from 363 Dutch CD patients and a cohort of Dutch control individuals. Haplotype-tagging single nucleotide polymorphisms (SNPs) complemented with selected variants of functional importance in COMT, DAT, TH, MAO-A and -B, DDC and DBH were investigated. We tested the 143 markers in single-SNP, haplotype and epistasis analyses. We did not find an association with any of the selected 143 SNPs in these key dopamine genes. Our data shows that common variations in key genes of the dopamine pathway do not contribute to dystonia risk in the Dutch population. Possibly, risk alleles in this pathway may be rarer than detectable in this study, or might be located in downstream dopamine signaling pathway. Alternatively, found dopamine level changes are secondary to the dystonia disease processes.

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BACKGROUND AND PURPOSE: The purpose of this study was to determine the incidence of adult cerebral venous thrombosis. METHODS: A retrospective cross-sectional study was conducted among all 19 hospitals located in 2 Dutch provinces serving 3.1 million people. Adult cerebral venous thrombosis cases diagnosed between January 1, 2008, and December 31, 2010, were identified using the Dutch financial coding system for hospital care and the International Classification of Diseases, 9th Revision. Medical records of potential patients were hand searched to identify cerebral venous thrombosis cases. The Dutch National Bureau for Statistics provided population figures of the 2 provinces during 2008 to 2010. RESULTS: Among 9270 potential cases, we identified 147 patients diagnosed with cerebral venous thrombosis. Of these, 53 patients did not meet the inclusion criteria; therefore, 94 patients were included in the analysis. The overall incidence was 1.32 per 100 000 person-years (95% CI, 1.06-1.61). Among women between the ages of 31 and 50 years, the incidence was 2.78 (95% CI, 1.98-3.82). CONCLUSIONS: The incidence of cerebral venous thrombosis among adults is probably higher than previously believed.

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BACKGROUND: The focal primary torsion dystonias (FPTDs) form a group of clinical heterogeneous syndromes and can be considered a genetic complex disease; it is thought to be primed by genetic variants with variable impact and triggered by non-genetic factors. Thorough clinical description of FPTDs cohorts is sparse but essential for further progress in genetic research. OBJECTIVE: To establish suggested relations between age at onset (AaO), site and family history in a large focal dystonias cohort and gain more insight into familial clustering for genetic research. PATIENTS AND METHODS: A prospective cohort study between March 2008 and March 2011, including 676 FPTD patients attending the botulinum toxin outpatient clinics of six Dutch movement disorder centres. RESULTS AND CONCLUSIONS: Of all of the FPTD patients, 25% had a familial predisposition; in 2.4% a Mendelian inheritance pattern was noted. With a stronger family history, a significantly lower AaO was seen in all focal dystonias. In both the sporadic and familial focal dystonia groups, AaO had an effect on the distribution of dystonia, with a caudal to cranial tendency. In all focal dystonia forms, women were more frequently affected, except for writer's cramp. Careful clinical characterisation will allow the formation of phenotype subgroups. We suggest that genetic research into FPTDs will benefit from this approach and discuss genetic research strategies to decipher the complex background of focal dystonias.

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Mutations in THAP1, a gene encoding a nuclear pro-apoptotic protein, have been associated with DYT6 dystonia. First reports on the phenotype of DYT6 dystonia show an early onset dystonia with predominant cranio-cervical and laryngeal involvement. Here we assessed the frequency and phenotype of THAP1 mutation carriers in a large Dutch cohort of adult-onset (≥26 years) dystonia (n = 388) and early-onset dystonia (n = 67) patients. We describe the phenotype of DYT6 dystonia patients and their response on GPi DBS. Overall, 3 nonsynonymous heterozygous mutations were detected in the early-onset group (4.5%). Two DYT6 families were identified, showing a heterozygous phenotype. All patients had segmental or generalized dystonia, often associated with profound oromandibular and laryngeal involvement. No nonsynonymous mutations were found in patients with adult-onset focal dystonia. Rare synonymous variants were identified in conserved regions of THAP1, two in the adult-onset cervical dystonia group and one in the control group. Four DYT6 dystonia patients were treated with GPi DBS with moderate to good response on motor function but marginal benefit on speech.

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The kinematics and neurophysiological aspects of eyelid movements were examined during spontaneous, voluntary, air puff, and electrically induced blinking in healthy human subjects, using the direct magnetic search coil technique simultaneously with electromyographic recording of the orbicularis oculi muscles (OO-EMG). For OO-EMG recordings, surface electrodes were attached to the lower eyelids. To measure the vertical lid displacement, a search coil with a diameter of 3 mm was placed 1 mm from the rim on the upper eyelid on a marked position. Blink registrations were performed from the zero position and from 28 randomly chosen positions. Blinks elicited by electrical stimulation of the supraorbital nerve had shortest duration and were least variable. In contrast, spontaneous blinks had longer duration and greater variability. Blinks induced by air puff had a slightly longer duration and similar variability as electrically induced blinks. There was a correlation between the maximal down phase amplitude and the integrated OO-EMG. Blink duration and maximal down phase amplitude were affected by eye position. Eyes positioned 30 degrees above horizontal displayed the shortest down phase duration and the largest maximal down phase amplitude and velocity. At 30 degrees below horizontal, blinks had the longest total duration, the longest down phase duration, and the lowest maximal down phase amplitude and velocity. The simultaneously recorded integrated OO-EMG was largest in the 30 degrees downward position. In four subjects, the average blinking data showed a linear relation between eye position and OO-EMG, maximal down phase amplitude, and maximal downward velocity.

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IMPLICATIONS: In this case report we describe a technique used to provide local analgesia for surgical procedures. Although this technique has a reduced risk of complications, we present a patient who experienced a life-threatening paralysis without loss of consciousness during an attempted brachial plexus block with a posterior approach.

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