Georg Kägi

Distinguishing SWEDDs Patients with Asymmetric Resting Tremor from Parkinson's Disease: A Clinical and Electrophysiological Study

Approximately 10% of patients diagnosed clinically with early Parkinsons disease (PD) have normal dopaminergic functional imaging (Scans Without Evidence of Dopaminergic Deficit [SWEDDs]). An important subgroup of SWEDDs are those with asymmetric rest tremor resembling parkinsonian tremor. Clinical and pathophysiological features which could help to distinguish SWEDDs from PD have not been explored. We therefore studied clinical details including non‐motor symptoms in 25 tremulous SWEDDs patients in comparison to 25 tremor‐dominant PD patients. Blinded video rating was used to compare examination findings. Electrophysiological tremor parameters and also response to a cortical plasticity protocol using paired associative stimulation (PAS) was studied in 9 patients with SWEDDs, 9 with tremor‐dominant PD (with abnormal dopamine transporter single photon emission computed tomography findings), 8 with segmental dystonia, and 8 with essential tremor (ET). Despite clinical overlap, lack of true bradykinesia, presence of dystonia, and head tremor favored a diagnosis of SWEDDs, whereas re‐emergent tremor, true fatiguing or decrement, good response to dopaminergic drugs, and presence of non‐motor symptoms favored PD. A single tremor parameter could not differentiate between groups, but the combination of re‐emergent tremor and highest tremor amplitude at rest was characteristic of PD tremor. SWEDDs and segmental dystonia patients exhibited an abnormal exaggerated response to the PAS protocol, in contrast to a subnormal response in PD and a normal response in ET. We conclude that despite clinical overlap, there are features that can help to distinguish between PD and SWEDDs which may be useful in clinical practice. The underlying pathophysiology of SWEDDs differs from PD but has similarities with primary dystonia.

The role of DAT-SPECT in movement disorders

Dopamine transporter (DAT) imaging is a sensitive method to detect presynaptic dopamine neuronal dysfunction, which is a hallmark of neurodegenerative parkinsonism. DAT imaging can therefore assist the differentiation between conditions with and without presynaptic dopaminergic deficit. Diagnosis of Parkinson disease or tremor disorders can be achieved with high degrees of accuracy in cases with full expression of classical clinical features; however, diagnosis can be difficult, since there is a substantial clinical overlap especially in monosymptomatic tremor (dystonic tremor, essential tremor, Parkinson tremor). The use of DAT-SPECT can prove or excludes with high sensitivity nigrostriatal dysfunction in those cases and facilitates early and accurate diagnosis. Furthermore, a normal DAT-SPECT is helpful in supporting a diagnosis of drug-induced-, psychogenic- and vascular parkinsonism by excluding underlying true nigrostriatal dysfunction. This review addresses the value of DAT-SPECT and its impact on diagnostic accuracy in movement disorders presenting with tremor and/or parkinsonism.

Lesion Location Predicts Transient and Extended Risk of Aspiration After Supratentorial Ischemic Stroke

Background and Purpose— To assess the association of lesion location and risk of aspiration and to establish predictors of transient versus extended risk of aspiration after supratentorial ischemic stroke. Methods— Atlas-based localization analysis was performed in consecutive patients with MRI-proven first-time acute supratentorial ischemic stroke. Standardized swallowing assessment was carried out within 8±18 hours and 7.8±1.2 days after admission. Results— In a prospective, longitudinal analysis, 34 of 94 patients (36%) were classified as having acute risk of aspiration, which was extended (≥7 days) or transient (<7 days) in 17 cases. There were no between-group differences in age, sex, cause of stroke, risk factors, prestroke disability, lesion side, or the degree of age-related white-matter changes. Correcting for stroke volume and National Institutes of Health Stroke Scale with a multiple logistic regression model, significant adjusted odds ratios in favor of acute risk of aspiration were demonstrated for the internal capsule (adjusted odds ratio, 6.2; P<0.002) and the insular cortex (adjusted odds ratio, 4.8; P<0.003). In a multivariate model of extended versus transient risk of aspiration, combined lesions of the frontal operculum and insular cortex was the only significant independent predictor of poor recovery (adjusted odds ratio, 33.8; P<0.008). Conclusions— Lesions of the insular cortex and the internal capsule are significantly associated with acute risk of aspiration after stroke. Combined ischemic infarctions of the frontal operculum and the insular cortex are likely to cause extended risk of aspiration in stroke patients, whereas risk of aspiration tends to be transient in subcortical stroke.

Dysphagia in Acute Stroke: Incidence, Burden and Impact on Clinical Outcome

Background Reported frequency of post-stroke dysphagia in the literature is highly variable. In view of progress in stroke management, we aimed to assess the current burden of dysphagia in acute ischemic stroke. Methods We studied 570 consecutive patients treated in a tertiary stroke center. Dysphagia was evaluated by using the Gugging Swallowing Screen (GUSS). We investigated the relationship of dysphagia with pneumonia, length of hospital stay and discharge destination and compared rates of favourable clinical outcome and mortality at 3 months between dysphagic patients and those without dysphagia. Results Dysphagia was diagnosed in 118 of 570 (20.7%) patients and persisted in 60 (50.9%) at hospital discharge. Thirty-six (30.5%) patients needed nasogastric tube because of severe dysphagia. Stroke severity rather than infarct location was associated with dysphagia. Dysphagic patients suffered more frequently from pneumonia (23.1% vs. 1.1%, p<0.001), stayed longer at monitored stroke unit beds (4.4±2.8 vs. 2.7±2.4 days; p<0.001) and were less often discharged to home (19.5% vs. 63.7%, p = 0.001) as compared to those without dysphagia. At 3 months, dysphagic patients less often had a favourable outcome (35.7% vs. 69.7%; p<0.001), less often lived at home (38.8% vs. 76.5%; p<0.001), and more often had died (13.6% vs. 1.6%; p<0.001). Multivariate analyses identified dysphagia to be an independent predictor of discharge destination and institutionalization at 3 months, while severe dysphagia requiring tube placement was strongly associated with mortality. Conclusion Dysphagia still affects a substantial portion of stroke patients and may have a large impact on clinical outcome, mortality and institutionalization.

The Phenotypic Spectrum of DYT24 Due to ANO3 Mutations

Genes causing primary dystonia are rare. Recently, pathogenic mutations in the anoctamin 3 gene (ANO3) have been identified to cause autosomal dominant craniocervical dystonia and have been assigned to the dystonia locus dystonia‐24 (DYT24). Here, we expand on the phenotypic spectrum of DYT24 and provide demonstrative videos. Moreover, tremor recordings were performed, and back‐averaged electroencephalography, sensory evoked potentials, and C‐reflex studies were carried out in two individuals who carried two different mutations in ANO3. Ten patients from three families are described. The age at onset ranged from early childhood to the forties. Cervical dystonia was the most common site of onset followed by laryngeal dystonia. The characteristic feature in all affected individuals was the presence of tremor, which contrasts DYT24 from the typical DYT6 phenotype. Tremor was the sole initial manifestation in some individuals with ANO3 mutations, leading to misdiagnosis as essential tremor. Electrophysiology in two patients with two different mutations showed co‐contraction of antagonist muscles, confirming dystonia, and a 6‐Hz arm tremor at rest, which increased in amplitude during action. In one of the studied patients, clinically superimposed myoclonus was observed. The duration of the myoclonus was in the range of 250 msec at about 3 Hz, which is more consistent with subcortical myoclonus. In summary, ANO3 causes a varied phenotype of young‐onset or adult‐onset craniocervical dystonia with tremor and/or myoclonic jerks. Patients with familial cervical dystonia who also have myoclonus‐dystonia as well as patients with prominent tremor and mild dystonia should be tested for ANO3 mutations.

Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome

Background— We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). Methods and Results— This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8–22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1–1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. Conclusions— IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.

Nonmotor Symptoms in Parkin Gene-Related Parkinsonism

The aim of the study was to explore the prevalence and differences of nonmotor symptoms (NMSs) in patients with young‐onset Parkinsons disease (YOPD) with and without mutations in the Parkin gene and late‐onset Parkinsons disease (LOPD). Twenty‐seven patients with YOPD and 27 with LOPD, as well as 16 patients with homozygous or compound heterozygote Parkin mutations filled in the nonmotor symptoms questionnaire, a 30‐item self‐completed questionnaire that addresses various NMSs. Overall, NMSs were more prevalent in YOPD (12.07 ± 3.9; P = 0.009) and LOPD (13.26 ± 5.8; P = 0.001) compared with Parkin mutation carriers (7.38 ± 4.2). Dribbling of saliva, vivid dreams, loss of smell, and urinary urgency were more prevalent in YOPD compared with Parkin mutation carriers. Only anxiety was more prevalent in the latter. Apart from anxiety, NMSs appear to be less prevalent in Parkin gene‐related parkinsonism. Although these results need further study, the presented data might be helpful in the clinical recognition of specific phenotypes and genotypes in YOPD. The data are in keeping with a different pathological disease process in Parkin gene‐related parkinsonism.

Sensory tricks in primary cervical dystonia depend on visuotactile temporal discrimination

A characteristic feature of primary cervical dystonia is the presence of “sensory tricks” as well as the impairment of temporal and spatial sensory discrimination on formal testing. The aim of the present study was to test whether the amount of improvement of abnormal head deviation due to a sensory trick is associated with different performance of temporal sensory discrimination in patients with cervical dystonia. We recruited 32 patients with cervical dystonia. Dystonia severity was assessed using the Toronto Western Spasmodic Torticollis Rating Scale. Patients were rated according to clinical improvement to a sensory trick and assigned to 1 of the following groups: (1) no improvement (n = 6), (2) partial improvement (n = 17), (3) complete improvement (n = 9). Temporal discrimination thresholds were assessed for visual, tactile, and visuotactile modalities. Disease duration was shorter (P = .026) and dystonia severity lower (P = .033) in the group with complete improvement to sensory tricks compared with the group with partial improvement to sensory tricks. A significant effect for group and modality and a significant interaction between group × modality were found, with lower visuotactile discrimination thresholds in the group with complete improvement to sensory tricks compared with the other groups. In primary cervical dystonia, a complete resolution of dystonia during a sensory trick is associated with better visuotactile discrimination and shorter disease duration compared with patients with less effective sensory tricks, which may reflect progressive loss of adaptive mechanisms to basal ganglia dysfunction.

Mental rotation of body parts and sensory temporal discrimination in fixed dystonia.

Fixed dystonia is an uncommon but severely disabling condition typically affecting young women following a minor peripheral injury. There is no evidence of any structural lesions of the central nervous system nor any clear peripheral nerve or root damage. Electrophysiological techniques such as short intracortical inhibition, cortical silent period and a plasticity inducing protocol have revealed similarities but also differences compared to classical mobile dystonia. To further explore the pathophysiology of fixed dystonia we compared mental rotation of body parts and sensory temporal discrimination in 11 patients with fixed dystonia, 11 patients with classical mobile dystonia and 10 healthy controls. In the mental rotation task subjects were presented with realistic photos of left or right hands, feet and the head of a young women with a black patch covering the left or the right eye in six different orientations. Subjects had to verbally report the laterality of the presented stimuli. To assess sensory temporal discrimination subjects were asked to discriminate whether pairs of visual, tactile (electrical), or visuo‐tactile stimuli were simultaneous or sequential (temporal discrimination threshold) and in the latter case which stimulus preceded the other (temporal order judgement). In accordance with previous studies patients with mobile dystonia were abnormal in mental rotation and temporal discrimination, whereas patients with fixed dystonia were only impaired in mental rotation. Possible explanations for this deficit may include the influence of the abnormal body posture itself, a shared predisposing pathophysiology for mobile and fixed dystonia, or a body image disturbance. These findings add information to the developing pathophysiological picture of fixed dystonia.

Arm swing is reduced in idiopathic cervical dystonia

Arm swing is typically reduced in people with Parkinsonism, and also in those with pyramidal dysfunction. We have previously observed that patients with focal arm dystonia can also have reduced arm swing. However, arm swing has not been formally studied in adult‐onset primary cervical dystonia (AOPCD). We assessed arm swing in 100 consecutive patients diagnosed with AOPCD and 50 healthy controls. Reduced arm swing was more common in patients with AOPCD compared with healthy controls (55% vs. 6%, P < 0.001) and was more often abnormal on the same side as the direction of head turning (P < 0.05). Women with AOPCD had more often reduced arm swing compared with men (P = 0.002). Reduced arm swing is common in AOPCD. It may indicate segmental spread of subtle motor dysfunction or it may be a feature of dystonia per se.