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Abstract Background & Objectives Calcitonin gene-related peptide ligand/receptor (CGRP) antibodies effectively reduce headache frequency in migraine. It is understood that they act peripherally, which raises the question whether treatment merely interferes with the last stage of headache generation or, alternatively, causes secondary adaptations in the central nervous system and might thus possess disease modifying potential. This study addresses this question by investigating the nociceptive blink reflex (nBR), which is closely tied to central disease activity, before and after treatment with CGRP antibodies. Methods We enrolled 22 patients suffering episodic migraine (21 female, 46.2 ± 13.8 years of age) and 22 age-/gender-matched controls. Patients received assessments of the nBR (R2 component, 10 trials, 6 stimuli/trial) before (V0) and three months (V3) after treatment with CGRP antibodies started, controls were assessed once. The R2 area (R2a) and habituation (R2h; gradient of R2a against stimulus order) of the stimulated/non-stimulated side (_s/_ns) following repeated supraorbital stimulation provide a direct readout of brainstem excitability and habituation as key mechanisms in migraine. Results All patients showed a substantial reduction of headache days/month (V0: 12.4±3.3, V3: 6.6 ± 4.9). R2a_s (Fglobal=5.86, p

Background and purpose: Diagnosing a patient with headache as a migraineur is critical for state-of-the-art migraine management. Screening tools are imperative means to improve the diagnostic yield in the primary care settings and specialized clinics. This study aims to translate and assess the diagnostic accuracy of a German version of the ID Migraine™ as a widely used and efficient screening instrument. Methods: The Functional Assessment of Chronic Illness Therapy translation methodology was used to translate the original three-item ID Migraine ™, including a fourth question for aura, from the English language into the German language. Diagnostic accuracy of the German ID Migraine ™ and predictors of false screening results were assessed among patients presenting to a headache outpatient clinic of a tertiary care center in Germany over a 6-month period. Results: The translation procedure yielded a harmonized German ID Migraine ™ and its diagnostic accuracy was assessed in 105 patients (80 female, 46.5 ± 17.2 years of age), including 79 patients (75.2%) with migraine. The three-item German ID Migraine ™ provides a sensitivity of 99%, specificity of 68%, and positive and negative predictive values of 90% and 95%, respectively, using a cutoff of ≥2. Positive and negative predictive values in a general headache population are estimated to be 74% and 98%, respectively. The aura question identified 18 out of 20 migraineurs with aura. Conclusions: The German ID Migraine ™ is an accurate screening tool for migraine even in a challenging population of a specialized outpatient clinic. Its diagnostic accuracy indicates a potential utility for screening in primary health care.

(1) Background: Headache disorders are among the most disabling medical conditions but the supply with experienced providers is outpaced by the demand for service. It is unclear to what extent particularly patients in rural regions are affected by limited access to comprehensive care. Furthermore, it is unknown what role general practitioners (GPs) play in headache care. (2) Methods: First-time consultations to a specialised headache clinic at a tertiary care centre were asked to participate. Their socio-demographic background, general and headache-specific medical history, disability and quality of life (QoL) were assessed. Additionally, 176 GPs in neighbouring districts were contacted regarding headache management. (3) Results: We assessed 162 patients with first-time consultations (age 46.1 ± 17.0 years, 78.1% female), who suffered from migraine (72%), tension type, cluster and secondary headaches (each 5–10%). About 50% of patients received a new headache-diagnosis and 60% had treatment inconsistent with national guidelines. QoL was significantly worse in all domains compared to the general population. About 75% of GPs see headache patients at least several times per week, and mostly treat them by themself. (4) Conclusions: More than every second headache patient was neither correctly diagnosed nor received guideline adherent treatment. Headache-related disability is inferior to what is expected from previous studies. Access to specialised health care is more limited in rural than in urban regions in Germany and GPs request more training.

Dystonia is a heterogeneous group of hyperkinetic movement disorders. The unifying descriptor of dystonia is the motor manifestation, characterized by continuous or intermittent contractions of muscles that cause abnormal movements and postures. Additionally, there are psychiatric, cognitive, and sensory alterations that are possible or putative non-motor manifestations of dystonia. The pathophysiology of dystonia is incompletely understood. A better understanding of dystonia pathophysiology is highly relevant in the amelioration of significant disability associated with motor and non-motor manifestations of dystonia. Recently, diminished olfaction was found to be a potential non-motor manifestation that may worsen the situation of subjects with dystonia. Yet, this finding may also shed light into dystonia pathophysiology and yield novel treatment options. This article aims to provide background information on dystonia and the current understanding of its pathophysiology, including the key structures involved, namely, the basal ganglia, cerebellum, and sensorimotor cortex. Additionally, involvement of these structures in the chemical senses are reviewed to provide an overview on how olfactory (and gustatory) deficits may occur in dystonia. Finally, we describe the present findings on altered chemical senses in dystonia and discuss directions of research on olfactory dysfunction as a marker in dystonia.

Pathogenic variants in EEF1A2 , a gene encoding a eukaryotic translation elongation factor, have been previously reported in pediatric cases of epileptic encephalopathy and intellectual disability. We report a case of a 17-year-old male with a prior history of epilepsy, autism, intellectual disability, and the abrupt onset of choreo-athetotic movements. The patient was diagnosed with an EEF1A2 variant by whole exome sequencing. His movement disorder responded dramatically to treatment with tetrabenazine. To the best of our knowledge, this is the first report of successful treatment of a hyperkinetic movement disorder in the setting of EEF1A2 mutation. A trial with tetrabenazine should be considered in cases with significant choreoathetosis.

Tourette syndrome is a chronic tic disorder characterized by motor and vocal tics. Comorbidities such as attention deficit hyperactivity disorder and obsessive compulsive disorder can be found. The overlap between neuroanatomical regions and neurotransmitter systems in the olfactory system and the pathophysiology of Tourette syndrome let us hypothesize altered olfactory performance in Tourette syndrome. The main objective of this study was to systematically assess olfactory functioning in subjects with Tourette syndrome and to compare it to healthy controls. We assessed 28 adults with Tourette syndrome (age 33.1±9.4 years, disease duration 23.7±9.7 years) and 28 healthy controls (age 32.9±9.0 years) matched in regard to age, sex, education and smoking habits. The "Sniffin Sticks" test battery was applied to assess odor threshold, discrimination, and identification. Additionally, the combined score of the odor threshold test, the odor discrimination test and the odor identification test of the "Sniffin Sticks" test battery was calculated. Although it was not the primary aim of this study, we assessed whether tics and comorbidity could contribute to olfactory alterations in adults with Tourette syndrome. Therefore, clinical scores were used to assess severity of tics and co-morbidity such as attention deficit hyperactivity disorder, obsessive compulsive disorder, anxiety and depression in subjects with Tourette syndrome. Pathology of the nasal cavities was excluded with rhinoendoscopy. Independent sample t-tests were applied to compare performance in olfactory tests. In the case of statistically significant differences (critical p-value: 0.05), multiple linear regression analysis was carried out to explore whether tic severity, social impairment, co-morbidity or medical treatment had an impact on the differences found. Descriptive values are reported as mean ± standard deviation. Tourette syndrome subjects showed lower combined scores (Tourette syndrome subjects 31.9 ± 5.1 versus healthy controls 35.0 ± 3.1; p = 0.007), odor identification scores (Tourette syndrome subjects 12.4 ± 2.0 versus healthy controls 13.7 ± 1.4; p = 0.008) and odor discrimination scores (Tourette syndrome subjects 12.1 ± 2.1 versus healthy controls 13.2 ± 1.6; p = 0.041) in comparison to healthy subjects, while there was no difference in odor threshold (Tourette syndrome subjects 7.3 ± 2.7 versus healthy controls 8.1 ± 2.2; p = 0.22). Seven out of 28 Tourette syndrome subjects (25%) scored in the range of the age- and sex-dependent combined score for hyposmia, while two of 28 healthy controls (7%) had a similar low combined score. None of the participants were found to have functional anosmia. Multiple linear regression analyses suggest that social impairment may a predictor for low combined score and odor identification score in Tourette syndrome subjects (p = 0.003). Compared to healthy controls, altered olfaction in adults with Tourette syndrome was found in this study. Normal odor threshold level but lower scores at tasks involving supra-threshold odor concentrations point towards a central-nervous alteration in the processing of olfactory information in Tourette syndrome.

Parkinson's disease (PD) is characterized by typical extrapyramidal motor features and increasingly recognized non-motor symptoms such as working memory (WM) deficits. Using functional magnetic resonance imaging (fMRI), we investigated differences in neuronal activation during a motor WM task in 23 non-demented PD patients and 23 age- and gender-matched healthy controls. Participants had to memorize and retype variably long visuo-spatial stimulus sequences after short or long delays (immediate or delayed serial recall). PD patients showed deficient WM performance compared to controls, which was accompanied by reduced encoding-related activation in WM-related regions. Mirroring slower motor initiation and execution, reduced activation in motor structures such as the basal ganglia and superior parietal cortex was detected for both immediate and delayed recall. Increased activation in limbic, parietal and cerebellar regions was found during delayed recall only. Increased load-related activation for delayed recall was found in the posterior midline and the cerebellum. Overall, our results demonstrate that impairment of WM in PD is primarily associated with a widespread reduction of task-relevant activation, whereas additional parietal, limbic and cerebellar regions become more activated relative to matched controls. While the reduced WM-related activity mirrors the deficient WM performance, the additional recruitment may point to either dysfunctional compensatory strategies or detrimental crosstalk from "default-mode" regions, contributing to the observed impairment.

Several lines of evidence point to an involvement of the olivo-cerebellar system in the pathogenesis of essential tremor (ET), with clinical signs of cerebellar dysfunction being present in some subjects in the advanced stage. Besides motor coordination, the cerebellum is critically involved in motor learning. Evidence of motor learning deficits would strengthen the hypothesis of olivo-cerebellar involvement in ET. Conditioning of the eyeblink reflex is a well-established paradigm to assess motor learning. Twenty-three ET subjects (13 males, 10 females; mean age 44.3 ± 22.3 years, mean disease duration 17.4 ± 17.3 years) and 23 age-matched healthy controls were studied on two consecutive days using a standard delay eyeblink conditioning protocol. Six ET subjects exhibited accompanying clinical signs of cerebellar dysfunction. Care was taken to examine subjects without medication affecting central nervous functioning. Seven ET subjects and three controls on low-dose beta-blocker treatments, which had no effect on eyeblink conditioning in animal studies, were allowed into the study. The ability to acquire conditioned eyeblink responses was significantly reduced in ET subjects compared with controls. Impairment of eyeblink conditioning was not due to low-dose beta-blocker medication. Additionally, acquisition of conditioned eyeblink response was reduced in ET subjects regardless of the presence of cerebellar signs in clinical examination. There were no differences in timing or extinction of conditioned responses between groups and conditioning deficits did not correlate with the degree of tremor or ataxia as rated by clinical scores. The findings of disordered eyeblink conditioning support the hypothesis that ET is caused by a functional disturbance of olivo-cerebellar circuits which may cause cerebellar dysfunction. In particular, results point to an involvement of the olivo-cerebellar system in early stages of ET. [ABSTRACT FROM AUTHOR]