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Background: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD)., Objective: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL)., Patients and Methods: PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL., Results: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (β = 0.073; P = 0.027; R 2  = 0.62) and to develop disabling LID at V5 (β = 0.088; P = 0.009; R 2  = 0.73) were independently associated with a higher score on the PDQ-39SI., Conclusion: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL., (© 2024 International Parkinson and Movement Disorder Society.)

Background: Cognitive reserve (CR) is the mismatch between preserved cognition and neuropathological damage. Amyloidopathy in Parkinson's disease (PD) could be associated with faster progression to dementia, but the putative protective effect of CR is unknown., Objectives: To evaluate the effect of CR on β-amyloid burden and brain metabolism in non-demented PD subjects., Methods: Participants with PD (n = 53) underwent a clinical evaluation, [ 18 F]-fluorodeoxyglucose and [ 18 F]-flutemetamol positron emission tomography magnetic resonances, and were classified according to CR. The metabolic pattern of 16 controls was compared to PD subjects., Results: The PD subjects showed hypometabolism mainly in the bilateral posterior cortex. Superior-CR subjects (n = 22) exhibited better cognitive performance, increased amyloid burden, and higher metabolism in several right hemisphere areas compared to low-medium-CR subjects (n = 31)., Conclusions: Higher CR in non-demented PD is associated with better cognitive performance, which might reduce vulnerability to the effect of β-amyloid. Whether superior CR leads to protection against metabolic deterioration, and predominantly right hemisphere involvement, deserves further exploration., (© 2024 International Parkinson and Movement Disorder Society.)

Background and Purpose: The microtubule-associated protein tau (MAPT) H1 homozygosity (H1/H1 haplotype) is a genetic risk factor for neurodegenerative diseases, such as Parkinson's disease (PD). MAPT H1 homozygosity has been associated with conversion to PD; however, results are conflicting since some studies did not find a strong influence. Cortical hypometabolism is associated with cognitive impairment in PD. In this study, we aimed to evaluate the metabolic pattern in nondemented PD patients MAPT H1/H1 carriers in comparison with MAPT H1/H2 haplotype. In addition, we evaluated domain-specific cognitive differences according to MAPT haplotype., Methods: We compared a group of 26 H1/H1 and 20 H1/H2 carriers with late-onset PD. Participants underwent a comprehensive neuropsychological cognitive evaluation and a [18F]-Fluorodeoxyglucose PET-MR scan., Results: MAPT H1/H1 carriers showed worse performance in the digit span forward test of attention compared to MAPT H1/H2 carriers. In the [18F]-Fluorodeoxyglucose PET comparisons, MAPT H1/H1 displayed hypometabolism in the frontal cortex, parahippocampal, and cingulate gyrus, as well as in the caudate and globus pallidus., Conclusion: PD patients MAPT H1/H1 carriers without dementia exhibit relative hypometabolism in several cortical areas as well as in the basal ganglia, and worse performance in attention than MAPT H1/H2 carriers. Longitudinal studies should assess if lower scores in attention and dysfunction in these areas are predictors of dementia in MAPT H1/H1 homozygotes., (© 2023 American Society of Neuroimaging.)

Background and Purpose: In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015)., Methods: This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants., Results: In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 ± 8.9 years old, 60.3% males), 273 caregivers (58.5 ± 11.9 years old, 31.8% males) and 207 controls (61 ± 8.3 years old, 49.5% males). The mean disease duration was 5.5 ± 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4 ± 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging)., Conclusions: Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them., (© European Academy of Neurology 2019.)

Essential tremor is the most common movement disorder in adults. In patients who are not responsive to medical treatment, functional neurosurgery and, more recently, transcranial MR-guided focused ultrasound thalamotomy are considered effective therapeutic approaches. However, the structural brain changes following a thalamotomy that mediates the clinical improvement are still unclear. In here diffusion weighted images were acquired in a cohort of 24 essential tremor patients before and 3 months after unilateral transcranial MR-guided focused ultrasound thalamotomy targeting at the posteroventral part of the VIM. Microstructural changes along the DRTT were quantified by means of probabilistic tractography, and later related to the clinical improvement of the patients at 3-months and at 1-year after the intervention. In addition the changes along two neighboring tracts, that is, the corticospinal tract and the medial lemniscus, were assessed, as well as the relation between these changes and the presence of side effects. Thalamic lesions produced local and distant alterations along the trajectory of the DRTT, and each correlated with clinical improvement. Regarding side effects, gait imbalance after thalamotomy was associated with greater impact on the DRTT, whereas the presence of paresthesias was significantly related to a higher overlap between the lesion and the medial lemniscus. This work represents the largest series describing the microstructural changes following transcranial MR-guided focused ultrasound thalamotomy in essential tremor. These results suggest that clinical benefits are specific for the impact on the cerebello-thalamo-cortical pathway, thus reaffirming the potential of tractography to aid thalamotomy targeting., (© 2019 Wiley Periodicals, Inc.)

Background: The clinical features of cluster headache (CH) disclose some vascular changes in the symptomatic region, but few instrumental studies have assessed orbital hemodynamics in patients with this disorder., Methods: Orbital blood flow reactivity elicited by Valsalva maneuver (VM) was studied with ophthalmic artery eco-Doppler in 16 patients (14 men and 2 women; mean age: 41.2) suffering from episodic CH and in 18 healthy controls. Patients were examined twice: first, in a cluster period (between pain attacks), and second, in a remission period. Each time peak-systolic and end-diastolic flow velocities were recorded in both ophthalmic arteries at rest and during all phases of VM., Results: Valsalva phase IV was consistently associated with an increment of blood flow velocities through the ophthalmic arteries. Unlike controls, patients showed an asymmetric vascular reactivity. In the cluster period peak-systolic flow velocity increments were lower on the symptomatic side than on the asymptomatic side (14.1% vs. 34.4%; P < .001), while in remission end-diastolic flow velocity increments were higher in the previously symptomatic orbit (129% vs. 72.9%; P < .05). Vascular reactivity on the asymptomatic side was always similar to that of healthy controls., Conclusions: In episodic CH, the symptomatic orbit shows an abnormal vascular reactivity. During the cluster period, basal vasodilation and hyperemia could preclude it from admitting a much greater amount of blood at the end of Valsalva. During remission, there might be some latent vascular changes that lead to supersensitive vasodilator responses and/or opening of arteriovenous shunts under certain circumstances such as Valsalva. These phenomena could be relevant in the pathophysiology of CH.

Objective: To study the clinical features of nummular headache (NH) and get an approach to its epidemiology., Background: NH has been recently described as a primary disorder characterized by head pain exclusively felt in a small rounded area typically 2-6 cm in diameter., Methods: Through a 1-year period we have studied all patients referred to our neurologic clinic because of head pain exclusively felt in a small-circumscribed area, and not attributed to another disorder. All the patients had normal neurological, analytical, and neuroimaging examinations. All the patients belonged within the same regional care system comprising 220,000 inhabitants., Results: A total of 11 females and 3 males were studied. Based in our hospital series, the incidence was 6.4/100,000/year. The mean age at the onset was 38 years (range: 13-72). Only three patients had another concurrent headache: migraine (n = 2), and trigeminal neuralgia (n = 1) which proved to have an independent course. All the patients reported head pain exclusively felt in either a rounded (n = 12) of 1-6 cm diameter, or an oval area (n = 2) of 5 x 3 cm, and 2 x 3 cm, respectively. Both size and shape of the painful area remained constant since the onset of symptoms. The location of the symptomatic area was mostly parietal (n = 7) or temporal (n = 5), but also frontal (n = 1) and in occiput (n = 1). The background pain was mostly mild-to-moderate, but also moderate-to-severe pain was reported. Exacerbations-either spontaneous or precipitated by combing hair or touching the symptomatic area-were reported by 8 patients. The temporal pattern was chronic-continuous (n = 7) and episodic (n = 7). Ten patients reported a variable combination of sensory disturbance (tenderness, hypoesthesia, hyperalgesia, and allodynia) in the symptomatic area. There were no autonomic accompaniments. Treatment was generally not necessary. When needed, standard oral doses of paracetamol usually sufficed., Conclusions: NH emerges as a clear-cut clinical picture. It is a noninfrequent primary headache. The particular topography suggests the pain has a probable epicranial source conveyed by, or originated in, one/a few terminal branch(es) of the cutaneous nerves of the scalp.