Objective:Anti-IgLON5 disease is a recently described neurological disease that shares features of autoimmunity and neurodegeneration. Abnormal movements appear to be frequent and important but have not been characterized and are under-reported. Here we describe the frequency and types of movement disorders in a series of consecutive patients with this disease.Methods:In this retrospective, observational study, the presence and phenomenology of movement disorders were assessed with a standardized clinical questionnaire. Available videos were centrally reviewed by three experts in movement disorders.Results:Seventy two patients were included. In 41 (57%) the main reason for initial consultation was difficulty walking along with one or several concurrent movement disorders. At the time of anti-IgLON5 diagnosis, 63 (87%) patients had at least one movement disorder with a median of three per patient. The most frequent abnormal movements were gait and balance disturbances (52 patients, 72%), chorea (24, 33%), bradykinesia (20, 28%), dystonia (19, 26%), abnormal body postures or rigidity (18, 25%), and tremor (15, 21%). Other hyperkinetic movements (myoclonus, akathisia, myorhythmia, myokymia, or abdominal dyskinesias) occurred in 26 (36%) patients. The craniofacial region was one of the most frequently affected by multiple concurrent movement disorders (23 patients, 32%) including dystonia (13), myorhythmia (6), chorea (4) or myokymia (4). Considering any body region, the most frequent combination of multiple movement disorders consisted of gait instability or ataxia associated with craniofacial dyskinesias or generalized chorea observed in 31(43%) of patients. In addition to abnormal movements, 87% of patients had sleep alterations, 74% bulbar dysfunction, and 53% cognitive impairment. Fifty-five (76%) patients were treated with immunotherapy, resulting in important and sustained improvement of the movement disorders in only seven (13%) cases.Conclusions:Movement disorders are a frequent and leading cause of initial neurological consultation in patients with anti-IgLON5 disease. Although multiple types of abnormal movements can occur, the most prevalent are disorders of gait, generalized chorea, and dystonia and other dyskinesias that frequently affect craniofacial muscles. Overall, anti-IgLON5 disease should be considered in patients with multiple movement disorders, particularly if they occur in association with sleep alterations, bulbar dysfunction, or cognitive impairment.
Objective: Autoantibody-mediated forms of encephalitis (AE) include neurological disorders characterized by subacute memory loss, movement disorders, and, often, frequent, focal epileptic seizures. Yet, the electrophysiological effects of these autoantibodies on neuronal function have received little attention. In this study, we assessed the effects of CSF containing autoantibodies on intrinsic and extrinsic properties of hippocampal neurons, to define their epileptogenic potential. Methods: We compared the effects of CSF containing leucine-rich glioma inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and c-aminobutyric acid receptor B (GABA B R) antibodies on ex vivo electrophysiological parameters after stereotactic hippocampal inoculation into mice. Wholecell patch-clamp and extracellular recordings from CA1 pyramidal neurons and CA3-CA1 field recordings in ex vivo murine brain slices were used to study neuronal function. Results: By comparison to control CSF, AE CSFs increased the probability of glutamate release from CA3 neurons. In addition, LGI1-and CASPR2 antibodies containing CSFs induced epileptiform activity at a population level following Schaffer collateral stimulation. CASPR2 antibody containing CSF was also associated with higher spontaneous firing of CA1 pyramidal neurons. On the contrary, GABA B R antibody containing CSF did not elicit changes in intrinsic neuronal activity and field potentials. Interpretation: Using patient CSF, we have demonstrated that the AE-associated antibodies against LGI1 and CASPR2 are able to increase hippocampal CA1 neuron excitability, facilitating epileptiform activity. These findings provide in vivo pathogenic insights into neuronal dysfunction in these conditions.
Approximately 15 % of PD patients with Parkinson Disease (PD) have the familial type and 5-10 % of these are known to have monogenic forms with either an autosomal dominant or a recessive inheritance pattern. Here, we report on a family carrying the A53T SNCA mutation and we review SNCA mutation phenotypes by comparing point mutations within each other as well as with duplication and triplication.
Brain single-photon-emission-computerized tomography (SPECT) with 123I-ioflupane (123I-FP-CIT) is useful to diagnose Parkinson disease (PD). To investigate the diagnostic performance of 123I-FP-CIT brain SPECT with semiquantitative analysis by Basal Ganglia V2 software (BasGan), we evaluated semiquantitative data of patients with suspect of PD by a support vector machine classifier (SVM), a powerful supervised classification algorithm.123I-FP-CIT SPECT with BasGan analysis was performed in 90 patients with suspect of PD showing mild symptoms (bradykinesia-rigidity and mild tremor). PD was confirmed in 56 patients, 34 resulted non-PD (essential tremor and drug-induced Parkinsonism). A clinical follow-up of at least 6 months confirmed diagnosis. To investigate BasGan diagnostic performance we trained SVM classification models featuring different descriptors using both a “leave-one-out” and a “five-fold” method. In the first study we used as class descriptors the semiquantitative radiopharmaceutical uptake values in the left (L) and right (R) putamen (P) and in the L and R caudate nucleus (C) for a total of 4 descriptors (CL, CR, PL, PR). In the second study each patient was described only by CL and CR, while in the third by PL and PR descriptors. Age was added as a further descriptor to evaluate its influence in the classification performance.123I-FP-CIT SPECT with BasGan analysis reached a classification performance higher than 73.9% in all the models. Considering the “Leave-one-out” method, PL and PR were better predictors (accuracy of 91% for all patients) than CL and CR descriptors; using PL, PR, CL, and CR diagnostic accuracy was similar to that of PL and PR descriptors in the different groups. Adding age as a further descriptor accuracy improved in all the models. The best results were obtained by using all the 5 descriptors both in PD and non-PD subjects (CR and CL + PR and PL + age = 96.4% and 94.1%, respectively). Similar results were observed for the “five-fold” method.123I-FP-CIT SPECT with BasGan analysis using SVM classifier was able to diagnose PD. Putamen was the most discriminative descriptor for PD and the patient age influenced the classification accuracy.
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