Dystonic Episodes Research Articles

Seizure and movement disorder in CACNA1E developmental and epileptic encephalopathy: Two sides of the same coin or same side of two different coins?

Pathogenic variants in CACNA1E are associated with early-onset epileptic and developmental encephalopathy (DEE). Severe to profound global developmental delay, early-onset refractory seizures, severe hypotonia, and macrocephaly are the main clinical features. Patients harboring the recurrent CACNA1E variant p.(Gly352Arg) typically present with the combination of early-onset DEE, dystonia/dyskinesia, and contractures. We describe a 2-year-and-11-month-old girl carrying the p.(Gly352Arg) CACNA1E variant. She has a severe DEE with very frequent drug-resistant seizures, profound hypotonia, and episodes of dystonia and dyskinesia. Long-term video-EEG-monitoring documented subsequent tonic asymmetric seizures during wakefulness and mild paroxysmal dyskinesias of the trunk out of sleep which were thought to be a movement disorder and instead turned out to be focal hyperkinetic seizures. This is the first documented description of the EEG findings in this disorder. Our report highlights a possible overlap between cortical and subcortical phenomena in CACNA1E-DEE. We also underline how a careful electro-clinical evaluation might be necessary for a correct discernment between the two disorders, playing a fundamental role in the clinical assessment and proper management of children with CACNA1E-DEE.

Classical homocystinuria presenting with transient basal ganglia pathology and dystonia.

Classical homocystinuria is caused by pathogenic variants in the CBS gene leading to a deficiency of the vitamin B6-dependent enzyme cystathionine beta synthase. The disease is typically associated with high blood homocysteine concentrations. Clinical features include developmental delay/intellectual disability, psychiatric problems, thromboembolism, lens dislocation, and marfanoid habitus. We report on a child with classical homocystinuria presenting with acute episodes of dystonia and symmetrical basal ganglia abnormalities mimicking a mitochondrial disease. After starting treatment with vitamin B6, homocysteine levels rapidly normalized and dystonic episodes did not re-occur. Moreover, brain-imaging findings almost completely disappeared. The case illustrates that homocystinuria should be considered as a treatable differential diagnosis of dystonia.

Myelin oligodendrocyte glycoprotein antibody‐associated disease presenting with dystonia

AbstractMyelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) commonly presents as optic neuritis or transverse myelitis. We report an atypical clinical presentation for MOGAD in a 28‐year‐old female experiencing right‐arm dystonic episodes. MRI scans demonstrated multifocal periventricular and subcortical lesions, including in the left centrum semiovale and corona radiata. Despite the atypical presentation, her clinical, serological, and radiographic features favor a MOGAD diagnosis. This report emphasizes the heterogeneity of MOGAD phenotypes and the need to consider MOGAD, even in a non‐typical presentation.

CAFFEINE INDUCED CERVICAL DYSTONIA-A CASE STUDY

Dystonia is a movement disorder characterised by involuntary, extended, patterned, and often repetitive muscle contractions of skeletal muscles, frequently causing twisting movements or abnormal postures. Recent studies have shown that stress and coffee consumption can precipitate dystonic attacks. Many people, due to their diligent life schedules and increased physical inactivity due to less work-life balance, have been identified as the major cause of this neurological movement disorder. The action of caffeine and other CNS stimulants may be related to dystonic episodes in an individual. Cervical dystonia is specifically characterised by involuntary muscle contraction of the trapezius muscle, pain in the cervical region, numbness in one or both arms, and restricted movement. Proper understanding and management of spasmodic torticollis are necessary to avoid discomfort and progress towards a healthy life. The case study aims to highlight the role of physical activity along with proper work-life balance to live a healthy lifestyle and minimise the frequency of muscle spasm attacks caused by spasmodic torticollis. The role of clinicians such as physicians and clinical pharmacists in understanding and managing the disease is critical and crucial for a better quality of life and leading a stress-free life.

Altered brain state during episodic dystonia in tottering mice decouples primary motor cortex from limb kinematics.

Episodic Ataxia Type 2 (EA2) is a rare neurological disorder caused by a mutation in the CACNA1A gene, encoding the P/Q-type voltage-gated Ca2+ channel important for neurotransmitter release. Patients with this channelopathy exhibit both cerebellar and cerebral pathologies, suggesting the condition affects both regions. The tottering (tg/tg) mouse is the most commonly used EA2 model due to an orthologous mutation in the cacna1a gene. The tg/tg mouse has three prominent behavioral phenotypes: a dramatic episodic dystonia; absence seizures with generalized spike and wave discharges (GSWDs); and mild ataxia. We previously observed a novel brain state, transient low-frequency oscillations (LFOs) in the cerebellum and cerebral cortex under anesthesia. In this study, we examine the relationships among the dystonic attack, GSWDs, and LFOs in the cerebral cortex. Previous studies characterized LFOs in the motor cortex of anesthetized tg/tg mice using flavoprotein autofluorescence imaging testing the hypothesis that LFOs provide a mechanism for the paroxysmal dystonia. We sought to obtain a more direct understanding of motor cortex (M1) activity during the dystonic episodes. Using two-photon Ca2+ imaging to investigate neuronal activity in M1 before, during, and after the dystonic attack, we show that there is not a significant change in the activity of M1 neurons from baseline through the attack. We also conducted simultaneous, multi-electrode recordings to further understand how M1 cellular activity and local field potentials change throughout the progression of the dystonic attack. Neither putative pyramidal nor inhibitory interneuron firing rate changed during the dystonic attack. However, we did observe a near complete loss of GSWDs during the dystonic attack in M1. Finally, using spike triggered averaging to align simultaneously recorded limb kinematics to the peak Ca2+ response, and vice versa, revealed a reduction in the spike triggered average during the dystonic episodes. Both the loss of GSWDs and the reduction in the coupling suggest that, during the dystonic attack, M1 is effectively decoupled from other structures. Overall, these results indicate that the attack is not initiated or controlled in M1, but elsewhere in the motor circuitry. The findings also highlight that LFOs, GSWDs, and dystonic attacks represent three brain states in tg/tg mice.

Extrapyramidal syndrome in a breastfed child, relevance of toxicological analysis

The passage of drugs in breast milk may be responsible for toxicity in breastfed children. We report here a case of passage of metoclopramide, an antiemetic neuroleptic, in breast milk, causing an extrapyramidal syndrome in the child, revealed in blood and hair. Case: a 21-week-old child was brought by his parents to the pediatric neurology department for consultation following two episodes of unexplained extrapyramidal syndrome. The little G., fed by mixed breastfeeding, presented a first episode of unexplained acute dystonia (generalized hypertonia with legs in extension and arms flexed against the chest, ceiling gaze, opisthonos) and two weeks later, a new episode of acute extrapyramidal syndrome, which resolved in a few hours. Both events required emergency hospitalization. During the second episode, diazepam 0.5 mg/kg IV was initiated, unsuccessfully. The anamnesis revealed that the mother had taken a rectal suppository of metoclopramide (10 mg) 48 hours before the first episode. An MRI was performed on arrival at the emergency room. Blood toxicology analysis was performed two days after the first episode. A 3-cm strand of brown hair was collected one month after the second episode. The entire sample (13 mg) was analyzed without segmentation. It should also be noted that the father had retractile capsulitis, treated with codeine paracetamol, and that the child had received paracetamol for teething. The child had no further episodes of dystonia since the second event. The MRI was normal. The child's blood toxicology analysis revealed the presence of metoclopramide at a concentration of 8 ng/mL. Hair analysis revealed metoclopramide at a relatively high concentration (1058 pg/mg), as well as paracetamol (31 ng/mg), lidocaine (34 pg/mg), diazepam (3 pg/mg) and its metabolite nordazepam (5 pg/mg), and codeine (16 pg/mg) in the analyzed hair of child G. The presence of diazepam and its metabolite can be explained by medical care. The low concentration of codeine without its metabolite morphine, may suggest an external contamination by the environment, contact with people who had consumed this molecule (bedding, caressing, etc.), especially the child's father. The presence of metoclopramide in the blood and hair is compatible with a passage of breast milk to the child. According to the literature, less than 5% of the maternal dose is found in the child. Adverse effects such as intestinal disorders, drowsiness, agitation, hypertonia have already been described in breastfed children (EMA. Metoclopramide Assessment report, 2013). This case illustrates the passage into breast milk of rectally administered metoclopramide in the mother and the toxic effects of this molecule in the child. The interpretation of hair analysis in infants remains nevertheless delicate to discriminate consumption from environmental contamination.

Functional abnormalities in the cerebello-thalamic pathways in a mouse model of DYT25 dystonia.

Dystonia is often associated with functional alterations in the cerebello-thalamic pathways, which have been proposed to contribute to the disorder by propagating pathological firing patterns to the forebrain. Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia. DYT25 (Gnal+/-) mice carry a heterozygous knockout mutation of the Gnal gene, which notably disrupts striatal function, and systemic or striatal administration of oxotremorine to these mice triggers dystonic symptoms. Our results reveal an increased cerebello-thalamic excitability in the presymptomatic state. Following the first dystonic episode, Gnal+/- mice in the asymptomatic state exhibit a further increase of the cerebello-thalamo-cortical excitability, which is maintained after θ-burst stimulations of the cerebellum. When administered in the symptomatic state induced by a cholinergic activation, these stimulations decreased the cerebello-thalamic excitability and reduced dystonic symptoms. In agreement with dystonia being a multiregional circuit disorder, our results suggest that the increased cerebello-thalamic excitability constitutes an early endophenotype, and that the cerebellum is a gateway for corrective therapies via the depression of cerebello-thalamic pathways.

Vibro-Tactile Stimulation as a Non-Invasive Neuromodulation Therapy for Cervical Dystonia: A Case Study.

Cervical dystonia (CD) is a type of focal dystonia that is characterized by involuntary neck postures. The underlying neurophysiology mechanism of CD is unknown, but there is increasing empirical evidence that motor deficits of CD are associated with somatosensory and proprioceptive deficits in the upper limb area. Vibro-tactile stimulation (VTS) is a non-invasive somatosensory stimulation approach where afferent signals from the vibrated muscle and tactile mechanoreceptors modulate cortical activity. Previous studies have shown that VTS could be an effective neuromodulation therapy for treating laryngeal dystonia. This proof-of-concept study examined the effect of VTS on alleviating the involuntary cervical muscle contractions in a female participant with intermittent torticollis. VTS was applied sequentially on four neck positions: bilateral trapezius (TRP) and bilateral sternocleidomastoid (SCM). Each VTS site was vibrated continuously for six minutes. The kinematics and underlying neck muscle activities during dystonic neck movements were examined with acceleration and surface electromyography (sEMG). To quantify the efficacy of VTS, two acceleration features and one sEMG feature were derived: (1) number of acceleration peaks per minute; (2) peak amplitude of acceleration (PAA); (3) change in power of sEMG after VTS. The frequency of intermittent dystonic neck movements decreased by 60% after VTS. In addition, PAA during dystonic episodes was drastically reduced after VTS when compared to baseline. Third, the effectiveness of VTS in alleviating dystonic muscle spasms depended on the site of vibration. For this participant, the left trapezius muscle was shown as the optimal vibration site reducing sEMG signal power by 15% across all recorded muscles. This case study offered preliminary insight into the assumed effectiveness of neck muscle VTS as a treatment for CD. Our participant experienced pain relief after VTS with measured improvements reflected by electrophysiological and kinematic data. A systematic study with a larger sample size is required in the future to validate the effectiveness of VTS for treating symptoms in CD.

RHOBTB2 gene associated epilepsy and paroxysmal movement disorder: two cases report and literature review

BackgroundRHOBTB2 gene is associated with developmental and epileptic encephalopathy-64(DEE-64), which is characterized by epilepsy, developmental delay, microcephaly, unspecific facial dysmorphism, and paroxysmal movement disorders. Most previous studies showed that the phenotypes of RHOBTB2 gene include developmental and epileptic encephalopathy(DEE) and DEE with paroxysmal movement disorders. Only one study showed that patient with RHOBTB2 variant had paroxysmal movement disorders with no epilepsy.Case presentationsTwo cases with RHOBTB2 variants are presented here: Case one was diagnosed as DEE, he had recurrent afebrile focal status epilepticus and paroxysmal extrapyramidal symptoms in infancy. Interictal electroencephalogram (EEG) showed focal discharges. Brain magnetic resonance imaging (MRI) showed cortical dysplasia. Epilepsy of case one was refractory. Nevertheless, case two only showed paroxysmal movement disorders alone in adolescence. Video EEG showed focal discharges during an interictal dystonic episode and he brain MRI was normal.ConclusionThe phenotypes of RHOBTB2 gene include DEE, paroxysmal movement disorders, and DEE with paroxysmal movement disorders. RHOBTB2 can be one of the pathogenic genes of paroxysmal movement disorders.

Microencephaly in macrocephaly: Rare report of two siblings with glutaric aciduria type 1

Glutaric aciduria type 1 is an autosomal recessive disorder caused by mutations in GCDH gene on chromosome 19 leading to the deficiency of glutaryl-CoA dehydrogenase which causes an abnormal metabolism of lysine, hydroxylysine and tryptophan with resultant accumulation of glutaric acid and 3-hydroxy glutaric acid. Usual presentations include macrocephaly with recurrent dystonic episodes, along with developmental regression. The diagnosis is based on characteristic magnetic resonance imaging finding of widening of sylvian fissures and urinary tandem mass spectroscopic analysis of excess glutarylcarnitine and hydroxyglutaric acid. Management includes lysine-free diet and carnitine supplementation.

Deep brain stimulation by optimized stimulators in a phenotypic model of dystonia: Effects of different frequencies

Deep brain stimulation (DBS) of the globus pallidus internus (GPi, entopeduncular nucleus, EPN, in rodents) has become important for the treatment of generalized dystonia, a severe and often intractable movement disorder. It is unclear if lower frequencies of GPi-DBS or stimulations of the subthalamic nucleus (STN) are of advantage. In the present study, the main objective was to examined the effects of bilateral EPN-DBS at different frequencies (130 Hz, 40 Hz, 15 Hz) on the severity of dystonia in the dtsz mutant hamster. In addition, STN stimulations were done at a frequency, proven to be effective by the present EPN-DBS in dystonic hamsters. In order to obtain precise bilateral electrical stimuli with magnitude of 50 μA, a pulse width of 60 μs and defined frequencies, it was necessary to develop a new optimized stimulator prior to the experiments. Since the individual highest severity of dystonic episodes is known to be reached within three hours after induction in dtsz hamsters, the duration of DBS was 180 min. During DBS with 130 Hz the severity of dystonia was significantly lower within the third hour than without DBS in the same animals (p < 0.05). DBS with 40 Hz tended to exert antidystonic effects after three hours, while 15 Hz stimulations of the EPN and 130 Hz stimulations of the STN failed to show any effects on the severity. DBS of the EPN at 130 Hz was most effective against generalized dystonia in the dtsz mutant. The response to EPN-DBS confirms that the dtsz mutant is suitable to further investigate the effects of long-term DBS on severity of dystonia and neuronal network activities, important to give insights into the mechanisms of DBS.

Paroxysmal and non-paroxysmal dystonia in 3 patients with biallelic ECHS1 variants: Expanding the neurological spectrum and therapeutic approaches

BackgroundECHS1 encodes the mitochondrial short chain enoyl CoA hydratase 1 (SCEH). Biallelic ECHS1 variants have been associated with Leigh-like presentations and milder phenotypes with paroxysmal exercise-induced dystonia. Patients/methodsWe used exome sequencing to investigate molecular bases of paroxysmal and non-paroxysmal dystonia in three patients and performed functional studies in fibroblasts. Disease presentation and response upon dietary interventions were documented. ResultsWe identified compound heterozygous ECHS1 missense variants in all individuals; all of them harbouring an c.518C > T (p.Ala173Val) variant. SCEH activity was impaired in patients’ fibroblasts, respiratory chain-, and pyruvate-dehydrogenase-complex activities were normal in one individual.Patient 1 presented from the age of 2.5 years on with paroxysmal opisthotonic posturing. Patient 2 had a first metabolic crisis at the age 20 months developing recurrent exercise-induced dystonic episodes. Disease history of patient 3 was unremarkable for neurological findings until he first presented at the age of 20 years with persistent dystonia. Ketogenic diet had beneficial effects in patient 1. Neither ketogenic nor low protein diets led to milder symptoms in patient 2. Patient 3 benefits from low protein diet with improvement of his torticollis. ConclusionsIn line with literature, our findings corroborate that the pathogenic ECHS1 variant c.518C > T (p.Ala173Val) is associated with milder phenotypes characterized by paroxysmal and non-paroxysmal dystonia. Because of the potentially treatable defect, especially in milder affected patients, it is important to consider SCEH deficiency not only in patients with Leigh-like syndrome but also in patients with paroxysmal dystonia and normal neurological findings between episodes.

SP7 Switching to clonidine transdermal patches in four paediatric cases: strategies benefits and challenges

BackgroundClonidine is an alpha-2 agonist acting in the central nervous system (CNS) and licensed for use in all grades of hypertension, prophylactic management of migraine or recurrent vascular headache and management of vasomotor conditions.1 In paediatrics, clonidine has been used for a variety of indications which include use as pre-medication, as analgesia adjuvant, for sedation in paediatric intensive care units (PICU), treatment of spasticity and dystonias, prevention of emergency agitation and in hypertension.2 Oral clonidine has a short half-life of 12 to 16 hours and is associated with peaks and troughs in drug concentration resulting in 2 to 8 hourly dosing intervals. Long-term intravenous clonidine is unviable for a variety of reasons which includes intravenous (IV) access, infection risks and complex ongoing management. Clonidine transdermal patches, approved for use in 1984, provide approximately constant therapeutic drug level for 7 days3 and may represent a viable option for paediatric patients on long-term clonidine.AimTo describe the strategies adopted in converting four paediatric patients to clonidine transdermal patches from either enteral or parenteral clonidine; the benefits and challenges of the conversion.MethodThe intrinsic characteristics of clonidine transdermal patches4 and the therapeutic/clinical goal for each patient informed the switch strategy. Evaluation of the effect of switch was done at least three months after switch through consented open interviews with stakeholders, and evaluation of clinical symptoms.ResultsThe switch strategy to clonidine patch is complex and different for each patient. The factors to consider include: (i) clinical/therapeutic goal for the patient; (ii) the characteristics of the patch (iii) patient’s characteristics – weight and surface area; (iv) detailed counselling of patients and carers; (v) individualised prescription; (vi) ongoing review of supply and patch effectiveness. All patients were switched to patches and achieved approximately equivalent clinical effects, although one child required further dose adjustment. One parent considered the switch to patches to be very good:‘We struggled....we employed the services of night carers four times a week...and we were too exhausted. (The change) has a massive impact on everyone’s quality of life...it has been brilliant’.Another parent observed that the application of patches was not difficult and that the change has been good:‘The nurse gives me the patch, I label them and make three lines on the child’s skin and rotate the patch, so there is always a space spare for 2 weeks before re-applying there again. It is not difficult’.In a clinic letter for another child who was switched to patches, the clinician noted:‘Since he changed to the patches there was no change in his dystonia (and) he has tolerated well. According to mother the main trigger for his dystonic episodes is heat’.One of the nurses looking after another child considered the switch overall to be poor to fair:‘(Using patches) is good in general as they (children) are not attached to pump and easy to move them around...(however) for him (this child), he was too sweaty and patch will fall off...his skin is really dry/red around the cover patches. It would be better if you didn’t have as many as nine patches to apply. It is difficult to wash him with so many patches. He responded better with IV clonidine but we were able to get him off infusion to patches. Education on what to do when it (the patch) falls off will be really useful’.ConclusionThe use of clonidine transdermal patches is a viable option for children needing long-term clonidine. This option has the potential to offer significant cost saving to the National Health Service (NHS) and improved quality of life of children and their carers; especially in those cared for at home. The strategy for conversion is complex and requires taking a number of factors into account. Switch to transdermal patches will not be suitable for all patients and criteria for selecting suitable patients and a generalised framework for switching are yet to be fully described.ReferencesSPC. Clonidine 25 mg tablets BP. Summary of Product Charcteristics 2015. Retrieved June 27, 2019, from Electronic Medicines Compendium: https://www.medicines.org.ukBasker S, Singh G, Jacob R. Clonidine in paediatrics - a review. Indian J Anaesth 2009;53:270–80.SPC. Catapres-TTS. Summary of Product Charcteristics 2016. Retrieved June 27, 2019, from https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Catapres%20TTS/CatapresTTS.pdfSica DA, Grubbs R. Transdermal clonidine: therapeutic considerations. The Journal of Clinical Hypertension 2005;7:558–562.

Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED).

Four female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress, were investigated in a retrospective multi-center investigation aiming to characterize the clinical phenotype and its underlying molecular etiology. Three dogs were closely related and their pedigree suggested autosomal dominant inheritance. Laboratory diagnostic findings included mild lactic acidosis and lactaturia, mild intermittent serum creatine kinase (CK) elevation and hypoglycemia. Electrophysiological tests and magnetic resonance imaging of the brain were unremarkable. A muscle/nerve biopsy revealed a mild type II fiber predominant muscle atrophy. While treatment with phenobarbital, diazepam or levetiracetam did not alter the clinical course, treatment with a gluten-free, home-made fresh meat diet in three dogs or a tryptophan-rich, gluten-free, seafood-based diet, stress-reduction, and acetazolamide or zonisamide in the fourth dog correlated with a partial reduction in, or even a complete absence of, dystonic episodes. The genomes of two cases were sequenced and compared to 654 control genomes. The analysis revealed a case-specific missense variant, c.1658G>A or p.Arg553Gln, in the PCK2 gene encoding the mitochondrial phosphoenolpyruvate carboxykinase 2. Sanger sequencing confirmed that all four cases carried the mutant allele in a heterozygous state. The mutant allele was not found in 117 Shetland Sheepdog controls and more than 500 additionally genotyped dogs from various other breeds. The p.Arg553Gln substitution affects a highly conserved residue in close proximity to the GTP-binding site of PCK2. Taken together, we describe a new form of paroxysmal exercise-induced dyskinesia (PED) in dogs. The genetic findings suggest that PCK2:p.Arg553Gln should be further investigated as putative candidate causal variant.

Novel mutation of the PRRT2 gene in two cases of paroxysmal kinesigenic dyskinesia: Two case reports.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare condition characterized by recurrent brief episodes of dystonia, chorea, athetosis or any combination of these, without alterations of consciousness. The proline-rich transmembrane protein 2 (PRRT2) gene has been widely investigated as a causative gene of PKD. To date, a cluster of pathogenic variants associated with PKD have been identified in the PRRT2 gene. In the present case report, two Chinese patients with sporadic PKD are discussed. Genetic analysis revealed a de novo heterozygous missense mutation, c.955G>T (p.Val319Leu) in exon 3 of the PRRT2 gene. Compared with the commonly reported clinical manifestation of PRRT2-associated PKD, the patients in this report showed several primary distinctive features. The mutations identified in the present analysis expand upon the mutation spectrum of the PRRT2 gene, and this newly found variant further reinforces the importance of the PRR2 gene in PKD.

PGR - 2 Neuropsychology’s Role in Identifying Functional Neurological Disorder

Abstract Objective To outline the usefulness of neuropsychological evaluation in identifying functional neurological disorder. Functional neurological disorder accounts for an estimated 16% of neurology referrals and is a “crisis of neurology” (Edwards &amp; Bhatia, 2012). Adolescents with a history of neurologic compromise, including autoimmune disorders, are at increased risk for comorbid functional neurological disorder (Reuber, Mitchell, Howlett, Crimlisk, &amp; Grünewald, 2005). Method 16-year-old female with a history of Hoshimoto’s encephalopathy referred by her neurologist. Following diagnosis and treatment, she developed a constellation of symptoms, including wide set gait, nystagmus, incontinence, and dystonic episodes. She also reported lapses in memory that lasted a few minutes at a time. During these episodes, she forgot who her mother was and forgot details about her home, which resulted in panic. Results Two neuropsychological evaluations were completed over two years. Psychometric intelligence declined by two standard deviations compared to previous testing one year before. Her performance on memory tasks declined dramatically as well. Despite these declines, there was no decline in activities of daily living. She failed embedded and stand-alone performance validity measures (RDS = 4; TOMM = 29, 30, 28). These findings were described to her neurologist and psychiatrist and we discussed the importance of identifying functional symptoms in the context of her medical history. Conclusions Our evaluation identified significant discrepancies between neuropsychological performance and daily cognitive functioning. The memory lapses she described were inconsistent with any known etiology or illness. Neuropsychological evaluation identified symptoms of a functional nature and assisted in appropriate treatment planning.

Sandifer’s Syndrome in a 3-Month-Old Male Infant: A Case Report

Background: Sandifer syndrome (SS) is the association of gastroesophageal reflux disease (GERD) with neurological manifestations (spastic torticollis and paroxysmal dystonic postures with arching of the back and rigid opisthotonic posturing. Case presentation: A 3-month-old male infant presented to our emergency department with torticollis and dystonic episodes for two months associated with vomiting. These movements were observed during or just after feeding. Since the patient developed regurgitations with torticollis and dystonic episodes with arching of the back and rigid opisthotonic posturing. The electroencephalogram was normal. Barium swallow/meal examination revealed GERD without evidence of hiatus hernia. Apgar scores were 7 at 1 min and 9 at 5 min. Conclusion: Early recognition and treatment of GERD in patients with Sandifer syndrome enhance the success of medical management and contributes to improved quality of life for patients with brain damage. The paroxysmal dystonic behaviors were dramatically disappeared completely after medical management in this patient.

Oscillatory Cortical Activity in an Animal Model of Dystonia Caused by Cerebellar Dysfunction.

The synchronization of neuronal activity in the sensorimotor cortices is crucial for motor control and learning. This synchrony can be modulated by upstream activity in the cerebello-cortical network. However, many questions remain over the details of how the cerebral cortex and the cerebellum communicate. Therefore, our aim is to study the contribution of the cerebellum to oscillatory brain activity, in particular in the case of dystonia, a severely disabling motor disease associated with altered sensorimotor coupling. We used a kainic-induced dystonia model to evaluate cerebral cortical oscillatory activity and connectivity during dystonic episodes. We performed microinjections of low doses of kainic acid into the cerebellar vermis in mice and examined activities in somatosensory, motor and parietal cortices. We showed that repeated applications of kainic acid into the cerebellar vermis, for five consecutive days, generate reproducible dystonic motor behavior. No epileptiform activity was recorded on electrocorticogram (ECoG) during the dystonic postures or movements. We investigated the ECoG power spectral density and coherence between motor cortex, somatosensory and parietal cortices before and during dystonic attacks. During the baseline condition, we found a phenomenon of permanent adaptation with a change of baseline locomotor activity coupled to an ECoG gamma band increase in all cortices. In addition, after kainate administration, we observed an increase in muscular activity, but less signs of dystonia together with modulations of the ECoG power spectra with an increase in gamma band in motor, parietal and somatosensory cortices. Moreover, we found reduced coherence in all measured frequency bands between the motor cortex and somatosensory or parietal cortices compared to baseline. In conclusion, examination of cortical oscillatory activities in this animal model of chronic dystonia caused by cerebellar dysfunction reveals a disruption in the coordination of neuronal activity across the cortical sensorimotor/parietal network, which may underlie motor skill deficits.

Status dystonicus due to missense variant in ARX: Diagnosis and management

Movement disorders are increasingly identified in infantile encephalopathies due to single gene disorders (e.g. SCN2A, CDKL5, ARX). The associated movement disorder can be challenging to recognise and treat. We report a 2 year-old boy with a background history of Ohtahara syndrome due to a missense variant in ARX (the aristaless-related homeobox gene) who subsequently developed status dystonicus. ARX is a transcription factor that plays a critical role in cortical neuronal development and is associated with a range of important neurodevelopmental disorders depending on the site of the pathogenic variant. Cases of status dystonicus are described with variants affecting the polyalanine expansion region of ARX but have not been reported previously with variants affecting the aristaless domain of ARX as in this case. Dystonic episodes posed a challenge in recognition and treatment, including confusion with status epilepticus. We discuss the difficulties in diagnosis and management of status dystonicus, an underreported life-threatening emergency in children.

32. Facio-brachial dystonic seizures in LGI1 Limbic Encephalitis: Analysis of video EEG monitoring in a small group of patients

Leucine-rich glioma inactivated 1(LGI1) antibodies are frequently associated with a common form of limbic encephalitis (LE) presenting with cognitive impairment, tonic-clonic and distinctive facio-brachial dystonic seizures (FBDS), not related with a specific EEG pattern. We describe clinical-EEG features of three patients with LGl1-LE with different response to immunotherapy. Three pts, admitted to our Neurology department for LE with positive test for LGI1 antibodies, performed video-EEG monitoring and immunotherapy. Video and still images showed frequently (3–40 episodes/day) paroxysmal brief events characterized by facial grimacing and sometimes dystonic arm posturing, with alternating side, suggestive for FBDS. We observed electrodecremental events (EDEs) or a contralateral slow-wave before “dystonic seizures” but not a clear ictal-EEG pattern. In all of the patients interictal EEG was normal. Furthermore, Video-EEG monitoring revealed multiple daily electrographic temporal seizures. Immunotherapy were associated with control of FBDS in two of three presented patients, with different latency. Video-EEG monitoring of our LGI1-LE patients showed frequent FBDS and bilateral temporal seizures. The lack of a clear ictal-EEG pattern for FBDS and the positive response to immunotherapy, support the hypothesis that dystonic episodes does not have a cortical origin, but are rather related to a possible basal ganglionic dysfunction.