Oral Dyskinesia Research Articles

Stroke and Stroke-Like Episodes: Recurrent Manifestations in GLUT1 Deficiency Syndrome

BackgroundSince the initial description of glucose transporter-1 deficiency syndrome (Glut1-DS) the phenotype of the condition has expanded, even leading to the recognition of atypical manifestations. We report on eight patients with Glut1-DS who experienced at least one episode of acute focal neurological deficits. MethodsWe conducted a retrospective analysis, collecting clinical, electrophysiological, neuroradiological, and genetic information. We focused in particular on three well-documented cases. ResultsAmong 42 patients with Glut1-DS, eight individuals aged between six and 38 years presented with an acute onset of neurological disturbances: dysarthria/aphasia, oral dyskinesia, swallowing difficulties, paresthesia, facial palsy, hemi/monoplegia, vomiting, headache, and behavioral disturbances. When performed, magnetic resonance imaging (MRI) revealed signs of venous congestion and hypoperfusion and electroencephalography showed focal contralateral slowing. Deficits were transient in all patients but one. Four patients (50%) were on a ketogenic diet (KD), and two of these patients had lower than usual ketonemia levels during the episode. In two patients, MRI demonstrated the presence of an ischemic brain lesion. ConclusionsIn Glut1-DS, stroke-like episodes are a recurrent manifestation, particularly during early adulthood, and they were reported in 19% of the patients in our cohort. Stroke mimics should be considered a key feature of Glut1-DS, as other paroxysmal disorders. It remains to be established whether a KD can prevent the recurrence of episodes and, if so, at what level of ketosis. Further observations are needed to confirm the correlation between Glut1-DS and ischemic stroke.

Movement disorders of the stomatognathic system: A blind spot between dentistry and medicine.

Movement disorders of the stomatognathic system include oromandibular dystonia (OMD), oral dyskinesia, sleep/awake bruxism, functional (psychogenic) stomatognathic movement disorders (FSMDs), tremors, and hemimasticatory spasm (HMS). Most patients first consult dentists or oral surgeons. The differential diagnoses of these involuntary movements require both neurological and dental knowledge and experience, and some of these movement disorders are likely to be diagnosed as bruxism or temporomandibular disorders (TMDs) by dental professionals. However, excepting movement disorder specialists, neurologists may find it difficult to differentially diagnose these disorders. Patients may visit numerous medical and dental specialties for several years until a diagnosis is made. Therefore, movement disorders of the oral region may represent a blind spot between dentistry and medicine.The present narrative review aimed to describe the clinical characteristics and differential diagnoses of some movement disorders, as well as the problems bridging dentistry and medicine. Movement disorders have the following characteristic clinical features: OMD - task specificity, sensory tricks and the morning benefit; FSMDs - inconsistent and incongruous symptoms, spreading to multiple sites and the lack of sensory tricks; and HMS - the paroxysmal contraction of unilateral jaw-closing muscles, the persistence of symptoms during sleep and the loss of a silent period. A careful differential diagnosis is essential for the adequate and effective treatment of each involuntary movement. Refining the latest definition of bruxism may be necessary to prevent the misdiagnosis of involuntary movements as bruxism.Both dental and medical professionals should take an interest in the movement disorders of the stomatognathic system, and these disorders should be diagnosed and treated by a multidisciplinary team.

Genetic effects in a progressive model of parkinsonism induced by reserpine

We investigated the locomotor, emotional, physiological, and neurobiological effects induced by low-dose reserpine repeated treatment (0.1mg/kg; 14 injections) in males from the Lewis (LEW), Spontaneously Hypertensive Rats (SHR), and SHR.LEW-(D4Rat76-D4Mgh11) (SLA16) isogenic rat strains, which have different genetic backgrounds on chromosome 4. Behavioral responses in the catalepsy, open-field, and oral movements' tests were coupled with blood pressure, body weight, and striatal tyrosine hydroxylase (TH) level assessments to establish neurobiological comparisons between reserpine-induced impairments and genetic backgrounds RESULTS: Results revealed the SHR strain was more sensitive in the catalepsy test and exhibited higher TH immunoreactivity in the dorsal striatum. The SLA16 strain presented more oral movements, suggesting increased susceptibility to develop oral dyskinesia. Our results showed the efficacy of repeated treatment with a low dose of reserpine and demonstrated, for the first time, the genetic influence of a specific region of chromosome 4 on the expression of these effects.

Botulinum Toxin Therapy for Oromandibular Dystonia and Other Movement Disorders in the Stomatognathic System.

Various movement disorders, such as oromandibular dystonia, oral dyskinesia, bruxism, functional (psychogenic) movement disorder, and tremors, exist in the stomatognathic system. Most patients experiencing involuntary movements due to these disorders visit dentists or oral surgeons, who may be the first healthcare providers. However, differential diagnoses require neurological and dental knowledge. This study aimed to review scientific advances in botulinum toxin therapy for these conditions. The results indicated that botulinum toxin injection is effective and safe, with few side effects in most cases when properly administered by an experienced clinician. The diagnosis and treatment of movement disorders in the stomatognathic system require both neurological and dental or oral surgical knowledge and skills, and well-designed multicenter trials with a multidisciplinary team approach must be necessary to ensure accurate diagnosis and proper treatment.

Mental disorders in the dental practice. Psychotic disorders in the schizophrenia spectrum

Patients with a psychotic disorder have certain symptoms, movement disorders resulting from the pharmacological effects of medication. Knowing about this is important to the patients' dental treatment. A very small group will present with delusions about teeth or the benevolent or malevolent intentions of the dentist. Negative symptoms are an important characteristic of schizophrenic psychoses, meaning the absence of normal behaviour. Patients neglect personal hygiene and their lives have hardly any structure. They do not concern themselves with appointments, daily routines and social expectations. In such cases, prosthetic measures may be necessary. In addition, antipsychotic medications have adverse effects such as increased risk of caries, bruxism, oral and facial tardive dyskinesia, xerostomia, swallowing disorders and orthostatic hypotension. Suggestions for dental treatment and advice on how best to approach these patients are provided.

En mann i 50-årene med økende motoriske svingninger, søvnvansker og mental endring

A man in his fifties with advanced Parkinson´s disease was admitted with increasing motor fluctuations including dyskinesias, as well as hallucinations and delusions. After reduction of oral dopaminergic treatment, the dyskinesias improved, but the psychotic symptoms persisted. They were perceived as levodopa-induced, despite concurrent prominent bradykinetic-rigid symptoms. Dopaminergic treatment was therefore discontinued. He subsequently developed hyperthermia, severe generalised rigidity and akinesia, and autonomic instability. Parkinsonism-hyperpyrexia syndrome was diagnosed, and continuous intraduodenal levodopa/carbidopa infusion was initiated. Despite this, he had several episodes of respiratory distress requiring mechanical ventilation, as well as bradycardia and a single asystole. Although motor and autonomic dysfunction slowly improved, severe akinetic-rigid and neuropsychiatric symptoms persisted, with poor response to increased levodopa. On vital indication, electroconvulsive therapy was performed with clear improvement of mobility and mental state. A hip fracture requiring surgery necessitated discontinuation of ECT, which failed to show equivalent effect when resumed. His condition was considered terminal and all active treatment ceased, resulting in death a few weeks later. Parkinsonism-hyperpyrexia syndrome can develop if dopaminergic treatment is reduced abruptly and excessively. Coexistence of confusion and/or psychosis and clear bradykinetic-rigid symptoms should alarm the clinician. Dopaminergic treatment should not be discontinued, but given intraduodenally. ECT can be effective if started sufficiently early and administered frequently.

Beyond Dravet Syndrome: Characterization of a Novel, More Severe SCN1A-Linked Epileptic Encephalopathy.

To define a distinct SCN1A developmental and epileptic encephalopathy with early onset, profound impairment, and movement disorder. A case series of 9 children were identified with a profound developmental and epileptic encephalopathy and SCN1A mutation. We identified 9 children 3 to 12 years of age; 7 were male. Seizure onset was at 6 to 12 weeks with hemiclonic seizures, bilateral tonic-clonic seizures, or spasms. All children had profound developmental impairment and were nonverbal and nonambulatory, and 7 of 9 required a gastrostomy. A hyperkinetic movement disorder occurred in all and was characterized by dystonia and choreoathetosis with prominent oral dyskinesia and onset from 2 to 20 months of age. Eight had a recurrent missense SCN1A mutation, p.Thr226Met. The remaining child had the missense mutation p.Pro1345Ser. The mutation arose de novo in 8 of 9; for the remaining case, the mother was negative and the father was unavailable. Here, we present a phenotype-genotype correlation for SCN1A. We describe a distinct SCN1A phenotype, early infantile SCN1A encephalopathy, which is readily distinguishable from the well-recognized entities of Dravet syndrome and genetic epilepsy with febrile seizures plus. This disorder has an earlier age at onset, profound developmental impairment, and a distinctive hyperkinetic movement disorder, setting it apart from Dravet syndrome. Remarkably, 8 of 9 children had the recurrent missense mutation p.Thr226Met. SCN1A Gain of Function in Early Infantile Encephalopathy Berecki G, Bryson A, Terhag J, et al. Ann Neurol. 2019; 85:514-525. To elucidate the biophysical basis underlying the distinct and severe clinical presentation in patients with the recurrent missense SCN1A variant, p.Thr226Met. Patients with this variant show a well-defined genotype-phenotype correlation and present with developmental and early infantile epileptic encephalopathy that is far more severe than typical SCN1A Dravet syndrome. Whole cell patch clamp and dynamic action potential clamp were used to study T226M Nav 1.1 channels expressed in mammalian cells. Computational modeling was used to explore the neuronal scale mechanisms that account for altered action potential firing. T226M channels exhibited hyperpolarizing shifts of the activation and inactivation curves and enhanced fast inactivation. Dynamic action potential clamp hybrid simulation showed that model neurons containing T226M conductance displayed a left shift in rheobase relative to control. At current stimulation levels that produced repetitive action potential firing in control model neurons, depolarization block and cessation of action potential firing occurred in T226M model neurons. Fully computationally simulated neuron models recapitulated the findings from dynamic action potential clamp and showed that heterozygous T226M models were also more susceptible to depolarization block. From a biophysical perspective, the T226M mutation produces gain of function. Somewhat paradoxically, our data suggest that this gain of function would cause interneurons to more readily develop depolarization block. This "functional dominant negative" interaction would produce a more profound disinhibition than seen with haploinsufficiency that is typical of Dravet syndrome and could readily explain the more severe phenotype of patients with T226M mutation.

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia.

Schizophrenia is considered a debilitating neurodevelopmental psychiatric disorder and its pharmacotherapy remains problematic without recent major advances. The development of interventions able to prevent the emergence of schizophrenia would therefore represent an enormous progress. Here, we investigated whether treatment with cannabidiol (CBD – a compound of Cannabis sativa that presents an antipsychotic profile in animals and humans) during peri-adolescence would prevent schizophrenia-like behavioral abnormalities in an animal model of schizophrenia: the spontaneously hypertensive rat (SHR) strain. Wistar rats and SHRs were treated with vehicle or CBD from 30 to 60 post-natal days. In experiment 1, schizophrenia-like behaviors (locomotor activity, social interaction, prepulse inhibition of startle and contextual fear conditioning) were assessed on post-natal day 90. Side effects commonly associated with antipsychotic treatment were also evaluated: body weight gain and catalepsy throughout the treatment, and oral dyskinesia 48 h after treatment interruption and on post-natal day 90. In experiment 2, serum levels of triglycerides and glycemia were assessed on post-natal day 61. In experiment 3, levels of BDNF, monoamines, and their metabolites were evaluated on post-natal days 61 and 90 in the prefrontal cortex and striatum. Treatment with CBD prevented the emergence of SHRs’ hyperlocomotor activity (a model for the positive symptoms of schizophrenia) and deficits in prepulse inhibition of startle and contextual fear conditioning (cognitive impairments). CBD did not induce any of the potential motor or metabolic side effects evaluated. Treatment with CBD increased the prefrontal cortex 5-HIAA/serotonin ratio and the levels of 5-HIAA on post-natal days 61 and 90, respectively. Our data provide pre-clinical evidence for a safe and beneficial effect of peripubertal and treatment with CBD on preventing positive and cognitive symptoms of schizophrenia, and suggest the involvement of the serotoninergic system on this effect.

Oromandibular dystonia screening questionnaire for differential diagnosis.

Oromandibular dystonia, which is characterized by stereotypic, task-specific, or sustained contractions of masticatory and/or lingual muscles, is frequently misdiagnosed as temporomandibular disorders or psychogenic disease. Diagnostic delay in oromandibular dystonia is not acceptable; thus, a screening tool that can distinguish this condition from a temporomandibular disorder may be helpful for medical professionals unfamiliar with involuntary movements or temporomandibular disorders. A questionnaire that included questions on the clinical features of oromandibular dystonia, such as stereotypy, task-specificity, sensory tricks, and morning benefit, and included questions to rule out temporomandibular disorders (total point range 0-40) was administered to 553 patients suspected to have involuntary movements. Based on a careful examination and the differential diagnosis, the patients were divided into four groups: oromandibular dystonia (n= 385), oral dyskinesia (n= 84), psychogenic (functional) movement disorder (n= 50), and temporomandibular disorders (n= 34). The questionnaire had a high level of internal consistency as measured by the Cronbach's α (0.91), and item-total correlation was significant (p < 0.001). The test-retest reliability on two separate occasions showed a significant correlation (p < 0.001). Mean total scores of the questionnaire significantly differed among oromandibular dystonia (32.0), temporomandibular disorders (10.4; one-way analysis of variance, p < 0.001), oral dyskinesia (21.0; p < 0.001), and psychogenic (functional) movement disorder (13.7; p < 0.001). Findings of this study suggest that the present questionnaire is a simple diagnostic tool that is useful for tentative differentiation of oromandibular dystonia from temporomandibular disorders. This screening tool can be used to distinguish oromandibular dystonia from temporomandibular disorders.

Lamotrigine Rechallenge in Treatment-Resistant Bipolar Disorder

Although lamotrigine may be useful for treating patients with treatment-resistant bipolar disorder, some lamotrigine-associated adverse effects, including mild to moderate skin rash, may prevent the continuation of treatment. We investigated lamotrigine rechallenge for the treatment of bipolar disorder. The present study was based on retrospective chart review of outpatients with bipolar disorder (DSM-5 criteria) who visited the hospital's psychiatric department between July 2011 and August 2017. The review revealed 12 patients with bipolar disorder who underwent lamotrigine rechallenge following lamotrigine discontinuation due to various adverse reactions, including skin rash. None of the patients showed Stevens-Johnson syndrome. All patients suffered from treatment-resistant bipolar disorder that was refractory to treatments other than lamotrigine. For each patient, the severity of the adverse reaction to lamotrigine was weighed against the potential for therapeutic benefit. In 9 of 12 cases, a positive outcome of lamotrigine rechallenge was observed. In all cases with initial skin rash with very slow titration of lamotrigine, rechallenge was successful with no recurrence of the rash. In the 3 cases for which lamotrigine was unsuccessful, lamotrigine was discontinued owing to movement disorders, ie, oral dyskinesia and action tremor, and liver dysfunction, respectively. The present results suggest that lamotrigine rechallenge may be a viable option for treatment-resistant bipolar disorder.

Drooling in cerebral palsy and its relationship with dysphagia and gross motor functioning

Objective To analyze the incidence and severity of drooling in children with cerebral palsy and explore its correlation with oral dyskinesia, dysphagia and gross motor function. Methods A hundred children with cerebral palsy treated in Qingdao Women′s and Children′s Hospital between July 2013 and 2016 and 50 healthy children examined in the health examination center were assessed using the drooling severity scale, oral motor assessment, a dysphagia disorders survey (DDS) and the gross motor function classification system (GMFCS). The relationship between drooling severity, oral dyskinesia, dysphagia and their gross motor function was analyzed. Results Of the 100 children with cerebral palsy, 32% displayed drooling (at levels II through V), which was significantly higher than among the healthy controls. Another sixty-eight displayed level I drooling. The severity of drooling was significantly different among children with different cerebral palsies. The drooling of children with spastic quadriplegia, dyskinesia or mixed-type cerebral palsy was the most severe, followed by those with ataxia and spastic diplegia whose drooling was often mild. No hemiplegic child drooled at level II. Drooling severity was negatively correlated with the oral motor score, but positively correlated with the average DDS and GMFCS scores. Conclusions About one third of cerebral palsy children suffer from drooling. Their drooling severity is closely associated with the type of the cerebral palsy, oral dyskinesia, dysphagia and GMFCS levels. Key words: Cerebral palsy; Drooling; Gross motor function classification; Dysphagia; Oral motor dysfunction

Effects of Fish and Grape Seed Oils as Core of Haloperidol-Loaded Nanocapsules on Oral Dyskinesia in Rats.

Haloperidol is a widely used antipsychotic, despite the severe motor side effects associated with its chronic use. This study was carried out to compare oral dyskinesia induced by different formulations of haloperidol-loaded nanocapsules containing caprylic/capric triglycerides, fish oil or grape seed oil (GSO) as core, as well as free haloperidol. Haloperidol-loaded lipid-core nanocapsules formulations were prepared, physicochemical characterized and administered (0.5mgkg-1-ip) to rats for 28days. Oral dyskinesia was evaluated acutely and subchronically and after that cell viability and free radical generation in cortex and substantia nigra. All formulations presented satisfactory physicochemical parameters. Acutely, all formulations were able to prevent oral dyskinesia development in comparison to free haloperidol, except haloperidol-loaded nanocapsules containing GSO, whose effect was only partial. After subchronic treatment, all haloperidol-loaded nanocapsules formulations prevented oral dyskinesia in relation to free drug. Also, haloperidol-loaded nanocapsules containing fish oil and GSO were more effective than caprylic/capric triglycerides nanocapsules and free haloperidol in cell viability preservation and control of free radical generation. Our findings showed that fish oil formulation may be considered as the best formulation of haloperidol-loaded lipid-core nanocapsules, being able to prevent motor side effects associated with chronic use of antipsychotic drugs, as haloperidol.

Purposeless oral activity induced by meta-chlorophenylpiperazine (m-CPP): Undefined tic-like behaviors?

BackgroundThe pathophysiological hypothesis underlying tic disorders in Tourette syndrome (TS) is that basal ganglia are not capable of properly filtering cortical information, leading patients with difficulties in inhibiting unwanted behaviors or impulses. One of the main challenges for furthering such a hypothesis is to find appropriate animal models summarizing some aspects of the disease. MethodsIt has been established for more than 25 years in rodents that the prototypical serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) elicits purposeless oral movements including chewing behavior. These bouts of oral movements, originally thought to mimic human oral dyskinesia consequent to long-term administration of antipsychotic drugs or parkinsonian tremor, could correspond to an undefined form of tics. Here, we describe the nature of the purposeless oral movements triggered by m-CPP and other agonists which could be associated with obsessive compulsive disorders. We report the pharmacology of this response with a focus on the 5-HT2C receptor subtype and the degree to which the dopaminergic and cholinergic systems are involved. The orofacial dyskinetic effects are related to the action of these compounds in associative/limbic territories of the basal ganglia, rather than sensorimotor ones, as expected from the human disease. ConclusionIn spite of the low translational value of these oral movements, the neurobiological analysis of these oral movements could help to a better understanding of the pathophysiology of tics and compulsive disorders often cormorbid with TS.

Preclinical Characterization of SAGE-217 in a Rodent Model of Oral Dyskinesia (P5.021)

Preclinical Characterization of SAGE-217 in a Rodent Model of Oral Dyskinesia (P5.021)

A rare instance of tardive dyskinesia with SSRI use: A case study

IntroductionCase presentation of a middle aged lady Mrs. C.K., who developed tardive dyskinesia (TD) after a trial of an SSRI.Case reportA 49-year-old Australian aboriginal lady, presented with involuntary movement of her face (bucco-linguo masticatory), movements after a 3 months trial of sertraline (maximum dose of 100 mg daily) for her depressive illness. There was no history of trials with anti-psychotics or any other medications, which may have caused the oral dyskinesias. Routine examinations including cognitive testing, EEG and MRI revealed no pathological findings. Her sertraline was ceased and she was commenced on mirtazapine 15 mg at night, which was hiked to 30 mg after 1 week and continued on this dose over the next 3 months. She exhibited good improvement in her depressive symptoms and a significant attenuation of her TD's. Involuntary movement scale rating: she was rated on the abnormal involuntary movement scale (AIMS) and showed gradual improvement in the severity of her orofacial dyskinetic movement. Her scores were–initial presentation (scored 22/36); at 4 weeks (9/36); 8 weeks (6/36) and at 16 weeks (4/36).DiscussionAlthough TD's are seen in approximately 1 to 5% of mental health patients treated with anti-psychotics (and some other medications like Levodopa, Metochlorpromide, etc.), research studies on SSRI's causing TD's are rare and few (Leo et al., 1996; Gerber et al., 1998).ConclusionsTo alert and educate clinicians about a relatively rare adverse-effect of SSRI producing an involuntary movement disorder.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and α-Synuclein Expression.

Reserpine is an irreversible inhibitor of vesicular monoamine transporter-2 (VMAT2) used to study Parkinson’s disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low-dose of reserpine was proposed as a progressive model of PD. Rats under this treatment show progressive catalepsy behavior, oral movements and spontaneous motor activity decrement. In parallel, compared to Wistar rats, spontaneously hypertensive rats (SHR) are resistant to acute reserpine-induced oral dyskinesia. We aimed to assess whether SHR would present differential susceptibility to repeated reserpine-induced deficits in the progressive model of PD. Male Wistar and SHR rats were administered 15 subcutaneously (s.c.) injections of reserpine (0.1 mg/kg) or vehicle, every other day and motor activity was assessed by the catalepsy, oral movements and open field tests. Only reserpine-treated Wistar rats presented increased latency to step down in the catalepsy test and impaired spontaneous activity in the open field. On the other hand, there was an increase in oral movements in both reserpine-treated strains, although with reduced magnitude and latency to instauration in SHR. After a 15-day withdrawn period, both strains recovered from motor impairment, but SHR animals expressed reduced latencies to reach control levels. Finally, we performed immunohistochemistry for tyrosine hydroxylase (TH) and α-synuclein (α-syn) 48 h after the last injection or 15 days after withdrawn. Reserpine-treated animals presented a reduction in TH and an increase in α-syn immunoreactivity in the substantia nigra and dorsal striatum (dSTR), which were both recovered after 15 days of withdraw. Furthermore, SHR rats were resistant to reserpine-induced TH decrement in the substantia nigra, and presented reduced immunoreactivity to α-syn in the dSTR relative to Wistar rats, irrespective of treatment. This effect was accompanied by increase of malondaldhyde (MDA) in the striatum of reserpine-treated Wistar rats, while SHR presented reduced MDA in both control and reserpine conditions relative to Wistar strain. In conclusion, the current results show that SHR are resilient to motor and neurochemical impairments induced by the repeated low-dose reserpine protocol. These findings indicate that the neurochemical, molecular and genetic differences in the SHR strain are potential relevant targets to the study of susceptibility to PD.

Oral Appliance Therapy for Severe Ulcerative Stomatitis of a Patient with Oral Dyskinesia：A Case Report

Oral Appliance Therapy for Severe Ulcerative Stomatitis of a Patient with Oral Dyskinesia：A Case Report

A case of successful registration of interocclusal relation for a patient with oral dyskinesia using nitrous oxide and oxygen

A case of successful registration of interocclusal relation for a patient with oral dyskinesia using nitrous oxide and oxygen

Nigella sativa Oil Reduces Extrapyramidal Symptoms (EPS)-Like Behavior in Haloperidol-Treated Rats.

The symptoms of Parkinsonism and oral dyskinesia have been showing to be induced by neuroleptics that significantly affect its clinical use. In this study, we investigate whether Nigella sativa-oil (NS) (black cumin seeds)-a traditional medicine used for the seizure treatment in eastern country-may reduce the haloperidol (HAL)-induced extrapyramidal symptoms (EPS)-like behavior in rats. After combine treatment with HAL (1mg/kg) on NS (0.2ml/rat), rats displayed a significant decreased EPS-like behavior including movement disorders and oral dyskinesia as compared to controls. Immunohistochemical analysis indicates that NS reduced astrogliosis in caudate and accumbens nuclei. These results suggest that NS may consider as an adjunct to antipsychotics to reduce the EPS-like side effect.

Involuntary movements and coma as the prognostic marker for acute encephalopathy with biphasic seizures and late reduced diffusion

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) occurs in children associated with infection. It is characterized by a prolonged febrile seizure in the first phase, and a cluster of seizures, deterioration of consciousness and the white matter lesions with reduced diffusion in the second phase. The patients often have severe neurological sequelae, but the prognostic indicators remain unknown. The present study aimed to clarify the characteristics of AESD patients who subsequently exhibited severe neurological sequelae. We retrospectively analyzed the clinical and laboratory findings along with the brain imaging in patients who had severe (n=8) and non-severe neurodevelopmental outcomes (n=12). Severe group more frequently showed coma (p=0.014) or involuntary movements including dystonia and oral dyskinesia (p=0.018) before the second phase than non-severe group. Severe group exhibited higher levels of serum alanine aminotransferase than non-severe group (p=0.001). Quantitatively assessed MRI in the second phase revealed that severe group had more extensive lesions than non-severe group, in the anterior (p=0.015) and posterior parts (p=0.011) of the cerebrum and basal ganglia (p=0.020). Early appearing involuntary movements or coma might account for the extension of acute brain lesions and the poor neurological outcomes in AESD patients.