Choreoathetotic Movements Research Articles

The Impact of Revascularization in a Patient with Atypical Manifestations of Hypoperfusion

Background and Objectives: Carotid revascularization is one of the most effective treatment options in patients with severe carotid artery stenosis causing hypoperfusion in basal ganglia. Atypical manifestations include hyperkinetic movements, noted as extremely rare. We report a case about a patient with 2-months-long complaints of Uncontrollable movements in his right side of the body subsided after carotid revascularization. Case presentation: A 71-year-old male was admitted to Pauls Stradins Clinical University Hospital with the main complaints of 2-months-long uncontrollable movements in his right hand and his right leg. When performing coordination tasks, slight inaccuracy was noted with the right-side extremities. Hyperkinetic movements—choreoathetosis in the right side of the patient’s face, arm, and leg—were seen. Computed tomography angiography revealed subocclusion in the proximal segment of the left internal carotid artery and 30% stenosis in the proximal segment of the right internal carotid artery. The patient was consulted by a vascular surgeon. Eversion endarterectomy of the left internal carotid artery was performed. The early postoperative period occurred without complications. The patient was discharged from the hospital 2 days after the surgery in good overall health condition. Two months later, choreoathetotic movements in his right side of the body had markedly decreased. No focal neurologic deficits were noted. Conclusions: Revascularization may be effective by eliminating emboli and stenosis, leading to hypoperfusion in watershed territories. A case of a 71-year-old male patient with the main complaints of 2-months-long uncontrollable movements in his right side of the body subsiding after carotid revascularization was demonstrated. It is vital to recognize atypical manifestations of hypoperfusion, associated with stenosis in internal carotid arteries, to early make a diagnosis, to perform an appropriate treatment, and to reduce the risk of cerebral infarction in the future, resulting in a longer high-quality life for the patient.

A Patient with Glucose Transporter Type 1 Deficiency Syndrome

Glucose transporter type 1 deficiency syndrome (GLUT-1 DS) is an inborn error of metabolism that results in defective glucose transport and consequently a reduced supply of glucose to the brain. Here, we describe a patient with a molecularly proven GLUT-1 mutation who presented with severe paroxysmal choreoathetosis. Different regional changes involving bilateral mesial temporal lobes were revealed using positron-emission tomography (PET). Several cases of GLUT-1 DS have been studied from the point of view of hyperkinetic movement disorders rather than epilepsy and ataxia. It is usual for these patients to first present with dystonia, choreoathetosis, parkinsonism, and paroxysmal exercise-induced dyskinesia, including dystonic, choreoathetotic, and ballistic movements. F18-fluorodeoxyglucose PET revealed hypometabolism in bilateral mesial temporal lobes along with the cerebellar cortex, confirming an impaired glucose metabolism effect on the area responsible for the extrapyramidal movement disorders.

Cerebral venous thrombosis in pregnancy: a case report

Cerebral venous thrombosis (CVT) is a rare, multi-symptomatic, and serious complication in pregnancy. CVS constitutes 2% of the causes of strokes in pregnancy. The most common symptoms of cerebral venous thrombosis are: headaches (74%), seizures (50%), limb paresis (38%), disturbed consciousness (45%), visual disturbances (24%). We present our 28-year-old pregnant patient because the dominant symptom was hemi -choreoathetotic movement, which made the daily life very difficult. After the differential diagnostic examinations we recognized cerebral venous thrombosis. After anti-clotting treatment, the symptoms resolved. We would like to point out that such a disorder in pregnant women may also be a symptom of cerebral venous thrombosis.

Mice with Gnao1 G203R Gain‐of‐Function (GOF) Mutation Phenocopy Combined Movement Disorder and Seizures of Patients

Patients with de novo mutations in the gene for Gao (GNAO1) exhibit either early infantile epileptic encephalopathy (EIEE17) or neurodevelopmental delay with involuntary movements (NEDIM). Gao is the a subunit of the most abundant heterotrimeric G protein in brain. As with other Gi/o family G proteins, it can signal directly to effectors or by release of free Gbg resulting in inhibition of adenylyl cyclase or modulation of Ca++ and K+ ion channels. Loss‐of‐Function (LOF) alleles in GNAO1 result in epilepsy while GOF mutations result in movement disorder with or without seizures. Here we report the first mouse model of a human GNAO1 encephalopathy. Heterozygous GOF mutant mice (Gnao1+/G203R) were created using CRISPR/Cas9 to determine whether they replicate the clinical pattern of children with de novo GNAO1+/G203R mutations who display epilepsy as well as severe choreoathetosis and dystonia. There was a striking sex difference in the observed phenotypes. Male Gnao1+/G203R mice displayed significant deficits in open field, Rotarod®, Digigait®, and grip strength assessments. Also, they had enhanced seizure susceptibility in pentylenetrazol (PTZ) kindling studies. None of these differences were seen in female mice. Unlike children with the GNAO1 G203R mutation, there were no obvious dystonic or choreoathetotic movements or postures at baseline. After administration of oxotremorine, however, male Gnao1+/G203R mice displayed more forelimb raising and hindlimb splaying than was observed in WT mice. This novel model phenocopies the combined epilepsy and movement disorder phenotype of children with GNAO1 G203R mutations. These mice should facilitate studies of neural mechanisms and permit preclinical drug repurposing.Support or Funding InformationSupported by grants from the MSU Clinical and Translational Science Institute and The Bow Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

CASES OF FRONTO TEMPORAL DEMENTIA PRESENTING WITH PSYCHOSIS

Introduction Fronto Temporal Dementia presents in varied clinical situations, here we are presenting 2 cases that presented to Neurologist with Behavioural symptoms with No cognitive decline and symptoms suggestive of Psychosis. Both the cases were treated with neuroleptics and were considered to be Psychosis. MRI of the brain and Labs were normal. Only PET CT Scan of the brain showed probable Fronto Temporal Dementia. Methods Report of case series Results CASE 1 • 62 Year old female from middle socio economic status, Homemaker with Family history of psychiatric illness in brother was referred by the neurology team with behavioural manifestations, Initially presented with irrelevant talk, talking to self since last 2 years. She gradually started becoming withdrawn, but managed to be independent in her Activities of Daily Living till few months back.Since the last couple of months she was not interested to her house hold chores, confining herself to indoors, and reduced self care. Since couple of months predominantly silent, occasionally responds to what family says and at times does the opposite. No hallucinations and delusions. No history of clear cognitive decline except for occasionally misplacing things which was felt normal. On examination: she was able to walk, mute, active and passive negativism. Labs and MRI brain done were within normal limits. No other significant medical history was present. A Diagnosis of “Catatonia” was made, Trial of lorazepam was given with mild improvement in speech and communication, food intake was better, obeying simple commands better. In discussion with neurologist and a trial of ECT was considered. AS the improvement was marginal a PET CT Scan was done which was Suggestive of Fronto Temporal Dementia. CASE 2 • A 60 year old lady, divorced in a couple of years after marriage, coping well worked as a teacher, Pre-morbidly stubborn and demanding, Family history of depressive disorder in first degree relative Behavioural changes noted at the age of 50 years manifested by being withdrawn, reduced involvement in regular activities, increased food consumption reduced self care, would pass urine stools at inappropriate places and be unmindful. Admitted at general hospital-diagnosed to have Hypertension, Diabeted Mellitus, Hypothyroidism and Irritable Bowel Syndrome. She occasionally mentioned people were talking about her but difficult to elicit other psychotic Symptoms. She was shifted to old age home at Hyderabad where she had leg pains and diagnosed as RLS and responded to treatment. MRI of the brain was normal. During subsequent follow up with the Neurologist she was noted to be “depressed” and started on Escitalopram-unclear response. In the next few months the episodes of passing stools inappropriately came down, hyperphagia persisted and would occasionally report of apprehension that someone may harm her and could see some vague shadows. This prompted her to be started on Amsulpride but stopped in few days as developed EPS at about 200mg/day. Despite stopping medications she started having significant increase in appetite, would start intruding into other peoples rooms and take whatever food items were there. She was subsequently told not to come into the common mess as she would consume large proportions of food from others plate as well. She was threatened to be thrown out of the old age home and they only agreed if she will be restricted to room. Being off all medications, noted to have occasional forgetfulness. Her “hyperphagia” continued and started developing involuntary Right upper limb choreo-athetotic movements. She also was noted to have repeated touching and rubbing of the face. A PET CT scan of the Brian was suggestive of Fronto Temporal Dementia. Conclusions A diagnosis of Fronto temporal Dementia should be suspected in all cases presenting with late onset psychosis and mild cognitive disturbances. Implication of the the diagnosis and treatment will be discussed. This research was funded by NIL

Oxidative stress and mitochondrial dynamics malfunction are linked in Pelizaeus-Merzbacher disease.

Pelizaeus‐Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by variations in the proteolipid protein gene PLP1, which encodes the two major myelin proteins of the central nervous system, PLP and its spliced isoform DM20, in oligodendrocytes. Large duplications including the entire PLP1 gene are the most frequent causative mutation leading to the classical form of PMD. The Plp1 overexpressing mouse model (PLP‐tg66/66) develops a phenotype very similar to human PMD, with early and severe motor dysfunction and a dramatic decrease in lifespan. The sequence of cellular events that cause neurodegeneration and ultimately death is poorly understood. In this work, we analyzed patient‐derived fibroblasts and spinal cords of the PLP‐tg66/66 mouse model, and identified redox imbalance, with altered antioxidant defense and oxidative damage to several enzymes involved in ATP production, such as glycolytic enzymes, creatine kinase and mitochondrial proteins from the Krebs cycle and oxidative phosphorylation. We also evidenced malfunction of the mitochondria compartment with increased ROS production and depolarization in PMD patient's fibroblasts, which was prevented by the antioxidant N‐acetyl‐cysteine. Finally, we uncovered an impairment of mitochondrial dynamics in patient's fibroblasts which may help explain the ultrastructural abnormalities of mitochondria morphology detected in spinal cords from PLP‐tg66/66 mice. Altogether, these results underscore the link between redox and metabolic homeostasis in myelin diseases, provide insight into the pathophysiology of PMD, and may bear implications for tailored pharmacological intervention.

Methamphetamine-induced choreoathetosis: A case report

We describe the case of a 23-year-old male with a past psychiatric history of Obsessive Compulsive disorder, Generalized Anxiety Disorder, Cannabis Use Disorder, and a reported history of Bipolar II Disorder and ADHD, and no past medical history, who presented to the hospital for a psychiatric evaluation of erractic behavior. Per his family's report, the patient has not been attending to his activities of daily living and has had poor sleep and significant weight loss for the past month. In the days preceding his presentation, he has experienced worsening irritability and rapid speech, and has been responding to internal stimuli and displaying odd repetitive movements of his extremities. On interview, the patient reported non-compliance to his prescribed Lithium and Paroxetine for the past three months. He also noted recently smoking methamphtamine on a daily basis for the past month and intermittently abusing cannabis, benzodiazepines and cocaine. His urine drug screen was positive for cannabinoids and amphetamines and the rest of his medical workup was within normal limits. On physical exam, he exhibited involuntary writhing and twisting movements of his extremities. An atypical antipschotic was prescribed, after which his choreoathetotic movements resolved within 24 hours. The purpose of this poster is to highlight the possibility of developing chorea as a result of methamphetamine use, given the rarity of such cases, and to discuss whether the resolution of his neurological symptoms were a result of antipsychotic administration or were simply due to the natural course of methamphetamine discontinuation during hospitalization.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Extensive intracranial calcification presenting with neurological symptoms due to primary hypoparathyroidism and secondary hyperparathyroidism: Two case reports

Metastatic calcification involving basal ganglion in idiopathic hypoparathyroidism (IHPT) and intracranial vascular calcification in secondary hyperparathtyroidism (SHPT) in end-stage renal disease (ESRD) on hemodialysis are not uncommon. Extensive bilateral symmetrical intracranial calcification involving basal ganglion, cerebellum and white matter presenting with neurological symptoms has been rarely reported in literature. We report 2 such cases. The first case belongs to a 56 year-old lady with IHPT with extensive intracranial calcification who presented with choreoathetotic movements. The second case is concerning a 14 year-old boy with SHPT with ESRD on hemodialysis with extensive intracranial calcification who presented with seizures. The possible pathogenesis of extensive metastatic calcification and treatment was discussed with review of literature.

NMDA-receptor encephalitis: An unsual case of refractory status epilepticus

Objective: Case report of NMDA receptor encephalitis in a young man with early refractory status epilepticus and atypical radiological findings. Background: Anti-NMDA receptor encephalitis is an autoimmune disorder due to antibodies to the NR1-NR2B heterodimer of NMDA receptor. On imaging, it typically presents with T2 hyperintensities in mesio-temporal lobes, cerebral cortex and basal ganglia. We present a case with a dramatic clinical evolution and novel imaging findings. Design/Methods: Case report and review of imaging. Results: 29-year-old male presented with mood disturbance followed by partial-complex seizures, facial dyskinesia and choreo-athetotic movements. Initial MRI showed subtle T2-hyperintensities in mesio-temporal lobes. Diagnosis of NMDA-receptor encephalitis was confirmed after CSF antibody detection. Prior to diagnostic confirmation, he developed refractory status epilepticus, and concomitant signs of herniation. A repeated MRI showed increased T2-hyperintensities of thalami and mesencephalon, with cerebellar involvement and transtentorial/foraminal herniation. Restricted diffusion was documented in the cerebellar cortex/thalami/putamina and caudate. IV corticosteroids and hypertonic fluid reversed herniation, and halted the seizures. Conclusions: To our knoweldge, we report the first case report of uncal and tonsillar herniation in NMDA-r encephalitis secondary to atypical, predominant cerebellar involvement. This case highlights life-threatening manifestation that physicians might encounter, and a possible role for high dose IV corticosteroids as an adjunct treatment for brain edema and seizures.

OP62 – 2508: Anti-NMDA receptor antibody status in 3 cases of infant choreo-athetotic movement disorder following HSV-1 encephalitis

Objective Herpes simplex encephalitis (HSE) is the most common single cause of viral encephalitis in children. In some cases, secondary neurological decline occurs within weeks after HSE mimicking early relapse. Symptoms in this phase often include extrapyramidal choreo-athetotic movement disorders. An autoimmune component has long been suspected in these relapses. Aim of this study was to assess whether antibodies against N-methyl-D-aspartate receptors (NMDARs) may be part of this mechanism. Methods We present a case series of 3 pediatric patients treated with immunomodulation and plasmapheresis for choreo-athetotic movement disorder after HSE. Clinical and serological data were evaluated retrospectively. Anti-neuronal antibodies were assessed from frozen serum and CSF samples using tissue-based and cell-based assays. Results Childrens' median age was 8 months (range 6–11; 3 male). The extrapyramidal choreo-athetotic movement disorder developed 15 to 35 days after onset of encephalitis. All three patients were in need of tube feeding because of pharyngeal dyskinesias. Corticosteroids were administered in 2 cases. All patients received intravenous immunoglobulins and plasmapheresis. The treatment with plasmapheresis started 6–16 days after the onset of the movement disorder and was performed 7–9 times in a period of 14–22 days. In two cases a remission was achieved and in one case only a slight symptom relief was noticed. Two out of three patients revealed positive NMDAR antibodies. In one patient antineuronal antibodies were not detectable. Conclusion Increasing reports on NMDAR antibody related symptoms after HSE strengthen the importance of analyzing anti-neuronal antibodies at earliest clinical clues and to treat with immune modulatory agents. Interestingly, one of our patients with extrapyramidal movement disorder was negative for NMDAR Abs in spite of striking clinical similarities with NMDAR positive patients. This finding might either suggest insufficient sensitivity of anti-neuronal antibody screening methods or indicate presence of currently unknown antibodies causing similar clinical presentation.

PP03.15 – 2755: Clinical metabolomics reveals a novel plasma biomarker for Snyder Robinson syndrome (X-linked spermine synthase deficiency)

Objective Clinical metabolomics has emerged as a powerful tool to study metabolic perturbations in various diseases and to unravel novel biomarkers. In a monocenter study on metabolic-genetic research into epileptic encephalopathies, we applied untargeted metabolomics in parallel with exome sequencing in twin brothers with epileptic encephalopathy of unknown etiology. Genetic analysis confirmed Snyder-Robinson syndrome (SRS), a rare X-linked mental retardation syndrome. The underlying spermine synthase (SMS) deficiency affects polyamine metabolism and reduces intracellular spermine. So far, the diagnosis of SRS relied on a reduced spermine/spermidine ratio in lymphoblasts and/or sequencing of the SMS gene. Case The male monozygotic twins presented with developmental delay, progressive microcephaly and discrete dysmorphic features. From the age of 12 months, they developed therapy-resistant seizures with recurrent irregular myoclonic jerks and serial spasms in twin A. The EEG showed an abnormal background activity and multifocal and generalized spike waves. Additional atonic and tonic seizures and atypical absences occurred in both. At the age of 15 months, they developed a severe encephalopathy with frequent seizures, loss of milestones, impairment of visual interaction and a transient choreo-athetotic movement disorder. Both twins showed signs of osteopenia, twin B suffered a non-traumatic clavicular fraction at 23 months. Methods Clinical exome sequencing was applied in both twins and their parents. Sanger sequencing was applied to confirm the candidate variant. An untargeted plasma metabolomics analysis was performed by liquid chromatography–high-resolution mass spectrometry (LC-MS). Results Exome sequencing revealed a novel SMS missense mutation. Discriminant statistical analysis of the LC-MS data showed a distinct plasma metabolomics profile while comparative analysis versus age-matched controls revealed significantly elevated levels of N-acetylspermidine, a metabolite involved in spermine metabolism. Conclusion A combined clinical “omics” approach revealed N-acetylspermidine as a novel plasma biomarker for spermine synthase deficiency and identified a novel missense mutation in twin boys with SRS.

Infantile Epileptic Encephalopathy, Transient Choreoathetotic Movements, and Hypersomnia due to a De Novo Missense Mutation in the SCN2A Gene

Mutations of the SCN2A gene have originally been described in association with benign familial neonatal-infantile seizures (BFNIS). Recently, single patients with more severe phenotypes and persisting epileptic encephalopathies have been recognized. We report the case of a girl with severe infantile onset epileptic encephalopathy and a de novo missense mutation in the SCN2A gene (c.4025T > C/ = ; p.L1342P/ = ), who presented with a transient choreatic movement disorder, hypersomnia, and progressive brain atrophy. Whole exome sequencing did not reveal any other disease causing mutation. Our patient contributes to the expanding phenotypic spectrum of SCN2A-related disorders and underlines the importance of genetic workup in epileptic encephalopathies.

Sympathomimetic syndrome, choreoathetosis, and acute kidney injury following “bath salts” injection

"Bath salts" is a well known street drug which can cause several cardiovascular and neuropsychiatric symptoms. However, only one case of acute kidney injury has been reported in the literature. We present a case with sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, and acute kidney injury following the use of bath salts. A 37-year-old man with past medical history of hypertension and depression was brought to the emergency center with body shaking. Three days before admission he injected 3 doses of bath salts intravenously and felt eye pain with blurry vision followed by a metallic taste, strange smells, profuse sweating, and body shaking. At presentation he had a sympathomimetic syndrome including high blood pressure, tachycardia, tachypnea, and hyperhydrosis with choreoathetotic movements. Laboratory testing revealed leukocytosis and acute kidney injury with a BUN of 95 mg/ dL and a creatinine of 15.2 mg/dL. Creatine kinase was 4,457 IU/dL. Urine drug screen is negative for amphetamine, cannabinoids, and cocaine; blood alcohol level was zero. During his ICU stay he became disoriented and agitated. Supportive treatment with 7.2 liters of intravenous fluid over 3 days, haloperidol, and lorazepam gradually improved his symptoms and his renal failure. Bath salts contain 3,4-methylenedioxypyrovalerone, a psychoactive norepinephrine and dopamine reuptake inhibitor. Choreoathetosis in this patient could be explained through dopaminergic effect of bath salts or uremic encephalopathy. The mechanism for acute kidney injury from bath salts may involve direct drug effects though norepinephrine and dopamine-induced vasoconstriction (renal ischemia), rhabdomyolysis, hyperthermia, and/or volume contraction.

Choreoathetosis in a patient with neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorder (NMOSD) is a multifocal central nervous system demyelinating disease, and is associated with NMO-immunoglobulin G or anti-astrocyte water channel aquaporin-4 antibody. We report a 74-year-old woman with NMOSD who presented choreoathetosis. She developed left upper limb weakness and sensory impairment below the left C2 level, and the lesion was located primarily in the gray matter from the lower brainstem to the C6 level. Her symptoms were ameliorated after steroid pulse therapy, but painful tonic spasms (PTS) occurred in the affected limb. After gabapentin (600 mg/day) was started for the PTS, choreoathetotic movement appeared in her left upper limb. We suggest that modification of the gamma aminobutyric acid receptor activity and the cervical gray matter lesion had a role in the development of choreoathetosis.

Mutation in PNPT1, which Encodes a Polyribonucleotide Nucleotidyltransferase, Impairs RNA Import into Mitochondria and Causes Respiratory-Chain Deficiency

Multiple-respiratory-chain deficiency represents an important cause of mitochondrial disorders. Hitherto, however, mutations in genes involved in mtDNA maintenance and translation machinery only account for a fraction of cases. Exome sequencing in two siblings, born to consanguineous parents, with severe encephalomyopathy, choreoathetotic movements, and combined respiratory-chain defects allowed us to identify a homozygous PNPT1 missense mutation (c.1160A>G) that encodes the mitochondrial polynucleotide phosphorylase (PNPase). Blue-native polyacrylamide gel electrophoresis showed that no PNPase complex could be detected in subject fibroblasts, confirming that the substitution encoded by c.1160A>G disrupts the trimerization of the protein. PNPase is predominantly localized in the mitochondrial intermembrane space and is implicated in RNA targeting to human mitochondria. Mammalian mitochondria import several small noncoding nuclear RNAs (5S rRNA, MRP RNA, some tRNAs, and miRNAs). By RNA hybridization experiments, we observed a significant decrease in 5S rRNA and MRP-related RNA import into mitochondria in fibroblasts of affected subject 1. Moreover, we found a reproducible decrease in the rate of mitochondrial translation in her fibroblasts. Finally, overexpression of the wild-type PNPT1 cDNA in fibroblasts of subject 1 induced an increase in 5S rRNA import in mitochondria and rescued themitochondrial-translation deficiency. In conclusion, we report here abnormal RNA import into mitochondria as a cause of respiratory-chain deficiency.

Early-onset Ataxia With Progressive External Ophthalmoplegia Associated With POLG Mutation

Autosomal recessive ataxias caused by mutations of the polymerase γ (POLG) gene make an important group of progressive ataxias accompanied by a diverse spectrum of neurological disorders. Because the clinical picture can be quite miscellaneous, it is challenging to assort patients to any of the currently described syndromes; therefore, to provide such a patient with a conclusive diagnosis can be challenging for the neurologist. A typical magnetic resonance imaging finding is probably the most useful landmark in the diagnostic process, which will steer the clinician toward POLG gene testing. To illustrate this, we present a case of progressive ataxia caused by A467T and W748S mutations of POLG gene, who presented with overlapping symptoms of autosomal recessive mitochondrial ataxic syndrome and SANDO, as well as choreoathetotic movements and dysphonia. After lengthy investigations, magnetic resonance imaging showed T2 and FLAIR hyperintensities in the thalamus, inferior olives, and cerebellum, which led us to the analysis of POLG mutations.

Alternating Hemiplegia of Childhood in Chinese Following Long-Term Treatment With Flunarizine or Topiramate

ABSTRACTObjective: Alternating hemiplegia of childhood (AHC) is a rare and intractable disorder. The etiology and standard therapy of AHC remain unknown. The long-term effects of flunarizine or topiramate on patients with AHC are still not clear. Methods: Fifteen patients were investigated in this study. Their neurological disturbance and mental retardation after drug therapy were evaluated. Results: Nine patients treated with flunarizine therapy and three children with topimarate treatment presented with shorter duration or less frequency of the hemiplegic attacks. These drug responsive patients also showed improvements on neurological disturbance including eye movement disorder, choreoathetotic movements, dystonia, and ataxia. However, seizure episodes and cognitive impairments were not alleviated in AHC with long-term drug therapy. Conclusions: The findings from the present study support flunarizine or topitamate as the rational treatment for AHC.

A Japanese Adult Case of Megalencephalic Leukoencephalopathy with Subcortical Cysts with a Good Long-term Prognosis

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a recently recognized neurological disease, and mutations in the MLC1 gene have been identified as the cause of the disorder. A 54-year-old Japanese woman with macrocephaly presented with progressive mental decline, gait disturbance due to spasticity and ataxia, and choreoathetotic movement in the left upper extremity. Brain magnetic resonance imaging (MRI) revealed characteristic subcortical cysts in addition to diffuse white matter involvement. Genetic analysis of the MLC1 gene identified an S93L mutation in a homozygous state. This case is particularly valuable because of the lack of knowledge on the long-term prognosis of MLC.

Unlocking the genetics of paroxysmal kinesigenic dyskinesia

Paroxysmal kinesigenic dyskinesia (PKD, or paroxysmal kinesigenic choreoathetosis) is a rare and remarkable hereditary disorder that was recognized as early as 1892 and defined more precisely during the 20th century (Mount and Reback, 1940; Kertesz, 1967; Richards and Barnett, 1968; Lance, 1977; Kato et al ., 2006). Patients with PKD experience recurrent and brief episodes of dystonic or choreoathetotic involuntary movements that are induced by sudden motion, such as standing up quickly or being startled (Bruno et al ., 2004; Bhatia, 2011). Although this disorder can be very disabling if undiagnosed, its outcome is usually benign when treated with low doses of anti-convulsants such as carbamazepine or phenytoin. Most patients with primary idiopathic forms of PKD report a family history of the disease compatible with autosomal dominant inheritance. The first locus for PKD, identified in 1999 on chromosome 16p11.2-q12.1 (EKD1, Fig. 1) overlaps with another locus identified for infantile convulsions and paroxysmal choreoathetosis (ICCA) (Szepetowski et al ., 1997; Tomita et al ., 1999). ICCA is also inherited in an autosomal dominant fashion and is characterized by benign afebrile infantile convulsions that start within the first year of life and usually stop by 3 years of age, variably associated with paroxysmal dyskinesia (Table 1). Benign familial infantile convulsions, ICCA and PKD have thus been proposed to be different expressions of the same disorder or allelic disorders (Caraballo et al ., 2001). Linkage of families with PKD, ICCA and benign familial infantile convulsions to the same region on chromosome 16 has been confirmed by many groups, but despite the sequencing of the 157 genes contained in the region, the causative one has remained a mystery for more than a decade (Kikuchi et al ., 2007). Figure 1 Schematic representation of chromosome 16, showing the overlapping loci …

Early plasmapheresis in 3 consecutive cases of choreo-athetotic movement disorder after HSV-1 encephalitis

The incidence of herpes simplex virus type 1 (HSV-1) encephalitis represents 1 of 250.000 to 500.000. Despite antiviral treatment, the rate of mortality and neurological sequelae is high. Secondary extrapyramidale, choreo-athetotic movements are a rare, but severe sequela after HSV-1 encephalitis with unknown pathogenesis. Beside the resumption of viral replication and the primary involvement of the basal ganglia, an immune- mediated pathogenesis is incremental up for discussion, due to the fact that immune modulating treatment yields symptom relief. To the best of our knowledge this is the first case series of patients treated with plasmapheresis for choreo-athetotic movement disorder after HSV-1 encephalitis.