Movement Disturbances Research Articles

A Novel Mutation in ELOVL4 Leading to Spinocerebellar Ataxia (SCA) With the Hot Cross Bun Sign but Lacking Erythrokeratodermia: A Broadened Spectrum of SCA34.

Although mutations in 26 causative genes have been identified in the spinocerebellar ataxias (SCAs), the causative genes in a substantial number of families with SCA remain unidentified. To identify the causative gene of SCA in 2 Japanese families with distinct neurological symptoms and radiological presentations. Clinical genetic study at a referral center of 11 members from 2 Japanese families, which started in 1997. Results of neurological examinations and radiological evaluations. The causative mutation was identified using genome-wide linkage analysis and next-generation sequencing. Affected members (9 of 11 members [81.8%]) showed slowly progressive cerebellar ataxia (all 9 members [100%]), ocular movement disturbance (all 9 members [100%]), and pyramidal tract signs (8 of 9 members [88.9%]) with an age at onset between the second and sixth decades of life. Besides cerebellar and pontine atrophy, magnetic resonance imaging of the brain revealed the hot cross bun sign (4 of 6 members [66.7%]), pontine midline linear hyperintensity (2 of 6 members [33.3%]), or high intensity in the middle cerebellar peduncle (1 of 6 members [16.7%]), which are all reminiscent of multiple system atrophy in tested patients. Using linkage analysis combined with exome and whole-genome sequencing, we identified a novel heterozygous mutation in the ELOVL fatty acid elongase 4 (ELOVL4) gene (c.736T>G, p.W246G) in both families. Haplotype analysis indicated that it was unlikely that these 2 Japanese families shared a common ancestor. Although a missense mutation in ELOVL4 (c.504G>C, p.L168F) was recently reported to be associated with SCA with erythrokeratodermia variabilis (SCA34) in a French-Canadian family, signs of erythrokeratodermia variabilis were absent in our families. Combined with the results of the family with SCA34 reported previously, this report confirms that mutations in ELOVL4 can cause dominantly inherited neurodegeneration severely affecting the cerebellum and brainstem. We should be aware that the presence of multiple system atrophy-like features on magnetic resonance imaging scans, together with cerebellar and brainstem atrophy, suggests SCA34, even when erythrokeratodermia variabilis is absent. The present study further broadened the spectrum of the clinical presentations of SCA34 associated with mutations in ELOVL4, which is involved in the biosynthesis of very long-chain fatty acids.

The association between alterations of eye movement control and cerebral intrinsic functional connectivity in Parkinson's disease.

Patients with Parkinson's disease (PD) present with eye movement disturbances that accompany the cardinal motor symptoms. Previous studies have consistently found evidence that large-scale functional networks are critically involved in eye movement control. We challenged the hypothesis that altered eye movement control in patients with PD is closely related to alterations of whole-brain functional connectivity in association with the neurodegenerative process. Saccadic and pursuit eye movements by video-oculography and 'resting-state' functional MRI (3 Tesla) were recorded from 53 subjects, i.e. 31 patients with PD and 22 matched healthy controls. Video-oculographically, a broad spectrum of eye movement impairments was demonstrated in PD patients vs. controls, including interrupted smooth pursuit, hypometric saccades, and a high distractibility in anti-saccades. Significant correlations between altered oculomotor parameters and functional connectivity measures were observed, i.e. the worse the oculomotor performance was, the more the regional functional connectivity in cortical, limbic, thalamic, cerebellar, and brainstem areas was decreased. Remarkably, decreased connectivity between major nodes of the default mode network was tightly correlated with the prevalence of saccadic intrusions as a measure for distractability. In conclusion, dysfunctional eye movement control in PD seems to be primarily associated with (cortical) executive deficits, rather than being related to the ponto-cerebellar circuits or the oculomotor brainstem nuclei. Worsened eye movement performance together with the potential pathophysiological substrate of decreased intrinsic functional connectivity in predominantly oculomotor-associated cerebral functional networks may constitute a behavioral marker in PD.

Assessing the burden on primary caregivers of children with cerebral palsy and its relation to quality of life and socioeconomic aspects

Children with Cerebral Palsy (CP) present a permanent disturbance of posture and movement, characterized by a motor loss that causes difficulty in the execution of day-to-day activities and a consequent occupational dependence. Therefore, the task of assisting children with CP can lead to the caregivers’ tiredness, isolation, and stress, also generating a physical and emotional burden and a possible decrease in the quality of life of this population. Objective: To evaluate the burden on the primary caregivers of children with CP, comparing the quality of life and the age between caregivers with and without excessive burden, as well as to compare the economic class and work status variables to the burden variable. Method: The study was characterized as analytical and transversal. There were 31 primary caregivers of children from 0 to 18 years old with a CP diagnosis who participated in the study. The instruments utilized in the research were a socio-demographic questionnaire designed to characterize the sample, the questionnaire from the Associação Brasileira de Empresas de Pesquisa (ABEP) for economic classification, the Medical Outcome Study 36 (SF-36) for the assessment of the caregivers’ quality of life, and the Zarit Burden Interview (ZBI) to assess the caregiver’s subjective and objective burdens. Results: The results pointed out that 67.7% of the caregivers presented burden and that the averages of some domains of the SF-36 (“limitation by physical aspects”, “pain”, “vitality” and “limitation by social aspects”) for this group were significantly smaller than for the group with no burden. There was no statistically significant association in the chi-square test between the socioeconomic class of the caregivers and the burden and between the work status and the burden. Conclusion: The presence of burden on caregivers of children with CP is related to a lesser quality of life, but the burden was not associated with the caregiver’s age, work status, or economic class.

Magnesium Supplementation Prevents and Reverses Experimentally Induced Movement Disturbances in Rats: Biochemical and Behavioral Parameters.

Reserpine administration results in a predictable animal model of orofacial dyskinesia (OD) that has been largely used to access movement disturbances related to extrapyramidal oxidative damage. Here, OD was acutely induced by reserpine (two doses of 0.7mg/kg subcutaneous (s.c.)), every other day for 3days), which was administered after (experiment 1) and before (experiment 2) magnesium (Mg) supplementation (40mg/kg/mL, peroral (p.o.)). In experiment 1, Mg was administered for 28days before reserpine treatment, while in experiment 2, it was initiated 24h after the last reserpine administration and was maintained for 10 consecutive days. Experiment 1 (prevention) showed that Mg supplementation was able to prevent reserpine-induced OD and catalepsy development. Mg was also able to prevent reactive species (RS) generation, thus preventing increase of protein carbonyl (PC) levels in both cortex and substantia nigra, but not in striatum. Experiment 2 (reversion) showed that Mg was able to decrease OD and catalepsy at all times assessed. In addition, Mg was able to decrease RS generation, with lower levels of PC in both cortex and striatum, but not in substantia nigra. These outcomes indicate that Mg is an important metal that should be present in the diet, since its intake is able to prevent and minimize the development of movement disorders closely related to oxidative damage in the extrapyramidal brain areas, such as OD.

A novel mouse model of creatine transporter deficiency

Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and behavioral disturbances, language and speech impairment ( OMIM #300352).CCDS1 is still an untreatable pathology that can be very invalidating for patients and caregivers. Only two murine models of CCDS1, one of which is an ubiquitous knockout mouse, are currently available to study the possible mechanisms underlying the pathologic phenotype of CCDS1 and to develop therapeutic strategies. Given the importance of validating phenotypes and efficacy of promising treatments in more than one mouse model we have generated a new murine model of CCDS1 obtained by ubiquitous deletion of 5-7 exons in theSlc6a8gene. We showed a remarkable Cr depletion in the murine brain tissues and cognitive defects, thus resembling the key features of human CCDS1. These results confirm that CCDS1 can be well modeled in mice. This CrT−/ymurine model will provide a new tool for increasing the relevance of preclinical studies to the human disease.

Embodied-enactive clinical reasoning in physical therapy

Clinical reasoning is essential in physical therapy practice. Instrumental approaches and more recent narrative approaches to clinical reasoning guide physical therapists in their understanding of the patient’s movement disturbances and help them to plan strategies to improve function. To the extent that instrumental and/or narrative models of clinical reasoning represent impairments as mere physical disturbances, we argue that such models remain incomplete. We draw on a phenomenologically inspired approach to embodied cognition (termed “enactivism”) to suggest that the dynamics of lived bodily engagement between physical therapist and patient contribute to and help to constitute the clinical reasoning process. This article outlines the phenomenologically informed enactive perspective on clinical reasoning, with special reference to clinical work that addresses impairments as sequelae of neurological diseases.

Investigations in vitro on the behaviour of chromosomes and the mitotic apparatus in endosperm cells of Haemanthus katherinae Baker treated with oleander glycosides

The effect of oleander glycosides on dividing endosperm cells of <i>Haemanthus katherine</i> was investigated in vitro. The disturbances in the successive cell division phases were analysed in reference to cytokinesis. A strong tendency was noted to restitution nuclei formation in all phases of mitosis, and particularly in prophase. The observed chromosome pattern is the result of disturbances in prometaphase and anaphase chromosome movements owing to disturbances in the function of 'the 'mitotic spindle. It is probable that oleander glycosides inhibit formatiom of 'the microtubules of the mitotic spindle and disorganize the already formed spindle. They cause minor disturbances in cytokinesis, although frequently cell plates arise in quite unexpected places. The results of the present study are compared with those obtained in the case of root meristematic cells (Tarkowska, 1971a, b).

Reversible Splenial Lesion Syndrome (Resles) in a Patient with Clinically Mild Tick-Borne Encephalitis and Hyponatremia

Introduction: Reversible splenial lesion syndrome (RESLES) is a clinicoradiological syndrome of varied etiology, characterized by transient lesions involving the splenium of the corpus callosum (SCC). Clinical presentation is nonspecific and depends on etiology. In the case of infectious disease the syndrome is also called mild encephalitis with reversible splenial lesion (MERS). Hyponatremia is often described in patients with RESLES. Here we present a patient case of RESLES/MERS in a patient with tick-borne encephalitis (TBE) accompanied by mild hyponatremia. Case Presentation: A 46-year-old man presented with malaise, fever, headache, discrete nuchal rigidity, brain stem symptoms (disturbance of ocular movements, gait ataxia) and mild cognitive and psychomotor impairment. Cerebrospinal fluid analysis at two different time points showed a lymphocytic pleocytosis and seroconversion for anti-TBEIgM/- IgG, serum biochemical analysis a mild hyponatremia. Magnetic resonance imaging (MRI) of the brain on day four after admission revealed a distinct signal hyperintensity on T2/FLAIR sequences in the SCC associated with diffusion restriction and low apparent diffusion coefficient (ADC) values on diffusion-weighted sequences. On T1-weighted images no contrast enhancement was detectable. Until the diagnosis of TBE the patient was treated with intravenous ceftriaxone, ampicillin and acyclovir. The patient recovered completely within three weeks. The T2/FLAIR hyperintense and diffusion-restricted lesion of the SCC was completely resolved ten days after the first MRI. Conclusion: TBE accompanied by hyponatremia may lead to RESLES/MERS, a clinicoradiological syndrome with reversible non-enhancing lesion of the SCC and excellent prognosis. Neuroradiological findings in RESLES are very similar to findings described in patients with osmotic demyelination syndromes like central pontine myelinolysis or extrapontine myelinolysis.

The influence of immediate complete anterior guidance development technique on subjective symptoms in Myofascial pain patients: Verified using digital analysis of occlusion (Tek-scan) for analysing occlusion: A 3 years clinical observation.

Objectives:The purpose of this study is to evaluate the effect of occlusal equilibration using immediate complete anterior guidance development (ICAGD) technique by Kerstein and Farrell on the subjective symptoms of myofascial pain. This technique is the most advanced verifiable and measurable way of digitally analyzing the occlusion using T-scan technology. The primary objective is to reduce the anterior disclusion time to <0.4 s and the secondary objective is to reduce the signs and symptoms of myofascial pain.Materials and Methods:This study is to assess the reducing effects of subjective symptoms of 100 patients diagnosed as myofascial pain patients treated by ICAGD technique as described by Kerstein and Farrell. The common complaints of the patients were a pain in the masseter and temporal muscles, jaw tiredness in the mornings, night bruxing and difficulty in chewing. In this technique occlusal equilibration involves removal of posterior interferences and establish anterior guidance. The patients were treated over three visits 1-week apart and followed for 3 years with an interval of 3 months for the subsequent visits. A visual analog ordinal scale is used to rate the symptoms. The symptoms reduction occurred for all the patients after the first correction in about 5–10 days. In about a period of 3 years review, no recurrence was seen of the chronic myofascial symptoms.Results:In spite of the chronic nature of the patient's symptoms, symptom reduction occurred in a week's time. This was assessed by the results of the ordinal scale values. This agrees with the studies of Kerstein and Farrell.Conclusion:Equilibration of occlusion using digital analysis by T-scan in which force is quantified against time, should be done to establish free functional movements without any interference; otherwise the disturbances in the excursive movements may lead to muscle dysfunction at later years.

Treatment of Psychotic Symptoms in ParkinsonÂ’s Disease

The treatment of Parkinson’s disease with l-dopa and a decarboxylase inhibitor, with dopamine agonists or with NMDA antagonists can cause psychotic symptoms. Neural networks are described in the mesolimbic system in order to explain this adverse effect. The psychotic symptoms are treated with second-generation antipsychotic drugs which do not worsen movement disturbances. Among these drugs, the administration of clozapine and quetiapine is recommended to treat psychotic symptoms in Parkinson’s disease.

Echogenicity of basal ganglia structures in different Huntington's disease phenotypes.

In Huntington's disease (HD), a neurodegenerative-inherited disease, chorea as the typical kind of movement disorder is described. Beside chorea, however, all other kinds of movement disturbances, such as bradykinesia, dystonia, tremor or myoclonus can occur. Aim of the current study was to investigate alterations in the echogenicity of basal ganglia structures in different Huntington's disease phenotypes. 47 patients with manifest and genetically confirmed HD were recruited. All participants underwent a thorough neurological examination. According to a previously described method, classification into predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes was performed depending on subscores of the Unified Huntington's Disease Rating Scale. In addition, findings in juvenile HD were compared to adult HD. Transcranial sonography was performed by investigators blinded to clinical classification. There were no significant differences in basal ganglia echogenicities between the three phenotypes. Size of echogenic area of substantia nigra (SN) correlated positively with CAG repeat and bradykinesia subscore, and negatively with age of onset and chorea subscore. Comparing juvenile and adult HD subtypes, SN hyperechogenicity was significantly more often detectable in the juvenile form (100 vs. 29.3 %, p = 0.002). Regarding echogenicity of caudate or lentiform nuclei, no significant differences were detected. HD patients with the juvenile variant exhibit marked hyperechogenicity of substantia nigra. No significant differences in basal ganglia echogenicities between predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes were detected.

Hard Disk Drive Mechanism Vibration Damping Using Disturbance Observer

Variety of the usage in Hard Disk Drives relies on the high speed, positioning system precision and reliability of their control mechanisms. Vibration is one of the most important concerns in the control mechanisms due to rotational movement of the HDD drivers and the data head speed so as to keep the performance under control, the movement disturbances should be accurately monitored. Disturbance Observers (DOBs) increase the control system robustness whilst improving the dynamic performance of the systems without employing sophisticated calculations and prerequisite; the plant inverse model calculation is eliminated in this method which empowers the usage and simplifies its implementation. This paper focuses on the suppression of vibration using Disturbance Observer and compares it with PID controller and Intelligent Active Force Controller to figure out the advantages of DOB.

The cerebellum: from development to structural complexity and motor learning.

The cerebellum: from development to structural complexity and motor learning.

A novel mouse model of creatine transporter deficiency

Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and behavioral disturbances, language and speech impairment ( OMIM #300352).CCDS1 is still an untreatable pathology that can be very invalidating for patients and caregivers. Only two murine models of CCDS1, one of which is an ubiquitous knockout mouse, are currently available to study the possible mechanisms underlying the pathologic phenotype of CCDS1 and to develop therapeutic strategies. Given the importance of validating phenotypes and efficacy of promising treatments in more than one mouse model we have generated a new murine model of CCDS1 obtained by ubiquitous deletion of 5-7 exons in the Slc6a8 gene. We showed a remarkable Cr depletion in the murine brain tissues and cognitive defects, thus resembling the key features of human CCDS1. These results confirm that CCDS1 can be well modeled in mice. This CrT −/y murine model will provide a new tool for increasing the relevance of preclinical studies to the human disease.

DETERMINATION OF INDIVIDUAL FEATURES OF BALANCE RETAINING IN PATIENTS WITH CEREBRAL PALSY USING STABILOMETRY TESTING

The practical aim of the research is to develop a methodology for assessing the functional state of the musculoskeletal system in the case of complex human pathologies and associated injuries with the objective distinction of interdependent anatomical and functional disorders in the osteoarticular system, nervous and muscular subsystems, identification pathology severity in the separate subsystems and the degree of influence for each of them on the movement organization as a whole. In patients with cerebral palsy the neurological movement disturbance is a priority component, differentiation of which may by difficult due to lack of tools to evaluate objectively and display the features of functioning nervous system in normal and pathological conditions. The authors propose a set of interval indicators of stabilometric study and method to use it providing the more qualitative consideration individual characteristics and the formation of clinically interpretable representation of a visual results image as compared with the standard vector and frequency indicators.

DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients.

To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels. Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay. Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients. DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.

Burkitt lymphoma presenting rapid progression from unilateral to bilateral cavernous sinus syndrome as the initial symptom

AbstractA 62‐year‐old woman experienced right cavernous sinus syndrome and developed left cavernous sinus syndrome after 2 weeks. Subsequently, the patient developed gingival swelling and biopsy was carried out. The patient was diagnosed as having Burkitt lymphoma with central nervous system and orbital infiltration. Chemotherapy resolved the eye movement disturbance, but the other symptoms persisted. Burkitt lymphomas that initially present with bilateral cavernous sinus syndrome are rare. However, we emphasize that the general clinician should be alerted to identify the possibility of lymphoma if clinical symptoms indicate rapid progression like from unilateral to bilateral cavernous sinus syndrome in 2 weeks.

A novel mouse model of creatine transporter deficiency.

Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and behavioral disturbances, language and speech impairment ( OMIM #300352). CCDS1 is still an untreatable pathology that can be very invalidating for patients and caregivers. Only two murine models of CCDS1, one of which is an ubiquitous knockout mouse, are currently available to study the possible mechanisms underlying the pathologic phenotype of CCDS1 and to develop therapeutic strategies. Given the importance of validating phenotypes and efficacy of promising treatments in more than one mouse model we have generated a new murine model of CCDS1 obtained by ubiquitous deletion of 5-7 exons in the Slc6a8 gene. We showed a remarkable Cr depletion in the murine brain tissues and cognitive defects, thus resembling the key features of human CCDS1. These results confirm that CCDS1 can be well modeled in mice. This CrT (-/y) murine model will provide a new tool for increasing the relevance of preclinical studies to the human disease.

Levodopa-Dependent Movement Disorder and Oligoastrocytoma Double Trouble or Dependent from Each Other?

Background: Inborn errors of neurotransmission and decreased function of the dopaminergic and serotoninergic systems could often lead to movement disturbances and impaired development.

Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's

Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's