A Classic Cornelia De Lange Syndrome Type 5 (CdLS5) With a De Novo Missense Variation of p.Gly210Arg in the HDAC8 Gene With a Novel Phenotype of Generalized Dystonia.

Cornelia de Lange syndrome (CdLS) is a rare neurodevelopmental disorder characterized by distinct dysmorphic facies, skeletal anomalies, and failure to thrive. CdLS type 5 (CdLS5) is caused by the HDAC8 gene mutations on chromosome Xq13.1 with X-linked dominant inheritance. We report our observation of an individual with CdLS5 with de novo missense mutation presenting with a novel phenotype of generalized dystonia. A four-month-old girl, second born to a non-consanguineous couple, presented with developmental delay, failure to thrive, and spastic quadriparesis. She had a history of intrauterine growth retardation in the third trimester of pregnancy. Facial gestalt was suggestive of CdLS. She had marked axial and appendicular dystonia. A skeletal survey and magnetic resonance imaging (MRI) with magnetic resonance spectroscopy (MRS) brain studies were normal. Genetic testing revealed a heterozygous missense variation c.628G>C in the HDAC8 gene. She was treated with trihexyphenidyl and clonazepam, followed by syndopa. On follow-up assessment at 22 months of age, the dystonia gradually improved but not entirely over time with medication. It is already known that single gene disorders, including SCN1A, SCN2A, KCNQ2, PRRT2, and pyridoxine deficiency, can result in isolated dystonia; we add CdLS5 (HDAC8 variation) to this expanding spectrum.

The Collicular-Pulvinar-Amygdala Axis and Adult-Onset Idiopathic Focal Dystonias.

Adult-onset idiopathic focal dystonias (AOIFD) are the most common type of dystonia. It has varied expression including multiple motor (depending on body part affected) and non-motor symptoms (psychiatric, cognitive and sensory). The motor symptoms are usually the main reason for presentation and are most often treated with botulinum toxin. However, non-motor symptoms are the main predictors of quality of life and should be addressed appropriately, as well as treating the motor disorder. Rather than considering AOIFD as a movement disorder, a syndromic approach should be taken, one that accommodates all the symptoms. Dysfunction of the collicular-pulvinar-amygdala axis, with the superior colliculus as a central node, can explain the diverse expression of this syndrome.

Movement Disorders in Inherited Metabolic Diseases in Children.

Movement disorders are one of the important neurological manifestations of inherited metabolic disorders. Important clues to the presence of an underlying inborn error of metabolism are early onset, presence of neuroregression or degeneration, parental consanguinity, sibling affection, paroxysmal events, waxing and waning course, skin or hair changes, absence of a perinatal insult or any structural cause, and presence of identifiable triggers. It is particularly important to recognize this class of movement disorders as several of them are eminently treatable and may often need disease-specific therapy besides symptomatic treatment. The current review focusses on the movement disorders associated with inherited metabolic defects in children, with emphasis on treatable disorders.

[Segawa's syndrome]. / Sindrom Segavy.

The authors present a case-report of Segawa's syndrome. Clinical characteristics, genetic background and treatment options with special emphasis on a differential diagnosis are discussed.

Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update. II. Hyperkinetic disorders.

Extrapyramidal movement disorders comprise hypokinetic-rigid and hyperkinetic or mixed forms, most of them originating from dysfunction of the basal ganglia (BG) and their information circuits that have been briefly reviewed in part 1 of the papers on neuropathology and pathogenesis of extrapyramidal movement disorders. The classification of hyperkinetic forms distinguishes the following: (1) chorea and related syndromes; (2) dystonias (dyskinesias); (3) tics and tourette disorders; (4) ballism; (5) myoclonic and startle disorders; and (6) tremor syndromes. Recent genetic and molecular classification distinguishes the following: (1) polyglutamine disorders (Huntington's disease and related disorders); (2) pantothenate kinase associated neurodegeneration; (3) Wilson's disease and related disorders; and (4) other hereditary neurodegenerations without hitherto detected genetic or specific markers. The diversity of phenotypes is related to the deposition of pathologic proteins in distinct cell populations, causing neurodegeneration due to genetic and environmental factors, but there is frequent overlap between various disorders. Their etiopathogenesis is still poorly understood but is suggested to result from an interaction between genetic and environmental factors, multiple etiologies, and noxious factors (protein mishandling, mitochondrial dysfunction, oxidative stress, excitotoxicity, energy failure, chronic neuroinflammation), being more likely than one single factor. Current clinical consensus criteria have increased the diagnostic accuracy of most neurodegenerative movement disorders, but for their definite diagnosis, histopathological confirmation is required. A timely overview of the neuropathology and pathogenesis of the major hyperkinetic movement disorders is presented.

Management of common adverse effects of antipsychotic medications.

The benefits of antipsychotic medications are sometimes obscured by their adverse effects. These effects range from relatively minor tolerability issues (e.g., mild sedation or dry mouth) to very unpleasant (e.g., constipation, akathisia, sexual dysfunction) to painful (e.g., acute dystonias) to disfiguring (e.g., weight gain, tardive dyskinesia) to life-threatening (e.g., myocarditis, agranulocytosis). Importantly, adverse effect profiles are specific to each antipsychotic medication and do not neatly fit into first- and second-generation classifications. This paper reviews management strategies for the most frequent side effects and identifies common principles intended to optimize net antipsychotic benefits. Only use antipsychotics if the indication is clear; only continue antipsychotics if a benefit is discernible. If an antipsychotic is providing substantial benefit, and the adverse effect is not life-threatening, then the first management choice is to lower the dose or adjust the dosing schedule. The next option is to change the antipsychotic; this is often reasonable unless the risk of relapse is high. In some instances, behavioral interventions can be tried. Finally, concomitant medications, though generally not desirable, are necessary in many instances and can provide considerable relief. Among concomitant medication strategies, anticholinergic medications for dystonias and parkinsonism are often effective; beta-blockers and anticholinergic medications are useful for akathisia; and metformin may lead to slight to moderate weight loss. Anticholinergic drops applied sublingually reduce sialorrhea. Usual medications are effective for constipation or dyslipidemias. The clinical utility of recently approved treatments for tardive dyskinesia, valbenazine and deutetrabenazine, is unclear.

Aplicaciones de la toxina botulínica en afecciones palpebrales / Uses of botulinum toxin in eyelid diseases

La toxina botulínica es un potente inhibidor neuromuscular altamente específico que produce una denervación química al bloquear la liberación de acetilcolina en la placa motora. Es sintetizada por Clostridium botulinum. Es un fármaco de alto valor terapéutico en las alteraciones de los anexos oculares; puede indicarse con muy buenos resultados en afecciones como el blefarospasmo primario, el espasmo hemifacial, el chalazión, el entropion espasmódico, la retracción palpebral, la ptosis de la ceja, la mioquimia palpebral y en el tratamiento de líneas de expresión facial, con muy buenos resultados estéticos. Se realizó una búsqueda bibliográfica y en Internet utilizando distintas bases de datos como Medline, Google, Bireme, PubMed.gov, así como artículos relevantes de la Academia americana de Oftalmología y Neurología con el objetivo de describir las aplicaciones de la neurotóxica botulínica en las afecciones de los anexos oculares(AU)

Botulinum toxin is a highly specific potent neuromuscular inhibitor that produces a chemical denervation when blocking the release of acetylcholine in the motor plaque. It is synthesized by clostridium botulinum. It is a drug with high therapeutic value to treat ocular adnexas and may be indicated for primary blepharospasm, hemifacial spasm, chalazion, spasmodic entropion, palpebral retraction, eye brow ptosis, palpebral myokymia and in treating expression lines of the face, all with very good esthetic results. Literature search was made in Internet by using databases such as Medline, Google, Bireme, PubMed.gov, as well as outstanding articles of the American Academy of Ophthalmology and Neurology with the objective of describing the uses of botulinum toxin for ocular adnexa diseases(AU)

Aplicaciones de la toxina botulínica en afecciones palpebrales / Uses of botulinum toxin in eyelid diseases

La toxina botulínica es un potente inhibidor neuromuscular altamente específico que produce una denervación química al bloquear la liberación de acetilcolina en la placa motora. Es sintetizada por Clostridium botulinum. Es un fármaco de alto valor terapéutico en las alteraciones de los anexos oculares; puede indicarse con muy buenos resultados en afecciones como el blefarospasmo primario, el espasmo hemifacial, el chalazión, el entropion espasmódico, la retracción palpebral, la ptosis de la ceja, la mioquimia palpebral y en el tratamiento de líneas de expresión facial, con muy buenos resultados estéticos. Se realizó una búsqueda bibliográfica y en Internet utilizando distintas bases de datos como Medline, Google, Bireme, PubMed.gov, así como artículos relevantes de la Academia americana de Oftalmología y Neurología con el objetivo de describir las aplicaciones de la neurotóxica botulínica en las afecciones de los anexos oculares(AU)

Botulinum toxin is a highly specific potent neuromuscular inhibitor that produces a chemical denervation when blocking the release of acetylcholine in the motor plaque. It is synthesized by clostridium botulinum. It is a drug with high therapeutic value to treat ocular adnexas and may be indicated for primary blepharospasm, hemifacial spasm, chalazion, spasmodic entropion, palpebral retraction, eye brow ptosis, palpebral myokymia and in treating expression lines of the face, all with very good esthetic results. Literature search was made in Internet by using databases such as Medline, Google, Bireme, PubMed.gov, as well as outstanding articles of the American Academy of Ophthalmology and Neurology with the objective of describing the uses of botulinum toxin for ocular adnexa diseases(AU)

Dystonia rating scales: critique and recommendations.

Many rating scales have been applied to the evaluation of dystonia, but only few have been assessed for clinimetric properties. The Movement Disorders Society commissioned this task force to critique existing dystonia rating scales and place them in the clinical and clinimetric context. A systematic literature review was conducted to identify rating scales that have either been validated or used in dystonia. Thirty-six potential scales were identified. Eight were excluded because they did not meet review criteria, leaving 28 scales that were critiqued and rated by the task force. Seven scales were found to meet criteria to be "recommended": the Blepharospasm Disability Index is recommended for rating blepharospasm; the Cervical Dystonia Impact Scale and the Toronto Western Spasmodic Torticollis Rating Scale for rating cervical dystonia; the Craniocervical Dystonia Questionnaire for blepharospasm and cervical dystonia; the Voice Handicap Index (VHI) and the Vocal Performance Questionnaire (VPQ) for laryngeal dystonia; and the Fahn-Marsden Dystonia Rating Scale for rating generalized dystonia. Two "recommended" scales (VHI and VPQ) are generic scales validated on few patients with laryngeal dystonia, whereas the others are disease-specific scales. Twelve scales met criteria for "suggested" and 7 scales met criteria for "listed." All the scales are individually reviewed in the online information. The task force recommends 5 specific dystonia scales and suggests to further validate 2 recommended generic voice-disorder scales in dystonia. Existing scales for oromandibular, arm, and task-specific dystonia should be refined and fully assessed. Scales should be developed for body regions for which no scales are available, such as lower limbs and trunk.

Morbilidad por trastornos del movimiento en la consulta de Neurología / Morbidity due to movement disorders in the Neurology Department

Se realizó un estudio observacional, descriptivo y transversal de 175 pacientes con trastornos del movimiento que asistieron a la Consulta de Neurología del Hospital General Docente "Dr. Juan Bruno Zayas Alfonso" desde el 2007 hasta el 2010, con vistas a describir la morbilidad en estos. Dichas afecciones iniciaron durante la quinta y sexta décadas de la vida en la mayoría de los integrantes de la casuística, con una frecuencia superior de la enfermedad de Parkinson, el temblor esencial y las distonías, y prevalencia del sexo masculino y el color de la piel mestizo. La electromiografía de los músculos agonistas y antagonistas evidenció el predominio del temblor de reposo y la disfunción en la inhibición recíproca, sobre todo en la enfermedad de Parkinson.

An observational, descriptive and cross-sectional study of 175 patients with movement disorders who attended the Neurology Department in "Dr. Juan Bruno Zayas Alfonso" Teaching General Hospital was carried out from 2007 to 2010, aimed at describing the morbidity in them. These disorders began during the fifth and sixth decades of life in most of the members of the case material, with a higher frequency of Parkinson disease, the essential tremor and dystonias, and prevalence of the male sex and half-bred skin. The electromyography of the agonistic and antagonistic muscles evidenced the prevalence of the rest tremor and the disorder in the reciprocal inhibition, mainly in the Parkinson disease.

Update on pediatric dystonias: etiology, epidemiology, and management.

Dystonia is a movement disorder characterized by sustained muscle contractions producing twisting, repetitive, and patterned movements or abnormal postures. Dystonia is among the most commonly observed movement disorders in clinical practice both in adults and children. It is classified on the basis of etiology, age at onset of symptoms, and distribution of affected body regions. ETIOLOGY: The etiology of pediatric dystonia is quite heterogeneous. There are many different genetic syndromes and several causes of symptomatic syndromes. Dystonia can be secondary to virtually any pathological process that affects the motor system, and particularly the basal ganglia. CLASSIFICATION: The etiological classification distinguishes primary dystonia with no identifiable exogenous cause or evidence of neurodegeneration and secondary syndromes. TREATMENT: Treatment for most forms of dystonia is symptomatic and includes drugs (systemic or focal treatments, such as botulinum toxin) and surgical procedures. There are several medications including anticholinergic, dopamine-blocking and depleting agents, baclofen, and benzodiazepines. In patients with dopamine synthesis defects L-dopa treatment may be very useful. Botulinum toxin treatment may be helpful in controlling the most disabling symptoms of segmental or focal dystonia. Long-term electrical stimulation of the globus pallidum internum appears to be especially successful in children suffering from generalized dystonia.

Botulinum toxin-A targeted for focal/ multifocal dystonias- An open- label application in X-linked Dystonia-Parkinsonism

Targeted for relief of spasms, posturing, pain, impaired function and disfigurement, botulinum toxin type-A (BoNT-A) was injected in dystonias of X-linked dystonia-parkinsonism (XDP). From 1992-2012, focal/ multifocal dystonia combinations were injected in XDP at the following regions: Peri-ocular (21 cases), oromandibular (50 cases), ligual (35 cases), laryngeal (5 cases), cervical (56 cases), truncalaxil (24 cases) upper limbs (13 cases) and lower limbs (18 cases). Pain was frequently reported in 40/50 cases with oromandibular dystonia, 28/56 cases with cervical dystonia, 18/24 cases with truncal-axil dystonia and 16/31 cases with limb dystonia. Outcomes were assessment through the global dystonia rating scale (DRS) at week 4, VAS pain reduction at week 4, duration of BoNT-A effects and safety. Cranial, laryngeal and cervical dystonia showed substantial improvement (DRS median score of 3-4), whereas truncal-axil and limb dystonias showed moderate improvement (DRS median score of 2), following BoNT-A. Pain reduction ranged from 30-100% (VAS), for those dystonias that reported co-morbid pain. BoNT-A effects had a duration ranging from 8-20 weeks. Procedures were generally well tolerated, and the adverse events were most significant in laryngeal injections (voice breathiness, but was eventually followed by a strong voice). The other events were mouth dryness, dysphagia and weekness in oromandibular, cervical and limb dystonias, respectively. Therefore, BoNT-A is a safe and valuable therapeutic option for the dystonias of XDP, especially the disabling and painful dystonias. BoNT-A injection working protocols could be adopted in dystonia that adheres to cost minimization (e.g. lower dose end per selected muscles), yet achieving a substantial benefit, and a reduced adverse event profile. Futhermore, this present study allowed us to recommend a "high potency, low dillution" of BoNT-A in oromandibular, linual, laryngeal, cervical and distal limb dystonias. In dystonias of the abdominal, paraspinal and proximal limb muscles, the "low potency, high dilution" BoNT-A injection protocol could be adopted.