Effect of acupuncture treatment on nonketotic hyperglycemic hemichorea-hemiballismus: a case report.

Nonketotic hyperglycemic hemichorea-hemiballismus is a rare syndrome in the clinic, and treatment is often delayed. Hypoglycemic therapy is the most widely used and effective treatment, but some patients experience a slower improvement. Other symptomatic treatment medicines have some degree of side effects. Acupuncture treatment is beneficial for hemichorea-hemiballismus. A male patient, aged 59 years, first visited our hospital outpatient department due to motor agitation with involuntary movements of the right limb. He had a history of type 2 diabetes mellitus and poor blood glucose control. His serum glucose was 26.5 mmol/L (normal: 4.4-6.1 mmol/L), and magnetic resonance imaging demonstrated an irregular area of high signal intensity in T1-weighted imaging, low signal intensity on T2-weighted imaging, and high signal intensity in the left corpus striatum in T2-FLAIR imaging. Hospitalization was recommended for the patient. After ruling out other possibilities, he was eventually diagnosed with nonketotic hyperglycemic hemichorea-hemiballismus. Intensive glycemic control was immediately started with subcutaneous injection and acupuncture treatment at "governor vessel 13 acupoints", and the involuntary movements completely disappeared on the ninth day of hospitalization. The pathophysiology of nonketotic hyperglycemic hemichorea-hemiballismus is unclear. Different patient histories lead to different brain tissue conditions, and relapses and uncontrolled blood glucose add difficulties to treatment. According to Traditional Chinese Medicine theory, insufficient kidney essence leads to brain dystrophy and causes the symptoms of hemichorea-hemiballismus. Research evidence has shown that acupuncture at "governor vessel 13 acupoints" has a beneficial treatment effect on nonketotic hyperglycemic hemichorea-hemiballismus.

Deep Brain Stimulation for the Treatment of Hemichorea: Case Series and Literature Review.

Background: Hemichorea (HC) and its severe form hemiballismus (HB) are rare movement disorders which can be medically refractory to treatments and may need surgical intervention. Case Report: We report 3 patients with HC-HB who had meaningful clinical improvement with unilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi). We identified 8 prior cases of HC-HB treated with GPi-DBS, and a majority of these patients experienced significant improvement in their symptoms. Discussion: GPi-DBS can be considered in medically refractory HC-HB in carefully selected patients. However, data is limited to small case series and further studies are needed.

[Treatment Methods for Dystonia, Myoclonus, and Chorea].

Abnormal involuntary movement (AIM) are usually classified into hypokinesia and hyperkinesia group. Hyperkinesia-AIM includes myoclonus, chorea, ballism, dystonia, athetosis, and more. Of these, dystonia, myoclonus, and chorea are frequent movement disorders. From a neurophysiological point of view, the mechanism of motor control by the basal ganglia is thought to consist of three pathways: hyperdirect, direct, and indirect. Hyperkinetic-AIMs are likely caused by the dysfunction of any of these three pathways, leading to malfunction in either presurround inhibition, initiation of motor performance, or postsurround inhibition. These dysfunctions are assumed to stem from regions, such as the cerebral cortex, white matter, basal ganglia, brainstem, and cerebellum. Drug therapies that consider the pathogenesis mechanism are desirable. Here, we presented an overview of treatment methods for hyperkinetic-AIMs.

Chorea: An unusual manifestation of endocrine diseases.

Chorea is a movement disorder involving involuntary movements of muscles of the face, neck, and limbs, usually caused by basal ganglia lesions. As an important part of the presentation of many neurological diseases, chorea is also an unusual manifestation of endocrine diseases and can be challenging to diagnose. Although the most common etiology of chorea is genetic, it is vital to identify acquired or symptomatic chorea, as these are potentially treatable conditions. This review summarizes the latest developments in various endocrine disease-related chorea, which will help clinicians to correctly identify and accurately treat it.

Deep brain stimulation effect in genetic dyskinetic cerebral palsy: The case of ADCY5- related disease.

BACKGROUND: Cerebral Palsy (CP) represents a frequent cause of disability in childhood. Early in life, genetic disorders may present with motor dysfunction and diagnosed as CP. Establishing the primary, genetic etiology allows more accurate prognosis, genetic counselling, and planning for symptomatic interventions in homogeneous etiological groups. Deep brain stimulation (DBS) is recommended in refractory movement disorders, including isolated pediatric dystonias. For dystonia evolving in more complex associations in genetic CP, the effect of DBS is still understudied and currently only sporadically described. OBJECTIVES: To report the effect of DBS applied to the globus pallidus pars interna (GPi) in children with complex movement disorders caused by pathogenic ADCY5 variants, diagnosed as dyskinetic CP previous to genetic diagnostic. METHODS: We conducted a retrospective study on evolution of treatment with DBS in ADCY5-related disease. A standardized proforma including the different type of movement disorders and associated neurological signs was completed at each follow-up time, based on video recordings, as well as functional assessments used in children with CP. RESULTS: Four children (mean of age, 13 ± 2.9 years) received GPi-DBS. The same de novo pathogenic missense variant (c.1252C > T, p.R418W) was identified in three out of four and a splice site variant (c.2088 + 2G > T) in one subject. Developmental delay and overlapping features including axial hypotonia, chorea, dystonic attacks, myoclonus, and cranial dyskinesia were present. The median age at DBS was 9 years and follow-up with DBS, 2.6 years. We identified a pattern of clinical response with early suppression of dystonic attacks, followed by improvement of myoclonus and facial dyskinesia. Effect on chorea was delayed and more limited. Two patients gained notable functional benefit related to sitting, standing, gait, use of upper limbs and speech. CONCLUSION: ADCY5-related disease may benefit from GPi-DBS. The most significant clinical response relates to the early and sustained benefit on dystonic attacks and a variable but still positive response on the other hyperkinetic features. Genetic etiology of CP will contribute to further elucidate genotype-phenotype correlations and to refine DBS indication as network-related symptomatic interventions.

Elective and Emergency Deep Brain Stimulation in Refractory Pediatric Monogenetic Movement Disorders Presenting with Dystonia: Current Practice Illustrated by Two Cases.

BACKGROUND: Dystonia is characterized by sustained or intermittent muscle contractions, leading to abnormal posturing and twisting movements. In pediatric patients, dystonia often negatively influences quality of life. Pharmacological treatment for dystonia is often inadequate and causes adverse effects. Deep brain stimulation (DBS) appears to be a valid therapeutic option for pharmacoresistant dystonia in children. METHODS: To illustrate the current clinical practice, we hereby describe two pediatric cases of monogenetic movement disorders presenting with dystonia and treated with DBS. We provide a literature review of similar previously described cases and on different clinical aspects of DBS in pediatric dystonia. RESULTS: The first patient, a 6-year-old girl with severe dystonia, chorea, and myoclonus due to an ADCY5 gene mutation, received DBS in an elective setting. The second patient, an 8-year-old boy with GNAO1-related dystonia and chorea, underwent emergency DBS due to a pharmacoresistant status dystonicus. A significant amelioration of motor symptoms (65% on the Burke-Fahn-Marsden Dystonia Rating Scale) was observed postoperatively in the first patient and her personal therapeutic goals were achieved. DBS was previously reported in five patients with ADCY5-related movement disorders, of which three showed objective improvement. Emergency DBS in our second patient resulted in the successful termination of his GNAO1-related status dystonicus, this being the eighth case reported in the literature. CONCLUSION: DBS can be effective in monogenetic pediatric dystonia and should be considered early in the disease course. To better evaluate the effects of DBS on patients' functioning, patient-centered therapeutic goals should be discussed in a multidisciplinary approach.

Dystonia, Chorea, and Ataxia: Three Challenging Cases.

Movement disorders comprise a heterogeneous and complex group of neurological disorders that increase (hyperkinetic) or decrease (hypokinetic) the speed or amplitude of movements, or disrupt their coordinated sequencing. In this article, we describe three instructive cases, exemplifying classic movement disorders, namely dystonia, chorea, and ataxia. We highlight the diagnostic approach based on clinical clues, syndromic reasoning, evaluation, and management recommendations. Each case ends with key messages for the clinicians.

Childhood Neurologic Conditions: Movement Disorders.

Most movement disorders in children are hyperkinetic. The most common type is tic disorders, which can involve motor and phonic tics and are classified as simple or complex. Motor or phonic tics that persist for more than 1 year are defined as persistent (chronic) tic disorder. Tourette syndrome can be diagnosed if a child has multiple motor tics and at least one phonic tic for more than 1 year with onset before age 18 years. Children with Tourette syndrome may have symptoms of attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, depression, or behavioral disorders. Chorea can be seen as a symptom of rheumatic fever (Sydenham chorea), in children with a history of kernicterus, and in dyskinetic cerebral palsy. Chorea also may be part of an underlying metabolic or genetic condition. Dystonia is characterized by repetitive contortions and posturing of the limbs and body. It can be isolated or part of an underlying neurologic condition. Tremor can occur as a manifestation of essential tremor or can be an enhanced physiologic tremor exacerbated by drugs, illness, or stimulants. Ataxia most often is seen as a postinfectious or postvaccination acute cerebellar ataxia. Progressive ataxias are consistent with an underlying metabolic or genetic condition. Transient and developmental movement disorders include benign neonatal sleep myoclonus, jitteriness in neonates, shuddering, and stereotypies.

Chorea.

PURPOSE OF REVIEW: This article provides an overview of the diagnostic and therapeutic approach to a patient with chorea. The phenomenology of chorea is described in addition to other common hyperkinetic movements that may be mistaken for or coexist with chorea. Chorea can be acquired or hereditary. Key historical and clinical features that can aid in determining the etiology are reviewed, and pharmacologic and nonpharmacologic treatment strategies are discussed. RECENT FINDINGS: Clinical investigations are under way to target transcription and translation of the mutant huntingtin protein as a potential disease-modifying strategy in Huntington disease (HD). Additional heritable factors have been revealed through genome-wide association studies. Symptom-focused treatments for HD are are being studied, including a third vesicular monoamine transporter-2 (VMAT2) inhibitor for chorea attenuation and drugs to target irritability and cognitive impairment. Increased availability of genetic testing has led to increased awareness of HD mimics (eg, C9orf72 and IgLON5). SUMMARY: Chorea is a relatively common hyperkinetic disorder with a broad differential. The first step in the approach to a patient with chorea is accurately defining the phenomenology. Once it has been determined that the patient has chorea, the investigation into determining an etiology can begin. Factors such as age of onset, time course, family history, unique clinical features, and imaging and laboratory findings can guide the diagnosis. Treatments for most causes of chorea are purely symptomatic, although it is important to recognize causes that are reversible or have disease-modifying interventions.

Is deep brain stimulation effective in Huntington's Disease? - a systematic literature review.

INTRODUCTION: Huntington's Disease (HD) is an autosomal dominant neurodegenerative disorder. Substantial for a diagnosis of the disease are motor disorders, with chorea as a hallmark symptom. Other disease manifestations include cognitive dysfunction and psychiatric disorders. Currently, pharmacological treatment plays the most important role in the therapy of HD patients. However, deep brain stimulation (DBS) is considered a potential therapeutic option. AIM OF THE STUDY: Systematic review of current literature on DBS efficacy and safety in the management of motor, behavioural and cognitive functions in patients with HD. MATERIAL AND METHODS: A systematic review was conducted with the use of the Scopus database and the following search criteria: TITLE (huntington*) AND TITLE-ABS-KEY ('deep brain stimulation' OR 'neuromodulation'). Our search criteria included original studies with at least five patients, reporting any motor, cognitive and/or behavioural, and functional assessment data with at least a 6-month follow-up. Finally, four selected publications were analysed. RESULTS: In all analysed publications, we found a statistically significant improvement of Unified Huntington's Disease Rating Scale (UHDRS) chorea subscore by an average of 40, to over 60% after DBS implantation. Heterogeneous results were obtained for UHDRS total motor score. DBS did not improve functional capacity of HD patients in the analysed studies. We found no systematic assessment concerning the effect of DBS in HD on behaviour, cognition or speech. CONCLUSIONS: DBS implantation could be considered as a therapeutic option for patients with severe, drug-resistant chorea. However, the evidence for this is limited. To date, no high-quality data based on randomised controlled trials supports the long-term safety and efficacy of DBS in HD. This treatment option should therefore currently be considered as investigational.

Adult-onset sporadic chorea: real-world data from a single-centre retrospective study.

BACKGROUND: Adult-onset sporadic chorea includes a wide and heterogeneous group of conditions whose differential diagnosis and treatments are often challenging and extensive. OBJECTIVES: To analyse retrospectively cases of adult-onset sporadic chorea from a single Italian centre to provide insights for a practical approach in the management of these patients. METHODS: A total of 11,071 medical charts from a 9-year period (2012-2020) were reviewed, identifying 28 patients with adult-onset sporadic chorea (genetic forms excluded). All available data regarding phenomenology, diagnostic workup, aetiology, treatments, and long-term outcome from this cohort were collected and analysed. RESULTS: Adult-onset sporadic chorea occurred more frequently in females and presented with an acute-subacute onset. Cerebrovascular diseases accounted for 68% of aetiology; further causes were structural brain lesions, internal diseases, and other movement disorder syndromes. Clinical course was mild, with spontaneous resolution or minimal disturbances in 82% of cases. Neuroimaging was fundamental to diagnose 76% of adult-onset sporadic chorea, an appropriate clinical examination contributed to the 14% of diagnoses, whereas basic laboratory tests to the 10%. CONCLUSIONS: Revision of real-world data of adult-onset sporadic chorea patients from a single Italian cohort suggests that an accurate clinical examination, neuroimaging, and routine laboratory tests are useful to identify those cases underlying potentially severe but treatable conditions. Although in the majority of cases adult-onset sporadic chorea has mild clinical course and good response to symptomatic treatments, it is essential to run a fast diagnostic workup.

Tics, tremors and other movement disorders in childhood.

Movement disorders presenting in childhood include tics, dystonia, chorea, tremor, stereotypy, myoclonus, and parkinsonism, each of which can be part of various clinical syndromes with distinct etiologies.  Some of these conditions are benign and require only reassurance; others are bothersome and require treatment, or may be clues that herald underlying pathology.  Answers lie in the inherent characteristics of the movements themselves, together with the clinical context provided in the history obtained by the examiner.  The aim of this review is to present an overview of the categories of involuntary movements, along with examples of common acquired and genetic causes, and an approach to history-taking, examination, and treatment.

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China.

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.

Does pallidal neuromodulation influence cognitive decline in Huntington's disease?

OBJECTIVE: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder associated with motor, psychiatric and cognitive deterioration over time. To date, Continuous Electrical Neuromodulation (CEN) of the globus pallidus internus (GPi) has been reported to improve chorea but little is known about cognitive progression in these patients. We propose to examine CEN impact on expected cognitive decline throughout long-term neuropsychological assessment of a cohort of HD patients. METHOD: 13 consecutive HD patients underwent GPi neuromodulation between January 2008 and February 2019. Over a 5-year follow-up period, they received systematic pre- and post-operative assessment according to the existing protocol in our unit. The main outcome measure was the total score obtained on the Mattis Dementia Rating Scale (MDRS) as an indicator of global cognitive function. RESULTS: Chorea decreased in all patients postoperatively with a mean improvement of 56% despite disease progression over time, according to previous studies. Moreover we found that the global cognitive profile of HD patients treated with CEN was stable during the first 3 years of treatment. CONCLUSION: We report an unexpected positive influence of GPi continuous electrical neuromodulation on the progression of global cognitive functioning in operated HD patients. This is the most important group of patients treated with this method to our knowledge whatever the sample size remains small. This result provides promising evidence of GPi-CEN efficacy not only in reducing chorea, but also in delaying cognitive decline in HD patients operated at an early stage of the disease.

Hypoxaemia and interstitial lung disease in an infant with hypothyroidism and hypotonia.

A 7-month-old-term male infant presented with cough, tachypnoea, hypoxaemia and post-tussive emesis. Clinical history was significant for respiratory failure and pulmonary hypertension in the neonatal period requiring assisted ventilation, congenital hypothyroidism, mild hypotonia, recurrent respiratory infections, hypoxaemia requiring supplemental oxygen and nasogastric tube feeds. Physical examination showed tachypnoea, coarse bilateral breath sounds and mild hypotonia. Chest radiograph revealed multifocal pulmonary opacities with coarse interstitial markings and right upper lobe atelectasis. Following antibiotic therapy for suspected aspiration pneumonia, chest CT scan was performed and showed multiple areas of pulmonary consolidation and scattered areas of bilateral ground-glass opacities. Genetic studies showed a large deletion of chromosome 14q13.1-14q21.1, encompassing the NK2 homeobox 1 (NKX2-1) gene consistent with a diagnosis of brain-thyroid-lung (BTL) syndrome. Our case highlights the importance of genetic studies to diagnose BTL syndrome in infants with hypothyroidism, hypotonia and lung disease.

Treatment of Secondary Chorea: A Review of the Current Literature.

Background: Chorea consists of involuntary movements affecting the limbs, trunk, neck or face, that can move from one body part to another. Chorea is conceptualized as being "primary" when it is attributed to Huntington's disease (HD) or other genetic etiologies, or "secondary" when it is related to infectious, pharmacologic, metabolic, autoimmune disorders, or paraneoplastic syndromes. The mainstay of the secondary chorea management is treating the underlying causative disorder; here we review the literature regarding secondary chorea. We also discuss the management of several non-HD genetic diseases in which chorea can be a feature, where metabolic targets may be amenable to intervention and chorea reduction. Methods: A PubMed literature search was performed for articles relating to chorea and its medical and surgical management. We reviewed the articles and cross-references of pertinent articles to assess the current clinical practice, expert opinion, and evidence-based medicine to synthesize recommendations for the management of secondary chorea. Results: There are very few double-blind randomized controlled trials assessing chorea treatments regardless of etiology. Most recommendations are based on small open-label studies, case reports, and expert opinion. Discussion: Treatment of secondary chorea is currently based on expert opinion, clinical experience, and small case studies, with limited evidence-based medical data. When chorea is secondary to an underlying infection, medication, metabolic abnormality, autoimmune process, or paraneoplastic illness, the movements typically resolve following treatment of the underlying disease. Tardive dyskinesia is most rigorously studied secondary chorea with the best evidence-based medicine treatment guidelines recommending the use of pre-synaptic dopamine-depleting agents. Even though there is an insufficient pool of EBM, small clinical trials, case reports, and expert opinion are valuable for guiding treatment and improving the quality of life for patients with chorea. Highlights: There is a dearth of well-controlled studies regarding the treatment of chorea. Expert opinion and clinical experiences are fundamental in guiding chorea management and determining successful treatment. In general, secondary chorea improves with treating the underlying medical abnormality; treatments include antibiotics, antivirals, immunosuppression, dopamine depleting agents, chelation, and supportive care.

Chorea in children: etiology, diagnostic approach and management.

Chorea is defined by the presence of abnormal, involuntary, continuous, random movements that results from a number of autoimmune, hereditary, vascular, metabolic, drug-induced and functional (psychogenic) causes. Chorea may present at all stages of life, from newborns to elderly individuals. While Huntington disease is the main suspicion in adults presenting with chorea, once a drug-induced or parkinsonian dyskinesia have been ruled out; Huntington disease exceptionally presents with chorea in children. Sydenham chorea is considered the most common cause of acute childhood-onset chorea, but its prevalence has decreased in Western countries. However, in younger children other etiologies such as dyskinetic cerebral palsy, anti-NMDAR receptor encephalitis, other autoimmune conditions, or mutations in NKX2-1, ADCY-5, FOXG1, GNAO1, GPR88, SLC2A1, SQSTM1, ATP8A2, or SYT-1 should be considered. In this manuscript, we review the main causes, diagnosis and management of chorea in children.

Combined mutations of NKX2-1 and surfactant protein C genes for refractory low oxyhemoglobin saturation and interstitial pneumonia: A case report.

RATIONALE: Mutations of the NKX2-1 gene are associated with brain-lung-thyroid syndrome, which is characterized by benign hereditary chorea, hypothyroidism, and pulmonary disease with variable presentation. Surfactant protein C (SFTPC) gene mutations result in chronic interstitial lung disease in adults or severe neonatal respiratory distress syndrome. PATIENT CONCERNS: Recurrent hypoxemia was observed shortly after birth in a baby at a gestational age of 40 weeks and birth weight of 3150 g. The need for respiratory support gradually increased. He had hypothyroidism and experienced feeding difficulties and irritability. DIAGNOSIS: Genetic examination of the peripheral blood revealed combined mutations of the NKX2-1 and SFTPC genes. INTERVENTIONS: The patient was administered respiratory support, antibiotics, low-dose dexamethasone, supplementary thyroxine, venous nutrition, and other supportive measures. OUTCOMES: The patient's guardian stopped treatment 3 months after commencement of treatment, due to the seriousness of his condition and the patient died. LESSONS: Combined mutations of NKX2-1 and SFTPC genes are very rare. Thus, idiopathic interstitial pneumonia with hypothyroidism and neurological disorders require special attention.