Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3^rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB₁, vitaminB₂, vitaminB₆, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.
Humans ; Male ; Acidosis, Lactic ; Brain ; Brain Stem ; Dystonia ; Dystonic Disorders ; Mitochondrial Diseases ; Infant

X-linked dystonia-parkinsonism (XDP) is an adult-onset debilitating neurodegenerative disorder presenting with motor and nonmotor symptoms. The treatment options for XDP are limited. We described a patient with XDP who underwent a unilateral transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) pallidothalamic tractotomy with a one-year follow-up. The patient reported an immediate improvement in his pain after the procedure. Compared to baseline, there was an improvement in his scores in the dystonia (31%), parkinsonism (35.1%), and activities of daily living (71%) subscales at 1-year follow up. The overall improvement at one year was 46%. There were no adverse events noted. Additional studies with larger sample size and follow-up would be needed to document its long-term safety and efficacy.
Dystonia 3, Torsion, X-Linked ; Dystonic Disorders ; Genetic Diseases, X-Linked

OBJECTIVE: To explore the clinical characteristics and genetic variants in a child with tyrosine hydroxylase-deficient infantile Parkinsonism with motor delay. METHODS: Clinical feature of the patient was summarized. Genomic DNA was extracted from peripheral blood samples taken from the child and her family members. All exons of GCH1, TH and SPR genes were subjected to targeted capture and next-generation sequencing. Suspected variants were verified by Sanger sequencing. RESULTS: The child could not sit alone at 7 month and 11 days. Physical examination suggested motor retardation and hypotonia, limb stiffness, head nodding, slight torticollis, and language and intellectual developmental delays. She developed involuntary shaking of limbs at 3 month old, which lasted approximately 10 seconds and aggregated with excitement and before sleeping. Cranial MRI revealed widening of subarachnoid space on the temporomandibular and particularly temporal sides. Genetic testing revealed that she has carried a nonsense c.457C>T (p.R153X) variant, which was known to be pathogenic, and a novel missense c.720C>G (p.I240M) variant of the TH gene. The two variants were derived from her father and mother, respectively. CONCLUSION The child was diagnosed as tyrosine hydroxylase-deficient infantile Parkinsonism with motor delay due to compound heterozygous variants of the TH gene. Above finding has enriched the spectrum of TH gene variants.
Brain ; diagnostic imaging ; Codon, Nonsense ; Dystonic Disorders ; congenital ; genetics ; Female ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Magnetic Resonance Imaging ; Mutation ; Parkinsonian Disorders ; genetics ; Tyrosine 3-Monooxygenase ; genetics

Deep brain stimulation (DBS) in internal globus pallidus is considered to be a good option for controlling generalized dystonia in patients with this condition. In this relation, it is known that DBS has already been shown to have significant effects on primary dystonia, but is seen as controversial in secondary dystonia including cerebral palsy (CP). On the other hand, intrathecal baclofen (ITB) has been known to reduce spasticity and dystonia in patients who did not respond to oral medications or botulinum toxin treatment. Here, we report a patient with dystonic CP, who received the ITB pump implantation long after the DBS and who noted remarkable improvement in the 36-Item Short Form Health Survey, Dystonia Rating Scale, Modified Barthel Index, and visual analog scale scores for pain after an ITB pump implantation was used as compared with DBS. To our knowledge, the present case report is the first to demonstrate the effects of an ITB pump on reducing pain and dystonia and improving quality of life and satisfaction, compared with DBS in a patient with CP.
Baclofen ; Botulinum Toxins ; Cerebral Palsy ; Deep Brain Stimulation ; Dystonia ; Dystonic Disorders ; Globus Pallidus ; Hand ; Health Surveys ; Humans ; Muscle Spasticity ; Quality of Life ; Visual Analog Scale

OBJECTIVE: To determine whether the use of unique customized spectacles provided with modified side arms may be helpful in reducing benign essential blepharospasm (BEB) in patients describing periocular sensory tricks (ST). METHODS: A prospective descriptive study of patients with BEB with positive periocular or temporal region ST phenomenon response under the care of the Botox Clinic at Moorfields Eye Hospital, London, UK. Nine consecutive patients with BEB describing ST were recruited, and the disease frequency and severity were assessed with the Jankovic Rating Scale (JRS) and the Blepharospasm Disability Index (BSDI) before and after the use of the sensory trick frames (STF). RESULTS: A reduction in the score was noted in both severity (p = 0.0115) and frequency patterns (p = 0.0117) in the JRS in patients using the STF. A significant reduction of the BSDI score was also observed (p = 0.0314). CONCLUSION: All the patients selected and fitted with the STF had a reduction in spasms and related symptoms. This new device may be helpful in some selected BEB patients who previously responded positively to periocular pressure alleviating maneuvers.
Arm ; Blepharospasm ; Botulinum Toxins ; Dystonic Disorders ; Eyeglasses ; Humans ; Prospective Studies ; Spasm ; Temporal Lobe

We present a 47-year-old right-handed woman with a 15-year history of writer's cramp who was provided with six sessions of cathodal transcranial direct current stimulation (tDCS) combined with observation of writing actions performed by a healthy subject and electromyographic (EMG) biofeedback training to decrease EMG activities in her right forehand muscles while writing for 30 min for 4 weeks. She showed improvement in dystonic posture and writing speed after the intervention. The writing movement and writing speed scores on a writer's cramp rating scale decreased, along with writing time. Our findings demonstrated that cathodal tDCS combined with action observation and EMG biofeedback training might improve dystonic writing movements in a patient with writer's cramp.
Biofeedback, Psychology ; Dystonic Disorders ; Female ; Healthy Volunteers ; Humans ; Middle Aged ; Muscles ; Posture ; Transcranial Direct Current Stimulation ; Writing

OBJECTIVE: To report demographic data from a large cohort of patients with oromandibular dystonia (OMD). METHODS: This is a retrospective review of patients with OMD referred to our institution between 1989 and 2015. Demographic (age of onset, gender, and familial history of dystonia) and clinical (type of OMD, associated dystonia, and etiology of dystonia) data were collected from a cohort of 240 individuals. RESULTS: The mean age of onset of OMD was 51.6 years old, with a female predominance (2:1). A family history of dystonia was found in 6 patients (2.5%). One hundred and forty-nine patients (62.1%) had the jaw-opening type of OMD, 48 patients (20.0%) had the jaw-closing type, and 43 patients (17.9%) had a mixed form of OMD. Lingual dystonia was also present in 64 (26.7%) of these patients. Eighty-two patients (34.2%) had a focal dystonia, 131 patients (54.6%) had a segmental dystonia, and 27 patients (11.3%) had a generalized dystonia. One hundred and seventy-one patients (71.3%) had idiopathic OMD. CONCLUSION: OMD is a chronic and disabling focal dystonia. Our study found a prevalence of female patients, an onset in middle age and a predominantly idiopathic etiology. Unlike other studies, jaw-opening was found to be the most frequent clinical type of OMD.
Age of Onset ; Cohort Studies ; Demography ; Dystonia ; Dystonic Disorders ; Female ; Humans ; Middle Aged ; Movement Disorders ; Prevalence ; Retrospective Studies

OBJECTIVE: The inability to propel a bolus of food successfully from the posterior part of the oral cavity to the oropharynx is defined as transfer dysphagia. The present case series describes the varied presentation of transfer dysphagia due to focal dystonia and highlights the importance of early detection by following up on strong suspicions. METHODS: We describe seven cases of transfer dysphagia due to focal dystonia. Transfer dysphagia as a form of focal dystonia may appear as the sole presenting complaint or may present with other forms of focal dystonia. RESULTS: Four out of seven patients had pure transfer dysphagia and had previously been treated for functional dysphagia. A high index of suspicion, barium swallow including videofluoroscopy, associated dystonia in other parts of the body and response to drug therapy with trihexyphenidyl/tetrabenazine helped to confirm the diagnosis. CONCLUSION: Awareness of these clinical presentations among neurologists and non-neurologists can facilitate an early diagnosis and prevent unnecessary investigations.
Barium ; Deglutition Disorders ; Diagnosis ; Drug Therapy ; Dystonia ; Dystonic Disorders ; Early Diagnosis ; Humans ; Mouth ; Oropharynx

OBJECTIVETo explore genetic mutations and clinical features of a pedigree affected with dopa-responsive dystonia.

METHODSPCR and Sanger sequencing were applied to detect mutations of the GCH1 gene among 7 members from the pedigree.

RESULTSThe family was detected to have a known heterozygous mutation of the GCH1 gene (c.550C>T). For the 7 members from the pedigree, the age of onset has ranged from 13 to 60 years. The mother of the proband has carried the same mutation but was still healthy at 80. The symptoms of the other three patients were in slow progression, with diurnal fluctuation which can be improved with sleeping, dystonias of lower limbs, and tremor of both hands. Treatment with small dose of levodopa has resulted in significant improvement of clinical symptoms. By database analysis, the c.550C>T mutation was predicted as probably pathological.

CONCLUSIONThe c.550C>T mutation probably underlies the disease in this pedigree. The clinical phenotypes of family members may be variable for their ages of onset. Some may even be symptom free.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Base Sequence ; DNA Mutational Analysis ; Dystonic Disorders ; enzymology ; genetics ; Female ; GTP Cyclohydrolase ; genetics ; Heterozygote ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Pedigree ; Phenotype ; Young Adult

Focal dystonia is a neurological condition affecting a muscle or group of muscles in a specific part of the body, leading to involuntary muscular contractions. This condition is often treated with medications including muscle relaxants and injections of botulinum toxin. However, some cases do not respond to normal modes of treatment. Deep brain stimulation (DBS) can be a therapeutic option for patients who are resistant to medical treatment. We report a case of fibromyalgia accompanied by focal hand dystonia, where unilateral DBS improved the patient's focal dystonic movement. We also present a review of the relevant literature.
Botulinum Toxins ; Deep Brain Stimulation* ; Dystonia* ; Dystonic Disorders ; Fibromyalgia* ; Hand ; Humans ; Muscle Contraction ; Muscles