ABSTRACT
OBJECTIVE: Novel deep brain stimulation (DBS) systems allow directional and short-pulse stimulation to potentially improve symptoms and reduce side effects. The aim of this study was to investigate the effect of short-pulse and directional stimulation, in addition to a combination of both, in the ventral intermediate thalamus (VIM)/posterior subthalamic area (PSA) on tremor and stimulation-induced side effects in patients with essential tremor. MATERIALS AND METHODS: We recruited 11 patients with essential tremor and VIM/PSA-DBS. Tremor severity (Fahn-Tolosa-Marin), ataxia (International Cooperative Ataxia Rating Scale), and paresthesia (visual analog scale) were assessed with conventional omnidirectional and directional stimulation with pulse width of 60 µs and 30 µs. RESULTS: All stimulation conditions reduced tremor. The best directional stimulation with 60 µs reduced more tremor than did most other stimulation settings. The best directional stimulation, regardless of pulse width, effectively reduced stimulation-induced ataxia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. All new stimulation modes reduced occurrence of paresthesia, but only the best directional stimulation with 30 µs attenuated paresthesia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. The best directional stimulation with 30 µs reduced tremor, ataxia, and paresthesia compared with conventional stimulation in most patients. Correlation analyses indicated that more anterior stimulation sites are associated with stronger ataxia reduction with directional 30 µs than with conventional 60 µs stimulation. CONCLUSION: Directional and short-pulse stimulation, and a combination of both, revealed beneficial effects on stimulation-induced adverse effects.
Subject(s)
Deep Brain Stimulation , Essential Tremor , Humans , Essential Tremor/therapy , Tremor/therapy , Deep Brain Stimulation/adverse effects , Paresthesia/etiology , Paresthesia/therapy , Thalamus/physiology , Ataxia/etiology , Treatment OutcomeABSTRACT
Constipated patients are frequently referred to gastroenterologists for symptoms refractory to lifestyle modifications and laxatives. Dyssynergic defecation, the dyscoordination of rectoanal, abdominal, and pelvic floor muscles to facilitate defecation, is a major cause of refractory primary constipation. Understanding of the diagnosis, evaluation, and management of dyssynergic defecation and other evacuation disorders will allow providers to effectively manage these patients. This review focuses on the definition, pathophysiology, evaluation, and treatment of dyssynergic defecation and other evacuation disorders. Emerging treatments for these disorders include home biofeedback therapy for dyssynergic defecation and translumbosacral neuromodulation therapy for levator ani syndrome.
Subject(s)
Constipation , Defecation , Ataxia/diagnosis , Ataxia/etiology , Ataxia/therapy , Biofeedback, Psychology , Constipation/diagnosis , Constipation/etiology , Constipation/therapy , Defecation/physiology , Humans , LaxativesABSTRACT
INTRODUCTION: Sensory ataxia is a dysfunction of dynamic balance due to impairment of sensory input into the control of movement. The sequelae of stroke, such as hemiplegia, somatosensory impairment, and impaired balance may cause significant disability and may affect patients' quality of life. In addition to rehabilitation programs, acupuncture therapy has been applied to stroke patients and is recommended as a complementary therapy in stroke rehabilitation. PATIENT CONCERNS: A 70-year-old male had a sudden onset of conscious loss. The brain computed tomography showed intracerebral hemorrhage with subdural hemorrhage and subarachnoid hemorrhage. DIAGNOSIS: Intracerebral hemorrhagic stroke was diagnosed. INTERVENTIONS: He received craniotomy with hematoma evacuation immediately and waked up 3 weeks with bilateral hemiparesis (right side weaker than left), impaired position sensation and tactile perception in the right lower limb. He then began to receive rehabilitation therapy and had significant improvement in muscle strength and static balance, but no improvement in tactile perception of position sense in the right lower limbs and reached plateau. Then he received acupuncture therapies to Yongquan (KI1), Tongtien (BL7) and Houxi (SI3). OUTCOMES: The patient's walking ability recovered after receiving rehabilitation programs for 3 years, but the impairment in proprioception and dynamic balance persisted. The perception and dynamic balance had significantly improved after patient received acupuncture therapy, especially the acupuncture point of Yongquan (KI1). CONCLUSION: The clinical effect of acupuncture in combination with conventional rehabilitation therapy for neurological impairment recovery, improving activity of daily living performance and improving post-stroke imbalance was explored. We hope that this report can facilitate further well controlled quantitative objective studies on a big size of samples.
Subject(s)
Acupuncture Therapy/standards , Ataxia/etiology , Ataxia/therapy , Cerebral Hemorrhage/complications , Acupuncture Therapy/methods , Aged , Cerebral Hemorrhage/physiopathology , Cerebral Hemorrhage/therapy , Humans , Male , Tomography, X-Ray Computed/methodsABSTRACT
Background Coenzyme Q10 (CoQ10) serves as a shuttle for electrons from complexes I and II to complex III in the respiratory chain, and has important functions within the mitochondria. Primary CoQ10 deficiency is a mitochondrial disorder which has devastating effects, and which may be partially treated with exogenous CoQ10 supplementation. Case presentation A 9-month-old girl patient was referred to our clinic due to growth retardation, microcephaly and seizures. She was the third child of consanguineous parents (first-degree cousins) of Pakistani origin, born at 38 weeks gestation, weighing 2000 g after an uncomplicated pregnancy, and was hospitalized for 3 days due to respiratory distress. She had sustained clonic seizures when she was 4 months old. Physical examination showed microcephaly, truncal hypotonia and dysmorphic features. Metabolic tests were inconclusive. Abdominal ultrasonography revealed cystic appearance of the kidneys. Non-compaction of the left ventricle was detected in echocardiography. Cranial magnetic resonance imaging (MRI) showed hypoplasia of the cerebellar vermis and brain stem, corpus callosum agenesis, and cortical atrophy. A panel testing of 450 genes involved in inborn errors of metabolism (IEM) was performed that showed a novel frameshift c.384delG (Gly129Valfs*17) homozygous mutation in COQ9. A treatment of 5 mg/kg/day exogenous CoQ10 was started when she was 10 months old, and the dosage was increased to 50 mg/kg/day after the exact diagnosis. No objective neurological improvement could be observed after the adjustment of the drug dosage. Conclusions We report a case of CoQ10 deficiency due to a novel COQ9 gene mutation that adds clinical data from a newly diagnosed patient. Our case also outlines the importance of genetic panels used for specific diseases including IEM.
Subject(s)
Ataxia/etiology , Mitochondria/pathology , Mitochondrial Diseases/etiology , Muscle Weakness/etiology , Mutation , Rare Diseases/etiology , Ubiquinone/deficiency , Ataxia/pathology , Female , Humans , Infant , Mitochondria/genetics , Mitochondrial Diseases/pathology , Muscle Weakness/pathology , Prognosis , Rare Diseases/pathology , Ubiquinone/geneticsABSTRACT
Cerebellar ataxia is a hallmark of coenzyme Q10 (CoQ10) deficiency associated with COQ8A mutations. We present four patients, one with novel COQ8A pathogenic variants all with early, prominent handwriting impairment, dystonia and only mild ataxia. To better define the phenotypic spectrum and course of COQ8A disease, we review the clinical presentation and evolution in 47 reported cases. Individuals with COQ8A mutation display great clinical variability and unpredictable responses to CoQ10 supplementation. Onset is typically during infancy or childhood with ataxic features associated with developmental delay or regression. When disease onset is later in life, first symptoms can include: incoordination, epilepsy, tremor, and deterioration of writing. The natural history is characterized by a progression to a multisystem brain disease dominated by ataxia, with disease severity inversely correlated with age at onset. Six previously reported cases share with ours, a clinical phenotype characterized by slowly progressive or static writing difficulties, focal dystonia, and speech disorder, with only minimal ataxia. The combination of writing difficulty, dystonia and ataxia is a distinctive constellation that is reminiscent of a previously described clinical entity called Dystonia Ataxia Syndrome (DYTCA) and is an important clinical indicator of COQ8A mutations, even when ataxia is mild or absent.
Subject(s)
Ataxia , Disease Progression , Dystonic Disorders , Handwriting , Heterozygote , Mitochondrial Diseases , Mitochondrial Proteins/genetics , Muscle Weakness , Ubiquinone/deficiency , Adult , Ataxia/complications , Ataxia/epidemiology , Ataxia/etiology , Ataxia/genetics , Ataxia/physiopathology , Child , Dystonic Disorders/epidemiology , Dystonic Disorders/etiology , Dystonic Disorders/genetics , Dystonic Disorders/physiopathology , Female , Humans , Male , Middle Aged , Mitochondrial Diseases/complications , Mitochondrial Diseases/epidemiology , Mitochondrial Diseases/genetics , Mitochondrial Diseases/physiopathology , Muscle Weakness/complications , Muscle Weakness/epidemiology , Muscle Weakness/genetics , Muscle Weakness/physiopathology , Ubiquinone/genetics , Young AdultABSTRACT
BACKGROUND: Many different oligosynaptic reflexes are known to originate in the lower brainstem which share phenomenological and neurophysiological similarities. OBJECTIVE: To evaluate and discuss the differences and aberrancies among these reflexes, which are hard to discern clinically using neurophysiological investigations with the help of a case report. METHODS: We describe the clinical and neurophysiological assessment of a young man who had a childhood history of opsoclonus-myoclonus syndrome with residual mild ataxia and myoclonic jerks in the distal extremities presenting with subacute onset total body jerks sensitive to sound and touch (in a limited dermatomal distribution), refractory to medications. RESULTS: Based on clinical characteristics and insights gained from neurophysiological testing we could identify a novel reflex of caudal brainstem origin. CONCLUSIONS: The reflex described is likely an exaggerated normal reflex, likely triggered by a dolichoectatic vertebral arterial compression and shares characteristics of different reflexes known to originate in caudal brainstem, which subserve distinctive roles in human postural control.
Subject(s)
Brain Stem/physiopathology , Reflex, Abnormal/physiology , Reflex, Startle/physiology , Vertebrobasilar Insufficiency/physiopathology , Acoustic Stimulation , Adult , Ataxia/etiology , Brain Stem/diagnostic imaging , Cognitive Dysfunction/etiology , Electromyography , Humans , Male , Myoclonus/etiology , Opsoclonus-Myoclonus Syndrome/complications , Physical Stimulation , Touch , Vertebral Artery , Vertebrobasilar Insufficiency/complications , Vertebrobasilar Insufficiency/diagnostic imagingABSTRACT
Importance: Clinical trials have confirmed the efficacy of focused ultrasound (FUS) thalamotomy in essential tremor, but its effectiveness and safety for managing tremor-dominant Parkinson disease (TDPD) is unknown. Objective: To assess safety and efficacy at 12-month follow-up, accounting for placebo response, of unilateral FUS thalamotomy for patients with TDPD. Design, Setting, and Participants: Of the 326 patients identified from an in-house database, 53 patients consented to be screened. Twenty-six were ineligible, and 27 were randomized (2:1) to FUS thalamotomy or a sham procedure at 2 centers from October18, 2012, to January 8, 2015. The most common reasons for disqualification were withdrawal (8 persons [31%]), and not being medication refractory (8 persons [31%]). Data were analyzed using intention-to-treat analysis, and assessments were double-blinded through the primary outcome. Interventions: Twenty patients were randomized to unilateral FUS thalamotomy, and 7 to sham procedure. The sham group was offered open-label treatment after unblinding. Main Outcomes and Measures: The predefined primary outcomes were safety and difference in improvement between groups at 3 months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor (CRST). Secondary outcomes included descriptive results of Unified Parkinson's Disease Rating Scale (UPDRS) scores and quality of life measures. Results: Of the 27 patients, 26 (96%) were male and the median age was 67.8 years (interquartile range [IQR], 62.1-73.8 years). On-medication median tremor scores improved 62% (IQR, 22%-79%) from a baseline of 17 points (IQR, 10.5-27.5) following FUS thalamotomy and 22% (IQR, -11% to 29%) from a baseline of 23 points (IQR, 14.0-27.0) after sham procedures; the between-group difference was significant (Wilcoxon P = .04). On-medication median UPDRS motor scores improved 8 points (IQR, 0.5-11.0) from a baseline of 23 points (IQR, 15.5-34.0) following FUS thalamotomy and 1 point (IQR, -5.0 to 9.0) from a baseline of 25 points (IQR, 15.0-33.0) after sham procedures. Early in the study, heating of the internal capsule resulted in 2 cases (8%) of mild hemiparesis, which improved and prompted monitoring of an additional axis during magnetic resonance thermometry. Other persistent adverse events were orofacial paresthesia (4 events [20%]), finger paresthesia (1 event [5%]), and ataxia (1 event [5%]). Conclusions and Relevance: Focused ultrasound thalamotomy for patients with TDPD demonstrated improvements in medication-refractory tremor by CRST assessments, even in the setting of a placebo response. Trial Registration: ClinicalTrials.gov identifier NCT01772693.
Subject(s)
Parkinson Disease/therapy , Thalamus , Tremor/therapy , Ultrasonic Therapy/methods , Aged , Ataxia/etiology , Double-Blind Method , Female , Humans , Male , Middle Aged , Paresthesia/etiology , Parkinson Disease/complications , Parkinson Disease/physiopathology , Pilot Projects , Treatment Outcome , Tremor/etiology , Tremor/physiopathology , Ultrasonic Therapy/adverse effectsABSTRACT
RATIONALE: We report on a patient with mild traumatic brain injury (TBI) by follow-up diffusion tensor tractography (DTT), and observed for approximately nine monthsby serial diffusion tensor tractography (DTT). PATIENT CONCERNS: A 66-year-old male patient was injured in a car crash. Approximately four weeks after the crash, he developed a tremor in the right hand and leg. His symptoms worsened over time. DIAGNOSES: Approximately six months after the crash, he developed a mild tremor in the left hand. Nine months after the crash, he manifested severe tremor in his right hand, mild resting and intentional tremor in his left hand and both legs, and mild trunkal ataxia. INTERVENTIONS: N/A. OUTCOMES: On 3-week DTT, well reconstructed DRTTs were observed in both hemispheres, except for the thinned lower portion of the right DRTT. On 9-month DTT, the right lower DRTT had thinned compared with the 3-week DTT and showed a disruption at the upper portion. The left DRTT showed thinning in the lower portion and tearing in the upper portion compared with 3-week DTT. LESSONS: Aggravation of an injured DRTT was demonstrated in a patient with mild TBI, using serial DTT examination.
Subject(s)
Brain Concussion/complications , Cerebellar Nuclei/injuries , Thalamus/injuries , Accidents, Traffic , Aged , Ataxia/etiology , Brain Concussion/diagnostic imaging , Cerebellar Nuclei/diagnostic imaging , Diffusion Tensor Imaging , Efferent Pathways/diagnostic imaging , Efferent Pathways/injuries , Follow-Up Studies , Hand/physiopathology , Humans , Leg/physiopathology , Male , Thalamus/diagnostic imaging , Tremor/etiologyABSTRACT
RATIONALE: Several studies using diffusion tensor tractography (DTT) have reported on injury in the dentato-rubro-thalamic tract (DRTT) in patients with brain injury. However, there is no study of injury in the DRTT following cerebellar infarct. We report on patients with injury in the DRTT following cerebellar infarct, demonstrated on DTT. PATIENT CONCERNS: Three patients with cerebellar infarct were enrolled in this study. Diffusion tensor imaging data were acquired at 3 weeks (patient 1) and 2 weeks (patients 2 and 3) after onset and the DRTT was reconstructed. The Scale for Assessment and Rating of Ataxiaand the Functional Ambulation Category were used for evaluation of ataxia and gait function. DIAGNOSES AND OUTCOMES: With clinical evaluation, patient 1 scored 18, patient 2 scored 22, and patient 3 scored 28 points on the Scale for Assessment and Rating of Ataxia. On the Functional Ambulation Category patient 1 scored 2, patient 2 scored 2, and patient 3 scored 1 point. DRTT abnormalities were as follows: discontinuation (the upper portion of the left DRTT in the patient 1), narrowing (the lower portion of the left DRTT in patient 2, and the whole right DRTT in the patient 3), and nonreconstruction (the left DRTT in the patient 3). LESSONS: Using DTT, we demonstrated injury in the DRTT in 3 patients with severe ataxia following cerebellar infarct. We believe that evaluation of the DRTT would be helpful in patients who develop ataxia following cerebellar infarct.
Subject(s)
Brain Infarction/diagnostic imaging , Cerebellar Nuclei/diagnostic imaging , Thalamus/diagnostic imaging , Aged , Ataxia/diagnostic imaging , Ataxia/etiology , Brain Infarction/complications , Diffusion Magnetic Resonance Imaging , Diffusion Tensor Imaging , Female , Humans , Male , Middle Aged , Neural Pathways/diagnostic imaging , Severity of Illness IndexABSTRACT
OBJECTIVE: To compare the effects between plum-blossom needle tapping at Jiaji (EX-B 2) combined with rehabilitation and simple rehabilitation for ataxia of cerebellar apoplexy. METHODS: Sixty patients with ataxia of cerebellar apoplexy were randomly divided into an observation group,and a control group,30 cases in each one. Conventional rehabilitation training was applied in the control group. While based on the treatment as that of the control group, plum-blossom needle tapping at Jiaji (EX-B 2) was used in the observation group. All the treatment was given for 4 weeks. International cooperative ataxia rating scale (ICARS), Berg balance scale (BBS) and Barthel index (BD were observed before treatment,after 2-week treatment and 4-week treatment. Also, clinical effects After treating for 2 weeks and for 4 weeks, the results of ICARS,BBS and BI were obvi were compared. RESULTS: After treating for 2 weeksand for 4 weeks, the results of ICARS, BBS and BI were obviously better than those before treatment in the two groups (all P<0.05). After 2-week treatment,there was no sta tistical significance between the two groups (all P>0. 05). After 4-week treatment,all the scores of the observation group were apparently superior to those of the control group (all P<0. 05). The total effective rate was 96. 7% (29/30) in the observation group, better than 80. 0% (24/30) in the control group after 4-week treatment (P<0. 05). CCONCLUSION:Plum-blossom needle tapping at Jiaji(EX-B 2) combined with rehabilitation training markedly improve the coordination and balance functions and activities of daily life, which are better than simple rehabilitation.
Subject(s)
Acupuncture Points , Acupuncture Therapy , Ataxia/rehabilitation , Ataxia/therapy , Stroke/complications , Acupuncture Therapy/methods , Aged , Ataxia/etiology , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Needles , Treatment OutcomeSubject(s)
Ataxia/etiology , Ataxia/surgery , Fragile X Syndrome/complications , Magnetic Resonance Imaging/methods , Neurosurgical Procedures/methods , Surgery, Computer-Assisted/methods , Thalamus/diagnostic imaging , Thalamus/surgery , Tremor/etiology , Tremor/surgery , Ultrasonography/methods , Ataxia/diagnostic imaging , Fragile X Syndrome/diagnostic imaging , Humans , Male , Middle Aged , Parkinsonian Disorders/etiology , Parkinsonian Disorders/surgery , Tremor/diagnostic imagingABSTRACT
A 22-year-old woman presented with progressive sensory ataxia and optic neuropathy. Previous investigation by her general practitioner had found a low serum vitamin B12, which had been corrected with oral supplementation. Neurological investigations showed raised plasma homocysteine and methylmalonic acid towards the upper limit of normal with a low serum vitamin B12 MRI showed an extensive cord lesion in keeping with subacute combined degeneration of the spinal cord. We treated her with high dose parenteral vitamin B12 and she has made a partial recovery. We discuss the management of patients who present with neurological manifestations of vitamin B12 deficiency; highlighting the fact that parenteral replacement is needed in such cases, even if the serum vitamin B12 level appears to be normal. We also discuss ancillary investigations that should be performed in patients with suspected vitamin B12 deficiency.
Subject(s)
Ataxia/etiology , Optic Neuritis/etiology , Vitamin B 12 Deficiency/complications , Adult , Female , Humans , Magnetic Resonance Imaging , Spinal Cord , Vitamin B 12 , Young AdultABSTRACT
We report the case of a 67-year-old woman with Wernicke's encephalopathy(WE), who had been suffering from repeated vomiting and poor oral intake due to both reflux esophagitis and atrophic gastritis. She presented with altered of consciousness, horizontal nystagmus, and gait disturbance, and acute deterioration of consciousness was observed after starting peripheral parenteral nutrition (PPN). Brain MRI showed bilateral high intensity lesions in the medial thalamus and the dorsal midbrain on FLAIR and T2-weighted images. Although brain MRI characteristics are useful for diagnosing WE, it is possible that there are no abnormal MRI findings in its early stages. In addition, only 10-20% of WE cases present with the classical clinical triad of confusion, ophthalmoplegia, and ataxia. Therefore, confirming the diagnosis can be challenging. In general, rapid improvement of symptoms is observed with prompt vitamin B1 supplementation. However, delays in treatment can result in irreversible amnesia and ataxia. Furthermore, in the state of vitamin B1 deficiency, even PPN, not just total parenteral nutrition, can worsen symptoms, and this deterioration is attributed to the glucose load.
Subject(s)
Consciousness Disorders/etiology , Parenteral Nutrition/adverse effects , Wernicke Encephalopathy/etiology , Acute Disease , Aged , Ataxia/etiology , Female , Humans , Magnetic Resonance Imaging , Vomiting/etiologyABSTRACT
CASE DESCRIPTION: An 11-year-old male breeding alpaca was evaluated for a 2-day history of lowered head carriage and lethargy. CLINICAL FINDINGS: On initial examination, the alpaca had signs of lethargy and lowered carriage of the head and neck, but no specific neurologic deficits. Medical management improved the clinical signs, but 8 months later, the alpaca developed acute, progressive general proprioceptive ataxia affecting all 4 limbs and was referred for further evaluation and treatment. Magnetic resonance imaging and CT identified disruption of the normal osseous architecture of C7 and T1. Medical management was attempted, but because of a lack of improvement, the patient underwent surgery 14 months after initial examination. TREATMENT AND OUTCOME: A dorsal laminectomy of C7 and T1 via a dorsal midline approach was performed, and the spinous processes of both vertebrae were removed prior to removal of the overlying lamina. Free dorsal expansion of the spinal cord was ensured by resection of the ligamentum flavum. Six months after surgery, the alpaca had returned to successful breeding with 7 hembra bred in the first year after surgery, producing 6 crias, and 4 crias in the second year. The patient was eventually euthanized 28 months after surgery because of neurologic deterioration but was still ambulatory at that time. CONCLUSIONS AND CLINICAL RELEVANCE: A good outcome with adequate alleviation of clinical signs and breeding soundness for > 2 years following dorsal laminectomy was achieved in this camelid patient. The surgical approach was similar to that in other species and was associated with mild postoperative morbidity. Veterinarians treating camelids should be aware of the initial clinical signs and treatment options for cervical vertebral stenotic myelopathy. In acute cases, the signs of reduced cervical mobility and pain on manipulation should prompt investigation including appropriate diagnostic imaging. Timely surgical intervention should be considered in patients that respond poorly to medical treatment to avoid irreversible spinal cord injury and optimize outcome.
Subject(s)
Camelids, New World , Cervical Vertebrae/pathology , Spinal Cord Diseases/veterinary , Spinal Stenosis/veterinary , Animals , Ataxia/etiology , Ataxia/surgery , Ataxia/veterinary , Cervical Vertebrae/surgery , Laminectomy/veterinary , Male , Posture , Spinal Cord Diseases/surgery , Spinal Stenosis/surgerySubject(s)
Ataxia/etiology , Celiac Disease/complications , Diet, Gluten-Free , Leukoencephalopathies/etiology , Mental Disorders/etiology , Biopsy , Celiac Disease/diagnosis , Celiac Disease/diet therapy , Celiac Disease/psychology , Cross Reactions , Duodenum/pathology , Female , Folic Acid Deficiency/complications , Folic Acid Deficiency/drug therapy , Frontal Lobe/physiopathology , Humans , IgA Deficiency/complications , Iron/therapeutic use , Iron Deficiencies , Leukoencephalopathies/diagnostic imaging , Leukoencephalopathies/physiopathology , Leukoencephalopathies/psychology , Magnetic Resonance Imaging , Mental Disorders/physiopathology , Purkinje Cells/immunology , Tremor/etiology , Young AdultABSTRACT
BACKGROUND: It has been demonstrated that glucose transporter (GLUT1) deficiency in a mouse model causes a diminished cerebral lipid synthesis. This deficient lipid biosynthesis could contribute to secondary CoQ deficiency. We report here, for the first time an association between GLUT1 and coenzyme Q10 deficiency in a pediatric patient. CASE PRESENTATION: We report a 15 year-old girl with truncal ataxia, nystagmus, dysarthria and myoclonic epilepsy as the main clinical features. Blood lactate and alanine values were increased, and coenzyme Q10 was deficient both in muscle and fibroblasts. Coenzyme Q10 supplementation was initiated, improving ataxia and nystagmus. Since dysarthria and myoclonic epilepsy persisted, a lumbar puncture was performed at 12 years of age disclosing diminished cerebrospinal glucose concentrations. Diagnosis of GLUT1 deficiency was confirmed by the presence of a de novo heterozygous variant (c.18+2T>G) in the SLC2A1 gene. No mutations were found in coenzyme Q10 biosynthesis related genes. A ketogenic diet was initiated with an excellent clinical outcome. Functional studies in fibroblasts supported the potential pathogenicity of coenzyme Q10 deficiency in GLUT1 mutant cells when compared with controls. CONCLUSION: Our results suggest that coenzyme Q10 deficiency might be a new factor in the pathogenesis of G1D, although this deficiency needs to be confirmed in a larger group of G1D patients as well as in animal models. Although ketogenic diet seems to correct the clinical consequences of CoQ deficiency, adjuvant treatment with CoQ could be trialled in this condition if our findings are confirmed in further G1D patients.
Subject(s)
Ataxia/etiology , Glucose Transporter Type 1/deficiency , Mitochondrial Diseases/etiology , Muscle Weakness/etiology , Ubiquinone/deficiency , Adolescent , Ataxia/diagnosis , Ataxia/diet therapy , Cation Transport Proteins , Diet, Ketogenic , Dietary Supplements , Female , Glucose Transporter Type 1/genetics , Humans , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/diet therapy , Muscle Weakness/diagnosis , Muscle Weakness/diet therapy , Mutation , Sodium-Hydrogen Exchanger 1 , Sodium-Hydrogen Exchangers , Ubiquinone/analogs & derivatives , Ubiquinone/therapeutic use , Vitamins/therapeutic useABSTRACT
The experiences and characteristics of professor ZHANG Yu-lian in regulating marrow sea acupuncture for treatment of post-stroke ataxia is introduced. Professor ZHANG established regulating marrow sea acupuncture based on the fundamentals of traditional Chinese medicine combined with brain functional region projection and cerebrovascular distribution of modern medicine. "Three acupoints regulating balance" "3 acupoints regulating transportation" "3 acupoints regulating tremor" and Fengchi (GB 20), Fengfu (GB 16), Wangu (GB 12), Tianzhu (BL 10) and C3-C6 Jiaji (Ex-B2) acupoints were applied in this kind of manipulation. We combined holding spirits of doctor and patient together, and controlled the sensation transduction with different manipulations to reach the foci, which emphasis on the doctor-patient cooperation and body-mind co-regulation, finally promote patients' comprehensive rehabilitation.
Subject(s)
Acupuncture Therapy/methods , Ataxia/therapy , Stroke/complications , Acupuncture Points , Acupuncture Therapy/history , Ataxia/etiology , Ataxia/history , China , History, 20th Century , History, 21st Century , HumansABSTRACT
Till date, an exact causative pathway responsible for neurodegeneration in Huntington's disease (HD) remains elusive; however, mitochondrial dysfunction appears to play an important role in HD pathogenesis. Therefore, strategies to attenuate mitochondrial impairments could provide a potential therapeutic intervention. In the present study, we used curcumin encapsulated solid lipid nanoparticles (C-SLNs) to ameliorate 3-nitropropionic acid (3-NP)-induced HD in rats. Results of MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and succinate dehydrogenase (SDH) staining of striatum revealed a marked decrease in Complex II activity. However, C-SLN-treated animals showed significant increase in the activity of mitochondrial complexes and cytochrome levels. C-SLNs also restored the glutathione levels and superoxide dismutase activity. Moreover, significant reduction in mitochondrial swelling, lipid peroxidation, protein carbonyls and reactive oxygen species was observed in rats treated with C-SLNs. Quantitative PCR and Western blot results revealed the activation of nuclear factor-erythroid 2 antioxidant pathway after C-SLNs administration in 3-NP-treated animals. In addition, C-SLN-treated rats showed significant improvement in neuromotor coordination when compared with 3-NP-treated rats. Thus, the results of this study suggest that C-SLNs administration might be a promising therapeutic intervention to ameliorate mitochondrial dysfunctions in HD.