Muscle Stretch Reflexes Research Articles

Hemispheric encephalitis secondary to HAV

A 2-year male child, presented to National Institute of Child Health (NICH), with acute onset high grade fever and focal left sided seizures for 1 day, followed by left hemiparesis and encephalopathy. Developmental and family history was unremarkable. On physical examination, patient’s body temperature rose up to 38.7 °C. Though he had pallor along with hepatomegaly, there were no signs of jaundice or ascites. Central nervous system examination showed encephalopathy as well as positive neck stiffness. Motor system examination revealed generalized decrease in bulk of upper and lower limbs, but rest of the findings were localized to left side of the body, showing hypertonia, decreased power, brisk muscle stretch reflex, and positive ankle clonus and left Babinski sign.
 Blood investigations showed anemia (hemoglobin 9.1g/dl), leukocytosis (white blood cells 22.1 cells/μL) and raised aspartate aminotransferase (AST) levels (826 IU/L). Total bilirubin and direct bilirubin levels were normal (0.3 mg/dL and 0.1 mg/dL, respectively). Serum ammonia (64 μg/dL) and lactic acid (1.6 μg/dL) levels were also within normal ranges. The cerebrospinal fluid (CSF) was also clear, with 0 leukocytes/μL, protein levels of 25 mg/dL, and normal glucose levels (82 mg/dL), no organism was seen on gram stain. Hepatitis A Ig M antibody came out to be reactive.
 Brain computed tomography showed large hypo density along with effacement of sylvian fissure, sulci, gyri on right side involving frontal, parietal, and temporal and occipital lobe on ipsilateral side. On post contrast, there was remarkable meningeal enhancement on right side. MRI brain revealed cortical and subcortical large area of abnormal signal intensity seen in fronto-parietal and occipital cortex on the right side along with laminar necrosis.
 Seizures were controlled by given intravenous injection phenytoin and leviteracetam in bolus and then maintenance doses. Intravenous acyclovir was started
 due to clinical suspicion of herpes encephalitis but was stopped after observing clinical improvement and identification of Ig M antibody of HAV. Patient conscious level improved after 2 weeks. AST levels also decreased to 20 IU/L and he was discharged with advice to follow up after 14 days

Characteristics of "deqi" and myoelectricity in different tissue structures of acupoint

To investigate the effect of acupuncture in different tissue structures on deqi and the electromyography of acupoint area. Twenty healthy subjects, respectively accepted 4 kinds of needling stimulation, i.e. stimulating skin at Zusanli (ST36), stimulating ST36 with and without skin anesthesia using compound lidocaine cream, and stimulating at Dubi (ST35) without skin anesthesia. Deqi sensation of the acupuncturist and subjects were measured according to MGH Acupuncture Sensation Scale (MASS) during needling, and the myoelectricity around the acupoints was recorded simultaneously. The occurrence rate and intensity of the different deqi sensations, the relationship between the acupuncturist's and subjects' deqi sensations, and the integrated electromyogram (iEMG) were analyzed. Sharp pain and tingling were the main sensations during skin needling at ST36. Fullness, dull pain, soreness and acupuncturist's tightness were the main sensations during needling with or without skin anesthesia at ST36. Fullness was the main sensation during needling at ST35, while the intensity was lower than that during needling at ST36. A positive correlation in the intensity was found between subjects' fullness and acupuncturist's tightness during needling with or without skin anesthesia at ST36. The subjects' fullness appeared earlier about 5 seconds than acupuncturist's tightness. The iEMGs during subjects' fullness and acupuncturist's tightness were 2-3 times of that before needling. Deqi sensations such as subjects' fullness, dull pain, soreness and acupuncturist's tightness are mainly related to the activity of the muscles under the acupoints. Subjects' fullness and acupuncturist's tightness always appear together. Acupuncturist's tightness may be mediated by the muscle stretch reflex induced by needling stimulation.

The Flexor Pollicis Longus Reflex: Interrater and Intrarater Reliability in Comparison With Established Muscle Stretch Reflexes.

The aim of this study was to investigate the interrater reliability and intrarater reliability of the flexor pollicis longus muscle stretch reflex (FPLR) and compare it with clinically established reflexes. A total of 71 healthy volunteers participated. The FPLR, biceps reflex, brachioradialis reflex, and patellar tendon reflex of each participant were tested bilaterally and rated by eight examiners (four experienced, four inexperienced). For intrarater reliability evaluation, five examiners rated the reflexes of four volunteers at four different points in time. Analysis of the interrater reliability with Gwet's AC1 demonstrated almost perfect agreement for FPLR (Gwet's AC1 = 0.90), biceps reflex (Gwet's AC1 = 0.90), and patellar tendon reflex (Gwet's AC1 = 0.95) when using binary data (reflex present vs. absent). Only fair agreement was found for the brachioradialis reflex (Gwet's AC1 = 0.56). Experienced raters had a higher agreement than inexperienced raters did when rating the biceps reflex and the patellar tendon reflex. The intrarater reliability was almost perfect for the patellar tendon reflex (Gwet's AC1 = 0.94), followed by the FPLR (Gwet's AC1 = 0.83) with substantial agreement and the biceps reflex (Gwet's AC1 = 0.57) with moderate agreement. The FPLR is a reliable diagnostic neuromuscular test and may therefore be useful in the clinical examination for C8/T1 nerve root lesions or pathologies of the interosseous anterior nerve. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. Upon completion of this article, the reader should be able to: (1) Elicit the flexor pollicis longus muscle stretch reflex; (2) Discuss the disadvantage of kappa statistics in assessing the interrater reliability when the prevalence of the studied trait is very high or very low; and (3) Name the spinal nerves involved in the innervation of the flexor pollicis longus muscle. Advanced. The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Fluctuating Weakness in an 18-Month-Boy: Congenital Myasthenia

AbstractIn this article, we reported a case of an 18-month-old male child patient who presented with motor predominant delay in attaining developmental milestones and early onset fatiguable weakness with ptosis and ophthalmoparesis. This ptosis and ophthalmoparesis typically worsened with progression of the day. Examination showed proximal weakness with preserved muscle stretch reflexes. Electrophysiology showed characteristic decrement on repetitive nerve stimulation test that localized to disorders of the neuromuscular junction. Next-generation sequencing showed a pathogenic variant of CHRNE that was responsible for congenital myasthenic syndrome. Such variants show increased improvement with salbutamol in addition to anticholinesterase inhibitors. Hence, the patient was started on pyridostigmine, and the plan was to add on salbutamol on follow-up if optimal improvement does not occur.

Biofeedback-driven gaming to reduce muscle stretch reflexes

Biofeedback-driven gaming to reduce muscle stretch reflexes

MNIS+7 and lower limb function in inotersen treatment of hereditary transthyretin-mediated amyloidosis.

IntroductionInotersen, an antisense oligonucleotide inhibitor of transthyretin (TTR) protein production, demonstrated significant benefit versus placebo in the modified Neuropathy Impairment Score (NIS) +7 neurophysiologic tests (mNIS+7) in patients with hereditary TTR‐mediated amyloidosis (hATTR) with polyneuropathy. This analysis assessed the mNIS+7 components by anatomic location and the lower limb function (LLF) test.MethodsAdults with hATTR in the NEURO‐TTR trial (NCT01737398) were randomly assigned to receive weekly doses of subcutaneous inotersen 300 mg or placebo for 65 weeks. The mNIS+7 and LLF were assessed at 35 and 66 weeks.ResultsAll major mNIS+7 components (muscle weakness, muscle stretch reflexes, sensation) and the LLF showed significant efficacy in patients receiving inotersen versus placebo; however, NIS‐reflexes (upper limb), touch pressure (upper and lower limbs), and heart rate during deep breathing did not show significant effects.DiscussionThe results of this analysis reinforce the beneficial effect of inotersen on slowing neuropathy progression in patients with hATTR polyneuropathy.

Selective dorsal rhizotomy: functional anatomy of the conus-cauda and essentials of intraoperative neurophysiology.

Spasticity is the result of an exaggeration of the monosynaptic muscle stretch reflex due to lesions affecting the central nervous system, in particular an upper motor neuron lesion. Selective dorsal rhizotomy (SDR) is a surgical technique developed to treat spastic diplegia, one of the common forms of cerebral palsy, resulting from the lack of supraspinal inhibitory controls. The aim of SDR is to identify and cut a critical amount of the sensory rootlets, in particular those contributing the most to spasticity, in order to relieve the patient from lower limb spasticity while preserving motor strength and sphincter control. Various surgical techniques to perform SDR have been proposed over time. Similarly, intraoperative neurophysiology (ION)-first introduced by Fasano and colleagues in 1976-is a safe and effective tool to guide the surgeon in the procedure of SDR, but different ION strategies are used by different authors, and the value of ION itself has been questioned. The purpose of this paper is to review the anatomo-physiological background of SDR, the historical development of the surgical technique, and the essential principles of ION. While some surgeons privilege a single-level approach and others a multi-level approach, nowadays, there are still neither agreement nor guidelines on the percentage of roots to be cut. Rather, a tailored approach based on both the preoperative functional status as well as intraoperative ION findings seems reasonable. ION is considered not essential to decide the percentage of roots to cut, but it assists to distinguish between ventral and dorsal roots, and to preserve sphincterial function, whenever S2 rootlets are included in SDR. To optimize the balance between reduction of spasticity and preservation of motor strength while minimizing the neurological damage remains the main goal of SDR.

A Rare Complication of Bariatric Surgery; Guillain Barre Syndrome

Objectives: Guillain-Barre Syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Laparoscopic Sleeve Gastrectomy (LSG), used of morbid obesity, is the standard surgical treatment method for Bariatric Surgery (BS). Neurological complications of BS are also increasing with growing obesity prevalence. We present a case of developed acute polyneuropathy after BS. Study Design-Methods: The presentation of GBS is ascending paralysis, reduction/loss of muscle stretch reflexes, and albumino-cytologic dissociation in the CSF. The diagnosis was made using anamnesis, neurological examination, Electroneuromyography (ENMG) and laboratory findings. Results: Neurological complications of BS are usually related to micronutrients deficiencies secondary to malabsorbtion after surgery. The complications are seen variable which are count encephalopathy, optic neuropathy, myelopathy, polyradiculoneuropathy, and polyneuropathy. Conclusions: Among these, GBS appears to be a very rare complication in BS. It is important to consider the diagnosis of peripheral neuropathy, and discrimination of GuillainBarré syndrome. Because of, their treatments are different.

Treatment Response to Botulinum Neurotoxin-A in Children With Cerebral Palsy Categorized by the Type of Stretch Reflex Muscle Activation.

While Botulinum NeuroToxin-A (BoNT-A) injections are frequently used to reduce the effects of hyperactive stretch reflexes in children with cerebral palsy (CP), the effects of this treatment vary strongly. Previous research, combining electromyography (EMG) with motion analysis, defined different patterns of stretch reflex muscle activation in muscles, those that reacted more to a change in velocity (velocity dependent –VD), and those that reacted more to a change in length (length dependent –LD). The aim of this study was to investigate the relation between the types of stretch reflex muscle activation in the semitendinosus with post-BoNT-A outcome as assessed passively and with 3D gait analysis in children with spastic CP. Eighteen children with spastic CP (10 bilaterally involved) between the ages of 12 and 18 years were assessed before and on average, 8 weeks post-treatment. EMG and motion analysis were used to assess the degree and type of muscle activation dependency in the semitendinosus during passive knee extensions performed at different joint angular velocities. Three-dimensional gait analysis was used to assess knee gait kinematics as a measure of functional outcome. Pre-treatment, 9 muscles were classified as VD and 9 as LD, but no differences between the groups were evident in the baseline knee gait kinematics. Post-treatment, stretch reflex muscle activation decreased significantly in both groups but the reduction was more pronounced in those muscles classified pre-treatment as VD (−72% vs. −50%, p = 0.005). In the VD group, these changes were accompanied by greater knee extension at initial contact and during the swing phase of gait. In the LD group, there was significantly increased post-treatment knee hyperextension in late stance. Although results vary between patients, the reduction of stretch reflex muscle activation in the semitendinosus generally translated to an improved functional outcome, as assessed with 3D gait analysis. However, results were less positive for those muscles with pre-treatment length-dependent type of stretch reflex muscle activation. The study demonstrates the relevance of categorizing the type of stretch reflex muscle activation as a possible predictor of treatment response.

Increased shoulder muscle stretch reflex elicitability in supine subject posture

Increased shoulder muscle stretch reflex elicitability in supine subject posture

Design of Muscle Reflex Control for Upright Standing Push-Recovery Based on a Series Elastic Robot Ankle Joint.

In physical human–robot interaction environment, ankle joint muscle reflex control remains significant and promising in human bipedal stance. The reflex control mechanism contains rich information of human joint dynamic behavior, which is valuable in the application of real-time decoding motion intention. Thus, investigating the human muscle reflex mechanism is not only meaningful in human physiology study but also useful for the robotic system design in the field of human–robot physical interaction. In this paper, a specialized ankle joint muscle reflex control algorithm for human upright standing push-recovery is proposed. The proposed control algorithm is composed of a proportional-derivative (PD)-like controller and a positive force controller, which are employed to mimic the human muscle stretch reflex and muscle tendon force reflex, respectively. Reflex gains are regulated by muscle activation levels of contralateral ankle muscles. The proposed method was implemented on a self-designed series elastic robot ankle joint (SERAJ), where the series elastic actuator (SEA) has the potential to mimic human muscle–tendon unit (MTU). During the push-recovery experimental study, the surface electromyography (sEMG), ankle torque, body sway angle, and velocity of each subject were recorded in the case where the SERAJ was unilaterally kneed on each subject. The experimental results indicate that the proposed muscle reflex control method can easily realize upright standing push-recovery behavior, which is analogous to the original human behavior.

Bone-conducted vestibular and stretch reflexes in human neck muscles.

In normal humans, tapping the forehead produces a neck muscle reflex that is used clinically to test vestibular function, the cervical vestibular evoked myogenic potential (cVEMP). As stretch receptors can also be activated by skull taps, we investigated the origin of the early and late peaks of the bone-conducted cVEMP. In twelve normal participants, we differentially stimulated the vestibular and neck stretch receptors by applying vibration to the forehead (activating both vestibular and stretch receptors) and to the sternum (activating mainly stretch receptors). Patients with bilateral vestibulopathy (BVP; n = 26) and unilateral vestibular loss (uVL; n = 17) were also investigated for comparison. Comparison of peaks in normal subjects suggested that the early peaks were vestibular-dependent, while the later peaks had mixed vestibular and stretch input. The late peaks were present but small (1.1 amplitude ratio) in patients with BVP and absent VEMPs, confirming that they do not strictly depend on vestibular function, and largest in age-matched controls (1.5 amplitude ratio, p = 0.049), suggesting that there is an additional vestibular reflex at this latency (approx. 30ms). Patients with uVL had larger late peaks on the affected than the normal side (1.4 vs 1.0 amplitude ratio, p = 0.034). The results suggest that the early responses in SCM to skull vibration in humans are vestibular-dependent, while there is a late stretch reflex bilaterally and a late vestibular reflex in the contralateral muscle.

Spinal Circuits Mediate a Stretch Reflex Between the Upper Limbs in Humans

Inter-limb reflexes play an important role in coordinating behaviors involving different limbs. Previous studies have demonstrated that human elbow muscles express an inter-limb stretch reflex at long-latency (50–100 ms), a timing consistent with a trans-cortical linkage. Here we probe for inter-limb stretch reflexes in the shoulder muscles of human participants. Unexpected torque pulses displaced one or both shoulders while participants adopted a steady posture against background torques. The results demonstrated inter-limb stretch reflexes occurring at short-latency for both shoulder extensors and flexors; the rapid timing (36–50 ms) must involve a spinal linkage for the two arms. Inter-limb stretch reflexes were also observed at long-latency yet they were opposite to the preceding short-latency; when the short-latency stretch reflex was excitatory then the long-latency stretch reflex was inhibitory and vice versa. Comparing the responses to contralateral arm displacement to those during simultaneous displacement of both arms revealed that inhibitory inter-limb stretch reflexes are independent of within-limb stretch reflexes, but that excitatory inter-limb stretch reflexes are suppressed by within-limb stretch reflexes. Our results provide the first demonstration of short-latency inter-limb stretch reflexes in the upper limb of humans and reveal interacting spinal circuits for within-limb and inter-limb stretch reflexes.

PMP22 Gene-Associated Neuropathies: Phenotypic Spectrum in a Cohort from India.

Reports of spectrum of clinical manifestations in PMP22 gene-associated neuropathies (duplication/mutations) are scarce. To identify the frequency of PMP22 gene variations and establish their genotype-phenotype correlation. Patients with suspected genetic demyelinating neuropathy (n = 128) underwent evaluation for copy number variations and point mutations in PMP22 gene by multiplex ligation-dependent probe amplification (MLPA) and direct sequencing respectively. Of these, only 27 patients (M:F:19:8) from 18 families had PMP22 gene-associated neuropathy; they were subsequently analyzed for genotype-phenotype correlation. Twenty-five patients had PMP22 duplication while two patients had PMP22 missense mutations (p.A114V and p.L80P). Age at onset of neuropathy ranged from infancy to 63years and symptom duration ranged from 2 to 32years. Cranial nerve dysfunction in the form of ptosis, ophthalmoplegia, bifacial weakness, and sensorineural hearing loss was observed in addition to a number of systemic features. Three patients were asymptomatic. All except one patient were ambulant. Velocity of median nerve and amplitude of evoked motor responses from common peroneal nerve were significantly reduced in male patients. There was significantly worse disability in the late-onset group as compared with the early-onset group. Otherwise, the mean age at onset, frequency of skeletal deformities, patterns of motor weakness, muscle stretch reflexes, sensory impairment, disability rating scales, and electrophysiological parameters were comparable irrespective of gender, onset age, family history and ulnar nerve conduction velocities. The relatively low frequency of PMP22 duplication in the present cohort warrants a more comprehensive search to establish the genetic etiology. Further research into the role of other genetic variants as well as modifier genes and their effect on phenotypic heterogeneity is indicated.

Biomechanical Characteristics of Single Leg Jump in Collegiate Basketball Players Based on Approach Technique

Our study investigated the characteristics of the biomechanics of lower extremities during running single leg jump (RSJ) in collegiate basketball players. Twelve division III male basketball players voluntarily participated in this study. They performed three trials of the running single leg jump with two approach speeds (fast and preferred) randomly. The kinematic data were collected by motion analysis system (200 Hz), and kinetic data were collected using the AMTI force platform (1000 Hz), and electromyography (EMG) data were recorded by the Delsys surface Electromyography (EMG) system (2000 Hz). Kinematic, kinetic and EMG signal were synchronized using EvaRT 4.6. Peak Ground reaction force, eccentric loading rate (ELR), gastrocnemius (GA) of pre-activation phase, and tibialis anterior (TA) of push-off phase were found significantly larger in the fast approach speed (p < 0.05). RSJ improves muscle activation level and stretch reflex. Higher activation of TA and GA during RSJ may have the benefit of decreasing risk of injury and jump training. Thus, it is helpful in muscle stretch adaptation.

Commentary: Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS) with Chronic Cough and Preserved Muscle Stretch Reflexes: Evidence for Selective Sparing of Afferent Ia Fibres

Commentary: Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS) with Chronic Cough and Preserved Muscle Stretch Reflexes: Evidence for Selective Sparing of Afferent Ia Fibres

Diet-induced obesity decreases rate-dependent depression in the Hoffmann's reflex in adult mice.

Obesity is associated with balance and motor control deficits. We have recently shown that Group Ia muscle spindle afferents, the sensory arm of the muscle stretch reflex, are less responsive in mice fed a high‐fat diet. Here we test the hypothesis that reflex excitability to sensory information from Group Ia muscle spindle afferents is altered in a mouse model of diet‐induced obesity. We measured the anesthetized Hoffmann’s or H‐reflex, the electrical analog of the muscle stretch reflex. Adult mice of both sexes were fed a control diet (CD; 10% kcal from fat) or a high‐fat diet (HFD; 60% kcal from fat) for 5, 10, or 15 weeks. We used three quantitative measures of H‐reflex excitability: (1) H‐reflex latency; (2) the percentage of motor neurons recruited from electrical stimulation of Group Ia muscle spindle afferents (Hmax/Mmax); and (3) rate‐dependent depression (RDD), the decrease in H‐reflex amplitude to high frequency stimulation (20 stimuli at 5 Hz). A HFD did not significantly alter H latency (P = 0.16) or Hmax/Mmax ratios (P = 0.06), but RDD was significantly lower in HFD compared to CD groups (P < 0.001). Interestingly, HFD males exhibited decreased RDD compared to controls only after 5 and 10 weeks of feeding, but females showed progressive decreases in RDD that were only significant at 10 and 15 weeks on the HFD. These results suggest that high‐fat feeding increases H‐reflex excitability. Future studies are needed to determine whether these changes alter muscle stretch reflex strength and/or balance and to determine the underlying mechanism(s).

A computer simulation study on the influences of loss and damage of primary muscle spindle afferents on soleus muscle stretch reflex.

Sensory loss is detrimental to sensorimotor control. Several studies have reported that loss and/or damage of primary (Ia) muscle spindle afferents significantly influence the stretch reflex responses of leg and foot muscles. However, a systematic experimental evaluation on how the impairment of Ia muscle spindle afferents affects the stretch reflex is difficult due to technical and ethical issues. In the present study, the aim was to use computer simulations of a multiscale neuromusculoskeletal model to investigate how changes in: i) the number of Ia afferents, ii) the synaptic conductance between Ia sensory fibers and spinal motor neurons (MNs), and iii) the conduction velocities (CVs) of Ia afferents, would influence the stretch reflex of a leg muscle (soleus). Simulation results showed that both anatomical and functional loss of Ia afferents exerted an influence on the amplitude of short-latency stretch reflex response (M1) and the late phase of medium-latency response (M2). Additionally, changes in CVs of Ia afferents mainly influenced the latency of M1 and the amplitude of M2. Our findings provide conceptual evidence that a combination of anatomical and functional loss, as well as changes in CVs of Ia afferents due to demyelination, can explain the stretch reflex responses observed in peripheral neuropathies.

GUILLAIN-BARRE SYNDROME: A CASE REPORT

Guillain-Barre syndrome (GBS) is a complicated degenerative neurological disorder which can be acute or chronic in nature. It is an acquired condition which is characterized by progressive, symmetrical, proximal and distal tingling and weakness. Muscle stretch reflexes are decreased to absent and loss of sensation is common. Etiology remains unclear but pathophysiology includes demyelination of spinal nerve roots. Death is rare. Early diagnosis and prompt referral should occur in severe cases due to the incidence of potential ventilation failure and cardiovascular instability in some patients. The case of a 26-year-old male presenting to a physician is described. The importance of a correct diagnosis by the physician and the subsequent management is reviewed.&#x0D; Key words: Guillain-Barre syndrome, extremity weakness, peripheral nerves, trauma

Long Term Follow up of Cerebellar Ataxia CA) and MRI Lesions Which Responded to Copper (Cu) Supplementation (P12-055-19)

ObjectivesCu deficiency (CuD) produces anemia and leukopenia. CuD neurologic dysfunction can also occur. We follow a patient with CuD with CA and MRI lesions that responded to Cu replacement. MethodsA 64-year-old male with progressive ataxia and neuropathy was found to have a significant CuD (copper level 38 mmol/L, normal range 70–175) 7 years ago. The etiology of CuD was unknown. There was no previous gastric surgery, malabsorption, ingestion of zinc containing products or medications associated with Cu loss.He had an ataxic gait with a steppage component. Muscle stretch reflexes were brisk at the knees and absent at the ankles. He had length dependent loss to all modalities. Other etiologies for CA were not found. The blood smear showed anisocytes and poikilocytes, but anemia and leukopenia were absent. He became wheelchair bound after several weeks.Brain MRI without contrast revealed non-enhancing symmetric T2 signal prolongation of the medial cerebellar white matter extending into left middle cerebral peduncle. Neuroconductive studies showed moderate-to-severe axonal sensorimotor polyneuropathy. ResultsCu supplementation with using 5 mg cupric oxide daily raised serum Cu to 97 mmol/L. Symptoms improved after 1 month. Brain MRI 3 months later showed no cerebellar lesions with serum Cu of 123 mmol/L. At this point he was able to walk with a cane. His gait disturbance further improved to the extent that he was able to walk without assistance or support. His follow up Cu levels remain in the normal range (last value = 128 mmol/L). ConclusionsCu is a component of the neurologic metalloenzymes cytochrome-c oxidase (CcO), Cu-zinc superoxide dismutase, tyrosinase, dopamine β-hydroxylase, peptidylglycine α-amidating monooxygenase and ceruloplasmin. Cu and iron pass electrons through CcO to oxygen, forming water. CuD impacts the electron transport chain, impairing ATP production which injures susceptible tissues.This case demonstrates the reversibility of neurologic dysfunction and MRI lesions by means of correcting CuD. Our 7-year follow up period confirms the validity of the pathogenesis and management. Further study is needed to identify the specific roles of Cu metabolism in such cases and the individual factors allowing for the dramatic response we observed. Funding Sourcesnone.