Botulinum toxin type A injection combined with biofeedback in the treatment of spastic pelvic floor syndrome

BACKGROUND Spastic pelvic floor syndrome(SPFS)is a refractory pelvic floor disease characterized by abnormal(uncoordinated)contractions of the external anal sphincter and puborectalis muscle during defecation,resulting in rectal emptation and obstructive constipation.The clinical manifestations of SPFS are mainly characterized by difficult defecation,often accompanied by a sense of anal blockage and drooping.Manual defecation is usually needed during defecation.From physical examination,it is commonly observed that the patient's anal muscle tension is high,and it is difficult or even impossible to enter with his fingers.AIM To investigate the characteristics of anorectal pressure and botulinum toxin A injection combined with biofeedback in treating pelvic floor muscle spasm syndrome.METHODS Retrospective analysis of 50 patients diagnosed with pelvic floor spasm syndrome.All patients underwent pelvic floor surface electromyography assessment,anorectal dynamics examination,botulinum toxin type A injection 100 U intramuscular injection,and two cycles of biofeedback therapy.RESULTS After the botulinum toxin A injection combined with two cycles of biofeedback therapy,the patient's postoperative resting and systolic blood pressure were significantly lower than before surgery(P<0.05).Moreover,the electromyography index of the patients in the resting stage and post-resting stages was significantly lower than before surgery(P<0.05).CONCLUSION Botulinum toxin A injection combined with biofeedback can significantly reduce pelvic floor muscle tension in treating pelvic floor muscle spasm syndrome.Anorectal manometry is an effective method to evaluate the efficacy of treatment objectively.However,randomized controlled trials are needed.

An overview of acupuncture for the treatment of limb spasticity in cerebral palsy-A mini review

Cerebral palsy is a common chronic disabling disease in children with special needs,and rehabilitation for cerebral palsy is characterized by a long period,multiple methods and limited efficacy.Due to the limited motor function of cerebral palsy patients,the quality of life of patients is reduced,and their ability to participate in society is reduced,so the improvement of patients’motor function has become an important goal of cerebral palsy rehabilitation.The motor function of cerebral palsy has become an important goal of cerebral palsy rehabilitation.Limb spasticity is one of the main clinical signs of cerebral palsy patients,and the more severe the limb spasticity is,the greater the impact on the patient's motor function,so improving limb spasticity in patients with cerebral palsy is particularly important.Acupuncture,as a Chinese medicine treatment method,has been widely used in the clinical treatment of cerebral palsy in China,and has shown certain efficacy.To promote the clinical application of acupuncture technique in cerebral palsy limb spasticity,this paper analyses and summarizes the relevant literature on acupuncture treatment of cerebral palsy limb spasticity summarizes the current status of the clinical application of acupuncture in cerebral palsy limb spasticity,and provides clinical references for the reasonable application of acupuncture in cerebral palsy limb spasticity.

Comprehensive Rehabilitation Therapy of Traditional Chinese Medicine Combined with Modern Rehabilitation Training Improves the Spasticity and Motor Function of Hemiplegia after Stroke

Objective:To analyze the impact of comprehensive rehabilitation therapy of traditional Chinese medicine(TCM)(based on modern rehabilitation training)on the spasticity and motor function in stroke patients with hemiplegia.Methods:Seventy-nine stroke and hemiplegia patients admitted to the hospital from June 2021 to June 2023 were selected and randomly divided into a control group(39 cases)using modern rehabilitation training,and an observation group combined with comprehensive TCM rehabilitation therapy(40 cases),over 1 month.The clinical index data of the two groups were compared.Results:There were differences in the clinical index data between the two groups.The total effective rate after 2 treatment in the observation group(92.50%)was higher than that of the control group(74.36%)(χ^(2)=4.727,P<0.05).All central sensitization inventory(CSI)and stroke quality of life(PRO)scores in both groups were lower after treatment,with the observation group having lower scores as compared to the control group(P<0.05).The scores of FMA(upper limbs,lower limbs),Barthel index scores,and Functional Ambulation Categories(FAC)scores of both groups increased after treatment,with the observation group having higher scores as compared to the control group(P<0.05).Conclusion:Comprehensive TCM rehabilitation therapy had a significant therapeutic effect on patients with hemiplegia after stroke.It improved the patient’s spasticity,limb movement,and walking function.Their daily living abilities and quality of life were also enhanced.

Clinical Study on Improving Articulation Clarity in Spastic Cerebral Palsy with 120 Cases of Oral-Facial Acupressure Combined with Oral Placement Therapy

Objective:To observe the efficacy of oral-facial acupressure combined with oral placement therapy(OPT)in improving articulation clarity in 120 children with spastic cerebral palsy,and to explore effective therapeutic solutions for speech disorders associated with spastic cerebral palsy.Methods:A total of 120 children with spastic cerebral palsy and speech disorders,meeting the inclusion criteria,were randomly assigned into two groups:60 cases in the treatment group and 60 cases in the control group.The treatment group received orofacial acupressure combined with OPT,while the control group received only OPT.The Oral Motor Function Assessment Scale(OMFAS),developed by the China Rehabilitation Research Centre(CRRC),was used to evaluate the treatment outcomes before and after the intervention.Results:After the treatment,both the treatment and control groups showed improved mobility of the mandible,lips,and tongue.However,the treatment group exhibited significantly better improvement than the control group,with the difference between the two groups being statistically significant(P<0.05).Conclusion:Oral-facial acupressure combined with OPT can effectively improve articulation clarity in children with spastic cerebral palsy.This combined therapy is recommended for clinical promotion and application.

Association between brain N-acetylaspartate levels and sensory and motor dysfunction in patients who have spinal cord injury with spasticity:an observational case-control study

Spinal cord injury is a severe and devastating disease,and spasticity is a common and severe complication that is notoriously refractory to treatment.However,the pathophysiological mechanisms underlying spasticity and its development remain largely unknown.The goal of the present study was to find differences,if any,in metabolites of the left precentral gyrus and basal ganglia of patients who have spinal cord injury with or without spasticity,and to explore the relationship between the brain metabolite concentrations and clinical status.Thirty-six participants were recruited for magnetic resonance spectroscopic examination:23 with spinal cord injury(12 with spasticity and 11 without spasticity)and 13 healthy controls.We acquired localized proton spectra from the precentral gyrus and basal ganglia via 10 mm^(3) voxels.Notably,univariate linear regression analysis demonstrated that the lower that the N-acetylaspartate concentration(a marker for neuronal loss)was in the precentral gyrus of the patients,the lower their ASIA(American Spinal Injury Association)light-touch scores,pinprick scores,and motor scores.Additionally,longer durations of injury were associated with higher N-acetylaspartate levels in the precentral gyrus.Compared with the healthy participants and patients without spasticity,N-acetylaspartate levels in the patients with spasticity were significantly lower in both the precentral gyrus and basal ganglia.Lower N-acetylaspartate levels also correlated with greater sensory and motor dysfunction in the patients who had spinal cord injury with spasticity.

Extracorporeal shock wave for plantar flexor spasticity in spinal cord injury:A case report and review of literature

BACKGROUND Approximately 65%-78%of patients with a spinal cord injury(SCI)develop any symptom of spasticity.The aim of this study was to investigate the tolerability and short-term effects of radial extracorporeal shock wave therapy(r ESWT)on plantar flexor spasticity in a patient with incomplete SCI.CASE SUMMARY An 18-year-old man with an incomplete SCI completed five sessions of r ESWT.The primary outcomes were the changes in ankle-passive range of motion(APROM)and passive resistive force to ankle dorsiflexion.The outcomes were assessed at baseline(T0),immediately after treatment(T1)and 1 wk after the end of treatment(T2).The A-PROM increased by 15 degrees at T1 and 25 degrees at T2 compared with T0.The passive resistive force to ankle dorsiflexion at low velocity decreased by 33%at T1 and 55%at T2 in the gastrocnemius muscle and by 41%at T1 and 39%at T2 in the soleus muscle compared with T0.At high velocity,it also decreased by 44%at T1 and 30%at T2 in the gastrocnemius muscle compared with T0.However,in the soleus muscle,the change was minor,with a decrease of 12%at T1 and increased by 39%at T2 compared with T0.CONCLUSION In this patient,the findings showed that r ESWT combined with conventional therapy was well-tolerated and could be effective in improving A-PROM and passive resistive force to ankle dorsiflexion in the short-term.Further randomized controlled clinical trials with longer period of follow-up are necessary to confirm the results obtained in patients with SCI.

Novel mutation of SPG4 gene in a Chinese family with hereditary spastic paraplegia:A case report

BACKGROUND Hereditary spastic paraplegia(HSP)is a group of neurogenetic diseases of the corticospinal tract,accompanied by distinct spasticity and weakness of the lower extremities.Mutations in the spastic paraplegia type 4(SPG4)gene,encoding the spastin protein,are the major cause of the disease.This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene.CASE SUMMARY A 44-year-old male was admitted to our hospital for long-term right lower limb weakness,leg stiffness,and unstable walking.His symptoms gradually worsened,while no obvious muscle atrophy in the lower limbs was found.Neurological examinations revealed that the muscle strength of the lower limbs was normal,and knee reflex hyperreflexia and bilateral positive Babinski signs were detected.Members of his family also had the same symptoms.Using mutation analysis,a novel heterozygous duplication mutation,c.1053dupA,p.(Gln352Thrfs*15),was identified in the SPG4 gene in this family.CONCLUSION A Chinese family with HSP had a novel mutation of the SPG4 gene,which is autosomal dominant and inherited as pure HSP.The age of onset,sex distribution,and clinical manifestations of all existing living patients in this family were analyzed.The findings may extend the current knowledge on the existing mutations in the SPG4 gene.

Expression of DRD1 mRNA after Spinal Cord Injury Induced Spasticity in Rats

[Objectives]To investigate the spasticity of rat tail and the expression of dopamine receptor-1(DRD1)mRNA in the spinal cord after spinal cord injury(SCI)induced tail spasticity in rats.[Methods]Adult male Wistar rats were randomly divided into Sham group and SCI group.The second sacral spinal cord(S2)segment of SCI rats was completely transected.60 d after operation,the rat tail spasticity was scored,and then the spinal cord tissues below the level of S2 spinal cord transection were taken.The expression of DRD1 mRNA in the sacrococcygeal spinal cord was detected by qPCR.In addition,3 normal rats were used for DAR/neuronal nuclei(NeuN)and DRD1/choline acetyltransferase(ChAT)immunofluorescence staining to study the distribution of DRD1 in spinal cord and the properties of DRD1 positive cells.[Results]60 d after operation in SCI group,the tail spasticity of rats developed fully,and the symptoms of spasticity were typical.qPCR results showed that the expression of DRD1 mRNA in SCI group was significantly lower than that in Sham group(P<0.05).DRD1 was widely distributed in the dorsal horn,intermediate zone and ventral horn at the sacrococcygeal end of the rat spinal cord.[Conclusions]The decrease of DRD1 mRNA expression after SCI may be related to the occurrence and development of spasticity.

Systematic evaluation of the efficacy and safety of botulinum toxin type A in the treatment of spastic cerebral palsy

Background:Botulinum toxin type A(BTX-A)is a neuromuscular blocking agent.BTX-A inhibits acetylcholine release,causes neuromuscular transmission impairment,and decreases muscle spasms.Objective:To explore the efficacy and safety of BTX-A injection in the treatment of spastic cerebral palsy through systematic evaluation and to provide a reference for the clinical use of BTX-A.Methods:We used“Cerebral palsy”and“BTX-A”as the subject terms and used a combination of subject terms and free words for the search.We searched 7 databases,including CNKI,Wanfang,VIP,Sinomed,PubMed,Embase,and Web of science.Based on the inclusion and exclusion criteria,we screened the articles by reading their titles,abstracts,and full texts and finally included relevant literature for systematic evaluation.Result:A total of 93 papers were systematically evaluated,revealing that BTX-A injection treatment can effectively reduce muscle tone,increase joint mobility,improve gait and motor posture,and enhance gross motor movements in patients with spastic cerebral palsy.The benefits of BTX-A treatment can be sustained for 3–6 months,with motor ability improvement lasting up to 1 year.Combining BTX-A treatment with rehabilitation or external fixation therapy can enhance its efficacy.However,the effectiveness of BTX-A treatment is influenced by several factors,such as the dosage,number of injections,and patient age.Adverse reactions to BTX-A treatment are typically mild and can be relieved within 1–2 weeks.Conclusion:BTX-A injection is relatively safe but reversible.

Effects of Microselective Neurotomy on Focal Spasticity and Description of the Surgical Technique

We studied the microselective neurotomy (MSN) and its advantages to alleviate disabling spasticity. The best indication for MSN is focal spasticity. We performed 298 MSN, 87 nerves on the upper limb, 211 nerves on the lower limb) in 68 patients. The initial causes were: stroke, cranial trauma, postoperative complications and multiple sclerosis. MSN procedures were performed on the median nerve (n = 40) for wrist and finger flexion;musculo-cutaneus nerve (n = 38) for elbow flexion;ulnaris nerve (n = 9) for cubital deviation of the hand;gastrocnemius nerve (n = 98) and soleus nerve (n = 49) for equinus foot, tibial posterior nerve (n = 45) for varus foot, and fascicles (or bundles) of the flexor digitorum for “claw” toes (n = 19). The main preoperative test to identify the responsible nerve was a neuromuscular block with local anesthesia (lidocaine or bupivacaine) injected into the site of the nerve connecting the spastic muscle. During surgery, the identified nerve was exposed and its epineurium opened. Nerve bundles were teased apart into individual rootlets and a number of rootlets cut were previously planned, according to the spasticity. Follow-up was performed for up to 10 years, with a mean period of 29 months. Results demonstrated a reduction of limb spasticity of 2 to 3 points: modified Ashworth scale (MAS). Pain and clonus were also diminished in the affected limb. In some cases, voluntary movement was once again possible. MSN is a useful alternative in those cases of focal spasticity where physiotherapy and nerve block with botulinum toxin or phenol no longer produce satisfactory results.

Effect of acupuncture on inflammatory cytokines expression of spastic cerebral palsy rats

Objective:To To investigate the effect of acupuncture on the tumor necrosis factor- α(TNF-α),interleukin-6(IL-6),C-reactive protein(CRP),nitric oxide synthase(NOS) content and muscular tension of spasticity cerebral palsy rat model.Methods:The rats with spastic cerebral palsy were randomly divided into the control group,model group and acupuncture group.After successful modeling,the muscular tension and the content of TNF- α,IL-6,CRP.NOS were measured.Results:The serum TNF- α,IL—6,CRP,NOS content were significantly decreased in the acupuncture group(P<0.05).The low and high shear viscosity of whole blood of the acupuncture group were significantly lower than the control group and the model group(P<0.05).The erythrocyte electrophoresis indexes in the acupuncture group were significantly lower than that in the model group and the control group(P<0.05).Acupuncture significantly reduced the muscular tension of spastic cerebral palsy rat and increased the active extent in the paralytie extremity(P<0.05),but it could not be restored to normal level.Compared with the control group,the difference had significant(P<0.05).Conclusions:Acupuncture treatment can inhibit the release of inflammatory cells after brain injury,then reduce immune injury,relieve muscle spasms and reduce muscular tension.

Outcomes in spasticity after repetitive transcranial magnetic and transcranial direct current stimulations

Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhib- its satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the efficacy of non-invasive brain stimulations in im- proving the spasticity post-stroke, more prospective cohort studies involving large sample sizes are needed.

Botulinum toxin injection improved voluntary motor control in selected patients with post-stroke spasticity

The effect of botulinum toxin type A injection on voluntary grip control was examined in a 53-year-old female, who sustained a hemorrhagic right middle cerebral artery stroke 3 years previously, which resulted in finger flexor spasticity and residual weak finger/wrist extension. The patient received 50 units of botulinum toxin type A injection each to the motor points （2 sites/muscle） of the left flexor digitorum superficialis and flexor digitorum profundus, respectively. Botulinum toxin injection led to weakness and tone reduction in the spastic finger flexors, but improved grip release time in grip initiation/release reaction time tasks. Improved release time was accompanied by shortened extensor electromyography activity, and improved release time likely correlated with blocked co-contraction of finger flexors during voluntary finger extension. This case report demonstrated that botulinum toxin injection improved voluntary motor control of the hand in a chronic stroke patient with residual finger extension.

Establishing a rat model of spastic cerebral palsy by targeted ethanol injection

Spastic cerebral palsy is generally considered to result from cerebral cortical or pyramidal tract damage. Here, we precisely targeted the left pyramidal tract of 2-month-old Sprague-Dawley rats placed on a stereotaxic instrument under intraperitoneal anesthesia. Based on the rat brain stereotaxic map, a 1-mm hole was made 10 mm posterior to bregma and 0.8 mm left of sagittal suture. A microsyringe was inserted perpendicularly to the surface of the brain to a depth of 9.7 mm, and 15 wL of ethanol was slowly injected to establish a rat model of spastic cerebral palsy. After modeling, the rats appeared to have necrotic voids in the pyramidal tract and exhibited typical signs and symptoms of flexion spasms that lasted for a long period of time. These findings indicate that this is an effective and easy method of establishing a rat model of spastic cerebral palsy with good reproducibility. Ethanol as a chemical ablation agent specifically and thoroughly damages the py- ramidal tract, and therefore, the animals display flexion spasms, which are a typical symptom of the disease.

Dry needling at myofascial trigger points mitigates chronic post-stroke shoulder spasticity

Post-stroke spasticity is associated with restriction in the range of motion of the shoulder.Reducing muscular dystrophy may help relieve muscular dysfunction in patients with post-stroke shoulder spasticity.Dry needle therapy is a method of needling the trigger points using a syringe needle without the use of a drug.Dry needle therapy is commonly used for pain at the shoulder,neck,waist,and back.In this case study,a 62-year-old male patient affected with cerebral hemorrhage of the right frontal lobe had received rehabilitative treatment for 12 years.However,he still experienced shoulder spasticity.The patient received daily dry needling at the trigger points of infraspinatus,teres minor,posterior deltoid,and pectoralis major on 9 days.After the first and ninth treatment,the Modified Ashworth Scale and the passive range of motion of the shoulder was used to assess the effect of the treatment.The spasticity and range of motion of the shoulder showed obvious improvement.These results indicate that dry needling at the myofascial trigger points can effectively treat chronic poststroke shoulder spasticity.

Effects of High Frequency Repetitive Transcranial Magnetic Stimulation on KCC2 Expression in Rats with Spasticity Following Spinal Cord Injury

The effect of high-frequency repetitive transcranial magnetic stimulation（r TMS） on potassium-chloride cotransporter-2（KCC2） protein expression following spinal cord injury（SCI） and the action mechanism were investigated. SCI models were established in SD rats. Five groups were set up randomly： normal control group, SCI 7-day（7 D） model group, SCI 14-day（14 D） model group, SCI-7 DrTMS group and SCI-14 DrTMS group（n=5 each）. The rats in SCI rTMS groups were treated with 10 Hz rTMS from 8 th day and 15 th day after SCI respectively, once every day, 5 days every week, a total of 4 weeks. After the model establishment, motor recovery and spasticity alleviation were evaluated with BBB scale once a week till the end of treatment. Finally, different parts of tissues were dissected out for detection of variations of KCC2 protein using Western blotting and polymerase chain reaction（PCR） technique. The results showed that the BBS scores after treatment were significantly higher in SCI-7 DrTMS group than in SCI-14 DrTMS group（P〈0.05）. As compared with normal control groups, The KCC2 protein in SCI model groups was down-regulated after SCI, and the decrease was much more significant in SCI-14 D model group than in SCI-7 D group（P〈0.05）. As compared with SCI model groups, KCC2 protein in rTMS groups was up-regulated after the treatment（P〈0.05）. The up-regulation of KCC2 protein content and expression was more obvious in SCI-7 DrTMS group than in SCI-14 DrTMS group（P〈0.05）. It was concluded that 10 Hz rTMS can alleviate spasticity in rats with SCI, which might be attributed to the up-regulation of KCC2 protein. It was also suggested that the high-frequency rTMS treatment after SCI at early stage might achieve more satisfactory curative effectiveness.

Gait analysis of children with spastic hemiplegic cerebral palsy

An experiment was carried out in the key laboratory for Technique Diagnosis and Function Assessment of Winter Sports of China to investigate the differences in gait characteristics between healthy children and children with spastic hemiplegic cerebral palsy. With permission of their parents, 200 healthy children aged 3 to 6 years in the kindergarten of Northeastern University were enrolled in this experiment. Twenty children aged 3 to 6 years with spastic hemiplegic cerebral palsy from Shengjing Hospital, China were also enrolled in this experiment. Standard data were collected by simultaneously recording gait information from two digital cameras. DVracker was used to analyze the standard data. The children with hemiplegic cerebra palsy had a longer gait cycle, slower walking speed, and longer support phase than did the healthy children. The support phase was longer than the swing phase in the children with hemiplegic cerebral palsy. There were significant differences in the angles of the hip, knee, and ankle joint between children with cerebral palsy and healthy children at the moment of touching the ground and buffering, and during pedal extension. Children with hemiplegic cerebral palsy had poor motor coordination during walking, which basically resulted in a short stride, high stride frequency to maintain speed, more obvious swing, and poor stability.

Selective dorsal rhizotomy in cerebral palsy spasticity-a newly established operative technique in Slovenia: A case report and review of literature

BACKGROUND Spasticity affects a large number of children,mainly in the setting of cerebral palsy,however,only a few paediatric neurosurgeons deal with this problem.This is mainly due to the fact that until 1979,when Fasano has published the first series of selective dorsal rhizotomy(SDR),neurosurgeons were able to provide such children only a modest help.The therapy of spasticity has made a great progress since then.Today,peroral drugs,intramuscular and intrathecal medicines are available,that may limit the effects of the disease.In addition,surgical treatment is gaining importance,appearing in the form of deep brain stimulation,peripheral nerve procedures and SDR.All these options offer the affected children good opportunities of improving the quality of life.CASE SUMMARY A 15-year old boy is presented that was surgically treated for spasticity as a result of cerebral palsy.Laminotomy at L1 level was performed and L1 to S1 nerve roots were isolated and divided in smaller fascicles.Then,the SDR was made.CONCLUSION We describe a patient report and surgical technique of SDR that was performed in Slovenia for the first time.

Rescue axonal defects by targeting mitochondrial dynamics in hereditary spastic paraplegias

Impaired axonal development and degeneration underlie debilitating neurodegenerative diseases including hereditary spastic paraplegia, a large group of inherited diseases. Hereditary spastic paraplegia is caused by retrograde degeneration of the long corticospinal tract axons, leading to progressive spasticity and weakness of leg and hip muscles. There are over 70 subtypes with various underlying pathophysiological processes, such as defective vesicular trafficking, lipid metabolism, organelle shaping, axonal transport, and mitochondrial dysfunction. Although hereditary spastic paraplegia consists of various subtypes with different pathological characteristics, defects in mitochondrial morphology and function emerge as one of the common cellular themes in hereditary spastic paraplegia. Mitochondrial morphology and function are remodeled by mitochondrial dynamics regulated by several key fission and fusion mediators. However, the role of mitochondrial dynamics in axonal defects of hereditary spastic paraplegia remains largely unknown. Recently, studies reported perturbed mitochondrial morphology in hereditary spastic paraplegia neurons. Moreover, downregulation of mitochondrial fission regulator dynamin-related protein 1, both pharmacologically and genetically, could rescue axonal outgrowth defects in hereditary spastic paraplegia neurons, providing a potential therapeutic target for treating these hereditary spastic paraplegia. This mini-review will describe the regulation of mitochondrial fission/fusion, the link between mitochondrial dynamics and axonal defects, and the recent progress on the role of mitochondrial dynamics in axonal defects of hereditary spastic paraplegia.

Novel frameshift mutation in the SACS gene causing spastic ataxia of charlevoix-saguenay in a consanguineous family from the Arabian Peninsula:A case report and review of literature

BACKGROUND Familial cases of autosomal recessive spastic ataxia of charlevoix-saguenay have not been reported in the Arabian Peninsula,although the consanguineous marriage rate is very high.We report the first family from the Arabian Peninsula harboring a novel frameshift mutation in the SACS gene.CASE SUMMARY A 33-year-old man presented to our neurology clinic with balance problems and weakness of distal upper and lower limbs.He was previously clinically diagnosed with Friedreich's ataxia.However,the severity of polyneuropathy and the electrodiagnostic studies(EDX)findings are atypical features of Friedreich’s ataxia,and the deterioration was attributed to diabetic neuropathy.Close examination of other family members identified cerebellar ataxia,lower-limb pyramidal signs,peripheral neuropathy,and magnetic resonance imaging findings characterized by pontine linear hypointensities.Genetic testing for Friedreich’s ataxia did not yield a diagnosis.Whole exome sequencing identified a novel frameshift germline mutation in the SACS gene termed c.5824_5827delTACT using the transcript NM_014363.5,which is predicted to cause premature termination of the sacsin protein at amino acid position 1942(p.Tyr1942Metfs*9)and disrupts the sacsin SRR3 and domains downstream from it.The mutation segregated with the disease in the family.CONCLUSION Our data add to the spectrum of mutations in the SACS gene and argues for a need to implement suitably integrated clinical and diagnostic services,including next generation sequencing technology,to better classify ataxia in this area of the world.