Lower Limb Muscle Weakness Research Articles

Co-existence of peripheral neuropathy secondary to lead poisoning and chronic polymyositis: Case report

Abstract A case is presented on a 47-year-old man with chronic lead poisoning with typical symptoms after 5 years of occupational exposure. He consulted for generalized muscle weakness, early dysphagia, cephaloparesia, and paresthesias in upper and lower limbs. He also had atrophy and decreased proximal muscle strength (deltoid and medial vast) and in both flexor and extensor muscles of the neck. He had a history of high blood lead levels and peripheral neuropathy documented by electromyography. In addition to the diagnosis of lead poisoning, inflammatory myopathy was confirmed based on muscle enzyme elevation, muscular inflammation in magnetic resonance imaging, and typical findings in a muscle biopsy. To the best of our knowledge, this is the first report where both conditions are documented in one patient.

The application of MRI in sporadic inclusion-body myositis

Objective To investigate the characteristic MRI features of sporadic inclusion- body myositis (sIBM). Methods Clinical and MR imaging data of 6 patients with sIBM diagnosed by muscle biopsy from May 2013 to November 2014 were retrospectively analyzed. All patients showed insidious onset of lower limb muscle weakness and diagnosed as sIBM by muscle biopsies. All patients were evaluated by the score of the severity of fatty infiltration, inflammation and atrophy in MRI. Results All patients were observed fatty infiltration with different degrees. The fatty infiltration in thighs was characterized in a decreasing order of frequency: gluteus maximus (6 cases), vastuslateralis (6 cases), vastusintermedius (6 cases), vastusmedialis (6 cases), sartorius (5 cases), adductor magnus (5 cases), rectus femoris (4 cases), semi- membranosus (4 cases), semi- tendinosus (4 cases), biceps femoris (4 cases), gracilis (3 cases), adductor longus(2 cases).The fatty infiltration in thighs was characterized in a decreasing order of severity: vastuslateralis (3.2 points), vastusintermedius (3.2 points), vastusmedialis (3.0 points), adductor magnus (3.0 points), gluteus maximus (2.7 points), bicepsfemoris (2.2 points), semi-membranosus (2.1 points), semi- tendinosus (2.1 points), rectus femoris (1.5 points), sartorius (1.3 points), gracilis (0.8 points), adductor longus (0.7 points). All patients showed the features of distal distribution andsymmetry. Inflammation was observed in 3 patients. 1 patient only involved the vastuslateralis, the other 2 patients were observed muscle inflammation with different degrees in 12 muscles. Atrophy was observed in 5 patients. The atrophy in thighs was characterized in a decreasing order of frequency: vastuslateralis (5 cases), vastusintermedius (5 cases), vastusmedialis (4 cases), adductor magnus (4 cases), semi-membranosus (2 cases), rectus femoris (1 cases), sartorius (1 cases) and gluteus maximus; there was no atrophy in adductor longus, gracilis,semi-tendinosus, biceps femoris. Conclusion The MRI characteristic manifestations of sIBM is fatty infiltration and atrophy in the distal portion, particularly involving the vastuslateralis, vastusintermedius, vastusmedialis and adductor magnus. Key words: Magnetic resonance imaging; Myositis

Duchenne Muscular Dystrophy Mice and Men: Can Understanding a Genetic Cardiomyopathy Inform Treatment of Other Myocardial Diseases?

Duchenne muscular dystrophy mouse models have a predictable and reproducible time course of cardiomyopathy progression with discrete pathogenic steps, which closely parallel what we know occurs in the cardiomyopathy of patients with Duchenne muscular dystrophy. The slow progression of early pathogenic steps common to many cardiomyopathies may make Duchenne muscular dystrophy models useful for identifying novel treatment targets and testing the therapeutic value of new treatment paradigms for an at-risk patient population far beyond those with muscular dystrophies. Dilated cardiomyopathy is a leading cause of death in individuals affected by Duchenne muscular dystrophy (DMD), and nearly all DMD patients develop dilated cardiomyopathy by age 18. DMD and the milder Becker muscular dystrophy result from mutations in the X-linked gene encoding dystrophin, a membrane-associated protein that helps protect striated muscle cell membranes from damage. Clinical signs resulting from lower limb muscle weakness lead to DMD diagnosis typically by 5 years of age and loss of ambulation by 12 years of age. Skeletal myopathy in Becker muscular dystrophy has a later age of onset and slower progression than DMD, and dilated cardiomyopathy is the primary cause of mortality. Earlier ventilatory support for affected respiratory muscles and timely management of pulmonary infections have led to increased survival for DMD patients into their mid-twenties. These advances have made increasingly evident the underlying cardiomyopathy that presents as heart failure and often fatal arrhythmias in the later decades of life. Despite the devastating consequences of DMD cardiomyopathy, its unique features may provide new insights into myocardial disease. First, the consistent lag between evident skeletal myopathy and cardiomyopathy affords early detection and possible treatment of a patient population that is genetically programmed to develop cardiac dysfunction. Second, the myocardial disease exhibits a relatively slow progression, providing the ability to understand each step involved. Third, there are isogenic …

Essential amino acids to treat sarcopenia in patients with COPD?

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Beneficial effects of short-term Belt electrode Skeletal muscle Electrical Stimulation（B-SES）in a patient with lower limb muscle weakness followed by acute respiratory distress syndrome

Beneficial effects of short-term Belt electrode Skeletal muscle Electrical Stimulation（B-SES）in a patient with lower limb muscle weakness followed by acute respiratory distress syndrome

A Case of Neuromyopathy Due to Synthetic Antimalarial Drugs

Introduction: Synthetic anti malaria drugs has effectiveness in the treatment of many auto-immune diseases and principally the systemic erythematous lupus. The undesirable effects remain rare. The appearance of myopathy is considered as exceptional. We report observations which highlight the hypothesis of a double toxicity (Chloroquine and Hydroquinine). Observation: We report a case of 53 years old female patient treated chronically by Hydroquinidine and Escitalopram for Bouveret diseases which became asymptomatic. Later on, we had Chloroquine and Prednisone to the previous treatment. Prednisone was removed few months later because of a possible skin side effect. Due to the incomplete relief of joint pain we had Methotrexate to the treatment associated to Omeprazole. And the evolution was characterized by the appearance of lower limbs muscle weakness leading to the interruption of Methotrexate- Omeprazole association. Despite this interruption there was a worsening of the muscle weakness clinically and electro-physiologically diagnosed as myopathy which leads to the interruption of Chloroquine and Hydroquinidine. Other causes of myopathy have been ruled out after a large check-up and Methotrexate was re-introduced two months later with progressive regression of symptoms within six months. Discussion and conclusion: The appearance of myopathy in a patient treated by Chloroquine is extremely rare. Our observation highlights the toxicity of synthetic antimalarial drugs which can cause myopathy in some cases. The association of Chloroquine and Hydroquinidine seems potentially more toxic on muscles.

Recommendations for assessing and preventing falls in adults of all ages with rheumatoid arthritis

Rheumatoid arthritis (RA) is a debilitating disease that affects younger as well as older adults. It is associated with a high risk of injurious falls due to problems such as lower-limb muscle weakness, balance impairment, swollen and tender joints, pain, and fatigue. Falls are typically associated with older people; hence, many professionals do not recognise the risks for younger persons with diseases such as RA. Falls can lead to devastating consequences, such as fatalities, hip fractures (with 50% of those affected never regaining their previous level of mobility and 30% dying within 1 year), or loss of independence and confidence. Research has shown that many people are either unaware or deny their risk of falling. Therefore, it is important that health professionals, such as community nurses, are aware of the risk factors, methods of assessment, and evidence-based preventative measures, so that falls can be avoided in this population. This article presents research and practice implications for community nurses to enable them to assess, treat, and appropriately refer adults with RA who are also at risk of falls.

Inspiratory Muscle Weakness Is Associated With Exercise Intolerance in Patients With Heart Failure With Preserved Ejection Fraction: A Preliminary Study

BackgroundThe relationship between inspiratory muscle weakness (IMW) and exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) remains unestablished. Methods and ResultsThe present study enrolled 40 patients with HFpEF (EF ≥45%). IMW was defined as maximum inspiratory pressure <70% normal predicted values. The function of the diaphragm was assessed by means of ultrasound measurement of muscle thickening of the diaphragm. IMW was prevalent in 27.5% of patients. Patients with IMW had significantly lower vital capacity relative to normal predicted values (%VC), lower knee extensor muscle strength in relation to body weight (%KEMS), poorer nutritional status as assessed by means of the Geriatric Nutritional Risk Index, and shorter 6-minute walk distance (6MWD) compared with patients without IMW (all P < .05). Impaired diaphragm muscle thickening at end-inspiration (median value < 3.9 mm) was significantly associated with a high prevalence of IMW and reduced 6MWD (all P < .05). Subgroup analysis showed that IMW was accompanied by a further decrease in 6MWD in patients with restrictive pulmonary dysfunction (%VC <80%) or lower-limb muscle weakness (median %KEMS <30%; all P < .05). ConclusionsIMW is associated with exercise intolerance in patients with HFpEF.

The Generalized Log-Ratio Transformation: Learning Shape and Adjacency Priors for Simultaneous Thigh Muscle Segmentation.

We present a novel probabilistic shape representation that implicitly includes prior anatomical volume and adjacency information, termed the generalized log-ratio (GLR) representation. We demonstrate the usefulness of this representation in the task of thigh muscle segmentation. Analysis of the shapes and sizes of thigh muscles can lead to a better understanding of the effects of chronic obstructive pulmonary disease (COPD), which often results in skeletal muscle weakness in lower limbs. However, segmenting these muscles from one another is difficult due to a lack of distinctive features and inter-muscular boundaries that are difficult to detect. We overcome these difficulties by building a shape model in the space of GLR representations. We remove pose variability from the model by employing a presegmentation-based alignment scheme. We also design a rotationally invariant random forest boundary detector that learns common appearances of the interface between muscles from training data. We combine the shape model and the boundary detector into a fully automatic globally optimal segmentation technique. Our segmentation technique produces a probabilistic segmentation that can be used to generate uncertainty information, which can be used to aid subsequent analysis. Our experiments on challenging 3D magnetic resonance imaging data sets show that the use of the GLR representation improves the segmentation accuracy, and yields an average Dice similarity coefficient of 0.808 ±0.074, comparable to other state-of-the-art thigh segmentation techniques.

Sporadic inclusion body myositis: clinical, pathological, and genetic analysis of eight Polish patients.

Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in patients above 50 years of age. Its progressive course finally leads to immobilisation, and no effective therapy exists. Its pathogenesis includes both degenerative and inflammatory processes, however, its direct causes remain unknown. Therefore, a possible genetic background of the disease must also be considered. Here we report on twelve patients: eight with sporadic inclusion body myositis and four with other myopathies with rimmed vacuoles in muscle biopsy. All patients were evaluated clinically, morphologically, radiologically, and genetically. All patients with sIBM presented both shoulder and pelvic girdle muscle involvement. In addition, distal upper and lower limb muscle weakness was noted. Patients with other muscle disorders showed effects mainly in proximal muscles and marked calf muscle hypertrophy. In sIBM cases computed tomography of lower limb muscles revealed atrophy that was most pronounced within the quadriceps femoris and gracilis muscles in the thighs and within the medial head of the gastrocnemius muscle and the tibialis anterior muscle in the lower legs. On light microscopy mononuclear cell invasion of muscle fibres was present in six patients with sIBM. On electron microscopy myofibrillar disorganisation and mitochondrial abnormalities were noted in all sIBM patients, whereas cytoplasmic tubulofilamentous inclusions were seen in three patients and both cytoplasmic and nuclear inclusions in one of them. According to the criteria by Rose et al. (2011) six patients were classified as "clinico-pathologically defined IBM", one as "clinically defined IBM", and one as "probable IBM". Pathological deposits of TDP-43 were found in muscles in all sIBM as well as in control cases. Additionally, accumulation of other proteins thought to be associated with sIBM, like β-amyloid, -synuclein, and tau protein, was present in the most of examined biopsies. All twelve patients were screened for the presence of causative mutations in TARDBP, VCP, HNRNPA1, and HNRNPA2B1 genes. Additionally, analysis of C9ORF72 hexanucleotide repeat expansion was performed. No causative mutations were found in any of the patients. Our study provides the first - to our knowledge - comprehensive clinical, pathological, and genetic workup of a group of Polish patients.

Heart rate response during underwater treadmill training in adults with incomplete spinal cord injury.

Walking on a submerged treadmill can improve mobility in persons displaying lower limb muscle weakness and balance deficits. Little is known, however, regarding the effect of water treadmill exercise on cardiac performance in persons with incomplete spinal cord injury (iSCI). To assess heart rate response during underwater treadmill training (UTT) in adults with iSCI. Seven males and 4 females with iSCI (age = 48 ± 13 years; 5 ± 8 years after injury) completed 8 weeks of UTT (3 sessions per week; 3 walks per session) incorporating individually determined walking speeds, personalized levels of body weight unloading, and gradual, alternating increases in speed and duration. Heart rate was monitored during the last 15 seconds of the final 2 minutes of each walk. Over the course of 3 biweekly periods in which walking speed remained constant, heart rate fell by 7% (7 ± 1 b•min(-1); P < .001) in weeks 2 and 3, 14% (17 ± 6 b•min(-1); P < .001) in weeks 4 and 5, and 17% (21 ± 11 b•min(-1); P < .001) in weeks 6 and 7. In adults with iSCI, progressively greater absolute and relative reductions in submaximal exercise heart rate occurred after 2 months of UTT featuring a systematic increase in training volume.

Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2.

Spinal muscular atrophy is a disorder of lower motor neurons, most commonly caused by recessive mutations in SMN1 on chromosome 5q. Cases without SMN1 mutations are subclassified according to phenotype. Spinal muscular atrophy, lower extremity-predominant, is characterized by lower limb muscle weakness and wasting, associated with reduced numbers of lumbar motor neurons and is caused by mutations in DYNC1H1, which encodes a microtubule motor protein in the dynein-dynactin complex and one of its cargo adaptors, BICD2. We have now identified 32 patients with BICD2 mutations from nine different families, providing detailed insights into the clinical phenotype and natural history of BICD2 disease. BICD2 spinal muscular atrophy, lower extremity predominant most commonly presents with delayed motor milestones and ankle contractures. Additional features at presentation include arthrogryposis and congenital dislocation of the hips. In all affected individuals, weakness and wasting is lower-limb predominant, and typically involves both proximal and distal muscle groups. There is no evidence of sensory nerve involvement. Upper motor neuron signs are a prominent feature in a subset of individuals, including one family with exclusively adult-onset upper motor neuron features, consistent with a diagnosis of hereditary spastic paraplegia. In all cohort members, lower motor neuron features were static or only slowly progressive, and the majority remained ambulant throughout life. Muscle MRI in six individuals showed a common pattern of muscle involvement with fat deposition in most thigh muscles, but sparing of the adductors and semitendinosus. Muscle pathology findings were highly variable and included pseudomyopathic features, neuropathic features, and minimal change. The six causative mutations, including one not previously reported, result in amino acid changes within all three coiled-coil domains of the BICD2 protein, and include a possible 'hot spot' mutation, p.Ser107Leu present in four families. We used the recently solved crystal structure of a highly conserved region of the Drosophila orthologue of BICD2 to further-explore how the p.Glu774Gly substitution inhibits the binding of BICD2 to Rab6. Overall, the features of BICD2 spinal muscular atrophy, lower extremity predominant are consistent with a pathological process that preferentially affects lumbar lower motor neurons, with or without additional upper motor neuron involvement. Defining the phenotypic features in this, the largest BICD2 disease cohort reported to date, will facilitate focused genetic testing and filtering of next generation sequencing-derived variants in cases with similar features.

Slowly progressing lower motor neuron disease caused by a novel duplication mutation in exon 1 of the SOD1 gene

Familial amyotrophic lateral sclerosis accounts for about 5% of all cases of the neurodegenerative disorder amyotrophic lateral sclerosis. Genetic mutations in Cu/Zn superoxide dismutase (SOD1) have been associated with one kind of familial amyotrophic lateral sclerosis (ALS1). We identified a novel duplication mutation in exon 1 of the SOD1 gene in a Japanese family whose members had lower motor neuron diseases. The patients showed slow disease progression, with the onset of lower limb muscle weakness and exertional dyspnea. Some patients had mild motor and sensory neuropathy and/or bladder dysfunction, which is further evidence that SOD1 mutation results in a predominantly lower motor neuron phenotype.

Novel single base-pair deletion in exon 1 of XK gene leading to McLeod syndrome with chorea, muscle wasting, peripheral neuropathy, acanthocytosis and haemolysis

We present a 70-year-old male patient of Greek origin with choreatic movements of the tongue and face, lower limb muscle weakness, peripheral neuropathy, elevated creatinephosphokinase (CPK), acanthocytosis and haemolysis in the absence of Kell RBC antigens with an additional Factor IX-deficiency. Genetic testing for mutations in the three exons of the XK gene revealed a previously unreported hemizygous single base-pair frameshift deletion at exon 1 (c.229delC, p.Leu80fs). In conclusion, we hereby describe a rare phenotype of a patient with McLeod syndrome which was discovered coincidentally during routine blood group testing and consecutively genetically confirmed.

Increased Serum Creatine Kinase

A 38-year-old white male taxi driver was referred to a lipid clinic by his general practitioner for management of combined hyperlipidemia. He was a smoker with a 20 pack-year history. His father had died of myocardial infarction at age 55 years. Examination of this patient revealed a blood pressure of 136/99 mmHg and a body mass index of 29 kg/m2, with no clinical signs of hyperlipidemia. Cholesterol testing revealed a total serum cholesterol value of 251 mg/dL (6.5 mmol/L; reference interval, 3.7–7.0 mmol/L), an HDL concentration of 30.9 mg/dL (0.8 mmol/L; reference interval, 0.7–1.8 mmol/L), and triglycerides of 539 mg/dL (6.1 mmol/L; reference interval, 20%, indicative for primary prevention of hyperlipidemia with a statin, after changes in lifestyle (1). Baseline biochemical investigations before starting the statin showed a serum creatine kinase (CK)4 activity of 889 U/L (reference interval, 24–195 U/L) and an alanine aminotransferase activity of 61 U/L (reference interval, <50 U/L). The results of other tests were within their respective reference intervals: total bilirubin, 0.8 mg/dL (13 μmol/L; reference interval, <14 μmol/L); alkaline phosphatase, 95 U/L (reference interval, <150 U/L); and γ-glutamyltransferase, 49 U/L (reference interval, <50 U/L). The results of other laboratory investigations (including renal function, blood count, serum vitamin B12, folate, serum protein electrophoresis, antinuclear antibodies, C-reactive protein, and thyroid function) were normal. At 30 years of age, the patient's mother had been diagnosed with lower limb muscle weakness, which made her unable to dorsiflex her feet. His 48-year-old brother and 38-year-old maternal half-brother were both fine. ### QUESTIONS TO CONSIDER 1. What conditions can cause increased serum CK? 2. What other testing would be useful to help determine the cause of the increased CK? 3. Given this patient's family history, what condition should be …

Recovery from paraplegia with administration of erlotinib in a patient with lung adenocarcinoma.

Recovery from paraplegia with administration of erlotinib in a patient with lung adenocarcinoma.

Gait impairment in cervical spondylotic myelopathy: analysis of muscle activation timing

Introduction:Gait impairment is aprimary symptomof cervical spondylotic myelopathy (CSM). Analysis of the timing of muscle activation during gait, using surface electromyography (SEMG), can improve the understanding of a gait deficit. The aim of this study was to comparemuscle activation timing during gait in peoplewith untreated CSM and in ageand gendermatched healthy controls. Patients/Materials and Methods: Ethical approval was obtained from a hospital Ethics Committee. Sixteen people with untreated CSM were recruited consecutively from a neurosurgery clinic, and matched to healthy controls of the same age (±5 years) and gender. Participants from both groups completed at least ten walking trials at comfortable gait speed along a 10-metrewalkway. Healthy controls then completed a second set of ten walking trials at the same speed as the CSM participants to whom they were matched. SEMG signals were recorded during gait from rectus femoris, biceps femoris, tibialis anterior andmedial gastrocnemius using standard electrode recording and placement procedures. Signals were processed using MATLAB® and the timing of activation was extracted using a previously validated reliable method [1]. The duration of activation for each muscle was expressed as a percentage of gait cycle time. Data for CSM participants and healthy controls were compared using paired t-tests. Results: The mean comfortable walking speed of CSM participants was 1.12m/s, while healthy controls walked at a mean of 1.49m/s. Comparing both groups at comfortable walking speed, CSM participants demonstrated significantly prolonged activation of rectus femoris (33% gait cycle duration compared to 22% in healthy controls, p=0.04), biceps femoris (32% vs 22%, p=0.001) and tibialis anterior (42% vs 30%, p=0.007), but not medial gastrocnemius (32% vs 29%, p=0.4). Co-activation of rectus and biceps femoris was also prolonged in CSM (14% vs 9%, p=0.04). No differences were found in the co-activation time of tibialis anterior and medial gastrocnemius (7% vs 4%, p=0.17). The results of the matchedspeedanalysismirrored thefindingsat comfortable speed, with the samemuscles showing statistically significant differences between CSM participants and controls. Discussion and conclusions: This study was the first to identify andquantify abnormallyprolongeddurationof activationof the lower limb muscles as a feature of gait in CSM. The persistence of thesefindings atmatchedgait speed confirmed that thesewere features of abnormal neuromuscular control, andnot a consequence of slower gait speed. Prolonged duration of activation may be a strategy to compensate for lack of stability or weakness of lower limb muscles during gait. Reference

Postural control and isometric strength of leg extensor muscle in moderately physically active young and elderly men

not described. The aim of this study was to describe standing posture in relation to joint restrictions in children with bilateral CP. Patients/materials and methods: Standing posture in 26 children with CP, mean age 11y (SD 3y), and 19 typically developing children, was recorded for 30 s with 3D motion analysis. Fifteen children with ability to stand without support were designated CP-Group A (GMFCS I-III), and 11 who needed support for standing CP-Group B (GMFCS III-IV). All children were tested with their habitual footwear. Passive joint range of motion (ROM) was measured with a goniometer. Lower limb contractures were defined as passive ROM less than neutral joint position. Results: Unior bilateral joint contractures were equally presented among the children in both CP groups A and B; in the hip (4 vs 7), the knee (6 vs 9), and in the ankle (2 vs 3). CP-Group B presentedwith significantly less passive joint ROM than CPGroup A in hip extension (−4◦(SD 5◦) vs 1◦(SD 5◦), p=0.022), knee extension (−12◦(SD 10◦) vs 0◦(SD 6◦), p≤0.001), and ankle dorsiflexion (2◦(SD 13◦) vs 7◦(SD 7◦), p=0.009) (Fig. 1). Children in bothCP groupsA andB stoodwith significantlymore flexion than their passive jointROMin thehip (p≤0.001vsp=0.004 respectively), in the knee (p=0.003 vs p=0.003), and in the ankle in CP Group A (p=0.012 vs p=0.182) (Fig. 1). Discussion and conclusions: The flexed joint position during standing with respect to the passive joint extension ROM in both CP groups indicates that the children did not utilize their possible joint extensionROMduring upright standing. Kneeflexor spasticity was observed in both groups and might have contributed to difficulties to erect their lower limbs. The large difference between the joint position in the unloaded and the upright positions, in particular in the children who needed support (CPGroup B), might also be interpreted as lower limbmuscle weakness. Which factors contribute to the difficulties to align the body segments and maintain a stable body position with respect to gravity during standing in children with bilateral CP requires further exploration.

PWE-117 Prevalence of Falls in the Uk PBC Population

IntroductionPrevious studies have documented the prevalence of falls in PBC in a geographical area but there is no published data on the prevalence of falls in a national UK PBC...

A patient-derived stem cell model of hereditary spastic paraplegia with SPAST mutations

SUMMARYHereditary spastic paraplegia (HSP) leads to progressive gait disturbances with lower limb muscle weakness and spasticity. Mutations in SPAST are a major cause of adult-onset, autosomal-dominant HSP. Spastin, the protein encoded by SPAST, is a microtubule-severing protein that is enriched in the distal axon of corticospinal motor neurons, which degenerate in HSP patients. Animal and cell models have identified functions of spastin and mutated spastin but these models lack the gene dosage, mutation variability and genetic background that characterize patients with the disease. In this study, this genetic variability is encompassed by comparing neural progenitor cells derived from biopsies of the olfactory mucosa from healthy controls with similar cells from HSP patients with SPAST mutations, in order to identify cell functions altered in HSP. Patient-derived cells were similar to control-derived cells in proliferation and multiple metabolic functions but had major dysregulation of gene expression, with 57% of all mRNA transcripts affected, including many associated with microtubule dynamics. Compared to control cells, patient-derived cells had 50% spastin, 50% acetylated α-tubulin and 150% stathmin, a microtubule-destabilizing enzyme. Patient-derived cells were smaller than control cells. They had altered intracellular distributions of peroxisomes and mitochondria and they had slower moving peroxisomes. These results suggest that patient-derived cells might compensate for reduced spastin, but their increased stathmin expression reduced stabilized microtubules and altered organelle trafficking. Sub-nanomolar concentrations of the microtubule-binding drugs, paclitaxel and vinblastine, increased acetylated α-tubulin levels in patient cells to control levels, indicating the utility of this cell model for screening other candidate compounds for drug therapies.