Progressive Gait Deterioration Research Articles

Primary angiitis of the central nervous system as a mimic of multiple sclerosis: A case report

BackgroundPrimary angiitis of the central nervous system is a rare inflammatory vasculopathy and it is a difficult diagnosis to make because of its kaleidoscopic presentation and its multiple mimics, including multiple sclerosis. Case presentationA 21-year-old men presented a four-year history of progressive gait deterioration. Magnetic resonance imaging of the brain and spine showed hyperintense round-shaped lesions on T2 images, many with contrast enhancement, in supra/infratentorial and spinal segments. He received treatment for multiple sclerosis but presented clinical worsening, and follow-up neuroimaging showed persistent contrast enhancement lesions and a cerebellar hematoma. Brain biopsy was performed and demonstrated inflammatory infiltrations in blood vessels. The patient received 6 monthly schedules of 5 g methylprednisolone and 1 g cyclophosphamide with clinical stabilization. DiscussionOur patient presented a primary angiitis central nervous system according to the Birnbaum and Hellmann proposed criteria. This case reinforces the importance of advancing the differential diagnosis of patients that present red flags in brain neuroimaging. ConclusionThe presence of the micro/macrobleeds and persistent contrast enhancing lesions should raise the suspicion of vasculitis in the differential diagnosis of multiple sclerosis.

Quantitative Characterization of Motor Control during Gait in Dravet Syndrome Using Wearable Sensors: A Preliminary Study.

Dravet syndrome (DS) is a rare and severe form of genetic epilepsy characterized by cognitive and behavioural impairments and progressive gait deterioration. The characterization of gait parameters in DS needs efficient, non-invasive quantification. The aim of the present study is to apply nonlinear indexes calculated from inertial measurements to describe the dynamics of DS gait. Twenty participants (7 M, age 9–33 years) diagnosed with DS were enrolled. Three wearable inertial measurement units (OPAL, Apdm, Portland, OR, USA; Miniwave, Cometa s.r.l., Italy) were attached to the lower back and ankles and 3D acceleration and angular velocity were acquired while participants walked back and forth along a straight path. Segmental kinematics were acquired by means of stereophotogrammetry (SMART, BTS). Community functioning data were collected using the functional independence measure (FIM). Mean velocity and step width were calculated from stereophotogrammetric data; fundamental frequency, harmonic ratio, recurrence quantification analysis, and multiscale entropy (τ = 1...6) indexes along anteroposterior (AP), mediolateral (ML), and vertical (V) axes were calculated from trunk acceleration. Results were compared to a reference age-matched control group (112 subjects, 6–25 years old). All nonlinear indexes show a disruption of the cyclic pattern of the centre of mass in the sagittal plane, quantitatively supporting the clinical observation of ataxic gait. Indexes in the ML direction were less altered, suggesting the efficacy of the compensatory strategy (widening the base of support). Nonlinear indexes correlated significantly with functional scores (i.e., FIM and speed), confirming their effectiveness in capturing clinically meaningful biomarkers of gait.

Childhood Seeligmüller Strümpell Philip Disease: The First Case in Iraq and a Review of the Early Historic Documentation of the Disease in the Literature

Seeligmüller Strümpell Philip disease is characterized by familial progressive spastic paraplegia or paraparesis associated with a progressive deterioration of gait. The disorder is genetically heterogeneous and can be inherited in an autosomal dominant, autosomal recessive or X-linked recessive manner. The mode of inheritance involved has a direct impact on the chances of inheriting the disorder. The cornerstone of treatment is the use of various muscle relaxants. The disorder has not been reported or documented in Iraq. This paper aims to report the first case of childhood Seeligmüller Strümpell Philip disease in an Iraqi girl. Patients and Methods: A thirteen-year girl with childhood Seeligmüller Strümpell Philip disease who developed systemic lupus erythematosus is described and the early historic documentation of Seeligmüller Strümpell Philip disease in the medical literature is briefly updated. Results: The diagnosis of Seeligmüller Strümpell Philip disease in this girl was based on clinical findings and supported by electromyography and nerve conduction studies. Brain MRI showed normal findings. Few weeks before the patient was seen, they took her outside Iraq to Medipol Mega complex of Hospitals for treatment. They performed tenotomy and tenoplasty of the hip adductors, achilloplasty, and posterior capsule relaxation. When the girl was first seen at the Children Teaching Hospital of Baghdad Medical City, the parents regretted taking her outside Iraq for treatment as she didn’t show any improvement, and was still using the wheelchair. Conclusion: Unfortunately, the girl was seen too late, and despite consulting many doctors in Iraq and outside Iraq, she didn’t receive appropriate evidence based treatment and was treated unsatisfactorily surgically.

Calpain‐1 Knockout in Mice Causes Degeneration of Cerebellar Granule Cells and Ataxia

Abnormal apoptosis is one of the hallmarks of human neurodegenerative disorders, such as spinocerebellar ataxia (SCA), an inherited disease with progressive deterioration of gait and balance, associated with neuronal loss in cerebellum. A recent study reported that SCA in the Parson Russell Terrier dog breed was associated with a calpain‐1 null mutation. Contrary to the established view that overactivation of calpains, a family of calcium‐dependent proteases, leads to neurodegeneration, recent results have shown that synaptic N‐methyl‐D‐aspartate receptor (NMDAR)‐mediated calpain‐1 activation produces neuroprotection via degradation of PH domain and Leucine rich repeat protein phosphatase 1 (PHLPP1), and stimulation of the pro‐survival Protein Kinase B (Akt). Here, we report that the number of apoptotic neurons in various brain structures, including cerebellum, is higher in calpain‐1 knock out (CAPN1 KO) mice, as compared to wild‐type (wt) mice during the postnatal period (P7‐P10). Adult CAPN1 KO mice exhibited reduced granule cell density and impaired motor function. PHLPP1 was increased and p‐Akt decreased in cerebellum of CAPN1 KO mice, as compared to wt mice during postnatal development. Systemic injection (P1‐P7) of Bisperoxo Oxovanadate Dipotassium (BPV), an indirect activator of Akt, as well as crossing CAPN1 KO mice with PHLPP1 KO mice, rescued Akt activation, reduced apoptosis in the developing cerebellum, resulting in increased granule cell survival and improvement of motor function in adult mice. These findings further support the notion that CAPN1 is neuroprotective and suggests that it is a new candidate gene for ataxia.Funded by NINDS grant P0INS045260‐01.

X-linked spinal muscular atrophy in mice caused by autonomous loss of ATP7A in the motor neuron.

ATP7A is a copper-transporting P-type ATPase that is essential for cellular copper homeostasis. Loss-of-function mutations in the ATP7A gene result in Menkes disease, a fatal neurodegenerative disorder resulting in seizures, hypotonia and failure to thrive, due to systemic copper deficiency. Most recently, rare missense mutations in ATP7A that do not impact systemic copper homeostasis have been shown to cause X-linked spinal muscular atrophy type 3 (SMAX3), a distal hereditary motor neuropathy. An understanding of the mechanistic and pathophysiological basis of SMAX3 is currently lacking, in part because the disease-causing mutations have been shown to confer both loss- and gain-of-function properties to ATP7A, and because there is currently no animal model of the disease. In this study, the Atp7a gene was specifically deleted in the motor neurons of mice, resulting in a degenerative phenotype consistent with the clinical features in affected patients with SMAX3, including the progressive deterioration of gait, age-dependent muscle atrophy, denervation of neuromuscular junctions and a loss of motor neuron cell bodies. Taken together, these data reveal autonomous requirements for ATP7A that reveal essential roles for copper in the maintenance and function of the motor neuron, and suggest that SMAX3 is caused by a loss of ATP7A function that specifically impacts the spinal motor neuron.

Gait in Huntington's disease and the stride length-cadence relationship.

BackgroundThe progressive deterioration of gait in Huntington’s disease (HD) leads to functional decline and loss of function. To understand the underlying mechanisms responsible for the gait changes in HD, we examined the automatic control of gait by measuring the relationship between stride length and cadence. The relationship is strongly linked in healthy adults during automatic gait but disrupted in pathological gait disorders, such as Parkinson’s disease (PD).MethodsThe stride length cadence relationship was compared between seventeen participants with HD, twenty with PD and twenty one healthy older adults (HOA). Participants had their gait recorded at self-selected preferred, very slow, slow, fast and very fast speeds. Linear regression analysis was used to determine the slope and intercept of the relationship which were compared between groups. The adjustment of stride length and cadence when changing gait speeds was measured and compared within and between groups.ResultsLinearity was strong in all but two participants with HD and one with PD. Slope did not differ between groups (p > 0.05) but intercept was lower in the HD and PD groups compared to HOA (p < 0.05). Stride length was shorter in the HD and PD groups compared to controls at preferred and most adjusted speed conditions (p < 0.05) but cadence did not differ between groups (p > 0.05) regardless of speed. The HD group adjusted stride length and cadence similar to HOA when changing speed. The range of cadence across speed conditions did not differ between groups.ConclusionScaling of stride length but not the regulation of cadence was found to be disrupted in participants with HD.

Gowers′ intrasyringeal hemorrhage associated with Chiari type I malformation in Noonan syndrome

Background:Idiopathic hemorrhage in a syrinx is a rare entity known as Gowers’ intrasyringeal hemorrhage. Bleeding confined to the syrinx cavity causes severe, sometimes acute, neurological deficits. We report a case of intrasyringeal hemorrhage into a preexisting lumbosacral syrinx associated with Chiari type I malformation.Case Description:A 39-year-old female with Noonan syndrome underwent foramen magnum decompression and a cervical syrinx-subarachnoid shunt for Chiari type I malformation-associated syringomyelia 7 years ago. She presented progressive gait deterioration and acute urinary dysfunction, indicating conus medullaris syndrome. Initial magnetic resonance imaging revealed massive hemorrhage in the intrasyringeal cavity of the conus medullaris. The patient underwent surgical removal of the intrasyringeal hematoma and her neurological symptoms improved postoperatively.Conclusion:Although Gowers’ intrasyringeal hemorrhage is rare, this entity should be taken into consideration in patients with syringomyelia showing acute neurological deterioration.

A LATE ONSET ATAXIA WITH TELANGIECTASIA

Ataxia telangiectasia (AT) is a multisystem autosomal recessive disorder caused by mutations in the ATM gene found on the large arm of chromosome 11 (11q 22–23). The ATM gene encodes...

Relação entre aptidão física, atividade física e estabilidade postural

As aging advances there is a progressive deterioration of gait, with multiple risk factors that may contribute to falls. Falls are a public health problem ...

Progressive Gait Deterioration in Adolescents With Dravet Syndrome

To characterize changes in gait by age in patients with Dravet syndrome. Prospective, cross-sectional study. Tertiary children's hospital. Twenty-six subjects with Dravet syndrome, aged 2 to 34 years. Twenty-three patients had mutations of the sodium channel α1 subunit gene, SCN1A. Assessment via video gait analysis, physical examination of the lower limbs, use of the Functional Mobility Scale, and radiographs of the pelvis and feet. Classification of the sagittal gait pattern and foot posture, assessment of muscle extensibility and joint range, and rating of functional mobility. Children aged 0 to 5 years had a normal or near-normal gait, whereas 5 of 10 children aged 6 to 12 years and 8 of 9 children aged 13 years or older had crouch gait. Physical examination showed that with increasing age, passive knee extension (P = .008) and hip extension (P = .003) decreased, external tibial torsion (P = .007) and pes planovalgus (P = .05) increased, and increased hip internal rotation did not show age-related change (P = .27). The Functional Mobility Scale showed universal independent walking over 5 and 50 m; however, adolescents showed wide variation in their ratings over 500 m, indicating mobility ranging from wheelchair use to independent walking (P = .02). Children with Dravet syndrome show progressive gait deterioration in the second decade of life, with crouch gait and skeletal malalignment comprising increased femoral neck anteversion, external tibial torsion, and pes valgus. These age-related changes have a significant impact on mobility and independence in the community setting.

Ataxia telangiectasia with abnormal cellular immunity

Ataxia telangiectasia (AT) is an autosomal recessive syndrome characterized by progressive cerebellar ataxia, immunodeficiency, which usually takes the form of sinopulmonary infections, oculocutaneous telangiectasia, X-ray hypersensitivity, and predisposition to lymphoid malignancies. A case of ataxia telangiectasia in a Yemeni boy with cerebellar atrophy, mottled pigmentations, scarring, recurrent sinopulmonary infections, and elevated alfa-fetoprotein. Ataxia telangiectasia should be suspected in the presence of progressive gait deterioration, recurrent sinupulmonary infections, inverted T4/T8 ratio, reduced B-cell count and ocular/oculo-cutaneous telangiectasia and abnormal cellular immunity. Elevated alpha-feto protein is a confirmatory test and should be done in all patients with AT.

Camptocormia in a Patient with Parkinson Disease and a Myopathy with Nemaline Rods

Camptocormia, also referred to as bent spine, is a gait disorder characterized by hyperflexion of the thoracolumbar spine that develops in recumbent position while walking and that disappears in supine position. Myopathy is one of the frequent causes of camptocormia. A 77-yr-old male patient who was followed up with the diagnosis of rheumatoid arthritis for 2 yrs was admitted with progressive gait deterioration. Hyperflexion of trunk, disappearing in supine position, was detected and diagnosed as camptocormia. He also exhibited the signs of parkinsonism. A paraspinal muscle biopsy showed myopathy with rods in many muscle fibers. Camptocormia in this patient may be attributable to the myopathic weakness of thoracolumbar paraspinal muscles. The normal biceps brachii muscle biopsy refers to the isolated affection of paraspinal muscles in this patient. A camptocormia (bent spine) case of myopathy with nemaline rods associated with Parkinson disease is presented.

Neurosarcoidosis Presenting with Lower-Back and Leg Pain

Ozer F, Ozturk O, Meral H, Serdaroglu P, Yayla V: Camptocormia in a patient with Parkinson disease and a myopathy with nemaline rods. Am J Phys Med Rehabil 2007;86:3–6. Camptocormia, also referred to as bent spine, is a gait disorder characterized by hyperflexion of the thoracolumbar spine that develops in recumbent position while walking and that disappears in supine position. Myopathy is one of the frequent causes of camptocormia. A 77-yr-old male patient who was followed up with the diagnosis of rheumatoid arthritis for 2 yrs was admitted with progressive gait deterioration. Hyperflexion of trunk, disappearing in supine position, was detected and diagnosed as camptocormia. He also exhibited the signs of parkinsonism. A paraspinal muscle biopsy showed myopathy with rods in many muscle fibers. Camptocormia in this patient may be attributable to the myopathic weakness of thoracolumbar paraspinal muscles. The normal biceps brachii muscle biopsy refers to the isolated affection of paraspinal muscles in this patient. A camptocormia (bent spine) case of myopathy with nemaline rods associated with Parkinson disease is presented.

White Matter Lesions and Disequilibrium in Older People

To identify the cause of subcortical white matter lesions seen on magnetic resonance imaging in older patients with progressive deterioration of gait and balance. Postmortem examination of three patients with objective impairment of gait and balance thought to be due to subcortical white matter lesions identified on magnetic resonance imaging. Brain sections were stained with routine methods and for glial fibrillary acid protein using an immunoperoxidase technique. Part of a prospective study of gait and balance problems in older people. None had a history of hypertension or discrete strokelike episodes. Other than a few small infarcts in the basal ganglia and internal capsule in the patient with the mildest gait disorder, there were no gross or microscopic features on routine examination post mortem to explain the white matter hyperintensities on magnetic resonance imaging or the progressive gait deterioration. By contrast, immunohistochemical staining with anti-glial fibrillary acid protein showed prominent astrocytosis T2-weighted high-intensity signal areas on magnetic resonance imaging. The astrocytes presumably swell as they take up extravasated protein at the site of a breakdown in the blood-brain barrier, and the increased water content per unit volume increases the magnetic resonance imaging proton signal. We hypothesized that the astrocytes may have been initially activated by small infarcts or subclinical ischemia, but the process then became self-perpetuating, ultimately involving most of the white matter and producing the severe gait disorder.

Adult (Chronic) GM2 Gangliosidosis

Two adult Ashkenazi Jewish siblings have had slowly progressive deterioration of gait and posture since early childhood, distal to proximal muscle atrophy, pes cavus, foot drop, spasticity, mild ataxia of limbs and trunk, dystonic features, and dysarthria. Vision and optic fundi are normal, verbal intelligence is stable, and no seizures have occurred. The sister of the patients died at 16 years of age with the same illness. Autopsy showed diffuse neuronal storage, predominating in subcortical areas, consisting of membranocytoplasmic bodies, zebra bodies, and complex lamellar structures. GM2 ganglioside was increased in her brain. Hexosaminidase A was decreased in serum and leukocytes of the living patients, and was in the range for carriers of Tay-Sachs disease in their parents. The disease found in this family represents a new, more indolent variant of GM2 gangliosidosis.