mVEGAS - mobile smartphone-based spatiotemporal gait analysis in healthy and ataxic gait disorders.

BACKGROUND: Quantitative gait assessment is increasingly applied in fall risk stratification, diagnosis, and disease monitoring of neuro-geriatric gait disorders. Its broad application, however, demands for low-cost and mobile solutions that facilitate high-quality assessment outside laboratory settings. The aim of this study was to present and evaluate the concurrent validity of a mobile and low-cost gait assessment tool (mVEGAS) that combines body-fixed inertial sensors and a smartphone-based video capture for spatiotemporal identification of gait sequences. METHODS: Initially, we examined potential interferences of wearing mVEGAS with walking performance in a cohort of 20 young healthy individuals (31.1 ± 10.1 years; 8 females). Subsequently, we assessed the concurrent validity of mVEGAS as compared to a pressure-sensitive gait carpet (GAITRite) in a cohort of 26 healthy individuals (55.8 ± 14.3 years; 10 females) and 26 patients (55.7 ± 14.0; 14 females) with moderate to severe degrees of cerebellar gait ataxia. All participants were instructed to walk at preferred, slow, and fast walking speed and standard average and variability gait measures including velocity, stride length, stride time, base of support, swing and double support phase were examined for agreement between the two systems by absolute error and intraclass correlation coefficients (ICC). RESULTS: Wearing mVEGAS did only marginally interfere with normal walking behavior. mVEGAS-derived average and variability gait measures exhibited good to excellent concurrent validity in healthy individuals (ICCs ranging between 0.645 and 1.000) and patients with gait ataxia (ICCs ranging between 0.788 and 1.000) SIGNIFICANCE: mVEGAS may facilitate high-quality and long-term gait monitoring in different non-specialized environments such as medical practices, nursing homes or community centers.

Recoverin antibody-associated late-onset ataxia without retinopathy.

Acquired cerebellar ataxia is a rare, in many cases immune-modulated and paraneoplastic illness. Acute and slowly progredient processes are possible. An early treatment is important for a good clinical outcome. Here we present the case of female patient in her 60s with an antirecoverin associated cerebellitis without retinopathia and neoplasia. After an immunosuppressive therapy with steroids and rituximab the symptoms improved, and the progression could be stopped.

Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report.

BACKGROUND: The TWNK gene encodes the twinkle protein, which is a mitochondrial helicase for DNA replication. The dominant TWNK variants cause progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, while the recessive variants cause mitochondrial DNA depletion syndrome 7 and Perrault syndrome 5. Perrault syndrome is characterized by sensorineural hearing loss in both males and females and gonadal dysfunction in females. Patients with Perrault syndrome may present early-onset cerebellar ataxia, whereas middle-age-onset cerebellar ataxia caused by TWNK variants is rare. CASE PRESENTATION: A Japanese female born to consanguineous parents presented hearing loss at age 48, a staggering gait at age 53, and numbness in her distal extremities at age 57. Neurological examination revealed sensorineural hearing loss, cerebellar ataxia, decreased deep tendon reflexes, and sensory disturbance in the distal extremities. Laboratory tests showed no abnormal findings other than a moderate elevation of pyruvate concentration levels. Brain magnetic resonance imaging revealed mild cerebellar atrophy. Using exome sequencing, we identified a homozygous TWNK variant (NM_021830: c.1358G>A, p.R453Q). CONCLUSIONS: TWNK variants could cause middle-age-onset cerebellar ataxia. Screening for TWNK variants should be considered in cases of cerebellar ataxia associated with deafness and/or peripheral neuropathy, even if the onset is not early.

Methotrexate-associated lymphoproliferative disorders in the central nervous system and stomach: A case report.

RATIONALE: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a serious complication in patients treated using methotrexate. It occasionally develops in extra-nodal sites, but rarely in the central nervous system (CNS) or in 2 different sites at the same time. We present the rare case of a patient with rheumatoid arthritis who developed lymphoma in the CNS and stomach during MTX therapy. PATIENT CONCERNS: A 75-year-old Japanese man with rheumatoid arthritis who received methotrexate was admitted to our hospital because of gait ataxia and anorexia. DIAGNOSES: Imaging findings and biopsy led to a diagnosis of 2 different types of MTX-LPD in the central nervous system and stomach. INTERVENTIONS: The lesion in his stomach improved after methotrexate withdrawal, whereas the cerebellar mass required high-dose methotrexate and rituximab therapy. OUTCOMES: Complete remission has been maintained for the 2 years following the initiation of chemotherapy. LESSONS: In patients with RA who receive MTX and develop new neurological symptoms, CNS lymphoma as an MTX-LPD may be considered as a differential diagnosis.

Síndrome de WEBINO (wall-eyed bilateral internuclear ophthalmoplegia) secundario a ictus isquémico, a propósito de un caso / WEBINO syndrome (wall-eyed bilateral internuclear ophthalmoplegia) secondary to ischemic stroke, about a case

El síndrome de WEBINO (wall-eyed bilateral internuclear ophthalmoplegia) se caracteriza por un déficit bilateral en la aducción ocular, nistagmo horizontal bilateral a la abducción, así como la presencia de exotropía en la mirada primaria. Presentamos el caso de un paciente varón de 68 años que se presentó en el servicio de urgencias con diplopía de inicio súbito. La exploración fue compatible con síndrome de WEBINO, y también presentaba ataxia de la marcha. Entre los antecedentes relevantes, constaba que era trasplantado hepático en tratamiento con tacrolimus. Las exploraciones complementarias pusieron de manifiesto la existencia de una lesión isquémica en tegmento mesencefálico, involucrando el fascículo longitudinal medial de forma bilateral, así como el área pretectal. El síndrome de WEBINO es un síndrome poco frecuente. Entre las etiologías destacan la isquémica y la desmielinizante como las más frecuentes. En nuestro caso también se consideró la iatrogenia. La lesión asienta en un área anatómica específica, siendo clave su conocimiento para la realización de exploraciones complementarias que lleven al diagnóstico etiológico específico

WEBINO (wall-eyed bilateral internuclear ophthalmoplegia) syndrome is characterized by bilateral adduction impairment, nystagmus of the abducting eye, and primary gaze exotropia. We present the case of a 68 year-old man who was initially attended in emergency department with sudden onset diplopia. Neurological exploration revealed WEBINO and gait ataxia. Relevant medical history included liver transplantation and subsequent tacrolimus prescription. Complementary exams revealed ischemic lesion in mesencephalic tegmentum, involving medial longitudinal fasciculus and pretectal area. WEBINO syndrome is unfrequent. Among its etiologies, ischemic and demyelinating are the most frequent. In our case, iatrogenic etiology was also considered. Clinical recognition of this syndrome is required to perform adequate exams in order to reach diagnosis

A man in his sixties with gait ataxia, dysarthria and mild cognitive impairment. / En mann i 60-årene med gangvansker, dysartri og lett kognitiv svikt.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is an immune-mediated, treatable and inflammatory CNS disease first reported by Pittock et al. (2010). CASE PRESENTATION: We describe a 66-year-old man with previous history of diabetes, atrial fibrillation and hypertension, who was admitted to hospital with reduced general condition. He had experienced dizziness and unstable gait for a year, and had been periodically confused, especially in the previous month. MR imaging showed characteristic punctuate and curvilinear gadolinium enhancements in the pons. Our patient was diagnosed with CLIPPERS and was given corticosteroid treatment, initially methylprednisolone intravenously and then prednisone orally. Other differential diagnoses, such as CNS lymphoma, high-grade glioma, CNS vasculitis, neurosarcoidosis, demyelinating disease, Bickerstaff brainstem encephalitis, and acute disseminated encephalomyelitis were ruled out. The patient's condition improved dramatically after corticosteroid treatment. INTERPRETATION: In 2017, the diagnostic criteria for CLIPPERS were published. Based on these criteria we were able to diagnose this patient with possible CLIPPERS, consistent with clinical symptoms, MRI findings, absence of better explanations for the condition, and clinical and radiological improvement after treatment with corticosteroids. An unequivocal diagnosis of CLIPPERS can only be established by characteristic pathological findings.

WEBINO syndrome (wall-eyed bilateral internuclear ophthalmoplegia) secondary to ischemic stroke, about a case. / Síndrome de WEBINO (wall-eyed bilateral internuclear ophthalmoplegia) secundario a ictus isquémico, a propósito de un caso.

WEBINO (wall-eyed bilateral internuclear ophthalmoplegia) syndrome is characterized by bilateral adduction impairment, nystagmus of the abducting eye, and primary gaze exotropia. We present the case of a 68 year-old man who was initially attended in emergency department with sudden onset diplopia. Neurological exploration revealed WEBINO and gait ataxia. Relevant medical history included liver transplantation and subsequent tacrolimus prescription. Complementary exams revealed ischemic lesion in mesencephalic tegmentum, involving medial longitudinal fasciculus and pretectal area. WEBINO syndrome is unfrequent. Among its etiologies, ischemic and demyelinating are the most frequent. In our case, iatrogenic etiology was also considered. Clinical recognition of this syndrome is required to perform adequate exams in order to reach diagnosis.

A deep intronic splice variant advises reexamination of presumably dominant SPG7 Cases.

OBJECTIVE: To identify causative mutations in a patient affected by ataxia and spastic paraplegia. METHODS: Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were performed using patient's DNA sample. RT-PCR and cDNA Sanger sequencing were performed on RNA extracted from patient's fibroblasts, as well as western blot. RESULTS: A novel missense variant in SPG7 (c.2195T> C; p.Leu732Pro) was first found by whole-exome sequencing (WES), while the second, also unreported, deep intronic variant (c.286 + 853A>G) was identified by whole-genome sequencing (WGS). RT-PCR confirmed the in silico predictions showing that this variant activated a cryptic splice site, inducing the inclusion of a pseudoexon into the mRNA sequence, which encoded a premature stop codon. Western blot showed decreased SPG7 levels in patient's fibroblasts. INTERPRETATION: Identification of a deep intronic variant in SPG7, which could only have been detected by performing WGS, led to a diagnosis in this HSP patient. This case challenges the notion of an autosomal dominant inheritance for SPG7, and illustrates the importance of performing WGS subsequently or alternatively to WES to find additional mutations, especially in patients carrying one variant in a gene causing a predominantly autosomal recessive disease.

Vestibular dysfunction in acute traumatic brain injury.

Traumatic brain injury (TBI) is the commonest cause of disability in under-40-year-olds. Vestibular features of dizziness (illusory self-motion) or imbalance which affects 50% of TBI patients at 5 years, increases unemployment threefold in TBI survivors. Unfortunately, vestibular diagnoses are cryptogenic in 25% of chronic TBI cases, impeding therapy. We hypothesized that chronic adaptive brain mechanisms uncouple vestibular symptoms from signs. This predicts a masking of vestibular diagnoses chronically but not acutely. Hence, defining the spectrum of vestibular diagnoses in acute TBI should clarify vestibular diagnoses in chronic TBI. There are, however, no relevant acute TBI data. Of 111 Major Trauma Ward adult admissions screened (median 38-years-old), 96 patients (87%) had subjective dizziness (illusory self-motion) and/or objective imbalance were referred to the senior author (BMS). Symptoms included: feeling unbalanced (58%), headache (50%) and dizziness (40%). In the 47 cases assessed by BMS, gait ataxia was the commonest sign (62%) with half of these cases denying imbalance when asked. Diagnoses included BPPV (38%), acute peripheral unilateral vestibular loss (19%), and migraine phenotype headache (34%), another potential source of vestibular symptoms. In acute TBI, vestibular signs are common, with gait ataxia being the most frequent one. However, patients underreport symptoms. The uncoupling of symptoms from signs likely arises from TBI affecting perceptual mechanisms. Hence, the cryptogenic nature of vestibular symptoms in TBI (acute or chronic) relates to a complex interaction between injury (to peripheral and central vestibular structures and perceptual mechanisms) and brain-adaptation, emphasizing the need for acute prospective, mechanistic studies.

The Responsiveness of Triaxial Accelerometer Measurement of Gait Ataxia Is Higher than That of the Scale for the Assessment and Rating of Ataxia in the Early Stages of Spinocerebellar Degeneration.

We reported previously that the average medial-lateral gait amplitude while walking on a straight path determined using triaxial accelerometers fixed on the middle of the upper back may be a quantitative and concise indicator for the severity of cerebellar ataxia. Considering that gait ataxia is a typical initial symptom in a variety of spinocerebellar degeneration (SCD), we aimed to develop quantitative biomarkers for cerebellar ataxia as metric variables. We used triaxial accelerometers to analyze gait parameters in 14 patients with SCD at 3 points over 3 years (at baseline, 1.5 years and 3 years). Analysis of covariance (ANCOVA) models adjusted for the baseline scores were used to estimate sample sizes. The mean medial-lateral amplitude (ML) gained by a triaxial accelerometer fixed on upper back could detect the each 1.5-year change. In the 14 patients, the mean ML(m) was 0.032 ± 0.007(SD) at entry, 0.037 ± 0.008 after 1.5-year follow, and 0.042 ± 0.020 after 3-year follow. In contrast, SARA gait scores were 2.9, 2.9, and 3.0, respectively. The responsiveness of the quantitative evaluation of gait ataxia by triaxial accelerometers is higher than that of the SARA within a 1.5-year follow-up period. Gait analysis by triaxial accelerometers will be complementary to the evaluation of scales like SARA in the assessment of clinical severity of SCD patients in early stage.

Clinical Study on 3 Patients with Infarction of the Vermis/Tonsil in the Cerebellum.

BACKGROUND: Infarction of the vermis and the tonsil in the cerebellum presents as truncal and gait ataxia. Acute rotatory vertigo is often present in infarction of the nodulus in the caudal vermis, which is closely associated with the vestibular pathway, but is minor in infarction of the rostral vermis. The rostral vermis receives input from the dorsal spinocerebellar tract (DSCT) which conveys unconsciousness proprioceptive signals from the ipsilateral lower trunk and leg. The present study investigated the characteristics of infarction of the vermis and the tonsil. PATIENTS AND METHODS: Neuroradiological findings of 3 patients whose lesions were located in the vermis or the tonsil were analyzed. RESULTS: All lesions were located in the anterior lobe in the rostral vermis, the nodulus in the caudal vermis, or the tonsil. Truncal and gait ataxia were exhibited by 3 patients. Rotatory vertigo was exhibited by 2 patients whose lesions were located in the nodulus and the tonsil, but absent in a patient with infarction of the anterior lobe. Lateropulsion opposite the lesion was apparent in a patient with infarction of the tonsil. Gaze-evoked nystagmus was observed in 2 patients with infarction of the nodulus and the tonsil. CONCLUSIONS: The tonsil and the nodulus were considered to have a close relationship with the vestibular pathway. Absence of rotatory vertigo indicated impairment of the DSCT. Our data suggested that the cause of truncal and gait ataxia differed between the rostral vermis and the caudal vermis/tonsil.

Gait Disorders.

Walking is an extraordinarily complex task requiring integration of the entire nervous system, making gait susceptible to a variety of underlying neurologic abnormalities. Gait disorders are particularly prevalent in the elderly and increase fall risk. In this review we discuss an approach to the examination of gait and highlight key features of common gait disorders and their underlying causes. We review gaits due to lesions of motor systems (spasticity and neuromuscular weakness), the cerebellum and sensory systems (ataxia), parkinsonism, and frontal lobes and discuss the remarkably diverse phenomenology of functional (psychogenic) gait disorders. We offer a pragmatic approach to the diagnosis and management of neurologic gait disorders, because prompt recognition and intervention may improve quality of life in affected individuals.

Kinematic discrimination of ataxia in horses is facilitated by blindfolding.

BACKGROUND: Agreement among experienced clinicians is poor when assessing the presence and severity of ataxia, especially when signs are mild. Consequently, objective gait measurements might be beneficial for assessment of horses with neurological diseases. OBJECTIVES: To assess diagnostic criteria using motion capture to measure variability in spatial gait-characteristics and swing duration derived from ataxic and non-ataxic horses, and to assess if variability increases with blindfolding. STUDY DESIGN: Cross-sectional. METHODS: A total of 21 horses underwent measurements in a gait laboratory and live neurological grading by multiple raters. In the gait laboratory, the horses were made to walk across a runway surrounded by a 12-camera motion capture system with a sample frequency of 240 Hz. They were made to walk normally and with a blindfold in at least three trials each. Displacements of reflective markers on head, fetlock, hoof, fourth lumbar vertebra, tuber coxae and sacrum derived from three to four consecutive strides were processed and descriptive statistics, receiver operator characteristics (ROC) to determine the diagnostic sensitivity, specificity and area under the curve (AUC), and correlation between median ataxia grade and gait parameters were determined. RESULTS: For horses with a median ataxia grade ≥2, coefficient of variation for the location of maximum vertical displacement of pelvic and thoracic distal limbs generated good diagnostic yield. The hoofs of the thoracic limbs yielded an AUC of 0.81 with 64% sensitivity and 90% specificity. Blindfolding exacerbated the variation for ataxic horses compared to non-ataxic horses with the hoof marker having an AUC of 0.89 with 82% sensitivity and 90% specificity. MAIN LIMITATIONS: The low number of consecutive strides per horse obtained with motion capture could decrease diagnostic utility. CONCLUSIONS: Motion capture can objectively aid the assessment of horses with ataxia. Furthermore, blindfolding increases variation in distal pelvic limb kinematics making it a useful clinical tool.

Screening and referral for children with physical disabilities.

The clinical care of children with physical disabilities is a major priority for paediatricians and paediatric orthopaedic surgeons. Cerebral palsy (CP) is the prototypical condition and remains the most common cause of physical disability in developed countries. The incidence is approximately 2 per 1000 live births, translating to between 600 and 700 new children per annum in Australia, with approximately 34 000 children and adults currently living with CP. This figure is predicted to rise inexorably over the next 20 years. The care of children with physical disabilities, including those with CP, is usually coordinated by paediatricians, general practitioners and allied health teams including physiotherapists, with input from paediatric orthopaedic surgeons when appropriate. The emphasis in care for children with CP has moved from 'reactive' to 'proactive'. In the past, children are often referred when symptomatic, for example when a hip dislocation had occurred and became painful. The emphasis now is on coordinated, multidisciplinary care in which musculoskeletal manifestations of disability are identified by screening programmes. Systematic screening, especially when population-based and linked to a register, avoids children getting 'lost in the system'. Early and more effective interventions may be offered for the prevention of contractures, dislocation of the hip and spinal deformities. In this review, we will focus on the assessment of gait in children with physical disabilities, and monitoring for hip and spine deformity.