Jens A. Petersen

Chronic Cervical Spinal Cord Injury: DTI Correlates with Clinical and Electrophysiological Measures

Diffusion tensor imaging (DTI) is rarely applied in spinal cord injury (SCI). The aim of this study was to correlate diffusion properties after SCI with electrophysiological and neurological measures. Nineteen traumatic cervical SCI subjects and 28 age-matched healthy subjects participated in this study. DTI data of the spinal cord were acquired with a Philips Achieva 3 T MR scanner using an outer volume suppressed, reduced field of view (FOV) acquisition with oblique slice excitation and a single-shot EPI readout. Neurological and electrophysiological measures, American Spinal Injury Association (ASIA) impairment scale scores, and motor (MEP) and somatosensory evoked potentials (SSEP) were assessed in SCI subjects. Fractional anisotropy (FA) values were decreased in the SCI subjects compared to the healthy subjects. In upper cervical segments, the decrease in FA was significant for the evaluation of the entire cross-sectional area of the spinal cord, and for corticospinal and sensory tracts. A decreasing trend was also found at the thoracic level for the corticospinal tracts. The decrease of DTI values correlated with the clinical completeness of SCI, and with SSEP amplitudes. The reduced DTI values seen in the SCI subjects are likely due to demyelination and axonal degeneration of spinal tracts, which are related to clinical and electrophysiological measures. A reduction in DTI values in regions remote from the injury site suggests their involvement with wallerian axonal degeneration. DTI can be used for the quantitative evaluation of the extent of spinal cord damage, and eventually to monitor the effects of future regeneration-inducing treatments.

Spinal Cord Injury One-Year Evolution of Motor-Evoked Potentials and Recovery of Leg Motor Function in 255 Patients

Background. The description of the natural course of recovery from a spinal cord injury (SCI) with spontaneous improvement of neurological, neurophysiological, and functional measures is an important prerequisite in appraising effects of upcoming interventional therapies. Objective. To describe the spontaneous evolution of motor-evoked potentials of the anterior tibial muscle (TA-MEP) and their relation to outcomes of lower extremity motor scores (LEMS) and walking function in patients recovering from an acute SCI. Methods. TA-MEPs were assessed in 255 SCI subjects within 5 time intervals throughout the first year after SCI with combined neurological and functional measures. Tibial nerve conduction studies were performed to screen for peripheral nerve damage. Results. TA-MEP allowed stratification of SCI according to lesion severity and outcome. As MEP amplitudes increased over 12 months after SCI, this was paralleled by a significant improvement of LEMS and walking function. TA-MEP latencies remained usually stable. Conclusion. Clinical outcome and walking function after SCI can be predicted independent of clinical measures by assessment of TA-MEP reflecting corticospinal tract integrity.

Clinical diagnosis of bilateral vestibular loss: three simple bedside tests

Bilateral vestibular loss (BVL) may present with or without vertigo and hearing loss. Amongst the causes of BVL are vestibulotoxic antibiotics, autoimmune ear diseases, Menière’s disease and meningitis. Clinical diagnosis of BVL is based on the result of three simple bedside tests: a positive head impulse test, reduced dynamic visual acuity and a positive Romberg test on foam rubber. With these signs, diagnosis of severe BVL is usually straightforward to establish.

Spinal Cord Diffusion-Tensor Imaging and Motor-evoked Potentials in Multiple Sclerosis Patients: Microstructural and Functional Asymmetry

PURPOSE To assess possible association between intrinsic structural damage and clinical disability by correlating spinal cord diffusion-tensor (DT) imaging data with electrophysiological parameters in patients with a diagnosis of multiple sclerosis (MS). MATERIALS AND METHODS This study was approved by the local ethical committee according to the declaration of Helsinki and written informed consent was obtained. DT images and T1- and T2-weighted images of the spinal cord were acquired in 28 healthy volunteers and 41 MS patients. Fractional anisotropy (FA) and apparent diffusion coefficients were evaluated in normal-appearing white matter (NAWM) at the cervical level and were correlated with motor-evoked potentials (n = 34). Asymmetry index was calculated for FA values with corresponding left and right regions of interest as percentage of the absolute difference between these values relative to the sum of the respective FA values. Statistical analysis included Spearman rank correlations, Mann-Whitney test, and reliability analysis. RESULTS Healthy volunteers had low asymmetry index (1.5%-2.2%). In MS patients, structural abnormalities were reflected by asymmetric decrease of FA (asymmetry index: 3.6%; P = .15). Frequently asymmetrically affected among MS patients was left and right central motor conduction time (CMCT) to abductor digiti minimi muscle (ADMM) (asymmetry index, 15%-16%) and tibialis anterior muscle (TAM) (asymmetry index, 9.5%-14.1%). Statistically significant correlations of functional (ie, electrophysiological) and structural (ie, DT imaging) asymmetries were found (P = .005 for CMCT to ADMM; P = .007 for CMCT to TAM) for the cervical lateral funiculi, which comprise the crossed pyramidal tract. Interobserver reliability for DT imaging measurements was excellent (78%-87%). CONCLUSION DT imaging revealed asymmetric anatomic changes in spinal cord NAWM, which corresponded to asymmetric electrophysiological deficits for both arms and legs, and reflected a specific structure-function relationship in the human spinal cord.

Monitoring long-term efficacy of fampridine in gait-impaired patients with multiple sclerosis

Objective: To expand upon the limited knowledge of the long-term effects of prolonged-release (PR) fampridine in patients with multiple sclerosis (PwMS) regarding safety, walking improvements, and changes in drug responsiveness. Methods: Fifty-three PwMS who completed the FAMPKIN core study were included in this extension trial. Drug efficacy was assessed in an open-label and randomized double-blind, placebo-controlled study design with regular baseline assessments over a period of 2 years using the Timed 25-Foot Walk (T25FW), 6-Minute Walk Test (6MWT), and 12-item MS Walking Scale (MSWS-12) as outcome measures. Results: The data showed good tolerability and persisting efficacy of PR fampridine during long-term treatment in PwMS. Significant improvements in walking speed, endurance, and self-perceived ambulatory function were observed during open-label (T25FW: +11.5%; 6MWT: 10.7%; MSWS-12: 6.1 points) and double-blind controlled treatment with PR fampridine (T25FW: +13.1%; 6MWT: 11.9%; MSWS-12: 7.4 points). Several patients showed changes in drug responsiveness over time, resulting in an increased proportion of patients exceeding 10% or 20% improvements in walking measures after long-term treatment. Conclusions: Efficacy and tolerability data confirmed PR fampridine as a valuable long-term treatment for improving ambulatory function in gait-impaired PwMS. Similar results in open-label and double-blind phases reveal that the walking tests used are objective and reliable. The considerable proportion of patients in whom responsiveness to PR fampridine changed over time emphasizes the importance of regular reassessment of drug efficacy in clinical practice to optimize treatment. Such reassessments seem to be particularly important in patients with poor initial drug responses, as this group demonstrated enhanced responsiveness after long-term treatment. Clinicaltrials.gov identifier: NCT01576354. Classification of evidence: This study provides Class II evidence that PR fampridine significantly improved gait compared to placebo in a 2-week study in PwMS who had been using PR fampridine for 2 years.

Vestibular impairment in patients with Charcot-Marie-tooth disease.

Objective: This case-control study aimed to determine whether the imbalance in Charcot-Marie-Tooth (CMT) disease is caused only by reduced proprioceptive input or whether the involvement of the vestibular nerve is an additional factor. Methods: Fifteen patients with CMT disease (aged 48 ± 17 years; 8 women) underwent cervical vestibular-evoked myogenic potentials, which reflect otolith-spinal reflex function, and quantitative horizontal search-coil head-impulse testing, which assesses the high-acceleration vestibulo-ocular reflex of the semicircular canals. Results: Relative to healthy age-matched control subjects, cervical vestibular-evoked myogenic potentials were found to be impaired in 75% of patients (average p13 latency: 23.0 ± 2.7 milliseconds, p = 0.01; average n23 latency: 29.0 ± 1.8 milliseconds, p = 0.01) and the quantitative head-impulse test in 60% of patients (average gain ± 1 SD: 0.67 ± 0.24, p < 0.001). All patients with head-impulse test impairment also showed cervical vestibular-evoked myogenic potential abnormalities, while the reverse was not true. Conclusions: We conclude that the neuropathic process in patients with CMT disease frequently involves the vestibular nerve and that cervical vestibular-evoked myogenic potentials may be more sensitive than quantitative head-impulse testing for detecting vestibular involvement, in particular at an early disease stage.

The pivotal sign of CANVAS

A 75-year-old woman complained about insecure gait since age 55. Clinical examination revealed signs of cerebellar ataxia, bilateral vestibulopathy, and peripheral sensory impairment. Sensory nerve action potentials were absent. The visually enhanced vestibulo-ocular reflex (VVOR) was impaired (video on the Neurology® Web site at www.neurology.org, figure 1) and the diagnosis of cerebellar ataxia (figure 2) with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) was made.1 CANVAS is considered to be a recessive disorder with a mean age at onset of 60 years.2 VVOR impairment is its characteristic clinical sign.2 It can only be elicited if both smooth-pursuit eye movements and the vestibulo-ocular reflex are deficient. Normally, both are redundant at low head velocities.2

The thermolabile variant of 5,10-methylenetetrahydrofolate reductase is a possible risk factor for amyotrophic lateral sclerosis

Abstract Hyperhomocysteinemia is a risk factor for neurodegeneration, and binding of copper by homocysteine is a putative underlying mechanism. As mutations of the copper-dependent superoxide dismutase are observed in familial ALS, we tested whether genetic variants with influence on homocysteine metabolism are associated with ALS. We compared the frequency of seven variants of genes involved in homocysteine metabolism in 162 patients with sporadic ALS and 162 controls who did not significantly differ in age (t = 1.27, p = 0.205) and gender (χ2 = 2.48, p = 0.115) using binary regression analysis. Results showed that the variant MTHFR c.677C>T was significantly associated with ALS, i.e. the T-allele was more frequent among patients. Explorative regression analysis revealed that MTHFR c.677C>T was not associated with spinal ALS, but with bulbar onset: CC/CT/TT in patients 0.33/0.51/0.16 versus 0.50/0.44/0.06 in controls; Wald = 5.73, p = 0.017. In addition, DHFR c.594+59del19bp was not associated with spinal, but with bulbar onset: del,del/del,ins/ins,ins in patients 0.16/0.67/0.18 versus 0.11/0.52/0.37 in controls; Wald = 5.02, p = 0.025. The other variants did not show significant associations. In summary, the variants MTHFR c.677C>T and DHFR c.594+59del19bp are involved in homocysteine metabolism. Homocysteine is neurotoxic and binds copper. Thus, the individual variability of homocysteine metabolism, e.g. due to genetic variants, may contribute to the vulnerability of ALS.

Anomalous origin of the right coronary artery from the pulmonary artery: a rare finding in an asymptomatic man

A 47-year-old Caucasian man was admitted to our hospital with a transient right-sided hemi-syndrome. Cerebral angiography revealed a stenotic left-sided middle cerebral artery. Transthoracic echocardiography and transoesophageal echocardiography did not identify a cardiac source of embolus; however, an abnormal right coronary artery (RCA) was suspected ( Panel A ). Cardiac computed …

Teaching NeuroImages: Variant of Guillain-Barré syndrome with spinal cord involvement

A 48-year-old man presented with ascending sensory deficits over 12 hours, followed by urinary retention. He had areflexia, mild lower extremity weakness, sensory ataxia, and a T2 sensory level. Smooth pursuit was impaired, but cranial nerves were otherwise normal. Diagnostic evaluation demonstrated CSF cytoalbuminologic dissociation and demyelinating polyneuropathy fulfilling the electrodiagnostic criteria for Guillain-Barré syndrome (GBS).1 Laboratory evaluation had normal results, including vitamin B12; anti–neuromyelitis optica, antineuronal, and ganglioside antibodies; and oligoclonal bands. Myelopathy was confirmed on MRI (figure). This case highlights that acquired acute demyelination may rarely affect the peripheral and CNS simultaneously (GBS–transverse myelitis overlap syndrome), likely related to common autoimmune-mediated pathomechanisms.2