MRI preclinical detection and asymptomatic course of a progressive multifocal leucoencephalopathy (PML) under natalizumab therapy.

Early detection of progressive multifocal leucoencephalopathy (PML) in the setting of natalizumab therapy currently is performed by rapid evaluation of new symptoms occurring in treated patients. The role of MR scanning has not been investigated but holds promise since MR detection is highly sensitive for PML lesions. The authors report a case of presymptomatic PML of the posterior fossa detected by MR scans. Immediate suspension of natalizumab and plasma exchanges resulted in a rapid decline of natalizumab serum concentration. Intravenous steroids started together with plasma exchanges followed by an oral tapering course were used to minimise the immune reconstitution inflammatory syndrome. No symptoms (beyond mild headache) developed, and the repeat PCR for JC Virus (JCV) DNA detection performed 10 weeks later was negative. This case suggests that: (1) periodic brain MR scans may detect signs of presymptomatic PML in MS patients treated with natalizumab, (2) corticosteroid management of inflammatory reaction may contribute to optimal control of the immune reconstitution inflammatory syndrome routinely seen with natalizumab-associated PML and (3) early radiological detection of PML can have an excellent outcome even in a clinically critical region and despite prior immunosuppressant exposure. The potential benefit of regular MR scanning just using the T2/FLAIR modalities could be further investigated in order to detect early natalizumab-associated PML, leading to benign outcomes.

Rapid, postmortem 9.4 T MRI of spinal cord injury: correlation with histology and survival times.

High field magnetic resonance imaging (MRI) has been increasingly used to assess experimental spinal cord injury (SCI). In the present investigation, after partial spinal cord injury and excision of the whole spine, pathological changes of the spinal cord were studied in spinal cord-spine blocks, from the acute to the chronic state (24 h to 5 months). Using proton density (PD) weighted imaging parameters at a magnetic field strength of 9.4 tesla (T), acquisition times ranging from <1 to 10 h per specimen were used. High in-plane pixel resolution (68 and 38 microm, respectively) was obtained, as well as high signal-to-noise ratio (SNR), which is important for optimal contrast settings. The quality of the resulting MR images was demonstrated by comparison with histology. The cord and the lesion were shown in their anatomical surroundings, detecting cord swelling in the acute phase (24 h to 1 week) and cord atrophy at the chronic stage. Haemorrhage was detected as hypo-intense signal. Oedema, necrosis and scarring were hyper-intense but could not be distinguished. Histology confirmed that the anatomical delimitation of the lesion extent by MRI was precise, both with high and moderate resolution. The present investigation thus demonstrates the precision of spinal cord MRI at different survival delays after compressive partial SCI and establishes efficient imaging parameters for postmortem PD MRI.

Motor fatigue measurement by distance-induced slow down of walking speed in multiple sclerosis.

BACKGROUND AND RATIONALE: Motor fatigue and ambulation impairment are prominent clinical features of people with multiple sclerosis (pMS). We hypothesized that a multimodal and comparative assessment of walking speed on short and long distance would allow a better delineation and quantification of gait fatigability in pMS. Our objectives were to compare 4 walking paradigms: the timed 25-foot walk (T25FW), a corrected version of the T25FW with dynamic start (T25FW(+)), the timed 100-meter walk (T100MW) and the timed 500-meter walk (T500MW). METHODS: Thirty controls and 81 pMS performed the 4 walking tests in a single study visit. RESULTS: The 4 walking tests were performed with a slower WS in pMS compared to controls even in subgroups with minimal disability. The finishing speed of the last 100-meter of the T500MW was the slowest measurable WS whereas the T25FW(+) provided the fastest measurable WS. The ratio between such slowest and fastest WS (Deceleration Index, DI) was significantly lower only in pMS with EDSS 4.0-6.0, a pyramidal or cerebellar functional system score reaching 3 or a maximum reported walking distance ≤ 4000 m. CONCLUSION: The motor fatigue which triggers gait deceleration over a sustained effort in pMS can be measured by the WS ratio between performances on a very short distance and the finishing pace on a longer more demanding task. The absolute walking speed is abnormal early in MS whatever the distance of effort when patients are unaware of ambulation impairment. In contrast, the DI-measured ambulation fatigability appears to take place later in the disease course.

Construction and validation of the Dynamic Parkinson Gait Scale (DYPAGS).

The dynamic evaluation of Parkinson's disease (PD)-related episodic gait disturbances in routine is challenging. Therefore, the aim of our study was to assess the reliability/validity of the Dynamic Parkinson Gait Scale (DYPAGS) composed of eight relevant items for the objective quantification of PD gait features: walking forwards/backwards/with dual-task, turning to both sides, imaginary obstacle avoidance with both legs and passing through narrow spaces. The scale was validated on thirty-five patients with mild to severe parkinsonism in their habitual "on-state". A shorter 6 item-version was designed on the basis of a principal component analysis. No significant floor/ceiling effect was detected. The internal consistency was excellent. The levels of interrater agreement, precision and minimal detectable change were adequate. The criterion-related validity was demonstrated by strong correlations with the DYPAGS scores and those at the gait subscales of the Tinetti Mobility Test and MDS-UPDRS. The construct validity was assessed by moderate-strong correlations with the Freezing of Gait Questionnaire, mobility index of the PD Questionnaire (PDQ-39), disease duration and levodopa equivalent daily doses. Statistical analyses using the coefficient of determination showed that both DYPGAS versions were superior to the other instruments to identify patients with gait disturbances with poorer response to dopaminergic treatment. Full and short DYPAGS are reliable instruments for the quantification of "on" PD-related episodic gait disturbances. The full version is sensitive to detect subtle disturbances in mild parkinsonism. The shorter one is easily administered and reliably quantifies gait disturbances in moderate to severe parkinsonism. We recommend their use for research and clinical practice.

Comparison of the timed 25-foot and the 100-meter walk as performance measures in multiple sclerosis.

BACKGROUND: Ambulation impairment is a major component of physical disability in multiple sclerosis (MS) and a major target of rehabilitation programs. Outcome measures commonly used to evaluate walking capacities suffer from several limitations. OBJECTIVES: To define and validate a new test that would overcome the limitations of current gait evaluations in MS and ultimately better correlate with the maximum walking distance (MWD). METHODS: The authors developed the Timed 100-Meter Walk Test (T100MW), which was compared with the Timed 25-Foot Walk Test (T25FW). For the T100MW, the subject is invited to walk 100 m as fast as he/she can. In MS patients and healthy control volunteers, the authors measured the test-retest and interrater intraclass correlation coefficient. Spearman rank correlations were obtained between the T25FW, the T100MW, the Expanded Disability Status Scale (EDSS), and the MWD. The coefficient of variation, Bland-Altman plots, the coefficient of determination, and the area under the receiver operator characteristic curve were measured. The mean walking speed (MWS) was compared between the 2 tests. RESULTS: A total of 141 MS patients and 104 healthy control volunteers were assessed. Minor differences favoring the T100MW over the T25FW were observed. Interestingly, the authors demonstrated a paradoxically higher MWS on a long (T100MW) rather than on a short distance walk test (T25FW). CONCLUSION: The T25FW and T100MW displayed subtle differences of reproducibility, variability, and correlation with MWD favoring the T100MW. The maximum walking speed of MS patients may be poorly estimated by the T25FW since MS patients were shown to walk faster over a longer distance.