Motor cortex metabolite alterations in amyotrophic lateral sclerosis assessed in vivo using edited and non-edited magnetic resonance spectroscopy.

Previous MRI and proton spectroscopy (1H-MRS) studies have revealed impaired neuronal integrity and altered neurometabolite concentrations in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). Here, we aim to use MRI with conventional and novel MRS sequences to further investigate neurometabolic changes in the motor cortex of ALS patients and their relation to clinical parameters. We utilized the novel HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy) MRS sequence to simultaneously quantify the inhibitory neurotransmitter GABA and antioxidant glutathione in ALS patients (n = 7) and healthy controls (n = 7). In addition, we have also quantified other MRS observable neurometabolites using a conventional point-resolved MR spectroscopy (PRESS) sequence in ALS patients (n = 20) and healthy controls (n = 20). We observed a trend towards decreasing glutathione concentrations in the motor cortex of ALS patients (p = 0.0842). In addition, we detected a 11% decrease in N-acetylaspartate (NAA) (p = 0.025), a 15% increase in glutamate + glutamine (Glx) (p = 0.0084) and a 21% increase in myo-inositol (mIns) (p = 0.0051) concentrations for ALS patients compared to healthy controls. Furthermore, significant positive correlations were found between GABA-NAA (p = 0.0480; Rρ = 0.7875) and NAA-mIns (p = 0.0448; Rρ = -0.4651) levels among the patients. NAA levels in the bulbar-onset patient group were found to be significantly (p = 0.0097) lower compared to the limb-onset group. A strong correlation (p < 0.0001; Rρ = -0,8801) for mIns and a weak correlation (p = 0.0066; Rρ = -0,6673) for Glx was found for the disease progression, measured by declining of the ALS Functional Rating Scale-Revised criteria (ALSFRS-R). Concentrations of mIns and Glx also correlated with disease severity measured by forced vital capacity (FVC). Results suggest that mean neurometabolite concentrations detected in the motor cortex may indicate clinical and pathological changes in ALS.

Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis.

AIMS: Amyotrophic lateral sclerosis (ALS) is the most common motor neuron degeneration disease with a diagnostic delay of about 1 year after symptoms onset. In ALS, blood neurofilament light chain (NfL) levels are elevated, but it is not entirely clear what drives this increase and what the diagnostic performance of serum NfL is in terms of predictive values and likelihood ratios. The aims of this study were to further explore the prognostic and diagnostic performances of serum NfL to discriminate between patients with ALS and ALS mimics, and to investigate the relationship between serum NfL with motor neuron degeneration. METHODS: The diagnostic performances of serum NfL were based on a cohort of 149 serum samples of patients with ALS, 19 serum samples of patients with a disease mimicking ALS and 82 serum samples of disease control patients. The serum NfL levels were correlated with the number of regions (thoracic, bulbar, upper limb and lower limb) displaying upper and/or lower motor neuron degeneration. The prognostic performances of serum NfL were investigated based on a Cox regression analysis. RESULTS: The associated predictive values and likelihood ratio to discriminate patients with ALS and ALS mimics were established. Serum NfL was associated with motor neuron degeneration driven by upper motor neuron (UMN) degeneration and was independently associated with survival in patients with ALS. CONCLUSIONS: Altogether, these findings suggest that elevated serum NfL levels in ALS are driven by UMN degeneration and the disease progression rate and are independently associated with survival at time of diagnosis.

Cervical spinal cord injuries in patients with refractory epilepsy.

The incidence of cervical spinal cord injuries (c-SCI) in patients with refractory epilepsy is 30-40 times higher than in the normal population. The injuries occur after seizure-related falls. Risk factors and pitfalls in diagnosis are discussed. Awareness of the risk within this population of developing c-SCI should receive more widely recognition, especially in centres that treat this population.

Randomized double-blind parallel-group study comparing cognitive effects of a low-dose lamotrigine with valproate and placebo in healthy volunteers.

PURPOSE: This study aimed at investigating the cognitive and mood effects of lamotrigine (LTG) versus valproate (VPA) and placebo (PBO). METHODS: By studying the effects in healthy volunteers, it is possible to separate the genuine effects of LTG from the cognitive improvements, caused by better seizure control. The study used a pretest-posttest comparison of 50 mg LTG, 900 mg VPA, or PBO in a double-blind single-dummy parallel-group design with 30 healthy volunteers. Study duration was 12 days (with a last control on day 13). Outcome measures included cognitive tests (FePsy neuropsychological test battery), mood scales (ASL; mood-rating scale), and a scale for subjective complaints (ABNAS Neurotoxicity scale). Total sleep time was controlled with actigraphic recordings. The results were analyzed by comparing the change over time (pretest with posttest) for the three treatments with Student's t tests. RESULTS: COGNITIVE TESTS: significant differences between the treatments were found for measurements of cognitive activation (i.e., three of the four simple reaction-time measurements showed statistically significant differences in change between PBO and LTG in favor of LTG (p=0.03; 0.03; 0.04); two of four tests showed statistically significant differences in change between LTG and VPA, both in favor of LTG (p=0.03; 0.05). SUBJECTIVE COMPLAINTS: the ABNAS-neurotoxicity scale reveals a significant reduction of drug-related cognitive complaints for the subjects taking LTG, relative to VPA (p=0.02). MOOD RATING: significant changes were found on the scale assessing "tiredness," showing increased tiredness/sedation for VPA relative to PBO (p=0.02) and on the "timid scale" for LTG reporting "being more at ease" compared with both PBO and VPA (p=0.02; 0.02). The general direction of change for the mood scales was toward "activation" for LTG (five of six scales improved), whereas for VPA, the reverse effect was found (four of six scales showed a change in the direction of "tiredness/sedation"). CONCLUSIONS: Short-term treatment in normal volunteers with a low dose of LTG resulted in improved cognitive activation on simple reaction-time measurements, a more positive subjective report about the impact of drug treatment relative to VPA, and mood changes concurring with the activating effect demonstrated by the cognitive tests.