CSF angiogenin levels in amyotrophic lateral Sclerosis-Frontotemporal dementia spectrum.

Objective: Angiogenin (ANG) is a pro-angiogenic and neurotrophic factor with an important role in stress-induced injury, by promoting neovascularization and neuronal survival. Identification of loss-of-function mutations and evidence of beneficial effect of ANG administration in transgenic SOD1G93A mice have linked ANG to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), stimulating interest in considering circulating ANG levels as an ALS disease biomarker although robust evidence is still lacking. Aim of our study was to assess differences of ANG levels in the cerebrospinal fluid (CSF) of a large cohort of patients with ALS and frontotemporal dementia (FTD) compared to controls and to explore correlations between ANG content and disease-related clinical variables. Methods: ANG levels were measured in CSF samples using a commercially available ELISA kit in 88 patients affected with ALS and/or FTD and 46 unrelated individuals (control group). Results: ANG levels didn't differ significantly between cases and controls. Patients with FTD or ALS-FTD showed significantly increased CSF concentration of ANG compared to ALS patients without dementia and controls in a multivariate regression model (p < 0.001). No correlations were found in ALS/FTD patients between ANG levels and clinical parameters, including age, presence of C9orf72 repeat expansion, body mass index (BMI). Conclusions: our findings highlight a role of ANG as CSF biomarker useful to identify ALS patients with concurrent FTD and suggest that it should be further explored as potential biomarker for FTD.

Diagnostic criteria for amyotrophic lateral sclerosis: A multicentre study of inter-rater variation and sensitivity.

OBJECTIVE: This study assesses inter-rater agreement and sensitivity of diagnostic criteria for amyotrophic lateral sclerosis (ALS). METHODS: Clinical and electrophysiological data of 399 patients with suspected ALS were collected by eleven experienced physicians from ten different countries. Eight physicians classified patients independently and blinded according to the revised El Escorial Criteria (rEEC) and to the Awaji Criteria (AC). Inter-rater agreement was assessed by Kappa coefficients, sensitivity by majority diagnosis on 350 patients with follow-up data. RESULTS: Inter-rater agreement was generally low both for rEEC and AC. Agreement was best on the categories "Not-ALS", "Definite", and "Probable", and poorest for "Possible" and "Probable Laboratory-supported". Sensitivity was equal for rEEC (64%) and AC (63%), probably due to downgrading of "Probable Laboratory-supported" patients by AC. However, AC was significantly more effective in classifying patients as "ALS" versus "Not-ALS" (p < 0.0001). CONCLUSIONS: Inter-rater variation is high both for rEEC and for AC probably due to a high complexity of the rEEC inherent in the AC. The gain of AC on diagnostic sensitivity is reduced by the omission of the "Probable Laboratory-supported" category. SIGNIFICANCE: The results highlight a need for initiatives to develop simpler and more reproducible diagnostic criteria for ALS in clinical practice and research.

Neurophysiology of the pelvic floor in clinical practice: a systematic literature review.

Neurophysiological testing of the pelvic floor is recognized as an essential tool to identify pathophysiological mechanisms of pelvic floor disorders, support clinical diagnosis, and aid in therapeutic decisions. Nevertheless, the diagnostic value of these tests in specific neurological diseases of the pelvic floor is not completely clarified. Seeking to fill this gap, the members of the Neurophysiology of the Pelvic Floor Study Group of the Italian Clinical Neurophysiology Society performed a systematic review of the literature to gather available evidence for and against the utility of neurophysiological tests. Our findings confirm the utility of some tests in specific clinical conditions [e.g. concentric needle electromyography, evaluation of sacral reflexes and of pudendal somatosensory evoked potentials (pSEPs) in cauda equina and conus medullaris lesions, and evaluation of pSEPs and perineal sympathetic skin response in spinal cord lesions], and support their use in clinical practice. Other tests, particularly those not currently supported by high-level evidence, when employed in individual patients, should be evaluated in the overall clinical context, or otherwise used for research purposes.

MRI and motor evoked potential findings in nondisabled multiple sclerosis patients with and without symptoms of fatigue.

Fatigue is a common symptom of multiple sclerosis (MS) even in the early phases of the disease, when neurological disability is usually still not present. To investigate the pathophysiology of fatigue we compared neurophysiological (motor evoked potentials of the four limbs, MEPs) and brain magnetic resonance imaging (MRI) findings in two groups of nondisabled MS patients, those with (n=15) and those without (n=15) fatigue. Fatigue was assessed by an interview and scored by the Fatigue Severity Scale. The two groups were matched for sex, age, disease duration, Expanded Disability Status Scale score, pyramidal Functional System (FS) score, and depression score. MEPs were abnormal in five patients with fatigue and in one patient without fatigue. A significant association was found between the patient scores on the Fatigue Severity Scale, and the burden of MRI lesions (r=0.5; P< 0.005). Significantly higher parietal lobe (P< 0.05), internal capsule (P< 0.05), and periventricular trigone (P< 0.05) lesion loads were found in patients with fatigue than in those without. Our results agree with a central nervous system origin of fatigue in MS patients. This symptom might be a consequence either of a functional deafferentation of the cortex due to cortico-subcortical interconnection damage or of a demyelination in critical sites of the CNS, such as the cortico-spinal tract.

Transcranial magnetic stimulation and silent period in spasmodic torticollis.

OBJECTIVE: Our objective was to study the corticobulbar projections to neck muscles in cervical dystonia. DESIGN: We compared both the motor evoked potentials and the electromyographic silent period after transcranial magnetic stimulation from sternocleidomastoid and trapezius muscles in a group of 13 patients with spasmodic torticollis with those of 20 healthy volunteers. RESULTS: With the target muscle at rest, no changes of motor threshold, motor evoked potentials latency, and amplitude were observed in dystonic patients. With facilitation, the mean amplitude of the motor evoked potentials was increased in patients compared with controls, the significant difference being for the trapezius muscle, whereas the latency did not differ between groups. The cortical silent period was significantly shorter in dystonic patients than in healthy subjects in both muscles. The duration of the cortical silent period recorded from the sternocleidomastoid muscle showed a positive correlation with the degree of neurologic disability assessed by Tsui's scale. No abnormalities of both nerve conduction velocity and peripheral silent period by stimulation of accessory nerve were found. CONCLUSIONS: These results indicate an impairment of the mechanisms of inhibitory motor control in patients with spasmodic torticollis, which could be the result of a decrease of the basal ganglia inhibitory output over the motor cortex.

Repeatability of surface EMG variables during voluntary isometric contractions of the biceps brachii muscle.

The repeatability of initial value and rate of change of mean spectral frequency (MNF), average rectified values (ARV) and muscle fiber conduction velocity (CV) was investigated in the dominant biceps brachii of ten normal subjects during sustained isometric voluntary contractions. Four levels of contraction were studied: 10%, 30%, 50% and 70% of the maximal voluntary contraction level (MVC). Each contraction was repeated three times in each of three different days for a total of nine contractions/level/subject and 90 contractions per level across the ten subjects. Repeatability was investigated using the Intraclass Correlation Coefficient (ICC) and the standard error of the mean (SEM) of the estimates for each subject. Contrary to observations in other muscles, CV estimates appeared to be very repeatable both within and between subjects. CV showed a small but significant increase when contraction force increased from 10% to 50% MVC but no change for further increase of force. As force increased, MNF showed a slight decrease possibly related to a wider spreading of the CV values. The rate of time decrement of MNF and CV increased with the level of contraction. The normalized decrement (% of initial value per second) was in general higher for MNF than for CV and was more repeatable between subjects at 10% MVC than at 70% MVC. A final observation is that a resting time of 5 minutes may not be sufficient after a contraction at 50% or 70% MVC.

Electrophysiologic studies in tarsal tunnel syndrome. Diagnostic reliability of motor distal latency, mixed nerve and sensory nerve conduction studies.

The tarsal tunnel syndrome (TTS) is an entrapment of the posterior tibial nerve at the ankle, which, like carpal tunnel syndrome, improves with surgery but needs an instrumental diagnosis to exclude other diseases. This study was performed to evaluate the diagnostic value of nerve conduction tests proposed for the diagnosis of TTS. Of the 13 patients who were investigated 12 had secondary unilateral and 1 idiopathic bilateral TTS. One or more neurophysiologic parameters were abnormal in all cases. The diagnostic value of each neurophysiologic parameter was calculated by comparing conduction on the affected side with conduction on the healthy side of each patient with TTS. The accuracies of the sensory nerve action potential and mixed nerve action potential, both after stimulation of the plantar nerves, were almost the same, with sensory nerve action potentials more sensitive and less specific and mixed nerve action potentials less sensitive and more specific. Because from the clinical point of view we must be more afraid of false-positive results, the mixed nerve action potential is recommended for presurgical diagnosis of TTS. Coexistence of mixed nerve and sensory nerve action potential abnormalities, especially if asymmetric, are highly indicative of TTS.