Marco Poloni

Circulating levels of tumour necrosis factor-α and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis

An immunologic pathogenesis for amyotrophic lateral sclerosis (ALS) has been recently proposed. We tested the whole tumour necrosis factor (TNF) system in the serum of 51 ALS patients at different stages of the disease and 36 healthy controls. Antigenic TNF-alpha and its soluble receptors (sTNF-Rs), measured by ELISA, were significantly higher in ALS patients than in healthy controls. However, biologically active TNF-alpha, corresponding to the sTNF-Rs-unbound trimeric TNFalpha molecule and assayed by its cytotoxic activity on a sensitive cell line, was similar between ALS patients and healthy controls. Neither antigenic TNF-alpha, bioactive TNF-alpha nor sTNF-Rs correlated with disease severity, disease duration, or weight loss. In conclusion, we reported an activation of the TNF system in ALS. The role of this activation in the pathogenesis of the disease remains elusive.

A Study to Compare Oral Sumatriptan with Oral Aspirin plus Oral Metoclopramide in the Acute Treatment of Migraine

In a double-blind, placebo-controlled study, the efficacy, safety and tolerability of 100 mg oral sumatriptan, given as a dispersible tablet, was compared with that of 900 mg oral aspirin plus 10 mg oral metoclopramide in the acute treatment of migraine. A total of 358 patients treated up to three migraine attacks within 3 months, recording clinical information on a diary card. In attack 1, headache relief after 2 h, defined as a reduction in severity from severe or moderate pain to mild or no pain, was recorded in 56% (74/133) of patients who took sumatriptan and 45% (62/138) of patients who took aspirin plus metoclopramide (p = 0.078). This analysis of the primary efficacy end point was not statistically significant. However, for attacks 2 and 3 (secondary end points), headache relief was achieved in 58 versus 36% of patients (p = 0.001) and 65 versus 34% of patients (p less than 0.001), respectively. Relief from nausea, vomiting, photophobia and phonophobia was similar in both treatment groups. Rescue medication was required by fewer patients treated with sumatriptan than by those who received aspirin plus metoclopramide (attack 1, 34 versus 56%, p less than 0.001; attack 2, 32 versus 51%, p = 0.001, and attack 3, 35 versus 54%, p = 0.001). Sumatriptan also produced a faster improvement and resolution of migraine attacks. Comparing the sumatriptan and aspirin plus metoclopramide treatment groups, complete resolution of the attack occurred within 6 h in 32 versus 19% (attack 1), 35 versus 23% (attack 2) and 32 versus 20% of patients (attack 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropsychological measures in amyotrophic lateral sclerosis and their relationship with CT scan-assessed cerebral atrophy

Abstract Twenty‐one male patients affected by ALS have been given a short neuropsychological battery and the results have been compared with those obtained by 21 male subjects affected by other non‐dementing neurological diseases. Only two ALS patients had definitely iow scores on WAIS (performance scale) and on learning tasks, both verbal and spatial, but the ALS group did not differ, on the whole, from the controls. No relationship was observed between cognitive impairment and cerebral atrophy assessed by computerized tomography. The conclusion is suggested that the cognitive impairment in ALS be a discrete, seldom occuring event.

Reliability of the El Escorial Diagnostic Criteria for Amyotrophic Lateral Sclerosis

Background: The El Escorial diagnostic criteria are the most commonly used in clinical studies and therapeutic trials in patients with amyotrophic lateral sclerosis (ALS). The accuracy of the El Escorial criteria was tested in clinical practice, but the reliability is unknown when the diagnosis of ALS must be assessed on the basis of medical records. Objective: To assess the reliability of the El Escorial criteria for the diagnosis of ALS in different settings. Design and Methods: Semistructured forms were used to include the main diagnostic information on 20 patients with definite (n = 6), probable (n = 6), possible (n = 6), and suspected ALS (n = 2) and 19 patients with clinical conditions considered in the differential diagnosis. Agreement was tested by comparing the diagnosis made by the attending physician (the ‘gold standard’) with that of 4 raters with different backgrounds: a teaching neurologist with research and practical experience in the field of motor neuron disorders, a neurologist with specific interest in motor neuron disorders and neurophysiological background, a neurophysiologist, and a general neurologist with only occasional ALS patients. Sources of disagreement were discussed and the agreement was tested further on the medical records of 98 additional cases taken from an ongoing ALS registry. Eight additional cases (ALS: 4; other conditions: 4) were examined directly by the 4 raters. Results: The interrater agreement on the medical records was poor (overall kappa 0.05–0.29). When the differential diagnosis was made between ALS (all diagnostic levels) and other conditions, interrater agreement was at best modest, with moderate variations when raters were compared in pairs (kappa 0.03–0.58) and when each rater was compared with the physician (kappa 0.27–0.51). Agreement was higher after direct examination of the patients (kappa 0.33–1) and increased significantly on the medical records after training (overall kappa 0.52–0.79). However, concordance was low (overall kappa 0.08–0.36), even after training, at the lowest diagnostic level (definite to suspected ALS vs. other conditions). Conclusions: The El Escorial criteria are a poor diagnostic indicator when patients’ records are examined. Although medical education significantly improves the reliability of the criteria, concordance is still modest when the diagnosis includes suspected ALS.

DNA repair mechanisms in neurological diseases: facts and hypotheses.

DNA repair mechanisms usually consist of a complex network of enzymatic reactions catalyzed by a large family of mutually interacting gene products. Thus deficiency, alteration or low levels of a single enzyme and/or of auxiliary proteins might impair a repair process. There are several indications suggesting that some enzymes involved both in DNA replication and repair are less abundant if not completely absent in stationary and non replicating cells. Postmitotic brain cell does not replicate its genome and has lower levels of several DNA repair enzymes. This could impair the DNA repair capacity and render the nervous system prone to the accumulation of DNA lesions. Some human diseases clearly characterized by a DNA repair deficiency, such as xeroderma pigmentosum, ataxia-telangiectasia and Cockayne syndrome, show neurodegeneration as one of the main clinical and pathological features. On the other hand there is evidence that some diseases characterized by primary neuronal degeneration (such as amyotrophic lateral sclerosis and Alzheimer disease) may have alterations in the DNA repair systems as well. DNA repair thus appears important to maintain the functional integrity of the nervous system and an accumulation of DNA damages in neurons as a result of impaired DNA repair mechanisms may lead to neuronal degenerations.

Cerebral mapping in subjects suffering from migraine with aura

Cerebral mapping of the spontaneous electroencephalographic activity was performed in 31 subjects suffering from migraine with aura and the results were compared with those of a matched control group. All the patients were examined during the interictal period. While traditional visual interpretation of EEG records was negative in all but five cases (16.1%) spectral analysis showed an asymmetry in alpha total power over the posterior regions in 13 cases (41.9%) and an asymmetry in alpha band peak frequency in 17 (54.8%). By means of cerebral mapping and statistical significance probability mapping we were able to demonstrate a significant increase in alpha total power in 13 cases (41.9%) and a regional increase in delta and theta total power in 20 cases (64.5%). In comparison with the control group, the migraine patients showed a widespread increase in slow activity (theta and delta) mostly over the temporal regions.

Cerebral atrophy in motor neuron disease evaluated by computed tomography

Thirty-two (64%) of 50 patients with motor neuron disease showed various patterns of cerebral atrophy (cortical, ventricular or both) at CT examination. The incidence of cerebral atrophy, particularly cortical atrophy, in motor neuron disease was greater than in a matched control group.

Voluntary muscle release is not accompanied by H-reflex inhibition in patients with upper moto neuron lesions

Changes in excitability of the soleus (Sol) monosynaptic reflex arc were investigated in spastic subjects, affected by amyotrophic lateral sclerosis (ALS), upon voluntary relaxation of tonic contraction of triceps surae muscle. Force and electromyograms (EMG) were recorded during triceps release, performed in response to an acoustic signal, in a reaction-time (RT) situation. Sol H-reflex was evoked at random during the task, and its amplitude was referred in time to the end of Sol EMG. At variance with the results for the same task in normal subjects, it was found that in ALS patients the RTs of the termination of EMG were longer than those of the beginning of the EMG, the decrease in force was prolonged and perturbed owing to intercurrent clonus-like EMG activity, and the H-reflex did not undergo the expected profound inhibition. It is suggested that the absence of the activation of presynaptic inhibitory mechanisms by the descending command to release brings about major disorders in voluntary muscle relaxation.

Fronto-Temporal Dementia and Motor Neuron Disease : a neuropsychological study

The neuropsychological follow‐up study of a 58‐year‐old man suffering from Motor Neuron Disease (ALS/MND) and Fronto‐Temporal Dementia (FTD) is reported. Neuromuscular signs first appeared at the age of 51 and slowly progressed to late bulbar involvement; behavioural symptoms of the frontal type first appeared around age 53; lastly, several neuropsychological symptoms suggestive of worsening temporal involvement supervened at age 57. Our patient died at 59 of respiratory failure with the classic clinical and neuroradiological picture of FTD. A short discussion addresses the controversial issue of the coupling of ALS/MND with Dementia and its possible interpretation as the expression of a chance association of relatively common diseases, versus that of a single multifaceted disease. The role of a detailed neuropsychological assessment is highlighted, within the context of increasingly specific diagnostic criteria for FTD.

Quantitative electroencephalography in amyotrophic lateral sclerosis

OBJECTIVES The authors evaluated quantitative EEG (QEEG) in patients with amyotrophic lateral sclerosis (ALS), in order to see if the confined cortical degeneration found in anatomical and functional examinations of central (rolandic) regions could give rise to abnormalities of cortical electrical activity. MATERIAL AND METHODS Eighteen patients with ALS were compared with 14 control subjects comparable for age and sex. The QEEG analysis was blind to the clinical data. Frequency analysis of 30 EEG epochs, each of 2.6 s duration, was performed. RESULTS QEEG in ALS patients showed a significant well-localized decrease of alpha activity only in the central regions, while theta and delta relative power did not show any difference from controls. CONCLUSION We suggest that QEEG is able to show evidence of subtle EEG changes probably due to loss of cells in the somatomotor cortex selectively affecting the generator sites.