Antonella Tribolo

Demyelination, Inflammation, and Neurodegeneration in Multiple Sclerosis Deep Gray Matter

Gray matter (GM) lesions are recognized as important components of the pathology of multiple sclerosis (MS), and involvement of the deep gray matter (DGM) is suggested by magnetic resonance imaging. The aims of this study were to determine the frequency and distribution of lesions and characterize the inflammatory and neurodegenerative changes in DGM of MS patients. Histochemistry, immunohistochemistry, and morphometry were performed on whole coronal sections of 14 MS and 12 control (6 normal, 6 from amyotrophic lateral sclerosis patients) brains. Demyelinating lesions were frequent in MS DGM; most often in the thalamus and caudate, but they were also seen in the putamen, pallidum, claustrum, amygdala, hypothalamus, and substantia nigra. Most DGM lesions involved both GM and white matter. Inflammation in active DGM lesions was similar to that in lesions only in white matter but was less intense, and there was a preponderance of activated microglia, scarce myelin-laden macrophages, and a lesser extent of axonal damage. Neuronal loss was observed both in DGM lesions and nondemyelinated DGM with neuron atrophy in nondemyelinated DGM. In conclusion, demyelination and neurodegenerative changes are common in MS DGM and may contribute to clinical impairment. Inflammation in DGM lesions is intermediate between the destructive inflammation of white matter lesions and the minimal inflammation of cortical lesions. We hypothesize that alterations of glutamate reuptake mechanisms may contribute to these differences.

Histologic prognostic factors in ependymoma

The prognostic value of a series of histologic signs and clinical features was studied in a series of 298 ependymomas, collected from different institutions. The distribution of tumor sites varied in relation to patient age, with infratentorial cases prevailing under 4 years. Life table univariate analysis demonstrated as highly significant prognostic factors: (1) the number of mitoses; (2) endothelial hyperplasia; (3) necrosis; (4) intracranial site; (5) age <4 years. Multivariate analysis by tumor site revealed mitoses cell density, age >16 years in supratentorial cases, and subependymoma in infratentorial cases to be prognostically important. Comparison of the anaplastic variant with the other tumor types in intracranial cases did not show a significant difference in survival even though the median survival time of anaplastic cases was shorter. The main conclusion is that the histological criteria employed to diagnose anaplasia in gliomas are not useful for recognizing anaplasia in ependymomas. The number of mitoses is a very important prognostic factor in supratentorial cases, whereas endothelial proliferations and necroses are much less important as prognostic factors than in gliomas.

Risk Factors in Motor Neuron Disease: A Case-Control Study

A case-control study of risk factors in 512 cases of motor neuron disease (MND) and 512 controls, affected by other neurological diseases, was performed. Clinical history showed a significant increase in gastric ulcer and mechanical injuries among MND cases, whereas the frequencies of operations, poliomyelitis, malignancies and autoimmune diseases were similar for cases and controls. The women affected by MND had a later menarche and an earlier menopause; therefore, the reproductive period was significantly shorter, supporting a possible role of sexual hormones in the pathogenesis of MND. The analysis of occupations showed an increased number of farmers and also of subjects exposed to chemical products among MND cases.

Friedreich's ataxia: a descriptive epidemiological study in an Italian population

All the cases of Friedreichs ataxia (FA) diagnosed between 1945 through 1984 among residents of a defined area of northwestern Italy were ascertained (N = 59). Cases were diagnosed according to the criteria of the “Quebec Cooperative Study on Friedreichs Ataxia (QCSFA)” with minor modifications. We identified 39 families with 47 probands and 12 secondary cases. Therefore ascertainment probability was 80%. Male to female ratio was 1:1. Pedigrees were compatible with autosomal recessive inheritance. Segregation ratio was 0.28 with both Weinbergs method and the “singles” method (under incomplete ascertainment). Point prevalence ratio was 1.2/100 000 population. Birth incidence rate was 1/36 000 live births. Gene frequency was estimated to be 1/191. The ratio of first‐cousin marriages observed among parents of FA patients (3%) was lower than expected from Dahlbergs formula (8%). This finding is not compatible with the hypothesis of genetic heterogeneity for FA.

Prevalence of hereditary ataxias and paraplegias in the province of Torino, Italy

A descriptive epidemiological survey of hereditary ataxias and spastic paraplegias was conducted in the province of Torino, Italy (2 327 996 inhabitants). On prevalence day (31 December 1982) 142 patients were alive. Total prevalence was 6.1 cases/100,000 inhabitants (95% confidence limits=5.1–7.0). The prevalence rate was 2.6 for recessive or sporadic juvenile ataxias, 1.3 for spastic paraplegias, 1.2 for autosomal dominant cerebellar ataxias, and 1.1 for late onset cerebellar ataxias. The prevalence of hereditary ataxias is similar in our province to that recorded in other populations, but hereditary spastic paraplegias are less frequent than in other populations.SommarioÈ stato condotto uno studio di epidemiologia descrittiva sulle atassie e paraplegie spastiche ereditarie nella provincia di Torino (2.327.996 abitanti). Al giorno di prevalenza (31 dicembre 1982), 142 pazienti erano vivi. La prevalenza totale era di 6.1 casi/100.000 abitanti (limiti di confidenza al 95%=5.1–7.0). La prevalenza era di 2.6 per le atassie recessive o sporadiche giovanili, 1.3 per le paraplegie spastiche, 1.2 per le atassie cerebellari dominanti, e 1.1 per le atassie cerebellari ad inizio tardivo. La prevalenza delle eredoatassie nella nostra provincia è simile a quella riscontrata in altre popolazioni, mentre meno frequenti sono le paraplegie spastiche ereditarie.

Motor neuron disease and malignancies: results of a population-based study

SummaryEight cases of malignancies with concurrent motor neuron disease (MND), derived from an unselected population representing all cases of MND diagnosed during a 15-year period in two Italian provinces, were studied to verify the existence of paraneoplastic forms of the disease. No statistically significant association between the two diseases was found. Therefore, from our findings the occurrence of a neoplasm in a patient affected by MND can be considered a chance association.

Sexual behaviors during sleep associated with polysomnographically confirmed parasomnia overlap disorder

Parasomnia overlap disorder (POD) refers to a sleep disorder characterized by the association of REM sleep behavior disorder (RBD) with NREM sleep parasomnia in the same patient. Sexual behaviors during sleep (SBS) can include most wakeful sexual activities and are classified in the ICSD-2 as a variant of confusional arousals and sleepwalking, both NREM parasomnias. A case of SBS associated with sleepwalking and possible RBD has been previously described, but it was not confirmed by polysomnography (PSG). We report two patients with SBS associated with POD documented by PSG. In one patient (60-year-old female) SBS was video-polysomnographically demonstrated: a few minute episode of masturbation occurring during slow-wave sleep (SWS) and preceded by hypersynchronous delta pattern. During the episode, the EEG pattern showed the persistence of delta rhythms with increasing alpha activity. When awoken by technicians, the patient was not aware of her sexual behavior and did not report any dream. The other patient, a 41-year-old male with a history of sleepwalking and RBD, was legally charged with repeatedly sexually fondling a young girl during the night. The POD was documented by PSG. The parasomnia defense, including sleepsex, was accepted by the Court and the patient was acquitted. This is an unprecedented report of SBS in patients with PSG-confirmed POD and of SBS documented during video-PSG.

A survival analysis of 155 cases of progressive muscular atrophy

ABSTRACT – We performed a survival analysis of 155 cases of progressive muscular atrophy (PMA). In about half the cases, hands were involved first, the lower limbs in 30% and the shoulder girdle in 23%. The lifetables of PMA, adjusted to the expected mortality, showed a survival rate of 61.3% and 56.4% at three and five years, respectively. The location of onset symptoms did not modify the life expectancy, whereas the age of the patients at the moment of first diagnosis had a great influence on the course of the disease. The patients were further subdivided in two groups on the basis of the diffusion of the neuromuscular damage at the moment of the diagnosis. The course of the patients with a localized disease was markedly better than that of subjects with widespread disease. Some hypotheses are made about the latter group of cases.

Increased oral nitric oxide in obstructive sleep apnoea

BACKGROUND Hypoxia and snoring-related mechanical trauma contribute to airway inflammation in obstructive sleep apnoea (OSA). Increased exhaled nitric oxide (FENO), an airway inflammation marker, has been reported in OSA patients. We propose the measure of NO in the oral cavity (oNO) as marker of oropharyngeal inflammation in OSA. METHODS We compared oNO and FENO of 39 OSA patients with those of 26 mild asthmatics (ASTHMA), 15 patients with chronic rhinitis or rhinosinusitis (CRS) and 24 healthy subjects. A special device was used for oNO measurement. Apnoea/hypopnoea index (AHI), oxygen desaturation index, mean and nadir SaO2 were calculated from the polysomnography. RESULTS oNO was significantly increased in OSA (104.2 95%CI 80.2-135.5ppb) as compared to ASTHMA (71.9 95%CI 56.3-91.9ppb; p=0.015), CRS (54.4 95%CI 40.2-73.7ppb; p=0.009) and healthy subjects (63.6 95%CI 59-73ppb; p<0.001). oNO was directly related to AHI (r=0.466, p=0.003) and to minutes slept with SaO2 <90% (r=0.471, p=0.011) and it was inversely related to nadirSaO2 (r=-0.393, p=0.018). FENO was highest in asthmatics (40.3 95%CI 32.5-50.1ppb) and only slightly elevated in OSA (23.1 95%CI 19,8-28.3ppb) and CRS (22.8 95%CI 16.8-32.5ppb). CONCLUSIONS The finding that oral NO is increased in OSA and is related to upper airway obstructive episodes and to hypoxemia severity, strengthens the clinical and pathogenic role of oral inflammation in OSA.

A follow-up study of 60 cases of chronic spinal muscular atrophy

Abstract60 cases of chronic spinal muscular atrophy (CSMA) were followed-up for a period varying from 5 to 40 years. The neuromuscular impairment was evaluated by Norris’ ALS score, both at the time of last examination and retrospectively at the time of diagnosis. Age at onset of symptoms was the most important factor in the progression of the neuromuscular damage. Monomelic or asymmetric location of symptoms at the time of diagnosis and duration of the disease were not significantly correlated to the worsening of ALS score.SommarioSessanta casi di atrofia muscolare spinale cronica (CSMA) sono stati seguiti per un periodo compreso tra 5 e 40 anni. Per mezzo dell’ALS score di Norris è stato quantificato il danno neuromuscolare, sia al momento dell’ultima visita, sia, retrospettivamente, al momento della diagnosi. Il più importante fattore nella definizione della progressione del deficit è risultato essere l’età all’esordio dei sintomi. Non è stata evidenziata una relazione significativa tra una localizzazione monomelica o asimmetrica dei sintomi ed il peggioramento dell’ALS score.