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Abnormalities of intracellular Ca2+ homeostasis and signalling as well as the down-regulation of neurotrophic factors in several areas of the central nervous system and in peripheral tissues are hallmarks of Huntington's disease (HD). As there is no therapy for this hereditary, neurodegenerative fatal disease, further effort should be made to slow the progression of neurodegeneration in patients through the definition of early therapeutic interventions. For this purpose, molecular biomarker(s) for monitoring disease onset and/or progression and response to treatment need to be identified. In the attempt to contribute to the research of peripheral candidate biomarkers in HD, we adopted a multiplex real-time PCR approach to analyse the mRNA level of targeted genes involved in the control of cellular calcium homeostasis and in neuroprotection. For this purpose we recruited a total of 110 subjects possessing the HD mutation at different clinical stages of the disease and 54 sex- and age-matched controls. This study provides evidence of reduced transcript levels of sarco-endoplasmic reticulum-associated ATP2A2 calcium pump (SERCA2) and vascular endothelial growth factor (VEGF) in peripheral blood mononuclear cells (PBMCs) of manifest and pre-manifest HD subjects. Our results provide a potentially new candidate molecular biomarker for monitoring the progression of this disease and contribute to understanding some early events that might have a role in triggering cellular dysfunctions in HD.

In 1906 Perusini began his scientific career publishing three papers. These articles were important for the understanding of degenerative dementia. Perusini studied the difference between Senile and Presenile Dementia. Emil Kraepelin distinguished its two forms, but Perusini didn't take a clear position because of his early heroic death on the slopes of Mount Sabotino on December in 1915.

Articular cysts of the atlantoaxial joint are infrequently described and probably an underreported cause of upper cervical spinal cord compression. The authors report on two patients with cysts located posteriorly of the dens in whom a C-1 and partial C-2 hemilaminectomy with subtotal resection of the cyst provided adequate and stable decompression 1 year postoperatively. The clinical and magnetic resonance imaging features and the surgical approach are discussed after a review of the literature.

This paper seeks to examine Perusini's scientific contribution to Alzheimer's disease, on the basis of critical reading of the three fundamental papers he produced between 1906 and 1911, and published between 1909 and 1911. The examination of three publications clearly shows that, after Alzheimer's concise clinical report of 3 November 1906, Perusini was responsible for more clearly defining its clinical and histopathological characteristics without ever claiming be the discoverer of the new disease. The paper also describes Alzheimer's express wish to entrust the investigation of the disease to Perusini, and the brilliant manner in which this was achieved. The on-going debate on the difference between senile and pre-senile dementia, which was originally raised by Kraepelin's distinction of the two forms, is also discussed.

We report the case of a 62-year-old man with no past CNS history who for some weeks had had fits of weeping that lasted from 30" to 3', precede by any aura; sensorium was clear; there were no symptoms of any kind after the paroxysm; in the course of them his facial expression was that of weeping with sobbing and tears, but no corresponding affective-emotional content, as reported by the patient, who was able to converse during these episodes. The fits were easily triggered by speaking. EEG during an episode showed a slight flattening of the trace, high voltage sharp waves at 4-6 c/s appeared, especially over the left hemisphere. CT brainscan and cerebral angiogram revealed a large space-occupying lesion of cystic-necrotic appearance with considerable mass effect and characteristics of glioblastoma. Treatment with barbiturates ended the paroxysmal weeping. We consider that these episodes were simple partial epileptic seizure according to the WHO classification of 1981.

We investigated two patients with the idiopathic hypereosinophilic syndrome and peripheral neuropathy. Clinical, EMG, and pathological findings were consistent with axonal polyneuropathy. Morphologic changes of the nerve biopsies suggested axonal damage secondary to increased endoneurial pressure from leakage of capillaries. We postulate that endothelial cell damage, followed by nerve edema, is the first step in the pathogenesis of peripheral neuropathy in these patients.

Intraneural cysts of the common peroneal nerve, as of other peripheral nerves, are rare. Their etiopathogenesis is unknown, though theories involving a tumor of synovial origin, mucoid degeneration or injury have all been proposed. An ex-amateur footballer with paralysis of the left CPN but unaffected peroneus longus proved, on surgical exploration of the CPN at the level of the head of the fibula, to have an intraneural cyst, which was removed. As it was a true intraneural cyst with no cleavage plane, no endothelial lining and no articular peduncle, and given the footballing history, the pathogenesis was considered to be traumatic. A year after cysts removal, the patient has fully regained the strength of the left foot.

We investigated the number of echinocytes, the serum hemopexin level, and spectrin band II phosphorylation in the blood of normal subjects, patients, and carriers of Duchenne dystrophy. The patients and carriers exhibited quantitatively significant differences with respect to controls.

Two cases of calcification of Striopallidodentate System will be considered. The first refers to a 20-years-old patient and features two small bilateral and symmetrical calcifications in the medial segment of globus pallidum. The first symptom, observed from the age 5 years was, behaviour disorder and, some years later, dystonia. The second case refers to a 54-years-old patient and features huge bilateral and symmetrical calcifications above and below the tentorium. The first symptoms started at the age of 32 with paraesthesiae and muscular contractions of the upper limbs, later with convulsive seizures and tetany and eventually right hemiplegia with aphasia. Study of Ca and P metabolism showed normoparathyroidism in the first case and idiopathic hypoparathyroidism in the second.

Because of previous reports of a possible correlation between echinocytogenesis and muscular dystrophies, we investigated the time-dependent development of echinocytes in the blood of normal subjects, patients, and healthy carries of Duchenne dystrophy. There was a quantitatively significant increase of echinocytes in patients and carriers.

A 65-year-old man with Tangier disease (analphalipoproteinemia) had had a progressive sensorimotor distal neuropathy with sensory ataxia for 1 year. Muscle biopsy demonstrated excess lipid vacuoles on histochemical and electron-microscopic techniques. Sural nerve biopsy showed a marked loss of large fibers and an increase in small myelinated fibers, with presence of remyelinating fibers and clusters of regeneration; a few aspects of active demyelination and some onion-like formations were also present. Lipid accumulation chiefly affected the Schwann cells of unmyelinated fibers and, to a lesser degree, of myelinated fibers, endoneurial fibroblast, and vasa nervorum. Teased fibers showed prevalent aspects of de-/remyelination and, often in association, marked myelin wrinkling suggesting axonal atrophy. This Tangier patient differs from known cases for the presence of a distal symmetrical sensorimotor polyneuropathy (not previously reported in Tangier disease) and because of the morphological findings of de-/remyelination coexisting with aspects of axonal atrophy and previous degeneration, and of lipid accumulation within striated muscle and vasa nervorum. This latter finding contrasts with the assumption that in Tangier disease vessel walls are not a site of lipid storage: probably the vasa nervorum are different, in this respect, from other vessels, because of the intense lipid metabolism of the nervous tissue. Thus we suggest that involvement of vasa nervorum in Tangier disease may be more important than previously suspected, possibly playing a role in the causation of neuropathy.

1 case of Duchenne Muscular Dystrophy (DMD) definite carrier, 3 probable and 17 possible (all analytically positive: "possible +") carriers were classed as Group A, 23 DMD possible carriers (all analytically negative "possible") as Group B and 26 normal subjects as Controls. The three groups were subjected to serum myoglobin (MGB) radioimmunoassay. Since the differences between MGB levels of Group A vs. Controls and Group A vs. Group B were statistically significant, it is suggested that the determination of MGB should be included among the tests for DMD carrier detection.

The frequency of consanguineous marriages up to second-cousin degree has been carefully established in the past for each of the 95 Italian provinces using the Archive of about 500,000 dispensations given by the Catholic church for such marriages over a 55-year period. It has therefore been possible to compare the frequency of consanguineous marriages observed among 83 couples of parents of Friedreich patients with the frequency of consanguineous marriages of the same degree in the different Italian provinces during the same years. From these data, an estimate of the incidence of the disease has been obtained for the whole nation (between 1/22,000 and 1/25,000). In Southern Italy, where 16 out of the 18 consanguineous marriages among Friedreich parents are concentrated, the incidence of the disease is similar (between 1/25,000 and 1/28,000). This study indicates that the Archive of consanguinity existing in Italy allows a reliable comparison of the frequency of consanguineous marriages among parents of patients with that of the general population. The same method can therefore be applied to the study of incidence of other autosomal recessive disorders in Italy.

On the light of previous reports on a possible correlation between echinocytogenesis and primitive muscular dystrophies, we have investigated the presence and time dependent development of echinocytes in the blood of normal subjects, patients and healthy carriers of D.M.D. A very few echinocytes are present in the fresh blood of all the patients and some carriers, but not in the blood of control normal subjects. With time, more echinocytes develop in all cases but much more markedly for sick people and carriers. These results might explain conflicting data on the echinocyte content in the blood reported in the literatura and provide a guideline for a correct analysis of the phenomenon and its possible relevance in the eugenetic diagnosis of carriers.

An X-linked adult-onset neurogenic muscular atrophy, chiefly proximal, with late involvement of the distal musculature and medulla oblongata was present in 4 members of a single kindred. Associated in all patients were gynecomastia, impotence and essential tremor. Frederickson type IV hyperlipemia was present in 1 patient. Hormonal stimulation tests in 2 patients elicited a borderline low testicular response in the younger of the 2 and a pathological response in the older patient. On the evidence of these and previously reported cases, Kennedy disease would appear to be characterized by an X-linked proximal neurogenic amyotrophy of adult onset and by a testicular endocrine deficit.

The Authors, after a brief review of the factors which influence the echino and stomatocytic erythrocyte's deformations and of the biochemical basis of these alterations, report the comparative study of the echino-stomatocytogenesis in both normal subjects and myodystrophic patients. In order to investigate whether this phenomenon is more developed in pathological condition, the results confirm that between normal subjects and myodystrophic patients or healthy carriers there is a quantitative significant difference which can be utilized for diagnostic and eugenic purposes. To obtain reliable results, the evaluation should be made at regular intervals of time from the blood drawing and after the exclusion of the presence of other disease or echino-stomatocytogenetic factors (drugs, etc.).