Amyotrophic lateral sclerosis in Sardinia (Italy): epidemiologic features from 1957 to 2000.

OBJECTIVES: To evaluate epidemiological variables of amyotrophic lateral sclerosis (ALS) in Sardinia (Italy) in the 1991-2000 periods and compare them with the preceding decades. MATERIAL AND METHODS: Survey, critical reappraisal or clinical re-evaluation of all ALS cases with onset in the decade 1991-2000; calculation of crude and age-adjusted incidence, duration of disease, survival rates and the latency between onset of symptoms and diagnosis. RESULTS: A significant increase in the mean annual incidence was observed in comparison with the values found in the two previous decades, 1971-1980 and 1981-1990. The distribution of the disease in various areas of the island was found to be not at all homogeneous. No significant modifications of the duration of the disease and survival rates were observed. CONCLUSION: The role of particular exogenous factors, albeit still unclear, can be invoked.

Sensitivity and specificity of the EEG versus CT in acute cortical and subcortical stroke.

122 patients with acute stroke were examined in order to demonstrate the sensitivity and the specificity of EEG versus CT findings, in distinguishing cortical from subcortical lesions. To do this the electroencephalographic diagnosis performed by two different electroencephalographers was compared with the neuroimaging diagnosis. The results showed a sensitivity of 77% and a specificity of 75%. Furthermore, the EEG findings can also provide physiopathological data, in that the cortical lesions are likely to be due to embolism, while the subcortical lesions are more likely to be due to the pathological process of the intracerebral blood-vessels and the lesions of the watershed territories to hemodynamic phenomena.

Visual evoked potentials in hypothyroidism: a long-term evaluation.

Visual Evoked Potentials (VEP) were measured in 9 new-diagnosed hypothyroid female patients--mean age 46 +/- 12 ys--before treatment, during (with monthly evaluations) thyroid hormone replacement therapy and after long-term therapy, at the achievement as well as one year after having achieved and maintained euthyroidism. Three of the hypothyroids had abnormally prolonged latencies (m.v. 131.7 +/- 7.9 ms), while 7 had lower than normal amplitude (m.v. 2.3 +/- 2.8 microV). No remarkable change of amplitude was observed after the achievement of euthyroidism, after a mean time of 5.9 +/- 4.9 months (range 2-14 months). A significant shortening of latency (m 128.3 +/- 7.6 ms), even still higher than the control value (m 122.7 +/- 3.7 ms) was found. Significant correlation between P100 latency and thyroid hormone levels was found for TT4 (r = 0.3353; p = 0.005), TT3 (r = 0.2568; p = 0.032) and FT4 (r = 0.3572; p = 0.002). No further improvement in P100 latency (m 129.5 +/- 7.2 ms; p = 0.037) was found one year after the achievement of euthyroidism, while a remarkable amplitude increase (m 9.2 +/- 3.4 micro; p = 0.001) was observed. Our findings indicate that, as well as other studied parameters, VEP are reversibly alterated in hypothyroidism, probably in relation to metabolic rather than to structural alterations. Moreover, VEP can represent a useful neurophysiologic parameter for quantitation of SNC involvement in hypothyroidism.

Dementia of Alzheimer type (DAT) in a man chronically exposed to pesticides.

A patient chronically exposed to pesticides with dementia of Alzheimer type (DAT) is presented. We evaluate the pathogenic role of these substances in the disease and suggest the usefulness of an epidemiological attention on the environmental factors in certain neurodegenerative diseases.

Thalamic hemorrhage. 30 cases studied: clinico-tomodensitometric correlations.

The clinico-tomographic correlations in 30 patients hospitalized for primary thalamic hemorrhage were studied. Arterial hypertension, observed in 90% of patients, represented the most important risk factor. Twenty-six subjects showed a sensory-motor hemisyndrome contralaterally to the lesion, nineteen showed alteration in level of consciousness from confusion to stupor and coma. Twelve subjects had poorly reactive pupils and eleven speech disturbances with involvement of the left thalamus. Seven patients died following hemorrhage; all subjects presented ventricular bleeding, severe disturbance of consciousness and arterial hypertension. On admission to hospital impairment of consciousness was the most significant unfavourable prognostic factor.

Rigidity and painful muscle spasms in a patient with probable myelitis.

We describe a case of continuous motor unit potential (MUP) activity of central origin (unlike stiff man syndrome and progressive encephalomyelitis) characterized clinically by rigidity, painful muscle spasms, abnormal postures and spinal myoclonus. The topography of the manifestations, the subacute and benign course, the presence of stable sequels 2 years after onset and a searching process of differential diagnosis lead us to attribute the condition to an inflammation of the cord, which makes the case of particular clinical interest.

Sclerosteosis: report of a case in a black African man.

Sclerosteosis is a rare genetic disorder of bone modelling, similar to, but distinct from, van Buchem disease; it has been described almost exclusively in Afrikaners of South Africa, a white population of Dutch ancestry. Isolated cases have been reported in a girl in Japan, a boy in Spain, and in multiracial families in Brazil and USA. Here we report a case of sclerosteosis in a black man born in Senegal. He presented with the full features of the disease: tall stature; syndactyly: nail dysplasia; massive sclerosis of the long tubular bones, the ribs, the pelvis and the skull; multiple cranial nerve involvement: optic atrophy, facial palsy and trigeminal neuralgia. Radiologic examination, visual and brainstem auditory evoked potentials, computerized tomography and magnetic resonance imaging of the skull were performed. This seems to be the first case of the disease in a black African individual, with no known relationship with Dutch ancestry.

Conjugal amyotrophic lateral sclerosis: a report on a couple from Sardinia, Italy.

A conjugal case of amyotrophic lateral sclerosis (ALS) observed in Sardinia, Italy is reported. This is believed to be the ninth such observation described in the literature. The couple had lived together for 38 years in a house adjacent to the distillery they owned. No exogenous factors were revealed which could explain the genesis of the disease in either patients. Particularly, exposure to alcohol does not appear to have been involved in causing ALS. On the basis of statistical and epidemiological evaluations, the most likely explanation is that this association was purely coincidental.

Segmental myoclonus in a young man who had had localized encephalitis in childhood.

A man who had had an episode of localized encephalitis, diagnosed as viral cerebellitis in childhood came to observation at the age of 23 for attacks of segmental myoclonus of the cervical axial musculature. BAEP changes at brainstem level in this case point to involvement of the Guillain-Mollaret triangle in the pathogenesis of this syndrome.

Cerebral toxoplasmosis in AIDS. Case report.

In a patient with AIDS presenting partial epilepsy cerebral toxoplasmosis was diagnosed on the serological and CT evidence. The diagnosis was confirmed by the immediate response to sulfonamide therapy.

Notalgia paresthetica following neuralgic amyotrophy: a case report.

We report the case of a patient who developed notalgia paresthetica during the recovery from a neuralgic amyotrophy. A 23-year-old woman had a typical neuralgic amyotrophy (severe shoulder pain, followed by a long thoracic nerve palsy); five months after the onset of pain, when scapular winging was improving, she began to feel a burning sensation in a restricted interscapular area, on the same side. Electromyography was consistent with a long thoracic nerve neuropathy, with minor neurogenic changes in deltoid and biceps brachii. Radiography of the spine was unremarkable. The notalgia paresthetica disappeared shortly before the complete recovery of scapular winging. The abnormal activation of shoulder girdle and spine extensor muscles during the time of long thoracic nerve palsy may explain the association between the two disorders.

Chronic delusional hallucinatory psychosis in early-onset Parkinson's disease: drug-induced complication or sign of an idiopathic psychiatric illness?

Chronic delusional psychosis with hallucinations (CDHP) is commonly assumed to complicate the later stages of Parkinson's disease, as a side effect of antiparkinsonian medication. We studied 7 patients with early onset PD, who had developed psychiatric manifestations consisting in CDHP after a few years of antiparkinsonian therapy. All patients underwent a neurological, psychiatric and brain imaging (CT or MRI) evaluation. Detailed clinical history was recorded in order to reveal prior psychiatric illness and to analyse the relationship between neurological disease, cognitive impairment and psychosis. Our findings suggest that CDHP occurring in patients with early onset PD, normal or slightly impaired cognitive functions and normal CT/MRI scans is invariably the expression of a coexisting psychiatric illness which prior to onset of the neurologic disease had not been correctly diagnosed and which has been disclosed by dopaminergic therapy.

Comparison of MRI, EEG, EPs and ECD-SPECT in Wilson's disease.

OBJECTIVES: The purpose of this study is to evaluate the efficiency of a few methodologies in detecting anatomo-functional brain abnormalities in patients with Wilson's disease. MATERIALS AND METHODS: Twenty-three patients with Wilson's disease underwent almost simultaneously brain magnetic resonance imaging (MRI), computerized electroencephalography (EEG), multimodal evoked potentials (EPs) and ECD single photon computerized tomography (SPECT) evaluation. The clinical picture was of the neurologic type in 8 patients and of the hepatic type in 15. RESULTS: MRI was abnormal in 7 patients with neurological manifestations. The EPs proved pathologic in 7 neurologically symptomatic patients and in 4 cases with hepatic form. These results agree with those reported in other case studies. The EEG records were abnormal only in 3 cases. Nevertheless, the most interesting finding of this study is the particular frequency (86%) of diffuse or focal decrease of ECD uptake shown by brain SPECT. CONCLUSION: We highlight the use of this interesting procedure in the therapeutic monitoring of this disease.

Bipolar affective disorder and Parkinson's disease: a rare, insidious and often unrecognized association.

Five patients (4 women) with Parkinson's disease (PD) and primary major psychiatric disorder (PMPD) meeting DSM-IV criteria for the diagnosis of bipolar affective disorder (BAD) were studied. Four patients had early onset PD. Four developed a severe psychiatric disorder a few years after starting dopaminergic therapy in presence of a mild motor disability and a mild cognitive impairment, with no evidence of cerebral atrophy at CT or MRI. Two patients developed a clear manic episode; the other three presented a severe depressive episode (in one case featuring a Cotard syndrome). None showed previous signs of long term L-dopa treatment syndrome (LTS), hallucinosis or other minor psychiatric disorders. The two manic episodes occurred shortly after an increase of dopaminergic therapy and in one case rapid cyclic mood fluctuations were observed. At the onset of psychiatric symptoms, all patients had an unspecific diagnosis of chronic delusional hallucinatory psychosis (CDHP).

Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein.

Sclerosteosis is an autosomal recessive sclerosing bone dysplasia characterized by progressive skeletal overgrowth. The majority of affected individuals have been reported in the Afrikaner population of South Africa, where a high incidence of the disorder occurs as a result of a founder effect. Homozygosity mapping in Afrikaner families along with analysis of historical recombinants localized sclerosteosis to an interval of approximately 2 cM between the loci D17S1787 and D17S930 on chromosome 17q12-q21. Here we report two independent mutations in a novel gene, termed "SOST." Affected Afrikaners carry a nonsense mutation near the amino terminus of the encoded protein, whereas an unrelated affected person of Senegalese origin carries a splicing mutation within the single intron of the gene. The SOST gene encodes a protein that shares similarity with a class of cystine knot-containing factors including dan, cerberus, gremlin, prdc, and caronte. The specific and progressive effect on bone formation observed in individuals affected with sclerosteosis, along with the data presented in this study, together suggest that the SOST gene encodes an important new regulator of bone homeostasis.

Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).

Sclerosteosis is a progressive sclerosing bone dysplasia with an autosomal recessive mode of inheritance. Radiologically, it is characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened and sclerotic skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients. By linkage analysis in one extended van Buchem family and two consanguineous sclerosteosis families we previously mapped both disease genes to the same chromosomal 17q12-q21 region, supporting the hypothesis that both conditions are caused by mutations in the same gene. After reducing the disease critical region to approximately 1 Mb, we used the positional cloning strategy to identify the SOST gene, which is mutated in sclerosteosis patients. This new gene encodes a protein with a signal peptide for secretion and a cysteine-knot motif. Two nonsense mutations and one splice site mutation were identified in sclerosteosis patients, but no mutations were found in a fourth sclerosteosis patient nor in the patients from the van Buchem family. As the three disease-causing mutations lead to loss of function of the SOST protein resulting in the formation of massive amounts of normal bone throughout life, the physiological role of SOST is most likely the suppression of bone formation. Therefore, this gene might become an important tool in the development of therapeutic strategies for osteoporosis.