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.

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.

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).

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.

Correlation between cerebral perfusion and hyperventilation enhanced focal spiking activity.

Single photon emission computed tomography (SPECT) has frequently been used to investigate cerebral brain perfusion (CBP) occurring ictally and inter-ictally in epileptic patients. Several studies have addressed the multimodal analysis of the modifications occurring in cerebral areas involved in seizure activity, by correlating SPECT with electroencephalografic (EEG) recordings during ictal and inter-ictal epileptiform lateralized discharges (IELDs). Although these studies have yielded interesting results, variations in regional CBP (rCBP) observed during ictal events are difficult to interpret since the areas of altered rCBP might reflect not only events restricted to the epileptogenic focus, but also large fluctuations determined by seizure spread. Inter-ictal rCBP correlates with the area generating the local EEG epileptogenic activity in a limited percentage of studies. Hyperventilation (HPV) represents a well established EEG activation procedure aimed at enhancing epileptiform discharges. Since HPV-enhanced IELDs may help analyze the CBP pathophysiology in inter-ictal epilepsy, in the present study we investigate this specific aspect co-registering EEG with SPECT in subjects affected by partial epilepsy responding to HPV with IELD enhancement without seizure precipitation. This study suggests a correlation between localized increase in rCBP and HPV-induced IELDs and provides a tool to discuss uncommon aspects of the physiology of rCBP during the inter-ictal state in the epileptogenic areas.

Association of monoamine oxidase B alleles with age at onset in amyotrophic lateral sclerosis.

An active role of monoamine oxidase B (MAO-B) in the pathogenesis of neurodegenerative disorders such as Parkinson's disease has been proposed as the enzyme is known to be a generator of free radicals which seem to be responsible for neuron oxidative damage. We evaluated the influence of MAO-B in the pathogenesis of the sporadic forms of Amyotrophic lateral sclerosis (ALS) by studying the MAO-B allele distribution in 51 patients and 71 healthy controls. MAO-B did not directly result in a risk factor for ALS but seemed to strongly influence age at onset. The mean ALS onset age was significantly higher in individuals carrying allele 5 compared to individuals without this allele (60.4 +/- 8.1 vs. 52.1 +/- 10.3 years; P = 0.004). These results, in agreement with findings in the literature, suggest an increased MAO-B expression in ALS and support the hypothesis that neuronal cell death in neurodegenerative diseases is triggered by astroglial reaction.

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.

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.

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.

Hippocampal theta activity after systemic administration of a non-peptide delta-opioid agonist in freely-moving rats: relationship to D1 dopamine receptors.

Hippocampal theta activity was acquired and processed off-line from digitized EEG recordings after subcutaneous (s.c.) administration of the non-opioid delta agonist BW 373U86 (0.5-2.5 mg/kg) in freely-moving rats. Relative theta power spectral analysis, implemented by a signal processing software, showed that BW 373U86 induced a dose-dependent increase in the slow component of theta band (Type 2 theta), while movement-related fast theta band (Type 1 theta) failed to show significant changes. Moreover, the increase in relative Type 2 theta power showed a maximal change at 1 mg/kg of BW 373U86, while higher doses, although effective in increasing relative Type 2 theta, induced locomotion and irregularly increased Type 1 hippocampal theta activity. The administration of 10.0 mg/kg of the delta antagonist Naltrindole (NLI) 30 min before BW 373U86, abolished hippocampal Type 2 theta increase. The rise of relative Type 2 theta power induced by BW 373U86 (1-2.5 mg/kg) was greatly attenuated by 0.1 mg/kg of the selective dopamine (DA) D1 antagonist SCH 23390. Administration of 0.1 mg/kg of SCH 23390 alone did not modify hippocampal Type 2 theta. These results indicate that delta receptors modulate the expression of hippocampal Type 2 theta and dopamine, through D1 receptors, exerts a permissive role on this influence.

Failure of naloxone to modify electroencephalogram interictal epileptiform discharges in patients with primary generalized epilepsy after slation.

Sleep deprivation (SD) is a method widely used to activate EEG epilept oform activity, but the basis of this effect remains unknown. One possibilty is that SD shares a common mechanism with physical and psychological stresses that also precipitate seizures. Because endogenous opioids are released during stress, opioids may play a role in enhancing epileptiform EEG patterns after SD. We report the effects of SD on EEG epileptiform activity in a small but highly homogeneous population of 13 epileptic patients with idiopathic (primary) generalized epilepsy (IGE). SD increased EEG interictal epileptiform discharges (IEDs); this activation was not modified by naloxone (NAL). Our results, in contrast to those of previous investigations of localization-related epilepsy, which showed an increase in IEDs after NAL administration, suggest a possible difference in the mechanism whereby SD enhances IEDs in IGE and localization-related epilepsy.

Microdialysis measurement of cortical and hippocampal acetylcholine release during sleep-wake cycle in freely moving cats.

The variations of Acetylcholine (ACh) release in the cerebral cortex and dorsal hippocampus were monitored by microdialysis during the electroencephalographically recorded sleep-waking cycle in freely moving cats. The results show a state-dependent variation in ACh output in both the cortex and the hippocampus. ACh release increased by approximately 100% during quiet waking (QW) and by 175% during active waking (AW) as referred to slow wave sleep (SWS) baseline. In contrast, a clear difference between the two areas was observed during REM sleep. During this stage ACh release in the cortex reached approximately the same values observed during QW, while in the hippocampus ACh release rose to about 4-fold the level obtained during SWS or twice that of QW. The results support the idea that the increase in ACh release in the cortex reflects the desynchronized EEG of wakefulness and REM sleep, while the marked increase of ACh during REM in the hippocampus may be related to the sustained theta activity in this area.

Epilepsy in congenital lipodystrophy. Case report.

A case of congenital lipodystrophy complicated by complex-partial epilepsy is reported in a nine-year-old girl. The peculiarity of this rare case is represented by partial complex epilepsy with diffuse electroencephalographic alterations represented by a continuous seizure-like pattern that persisted unmodified despite the successful antiepileptic treatment. Although the etiopathology of lipodystrophy is, at present, still elusive, we hypothesize that the primitive dysfunction of lipidic metabolism plays a critical role in both determining central nervous system (CNS) alterations and the findings that characterized this extremely rare disease.

Refining the position of Wilson disease by linkage disequilibrium with polymorphic microsatellites.

Wilson disease (WND) is an autosomal recessive disorder that is due to an inability of the liver to eliminate copper. Copper buildup in the liver, brain, kidney, and other tissues can result in liver cirrhosis, neurologic and psychiatric defects, and other problems. We have localized the disease-containing region to between D13S31 and D13S59, with > 70 multiply affected families, and have constructed a YAC contig of > 4.5 Mb that spans these loci and orders nine highly polymorphic microsatellites. Here we present an analysis of disequilibrium with markers in this interval and provide evidence for strong allelic associations between AFM084xc5 alleles and WND alleles in European, Middle Eastern, and East Asian populations. Significant but weaker allelic associations were also observed between WND alleles and alleles at D13S137 and D13S169. The strength of the association between AFM084xc5 and WND in all non-Sardinian populations combined (linkage-disequilibrium coefficient [phi] = .61) suggests that the number of mutations accounting for WND is less than expected on the basis of the variety of clinical symptoms that are observed.

Polymorphic microsatellites and Wilson disease (WD).

Wilson disease (WD), an autosomal recessive disorder of copper metabolism, has been previously mapped to chromosome 13q. Highly informative PCR-based polymorphic microsatellites closely linked to the WD locus (WND) at 13q14.3, as well as sequence-tagged sites for closely linked loci, are described. Two polymorphic microsatellite markers at D13S118 and D13S119 lie within 3 cM of WND. Two others (D13S227 and D13S228) were derived from a yeast artificial chromosome containing D13S31. These were placed on a genetic linkage map of chromosome 13 and were typed in 74 multiplex WD families from a variety of geographic origins (166 affected members). Multipoint analysis provides very high odds that the location of WND is between D13S31/D13S227/D13S228 and D13S59. Previous odds with RFLP-based markers were only 7:1 more likely than any other location. Current odds are 5,000:1. Preclinical testing of three cases of WD by using the highly informative polymorphic microsatellite markers is described. The markers described here ensure that 95% of predictive tests using DNA from both parents and from at least one affected sib will have an accuracy > 99%.

Altered EEG pattern in aromatic hydrocarbon intoxication. A case report.

A case of acute intoxication after both cutaneous and inhalatory absorption of a mixture of organic solvents (toluene and benzene) is reported. The peculiarity of this case is represented by the abnormal EEG findings: paroxysmal slow waves at the beginning of the intoxication, persisting, although attenuated, days after the patient's complete recovery. Moreover, the fact that other investigations were normal gives further support to the significance of routine EEG recording in monitoring the involvement of CNS in cases of acute exposure to aromatic organic solvents.

Amyotrophic lateral sclerosis in Sardinia, Italy: an epidemiologic study.

The authors carried out an epidemiologic study on amyotrophic lateral sclerosis in Sardinia for the years 1957 through 1990. The duration of the disease and survival were significantly shorter in bulbar form. The distribution of ALS in various areas of the island was found to be not at all homogeneous. Mean yearly incidence showed no significant variations in the decades 1971-80 and 1981-90. In the last decade, an increase of bulbar forms was observed.

Clonidine prevents corticotropin releasing factor-induced epileptogenic activity in rats.

Studies have shown that intracerebroventricular (i.c.v.) injection (10-20 micrograms) of corticotropin releasing factor (CRF) in rats induces epileptiform activity characterized by a regular (pacemaker-like) spiking pattern located in hippocampal leads. CRF has also been shown to increase the firing rate of noradrenergic neurons in the locus ceruleus. Our experiments clarified the possible role of norepinephrine (NE) in mediating hippocampal activity of CRF. Intraperitoneal (i.p.) injection of the alpha 2-agonist clonidine at a dose of 0.5-5 micrograms/kg prevented, in a dose-related manner, the hippocampal epileptiform activity induced by CRF (20 micrograms i.c.v.). Our results suggest a possible role of NE in CRF-induced spiking activity.

Predictive testing for Wilson's disease using tightly linked and flanking DNA markers.

We studied DNA polymorphisms for five new chromosome 13 markers in 52 Wilson's disease (WD) families from Europe, North America, and the Middle East. There was significant evidence for linkage between the Wilson's disease locus (WND) and all the marker loci. Multilocus linkage analysis, using a genetic linkage map established from reference pedigrees, suggested that WND is most likely between D13S31 and D13S59, at distances of 0.4 and 1.2 centimorgans, respectively. Our results suggest that the chromosomal location of the Wilson's disease gene is the same in all families from the populations studied. This evidence and the availability of many close, flanking, and polymorphic DNA markers make possible accurate and informative testing of potential carriers and WD homozygotes in families with at least one previously affected child. An advantage of a genetic linkage test over other laboratory methods for prediction of genotype in WD is that a reliable diagnosis can be made at a much earlier stage in life, including prenatally. In addition, DNA testing can be used in place of an invasive liver biopsy procedure to confirm a diagnosis in patients with borderline serum ceruloplasmin levels. Presymptomatic identification will also allow therapeutic intervention to prevent symptoms before irreparable liver or neurologic damage occurs. We describe the implementation of prenatal and preclinical diagnosis for two families with WD.