Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

Wearing-off detection in clinical practice: the wearing off real practice key (WORK-PD) study in Parkinson's disease.

OBJECTIVE: Verifying the validity and feasibility of the WOQ-19 as a useful tool in routine clinical practice and in management of patients. METHODS: 532 consecutive Parkinson's disease (PD) patients were recruited from 6 different neurological outpatient units, specialized in movement disorders, of central Italy. Inclusion criteria were diagnosis of PD and any current pharmacological treatment of PD while exclusion criteria were evident cognitive or depressive impairment, infusion with dopamine agonists or Duodopa, or Deep Brain Stimulation therapy. Patients were asked to complete the Italian version of WOQ-19 before the neurological visit. A medical form for the collection of demographic and clinical data of patients and for the evaluation of comprehensibility and usability the WOQ-19 was filled by the neurologist during the visit. RESULTS: Our data confirmed that WOQ-19 was able to identify WO in 69% of patients, a percentage similar to the recently reported in the Italian WOQ-19 validation study. Motor symptoms were more frequent than non-motor symptoms (80% vs. 20%). Patients who experienced WO had a higher age of PD onset, more severe disease, longer disease duration and were more likely to be female. CONCLUSIONS: The WOQ-19 was understandable for the patient, easily administered and suitable for routine outpatient use. It could be also particularly useful in clinical practice in the early identification of non-motor symptoms, often under reported by patients and revealed only with clinical support.

Cholinergic and non-cholinergic forebrain projections to the interpeduncular nucleus.

A combined fluorescent retrograde tracing and acetylcholinesterase (AChE) histochemical technique was used for the study of some forebrain projections to the interpeduncular nucleus (IPN). After injections of a fluorescent tracer into the IPN, the distribution of AChE-containing and of fluorescent retrogradely labeled neurons was simultaneously studied in the habenular nuclei, medial septum and diagonal band of Broca. In all these regions, the majority of retrogradely labeled neurons also contained AChE: neurons located in the habenular nuclei stained lightly or moderately for the enzyme, while neurons located in the diagonal band and medial septum displayed intense AChE staining and were classified as putatively cholinergic perikarya. In all regions, a minority of labeled neurons did not stain for AChE, and were identified as non-cholinergic neurons projecting to the IPN. The present study shows the existence of a biochemical heterogeneity in the habenulo-interpeduncular and telencephalo-interpeduncular pathways, and indicates that the latter contains putatively cholinergic as well as non-cholinergic fibers.

Quantitative pharmacohistochemistry of acetylcholinesterase in neostriatum of inbred strains of mice.

A quantitative pharmacohistochemical technique has been used in the present study to assay acetylcholinesterase (AChE) activity in the neostriatum of C57BL/6 and DBA/2 mice. This technique permits the measurement of enzyme activity into microscopically defined compartments and is suitable for the study of striatal AChE-containing, putatively cholinergic, neurons. Microphotometric measurements have been performed in the cytoplasm of AChE-containing perikarya and in the striatal matrix: in both compartments, AChE activity was significantly higher in DBA/2 than in C57BL/6 mice. The present data show that AChE quantitative pharmacohistochemistry is suitable for studying the enzyme activity in nervous tissue and, particularly, in the cytoplasm of individual AChE-containing neurons. In addition, interstrain comparison indicates the presence of a genetically determined higher AChE content in striatal neurons of the DBA/2 strain.

Genetically determined cholinergic deficiency in the forebrain of C57BL/6 mice.

This study demonstrates that a deficiency of forebrain cholinergic neurons occurs in C57BL/6 (C57) mice, a strain characterized by poor learning capabilities. The brains of 21-day-old and 18-week-old C57 and DBA/2 (DBA) mice were studied by means of acetylcholinesterase (AChE) histochemistry and of choline acetyltransferase (ChAT) immunocytochemistry. Computer-assisted image analysis was performed on sections through the medial septum, the diagonal band of Broca, the basal nucleus of Meynert and the neostriatum. As compared to the DBA strain, C57 mice had a reduced number of forebrain cholinergic neurons. This feature was present at the age of 21 days and persisted to 18 weeks. Between-strain variations in the density of neurons were more obvious in ChAT-stained material than in AChE-stained sections. These data show that C57 mice can be regarded as a genetic mutant, whose phenotype is characterized by a reduced number of forebrain cholinergic neurons and by cognitive abnormalities. C57 mice represent a valuable model for studying the influence of genetic factors on central nervous system cholinergic mechanisms and the effects of genetically determined cholinergic deficiency on behavior and learning.

Strain-dependent variations in the number of forebrain cholinergic neurons.

The morphological organization of putatively cholinergic neurons was studied in the forebrain of two inbred mouse strains (C57BL/6 and DBA/2) by means of acetylcholinesterase pharmacohistochemistry. In both strains, putatively cholinergic perikarya were seen in the caudato-putamen, medial septum, diagonal band, and basal nucleus of Meynert: in all these regions, their distribution was similar in both strains, but their density was significantly higher (from 20 to 32%) in DBA/2 mice. The present data demonstrate the existence of genetically determined differences in the organization of forebrain cholinergic systems.

Aging is associated with a diffuse impairment of forebrain cholinergic neurons.

The study evaluates whether any degenerative changes affect forebrain cholinergic systems during natural aging. The medial septal nucleus, the nuclei of the diagonal band, the neostriatum, and the basal nucleus were studied in adult and aged Wistar rats. Butcher's technique for acetylcholinesterase allowed us to identify neurons located in these forebrain nuclei, which stained intensely or moderately for the enzyme and were putatively cholinergic. The size of forebrain regions containing stained neurons, and the number and size of stained perikarya located therein, were measured. In aged rats, the size of forebrain cholinergic nuclei was reduced by an average of 26%. The density of neurons located in these regions was also significantly lower in aged rats than in controls; intensely stained neurons displayed a mean reduction of 27.81%, while intensely and moderately stained perikarya together were reduced by 25.43%. Cross-sectional area of the stained perikarya was also reduced in aged rats by 32.87%. These data show that the number of forebrain acetylcholinesterase-containing neurons is reduced in aged rats. They are consistent with the hypothesis that natural aging brings about a diffuse and homogeneous depletion of forebrain cholinergic perikarya. Neurons which are viable, and can be selectively stained, show morphological alterations, which are likely to be related to a degenerative process.

Age-dependent loss of cholinergic neurones in basal ganglia of rats.

A morphometric study of the striatal complex has been performed in adult and aged rats, by means of Butcher's acetylcholinesterase (AChE) staining. The size of neostriatum, and the number of putatively cholinergic AChE-positive perikarya, are significantly reduced in two-year-old rats. Consequently, mean cell density is decreased in the striatal complex by 15.58%; age-dependent loss is more pronounced: (1) in the dorsal and lateral parts of neostriatum, which in adults have a higher neural density; and (2) in the ventromedial part, which in the aged becomes almost void of neurones. It is concluded that depletion of cholinergic perikarya is a specific feature of natural ageing, which affects diffusely the neostriatum, and particularly its ventromedial territories.

Organization of central nervous system dopaminergic pathways.

In the present paper the organization of central nervous system dopaminergic pathways is concisely reviewed. Six dopaminergic systems are described: the midbrain efferent system, the tubero-infundibular, the diencephalo-spinal, the incerto-hypothalamic, the periventricular, and the retinal systems. Anatomo-functional correlations can be presently outlined for most dopamine-containing networks, and anatomo-clinical studies indicate that they are globally affected in patients suffering from Parkinson's disease.

A genetic study of neostriatal cholinergic neurones in C57BL/6 and DBA/2 mice.

In the present study Butcher's pharmaco-histochemical technique for acetylcholinesterase has been employed for a morphometrical analysis of striatal cholinergic neurones in crossbred C57BL/6 x DBA/2 F1 mice. The general organization of neostriatal cholinergic systems in hybrid mice was similar to that of parent strains. However, as shown by morphometry, the size of neostriatum in hybrids was larger than that of both parental strains, and the density of striatal cholinergic neurones was significantly lower than that of DBA/2 mice, being close to that of the C57BL/6 strain. The present data indicate that a reduced number of striatal cholinergic neurones is inherited as a dominant trait by these hybrid mice.

Neuropeptides in dopamine-containing regions of the brain.

This paper reviews evidence of direct interactions occurring in the central nervous system between peptide- and dopamine-containing neural networks. While it seems fairly clear that neuropeptides are involved in the process of interneuronal communication, their specific role appears to be different from that of classic transmitters (which include dopamine). Neuropeptides coexist with dopamine in specific dopamine-containing neurons; in addition they interact abundantly with the dopaminergic neurons, by acting either on the perikarya or on the dopaminergic nerve terminals. Such interactions are reciprocal and account for some behavioral correlates of neuropeptide and dopamine alterations in the brain. They also shed new light on the pathophysiology of neurological and psychiatric diseases associated with depletion or abundance of brain peptides.

Neuroleptic malignant syndrome and catatonia. A report of three cases.

In a series of 1007 consecutively admitted patients, 3 cases of neuroleptic malignant syndrome (NMS) were identified (0.3%). All three patients were affected by mood disorders with congruent psychotic features, had shown catatonia just before the onset of NMS, and had been treated with low neuroleptic doses. All of them presented low serum iron levels. The relationship between NMS and catatonia and possible therapeutic decisions are discussed.

Severe barbiturate withdrawal syndrome in migrainous patients.

Three patients who presented with grand mal seizures and an associated behavioral disorder were recognized as suffering from a severe butalbital withdrawal syndrome. All were migraineurs who had become dependent on barbiturates. We propose that the occurrence of seizures, psychotic behavior, or a recent personality change should be considered clues to possible barbiturate abuse in patients with migraine.

Histochemical demonstration of heavy metals in the reptilian archicortex.

The topographic distribution of heavy metals has been studied in the reptilian brain by means of Timm's sulphide silver method. Timm-positive histochemical reaction was detected in the archicortex and in the septum. In the first region, the staining pattern yielded evidence of cortical layering and the distribution of mossy fiber terminals. In the septum, uneven distribution of histochemical staining permitted identification of different functional territories. These data show that the reptilian archicortex is in many ways homologous to the mammalian hippocampus and fascia dentata, and also indicate that it undergoes significant remodeling during evolution.

Westphal-Strümpell disease: a case report with a new method of urinary copper evaluation.

A case of Westphal-Strümpell disease diagnosed by classical serum and urinary investigations is described. The efficacy of specific treatment was monitored by the values of urinary copper excretion, determined by a new quantitative chemical method, which is described in detail.

Transient alternating hemichorea as presenting sign of progressive supranuclear palsy.

We report the case of a man who developed unilateral alternating chorea four years before presenting a typical clinical form of Steele-Richardson-Olszewski syndrome. It is known that choreic dyskinesias may occur during the course of this syndrome but this is the first account of choreas presenting sign of the syndrome.