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Introduction The COVID-19 outbreak highly impacted the acute ischemic stroke care management. The primary end point of the study was to evaluate the impact of the COVID-19 outbreak and the following lockdown measures on our hub-and-spoke network; the secondary end point was to evaluate if the impact of the COVID-19 outbreak was different in hub-and-spoke centers. Methods This was a retrospective multicenter observational study conducted at the Stroke Units of Policlinico Gemelli, Ospedale San Filippo Neri, Ospedale di Belcolle, and Ospedale San Camillo de Lellis. We collected clinical reports of all consecutive patients admitted with diagnosis of acute ischemic stroke or transient ischemic attack (TIA) during the phase 1 of the lockdown period (11 March 2020–4 May 2020). As controls, we used all consecutive patients admitted for acute ischemic stroke or TIA in the same period of the previous year. Results A total of 156 and 142 clinical reports were collected in 2019 and 2020, respectively. During the COVID-19 outbreak, we observed a reduction of number of thrombolysis, a reduction of the length of hospitalization, and an increase of pneumonia. Regarding performance indicators, we observed an increase in onset-to-door time and in door-to-groin time. We did not observe any statistically significant interaction between year (2019 vs 2020) and facility of admission (hub vs spoke) on all variables analyzed. Discussion Our observational study, involving hub-and-spoke stroke network of a wide regional area, indicates that the COVID-19 outbreak impacted on the acute stroke management. This impact was equally observed in hub as well as in spoke centers.

Botulinum toxin (BT) is an effective and safe treatment for spasticity, with limited evidence in multiple sclerosis (MS). We aim to describe the use of BT for the management of MS spasticity in the clinical practice, its combination with other anti-spastic treatments in MS and possible MS clinical correlates. This is a multicentre cross-sectional observational study including 386 MS patients, receiving BT for spasticity in 19 Italian centres (age 53.6 ± 10.9 years; female 228 (59.1%); disease duration 18.7 ± 9.2 years; baseline Expanded Disability Status Scale (EDSS) 6.5 (2.0–9.0)). BT was used for improving mobility (n = 170), functioning in activities of daily living (n = 56), pain (n = 56), posturing-hygiene (n = 63) and daily assistance (n = 41). BT formulations were AbobotulinumtoxinA (n = 138), OnabotulinumtoxinA (n = 133) and IncobotulinumtoxinA (n = 115). After conversion to unified dose units, higher BT dose was associated with higher EDSS (Coeff = 0.591; p

A 74-years-old man experienced severe diplopia one month after recovery from an uncomplicated SARS-CoV-2 infection. Neurological examination was normal whereas ophthalmological examination showed bilateral exophthalmos with a complex ocular motility disorder characterized by a pseudo-internuclear ophthalmoplegia after fatigue associated to impairment of elevation and infraduction. Antibodies against TSH and acetylcholine receptors were positive; subsequent hormonal tests, ultrasonography of thyroid gland, single fiber electromyography and orbit MRI confirmed the diagnosis of concomitant Graves Disease (GD) and Myasthenia Gravis (MG). The coexistence between MG and GD is not rare but simultaneous onset after viral infection is very unsual. The complex ocular disorder simulated a deficit of the oculomotor nerve nuclei, and on clinical examination it posed some problems in the diagnosis. We suggest that recent SARS-COV-2 infection may have triggered a complex autoimmune response.

The diagnostic framework and the therapeutic management of patients with adult dystonia can represent a challenge for clinical neurologists. The objective of the present paper is to delineate diagnostic and therapeutic recommendations for dystonia provided by a panel of Italian experts afferent to the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin. We first discuss the clinical approach and the instrumental assessment useful for diagnostic purpose. Then, we analyze the pharmacological, surgical, and rehabilitative therapeutic options for adult dystonia. Finally, we propose a hospital-territory network model for adult dystonia management.

Background Many neurologic complications have been described after severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) including atypical cases of optic neuritis (ON), positive to myelin oligodendrocyte glycoprotein (MOG) IgG. Objective To report a case of MOG-IgG-associated ON and discuss why SARS-CoV-2 infection could be a potential trigger. Methods Retrospective single case report. Results We report a case of ON with positive MOG-IgG developed 15 days after presentation of SARS-CoV-2 infection. Conclusion This report suggests that SARS-CoV-2 infection may have triggered autoantibodies production against MOG leading to ON.

Background Adult-onset focal dystonia can spread to involve one, or less frequently, two additional body regions. Spread of focal dystonia to a third body site is not fully characterized. Materials and methods We retrospectively analyzed data from the Italian Dystonia Registry, enrolling patients with segmental/multifocal dystonia involving at least two parts of the body or more. Survival analysis estimated the relationship between dystonia features and spread to a third body part. Results We identified 340 patients with segmental/multifocal dystonia involving at least two body parts. Spread of dystonia to a third body site occurred in 42/241 patients (17.4%) with focal onset and 10/99 patients (10.1%) with segmental/multifocal dystonia at onset. The former had a greater tendency to spread than patients with segmental/multifocal dystonia at onset. Gender, years of schooling, comorbidity, family history of dystonia/tremor, age at dystonia onset, and disease duration could not predict spread to a third body site. Among patients with focal onset in different body parts (cranial, cervical, and upper limb regions), there was no association between site of focal dystonia onset and risk of spread to a third body site. Discussion and conclusion Spread to a third body site occurs in a relative low percentage of patients with idiopathic adult-onset dystonia affecting two body parts. Regardless of the site of dystonia onset and of other demographic/clinical variables, focal onset seems to confer a greater risk of spread to a third body site in comparison to patients with segmental/multifocal dystonia at onset.

Background The differentiation of functional dystonia from idiopathic dystonia may be clinically challenging. Objective To identify clinical features suggestive of functional dystonia to guide physicians to distinguish functional dystonia from idiopathic dystonia. Methods Patient data were extracted from the Italian Registry of Functional Motor Disorders and the Italian Registry of Adult Dystonia. Patients with functional and idiopathic dystonia were followed up at the same clinical sites, and they were similar in age and sex. Results We identified 113 patients with functional dystonia and 125 with idiopathic dystonia. Sudden onset of dystonia, evidence of fixed dystonia, and acute peripheral trauma before dystonia onset were more frequent in the functional dystonia group. No study variable alone achieved satisfactory sensitivity and specificity, whereas a combination of variables yielded 85% sensitivity and 98% specificity. A diagnostic algorithm was developed to reduce the risk of misclassifying functional dystonia. Conclusion Our findings extend the current diagnostic approach to functional dystonia by showing that clinical information about symptom onset, fixed dystonia, and history of peripheral trauma may provide key clues in the diagnosis of functional dystonia.

Background and aim In the scientific literature, there is unanimous consensus that hospitalization in stroke unit (SU) is the most important treatment for stroke patients. In this regard, the Act number 70/2015 by the Italian government identified specific skills that contribute to a classification of SU and outlined a “hub and spoke” stroke network. The aim of our study was to check the coverage of requirements of first and second level SU in the national territory and to shed light on any deficit or misdistribution of resources. Material and methods In 2019, a survey on the current situation related to stroke care in Italy was carried out by the Italian Society of Neurology (SIN), The Italian Stroke Organization (ISO), and the Association for the Fight against Stroke (A.L.I.Ce). Results First level SU was found to be 58 against a requirement, according to the Act 70/2015, of 240. Second level SU was found to be 52 compared with an expected requirement of 60. Neurointerventionists were 280 nationally, with a requirement of 240. A misdistribution of resources within individual regions was often seen. Conclusions The survey demonstrated a severe shortage of beds dedicated to cerebrovascular diseases, mainly because of lack of first level SU, especially in central and southern Italy. It also suggests that the current hub and spoke system is not yet fully implemented across the country and that resources should be better distributed in order to ensure uniform and fair care for all stroke patients on the whole territory.

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB—Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

Supplemental Digital Content is available in the text., Background and Purpose: We aimed to investigate the rate of hospital admissions for cerebrovascular events and of revascularization treatments for acute ischemic stroke in Italy during the coronavirus disease 2019 (COVID-19) outbreak. Methods: The Italian Stroke Organization performed a multicenter study involving 93 Italian Stroke Units. We collected information on hospital admissions for cerebrovascular events from March 1 to March 31, 2020 (study period), and from March 1 to March 31, 2019 (control period). Results: Ischemic strokes decreased from 2399 in 2019 to 1810 in 2020, with a corresponding hospitalization rate ratio (RR) of 0.75 ([95% CI, 0.71–0.80] P

Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain.

Background Acute peripheral trauma is a controversial risk factor for idiopathic dystonia. Materials and methods We retrospectively analyzed data from the Italian Dystonia Registry regarding the occurrence of acute peripheral trauma severe enough to require medical attention in 1382 patients with adult-onset idiopathic dystonia and 200 patients with acquired adult-onset dystonia. Results Patients with idiopathic and acquired dystonia showed a similar burden of peripheral trauma in terms of the number of patients who experienced trauma (115/1382 vs. 12/200, p = 0.3) and the overall number of injuries (145 for the 1382 idiopathic patients and 14 for the 200 patients with secondary dystonia, p = 0.2). Most traumas occurred before the onset of idiopathic or secondary dystonia but only a minority of such injuries (14 in the idiopathic group, 2 in the acquired group, p = 0.6) affected the same body part as that affected by dystonia. In the idiopathic group, the elapsed time between trauma and dystonia onset was 8.1 ± 9.2 years; only six of the 145 traumas (4.1%) experienced by 5/1382 idiopathic patients (0.36%) occurred one year or less before dystonia onset; in the acquired dystonia group, the two patients experienced prior trauma to the dystonic body part 5 and 6 years before dystonia development. Discussion and conclusion Our data suggest that the contribution of peripheral acute trauma to idiopathic dystonia is negligible, if anything, and likely involves only a small subset of patients.

Bladder dysfunction may cause disabling symptoms in Parkinson's disease (PD) patients. The majority patients' experience symptoms as urinary urgency and nocturia suggest overactive bladder. This seems to be due to an altered brain-bladder relationship because of alteration in fronto-basal ganglia D1-dopaminergic circuit that normally suppresses micturition-reflex. Previous studies demonstrated beneficial effect of D1/D2 dopamine-receptors chronic-stimulation on detrusor overactivity of PD-patients.The present study was aimed to evaluate possible effect of extended-release (ER) Levodopa administered at bed-time on both nocturia and nocturia-related quality-of-life (NQoL) in PD-patients.106 PD-patients (Hoehn and Yahr1 and 4, mean age 66 years, 59 females and 47 males) were enrolled by 7 Movement Disorders out-patients clinics. Patients undergo to International Prostatic Symptoms Scale-IPSS, including 1-item about nocturia (item 7), and to Nocturia Quality of Life-NQoL questionnaire, at baseline and after two-months of Extended-Release L-dopa (L-dopa/carbidopa or L-dopa benserazide) treatment at bed-time.Statistical analysis showed significant improvement on both total IPSS, item 7and NQoL scores following two-months ER L-dopa-treatment. ΔIPSS score inversely correlated with disease duration.This results support previous evidence of pathophysiological involvement of dopaminergic transmission on bladder dysfunction in PD.

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.

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.

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.

Objective To investigate the peripheral auditory pathway in Parkinson's disease (PD) by using objective, quantitative and non-invasive audiological techniques, transient-evoked (TEOAE) and distortion product (DPOAE) otoacoustic emissions, in order to detect subclinical alterations of cochlear functioning and possible changes after dopaminergic stimulation. Methods We enrolled 11 untreated de-novo PD patients and 11 age and sex-matched healthy controls. Subjects underwent a routine audiological evaluation and otoacoustic emission recordings. The patients were then slowly-titrated to a stable dose of 100 mg levodopa four times in a day. A post-treatment assessment was made in order to detect significant changes in audiological responses. Finally, possible associations between clinical data and hearing results were also evaluated. Results At pure-tone audiometry, higher auditory threshold levels were observed in PD when compared to the controls. Moreover, DPOAE responses in PD patients were found low at almost all tested frequencies, suggesting subclinical cochlear damage. Interestingly, after dopaminergic treatment, a significant increase in DPOAE responses was detected. Notably, DPOAE dysfunction correlated with clinical severity, whereas high hearing thresholds appeared positively related with more prolonged disease duration. Conclusions Our findings demonstrate that otoacoustic emission recording and pure-tone audiometry reveal levodopa-sensitive cochlear dysfunction and hearing loss in PD. A parallel improvement in subjective motor symptoms and DPOAE objective responses could help clinicians in monitoring therapeutic responses and dynamic changes during the course of the disease.

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis. Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death. Results: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007). Conclusion: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome. © 2013 American Academy of Neurology.

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.

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.

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 forebrin 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.

Three patients who presented with grand real 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.

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.

It is well established that the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to human beings or to non-human primates brings about a parkinsonian syndrome which closely resembles idiopathic Parkinson’s disease (Snyder and D’Amato, 1986). With few noticeable exceptions (Langston and Ballard 1983), the human cases of accidental exposure to MPTP were caused by acute administration of this toxin (i.e., a single or few repeated injections; Langston, 1987). Similarly, in order to obtain experimental animals which are clinically affected, monkeys are usually injected with repeated doses of MPTP over 2 to 5 days. Regimen varies according to the species. In marmosets, 4–5 daily injections of 1–4 mg/kg/day i.p. are effective so as to obtain animals which are obviously parkinsonian, but who can maintain themselves (Jenner et al., 1984). The resemblance of MPTP-induced parkinsonism to Parkinson’s disease is still an unsolved issue (Albanese 1989). Recently, Kish et al. (1988) found that, in patients affected by Parkinson’s disease, dopamine loss is more severe in the putamen than in the caudate nucleus, while in monkeys poisoned acutely with MPTP dopamine loss is higher in the caudate nucleus than in the putamen.

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.

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.

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.

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.

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.

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.

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.