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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

Virtually no neurologist nor psychiatrist today can be unaware of the diagnosis of Gilles de la Tourette syndrome (GTS). Although the eponymous description by Dr. Georges Gilles de la Tourette was published in 1885, familiarity with this syndrome has been achieved only recently. In this article, the two most renown accounts of exceptional individuals retrospectively diagnosed with GTS are critically analyzed: British lexicographer Samuel Johnson and Austrian musician Wolfgang Amadeus Mozart. In both cases, clinical descriptions have been retrieved from written documents predating Gilles de la Tourette's original publication. The case for Samuel Johnson having GTS is strong, mainly based on Boswell's extensive biographical account. Johnson was reported to have a great range of tics and compulsions, including involuntary utterances, repetitive ejaculations, and echo-phenomena. On the other hand, there is circumstantial evidence that Mozart may have had hyperactivity, restlessness, sudden impulses, odd motor behaviors, echo/palilalia, love of nonsense words, and scatology, the latter being documented in autograph letters ("coprographia"). However, the evidence supporting the core features of GTS, i.e., motor and vocal tics, is rather inconsistent. Thus, GTS seems to be an implausible diagnosis in Mozart's medical history and completely unrelated to his undisputed musical genius.

The aim of this study was to determine if blood chitotriosidase (Chit) activity and lysosomal enzyme levels might represent markers of disease activity and progression in amyotrophic lateral sclerosis (ALS). It is a survey clinic-based study performed in a tertiary ALS centre. Blood samples were obtained from 76 patients with ALS in different stages of the disease and from 106 healthy individuals serving as controls. Chit activity and the levels of acid alpha-glucosidase, acid alpha-galattosidase A, beta-glucocerebrosidase, and alpha- l- iduronidase were detected using the dried blood spots (DBS) technique. The CHIT1 genotype for exon 10 duplication and for the p.G102S variant was also determined. Chit activity was significantly higher in ALS patients than in healthy individuals. This difference was independent of the genotypes at CHIT1 functional variants. Chit were significantly higher in 34 rapidly progressing patients as compared to 42 with slowly progressive disease. Acid alpha-glucosidase was higher than normal and significantly correlated with the severity of the disease. Glucocerebrosidase and alpha- l- iduronidase activity were significantly lower in patients than in the controls. Alpha-galactosidase A was higher than normal only in rapidly progressing patients. We have employed a very simple and affordable laboratory test to measure blood Chit and lysosomal enzymes activity which could be easily included in the screening of ALS patients recruited in clinical trials. Remarkably, high levels of chitinase and alpha-galactosidase A could help to distinguish patients with fast progression from those with slow progression of the disease and possibly to follow the effects of treatments on neuroinflammation and autophagy.

Orthostatic hypotension is defined as the reduction of systolic blood pressure of at least 20 mmHg or the dropping of diastolic blood pressure of at least 10 mmHg within 3 minutes of standing compared to baseline values. It can be divided into neurogenic and non neurogenic forms. Neurogenic forms are caused by a primitive damage to autonomic nervous system, while drugs are the most common cause of non neurogenic orthostatic hypotension; they may also complicate or aggravate neurogenic forms. Many drugs can determine orthostatic hypotension, including both cardiovascular drugs and therapies used for neurological and psychiatric disorders. This effect is furthermore enhanced by multiple pharmacological treatments. It is important for the clinician to know the potential hazard of orthostatic hypotension, in order to avoid syncope, falls, hypoperfusion symptoms, excess of mortality and loss of compliance to treatment.

Autonomic failure is a common finding in patients with Parkinson disease (PD). Here we describe a patient with PD in whom autonomic symptoms began 3 years before motor deficits.

Background aims. Mesenchymal stem cells/marrow stromal cells (MSC) represent a promising tool for stem cell-based clinical trials in amyotrophic lateral sclerosis (ALS). We present the results of long-term monitoring of 19 ALS patients enrolled in two phase I clinical trials of autologous MSC transplantation. Methods. Nineteen patients (11 male and eightfemale) with ALS were enrolled in two consecutive phase I clinical trials. The patients were followed-up for 6-9 months and then treated with autologous MSC isolated from bone marrow and implanted into the dorsal spinal cord with a surgical procedure. The patients were monitored regularly before and after transplantation with clinical, psychological and neuroradiologic assessments every 3 months, at the tertiary referral ALS center in Novara (Italy), until death. Results. Follow-up brain magnetic resonance imaging (MRI) revealed no structural changes (including tumor formation) relative to the baseline throughout the follow-up. There was no deterioration in the psychosocial status and all patients coped well. No clear clinical benefits were detected in these patients but the recruitment and selection of appropriate patients into larger trials will be needed to test the efficacy of the treatment. Conclusions. This study is the first to show the safety of MSC transplantation in the central nervous system during a follow-up of nearly 9 years, and is in support of applying MSC-based cellular clinical trials to neurodegenerative disorders.

We report a case of conjugal amyotrophic lateral sclerosis (ALS) encountered in our tertiary ALS Centre. Family trees, possible environmental factors, and all known ALSassociated genes have been studied. The incidence of sporadic ALS ranges from 1.33 to 3.22 per 100,000, and the prevalence in Italy is 5.2 to 8.0 per 100,000 inhabitants [1]. Our patients lived in the Piedmont Region, in Northern Italy, where the incidence is 2.90/100,000 population, and the prevalence is 7.89 to 8.00/100,000 [2]. Since ALS is such a rare disease, chances of conjugal ALS are extremely low, estimated to be about 1 in 510,000 couples. To our knowledge only 20 cases have been reported of both spouses suffering from ALS [3–5]. In 2005, a 63-year-old man was diagnosed with spinal onset ALS after presenting with a two-year history of widespread fasciculations and progressive gait impairment. On neurological examination we found diffuse spontaneous fasciculations, moderate atrophy and weakness of limbs, with tendon hyperreflexia and Babinski sign. Electromyography (EMG) revealed diffuse fasciculation potentials and motor unit action potentials on voluntary activation, with complex and unstable morphology in all sampled upper and lower limb muscles. Transcranial magnetic stimulation detected a delay of the central motor conduction time in upper and lower limbs. The patient was a blacksmith, but serum and urinary heavy-metal concentrations were normal. Endocrine, paraneoplastic, autoimmune, and infective panels and cerebral spinal fluid results were also normal. He died of respiratory failure five years after initial presentation. Three years later, his 68-year-old non-consanguineous wife presented to our clinic with dysphonia, dyspnea at rest, and orthopnea. She was a saleswoman and had no contact with the husband’s workshop. Neurological examination demonstrated mild wasting and fasciculations of the tongue, and neck weakness. Widespread fasciculations were detected also in the limbs. Deep tendon reflexes were increased. The patient’s laboratory tests and MRI of the brain and spinal cord were normal. EMG showed diffuse involvement of the lower motor neuron in the limb and bulbar muscles, while electroneurography was normal. Pulmonary function was assessed, revealing a forced vital capacity of 45 %. The diagnosis of ALS with bulbar onset was confirmed, and she is still alive with noninvasive ventilation support. The patients were born in the same town of about 20,000 inhabitants, located in a rural area of the Piedmont region, and they lived there together for 30 years. In this area no cases of familiar ALS have been reported, and the incidence of the disease does not differ from that in other areas of the Piedmont region. Family trees of both patients, built from the second generation back (Fig. 1), established that the two subjects were not related and that no relative was ever affected by neurodegenerative disease. Both patients were screened for known ALS-associated genes (C9orf72; SOD1; TDP_43; FUS; Ataxin-2; uBQN2 ex4; PFN), and no mutations were detected. No common exposures were identified in regard to exogenous and environmental toxins such as radiation, food-borne pathogens, cosmetics, drugs, pesticides in agricultural environments; nor were there exposure risks from smoking, intense physical activity, or trauma. E. Bersano (&) S. Servo R. Cantello L. Mazzini Department of Neurology, ALS Center, Eastern Piedmont University, Maggiore della Carita Hospital, Novara, Italy e-mail: enricabersano@gmail.com

Background: Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterised by the presence of multiple motor and phonic tics. Recent brain imaging investigations with diffusion tensor imaging (DTI) techniques found reduced measures of connectivity in the corpus callosum of children with TS compared with healthy controls, thus raising the hypothesis that the reduced interhemispherical connectivity in TS reflects neural plasticity processes. Methods: We assessed corpus callosum white-matter connectivity with fractional anisotropy (FA) index from magnetic resonance-DTI in two monozygotic twins (male sex; age 20) discordant for the diagnosis of TS. Results: Both conventional morphological magnetic resonance images and fibre-tracking reconstruction failed to show any difference between the two twins. On the other hand, mean corpus callosum FA values were significantly lower in the affected twin than in the unaffected twin (p

Amyotrophic lateral sclerosis (ALS) is a devastating incurable neurodegenerative disease that targets motor neurons, manifesting as a linear decline in muscular function and leading to death within 2 - 5 years of diagnosis. The vast majority of ALS cases are sporadic, the aetiopathology of which is incompletely understood. Recent data have implicated the microenvironment of the motor neuron as a primary target of the pathophysiology. Any experimental therapeutic approach to ALS is very difficult because of some peculiarities of the disease, such as the unknown origin, the spatial diffusion of motor neuron loss and the paucity of animal models. Despite such daunting challenges, in experimental models a number of potential benefits of stem cells in ALS therapy have been demonstrated: by providing non-compromised supporting cells such as astrocytes, microglia or growth factor-excreting cells, onset can be delayed and survival increased. Moreover, in animal models of acute or chronic motor neuron injury, neural stem cells implanted into the spinal cord have been shown to differentiate into motor neurons, with some evidence of axonal sprouting and formation of nerumuscular junctions with host muscle. Here we summarise and discuss current preclinical and clinical evidence regarding stem cells application in ALS, particularly focusing on methodological issues.

Gilles de la Tourette syndrome is a neurodevelopmental disorder consisting of multiple motor and one or more vocal/phonic tics. Tourette's syndrome is increasingly recognized as a common neuropsychiatric disorder usually diagnosed in early childhood, and comorbid neuropsychiatric disorders occur in approximately 90% of patients; the most common of these are attention deficit hyperactivity disorder and obsessive-compulsive disorder. Depression is also common, with a lifetime risk of 10% of patients. Moreover, a high prevalence of personality disorders has been reported in preliminary investigations on Tourette's syndrome populations. This paper provides an updated review of the literature on the multifaceted phenotype of Tourette's syndrome, with special attention to the behavioral problems and the relationship between Tourette's syndrome and comorbid neuropsychiatric conditions. The issue of whether Tourette's syndrome should still be considered as a unitary nosological entity is also addressed.

Pathological gambling symptoms (PGS), that is, the subjective urge to gamble and the actual gambling behaviors, are currently acknowledged as relatively common symptoms among Western countries, with an estimated point prevalence of 0.6-1.1% in the general population. Converging evidence suggests that PGS are overrepresented in patients with neurological conditions affecting dopaminergic reward pathways, and can be expressed in both impulse control disorders and obsessive-compulsive spectrum disorders. This study explored the clinical correlates of PGS in patients with epilepsy. Eighty-eight consecutive adult outpatients recruited at three epilepsy clinics in northern Italy were assessed using the Gambling-Symptom Assessment Scale (G-SAS), along with a battery of psychometric instruments to index depression (Beck Depression Inventory [BDI]), anxiety (Spielberger State-Trait Anxiety Inventory [STAI]), and obsessionality (Yale-Brown Obsessive Compulsive Scale [YBOCS]) symptoms. On the G-SAS, patients with a diagnosis of temporal lobe epilepsy (TLE) reported a mean [sd] G-SAS score of 2.0 [5.7], significantly higher than patients with frontal lobe epilepsy (FLE) (0.6 [1.7]) and idiopathic generalized epilepsy (IGE) (0.4 [1.4]). Moreover, multiple regression analysis showed that G-SAS scores were selectively predicted by YBOCS scores, thus suggesting an association between the expression of obsessional spectrum symptoms and PGS in patients with TLE. Alterations in the mesolimbic reward system could represent the putative neuropathological substrate for this multifaceted clinical picture.

Ictal alterations of the level of general awareness and subjective content of consciousness play a pivotal role in the clinical phenomenology of epilepsy, and reflect the pathological involvement of different neurobiological substrates. However, no self-reported measures have been proposed for patients experiencing altered conscious states during seizures. This study describes the development and validation of a new scale for the quantitative assessment of the level and content of ictal consciousness, the Ictal Consciousness Inventory (ICI). The ICI is a 20-item questionnaire generated on the basis of interviews with patients, literature review, and consultation with experts. It was tested on a sample of 110 patients attending three different epilepsy clinics in Northern Italy, who also completed standardized clinical scales. Standard psychometric methods were used to demonstrate that this scale satisfies criteria for acceptability, reliability, and validity. The ICI is proposed as a user-friendly and clinically sound instrument for the measurement of ictal alterations of consciousness in patients with epilepsy.

We report on a 46-year-old male patient affected by amyotrophic lateral sclerosis (ALS) with bulbar onset. His family and medical history was not relevant. In February 2008, a paper published by Fornai et al. [3] suggested that daily lithium administration at a serum level of 0.4–0.8 mEq/L delays ALS progression in both the animal model and in patients. The patient asked to try this new therapy and lithium was prescribed for compassionate use 4 years after disease onset. On neurological examination we found mild atrophy and fasciculations of the tongue, severe dysarthria, and mild dysphagia. Jaw jerk and glabellar tap were absent. Light lower limb muscle weakness, rare diffused fasciculations, and normal muscle tone were detected. Reflexes were brisk in the lower limbs. Babinski sign was bilaterally found. Functional status was good (ALS-FRS 34/40). The patient started lithium assumption at very low dose (150 mg lithium carbonate/day) for 1 week and then increased to 300 mg/day. Lithium blood level was tested every 2 weeks in order to keep it at the lower therapeutic range (0.3 mEq/L). Associated medications were riluzole 100 mg/day, a-tocopherol 900 mg/day, trihexyphenidyl 4 mg/day (symptomatic of sialorrhea). There was no history of additional medication such as antidepressants or antipsychotics, thiazide diuretics, NSAIDS, or ACE inhibitors. Three months later, the patient began to complain of gait instability and frequent falling. Neurological examination showed festinating gait, diffuse bradykinesia, severe stiffness, and positive cogwheel phenomenon both in the upper and lower limbs. No lithium-induced postural tremor was detected. The lithium value was 0.31 mEq/L, and blood count, electrolytes, and renal and thyroid function were all normal. The patient described no concomitant episode of fever and diarrhea. Lithium was immediately discontinued. A therapeutic attempt with L-dopa was unsuccessful. Eight months after lithium discontinuation, the extrapyramidal features significantly improved, only festinating gait persisted. However, spasticity severely worsened and functional status was largely impaired (ALS-FRS = 20/40). On the brain MRI scans, hyperintensities of the corticospinal tract were detected bilaterally (as expected in ALS). SPECT with 1231-ioflupano (DAT-scan) showed normal dopaminergic function in the basal ganglia. The patient also tested negative for SOD1, TDP-43, and FUS gene mutations. This was a very rare case of acute lithium neurotoxicity with low serum level and in the absence of other intoxication symptoms or association with antipsychotic drugs. Movement disorders have been reported during lithium treatment, and are usually associated with high serum levels. To our knowledge, in only one patient Parkinsonism manifested during lithium treatment alone [2, 4] and in one patient with therapeutic levels [4]. Lithium is known to decrease the amount of dopamine in rat striatum and limbic forebrain and act as an anticholinesterase able to increase central cholinergic activity. Because serum lithium levels do not always reflect L. Mazzini, G. D. Oggioni, N. Nasuelli, S. Servo, L. Testa, and F. Monaco contributed equally to the manuscript.