Spectrum of sleep-disordered breathing and quality of sleep in adolescent and adult patients with spinal muscular atrophy.

Sleep-disordered breathing is common among children with spinal muscular atrophy, but has been hardly studied among adult subjects. Little is known about sleep quality in spinal muscular atrophy. The aims of this study were to evaluate occurrence and characteristics of sleep-disordered breathing and subjective sleep quality among adolescent and adult patients with spinal muscular atrophy type 2 or 3. Twenty patients aged 33.9 ± 15.2 years were studied. They underwent nocturnal cardiorespiratory monitoring, lung and muscular function evaluation, and were administered the Pittsburgh Sleep Quality Index questionnaire. Nineteen patients showed sleep-disordered breathing, with obstructive events in seven subjects and non-obstructive events in the remaining 12. In the latter group, 10 patients showed pseudo-obstructive hypopneas. Patients with non-obstructive sleep-disordered breathing were younger (p = 0.042), had a lower body mass index (p = 0.0001), were more often affected by spinal muscular atrophy type 2 (p = 0.001), and showed worse impairment of respiratory function than patients with obstructive sleep-disordered breathing. Ten patients were classified as poor sleepers and 10 patients good sleepers. In the whole sample, sniff nasal inspiratory pressure proved to be the only independent predictor of sleep quality (p = 0.009). In conclusion, sleep-disordered breathing is common even among adult patients with spinal muscular atrophy type 2 and 3, and may show either obstructive or different types on non-obstructive features. A worse respiratory muscle function is associated to non-obstructive sleep-disordered breathing and poorer sleep quality. Sleep quality should receive greater attention especially in patients with spinal muscular atrophy type 2, who have a poorer respiratory muscle function, as it could affect their quality of life.

Genetic screening for hereditary transthyretin amyloidosis with polyneuropathy in western Sicily: Two years of experience in a neurological clinic.

BACKGROUND AND PURPOSE: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. METHODS: A prospective systematic genetic screening for ATTRv-PN was proposed in patients presenting with a sensory-motor idiopathic polyneuropathy and two or more "red flags" among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients. RESULTS: In the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv-PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv-PN patients and 26 presymptomatic carriers) among 84 first-degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy. CONCLUSIONS: A systematic screening for ATTRv-PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow-up at the clinical onset.

Assessment of diagnostic criteria for multifocal motor neuropathy in patients included in the Italian database.

BACKGROUND AND PURPOSE: This study aimed to assess the diagnostic criteria, ancillary investigations and treatment response using real-life data in multifocal motor neuropathy (MMN) patients. METHODS: Clinical and laboratory data were collected from 110 patients enrolled in the Italian MMN database through a structured questionnaire. Twenty-six patients were excluded due to the unavailability of nerve conduction studies or the presence of clinical signs and symptoms and electrodiagnostic abnormalities inconsistent with the MMN diagnosis. Analyses were conducted on 73 patients with a confirmed MMN diagnosis and 11 patients who did not meet the diagnostic criteria. RESULTS: The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria were variably applied. AUTHOR: When applying the American Association of Electrodiagnostic Medicine criteria, an additional 17% of patients fulfilled the criteria for probable/definite diagnosis whilst a further 9.5% missed the diagnosis. In 17% of the patients only compound muscle action potential amplitude, but not area, was measured and subsequently recorded in the database by the treating physician. Additional investigations, including anti-GM1 immunoglobulin M antibodies, cerebrospinal fluid analysis, nerve ultrasound and magnetic resonance imaging, supported the diagnosis in 46%-83% of the patients. Anti-GM1 immunoglobulin M antibodies and nerve ultrasound demonstrated the highest sensitivity. Additional tests were frequently performed outside the EFNS/PNS guideline recommendations. CONCLUSIONS: This study provides insights into the real-world diagnostic and management strategies for MMN, highlighting the challenges in applying diagnostic criteria.

Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants.

BACKGROUND AND PURPOSE: There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated. METHODS: We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP. RESULTS: According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did. CONCLUSIONS: The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients.

Transcranial alternating current stimulation can modulate the blink reflex excitability. Effects of a 10- and 20-Hz tACS session on the blink reflex recovery cycle in healthy subjects.

BACKGROUND: The blink reflex excitability, assessed through paired electrical stimuli responses, has been modulated using traditional non-invasive neurostimulation techniques. Recently, transcranial Alternating Current Stimulation (tACS) emerged as a tool to modulate brain oscillations implicated in various motor, perceptual, and cognitive functions. This study aims to investigate the influence of 20-Hz and 10-Hz tACS sessions on the primary motor cortex and their impact on blink reflex excitability. MATERIALS AND METHODS: Fifteen healthy volunteers underwent 10-min tACS sessions (intensity 1 mA) with active/reference electrodes placed over C4/Pz, delivering 20-Hz, 10-Hz, and sham stimulation. The blink reflex recovery cycle (BRrc) was assessed using the R2 amplitude ratio at various interstimulus intervals (ISIs) before (T0), immediately after (T1), and 30 min post-tACS (T2). RESULTS: Both 10-Hz and 20-Hz tACS sessions significantly increased R2 ratio at T1 (10-Hz: p = 0.02; 20-Hz: p < 0.001) and T2 (10-Hz: p = 0.01; 20-Hz: p < 0.001) compared to baseline (T0). Notably, 20-Hz tACS induced a significantly greater increase in blink reflex excitability compared to sham at both T1 (p = 0.04) and T2 (p < 0.001). CONCLUSION: This study demonstrates the modulatory effect of tACS on trigemino-facial reflex circuits, with a lasting impact on BRrc. Beta-band frequency tACS exhibited a more pronounced effect than alpha-band frequency, highlighting the influential role of beta-band oscillations in the motor cortex on blink reflex excitability modulation.

AChR-seropositive myasthenia gravis in muscular dystrophy: diagnostic pitfalls and clinical management challenges.

The co-occurrence of genetic myopathies with myasthenia gravis (MG) is extremely rare, however a few studies have been reported. We aim to explore the link between genetically inherited muscle disorders and immune-mediated neuromuscular junction conditions, taking into account the diagnostic and therapeutic implications posed by these combined conditions. We searched all English medical papers registered in Web of Knowledge, PubMed, Google Scholar, and Science Direct between January 1987 concerning the association between muscular dystrophies (MD) and MG, also adding three new cases to the series reported so far. Three new clinical cases in which MG concurs with oculopharyngeal muscular dystrophy (OPMD) or facioscapulohumeral muscular dystrophy (FSHD) or myotonic dystrophy type 2 (DM2) were reported. A comprehensive literature review showed that FSHD is the dystrophy most frequently associated with generalized MG. The AChR antibody titer is high and neurophysiologic tests prove to be an essential tool for the diagnosis. The association between MG and MD is rare but should not be underestimated. The presence of unusual clinical features suggest investigating additional overlapping condition, especially when a treatable disease like MG is suspected.

Comorbidity in myasthenia gravis: multicentric, hospital-based, and controlled study of 178 Italian patients.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder with fluctuating weakness that causes significant disability and morbidity. Comorbidities may influence the course of MG, particularly in specific subgroups. The aim of this study is to investigate the frequency of comorbidities in MG patients compared to healthy controls (HC) and to evaluate their distribution according to age at disease onset, sex, and disease severity. METHODS: MG patients attending the University Hospital "Paolo Giaccone" in Palermo and "SS Annunziata" Hospital in Chieti were enrolled; HC were enrolled from the general population. Non-parametric statistics and logistic regression were used to assess the association of specific comorbidities according to age at disease onset, sex, disease subtypes, and severity of the disease. RESULTS: A total of 356 subjects were included in the study: 178 MG patients (46% F; median age 60 years [51-71]) and 178 sex- and age-matched HC (46% F, median age 59 years [50-66]). Overall, 86% of MG patients and 76% of HC suffered from comorbidities, and MG patients had a higher number of comorbidities compared to HC. Patients with late-onset suffered from more comorbidities than those with early-onset MG. Hypertension was more common in male patients with MG, while thymic hyperplasia, osteoporosis, and autoimmune diseases were more common in females. Respiratory disorders and thymoma were more common in patients with more severe disease (p < 0.05 for all comparisons). CONCLUSION: MG patients, particularly those with late onset, showed a higher prevalence of comorbidities than HC. Assessment of comorbidities in MG is an essential issue to identify the appropriate treatment and achieve the best management.

Unclassified clinical presentations of chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: To assess the ability of the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) clinical criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) to include within their classification the whole spectrum of clinical heterogeneity of the disease and to define the clinical characteristics of the unclassifiable clinical forms. METHODS: The 2021 EAN/PNS clinical criteria for CIDP were applied to 329 patients fulfilling the electrodiagnostic (and in some cases also the supportive) criteria for the diagnosis of CIDP. Clinical characteristics were reviewed for each patient not strictly fulfilling the clinical criteria ('unclassifiable'). RESULTS: At study inclusion, 124 (37.5%) patients had an unclassifiable clinical presentation, including 110 (89%) with a typical CIDP-like clinical phenotype in whom some segments of the four limbs were unaffected by weakness ('incomplete typical CIDP'), 10 (8%) with a mild distal, symmetric, sensory or sensorimotor polyneuropathy confined to the lower limbs with cranial nerve involvement ('cranial nerve predominant CIDP') and 4 (1%) with a symmetric sensorimotor polyneuropathy limited to the proximal and distal areas of the lower limbs ('paraparetic CIDP'). Eighty-one (65%) patients maintained an unclassifiable presentation during the entire disease follow-up while 13 patients progressed to typical CIDP. Patients with the unclassifiable clinical forms compared with patients with typical CIDP had a milder form of CIDP, while there was no difference in the distribution patterns of demyelination. CONCLUSIONS: A proportion of patients with CIDP do not strictly fulfil the 2021 EAN/PNS clinical criteria for diagnosis. These unclassifiable clinical phenotypes may pose diagnostic challenges and thus deserve more attention in clinical practice and research.

Expression pattern of matrix metalloproteinases-2 and -9 and their tissue inhibitors in patients with chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Matrix metalloproteinases (MMPs) are a heterogeneous family of endopeptidases that play a role in many physiological functions, including the immune response. An imbalance between the activity of MMPs and their physiological tissue inhibitors (TIMPs) has been proposed in the pathophysiology of different autoimmune disorders. We aimed to assess the plasmatic levels of MMP-2, MMP-9, and their inhibitors TIMP-1 and -2 in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). SUBJECTS AND METHODS: Twenty patients with CIDP and 20 age- and sex-matched healthy controls were enrolled. Plasma concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined by the enzyme-linked immunosorbent assay. RESULTS: CIDP subjects had higher MMP-9 concentrations along with TIMP-1 downregulation when compared to controls, with the consequent increase in the MMP-9/TIMP-1 ratio (p<0.000002 for all measures). Conversely, the concentration of MMP-2 was lower in the CIDP group (p<0.01) without changes in the TIMP-2 concentration. The MMP-2/TIMP-2 ratio was decreased in the patients' group (p<0.02). DISCUSSION: We provide first preliminary evidence that the plasmatic pattern of MMPs and TIMPs is markedly altered in patients with CIDP. Future studies are needed to assess the potential usefulness of these new biomarkers in the clinical setting.

Clinical presentation of strokes confined to the insula: a systematic review of literature.

BACKGROUND AND PURPOSE: The insular cortex serves a wide variety of functions in humans, ranging from sensory and affective processing to high-level cognition. Hence, insular dysfunction may result in several different presentations. Ischemic strokes limited to the insular territory are rare and deserve a better characterization, to be quickly recognized and to receive the appropriate treatment (e.g. thrombolysis). METHODS: We reviewed studies on patients with a first-ever acute stroke restricted to the insula. We searched in the Medline database the keywords "insular stroke" and "insular infarction", to identify previously published cases. Afterwards, the results were divided depending on the specific insular region affected by the stroke: anterior insular cortex (AIC), posterior insular cortex (PIC) or total insula cortex (TIC). Finally, a review of the clinical correlates associated with each region was performed. RESULTS: We identified 25 reports including a total of 49 patients (59.7 ± 15.5 years, 48% male) from systematic review of the literature. The most common clinical phenotypes were motor and somatosensory deficits, dysarthria, aphasia and a vestibular-like syndrome. Atypical presentations were also common and included dysphagia, awareness deficits, gustatory disturbances, dysautonomia, neuropsychiatric or auditory disturbances and headache. CONCLUSIONS: The clinical presentation of insular strokes is heterogeneous; however, an insular stroke should be suspected when vestibular-like, somatosensory, speech or language disturbances are combined in the same patient. Further studies are needed to improve our understanding of more atypical presentations.

Unusual Presentation of Bilateral Carotid Artery Dissection: The Importance of Reasoning Outside the Box.

A bilateral internal carotid artery dissection presenting with atypical symptoms of cerebral hypoperfusion has been rarely reported, especially in the absence of obvious precipitating factors. A middle-aged woman presented to the emergency department with a 2-day-history of progressive left arm numbness and weakness, confusion, disorientation and clumsiness worsened by upright position. A cerebral hypoperfusion condition was hypothesized and confirmed by a CT angiography, which showed bilateral internal carotid dissection with uncertain etiology. Screening for predisposing conditions to spontaneous carotid arteries dissection was basically negative. Regarding potential precipitating factors, the patient had used an electric olive harvester days before symptoms onset, without any painful sensation or sudden sequelae. Portable harvesters in olive growing transmit vibrations to the hand-arm system but it remains to be elucidated if hand-arm vibrations can be implicated in vessels wall injury and dissection. Bilateral carotid artery dissection is an infrequent and life-threatening condition which can rarely present with non-specific symptoms of cerebral hypoperfusion. The absence of typical symptoms and known precipitating factors can made the diagnosis quite hard to achieve.

Rituximab in AChR subtype of myasthenia gravis: systematic review.

Myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction characterised by an autoantibody against acetylcholine receptor (AChR-Ab), autoantibody against muscle-specific kinase (MuSK-Ab), lipoprotein-related protein 4 or agrin in the postsynaptic membrane at the neuromuscular junction. Many patients are resistant to conventional treatment and effective therapies are needed. Rituximab (RTX) is a monoclonal antibody directed against CD20 antigen on B cells which has been successfully employed in anti-MuSK-Ab+MG, but the efficacy in anti-AChR-Ab+MG is still debated. The purpose of this systematic review was to describe the best evidence for RTX in the acetylcholine receptor subtype. The authors undertook a literature search during the period of 1999-2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analys methodology, employing (myasthenia)+(gravis)+(RTX) as search terms. The analysis was confined to studies that include at least five patients with confirmed anti-AChR-Ab+MG. Thirteen studies have been selected, showing a good safety. The data obtained were heterogeneous in terms of posology, administration scheme and patients' evaluation, ranging from a minimum of two to a maximum of three cycles. RTX led to a sustained clinical improvement with prolonged time to relapse, in parallel to a reduction or discontinuation of other immunosuppressive therapies. Treatment with RTX appears to work in some but not all patients with anti-AChR-Ab+MG, but randomised controlled trials are needed. Future studies should take into account the subtype of MG and employ reliable measures of outcome and severity focusing on how to identify patients who may benefit from the treatment. Trial registration number: NCT02110706.

Diagnostic and therapeutic aspects of hemiplegic migraine.

Hemiplegic migraine (HM) is a clinically and genetically heterogeneous condition with attacks of headache and motor weakness which may be associated with impaired consciousness, cerebellar ataxia and intellectual disability. Motor symptoms usually last <72 hours and are associated with visual or sensory manifestations, speech impairment or brainstem aura. HM can occur as a sporadic HM or familiar HM with an autosomal dominant mode of inheritance. Mutations in CACNA1A, ATP1A2 and SCN1A encoding proteins involved in ion transport are implicated. The pathophysiology of HM is close to the process of typical migraine with aura, but appearing with a lower threshold and more severity. We reviewed epidemiology, clinical presentation, diagnostic assessment, differential diagnosis and treatment of HM to offer the best evidence of this rare condition. The differential diagnosis of HM is broad, including other types of migraine and any condition that can cause transitory neurological signs and symptoms. Neuroimaging, cerebrospinal fluid analysis and electroencephalography are useful, but the diagnosis is clinical with a genetic confirmation. The management relies on the control of triggering factors and even hospitalisation in case of long-lasting auras. As HM is a rare condition, there are no randomised controlled trials, but the evidence for the treatment comes from small studies.

Migraine as a Cortical Brain Disorder.

PURPOSE: Migraine is an exclusively human chronic disorder with ictal manifestations characterized by a multifaceted clinical complexity pointing to a cerebral cortical involvement. The present review is aimed to cover the clinical, neuroimaging, and neurophysiological literature on the role of the cerebral cortex in migraine pathophysiology. OVERVIEW: Converging clinical scenarios, advanced neuroimaging data, and experimental neurophysiological findings, indicate that fluctuating excitability, plasticity, and metabolism of cortical neurons represent the pathophysiological substrate of the migraine cycle. Abnormal cortical responsivity and sensory processing coupled to a mismatch between the brain's energy reserve and workload may ignite the trigeminovascular system, leading to the migraine attack through the activation of subcortical brain trigeminal and extra-trigeminal structures, and driving its propagation and maintenance. DISCUSSION: The brain cortex emerges as the crucial player in migraine, a disorder lying at the intersection between neuroscience and daily life. Migraine disorder stems from an imbalance in inhibitory/excitatory cortical circuits, responsible for functional changes in the activity of different cortical brain regions encompassing the neurolimbic-pain network, and secondarily allowing a demodulation of subcortical areas, such as hypothalamus, amygdala, and brainstem nuclei, in a continuous mutual crosstalk.

Migraine and Sport in a Physically Active Population of Students: Results of a Cross-Sectional Study.

OBJECTIVE: In this study, we explored the relationship between migraine and sport in a physically active population of students, analyzing the risk of migraine among sporty students. BACKGROUND: The relationship between sport and migraine is controversial; moreover, several studies report on sport as a migraine trigger, but there is evidence that physical activity could have a relevant role in migraine prevention. METHODS: A cross-sectional survey was conducted using the validated ID-migraine questionnaire including specific demo-anthropometric (gender, age, weight, height) and sports variables on a potentially active student population of the University of Palermo. Evaluation in putative migraine subjects of clinical features and disability was explored through the administration of the Italian version of the Migraine Disability Assessment Scale. Statistical analyses were performed using univariate and logistic regression analyses. RESULTS: Three hundred and ninety-three out of 520 students (210 F, mean age: 23.5 ± 0.7 years; 183 M; mean age: 20.5 ± 0.7 years) participated in this study. Migraine screened positive in 102 subjects (26.0%) and its prevalence was significantly higher among females (P < .001). An increased risk of migraine was found in females, and a protective effect of sport on the risk of migraine among females, but not among males. CONCLUSIONS: The role of exercise in migraine is still unclear. This study supports a protective role of sport in migraine reporting a protective effect in females. Further studies are needed to deepen the association between sport and migraine.

Clinico-diagnostic features of neuralgic amyotrophy in childhood.

Neuralgic amyotrophy (NA), even known as Personage-Turner's syndrome (PTS), is a neurologic condition, affecting the lower motor neurons of brachial plexus and/or individual nerves or nerve branches, characterized by pain, muscle weakness/atrophy, and sensory symptoms. NA has an acute/subacute onset, after an infection or vaccination; it is more common in male and is rare in the pediatric population. The etiology remains uncertain, being considered heterogeneous and multifactorial. A severe acute neurologic pain around the shoulder girdle is the classic presenting symptom at onset. As the pain subsides, weakness and paresis develop. NA is usually unilateral, but sometimes, a subclinical contralateral limb involvement could be present and bilateral affection has been described. The diagnosis is clinical, through a comprehensive history and neurological examination. However, electrophysiological testing and imaging are critical, because there is no diagnostic test for PTS and it remains a diagnosis of exclusion. Upper brachial plexus peripheral involvement with weakness of periscapular and perihumeral muscles is the classic presentation, associated with electrophysiological evidence of denervation in the affected muscles. Imaging, laboratory, and genetic testing can be useful for the differential diagnosis. NA is in most cases a self-limiting condition, and it is characterized by good recovery. Treatment of NA usually involves a combination of corticosteroids, analgesics, immobilization, and physical therapy, even if limited data are available in children. Physiotherapy is required to maintain muscle strength.

Misdiagnosis and pitfalls in Panayiotopoulos syndrome.

Panayiotopoulos syndrome (PS) is a frequent (6% among children of 1-15 years) and benign epileptic syndrome, characterized by predominantly autonomic symptoms (emesis, pallor, flushing, cyanosis, mydriasis/miosis, cardiorespiratory and thermoregulatory alterations, incontinence of urine and/or feces, hypersalivation, and modifications of intestinal motility) associated with simple motor focal seizures, which can be followed by secondary generalization. Panayiotopoulos syndrome can be extremely insidious, because it can mimic several condition, such as gastroenteritis, gastroesophageal reflux disease, encephalitis, syncope, migraine, sleep disorders, or even metabolic diseases. This peculiar pleiotropism should be kept in mind by child neurologists and pediatricians and general practitioners, because a wrong diagnosis may lead to inappropriate interventions. The consequences are high morbidity, costly mismanagement, and stress for children and their parents. The availability of electroencephalography (EEG) recording in pediatric Emergency Departments might be useful for a prompt and not-cost-consuming diagnosis. On the other hand, it is important to be aware of the possible, multifaceted, clinical presentations of PS and its clinical, radiological, and neurophysiological features in order to improve both recognition and management.

"Accent issue": foreign accent syndrome following ischemic stroke.

BACKGROUND: Foreign accent syndrome (FAS) is arare syndrome associated with altered speech rhythm and prosody, which listeners perceive as foreign; cerebrovascular accidents, tumors and multiple sclerosis are reported as possible causes of FAS. The pathophysiology of FAS is not yet understood. CASE PRESENTATION: A 68-year-old Italian man was admitted to the EmergencyDepartment for non-fluent aphasia and dysarthria. Computed tomography (CT) scan did not show abnormalities; the patient was treated with systemic thrombolysis. A repeated brain CT and magnetic resonance imaging (MRI) confirmed an infarct in the left primary motor cortex and mild extension to cortico-subcortical frontal regions. In the following days he gradually improved, speaking Italian fluently with a typical German accent. In conclusion, FAS is a rare motor speech disorder, often related to cerebrovascular accidents involving critical regions in the dominant hemisphere. In addition, the present case adds further evidence to the role of the left primary motor cortex in modulation of prosody. In rare cases FAS can be the only sign of stroke or can appear after recovery from post-stroke aphasia.