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Introduction: Patients with Chronic hypoparathyroidism (CHPT) receiving conventional treatment are exposed to several long-term complications including basal ganglia calcifications, posterior subcapsular cataract, kidney stones, and renal insufficiency. The aim of this study was to assess the prevalence and the associated factors of these complications in patients with CHPT., Methods: We conducted a cross-sectional study including 58 patients with CHPT. All participants underwent physical examination, biochemical assessment (total serum calcium, serum phosphorus, serum albumin, intact-PTH, serum magnesium, 25-hydroxy-vitamin D, serum creatinine, thyroid stimulating hormone (TSH), and 24-hour urinary calcium), slit lamp examination, brain computed tomography scan (CT-scan), and renal ultrasound., Results: Participants had a mean age of 52.6 ± 16.4 years and a gender ratio (women/men) of 3.5. Fahr syndrome, cataract, urolithiasis, and renal failure were found in 55%, 62%, 12%, and 17% of cases, respectively. CHPT duration >15 years (Adjusted-OR = 43.1, 95-CI: 2.63-703.06, p = 0.008) and poor adherence to treatment (Adjusted-OR = 8.04, 95%-CI: 1.52-42.42, p = 0.014) were independently associated with the risk of Fahr syndrome. Age >55 years (adjusted-OR = 5.07, 95-CI: 1.10-23.42, p = 0.037), disease duration >15 years (adjusted-OR = 20.21, 95-CI: 1.54-265.84, p = 0.022), and magnesium level <0.8 mmol/l (adjusted-OR = 36.46, 95-CI: 3.75-354.08, p = 0.002) were independently associated with the risk of subcapsular cataract. Only hypercalciuria (Adjusted-OR = 21.27, 95-CI: 2.31-195.91, p = 0.007) was an independent risk factor for kidney stones. Renal failure was not associated with kidney stones (p = 1). However, creatinine clearance was negatively correlated with age (r = -0.784; p < 10 -3 ) and disease duration (r = -0.352; p = 0.007)., Conclusion: Our results revealed high prevalences of neurological, ocular, and renal complications in patients with CHPT and emphasized the importance of regular biological monitoring, therapeutic adjustments, screening, and adherence to treatment in the prevention of these complications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Coronavirus disease 2019 (COVID-19) has been associated with a variety of neurological manifestations (i.e., anosmia, ageusia, myalgia, headache) and neurological syndromes (i.e., encephalopathy, ischemic and hemorrhagic stroke, myelitis, encephalitis) underlying different pathogenetic mechanisms. COVID-19 has also been associated with various movement disorders including acute or subacute parkinsonism. However, to date, only few cases of parkinsonism linked to COVID-19 have been reported, nevertheless raising the possibility of a post-viral parkinsonian syndrome. Furthermore, various studies in vitro and in animal models have highlighted a close relationship between SARS-CoV-2 virus and α-synuclein, leading to the hypothesis that COVID-19 could represent a factor favoring the long-term development of α-synucleopathies. In this chapter, we will discuss the pathophysiological mechanisms related to movement disorders' manifestations of COVID-19 focusing on the possible overlap between pathogenetic mechanisms of Parkinson's Disease and COVID-19., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Acute extrapyramidal movement disorders in dialysis patients are rare, inconsistently defined and have uncertain aetiology and prognosis., Aim: Define diagnostic criteria, prognosis and risk factors., Design and Methods: Retrospective case series review of 20 patients (14 female, mean age 62 years) receiving dialysis for a median of 15 (interquartile range 4-35) months who presented with acute parkinsonism (AP = 11) or chorea/athetosis (CA = 9)., Results: All patients had type 2 diabetes (HbA1c 6.8 ± 1.0) and had received metformin. Lactic acidosis was present in 2 patients at presentation and serum lactate was elevated in 7/15 patients tested. No patient had abnormal copper or thyroid metabolism and 5/8 patients tested returned marginal abnormalities in heavy metal screening. Magnetic resonance imaging (MRI) revealed characteristic bilateral symmetric T2 hyperintensity of the basal ganglia (BG), predominantly putamen and globus pallidus (the lentiform nucleus) and more extensive involvement of the external and internal capsules in patients with AP presentation. Post-mortem demonstrated cytotoxic necrosis of the BG. Therapy included thiamine, intensive dialysis and cessation of metformin. Two patients died acutely, nine recovered and nine had residual symptoms. Median survival did not differ by presentation: AP 24 [95% confidence interval (CI) 21-27] and CA 33 (95% CI 32-35) months, P = 0.21., Conclusions: There are two distinct clinical extrapyramidal movement disorders associated with specific diagnostic MRI imaging that support the diagnosis of the extrapyramidal syndromes of chronic kidney disease and dialysis. The associations with diabetes, metformin and metabolic acidosis suggest a common pathogenic mechanism but require additional study. Early recognition and treatment may improve outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Context: Hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone, which may be associated with soft tissue calcification in the basal ganglia of the brain., Objective: To assess the prevalence and factors involved in the pathophysiology of basal ganglia calcification (BGC) in the brain in chronic hypoparathyroidism and to evaluate proposed pathophysiologic mechanisms., Design: Case-control study with retrospective review of medical records over 20 years., Setting: Single academic medical center., Patients: 142 patients with chronic hypoparathyroidism and computed tomography (CT) head scans followed between January 1, 2000 and July 9, 2020, and 426 age- and sex-matched controls with CT head scans over the same interval., Interventions: None., Main Outcome Measures: Demographic, biochemical, and CT head imaging findings, with semiquantitative assessment of volumetric BGC., Results: The study found that 25.4% of 142 patients followed for a median of 17 years after diagnosis of chronic hypoparathyroidism had BGC, which developed at a younger age than in controls. BGC was 5.1-fold more common in nonsurgical patients and less common in postsurgical patients. Low serum calcium and low calcium/phosphate ratio correlated with BGC. Neither serum phosphorus nor calcium × phosphate product predicted BGC. Lower serum calcium was associated with greater volume of BGC. The extent of BGC varied widely, with nonsurgical patients generally having a greater volume and distribution of calcification., Conclusions: BGC is associated with low serum calcium and low serum calcium/phosphate ratio, which may be related to severity of the disease, its etiology, or duration of treatment., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Fahr's syndrome due to hypoparathyroidism refers to bilateral basal ganglia (BG) calcifications and manifests with movement disorders, seizures, cognitive and behavioral symptoms., Case Presentation: We report a case of a 74-year-old woman, who presented with parkinsonism due to post-surgical hypoparathyroidism and normal DaT scan, despite extensive calcifications of the BG, periventricular white matter, and cerebellum., Methods: A comprehensive literature review of all reported cases of Fahr's syndrome due to hypoparathyroidism was conducted in the electronic databases PubMed and Web of science. Moreover, demographic and clinical characteristics of the patients overall were calculated and associated with radiological findings., Results: We reviewed a total of 223 cases with Fahr's syndrome due to hypoparathyroidism (124 female, 99 male). Mean age on presentation was 44.6 ± 17.7 years. Thirty nine percent of patients had idiopathic hypoparathyroidism, 35.4 % acquired and 25.6 % pseudohypoparathyroidism. Almost half of the patients had tetany, seizures or a movement disorder and approximately 40 % neuropsychiatric symptoms. The patients with a movement disorder had a 2.23 likelihood of having neuropsychiatric symptoms as well (OR 2.23, 95 % CI 1.29-3.87). Moreover, there was a statistically significant association between the phenotype severity (i.e. the presence of more than one symptom) and the extent of brain calcifications (χ 2 = 32.383, p = 0.009)., Conclusion: Fahr's syndrome is a rare disorder, which nonetheless manifests with several neurological symptoms. A head CT should be considered for patients with hypoparathyroidism and neurological symptoms. More studies using DaT scan are needed to elucidate the effects of calcifications on the dopaminergic function of the BG., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Trans-cranial magnetic stimulation (TMS) can noninvasively modulate specific brain regions to dissipate symptoms in treatment-resistant schizophrenia (TRS). Citing impaired resting state connectivity between cerebellum and prefrontal cortex in schizophrenia, we aimed to study the effect of intermittent theta burst stimulation (iTBS) targeting midline cerebellum in TRS subjects on a randomized rater blinded placebo control study design. In this study, 36 patients were randomly allocated (using block randomization method) to active and sham iTBS groups. They were scheduled to receive ten iTBS sessions, two per day (total of 1200 pulses) for 5 days in a week. The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Schizophrenia Cognition Rating Scale (SCoRS), Simpson-Angus Extrapyramidal Side Effects Scale (SAS), and Clinical Global Impression (CGI) were assessed at baseline, after last session, and at 2 weeks post-rTMS. Thirty patients (16 and 14 in active and sham groups) completed the study. Intention to treat analysis (ITT) using mixed (growth curve) model analysis was conducted. No significant group (active vs sham) × time (pretreatment-end of 10th session-end of 2 weeks post iTBS) interaction was found for any of the variable. No major side effects were reported. Our study fails to show a significant effect of intensive cerebellar iTBS (iCiTBS) on schizophrenia psychopathology, cognitive functions, and global improvement, compared with sham stimulation, in treatment resistant cases. However, we conclude that it is safe and well tolerated. Trials using better localization technique with large sample, longer duration, and better dosing protocols are needed.

Background: A carotid web is a very rare vascular disease of the carotid artery, leading to thrombosis and ischemic stroke., Case Presentation: A 65-year-old male patient was admitted due to left limb weakness. On arrival, he had moderate left hemiplegia, neglect, and sensory loss; the National Institutes of Health Stroke Scale score was 8. Computed tomography angiography (CTA) and magnetic resonance (MR) examination were performed to determine the cause of basal ganglia infarction. Thin-section axial CTA showed a membrane-like structure in the posterior wall of the right common carotid artery. The sagittal reconstruction image showed a membrane-like protrusion in the posterior wall of the right common carotid artery under the right carotid sinus. The MR axial T2 image showed a membrane-like high-signal protrusion into the carotid artery lumen, which was diagnosed as a right carotid web. The patient was treated with dual antihypertensive therapy by adjusting blood pressure, controlling brain edema, improving cerebral circulation, and nourishing the nerves., Conclusion: Careful comparison of axial thin-layer CTA and MR axial T2 images combined with sagittal reconstruction of CTA images can greatly improve the diagnostic rate of carotid web.

Schizophrenia significantly limits social functioning with positive and negative symptoms and cognitive dysfunction. Blonanserin (LONASEN®), a novel second-generation antipsychotic approved for treating schizophrenia in Japan in 2008, reportedly shows beneficial effects on cognitive function as well as positive and negative symptoms, with potential for improving social functioning. To understand the safety and effectiveness of blonanserin in the real clinical practice, five Japanese post-marketing surveillances have been conducted and published to date. In this article, we reviewed all the Japanese post-marketing surveillances and discussed the clinical usefulness of blonanserin in patients with schizophrenia having diverse clinical characteristics. Adverse drug reactions, such as akathisia and extrapyramidal symptoms, were common in all surveillances. However, those specific to second-generation antipsychotics, such as weight gain and abnormalities in glycometabolism or lipid metabolism, were rarely observed. In addition, no adverse drug reactions apart from clinical trial results were found. Brief Psychiatric Rating Scale total scores in all surveillances significantly lowered at the last evaluation than at baseline. These results were consistent through 1-year of treatment, suggesting that effectiveness is maintained even after long-term use. In conclusion, blonanserin is considered a beneficial drug in real clinical practice for patients with schizophrenia having diverse characteristics., Competing Interests: Declaration of competing interest All the authors are employees of Sumitomo Dainippon Pharma Co, Ltd. The authors report no other conflicts of interest related to this work., (Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

There is evidence that glycemic fluctuations trigger vascular-mediated dysfunction in both the retina and the striatopallidal regions in patients with diabetes. The latter is associated with a variety of hyperkinetic disorders that are rare but disabling and potentially preventable. We conducted a systematic review of the potential association between diabetic retinopathy and the risk and prognosis of hyperkinetic disorders in patients with diabetes. We identified a total of 461 articles and 147 were eligible for review. Nine out of 147 articles (6.12%) reported 13 patients with information on diabetic retinopathy. Glycemic fluctuations were present at onset in 10 patients (77%) and retinopathy was present in nine of them (69.23%). The degree of retinopathy was reported in four patients. Two had severe, bilateral proliferative retinopathy, one had moderate-to-severe non-proliferative retinopathy and one had non-proliferative retinopathy. In the nine patients with retinopathy, hyperkinesia persisted, required higher doses of dopamine receptor antagonists or deep brain stimulation. Retinopathy was absent in four cases (30.77%). In these patients, hyperkinesia resolved spontaneously or with lower doses of dopamine receptor antagonists. Diabetic retinopathy could be an indirect marker of striatopallidal microangiopathy in patients with diabetes. The severity of retinopathy may be associated with increased risk or worse prognosis for patients who develop hyperkinetic disorders of the diabetic striatopathy spectrum. Early detection of retinopathy could identify patients in which avoiding glycemic fluctuations may prevent the development of striatopathy and hyperkinetic disorders., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A 64-year-old woman visited our hospital with early-onset dementia and progressive gait disturbance. She had demonstrated a mild communication disorder at the age of ~40 years; however, her psychiatric symptoms at that time were mild and were not accompanied by social problems. At the age of 59, she presented with memory loss, visual hallucinations, and delusions. Over the following five years she developed gait difficulties that gradually deteriorated and suffered frequent falls. On admission, neurological examinations revealed severe pyramidal and extrapyramidal signs of akinetic mutism. MRI of the brain showed cerebral atrophy, enlarged lateral ventricles, thinning of the corpus callosum, and leukoencephalopathy in the frontal-parietal lobes. Additionally, CT revealed a small spotty calcification in the frontal subcortical white matter. Genetic analysis revealed a single-base substitution (c.2330G>A/p.R777Q) in exon 18 of the colony stimulating factor 1 receptor (CSF1R) gene, encoding the CSF1R protein. She was diagnosed with hereditary diffuse leukoencephalopathy with spheroids (HDLS). HDLS is included in the differential diagnosis of early-onset dementia and should be considered in patients with mild personality change and abnormal behavior in the early course of the illness.

Calcifications of the basal ganglia are frequently seen on the cerebral CT scans and particularly in the globus pallidus. Their frequency increases physiologically with age after 50 years old. However, pathological processes can also be associated with calcium deposits in the gray nuclei, posterior fossa or white matter. Unilateral calcification is often related to an acquired origin whereas bilateral ones are mostly linked to an acquired or genetic origin that will be sought after eliminating a perturbation of phosphocalcic metabolism. In pathological contexts, these calcifications may be accompanied by neurological symptoms related to the underlying disease: Parkinson's syndrome, psychiatric and cognitive disorders, epilepsy or headache. The purpose of this article is to provide a diagnostic aid, in addition to clinical and biology, through the analysis of calcification topography and the study of different MRI sequences., (Copyright © 2020 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Beta-propeller protein-associated neurodegeneration (BPAN) is categorized in Neurodegeneration with brain iron accumulation. The clinical feature of BPAN is global developmental delay in early childhood, followed rapid progression of cognitive disfunction and parkinsonism in adulthood. This case was pointed out intellectual disability at the age of 9, followed left dominant progressive parkinsonism from the age of 31. Brain MRI showed the T 1 -weighted signal hyperintensity of the substantia nigra with a central band of hypointensity and the T 2 star weighted image hypointensity of substantia nigra and globus pallidus presenting dominant at right side. DAT SPECT also showed specific binding ratio decreased dominant in right side. She was diagnosed BPAN based on her genetic test revealing a novel mutation (c.411dupT) in WDR45. No studies reported detailed parkinsonism like laterality in BPAN. This case indicates the left dominant parkinsonism was caused by right dominant iron deposition to substantia nigra and globus pallidus in view of MRI findings and DAT SPECT.

Background: Basal ganglia (BG) lesions are rarely reported in patients with uremia and may manifest by movement disorders. However, their exact incidence and pathogenesis have not been extensively studied. This study aimed to determine the frequency, types, risk variables (clinical, laboratory, and imaging), and manifestations of BG lesions with uremia and patients' neurologic outcomes., Methods: This observational study included 70 adults (mean age: 45.87 ± 3.36 years; duration of uremia: 5.5 ± 1.5 years). They underwent extensive evaluations (clinical, laboratory, and neuroimaging) and had prospectively evaluated clinically every 3 months for 2 years. Repeated magnetic resonance imaging (MRI) brains were done to patients with movement disorders and correlated with their neurologic outcomes., Results: BG lesions were found in 15 patients (21.4%) and 6 (8.6%) had movement disorders [Parkinsonism (n = 4), choreo-dystonia (n = 1) and dystonia (n = 1)] after the onset of uremia (mean = 10 months). There were no characteristic risk variables that distinguished patients with movement disorders from those without. Five developed movement disorders prior to the period of the study and one was de novo. The majority was females and had diabetes and higher frequencies of abnormal renal dysfunction, metabolic derangements, and white matter hyperintensities in MRIs. Movement disorders persisted in all patients despite the resolution of neuroimaging in three patients., Conclusions: There is no clear threshold for renal failure to result in movement disorders due to BG lesions. The clinical outcome is variables depending on each patient's comorbidities and complications. Persistent neuronal damage (due to uremic toxins/metabolic/nutritional and ischemic/microvascular factors) has been suggested as the cause of poor neurologic outcomes.

Adult genetic disorders causing brain lesions have been mostly described as white matter vanishing diseases. We present here the investigations realized in patients referred for psychiatric disorder with magnetic resonance imaging showing atypical basal ganglia lesions. Genetic explorations of this family revealed a new hereditary disease linked to glutathione metabolism., (© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Background: Fahr's syndrome presenting multiple and symmetric calcification of basal ganglia and cerebral cortex is rare, and idiopathic hypoparatyroidism is known as one of the causes. The relationship between ossification of posterior longitudinal ligament (OPLL) and idiopathic hypoparatyroidism is also reported in a few cases. Here, we report a patient presenting concomitant Fahr's syndrome and thoracic OPLL developed by idiopathic hypoparatyroidism., Case Presentation: 53-year-old female patient presented myelopathic sign including gait disturbance and both leg weakness (Grade 3) for 4 months after slip down, and has the history of anti-epileptic medication for several years. Magnetic resonance imaging revealed cord compression by the mixed-type OPLL from T5 to T9, and decompressive surgery was planned. Sudden onset generalized tonic-clonic seizure attack developed before the surgery. Hypocalcemia (3.7 mg/dL) with QT prolongation on electrocardiogram, hypomagnesemia (1.4 mg/dL), hyperphosphatemia (7.7 mg/dL), hypoparathyroidism, and normal range of vitamin D was noted. Brain study showed Fahr's syndrome with multiple and symmetric calcification of basal ganglia, cerebral cortex, and cerebellum. Decompressive laminectomy was performed after transient correction of hypocalcemia. The myelopathic symptoms improved to normal walking by the 14-month follow-up. The cause of hypoparathyroidism was concluded to be idiopathic., Conclusion: Concomitant expression of Fahr's syndrome and OPLL related with idiopathic hypoparatyroidism is very rare. However, we recommend considering the possibility of hypoparathyroidism and Fahr's syndrome when we evaluate the patients with OPLL to avoid the risks of sudden onset seizure and cardiac arrhythmia due to cerebral lesions and hypocalcemia.

Purpose/background: Dopamine receptor blocking agents (DRBAs), also known as antipsychotics, are medications widely used to treat a growing number of mental health diagnoses. However, their utility is limited by the potential to cause serious adverse movement reactions. Akathisia, dystonia, parkinsonism, and tardive dyskinesia (collectively known as extrapyramidal symptoms or EPSs) are associated with reduced social and occupational functioning, negative patient attitudes toward treatment, and nonadherence to pharmacotherapy. Neuroleptic malignant syndrome is a life-threatening reaction that can result from DRBA use and cause musculoskeletal dysfunction. The aim of this study is to profile patients who have developed DRBA-related movement adverse effects and identify risk factors significantly associated with each subtype of EPSs or other movement disorders (OMDs) such as neuroleptic malignant syndrome., Methods/procedures: A report of all potential DRBA-related EPSs or OMDs occurrences within a large community hospital network was generated using International Classification of Diseases, Ninth Revision (ICD-9) and 10th Revision (ICD-10) billing codes. Each patient encounter was manually reviewed to confirm that a documented case of DRBA-related EPSs or OMDs had indeed occurred and subsequently determine the likely causative agent(s)., Findings/results: The resultant cohort of 148 patients experiencing unique DRBA-related EPS or OMD events was analyzed. The average patient was female, middle-aged, and overweight. The most common DRBAs precipitating EPSs or OMDs were haloperidol and quetiapine. In the population studied, age was significantly associated with the subtype of EPSs experienced such that those patients with akathisia and dystonia tended to be younger, whereas those with tardive dyskinesia tended to be older. Body mass index (BMI) category was also negatively correlated with the incidence of dystonia. In addition, it was observed that exposure to specific DRBAs, classes, and routes of administration significantly affected the risk of developing different subtypes of EPSs or OMDs in the study population., Implications/conclusions: To our knowledge, this is the first study to describe an association between age and BMI with the risk of akathisia and dystonia, respectively, in patients taking DRBAs. Other trends observed with age and BMI in patients developing DRBA-related EPSs support previously reported findings. Expanding the knowledge base of individual characteristics associated with the risk of developing different subtypes of EPSs or OMDs can help providers and patients anticipate and attempt to mitigate these reactions, and may ultimately improve adherence to DRBA therapy.

Competing Interests: No conflict of interests declared

Background: Clinical and radiological characteristics of middle cerebral artery (MCA) infarction may differ according to the location of occlusion., Objectives: We investigated the difference between proximal and distal symptomatic MCA occlusion (MCAO) in patients with ischemic stroke. The factors associated with the imaging characteristics were also analyzed., Methods: Patients with ischemic stroke due to MCAO were consecutively enrolled. The location of MCAO was determined by the ratio of the length of the ipsilesional MCA to that of the contralateral MCA and dichotomized to proximal and distal MCAO. Clinical and radiological characteristics were compared between patients with proximal and distal MCAO. Factors associated with the basal ganglia (BG) involvement, hemorrhagic transformation (HT), and neurological change during admission were investigated., Results: Among 181 included patients, MCAO location showed a bimodal peak (at the proximal [n = 99] and distal MCA [n = 82]). Proximal MCAO was more frequently associated with hyperlipidemia and large artery atherosclerosis, whereas distal MCAO was more frequently associated with hypertension, atrial fibrillation, and cardioembolic stroke. BG involvement was similar between the 2 groups (48 vs. 39%; p = 0.21), whereas HT was more frequent in distal MCAO (10 vs. 23%; p = 0.02). Among patients with proximal MCAO, hyperintense vessel sign was less frequently observed in those with a BG involvement than those without (38 vs. 60%; p = 0.03). Among those without BG involvement, the presence of HT was very low and similar between patients with proximal and distal MCAOs (1.9 vs. 2.0%). However, in patients with BG involvement, HT was more frequently observed in those with distal MCAO than in those with proximal MCAO (54.8 vs. 15.7%; p < 0.001). The presence of hyperintense vessel sign (OR 0.172, 95% CI 0.051-0.586; p = 0.005) and distal MCAO (OR 0.200, 95% CI 0.059-0.683; p = 0.011) was independently associated with improvement during admission., Conclusion: Proximal MCAO is more frequently associated with atherosclerosis, whereas distal MCAO is more frequently associated with cardioembolism. In proximal MCAO, the status of collateral flow presented by hyperintense vessel sign may affect the involvement of BG. In distal MCAO, distal migration of the embolus, which first impacted at the proximal MCA causing BG ischemia, may explain the high rate of HT by reperfusion injury. Hyperintense vessel sign and distal MCAO were independently associated with neurological improvement during admission., (© 2019 S. Karger AG, Basel.)

In the present work, we report the case of a patient presenting signs of Lewy body dementia (DLB) and frontotemporal dementia (FTD) throughout different phases of the disease. In January 2017, a 79-year-old right-handed living man was admitted to our Memory Clinic for the presence of behavioral disturbances and progressive cognitive decline. For the previous six years, he was monitored by other Neurological Clinics for the onset of extrapyramidal features. Indeed, through the first phase of the disease (2011-2014), the patient predominantly showed: extrapyramidal features, initial cognitive decline, sleep disturbances, and visual hallucinations, together with a reduced dopamine transporter uptake in basal ganglia at the DATscan, suggesting a diagnosis of DLB. In a second phase (2015-2017), while his extrapyramidal features remained substantially stable, his cognitive profile deteriorated, with an additional development of severe behavioral and neuropsychiatric disturbances. Again, a subsequent DATscan study was positive and slightly worse than the preceding one; however, the 18F-FDG PET showed reduced metabolic activity in the frontal and temporal lobes, with the occipital regions left spared. Genetic analysis revealed a hexanucleotide expansion in C9ORF72 (6//38 repeats; ITALSGEN NV <30). In conclusion, we report the case of a patient presenting, firstly, with probable DLB and, in a second phase, with predominant bvFTD features with stable parkinsonism. Even though some clinical and neuropsychological aspects can co-exist in different neurodegenerative diseases, we find such a significant intersection of clinical features to be fairly atypical. Moreover, what is challenging to define is whether the two clinical phenotypes are somehow lying on a continuum, or if they are two individual entities.

Aim: We describe the clinical and etiological profile of patients with Fahr's syndrome (FS)., Methods: Charts of sixteen patients diagnosed with FS between 1999 and 2014 were retrospectively assessed., Results:   The mean age at diagnosis was 44.68 years (11-67 years). The most main presenting neurological features were seizures in 6 cases, headaches in 5 cases and parkinson's syndrome in 3 cases. Psychiatric disorders were observed in 2 patients including memory loss and iritability. Hypocalcemia clinical features were observed in 7 cases. The mean value of hypocalcemia was 1.69 mmol/l. Etiologies included idiopathic hypoparathyroidism in 4 patients, pseudohypoparathyroidism in 5 cases, secondary hypoparathyroidism, isolated hypovitaminosis D and cerebral radiotherapy in one case for each and Fahr's disease in 4 patients.  Oral calcium and vitamin D substitution were started in patients with parathyroid disturbances with favorable outcome., Conclusion: In this report, we propose to discuss the clinical manifestations of FS, its etiologies especially parathyroid disturbances and its therapeutic modalities.

Fahr syndrome is a rare disorder, whose prevalence is lower than 0.5%. Clinical manifestations are variable ranging from mere behavioral disorders to tetany crises and severe neuropsychiatric manifestations. It may be idiopathic or secondary to numerous causes dominated by phosphocalcium metabolism disorders whose main cause is hypoparathyroidism. Positive diagnosis is based on radiology. We report the case of a 78-year old hypertensive female patient with a history of hypothyroidism, hypoparathyroidism after total thyroidectomy performed 30years before. She was treated with Levothyrox® 100 µg 2 capsules/day , One-Alpha® 1 μg 3 capsules/day and calperos® 2 capsules/day resulting in euthyroidia confirmed by clinical examination and laboratory tests and normal phosphocalcic test. Patient's outcome was marked, in 2010, by the development of rapidly worsening cognitive impairment and of early onset dementia in a few months. Neurological examination showed extrapyramidal syndrome. Cerebral CT scan showed large basal ganglia calcifications, white and gray linear substance near the junction, in the brain bulb and in the cerebellum. The diagnosis of Fahr syndrome, revealed by dementia occurred after a history of hypoparathyroidism, was then retained.

Background: The management of acute agitation in the emergency department often requires the administration of rapid-acting antipsychotic agents. However, there are few comparative studies and little guidance regarding the risks associated with use of such drugs in the acute setting., Objective: This structured evidence-based review compared the safety of antipsychotic pharmacotherapies for acute agitation using data from randomized controlled trials identified by a literature search of the PubMed database., Results: Based on findings from 34 blinded, randomized controlled trials, common acute adverse effects of second-generation antipsychotics and haloperidol were headache, dizziness, insomnia, and somnolence. There were some differences in incidence of extrapyramidal symptoms (EPS), degree of sedation, and acute QTc prolongations between agents., Conclusions: The results of this review demonstrate the improved safety (particularly regarding EPS and over-sedation) of certain newer-generation antipsychotic agents compared with haloperidol and benzodiazepines for the treatment of acutely agitated patients. The risk of prolonged QT interval and torsade de pointes needs to be considered with haloperidol and some of the second-generation antipsychotics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We presented the first case of bilateral striopallidodentate calcinosis secondary to Sjögren's syndrome. Further consideration should be given to the association between Sjögren's syndrome and bilateral striopallidodentate calcinosis, because Sjögren's syndrome is latent, but more frequent than other autoimmune diseases., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

The present report is of two patients who, immediately after internal carotid endarterectomy, presented with unexplained hemiplegia, despite normal findings on repeated MRI scans, which secondarily evolved into homolateral subacute corticobasal syndrome (CBS), with asymmetrical hemispheric hypometabolism and evidence of dopaminergic denervation. This prompted us to propose an hypothesis of transient cerebral hypoxia arising during the surgical clamping period that might have provoked a prolonged or permanent functional lesion of the left hemisphere and basal ganglia, with no visible infarction on MRI but only synaptic rearrangement of the neural networks, thereby revealing or exacerbating a potentially preexisting silent impairment., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Stereotactic needle biopsy, a standard of care for acquiring deep-seated pathology, has limitations and risks in some situations. We present an uncommon case with basal ganglia dematiaceous mycetoma. Due to the firm consistency of the lesion, the initial stereotactic needle biopsy failed to provide a diagnosis. In a second operation, transtubular excisional biopsy was successfully performed to remove the entire mycetoma. We reviewed recent case series of transtubular approaches to deep-seated brain lesions and suggest this method could be a rescue for a non-diagnostic stereotactic needle biopsy and even may be the approach of choice in some cases.

Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology, particularly cognitive impairment, of schizophrenia. Sarcosine, a glycine transporter I (GlyT-1) inhibitor, and sodium benzoate, a d-amino acid oxidase (DAAO) inhibitor, can both enhance NMDA receptor-mediated neurotransmission. We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients. Methods This study compared add-on sarcosine (2 g/day) plus benzoate (1 g/day) vs. sarcosine (2 g/day) for the clinical symptoms, as well as the cognitive and global functioning, of chronic schizophrenia patients in a 12-week, double-blind, randomised, placebo-controlled trial. Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks. Seven cognitive domains, recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee, were measured at weeks 0 and 12. Results Adjunctive sarcosine plus benzoate, but not sarcosine alone, improved the cognitive and global functioning of patients with schizophrenia, even when their clinical symptoms had not improved. Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia, further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms.

BACKGROUND Basal ganglia calcification (BGC) is a rare sporadic or hereditary central nervous system (CNS) abnormality, characterized by symmetric or asymmetric calcification of the basal ganglia. CASE REPORT We report the case of a 65-year-old Gypsy female who was admitted for a tetanic seizure, and who had a history of polyneuropathy, restless-leg syndrome, retinopathy, diabetes, hyperlipidemia, osteoporosis with consecutive hyperkyphosis, cervicalgia, lumbalgia, struma nodosa requiring thyroidectomy and consecutive hypothyroidism, adipositas, resection of a vocal chord polyp, arterial hypertension, coronary heart disease, atheromatosis of the aorta, peripheral artery disease, chronic obstructive pulmonary disease, steatosis hepatis, mild renal insufficiency, long-term hypocalcemia, hyperphosphatemia, impingement syndrome, spondylarthrosis of the lumbar spine, and hysterectomy. History and clinical presentation suggested a mitochondrial defect which also manifested as hypoparathyroidism or Fanconi syndrome resulting in BGC. After substitution of calcium, no further tetanic seizures occurred. CONCLUSIONS Patients with BGC should be investigated for a mitochondrial disorder. A mitochondrial disorder may also manifest as tetanic seizure.

Complex regional pain syndrome (CRPS) is a poorly understood pain disorder of the limbs. Maladaptive cortical plasticity has been shown to play a major role in its pathophysiological presentation. Recently, there is increasing interest in the role of the basal ganglia (BG), since clinical findings and neuroimaging studies point to possible BG involvement in CRPS. CRPS symptoms are often characterized by movement disorders associated with BG dysfunction. Very frequently, dystonia and tremor are reported and, to a lesser extent, myoclonus. Neuroimaging studies present inconsistent findings concerning altered brain networks and mainly focus on cortical areas. Subcortical contribution to this disorder has so far been neglected. Clinical data presenting BG dysfunction-related movement disorders in CRPS patients raise the hypothesis of BG dysfunction in this syndrome. Moreover, several neuroimaging studies documented abnormalities in the BG and in the frontal, parietal and limbic cortical areas. These regions are functionally and anatomically connected in motor, pain and working memory networks. Put together, these findings call for further characterization of the dynamic cortical and subcortical interactions in CRPS., Significance: This paper presents an overview of our current knowledge about BG pathology in CRPS. A better understanding of the involvement of the BG in the CRPS pathology holds the potential for developing and improving efficacious, mechanism-based treatment modalities., (© 2016 European Pain Federation - EFIC®.)

Chronic manganese (Mn) exposure is associated with neuromotor and neurocognitive deficits, but the exact mechanism of Mn neurotoxicity is still unclear. With the advent of magnetic resonance imaging (MRI), in-vivo analysis of brain structures has become possible. Among different sub-cortical structures, the basal ganglia (BG) has been investigated as a putative anatomical biomarker in MR-based studies of Mn toxicity. However, previous investigations have yielded inconsistent results in terms of regional MR signal intensity changes. These discrepancies may be due to the subtlety of brain alterations caused by Mn toxicity, coupled to analysis techniques that lack the requisite detection power. Here, based on brain MRI, we apply a 3D surface-based morphometry method on 3 bilateral basal ganglia structures in school-age children chronically exposed to Mn through drinking water to investigate the effect of Mn exposure on brain anatomy. Our method successfully pinpointed significant enlargement of many areas of the basal ganglia structures, preferentially affecting the putamen. Moreover, these areas showed significant correlations with fine motor performance, indicating a possible link between altered basal ganglia neurodevelopment and declined motor performance in high Mn exposed children., Competing Interests: The authors declare no competing financial interests.

Background: Evidence suggests that lacunar infarcts have different etiologies, possibly related to their anatomical location and vascular territory. We investigated the risk factor profiles of patients with new lacunar infarcts in the basal ganglia and deep white matter., Methods: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study, a prospective cohort on brain changes on MRI in patients with symptomatic atherosclerotic disease, 679 patients (57 ± 9 years) had vascular screening and MRI at baseline and after a mean follow-up of 3.9 years. We investigated the association between vascular risk factors at baseline and appearance of new lacunar infarcts in the basal ganglia and deep white matter at follow-up., Results: New lacunar infarcts appeared in 44 patients in the basal ganglia and in 37 patients in the deep white matter. In multivariable analysis, older age, history of cerebrovascular disease, and baseline white matter hyperintensity (WMH) volume were associated with increased risk of new lacunar infarcts in both locations. Hyperhomocysteinemia was associated with increased risk of lacunar infarcts in the basal ganglia (relative risk [RR] 2.0; 95% CI 1.0-4.2), whereas carotid stenosis >70% (RR 2.5; 95% CI 1.2-5.0), smoking (per 10 pack-year: RR 1.1; 95% CI 1.0-1.3), hypertension (RR 3.4; 95% CI 1.2-9.7), and progression of WMH volume (RR 2.4; 95% CI 1.1-5.2) were associated with increased risk of lacunar infarcts in the deep white matter., Conclusions: The different risk factor profiles for new lacunar infarcts in basal ganglia and deep white matter indicate different etiologies. The independent association between progression of WMH and new deep white matter lacunar infarcts suggest a common etiology for these radiological abnormalities., (© 2017 The Author(s) Published by S. Karger AG, Basel.)

Introduction: Parkinsonism may occur after brain lesions such as subarachnoid hemorrhage (1), hydrocephalus (2,3), slit ventricle (4), or shunt revision (5).Until now, pathogenesis remains unclear., Method: Case Report., Results: We described the case of a 53 years Caucasian male with subarachnoid hemorrhage after anterior communicating artery aneurysm rupture, with subsequent complications and early development of bilateral extrapiramidal symptoms. A DatSCAN showed an impairment of the nigro-sytriatal dopaminergic way. Levodopa therapy induced complete symptoms remission., Conclusions: Patient developed Parkinson Disease responding to Levodopa. Subarachnoid hemorrhage itself, shunt placement and revision, hydrocephalus, slit ventricle: all of these complications occurred and could be possible causes of shear, torsion, and ischemia of the nigrostriatal projection fibres.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are two atypical parkinsonian syndromes first described half a century ago. The spectrum of these conditions as well as, more generally, the concept of tauopathy have dramatically changed over the past decade and especially in recent years. In particular, clinicopathological correlations have led to the description of several subtypes of these diseases and the features they share with other neurodegenerative diseases. The present paper is a review of how the concepts of PSP and CBD have evolved over time. In particular, it focuses on the different presentations of the disease and the overlapping syndromes that can complicate the differential diagnoses. Also discussed are some of the tools that may prove useful in making a diagnosis. Indeed, differential diagnosis issues are of particular importance in light of the likely emergence of pathology-specific disease-modifying therapies in the near future., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

An 86-year-old woman with a one-year history of dementia was admitted to our hospital complaining of loss of appetite, hallucinations, and disturbance of consciousness. She gradually presented with chorea-like involuntary movements of the extremities. Diffusion-weighted magnetic resonance imaging (MRI) showed bilateral symmetrical hyperintense signals in the basal ganglia. The serum vitamin B12 level was below the lower detection limit of 50 pg/ml. The homocysteine level was markedly elevated at 115.8 nmol/ml. Anti-intrinsic factor and anti-parietal cell antibody tests were positive. Gastrointestinal endoscopy revealed atrophic gastritis. The patient was diagnosed with encephalopathy due to vitamin B12 deficiency caused by pernicious anemia. Involuntary movements and MRI abnormalities improved with parenteral vitamin B12 supplementation. Bilateral basal ganglia lesions are rare manifestations of adult vitamin B12 deficiency. The present case is considered valuable in identifying the pathophysiology of involuntary movement due to vitamin B12 deficiency.

Importance: Extrapyramidal movement disorders associated with mitochondrial disease are difficult to treat and can lead to considerable disability. Moreover, potential new treatment trials on the horizon highlight the importance of genotype-phenotype associations and deep phenotyping of the movement disorders related to mitochondrial disease., Objective: To describe the phenotype, genetic etiology, and investigation of extrapyramidal movement disorders in a large and well-defined mitochondrial disease cohort., Design, Setting, and Participants: An observational cohort study at a single national referral center. Among 678 patients (87% adults) followed up at the Newcastle mitochondrial disease specialized referral center between January 1, 2000, and January 31, 2015, 42 patients (12 pediatric, 30 adult) with genetic or biochemical evidence of mitochondrial disease and with 1 or more predefined extrapyramidal movement disorders (parkinsonism, dystonia, tremor, chorea, and restless legs syndrome) were included., Main Outcomes and Measures: We investigated the prevalence and genetic causes of dystonia and parkinsonism as well as radiological findings in the context of movement disorders in mitochondrial disease. All patients were interviewed and examined. All available medical notes and clinical, radiological, and genetic investigations were reviewed., Results: Forty-two patients (mean [SD] age, 37 [25] years; 38% female) with mitochondrial disease (12 pediatric [age range, 4-14 years], 30 adult [age range, 20-81 years]) with extrapyramidal movement disorders were identified. Dystonia manifested in 11 pediatric patients (92%), often in the context of Leigh syndrome; parkinsonism predominated in 13 adult patients (43%), among whom 5 (38%) harbored either dominant (n = 1) or recessive (n = 4) mutations in POLG. Eleven adult patients (37%) manifested with either generalized or multifocal dystonia related to mutations in mitochondrial DNA, among which the most common were the m.11778G>A mutation and mutations in MT-ATP6 (3 of 11 patients [27%] each). Bilateral basal ganglia lesions were the most common finding in brain magnetic resonance imaging, usually associated with generalized dystonia or Leigh syndrome., Conclusions and Relevance: Dystonia, often associated with Leigh syndrome, was the most common extrapyramidal movement disorder among pediatric patients with mitochondrial disease. Parkinsonism was the most prevalent extrapyramidal movement disorder in adults and was commonly associated with POLG mutations; dystonia was predominantly associated with mitochondrial DNA mutations. These findings may help direct genetic screening in a busy neurology outpatient setting.