Estimation of Ambulation and Survival in Neurodegeneration with Brain Iron Accumulation Disorders.

BACKGROUND: Neurodegeneration with Brain Iron Accumulation (NBIA) disorder is a group of ultra-orphan hereditary diseases with very limited data on its course. OBJECTIVES: To estimate the probability of preserving ambulatory ability and survival in NBIA. METHODS: In this study, the electronic records of the demographic data and clinical assessments of NBIA patients from 2012 to 2023 were reviewed. The objectives of the study and factors impacting them were investigated by Kaplan-Meier and Cox regression methods. RESULTS: One hundred and twenty-two genetically-confirmed NBIA patients consisting of nine subtypes were enrolled. Twenty-four and twenty-five cases were deceased and wheelchair-bound, with a mean disease duration of 11 ± 6.65 and 9.32 ± 5 years. The probability of preserving ambulation and survival was 42.9% in 9 years and 28.2% in 15 years for classical Pantothenate Kinase-Associated Neurodegeneration (PKAN, n = 18), 89.4% in 7 years and 84.7% in 9 years for atypical PKAN (n = 39), 23% in 18 years and 67.8% in 14 years for Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN, n = 23), 75% in 20 years and 36.5% in 33 years for Kufor Rakeb Syndrome (KRS, n = 17), respectively. The frequencies of rigidity, spasticity, and female gender were significantly higher in deceased cases compared to surviving patients. Spasticity was the only factor associated with death (P value = 0.03). CONCLUSIONS: KRS had the best survival with the most extended ambulation period. The classical PKAN and MPAN cases had similar progression patterns to loss of ambulation ability, while MPAN patients had a slower progression to death. Spasticity was revealed to be the most determining factor for death.

Neurodegeneration with Brain Iron Accumulation Disorders and Retinal Neurovascular Structure.

BACKGROUND: The unique neurovascular structure of the retina has provided an opportunity to observe brain pathology in many neurological disorders. However, such studies on neurodegeneration with brain iron accumulation (NBIA) disorders are lacking. OBJECTIVES: To investigate NBIA's neurological and ophthalmological manifestations. METHODS: This cross-sectional study was conducted on genetically confirmed NBIA patients and an age-gender-matched control group. The thickness of retinal layers, central choroidal thickness (CCT), and capillary plexus densities were measured by spectral domain-optical coherence tomography (SD-OCT) and OCT angiography, respectively. The patients also underwent funduscopy, electroretinography (ERG), visual evoked potential (VEP), and neurological examination (Pantothenate-Kinase Associated Neurodegeneration-Disease Rating Scale [PKAN-DRS]). The generalized estimating equation model was used to consider inter-eye correlations. RESULTS: Seventy-four patients' and 80 controls' eyes were analyzed. Patients had significantly decreased visual acuity, reduced inner or outer sectors of almost all evaluated layers, increased CCT, and decreased vessel densities, with abnormal VEP and ERG in 32.4% and 45.9%, respectively. There were correlations between visual acuity and temporal peripapillary nerve fiber layer (positive) and between PKAN-DRS score and disease duration (negative), and scotopic b-wave amplitudes (positive). When considering only the PKAN eyes, ONL was among the significantly decreased retinal layers, with no differences in retinal vessel densities. Evidence of pachychoroid was only seen in patients with Kufor Rakeb syndrome. CONCLUSION: Observing pathologic structural and functional neurovascular changes in NBIA patients may provide an opportunity to elucidate the underlying mechanisms and differential retinal biomarkers in NBIA subtypes in further investigations. © 2023 International Parkinson and Movement Disorder Society.

Transcranial sonography in neurodegeneration with brain iron accumulation disorders.

BACKGROUND: Transcranial Sonography is a non-invasive technique that has been used as a diagnostic tool for a variety of neurodegenerative disorders. However, the utility and potential application of this technique in NBIA disorders is scarce and inconclusive. METHODS: In this cross-sectional retrospective case-control study, the echogenicity of Substantia Nigra (SN), Lentiform Nucleus (LN), and Diameter of the Third Ventricle (DTV) were assessed by TCS in genetically confirmed NBIA patients referring to the movement disorder clinic. The normal echogenicity area of SN was defined based on the 90th percentile of an age-and-gender-matched control group. NBIA patients underwent neurologic examination at each visit, but their brain magnetic resonance imaging and demographics were extracted from electronic records. RESULTS: Thirty-five NBIA patients of four subtypes with a mean disease duration of 10.54 years and 35 controls were enrolled. The normally defined SN echogenicity in controls was 0.23 cm2. DTV and SN echogenicity areas were significantly higher in patients compared to the controls (P = 0.002 and < 0.001, respectively). Around 85% and 63% of the patients showed LN and SN hyperechogenicity at least on one side, respectively. Disease duration was positively correlated with DTV (r = 0.422, p = 0.015). Cases with Pantothenate Kinase Associated Neurodegeneration (n = 23) also had significantly higher DTV and SN echogenicity area compared to the controls. CONCLUSION: Despite most NBIA patients displayed increased DVT and higher SN and LN hyperechogenicity than healthy controls, the discriminatory role of TCS on different NBIA subtypes remains to be determined.

Coronavirus disease 2019 (COVID-19)-associated brain abscesses caused by Pseudomonas aeruginosa and Aspergillus fumigatus: two case and a review of the literature.

BACKGROUND: Bacterial and fungal superinfections are commonly reported in patients with coronavirus disease 2019. CASE PRESENTATION: We report the first case of brain and intramedullary abscesses caused by Pseudomonas aeruginosa and a rare case of brain abscesses caused by Aspergillus fumigatus in two post-coronavirus disease 2019 patients. The first patient-34-year-old Iranian woman-presented with weakness of the left upper limb, headaches, and lower limb paresthesia. She had a history of undiagnosed diabetes and had received corticosteroid therapy. The second patient-45-year-old Iranian man-presented with right-sided weakness and had a history of intensive care unit admission. Both patients passed away despite appropriate medical therapy. CONCLUSION: The immune dysregulation induced by coronavirus disease 2019 and its' treatments can predispose patients, especially immunosuppressed ones, to bacterial and fungal infections with unusual and opportunistic pathogens in the central nervous system. Pseudomonas aeruginosa and Aspergillus fumigatus should be considered as potential causes of brain infection in any coronavirus disease 2019 patient presenting with neurological symptoms and evidence of brain abscess in imaging, regardless of sinonasal involvement. These patients should get started on appropriate antimicrobial therapy as soon as possible, as any delay in diagnosis or treatment can be associated with adverse outcomes.

A new genetic variant, presenting as young onset rapidly progressive dementia and parkinsonism.

There are various neurodegenerative or hereditary causes of Parkinsonism. Therefore, clinicians should consider an increasing range of differential diagnoses when facing a patient with Parkinsonism, especially when associated with additional clinical features. Young-onset Parkinsonism, especially when accompanied by features uncommon in idiopathic Parkinson's disease raises the possibility of genetic etiology. Herein, we present a case of a 40-year-old man with genetic Parkinson's disease, presenting with rapidly progressive dementia. This round will describe our approach to this clinical presentation and the unveiling of a rare genetic condition.

Intravenous thrombolysis in a patient with acute ischemic stroke associated with a ruptured sinus Valsalva aneurysm: The first case report.

Sinus Valsalva aneurysms (SVA) are rare asymptomatic cardiac anomalies, which can rupture and cause heart failure, myocardial infarction and also, they can be a potential source for embolic strokes. We report the first case of a patient with acute ischemic stroke associated with a ruptured SVA, who was treated with intravenous thrombolysis (tPA) without further complications.

First-episode mania after COVID-19: A case series in Iran.

Background: Increasing reports of manic episodes in patients during acute infection with COVID-19 have been documented since the pandemic began, including individuals without a previous personal or family history of bipolar disorder. As infections and autoimmunity have putative roles in bipolar disorder, we aimed to document the clinical presentations, associated stressors, family aggregation patterns, and brain imaging and electroencephalographic correlates with a series of patients with episodes of mania that emerged shortly after COVID-19 infections. Methods: We obtained all relevant clinical information from 12 patients whose first manic episode started within a month of COVID-19 infection and were treated at Rasool-e-Akram hospital and Iran psychiatric hospital, two tertiary medical centers in Tehran, Iran, in 2021. Results: Patients had a mean age of 44. The interval between the onset of symptoms of COVID and mania ranged between 0 and 28 days (mean: 16.25, median: 14 days); it was observed to be shorter in patients with a family history of mood disorders but not in those receiving corticosteroids. Alongside a descriptive overview of our sample, we provide detailed narrative descriptions of two of the cases for illustrative purposes and discuss our observations in the context of other cases reported elsewhere and the state-of-the-art regarding infectious diseases, COVID-19, and bipolar disorder as reported in previous literature. Conclusion: Our case series documents observational and naturalistic evidence from a dozen of cases of mania in the context of acute COVID-19, which, while limited, calls for analytical research of the phenomenon, and points at a family history of bipolar disorder and the use of corticosteroids as factors for particular focus.

Seizure in Neurodegeneration with Brain Iron Accumulation: A Systematic Review.

BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) is a rare genetic disorder. Its clinical manifestations comprise a wide spectrum mainly movement disorders. Seizure as a clinical manifestation is known to occur in some NBIAs, but the exact prevalence of epilepsy in each individual disorder is not well elucidated. The aim of this review was to investigate the frequency of seizures in NBIA disorders as well as to determine the associated features of patients with seizures. METHOD: The electronic bibliographic databases PubMed, Scopus, Embase, and Google Scholar were systematically searched for all cases in any type of article from inception to December 16, 2019. All the reported cases of NBIA (with or without genetic confirmation) were identified. Case reports with an explicit diagnosis of any types of NBIA, which have reported occurrence (or absence) of any type of seizure or epilepsy, in the English language, were included. Seizure incidence rate, type, and age of onset were reported as frequencies and percentages. RESULT: 1698 articles were identified and 51 were included in this review. Of 305 reported cases, 150 (49.2%) had seizures (phospholipase A2-associated neurodegeneration (PLAN) = 64 (50.8%), beta-propeller protein-associated neurodegeneration (BPAN) = 57 (72.1%), pantothenate kinase-associated neurodegeneration (PKAN) = 11 (23.4%), and others = 18 (very variable proportions)). The most frequent seizure type in NBIA patients was generalized tonic-clonic seizure with the mean age of seizure onset between 2 and 36 years. However, most of these papers had been published before the new classification of epilepsy became accessible. Affected patients were more likely to be females. CONCLUSION: Seizures are common in NBIA, particularly in PLAN and BPAN. In PKAN, the most common type of NBIA, around 10% of patients are affected by seizures. BPAN is the most possible NBIA accompanying seizure. Most of the findings regarding the seizure characteristics in the NBIAs are biased due to the huge missing data. Therefore, any conclusions should be made with caution and need further investigations.

Acute disseminated encephalitis (ADEM) as the first presentation of COVID-19; a case report.

Introduction: and importance: Neurological ailments are reported during and after SARS-COV-2 infection. Case presentation: We report a 67-year-old Iranian man with COVID-19 infection and Acute Disseminated Encephalomyelitis (ADEM) whose neurological symptoms appeared before clinical and radiological pulmonary manifestations. Clinical discussion: COVID-19 can cause neurological complication without entering the CNS via para infectious inflammatory mechanisms. Conclusions: This report shows that ADEM might be among primary presentations of COVID-19.

Perioperative routine EEG can reliably predict de novo seizures after supratentorial craniotomy.

BACKGROUND: The contributing risk factors in development of seizure after supratentorial craniotomy, the optimal duration of prophylactic antiepileptic therapy, the high-risk patient to treat, and the drug of choice are subjects of debate as is the gold standard diagnostic tool for patient screening. Combining routine electroencephalography (EEG) with clinical data to identify high-risk patients and determine the ideal time of recording after surgery was the goal of this study. METHODS: In this prospective cohort, 59 patients were evaluated with three EEG recordings after different intervals of supratentorial craniotomy due to different etiologies and were followed for 9 months for development of seizures. Demographic and disease-related variables as well as EEG results were analyzed to determine the contributing risk factors for development of seizures. RESULTS: Neoplastic etiology and abnormal perioperative EEG (performed before surgery or in the first postoperative week) were the only independent variables associated with development of de novo seizure. CONCLUSION: Routine EEG in the perioperative period and neoplastic etiology are two independent powerful predictors of developing seizure after supratentorial craniotomy and may help deciding whether to continue prophylactic antiepileptic medications for an extended period or not.

Simultaneous Occurrence of Cerebral Venous Sinus Thrombosis and Immune Thrombocytopenic Purpura in a Patient with a History of COVID-19 Infection.

Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, multiple but rare complications of this infection have been described, comprising cerebral venous sinus thrombosis (CVST) and immune thrombocytopenic purpura (ITP). Although these two complications have been reported as separate entities, to the best of our knowledge, their concurrent presentation has not been reported. In this case report, we present a middle-aged man with a history of COVID-19 infection who developed a sudden-onset severe occipital headache followed by right-sided blindness (right homonymous hemianopia). Upon his diagnostic workup, brain computed tomography scan with and without contrast was indicative of thrombosis of the left transverse venous sinus and hemorrhagic venous infarction. In addition, laboratory data revealed thrombocytopenia, which upon investigation confirmed a diagnosis of ITP. We postulate three pathophysiological mechanisms for this circumstance: either COVID-19 infection caused ITP and then ITP gave rise to CVST, or COVID-19 complications themselves resulted in ITP and CVST independently and simultaneously, or another plausible mechanism is immune-mediated thrombocytopenia caused by the anti-platelet 4-factor antibody, which is the proposed mechanism for CVST after the COVID-19 vaccine.

Cervical longitudinally extensive myelitis after vaccination with inactivated virus-based COVID-19 vaccine.

Myelitis, including longitudinally extensive transverse myelitis (LTEM), is reported in more than forty patients after coronavirus disease 2019 (COVID-19). Among COVID-19 vaccines, only Oxford-AstraZeneca COVID-19 vaccine (AZD1222) has been associated with few cases of myelitis (1 LTEM). We report the first case of myelitis/LTEM after BBIBP-CorV/Sinopharm vaccine, interestingly presented as a hemicord syndrome. A 71-year-old male presented with left-side diplegia, right-side hemihyposthesis with facial sparing and impaired position sensation in left foot after vaccination with BBIBP-CorV. MRI revealed a longitudinal signal in left cervical hemicord. This is the first reported myelitis and LTEM with COVID-19 vaccines other than AZD1222.

Neurodegeneration with Brain Iron Accumulation and a Brief Report of the Disease in Iran.

Neurodegeneration with brain iron accumulation (NBIA) is a term used for a group of hereditary neurological disorders with abnormal accumulation of iron in basal ganglia. It is clinically and genetically heterogeneous with symptoms such as dystonia, dysarthria, Parkinsonism, intellectual disability, and spasticity. The age at onset and rate of progression are variable among individuals. Current therapies are exclusively symptomatic and unable to hinder the disease progression. Approximately 16 genes have been identified and affiliated to such condition with different functions such as iron metabolism (only two genes: Ferritin Light Chain (FTL) Ceruloplasmin (CP)), lipid metabolism, lysosomal functions, and autophagy process, but some functions have remained unknown so far. Subgroups of NBIA are categorized based on the mutant genes. Although in the last 10 years, the development of whole-exome sequencing (WES) technology has promoted the identification of disease-causing genes, there seem to be some unknown genes and our knowledge about the molecular aspects and pathogenesis of NBIA is not complete yet. There is currently no comprehensive study about the NBIA in Iran; however, one of the latest discovered NBIA genes, GTP-binding protein 2 (GTPBP2), has been identified in an Iranian family, and there are some patients who have genetically remained unknown.

Identical twins with progressive kyphoscoliosis and ophthalmoplegia.

The possible differential diagnoses for children presenting with kyphoscoliosis, skeletal deformities and ophthalmoplegia are diverse. We present 11-year-old identical twins with these symptoms, with interesting etiological concern for those practicing in the fields of neurology, pediatrics, spine surgery and related specialties. A new presentation for a rare genetic condition was the final diagnosis for our patients. In this movement disorder round we describe our approach to this clinical constellation and discuss clinical significance of this genetic condition.