Novel findings in a Swedish primary familial brain calcification cohort.

INTRODUCTION: Brain calcifications are frequent findings on imaging. In a small proportion of cases, these calcifications are associated with pathogenic gene variants, hence termed primary familial brain calcification (PFBC). The clinical penetrance is incomplete and phenotypic variability is substantial. This paper aims to characterize a Swedish PFBC cohort including 25 patients: 20 from seven families and five sporadic cases. METHODS: Longitudinal clinical assessment and CT imaging were conducted, abnormalities were assessed using the total calcification score (TCS). Genetic analyses, including a panel of six known PFBC genes, were performed in all index and sporadic cases. Additionally, three patients carrying a novel pathogenic copy number variant in SLC20A2 had their cerebrospinal fluid phosphate (CSF-Pi) levels measured. RESULTS: Among the 25 patients, the majority (76%) displayed varying symptoms during the initial assessment including motor (60%), psychiatric (40%), and/or cognitive abnormalities (24%). Clinical progression was observed in most patients (78.6%), but there was no significant difference in calcification between the first and second scans, with mean scores of 27.3 and 32.8, respectively. In three families and two sporadic cases, pathogenic genetic variants were identified, including a novel finding, in the SLC20A2 gene. In the three tested patients, the CSF-Pi levels were normal. CONCLUSIONS: This report demonstrates the variable expressivity seen in PFBC and includes a novel pathogenic variant in the SLC20A2 gene. In four families and three sporadic cases, no pathogenic variants were found, suggesting that new PFBC genes remain to be discovered.

GNB1 Encephalopathy: Clinical Case Report and Literature Review.

GNB1 encephalopathy is a rare genetic disease caused by pathogenic variants in the G Protein Subunit Beta 1 (GNB1) gene, with only around 68 cases documented worldwide. Although most cases had been caused by de novo germline mutations, in this case, the pathogenic variant was inherited from patient's mother, indicating an autosomal dominant inheritance pattern. The patient presented at 25 years of age with mild developmental delay and cognitive impairment, prominent generalized dystonia, and horizontal nystagmus which are all characterizing symptoms of GNB1 encephalopathy. Electroencephalography (EEG) showed no epileptiform patterns, and magnetic resonance imaging (MRI) revealed hypointensities in globus pallidus and dentate nucleus areas. The main theory for GNB1 encephalopathy pathogenesis is neuronal hyperexcitability caused by impaired ion channel regulation. Due to low specificity of symptoms, diagnosis relies on genetic testing. As there are no standardized GNB1 encephalopathy treatment guidelines, evaluation of different treatment options is based on anecdotal cases. Reviewing different treatment options, deep brain stimulation and intrathecal baclofen pump, as well as some other medications still in preclinical trials, seem to be the most promising.

Intracranial Epidermoid Cyst: A Volumetric Study of a Surgically Challenging Benign Lesion.

BACKGROUND: Intracranial epidermoid cysts are rare, benign tumors. Nevertheless, the microsurgical removal of these cysts is challenging. This is due to their capacity to adhere to the neurovascular tissue, as well as the associated difficulties in microsurgically peeling off their capsular wall hidden in dead angles. To better understand the rate of recurrence after surgical intervention, we have performed preoperative and postoperative volumetric analysis of epidermoid cysts, allowing the estimation of their growth rate after resection. METHODS: Imaging data from 22 patients diagnosed and surgically treated for an intracranial epidermoid cyst between 2000 and 2022 were retrospectively collected from 2 European neurosurgical centers with microsurgical expertise. Volumetric analysis was performed on magnetic resonance imaging data. RESULTS: Average cyst volume at diagnosis, before any surgery, measured in 12 patients was 28,877.6 ± 10,250.4 mm3 (standard error of the mean [SEM]). Estimated growth rate of incompletely resected epidermoids after surgery was 1,630.05 mm3 ± 729.95 (SEM). Assuming linear growth dynamics and normalizing to postoperative residual volume, the average postoperative growth rate corresponded to 61.5% ± 34.3% (SEM) of the postoperative residual volume per year. We observed signs of recurrence during a radiologic follow-up period of 6.0 ± 2.8 years (standard deviation) in more than 50% of our patients. CONCLUSIONS: Due to their slow-growing nature, epidermoid cysts can often reach a complex multicompartmental size before resection, even in young patients, thus requiring complex approaches with challenging capsular resection, which implies a high risk of nerve and vascular injury per se. Tumor recurrence may be predicted on the basis of postoperative volumetry.

A Young Girl with Acute Encephalopathy Who Presented with Status Epilepticus Following a Flu-Like Illness.

BACKGROUND Acute necrotizing encephalopathy of childhood (ANEC) is a rare form of acute encephalopathy in children that is characterized by rapid and progressive deterioration in the patient's clinical condition. Our aim in reporting the case is to highlight the importance of early diagnoses and aggressive early management of ANEC to achieve a better outcome. We report the case of a 5-year-old girl who presented with acute progressive encephalopathy with bilateral symmetrical thalamic involvement and brainstem lesion proceeded by a flu-like illness. CASE REPORT We report a 5-year-old girl who was previously healthy. She presented with rapid progressive encephalopathy and status epilepticus following a flu-like illness. Her magnetic resonance imaging (MRI) showed significance symmetrical bilateral thalamic enhancement with brainstem lesions, which is consistent with the diagnosis of ANEC of childhood, and her initial electroencephalogram (EEG) showed severe encephalopathy. Despite extensive management of ANEC, the patient showed a poor prognosis. CONCLUSIONS ANEC is a rare, specific, devastating condition in the pediatric population. Early diagnosis and aggressive management should be initiated immediately to avoid the high mortality associated with the condition. Furthermore, to highlight the importance of the clear history of the patient who presented with rapid and progressive deterioration in the level of consciousness and status epilepticus proceeded by viral illness, a rapid neuroradiological images such as brain MRI should be obtained to confirm the diagnosis of this rare condition. We also seek to increase awareness of this disorder among healthcare workers and general practitioners.

Clinical Evaluation of a 2-Minute Ultrafast Brain MR Protocol for Evaluation of Acute Pathology in the Emergency and Inpatient Settings.

BACKGROUND AND PURPOSE: The use of MR imaging in emergency settings has been limited by availability, long scan times, and sensitivity to motion. This study assessed the diagnostic performance of an ultrafast brain MR imaging protocol for evaluation of acute intracranial pathology in the emergency department and inpatient settings. MATERIALS AND METHODS: Sixty-six adult patients who underwent brain MR imaging in the emergency department and inpatient settings were included in the study. All patients underwent both the reference and the ultrafast brain MR protocols. Both brain MR imaging protocols consisted of T1-weighted, T2/T2*-weighted, FLAIR, and DWI sequences. The ultrafast MR images were reconstructed by using a machine-learning assisted framework. All images were reviewed by 2 blinded neuroradiologists. RESULTS: The average acquisition time was 2.1 minutes for the ultrafast brain MR protocol and 10 minutes for the reference brain MR protocol. There was 98.5% agreement on the main clinical diagnosis between the 2 protocols. In head-to-head comparison, the reference protocol was preferred in terms of image noise and geometric distortion (P < .05 for both). The ultrafast ms-EPI protocol was preferred over the reference protocol in terms of reduced motion artifacts (P < .01). Overall diagnostic quality was not significantly different between the 2 protocols (P > .05). CONCLUSIONS: The ultrafast brain MR imaging protocol provides high accuracy for evaluating acute pathology while only requiring a fraction of the scan time. Although there was greater image noise and geometric distortion on the ultrafast brain MR protocol images, there was significant reduction in motion artifacts with similar overall diagnostic quality between the 2 protocols.

Delayed encephalopathy after acute carbon monoxide poisoning: a case study.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a relatively rare inflammatory-associated neurometabolic complication. In this article, we present a case report of a 50-year-old male patient with a history of carbon monoxide poisoning. This acute poisoning, although successfully controlled during a stay in the intensive care unit of a local hospital, later led to persistent neurological symptoms. The patient was then treated in the inpatient unit of the rehabilitation clinic, where cognitive deterioration began to develop 20 days after admission. Subsequent examination using EEG and magnetic resonance imaging confirmed severe encephalopathy later complicated by SARS-CoV-2 infection with fatal consequences due to bronchopneumonia. Because currently there are no approved guidelines for the management of DEACMP, we briefly discuss the existing challenges for future studies, especially the application of rational immunosuppressive therapy already in the acute treatment phase of CO poisoning, which could prevent the development of a severe form of DEACMP.

[A case of Hashimoto's encephalopathy with acute onset of psychiatric symptoms and diffuse deep white matter lesions on brain MRI].

A 51-year-old man developed acute disturbances in consciousness and psychiatric symptoms one month prior to admission. He was referred and admitted to the Department of Psychiatry of our hospital and transferred to the neurology department because diffuse white matter lesions were found on his brain during MRI. 123I-IMP-SPECT showed extensive cerebral hypoperfusion mainly in the frontal lobes. Anti-Tg, anti-TPO, and anti-NAE antibodies were positive. These findings led to a diagnosis of Hashimoto's encephalopathy. The patient responded to steroid pulse therapy, high-dose steroid therapy, and intravenous immunoglobulin therapy, showing improvement in symptoms and imaging findings. Hashimoto's encephalopathy often presents with MRI findings similar to those of limbic encephalitis, when the patient presents with acute consciousness disturbance and psychiatric symptoms. However, this case showed diffuse white matter lesions, which may be clinically important for the differential diagnosis.

Clinical characteristics of SARS-CoV-2-associated encephalopathy in children: Nationwide epidemiological study.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sometimes triggers acute encephalopathy as a serious neurological complication in children. We previously reported the clinico-radiological findings of SARS-CoV-2-associated encephalopathy. The advent of the SARS-CoV-2 omicron variant led to a marked increase in pediatric patients with coronavirus disease 2019 (COVID-19); however, epidemiological changes with acute encephalopathy according to the emergence of SARS-CoV-2 have not yet been documented. Therefore, the present study investigated epidemiological differences in SARS-CoV-2-associated encephalopathy during the BA.1/BA.2 and BA.5 predominant periods and also between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. METHODS: We conducted a nationwide survey of SARS-CoV-2-associated encephalopathy in Japanese children between June and November 2022. We compared the present results during the BA.5 predominant period and previous findings during the BA.1/BA.2 predominant period. We also compared the clinico-radiological syndromes of encephalopathy between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. RESULTS: Although many patients with SARS-CoV-2-associated encephalopathy in the BA.5 predominant period had seizures as their initial symptoms, no significant differences were observed in the clinical features. Patients with SARS-CoV-2-associated encephalopathy had worse outcomes than those with non-SARS-CoV-2-associated encephalopathy (p-value = 0.003). Among 103 patients with SARS-CoV-2-associated encephalopathy, 14 (13.6%) had severe types of acute encephalopathy, namely, encephalopathy with acute fulminant cerebral edema (AFCE) and hemorrhagic shock and encephalopathy syndrome (HSES). Also, 28 (27.2%) patients with SARS-CoV-2-associated encephalopathy had poor outcome: severe neurological sequelae or death. Ninety-five patients (92.2%) were not vaccinated against SARS-CoV-2. CONCLUSIONS: In SARS-CoV-2-associated encephalopathy, high percentages of AFCE and HSES can result in poor outcomes.

The etiological spectrum of multiple ring-enhancing lesions of the brain: a systematic review of published cases and case series.

OBJECTIVE: Multiple ring-enhancing lesions of the brain are enigmatic neuroimaging abnormality. In this systematic review, we evaluated the etiological spectrum of these lesions. METHODS: This systematic review adhered to the PRISMA guidelines. We searched PubMed, Embase, Scopus, and Google Scholar up until 15 June 2023. We included case reports and case series. Quality evaluation of each case was based on selection, ascertainment, causality, and reporting. The extracted information included demographic characteristics, clinical features, type and number of multiple enhancing brain lesions, diagnostic procedures, final diagnoses, treatments, and patient outcomes. PROTOCOL REGISTRATION: PROSPERO CRD42023437081. RESULTS: We analyzed 156 records representing 161 patients, 60 of whom were immunocompromised. The mean age was 42.6 years, and 67% of patients experienced symptoms for up to 1 month. A higher proportion of immunocompromised patients (42% vs. 30%) exhibited encephalopathy. Chest or CT thorax abnormalities were reported in 27.3% of patients, while CSF abnormalities were found in 31.7%, more frequently among the immunocompromised. Definitive diagnoses were established via brain biopsy, aspiration, or autopsy in 60% of cases, and through CSF examination or other ancillary tests in 40% of cases. Immunocompromised patients had a higher incidence of Toxoplasma gondii infection and CNS lymphoma, while immunocompetent patients had a higher incidence of Mycobacterium tuberculosis infection and immune-mediated and demyelinating disorders. The improvement rate was 74% in immunocompetent patients compared to 52% in the immunocompromised group. CONCLUSION: Multiple ring-enhancing lesions of the brain in immunocompromised patients are more frequently caused by Toxoplasma gondii infections and CNS lymphoma. Conversely, among immunocompetent patients, Mycobacterium tuberculosis infection and immune-related demyelinating conditions are common.

A Young Woman With Hypertonia, Severe Scoliosis, and Encephalopathy.

A 31-year-old woman was seen with contractures in her fingers and toes, carpal inversion, dysarthria, dysphagia, hypertonia, decreased tendon reflexes, absence of Babinski sign, and no psychiatric problems and significant global atrophy. What is your diagnosis?

Novel Homozygous Variants of SLC13A5 Expand the Functional Heterogeneity of a Homogeneous Syndrome of Early Infantile Epileptic Encephalopathy.

BACKGROUND: Early infantile epileptic encephalopathy 25 (EIEE25) is a distinct type of neonatal epileptic encephalopathy caused by autosomal recessive mutations in the SLC13A5 gene. SLC13A5 encodes a transmembrane sodium/citrate cotransporter required for regulating citrate entry into cells. METHODS: Four families with recessively inherited epileptic encephalopathy were sequenced by clinically accredited laboratories using commercially available epilepsy gene panels. Patients were examined by a neurologist and were clinically diagnosed with infantile epileptic encephalopathy. RESULTS: We present four families with global developmental delay, intellectual disability, and defective tooth development with four novel homozygous mutations in SLC13A5. The neurological examination showed spastic quadriplegia with increased deep tendon reflexes. Brain magnetic resonance imaging showed nonspecific signal abnormality of the bilateral hemispheric white matter. Despite similar clinical features, the conditions were based on different molecular mechanisms acting on SLC13A5 (abnormal splicing, large-scale deletions, and tandem-residue insertion). CONCLUSIONS: Our results extend the landscape of autosomal recessive inherited homozygous mutations in SLC13A5 that cause a distinctive syndrome of severe neonatal epileptic encephalopathy. Our observations confirm the homogeneity of epileptic encephalopathy and dental abnormalities as a distinct clinical marker for EIEE25 despite the heterogeneous functional and mutational background.