Progressive Neurological Deterioration Research Articles

A case report of seronegative neuromyelitis optica spectrum disorder treated with corticosteroids and intravenous immunoglobulin

Neuromyelitis optical spectrum disorders (NMOSD) are inflammatory and demyelinating autoimmune diseases ofthe central nervous system. We present the case of a male patient with seronegative NMOSD, who presented with area postrema syndrome; During hospitalization, he presented progressive neurological deterioration. In T2 flair of the brain MRI, hyperintense intramedullary lesions were evidenced, in the area postrema, in the brainstem and bilateral periventricular regions; the AQP4 dosage in serum and CSF were negative. The patient received treatment with Human Immunoglobulin for five days, which had a partial response to treatment.

Structural and mechanistic insights into a lysosomal membrane enzyme HGSNAT involved in Sanfilippo syndrome

Heparan sulfate (HS) is degraded in lysosome by a series of glycosidases. Before the glycosidases can act, the terminal glucosamine of HS must be acetylated by the integral lysosomal membrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT). Mutations of HGSNAT cause HS accumulation and consequently mucopolysaccharidosis IIIC, a devastating lysosomal storage disease characterized by progressive neurological deterioration and early death where no treatment is available. HGSNAT catalyzes a unique transmembrane acetylation reaction where the acetyl group of cytosolic acetyl-CoA is transported across the lysosomal membrane and attached to HS in one reaction. However, the reaction mechanism remains elusive. Here we report six cryo-EM structures of HGSNAT along the reaction pathway. These structures reveal a dimer arrangement and a unique structural fold, which enables the elucidation of the reaction mechanism. We find that a central pore within each monomer traverses the membrane and controls access of cytosolic acetyl-CoA to the active site at its luminal mouth where glucosamine binds. A histidine-aspartic acid catalytic dyad catalyzes the transfer reaction via a ternary complex mechanism. Furthermore, the structures allow the mapping of disease-causing variants and reveal their potential impact on the function, thus creating a framework to guide structure-based drug discovery efforts.

Hyperornithinemia-hyperammonemia-homocitrullinuria: a rare neurometabolic disorder in two siblings.

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome is an extremely rare disorder of urea cycle, with few patients reported worldwide. Despite hyperammonemia control, the long-term outcome remains poor with progressive neurological deterioration. We report the clinical, biochemical, and molecular features of two Lebanese siblings diagnosed with this disorder and followed for 8 and 15years, respectively. Variable clinical manifestations and neurological outcome were observed. The patient with earlier onset of symptoms had a severe neurological deterioration while the other developed a milder form of the disease at an older age. Diagnosis was challenging in the absence of the complete biochemical triad and the non-specific clinical presentations. Whole exome sequencing revealed a homozygous variant, p.Phe188del, in the SLC25A15 gene, a French- Canadian founder mutation previously unreported in Arab patients. Hyperammonemia was controlled in both patients but hyperonithinemia persisted. Frequent hyperalaninemia spikes and lactic acidosis occured concomitantly with the onset of seizures in one of the siblings. Variable neurological deterioration and outcome were observed within the same family. This is the first report from the Arab population of the long-term outcome of this devastating neurometabolic disorder.

Endovascular Rescue of Previously Treated Carotid Aneurysm: Higher Radial Force 48-Wire Flow Diverter for Salvage of Collapsed 64-Wire Device With Braid Deformation: 2-Dimensional Operative Video.

Aneurysm treatment presents various therapeutic options. Flow diverters (FD) stents are a revolutionizing endovascular technique for previously untreatable aneurysms.1 FD stents have documented success rates up to 95% and complication rates as low as 2.3%.2 This modality has proven its effectiveness and safety, but it is critical to consider potential complications. Complications include vascular-related problems such as perforation, occlusion, cerebral hyperperfusion, stent thrombosis, restenosis, and embolic events.3 To date, there is no standardized definition for braid collapse and fish-mouthing; however, braid collapse has been reported to occur at a rate of 1% and the latter at a rate of 3%.4 This technical video presents a case of a 51-year-old woman initially treated with a Surpass Evolve flow diverter (Stryker) for a right ophthalmic aneurysm. Secondary to device malapposition and collapse, she developed recurrent ischemic progressive neurologic impairment symptoms. The braid collapse was treated using a Pipeline Embolization device 3.25 × 20 mm (Medtronic) because this device exhibited a larger partial compressive force when compared with the 64-wire device.5 The procedure was uneventful and significantly improved the patient's neurologic symptoms. This technical video illustrates rescue stenting as a salvage intervention for FD collapse cases. The patient gave informed consent for surgery. Institutional review board approval was deemed unnecessary.

Diagnosis and Management of Thoracic Myelopathy.

Thoracic myelopathy can be a challenging condition to diagnose and treat. Successful outcomes depend on early recondition of the pathology and appropriate surgical referral in cases of progressive neurologic deterioration. The thoracic cord is tethered in kyphosis by the dentate ligaments and contains a tenuous blood supply. These conditions make the thoracic cord particularly susceptible to external compression and ischemic damage. Careful preoperative planning with specific attention to the location and source of thoracic stenosis is critical to successful decompression and complication avoidance. The purpose of this discussion is to outline the common sources of thoracic myelopathy and current recommendations regarding diagnosis and management. The review concludes with an overview of the most up-to-date literature regarding clinical outcomes.

Study protocol: Early neurological deterioration in patients with minor stroke, frequency, predictors, and outcomes in Vietnam single-centre study.

Early neurological deterioration (END) is progressive neurological deterioration with an increase in NIHSS score of 2 points or more in the first 72 hours from the onset of acute ischemic stroke. END increases the risk of poor clinical outcomes at day 90 of ischemic stroke. We will study the frequency, predictors, and outcomes of patients with END in a case-control study at a comprehensive stroke centre in Vietnam. of the design is a descriptive observational study, longitudinal follow-up of patients with minor stroke hospitalized at the Stroke Center of Bach Mai Hospital from December 1, 2023, to December 1, 2024. Minor stroke patients characterized by NIHSS score ≤ 5 hospitalized within 24 hours of symptom onset will be recruited. The estimated END rate is about 30%, relative accuracy ε = 0.11, 95% reliability, expected 5% of patients lost data or follow-up, and an estimated sample size of 779 patients. This study will help determine the END rate in patients with minor stroke and related factors, thereby building a prognostic model for END. Our study determined the END rate in patients with minor stroke in Vietnam and also proposed risk factors for minor stroke management and treatment.

Long-term efficacy of intrathecal cyclodextrin in patients with Niemann-Pick disease type C

Background and objectivesNiemann–Pick type C (NPC) is a rare lysosomal storage disease characterized by hepatosplenomegaly and progressive neurological deterioration due to abnormal intracellular cholesterol transport. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPBCD) is an effective treatment for NPC; however, few reports have shown its long-term efficacy and safety. To demonstrate long-term efficacy and safety of intrathecal HPBCD (IT-HPBCD) treatment for NPC, we herein reports five patients with NPC treated using IT-HPBCD for 4–11 years. Cases and resultsPatients’ ages at the onset ranged from 1.5 to 20 years. Notably, all patients showed rapid disease progression despite treatment with miglustat before IT-HPBCD treatment. Similarly, some patients showed transient improvement; however, all patients’ conditions stabilized after long-term IT-HPBCD therapy. Mild-to-moderate hearing loss was observed in three patients. Furthermore, long-term treatment with IT-HPBCD may suppress neurological deterioration in patients with NPC; however, patients still experience some disease progression. ConclusionsLong-term treatment with IT-HPBCD may suppress neurological deterioration in patients with NPC; however, the treatment outcome is dependent on the neurological status at the time of diagnosis, and disease progression is not completely inhibited. Awareness of the disease and newborn screening is needed for earlier disease detection. In addition, further optimization of the treatment protocol and additional treatments are needed to improve patient outcomes.

Genetic and phenotypic landscape of pediatric-onset epilepsy in 142 Indian families: Counseling and therapeutic implications.

The application of genomic technologies has led to unraveling of the complex genetic landscape of disorders of epilepsy, gaining insights into their underlying disease mechanisms, aiding precision medicine, and providing informed genetic counseling. We herein present the phenotypic and genotypic insights from 142 Indian families with epilepsy with or without comorbidities. Based on the electroclinical findings, epilepsy syndrome diagnosis could be made in 44% (63/142) of the families adopting the latest proposal for the classification by the ILAE task force (2022). Of these, 95% (60/63) of the families exhibited syndromes with developmental epileptic encephalopathy or progressive neurological deterioration. A definitive molecular diagnosis was achieved in 74 of 142 (52%) families. Infantile-onset epilepsy was noted in 81% of these families (61/74). Fifty-five monogenic, four chromosomal, and one imprinting disorder were identified in 74 families. The genetic variants included 65 (96%) single-nucleotide variants/small insertion-deletions, 1 (2%) copy-number variant, and 1 (2%) triplet-repeat expansion in 53 epilepsy-associated genes causing monogenic disorders. Of these, 35 (52%) variants were novel. Therapeutic implications were noted in 51% of families (38/74) with definitive diagnosis. Forty-one out of 66 families with monogenic disorders exhibited autosomal recessive and inherited autosomal dominant disorders with high risk of recurrence.

Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association.

Cerebral venous thrombosis accounts for 0.5% to 3% of all strokes. The most vulnerable populations include young individuals, women of reproductive age, and patients with a prothrombotic state. The clinical presentation of cerebral venous thrombosis is diverse (eg, headaches, seizures), requiring a high level of clinical suspicion. Its diagnosis is based primarily on magnetic resonance imaging/magnetic resonance venography or computed tomography/computed tomographic venography. The clinical course of cerebral venous thrombosis may be difficult to predict. Death or dependence occurs in 10% to 15% of patients despite intensive medical treatment. This scientific statement provides an update of the 2011 American Heart Association scientific statement for the diagnosis and management of cerebral venous thrombosis. Our focus is on advances in the diagnosis and management decisions of patients with suspected cerebral venous thrombosis. We discuss evidence for the use of anticoagulation and endovascular therapies and considerations for craniectomy. We also provide an algorithm to optimize the management of patients with cerebral venous thrombosis and those with progressive neurological deterioration or thrombus propagation despite maximal medical therapy.

Transradial access embolization of carotid-cavernous fistulae: Case report.

Carotid-Cavernous sinus fistula (CCF) represents a misdiagnosed condition with potential repercussion in functional, neurological, and social roles of patients with this disease. Earlier reports remark on the efficiency and safety of endovascular therapy with resolution of the symptoms were performed appropriately. We present a case of a male patient from a developing country, with gunshot wound head trauma history and short-term progressive functional and neurological impairment in the presence of intracranial hypertension and ocular symptoms who developed a large CFF, subsequently treated by transradial access embolization. We aim to describe the real-world experience in diagnosis and treatment of CCFs, emphasizing on the scope and outcomes of the endovascular treatment. This case supports worldwide experience, positioning endovascular therapy as an effective strategy in the resolution of CFFs, and the relevance of suspecting this disease in the presence of typical symptoms, even if they are rapidly progressive.

Rehabilitation of COVID-19 Patients with Cognitive, Autonomic and Insomnia Disorders Using Medicinal Leech Therapy

New coronaNew coronavirus disease (COVID-19) pandemic is a historical and urgent issue worldwide. The long-term consequences of the disease are neurological disorders, which need further investigation in terms of treatment and prevention. Apart from the traditional medical approach, management of cognitive, autonomic and sleep complications may be rehabilitated using medicinal leeches. The purpose of this study is to compare the neurological condition of COVID-19 patients before and after hirudotherapy. This cross-sectional study was conducted from January to December 2021 at the medical centre of the Khoja Akhmet Yassawi International Kazakh-Turkish University. The research population consisted of 83 patients with mild and severe forms of COVID-19 (more than 6 months), who underwent medicinal leech therapy (MLT). MLT was applied to the patients on the 6th and 11th days and their assessment of cognitive, autonomic and sleep disorders were carried out. Statistical analysis was carried out using SPSS Statistics (version 20.0, IBM, USA). The results of studies indicate a progressive neurological deterioration in COVID-19 patients. Neuropsychological observations in patients taking a full course of MLT showed an objective improvement in their cognitive, autonomic and sleep disorders. In particular, the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Montreal Cognitive Assessment (MoCA) Scale, Schulte Tables, Spielberger-Khanin Anxiety Scale (SKAS), Beck depression inventory (BDI), Study scheme to identify signs of autonomic disorders, Epworth Sleepiness Scale (ESS), Index of Severity of Sleep Disorders (ISSD) values improved after the MLT procedures.

Intravascular large cell B lymphoma presenting as central nervous system pseudo-vasculitis: A rare diagnostic challenge.

Intravascular large B cell lymphoma (IVLBCL) is a very rare subtype of aggressive non-Hodgkin B cell lymphoma characterized by intravascular proliferation of clonal B lymphocytes, classically associated with pulmonary and cutaneous disease and, less frequently, with central nervous system (CNS) involvement. Brain imaging findings are usually non-specific, with evidence of multiple vascular occlusions and stroke as non-specific multifocal abnormalities. We present an exceptionally rare case of IVLBCL in a patient with unexplained inflammatory syndrome with B symptoms and rapidly progressive neurological impairment, with multifocal hemorrhagic and tumefactive brain lesions seen on MRI. We suggest that in this clinical setting, the presence of tumefactive and hemorrhagic lesions should raise suspicion for IVLBCL and lead to the decision to perform a biopsy, which, nonetheless, remains the diagnostic gold standard.

Progressive Multifocal Leukoencephalopathy in Systemic Lupus Erythematosus: A Consequence of Patient-Intrinsic or -Extrinsic Factors?

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by reactivation of the polyomavirus JC (JCV) typically in immunocompromised individuals. The risk of PML among rheumatic diseases may be higher for systemic lupus erythematosus (SLE), without, however, a clear association with the type and intensity of background therapy. We present the development and outcome of PML in a 32-year-old female lupus patient under mild immunosuppressive treatment, yet with marked B-cell lymphopenia in the peripheral blood and bone marrow (<1% of total lymphocytes). Despite treatment with the immune checkpoint inhibitor pembrolizumab, the patient showed progressive neurological and brain imaging deterioration and eventually died 15 months after PML diagnosis. To unveil possible underlying genetic liabilities, whole exome sequencing was performed which identified deleterious variants in GATA2 and CDH7 genes, which both have been linked to defective T- and/or B-lymphocyte production. These findings reiterate the possible role of disease-/patient-intrinsic factors, rather than that of drug-induced immunosuppression, in driving immune dysregulation and susceptibility to PML in certain patients with SLE.

Successful Use of Therapeutic Plasma Exchange Following Red Blood Cell Exchange for Severe Acute Chest Syndrome: A Single Institution Experience

Introduction: Severe acute chest syndrome (ACS) is a potentially fatal complication of sickle cell disease (SCD) that can progress to multiorgan failure. Treatment includes red blood cell (RBC) exchange to improve oxygenation and reduce vaso-occlusion by decreasing the proportion of hemoglobin (Hb) S. Patients with poor response to RBC exchange are at high risk for mortality. Therapeutic plasma exchange (TPE) may be beneficial in cases of severe organ dysfunction refractory to RBC exchange. TPE is postulated to remove pro-inflammatory cytokines, reduce circulating free hemoglobin, and decrease complement products that contributes to vaso-occlusion and inflammation. The use of TPE for severe ACS and multiorgan failure has been rarely described in adult patients and is even less commonly described for pediatric patients. Aim: To describe use of TPE for the management of severe ACS with multiorgan failure in two pediatric patients and one young-adult patient who did not respond to standard medical management with RBC exchange transfusion. Methods: Case reports Case 1: A six-year-old male with homozygous SCD (HbSS) and moderate persistent asthma was admitted for ACS. His course was complicated by hypoxemia requiring intubation, oliguria, and hypotension. On hospital day 3, he underwent RBC exchange with four units of RBCs. Despite decrease of Hb S to 15%, he remained hypoxic on high ventilatory support and developed acute respiratory distress syndrome. After multidisciplinary discussion, TPE was trialed in hopes of improving oxygenation and reversing multiorgan dysfunction. He underwent 3 TPEs, each with 1.5 total plasma volume (TPV) using 5% albumin (days 4, 5 and 7). After a single session of TPE, his oxygenation saturations improved to the 90s, and his ventilator support was weaned. He was extubated on day 8 and was discharged on day 13 in stable condition. Case 2: A sixteen-year-old male with HbSS, recurrent hyper-hemolytic syndrome, and sickle cell hepatopathy was admitted for medical optimization before scheduled cholecystectomy. His Hb was raised pre-operatively with erythropoietin, in lieu of RBC transfusion, due to history of severe refractory hyper-hemolysis with transfusions. He underwent uncomplicated cholecystectomy on hospital day 2. On day 3, he developed ACS, septic shock, and an exacerbation of known hepatopathy. He was intubated and underwent RBC exchange with 8 units of RBCs. His Hb S decreased to 20% but he had no improvement in clinical status. High-dose steroids and TPE were then trialed. The use of TPE was dual purposed to reduce inflammatory cytokines contributing to systemic dysfunction and to prevent hyper-hemolysis following exchange transfusion. He underwent 3 TPEs each with 1.5 TPV using 5% albumin for three days (days 5, 6, and 7). Throughout his course of TPE, he was extubated (day 6), weaned off pressor support (day 6), and his liver dysfunction began to improve (day 7). He was discharged home on day 16. Case 3: A thirty-five-year-old female with HbSS without chronic complications was transferred from an outside hospital where she presented 3 days prior with ACS and progressive neurologic deterioration with minimal responsiveness. Imaging revealed diffuse pulmonary infiltrates and extensive cerebral micro emboli consistent with fat embolism syndrome. She underwent RBC exchange on the day of arrival to our facility (hospital day 4) with 5 units of RBCs. Her Hb S decreased to 20% but she had no improvement in neurologic function. After multidisciplinary evaluation, TPE was trialed alongside high-dose steroids. She underwent 5 TPEs each with 1.0 TPV using 5% albumin (days 5, 6, 8, 9, and 12). Shortly after initiating TPE, she began recovering neurologically with eye-opening, response to noxious stimuli, and tracking (day 6). After 3 days of TPE, CRP fell from 21 to 5 and ESR from 49 to 23 (day 8). She followed commands on day 10 and was taken off oxygen on day 15. She was discharged to a rehabilitation facility on day 30 with significant improvements in mental status, cognition, and functional abilities. Conclusions: TPE for three to five days should be considered in patients with severe ACS and multiorgan failure with high risk of mortality when standard management fails. The early initiation of TPE likely contributed to the successful recoveries of these three cases. Further studies are needed to delineate the role of TPE in the management of acute complications of SCD.

The experiences of parents of children diagnosed with cerebral adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is a rare X-linked neurodegenerative disease, affecting the brain, spinal cord and adrenal cortex. Childhood cerebral ALD (CCALD) is the most severe form of disease, involving rapidly progressive neurological deterioration. The treatment option for CCALD is allogenic haemopoietic stem cell transplant, which is only successful for early-stage disease. Parents' experiences of CCALD can inform healthcare delivery. To detail the experiences of parents of children diagnosed with cerebral ALD. A descriptive qualitative study. Parents were recruited via a UK-based community support organisation. Data collection involved single semi-structured interviews structured around a topic guide and conducted remotely. Data were analysed using the thematic analysis approach. Twelve parents from 11 families with a total of 16 children with ALD contributed to the study. Their 16 children with ALD followed one of three disease pathways, determined by the extent of neurological damage at diagnosis. Three themes, and their respective sub themes, describe the pathways and what they meant for parents. 'No possibility of treatment' concerns situations when CCALD was diagnosed at an advanced stage, the landslide of deterioration parents witnessed and their efforts to maintain normality. 'Close to the treatment threshold' describes situations where a small treatment window required parents to make agonising treatment decisions. 'Watching and waiting' explains the challenges for parents when disease was detected early enabling children to benefit from timely treatment. Parents' experiences were largely defined by the extent of cerebral damage at diagnosis, which determined the availability and success of treatment. There were specific challenges related to the three situations, indicating areas where support from health and care services may help parents deal with this devastating diagnosis. This study indicates support needs of parents across the spectrum of CCALD diagnoses and highlights the critical importance of early diagnosis.

GNAQ/GNA11 Mosaicism Causes Aberrant Calcium Signaling Susceptible to Targeted Therapeutics

Mosaic variants in genes GNAQ or GNA11 lead to a spectrum of vascular and pigmentary diseases including Sturge-Weber syndrome, in which progressive postnatal neurological deterioration led us to seek biologically targeted therapeutics. Using two cellular models, we find that disease-causing GNAQ/11 variants hyperactivate constitutive and G-protein coupled receptor ligand-induced intracellular calcium signaling in endothelial cells. We go on to show that the aberrant ligand-activated intracellular calcium signal is fueled by extracellular calcium influx through calcium-release-activated channels. Treatment with targeted small interfering RNAs designed to silence the variant allele preferentially corrects both the constitutive and ligand-activated calcium signaling, whereas treatment with a calcium-release-activated channel inhibitor rescues the ligand-activated signal. This work identifies hyperactivated calcium signaling as the primary biological abnormality in GNAQ/11 mosaicism and paves the way for clinical trials with genetic or small molecule therapies.

Spinal epidural abscess as predicting factor for the necessity of early surgical intervention in patients with pyogenic spondylitis

BackgroundPyogenic spondylitis is a condition with low incidence that can lead to neurological sequelae and even life-threatening conditions. While conservative methods, including antibiotics and bracing, are considered the first-line treatment option for pyogenic spondylitis, it is important to identify patients who require early surgical intervention to prevent progressive neurologic deficits or deterioration of the systemic condition. Surgical treatment should be considered in patients with progressive neurologic deficits or deteriorating systemic condition. However, currently, there is a lack of treatment guidelines, particularly with respect to whether surgical treatment is necessary for pyogenic spondylitis. This study aims to analyze the radiological epidural abscess on MRI and clinical factors to predict the need for early surgical intervention in patients with pyogenic spondylitis and provide comprehensive insight into the necessity of early surgical intervention in these patients.MethodsThis study retrospectively reviewed 47 patients with pyogenic spondylitis including spondylodiscitis, vertebral osteomyelitis, epidural abscess, and/or psoas abscess. All patients received plain radiographs, and a gadolinium-enhanced magnetic resonance imaging (MRI) scan. All patients have either tissue biopsies and/or blood cultures for the diagnosis of a pathogen. Demographic data, laboratory tests, and clinical predisposing factors including comorbidities and concurrent other infections were analyzed.ResultsWe analyzed 47 patients, 25 of whom were female, with a mean age of 70,7 years. MRI revealed that 26 of 47 patients had epidural abscesses. The surgical group had a significantly higher incidence of epidural abscess than the non-surgical group (p = 0.001). In addition, both CRP and initial body temperature (BT) were substantially higher in the surgical group compared to the non-surgical group. There was no significant difference between the surgical group and the non-surgical group in terms of age, gender, comorbidities, and concurrent infectious disorders, as well as the number of affected segments and affected spine levels. However, the surgical group had lengthier hospital stays and received more antibiotics.ConclusionThe presence of an epidural abscess on MRI should be regarded crucial in the decision-making process for early surgical treatment in patients with pyogenic spondylitis in order to improve clinical outcomes.

Acute disseminated toxoplasmosis in an immunocompetent adult patient. Case report

Abstract Introduction: Toxoplasmosis is a disease of global distribution caused by the parasite Toxoplasma gondii, which develops differently depending on the immunologic status of the patient. In immunocompetent patients, it is usually asymptomatic and complications such as pneumonitis, encephalitis, or multiple organ dysfunction are rare. The following is the case of an immunocompetent patient with acute disseminated toxoplasmosis. Case report: A 42-year-old man, with no history of immunocompromise, or relevant medical, family or personal history, was transferred to the emergency department of a tertiary care institution in the city of Bogotá D.C. (Colombia) due to a fever that had lasted for a month, headache, and progressive neurological deterioration. Studies looking for other infectious etiologies, as well as for autoimmunity, neoplasms, and metabolic disorders, were negative. Computed tomography (CT) of the skull showed findings of meningoencephalitis. He was considered as a possible case of toxoplasmosis and treatment with trimethoprim/sulfamethoxazole was initiated. During his stay in the intensive care unit (ICU), he developed multiple organ dysfunction syndrome (MODS) and ultimately died. The post-mortem histopathological study of tissues reported the presence of Toxoplasma gondii bradyzoites, which confirmed the diagnosis of acute toxoplasmosis. Conclusions: Acute disseminated toxoplasmosis is a diagnostic challenge because it can mimic other etiologies. A timely diagnosis may prevent medical complications and increase the patient's chances of recovery. Knowledge about this disease in immunocompetent patients is a subject being developed.

Endoscopic Transoral Odontoidectomy of Craniovertebral Junction Rheumatoid Arthritis With the Help of Real-Time Fluoroscopy and Intraoperative Computed Tomography.

Rheumatoid arthritis (RA) involvement in the craniovertebral junction (CVJ) is a rare condition after antirheumatoid medications, nevertheless still exists. Neurological deterioration of the patient makes surgery inevitable. Seventy-seven years old man without antirheumatoid treatment presented with progressive neurological deterioration and CVJ involvement of RA with severe cord compression with myelomalacia. The patient underwent endoscopic transoral odontoidectomy with real-time fluoroscopy and intraoperative computed tomography. Even though radiological improvement has been achieved the patient died because of pulmonary complications. Rheumatoid arthritis of CVJ is a life-threatening medical condition. Surgical procedures will be safer by using endoscopy and intraoperative radiological imaging techniques.

Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum

BackgroundSpinal muscular atrophy (SMA) could be classified as 5q and non-5q, based on the chromosomal location of causative genes. A rare form of non-5q SMA is an autosomal-recessive condition called spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), phenotypically characterized by myoclonic and generalized seizures with progressive neurological deterioration. SMA-PME is a clinically heterogeneous disorder that arises from biallelic pathogenic variants in ASAH1 gene.MethodsFollowing clinical and primary laboratory assessments, whole-exome sequencing was performed to detect the disease-causing variants in three cases of SMA-PME from different families. Also, Multiplex ligation-dependent probe amplification (MLPA) was employed for determining the copy numbers of SMN1 and SMN2 genes to rule out 5q SMA.ResultsExome sequencing revealed two different homozygous missense mutations (c.109 C > A [p.Pro37Thr] or c.125 C > T [p.Thr42Met]) in exon 2 of the ASAH1 gene in the affected members of the families. Sanger sequencing of the other family members showed the expected heterozygous carriers. In addition, no clinically relevant variant was identified in patients by MLPA.ConclusionThis study describes two different ASAH1 mutations and the clinical picture of 3 SMA-PME patients. In addition, previously reported mutations have been reviewed. This study could help to fortify the database of this rare disease with more clinical and genomic data.