Neurological involvement in patients with primary immunodeficiency.

INTRODUCTION: Primary immunodeficiency diseases (PID) are defined by recurrent infections, allergies, autoimmunity, and malignancies. Neurologic symptoms are one of the major components of some immunodeficiency syndromes, such as Ataxia-Telangiectasia (AT), Nijmegen breakage syndrome (NBS), and Purine Nucleoside Phosphorylase (PNP) deficiency, which are considered as the primary involvement. Various pathological mechanisms, DNA repair disorders, metabolic abnormalities, and autoimmune phenomena have also been linked with neurological conditions. MATERIALS AND METHOD: We retrospectively assessed the neurological involvement in 108 patients out of 6000 with PID in this study. RESULTS: The female/male ratio of the cases was 49/59, and the median age was 13 years (min = 1; max = 60). Neurological problems were detected at a median age of 7 years (min = 0.5; max = 30). Di George Syndrome (DGS) and CVID (common variable immunodeficiency) were the most common diseases in our cohort (n = 31, 30% and n = 30, 27%, respectively). The most frequent outcomes were cognitive delay (n = 63, 58%), epilepsy (n = 25, 23%), and ataxia (n = 20, 18%). Central nervous system involvement was found in 99% of the patients (n = 107), and peripheral nervous system complication was found in only one patient with CVID and chronic inflammatory demyelinating polyneuropathy (CDIP). Cranial MRI was found to be abnormal in 74% (n = 80) of the patients. MRI findings included cerebellar atrophy (n = 33, 34%), white matter lesion (n = 27, 28.4%), cerebral atrophy (n = 21, 22.3%), gray matter lesion (n = 6, 6.3%), hydrocephalus (n = 5, 5,3%), and pituitary gland lesion (n = 3, 3.2%), intracranial hemorrhage (n = 3, 3%), intracranial vasculitis (n = 3, 2.7%), and arterio-venous malformation (n = 1, 0,9%). Primary involvement (a component of the disease) was 60% (n = 65), and secondary (infection or autoimmunity) and tertiary involvements (structural or incidental lesions) contributed 20% (n = 20) each in the patients. CONCLUSION: In this study, we describe the various neurologic findings of patients with PID. The neurologic presentation may represent the initial manifestation of certain types of PID. Early diagnosis and treatment are essential to prevent or reduce further neurologic damages.

Neuro-Behçet is a rare disease but should be considered in all kinds of neurological findings, even in childhood.

OBJECTIVES: Behçet's disease (BD) is a vasculitis characterised by eye, musculoskeletal, neurological and gastrointestinal involvement, in addition to recurrent oral ulcers. Neuro-Behçet is the term used to define the nervous system involvement in BD and is very rarely seen in childhood. This study aims to show that neuro-Behçet can manifest a clinical course involving all kinds of neurologic findings in the paediatric population. METHODS: The Clinic of Paediatric Neurology at Uludag University provides tertiary treatment for children up to eighteen years of age in Bursa, Turkey. Five patients who were clinically diagnosed with Neuro-Behçet in the last 5 years were included in the study. RESULTS: Seizure, myopathy, transverse myelitis, polyneuropathy, venous thrombosis and facial nerve paralysis were respectively seen in the patients. CONCLUSIONS: Neuro-Behçet is rare in children, but it is important to know that it can cause various neurological findings, and also systemic findings should be taken into consideration in the diagnosis of neurological diseases. Studies on the neurological involvement of BD in children are inadequate. We believe that paediatric neurologists should be more aware of the neuro-Behçet condition.

Pediatric-Onset Chronic Inflammatory Demyelinating Polyneuropathy: A Multicenter Study.

BACKGROUND: To evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. METHODS: The clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. RESULTS: A total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 44.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). CONCLUSIONS: This multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.

Re-examining the characteristics of pediatric multiple sclerosis in the era of antibody-associated demyelinating syndromes.

BACKGROUND: The discovery of anti-myelin oligodendrocyte glycoprotein (MOG)-IgG and anti-aquaporin 4 (AQP4)-IgG and the observation on certain patients previously diagnosed with multiple sclerosis (MS) actually have an antibody-mediated disease mandated re-evaluation of pediatric MS series. AIM: To describe the characteristics of recent pediatric MS cases by age groups and compare with the cohort established before 2015. METHOD: Data of pediatric MS patients diagnosed between 2015 and 2021 were collected from 44 pediatric neurology centers across Türkiye. Clinical and paraclinical features were compared between patients with disease onset before 12 years (earlier onset) and ≥12 years (later onset) as well as between our current (2015-2021) and previous (<2015) cohorts. RESULTS: A total of 634 children (456 girls) were enrolled, 89 (14%) were of earlier onset. The earlier-onset group had lower female/male ratio, more frequent initial diagnosis of acute disseminated encephalomyelitis (ADEM), more frequent brainstem symptoms, longer interval between the first two attacks, less frequent spinal cord involvement on magnetic resonance imaging (MRI), and lower prevalence of cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCBs). The earlier-onset group was less likely to respond to initial disease-modifying treatments. Compared to our previous cohort, the current series had fewer patients with onset <12 years, initial presentation with ADEM-like features, brainstem or cerebellar symptoms, seizures, and spinal lesions on MRI. The female/male ratio, the frequency of sensorial symptoms, and CSF-restricted OCBs were higher than reported in our previous cohort. CONCLUSION: Pediatric MS starting before 12 years was less common than reported previously, likely due to exclusion of patients with antibody-mediated diseases. The results underline the importance of antibody testing and indicate pediatric MS may be a more homogeneous disorder and more similar to adult-onset MS than previously thought.

Case report: early onset narcolepsy initially misdiagnosed as obstructive sleep apnea syndrome.

BACKGROUND: Narcolepsy is a chronic neurological syndrome, which is characterized by excessive sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis during the rapid eye movement period of sleep. This disease is commonly diagnosed within adulthood. However, the first symptoms often appear in childhood and/or adolescence. Pediatric cases of narcolepsy generally remain unrecognized and undiagnosed. Clinical heterogeneity, prolonged onset and diverse symptoms contribute to the delay in diagnosis and treatment in childhood. CASE: This report describes a case of narcolepsy in an 8,5-year-old male patient who was misdiagnosed as obstructive sleep apnea syndrome and many other diagnoses at different hospitals over a period of 3 years before the correct diagnosis was made. CONCLUSIONS: Narcolepsy in children is a rare neurological syndrome, which can occur with uncommon and atypical clinical presentations. In our case report we aimed to highlight pediatric narcolepsy, which could help to make more appropriate approaches and prevent misdiagnoses or diagnosis delay in these cases.

A rare case of juvenile amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a chronic motor neuron disease characterised by progressive weakness in striated muscles resulting from the destruction of neuronal cells. The term juvenile ALS (JALS) is used for patients whose symptoms start before 25 years of age. JALS may be sporadic or familial. CASE: Here, we present a sporadic case of JALS because of its rarity in children. The heterozygous p.Pro525Leu (c.1574C > T) variation was identified in the fused in sarcoma (FUS) gene. CONCLUSION: The p.Pro525Leu mutation in the FUS gene has been detected in patients with ALS, characterised by early onset and a severely progressive course.

Facial colliculus syndrome due to a Herpes simplex virus infection following Herpes labialis.

BACKGROUND: The facial colliculus is an elevated area that is formed by fibers from the motor nucleus of the 7`th cranial nerve as they loop over the abducens nucleus. Clinical signs and symptoms of facial colliculus lesions occur primarily due to injury to the abducens nerve nucleus, the facial nerve fibers around the abducens nucleus, paramedian pontine reticular formation, and the medial longitudinal fasciculus. The etiology of facial colliculus lesions varies by age. While tumors, demyelinating lesions, and viral infections can be involved in young individuals` etiology, vascular ischemia is a common causative factor in older people. CASE: In this paper, we present a case of facial colliculus syndrome due to its rare occurrence in a young patient; who developed the signs and symptoms after a herpes infection. CONCLUSION: Facial colliculus syndrome is rare and the treatment is based on etiology.

Reliability of CT angiography scoring systems used for brain death and the effect of cranial interventions on the results.

OBJECTIVE: To assess vascular opacifications, the efficiency, and interobserver agreement (IOA) of five different computed tomography angiography (CTA) brain death (BD) scoring systems in patients with and without cranial interventions, for determining alternative findings correctly supporting BD diagnosis by CTA even in cranial intervention presence. METHODS: 45 patients clinically identified with BD and evaluated with CTA were included. IOA of five different scoring systems used for CTA BD diagnosis, the effect of intracranial interventions on scoring systems, and vascular opacification were evaluated. RESULTS: IOA was almost perfect (κ = 0.843-0.911, p < 0.05) and substantial (κ = 0.771-0.776, p < 0.05) in all scoring systems. Significant relationships were observed between craniectomy presence and middle cerebral artery M4 segment and internal cerebral vein (ICV) opacification. No opacification was observed in straight sinus (SS) by observers in any of the craniectomized patients. CONCLUSION: IOA of CTA scoring systems is adequate. But a significant degree of false-negative results is observed due to ICV filling in craniectomy cases. Opacification presence in SS can give an idea of BD in these cases.

Neurological involvement in patients with primary immunodeficiency

Introduction: Primary immunodeficiency diseases (PID) are defined by recurrent infections, allergies, autoimmunity, and malignancies. Neurologic symptoms are one of the major components of some immunodeficiency syndromes, such as Ataxia-Telangiectasia (AT), Nijmegen breakage syndrome (NBS), and Purine Nucleoside Phosphorylase (PNP) deficiency, which are considered as the primary involvement. Various pathological mechanisms, DNA repair disorders, metabolic abnormalities, and autoimmune phenomena have also been linked with neurological conditions. Materials and method: We retrospectively assessed the neurological involvement in 108 patients out of 6000 with PID in this study. Results: The female/male ratio of the cases was 49/59, and the median age was 13 years (min = 1; max = 60). Neurological problems were detected at a median age of 7 years (min = 0.5; max = 30). Di George Syndrome (DGS) and CVID (common variable immunodeficiency) were the most common diseases in our cohort (n = 31, 30% and n = 30, 27%, respectively). The most frequent outcomes were cognitive delay (n = 63, 58%), epilepsy (n = 25, 23%), and ataxia (n = 20, 18%). Central nervous system involvement was found in 99% of the patients (n = 107), and peripheral nervous system complication was found in only one patient with CVID and chronic inflammatory demyelinating polyneuropathy (CDIP). Cranial MRI was found to be abnormal in 74% (n = 80) of the patients. MRI findings included cerebellar atrophy (n = 33, 34%), white matter lesion (n = 27, 28.4%), cerebral atrophy (n = 21, 22.3%), gray matter lesion (n = 6, 6.3%), hydrocephalus (n = 5, 5,3%), and pituitary gland lesion (n = 3, 3.2%), intracranial hemorrhage (n = 3, 3%), intracranial vasculitis (n = 3, 2.7%), and arterio-venous malformation (n = 1, 0,9%) (AU)