Clinical and laboratory findings and etiologies of genetic homocystinemia: a single-center experience.

BACKGROUND: Homocysteine (Hcy) is an endogenous nonprotein sulfur-containing amino acid biosynthesized from methionine by the removal of its terminal methyl group. Hyperhomocysteinemia (HHcy) has been linked to many systemic disorders, including stroke, proteinuria, epilepsy, psychosis, diabetes, lung disease, and liver disease. The clinical effects of high serum Hcy level, also known as hyperhomocysteinemia, have been explained by different mechanisms. However, little has been reported on the clinical and laboratory findings and etiologies of genetic HHcy in children. This study aimed to examine the relationships between clinical features, laboratory findings, and genetic defects of HHcy. METHODS: We retrospectively evaluated 20 consecutive children and adolescents with inherited HHcy at the pediatric neurology division of Baskent University, Adana Hospital (Adana, Turkey) between December 2011 and December 2022. RESULTS: Our main finding is that the most common cause of genetic HHcy is MTHFR mutation. The other main finding is that the Hcy level was higher in patients with CBS deficiency and intracellular cbl defects than in MTHFR mutations. We also found that clinical presentations of genetic HHcy vary widely, and the most common clinical finding is seizures. Here, we report the first and only case of a cbl defect with nonepileptic myoclonus. We also observed that mild and intermediate HHcy associated with the MTHFR mutation may be related to migraine, vertigo, tension-type headache, and idiopathic intracranial hypertension. Although some of the patients were followed up in tertiary care centers for a long time, they were not diagnosed with HHcy. Therefore, we suggest evaluating Hcy levels in children with unexplained neurological symptoms. CONCLUSIONS: Our findings suggest that genetic HHcy might be associated with different clinical manifestations and etiologies. Therefore, we suggest evaluating Hcy levels in children with unexplained neurologic symptoms.

Evaluation of nutritional status in pediatric intensive care unit patients: the results of a multicenter, prospective study in Turkey.

Introduction: Malnutrition is defined as a pathological condition arising from deficient or imbalanced intake of nutritional elements. Factors such as increasing metabolic demands during the disease course in the hospitalized patients and inadequate calorie intake increase the risk of malnutrition. The aim of the present study is to evaluate nutritional status of patients admitted to pediatric intensive care units (PICU) in Turkey, examine the effect of nutrition on the treatment process and draw attention to the need for regulating nutritional support of patients while continuing existing therapies. Material and Method: In this prospective multicenter study, the data was collected over a period of one month from PICUs participating in the PICU Nutrition Study Group in Turkey. Anthropometric data of the patients, calorie intake, 90-day mortality, need for mechanical ventilation, length of hospital stay and length of stay in intensive care unit were recorded and the relationship between these parameters was examined. Results: Of the 614 patients included in the study, malnutrition was detected in 45.4% of the patients. Enteral feeding was initiated in 40.6% (n = 249) of the patients at day one upon admission to the intensive care unit. In the first 48 h, 86.82% (n = 533) of the patients achieved the target calorie intake, and 81.65% (n = 307) of the 376 patients remaining in the intensive care unit achieved the target calorie intake at the end of one week. The risk of mortality decreased with increasing upper mid-arm circumference and triceps skin fold thickness Z-score (OR = 0.871/0.894; p = 0.027/0.024). The risk of mortality was 2.723 times higher in patients who did not achieve the target calorie intake at first 48 h (p = 0.006) and the risk was 3.829 times higher in patients who did not achieve the target calorie intake at the end of one week (p = 0.001). The risk of mortality decreased with increasing triceps skin fold thickness Z-score (OR = 0.894; p = 0.024). Conclusion: Timely and appropriate nutritional support in critically ill patients favorably affects the clinical course. The results of the present study suggest that mortality rate is higher in patients who fail to achieve the target calorie intake at first 48 h and day seven of admission to the intensive care unit. The risk of mortality decreases with increasing triceps skin fold thickness Z-score.

The Effects of Protein Intake on Clinical Outcome in Pediatric Intensive Care Units.

OBJECTIVE: Factors such as increased metabolic needs and inadequate calorie and protein intake increase the risk of malnutrition in critically ill children admitted to the pediatric intensive care unit. This study aimed to determine the risk of malnutrition and associated clinical outcomes. MATERIALS AND METHODS: Data from all patients aged 1 month to 18 years in 4 pediatric intensive care units in Adana, Turkey, were prospectively collected. Patient anthropometric data, the duration of mechanical ventilation, the length of stay in pediatric intensive care unit, 60-day mortality, nutritional status, and calorie and protein intake were recorded. RESULTS: A total of 111 patients were included in the study. There was a significant difference between survivor and non-survivor patients in terms of calorie and protein intake 48 hours after admission and protein intake on the seventh day after admission (P = .001, P = .000, and P = .003, respectively). No significant correlation was found between the length of pediatric intensive care unit stay, sepsis, and calorie intake in the first week. It was found that 1 g/kg/ day increase in protein intake on the seventh day of intensive care hospitalization decreased the risk of mechanical ventilation by 0.49 times (P = .035; sensitivity: 83.3%; specificity: 34.5%). CONCLUSION: Nutritional status should be evaluated fully in patients admitted to the pediatric intensive care unit and early detected malnutrition should be monitored closely to determine the need for early intervention. The risk of developing malnutrition is high in critically ill children. Providing the necessary energy and protein intake with nutritional therapy affects the clinical course in children with critical illness. Protein intake causes prolongation of mechanical ventilation time, delaying clinical recovery.

Role of automated red blood cell exchange in the treatment of aluminum phosphide poisoning: A case report and review of the literature.

Aluminum phosphide (AIP) is a fumigant commonly used in agricultural areas. AIP is frequently misused for suicidal purposes because it is easily accessible. AIP poisoning causes severe metabolic acidosis, resistant hypotension, acute respiratory distress syndrome, and multiorgan failure with cardiogenic shock. Despite supportive management and intensive care, most patients die following AIP ingestion because there is no specific antidote. In this case report we present a 15-year-old female who presented with vomiting, coma and epigastric pain. She developed resistant metabolic acidosis and hypotension due to AIP poisoning. Although supportive treatment did not result in clinical improvement, she was successfully treated with automated red blood cell exchange. Automated red blood cell exchange is a procedure which is used to exchange the patient erythrocyte mass with donor red blood cell. Although automated red blood cell exchange is a preferred treatment method in the complications of sickle cell anemia, some blood diseases and infectious diseases such as malaria and babesiosis, there is little information about its use in poisoning. To the best of our knowledge, this is the first child with AIP poisoning who was treated with automated red blood cell exchange.

The Role of Therapeutic Plasma Exchange in the Treatment of Childhood Intoxication: A Single-Center Experience.

OBJECTIVES: Therapeutic plasma exchange is used to treat neurologic, hematological, renal, and autoimmune diseases with a known or suspected etiopathogenesis. However, there is incomplete understanding of the use of therapeutic plasma exchange in pediatric cases of intoxication. This study investigated 5 years of experience with therapeutic plasma exchange to treat intoxication cases. DESIGN: A retrospective, case series, single-center study. SETTING: PICU of Baskent University, Dr. Turgut Noyan Teaching, and Medical Research Center Hospital in Adana, Turkey. PATIENTS: Fourteen patients diagnosed with intoxication who underwent therapeutic plasma exchange between January 2013 and January 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data pertaining to 14 patients, including their medical history (exposure to drugs/toxicants), demographics, initial presentation, and severity of clinical symptoms (requirement of mechanical ventilation, Glasgow Coma Scale score, and the pediatric severity of illness score [Pediatric Logistic Organ Dysfunction] were retrospectively reviewed. The most common indication for therapeutic plasma exchange was multiple drug intoxication, followed by amitriptyline, Amanita phalloides mushroom, carbamazepine, mercury, verapamil, and botulism. All patients underwent therapeutic plasma exchange and two patients underwent hemodialysis before therapeutic plasma exchange. There was no mortality or complications related to the therapeutic plasma exchange procedure. Clinical improvement was observed after therapeutic plasma exchange in 13 of the 14 patients; one patient with verapamil intoxication died. CONCLUSIONS: Therapeutic plasma exchange appears to be safe and effective for treating pediatric cases of intoxication, including multidrug and amitriptyline intoxication, and is associated with significant recovery in the majority of severely affected patients. Treatment of intoxication with therapeutic plasma exchange should be guided primarily by the properties of the causative toxic substances/drugs, and consideration of patient age, the severity of clinical symptoms, Pediatric Logistic Organ Dysfunction score and response to initial supportive and antidotal treatment.

Correction to: Overview of therapeutic plasma exchange in pediatric neurology: a single-center experience.

Unfortunately, the immediate following sentences were incorrectly published in Material and Method section of the original article.

Overview of therapeutic plasma exchange in pediatric neurology: a single-center experience.

Therapeutic plasma exchange (TPE) is used in the treatment of neurological, hematological, renal and autoimmune diseases with known or suspected immune pathogenesis. In comparison with neurological diseases of adults, knowledge about the use of TPE in children is incomplete. We report our experience on TPE in children with neurological diseases in a single institution and describe the underlying etiology, clinical course, treatment and outcome. We retrospectively evaluated 22 consecutive children (12 girls, 10 boys, aged 2-16 years) who underwent TPE in the pediatric intensive care unit between January 2010 and January 2017. There were 135 TPE procedures with median 6 TPE sessions per patient. Fresh frozen plasma was used as a replacement fluid in all cases. Most common indications were inflammatory polyneuropathy followed by acquired demyelinating diseases of the central nervous system. Other indications were autoimmune encephalitis and paraneoplastic limbic encephalitis. No mortality was recorded during TPE. The complication rate was 2.2% and consisted of transient events like hypotension and allergic reactions. Therapetic plasma exchange is one of the safe methods of treatment for neuroimmunological disorders in children, with Guillain-Barré syndrome as the most common indication.

Sadfly fever: two case reports.

Sandfly fever, also known as 'three-day fever' or 'pappataci fever' or 'Phlebotomus fever' is a viral infection that causes self-limited influenza-like symptoms and characterized by a rapid onset. The disease occurs commonly in endemic areas in summer months and especially in August during which sandflies are active. In this article, two siblings who presented with high fever, redness in the eyes, headache, weakness, malaise and inability to walk, who were found to have increased liver function tests and creatine kinase levels and who were diagnosed with sadfly fever with positive sadfly IgM and IgG antibodies are reported because of the rarity of this disease.

Serum vitamin B12, folic acid, and homocysteine levels in children with febrile seizure.

The aim of this study is to investigate the associations between febrile seizure and serum levels of vitamin B12, folic acid, and homocysteine. One hundred and four children who presented with febrile seizure and 75 controls who presented with febrile illness unaccompanied by seizure were enrolled into the study. Mean levels of vitamin B12, folic acid and homocysteine were compared between two groups. Mean vitamin B12 level in the febrile seizure group was significantly lower than the control group. The febrile seizure patients with 3 or more had significantly lower serum folic acid than the subgroups with two or one episode only. Serum concentrations of folic acid were significantly lower in the febrile seizure subgroup with body temperature 37.5-39.0˚C at time of convulsion. Low serum vitamin B12 may reduce a child's threshold for seizure and may be a risk factor for febrile seizure. Low serum folic acid level may be predisposed to recurrent febrile seizure.

Optic neuritis as a presenting symptom of Mycoplasma pneumoniae infection.

A broad range of neurologic disorders has been described in children infected with Mycoplasma pneumoniae, of which encephalitis is among the most common. In contrast, the association between optic neuritis and Mycoplasma pneumoniae infection has been rarely described in children. We report a case of a 12-year-old girl who was seropositive for antibodies against Mycoplasma pneumoniae and presented with optic neuritis without respiratory symptoms or other neurologic findings.

Congenital segmental spinal muscular atrophy: a case report.

Spinal muscular atrophies are genetic disorders in which anterior horn cells in the spinal cord and motor nuclei of the brainstem are progressively lost. We present a patient with arthrogryposis due to congenital spinal muscular atrophy predominantly affecting the upper limbs. Spinal muscular atrophies with onset at birth may be a cause of arthrogryposis. Localized forms of neurogenic arthrogryposis have been divided into cervical and caudal forms. Our case is similar to the cases described by Hageman et al (J Neurol Neurosurg Psychiatry 1993;56:365-368): severe symmetric lower motor neuron deficit in the upper extremities at the time of birth, no history of injury to the cervical spinal cord or the brachial plexus during delivery, and severe muscle wasting suggesting chronic denervation in utero. Because there was improvement of our patient's situation, her disease was also possibly nonprogressive and sporadic. To our knowledge, this is the first reported case of a Turkish patient with congenital cervical spinal muscular atrophy. Congenital cervical spinal muscular atrophy affecting predominantly the upper limbs is a relatively rare form of motor neuron disease and should be considered in the differential diagnosis of infants with congenital contractures and severe muscle weakness by wasting mainly confined to the upper limbs.

Overview of pediatric peripheral facial nerve paralysis: analysis of 40 patients.

Peripheral facial nerve paralysis in children might be an alarming sign of serious disease such as malignancy, systemic disease, congenital anomalies, trauma, infection, middle ear surgery, and hypertension. The cases of 40 consecutive children and adolescents who were diagnosed with peripheral facial nerve paralysis at Baskent University Adana Hospital Pediatrics and Pediatric Neurology Unit between January 2010 and January 2013 were retrospectively evaluated. We determined that the most common cause was Bell palsy, followed by infection, tumor lesion, and suspected chemotherapy toxicity. We noted that younger patients had generally poorer outcome than older patients regardless of disease etiology. Peripheral facial nerve paralysis has been reported in many countries in America and Europe; however, knowledge about its clinical features, microbiology, neuroimaging, and treatment in Turkey is incomplete. The present study demonstrated that Bell palsy and infection were the most common etiologies of peripheral facial nerve paralysis.

Tic disorder probably associated with steroid responsive encephalopathy with autoimmune thyroiditis (SREAT).

Steroid responsive encephalopathy with autoimmune thyroiditis (SREAT), a rare disorder in individuals of all age groups, including children, is characterized by high titers of anti-thyroid peroxidase antibodies. The present report concerns a previously healthy 12-y-old boy who presented with motor tics. The patient underwent an extensive work-up to identify the underlying etiologies and risk factors predisposing him to tic disorder. Based on the clinical and laboratory results, a diagnosis of SREAT was made. Although some studies have reported associated behavioral and cognitive changes, myoclonus, seizures, pyramidal tract dysfunction, psychosis, and coma. The authors describe a case of tic disorder, probably due to SREAT, as well as its course of treatment.

Association between hypocapnia and febrile seizures.

The purpose of this study is to determine whether hyperthermia-induced hyperventilation with subsequent hypocapnia is relevant to febrile seizures in children. This is only the second study to measure pCO2 and pH values in children with febrile seizures. This prospective case-control study enrolled 18 children who presented with febrile seizures and 18 children who presented with a febrile illness without seizures. Venous blood gas analyses were measured both from the febrile seizure and control group. There was no significant difference in mean blood pH between the febrile seizure and control groups but blood pCO2 was significantly lower in the febrile seizure group. Patients with complex febrile seizures exhibited significantly lower pCO2 levels within 1 hour of seizure onset than patients with simplex febrile seizures. These data indicate that febrile seizures may be associated with hyperventilation and that the ensuing hypocapnia may contribute to the development of febrile seizures.

Cerebellar mutism caused by primary varicella infection in an immunocompetent child.

Varicella (chickenpox) is a common childhood infection caused by the varicella-zoster virus, which is often self-limiting and usually benign. Although uncommon, neurologic complications of varicella have been documented that include postinfectious cerebellar ataxia, meningoencephalitis, Reye syndrome, myelitis, optic neuritis, stroke, Guillain-Barré syndrome, seventh cranial nerve palsy, and Ramsay-Hunt syndrome. In this case study, the authors describe a 7-year-old girl who presented with varicella skin rash with unsteady gait and anarthria on day 2, and her condition was attributed to cerebellar mutism. To date, this complication has never been reported in a child with primary varicella infection. Therefore, this case study documents a rare but serious complication of childhood chickenpox.

Long-term accidental overdose of levetiracetam in an infant.

Levetiracetam is one of the new anticonvulsant drugs that has a high therapeutic index and potential antiepileptogenic effects. Herein, we report a patient with multidrug refractory epilepsy and Ohtahara syndrome who was accidentally administered 300 mg/kg/d for 35 days by her mother. To our knowledge, there are only a few cases of accidental overdose of levetiracetam in pediatric patients reported in the literature, and this case study is the first to report such a high and long-term dose in an infant who showed no adverse effects.

Efficacy of topical 0.05% cyclosporine treatment in children with severe vernal keratoconjunctivitis.

We aimed to determine the efficacy of topical cyclosporine in children with vernal keratoconjunctivitis refractory to topical mast cell stabilizer and antihistamine therapy. Thirty-one patients, 24 boys and 7 girls younger than 16 years of age, were included in the study. All patients were scored on a four-point scale from 0 to 3 for symptoms and signs. Each patient received topical cyclosporine 0.05% emulsion (Restasis, Allergan Inc., Irvine, CA, USA) four times daily in addition to preservative-free artificial tears and was followed for 6 months. The data was recorded before the initiation of treatment (day 0) and at the 1st, 3rd, and 6th months following treatment. After six months of treatment, severity of all symptoms and signs showed a statistically significant decrease (p<0.05). Patients did not report any serious adverse effects. Topical cyclosporine 0.05% emulsion treatment is a safe and effective treatment option for controlling the symptoms and signs of vernal keratoconjunctivitis in children.

Acute disseminated encephalomyelitis in children and adolescents: a single center experience.

BACKGROUND: Acute disseminated encephalomyelitis is an immune-mediated disease that produces multiple inflammatory lesions in the brain and spinal cord. METHODS: This study retrospectively evaluated 15 children with acute disseminated encephalomyelitis in children and adolescents from a single institution in Adana, Turkey. RESULTS: The patients presented in a seasonal distribution, with 73.3%: (11/15) presenting in winter or spring. The majority of patients (13/15, 86.7%) had a history of acute febrile illness 2 to 40 days before presentation, and five children had serologic evidence of specific triggers: mycoplasma (2 children), influenza-A (H1N1) (1 child), or Epstein-Barr virus. All children were treated with a standard protocol of 3 to 5 days of intravenous administration of methylprednisolone and intravenous immunoglobulin for patients who continued to deteriorate. Oseltamivir and clarithromycin were administered in patients with influenza-A (H1N1) and mycoplasma according to the serology. In 13 patients, all neurologic signs and symptoms resolved after treatment. Only one patient was left with severe neurologic sequelae and another child had recurrent attacks and was ultimately diagnosed with possible multiple sclerosis. CONCLUSIONS: The present series demonstrates that acute disseminated encephalomyelitis in children occurs predominantly in winter or spring and often follows an upper respiratory tract illness for those along the southern coast of Anatolia (Mediterranean region). Early treatment with immunomodulative agents is recommended and is likely to result in a favorable outcome or full recovery. This study also suggests benefit from antiviral and antibiotic treatment initiated as soon as possible after the onset of illness.

Central retinal artery occlusion in a 13-year-old child as a presenting sign of hyperhomocysteinemia together with high lipoprotein(a) level.

BACKGROUND: We describe a child with central retinal artery occlusion and hyperhomocysteinemia. METHODS: A 13-year-old girl developed sudden vision loss and was hospitalized for diagnosis and treatment. RESULTS: Her physical examination was normal except for her ophthalmologic examination. Her serum homocysteine level and lipoprotein(a) were elevated to 45.27 µmol/L and 61 mg/dL 0-29 mg/dL, respectively. A homozygous mutation was identified for methylenetetrahydrofolate reductase at position C677T. CONCLUSION: This report documents central retinal artery occlusion associated with the risk factors of hyperhomocysteinemia caused by methylenetetrahydrofolate reductase C677 T mutation and high lipoprotein(a) level in a child. Retinal artery occlusion is rare in children. This patient emphasizes the need for a systemic evaluation for hyperhomocysteinemia and lipoprotein(a) levels in children with retinal vascular occlusion of uncertain etiology.