Autoimmune Encephalitis with Autoantibodies to NMDAR1 following Herpes Encephalitis in Children and Adolescents.

Herpes simplex virus (HSV) type 1 is a frequent pathogen causing infectious encephalitis (HSVE). Early treatment with intravenous acyclovir has led to a significant decrease in mortality. However, especially in children, deterioration during or after HSVE may occur without any evidence of HSV reactivation or improvement following repeated antiviral therapy. Here, we report 15 patients (age range 3 months to 15 years) who suffered from autoimmune encephalitis with autoantibodies to NMDAR1 following Herpes encephalitis, presenting with movement abnormalities (young children) or neuropsychiatric symptoms (older children) as major complaints, respectively. The diagnosis was based on positive cerebrospinal fluid (CSF) and/or serum anti-NMDAR-antibodies with two children showing only positive CSF antibody findings. The time lag between first symptoms and diagnosis of autoimmune encephalitis was significantly longer than between first symptoms and diagnosis of HSVE (p <0.01). All patients improved during immunosuppressive treatment, during which plasmapheresis or rituximab treatments were applied in 11 patients, irrespective of their age. Despite immunotherapy, no patients relapsed with HSVE. Early diagnosis and treatment of autoimmune encephalitis after HSVE may be associated with a better outcome so that high clinical awareness and routine testing for anti-NMDAR-antibodies after HSVE seems advisable. If autoimmune encephalitis is suspected, antibody testing should also be performed on CSF if negative in serum.

Involuntary Movements in Cobalamin Deficiency.

OBJECTIVE: Neurologic problems are frequently described in infants with nutritional vitamin B12 (cobalamin) deficiency.Major neurologic consequences of infantile cobalamin deficiency include delays or regression in neurodevelopment and the occurrence of involuntary movements METHODS: We reviewed the medical records of infants with cobalamin deficiency and divided infants with involuntary movements into two groups as those, who developed involuntary movements during vitamin B12 supplementation (Group I) and those, who developed involuntary movements prior to supplementation therapy (Group II). RESULTS: We evaluated a total of 32 infants with the diagnosis of cobalamin deficiency. Involuntary movements were observed in 12 out of 32 infants. Group I and Group II consisted of 6 infants each. Of the infants with involuntary movements, five were exclusively breastfed until the time of diagnosis. The majority of infants in Group II had choreoathetoid movements; twitching and myoclonus in the face, tongue, and lips, and tremor in the upper extremities. These involuntary movements disappeared in one to three weeks after clonazepam therapy. In Group I; shaking movements, myoclonus, tremor, and twitching or protrusion were observed in patients' hands, feet, tongue, and lips on the 3rd-5th day of cobalamin supplementation. These involuntary movements disappeared within 5-12 days of clonazepam therapy. CONCLUSION: Recognition of nutritional cobalamin deficiency is important to perform a differential diagnosis of the condition from seizures or other causes of involuntary movements and avoid aggressive therapy and over treatment.

Effect of Chronic Valproic Acid Use on Anterior Cerebral Blood Flow of Children with Idiopathic Generalized Epilepsy.

OBJECTIVE: Cerebral blood flow has been blamed as a factor in the negative effect of antiepileptic drugs on neurocognition. This study aimed to investigate whether valproic acid (VPA), used for the treatment of idiopathic generalized epilepsy (IGE), causes a change in cerebral blood flow in children. METHODS: Included in this study were 33 children who were receiving VPA for IGE and 34 age-matched controls. Doppler and spectral measurements in common carotid artery (CCA), left and right internal CA (ICA) and external CA (ECA), anterior cerebral artery (ACA) and middle cerebral artery (MCA) were performed and the maximum velocity (VM), end-diastolic velocity (EDV), resistive index (RI), pulsatility index (PI) and flow rate (FR) were calculated. RESULTS: The mean age of drug and control groups were 9.33 plus or minus 2.11, and 9.74 plus or minus 2 years, respectively. Follow-up of patients was 17.7 plus or minus 3.2 months. The period of VPA treatment was 17.4 plus or minus 3.4 months. No statistically significant differences were found between control and VPA group for the VM, EDV, RI, PI, and FR values obtained from the bilateral ICA, ACA, and MCA. CONCLUSIONS: The results showed that VPA in therapeutic doses did not affect anterior cerebral blood flow. However according to result, it is still difficult to conclude that neurocognitive deterioration is not observed in patients receiving VPA.

The relationship between migraine and right-to-left shunt in children.

UNLABELLED: Migraine is the most common headache in childhood, and there are some reports that suggest the relationship between migraine and right-to-left shunt. The aim of this study was to evaluate the frequency of right-to-left shunt in children with migraine with aura and compare it with children with migraine without aura, and in healthy children. In a cross-sectional case-control study, we assessed 20 children with migraine with aura, 20 migraine without aura and 20 healthy age, and gender-matched control group. We determined the frequency of right-to-left shunt by transcranial doppler with contrast and transthoracic echocardiography without contrast. The dopplers and echocardiograms were performed blindly by the same examiners during headache-free periods. The presence of right-to-left shunt was found in 13/20 patients with migraine with aura compared with five of 20 migraine without aura and four of 20 control subjects. The frequency of right-to-left shunt in migraine with aura was statistically different from the other two groups (P < 0.005). There was no association between right-to-left shunt and frequency of attacks, duration and intensity of attacks, uni/bilateral occurence, familial occurrence, gender and age of patients. CONCLUSION: our findings suggest possible association of migraine with aura and right-to-left shunt. It seems that right-to-left shunt does not influence the clinical features of migraine.

Adverse effect of phenytoin on glucocorticoid replacement in a child with adrenal insufficiency.

Chronic administration of antiepileptic agents such as phenytoin can increase clearance rates of cortisol and synthetic glucocorticoids through hepatic microsomal enzyme induction. However, data concerning an adverse interaction between antiepileptic and steroid drugs are scarce. We herein report an adolescent boy with primary adrenal insufficiency that developed glucocorticoid deficiency after added phenytoin treatment. The patient had an increased requirement for hydrocortisone replacement, and two episodes of vomiting, hyponatremia and mild hypoglycemia. His ACTH levels were markedly elevated. Fifteen days after stopping phenytoin, his serum ACTH concentration returned to normal range. Even though the hydrocortisone dose was gradually decreased, hyponatremia and vomiting have not recurred. In conclusion, we suggest that drugs such as phenytoin affecting hepatic clearance of synthetic glucocorticoids and mineralocorticoids should not be preferred for therapy in patients with adrenal insufficiency. If their use is vital, one should be aware of increased replacement requirements for steroid drugs, and patients should be closely monitored.

Matching algorithm for improving ride-sharing by incorporating route splits and social factors.

Increasing traffic congestion and the advancements in technology have fostered the growth of alternative transportation modes such as dynamic ride-sharing. Smartphone technologies have enabled dynamic ride-sharing to thrive, as this type of transportation aims to establish ride matches between people with similar routes and schedules on short notice. Many automated matching methods are designed to improve system performance; such methods include minimizing process time, minimizing total system cost or maximizing total distance savings. However, the results may not provide the maximum benefits for the participants. This paper intends to develop an algorithm for optimizing matches when considering participants' gender, age, employment status and social tendencies. The proposed matching algorithm also splits unmatched parts of drivers' routes and creates new travel requests to find additional matches using these unmatched parts. Accordingly, this paper performs an extensive simulation study to assess the performance of the proposed algorithm. The simulation results indicate that route splits may increase the number of matches significantly when there is a shortage of drivers. Furthermore, the paper demonstrates the effects and potential benefits of utilizing a social compatibility score in the objective function.

A clinically isolated syndrome: a challenging entity: multiple sclerosis or collagen tissue disorders: clues for differentiation.

Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations of a number of diseases such as multiple sclerosis (MS) and collageneous tissue disorders. In the present study, particular systemic lupus erythematosus (SLE) and primary Sjogren syndrome (pSS) patients, who were followed up with the initial diagnosis of possible MS with no evidence of collagen tissue disorders for several years, are described. Five patients with the final diagnosis of SLE and five pSS patients are evaluated with their neurologic, systemic and radiologic findings.Over several years, all developed some systemic symptoms like arthritis, arthralgia, headache, dry mouth and eyes unexpected in MS. During the regular and close follow-up laboratory evaluations of vasculitic markers revealed positivity, leading to the final definite diagnosis of SLE or pSS. Patients with atypical neurological presentation of MS, a relapsing remitting clinical profile, or lack of response to the regular MS treatment should be evaluated for the presence of a connective tissue disease. Various laboratory tests, such as cerebrospinal fluid findings, autoantibodies profile, markers, cranial and spinal magnetic resonance imaging, can be helpful for the differential diagnosis. Lack of response to the regular multiple sclerosis treatment, even increasing rate of relapses can force the clinician for the differential diagnosis. In particular cases an accurate diagnosis can only be made after close follow-up.

Quantitative assessment of muscular stiffness in children with cerebral palsy using acoustic radiation force impulse (ARFI) ultrasound elastography.

PURPOSE: To evaluate the feasibility of quantitative analysis of muscle stiffness in the medial gastrocnemius muscle (GCM) by acoustic radiation force impulse (ARFI) ultrasound elastography in children with spastic cerebral palsy (CP). METHODS: Seventeen children with spastic CP and 25 healthy children participated in the study between the years 2016-2017. The medial GCM in the CP group was assessed using the Modified Ashworth Scale (MAS) by a physiatrist. ARFI was used to measure the shear-wave velocities (SWVs) of the medial GCM. The mean SWV value for each MAS score was calculated and used for statistics. RESULTS: The mean SWV values of the medial GCM in the CP and healthy groups were 3.17 ± 0.81 m/s (mean ± SD) and 1.45 ± 0.25 m/s (mean ± SD), respectively. The SWV of the medial GCM significantly increased in the CP patients when compared with controls (p < 0.001). In addition, the SWV values were correlated with the MAS scores (p < 0.001). The interobserver agreement expressed as the interclass correlation coefficient was 0.65 (95% CI 0.33-0.84, p < 0.001). CONCLUSIONS: ARFI imaging demonstrated a difference in muscle stiffness in the medial GCM between the CP and healthy groups. This method is a feasible imaging modality for the noninvasive assessment of contracting muscles in children with CP.

White matter alteration in a patient with Graves' disease.

A case of Graves' disease with white matter abnormalities is presented here. The diagnosis as Graves' disease was made when the patient was 5 years old, and a subtotal thyroidectomy was performed when she was 10. Her neurological symptoms began at age 19 with paresthesia of her legs and lower body. Cranial magnetic resonance imaging was normal; thoracic magnetic resonance imaging revealed demyelinating lesions. Intravenous pulse steroid therapy improved her symptoms. Ten months later she described dizziness, lower body paresthesia, and ataxia. Both her cranial and thoracic magnetic resonance imagings revealed demyelinating lesions. After pulse steroid therapy, glatiramer acetate therapy was initiated with diagnosis of an autoimmune multiphasic demyelinating syndrome. Five months later, she presented with right-sided mild optic neuritis followed by rapid spontaneous remission. Antithyroglobulin antibody levels remained normal; antithyroid peroxidase antibody level was high. This presents a rare case of Graves' disease associated with multiphasic demyelinating autoimmune syndrome.

Bilateral basal ganglia lesions after hypoglycemic coma in a 6-year-old child.

Imaging findings of brain damage due to neonatal hypoglycemia are known; however, the effect of childhood hypoglycemia on the brain has not been described well. The authors present the case of a 6-year-old girl who had seizures secondary to hypoglycemia followed up for 1 year as epilepsy. The patient had experienced a hypoglycemic coma attack about 1 year before. Brain magnetic resonance imaging showed atrophy of the cerebrum and cerebellum and bilateral symmetrically hyperintense lesions in the putamina. The patient was diagnosed with hypoglycemia due to hyperinsulinism.

[A herpes simplex virus encephalitis case with no clinical response to acyclovir treatment]. / Asiklovir tedavisine klinik yanit alinamayan bir herpes simpleks virus ensefaliti olgusu.

In spite of high rates of morbidity and mortality in herpes simplex virus (HSV) encephalitis, however, it is one of the exceptional viral infections with specific and effective therapy. In this report a HSV encephalitis case who was clinically unresponsive to acyclovir treatment, has been presented. An 11 months old girl patient has been brought to our clinic with the complaints of high fever and focal convulsions. Analysis of cerebrospinal fluid (CSF) revealed decreased glucose level and abundant red blood cells, despite it was not traumatic. The other CSF biochemical findings were found normal. Viral serology performed with CSF yielded negative result for HSV-1 IgG, positive result for HSV-2 IgG, and negative result for HSV-1/2 IgM, however, antibody index could not be estimated since it was not possible to obtain a simultaneous serum sample. Cranial magnetic resonance imaging (MRI) showed contrast material enhancement on bilateral temporal lobes. There was no growth in the CSF cultures. Acyclovir therapy (30mg/kg/day) was started with the prediagnosis of herpes encephalitis. In the third week of therapy CSF analysis was repeated because of the presence of partial paroxysmal attacts and absence of sufficient clinical improvement. In this CSF sample HSV-1 DNA was found positive by real-time polymerase chain reaction. Since CSF findings were still abnormal and the clinical picture worsened despite 21 days of therapy, the dose of acyclovir was increased to 60 mg/kg/day (3 weeks) with a possible drug resistance problem. Control brain MRI showed contrast enhancement on bilateral temporal lobes, with more intensivity in left, and encephalomalacia. Valproic acid and haloperidol were given to the patient for the treatment of permanent partial paroxysms and orofacial dyskinesis, developing in the follow-up period, respectively. After getting these complications under control, the patient was discharged and taken into follow-up. As a result, although it could not be possible to confirm the drug resistance by molecular methods, it was thought that this might be both a clinical and virological resistance phenomenon, because of the detection of HSV-DNA in the CSF sample during the period of severity of the illness.

Susac's Syndrome (Retinocochleocerebral Vasculopathy): Follow-up of a Pediatric Patient.

Susac's syndrome (SS) is a triad of encephalopathy, branch retinal artery occlusion (BRAO), and sensorineural hearing loss as a result of microvascular occlusions of the brain, retina, and inner ear. It is also a disorder of autoimmune endotheliopathy. SS usually affects young women between the age of 20 and 40 years. SS can be misdiagnosed as multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM) because of similar findings. A 15-year-old girl presented in June 2015 with vomiting and severe headache. Cerebral magnetic resonance imaging revealed multiple lesions in the corpus callosum. Cerebrospinal fluid findings gave normal results. The initial diagnosis was MS and steroid (1000 mg/day) was given. She started to describe hallucinations and became paraplegic. She then underwent plasmapheresis five times without response. Her electroencephalogram was diffusely slow with 2-3 Hz delta rhythm at the frontal regions. Audiological examination showed that she had sensorineural hearing loss in her left ear. Ophthalmologic evaluation revealed BRAO in both eyes. On the basis of these findings, she was diagnosed with SS and treated with intravenous immunoglobulin (IVIG) and aspirin. After monthly treatment with IVIG for 6 months, the patient has almost fully recovered. SS should be kept in mind in the differential diagnosis of MS and ADEM.

Nonconvulsive status epilepticus on electroencephalography in a case with subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis is a neurodegenerative disease with a poor prognosis. We report a case of a 5 1/2-year-old boy who had emotional lability, cognitive difficulties, and myoclonia after a mild closed head injury. The magnetic resonance image of the brain and computed tomographic scan of the head were normal. His electroencephalogram (EEG) showed continuous nonconvulsive status epilepticus activity, which could not be suppressed with intravenous diazepam. After treatment with phenytoin for 2 days, an EEG showed periodic high-amplitude sharp-and-slow-wave complexes, which were also not suppressed with intravenous diazepam. Since the patient had measles at 5 months of age, subacute sclerosing panencephalitis was considered, and the diagnosis was confirmed by the presence of measles antibodies in cerebrospinal fluid.

Subacute sclerosing panencephalitis: is there something different in the younger children?

Subacute sclerosing panencephalitis is a rare, slow viral infection caused by a defective measles virus. Although it is a rare disease, it is still important in developing countries. The onset is generally between the ages of 5-15 years. We reported the clinical and laboratory profile and nature of 9 patients under the age of 4 years with SSPE. Although it is known that a few patients with SSPE have an acute and rapidly fulminating course, in this study rate of progression was rapidly progressive in 6 patients and progressive in 3 of them on admission. Unfortunately, 4 of them were lost to follow up because of address and/or telephone number alterations. Although the number of patients in this study is not sufficient, we suggest that SSPE patients under the age of 4 years have a poor prognosis as a result of progressive or rapidly progressive course despite medical treatment.

Diagnostic criteria of pediatric migraine without aura.

The objectives of this study were to assess the validity of the International Classification of Headache Disorders-I (ICHD-I) and the International Headache Society-Revised (IHS-R) criteria and to evaluate the other headache features that are not included in these criteria for migraine without aura in the pediatric population. One hundred and thirty-two children who referred to our clinic with the complaint of chronic or recurrent headache were evaluated. Clinical diagnosis of the pediatric neurologist was used as the gold standard in evaluating the validity of ICHD-I and IHS-R criteria and the other headache features. After eliminating patients with other migraine types, secondary headache, and missing data, 92 patients were included in the study according to their records. Sixty-one children (66.3%) were diagnosed as migraine without aura. Using the clinical diagnosis as the gold standard, the specificity of ICHD-I criteria was detected as 93.5%, while the sensitivity was detected as 36.1%. IHS-R criteria had 90.3% specificity and 78.7% sensitivity. Relief of headache with sleeping or lying down in a dark, quiet room was found to be the highest specific and sensitive factor of the other headache features not included in these criteria. IHS-R criteria were found to be more valid in the diagnosis of migraine without aura than ICHD-I criteria. IHS-R criteria are recommended both in clinical practice and in the studies requiring migraine without aura case definitions in the pediatric population.

Heart rate variability and autonomic dysfunction in SSPE.

Autonomic nervous system involvement in subacute sclerosing panencephalitis was studied in 29 patients by analysis of heart rate variability and compared with a control group which consisted of 20 age- and sex-matched healthy subjects. Holter recordings for 24 hours were obtained, and all recordings were analyzed using time-domain parameters. The patients with subacute sclerosing panencephalitis were found to have significantly lower values of standard deviation of all normal sinus intervals and triangular index when compared with the control group. Of 23 patients who had regular follow-up, 15 died in a period ranging from 1 to 13 months. Twelve of these patients had heart rate variability parameters lower than normal, but no significant difference was observed between the heart rate variability values of patients who survived or died. Also, there was no association between brain magnetic resonance imaging findings and heart rate variability indices. It is concluded that patients with subacute sclerosing panencephalitis have autonomic dysfunction; and this was thought to be mainly due to central involvement.

A comparison of buccal midazolam and rectal diazepam for the acute treatment of seizures.

In this study, the authors aimed to evaluate buccal midazolam as a practical and safe alternative medication for children who suffer from seizures in the emergency setting and in home practice or anywhere. The effects and side effects of buccal midazolam and rectal diazepam were compared in the treatment of acute convulsions in 43 children, ranging in age from 2 months to 12 years who were seen at the emergency service of the children hospital. Midazolam was given on the even days of the month and diazepam was given on the odd days. In the midazolam group, the seizures of 18/23 (78%) patients terminated in 10 minutes; however 5/23 (22%) patients did not respond. In the diazepam group 17/20 (85%) patients responded in 10 minutes, but 3/20 (15%) did not respond. Midazolam was found to be as effective as diazepam and the difference was not statistically significant (p<0.05). Response periods of the 2 drugs showed no significant difference (p>0.05). The need for a second drug for seizures that did not stop with the first drug was equal, and the difference was not statistically significant (p>0.05). They did not observe any serious complications. In conclusion, buccal midazolam is safe and as effective as rectal diazepam for the treatment of seizures.

L-2-hydroxyglutaric aciduria: a report of 29 patients.

L-2-hydroxyglutaric aciduria (L2HGA) is a chronic slowly progressive neurodegenerative disease characterized mainly by psychomotor developmental delay and cerebellar dysfunction. We report the clinical, biochemical, and neuroimaging features of 29 patients from 22 families. The mean age at the time of diagnosis was 13.4 years (2.5-32 years). The mean follow-up period of patients was four years (1.5-16 years). The main clinical findings were mental retardation and cerebellar involvement with ataxic gait and intentional tremor. Additional findings were mental retardation, macrocephaly and seizures. Diagnosis was confirmed by increased urinary excretion of L-2-hydroxyglutaric acid in all patients and highly specific magnetic resonance imaging (MRI) pattern showing subcortical leukoencephalopathy with bilateral high signal intensity in dentate nuclei and putamens. During the follow-up period, all patients had a static encephalopathy course. The underlying metabolic defect and the possible role of L-2-hydroxyglutaric acid are studied in a subgroup of these families and under evaluation for publication.

Retrospective evaluation of interferon-beta treatment in subacute sclerosing panencephalitis.

BACKGROUND: Few effective treatment methods are available for subacute sclerosing panencephalitis (SSPE),an infection associated with the measles virus. Interferons have shown some benefit in previous studies and clinical practice. OBJECTIVE: The purpose of this study was to compare the efficacy of 2 different regimens of interferon-beta(IFN-beta) in the treatment of SSPE in pediatric patients. METHODS: We retrospectively compared the results obtained with 2 regimens of IFN-beta1a: 60 microg administered intramuscularly once weekly (IFN-beta 1/wk), or 22 microg administered subcutaneously 3 times per week (IFN-beta 3/wk). All patients also received oral inosiplex 50 to 100 mg/kg daily, a treatment known to have partial efficacy in SSPE. Patients who continued treatment for at least 3 months and had at least 1 year of follow-up data were evaluated. Clinical parameters included the Neurological Disability Index (NDI), a measurement of mental, motor, and sensory functions; disease stage; and mental status. Data obtained at 6 and 12 months were compared with those at the time of diagnosis, and the percent change from baseline was calculated. A satisfactory clinical response was defined as reduction or stabilization of the NDI or stage improvement at 6 or 12 months. RESULTS: Patients treated with IFN-beta 3/wk had increased survival time (P < 0.02) and higher clinical response rates compared with those treated with IFN-beta 1/wk (P < 0.05). When stage 2 and stage 3 patients were evaluated separately, survival was significantly longer (P = 0.007) and the rate of progression slower in both stage groups with IFN-beta 3/wk. CONCLUSION: The results obtained for this patient sample suggest that IFN-beta administered subcutaneously times per week combined with inosiplex may be an effective treatment option in SSPE. This treatment regimen warrants further study.

Combined treatment with subcutaneous interferon-alpha, oral isoprinosine, and lamivudine for subacute sclerosing panencephalitis.

We compared patients with subacute sclerosing panencephalitis who received treatment according to our protocol for at least 6 months (19 patients) with the patients who could not receive any treatment (13 patients). The treatment protocol consisted of oral isoprinosine (100 mg/kg/day), subcutaneous interferon alpha-2a (10 mU/m2/three times a week), and oral lamivudine (10 mg/kg/day). There were no statistical differences between the two groups according to Neurological Deficit Index, clinical stage, and average age on admission and also on the final evaluation after treatment. The mortality rates of both groups were similar: 3 (15.7%) for the treatment group and 6 (46%) for controls. The remission rates for the treatment and control groups were 7 of 19 (36.8%) and 0 of 13 (0%), respectively, and the difference was statistically significant (P = .036). The mean survival period of the treatment group was significantly longer than that of the control group (P = .01). In conclusion, this combination treatment protocol resulted in higher remission rates and longer survival periods when compared with controls, as well as a remission rate that was better than the spontaneous remission rate of 5%. For this reason, and as well as because interferon-alpha therapy has an easier route of application and a higher family compliance, we have considered this an alternative protocol for patients with subacute sclerosing panencephalitis.