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.

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.

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.

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.

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.

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.

Lack of association of the CD14/C -- 159T polymorphism with susceptibility and progression parameters in Turkish multiple sclerosis patients.

Soluble (s) CD14, being a receptor for lipopolysaccharides (LPSs) may inhibit LPS-triggered apoptosis and T lymphocyte proliferation. C to T exchange at position -159 in the promoter region of the CD14 gene might lead to higher sCD14 levels. Limited number of groups have studied whether these polymorphisms might influence the development of organ specific autoimmunity and whether higher CD14 levels are associated with increased levels of cytokines trigerring inflammatory processes. However their data contradict each other. In this study serum levels of sCD14 based on ELISA were measured in 77 treatment-naive patients and in 67 healthy controls. As the C-159T proximal promoter region regulates sCD14 levels, we investigated whether C-159T polymorphism is related to progression index in 250 MS patients vs. 183 healthy controls. CD14 polymorphism frequency between the healthy controls and the MS patients were not significantly different. While TT genotype of MS patients demonstrated significantly lower sCD14 levels compared to CC genotype; this difference was not reflected on the disease progression index. Our study that extends the prior data of previous studies reflects that sCD14 do not appear to be a solely prominent element of innate immunity in MS.

Charles Bonnet syndrome after herpes simplex encephalitis.

Visual impairment associated with Charles Bonnet syndrome is rarely reported in childhood. We describe a child who presented with visual hallucinations and postinfectious bilateral retrobulbar optic neuritis. The patient had undergone acyclovir therapy for 3 weeks because of herpes encephalitis. Four days after therapy was completed, he experienced visual impairment in both eyes. He manifested a bilateral decrease in visual acuity, with normal funduscopic findings. The patient experienced visual hallucinations for about 1 week, and then experienced total loss of vision. During his hallucinations, the patient did not exhibit behavioral changes or cognitive impairment. The visual hallucinations included unfamiliar children hiding under his bed, and he spoke to someone whom he did not know. Magnetic resonance imaging indicated bilateral optic nerve hyperintensity on T(2)-weighted and contrast-enhanced images. The patient received corticosteroid therapy for his retrobulbar optic neuritis, and his vision returned to normal after 1 month. Although rare, visual impairment can be associated with complex visual hallucinations indicative of Charles Bonnet syndrome.

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.

Propriospinal myoclonus in a child.

A 6-year-old girl was experiencing repetitive involuntary and massive jerks immediately involving limbs and trunk. The first motor events appeared approximately at 1 year old and only 5 months after a back trauma. Myoclonus became progressively more frequent and more violent, causing episodes of falls. Neurological examination showed jerks characterized by upper limb abduction, lower limb abduction, and head-body hyperextension. Apart from these motor events, the neurological examination was normal. The results of vitamin B(12) and folate, antinuclear antibody, anti-DNA, anti-Tiroglobulin, anti-thyroid peroxidase antibody, lupus anticoagulant, anti-cardiolipin antibody, rheumatoid factor, and C3 and C4 were unexceptional. Electroencephalography and brain and spinal magnetic resonance imaging were unremarkable. Electromyographic records with surface electrodes showed that duration of myoclonic jerks was ranging from 100 to 300 ms. We thought she had propriospinal myoclonus because of presence of the spreading through the shoulder, upper limbs, and lower limbs in addition to thoracolumbar paraspinal muscles.

Serum and cerebrospinal fluid cytokine concentrations in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disease due to persistent measles virus infection. Its immunopathogenesis is unknown. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-6, IL-10 and IL-4 concentrations were measured in cerebrospinal fluid (CSF) and serum samples from 30 SSPE patients and 19 control subjects by cytometric bead array. CSF and serum IFN-gamma, IL-12 and IL-18 levels were measured in 18 SSPE patients by ELISA. Serum IL-4 and IL-10 (p<0.001), CSF IL-4 (p<0.001) and IL-6 (p=0.049) concentrations were lower, and serum IL-2 concentrations, higher (p=0.001) in SSPE patients. Serum TNF-alpha and IL-6, CSF TNF-alpha, IL-10, and IL-2 concentrations were not different between SSPE and control groups. Serum IFN-gamma levels were higher in stage I and II than stage III patients (p<0.05), whereas there was no difference between stages in terms of other cytokines. The levels of Th2-type cytokines: IL-4, IL-6 and IL-10 were suppressed in our SSPE cases. This finding, along with relatively elevated IFN-gamma and IL-2 levels, may suggest more active effector T cells compared to regulatory T cells (Treg), especially induced Treg, in early disease. High serum IL-2 concentrations might indicate peripheral Th1 activation. Discrepancies between various reports in the literature should be examined in view of the ages, stage and treatments of the patients studied. The interplay of various cytokines or cellular systems which may vary over time and between patients. Studies of treatment measures favoring the preservation of the early inflammatory response may be of interest in SSPE.

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.

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.

Carbamazepine poisoning managed with haemodialysis and haemoperfusion in three adolescents.

Carbamazepine is a widely used antiepileptic agent. Accidental or suicidal overdose in children is not uncommon. Acute toxicity is associated with seizures, coma, arrhythmias and death in severe cases. Here we report three adolescents with carbamzepine overdose, two managed with standard low-flux haemodialysis and one with charcoal haemoperfusion. Our report emphasizes that haemodialysis might be a cheaper and easier alternative for carbamazepine overdose in milder cases, with fewer side-effects than haemoperfusion.

[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.

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.