Multiple encephalopathy syndrome: a case of a novel radiological subtype of acute encephalopathy in childhood.

INTRODUCTION: This report presents the case of a novel subtype of acute encephalopathy syndrome in childhood found in a patient with influenza type A infection; the patient exhibited evident magnetic resonance imaging (MRI) findings. CASE REPORT: A 4-year-old boy was transferred to our hospital for prolonged (lasting 60 min) status epilepticus with influenza encephalopathy. Mild brain hypothermia therapy was applied for 72 h, followed by targeted temperature management for 96 h with mechanical ventilation in the intensive care unit. Moreover, methylprednisolone pulse therapy and immunoglobulin therapy were administered. One month after the treatment, his physical status recovered such that he was able to run, take food orally, communicate verbally, and successfully return to kindergarten. Interestingly, serial MRI studies revealed findings that were compatible with 1) acute necrotizing encephalopathy (ANE), 2) mild encephalitis/encephalopathy with a reversible splenial lesion (MERS type II), 3) acute cerebellitis, and 4) acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) on days 2, 4, 7, and 16, respectively. CONCLUSIONS: To the best of our knowledge, these significant MRI findings associated with acute encephalopathy have never been reported. Thus, herein, we propose the new term radiological "multiple encephalopathy syndrome (MES)" based on our case of acute encephalopathy in childhood.

An infantile late-onset case Group of B Streptococcus meningitis diagnosed with a rapid latex kit.

Globally, vaccination has reduced the prevalence of meningitis caused by Streptococcus pneumoniae Neisseria meningitidis, and Haemophilus influenzae. However, neonatal Group B Streptococcus (GBS) meningitis continues to remain a problematic infection of the central nervous system. Here, we report a case of bacterial meningitis in a 34-day old male baby who presented with fever. A cerebrospinal fluid (CSF) test on the day of admission showed an increase in cell count with decreased glucose level. A rapid latex test of the CSF using a commercial kit diagnosed the causative pathogen as GBS. We administered the antibiotics ampicillin, cefotaxime, gentamicin and panipenem/betamipron to the patient for over 14 days. Partial seizures were frequently observed during the course and were well-controlled with midazolam and phenobarbital. Brain magnetic resonance imaging on day 17 showed subdural hygroma in the frontal region, and 99mTc ethyl-cysteinate dimer-single photon emission computed tomography confirmed a decreased cerebral blood flow predominantly in the left frontal region. After three years of follow-up, the condition of the patient improved without any neurological sequelae. Our report highlights that rapid identification of the causative organism is essential in infantile late-onset meningitis. In addition, we consider that the latex kit-based rapid testing of CSF is beneficial for identifying the causative agent of bacterial meningitis.

Immature ovarian teratoma with anti-NMDA-receptor encephalitis in a 13-year-old Japanese female patient.

We report a 13-year-old Japanese female with ovarian teratoma due to anti-NMDAR encephalitis. The patient was admitted with psychiatric symptoms, including memory impairment, insomnia, binge eating and mouth and hand twisting, associated with constipation. Serum alphafetoprotein and neopterin levels were elevated 102 ng/mL and 19 pmol/mL, respectively. Electroencephalography showed epileptic spikes in frontal and temporal regions. Cerebrospinal fluid (CSF) examination exhibited a pleocytosis. Thereafter, her consciousness level immediately worsened. Brain magnetic resonance imaging (MRI) noted hyper intense lesions in bilateral hippocampi, she was diagnosed with limbic encephalitis. Abdominal echogram showed a solid right ovarian tumour. and also confirmed as a tumour by abdominal MRI. The next day, right ovariectomy was performed and she treated two courses of methyl-prednisolone steroid pulse with high-dose immunoglobulins. Later days, CSF analysis revealed anti- NMDAR antibodies. Pathological diagnosis of the tumour was immature round shaped grade 3 ovarian teratoma, measuring 11cm. Two years follow up after admission, she completely recovered and no neurological sequelae.

Successful mild brain hypothermia therapy followed by targeted temperature management for pediatric hemorrhagic shock and encephalopathy syndrome.

OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is the most severe form of acute encephalopathy that progresses rapidly, often resulting in death or severe neurological sequelae. We report the case of a 4-year-old girl with HSES with shock and impaired consciousness. PATIENT AND METHODS: Blood test results showed hypercytokinemia, and the 4-year-old patient was immediately admitted to the intensive care unit. Within 4 h of symptom onset, she received mild brain hypothermia therapy with a target body temperature of 35°C. Methylprednisolone pulse, high dose immunoglobulin, and large doses of circulatory drugs were administered. RESULTS: After 72 h of brain hypothermia therapy, targeted temperature management with a target body temperature between 36°C and 37°C was continued for 96 h. The patient was diagnosed with HSES based on acute encephalopathy with shock, hypercytokinemia, low platelet count, coagulation disorder, renal damage, and intestinal bleeding. Magnetic resonance imaging results revealed no signs of any specific acute encephalopathy. She was discharged without neurological sequelae 28 days after symptom onset. CONCLUSIONS: Mild brain hypothermia therapy initiated in the early stages followed by targeted temperature management may be an effective way to improve neurological outcomes in children suffering from HSES.

A girl with acute encephalitis followed by acute cerebellitis/cerebellopathy.

OBJECTIVE: The purpose of this study is to bring attention to a case of acute encephalitis not concurrent with acute cerebellitis. CASE PRESENTATION: Five days after onset of common cold symptoms, a 17-months-old girl suffered convulsions, vomiting and respiratory arrest. On exam, she had pharyngeal inflammation, brisk deep tendon reflexes, respiratory acidosis, leukocytosis, negative rapid antigen tests, and segmental pneumonia. Brain CT and MRI/MRA were negative, and EEG was consistent with acute encephalitis. Following hypothermic therapy, methylprednisolone pulse therapy and cefotaxime, she recovered. Four days after discharge, she sustained limb and truncal ataxia associated with normal EEG, followed by bilateral intention tremor. Blood and CSF chemistry and cell counts were normal. Brain MRI revealed high intensity signals in the dentate nuclei and enhancement in the cerebellar white matter, suggestive of acute cerebellitis/cerebellopathy. SPECT imaging showed reduced blood flow in the cerebellum, right thalamus and brain stem. Following short-term administration of g-globulin and prednisolone, she regained her ability to sit and, eventually, to walk. Four months after initial presentation, her brain MRI was normal. No relapse has occurred in 5 years. CONCLUSIONS: The uncommon sequential development of acute encephalitis followed by acute cerebellitis suggests an immune-mediated cerebellar ataxia.

Long-term survival of a patient with acute neonatal-onset metabolic encephalopathy with carbamoyl phosphate synthetase 1 deficiency.

OBJECTIVE: Long-term survival of patients with neonatal-onset carbamoyl-phosphate synthetase 1 deficiency (CPS1D), an autosomal recessive disorder characterized by repeated, life-threatening hyperammonemia, is rare. We describe the diagnosis and clinical management of a teenager with neonatal-onset CPS1D who did not undergo therapeutic liver transplantation. CASE REPORT: Following emergent neonatal therapy, the patient was diagnosed with CPS1D based on clinical, radiological, biochemical and genetic analyses. Her clinical course, neurobehavioral development and therapeutic interventions are presented and discussed. RESULTS: Born from nonconsanguineous parents, the proband underwent phototherapy for neonatal jaundice, associated with acute encephalopathy, apnea and cerebral edema. Based on blood and urinary biochemical abnormalities, neonatal-onset CPS1D was diagnosed. Her hyperammonemia was corrected by hemodialysis, followed by sodium benzoate, L-arginine, levocarnitine and protein-free diet therapy. Because of a relapse and persistent neurobehavioral regression by age 1, a planned liver transplantation was cancelled. At age 10, sodium phenylbutyrate was substituted as ammonia scavenger. Genetic testing revealed compound heterozygote c.2359C>T (R787X) and c.236+6T>C variants of CPS1, confirming her diagnosis. Despite severe neurological sequelae, the patient is 16 and in stable condition. CONCLUSIONS: Our case suggests that early hemodialysis and pharmacologic interventions for acute neonatal hyperammonemia can improve the prognosis of patients with neonatal-onset CPS1D.

Sociological histories on epilepsy as "causes for disqualification" stipulated in the Japanese Road Traffic Act of 1960 and Revised Road Traffic Act of 2001.

In the wake of successive cases of fatal accidents caused by patients behind the wheel whose driving was likely to be hindered due to paroxysmal diseases, including epilepsy, there has been an outcry from victims demanding stricter criminal penalties against the perpetrators due to negligence. As a result of this action, a revised Road Traffic Act was put into effect in Japan on June 14, 2013. This act established new penal provisions against any person who provides false statements on his/her medical condition(s) when acquiring or renewing a driver's license. In this paper, the social circumstances will be introduced regarding road traffic in Japan when the Road Traffic Act, the origin of today's revised Road Traffic Act, was enacted in 1960. An overview of the reasons behind the enactment of the original act will be provided. Additionally, the handling of patients with "provisions for disqualification," whose driving is likely to be hindered due to paroxysmal diseases, including "epilepsy," will be reviewed. This handling attracted repeated controversy during the enactment of the original act and will also be reviewed. One significant change in wording from "absolute causes for disqualification" in the Road Traffic Act of 1960 to "relative causes for disqualification" in the Revised Road Traffic Act of 2001 also will be discussed from a medical sociology perspective. Finally, the social status and socio-economic position of drivers with paroxysmal diseases, as it pertains to influences on lawmakers, will be discussed.

Long-term survival of full trisomy 13 in a 14 year old male: a case report.

Long term survival for the cases of trisomy 13 into over a first decade is very rare. We reported here the case of a 14-year-old male karyotype with full type of trisomy 13. In this clinical phenomenon, the case had typical facial, finger and limb anomalies for trisomy 13. Arterial septal defect and patent ductus arteriosus were recognized using ultrasonography after birth. Major cerebral malformation such as holoprosencephaly or cerebellar hypoplasia were also not revealed. After 5 months of his age, artificial ventilation therapy for dyspnea associated with laryngomalacia was required. A tracheotomy was performed at 6 months of his age. After 12 years old, intractable partial epilepsy was recognized. For his partial seizures, a treatment with a combination of two anti-epileptic drugs, valproic acid and levetiracetam, were advised. Now he is alive for 14-years-old and he is the 4th longest surviving patient with full karyotype of trisomy 13.

Epilepsy-related automobile accidents in Japan: legal changes about a precedent and penal regulations.

In Japan, having epilepsy was defined as an absolute disqualification for driving license in the Road Traffic Act enacted in 1960. In view of subsequent changes in domestic road traffic conditions and advances in epilepsy treatment and owing to efforts by interested parties, the 2002 revision of the Road Traffic Act conditionally permitted epileptic patients to obtain a driver's license. However, as fatal traffic accidents associated with driving by epileptic patients continued thereafter, their legal responsibility for driving a car was extensively discussed in newspapers and other media as well as in the Diet. In June 2013, the Road Traffic Act was again revised to incorporate punitive clauses applicable to those with difficulty in driving (not limited to epilepsy only but including various diseases and conditions) who falsely claimed that they had no driving difficulty in the procedure for obtaining or renewing their driver's license. With this revision marking a turning point, the Act on Punishment for Acts That Cause Death or Injury to Others by Driving a Car was enforced as a new statute in May 2014. This paper presents five cases of traffic accidents involved with epileptic patients to explain the impact of these accidents on the 2013 legal revision and a subsequent trend of toughening of legal penalties.

Drop episodes improved after tracheotomy: a case of Coffin-Lowry syndrome associated with obstructive sleep apnea syndrome.

Some cases of Coffin-Lowry syndrome recognized episodic drops and it tended to be intractable for medical treatment. We reported here a patient with the Coffin-Lowry syndrome associated with obstructive sleep apnea syndrome (OSAS). The patient had epileptic seizures and drop attacks only during night-time and it was not recognized during the daytime. His sleep-induced electroencephalogram was normal. At 12-years old of his age, his OSAS was worse, so we performed a tracheotomy. Notably after the operation, his epileptic episodes were disappeared.

Del(18)(q12.2q21.1) syndrome: a case report and clinical review of the literature.

The terminal deletion of the long arm of chromosome 18 is relatively common among cytogenetic abnormalities, which occur incidentally in approximately 1 in 40,000 live births. Proximal interstitial deletions of the long arm of chromosome 18 are less frequent. The critical region on chromosome 18 of this syndrome is del(18)(q12.2q21.1) and has recently been recognized as a new clinical entity. We describe a 8-year-old boy with developmental delay, obesity, and epilepsy, with characteristic facial anomalies in whom G-banding chromosome analysis revealed a unique karyotype of 46, XY, del(18)(q12.2q21.1). The patient was diagnosed with interstitial deletion chromosome 18q-syndrome. He received weight control therapy from a medical dietitian. For his epilepsy, he was administered oral carbamazepine at 4 mg/kg/day. At age six, he entered a special needs elementary school. After entering school, he often showed hyperkinesis, and was diagnosed with attention deficit hyperactivity disorder with mild mental retardation. Because patients with only del(18)(q12.2q21.1) have no serious associated malformations, physicians should be aware that even adult patients may have 18q-syndrome. Therefore, if epilepsy occurs in patients with minor facial anomalies, psychomotor retardation, obesity, and the possibility of 18q-syndrome with del(18)(q12.2q21.1) should be kept in mind, and chromosome testing should be performed.

Treatment with mild brain hypothermia for cardiopulmonary resuscitation after myoclonic seizures in infant with robertsonian type of trisomy 13.

Congenital chromosomal abnormality with trisomy 13 is known to be associated with poor life prognosis and lethal. Therefore, physician advice the patients be kept in intensive treatment with resuscitation and state of the art intensive care when sudden change in the general condition with this trisomy is observed. We report herein, the treatment with mild brain hypothermia therapy for cardiopulmonary resuscitation after myoclonic seizures in infant with Robertsonian type of trisomy 13 in intensive care unit. Our study indicated that brain hypothermia therapy and steroid pulse therapy on an infant who was believed to have post-resuscitation hypoxic encephalopathy was highly effective as the patient's general condition recovered to the original state after four months.

Acute encephalopathy associated with hemolytic uremic syndrome caused by Escherichia coli O157: H7 and rotavirus infection.

We reported a case of a 22-months child with hemolytic uremic syndrome associated with encephalopathy. As the cause of this case, the involvements of verotoxin 1 and 2 caused by O157: the H7 strain of the enterohemorrhagic Escherichia coli and rotavirus were presumed. We administered brain hypothermic therapy and steroid pulse therapy in the intensive care unit, but we were not able to save his life and the child died on the 6th day from the onset.

Serial EEG study in a girl with Landau-Kleffner syndrome associated with continuous spikes and waves during slow sleep.

Landau-Kleffner syndrome (LKS) is rare epileptic encephalopathy in childhood, characterized by both acquired epileptic aphasia and abnormal epileptiform discharges in electroencephalogram (EEG). We herein report a serial EEG study in LKS. A 22-month old girl was referred to our hospital because of frequently partial seizures in her left upper limb. On EEG performed and multiforcal spikes were recognized. Oral treatment of carbamazepine was started but her seizures were not controlled. Her language ability did not progress after 2 years of her age. At age 4 years, carbamazepine was switched to valproic acid, leading to reduction in the frequency of seizure episodes. She was able to speak two-word sentences at 4 years of age, but her word output gradually decreased. At 5 years of age, addition of zonisamide further reduced the frequency of seizure episodes, but failed to achieve complete control of seizures. She increasingly asked for questions to be repeated. Auditory brainstem response testing performed at the department of otolaryngology revealed normal hearing ability. She was diagnosed as having intellectual deficits with an intelligence quotient (IQ) of 61 at 7 years of age. The EEG at 8 years of age showed continuous spikes and waves during slow sleep (CSWS), leading to a diagnosis of LKS. After age 11 years, the CSWS on EEG improved without requiring a change in antiepileptic drugs (AEDs). Treatment with the oral AEDs was discontinued at 13 years of her age. Her IQ at 13 years of age was in the low 70s.

An infant with steroid-refractory cytomegalovirus-associated ADEM who responded to immunoglobulin therapy.

Acute disseminated encephalomyelitis (ADEM) develops via an immunological mechanism. We encountered a 10-month-old infant with a rare pathogenesis of cytomegalovirus (CMV)-related ADEM. The patients complaints were; protracted fever; consciousness disorder; and affected cervical stability. Cerebral magnetic resonance imaging (MRI) 9 days after onset, revealed a disseminated lesion, suggesting ADEM. Pulse therapy with methylprednisolone at 30 mg/kg was performed for 3 days. However, its clinical efficacy was not marked. Therapy with immunoglobulin (IVIg) at 400 mg/kg/day was started 15 days after onset, and continued for 5 days. This markedly improved the consciousness level and muscle strength, and the infant was discharged without neurological sequelae. ADEM showed a monophasic course, and the infant's subsequent growth has been favorable. Altough the number of case reports is small, massive-IVIg therapy should be considered in patients with steroid-refractory ADEM, as demonstrated in this case study.

Brain hypothermia therapy for status epilepticus in childhood.

OBJECTIVE: At the Dokkyo Medical University Hospital, we introduced a brain hypothermia therapy protocol for treating childhood status epilepticus and acute encephalitis/encephalopathy in 2004. PATIENTS AND METHODS: This protocol focuses on infants with a minimum age of six months or 7.5 kg in weight. Applicable diseases include acute encephalitis/encephalopathy occurring from status epilepticus or seizures lasting for 30 minutes or longer, in cases such as near drowning, hypoxic-ischemic encephalopathy, post-resuscitation encephalopathy, cardio-respiratory arrest, severe head injury, or other diagnoses in which the pediatric neurologist recognizes the possibility of neurological complications. Brain hypothermia therapy is managed within the intensive care unit (ICU). RESULTS: The target body temperature is a bladder or rectum temperature of 34.0 to 35.0 degrees. This body temperature is reduced to the target temperature within six hours of the seizures. Hypothermia is maintained for 48 hours and concomitant steroid pulse therapy may be used at appropriate times. Sodium thiopental is used to sedate and rewarming is carried out at 0.5 degrees per 12 hours. Osmotic diuretics, muscle relaxants and circulatory antagonists may be concomitantly used at appropriate times. CONCLUSIONS: This paper reviews the brain hypothermia therapy protocol.

Partial epilepsy and developmental delay in infant with ring chromosome 14.

Ring chromosome 14 (r14) is clinically characterized by early-onset epilepsy, mental retardation, delayed speech, microcephaly, extremely mild facial dysmorphisms and ophthalmologic abnormalities. We report a case presenting with partial seizures and delayed development in infancy in which r14 was diagnosed based on chromosomal analysis. The patient was a girl with a normal family and delivery history. Afebrile generalized convulsions developed at age 9 months, and phenobarbital was started, but was changed to zonisamide due to impaired liver function. Chromosome analysis led to a diagnosis of 46, XX, r(14) (p11.2q32.3). At age 5 years, while under treatment with zonisamide and clobazam, epilepsy was characterized by multiple daily episodes of complex partial seizures. Although there are no consistent brain MRI or electroencephalogram findings, experienced pediatric neurologists can make a diagnosis based on facial dysmorphisms. When refractory epilepsy is encountered in infancy with developmental delay of unknown cause, chromosome analysis should be performed.