Importance Children and youths who are prescribed antipsychotic medications have multiple, potentially fatal, dose-related cardiovascular, metabolic, and other adverse events, but whether or not these medications are associated with an increased risk of death is unknown. Objective To compare the risk of unexpected death among children and youths who are beginning treatment with antipsychotic or control medications. Design, Setting, and Participants This retrospective cohort study was conducted from 1999 through 2014 and included Medicaid enrollees aged 5 to 24 years in Tennessee who had no diagnosis of severe somatic illness, schizophrenia or related psychoses, or Tourette syndrome or chronic tic disorder. Data analysis was performed from January 1, 2017, to August 15, 2018. Exposures Current, new antipsychotic medication use at doses higher than 50 mg (higher-dose group) or 50 mg or lower chlorpromazine equivalents (lower-dose group) as well as control medications (ie, attention-deficit/hyperactivity disorder medications, antidepressants, or mood stabilizers) (control group). Main Outcomes and Measures Deaths during study follow-up while out of hospital or within 7 days after hospital admission, classified as either deaths due to injury or suicide or unexpected deaths. Secondary outcomes were unexpected deaths not due to overdose and death due to cardiovascular or metabolic causes. Results This study included 189 361 children and youths in the control group (mean [SD] age, 12.0 [5.1] years; 43.4% female), 28 377 in the lower-dose group (mean [SD] age, 11.7 [4.4] years; 32.3% female), and 30 120 in the higher-dose group (mean [SD] age, 14.5 [4.8] years; 39.2% female). The unadjusted incidence of death in the higher-dose group was 146.2 per 100 000 person-years (40 deaths per 27 354 person-years), which was significantly greater than that in the control group (54.5 per 100 000 population; 67 deaths per 123 005 person-years) (P  Conclusions and Relevance The findings suggest that antipsychotic use is associated with increased risk of unexpected death and appear to reinforce recommendations for careful prescribing and monitoring of antipsychotic treatment for children and youths and to underscore the need for larger antipsychotic treatment safety studies in this population.

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Association of Antipsychotic Treatment With Risk of Unexpected Death Among Children and Youths.

The Brain’s Heart – Therapeutic Opportunities for Patent Foramen Ovale (PFO) and Neurovascular Disease

Environmental, dietary and case-control study of Nodding Syndrome in Uganda: A post-measles brain disorder triggered by malnutrition?

Subacute sclerosing panencephalitis is a progressive neurodegenerative disease. It usually occurs 7–10 years after measles infection. The clinical course is characterized by progressive cognitive decline and behavior changes followed by focal or generalized seizures as well as myoclonus, ataxia, visual disturbance, and later vegetative state, eventually leading to death. It is diagnosed on the basis of Dyken’s criteria. There is no known cure for subacute sclerosing panencephalitis to date, but it is preventable by ensuring that an effective vaccine program for measles is made compulsory for all children younger than 5 years in endemic countries.

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Subacute sclerosing panencephalitis - current perspectives.

International Headache Society published the International Classification of Headache Disorders 2nd Edition (ICHD‐II) in 2004. In response to this development, the “Clinical Practice Guideline for Chronic Headache” was compiled in Japan by the Study Group for Chronic Headache Clinical Practice Guideline Development. In 2006, the book entitled “The Clinical Practice Guideline for Chronic Headache (edited by Japanese Headache Society)” was published as the first edition. As triptans have become widely used, clinical practice for chronic headache has also been changed in Japan and there was a need to revise the first edition. Essentially based on the first edition, the new guideline has added the latest information and presented the concept of international standards of chronic headache care. This guideline included eight chapters and appendix: I. headache: general considerations, II. migraine, III. tension‐type headache, IV. trigeminal autonomic cephalalgias, V. other primary headache disorders, VI. medication‐overuse headache, VII. headaches in children, and VIII. genetics. We have published the second version in Japanese in 2013, but 1 month after we published the original guideline, the International Classification of Headache Disorders 3rd Edition beta version (ICHD‐3beta) was published. We changed this guideline to the new version in English based on ICHD‐3beta. This guideline is the final product of the Committee's efforts in 2015, which was opened in the home page of the Japanese Headache Society. This manuscript was written to show the main part of this guideline as Recommendation of each CQ. Among 121 CQs, only five CQ was selected to present full sentences including not only Recommendation but also other parts.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ncn3.12322

Clinical practice guideline for chronic headache 2013

SUMMARY Introduction L-2-Hydroxyglutaric aciduria (L-2-HGA) is an autosomal recessive neurometabolic disease with a slowly progressive course and characterized by increased levels of hydroxyglutaric acid in urine, cerebrospinal fluid and plasma. In this condition clinical features mainly consist of mental deterioration, ataxia and motor deficits. Case Outline The patient is a 16-year-old girl, the first and only child of healthy, non-consanguineous parents of Serbian origin. At the age of 4 years her walk became unsteady and ataxic. Other signs of cerebellar involvement were soon observed. Head circumference was above two standard deviations (55 cm). Mild mental retardation was revealed by formal intelligence testing (IQ 60). MR examination of the brain showed confluent subcortical white matter lesions spread centripetally, and atrophy of the cerebellar vermis with involvement of dentate nuclei, without deep white matter abnormalities. Laboratory investigation revealed increased amounts and a very large peak of HGA in urine and plasma. Enantiomeric analysis confirmed the L-configuration (>90%) establishing the diagnosis of L-2-HGA. The first epileptic seizure, partial with secondary generalization, occurred at age of 8 years. Favorable seizure control was achieved. A slow progression of neurological impairment was noted. Therapeutic trials with oral coenzyme Q10 and with oral riboflavin showed no biochemical and clinical effects. Recently, the diagnosis was proven by the presence of a mutation in the L-2-HGA gene. Conclusion To our knowledge, this is the first report of L-2-HGA in Serbia. L-2-HGA must be considered in the differential diagnosis based on specific findings in cranial MRI.

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L-2-Hydroxyglutaric aciduria: a case report.

Introduction. Subacute sclerosing panencephalitis (SSPE) is a rare,
 progressive, fatal neurodegenerative disease of childhood and early
 adolescence caused by defective measles virus. The initial symptoms of SSPE
 usually involve regression in cognitive functioning and behavior or recurrent
 myoclonic jerks. Seizures revealing SSPE and epilepsy during the clinical
 course can occur. Objective. The aim of the study was to analyze clinical and
 EEG characteristics of both initially occurred seizures and epilepsy which
 developed in the course of the disease. Methods. Retrospective study was
 carried out on 19 children (14 boys, 5 girls) with SSPE diagnosed and treated
 at our Clinic from 1995 to 2010. Seizures revealed SSPE in our patients aged
 from 6.5 to 11.5 years (mean 8.6 years). Results. SSPE onset ranged from 4.5
 to 16.5 years (mean 10.05). Complete vaccination was performed in nine
 patients. Cognitive and behavioral decline was preceeded by 6-18 months in
 two children with intractable focal motor seizures with secondary
 generalization, one child with complex partial seizures and one with atypical
 absences. During the clinical course of the disease epilepsy developed in 10
 (52.6%) cases, including four patients with seizures as the initial SSPE
 sign. It occurred mainly in the first year, while in three cases seizures
 appeared between 1 and 5 years of the disease evolution. Myoclonus was
 present independently from seizures. No significant inter-group differences
 were found relating to the type of SSPE progression and history of epilepsy.
 The only child with fulminant SSPE presented with initial seizures. Favorable
 seizure control was achieved in 60.0% patients. Intractable epilepsy
 developed in four patients. Conclusion. Atypical SSPE presentation can
 include mainly focal intractable seizures. Epilepsy developed during clinical
 course in 52.6% cases. No significant influence was found of the history of
 epilepsy on the type of SSPE progression.

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Epilepsy in children with subacute sclerosing panencephalitis.

Introduction. Juvenile myoclonic epilepsy is considered to be a chronic
 disease requiring lifelong antiepileptic treatment. The aim of this study was
 both to identify factors predicting the kind of seizure control and to
 investigate the outcome in patients after therapy withdrawal. Material and
 Methods. The study included 87 patients (49 female, 38 male), aged from 17.5
 to 43.5 years, referred to our Department between 1987 and 2008, with the
 seizure onset at the age of 14.3+2.9, and followed up for 13.3+5.8 years on
 average (from 5 to 23 years). Results. Sixty seven (77.0%) patients were
 fully controlled; whereas 13.8% had persistent seizures and 9.2% showed
 pseudoresistance. The combination of three seizure types and focal
 electroencephalogram features were independent factors of poor seizure
 control. Therapy was discontinued in 34 patients either by the treating
 physician (in 21 patients) or by the patients themselves (in 13 cases). In 18
 subjects, all seizure types relapsed after 1.1 year on average (from 7 days
 to 4 years) and therapy was resumed in them. All patients but three (10/13),
 who stopped the treatment themselves, experienced recurrences. Seizure
 freedom off drugs was recorded in 10.3% patients. Nonintrusive myoclonic
 seizures recurred in 0.5-3 years as their only seizure type in four patients,
 but without reintroducing medication in three patients. Conclusion
 Combination of seizure types and focal electroencephalogram features are
 significant factors of pharmacoresistancy. Continuous pharmacotherapy is
 required in majority of patients, although about 10% of them appear to have
 permanent remission without therapy in adolescence.

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Terminal remission is possible in some patients with juvenile myoclonic epilepsy without therapy.

Introduction. It is largely known that some antipsychotic agents could have
 proconvulsive and proepileptogenic effects in some patients and could induce
 EEG abnormalities as well. However, the association of status epilepticus
 with certain antipsychotic drugs has been very rarely reported. Case Report.
 A case of an 18-year-old adolescent girl, with chlorpromazine therapy started
 for anxiety-phobic disorder was reported. Her personal history disclosed
 delayed psychomotor development. Shortly after the introduction of the
 neuroleptic chlorpromazine therapy in minimal daily dose (37.5 mg), she
 developed myoclonic status epilepticus, confirmed by the EEG records.
 Frequent, symmetrical bilateral myoclonic jerks and altered behavior were
 associated with bilateral epileptiform discharges of polyspikes and
 spike-wave complexes. This epileptic event lasted 3.5 hours and it was
 stopped by the parenteral administration of valproate and lorazepam; she was
 EEG monitored until stable remission. Status epilepticus as initial epileptic
 event induced by neuroleptic agent was not previously reported in our
 national literature. Conclusion. Introduction of chlorpromazine to a patient
 without history of seizures is associated with the evolution of an epileptic
 activity, including the occurrence of status epilepticus. Clinical evaluation
 of the risk factors possibly related to chlorpromazine-induced seizure is
 recommended in individual patients before administering this drug.

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[Chlorpromazine-induced status epilepticus: a case report].

To assess the incidence of children with various types of migraine, an investigation was carried out from 1988 to 2008, on 30636 children (50.38% male, 49.62% female), in nine towns of the north province of Serbia. Migraine was reported in 8.63% children aged 3 to 17 (8.0% male, 9.6% female) as well as in 3.87% children aged 3-7 (4.2% boys, 3.57% girls). The proportion of children with either migraine or non-migraine headaches increased with their age, from 2.65% to 11.72% in boys, and from 2.71% to 15.86% in girls. Such increasing trend was also found for migraine with aura (from 1.8% to 32.7%). Children with migraine with aura showed their pick at the age of 9, while other migraine syndromes had the most frequent appearance at the age of 5 years. Migraine with aura accounted for 25.55%, migraine without aura for 67.21% and other migraine syndromes for 7.23% of investigated subjects with migraine. The average age of the migraine diagnosis was 5 years 1.8 months, while it was 4 years 11.4 months for migraine with aura, 5 years 7.2 months for migraine without aura and 3 years 7.2 months for other migraine syndromes. Migraine is much more frequent in second born children and in these from incomplete families. Migraine with aura appeared mostly in children coming from family with median socioeconomic welfare, while poor family welfare was predominant in children with migraine without aura. The length of breast-feeding influenced the appearance of the migraine in general, showing reciprocal influence of the length of breast-feeding on the appearance of migraine. Migraine was more often found (39.4%) among children who earlier joined nursery schools on a whole-day stay basis. Children with migraine have been diagnosed and treated by neuropaediatricians or neurologists in 55.4% cases (70.0% migraine with aura, 42.7% migraine without aura and 92.4% children with other migraine syndromes).

Nebojša J Jović

Papers

L-2-Hydroxyglutaric aciduria: a case report.

Epilepsy in children with subacute sclerosing panencephalitis.

Terminal remission is possible in some patients with juvenile myoclonic epilepsy without therapy.

[Chlorpromazine-induced status epilepticus: a case report].

Migraine in children-migraine syndrome in children of Vojvodina.