A novel rearrangement of occludin causes brain calcification and renal dysfunction.

Pediatric intracranial calcification may be caused by inherited or acquired factors. We describe the identification of a novel rearrangement in which a downstream pseudogene translocates into exon 9 of OCLN, resulting in band-like brain calcification and advanced chronic kidney disease in early childhood. SNP genotyping and read-depth variation from whole exome sequencing initially pointed to a mutation in the OCLN gene. The high degree of identity between OCLN and two pseudogenes required a combination of multiplex ligation-dependent probe amplification, PCR, and Sanger sequencing to identify the genomic rearrangement that was the underlying genetic cause of the disease. Mutations in exon 3, or at the 5-6 intron splice site, of OCLN have been reported to cause brain calcification and polymicrogyria with no evidence of extra-cranial phenotypes. Of the OCLN splice variants described, all make use of exon 9, while OCLN variants that use exons 3, 5, and 6 are tissue specific. The genetic rearrangement we identified in exon 9 provides a plausible explanation for the expanded clinical phenotype observed in our individuals. Furthermore, the lack of polymicrogyria associated with the rearrangement of OCLN in our patients extends the range of cranial defects that can be observed due to OCLN mutations.

Is temperature regulation different in children susceptible to febrile seizures?

OBJECTIVE: To examine the relationship between the presence and magnitude of fever and susceptibility to febrile seizures, defined as a known family history of febrile seizures. METHODS: Reanalysis of a case-control study dataset (Am J Dis Child. 1993; 147: 35-39). The magnitude of presenting fever was examined between the incident febrile seizure group (N = 75) and febrile control group (N = 150) for a family history of febrile seizures. The presence of fever was examined between the febrile control group (N = 150) and the afebrile control group (N = 150) for a family history of febrile seizures. RESULTS: Children with incident febrile seizures had a higher temperature in the emergency department than febrile controls (39.3 degrees C vs 39.0 degrees C, p = .004). Febrile control children with a known family history of febrile seizures had higher temperatures than those without a known family history (39.5 degrees C vs 38.9 degrees C, p = .04). A model of fever magnitude within the febrile group (seizures and controls) suggested that most of this relationship was on the basis of family history of febrile seizures rather than seizure or control status, with a possibility of interaction. Within the control children (febrile and afebrile), a known family history of febrile seizures was associated with fever (OR 3.4, 95% CI: 1.1,10.7). CONCLUSIONS: Children susceptible to febrile seizures through a known family history of febrile seizures appear more likely to present to emergency departments with fever, and when compared to their febrile counterparts, a fever of higher magnitude. This data supports Rantala's assertion "It may be that regulation of temperature is different in children susceptible to febrile seizures".

Caffeine as an adjuvant to ibuprofen in treating childhood headaches.

In adults, caffeine has been shown to enhance the effectiveness of most analgesics, including ibuprofen. This double-blind cross-over pilot study evaluated the effect of ibuprofen and caffeine compared with ibuprofen and placebo in 12 children with headaches. Patients completed diaries for both headaches. Outcome measures included a five-faces severity scale, a measure of clinical disability, and a scale of pain severity. Comparison of the cumulative response scores revealed a trend toward a greater response to ibuprofen-caffeine treatment of headaches (P = 0.14, P = 0.09, and P = 0.07 for the three measures, respectively). Further larger studies are needed to confirm this effect and to identify potential responders.

Descriptive epidemiology of concussion.

To describe the epidemiology of reported concussion derived from a large, nationally representative health survey, the microdata files of the Canadian National Population Health Survey (1996-1997) were analyzed. Respondents reported whether they had "any injuries that were serious enough to limit their normal activities" in the preceding 12 months and the nature of the most serious injury. A total of 99.8% of 81,804 eligible respondents, representing 28,606,100 Canadians, reported their injury experience within the preceding year, with 89 reporting a concussion. The annual prevalence of Canadians reporting a concussion as their most serious injury was 110 per 100,000 population (95% confidence interval: 80, 140). Those reporting concussion were more likely to be younger (P < 0.001) and male (P = 0.02). Males were significantly overrepresented in the 16-34 year-old group (P = 0.004). More than 54% of all concussions were sport-related (95% confidence interval: 39%, 67%), occurring at a place for recreation or sport, with sport having a role in >85% of concussions in the 16-34 year-old group. This study presents annual prevalence estimates of reported concussion, derived from a sizeable, nationally representative population survey.

Activity levels among adolescents with migraine.

Data was analyzed from the nationally representative Canadian Community Health Survey. A total of 17,549 adolescents reported whether they had "migraine headaches" (response rate 99.9%) and in what exercise activities they participated. Those with migraine reported more daily activity than migraine-free peers when corrected for age and sex. They were as likely to play contact sports but were more involved in other noncompetitive activities, such as walking (P<0.001), gardening and yard work (P=0.008), jogging and running (P=0.002), and fishing (P=0.03). Canadian adolescents with migraine are therefore overall more active than their peers without migraine.

Successful treatment of severe infantile hyperekplexia with low-dose clobazam.

We report two cases of severe infantile hyperekplexia successfully treated with low-dose clobazam. The first case presented at 6 weeks of age with multiple episodes consisting of difficulty diapering because of stiffness and loud inspiratory noises followed by breath-holding in inspiration. She was diagnosed with hyperekplexia and started on clonazepam 0.05 mg daily. This was discontinued because of excessive sleepiness. The second case presented at 3 weeks of age with episodes of crying that would change in pitch and then abruptly stop, followed by leg and arm extension and stiffening. On occasion, there was cyanosis, and she received mouth-to-mouth resuscitation. She was diagnosed with hyperekplexia at 9 months of age. Both infants were treated with clobazam (0.25 and 0.3 mg/kg/day respectively), resulting in resolution of symptoms with no side effects. During treatment, both had minimal startle response to various stimuli and have now been successfully weaned from clobazam. Low-dose clobazam is effective in the treatment of hyperekplexia and is well tolerated in infants.

Fever-induced dystonia.

The etiology of dystonia in children is often elusive. We report two children with fever-induced dystonia, an association which has not been previously reported. Both children had episodes of lower extremity dystonia with inversion of the feet and dorsiflexion of the great toes. Events began at 2 years of age, were preceded by febrile illness, and lasted for up to 24 hours. In both children, one of the parents had a history of similar but milder symptoms in childhood. Between spells the children were neurologically normal. Multiple investigations, including metabolic and imaging studies, were normal and therapies were ineffective. As the children aged the dystonic events occurred less frequently. This dystonic syndrome is a previously unrecognized benign episodic movement disorder of childhood.

The utility of the physical examination and investigations in the pediatricneurology consultation.

For most consultations the diagnosis is established by a thorough clinical history. We prospectively assessed the impact of each component of the pediatric neurologic consultation in 500 consecutive referrals to a tertiary care pediatric neurology clinic. Diagnosis and management decisions were declared for each patient by the consultant after each stage of the consultation process (1: receipt of consultation letter, 2: history, 3: physical examination and 4: receipt of investigation results). We found that the physical examination and investigations influenced management decisions for less than 6%. Specifically the examination was never influential for children with headaches, Tourette syndrome, developmental delay or attention-deficit-hyperactivity disorder (ADHD). Investigations never influenced management for those with Tourette syndrome, ADHD, or cerebral palsy. Therefore for the majority of children the critical component of the pediatric neurology consultation is a detailed clinical history.

What do patients and families want from a child neurology consultation?

Understanding what patients and their parents want is essential to plan appropriate patient-centered care. Questionnaires were distributed to 500 consecutive children and parents seen for their first pediatric neurology consultation. Both patients and their families answered questions about their expectations of the consultation, their level of worry, and the Penn State Worry Questionnaire. The 5 most important issues for the parents were to get information, to work with the doctor to manage the problem, to have questions answered, to find out what was wrong, and to discuss the impact on the child's life. The children had very similar priorities. The 5 least important concerns for parents were to get a prescription, blood tests, to talk to others with similar problems, to get a radiograph/computed tomography/magnetic resonance imaging (MRI) and to be told nothing is wrong. The pediatric neurologists did well in anticipating these priorities but had more difficulty appreciating parent and patient level of worry.

Concussion or mild traumatic brain injury: parents appreciate the nuances of nosology.

We explored whether parents of our pediatric patients valued the diagnostic terms "concussion," "minor traumatic brain injury," and "mild traumatic brain injury" as equivalent or nonequivalent. 1734 of 2304 parents attending a regional pediatric emergency department completed a brief questionnaire assessing the equivalence or nonequivalence of the diagnostic terms "concussion," "minor traumatic brain injury," and "mild traumatic brain injury" in a pairwise fashion. Many parents viewed these diagnostic terms as equivalent, when assessed side by side. For those who considered these diagnostic terms nonequivalent, concussion was regarded as considerably "better" (or less "worse") than minor traumatic brain injury (P < 0.001, χ(2) test) or mild traumatic brain injury (P < 0.001, χ(2) test). A moderate degree of variability was evident in parent/guardian responses. As a group, parents reported that concussion or mild/minor traumatic brain injuries are valued equivalently. However, many parents considered them different, with concussion reflecting a "better" (or less "worse") outcome.