Atypical idiopathic intracranial hypertension presenting as cyclic vomiting syndrome: a case report.

BACKGROUND: Idiopathic intracranial hypertension is a disorder of increased intracranial pressure in the absence of cerebrospinal outflow obstruction, mass lesion, or other underlying cause. It is a rare phenomenon in prepubertal children and is most typically found in women of childbearing age. The classic presentation consists of headaches, nausea, vomiting, and visual changes; however, children present more atypically. We report a case of idiopathic intracranial hypertension in an otherwise healthy, 4-year-old child with atypical symptoms resembling those of cyclic vomiting syndrome. CASE PRESENTATION: A 4-year-old Caucasian, otherwise healthy, male child presented to our emergency department with episodic intermittent early-morning vomiting occurring once every 1-3 weeks without interepisodic symptoms, starting 10 months prior. With outpatient metabolic, autoimmune, endocrine, allergy, and gastroenterology work-up all unremarkable, he was initially diagnosed with cyclic vomiting syndrome. Discovery of mild optic nerve sheath distension on magnetic resonance imaging of the brain 10 months after symptom onset led to inpatient admission and a lumbar puncture notable for an opening pressure of 47 mmHg, with normal cell count and protein levels. He had no changes in visual acuity or optic disc edema on dilated fundoscopic examination. The patient was started on acetazolamide, with resolution of episodic emesis at his last follow-up visit 12 weeks after discharge. CONCLUSIONS: Idiopathic intracranial hypertension presents atypically in prepubescent children, with about one-fourth presenting asymptomatically, and only 13-52% presenting with "classic" symptoms. With a prevalence of only 0.6-0.7 per 100,000, much remains unknown regarding the underlying pathophysiology in this demographic. Cyclic vomiting syndrome, however, has a much higher prevalence in this age group, with a prevalence of 0.4-1.9 per 100. It is thought to be an idiopathic, periodic disorder of childhood, often linked to neurological conditions such as abdominal migraines, epilepsy, mitochondrial disorders, and structural lesions such as chiari malformation and posterior fossa tumors. While cyclic vomiting syndrome is thought to have a benign course, untreated idiopathic intracranial hypertension can have long-term detrimental effects, such as visual loss or even blindness. We present a case of idiopathic intracranial hypertension presenting with symptoms resembling cyclic vomiting syndrome in a 4-year-old child, diagnosed 10 months after initial onset of symptoms. We aim to demonstrate the need for a high level of clinical suspicion and the need for further investigation into underlying pathophysiology in this vulnerable population.

Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder.

GEMIN5, an RNA-binding protein is essential for assembly of the survival motor neuron (SMN) protein complex and facilitates the formation of small nuclear ribonucleoproteins (snRNPs), the building blocks of spliceosomes. Here, we have identified 30 affected individuals from 22 unrelated families presenting with developmental delay, hypotonia, and cerebellar ataxia harboring biallelic variants in the GEMIN5 gene. Mutations in GEMIN5 perturb the subcellular distribution, stability, and expression of GEMIN5 protein and its interacting partners in patient iPSC-derived neurons, suggesting a potential loss-of-function mechanism. GEMIN5 mutations result in disruption of snRNP complex assembly formation in patient iPSC neurons. Furthermore, knock down of rigor mortis, the fly homolog of human GEMIN5, leads to developmental defects, motor dysfunction, and a reduced lifespan. Interestingly, we observed that GEMIN5 variants disrupt a distinct set of transcripts and pathways as compared to SMA patient neurons, suggesting different molecular pathomechanisms. These findings collectively provide evidence that pathogenic variants in GEMIN5 perturb physiological functions and result in a neurodevelopmental delay and ataxia syndrome.

Post-Trial Sustainability and Scalability of the Benefits of a Medical Home for High-Risk Children with Medical Complexity.

OBJECTIVE: To assess the sustainability of the benefits relative to usual care of a medical home providing comprehensive care for high-risk children with medical complexity (≥2 hospitalizations or ≥1 pediatric intensive care unit [PICU] admission in the year before enrollment) after we made comprehensive care our standard practice and expanded the program. STUDY DESIGN: We conducted pre-post comparisons of the rate of children with serious illness (death, PICU admission, or >7-day hospitalization) and health-system costs observed after program expansion (March 2014-June 2015) to those during the clinical trial (March 2011-August 2013) for each of the trial's treatment groups (usual care, n = 96, and comprehensive care, n = 105; primary analyses), and among all children given comprehensive care (nPost-trial = 233, including trial usual care children who transitioned to comprehensive care post-trial and newly enrolled medically complex children, and nTrial = 105; secondary analyses). We also analyzed the findings for the trial patients as a 2-phase stepped-wedge study. RESULTS: In intent-to-treat analyses, rates of children with serious illness and costs were reduced or unchanged post-trial vs trial for the trial's usual care group (rate ratio [RR], 0.36; 95% CI, 0.20-0.64; cost ratio [CR], 0.68; 95% CI, 0.28-1.68), the trial's comprehensive care group (RR, 0.74; 95% CI, 0.39-1.41; CR, 0.67; 95% CI, 0.51-0.89), and among all children given comprehensive care (RR, 0.97; 95% CI, 0.61-1.52; CR, 0.75; 95% CI, 0.61-0.93). Conservative stepped-wedge analyses identified overall benefits with comprehensive care across both study periods (RR, 0.46; 95% CI, 0.30-0.72; CR, 0.64; 95% CI, 0.43-0.99). CONCLUSIONS: Major benefits of comprehensive care did not diminish with post-trial program expansion.

Difference in central and peripheral recovery in a patient with severe axonal motor neuropathy and central nervous system involvement and review of literature.

In the literature, the term fulminant Guillain-Barré syndrome is used to refer to patients with Guillain-Barré syndrome with rapidly progressive and severe weakness and/or comatose state mimicking brain death. We present the case of a 53-year-old man with fulminant Guillain-Barré syndrome with discrepancy in central nervous system and peripheral nervous system recovery. Our review of literature confirms that these patients often have good and relatively rapid recovery of central nervous system function, whereas peripheral nervous system function is relatively delayed and often incomplete.