ATP1A3-related disorders in the differential diagnosis of acute brainstem and cerebellar dysfunction.

Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia-Parkinsonism (RDP), and CAPOS syndrome (Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural hearing loss) are all caused by mutations in the same gene: ATP1A3. Although initially they were considered separate disorders, recent evidence suggests a continuous clinical spectrum of ATP1A3-related disorders. At onset all these disorders can present with acute brainstem dysfunction triggered by a febrile illness. An infectious or autoimmune disorder is usually suspected. A genetic disorder is rarely considered in the first acute episode. We present three patients with ATP1A3 mutations: one patient with AHC, one patient with RDP, and one patient with CAPOS syndrome. We describe the acute onset and overlapping clinical features of these three patients with classical phenotypes. These cases highlight ATP1A3-related disorders as a possible cause of acute brainstem dysfunction with normal ancillary testing.

Long-term normalization of cognitive and psychopathological alterations in a juvenile Niemann-Pick type C case.

Niemann-Pick type C (NP-C) disease is a neurovisceral atypical lysosomal lipid storage disorder with a poor prognosis. We present the 5-year neuropsychological follow-up of a patient with juvenile onset NP-C, spanning the pre-diagnostic stage to the period after treatment with miglustat (Actelion Pharmaceuticals Inc., CA, US). In the initial stages of the disease, the patient presented behavioral dysexecutive symptoms resembling those frequently observed in adult-onset forms and frontotemporal dementia, which frequently makes early diagnosis difficult in children. After 4 years of treatment, the impaired cognitive function and behavioral dysexecutive syndrome had been completely reversed. The variability of NP-C disease makes early diagnosis challenging. Evaluations of long-term neuropsychological development can help diagnose this neurodegenerative disease and document its progression.

Enterovirus A71 Infection and Neurologic Disease, Madrid, Spain, 2016.

We conducted an observational study from January 2016 through January 2017 of patients admitted to a reference pediatric hospital in Madrid, Spain, for neurologic symptoms and enterovirus infection. Among the 30 patients, the most common signs and symptoms were fever, lethargy, myoclonic jerks, and ataxia. Real-time PCR detected enterovirus in the cerebrospinal fluid of 8 patients, nasopharyngeal aspirate in 17, and anal swab samples of 5. The enterovirus was genotyped for 25 of 30 patients; enterovirus A71 was the most common serotype (21/25) and the only serotype detected in patients with brainstem encephalitis or encephalomyelitis. Treatment was intravenous immunoglobulins for 21 patients and corticosteroids for 17. Admission to the pediatric intensive care unit was required for 14 patients. All patients survived. At admission, among patients with the most severe disease, leukocytes were elevated. For children with brainstem encephalitis or encephalomyelitis, clinicians should look for enterovirus and not limit testing to cerebrospinal fluid.

Detection by Urinary GAG Testing of Mucopolysaccharidosis Type II in an At-Risk Spanish Population.

Hunter syndrome (Mucopolysaccharidosis type II) is an inherited lysosomal storage disorder with potentially severe degenerative consequences. Clinical diagnosis is not easy, although biochemical confirmation is straightforward, and sometimes patients are diagnosed at a late age. It is widely believed, for inborn errors of metabolism in general, that early diagnosis and management is of paramount importance for improving the prognosis of the disease. The objective of this study was to identify specific populations at risk of suffering from Hunter syndrome. Urine samples were obtained from children between the ages of 0 to 18, belonging to known risk groups of mucopolysaccharidosis (MPS) type II, for the semi-quantitative (GAG test) and quantitative determination of glycosaminoglycans (GAG). One case of Hunter syndrome was found among the 130 samples that were collected and analysed. This study supports the feasibility of early diagnosis and the usefulness of screening tests for MPS II in specific paediatric populations.

Phenytoin-induced visual disturbances mimicking Delirium Tremens in a child.

Delirium Tremens is quite rare in children and it is usually caused by withdrawal or abstinence from alcohol, barbiturates and other major tranquilizers. The usual symptoms of Delirium Tremens include severe altered mental status with confusion, delusions, hallucinations, and severe agitation. Although psychosis is a recognized manifestation of Phenytoin toxicity, visual hallucinations are not. This study reports the case of a 4-year-old male with febrile seizures plus syndrome who developed acute complex visual hallucinations and psychomotor agitation early after therapy with intravenous Phenytoin was administered. These visual hallucinations mimicked those linked to Delirium Tremens and were not associated with an encephalopathy or other known neuropsychiatric side effects of this drug. Moreover, the hallucinations occurred while serum Phenytoin concentrations were below therapeutic range. We made an extensive investigation in order to exclude a non-convulsive Status Epilepticus, a Central Nervous System infection, a metabolic disorder, an underlying psychiatric disease and a possible drug toxicity. The temporal relationship between initiation of Phenytoin and onset of visual hallucinations and resolution of symptoms with withdrawal of Phenytoin suggests that the visual disturbances were probably due to that antiepileptic drug.