Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature.

Pontocerebellar hypoplasia type 1 (PCH1) is a major cause of non-5q spinal muscular atrophy (SMA). We screened 128 SMN1-negative SMA patients from Bulgaria for a frequent mutation -p.G31A in EXOSC3, and performed a literature review of all genetically verified PCH1 cases. Homozygous p.G31A/EXOSC3 mutation was identified in 14 Roma patients, representing three fourths of all our SMN1-negative Roma SMA cases. The phenotype of the p.G31A/EXOSC3 homozygotes was compared to the clinical presentation of all reported to date genetically verified PCH1 cases. Signs of antenatal onset of disease present at birth were common in all PCH1 sub-types except in the homozygous p.D132A/EXOSC3 patients. The PCH1sub-types with early death (between ages 1 day and 17 months), seen in patients with p.G31A/EXOSC3 or SLC25A46 mutations have a SMA type 1-like clinical presentation but with global developmental delay, visual and hearing impairment, with or without microcephaly, nystagmus and optic atrophy. Mutations with milder presentation (homozygous p.D132A/EXOSC3 or VRK1) may display additionally signs of upper motor neuron impairment, dystonia or ataxia and die at age between 5 and 18 years. Other EXOSC3 mutations and EXOSC8 cases are intermediate - SMA type 1-like presentation, spasticity (mostly in EXOSC8) and death between 3 months and 5 years. There is no correlation between neurological onset and duration of life. We add marble-like skin and congenital laryngeal stridor as features of PCH1. We show that imaging signs of cerebellar and pontine hypoplasia may be missing early in infancy. EMG signs of anterior horn neuronopathy may be missing in PCH1 patients with SLC25A46 mutations. Thus, there is considerable phenotypic variability in PCH1, with some cases being more SMA-like, than PCH-like. Detailed clinical evaluation and ethnicity background may guide genetic testing and subsequent genetic counseling.

Acute confusional migraine: is it a distinct form of migraine?

UNLABELLED: The International Classification of Headache Disorders (ICHD-II) - 2004 recognises many migraine variants (different from migraine without aura and migraine with typical aura), but acute confusional migraine (ACM) remains unclassified and most clinicians are not well acquainted with it. AIM: The aim of this study was to illustrate ACM in the neuropaediatric practice, to discuss its place in the ICHD-II and to propose diagnostic criteria. PATIENTS AND METHODS: A total of 2509 files of newly diagnosed patients, aged 0-18 years, treated as in- and outpatients in the Neuropaediatric Ward at the Plovdiv Medical University Hospital between 2002 and 2006 were screened retrospectively. Their diagnosis was based on detailed medical history, physical and neurological examination, additional functional, imaging and laboratory investigations. Migraine and migraine variants were diagnosed according to ICHD-II, but specific forms (e.g. ACM and Alice in wonderland syndrome) were also included. RESULTS: One hundred and eleven patients met the diagnostic criteria for migraine. Migraine variants comprised 24.3% of all migraine cases. In particular, ACM represented 11.1% of migraine variants or 2.7% of migraine and 0.12% of all paediatric neurological diseases. Here, we report three cases of ACM with analysis of the typical clinical and EEG features, review the literature and propose diagnostic criteria. CONCLUSION: ACM may present as either the only manifestation of a migraine attack or in the context of other migraine forms. ACM should have its own distinct place in the ICHD-II, may be as a subtype of migraine with complex aura.

Evaluation of diagnostic and prognostic value of clinical characteristics of migraine and tension type headache included in the diagnostic criteria for children and adolescents in International Classification of Headache Disorders--second edition.

UNLABELLED: Data about the sensitivity and the specificity of the items included in the diagnostic criteria for migraine and tension type headache (TTH) in children is limited and sometimes controversial. AIM: To evaluate the diagnostic value of characteristics of migraine and TTH included in the diagnostic criteria of ICHD-II and according to results to suggest additional criteria for diagnostic differentiation of primary paediatric headache. PATIENTS AND METHODS: The investigation consisted of an epidemiological school-based study (1029 pupils completed the study and 412 had chronic or recurrent headache) and a clinical study conducted in Paediatric Neurology Ward and outpatient clinic (203 patients with chronic or recurrent headache). Inclusion criterion was at least two episodes of headache during the last year. Exclusion criteria were: headache occurring only during acute infections; withdrawal of informed consent. ICHD - II was used to classify headache. The diagnostic value of characteristics of migraine and TTH was measured using sensitivity, specificity, odds ratio and area under receiver operating characteristic curve (AUC). RESULTS: Regarding the AUC, the best diagnostic items for migraine are: moderate or severe intensity or only severe intensity, pain aggravation by physical activity, pulsating quality, respectively, for TTH - no photophobia, no nausea, no aggravation by physical activity, mild or moderate intensity and non-pulsating quality. The most significant symptom for increasing the migraine risk was pulsating pain and the most significant items for TTH risk were no photophobia, bilateral location and no nausea. Family history of migraine also increased migraine risk and could be either included in the diagnostic criteria for migraine or recommended as additional item in differentiating migraine and TTH with overlapping diagnostic criteria. According to AUC, we could recommend changing the content of the item of intensity for migraine as only severe intensity.