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Three Part Question

In [children with isolated microcephaly without neurological deficits or severe developmental delay] does [routine MRI brain scan]help in [making a diagnosis]?

Clinical Scenario

A 7-year-old boy was referred for medical assessment, as part of the process of producing a statement of special educational needs. He had mild learning difficulties and parents were concerned that he was not receiving the support he needed at school. There had been no medical concerns in the past and there was no family history of note. On examination, the boy was noted to be micro cephalic with head circumference on the 9th centile, while his height and weight were on the 50th centile. His father’s head circumference was on the 50th centile. Neurological examination was normal. Should this boy be referred for an MRI scan of the brain?

Search Strategy

Secondary sources: Cochrane library
Primary sources: Pub Med, and Medline 1950 to date and Embase 1974 to date using Dialog Data Star.

Search terms used were “microcephaly AND (imaging OR neuroimaging OR MRI)”
Search was limited to English literature

Search Outcome

Search of the primary source did not yield any results. Secondary sources yielded 381 and 518 hits respectively. After excluding case reports and reports of neuroimaging in children with microcephaly as part of a syndrome, 3 relevant studies were identified

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Steinlin et al 1991	33 children with OFC below the 3rd centile. Those with secondary microcephaly were excluded. Age range was 1 month to 11 years	Cohort study(level of evidence-4)	Abnormal MRI	30/33.Excluding those with dysmorphism and severe neurological and developmental impairments 2/3 had abnormal MRI. Of the 2 with abnormal MRI, one patient did not have any developmental delay at the time of evaluation at 25 months of age.	The abnormal MRI findings in the group with mild or no developmental delay were patchy dysmyelination, enlarged cisterna magna and clumsy gyri. The significance of these is not known.
Custer et al 2000	29 patients aged 1 to 48 months; all had OFC that was 2SD below mean. All had normal karyotype	Retrospective cohort(level of evidence-4)	Abnormal CT/MRI	16/29 had abnormal MRI. Those with abnormal imaging also had lower developmental scores (Mean <52 vs >70, p <0.05	Either CT or MRI had been used as the imaging modality. 6 patients with ‘normal imaging’ had CT only and may well have had abnormalities that might have been picked up on MRI Does not include any patients with microcephaly and mild or no developmental delay
Sugimoto et al 1993	55 children aged 2 months to 11 years, 41 were <3 years old, all had OFC <= 2SD below mean, included children with secondary or acquired microcephaly	Cohort study(level of evidence-4)	Abnormal MRI	44/55 was abnormal. 34 patients had underlying syndrome or developmental abnormalities in the prenatal period. Of the remaining 21 all had multiple neurological handicaps	Does not include any patients with microcephaly and mild or no developmental delay

Comment(s)

In one population study of children with mental retardation identified through special schools, educational psychology services, agencies such as national centres for epilepsy and child psychiatry and local genetics department, 11% of children with mild mental retardation (IQ 50-70) were micro cephalic with OFC <10th centile. Conversely, there are studies on autosomal dominant microcephaly where intellectual functioning has been found to be normal. In the above mentioned population study, 36% of all children with mental retardation were micro cephalic (OFC <10th centile). 22% of these children had severe mental retardation (IQ<50). The authors state that 22% had OFC <2.5th centile leading to the inference that the severity of microcephaly had a direct correlation with the severity of learning difficulties However, the usefulness of brain imaging in non-syndromic microcephaly occurring in isolation, without neurological signs or severe developmental delay, is not known. The 3 studies identified here are cohort studies. Steinlin et al had 3 patients with mild or no developmental delay, of whom 2 had abnormal MRI. In Custer et al’s study, it is not clear as to whether any of the children with abnormal imaging had normal developmental scores. All the children with abnormal MRI in Sugimoto et al’s study had severe developmental delay or neurological impairments. In summary, only 2 out of 3 patients with isolated microcephaly had an abnormal MRI. As pointed out by Steinlin et al, the subtle findings seen on the MRI scan of these patients, such as patchy dysmyelination, enlarged cisterna magna and clumsy gyri, may not be of diagnostic significance. Therefore it is possible that routine neuroimaging may provoke anxiety without serving diagnostic or prognostic use.

Clinical Bottom Line

Children with mild learning difficulties without any other neurological problems can present with microcephaly [Grade B] Routine neuroimaging has a low diagnostic yield and does not have any clear influence on the management of these patients [Grade D]

References

1. Steinlin M, Zürrer M, Martin E, Boesch C, Largo RH, Boltshauser E. Contribution of magnetic resonance imaging in the evaluation of microcephaly Neuropediatrics 1991 Nov;22(4):184-9
2. Custer DA, Vezina LG, Vaught DR, Brasseux C, Samango-Sprouse CA, Cohen MS, Rosenbaum KN. Neurodevelopmental and neuroimaging correlates in nonsyndromal microcephalic children. J Dev Behav Pediatr 2000 Feb;21(1):12-8.
3. Sugimoto T, Yasuhara A, Nishida N, Murakami K, Woo M, Kobayashi Y. MRI of the head in the evaluation of microcephaly. Neuropediatrics 1993 Feb;24(1):4-7