Differences and similarities in the evolution of morphologic brain abnormalities between paediatric and adult-onset multiple sclerosis.

BACKGROUND: Paediatric-onset multiple sclerosis (pMS) is multiple sclerosis (MS) occurring before the age of 18 years and may present and develop differently from adult-onset MS (aMS). Whether there are also differences regarding the accrual of brain changes is largely unknown. METHODS: We compared the evolution of the T2- and T1-lesion load (LL), the black hole ratio (BHR), and annualised brain volume change (aBVC) between 21 pMS patients (age at onset: 14.4±2.3 years) and 21 aMS patients (age at onset: 29.4±6.5 years) matched for disease duration (pMS: 1.0±1.8 years; aMS: 1.6±1.7 years, p=0.27). Follow-up was for 4.2±3.7 years in pMS and 3.1±0.6 years in aMS. Clinical comparisons included the course of disability assessed with the Expanded Disability Status Scale (EDSS) score and annualised relapse rate (ARR). RESULTS: At baseline, pMS and aMS had similar EDSS, T1-LL, BHR, whereas T2-LL was higher in aMS (aMS: 9.2±11.6 ccm; pMS: 4.1±6.2 ccm, p=0.02). The change of T2-LL and T1-LL during the observation period was similar in both groups. At follow-up, disability was lower in pMS (EDSS score in pMS: 0.9±0.9; aMS: 1.7±1.3, p=0.04), despite a significantly higher accrual of destructive brain lesions (BHR in pMS: 23.7±23.7%; aMS: 5.9±4.0%, p=0.02) and a similar rate of brain volume loss. CONCLUSION: Our observation of a morphologically more aggressive disease evolution paralleled by less disability in pMS than in aMS (defined using EDSS) suggests a higher compensatory capacity in pMS. This fact may obscure the need for treatment of pMS patients with disease modifying treatments (DMTs) based solely on clinical observation.

Clinical neurophysiology in GJA12-related hypomyelination vs Pelizaeus-Merzbacher disease.

BACKGROUND: Among the hypomyelinating leukoencephalopathies with onset in childhood, Pelizaeus-Merzbacher disease (PMD) and Pelizaeus-Merzbacher-like disease (PMLD) constitute a large subgroup with almost indistinguishable clinical and neuroradiologic features. Whereas PMD is due to X-linked PLP1 mutations, PMLD is genetically heterogeneous, with about 8% of patients carrying autosomal recessive GJA12/GJC2 mutations. The aim of this study was to evaluate whether neurophysiologic testing may separate PMD from GJA12/GJC2-associated PMLD. METHODS: Retrospective data collection study with reevaluation of evoked potentials (EP) and nerve conduction studies (NCS) in 10 patients from 7 families with PMLD due to various GJA12/GJC2 mutations and 8 boys from 7 families with classic PMD caused by a PLP1 duplication or missense mutation. RESULTS: In brainstem auditory EP, waves III-V were absent in all patients with PMD, but clearly recordable in 11 of 13 investigations in 8 patients with PMLD. Visual evoked potentials and somatosensory evoked potentials revealed conduction delay in both PMD and PMLD, without significant difference. NCS were normal in all patients with PMD and indicated mild peripheral neuropathy in only 2 of 10 patients with PMLD. CONCLUSION: In a patient with clinical and neuroradiologic features of Pelizaeus-Merzbacher disease/Pelizaeus-Merzbacher-like disease and a pedigree consistent with both conditions, brainstem auditory evoked potentials provide good selectivity between these disorders and point in the right direction for identifying the primary genetic defect.

The clinical spectrum of mitochondrial disease in 75 pediatric patients.

The clinical presentation of mitochondrial disorders in childhood is highly variable causing difficulties in diagnosis and management. We assessed records of 75 children (48 male, 27 female) with a biochemically and/or molecularly established mitochondrial disorder in a retrospective, multicentric study. The predominant biochemical defect was an isolated respiratory chain complex IV, followed by respiratory chain complex I, combined respiratory chain, and isolated pyruvate dehydrogenase complex (PDHC) deficiencies. For the 75 patients, the predominant clinical presentations were a nonspecific encephalomyopathy (n = 34) and Leigh syndrome (n = 17). Classical mitochondrial syndromes with associated mutations of the mitochondrial DNA were rare (n = 12). Eleven children had a lethal infantile mitochondrial disease (LIMD). This group comprised a considerable variety of clinical pictures, and the cohort was big enough to show the high frequency and wide spectrum of nonneuromuscular symptoms in mitochondrial disorders in childhood.