NCT01590589.

Objective Because patients homozygous for Huntington disease (HD) receive the gain-of-function mutation in a double dose, one would expect a more toxic effect in homozygotes than in heterozygotes. Our aim was to investigate the phenotypic differences between homozygotes with both alleles ≥36 CAG repeats and heterozygotes with 1 allele ≥36 CAG repeats. Methods This was an international, longitudinal, case-control study (European Huntington's Disease Network Registry database). Baseline and longitudinal total functional capacity, motor, cognitive, and behavioral scores of the Unified Huntington's Disease Rating Scale (UHDRS) were compared between homozygotes and heterozygotes. Four-year follow-up data were analyzed using longitudinal mixed-effects models. To estimate the association of age at onset with the length of the shorter and larger allele in homozygotes and heterozygotes, regression analysis was applied. Results Of 10,921 participants with HD (5,777 female [52.9%] and 5,138 male [47.0%]) with a mean age of 55.1 ± 14.1 years, 28 homozygotes (0.3%) and 10,893 (99.7%) heterozygotes were identified. After correcting for multiple comparisons, homozygotes and heterozygotes had similar age at onset and UHDRS scores and disease progression. In the multivariate linear regression analysis, the longer allele was the most contributing factor to decreased age at HD onset in the homozygotes (p < 0.0001) and heterozygotes (p < 0.0001). Conclusions CAG repeat expansion on both alleles of the HTT gene is infrequent. Age at onset, HD phenotype, and disease progression do not significantly differ between homozygotes and heterozygotes, indicating similar effect on the mutant protein. Classification of evidence This study provides Class II evidence that age at onset, the motor phenotype and rate of motor decline, and symptoms and signs progression is similar in homozygotes compared to heterozygotes.

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Idiopathic spinal cord herniation (ISCH) is a relatively rare and frequently misdiagnosed condition. It preferentially affects women and causes progressive thoracic myelopathy that presents as a Brown-Séquard syndrome or as spastic paraparesis. Although its etiology and pathogenesis are controversial, ISCH is characterized by the presence of an anterior dural defect that allows the incarceration of a segment of the cord. Typically, a C-shaped ventral displacement and kinking of the cord are visible on sagittal MRI. Surgery aimed at stopping or reversing myelopathic symptoms is usually recommended for symptomatic patients. Surgical options include reduction of the hernia and direct suturing, or enlargement of the dural defect, with or without patching. Suturing under the cord in a very tight space can be troublesome and may lead to neurological deterioration. The authors present the case of a symptomatic ISCH in which nonpenetrating titanium microstaples were used to close the dural defect after cord reduction. The patient experienced a good outcome, and the follow-up MRI study showed adequate cord repositioning and stability of the suture. The use of microstaples, which allows for an easier and faster dural closure than conventional suturing, is a novel technical adjunct that has not been previously reported for this condition. In addition, microstaples produce minimal metallic artifact that does not hinder the quality of follow-up MR images.

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Background Insulin‐like growth factor 1 (IGF‐1) seems to be involved in the neural circuits associated with social cognition and brain structure. Objectives To investigate the association of IGF‐1 levels with social cognition and brain structure in Huntington's disease (HD). Methods We evaluated social cognition using the Ekman test in 22 HD patients and 19 matched controls. Brain structure was assessed using standard volume‐based voxel‐based morphometry and surface‐based cortical thickness pipeline. We analyzed the association of IGF‐1 levels with social cognition and brain structure using adjusted regression analysis. Results Social cognition was worse in HD patients (P < 0.001), on antidopaminergic drugs (P = 0.02), and with lower IGF‐1 levels (P = 0.04). In neuroimaging analyses, lower IGF‐1 levels were associated with social cognition impairment and atrophy mainly in frontotemporal regions (P < 0.05 corrected). Conclusions In HD, abnormal IGF‐1 function seems to be associated with brain atrophy leading to clinical deficits in social cognition.