A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.

Limb girdle muscular dystrophy type 2A is the most common limb girdle muscular dystrophy form worldwide. Although strict recessive inheritance is assumed, patients carrying a single mutation in the calpain 3 gene (CAPN3) are reported. Such findings are commonly attributed to incomplete mutation screening. In this investigation, we report 37 individuals (age range: 21-85 years, 21 females and 16 males) from 10 families in whom only one mutation in CAPN3 could be identified; a 21-bp, in-frame deletion (c.643_663del21). This mutation co-segregated with evidence of muscle disease and autosomal dominant transmission in several generations. Evidence of muscle disease was indicated by muscle pain, muscle weakness and wasting, significant fat replacement of muscles on imaging, myopathic changes on muscle biopsy and loss of calpain 3 protein on western blotting. Thirty-one of 34 patients had elevated creatine kinase or myoglobin. Muscle weakness was generally milder than observed in limb girdle muscular dystrophy type 2A, but affected the same muscle groups (proximal leg, lumbar paraspinal and medial gastrocnemius muscles). In some cases, the weakness was severely disabling. The 21-bp deletion did not affect mRNA maturation. Calpain 3 expression in muscle, assessed by western blot, was below 15% of normal levels in the nine mutation carriers in whom this could be tested. Haplotype analysis in four families from three different countries suggests that the 21-bp deletion is a founder mutation. This study provides strong evidence that heterozygosity for the c.643_663del21 deletion in CAPN3 results in a dominantly inherited muscle disease. The normal expression of mutated mRNA and the severe loss of calpain 3 on western blotting, suggest a dominant negative effect with a loss-of-function mechanism affecting the calpain 3 homodimer. This renders patients deficient in calpain 3 as in limb girdle muscular dystrophy type 2A, albeit in a milder form in most cases. Based on findings in 10 families, our study indicates that a dominantly inherited pattern of calpainopathy exists, and should be considered in the diagnostic work-up and genetic counselling of patients with calpainopathy and single-allele aberrations in CAPN3.

Arterial ischemic stroke as a complication to disseminated infection with Fusobacterium necrophorum.

Lemierre syndrome (LS) is a rare complication of oropharyngeal and odontogenic infections in otherwise healthy young individuals. It is characterized by septic internal jugular vein thrombophlebitis and disseminated metastatic abscesses. Cerebral arterial ischemic stroke is rarely seen in LS. The authors present a 14-year-old, previously healthy girl, who developed cerebral arterial infarction following acute tonsillitis and abscess formations due to Fusobacterium necrophorum.

Longitudinally extensive transverse myelitis and Hepatitis C-a case report and literature review.

Tractopathy lesions in the spinal cord associated with HCV infection, which normalized on MRI after antiviral treatment, are described. These specific MRI findings can be used in the diagnosis and treatment of secondary causes of transverse myelitis.

Magnetic resonance imaging of the intraluminal thrombus in abdominal aortic aneurysms: a quantitative and qualitative evaluation and correlation with growth rate.

BACKGROUND: The role of the intraluminal thrombus (ILT) in abdominal aortic aneurysm (AAA) growth remains incompletely understood. MRI is superior to other methods in depicting the morphology of the ILT. This study brings preliminary, but novel information on the presence and morphological characteristics of the ILT and AAA growth rates in a screening cohort. METHODS: Cohort study with 46 patients from the Viborg Vascular Trial. All underwent one non-contrast-enhanced magnetic resonance imaging (MRI) at the end of follow-up. ILT presence was noted and, if present, it was allocated to one of four morphological categories based on visual appearance and signal intensity on T2 weighted images. RESULTS: The mean growth rate was 1.95 mm/year ±0.87 (SD). The observation time was 5.59±0.63 (SD) years. ILT was present in AAA size groups as follows: 30-34.9 mm 20.00%, 35-39.9 mm 88.89%, 40-44.9 mm 81.25%, 45-49.9 mm 100% and 50-54.9 mm 100%. Out of 46, 8 had no ILT at the time of MRI. The presence of any sort of ILT yielded a significantly increased unadjusted and an adjusted growth rate of 1.09 mm/year (95% CI: 0.48; 1.70) and 1.24 mm/year (95% CI: 0.64; 1.83), respectively. All four thrombus types were retrospectively associated with an increased recorded growth rate compared with "no thrombus". Presence of a thin circumferential thrombus was retrospectively associated with the highest increase in growth rate, viz. 2.09 mm/year (95% CI: 1.23; 2.95). CONCLUSIONS: We observed faster growth rate in those AAA that had developed an ILT. Even faster growth was observed amongst those AAA containing a thin ILT located along the inner circumference.

Lumbar Osteophyte Avid on 68Ga-Prostate-Specific Membrane Antigen PET/CT.

A 75-year-old man with recently diagnosed high-risk prostate cancer was referred for primary staging with Ga-prostate-specific membrane antigen (PSMA) PET/CT. The scan revealed intense Ga-PSMA uptake in a lumbar osteophyte on the right side of level L2/L3, whereas several other spinal osteophytes showed no Ga-PSMA uptake. MRI findings in the L3 vertebra was consistent with a benign Modic type 1 lesion, but MRI showed no signs of malignancy in the osteophyte with high Ga-PMSA uptake. This case presents an osteophyte as an addition to the list of potential benign pitfalls to be aware of when interpreting Ga-PSMA PET/CT.

[Intervertebral discitis in children].

Intervertebral discitis is a rare disorder which is easily missed. It presents with non-specific symptoms such as irritability, abdominal pain, decreased appetite and limping. The infection parameters can be normal, and blood cultures are often negative. The pathogenesis is not established but infectious, and inflammatory aetiologies have been suggested. Diagnostic golden standard is magnetic resonance imaging. The treatment is immobilization, anti-inflammatory drugs and often antibiotics. Early treatment is important to reduce the risk of complications such as nerve damage and spine fusion.

The Danish PET/depression project: performance on Stroop's test linked to white matter lesions in the brain.

The Stroop test (ST) assesses the integrity of prefrontal and cingulate functioning. Patients with major depression perform poorly on the ST, pointing to disturbed function in these areas. We therefore used positron emission tomography to study 41 in-patients with major depression and 46 age- and gender-matched controls during neuropsychological activation with the ST. Magnetic resonance imaging was used for coregistration and for description of the localization of white matter lesions (WML). The cerebral blood flow (CBF) changes during ST were mapped for each of the two study groups, and inter-group differences were calculated on a voxel-by-voxel basis. The patients were followed for 3 to 5 years to ensure diagnostic stability. The control group activated anterior cingulate regions, prefrontal cortices, insula, thalamus and cerebellum. Despite the patients' slower performance with more errors, no significant differences were found comparing the activations in the two groups. The performance was, however, correlated to the number of WML in frontal lobes, insula and adjacent to the basal ganglia, whereas WML in other locations was not related to performance. We thus partly explain the poorer performance by increased frequency of WML in frontostriatal pathways in the depressed patients, impairing neurotransmission.

Reversible magnetic resonance imaging and spectroscopy abnormalities in the course of vigabatrin treatment for West syndrome.

Transient magnetic resonance imaging (MRI) hyperintensity of globus pallidi, thalami, dentate nuclei and cerebral peduncles has recently been described in a significant number of young children during treatment with vigabatrin for infantile spasms. We describe two children with infantile spasms treated with vigabatrin, investigated with consecutive MRI as well as magnetic resonance spectroscopy (MRS). Hyperintensity developed during high dose vigabatrin treatment and remitted totally after dose reduction in one case, and cessation in the other. Abnormalities on MRS, suggesting an increase in the glutamine-glutamate complex in the basal ganglia, were found in both cases while on vigabatrin treatment. These changes remitted in the first case after reduction of vigabatrin dose and when seizure free and with a normalized EEG, but persisted in the second case following cessation of vigabatrin without remission of seizure activity.

[Infantile haemangioma and intracranial vascular malformation]. / Et barn med infantile haemangiomer og malformationer.

A two-week-old female infant presented with a large haemangioma in the left superior palpebra, preventing her from opening the eye. Cerebral magnetic resonance imaging with angiography revealed another two facial haemangiomas and agenesia of the left internal carotid artery. The combination of facial haemangiomas and intracranial vascular malformation is diagnostic for the PHACES syndrome. When given oral prednisolone, the haemangioma regressed, allowing her to open the eye. She was treated for 29 weeks with slow tapering. Growth stagnation occurred during treatment, but otherwise her development was normal.