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In early-onset (EO) cblC deficiency (MMACHC), hydroxocobalamin dose-intensification (OHCBL-DI) improved biochemical and clinical outcome. In mammals, Cobalamin is reduced, in a reaction mediated by MMACHC. Pathogenic variants in MMACHC disrupt the synthesis pathway of methyl-cobalamin (MetCbl) and 5'-deoxy-adenosyl-cobalamin (AdoCbl), cofactors for both methionine synthase (MS) and methyl-malonyl-CoA mutase (MCM) enzymes. In 5 patients (pts.), with EO cblC deficiency, biochemical and clinical responses were studied following OHCbl-DI (mean ± SD 6,5 ± 3,3 mg/kg/day), given early, before age 5 months (pts. 1, 2, 3 and 4) or lately, at age 5 years (pt. 5). In all pts., total homocysteine (tHcy), methyl-malonic acid (MMA) and Cob(III)alamin levels were measured. Follow-up was performed during 7 4/12 years (pts. 1, 2, 3), 3 3/12 years (pt. 4) and 3 4/12 years (pt. 5). OHCbl was delivered intravenously or subcutaneously. Mean ± SD serum Cob(III)alamin levels were 42,2 × 10 6  ± 28, 0 × 10 6  pg/ml (normal: 200-900 pg/ml). In all pts., biomarkers were well controlled. All pts., except pt. 5, who had poor vision, had central vision, mild to moderate nystagmus, and with peri-foveolar irregularity in pts. 1, 2 and 4, yet none had the classic bulls' eye maculopathy and retinal degeneration characteristic of pts. with EO cblC deficiency. Only pt. 5, had severe cognitive deficiency. Both visual and cognitive functions were better preserved with early than with late OHCBL-DI. OHCBL-DI is suggested to bypass MMACHC, subsequently to be rescued by methionine synthase reductase (MSR) and adenosyl-transferase (ATR) to obtain Cob(I)alamin resulting in improved cognitive and retinal function in pts. with EO cblC deficiency., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Autosomal recessive or X-linked inborn errors of intracellular cobalamin metabolism can lead to methylmalonic aciduria and homocystinuria. In neonates, both increased cerebrospinal fluid glycine and cerebrospinal fluid/plasma glycine ratio are biochemical features of nonketotic hyperglycinemia., Methods: We describe a boy presenting in the neonatal period with hypotonia, tonic, clonic, and later myoclonic seizures, subsequently evolving into refractory epilepsy and severe neurocognitive impairment., Results: Increased cerebrospinal fluid glycine and cerebrospinal fluid to plasma glycine ratio were indicative of nonketotic hyperglycinemia. Early magnetic resonance imaging showed restricted diffusion and decreased apparent diffusion coefficient values in posterior limb of internal capsules and later in entire internal capsules and posterior white matter. Sequencing did not show a mutation in AMT, GLDC, or GCSH. Biochemical analysis identified persistently increased cerebrospinal fluid levels of glycine and methylmalonic acid and increased urinary methylmalonic acid and plasma homocysteine levels, which improved on higher parenteral hydroxocobalamin dose. Exome sequencing identified a known pathogenic sequence variant in X-linked cobalamin (HCFC1), c.344C>T, p. Ala115Val. In addition, a hemizygous mutation was found in the ATRX (c. 2728A>G, p. Lys910Glu). Retrospective review of two other patients with X-linked cobalamin deficiency also identified increased cerebrospinal fluid glycine levels., Conclusions: This boy had X-linked cobalamin deficiency (HCFC1) with increased cerebrospinal fluid glycine and methylmalonic acid and increased cerebrospinal fluid to plasma glycine ratio suggesting a brain hyperglycinemia. Putative binding sites for HCFC1 and its binding partner THAP11 were identified near genes of the glycine cleavage enzyme, providing a potential mechanistic link between HCFC1 mutations and increased glycine., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Herpes encephalitis can be a life-threatening condition, despite early instauration of acyclovir treatment. In particular patients may succumb to rapidly progressive cerebral oedema. We report a 66-year patient with a Glasgow Coma Score (GCS) of 6 and incipient uncus herniation of the right temporal lobe on the third day. Decompressive hemicraniectomy was immediately performed. The long-term outcome was satisfactory with unassisted gait and a Barthel Index score of 70 after 9 months.

Herpes encephalitis can be a life-threatening condition, despite early instauration of acyclovir treatment. In particular patients may succumb to rapidly progressive cerebral oedema. We report a 66-year patient with a Glasgow Coma Score (GCS) of 6 and incipient uncus herniation of the right temporal lobe on the third day. Decompressive hemicraniectomy was immediately performed. The long-term outcome was satisfactory with unassisted gait and a Barthel Index score of 70 after 9 months.

We report a rare case of an extracranial internal carotid artery aneurysm (EICAA) discovered incidentally by color Doppler sonography (CDUS) and confirmed by CT angiography with three-dimensional reconstructions. As both brain MRI and cerebral angiography were normal and the patient remained asymptomatic, he was neither operated on nor stented but was discharged with appropriate antiplatelet therapy. The volume of his EICAA is checked regularly by CDUS.

Soft tissue sarcoma surgery is based on techniques that are in the process of ongoing development. In this study, the case is reported of a female patient who was operated on at the age of 14 years for a primary synoviosarcoma of the dominant hand, which was treated by conservative surgery and 60 Gy adjuvant radiotherapy. Twenty-two years later, she presented with a clinical picture of recurrence, but with no detectable metastases. Amputation of the distal third of the forearm was performed. The anatomopathological examination showed the presence of a myxoid malignant fibrous histiocytoma. It was considered that this tumor had been radiation-induced. All the distinct diagnostic criteria were met, i.e., a latency of over two years, different diagnosis and the appearance of the tumor within (or next to) the irradiated field. Both the diagnostic methods (MRI, tumor biopsy, and CT scan of the chest to investigate possible tumor spread) and the surgical approach have been discussed. The latter has altered over the years from being systematically radical (amputation or compartimental resection) to systematically conservative (good local control via radiotherapy). The modern attitude reflects a return to a more balanced approach. The frequency of such tumors has probably been underestimated in reports in the literature, as the latency period can sometimes exceed 30 years, and an accurate determination of the etiology is not always possible. Two main factors should be taken into account in treatment strategy: i) distant metastases of high-grade soft tissue sarcomas often appear early in the course of the disease, and are not affected by surgery at the primary site; ii) local recurrence, which is associated with high morbidity, and is directly connected with incomplete resection. Technical progress and a multidisciplinary approach have resulted in more sophisticated treatment (allowing a larger surgical resection area, and better residual function). Surgical management remains the treatment of choice, as radiotherapy and chemotherapy have not demonstrated any positive effect on patient survival.

The sensitivity of diffusion-weighted MR imaging to detect a lesion within 6 hours of stroke onset was approximately 90%. The false negative results were usually small lesions (1 ml), were seen early, and were usually located in the brain stem. The specificity of this technique was nearly 100% when it was used correctly. The volume and the value of the apparent diffusion coefficient of the detected lesions provided prognostic information. After injection of a contrast agent (perfusion imaging), a time series of volumes were obtained using a T2* sensitive gradient echo EPI sequence. Hemodynamic perturbations of the cerebral parenchyma could be detected as well as the type of perturbation in the lesion. A map representing the mean transit time for each voxel was used to define the maximum volume of the perturbation. A hemodynamic penumbra was defined to be when this volume was larger than the volume detected on the diffusion images. The quantitative measure of cerebral blood flow could predict the irreversibility of the lesions when the value was below 18 ml/min/100g, and the extension of the ischemia in the penumbra zone when the value was below a threshold of 30 ml/min/100g.

Three different deconvolution techniques for quantifying cerebral blood flow (CBF) from whole brain T*(2)-weighted bolus tracking images were implemented (parametric Fourier transform P-FT, parametric single value decomposition P-SVD and nonparametric single value decomposition NP-SVD). The techniques were tested on 206 regions from 38 hyperacute stroke patients. In the P-FT and P-SVD techniques, the tissue and arterial concentration time curves were fit to a gamma variate function and the resulting CBF values correlated very well (CBF(P-FT) = 1.02 x CBF(P-SVD), r(2) = 0.96). The NP-SVD CBF values (i.e., original unfitted curves were used) correlated well with the P-FT CBF values only when a sufficient number of time series volumes were acquired to minimize tracer time curve truncation (CBF(P-FT) x 0.92 x CBF(NP-SVD), r(2) = 0.88). The correlation between the fitted CBV and the unfitted CBV values was also maximized in regions with minimal tracer time curve truncation (CBV(fit) = 1.00 x CBV(unfit), r(2) = 0.89). When a sufficient number of time series volumes could not be acquired (due to scanner limitations) to avoid tracer time curve truncation, the P-FT and P-SVD techniques gave more reliable estimates of CBF than the NP-SVD technique.

The case of a 19-year old patient suffering of transient metamorphopsia restricted to familiar faces and familiar objects is reported. This clinical sign resulted from a small right occipitotemporal haemorrhage due to a sub-cortical metastasis. The patient claimed that faces are distorted and look more pleasant. There were neither visual field defects nor visual agnosia. MRI revealed a small high signal area in the right fusiform gyrus. The structural and functional aspects of the metamorphopsia are documented and discussed in relation to aperceptive prosopagnosia. More specifically, it is suggested that facial metamorphopsia and aperceptive prosopagnosia express the same underlying disorder differing only in terms of severity.