Upregulation of Heat-Shock Protein (hsp)-27 in a Patient with Heterozygous SPG11 c.1951C>T and SYNJ1 c.2614G>T Mutations Causing Clinical Spastic Paraplegia.

We report a 49-year-old patient suffering from spastic paraplegia with a novel heterozygous mutation and analyzed the levels of heat shock proteins (hsp)-27, dopamine (DA), and its metabolites in their cerebrospinal fluid (CSF). The hsp27 protein concentration in the patient's CSF was assayed by an ELISA kit, while DA levels and its metabolites in the CSF, 3,4-dihydroxyphenylacetic acid (DOPAC), Cys-DA, and Cys-DOPA were measured by HPLC. Whole exome sequencing demonstrated SPG-11 c.1951C>T and novel SYNJ1 c.2614G>T mutations, both heterozygous recessive. The patient's DA and DOPAC levels in their CSF were significantly decreased (53.0 ± 6.92 and 473.3 ± 72.19, p < 0.05, respectively) while no differences were found in their Cys-DA. Nonetheless, Cys-DA/DOPAC ratio (0.213 ± 0.024, p < 0.05) and hsp27 levels (1073.0 ± 136.4, p < 0.05) were significantly higher. To the best of our knowledge, the c.2614G>T SYNJ1 mutation has not been previously reported. Our patient does not produce fully functional spatacsin and synaptojanin-1 proteins. In this line, our results showed decreased DA and DOPAC levels in the patient's CSF, indicating loss of DAergic neurons. Many factors have been described as being responsible for the increased cys-DA/DOPAC ratio, such as MAO inhibition and decreased antioxidant activity in DAergic neurons which would increase catecholquinones and consequently cysteinyl-catechols. In conclusion, haploinsufficiency of spatacsin and synaptojanin-1 proteins might be the underlying cause of neurodegeneration produced by protein trafficking defects, DA vesicle trafficking/recycling processes, autophagy dysfunction, and cell death leading to hsp27 upregulation as a cellular mechanism of protection and/or to balance impaired protein trafficking.

Breath-Hold Diving-Related Decompression Sickness with Brain Involvement: From Neuroimaging to Pathophysiology.

Central nervous system involvement related to decompression sickness (DCS) is a very rare complication of breath-hold diving. So far, it has been postulated that repeated dives with short surface intervals represent a key factor in the development of breath-holding-related DCS. We report the case of a breath-hold diver who, after repeated immersion, developed DCS with brain involvement. After treatment in a hyperbaric chamber, there was a clinical improvement in the symptoms. Magnetic resonance imaging of the brain showed hyperintense lesions in long-time repetition sequences (FLAIR, T2WI) in the left frontal and right temporal lobes. Diffusion-weighted imaging (DWI) sequences and the apparent diffusion coefficient (ADC) map were characteristic of vasogenic edema, allowing us to exclude the ischemic nature of the process. These findings, together with the acute clinical presentation, the resolution of lesions in evolutionary radiological controls and the possible involvement of blood-brain barrier/endothelial dysfunction in DCS, could suggest a new form of posterior reversible encephalopathy syndrome (PRES)-like presentation of DCS. This would represent a novel mechanism to explain the pathophysiology of this entity. We conducted a literature review, analyzing the pathophysiological and neuroimaging characteristics of DCS in breath-hold diving based on a case of this rare disease.

Antiseizure medication for brain metastasis-related epilepsy: Findings of optimal choice from a retrospective cohort.

OBJECTIVE: To analyze the prevalence of antiseizure medication (ASM) in patients with brain metastasis-related epilepsy (BMRE) treated with radiosurgery and the relationship between ASM and psychiatric comorbidity. MATERIAL AND METHODS: This is a cross-sectional observational design study with retrospective review of medical records of all patients with brain metastases treated with volumetric modulated arc therapy radiosurgery (VMAT-RS) between 2012 and 2018 in a tertiary oncology center. We included those patients with BMRE, analyzing the clinical and demographic data, with special attention to psychiatric comorbidities and the use of ASM. RESULTS: Of the 121 patients with brain metastases included for treatment with VMAT-RS, a total of 38 presented BMRE. The most widely used ASM as first-line treatment was levetiracetam (89%). Only 8% of the patients received sodium channel blockers. The most common psychiatric comorbidity was depression (42.1%). CONCLUSIONS: Levetiracetam is the most widely used ASM in patients with BMRE treated with VMAT-RS. Nevertheless, common psychiatric comorbidities in this population might change the decision-making of ASM choice.

Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A.

We aimed to determine if an adolescent patient presenting with neurological impairment has xeroderma pigmentosum (XP). For this purpose, whole-exome sequencing was performed to assess mutations in XP genes. Dermal fibroblasts were established from a skin biopsy and XPA expression determined by immunoblotting. Nucleotide excision repair (NER) capacity was measured by detection of unscheduled DNA synthesis (UDS) in UVC-irradiated patient fibroblasts. Genetic analysis revealed two recessive mutations in XPA, one known c.682C>T, p.Arg228Ter, and the other c.553C>T, p.Gln185Ter, only two cases were reported. XPA protein was virtually undetectable in lysates from patient-derived fibroblast. The patient had significantly lower UV-induced UDS (3.03 ± 1.95%, p < 0.0001) compared with healthy controls (C5RO = 100 ± 12.2; C1UMN = 118 ± 5.87), indicating significant NER impairment. In conclusion, measurement of NER capacity is beneficial for the diagnosis of XP and in understanding the functional impact of novel mutations in XP genes. Our findings highlight the importance of neurologists considering XP in their differential diagnosis when evaluating patients with atypical neurodegeneration.

Erdheim-Chester disease mimicking multiple sclerosis or a new association?

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis that presents potential impairment of the central nervous system (CNS). Frequent CNS impairment makes ECD a disease worth considering in the differential diagnosis of multiple sclerosis (MS). We report the case of a patient initially diagnosed with relapsing-remitting MS with an atypical course who developed ECD during the disease progression. Given the patient's clinical-radiological characteristics, two diagnostic possibilities were proposed: the coexistence of both diseases or a new presentation of ECD mimicking MS. We conducted a literature review, analyzing the various diagnostic and therapeutic possibilities.

Encoding deficits in low-educated individuals with non-amnestic Mild Cognitive Impairment. Analysis of memory processes using the Item Specific Deficit Approach.

This work aims to analyze encoding impairments using new assessment scores in patients with naMCI who present to memory clinics with subjective cognitive complaints. The sample included 102 participants, of whom 28 were classified as healthy controls (HC), 24 as amnestic MCI (aMCI), 24 as naMCI and 26 patients as Alzheimer's disease (AD). Research outcomes were the Encoding, Consolidation and Retrieval deficit indices from the Item Specific Deficit Approach, and traditional indices (immediate total recall, delayed cued recall, delayed total recall) derived from the Free and Cued Selective Reminding Test (FCSRT). We found no differences in immediate recall or delayed recall between HC and naMCI on the FCSRT, both scoring higher than aMCI and AD. naMCI showed encoding deficits in between HC and aMCI, with no differences between naMCI and HC on consolidation or retrieval deficit indices. The ISDA indices were better than traditional indices to discriminate between HC and naMCI (sensitivity: 70.8%, specificity: 78.6%), whereas the opposite pattern was found between naMCI and aMCI (sensitivity: 70.8%, specificity: 91.7%). New indices derived from neuropsychological tests may help to identify objective memory impairments in naMCI. Whether these new indices are useful for predicting conversion to AD needs further research.

A Well-Tolerated and Effective Antiepileptic Drug for Patients With Myasthenia Gravis at Last?

Antiepileptic drugs have been known to worsen myasthenia gravis (MG) symptoms, and therefore, in patients who suffer both conditions (myasthenia and epilepsy), treatment selection is difficult. We report 2 cases of patients with MG who were safely treated with lacosamide. Evidence about antiepileptic drug treatment and adverse effects in MG is reviewed.