OBJECTIVETo report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) who acutely developed a hypokinetic-rigid syndrome.
METHODSPatient data were obtained ...from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. I-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum.
RESULTSWe report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS–CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment.
CONCLUSIONThis case study provides clinical and functional neuroimaging evidence to support that SARS–CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.
Neuroinflammation is a common feature in Alzheimer’s (AD) and Parkinson’s (PD) disease. In the last few decades, a testable hypothesis was proposed that protein-unfolding events might occur due to ...neuroinflammatory cascades involving alterations in the crosstalk between glial cells and neurons. Here, we tried to clarify the pattern of two of the most promising biomarkers of neuroinflammation in cerebrospinal fluid (CSF) in AD and PD. This study included cognitively unimpaired elderly patients, patients with mild cognitive impairment, patients with AD dementia, and patients with PD. CSF samples were analyzed for YKL-40 and C-reactive protein (CRP). We found that CSF YKL-40 levels were significantly increased only in dementia stages of AD. Additionally, increased YKL-40 levels were found in the cerebral orbitofrontal cortex from AD patients in agreement with augmented astrogliosis. Our study confirms that these biomarkers of neuroinflammation are differently detected in CSF from AD and PD patients.
Late onset distal myopathy: A new telethoninopathy Blanco-Palmero, Víctor Antonio; Hernández-Laín, Aurelio; Uriarte-Pérez de Urabayen, David ...
Neuromuscular disorders : NMD,
January 2019, 2019-01-00, Letnik:
29, Številka:
1
Journal Article
Recenzirano
•A patient with a novel homozygous mutation in TCAP (c.256C > T) is described.•First report of telethonin defficiency presenting as late onset distal myopathy.•NGS techniques are expanding the ...clinical spectrum of a large number of myopathies.
Background
The SORL1 gene encodes a type‐I transmembrane protein termed sortilin‐related receptor (SorLA). SorLA regulates the intracellular transport and processing of the amyloid precursor protein ...in neurons, and therefore, it has been implicated in the pathogenesis of Alzheimer’s disease (AD). Several SORL1 mutations have been described as a risk factor for AD, especially rare missense and non‐coding variants. To date, there are no reports of nonsense SORL1 mutations in homozygosis. Also, the relationship between cerebral amyloid angiopathy (CAA) and SORL1 mutations is not well established.
Method
Case report.
Results
A 62‐year‐old man was referred to our department complaining of a 3‐year history of apathy, memory complaints and spatial difficulties. His family history was remarkable for early onset dementia in his father and behavioural problems in his mother starting at the age of 80. Neuropsychological testing showed moderate episodic memory impairment, mild ideomotor apraxia and mild dysexecutive symptoms. The MRI showed marked global atrophy, superficial siderosis and multiple cortico‐subcortical microhemorrhages, fulfilling Boston criteria for probable CAA. Genetic testing using whole exome revealed the variant c.364C>T (p.R122*) in SORL1 gene (NM_003105.5) in homozygosis. In addition, APOE genotype was 3/3.
Conclusion
we describe a novel SORL1 mutation associated with AD. This is the first human report of a SORL1 nonsense mutation in homozygosis. SORL1 could play a role in the development of CAA.
Abstract
Background
The
SORL1
gene encodes a type‐I transmembrane protein termed sortilin‐related receptor (SorLA). SorLA regulates the intracellular transport and processing of the amyloid precursor ...protein in neurons, and therefore, it has been implicated in the pathogenesis of Alzheimer’s disease (AD). Several
SORL1
mutations have been described as a risk factor for AD, especially rare missense and non‐coding variants. To date, there are no reports of nonsense
SORL1
mutations in homozygosis. Also, the relationship between cerebral amyloid angiopathy (CAA) and
SORL1
mutations is not well established.
Method
Case report.
Results
A 62‐year‐old man was referred to our department complaining of a 3‐year history of apathy, memory complaints and spatial difficulties. His family history was remarkable for early onset dementia in his father and behavioural problems in his mother starting at the age of 80. Neuropsychological testing showed moderate episodic memory impairment, mild ideomotor apraxia and mild dysexecutive symptoms. The MRI showed marked global atrophy, superficial siderosis and multiple cortico‐subcortical microhemorrhages, fulfilling Boston criteria for probable CAA. Genetic testing using whole exome revealed the variant c.364C>T (p.R122*) in
SORL1
gene (NM_003105.5) in homozygosis. In addition,
APOE
genotype was 3/3.
Conclusion
we describe a novel
SORL1
mutation associated with AD. This is the first human report of a
SORL1
nonsense mutation in homozygosis.
SORL1
could play a role in the development of CAA.
To assess the feasibility and effects on manual dexterity and the quality of life (QoL) of a 12-week home calligraphic training program in patients with Parkinson's disease (PD).
A pilot study with ...participants recruited from the Movement Disorders consultation at the Hospital 12 de Octubre (Madrid). The main outcome, manual dexterity, was assessed using the Purdue Pegboard Test (PPT). Secondary outcomes included clinical rating scales that contemplate aspects related to manual dexterity (DextQ-24, UPDRSII, UPDRSIII), and QoL (PDQ-39 and EuroQoL-5D).
Thirty PD patients (57% males) with a mean age of 66.11 (9.76) years and 93% adherence rate. The PPT scores improved significantly (p < 0.0001) from T0 (start of the study) to T1 (after 24 weeks). No statistically significant change was found in DextQ-24, UPDRS-II and UPDRS-III, but a clear improvement was observed in the QoL measurement: EuroQoL-5D (p < 0.0001), PDQ-39 (p < 0.0001) and modified PDQ-39 (p = 0.022).
This is the first study to demonstrate the feasibility and improvement in hand dexterity assessed by the PPT for patients diagnosed with PD after a 12-week home calligraphic training program. A significant improvement was noted in the QoL measurements, such as the PDQ-39, modified PDQ-39, and EuroQoL-5D.
Implications for Rehabilitation
Most patients with Parkinson's disease suffer from impaired manual dexterity, making it difficult to perform activities of daily living such as eating, buttoning, or shaving.
A 12-week home calligraphic training program could improve hand dexterity in these patients.
The advantage of this home calligraphic trainingis is that it is an easy-to-perform, low-cost and no side effects.
This training also improves their quality of life.
Objective:
SQSTM1-variants associated with frontotemporal lobar degeneration have been described recently. In this study, we investigated a heterozygous in-frame duplication c.436_462dup p. ...(Pro146_Cys154dup) in the SQSTM1 gene in a family with a new phenotype characterized by a personality disorder and behavioral variant frontotemporal dementia (bvFTD). We review the literature on frontotemporal dementia (FTD) associated with SQSTM1. Methods: The index case and relatives were described, and a genetic study through Whole Exome Sequencing was performed. The literature was reviewed using Medline and Web of Science. Case reports, case series, and cohort studies were included if they provided information on SQSTM1 mutations associated with FTD. Results: Our patient is a 70-year-old man with a personality disorder since youth, familial history of dementia, and personality disorders with a 10-year history of cognitive decline and behavioral disturbances. A diagnosis of probable bvFTD was established, and the in-frame duplication c.436_462dup in the SQSTM1 gene was identified. Segregation analysis in the family confirmed that both affected sons with personality disorder were heterozygous carriers, but not his healthy 65-year-old brother. A total of 14 publications about 57 patients with SQSTM1-related FTD were reviewed, in which the bvFTD subtype was the main phenotype described (66.6%), with a predominance in men (63%) and positive family history in 61.4% of the cases. Conclusions: We describe a heterozygous in-frame duplication c.436_462dup p.(Pro146_Cys154dup) in the SQSTM1 gene, which affects the zinc-finger domain of p62, in a family with a personality disorder and bvFTD, expanding the genetics and clinical phenotype related to SQSTM1.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or ...family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene.
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