scholarly journals Giant axonal neuropathy: The first Iranian case with a variation in the gigaxonin gene and a glance to the other cases

2021 ◽  
Author(s):  
Mohammad Vafaee-Shahi ◽  
Saeideh Ghasemi ◽  
Masood Ghahvechi-Akbar ◽  
Leila Tahernia ◽  
Atefeh Davarzani ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Axonal Neuropathy ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Lower Limbs ◽  
Allelic Heterogeneity ◽  
Giant Axonal Neuropathy ◽  
Phenotypic Data ◽  
Her Family ◽  
Sensorimotor Polyneuropathy

Background: Giant axonal neuropathy (GAN) is a very rare fatal neurodegenerative disorder with clinical and allelic heterogeneity. The disease is caused by mutations in the GAN (gigaxonin) gene. Herein, we reported the clinical presentations and results of genetic analysis of the first Iranian GAN case. Methods: Phenotypic data were obtained by neurologic examination, brain magnetic resonance imaging (MRI), electromyography (EMG), electroencephalography (EEG), and sonography from the proband. Deoxyribonucleic acid (DNA) was isolated from peripheral blood leucocytes and whole exome sequencing (WES) was performed. The candidate variant was screened by Sanger sequencing in the proband and her family members. Results: The proband was a 7-year-old girl who was admitted with a chief complaint of ataxia, muscle weakness, delayed developmental milestones, and history of psychiatric disorders. She was very moody and had clumsy gait, decreased deep tendon reflexes (DTRs) of lower limbs, and kinky hair. The brain MRI revealed white matter abnormality. The EMG revealed that her disease was compatible with the chronic axonal type of sensorimotor polyneuropathy; however, her EEG was normal. Results of the WES revealed a homozygous variant; c.G778T:p.E260* in the GAN gene, indicating the GAN disorder. Conclusion: The present study affirmed GAN allelic heterogeneity and resulted in the expansion of the phenotypic spectrum of GAN pathogenic variants. Identification of more families with mutations in GAN gene helps to further understand the molecular basis of the disease and provides an opportunity for genetic counseling especially in the populations with a high degree of consanguineous marriage such as the Iranian population.

scholarly journals GALC mutations in Chinese patients with late-onset Krabbe disease: a case report

2019 ◽  
Author(s):  
Shunzhi Zhuang ◽  
Lingen Kong ◽  
Caiming Li ◽  
Likun Chen ◽  
Tingting Zhang
Keyword(s):  
Vision Loss ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Molecular Data ◽  
Krabbe Disease ◽  
Chinese Patients ◽  
Corticospinal Tracts ◽  
Magnetic Resonance Imaging Mri

Abstract Background: Krabbe disease (also known as globoid cell leukodystrophy) is an autosomal recessive neurodegenerative disorder caused by a deficiency of the enzyme -galactocerebrosidase (galactosylceramidase, GALC). The deficiency of GALC leads to accumulation of galactosylceramide and psychosine, the latter GALC substrate having a potential role in triggering demyelination. Typically, the disease has an infantile onset, with rapid deterioration in the first few months, leading to death before the age of 2 years. The late onset forms (late-infantile, juvenile, and adult forms) are rare with variable clinical outcomes, presenting spastic paraplegia as the main symptom. Case presentation: We recruited a family with two affected individuals. The proband (Patient 1), a 25-year-old male, was presented with slow progressive spastic gait disturbance and vision loss, suffering since the 5th year of life. His elder sister (Patient 2), became wheelchair-bound and demented at the age of 22 years. Brain magnetic resonance imaging (MRI) showed increased signal intensity in the white matter along with the involvement of the bilateral corticospinal tracts. GALC deficiency was confirmed by biochemical analysis. DNA sequencing revealed two mutations (c.865G>C: p. G289R and c.136G>T: p. D46Y) in GALC. The clinical characteristics, brain MRI, biochemical and molecular findings led to the diagnosis of Krabbe disease. Conclusion: Clinical and neuroimaged signs, positive enzymatic analysis and molecular data converged to definite diagnosis in this neurodegenerative disease.

Giant Axonal Neuropathy – a neurodegenerative disorder – a novel mutation in the GAN-Gen

2005 ◽  
Vol 36 (02) ◽  
Author(s):  
K Marquard ◽  
B Rautenstrauss ◽  
K Huehne ◽  
B Sasse ◽  
H Wörle ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Novel Mutation ◽  
Axonal Neuropathy ◽  
Giant Axonal Neuropathy

Giant Axonal Neuropathy in Siblings

2008 ◽  
Vol 39 (01) ◽  
Author(s):  
A Naussed ◽  
I Heidrich ◽  
I Schreyer ◽  
HJ Mentzel ◽  
U Brandl
Keyword(s):  
Axonal Neuropathy ◽  
Giant Axonal Neuropathy

scholarly journals Sirenomelia: two case reports

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Asiyeh Shojaee ◽  
Firooze Ronnasian ◽  
Mahdiyeh Behnam ◽  
Mansoor Salehi
Keyword(s):  
Case Reports ◽  
Three Dimensional ◽  
First Trimester ◽  
Mendelian Inheritance ◽  
Lower Limbs ◽  
Congenital Deformity ◽  
White Family ◽  
Her Family ◽  
Caudal Regression ◽  
History Of

AbstractBackgroundSirenomelia, also called mermaid syndrome, is a rare lethal multi-system congenital deformity with an incidence of one in 60,000–70,000 pregnancies. Sirenomelia is mainly characterized by the fusion of lower limbs and is widely associated with severe urogenital and gastrointestinal malformations. The presence of a single umbilical artery derived from the vitelline artery is the main anatomical feature distinguishing sirenomelia from caudal regression syndrome. First-trimester diagnosis of this disorder and induced abortion may be the safest medical option. In this report, two cases of sirenomelia that occurred in an white family will be discussed.Case presentationWe report two white cases of sirenomelia occurring in a 31-year-old multigravid pregnant woman. In the first pregnancy (18 weeks of gestation) abortion was performed, but in the third pregnancy (32 weeks) the stillborn baby was delivered by spontaneous vaginal birth. In the second and fourth pregnancies, however, she gave birth to normal babies. Three-dimensional ultrasound imaging showed fusion of the lower limbs. Neither she nor any member of her family had a history of diabetes. In terms of other risk factors, she had no history of exposure to teratogenic agents during her pregnancy. Also, her marriage was non-consanguineous.ConclusionThis report suggests the existence of a genetic background in this mother with a Mendelian inheritance pattern of 50% second-generation incidence in her offspring.

scholarly journals Coexistence of neuronal intranuclear inclusion disease and amyotrophic lateral sclerosis: an autopsy case

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Atsuhiko Sugiyama ◽  
Takahiro Takeda ◽  
Mizuho Koide ◽  
Hajime Yokota ◽  
Hiroki Mukai ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Repeat Expansion ◽  
Cerebellar Hemisphere ◽  
Intranuclear Inclusions ◽  
Intranuclear Inclusion ◽  
Neuronal Intranuclear Inclusion ◽  
Lateral Sclerosis

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS. Case presentation A 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient. Conclusions We describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes.

scholarly journals Explaining intermediate filament accumulation in giant axonal neuropathy

Rare Diseases ◽  
2013 ◽  
Vol 1 (1) ◽  
pp. e25378 ◽  
Author(s):  
Puneet Opal ◽  
Robert D. Goldman
Keyword(s):  
Intermediate Filament ◽  
Axonal Neuropathy ◽  
Giant Axonal Neuropathy

Generalized giant axonal neuropathy

1977 ◽  
Vol 40 (3) ◽  
pp. 213-218 ◽  
Author(s):  
J�rgen Peiffer ◽  
Wolfgang Schlote ◽  
Albert Bischoff ◽  
Eugen Boltshauser ◽  
G�nter M�ller
Keyword(s):  
Axonal Neuropathy ◽  
Giant Axonal Neuropathy

Abstract 14258: Modulation of Kynurenine Pathway to Prevent Brain Injury After Cardiac Arrest and Cardiopulmonary Resuscitation in Mice

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Aurora Magliocca ◽  
Carlo Perego ◽  
Francesca Motta ◽  
Giulia Merigo ◽  
Francesca M Fumagalli ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Neurological Outcome ◽  
Diffusion Tensor ◽  
Neuroprotective Effect ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Kynurenine Pathway ◽  
Baseline Heart Rate ◽  
Brain White Matter ◽  
Fluoro Jade B

Introduction: Kynurenine pathway (KP) is emerging as one of the potential components affecting cardiac arrest (CA) outcomes. The aim of this study is to evaluate the effects of KP inhibition through genetic deletion of the rate-limiting enzyme of the KP, indoleamine-2,3-dyoxygenase (IDO) on survival and neurological outcome after CA. Methods and Results: Sixteen adult male wild-type (WT) and IDO-deleted (IDO -/- ) mice were subjected to 8 min untreated CA followed by resuscitation. At baseline heart rate and mean arterial pressure (MAP) did not differ among groups. At the time of return of spontaneous circulation, 30 and 60 min later, MAP was higher in the IDO -/- group compared to the WT one (p=0.0005). IDO -/- mice showed higher survival compared to WT at 7 days after CA (68.5% in IDO -/- vs 37.5% in WT; log rank p=0.036). Neurological function was higher in IDO -/- than in WT mice during the 7 days following CA (p=0.0124). IDO -/- mice also showed an improved locomotor function compared to WT mice (p=0.037). Brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) sequences showed a reduction in fractional anisotropy in the external capsule of the corpus callosum in WT mice compared to IDO -/- mice at 7 days after resuscitation (p=0.015). We then treated additional IDO -/- mice with L-kyn 15 min before CA, to revert the IDO -/- phenotype. Brain MRI with diffusion-weighted imaging (DWI) sequences and histological analysis were performed 24h after CA in WT, IDO -/- , and IDO -/- +L-Kyn mice. Brain MRI revealed restriction of water diffusivity 24h after CA in WT mice. IDO-deletion reduced water diffusion abnormalities while the beneficial effect was reverted in the L-kyn group (p=0.01). Degenerating neurons in the frontal cortex, represented as Fluoro-Jade B positive cells, were more numerous in WT compared to IDO -/- mice; L-kyn halted this IDO deletion-induced reduction in degenerating cells (p=0.05). Conclusion: KP inhibition improves survival and neurological outcome after CA. The neuroprotective effect of IDO-deletion was associated with preservation of brain white matter microintegrity and with reduction of cerebral cytotoxic edema. Reversal of these beneficial effects by L-kyn administration in IDO -/- mice further confirm the KP role in CA outcome.

Yield of Brain Magnetic Resonance Imaging in Epilepsy Diagnosis from 1998 to 2020: A Large Retrospective Cohort Study

2021 ◽  
Author(s):  
Tomer Stern ◽  
Liora Kornreich ◽  
Hadassa Goldberg
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Focal Epilepsy ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Infantile Spasms ◽  
Mesial Temporal Sclerosis ◽  
Resonance Imaging ◽  
Brain Abnormalities ◽  
Epilepsy Diagnosis

Abstract Background We aimed to find the clinical significance of brain abnormalities on magnetic resonance imaging (MRI) in epilepsy and the lateralization of these findings with electroencephalogram (EEG). Methods We retrospectively analyzed the results of all EEGs and brain MRIs of 600 consecutive epilepsy patients from 1998 to 2020. Results Data were available for 563 cases (267 females). Ninety percent of the patients were 18 years old or younger. A total of 345 patients (61.3%) had focal epilepsy, 180 (32%), generalized, and 38 (6.7%), inconclusive. In 187 (33.2%), the first MRI was abnormal and in 81 (out of 108 repeated MRI), the second was pathological. The most frequent brain abnormalities were cortical dysplasia in 41 (18.1%), other structural abnormalities in 25 (11%), various phacomatoses in 23 (10.1%), and mesial temporal sclerosis in 17 (7.5%). Among 226 patients with abnormal MRI, 171 (75.6%) had focal epilepsy when compared with 36 (15.9%) with generalized epilepsy (p <0.001). In 121 patients (53.5%), the result of the abnormal MRI contributed significantly to the understanding of the epilepsy etiology. The side of abnormality was lateralized to the EEG focus in 120 cases (53%); in 10/15 cases with infantile spasms (66%), MRI was significantly abnormal. In 33, in whom the first MRI was normal, a second MRI revealed a significant abnormality. Conclusion Brain MRI is an important tool in epilepsy diagnosis, mainly in focal seizures and infantile spasms. A repeat MRI is mandatory in intractable focal cases to improve the yield of this test.

Pediatric Reversible Cerebral Vasoconstriction Syndrome: Two Unique Cases with a Review of all Reported Children

2021 ◽  
Author(s):  
Neelu Desai ◽  
Rahul Badheka ◽  
Nitin Shah ◽  
Vrajesh Udani
Keyword(s):  
Magnetic Resonance ◽  
Cerebral Arteries ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Reversible Cerebral Vasoconstriction Syndrome ◽  
Neurological Deficits ◽  
Cerebral Vasoconstriction ◽  
Magnetic Resonance Imaging Mri ◽  
Reversible Encephalopathy ◽  
Mr Angiogram

AbstractReversible cerebral vasoconstriction syndrome (RCVS) has been well described in adults, but pediatric cases are yet under recognized. We describe two children with RCVS and review similar already published pediatric cases. The first patient was a 10-year-old girl who presented with severe headaches and seizures 3 days after blood transfusion. Brain magnetic resonance imaging (MRI) showed changes compatible with posterior reversible encephalopathy syndrome and subarachnoid hemorrhage. Magnetic resonance angiogram showed diffuse vasoconstriction of multiple cerebral arteries. The second patient was a 9-year-old boy who presented with severe thunderclap headaches. Brain MRI showed isolated intraventricular hemorrhage. Computed tomography/MR angiogram and digital subtraction angiogram were normal. A week later, he developed focal neurological deficits. Repeated MR angiogram showed diffuse vasospasm of multiple intracranial arteries. Both children recovered completely. A clinico-radiological review of previously reported childhood RCVS is provided.

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