Involvement Of Dentate Nuclei Research Articles

L-2-hydroxyglutaric aciduria - review of literature and case series.

The authors report two sisters with L2HGA from Pakistan born to consanguineous parents. The 15- and 17-year-old girls presented with psychomotor delay, seizures, ataxia, intentional tremors, and dysarthria. Both had normal anthropometric measurements for age. Exaggerated tendon reflexes and bilateral sustained ankle clonus were observed in addition to cerebellar signs. Urine organic acids analysis showed marked excretion of 2-hydroxyglutaric acid, chiral differentiation of 2-hydroxyglutaric acid showed it to be L2HGA. Brain MRI of the 15-year-old showed diffuse subcortical white matter changes evident by T2/FLAIR hyperintense signals bilaterally, particularly in the frontal region in the centripetal distribution with some diffusion restriction along involvement of globus pallidus. The characteristic MRI pattern raised the suspicion of L2HGA. Targeted L2HGDH sequencing identified a homozygous pathogenic variant, c.829C>T (p.Arg227*) in L2HGDH gene in both girls. Both parents were heterozygous carriers of the familial variant. Neuroradiological features of centripetal subcortical leukoencephalopathy with basal ganglia and dentate nuclei involvement are rather specific to L2HGA and should lead to further biochemical investigations to look for L2HGA and L2HGDH gene sequencing.

Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments.

We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy. We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aβ (amyloid-β) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups. The frequency of Aβ positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P<0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7, P=0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P=0.047). The lobar cerebellar group had a higher Aβ positivity (75% versus 28.6%, P=0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P=0.041) than the dentate group. Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.

POLR3A variants with striatal involvement and extrapyramidal movement disorder

Biallelic variants in POLR3A cause 4H leukodystrophy, characterized by hypomyelination in combination with cerebellar and pyramidal signs and variable non-neurological manifestations. Basal ganglia are spared in 4H leukodystrophy, and dystonia is not prominent. Three patients with variants in POLR3A, an atypical presentation with dystonia, and MR involvement of putamen and caudate nucleus (striatum) and red nucleus have previously been reported. Genetic, clinical findings and 18 MRI scans from nine patients with homozygous or compound heterozygous POLR3A variants and predominant striatal changes were retrospectively reviewed in order to characterize the striatal variant of POLR3A-associated disease. Prominent extrapyramidal involvement was the predominant clinical sign in all patients. The three youngest children were severely affected with muscle hypotonia, impaired head control, and choreic movements. Presentation of the six older patients was milder. Two brothers diagnosed with juvenile parkinsonism were homozygous for the c.1771-6C > G variant in POLR3A; the other seven either carried c.1771-6C > G (n = 1) or c.1771-7C > G (n = 7) together with another variant (missense, synonymous, or intronic). Striatal T2-hyperintensity and atrophy together with involvement of the superior cerebellar peduncles were characteristic. Additional MRI findings were involvement of dentate nuclei, hila, or peridentate white matter (3, 6, and 4/9), inferior cerebellar peduncles (6/9), red nuclei (2/9), and abnormal myelination of pyramidal and visual tracts (6/9) but no frank hypomyelination. Clinical and MRI findings in patients with a striatal variant of POLR3A-related disease are distinct from 4H leukodystrophy and associated with one of two intronic variants, c.1771-6C > G or c.1771-7C > G, in combination with another POLR3A variant.

Evaluation of clinical, neuroradiologic, and genotypic features of patients with L-2-hydroxyglutaric aciduria.

Aim:L-2-hydroxyglutaric aciduria is a slowly progressive neurometabolic disorder caused by an enzymatic deficiency of L-2-hydroxyglutarate dehydrogenase. Here, we aimed to evaluate the clinical, neuroradiologic, and genotypic characteristics of patients with L-2-hydroxyglutaric aciduria who were followed in our outpatient clinic.Material and Methods:Twenty-five patients with L-2-hydroxyglutaric aciduria were enrolled in the study. Data regarding demographic, clinical, and neuroradiologic findings and molecular analysis were evaluated retrospectively.Results:The mean age of patients at the time of diagnosis was 12.09±8.02 years, whereas the mean age at the time of the first symptoms was 39.47±29.96 months. Diagnostic delay was found as 9.95±7.78 years. Developmental delay, decrease in school success, and seizures were the most common initial symptoms; however, behavioral problems and seizures became more prominent in the disease course. At the time of diagnosis, mental retardation and at least one pathologic cerebellar finding were detected in all symptomatic patients. Three patients developed brain tumors. The most common neuroimaging findings were subcortical white matter changes and cerebellar dentate nucleus involvement. In one patient, there was only isolated basal ganglia involvement without white matter lesions. Patients with similar genotypic features exhibited different clinical and radiologic findings.Conclusion:Although clinical symptoms appear early in L-2-hydroxyglutaric aciduria, there is approximately a ten-year delay in diagnosis. In subjects in whom brain tumor is detected in early childhood, L-2-hydroxyglutaric aciduria should be considered in the differential diagnosis in the presence of mental retardation accompanied by developmental delay, cerebellar and pyramidal findings, and behavior disorders in a wide spectrum ranging from autism spectrum disorder to psychosis. In patients with L-2-hydroxyglutaric aciduria, incipient headache, tinnitus, altered consciousness, and seizures can be indicative of brain tumors.

Clinicoradiological Spectrum of L-2-Hydroxy Glutaric Aciduria: Typical and Atypical Findings in an Indian Cohort.

Context:Neurometabolic disorders form an important group of potentially treatable diseases. It is important to recognize the clinical phenotype and characteristic imaging patterns to make an early diagnosis and initiate appropriate treatment. L-2-hydroxy glutaric aciduria (L2HGA) is a rare organic aciduria with a consistent and highly characteristic imaging pattern, which clinches the diagnosis in most cases.Aims:The study aims to describe the clinical profile, magnetic resonance imaging (MRI) patterns, and outcome in a cohort of children with L2HGA and to assess the clinicoradiological correlation.Materials and Methods:This is a retrospective descriptive study done at the Department of Radiodiagnosis and Neurological Sciences of our institution. Clinical and radiological findings of children diagnosed with L2HGA over an 8-year period (2010–2017) were collected and analyzed. Descriptive statistical analysis of clinical and imaging data was performed.Results:There were six girls and four boys. A total of 14 MRI brain studies in 10 patients with the diagnosis were analyzed. MRI of all patients showed a similar pattern with extensive confluent subcortical white-matter signal changes with symmetrical involvement of dentate nuclei and basal ganglia. In two children who presented with acute decompensation, there was asymmetric cortical involvement and restricted diffusion, which are previously unreported. There was no significant correlation between the radiological pattern with the disease duration, clinical features, or course of the disease.Conclusion:MRI findings in L2HGA are highly consistent and diagnostic, which helps in early diagnosis, particularly in resource-constraint settings, where detailed metabolic workup is not possible. The article also describes novel clinical radiological profile of acute encephalopathic clinical presentation.

Clinical Value of Dorsal Medulla Oblongata Involvement Detected With Conventional Magnetic Resonance Imaging for Prediction of Outcome in Children With Enterovirus 71-Related Brainstem Encephalitis

Brainstem encephalitis is the most common neurologic complication after enterovirus 71 infection. The involvement of brainstem, especially the dorsal medulla oblongata, can cause severe sequelae or death in children with enterovirus 71 infection. We aimed to determine the prevalence of dorsal medulla oblongata involvement in children with enterovirus 71-related brainstem encephalitis (EBE) by using conventional magnetic resonance imaging (MRI) and to evaluate the value of dorsal medulla oblongata involvement in outcome prediction. Forty-six children with EBE were enrolled in the study. All subjects underwent a 1.5 Tesla MRI examination of the brain. The disease distribution and clinical data were collected. Dichotomized outcomes (good vs. poor) at longer than 6 months were available for 28 patients. Logistic regression was used to determine whether the MRI-confirmed dorsal medulla oblongata involvement resulted in improved clinical outcome prediction when compared with other location involvement. Of the 46 patients, 35 had MRI evidence of dorsal medulla oblongata involvement, 32 had pons involvement, 10 had midbrain involvement and 7 had dentate nuclei involvement. Patients with dorsal medulla oblongata involvement or multiple area involvement were significantly more often in the poor outcome group than in the good outcome group. Logistic regression analysis showed that dorsal medulla oblongata involvement was the most significant single variable in outcome prediction (predictive accuracy, 90.5%), followed by multiple area involvement, age and initial Glasgow Coma Scale score. Dorsal medulla oblongata involvement on conventional MRI correlated significantly with poor outcomes in EBE children, improved outcome prediction when compared with other clinical and disease location variables, and was most predictive when combined with multiple area involvement, Glasgow Coma Scale score and age.

Metronidazole Induced Encephalopathy: A Case Report Showing Devastating Course on Consecutive MR Imaging

: Metronidazole-induced encephalopathy is a rare neurologic adverse effect of an antibiotic drug ‘metronidazole’. Although it is usually reversible with immediate cessation of the drug, it can also be fatal when used continuously. Here, we present a 72- year-old female who was on metronidazole for a total of 46 consecutive days. Her initial MRI on the 22nd day of medication use revealed a typical involvement of the cerebellar dentate nuclei, corpus callosum splenium, and periaqueductal midbrain, suggesting metronidazole-induced encephalopathy. However, she continued the medication for another 24 days, until she revisited our emergency department with mental status change. Her consecutive MRI showed diffuse cerebral and brainstem involvement, as well as a more prominent involvement of the dentate nuclei and splenium. We present this case to highlight that it is possible for metronidazole-induced toxic encephalopathy to worsen without immediate withdrawal of the offending drug.

Parkinsonism and Tremor in a Patient with Plasmodium vivax Malaria.

BackgroundA 57-year-old male diagnosed with Plasmodium vivax malaria presented with a subacute onset of hand tremor, slowness, and gait difficulty.PhenomenologyA bilateral upper extremity kinetic tremor was seen, as well as a right upper extremity rigidity and body bradykinesia.Educational ValueParkinsonism and tremor are neurological manifestations that may occur in malaria as a result of globus pallidi and dentate nuclei involvement.

Parkinsonism and Tremor in a Patient with &lt;i&gt;Plasmodium vivax&lt;/i&gt; Malaria

<strong>Background:</strong> A 57-year-old male diagnosed with <em>Plasmodium vivax</em> malaria presented with a subacute onset of hand tremor, slowness, and gait difficulty. <strong>Phenomenology:</strong> A bilateral upper extremity kinetic tremor was seen, as well as a right upper extremity rigidity and body bradykinesia. <strong>Educational Value:</strong> Parkinsonism and tremor are neurological manifestations that may occur in malaria as a result of globus pallidi and dentate nuclei involvement.

MRI features of Langerhans cell histiocytosis in central nervous system in children

Objective To explore the MRI features of Langerhans cell histiocytosis (LCH) in central nervous system (CNS) in children. Methods Clinical and MRI data of 25 cases with LCH in CNS from three children's hospitals between January 2009 and December 2014 were retrospectively studied. All cases were confirmed by surgery or biopsy. All cases underwent non-contrast and contrast pituitary and/or cranial MRI examinations. The location, morphology, MRI signal and enhanced patterns of LCH lesions were observed and analyzed. Result A total of 17 cases had hypothalamic-pituitary LCH, with 2 of them complicated with pineal cyst, 2 complicated with brain parenchymal lesions, and one complicated with both pineal cyst and brain parenchymal lesions. MR images showed that neurohypophysis lost its original hyper-intensity on T1WI, and nodular or homogeneous thickening was seen in the pituitary stalks. Dura matter was involved in 3 cases, 2 of them had single lesion, and the other one got multiple lesions. Neoplasm in choroid plexus was seen in trigone of left lateral ventricles in one case. Three cases with pineal gland involved demonstrated cystic change. Four cases had gray matter involved, with cerebellar dentate nuclei involvement in 2 cases, and both thalamus and basal ganglia involvement in the other two cases. Three cases showed white matter involvement without obvious Virchow-Robin space enlargement and brain atrophy. Conclusions MR imaging of LCH in CNS shows certain specific characteristics. The diagnosis can be made comprehensively based on both clinic features and other imaging findings. Key words: Histiocytosis, Langerhans-cell; Magnetic resonance imaging; Diabetes insipidus, neurogenic

Reversible Inferior Colliculus Lesion in Metronidazole-Induced Encephalopathy

This is to present reversible inferior colliculus lesions in metronidazole-induced encephalopathy, to focus on the diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging. From November 2005 to September 2007, 8 patients (5 men and 3 women) were diagnosed as having metronidazole-induced encephalopathy (age range; 43-78 years). They had been taking metronidazole (total dosage, 45-120 g; duration, 30 days to 2 months) to treat the infection in various organs. Initial brain magnetic resonance imaging (MRI) were obtained after the hospitalization, including DWI (8/8), apparent diffusion coefficient (ADC) map (4/8), FLAIR (7/8), and T2-weighted image (8/8). Follow-up MRIs were performed on 5 patients from third to 14th days after discontinuation of metronidazole administration. Findings of initial and follow-up MRIs were retrospectively evaluated by 2 neuroradiologists by consensus, to analyze the presence of abnormal signal intensities, their locations, and signal changes on follow-up images. Initial MRIs showed abnormal high signal intensities on DWI and FLAIR (or T2-weighted image) at the dentate nucleus (8/8), inferior colliculus (6/8), corpus callosum (2/8), pons (2/8), medulla (1/8), and bilateral cerebral white matter (1/8). High-signal intensity lesions on DWI tended to show low signal intensity on ADC map (3/4), but in one patient, high signal intensity was shown at bilateral dentate nuclei on not only DWI but also ADC map. All the lesions in dentate, inferior colliculus, pons, and medullas had been resolved completely on follow-up MRIs in 5 patients, but in 1 patient of them, corpus callosal lesion persisted. Reversible inferior colliculus lesions could be considered as the characteristic for metronidazole-induced encephalopathy, next to the dentate nucleus involvement.

L-2-Hydroxyglutaric Aciduria and Brain Tumors in Children with Mutations in theL2HGDHGene: Neuroimaging Findings

L-2-Hydroxyglutaric aciduria (L-2-HGA, MIM 236792) is a rare autosomal recessive neurodegenerative disorder characterized by psychomotor delay, cerebellar and extrapyramidal signs and subcortical leukoencephalopathy with basal ganglia and dentate nuclei involvement. Mutations in the gene L2HGDH ( C14ORF160/DURANIN/) have been identified as causative for L-2-HGA. A feature disproportionally associated with L-2-HGA is the development of malignant brain tumors. In our cohort of 40 patients with L-2-HGA, two developed medulloblastoma and glioblastoma multiforme during the course of the disease. Two missense mutations in two patients were identified in the L2HGDH gene in exon 3 (c.292C-->T) and in exon 7 (c.887T-->A). Both mutations were present in the homozygous state. Serial MR imaging findings as well as MR spectroscopy imaging is reported in a patient who developed glioblastoma multiforme.

Dentate nuclei involvement in AIDS patients with CNS cryptococcosis: imaging findings with pathologic correlation.

Our goal was to describe the involvement of the dentate nuclei in AIDS patients with CNS cryptococcosis since this finding has not been emphasized in previous radiological literature. Plain and contrast-enhanced CT of the brain (10 and 10), MR studies (1 premortem and 1 postmortem), and autopsy findings in 11 AIDS patients with CNS cryptococcosis were reviewed. The imaging studies and pathological specimens were analyzed for signs of meningitis, presence of dilated Virchow-Robin spaces, gelatinous pseudocysts, cryptococcoma, ventriculomegaly, choroid plexus, and ependymal lesions. Five of 11 patients were found at autopsy to have macroscopically visible "cystic" lesions in the dentate nuclei that were not detected on CT (10 patients), but were seen on premortem MR (1 patient). Macroscopic supratentorial (basal ganglia, thalamic, midbrain) lesions were detected by CT in 5 of 11 patients and by MR in 2 of 2 patients. Enhancement of the leptomeninges was seen in only 1 patient by CT despite pathological evidence of cryptococcal meningitis in all 11 patients. Dilated Virchow-Robin spaces were seen in all 11 pathologic specimens and in the 2 MR studies but not on CT. Communicating hydrocephalus was detected by CT in two patients. CT scans of the brain underestimate infratentorial parenchymal cryptococcal disease. MR is a more sensitive procedure to evaluate cerebellar and brainstem cryptococcosis, including the dentate nuclei, which in our autopsy series was not an uncommon site to be infected with cryptococcal gelatinous pseudocysts.

Cerebellar Mutism after Posterior Fossa Surgery

A large midline posterior fossa medulluloblastoma and a cerebellar arteriovenous malformation with associated clot were moved with postoperative mutism. Mutism was immediate and resolved into an ataxic dysarthria with residual mild dysarthria at 3 months. The literature is reviewed, and the clinicopathological and neurophysiological data of cerebellar function in speech are discussed. Acute injury to the midportion of the cerebellum with or without dentate nuclear involvement can cause a spectrum of speech disturbances. The more widespread the injury to the midportion of the cerebellum with dentate nuclei involvement the greater the risk of developing postoperative mutism.

Cerebellar changes in 50 cases of Creutzfeldt-Jakob disease with emphasis on granule cell atrophy variant.

Cerebellar changes have been found in 41/50 cases of Creutzfeldt-Jakob disease. They were severe in 9 cases. We did not find significant correlation between the cerebellar symptoms and signs pointed out in clinical records and prominent cerebellar changes. The only exception consisted in dentate nucleus involvement which was more frequently related to those symptoms and signs. 5 of the cases with severe changes were characterized by predominant granule cell atrophy without kuru plaques. The mean age of death (56.0) was significantly lower in this variant than that of patients with other cerebellar changes (64.4) (p less than 0.01). The granule cell atrophy seems a distinct variant on the basis of age of death and pathological changes. However, it is not characterized by the presence of kuru plaques.