Dentate Nucleus Hyperintensity Research Articles

Cerebello-Cortical Alterations Linked to Cognitive and Social Problems in Patients With Spastic Paraplegia Type 7: A Preliminary Study.

Spastic paraplegia type 7 (SPG7), which represents one of the most common forms of autosomal recessive spastic paraplegia (MIM#607259), often manifests with a complicated phenotype, characterized by progressive spastic ataxia with evidence of cerebellar atrophy on brain MRI. Recent studies have documented the presence of peculiar dentate nucleus hyperintensities on T2-weighted images and frontal executive dysfunction in neuropsychological tests in SPG7 patients. Therefore, we decided to assess whether any particular MRI pattern might be specifically associated with SPG7 mutations and possibly correlated with patients' cognitive profiles. For this purpose, we evaluated six SPG7 patients, studying the cerebello-cortical network by MRI voxel-based morphometry and functional connectivity techniques, compared to 30 healthy control subjects. In parallel, we investigated the cognitive and social functioning of the SPG7 patients. Our results document specific cognitive alterations in language, verbal memory, and executive function in addition to an impairment of social task and emotional functions. The MRI scans showed a diffuse symmetric reduction in the cerebellar gray matter of the right lobule V, right Crus I, and bilateral lobule VI, together with a cerebral gray matter reduction in the lingual gyrus, precuneus, thalamus, and superior frontal gyrus. The evidence of an over-connectivity pattern between both the right and left cerebellar dentate nuclei and specific cerebral regions (the lateral occipital cortex, precuneus, left supramarginal gyrus, and left superior parietal lobule) confirms the presence of cerebello-cortical dysregulation in different networks involved in cognition and social functioning in SPG7 patients.

Novel genotype-phenotype and MRI correlations in a large cohort of patients with SPG7 mutations.

ObjectiveTo clinically, genetically, and radiologically characterize a large cohort of SPG7 patients.MethodsWe used data from next-generation sequencing panels for ataxias and hereditary spastic paraplegia to identify a characteristic phenotype that helped direct genetic testing for variations in SPG7. We analyzed MRI. We reviewed all published SPG7 mutations for correlations.ResultsWe identified 42 cases with biallelic SPG7 mutations, including 7 novel mutations, including a large multi-exon deletion, representing one of the largest cohorts so far described. We identified a characteristic phenotype comprising cerebellar ataxia with prominent cerebellar dysarthria, mild lower limb spasticity, and a waddling gait, predominantly from a cohort of idiopathic ataxia. We report a rare brain MRI finding of dentate nucleus hyperintensity on T2 sequences with SPG7 mutations. We confirm that the c.1529C>T allele is frequently present in patients with long-standing British ancestry. Based on the findings of the present study and existing literature, we confirm that patients with homozygous mutations involving the M41 peptidase domain of SPG7 have a younger age at onset compared to individuals with mutations elsewhere in the gene (14 years difference, p < 0.034), whereas c.1529C>T compound heterozygous mutations are associated with a younger age at onset compared to homozygous cases (5.4 years difference, p < 0.022).ConclusionsMutant SPG7 is common in sporadic ataxia. In patients with British ancestry, c.1529C>T allele represents the most frequent mutation. SPG7 mutations can be clinically predicted by the characteristic hybrid spastic-ataxic phenotype described above, along with T2 hyperintensity of the dentate nucleus on MRI.

Dechelation (Transmetalation): Consequences and Safety Concerns With the Linear Gadolinium-Based Contrast Agents, In View of Recent Health Care Rulings by the EMA (Europe), FDA (United States), and PMDA (Japan).

The issue of dechelation (transmetallation) in vivo after administration of the linear gadolinium-based contrast agents, and potential safety concerns, is considered on the basis of an extensive, focused literature review. Early indications of potential problems included the high level of excess ligand used in the formulation of 2 agents (indeed the 2 least stable thermodynamically) and interference with laboratory tests when blood was drawn from patients relatively soon after administration of these same agents. The advent of nephrogenic systemic fibrosis in the late 2000s raised additional major concerns.The correlation in 2014 of dentate nucleus hyperintensity on precontrast T1-weighted scans with multiple prior injections of linear gadolinium chelates, in patients with normal renal function, has driven subsequent research concerning dechelation of these agents in vivo. Unexpectedly high levels of gadolinium in the bone, skin, and liver have been found long term after administration, in animal models and in humans, although the latter data are limited. Bone may serve as a long-term reservoir, with a residual excretion phase for gadolinium after intravenous injection of the linear agents due to a subsequent slow release from bone. Many different patient populations could be vulnerable and potentially later develop clinical symptoms, although at this stage there are only limited data and small retrospective uncontrolled studies. Possible vulnerable populations include children, menopausal women, patients with osteoporosis (who are predisposed to fractures and often slow to heal or heal poorly), those receiving multiple doses, those with proinflammatory conditions, moderate renal dysfunction, or an undefined genetic predisposition. Of particular concern would be nephrogenic systemic fibrosis-like symptoms-including particularly pain and skin/joint symptoms, or disease related to the incorporation of gadolinium in hydroxyapatite in bone, in small subgroups of patients with a not yet defined propensity and/or cofactor. These concerns have led to withdrawal of the linear agents from the largest clinical market, Europe, with the exception of the hepatobiliary agents for delayed liver imaging, an indication that cannot be fulfilled by the current macrocyclic gadolinium chelates (for which these concerns do not apply).

Development of High Signal Intensity within the Globus Pallidus and Dentate Nucleus following Multiple Administrations of Gadobenate Dimeglumine.

Previous studies have evaluated various gadolinium based contrast agents and their association with gadolinium retention, however, there is a discrepancy in the literature concerning the linear agent gadobenate dimeglumine. Our aim was to determine whether an association exists between the administration of gadobenate dimeglumine and the development of intrinsic T1-weighted signal in the dentate nucleus and globus pallidus. In this single-center, retrospective study, the signal intensity of the globus pallidus, dentate nucleus, thalamus, and middle cerebellar peduncle was measured on unenhanced T1-weighted images in 29 adult patients who had undergone multiple contrast MRIs using exclusively gadobenate dimeglumine (mean, 10.1 ± 3.23 doses; range, 6-18 doses). Two neuroradiologists, blinded to the number of prior gadolinium-based contrast agent administrations, separately placed ROIs within the globi pallidi, thalami, dentate nuclei, and middle cerebellar peduncles on the last MR imaging examinations. The correlations between the globus pallidus:thalamus and the dentate nucleus:middle cerebellar peduncle signal intensity ratios with the number of gadolinium-based contrast agent administrations and cumulative dose were tested with either 1-tailed Pearson or Spearman correlations. A priori, P < .05 was considered statistically significant. Both the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncle ratios showed significant correlation with the number of gadolinium-based contrast agent administrations (r = 0.39, P = .017, and r = 0.58, P = .001, respectively). Additionally, the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncle ratios showed significant correlation with the cumulative dose of gadobenate dimeglumine (r = 0.48, P = .004, and r = 0.43, P = .009, respectively). Dentate nucleus hyperintensity was qualitatively present on the last MR imaging in 79.3%-86.2% of patients and in all patients who had received >10 doses. At high cumulative doses (commonly experienced by patients, for example, with neoplastic disease), gadobenate dimeglumine is associated with an increase in the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncles signal intensity ratios.

Isoniazid-Induced Facial Tics in a Patient on Hemodialysis

We report isoniazid (INH) induced tics in one male patient on hemodialysis at end-stage renal failure. He had pulmonary tuberculosis, accepted isoniazid, rifampin, ethambutol, pyrazinamide and rifampicin. He developed tics on both sides of the face. Surprisingly, he was also found the bilateral symmetrical frontal lobe and dentate nucleus hyperintensities on T2-weighted and T2 FLAIR MR imaging. After excluding other causes, INH induced neurological side effect was suspected so the drug was stopped, pyridoxine was added and hemoperfusion was applicated. Tics disappeared after 1 week.

Clinical aspects of neuroregression: our experience on batten disease.

Neuroregression in a child is an important clinical problem faced by a pediatric neurologist. Depending on the initial clinical features they can be broadly divided into grey matter disorders, white matter disorders or combined. The age of onset and the progression of symptoms also help us in further characterization. Involvement of other systems and neuroimaging findings helps us in formulating the differential diagnosis and guides us in the laboratory evaluation and selection of appropriate confirmatory tests. After brief discussion on the clinical approach to neuroregression, here I would like to present our experience with one of the important poliodystrophies in children- Neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinosis is a group of progressive neurodegenerative disorders characterized by accumulation of ceroid lipopigment in lysosomes in neurons and other cell types. Over a period of four years we have diagnosed 20 children with neuronal ceroid lipofucinosis. Of the 20 patients, 5 had infantile type and 15 had late-infantile neuronal ceroid lipofuscinosis. Diagnosis was confirmed by appropriate enzyme assay. Clinical presentation was quite varied. Common presenting features included refractory seizures, developmental delay/regression, and abnormal movements. Visual failure was not common in the present case series, and novel neuroimaging finding in the form of isolated dentate nucleus hyperintensities in PPT related neuronal ceroid lipofuscnioses was noted. During follow-up, all patients had a progressive downhill course and one patient died. Prenatal diagnosis could be offered to one family. Our experience suggests that infantile and late-infantile neuronal ceroid lipofuscinosis is not uncommon in this region of the country and the phenotype is different.

Sensory neuropathy, cataract and bilateral dentate nucleus hyperintensity in industrial solvent toxicity: a rare clinical and neuroimaging correlation

Sensory neuropathy, cataract and bilateral dentate nucleus hyperintensity in industrial solvent toxicity: a rare clinical and neuroimaging correlation

Clinico-investigative profile of infantile and late-infantile neuronal ceroid lipofuscinoses

Neuronal ceroid lipofuscinosis is a group of progressive neurodegenerative disorders characterized by accumulation of ceroid lipopigment in lysosomes in neurons and other cell types. This study is a retrospective review of charts of patients with a diagnosis of infantile and late-infantile neuronal ceroid lipofuscinosis seen between January 2009 and December 2011. Of the 16 patients, 5 had infantile type and 11 had late-infantile neuronal ceroid lipofuscinosis. Diagnosis was confirmed by appropriate enzyme assay. Clinical presentation was quite varied. Common presenting features included refractory seizures, developmental delay/regression, and abnormal movements. Visual failure was not common in the present case series, and novel neuroimaging finding in the form of isolated dentate nucleus hyperintensities were noted. During follow-up, all patients had a progressive downhill course and one patient died. Prenatal diagnosis could be offered to one family. This study suggests that infantile and late-infantile neuronal ceroid lipofuscinosis is not uncommon in this region of the country and the phenotype may be different.

Bilateral dentate nucleus hyperintensities

C. Metronidazole. Bilateral dentate nucleus hyperintensitiesJournal of Clinical NeuroscienceVol. 17Issue 11PreviewA 61-year-old man, six weeks following an orthotopic cardiac transplant for hypertrophic cardiomyopathy, presented with dysarthria, ataxia and confusion. On examination he was found to be dysarthric and to display dysmetria and dyssynergia on finger-nose testing, and markedly hypometric saccades to target. Gross truncal ataxia was present in the seated position and there was impairment of the visually enhanced vestibulo-ocular reflex. Assessment of power was normal throughout and sensory modalities including pin prick and vibration sense perception were intact. Full-Text PDF

Bilateral dentate nucleus hyperintensities

A 61-year-old man, six weeks following an orthotopic cardiac transplant for hypertrophic cardiomyopathy, presented with dysarthria, ataxia and confusion. On examination he was found to be dysarthric and to display dysmetria and dyssynergia on finger-nose testing, and markedly hypometric saccades to target. Gross truncal ataxia was present in the seated position and there was impairment of the visually enhanced vestibulo-ocular reflex. Assessment of power was normal throughout and sensory modalities including pin prick and vibration sense perception were intact.