Caudate Atrophy Research Articles

Excessive blinking as an initial manifestation of juvenile Huntington’s disease

Juvenile Huntington's disease (JHD) is mostly characterized by rigidity, myoclonus, bradykinesia, dystonia and seizure. We report a 9-year-old male JHD patient presenting excessive blinking as the initial symptom two years prior to typical JHD symptoms. Genetic analysis revealed expansion of 108 CAG repeats and magnetic resonance imaging showed caudate atrophy with lateral ventricular enlargement.

P1-217: Automated 3D mapping of caudate atrophy and ventricular enlargement in Parkinson's disease with and without dementia

P1-217: Automated 3D mapping of caudate atrophy and ventricular enlargement in Parkinson's disease with and without dementia

IC-P2-072: Automated 3D mapping of caudate atrophy and ventricular enlargement in Parkinson's disease with and without dementia

IC-P2-072: Automated 3D mapping of caudate atrophy and ventricular enlargement in Parkinson's disease with and without dementia

Voxel-based morphometry reveals extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism

Objectives To determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients. Design Forty-three older PD patients (≥65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive and dopamine non-responsive signs) and neuropsychological testing (memory: California Verbal Learning Test (CVLT)) and a composite of index of executive function (EF): Stroop Interference, Trail Making Test Part B, and digit ordering. All underwent volumetric MRI scans analyzed using voxel-based morphometry (VBM). Group comparisons, and the correlations between MRI gray and white matter volume and motor and cognitive measures were controlled for age, sex and intracranial volume. Cerebellar volume was independently measured using a validated extraction method. Results Patients and controls were matched for demographics and global cognitive measures. VBM indicated significant gray matter (GM) atrophy in the cerebellum in PD and was confirmed independently. Poor memory was associated with GM atrophy in the left (uncus, middle temporal and fusiform gyri) and right temporal lobes and left putamen. Dopamine non-responsive motor signs and EF were associated with caudate atrophy. EF was also associated with GM atrophy in the middle temporal gyri, the left precuneus and cerebellum. Conclusions Cortical and striatal atrophy were associated with dopamine non-responsive motor signs and cognitive impairment and provide a morphologic correlate for progression of PD. Cerebellar atrophy was found in older PD patients.

Regional grey matter atrophy in clinically isolated syndromes at presentation

Background:The presence and degree of neuronal degeneration already existing in patients at their initial presentation with a clinically isolated syndrome suggestive of multiple sclerosis (CIS) is unclear, and whole brain...

Caudate Nucleus Atrophy Associated with HIV Encephalitis

Central nervous system infection with the human immunodeficiency virus (HIV) may be associated with neurological disease ranging from mild cognitive changes to dementia. Recent imaging studies have linked atrophy of the caudate nucleus with cognitive impairment in HIV infection. Here we report the neuropathological findings in a 43 year‐old man with HIV infection and altered mental status who died after an acute illness. General autopsy findings included cirrhosis of the liver, consistent with a history of hepatitis B and C infection, acute and chronic pancreatitis, mitral valvulopathy, and end‐stage kidney disease. Gross brain findings revealed mild frontal lobe atrophy, bilateral severe atrophy of the head and body of the caudate nucleus, and moderate diffuse ventricular enlargement. Microscopic sections identified numerous microglial nodules and p24 immunoreactive multinucleated giant cells throughout deep gray nuclei and white matter, consistent with HIV encephalitis (HIVE). Microscopic findings in the caudate nucleus revealed severe neuronal loss and astrocytosis, reminiscent of Huntington disease (HD) although the Vonsattel gradient of changes was not seen. Further pathological studies of the caudate nucleus in HIV infection may yield insights into the basis of cognitive deficits in HIVE and possibly other disorders of caudate atrophy associated with cognitive decline, such as HD.

Basophilic inclusion body disease and neuronal intermediate filament inclusion disease: a comparative clinicopathological study

While both neuronal intermediate filament inclusion disease (NIFID) and basophilic inclusion body disease (BIBD) show frontotemporal lobar degeneration and/or motor neuron disease, it remains unclear whether, and how, these diseases differ from each other. Here, we compared the clinicopathological characteristics of four BIBD and two NIFID cases. Atypical initial symptoms included weakness, dysarthria, and memory impairment in BIBD, and dysarthria in NIFID. Dementia developed more than 1 year after the onset in some BIBD and NIFID cases. Upper and lower motor neuron signs, parkinsonism, and parietal symptoms were noted in both diseases, and involuntary movements in BIBD. Pathologically, severe caudate atrophy was consistently found in both diseases. Cerebral atrophy was distributed in the convexity of the fronto-parietal region in NIFID cases. In both BIBD and NIFID, the frontotemporal cortex including the precentral gyrus, caudate nucleus, putamen, globus pallidus, thalamus, amygdala, hippocampus including the dentate gyrus, substantia nigra, and pyramidal tract were severely affected, whereas lower motor neuron degeneration was minimal. While alpha-internexin-positive inclusions without cores were found in both NIFID cases, one NIFID case also had alpha-internexin- and neurofilament-negative, but p62-positive, cytoplasmic spherical inclusions with eosinophilic p62-negative cores. These two types of inclusions frequently coexisted in the same neuron. In three BIBD cases, inclusions were tau-, alpha-synuclein-, alpha-internexin-, and neurofilament-negative, but occasionally p62-positive. These findings suggest that: (1) the clinical features and distribution of neuronal loss are similar in BIBD and NIFID, and (2) an unknown protein besides alpha-internexin and neurofilament may play a pivotal pathogenetic role in at least some NIFID cases.

Chorea-acanthocytosis in monozygotic twins: clinical findings and neuropathological changes as detected by diffusion tensor imaging, FDG-PET and 123I-β-CIT-SPECT

We report on two 33 years old monozygotic twins with chorea-acanthocytosis (ChAc) misdiagnosed as schizophrenia and Tourette syndrome, respectively. Although the patients shared several clinical similarities, there were also some clear differences: twin 1 presented initially with an acute episode of a paranoid schizophrenia, while twin 2 suffered from generalized epileptic seizures. In both twins, MRI demonstrated caudate nucleus atrophy and an increased apparent diffusion coefficient (ADC) in the striatum bilaterally with right sided predominance. (18)F-FDG PET showed bilaterally reduced glucose utilization in the striatum with clearly pronounced reduction on the right side compared to the left and in twin 1 compared to twin 2. Ratios of binding to striatal dopamine transporters (DAT) and serotonin transporters in the hypothalamus midbrain area as determined using (123)I-beta-CIT-SPECT fell within the normal ranges. However, in twin 1 a significant difference in binding to presynaptic DAT with marked reduction on the right hemisphere was observed. Right hemispheric accentuated changes measured by MRI, FDG-PET, and (123)I-beta-CITSPECT correspond to more severe hyperkinetic movements on the left part of the body in both twins. Different neuro-psychiatric features in this monocygotic twin pair suggest that not only genetic but also environmental factors contribute to the clinical symptomatology. Our findings suggest that the main neuropathological process in ChAc is located in the striatum, involving microstructural alterations, and disturbance of metabolism and dopaminergic neurotransmission.

Putaminal involvement in Rasmussen encephalitis

Rasmussen encephalitis (RE) is a rare devastating disease of childhood causing progressive neurological deficits and intractable seizures, typically affecting one hemisphere. Characteristic MRI features include progressive unihemispheric focal cortical atrophy and grey- or white-matter high-signal changes and basal ganglion involvement, particularly of the caudate nucleus. To analyse the pattern of involvement of different brain structures in a series of patients with RE and to attempt clinical correlation. We reviewed the medical records and neuroimaging data of 12 patients diagnosed with RE satisfying the European Consensus Statement diagnostic criteria. The disease manifested as seizures in all patients and was refractory; epilepsia partialis continua was a notable feature (nine patients). Hemiparesis of varying grades was noted in all but one patient; none had extrapyramidal signs. Neuroimaging showed cortical involvement in the insular/periinsular regions in 11 patients. Caudate atrophy was noted in ten patients. Putaminal atrophy was seen in nine patients, six of whom had additional hyperintense signal changes. Our study highlights frequent putaminal atrophy and signal changes in RE, which suggests a more extensive basal ganglion involvement than emphasized previously. Recognition of putaminal changes may be a useful additional tool in the radiological diagnosis of RE.

Assessment of simple movements reflects impairment in Huntington's disease

Clinical rating, caudate atrophy, disturbed movement performance, neuropsychological testing, and age-related genetic disease load (CAG index) are tools that reflect impairment after onset of Huntington's disease (HD). Objectives were to compare scored HD symptoms, results of neuropsychological testing and of instrumental measurement of simple motion sequences, assess caudate atrophy and CAG index, and investigate their relation to each other in 131 subjects of various HD stages. Caudate atrophy and CAG index significantly increased in advanced HD patients. Motor test results significantly differed between HD patients and 49 controls, but not between HD gene carriers and controls. Instrumental test outcomes, scored HD intensity, caudate atrophy, and CAG index significantly correlated to each other. Neuropsychological testing, which we only performed in the HD gene carriers and the previously untreated HD patients, reflected the early appearance of HD symptoms and correlated with the motor test results. Results of our applied instrumental tool measure impaired movement performance, which is not specific for HD, but reflects the various methods assessed and the slowly evolving symptoms of the degenerative process in HD.

IT15 Gene Analysis in Two Pedigrees of Huntington’s Disease

To investigate the relationship between the clinical features and (CAG)n trinucleotide repeats in two pedigrees of Chinese Huntington's disease (HD). Clinical and neuroimaging features, the age of disease onset and pattern of transmission of the patients were studied in the two pedigrees of HD. Genomic DNA of 42 family members was used for amplification of the (CAG)n repeats of IT15 gene by PCR. The numbers of (CAG)n were determined by electrophoresis through a 6% polyacrylamide gel and direct sequence analysis. Results showed that patients in pedigree 1 were absent of the typical triad of HD symptoms or caudate atrophy. A total of 9 (5 patients and 4 asymptomatic) out of 18 family members had 40-50 (CAG)n repeats in the IT15 gene. In pedigree 2, all the patients were characterized by a triad of symptoms, including motor disturbance, cognitive impairment and psychiatric features. Three patients and two asymptomatic relatives had more than 50 (CAG)n repeats in the IT15 gene. In conclusion, the clinical symptoms are partly determined by (CAG)n repeats in the IT15 gene. The age of onset was correlated with (CAG)n repeats over 50, and the phenomenon called "anticipation" was found to have played a role.

McLeod Syndrome: life-long neuropsychiatric disorder due to a novel mutation of the XK gene

A 50-year-old man presented with worsening, virtually lifelong, chorea and progressive behavioural disturbance, involving disinhibition and hoarding, over 10 years. Clinical assessment revealed chorea, dysarthria, areflexia, an inappropriately jovial, impulsive manner and neuropsychological evidence of frontosubcortical dysfunction. Investigation results included an elevated creatine kinase, caudate atrophy and hypoperfusion, acanthocytes in the peripheral blood and the McLeod phenotype. DNA studies demonstrated a single-base deletion at position 172 in exon 1 of the XK gene, giving rise to a premature stop codon at position 129 in exon 2.

The Clock Drawing Test: Diagnostic, Functional, and Neuroimaging Correlates in Older Medically Ill Adults

This study evaluated the clock drawing test (CDT), a screening test sensitive to executive function, in 70 elderly psychiatric consultation patients. The CDT was compared to the Mini-Mental Status Examination (MMSE) on associations with psychiatric diagnoses, disposition status and radiographic findings. CDT and MMSE were correlated, and scores differed across psychiatric subgroups. In multivariate analysis, only age and CDT predicted disposition status. A lower CDT score correlated with a higher intercaudate ratio, indicating greater caudate atrophy. These findings suggest that the CDT indicates underlying subcortical pathology and deficiencies in executive function important for self-care.

The Clock Drawing Test: Diagnostic, Functional, and Neuroimaging Correlates in Older Medically Ill Adults

This study evaluated the clock drawing test (CDT), a screening test sensitive to executive function, in 70 elderly psychiatric consultation patients. The CDT was compared to the Mini-Mental Status Examination (MMSE) on associations with psychiatric diagnoses, disposition status and radiographic findings. CDT and MMSE were correlated, and scores differed across psychiatric subgroups. In multivariate analysis, only age and CDT predicted disposition status. A lower CDT score correlated with a higher intercaudate ratio, indicating greater caudate atrophy. These findings suggest that the CDT indicates underlying subcortical pathology and deficiencies in executive function important for self-care.

Grey matter loss in relapsing–remitting multiple sclerosis: A voxel-based morphometry study

Global grey matter (GM) loss has been reported in multiple sclerosis (MS). We addressed the question of if and where GM loss is localized by means of optimized voxel-based morphometry, applied to MRI studies of 51 patients with clinically defined relapsing–remitting MS and 34 age-matched normal subjects, segmented into normal and abnormal brain tissues using a multiparametric approach. Segmented GM volumes were subsequently compared on a voxel-by-voxel basis to highlight regions of relative GM loss ( P < 0.05, corrected for multiple comparisons at AnCova). Additionally, localized differences in brain asymmetry between the MS and the control groups were assessed by comparing on a voxel-by-voxel basis maps of GM differences between the two hemispheres ( P < 0.05 corrected for multiple comparisons). In MS patients, GM volume was significantly decreased at the level of the left fronto-temporal cortex and precuneus, as well as of anterior cingulate gyrus and of caudate nuclei bilaterally. The only cortical region of significant GM loss in the right hemisphere was located in the postcentral area. Furthermore, GM loss regions were colocalized with increased GM asymmetries (Left < Right) in MS, confirming a preferential left-sided GM loss. Caudate atrophy correlated with lesion load, while no correlation between cortical regional GM loss and disease duration, clinical status or lesion load emerged. Our findings suggest that in RR-MS cortical GM reduction preferentially involves left fronto-temporal structures and deep GM, the latter correlating preferentially to global lesion load.

Differential effect of Huntington's and Parkinson's diseases in programming motor sequences of varied lengths

Parkinson's disease (PD) and Huntington's disease (HD) patients have difficulties executing sequential movements. Attention control and short-term memory probably play an important role in programming sequential movements. To investigate the contribution of these cognitive factors to programming and executing visuomotor sequences in HD and PD patients a computerized version of the Corsi Block Tapping-Test was employed. the performance of 11 patients with early stage PD, 11 HD patients with borderline to mild caudate atrophy and 20 healthy subjects was compared. The task was a reaction time task where targets were illuminated in groups of sequences increasing from 2 items to 5 items. Subjects reproduced the sequence (pressing the illuminated target) in the same order of appearance. Reaction Times and movement times were recorded. PD patients had increasing difficulties in programming and executing series greater than three components. HD patients did not differ significantly from the controls, although they showed a tendency to lose accuracy in the longer series. Both patient groups did not differ in their attention span. In PD although the spatial information may be well stored, they have difficulty accessing it when their attention is overloaded, leading to poor encoding and slow information processing. This process interferes with programming and execution of movement sequences. HD patients in the early stages of the illness seem to have more attention resources than PD patients, so that they start to show more problems in executing visuomotor sequences with longer movement sequences than PD patients.

Clinical and neuropathologic variation in neuronal intermediate filament inclusion disease

Recently described neuronal intermediate filament inclusion disease (NIFID) shows considerable clinical heterogeneity. To assess the spectrum of the clinical and neuropathological features in 10 NIFID cases. Retrospective chart and comprehensive neuropathological review of these NIFID cases was conducted. The mean age at onset was 40.8 (range 23 to 56) years, mean disease duration was 4.5 (range 2.7 to 13) years, and mean age at death was 45.3 (range 28 to 61) years. The most common presenting symptoms were behavioral and personality changes in 7 of 10 cases and, less often, memory loss, cognitive impairment, language deficits, and motor weakness. Extrapyramidal features were present in 8 of 10 patients. Language impairment, perseveration, executive dysfunction, hyperreflexia, and primitive reflexes were frequent signs, whereas a minority had buccofacial apraxia, supranuclear ophthalmoplegia, upper motor neuron disease (MND), and limb dystonia. Frontotemporal and caudate atrophy were common. Histologic changes were extensive in many cortical areas, deep gray matter, cerebellum, and spinal cord. The hallmark lesions of NIFID were unique neuronal IF inclusions detected most robustly by antibodies to neurofilament triplet proteins and alpha-internexin. NIFID is a neuropathologically distinct, clinically heterogeneous variant of frontotemporal dementia (FTD) that may include parkinsonism or MND. Neuronal IF inclusions are the neuropathological signatures of NIFID that distinguish it from all other FTD variants including FTD with MND and FTD tauopathies.

In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease.

To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Onset and rate of striatal atrophy in preclinical Huntington disease.

Huntington disease (HD) is characterized by striatal atrophy that begins long before the onset of motor symptoms. To determine when striatal atrophy begins, the extent and rate of atrophy before diagnosis of motor symptoms, and whether striatal atrophy can predict when symptom onset will occur. Caudate and putamen volumes were measured on MRI scans of 19 preclinical subjects with the HD gene expansion who were very far (9 to 20 years) from estimated onset, and on serial scans from 17 preclinical subjects, six of whom were diagnosed with HD within 5 years after the initial scan. Striatal volumes were significantly smaller for the subjects who were very far from estimated onset than for age-matched control subjects. Statistical models fit to the longitudinal data suggest that rate of caudate atrophy becomes significant when subjects are approximately 11 years from estimated onset and rate of putamen atrophy becomes significant approximately 9 years prior to onset. In the six incident cases, caudate and putamen were approximately one-third to one-half of normal volume at diagnosis, and caudate volume alone was able to predict with 100% accuracy those subjects who would be diagnosed within 2 years of imaging. Striatal atrophy begins many years prior to diagnosable HD, and assessment of atrophy on MRI may be very useful in both predicting HD onset and in tracking progression in future therapeutic trials in preclinical subjects.

Neuroacanthocytosis misdiagnosed as Huntington's disease: a case report

A patient with the typical features of neuroacanthocytosis is reported. Chorea, tics, personality changes and caudate atrophy on cranial MRI resulted in an erroneous diagnosis of Huntington's disease elsewhere. Attention to other features viz., absence of ocular motility disturbances, amyotrophy, areflexia, EMG evidence of axonopathy, raised serum creatinine phosphokinase (CPK) levels and the typical erythrocytic acanthocytosis enabled us to establish the correct diagnosis. The typical features of the disease as seen in the patient are discussed. In view of the implications for genetic counseling, careful clinical and laboratory evaluation is always warranted to exclude neuroacanthocytosis in all suspected cases of Huntington's disease.