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Journal of Neuropathology and... Mar 2009A pathologic hallmark of Huntington disease (HD) is the presence of intraneuronal aggregates of polyglutamine-containing huntingtin protein fragments. Monoclonal...
A pathologic hallmark of Huntington disease (HD) is the presence of intraneuronal aggregates of polyglutamine-containing huntingtin protein fragments. Monoclonal antibody 1C2 is a commercial antibody to normal human TATA-binding protein that detects long stretches of glutamine residues. Using 1C2 as a surrogate marker formutant huntingtin protein, we immunostained 19 HD cases, 10 normal controls, and 10 cases of frontotemporal degeneration with ubiquitinated inclusions as diseased controls. In the HD cases, there was consistent 1C2 immunoreactivity in the neocortex, striatum, hippocampus, lateral geniculate body, basis pontis, medullary reticular formation, and cerebellar dentate nucleus. The normal and diseased controls demonstrated 1C2 immunoreactivity only in the substantia nigra, locus coeruleus, and pituitary gland. Staining of 5 HD cases and 5 normal controls revealed a less consistent and less diagnostically useful morphologic immunoreactivity profile. These results indicate that widespread 1C2 immunoreactivity is present in diverse central nervous system areas in HD, and that in the appropriate setting, 1C2 staining can be a useful tool in the postmortem diagnosis of HD when neuromelanin-containing neuronal populations are avoided.
Topics: Adult; Aged; Antibodies, Monoclonal; Brain; Child; Female; Humans; Huntington Disease; Male; Middle Aged; Peptides
PubMed: 19225411
DOI: 10.1097/NEN.0b013e318198d320 -
Proceedings of the National Academy of... Jan 2006The posterior cingulate and the medial parietal cortices constitute an ensemble known as the posteromedial cortex (PMC), which consists of Brodmann areas 23, 29, 30, 31,...
The posterior cingulate and the medial parietal cortices constitute an ensemble known as the posteromedial cortex (PMC), which consists of Brodmann areas 23, 29, 30, 31, and 7m. To understand the neural relationship of the PMC with the rest of the brain, we injected its component areas with four different anterograde and retrograde tracers in the cynomolgus monkey and found that all PMC areas are interconnected with each other and with the anterior cingulate, the mid-dorsolateral prefrontal, the lateral parietal cortices, and area TPO, as well as the thalamus, where projections from some of the PMC areas traverse in an uninterrupted bar-like manner, the dorsum of this structure from the posteriormost nuclei to its rostralmost tip. All PMC regions also receive projections from the claustrum and the basal forebrain and project to the caudate, the basis pontis, and the zona incerta. Moreover, the posterior cingulate areas are interconnected with the parahippocampal regions, whereas the medial parietal cortex projects only sparsely to the presubiculum. Although local interconnections and shared remote connections of all PMC components suggest a functional relationship among them, the distinct connections of each area with different neural structures suggests that distinct functional modules may be operating within the PMC. Our study provides a large-scale map of the PMC connections with the rest of the brain, which may serve as a useful tool for future studies of this cortical region and may contribute to elucidating its intriguing pattern of activity seen in recent functional imaging studies.
Topics: Animals; Brain; Brain Mapping; Gyrus Cinguli; Macaca; Models, Biological; Neural Pathways; Neurons; Parietal Lobe; Radionuclide Imaging; Synaptic Transmission; Thalamus; Time Factors
PubMed: 16432221
DOI: 10.1073/pnas.0507729103 -
Annals of Rehabilitation Medicine Dec 2012Central pontine myelinolysis is a rare neurologic disorder that is defined by demyelination of longitudinally descending tracts and transversly crossing fibers in the...
Central pontine myelinolysis is a rare neurologic disorder that is defined by demyelination of longitudinally descending tracts and transversly crossing fibers in the basis pontis. Frequently observed clinical manifestations of this disorder include sudden weakness, dysphagia, loss of consciouness and locked-in syndrome. However, there have been a few studies that reported a benign course of this disease, which include cerebellar signs, such as ataxia, intention tremor, and dysarthria. Here we report on a 53-year-old male with a history of liver cirrhosis who showed the cerebellar type of central pontine myelinolysis. The patient was diagnosed with central pontine myelinolysis based on clinical presentations and magnetic resonance imaging findings after a liver transplantation. Conventional magenetic resonance imaging (MRI) revealed the preservation of the corticospinal tract and abnormal pontocerebellar fibers. However, these findings were not sufficient to define the pathophysiology of our patient. Electrophysiologic analysis and diffusion tensor imaging (DTI) were performed to investigate cerebellar signs in this case. Delayed central motor conduction time (CMCT) to the tibialis anterior muscle with transcranial magnetic stimulation (TMS) was observed, which indicated demyelination of the corticospinal tract. Also, diffusion tensor imaging showed abnormal pontocerebellar fibers, which might have been caused by cerebellar dysfunction in our patient. A combination of TMS and DTI was also used to determine the pathophysiology of this disease.
PubMed: 23342326
DOI: 10.5535/arm.2012.36.6.887 -
The American Journal of Pathology Jun 1989The neuritic plaque is a characteristic finding in Alzheimer's disease. A major component of the plaque core is a 4.2 kd polypeptide, amyloid beta-protein (ABP), which...
The neuritic plaque is a characteristic finding in Alzheimer's disease. A major component of the plaque core is a 4.2 kd polypeptide, amyloid beta-protein (ABP), which is derived from the C-terminus of a larger precursor protein (ABPP). The authors have studied the transcription of ABPP mRNA in the adult rat brain by Northern analysis and in situ hybridization, and report that the ABPP gene gives rise to essentially the same multitranscript family of mRNAs as in the human, and that differential transcription patterns exist between brain and kidney. Morphologically, ABPP mRNA is expressed ubiquitously in neurons of the fore and hindbrain. ABPP transcripts also are present less frequently in occasional glial cells and at moderate to low frequency in nonneural cell types, namely, the choroid plexus epithelium, ependymal cells, and leptomeningeal membranes. Neuronal transcripts are most abundant in cerebral cortical layers II and V, the pyramidal cell layer of the hippocampus, the olfactory cortex, nucleus basis pontis, cranial nerve nuclei, and, significantly, in Purkinje cells and cerebellar granule cells. Because the cerebellum is relatively uninvolved in Alzheimer's disease, these findings suggest that high intraneuronal expression of ABPP may be a necessary but not sufficient requirement for plaque formation.
Topics: Alzheimer Disease; Amyloid; Amyloid beta-Protein Precursor; Animals; Blotting, Northern; Brain; Male; Neurons; Nucleic Acid Hybridization; Protease Inhibitors; Protein Precursors; RNA, Messenger; Rats; Rats, Inbred Strains; Transcription, Genetic
PubMed: 2502926
DOI: No ID Found -
BMJ Case Reports Nov 2015Pituitary gland duplication is a particularly rare finding. Different theories have been proposed to explain its pathogenesis, however, this phenomenon is not yet...
Pituitary gland duplication is a particularly rare finding. Different theories have been proposed to explain its pathogenesis, however, this phenomenon is not yet totally understood. Recently, duplication of the pituitary gland (DPG)-plus syndrome has been described, associating DPG with other blastogenic defects. We present the clinical and imaging findings of a newborn girl with DPG, associated with multiple other midline anomalies, including a nasopharyngeal teratoma, palate cleft deformity, bifid nasal bridge, tongue and uvula, hypoplasia of the basis pontis and corpus callosum, duplication of the basilar artery and hypothalamic hamartoma. We describe our patient's multidisciplinary team approach and emphasise the importance of reporting upcoming cases, in order to give more insight into the understanding of this complex entity.
Topics: Abnormalities, Multiple; Cleft Palate; Female; Humans; Infant, Newborn; Nasopharyngeal Neoplasms; Pituitary Gland; Syndrome; Tomography, X-Ray Computed; Tongue; Treatment Outcome
PubMed: 26564114
DOI: 10.1136/bcr-2015-212416 -
Journal of Neurophysiology Feb 2006The paramedian pontine reticular formation contains the premotoneuronal cell groups that constitute the saccadic burst generator and control saccadic eye movements....
The paramedian pontine reticular formation contains the premotoneuronal cell groups that constitute the saccadic burst generator and control saccadic eye movements. Despite years of study and numerous investigations, the rostral portion of this area has received comparatively little attention, particularly the cell type known as long-lead burst neurons (LLBNs). Several hypotheses about the functional role of LLBNs in saccade generation have been proposed, although there is little information with which to assess them. To address this issue, I mapped and recorded LLBNs in the rostral pons to measure their discharge characteristics and correlate those characteristics with the metrics of the concurrent saccades. On the basis of their discharge and location, I identified three types of LLBNs in the rostral pons: excitatory (eLLBN), dorsal (dLLBN), and nucleus reticularis tegmenti pontis (nrtp) LLBNs. The eLLBNs, encountered throughout the pons, discharge for ipsilateral saccades in proportion to saccade amplitude, velocity, and duration. The dLLBNs, found at the pontomesencephalic junction, discharge maximally for ipsilateral saccades of a particular amplitude, usually <10 degrees , and are not associated with a particular anatomical nucleus. The nrtp LLBNs, previously described as vector LLBNs, discharge for saccades of a particular direction and sometimes a particular amplitude. The discharge of the eLLBNs suggests they drive motor neurons. The anatomical projections of the nrtp LLBNs suggest that their involvement in saccade production is less direct. The discharge of dLLBNs is consistent with a role in providing the "trigger" signal that initiates saccades.
Topics: Action Potentials; Adaptation, Physiological; Animals; Biological Clocks; Macaca mulatta; Male; Neural Inhibition; Neurons; Pons; Saccades; Time Factors; Visual Pathways
PubMed: 16236783
DOI: 10.1152/jn.00760.2005 -
Cancer Research and Treatment Apr 2015A 60-year-old woman presented with cerebellar signs including dysarthria and ataxia, after intravenous infusion of cisplatin-based chemotherapy. Several blood tests...
A 60-year-old woman presented with cerebellar signs including dysarthria and ataxia, after intravenous infusion of cisplatin-based chemotherapy. Several blood tests showed mild neutropenia, normocytic normochromic anemia, but no evidence of a marked hyponatremia. Brain magnetic resonance imaging with diffusion-weighted sequences showed hyper-intense signal abnormalities in the extrapontine region, sparing the basis pontis. Here, we report on the case of a patient with reversible cerebellar ataxia related to extrapontine myelinolysis without hyponatremia after treatment with cisplatin-based chemotherapy for cholangiocarcinoma and discuss the literature on cerebellar ataxia in patients who underwent recent chemotherapy for malignancy.
PubMed: 25358385
DOI: 10.4143/crt.2013.145 -
PloS One 2014Spinocerebellar ataxia type 2 (SCA2) is the second most frequent autosomal dominant inherited ataxia worldwide. We investigated the capability of magnetic resonance...
Spinocerebellar ataxia type 2 (SCA2) is the second most frequent autosomal dominant inherited ataxia worldwide. We investigated the capability of magnetic resonance imaging (MRI) to track in vivo progression of brain atrophy in SCA2 by examining twice 10 SCA2 patients (mean interval 3.6 years) and 16 age- and gender-matched healthy controls (mean interval 3.3 years) on the same 1.5 T MRI scanner. We used T1-weighted images and tensor-based morphometry (TBM) to investigate volume changes and the Inherited Ataxia Clinical Rating Scale to assess the clinical deficit. With respect to controls, SCA2 patients showed significant higher atrophy rates in the midbrain, including substantia nigra, basis pontis, middle cerebellar peduncles and posterior medulla corresponding to the gracilis and cuneatus tracts and nuclei, cerebellar white matter (WM) and cortical gray matter (GM) in the inferior portions of the cerebellar hemisphers. No differences in WM or GM volume loss were observed in the supratentorial compartment. TBM findings did not correlate with modifications of the neurological deficit. In conclusion, MRI volumetry using TBM is capable of demonstrating the progression of pontocerebellar atrophy in SCA2, supporting a possible role of MRI as biomarker in future trials.
Topics: Adult; Aged; Atrophy; Case-Control Studies; Disease Progression; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Mesencephalon; Middle Aged; Spinocerebellar Ataxias
PubMed: 24586758
DOI: 10.1371/journal.pone.0089410 -
Human Pathology Aug 1993Multifocal necrotizing leukoencephalopathy (MNL) is characterized by multiple, usually microscopic, foci of necrosis confined primarily to the white matter of the basis...
Multifocal necrotizing leukoencephalopathy (MNL) is characterized by multiple, usually microscopic, foci of necrosis confined primarily to the white matter of the basis pontis, but sometimes found elsewhere in the central nervous system. All 16 patients in whom we identified MNL had underlying immunosuppression, either naturally occurring or iatrogenic, including the acquired immunodeficiency syndrome (seven patients), acute leukemias (four patients), and lymphoma (one patient). One patient each had severe combined immunodeficiency, orthotopic liver transplantation, Shwachman-Diamond syndrome, and idiopathic thrombocytopenic purpura treated with high-dose steroids. Histologically, lesions of MNL show demyelination, spongiosis, axonal swelling, minimal histiocytic infiltrates, and frequent axonal calcification. Multifocal necrotizing leukoencephalopathy lesions were found in the pons of all patients, most commonly in the crossing pontocerebellar fibers, but often in the descending white matter tracts and rarely in the tegmentum. Three cases also showed nonpontine foci of MNL involving the white matter of the medulla, cerebellum, and cerebral hemispheres. Multifocal necrotizing leukoencephalopathy is a distinct entity usually localized to the basis pontis and is most consistently associated with immunosuppression, but as yet lacks other clearly defined clinical correlates.
Topics: Adult; Aged; Child, Preschool; Female; HIV Infections; HIV-1; Humans; Immune Tolerance; Leukoencephalopathy, Progressive Multifocal; Male; Middle Aged; Nervous System; Pons
PubMed: 8375859
DOI: 10.1016/0046-8177(93)90140-c -
Acta Neuropathologica Dec 2007Neuroimaging studies indicate reduced volumes of certain gray matter regions in survivors of prematurity with periventricular leukomalacia (PVL). We hypothesized that...
Neuroimaging studies indicate reduced volumes of certain gray matter regions in survivors of prematurity with periventricular leukomalacia (PVL). We hypothesized that subacute and/or chronic gray matter lesions are increased in incidence and severity in PVL cases compared to non-PVL cases at autopsy. Forty-one cases of premature infants were divided based on cerebral white matter histology: PVL (n = 17) with cerebral white matter gliosis and focal periventricular necrosis; diffuse white matter gliosis (DWMG) (n = 17) without necrosis; and "Negative" group (n = 7) with no abnormalities. Neuronal loss was found almost exclusively in PVL, with significantly increased incidence and severity in the thalamus (38%), globus pallidus (33%), and cerebellar dentate nucleus (29%) compared to DWMG cases. The incidence of gliosis was significantly increased in PVL compared to DWMG cases in the deep gray nuclei (thalamus/basal ganglia; 50-60% of PVL cases), and basis pontis (100% of PVL cases). Thalamic and basal ganglionic lesions occur almost exclusively in infants with PVL. Gray matter lesions occur in a third or more of PVL cases suggesting that white matter injury generally does not occur in isolation, and that the term "perinatal panencephalopathy" may better describe the scope of the neuropathology.
Topics: Brain; Brain Damage, Chronic; Cerebellar Nuclei; Comorbidity; Female; Gliosis; Globus Pallidus; Humans; Infant; Infant, Newborn; Leukomalacia, Periventricular; Male; Nerve Degeneration; Nerve Fibers, Myelinated; Neurons; Premature Birth; Prevalence; Thalamus
PubMed: 17912538
DOI: 10.1007/s00401-007-0295-5