Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085632 (apathy)
 4,089 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deliberately increasing the number of hematopoietic stem and progenitor cells in the circulation allows faster and more efficient collection of sufficient cells for transplantation in both the allogeneic and autologous settings. These mobilized stem cells, when transplanted, provide quicker hematopoietic recovery for the patient than do nonmobilized blood stem cells or steady-state marrow-derived stem cells. Currently used clinical procedures to produce stem cell mobilization include administration of G-CSF or GM-CSF, either as single agents or in combination with myelosuppressive chemotherapy. Some autologous blood stem cell donors exhibit indifference to currently applied mobilization therapies. This failure to mobilize has been associated with prior stem cell toxic therapy, e.g., radiation therapy and chemotherapy, but the association is incomplete. The observation that occasional normal donors have failed to respond to mobilization therapy indicates that factors other than stem cell damage could also be involved. Recently, a murine model has provided evidence that a circulating factor inhibits mobilization in some settings. Preliminary investigations have suggested that a circulating factor may inhibit mobilization of human hematopoietic progenitor cells in some instances. Studies to identify this factor(s) are underway. The mechanisms of blood stem cell mobilization are still poorly understood and there continues to be the potential to improve this process.
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PMID:Mobilization of blood stem cells. 1101 56

We described the major diagnostic difficulties encountered in the case of a 25-year-old man with the pathological diagnosis of a germinoma. The patient initially developed an eating disorder at the end of 2003 and a character change ensued since the beginning of 2004. On admission in August 2004, his cardinal symptoms and signs included marked apathy, depersonalization, generalized muscle wasting, and decreased tendon reflexes. Brain T2-weighted (T2-WI) MR and FLAIR images showed high signal intensities in the suprasellar region and at the genu of the corpus callosum that extended along the sub-pia mater of the right anterior horn. These lesions showed mild enhancement on gadolinium-enhanced T1-WI. CSF examination revealed a mildly elevated level of protein and increased cell counts but did not show any malignant cells on repeated spinal tap. The patient's status remained practically unchanged till December 2004 when he developed diabetes insipidus. Soon afterward, the patient collapsed into akinetic mutism and developed corresponding new lesions at the tegmentum of the midbrain. These new lesions disappeared spontaneously and akinetic mutism regressed without any specific therapy. We tentatively diagnosed of neurosarcoidosis based on a characteristic progressive-regressive clinical course, CSF data, and radiological findings. Clinical symptoms and the enhanced masses on MRI were highly responsive to steroid therapy after which the patient was able to return home. However, disturbances in consciousness and tenacious vomiting recurred in September. Brain MRI revealed a markedly re-enlarged and easily enhanced mass at the right anterior horn, which extended into the cerebral aqueduct and resulted in obstructive hydrocephalus. On surgery, histopathological investigation revealed germinoma. This case highlights the need for careful discrimination between a slow growing germinoma and chronic granulomatous diseases of the brain such as neurosarcoidosis. Early histological investigation may be warranted in patients who present difficulties during differential diagnoses.
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PMID:[Germinoma presenting with personality and socio-behavioral abnormalities may challenge differential diagnoses]. 1871 99

A consecutive series of 79 patients with probable Alzheimer's disease were assessed with a structured psychiatric evaluation, and diagnoses of apathy and depression were made using standardized criteria. Three-dimensional MRI scans were obtained from all patients, and images were segmented into gray matter, white matter, and CSF. White matter hyperintensities were edited on segmented images, and lobar assignments (frontal, temporal, parietal, and occipital) were made based on Talairach coordinates. Patients with apathy showed a significantly larger volume of frontal white matter hyperintensities than patients without apathy. Patients with depression had a significantly larger volume of right parietal white matter hyperintensities than patients without depression. However, neither apathy nor depression was significantly associated with lobar gray or white matter atrophy. Frontal and right parietal white matter hyperintensities are the strongest brain structural correlates of apathy and depression in Alzheimer's disease.
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PMID:Neuroimaging correlates of apathy and depression in Alzheimer's disease. 1977 4

Mutations in the presenilin 1 (PSEN1) gene are the most frequent cause of familial Alzheimer's disease (AD), with at least 182 different mutations published to date. We report a 48-year-old woman (age at onset 47 years) who presented a progressive alteration of episodic memory, spatial disorientation, apathy, language disturbances and neglect of personal care. Her MMSE score was 20/30. The patient presented an unusually rapid deterioration and at 6 months follow-up her cognitive and functional status had worsened considerably (MMSE score of 11). Cranial MRI showed a bilateral atrophy with temporal and parietal predominance and the quantification of AD CSF biomarkers showed the typical AD signature. Family history evidenced an autosomal dominant pattern of inheritance. Mutational screening was performed by direct sequencing of exons 3-12 of PSEN1. The patient presented the 3/3 APOE genotype. Genetic analysis revealed a nucleotide substitution in exon 7 of PSEN1 gene, producing a missense mutation in codon 235 from leucine amino acid to arginine (L235R). This amino acid is conserved between presenilin-1 and presenilin-2 proteins. The L235R mutation had not been previously reported, although other mutations in the same residue have also been associated with familial early-onset AD, providing support for the importance of this residue for the presenilin-1 function.
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PMID:A novel PSEN1 gene mutation (L235R) associated with familial early-onset Alzheimer's disease. 2150 61

Behavioural variant frontotemporal dementia (bvFTD) is a clinically, genetically and pathologically heterogeneous neurodegenerative disorder caused by FTLD-tau, FTLD-TDP and FTLD-FUS pathologies. Clinically, patients present with behavioural symptoms that may include one or more of disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative, stereotyped and compulsive/ritualistic behaviour or hyperorality/dietary changes. Cognitive deficits, particularly executive dysfunction, are also seen. Neuroanatomically, patients have frontal and/or temporal lobe atrophy on neuroimaging. However, there is currently no clear correlation between the clinical and neuroanatomical phenotype in life and the underlying pathogenetics. With the advent of clinical trials in bvFTD, establishing the underlying pathology accurately during life will become increasingly important. This review therefore investigates current and future biomarkers that may help make a pathological diagnosis in life, i.e. bvFTD-tau, bvFTD-TDP and bvFTD-FUS, including clinical and neuropsychological data, neuroimaging, blood and CSF markers.
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PMID:Behavioural variant frontotemporal dementia--defining genetic and pathological subtypes. 2155 74

Sporadic Creutzfeldt-Jakob disease (sCJD) generally manifests itself by cognitive or rapidly progressive motor symptoms. An atypical onset or an unusual evolution may delay the diagnosis. Among patients with a confirmed diagnosis of sCJD following a post-mortem neuropathological examination at the Neuropathology Centre of Lille, France, those who had presented with atypical cognitive disorders at onset were included in the study. Four patients were included. The first patient (64-years-old) presented early language disorders, later accompanied by apathy and behavioral disorders. The prolonged course suggested a diagnosis of progressive primary aphasia. The second patient (68-years-old) presented with aphasia, apraxia, and ataxia of the right upper limb with parkinsonian syndrome, suggesting corticobasal degeneration. In the two last patients (58- and 61-years-old), the onset was marked by an anxiety-depression syndrome, falls, visual hallucinations, extra-pyramidal syndrome, and fluctuating cognitive decline. The diagnosis raised was probable Lewy body dementia. The 14.3.3 protein was found in two of the four cases. The clinical elements found may initially suggest focal atrophy or Lewy body dementia. A very rapid clinical deterioration generally suggests sCJD, but in the last case, the evolution was particularly slow. The diagnosis of sCJD must be considered in cases of rapid-onset dementia, even if all of the clinical criteria are not present. The detection of the 14.3.3 protein and multifold increase in total-Tau with normal or slightly increased phosphorylated-Tau in the CSF are additional arguments to reinforce the diagnosis. The post-mortem neuropathological examination is important to confirm the diagnosis.
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PMID:Unusual features of Creutzfeldt-Jakob disease followed-up in a memory clinic. 2447 91

Anti-NMDA receptor (NMDAR) encephalitis, formally recognized in 2007, has been increasingly identified as a significant cause of autoimmune and paraneoplastic encephalitis. Approximately 80% of the patients are females. The characteristic syndrome evolves in several stages, with approximately 70% of the patients presenting with a prodromal phase of fever, malaise, headache, upper respiratory tract symptoms, nausea, vomiting and diarrhoea. Next, typically within two weeks, patients develop psychiatric symptoms including insomnia, delusions, hyperreligiosity, paranoia, hallucinations, apathy and depression. Catatonic symptoms, seizures, abnormal movements, autonomic instability, memory deficits may also develop during the course of the disease. Presence of antibodies against the GluN1 subunit of the NMDAR in the CSF and serum confirm the diagnosis of NMDAR encephalitis, which also should prompt a thorough search for an underlying tumor. Age, gender, and ethnicity may all play a role, as black females older than 18 years of age have an increased likelihood of an underlying tumor. Treatment is focused on tumor resection and first-line immunotherapy [corticosteroids, plasma exchange, and intravenous immunoglobulin]. In non-responders, second- line immunotherapy [rituximab or cyclophosphamide or combined] is required. More than 75% of the patients recover completely or have mild sequelae, while the remaining patients end up demonstrating persistent severe disability or death. There is a paucity of literature on the management of psychiatric symptoms in this population. Given the neuropsychiatric symptoms in the relatively early phase of the illness, approximately 77 % of the patients are first evaluated by a psychiatrist. Earlier recognition of this illness is of paramount importance as prompt diagnosis and treatment can potentially improve prognosis. We describe two patients diagnosed with NMDAR encephalitis presenting with two different psychiatric manifestations. The first patient presented with psychotic mania and catatonic symptoms, while the second suffered from depression with psychotic and catatonic features refractory to psychotropic medications. We review of the use of psychotropic medications and ECT to address insomnia, agitation, psychosis, mood dysregulation and catatonia in NMDAR encephalitis.
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PMID:Management of psychiatric symptoms in anti-NMDAR encephalitis: a case series, literature review and future directions. 2473 34

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a newly recognized autoimmune central nervous system (CNS) inflammatory disorder, presenting with an array of neurological symptoms in association with autoantibodies against GFAP, a hallmark protein expressed on astrocytes. Limited knowledge is available on the disease pathogenesis and clinical outcome. Here, we report a case of autoimmune GFAP astrocytopathy presenting with encephalomyelitis and parkinsonism. Our patient was a 66-year old male who experienced progressive somnolence, apathy, anxiety, right arm tremor, urinary retention, progressive weakness, and falls over the course of three months, followed by acute delusional psychosis. His neurologic exam on hospital admission was notable for cognitive impairment, myoclonus, rigidity, right hand action tremor, bradykinesia, shuffling gait, and dysmetria. Cerebrospinal fluid examination showed elevated protein, lymphocytic pleocytosis, and one unique oligoclonal band. Magnetic resonance imaging (MRI) revealed non-specific T2/FLAIR hyperintensities in the brain and longitudinally extensive transverse myelitis in the cervical spine. FDG-PET showed a pattern of brain uptake suspicious for limbic encephalitis. Serum and CSF paraneoplastic panel showed presence of GFAP immunoglobulin G (IgG). Treatment with corticosteroids resulted in clinical and radiographic improvement. However, the patient was treated with anti-CD20 immunotherapy due to steroid-dependence. This case exemplifies the recently described neurologic syndrome of autoimmune GFAP astrocytopathy presenting with encephalomyelitis and parkinsonism, reversed by B lymphocyte depletion.
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PMID:A case of GFAP-astroglial autoimmunity presenting with reversible parkinsonism. 3188 22


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