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Progressive myoclonic encephalopathy in X-linked hypogamma-globulinemia. Case report, review of the literature and its relationship with progressive encephalopathy in children with A.I.D.S.

A 7-year-old boy suffering from X-linked hypogammaglobulinemia and progressive myoclonic encephalopathy is reported. The onset of neurological disturbances is at four years of age with ataxic gait and myoclonic jerks. The EEG shows a progressive slowing of background activity, bilateral diffuse and repetitive, pseudoperiodic, high amplitude slow waves, myoclonic jerks polygraphically documented. The CT-scan shows generalized cerebral atrophy, white matter hypodensity--principally in the frontal regions -, multiple nodular calcifications, also in the basal ganglia. Two years after the onset of neurological signs, the boy is completely bedridden, spastic, dement and blind; the myoclonic jerks persist. Finally the relationship is discussed with both the previously reported patients with the same affection, and with similar progressive encephalopathy in children suffering from A.I.D.S.

Acquired Immunodeficiency Syndrome↗

Acute poststreptococcal glomerulonephritis progressing to rapidly progressive glomerulonephritis.

We have reported a rare, well documented case of poststreptococcal glomerulonephritis followed by rapidly progressive glomerulonephritis after weeks of stable renal function. The patient was successfully treated with steroids, azathioprine, and plasmapheresis. Progression of stable proliferative poststreptococcal glomerulonephritis to rapidly progressive glomerulonephritis appears to be uncommon.

Acute Disease↗

North Carolina's dominant progressive foveal dystrophy: how progressive is it?

We studied 34 family members at risk of having dominant progressive foveal dystrophy of Lefler, Wadsworth, and Sidbury (also called North Carolina macular dystrophy) and found 17 to be affected. Fifteen of these affected subjects were observed over at least a 10-year period for evidence of progressive macular degeneration. Only one subject showed objective evidence of progressive deterioration in only one eye. Our findings further substantiate that this dystrophy generally has a stable course, contrary to its original description.

Adolescent↗

Failure of heparin to prevent progression in progressing ischemic infarction.

Anticoagulation with heparin is frequently recommended for patients with progressing ischemic cerebral infarction, yet little data is available detailing the acute results of treatment with this agent. We report the results of continuous intravenous heparin treatment in 36 consecutive patients admitted with progressing ischemic infarction, all of whom had computed tomography scans to exclude the diagnosis of hemorrhage prior to treatment. Overall, 18 of 36 (50%) had continued neurologic worsening despite treatment. The incidence of further worsening was greater in carotid territory infarctions (14 of 19, 74%) than in either vertebrobasilar (2 of 8, 25%) or lacunar (2 of 9, 22%) infarctions (p less than 0.05, Fisher's exact test). These observations suggest that additional controlled studies of the efficacy of heparin in progressing ischemic infarction are warranted.

Cerebral Infarction↗

The nature of cancer: morphogenesis and progressive (self)-disorganization in neoplastic development and progression.

The aberrant forms of life, neoplasia and cancer, are discussed under the events at the beginning of neoplasia and under five classes of neoplastic lesions. The lesional classes are: 1) The precursor state; 2) Intermediate lesions; 3) Primary cancer; 4) Metastasis; and 5) Metastasis from metastasis. The events at the beginning are a diverse group of agents and mechanisms that induce the lesions of the precursor state, not cancer. The lesions and events produced by induction are similar regardless of the agent. Thus, there must be similar biological principles and mechanisms operative in different neoplastic systems. The classes of neoplastic lesions and cancer are described and a theory derived therefrom. The theory is: Any perturbation that alters a cell or group of cells and their stroma so that they no longer respond appropriately to the forces of tissue, organ, and organismal maintenance, may induce a neoplastic system. The sequential progression of lesions of the induced neoplastic system is the result of a successive series of flaws in the continuum of reciprocal interactions between a group of cells and their stroma. The flaws, appearing seriatim, produce progressive (self)-disorganization of the lesions and progressive loss of response to the forces of tissue and organ maintenance.

Animals↗

PROGRESS - Perindopril Protection Against Recurrent Stroke Study: characteristics of the study population at baseline. Progress Management Committee.

OBJECTIVE: The primary aim of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) is to determine the effects of a long-term angiotensin converting enzyme (ACE)-inhibitor-based blood-pressure-lowering regimen on the risk of stroke among patients with a history of stroke or transient ischaemic attack (TIA). Secondary aims include investigation of the effects of treatment on total cardiovascular events, dementia and disability. DESIGN AND METHODS: PROGRESS is a double-blind, placebo-controlled randomized trial. Patients were randomly assigned to treatment with the ACE inhibitor perindopril (and the diuretic indapamide for those with no definite indication or contraindication to treatment with a diuretic) versus matching placebo(s). Both hypertensive and non-hypertensive patients were eligible for inclusion. Follow-up is scheduled for completion in 2001. The study is being conducted in 172 centres in 10 countries (Australia, Belgium, China, France, Italy, Ireland, Japan, New Zealand, Sweden and the United Kingdom). RESULTS: Recruitment was completed in November 1997, with 6105 patients randomized. Mean age of participants at study entry was 64 years, 30% of whom were female, 84% had an entry diagnosis of stroke, and the remainder had an entry diagnosis of TIA alone. Mean baseline blood pressure was 147/86 mm Hg, with about half the patients reporting current drug treatment for hypertension. At randomization, 58% of patients were assigned to combination treatment with both study drugs versus placebos, and 42% were assigned to perindopril alone versus placebo. CONCLUSIONS: The successful completion of recruitment, together with current indicators of statistical power, suggest that PROGRESS should achieve its primary aim on schedule.

Aged↗

[Histological observation of the effects of tangential excision within twenty-four postburn hours on the progressive injury of the progression of deep partial thickness burn wound].

OBJECTIVE: To evaluate the effects of early tangential excision on the prevention of the progression of deep partial thickness burn wound. METHODS: Twelve burn patients with deep partial thickness burn wound were enrolled and received tangential excision of the burn wound within 24 postburn hours (PBHs). The histological samples were harvested from the wound before and 5 - 7 postoperative days (PODs) after the operation and the wound without operation 5 - 7 postburn days (PBDs). The samples were observed by means of HE staining, Masson's staining and the labelling of Vimentin antigen positive cells by immunohistological skill. RESULTS: The inflammatory reaction of the burn wound without operation aggravated progressively along with that of disease and the tissue necrosis area enlarged. And the residual skin appendages disappeared due to the enhanced inflammatory reaction. The brown area expanded and light green area shrinked by Masson's staining. The Vimentin antigen positive cell count decreased significantly. But in the burn wound being performed tangential excision within 24 PBHs, focal inflammatory reaction exhibited evident ligher than that in burn wound without operation. Moreover, there appeared fresh granulation formation and partial epithelial coverage with no enlarged necrotic tissue area in the operated wound when compared with that in non-operated wound (P < 0.05). Furthermore, the light green area exhibited no obvious shrinking by Masson's staining and the Vimentin antigen positive cell count was much more in the operation area than that in non-operative area (P < 0.05). CONCLUSION: It might be beneficial to the host to perform tangential excision within 24 PBHs, which could remove burn wound necrotic tissue in time and hamper the progression of tissue degenerative injury. The healing process of deep partial thickness burn wound was therefore accelerated.

Adult↗

[An autopsied case of progressive systemic sclerosis with anti Wa antibody who showed a rapid progression].

An anti Wa antibody was reported as a new t-RNA related protein antibody in 1986. This autoantibody is now considered specific for the diagnosis of progressive systemic sclerosis (PSS). Up to date only 5 cases with anti Wa antibody have been identified. We report here an autopsied case of PSS with this antibody. A 53 years old female was admitted to our hospital because of dry cough and dyspnea in Sep 1987. There were fine crackles and chest X ray revealed interstitial pneumonia. The progressive respiratory failure was treated by steroid pulse therapy effectively. Sclerotic skin changes of hand began to appear in Sep 1988 and rapidly progressed to arms, chest and forehead by Dec 1988. A skin biopsy confirmed PSS changes. An anti Wa antibody was detected by double immunodiffusion and the protein antigen was associated with t-RNA when immunoprecipitation was conducted. She died of heart failure in July 1989. An autopsy revealed the diffuse fibrotic change of the heart and the lung. Cases with anti Wa antibody were shortly reviewed from the literature.

Autoantibodies↗

Protocols to demonstrate slowing of Alzheimer disease progression. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines. The Disease Progression Sub-Group.

Two suggested clinical trial designs for assessing progression of Alzheimer disease are the randomized withdrawal design and the randomized start design. The most promising of these, the randomized start design, has the potential to demonstrate a delay in progression, but there remain problematic design, ethical, and statistical issues to be solved before the protocol can be used in a clinical trial. The development of biological markers of the disease process using neuroimaging or other measures also may provide a robust method of measuring disease progression and demonstrating the biological effect of a drug on the disease process.

Aged↗

A clinicopathological study of vascular progressive supranuclear palsy: a multi-infarct disorder presenting as progressive supranuclear palsy.

BACKGROUND: Clinical features suggesting a diagnosis of progressive supranuclear palsy (PSP) include early falls, axial rigidity, vertical supranuclear ophthalmoplegia, and levodopa unresponsiveness. When these clinical features are present, the diagnosis is almost always PSP, yet vascular disease sometimes has a similar presentation, referred to as vascular PSP. OBJECTIVE: To evaluate clinical and pathologic features of cases of vascular PSP submitted to a PSP brain bank. DESIGN: Review of gross and microscopic neuropathological features, determination of tau haplotype, and medical record review of 4 patients with an antemortem diagnosis of PSP who did not meet the pathologic criteria for PSP and instead had vascular pathologic abnormalities. RESULTS: All patients had vertical supranuclear ophthalmoplegia, a history of falls, and a gradually progressive disease course. Falls began 1 year after symptom onset, and all patients had asymmetric findings on a neurological examination. A magnetic resonance imaging scan revealed lacunar basal ganglia infarcts in one patient and an increased T2-weighted signal in the corona radiata and centrum semiovale in another. Gross and microscopic neuropathological studies demonstrated infarcts in the cerebral cortex (n = 4), thalamus (n = 4), basal ganglia (n = 3), and cerebellum (n = 4). The brainstem was affected in one patient, but no infarcts were detected in the subthalamic nucleus or substantia nigra. Of the 4 patients, 3 carried an H2 tau haplotype, a rare occurrence in the general population. CONCLUSIONS: Asymmetric signs, falls after 1 year of symptom onset, vascular lesions on a magnetic resonance imaging scan, and an H2 tau haplotype may help differentiate vascular PSP from PSP. Thalamic and basal ganglia infarcts are common in patients with vascular PSP and, when present, may contribute to misdiagnosis.

Accidental Falls↗

Progressive change in primary progressive multiple sclerosis normal-appearing white matter: a serial diffusion magnetic resonance imaging study.

In spite of marked disability, patients with primary progressive multiple sclerosis (PPMS) display smaller lesion volumes on conventional magnetic resonance imaging (MRI) compared with other forms of multiple sclerosis (MS). Hence, damage to the normal-appearing brain tissue (NABT) may play an important role in explaining the pathogenesis of disability in PPMS. Diffusion-weighted MRI (DW-MRI) probes water diffusion in vivo that can be altered by pathologic changes. Using DW-MRI we investigated diffusion in the NABT of 15 patients with PPMS over one year. The average apparent diffusion coefficient (ADCav) was measured in 10 regions of interest located in the normal-appearing thalamus and the normal-appearing white matter (NAWM). Six healthy subjects served as a reference. In contrast to healthy subjects, patients with PPMS showed an increment within 12 months of the ADCav in NAWM which was associated with an increase of the T2- and T1-lesion volumes. The ADCav in frontal NAWM was associated with disability as measured by the MS Functional Composite Measure. Serial DW-MRI depicts progressive changes in the NAWM of patients with PPMS. Our preliminary findings suggest that the processes causing structural damage in NAWM and lesions in patients with PPMS are partially linked and that changes of water diffusion in NAWM depicted by DW-MRI are clinically relevant.

Adult↗

Primary progressive aphasia: a comparative study of progressive nonfluent aphasia and semantic dementia.

Primary progressive aphasia (PPA), a degenerative disorder, is often misdiagnosed as Alzheimer's disease. Its subtypes, semantic dementia (SD), and progressive nonfluent aphasia (PNFA), are often difficult to differentiate from each other. Our objective was to highlight the differences in the language profiles of patients with SD and PNFA. To bring out these differences, we report two patients with PPA, one with SD and the other with PNFA. They were administered the Western aphasia battery (WAB) and a semantic battery, which assesses semantic memory. The profiles of language impairment on the WAB indicated that the patient with PNFA had syntactic errors in expressive speech but relatively preserved semantics and comprehension, whereas the patient with SD had preserved syntax but made semantic errors in expressive speech, and had impaired comprehension. There were differences in their performance on the semantic battery too. The patient with SD made relatively less errors on confrontation naming, although on the pointing task he failed to point to those line drawings, which he was unable to name on confrontation. In contrast, the finding of the PNFA patient was the reverse of this. Supplementing conventional neuropsychological tests with formal tests for assessment of language functions is useful in the early diagnosis of PPA. The performance of PPA patients on a detailed assessment of language that includes use of formal tests such as the semantic battery helps to differentiate PNFA from SD.

Aged↗

Diagnostic accuracy of progressive supranuclear palsy in the Society for Progressive Supranuclear Palsy brain bank.

Diagnostic accuracy has been addressed previously for Parkinson's disease in a brain bank collection, but accuracy of progressive supranuclear palsy (PSP) has not been addressed in a similar setting. Clinical and genetic features of pathologically confirmed cases of PSP were compared with misdiagnosed cases to determine ways to improve diagnostic accuracy. Medical records were reviewed for 180 cases sent to the Society of Progressive Supranuclear Palsy Brain Bank that had standardized neuropathologic evaluations as well as determination of apolipoprotein E and tau genotypes. Of the 180 cases studied, 137 had PSP and 43 had other pathologic diagnoses. Corticobasal degeneration (CBD), multiple system atrophy (MSA), and diffuse Lewy body disease (DLBD) accounted for 70% of the misdiagnosed cases. History of tremor, psychosis, dementia, and asymmetric findings were more frequent in misdiagnosed cases. The frequency of H1 tau haplotype (93 vs. 80%) and H1H1 genotype (86 vs. 66%) were significantly greater and APOE epsilon4 carrier state was significantly less (17 vs. 41 %) in PSP compared with misdiagnosed cases. Pathologic evaluation of clinically diagnosed PSP remains important for definitive diagnosis, and CBD, MSA, and DLBD are the disorders most likely to be misdiagnosed as PSP. Tremor, psychosis, early dementia, asymmetric findings, absence of H1 haplotype, and presence of APOE epsilon4 should raise questions about a diagnosis of PSP.

Aged↗

Progressive neuropsychological and extrapyramidal deterioration resembling progressive supranuclear palsy: is aphasia relevant for correct diagnosis?

We describe the case of a woman presenting with a clinical syndrome closely resembling progressive supranuclear palsy, who also showed some progressive neuropsychological defects (aphasia and apraxia) not consistent with a simple loss of timing and activation as is generally postulated in this pathology. The case is discussed with regard to the definition of subcortical dementia and the possible alternative diagnosis of corticobasal degeneration.

Aged↗

Progression of MRI abnormalities in herpes simplex encephalitis despite clinical improvement: natural history or disease progression?

Herpes simplex virus encephalitis (HSVE) is associated with a high mortality rate and a high probability of neurological sequelae. Good results are obtained when HSVE is promptly diagnosed and treated with acyclovir. We present a 71-year-old woman with clinically diagnosed HSVE, confirmed by PCR detection of HSV-1 DNA in the cerebrospinal fluid. She was treated with acyclovir (30 mg/kg day) for two weeks. Clinical and neuropsychological assessments 6 months after admission were normal; however MRI at 2, 6 and 12 months showed progressive deterioration with extensive white matter and cortical damage. Imaging studies of a cohort of patients surviving PCR-confirmed HSVE are needed to determine whether this pattern is occasional or a frequent form of progression.

Acyclovir↗

Fear of progression in chronic diseases: psychometric properties of the Fear of Progression Questionnaire.

OBJECTIVE: The aim of this study was the development and psychometric testing of a new psychological questionnaire to measure the fear of progression (FoP) in chronically ill patients (cancer, diabetes mellitus and rheumatic diseases). METHODS: The Fear of Progression Questionnaire (FoP-Q) was developed in four phases: (1) generation of items (65 interviews); (2) reduction of items--the initial version of the questionnaire (87 items) was presented to 411 patients, to construct subscales and test the reliability; (3) testing the convergent and discriminative validity of the reduced test version (43 items) within a new sample (n=439); (4) translation--German to English. RESULTS: The scale comprised five factors (Cronbach's alpha >.70): affective reactions (13 items), partnership/family (7), occupation (7), loss of autonomy (7) and coping with anxiety (9). The test-retest reliability coefficients varied between .77 and .94. There was only a medium relationship to traditional anxiety scales. This is an indication of the independence of the FoP. Significant relationships between the FoP-Q and the patient's illness behaviour indicate discriminative validity. CONCLUSIONS: The FoP-Q is a new and unique questionnaire developed for the chronically ill. A major problem and source of stress for this patient group has been measuring both specifically and economically the FoP of an illness. The FoP-Q was designed to resolve this problem, fulfill this need and reduce this stress.

Adult↗

Progress in the characterization of slowly progressive autoimmune diabetes in adult patients (LADA or type 1.5 diabetes).

LADA or type 1.5 diabetes is a slowly progressive form of autoimmune diabetes of adults and represents a considerable proportion (about 5-10%) of all diabetic patients. Associations with high risk HLA genotypes and autoimmune phenomena (GAD, IA2, ICA) show similarities with type 1 diabetes, but phenotypical characteristics of these patients do not allow the correct identification without screening of GAD antibodies. The relatively low antibody titers against islet-cell antigens in LADA patients may be sign of a less aggressive form of autoimmune diabetes and could be responsible for the long non-insulin requirement phase of this diabetes type. Similar as in prediabetic relatives of type 1 diabetic patients the risk for beta cell failure in adult "type 2 diabetic" patients increases with the number of antibodies positive. Consequently, low titers of GAD--in particular in elderly patients--do not predict a progressive and rapid loss of beta-cell failure, when associations with high risk genotypes or other islet-cell antibodies are lacking. Patients with LADA share insulin resistance with type 2 diabetic patients, but display a more severe defect in stimulated beta-cell capacity than patients with classical type 2 diabetes. With respect to features of the metabolic syndrome, patients with LADA have lower BMI, blood pressure and triglyceride levels compared with classical type 2 diabetes patients. Early identification of LADA patients will be mandatory, when effective immune interventions are available for prevention of the beta-cell destructive process and insulin requirement of these patients.

Adult↗

Atypical progressive supranuclear palsy underlying progressive apraxia of speech and nonfluent aphasia.

Progressive supranuclear palsy (PSP) is a clinicopathological entity typically presenting as an akinetic rigid syndrome with early falls, axial rigidity, vertical supranuclear gaze palsy and levodopa resistance. Pathological features consist of tau deposition in neuronal and glial cells located mainly in subcortical and brainstem structures. Rare cases with the pathological diagnosis of atypical PSP have been described in which neocortical tau deposition is more widespread than what is usually seen in typical PSP. Progressive nonfluent aphasia (PNFA) is a syndrome characterized by spontaneous nonfluent speech and early preserved comprehension of language. Apraxia of speech (AOS) is a motor speech disorder that may be a feature of PNFA. We report the clinical and pathological findings of four cases that presented with features most consistent with PNFA predominated by AOS. Pathological features in these four cases included the typical features of PSP subcortically and in brainstem structures, but combined with tau-positive neuronal and glial pathology in the neocortex. Comprehensive semiquantitative analyses of tau burden including neurofibrillary tangles and pretangles, coiled bodies, tufted astrocytes and threads were undertaken in the four cases of atypical PSP and compared to 10 cases of typical PSP. Semiquantitative analysis demonstrated that in atypical PSP, the pathology shifts from subcortical grey and brainstem regions, commonly affected in typical PSP, towards neocortical regions. This shift in pathology accounts for the presentation of PNFA and AOS observed in our patients, as well as the lack of classic features of PSP. These cases demonstrate that atypical PSP can present as AOS and PNFA without the classic features of PSP.

Adult↗