HTLV-I associated myelopathy with macular degeneration

The authors report a case of macular involvement in a patient with HTLV-I associated myelopathy (HAM). The patient was a 10-year-old girl who noticed sudden decreased vision in her right eye in November 1987. The corrected visual acuity was 0.01 in the right eye and 1.0 in the left eye. Fundus examination of the right eye disclosed mild optic disc pallor. The macula appeared to have pigmentary mottling with superficial irregular retinal reflex that was three disc diameters in size. Fluorescein angiography revealed a discoid hypofluorescent area in the macula, surrounded by mottled hyperfluorescent areas. She had no contributory family history of ocular disease, but had a history of blood transfusion during an operation for patent ductus arteriosus and ventricular septal defect at the age of 8 months. In November 1990, she developed gait disturbance due to spastic paraparesis and was admitted to our hospital. Antibodies to HTLV-I were markedly elevated in serum (titer, 1:8192) and in cerebrospinal fluid (titer, 1: 1024). She was diagnosed as HAM. Two months later, she developed encephalopathy and bilateral optic disc atrophy.     

Choroidal neovascularization not associated with age-related macular degeneration

Choroidal neovascularization (CNV) is an important clinical finding that is associated with many ocular conditions, including inflammatory, infectious, degenerative, hereditary, and congenital disorders, ocular tumors, trauma, and a few miscellaneous disorders. The growth of new choroidal vessels beneath the retinal pigment epithelium is associated with specific clinical signs. The clinical recognition of CNV plays a key role in the prognosis and management of these disorders. The clinical presentation of each disorder associated with CNV is reviewed in this paper, with comments on the location and the frequency of CNV occurrence.     

Cerebellar degeneration associated with human immunodeficiency virus infection

Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. A primary cerebellar degeneration with HIV has not previously been reported. Ten patients were identified over an 8-year period at five medical centers. All patients had clinical, laboratory, and radiologic evaluations, and three had neuropathologic examinations. Patients presented with progressively unsteady gait, slurred speech, and limb clumsiness. Examination revealed gait ataxia, impaired limb coordination, dysarthria, and abnormal eye movements. Cognition, strength, and sensory function remained normal. CD4 lymphocyte counts varied between 10 and 437 cells/mm3. Neuroimaging studies showed prominent cerebellar atrophy. Neuropathology showed focal degeneration of the cerebellar granular cell layer and unusual focal axonal swellings in the brainstem and spinal cord. Cultures, histopathology, and immunochemical studies showed no conclusive evidence of infection. We report a syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection.     

Unilateral pigmentary degeneration of the retina associated with heterochromia iridis

BACKGROUND: For the past 5 years, a 56-year-old patient has been displaying monocular progressive pigmentary changes in the left eye. Heterochromy of the left eye has been known since childhood. The other eye is clinically and functionally normal. The patient was adopted and he has no children. Therefore, we have no family history. METHODS: The patient was examined clinically and by means of electroretinography, electrooculography, perimetry, computer tomography, pulsatile ocular blood flow (POBF) measurement, serology and Doppler sonography. RESULTS: Electrophysiology displayed a considerable reduction of scotopic and photopic ERGs, a reduced dark-through, and a reduced light-rise in the left eye, whereas the fellow eye was normal. The visual field was limited to 5 deg around the fixation point, and a peripheral crescent-shaped arch encircled the temporal-inferior quadrant concomitant to the pigmentary changes. By computer tomography and Doppler sonography a vascular affection was excluded. The left eye displayed lower POBF values. All serological tests were found negative. CONCLUSION: The clinical picture and negative exclusion criteria indicate a unilateral retinitis pigmentosa. However, with regard to the literature an unequivocal diagnosis can only be made upon hereditary evidence.     

Neuronal degeneration in the gerbil brainstem is associated with spongiform lesions

Spongiform lesions arise in dendrites and glia in the brainstem of domestic Mongolian gerbils. Most pronounced within the cochlear nucleus (CN), this disorder is dynamic and progressive; the lesions increase in number, size, and extent with age. It has not been clear whether these spongioid lesions either cause or are associated with significant neural degeneration. In contrast, feral Mongolian gerbils (wild-trapped in Tuva) and their offspring show few spongiform lesions. The Tuvan gerbils provide an appropriate within-species control. We compared degeneration in the brainstem of domestic and Tuvan gerbils using the amino-cupric-silver (ACS) stain of de Olmos et al. [(1994) Neurotoxicol. Teratol., 16:545-561]. Positive histologic controls were provided by cerebellar stab wounds in domestic gerbils and by unilateral kainic acid injections into the CN of Tuvan gerbils. The ACS stain revealed extensive degeneration of axons, terminals, dendrites, and neurons in the brainstem of domestic gerbils. Neurodegeneration was most pronounced in the CN and was coextensive with spongiform lesions. Neurodegeneration was also seen in the trapezoid body, lateral lemniscus, and inferior colliculus, but was less pronounced than in the CN. The cerebellar stab wounds resulted in silver-stained Purkinje cells restricted to the stab wound local region. Kainic acid produced extensive neuronal and spongiform degeneration of the injected CN that was very similar to that spontaneously occurring in domestic gerbils. In contrast, the non-injected CN of Tuvan gerbils showed no neuronal or spongiform degeneration with the ACS stain. We conclude that, in domestic gerbils, the naturally occurring spongiform lesions of the CN and the accompanying neurodegeneration are both results of a common mechanism, most probably excitotoxic.     

Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration

STUDY DESIGN: A study in genetic epidemiology of disc degeneration, based on lifetime exposure data, findings on magnetic resonance imaging, and genotyping of intragenic markers. OBJECTIVES: To pursue the potential correlation between common allelic variations in the vitamin D receptor locus and degeneration of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Familial aggregation has been observed in intervertebral disc degeneration, but the relative significance of the genetic component and shared environmental influences is unknown. The identification of relevant candidate genes associated with disc degeneration would specify a genetic component and increase our understanding of the etiopathogenesis of disc degeneration. METHODS: From the population-based Finnish Twin cohort, 85 pairs of male monozygotic twins were selected based on exposure to suspected risk factors for disc degeneration. Interview data were gathered on relevant lifetime exposures, and thoracic and lumbar disc degeneration was determined through quantitative and qualitative assessments of signal intensity on magnetic resonance imaging, and qualitative assessments of disc bulging and disc height narrowing. Possible associations were examined between disc degeneration measures and two polymorphisms of the coding region of the vitamin D receptor locus. RESULTS: Two intragenic polymorphisms of the vitamin D receptor gene revealed an association with disc degeneration. Quantitatively assessed signal intensities of thoracic and lumbar (T6-S1) discs were 12.9% worse in men with the Taql tt genotype and 4.5% worse in men with the Tt genotype, compared with signal intensity in men with the TT genotype (age adjusted P = 0.003). A similar pattern was found between disc signal intensity and Fokl genotypes; men with the ff and Ff genotypes had mean signal intensities that were 9.3% and 4.3% lower, respectively, than those in men with FF genotypes (age-adjusted P = 0.006). The summary scores of qualitatively assessed signal intensity, bulging, and disc height were 4.0% and 6.9% worse in men with Ff and ff genotypes, respectively, when compared with those in men with the FF genotype (age-adjusted P = 0.029). CONCLUSION: Specific vitamin D receptor alleles were associated with intervertebral disc degeneration as measured by T2-weighted signal intensity, demonstrating for the first time, the existence of genetic susceptibility to this progressive, age-related degenerative process.     

Cervical infarction associated with vertebral artery occlusion due to spondylotic degeneration: case report

Cases of cervical infarction with clearly documented evidence of the underlying aetiology and associated neuroradiological abnormalities have not been frequently reported. A rare case of cervical infarction caused by midvertebral artery occlusion due to spondylotic degeneration of the spine is described. The most probable aetiological factor affecting this disease entity, and the usefulness of magnetic resonance imaging in the detection of this rare lesion, are briefly discussed.     

Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease

Prostate apoptosis response-4 (Par-4) is a protein containing both a leucine zipper and a death domain that was isolated by differential screening for genes upregulated in prostate cancer cells undergoing apoptosis. Par-4 is expressed in the nervous system, where its function is unknown. In Alzheimer disease (AD), neurons may die by apoptosis, and amyloid beta-protein (A beta) may play a role in this. We report here that Par-4 expression is increased in vulnerable neurons in AD brain and is induced in cultured neurons undergoing apoptosis. Blockade of Par-4 expression or function prevented neuronal apoptosis induced by Ab and trophic factor withdrawal. Par-4 expression was enhanced, and mitochondrial dysfunction and apoptosis exacerbated, in cells expressing presenilin-1 mutations associated with early-onset inherited AD.     

Increase in interphotoreceptor matrix gelatinase A (MMP-2) associated with age-related macular degeneration

Matrix metalloproteinases have increasingly been shown to be associated with diseases involving neovascularization and/or abnormal cellular migration or proliferation. A number of diseases of this type affect the retina. In this study, the activity of gelatinase A (MMP-2), the most abundant matrix metalloproteinase in IPM (interphoto receptor matrix) and vitreous, was measured with respect to age in normal human donor eyes and compared to donors with age-related macular degeneration. IPM and vitreous were obtained from a total of 88 human donors. Samples for electrophoresis were normalized for protein content and subjected to quantitative gelatin zymography. The zymograms were scanned and then digitized and quantitated using the NIH 'Image' program. There was not a statistically significant change in the level of gelatinase A in IPM or vitreous as a function of age, although a slight downward trend was found in the total gelatinase A activity within the normal population. Likewise, when comparing normal and age-related macular degeneration donors, there was not a significant difference in the gelatinase A level in vitreous or in retina-associated IPM. However, the level of gelatinase A was nearly doubled specifically in retinal pigment epithelium-associated IPM from eyes with age-related macular degeneration [0.99 +/- 0.09 U mg-1 (56) vs 1.71 +/- 0.28 U mg-1 (14) (mean +/- S.E.M. (number), P < 0.0021; 1 unit = 1.0 ng gelatin cleaved h-1). Gelatinase A may be associated with the changes that occur in age-related macular degeneration, especially the neovascularization which accompanies the exudative ('wet') form of the disease.     

Chloroform-induced olfactory mucosal degeneration and osseous ethmoid hyperplasia are not associated with olfactory deficits in Fischer 344 rats

The Cd emission of a phosphate plant was clearly reflected by the Cd status of herbivorous European wood mice and common field voles as well as of European shrews taking in mostly animal food. The antagonistic effect of the emitted Cd and Mo better available for plants with high ground pH most probably caused the deterioration in the Cu status of the animals of both phases in the nutritional chain. The lower Ca, P, and Mg incorporation with European wood mouse and common field vole within the contaminated habitat might as well be owing to emission, whereas the lower Mn content in all three species rather has to be attributed to the lower Mn offer caused by the ground pH.     

Neonatal encephalopathy with neuronal vacuolar degeneration

Spontaneous augmented breaths (active sighs) reduced the tidal volume and inspiratory time of succeeding breaths; manual lung inflations (passive sighs) reduced the tidal volume but had little effect on inspiratory time. Sighs in air, whether active or passive, reduced tidal volume more than sighs in hyperoxia (100% oxygen or 33% oxygen in nitrous oxide) after both active and passive sighs (overall difference about 10%); the reduction in inspiratory time after a sigh was less affected by gas mixture. Calculated mean inspiratory flow was reduced after passive sighs, but active sighs were more likely to cause arousal, which complicated the analysis. Tidal volume was reduced after a sigh partly because of reduced peripheral chemoreceptor input, the main effect of which was to reduce inspiratory flow, and partly because inspiratory time was shorter. Although the chemoreceptors may affect inspiratory time after a sigh, the greater effect of active sighs compared with passive sighs makes it likely that the shortening was either part of the neural output that causes spontaneous sighs, or was caused by mechanoreceptor input not mimicked by manual lung inflation.     

Paraneoplastic cerebellar degeneration with asymmetrical pan-cerebellar syndrome

INTRODUCTION: Paraneoplasic cerebellar degeneration is seen clinically as a pancerebellar condition which is usually symmetrical. Different families of tumours are associated with this, particularly (in view of its frequency) oat cell pulmonary carcinoma, gynecological tumours and Hodgkin's lymphoma. CLINICAL CASE: Signs of cerebellar atrophy were seen on MR and cortical hypoperfusion was seen on Single Photon Emission Computerized Tomography (SPECT). We present the case of a 76 year old woman who presented with an asymmetrical pancerebellar disorder of gradual onset, with positive anti-self antibodies and undifferentiated carcinoma of the breast. CONCLUSIONS: Paraneoplasic cerebellar degeneration should be suspected in a patient with symmetrical, progressive cerebellar disease. The syndrome characteristically starts with a slightly uncoordinated gait. This progresses over a period of weeks or months to an ataxic gait with incoordination of the limbs, dysarthria and frequently nystagmus with oscilloscopy. No satisfactory treatment has been found for DCP in spite of trials with vitamins, corticosteroids, plasmapheresis and immunoglobulin infusion. Slight improvement may be seen after treatment of the primary tumour.     

Full-field electroretinograms in infants with hereditary tapetoretinal degeneration

Full-field electroretinograms were recorded from four infants (under the age of 12 months), with different types of tapetoretinal degeneration. Some of these patients, appear to have normal fundi. This article stresses the clinical usefulness of evaluation with electroretinography in young children.     

Reduced intracortical facilitation in patients with cerebellar degeneration

Susceptibility patterns of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium obtained from various hospitals of the Tohoku district were documented. MICs of 6 antimicrobial agents against a total of 480 strains (380 strains were MRSA and 100 were E. faecium) were estimated. All MRSAs were susceptible to vancomycin, teicoplanin and quinupristin/dalfopristin, but all of them were resistant to ampicillin and benzylpenicillin. None of the E. faecium strains were found to be resistant to vancomycin, teicoplanin and quinupristin/dalfopristin. Excluding these, almost all strains of E. faecium were resistant to the remaining drugs. These data suggest that despite the emergence of vancomycin resistance to E. faecium in Europe and in the United States, vancomycin, teicoplanin and quinupristin/dalfopristin will nevertheless provide effective bactericidal activity in the Tohoku area of Japan.     

Stress induced urinary incontinence in patients with spinocerebellar degeneration

To better understand genetic alterations in atypical adenomatous hyperplasia (AAH) of the prostate, we examined the prevalence of allelic imbalance at 5 microsatellite polymorphic markers on chromosomes 7q31-35, 8p12-21, 8p22, 8q22.2, and 18q12.2 from 15 patients with AAH. DNA samples were obtained from formalin-fixed paraffin-embedded sections using tissue microdissection. We found allelic imbalance in 7 of 15 (47%) cases of AAH. Genetic changes that commonly occur in early prostatic carcinogenesis and prostate carcinoma are found in AAH. Current data provide evidence of a genetic link between some cases of AAH and carcinoma.     

The behavioral syndrome caused by 3,3'-iminodipropionitrile and related nitriles in the rat is associated with degeneration of the vestibular sensory hair cells

Animals exposed to 3,3'-iminodipropionitrile (IDPN) or to several similar nitriles develop a permanent syndrome of behavioral abnormalities. The present work addressed the hypothesis that this syndrome is caused by a toxic effect of these nitriles on the peripheral vestibular system. Male Long-Evans rats were given acute doses of IDPN (0, 200, 400, 600, or 1000 mg/kg, ip) and assessed for a number of behaviors indicative of vestibular function at postdosing times ranging from 1 day to 9 weeks. The pathological effects of IDPN on the morphology of the vestibular sensory epithelia were studied by scanning electron microscopy at 1,2,4, and 21 days after exposure. The behavioral study revealed dose-dependent deficits in vestibular function after IDPN. Alterations in vestibular morphology occurred at the same doses of IDPN that induced behavioral changes (400-1000 mg/kg). The pathological alterations after IDPN consisted of degeneration of the vestibular sensory hair cells, and no hair cells remained in the vestibular receptors 3 weeks after the 1000 mg/kg dose. A good correlation was also found for the time-course characteristics of the behavioral and the morphopathological effects of IDPN. The vestibular sensory epithelia displayed a regional pattern of differential sensitivity to the toxic effect of IDPN. Both intraepithelial and interepithelial differences in sensitivity were found. Crotonitrile (250 mg/kg, ip), which induces the same behavioral syndrome, was found to induce also degeneration of the vestibular hair cells. We conclude that IDPN and the similar nitriles that cause the same behavioral abnormalities are toxic to the peripheral vestibular system.     

Genetic association of apolipoprotein E with age-related macular degeneration

Several investigators have studied the deficit in maximal voluntary force that is said to occur when bilateral muscle groups contract simultaneously. A true bilateral deficit (BLD) would suggest a significant limitation of neuromuscular control; however, some of the data from studies in the literature are equivocal. Our purpose was to determine whether there is a BLD in the knee extensors of untrained young male subjects during isometric contractions and whether this deficit is associated with a decreased activation of the quadriceps, increased activation of the antagonist muscle, or an alteration in motor unit firing rates. Twenty subjects performed unilateral (UL) and bilateral (BL) isometric knee extensions at 25, 50, 75, and 100% maximal voluntary contraction. Total UL and BL force (delta 3%) and maximal rate of force generation (delta 2.5%) were not significantly different. Total UL and BL maximal vastus lateralis electromyographic activity (EMG; 2.7 +/- 0.28 vs. 2.6 +/- 0.24 mV) and coactivation (0.17 +/- 0.02 vs. 0.20 +/- 0.02 mV) were also not different. Similarly, the ratio of force to EMG during submaximal UL and BL contractions was not different. Analysis of force production by each leg in UL and BL conditions showed no differences in force, rate of force generation, EMG, motor unit firing rates, and coactivation. Finally, assessment of quadriceps activity with the twitch interpolation technique indicated no differences in the degree of voluntary muscle activation (UL: 93.6 +/- 2.51 Hz, BL: 90.1 +/- 2.43 Hz). These results provide no evidence of a significant limitation in neuromuscular control between BL and UL isometric contractions of the knee extensor muscles in young male subjects.