Multiple sclerosis with early childhood onset: a case report

Vergani, Maria Isabel C.; Reimão, Rubens; Silva, Ana Maria Camara; Muskat, Mauro; Esposito, Sandro Blasi; Diament, Aron Judka

doi:10.1590/s0004-282x1988000200012

Cited by 11 publications

(5 citation statements)

References 13 publications

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“…Disruptions of mGluR‐activated Purkinje neuron processes such as LTD are likely to result in alterations in information processing within the cerebellar cortex, thus disrupting the subsequent output of the cerebellum to descending motor systems. Disturbances of cerebellar function are manifested primarily as symptoms of discoordinated movement and ataxia, which are common to both IL‐6 transgenic mice and a number of neurological disorders with elevated CNS IL‐6 expression, including AIDS dementia complex (Poser et al ., 1988; Graus et al ., 1990), Alzheimer's disease (Aikawa et al ., 1985; Vakili & Muller, 1987), systemic lupus erythematosus (Tuchman et al ., 1983; Singh et al ., 1988) and multiple sclerosis (Aikawa et al ., 1985; Vergani et al ., 1988; Davie et al ., 1995). Our results suggest that elevated levels of IL‐6 in these conditions could be an important contributing factor to the disturbances in cerebellar function.…”

Section: Discussionmentioning

confidence: 99%

Chronic interleukin‐6 exposure alters metabotropic glutamate receptor‐activated calcium signalling in cerebellar Purkinje neurons

Nelson

Netzeband

Gruol

2004

Eur J of Neuroscience

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Chronic central nervous system expression of the cytokine interleukin-6 (IL-6) is thought to contribute to the histopathological, pathophysiological, and cognitive deficits associated with various neurological disorders. However, the effects of chronic IL-6 expression on neuronal function are largely unknown. Previous studies have shown that chronic IL-6 exposure alters intrinsic electrophysiological properties and intracellular Ca2+ signalling evoked by ionotropic glutamate receptor activation in cerebellar Purkinje neurons. In the current study, using primary cultures of rat cerebellum, we investigated the effects of chronic IL-6 exposure on metabotropic glutamate receptor (mGluR)-activated Ca2+ signalling and release from intracellular Ca2+ stores. Chronic exposure (6-10 days) of Purkinje neurons to 500 units/mL IL-6 resulted in elevated resting Ca2+ levels and increased intracellular Ca2+ signals evoked by the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) compared to untreated control neurons. Chronic IL-6 treatment also augmented Ca2+ signals evoked by brief 100 mm K+ depolarization, although to a lesser degree than responses evoked by DHPG. Depleting intracellular Ca2+ stores with sarcoplasmic-endoplasmic reticulum ATPase inhibitors (thapsigargin or cyclopiazonic acid) or blocking ryanodine receptor-dependent release from intracellular stores (using ryanodine) resulted in a greater reduction of DHPG- and K+-evoked Ca2+ signals in chronic IL-6-treated neurons than in control neurons. The present data show that chronic exposure to elevated levels of IL-6, such as occurs in various neurological diseases, alters Ca2+ signalling involving release from intracellular stores. The results support the hypothesis that chronic IL-6 exposure disrupts neuronal function and thereby may contribute to the pathophysiology associated with many neurological diseases.

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Section: Discussionmentioning

confidence: 99%

Chronic interleukin‐6 exposure alters metabotropic glutamate receptor‐activated calcium signalling in cerebellar Purkinje neurons

Nelson

Netzeband

Gruol

2004

Eur J of Neuroscience

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“…Alterations in Purkinje neuron physiology would likely result in considerable alterations in information processing by the cerebellum in vivo, thus disrupting the output of the cerebellum to descending motor systems. Such disruption of cerebellar function can produce symptoms of discoordinated movement and ataxia, which are common to both the GFAP-IL6 transgenic mice and a number of neurological disorders with elevated CNS IL-6 expression, including AIDS dementia complex (Graus et al 1990;Poser et al 1988), Alzheimer's disease (Aikawa et al 1985;Vakili and Muller 1987), systemic lupus erythematosus (Singh et al 1988;Tuchman et al 1983), and multiple sclerosis (Aikawa et al 1985;Davie et al 1995;Vergani et al 1988). In addition, the changes in the physiology of cultured Purkinje neurons occurred in the absence of any gross structural abnormalities of these neurons, suggesting that IL-6, and perhaps other cytokines, can exert regulatory effects on CNS function during conditions of neuroinflammation or infection that precede, or are independent of, neuronal damage or death.…”

Section: Discussionmentioning

confidence: 99%

Chronic Interleukin-6 Exposure Alters Electrophysiological Properties and Calcium Signaling in Developing Cerebellar Purkinje Neurons in Culture

Nelson

Gruol

2002

Journal of Neurophysiology

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The cytokine interleukin-6 (IL-6) is chronically expressed at elevated levels within the CNS in many neurological disorders and may contribute to the histopathological, pathophysiological, and cognitive deficits associated with such disorders. However, the effects of chronic IL-6 exposure on neuronal function in the CNS are largely unknown. Therefore using intracellular recording and calcium imaging techniques, we investigated the effects of chronic IL-6 exposure on the physiological properties of cerebellar Purkinje neurons in primary culture. Two weeks of exposure to 1,000 units/ml (U/ml) IL-6 resulted in altered electrophysiological properties of Purkinje neurons, including a significant reduction in action potential generation, an increase in input resistance, and an enhanced electrical response to the ionotropic glutamate receptor agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) compared with untreated neurons. Lower concentrations of IL-6 (100 and 500 U/ml) had no effects on these electrophysiological parameters. However, neurons exposed to 500 U/ml chronic IL-6 resulted in significantly elevated resting levels of intracellular calcium as well as an increase in the intracellular calcium signal of Purkinje neurons in response to AMPA, effects not observed in neurons exposed to 1,000 U/ml chronic IL-6. Morphometric analysis revealed a lack of gross structural changes following chronic IL-6 treatment, such as in the number, size, and extent of dendritic arborization of Purkinje neurons in culture. Using immunohistochemistry, we found that cultured Purkinje neurons express both the IL-6 receptor and its intracellular signaling subunit, gp130, indicating that IL-6 may act directly on Purkinje neurons to alter their physiological properties. The present data show that chronic exposure to elevated levels of IL-6, such as occurs in various neurological diseases, produces alterations in several important physiological properties of Purkinje neurons and that these changes occur in the absence of neuronal toxicity, damage, or death. The results support the hypothesis that chronic IL-6 exposure can disrupt normal CNS function and thereby contribute to the pathophysiology associated with many neurological diseases.

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“…-~*~ Moreover, optic neuritis also developed in most cases during the subsequent course of the disease. 13234- [6][7][8][9] In early childhood patients with cerebellar ataxia, therefore, it is essential to differentiate timely MS initially, beginning with this sign from the more common, benign, and self-limiting condition, acute cerebellar ataxia.…”

Section: Discussionmentioning

confidence: 99%

“…It rarely occurs in early childhood and only a few patients have been reported with onset before the age of 3 years. [1][2][3][4][5][6][7][8][9] Pathologically, MS is characterized by numerous areas of demyelination, or 'plaques' in the white matter, which occasionally extend into the gray matter, and have been demonstrated by magnetic resonance imaging (MRI). However, few thalamic lesions in MS are yet described in the literature.…”

mentioning

confidence: 99%

An early‐onset case of multiple sclerosis with thalamic lesions on MRI

Asai

Inagaki

Maegaki

et al. 1994

Pediatrics International

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We present here an early-onset case of multiple sclerosis (MS) with thalamic lesions. The patient first experienced an episode of ataxic gait at 2 years 3 months of age, with spontaneous remission within 1 month. At 5 years 4 months, she was admitted because of cerebellar ataxia, oculomotor restriction and feeding difficulty. Magnetic resonance imaging (MRI) showed multiple well-defined lesions in the white matter of the cerebellum, mid-brain, periventricle and right frontal lobe. Cerebrospinal fluid (CSF) showed a mild elevation of both immunoglobulin G (IgG) and myelin basic protein (MBP). Serum anti-myelin antibody was also positive, although leukocytosis and elevation of C-reactive protein were not found. Methylprednisolone pulse therapy relieved symptoms within 2 weeks and the abnormal MRI and CSF findings gradually improved. At 6 years 6 months of age, she incurred a third episode of cerebellar ataxia and disturbance of consciousness. Magnetic resonance imaging revealed recurrence and extension of the previous lesions as well as new lesions in the thalamus and internal capsule. CSF IgG and MBP level showed a higher elevation than in the second episode. The combination of the cerebellar, brain-stem, cerebral and thalamic lesions with remission and exacerbation, supported by MRI and CSF findings, allowed the diagnosis of clinically definite MS to be made. This is one of the youngest cases of MS yet described, with the first attack occurring at 27 months of age. In addition, this case is unique for the involvement of the gray matter in the thalamus.

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Multiple sclerosis with early childhood onset: a case report

Cited by 11 publications

References 13 publications

Chronic interleukin‐6 exposure alters metabotropic glutamate receptor‐activated calcium signalling in cerebellar Purkinje neurons

Chronic interleukin‐6 exposure alters metabotropic glutamate receptor‐activated calcium signalling in cerebellar Purkinje neurons

Chronic Interleukin-6 Exposure Alters Electrophysiological Properties and Calcium Signaling in Developing Cerebellar Purkinje Neurons in Culture

An early‐onset case of multiple sclerosis with thalamic lesions on MRI

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