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Progression of optic neuritis to multiple sclerosis: an 8-year follow-up study.

OBJECTIVE: The relationship between acute monosymptomatic optic neuritis (AON) and subsequent multiple sclerosis (MS) is still doubtful. We investigated the risk of developing MS in patients from North Bavaria, who were suffering from AON. PATIENTS/METHODS: Twenty-nine patients with clinical evidence of AON were included in the study. Initial evaluation included brain resonance imaging (MRI) and a clinical neurological examination. Follow-up examinations were performed after 72-108 months (mean: 96 months) in 26 patients (three patients were lost to follow-up) and consisted of a second complete neurological examination. Diagnosis of MS was established according to the criteria of Poser CM, Paty DW, Scheinberg L. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983:13:227-231. RESULTS: At follow-up, 14 of 26 patients (54%) had converted to clinically definite MS. Nine patients (64%) had developed MS within 2 years after the onset of AON. CONCLUSION: We observed the development of MS in 54% of the 26 investigated AON patients. The exceptional feature of the present study was the relatively long follow-up period of 8 years.

Acute Disease↗

Schwann cell apoptosis in experimental autoimmune neuritis of the Lewis rat and the functional role of tumor necrosis factor-alpha.

Schwann cell (SC) apoptosis may be a critical factor challenging nerve remyelination and regeneration in experimental autoimmune neuritis (EAN) in the Lewis rat. We therefore analyzed the fate of SC during high-dose antigen therapy of adoptive transfer-(AT-) EAN using rhP2 protein. P2 antigen therapy was associated with an increase of tumor necrosis factor (serum levels 1 h after intravenous (i.v.) injection and an augmentation of T-cell apoptosis. Antigen specific therapy had no clear effect on SC apoptosis. The effects on SC apoptosis were determined by morphological criteria or by in situ tailing (IST) followed by immunocytochemical analysis. Secondly, we neutralized TNF-alpha, released in abundance by antigen treatment but only in small concentrations during natural disease course. We found that the addition of a TNF-alpha neutralizing antiserum resulted in a significant decrease in the rate of SC apoptosis in vivo compared to animals treated with control antigen rhP0 or with rhP2 only.

Adoptive Transfer↗

Attenuation of experimental autoimmune neuritis in the Lewis rat by treatment with an antibody to L-selectin.

The leukocyte adhesion molecule L-selectin plays a key role in the initial steps of transendothelial migration of T cells and monocytes. In this study we investigated the role of L-selectin in the pathogenesis of experimental autoimmune neuritis (EAN) an animal model of the Guillain-Barré syndrome. EAN was induced in Lewis rats by sensitization with peripheral nerve myelin. Treatment with HRL3, a monoclonal antibody to L-selectin, efficiently suppressed clinical signs of EAN. Histological examination of the peripheral nervous system (PNS) revealed a marked reduction of inflammatory infiltrates and demyelination during treatment with HRL3. We conclude that L-selectin-dependent mechanisms are of pathophysiological relevance in EAN. Modulation of L-selectin in vivo could be a novel therapeutic approach to autoimmune diseases of the PNS.

Animals↗

The kappa opioid agonist GR89,696 blocks hyperalgesia and allodynia in rat models of peripheral neuritis and neuropathy.

Previous work demonstrated that, in rats, intrathecal GR89696, a putative kappa-2 opioid receptor agonist, inhibited hyperalgesia to noxious heat in an inflamed hind paw (anti-hyperalgesic effect). Non-inflamed paws were not influenced by kappa-2 receptor activation. The question addressed in this study was whether GR89696 was as effective in blocking hyperalgesia and allodynia in nerve injury models as it was in the inflammation model. GR89696 (6 nmoles, i.t.) completely reversed the hyperalgesia and allodynia observed in both the neuropathy and neuritis models in all sensory tests. However, it did not alter sensory function in non-injured limbs nor in sham operated animals. Naloxone (1 mg/kg, i.p.) reversed the anti-hyperalgesic and anti-allodynic effects of GR89696. The mu agonist DAMGO (6 nmoles, i.t.) and the kappa-1 agonist U69593 (100 nmoles, i.t.) only partially reversed hyperalgesia and allodynia. These findings suggest that kappa-2 opioid receptors may be a useful target for the pharmacological control of hyperalgesia and allodynia.

Analgesics, Non-Narcotic↗

Circumferential wrapping of a flap around a scarred peripheral nerve for salvage of end-stage traction neuritis.

Nine patients with chronic severe pain due to end-stage traction neuritis of an intact peripheral nerve underwent external neurolysis and epineurectomy or epineurectomy and internal neurolysis followed by circumferential wrapping of the involved segment of nerve with a pedicle flap or free flap consisting of either subcutaneous fat tissue, fascia, or muscle. Seven patients (77%) followed for between 1 and 5 years had substantial relief of pain. Two patients (22%) had no decrease in their pain at all. Circumferential wrapping may cushion the nerve from external pressure on the overlying skin, may isolate the nerve from the traction forces of adjacent moving tendons to allow improved gliding of the nerve, and may promote revascularization of a scarred nerve. This surgery may be indicated for patients with persistent pain following multiple carpal tunnel or cubital tunnel surgeries.

Adult↗

Brachial neuritis presenting as anterior interosseous nerve compression--implications for diagnosis and treatment: a case report.

Brachial plexus neuropathy may present as an isolated peripheral nerve lesion, suggesting local compression, when in fact the pathophysiology is a diffuse proximal inflammation. The type of management depends on an accurate diagnosis of the diffuse lesion with electromyography. A descriptive case of isolated anterior interosseus nerve palsy is presented and the literature is reviewed. Analysis of the reported cases reveals that anterior interosseus nerve palsies resulting from different etiologies are included in the same series and that treatment recommendations are highly specialty-oriented. Cases of brachial plexus neuritis-induced anterior interosseus nerve palsy should be managed conservatively, while surgical decompression may be performed for specific instances of direct trauma.

Adult↗

Viral brachial neuritis in emergency medicine.

Brachial plexus neuritis is a rare neurologic disease that may be overlooked in emergency medicine because other conditions are much more common. We report a case of brachial plexus neuropathy due to cytomegalovirus infection. The diagnosis was based on history, clinical findings, laboratory tests, and electromyography. Early diagnosis and adequate treatment is important to avoid unnecessary investigation, prevent complications (especially adhesive capsulitis of the shoulder), and reassure the patient.

Adult↗

Influence of antioxidant enzymes in reduction of optic disc edema in experimental optic neuritis.

Acute experimental allergic optic neuritis was induced in 18 adult strain-13 guinea pigs. The animals were divided into three groups. The first group of six animals received intraperitoneal injections of saline, the second group received superoxide dismutase (SOD), and the third group received catalase, given daily, starting 1 week after encephalogenic myelin sensitization. Morphometric analysis of longitudinal histopathologic sections of the optic nerve head revealed that the animals treated with the antioxidant enzyme catalase had a statistically significant reduction of optic disc edema when compared to the saline-treated group. Although animals treated with SOD had less optic disc swelling than the saline-treated controls, the differences were not statistically significant. These results indicate that detoxification of hydrogen peroxide, released by invading inflammatory cells, can reduce the severity of axonal swelling within the optic nerve head.

Animals↗

Ulnar neuritis in Hansen's disease results of fifty neurolyses in the arm and elbow.

Fifty cases of ulnar nerve neuritis in Hansen disease are reported. The authors analyse the type of lesion, the clinical feature, the treatment, and the results of neurolysis. Many points are emphasized: the requirement to an association antileprosy, chemotherapy and corticotherapy with a careful neurolysis; pain and paresthesia were relieved immediately after neurolysis, recovery within two years after neurolysis; the amount of recovery was directly related to the extent and stage of involvement of the nerve; and thus the sooner procedure give the best result.

Adolescent↗

Paralytic brachial neuritis or Parsonage-Turner syndrome anterior interosseous nerve involvement. Report of three cases.

Paralytic brachial neuritis or Parsonage-Turner syndrome principally involves the shoulder girdle, rarely muscles moving the hand and fingers. Three cases are reported. After an acute episode with severe pain in the arm and fore-arm there appeared, a palsy of flexor pollicis longus and flexor indicis profundus, due to an isolated lesion of the anterior interosseous nerve. Two cases spontaneously recovered their full function, the third incompletely. Delay in recovery may be long; more than two years. Mechanical nerve entrapement should not be confused with this syndrome.

Adult↗

Calcium antagonists suppress experimental allergic neuritis (EAN).

We examined the influence of Ca++ antagonist drugs on immune response and the clinical course of experimental allergic neuritis (EAN). The Ca++ antagonists verapamil and flunarizine suppressed actively induced EAN in Lewis rats in a dose-dependent fashion when given continuously by osmotic pumps from the day of immunization. If given from onset of clinical signs, day 10 after immunization, verapamil alone had therapeutic effects. The beneficial effects of the drugs seem to be mediated primarily by an action on the autoimmune response, since in vitro lymphocyte proliferation in response to nervous tissue antigens was dose-dependently inhibited by both drugs, whereas the in vitro conductivity of demyelinated sciatic nerve was not significantly affected by the Ca++ antagonists. The suppressive effect on lymphocyte proliferation could partially be bypassed by protein kinase C activating phorbol ester alone or in combination with the Ca++ ionophore ionomycin, confirming a non-toxic effect of the Ca++ antagonists on lymphocytes.

Action Potentials↗

Exogenous soluble tumor necrosis factor receptor type I ameliorates murine experimental autoimmune neuritis.

Tumor necrosis factor (TNF) and its receptor (TNFR) have been strongly implicated in the pathogenesis of autoimmune disease. Soluble cytokine receptors may be shed naturally from cell membranes to inhibit cytokine activity. Experimental autoimmune neuritis (EAN) is a CD4 Th1 cell-mediated animal model of Guillain-Barré syndrome (GBS) in humans. In the present study, we investigated the effects of soluble TNFR type I (sTNFR I) in EAN induced in mice by P0 peptide 180-199 and Freund's complete adjuvant. Our data from two different therapeutic regimens indicate that the administration of sTNFR I effectively ameliorated the clinical and pathological signs of EAN, i.e., decreased its severity, shortened its duration, and reduced inflammatory cell infiltration into the peripheral nervous system. The suppression of clinical EAN was accompanied in vitro by a marked reduction in antigen-specific T-cell proliferation and IFN-gamma synthesis by spleen cells from sTNFR I-treated mice, compared to control mice treated with PBS. These data directly demonstrate a pivotal role for TNF in the development of EAN and also suggest that sTNFR I may have therapeutic potential for alleviating GBS in humans.

Animals↗

[Electrophysiological study of a family of subjects presenting primary hypertrophic neuritis].

Primary hypertrophic neuritis (hereditary motor and sensory neuropathy types I and III) can easily be characterized in affected families by nerve conduction measurement. Such a study is reported in a family with two affected subjects from two successive generations, a man and one of his daughters (type I). Nerve conduction velocities (NCV) were dramatically low (down to 10 m/sec) in three other subjects from the second generation without any obvious clinical symptom. These cases show again the lack of correlation between electrophysiological data and clinical features in these affections. They emphasize the usefulness of electrophysiological diagnosis among subjects without any obvious clinical sign.

Adolescent↗

Treatment of experimental allergic neuritis with prednisolone.

Experimental allergic neuritis (EAN) in Lewis rats was treated with prednisolone given prophylactically or therapeutically. Rats treated from the time of immunization with myelin or after the establishment of clinical disease improved more rapidly than controls. Treatment at the onset of clinical signs resulted in less severe disease and more rapid recovery. Rats treated just prior to the onset of clinical signs (day 10) did not develop significant clinical disease and appeared to have less inflammation in their nerves and nerve roots on microscopic examination.

Animals↗

Electrophysiological disorders in multiple sclerosis and optic neuritis.

Visual evoked response (VER), auditory brainstem evoked response (ABER), somatosensory evoked response (SSER), blink reflex and electronystagmographic (ENG) investigative methods were applied to a group of 89 patients with Multiple Sclerosis (MS) and Optic Neuritis (ON). The MS patients were classified as definite (n = 31), probable (n = 31) and possible (n = 27). The aim of this study was to determine the diagnostic value of the five electrophysiological tests in MS. VER and ABER recordings were found to reveal the highest number of asymptomatic abnormalities (33 and 31 percent respectively). The combination of VER, ABER and ENG revealed all possible electrophysiological disorders. As these tests are completely non-invasive it is proposed, that a combination of two of these three tests is useful for the detection of a second silent lesion in patients with suspected MS showing purely spinal signs (VER, ENG, ABER) and/or a history of uncomplicated ON (ABER, ENG).

Adult↗

CSF myelin basic protein levels in acute optic neuritis and multiple sclerosis.

Normal CSF-MBP levels as determined by a RIA were less than 6.2 ng/ml CSF (mean 3.9). Eighty percent of patients with acute optic neuritis have CSF-MBP levels greater than 6.2 ng/ml (mean 7.6 ng/ml CSF). Five of 7 patients with acute internuclear ophthalmoplegia due to an initial exacerbation of demyelination have CSF-MBP levels above 6.2 ng/ml (mean 6.8 ng/ml). Fifty percent of MS patients with chronic progressive disease have CSF-MBP levels above 6.2 ng/ml (mean 6.7 ng/ml). MS patients experiencing monosymptomatic exacerbations show elevated CSF-MBP levels in 75% in 75% of cases (mean 8.2 ng/ml). MS patients experiencing polysymptomatic exacerbations show significantly higher levels of CSF-MBP (mean 22.3 ng/ml) than the patients with monosymptomatic exacerbations. Ninety-five percent of MS patients experiencing polysymptomatic exacerbations have elevated levels of CSF-MBP.

Acute Disease↗

Normalisation of visual evoked potentials after optic neuritis.

Normalisation of the visual evoked potential (VEP) in patients with optic neuritis (ON) appears to be a rare phenomenon. However, although several workers have indicated that it can happen, they have not followed up with subsequent VEP tests to confirm how long the VEP latency of the affected eye remains in the normal range. To resolve this, 18 patients with a clinical diagnosis of acute unilateral ON were followed for 5 years with repeated VEP tests to determine if the latency of the P2 wave from affected eye could return to the normal range. Furthermore, in cases where the latency returned to normal, the length of time that it remained so was also assessed. The normal range for the latency of the P2 wave was determined by measuring VEPs from a group of 18 healthy control subjects with a similar age distribution to the patients. This established an upper limit of 115.9 ms. At presentation the mean P2 latency of the affected eyes of the patients was 140 ms with a standard deviation of 16 ms. In general, the VEP latencies remained constant over the period of the investigation. However two patients demonstrated a return to normal latencies but this was only temporary. Their latencies become prolonged again within 2 years. These results provide evidence that the delayed P2 latency observed in patients with ON can return to the normal range in a small percentage of cases. However, this improvement may spontaneously deteriorateonce more as a result of further episodes of subacute demyelination.

Acute Disease↗