Acute Fulminant Multiple Sclerosis and Plasma Exchange

Abstract

Acute fulminant multiple sclerosis (MS) is exceptional and often resistant to corticotherapy [1]. We report on an additional case which dramatically and rapidly recovered with serial plasma exchanges (PE) followed by immunosuppressive therapy.A 23-year-old woman gave birth in December 1995. Three months later, she presented with dizziness, unsteady gait, tinnitus and important tiredness. Eleven days later, she was admitted because of the sudden appearance of speech disturbances. General examination was normal. Neurological examination showed partial motor aphasia, central vestibular syndrome, tetrapyramidal syndrome with hyperreflexia and Babinski’s sign, mild left cerebellar syndrome and abolition of pharyngeal reflex; there was no motor deficit. Laboratory tests were normal including serological tests for syphilis, Borrelia burgdorferi, viral and rheumatismal diseases. CSF examination showed a moderate lymphocytic pleiocytosis (27 lymphocytes/mm3) and several oligoclonal specific IgG bands.Visual- (pattern reversal stimulus) and somatosensory-evoked potentials were abnormal. Brain CT scan showed a slight hypodensity in the left ventricular junction. Cerebral magnetic resonance imaging (MRI) showed several periventricular confluent hyperintense T2-weighted lesions (fig. 1) in the white matter, corpus callosum and left cerebellar peduncle. Some lesions were enhanced after intravenous injection of gadolinium on T1-weighted images. On the 14th day, intravenous methylprednisolone (1 g/day for 7 days, followed by 0.5 g/day for 3 days) was started. The neurologic symptoms quickly improved with the disappearance of nystagmus and aphasia. However, on the 19th day she developed a tetraparesis and her clinical condition deteriorated despite the continuation of corticosteroids. Motor aphasia worsened, swallowing and sphincter disorders appeared. Control CSF examination showed 7 lymphocytes, normal glucose and protein levels. Lower limb somatosensory-evoked potentials deteriorated. Cerebral MRI showed new confluent lesions in the corpus callosum and right cerebellar peduncle. The size of the other lesions was increased. On the 24th day, the patient presented with a severer tetraparesis, a partial impairment of consciousness and respiratory failure. The expanded disability status scale (EDSS) scored 9.5. Nine PE were performed in 15 days (50 ml plasma/kg exchanged with 5% albumin). Oral methylprednisolone (64 mg/day) was progressively tapered (4 mg every 3 days). After the third PE, the neurological condition dramatically improved. She slowly recovered her strength and the swallowing troubles progressively resolved. On the 44th day the EDSS score was 7. PE were followed by intravenous mitoxantrone (12 mg/m2), every 3 weeks for the first 3 infusions and thereafter every 3 months. At 3 months, EDSS was 2. At 6 months, neurological examination only showed intention tremor and the patient was fully independent (EDSS at 1). Somatosensory-evoked potentials were improved. At 20 months, cerebral MRI demonstrated persistent lesions without contrast enhancement.Fulminant or malignant MS is characterized by a rapid progressive course, leading to significant disability in multiple neurological systems or death in a relatively short time after disease onset [2]. It mainly affects young patients and seems to be resistant to corticoids. At autopsy, the lesions are often of macroscopic sizes and sometimes confluent.Usefulness of PE in MS is controversial. Most studies [3, 4, 5]have been performed in chronic MS with contradictory results and few in acute attacks of MS [6]. Khatri et al. [7]reported the case of a pregnant woman presenting with a severe attack of MS which improved with PE. Rodriguez et al. [1]have reported 6 cases of fulminant MS unresponsive to corticoids. PE allowed a dramatic improvement in 5 of them and a moderate one in 1. The clinical benefits persisted for 6–22 months. As in our case, clinical improvement was observed after the second or the third PE. The mechanism of PE in acute MS remains unknown. The therapeutic response might be due to the removal of circulating factors, such as immunoglobulins, complement components or interleukins. PE might increase the effectiveness of immunosuppressive drugs [8].In addition to the 6 cases previously reported, our case supports the assumption that PE could be helpful as an alternative treatment, which has few side effects. The high cost of PE should however limit its use in patients with fulminant MS unresponsive to corticoids. Large randomized studies are still needed to confirm the potential benefit of PE in acute fulminant MS, although the rarity of these cases will make them difficult to set up in a large scale.