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Generally, inflammatory demyelinating diseases selectively affect either the central or peripheral myelin. Here we report a case of a severe combined central and peripheral demyelination, each of which contributed equally to the clinical syndrome.
A 32 year old female was admitted to a general district hospital with a 3 day history of aches in the legs, fever (38 °C), urinary retention and leg weakness. Neurological examination revealed a flaccid tetraparesis with abolished abdominal and ankle reflexes, diminished knee reflexes, bilateral extensor plantar responses, and sensory level at T12. The patient was given high dose intravenous prednisone (1 g) for 5 consecutive days. She became bedridden with complete paraplegia of the legs and was referred to our department. Upon admission, in addition to a flaccid tetraparesis (strength 1/5 in the legs and 4/5 to 4±5 in the arms, MRC grade) with abolished abdominal, knee and ankle reflexes, extensor plantar responses, and sensory level at T5, a bilateral gaze evoked nystagmus was detected. Urodynamic examination revealed an atonic bladder. Lumbar puncture revealed a pleocytosis (34/mm3; 84% lymphocytes) and a cerebrospinal fluid (CSF) protein of 132 mg/dl. Neither intrathecal immunoglobulin synthesis nor oligoclonal bands were detected. Complete microbiological and virological investigations on CSF and blood specimens were negative. Further negative findings included serum angiotensin converting enzyme, anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, and onconeuronal antibodies. Serological testing for anti-ganglioside antibodies (Ganglio-combi test; Bühlmann Laboratories) showed elevated titres for asialo-GM1 (4283 Bühlmann titre units (BTU); normal<1700), GM1 (2855 BTU; normal<1700) and GQ1b (4117 BTU; normal<1700). Magenetic resonance imaging (MRI) of the spinal cord depicted an extensive cervicothoracic myelopathy (fig 1A–D). On MR images of the brain, multiple dot-like cortical and subcortical lesions were delineated, predominantly located in the frontoparietal gray and white matter (fig 1E–G). Electrodiagnostic studies indicated a severe symmetrical demyelinating neuropathy with reduced motor conduction velocities (right peroneal nerve 12.8 m/s, right tibial nerve 16.0 m/s, and right median 44 m/s), prolonged distal latencies (right peroneal nerve 17.1 ms, right tibial nerve 14.5 ms, and right median 5.3 ms), and prolonged or absent F waves, with MUAP displaying temporal dispersion and diminished amplitudes, and with electromyographic signs of acute denervation. The sensory action potentials and conduction velocities were normal.
A whole body computed tomography scan, a salivary gland scintigraphy scan, and a lip biopsy were completely unremarkable. A diagnosis of a combination of acute disseminated encephalomyelopathy (ADEM) and demyelinating polyradiculoneuritis was made. The patient was given 30 g of intravenous immunoglobulin for 5 consecutive days (total 150 g). By day 10 after the start of the immunoglobulin treatment, the patient could stand upright for several seconds with support. As there was no further improvement during the following 2 weeks, the therapy was increased and the patient was treated with a total of six plasma exchanges on alternate days. Five days after the final plasma exchange, the patient could make her first steps with a walker. Six weeks after the final plasma exchange, MRI of the brain and spinal cord showed dramatic regression of the T2 hyperintensities. On follow-up 1 month later, the patient could walk 250 metres with a walker. On examination, no gaze evoked nystagmus was detected. Arm strength was normal. Internal rotation of the hips, hip and knee flexors, and knee extensors were 4/5 on the right and 5/5 on the left; ankle flexors and extensors and toe dorsiflexors were 4/5 bilaterally. The knee reflexes were sluggish and the ankle reflexes absent. Six months later the patient was able to walk 1000 metres without walking aids. The neurological examination revealed brisk knee and ankle reflexes. The 1 year follow-up showed a patient with normal leg strength and mild ataxia on heel to toe gait. The electrophysiological studies showed improvement of motor conduction velocities (right peroneal nerve 24.1 m/s, right tibial nerve 33.1 m/s, and right median 46.6 m/s) and distal latencies (right peroneal nerve 10.4 ms, right tibial nerve 9.5 ms, and right median 3.4 ms).
Our patient presented an acute demyelinating disorder affecting the central and peripheral nervous system simultaneously. After exclusion of other causes, the central nervous system involvement resembled the clinical and radiological characteristics of ADEM with long segmental spinal cord lesion. The peripheral nervous system involvement displayed the clinical, electrodiagnostic, CSF, and serological features of a demyelinating polyradiculoneuropathy.
Documented overlap of acquired acute central and peripheral system demyelination is very rare. Gamstrop and Blennow used the discriptive diagnosis of encephalomyeloradiculoneuropathy to designate paediatric cases of Guillain-Barré syndrome with presumed CNS involvement.1 Again in children, Amit et al. coined the entity of acute severe combined demyelination for cases in which central and peripheral nervous system pathology equally contributed to the overall clinical picture.2 An acute or subacute combined central and peripheral myelinopathy has been very rarely reported in adults,3,4 with no successful treatment regimens being documented.
In our patient, no improvement was seen after high dose intravenous prednisone therapy (5 g), but she dramatically improved on intravenous immunoglobulin and plasma exchange therapy. This finding extends the previous reports of the effectiveness of this therapeutic strategy in the patients with central or peripheral inflammatory demyelination who failed to respond to high dose steroid therapy. Even a delayed treatment (7 weeks after onset of the symptoms) with immunoglobulin induced a significant remission. Further clinical improvement was achieved with subsequent plasma exchange. Our finding supports the concept of immunomodulation using immunoglobulin and plasma exchange in steroid resistant combined central and peripheral inflammatory myelinopathy.
Acute demyelinating diseases are often preceded by an infection or vaccination and considered to be immune mediated. This case of a severe unrestricted demyelinating syndrome encourages the concept that an immunological attack can be directed against central and peripheral myelin in susceptible individuals.
Competing interests: none declared
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