We report a 60-year-old man with distal acquired demyelinating symmetric neuropathy, who manifested marked spinal root hypertrophy on magnetic resonance imaging. His sensorimotor symptoms were confined to the distal limb regions. The electrophysiological features fulfilled the diagnostic criteria of chronic inflammatory demyelinating polyneuropathy. Blood examination showed immunoglobulin G-λ gammopathy. Magnetic resonance imaging showed marked hypertrophy of the multiple spinal roots with gadolinium enhancement, accompanied by a tumor-like lesion with cord compression. Although how the neurological symptoms were confined to the distal regions despite the nerve root hypertrophy remains to be resolved, spinal root lesions should also be evaluated in distal acquired demyelinating symmetric neuropathy as well as classical chronic inflammatory demyelinating polyneuropathy.
Distal acquired demyelinating symmetric neuropathy (DADS) is an immunological disorder of peripheral nerves with exacerbation and remission or progressive courses, and is classified in the group of chronic inflammatory demyelinating polyneuropathy (CIDP). Classical CIDP shows manifestation in both proximal and distal extremities,[2, 3] whereas DADS is defined as a phenotype presenting only distal sensorimotor symptoms. Classical CIDP and DADS have common electrophysiological findings, and the reason that DADS exhibits predominantly distal limb involvement is still unknown. Summation of multiple or diffuse conduction slowing or block and secondary axonal degeneration might be a possible causative factor, resulting in a nerve-length-dependent manner of clinical presentation.
Recent studies have reported nerve enlargement often accompanied by spinal cord involvement in CIDP patients,[4, 5] but there has been no similar report in DADS. We herein describe a patient with DADS presenting spinal root hypertrophy, and discuss its pathomechanism.
A 60-year-old man with no family history showed repetitive motor weakness and dysesthesia in his hands and feet for 9 years. On admission, he presented motor paresis localized in the hand and distal lower legs, superficial hypoesthesia, and deep sensory disturbance in the distal areas of the extremities. The proximal muscles were intact. Deep tendon reflexes were absent, and there were no long tract signs or Babinski signs. There were no focal neurological signs suggesting segmental spinal root involvements. There were no palpable nerve enlargements in any regions of the extremities. Cerebrospinal fluid showed an albuminocytological dissociation with protein levels of 800–900 mg/dL. Nerve conduction study of the median and ulnar motor nerves showed prolongation of distal latencies (8–9 m/s), and marked slowing of conduction velocity (10–18 m/s), with partial conduction block (Fig. 1a,b). F wave latency was markedly prolonged up to 65 ms in both nerves. Motor responses of the tibial and peroneal nerves were not evoked. Sensory nerve action potentials were abolished in the upper and lower extremities. Peripheral and spinal components of somatosensory evoked potentials were also completely missing. He had positive immunoglobulin G-λ M proteins, but lacked an antimyelin-associated-glycoprotein (MAG) antibody. Gene analyses for peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and gap junction protein beta 1 (GJB1) were normal. He was diagnosed as having DADS associated with M protein. The coronal view of cervical magnetic resonance imaging (MRI) showed hypertrophy of multiple cervical roots with gadolinium enhancement (C4–C7, Fig. 1c), one of which was so enlarged as to compress the cervical cord at the level of left C5 (Fig. 1d). Lumbar MRI also showed prominent swelling of the cauda equina. Corticosteroid hormone and intravenous immunoglobulin therapy were effective for his gait disturbance and dysesthesia, but there were subsequent recurrences necessitating repetitive immunoglobulin therapy. The immunotherapy did not assuage the root enlargement.
The clinical presentation of distal dominant symmetric sensory abnormalities and weakness, with the demyelinative features of nerve conduction study, showed that the patient had DADS. The most noticeable finding in our patient was the nerve root hypertrophy, or mass formation, compressing the spinal cord, which has not been previously reported so far in DADS.
Classical CIDP and DADS have common electrophysiological findings, such as prolonged distal latencies or slowed conduction velocity. Their differentiation mainly depends on the distribution of affected regions. Nevertheless, responses to immunotherapy are often different: DADS with M proteins or anti-MAG antibody usually shows poorer responses to immunotherapy than classical CIDP, although idiopathic DADS not associated with M proteins or MAG might have a common pathogenesis to classical CIDP. This suggests that the M proteins or antibody play a role in the development of distal dominancy and the resistance to immunotherapy.
The present patient showed a significant discrepancy between the distal dominant manifestation and the striking spinal root lesions. Nerve hypertrophy, in general, relates to iterative demyelination and remyelination with onion bulb formation.[6, 7] Repetitive Schwann cell proliferation is thought to be a main cause of nerve hypertrophy in CIDP. The increased mucopolysaccharide and edema in the endoneurium might also contribute to nerve swelling. In this pathological aspect, the hypertrophied spinal root lesions in the present patient might have the same demyelinative process as classical CIDP, although the etiology of the distal dominant manifestations remains to be resolved. The proximal upper limb muscles, in particular, showed preserved power despite the hypertrophy of the C5 nerve root. This discrepancy might support the hypothesis that summation of multiple conduction impairments along long nerves causes the distal dominance of weakness dependent on a nerve-length-dependent manner.
Spinal cord compression by hypertrophied spinal roots in CIDP has recently been reported,[4, 5] but there have been no references to the phenotypes of CIDP. This is the first report of spinal root hypertrophy in DADS. Neurophysiological study occasionally has limitations in detecting localized spinal root lesions. Clinicians should pay more attention to most proximal nerve lesions and examine MRI, even in patients showing distal dominant clinical manifestations.
We thank Professor Satoshi Kuwabara, Department of Neurology, Chiba University School of Medicine, for useful comments for interpretation of the results and suggestions for the Discussion.