Diagnostic criteria for demyelinating polyneuropathy associated with monoclonal gammopathy

In order to define diagnostic criteria for the demyelinating polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS), we compared 30 patients with idiopathic chronic inflammatory demyelinating polyneuropathy (CIDP) without a monoclonal gammopathy, with 29 patients with polyneuropathy associated with MGUS. All 59 patients fulfilled research criteria for CIDP. In the patients with MGUS, sensory symptoms and signs predominated, there was usually no cranial nerve involvement, and the neuropathy was symmetrical with a slowly progressive course. On electrophysiological examination, an abnormal median nerve sensory action potential in combination with a normal sural nerve action potential (AMNS) was not found. In idiopathic CIDP patients, a preceding infection was frequent, motor features predominated, there was often cranial nerve involvement, the neuropathy could be asymmetrical, and AMNS was frequently found. Diagnostic criteria for demyelinating polyneuropathy associated with MGUS are presented.     

Chronic progressive steroid responsive axonal polyneuropathy: A CIDP variant or a primary axonal disorder?

Five patients are presented with chronic, progressive, predominantly motor polyneuropathy. CSF protein content was increased in four patients. Motor conduction velocities and EMG were consistent with axonal involvement. Sural nerve conductions were normal in all cases and sural nerve biopsy performed in one patient was normal. Serum antibodies to GM₁, GD_1a, GD_1b, and GM2 were negative. All patients improved after steroid treatment and 3 completely recovered. Because of therapeutic implications it is important to differentiate these patients from those with chronic idiopathic axonal neuropathies. It is unclear whether this is a primary axonal, probably immune-mediated, polyneuropathy, or whether it represents one extreme of the chronic inflammatory demyelinating polyradiculoneuropathy spectrum characterized by severe axonal loss. We suggest that the term “chronic inflammatory polyneuropathy,” encompassing cases from pure demyelinating to pure axonal neuropathies responsive to steroids, should be reinstated and that, like in Guillain—Barré syndrome, different subtypes should be individuated. © 1996 John Wiley & Sons, Inc.     

Focal cranial nerve involvement in chronic inflammatory demyelinating polyneuropathy: clinical and MRI evidence of peripheral and central lesions

Summary Five cases of chronic inflammatory demyelinating polyneuropathy are described in which cranial nerve involvement accompanied a more generalized neuropathy. Clinical, electrophysiological, radiological and nerve biopsy findings are presented. Cranial nerve lesions in this form of polyneuropathy may be related to lesions of the peripheral nerves or of the central nervous system, when they may be accompanied by MRI evidence of more widespread CNS demyelinating lesions. In cases of early onset, the occurrence of focal cranial nerve lesions may serve to distinguish chronic inflammatory from inherited demyelinating polyneuropathies.     

Early neurophysiological evolution of chronic inflammatory demyelinating polyneuropathy in a patient with Hashimoto's thyroiditis

A patient with a known history of hypothyroidism due to Hashimoto's thyroiditis presented with a subacute, progressive sensorimotor deficit that affected the upper limbs predominantly. The electrophysiological findings progressively evolved from multifocal motor conduction block to multifocal demyelinating sensory and motor nerve involvement with conduction block, and finally to findings fulfilling the diagnostic criteria of chronic inflammatory demyelinating polyneuropathy (CIDP). The patient did not respond adequately to intravenous immunoglobulin, whereas oral prednisone led to fast and complete recovery. This report discusses the evolution of early findings of CIDP, as well as its coexistence with Hashimoto's thyroiditis.     

"Chronic sensory demyelinating neuropathy": chronic inflammatory demyelinating polyneuropathy presenting as a pure sensory neuropathy.

The clinical electrophysiological and histological features of 10 cases of "chronic sensory demyelinating neuropathy" (CSDN) are reported. This entity is characterised by: 1) subacute or chronic progression; 2) pure sensory neuropathy; 3) high spinal fluid protein in the majority of cases; 4) electrophysiological evidence of demyelination affecting motor as well as sensory nerve fibres; 5) demyelination on sural nerve biopsy and 6) good response to immunotherapy in progressive phase. It is believed that this entity represents chronic inflammatory demyelinating polyneuropathy (CIDP) presenting as pure sensory neuropathy.     

Evoked potentials in chronic inflammatory demyelinating polyneuropathy

Eighteen patients with chronic inflammatory demyelinating polyneuropathy were studied with evoked potentials to assess for evidence of central nervous system demyelination. Both visual and brain-stem auditory evoked responses were obtained, and the results were compared with magnetic resonance imaging (MRI). An evoked potential was abnormal in nine of 18 patients, five of whom had central nervous system evidence of demyelination by MRI. Evoked potentials identified four patients with probable anterior optic pathway involvement that was not demonstrable by MRI. These findings continue to support that chronic inflammatory demyelinating polyneuropathy is associated with a central demyelinating disorder and more importantly emphasize the possibility of a common pathogenic mechanism in central and peripheral nerve demyelination.     

Intravenous immunoglobulin preparation attenuates neurological signs in rat experimental autoimmune neuritis with the suppression of macrophage inflammatory protein -1α expression

To clarify the mechanism of action of an intravenous immunoglobulin (IVIG) preparation in chronic inflammatory demyelinating polyneuropathy, the effects of IVIG were investigated using an experimental autoimmune neuropathy model in the rat. IVIG significantly suppressed the progression of neurologic signs and sciatic nerve conduction velocity with the inhibition of inflammatory cell infiltration, mainly of macrophages, to the peripheral nerves. A significant suppressive effect on the expression of macrophage inflammatory protein 1-α (MIP-1α) was simultaneously observed in the nerves. These results suggest that IVIG is effective for inflammatory demyelinating polyneuropathy by inhibiting the chemotactic factor of macrophages.     

Magnetic resonsance imaging of the cauda equina in chronic inflammatory demyelination polyneuropathy

We report a patient with biopsy proven chromic inflammatory demyelinating polyneuropathy whose magnetic resonance imaging demonstrated abnormal enhancement of the cauda equina after administration of gadolinium. Enhancement may reflect alteration of the blood- nerve barrier seconday to inflammation. Magnetic resonance imaging of th cauda equina could be a useful adjunct in the early diagnosis of chronic inflammatory demyelinationg polyneuropathy.     

Chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis

We report a patient with chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis (PBC). Except for minimal biochemical abnormalities, clinical symptoms of PBC were not observed, and we diagnosed our patient with asymptomatic PBC from the results of a liver biopsy. Although the patient noticed little muscle weakness, an electrophysiological study demonstrated slow conduction velocities and prolonged distal latencies, with definite conduction blocks in the median, ulnar, and tibial nerves. The disturbed sensory pattern was asymmetrical, and sensory nerve action potentials were not evoked. From these observations, we diagnosed this patient with chronic inflammatory demyelinating polyneuropathy. Neuropathy associated with PBC is very rare. We must differentiate demyelinating neuropathy with PBC in patients with asymmetrical sensory dominant neuropathy with high immunoglobulin M titers, and investigate for the presence of anti-mitochondrial antibodies to rule out a complication of asymptomatic PBC.     

Myasthenia gravis and chronic inflammatory demyelinating polyneuropathy in the same patient – a case report

Purpose: To investigate the clinical character, diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy accompanying myasthenia gravis so as to improve the understanding of such diseases.

Materials and methods: A case of chronic inflammatory demyelinating polyneuropathy combined with myasthenia gravis were analyzed retrospectively with review of the literature.

Results: This man was presented with chronic progressive sensory symptoms, flaccid tetraparesis, areflexia and protein-cell dissociation of cerebrospinal fluid. Nerve conduction study was indicative of demyelinating neuropathy. He was suspected as chronic inflammatory demyelinating polyneuropathy and treated with high-dose glucocorticoids. However, his condition worsened. Four months later, he was admitted and was diagnosed as combination of chronic inflammatory demyelinating polyneuropathy and myasthenia gravis. Good clinical results were observed after he was treated with pyridostigmine bromide, prednisone and mycophenolate mofetil.

Conclusions: This case warns clinicians to be aware of these two diseases presenting in the same patient, and the possible implications on treatment choices. A common immunological abnormality might exist in this rare association, but it still remains unknown.     

Chronic inflammatory demyelinating polyneuropathy caused by HIV infection in a patient with asymptomatic CMT 1A

It is well known that patients with Charcot-Marie-Tooth (CMT) disease are liable to present with episodes of cortisone-responsive demyelination, and a superimposed inflammatory component has been suggested. We report a patient who presented with a chronic inflammatory demyelinating polyneuropathy due to a recent HIV infection, which revealed a previously asymptomatic CMT 1A disease documented by identification of the characteristic duplication on the p11.2 region of chromosome 17. The inflammatory process was characterized by pathologic findings on a superficial peroneal nerve biopsy, and the patient improved significantly after corticotherapy. This report gives support to the hypothesis of a genetic susceptibility to inflammatory demyelinating processes in certain CMT kindreds.     

Clinicopathological and virological analyses of familial human T-lymphotropic virus type I-associated polyneuropathy

Human T-lymphotropic virus type I (HTLV-I) is known to be the causative agent of the chronic myelopathy, HTLV-I--associated myelopathy (HAM), and on rare occasions infection is also associated with the development of polyneuropathy. Here the authors present an HTLV-I--positive family of whom four members developed a chronic demyelinating polyneuropathy without HAM. Four female patients in a family from Hokkaido in Japan developed distal dominant paresthesia and muscle weakness in the second and third decades of their life. Neurological findings at ages ranging from 50 to 65 years included mild painful sensorimotor disturbances with atrophy of the distal parts of the extremities but without pyramidal signs or hyperactive tendon reflexes. Magnetic resonance imaging (MRI) findings of brain and spinal cord were unremarkable. Serum HTLV-I antibody levels were elevated at 1:8192 to 1:32,768, whereas those in cerebrospinal fluid were low at 1:4 to 1:8. Electrophysiological studies revealed polyphasic compound muscle action potentials with denervation potentials on nerve conduction studies and neurogenic patterns by electromyography, which were consistent with signs of chronic motor dominant demyelinating polyneuropathy. Sural nerve biopsy showed decreased myelinated fibers, occurrence of globule formation, myelin ovoid and remyelinated fibers, and an infiltration of CD68-positive macrophages with occasional CD4-positive T cells in the nerve fascicles. The polyneuropathy was responsive to steroid therapy. Analyses of serological human leukocyte antigen (HLA) types indicated that none of the patients possessed a high-risk HLA type known to be associated with adult T-cell leukemia (ATL), whereas they did have high responsive alleles to HTLV-I env similar to that observed in HAM. Nucleotide sequence analysis of the HTLV-I tax region demonstrated the B subgroup in all patients. This study suggests that HTLV-I infection can result in the development of a familial form of polyneuropathy that is associated with distinct HLA class I alleles, which might possibly involve a distinct virus subtype.     

Chronic inflammatory demyelinating polyneuropathy in childhood: clinical and electrophysiological features

Five children with chronic progressive polyneuropathy but no familial history of it showed electrophysiological evidence of demyelination with partial conduction block, temporal dispersion, and focal slowing of nerve conduction velocities in multiple nerves. These findings are indicative of an acquired demyelinating polyneuropathy that is chronic and inflammatory and differentiate this condition from most of the inherited neuropathies. It is very important to recognize this entity because of the avaibility of various treatments.     

Massive nerve root enlargement in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: To report three patients with chronic inflammatory demyelinating polyneuropathy (CIDP) presenting with symptoms suggestive of cervical (one patient) and lumbar root disease. METHODS: Nerve conduction studies, EMG, and nerve biopsy were carried out, having found the nerve roots to be very enlarged on MRI, CT myelography, and at surgery. RESULTS: Clinically, peripheral nerve thickening was slight or absent. Subsequently one patient developed facial nerve hypertrophy. This was mistaken for an inner ear tumour and biopsied, with consequent facial palsy. Neurophysiological tests suggested a demyelinating polyneuropathy. Sural nerve biopsy showed in all cases some loss of myelinated fibres, inflammatory cell infiltration, and a few onion bulbs. Hypertrophic changes were much more prominent on posterior nerve root biopsy in one patient: many fibres were surrounded by several layers of Schwann cell cytoplasm. There was an excellent response to steroids in two patients but not in the third (most advanced) patient, who has benefited only marginally from intravenous immunoglobulin therapy. CONCLUSIONS: MRI of the cauda equina may be a useful adjunct in the diagnosis of CIDP.     

Motor neuropathy with multifocal conduction blocks

We describe a patient with a chronic, symmetric, monophasic, acquired, pure motor, demyelinating polyneuropathy. Electrodiagnostic studies showed the presence of multifocal conduction blocks in motor nerves at sites not prone to compression. A sural nerve biopsy was normal. The patient responded to immunosuppressive therapy and plasma exchange. We postulate that this disorder is an unusual variant of chronic inflammatory polyradiculoneuropathy.     

Immune-mediated components of hereditary demyelinating neuropathies: lessons from animal models and patients

Most demyelinating forms of Charcot-Marie-Tooth type 1 (CMT1) neuropathy are slowly progressive and do not respond to anti-inflammatory treatment. In nerve biopsy samples, overt lymphocytic infiltration is absent, but pathological features typical of macrophage-related demyelination have been reported. In mouse models of CMT1, demyelination was substantially reduced when the mutants were backcrossed into an immunodeficient genetic background. A few individual patients with CMT1 respond to anti-inflammatory treatment; however, unlike most patients with CMT1, these patients show accelerated worsening of symptoms, inflammatory infiltrates in nerve biopsies, and clinical features resembling chronic inflammatory demyelinating polyneuropathy as well as CMT1. We conclude that in patients with typical CMT1 and in animal models, a cryptic and mild inflammatory process not responsive to standard anti-inflammatory treatment fosters genetically mediated demyelination.     

Upper limb pain in chronic demyelinating polyneuropathy: electrophysiological correlates

Pain is not usually considered a symptom of chronic relapsing demyelinating polyneuropathy. We report two patients with chronic demyelinating polyneuropathies in whom clinical and electrophysiological worsening was associated with the development of deep and distressing upper limb aching discomfort. One patient had a MGUS-associated hypertrophic demyelinating and prednisone-dependent polyneuropathy, followed over a course of two and a half years. His discomfort regularly predicted electrophysiological relapse of neuropathy, before more obvious clinical signs had emerged. Resolution of the discomfort also predicted subsequent clinical and electrophysiological improvement. Upper limb pain may be an important feature of early relapse in some patients with demyelinating polyneuropathies. Standardized serial electrophysiological testing in patients with chronic demyelinating polyneuropathy can be an important management tool in conjunction with clinical signs and symptoms.     

Up-regulation of cyclooxygenase-2 in inflammatory demyelinating neuropathy

To clarify the role of prostaglandins in peripheral nerve demyelination, we examined the expression of cyclooxygenase-2 (COX-2) using selected nerve specimens from patients with chronic inflammatory demyelinating polyneuropathy. COX-2 protein was up-regulated in macrophages causing active demyelination. In situ hybridization revealed that COX-2 mRNA signals were strongly expressed on macrophages adhering to the demyelinating nerve fibers at the endoneurium. This observation may provide a rationale for application of neuroprotective strategies employing COX-2 inhibitors in inflammatory demyelinating neuropathies.     

Clinical and electrophysiological parameters distinguishing acute‐onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy

Up to 16% of chronic inflammatory demyelinating polyneuropathy (CIDP) patients may present acutely. We performed a retrospective chart review on 30 acute inflammatory demyelinating polyneuropathy (AIDP) and 15 acute‐onset CIDP (A‐CIDP) patients looking for any clinical or electrophysiological parameters that might differentiate AIDP from acutely presenting CIDP. A‐CIDP patients were significantly more likely to have prominent sensory signs. They were significantly less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or need for mechanical ventilation. With regard to electrophysiological features, neither sural‐sparing pattern, sensory ratio >1, nor the presence of A‐waves was different between the two groups. This study suggests that patients presenting acutely with a demyelinating polyneuropathy and the aforementioned clinical features should be closely monitored as they may be more likely to have CIDP at follow‐up. Muscle Nerve, 2010     

Chronic inflammatory demyelinating polyneuropathy, phrenic nerve and respiratory symptoms

Respiratory involvement in chronic inflammatory demyelinating polyneuropathy (CIDP) has been very recently described. Phrenic nerve conduction studies have been described as useful to detect respiratory impairment in these patients. This study describes two patients with CIDP, in whom neurophysiological studies of the respiratory muscles were performed. The first patient had severe respiratory insufficiency, and phrenic nerve studies disclosed no motor responses and electromyography (EMG) of the diaphragm confirmed severe loss of motor units, bilaterally. On treatment, we documented clinical and neurophysiological improvement. In the second patient, phrenic nerve studies showed abnormal results; however, EMG of the diaphragm ruled out loss of motor units. The first case represents the risk of phrenic nerve involvement in this disorder, and the potential recovery on treatment. The second case illustrates that the temporal dispersion of the motor responses can be misleading, and EMG of diaphragm should be performed to confirm the loss of motor units.