Clinicopathological characteristics of subtypes of chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To evaluate the clinical and pathological correlations characterising each clinical subtype of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We assessed 106 consecutive patients who had CIDP fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society criteria and had been referred for sural nerve biopsy. Patients with anti-neurofascin 155, anti-contactin 1 and anti-LM1 antibodies were excluded. RESULTS: 55 patients were classified as having typical CIDP. Regarding atypical CIDP, the multifocal acquired demyelinating sensory and motor (MADSAM) (n=15), distal acquired demyelinating symmetric (DADS) (n=16) and pure sensory (n=15) forms were major subtypes, while the pure motor (n=4) and focal (n=1) forms were rare. Nerve conduction studies revealed that distal motor latencies and F-wave latencies were markedly prolonged in the typical CIDP group but relatively preserved in the MADSAM group. Motor conduction velocity was conspicuously slowed in the DADS group, and distal motor latencies were markedly prolonged in the pure sensory group. Sural nerve biopsy specimens from patients with MADSAM, DADS and pure sensory type tended to show extreme variation in myelinated fibre density among fascicles due to focal myelinated fibre loss or onion-bulb formation, whereas patients with typical CIDP tended to show mild fascicular variation. Epineurial lymphocytic infiltration was conspicuous in cases with marked fascicular variation in myelinated fibre density. CONCLUSIONS: Preferential involvement of distal and proximal segments and uniform pathological features in typical CIDP indicate a role of humoral factors at sites where the blood-nerve barrier is deficient. By contrast, focal lesions in MADSAM, DADS and pure sensory forms may share neuropathic mechanisms primarily affecting the nerve trunk.

Childhood CIDP: Study of 31 patients and comparison between slow and rapid-onset groups.

OBJECTIVES: To describe 31 children presenting a CIDP; to compare patients with rapid-onset disease vs. patients with slow-onset disease, a rapid-onset disease being defined by a time to peak impairment of less than 8 weeks. STUDY DESIGN: A retrospective chart review identified 31 patients completing criteria for childhood CIDP, with 24 "confirmed CIDP" and 7 "possible CIDP". Data collected were time to peak impairment, clinical presentation, cerebrospinal fluid analysis, nerve conduction study, nerve biopsy, treatments. Evaluation at the end of follow-up was reported according to modified Rankin scale. RESULTS: Thirteen patients (42%) exhibited symptoms in less than 2 months with more often cranial nerve abnormalities (38% vs. 6%, p = 0.059), and sensitive symptoms (62% vs. 11%, p = 0.0057). They evolved predominantly in a relapsing way (69% vs. 22%, p = 0.0047). Length of the disease was also longer in the rapid-onset group (5.5 years vs. 3.83 years) but without statistical difference. The slow-onset group exhibited more frequently ataxia at onset (28% vs. 8%, p > 0.05), and evolved predominantly in a progressive manner (61% vs. 15%, p > 0.05). Outcome was similar and good in the two groups. At least 3 out of the 4 major electrophysiological criteria were positive for 27/31 children (87%). Axonal involvement could be present very early. Immunoglobulins were given in 29 cases and corticosteroids in 22. A partial or complete recovery 1 month after first treatment was reported in 30 cases. Among second-line treatments, only azathioprine seemed effective in two out of three intractable children. CONCLUSIONS: The differences noted between the two groups should be tested in wider populations. Electrophysiological criteria are restrictive and axonal involvement should be studied. Prospective trials are required to find out the best first and second line treatments.

Does the chronic inflammatory demyelinating polyradiculoneuropathy due to secondary cause differ from primary?

BACKGROUND: The clinical presentation, neurophysiological findings, and outcome may vary between primary and secondary chronic inflammatory demyelinating polyradiculopathy (CIDP). OBJECTIVE: To compare clinical and electrodiagnostic features of primary and secondary CIDP. SETTING: Tertiary care teaching referral hospital. MATERIALS AND METHODS: The CIDP patients who were diagnosed as per European Federation of Neurological Societies/Peripheral Nerve Society criteria were included and subjected to detailed history and examinations. The clinical disability was graded on a 0-10 scale. Neurophysiology included motor and sensory nerve conductions and F wave studies of all four limbs. Based on investigations for underlying diseases, the patients were categorized into primary or secondary CIDP. Prednisolone was prescribed in all and azathioprine added in resistant cases. The secondary CIDP group received specific treatment in addition. The outcome was assessed at 3 months, 6 months, and last follow-up. RESULTS: A total of 65 patients aged 17 to 72 years were included and 20 were females. Twenty-five patients had secondary CIDP and include diabetes mellitus (16), POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) (4), monoclonal gammopathy of undetermined significance (2), myeloma (1), lymphoma (1), and malignancy (1). The secondary CIDP patients were older (48.35 vs 41.0 years), had less relapsing remitting (0 vs 6) and more frequent dysautonomia (7 vs 1). The demyelinating features were more marked in primary CIDP group and had better outcome compared with secondary CIDP. CONCLUSIONS: Of the total patients with CIDP, 38.5% of patients had secondary CIDP which was associated with progressive course, less demyelinating features, and worse prognosis.

Distal acquired demyelinating symmetric neuropathy associated with anti-GM1 antibodies: is this a CIDP variant?

Distal acquired demyelinating symmetric (DADS) neuropathy is clinically characterised by distal motor and sensory disturbances. Typically DADS does not respond or responds poorly to intravenous immunoglobulins (IVIg). We report the case of a 58-year-old patient who developed distal paraparesis. Serum electrophoresis demonstrated monoclonal IgM paraproteinemia having an anti-GM1 but no anti-MAG activity. Conduction velocities showed demyelinating pattern. Work-up excluded a lymphoproliferative disorder After IVIg treatment we observed a clinical and neurophysiological improvement. Regarding these peculiar findings, we suggest that DADS needs to be splitted in several forms determined among others by clinical, neurophysiological and antiganglioside profile and therapeutic response. We advocate to perform systematic antiganglioside antibodies assay additionnaly to anti-MAG when DADS is suspected in order to improve dysimmune neuropathies classification.

Research criteria for defining patients with CIDP.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is one of several chronic acquired demyelinating neuropathies that are considered to be autoimmune diseases. The prevalence of these illnesses may be underestimated because of limitations in clinical, serologic, and electrophysiologic diagnostic criteria. An Ad Hoc Subcommittee of the American Academy of Neurology (AAN) proposed a set of diagnostic criteria for CIDP to be used for research purposes, and several other criteria followed. Of these, the AAN electrophysiologic criteria are the most restrictive and fit only a subset of patients with CIDP. Other criteria, including the Inflammatory Neuropathy Cause and Treatment (INCAT) clinical and electrophysiologic criteria and the Nicolas or Thaisetthawatkul electrophysiologic criteria, are more sensitive and can therefore identify a broader range of patients with CIDP for clinical trials. Regardless of which criteria are chosen for use in clinical trials, patients who fall outside of these criteria may also have CIDP and may benefit from treatment. Unfortunately, because of the lack of clarity with regard to diagnostic criteria for CIDP, many patients remain untreated. In addition, certain CIDP variants may also respond to treatment. These include sensory CIDP, multifocal motor neuropathy (MMN) with or without conduction block, multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, distal acquired demyelinating sensory (DADS) neuropathy, and multifocal acquired sensory and motor (MASAM) neuropathy. Therefore, although patients may not meet the diagnostic criteria for inclusion in clinical trials of CIDP, they may still benefit from current and future treatments used in CIDP.

Distribution patterns of demyelination correlate with clinical profiles in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder having a wide clinical range, and is characterised by multifocal demyelination that can involve the distal nerve terminals, intermediate nerve segments, and nerve roots. OBJECTIVE: To investigate whether the distribution patterns of demyelination along the course of the nerve correlate with clinical profiles in patients with CIDP. METHODS: Motor nerve conduction studies were carried out on 42 consecutive patients. According to the physiological criteria for demyelination, the presence of a demyelinative lesion was determined in the distal nerve segments (distal pattern) or intermediate nerve segments (intermediate pattern), or in both (diffuse pattern). The serum concentration of tumour necrosis factor (TNF)-alpha was measured by immunoassay. RESULTS: Patients were classified as having a distal (n=10), intermediate (n=13), or diffuse (n=15) pattern, or were unclassified (n=4). Patients with the distal or diffuse pattern had common clinical features such as subacute onset, symmetric symptoms, and weakness involving proximal as well as distal muscles. Patients with the distal pattern had a good response to treatment and a monophasic remitting course, but the diffuse pattern was associated with a treatment dependent relapsing course, reflecting longer disease activity. The serum TNF-alpha concentrations increased only in the "diffuse" subgroup of patients, and this might be associated with breakdown of the blood-nerve barrier and therefore, involvement of the intermediate segments. The intermediate pattern was characterised by a chronic course, asymmetric symptoms, less severe disability, and refractoriness to treatments. CONCLUSIONS: CIDP consists of subtypes with varying predilections for lesions along the course of the nerve. The distribution patterns of conduction abnormalities may be useful in the prediction of outcome of patients with CIDP.

Chronic inflammatory demyelinating polyradiculoneuropathy: a study of proposed electrodiagnostic and histologic criteria.

OBJECTIVE: To examine the sensitivity of the 3 proposed electrodiagnostic (EDX) criteria for demyelination, the sensitivity and specificity of the proposed Ad Hoc Subcommittee of the American Academy of Neurology AIDS [Acquired Immunodeficiency Syndrome] Task Force histologic criteria (AAN criteria), the degree of agreement among these criteria, and the diagnostic value of sural nerve histologic criteria in patients with idiopathic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). DESIGN AND METHODS: A retrospective analysis of 24 patients with idiopathic CIDP and 12 patients with diabetic polyneuropathy (DP) who underwent comparable testing of clinical, histologic, and EDX features. RESULTS: We found 42%, 50%, and 79% sensitivity of the proposed EDX, AAN teased fiber, and AAN electron microscopic (EM) criteria, respectively, for demyelination in CIDP. The specificity of the proposed AAN teased fiber and EM criteria for demyelination was greater than 80% when tested against patients with DP. There was lack of agreement between the EDX and histologic criteria. Almost two thirds of patients with CIDP who met the EM criteria but none of the EDX criteria for demyelination showed a favorable response to immunomodulatory therapy. CONCLUSIONS: Sural nerve histologic criteria offer unique sensitivity and acceptable specificity toward the diagnosis of CIDP. Sural nerve biopsy should be considered when a clinical suspicion of CIDP remains in patients who do not meet the proposed EDX criteria for demyelination.