ARTICLE IN BRIEF
Dutch investigators have identified differences that could help clinicians differentiate patients with Guillain-Barré syndrome from those with chronic inflammatory demyelinating polyneuropathy with acute onset.
Many patients with Guillain-Barré syndrome (GBS) experience an episode of deterioration after beginning treatment, with symptoms similar to chronic inflammatory demyelinating polyneuropathy with acute onset (A-CIDP). Because of this, physicians often have difficulty making a correct diagnosis during the early stages of the disease.
Both GBS and A-CIDP are immune-mediated disorders, investigators noted in a report that appeared online before the May 25 print issue of Neurology. But based on a prospective study examining extended clinical outcomes, biological material, and electrophysiological data for a one-year period of patients with both disorders, the Dutch investigators have identified differences that could help clinicians differentiate patients with GBS from those with A-CIDP.
Ten percent of 170 subjects diagnosed with GBS had treatment-related fluctuations (GBS-TRF), and all of the episodes occurred within eight weeks after symptom onset, but typically at around four weeks, the investigators reported. Conversely, none of the eight patients found to have had A-CIDP began fluctuating until after eight weeks, and, unlike the GBS patients, they tended to have at least three episodes after that time.
A-CIDP was even more likely if a patient could still walk unaided, had no cranial nerve dysfunction, and had electrophysiological features compatible with CIDP, according to lead author Liselotte Ruts, MD, a research neurologist at Erasmus University in Rotterdam, the Netherlands.
Among the GBS patients, the median length of time before their first TRF was 18 days, but ranged from 10–54 days; 31 percent had a second TRF, but no additional fluctuations after 8 weeks.
A-CIDP patients were less severely affected, did not need artificial ventilation, rarely had cranial nerve dysfunction, and tended to have more CIDP-like electrophysiological abnormalities, according to the paper. GBS-TRF patients were more severely affected and had more sensory disturbances when compared to the GBS group without fluctuations.
The investigators concluded that a diagnosis of A-CIDP should be considered in patients diagnosed with GBS if they have TRF after eight weeks, or when these episodes occur three times or more, especially in patients who are able to walk independently, have no evidence of cranial nerve dysfunction, and have electrophysiological signs compatible with CIDP.
Using these differences, physicians should be able to initiate appropriate maintenance therapy for A-CIDP patients sooner, according to the researchers.
GBS-TRF patients are generally treated with a repeated course of intravenous immunoglobulin (IVIG) or plasma exchanges, while A-CIDP patients require long-term maintenance treatment with steroids, and IVIG or plasma exchange, with or without immunosuppressant drugs.
The team's initial observations were reported in a brief communication in Neurology in 2005. In that study they compared 11 patients with GBS and 13 with A-CIDP and concluded that A-CIDP should always be suspected when a patient diagnosed with GBS deteriorates after nine weeks, or when a patient experiences three or more treatment fluctuations.
CONFIRMATION IN EARLIER FINDINGS
In addition to the earlier study by Dr. Ruts and her team, the findings also corroborated the findings of a 2003 study by Japanese researchers who performed a retrospective review of the medical records of 663 patients diagnosed with GBS.
Published in the Journal of Neurology, the study reported that 13 patients relapsed at least eight weeks after responding to initial treatment with plasmapheresis or IVIG, and 11 of them were later found to have had CDIP. These patients progressed more slowly than did the GBS patients and in 11 cases, the time to relapse from the onset was more than four weeks. Two suffered a relapse between four and eight weeks from onset, and three patients also had had an antecedent infectious illness. CSF albumino-cytological dissociation was detected in six of the CDIP patients within two weeks of onset.
One of the authors of that study, Nobuhiro Yuki, MD, PhD, a senior research fellow in the departments of microbiology and medicine at the National University of Singapore, Malaysia, told Neurology Today in an e-mail that the new study confirms their earlier conclusion that doctors can make a distinction between GBS and CDIP patients after four weeks.
“Dr. Ruts and her colleagues previously reported, in the retrospective study, that CIDP should be suspected when a patient with GBS deteriorates after eight weeks from onset, or when deterioration occurs three times or more,” he said. “This prospective study confirms these earlier findings and our own.”
Some clinical and electrophysiological features also can be helpful for distinguishing A-CIDP from GBS, but cannot be used to define the disorder, he added. “Although time course is the most important factor distinguishing the two diseases at present, biomarkers such as auto-antibodies are likely to be identified in future studies.”
TREAT THE INDIVIDUAL
Neurology Professor Norman Latov, MD, PhD, who directs the Peripheral Neuropathy Center at Weill Medical College of Cornell University in New York City, told Neurology Today in an e-mail that there is no downside to the increased awareness about differentiating patients with the two conditions so they can be promptly treated in case of deterioration.
But he noted that not all patients will fit these profiles, so treatment needs to be tailored to the individual patient. At present, the diagnosis of CIDP requires demonstration of demyelinating changes, and progression for longer than three months, he said. Electrodiagnostic changes in GBS are more variable and progression is limited to eight weeks.
“This new data extends our ability to recognize CIDP in patients who present with a first episode of neuropathy. If there is deterioration after eight weeks, then the patient is more likely to have CIDP. Otherwise they are likely to have GBS,” he said.
GBS is a self-limiting disorder, while CIDP is a chronic disorder that may require repeated or maintenance therapy.
“By definition, if there is no stabilization or improvement by eight weeks, regardless of treatment, then the patient does not have GBS. The issue is more complicated in CIDP, as a patient may not respond to initial therapy, but respond to subsequent, more aggressive therapy,” Dr. Latov noted.
“Other than that, the level of disability is quite variable for both disorders, and depends on the severity of the nerve damage. Physicians should be alert to the possibility of deterioration after an initial response to treatment, in which case repeated treatments may be necessary to prevent irreversible damage and permanent disability.” •
• Ruts L, Drenthen J, van Doorn PA, et al, of the Dutch GBS Study Group. Distinguishing acute onset CIDP from fluctuating Guillain-Barré syndrome; a prospective study. Neurology 2010; Epub 2010 April 28
• Ruts L, van Koningsveld R, van Doorn P. Distinguishing acute-onset CIDP from Guillain–Barré syndrome with treatment related fluctuations. Neurology 2005;65:138–140.
• Odaka M, Yuki N, Hirata K. Patients with chronic inflammatory demyelinating polyneuropathy initially diagnosed as Guillain-Barré syndrome. J Neurol