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ELECTRODIAGNOSTIC DATA:
The above findings are felt to be most consistent with a diffuse, distal predominant, sensori-motor demyelinating neuropathy. Clinical considerations would include:
ELECTROPHYSIOLOGIC OVERVIEW: The data obtained, not only confirms a diagnosis of polyneuropathy, but provides further classification of a demyelinating disorder by meeting numerous criteria proposed by several investigators. Important to recognize is that not all authors are in unanimous agreement on the exact specifics of demyelniation. The following are some examples:
Important to recognize is that, while meeting the above criteria does substantiate the presence of a peripheral demeylinating disorder, the absence of such evidence does not necessarily exclude it from diagnostic consideration. Albers further demonstrated how the timing of the electrophysiologic exam can be a determinant in the percentage of individuals showing positive results, with only 50% of Guillain-Barre patients meeting his criteria in weeks 1-2, and 85 % meeting the criteria by week 3. In a subsequent paper, he further went on to describe how, due to the patchy nature of demyelinating conditions like AIDP, electrodiagnostic studies often fail to confirm the diagnosis in the earlier stages (101) An important adjunct to the early diagnosis of an acquired demyelinating neuropathy, and one that also helps to discriminate between a demyelinating and axonal disorder is termed the “sural sparing” pattern or “normal sural-abnormal median” pattern, which, when present, points strongly towards a demyelinating disorder. (4), (5). Sural sparing has been defnined as having either a normal (>6 uV) or relatively preserved Sural SNAP compared to at least two abnormal/absent upper extremity SNAPs (6). A normal Sural SNAP with absent or reduced Median and Ulnar SNAPs is felt to be a highly specific sensory finding in AIDP (4), (6), (7) This statement, however, is somewhat misleading in that the sural sparing pattern is also seen in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (8). In fact, the electrophysiologic features of CIDP and AIDP are very similar (9) and it is the time frame in which these evolve, rather than their electrodiagnostic features which differentiate one from the other. As such, the presence of the sural sparing pattern should be interpreted in light of the temporal profile of the illness, and considered indicative of an acquired demyelinating neuropathy rather than a distinct named entity such as Guillain-Barre. Another utility of sensory amplitude ratios, although not directly related to this case, has been found in the detection of mild, axonal peripheral neuropathies when the Sural/Radial amplitude ratio (SRAR) is below .4 (10) In addition to the above findings, our patient also exhibited an increased CMAP duration and decreased terminal latency index (TLI) in several motor nerves tested. In recent years, dispersion of the distal CMAP has emerged as a useful adjunct in the electrodiagnosis of CIDP by increasing sensitivity of the diagnosis, without compromising specificity. (11). More recently, Cleland et al (12) looked at distal CMAP duration, as an indicator of distal demyelination, in relationship to patients presenting with AIDP. In comparing AIDP (a primary demyelinating disorder) and Amyotrophic Lateral Sclerosis (a primary axonal disorder), they found that distal CMAP dispersion (defined as a distal CMAP duration > 8.5 msec) was found in 31% of all motor nerves tested in the AIDP cohort, and was present in at least one motor nerve in 66% of that group. In contrast, the ALS subjects showed only 3% of the nerves having an increased duration, in only 9% of the total number of patients tested. Their major conclusion was that the presence of distal CMAP dispersion discriminates reasonably well between a typical motor loss disorder and demyelinating conditions, but further more, that as a sole diagnostic criterion, it also performs as well or better than 4 previously published, and more complicated sets of electrodiagnostic standards for diagnosing AIDP. Knowing that nerve conduction slowing in disorders such as CIDP can, at times, overlap with hereditary demyelinating neuropathies (13), (14), (15), a comparison of CMAP duration between these two categories would seem clinically relevant. Recently, Stanton et al. (16) performed such a study. In their study, they compared CMAP duration and incidence of proximal-distal temporal dispersion in 91 patients with various forms of hereditary neuropathy, confirmed with genetic testing, to a cohort of 33 patients who had been diagnosed with CIDP. Although the mean distal CMAP dispersion was greater (10 +/- 4.3 msec) in the CIDP group as compared to the hereditary group (7.33 +/- 1.8 msec), a fair percentage of those with the hereditary conditions (33%) had one or more motor nerves which exceeded the cut off point of for distal CMAP duration of > 9 msec. The percent of CMT1A patients, having at least one nerve exceed this level was even greater at 43%. However, distal CMAP duration dispersion in two or more nerves was present in 39% of the CIDP cohort as compared to only 3.3% of those with hereditary neuropathies. The implicit message is to avoid making a snap judgment when the history and entirety of the electrodiagnostic data is not confirmatory and, to use genetic testing, when necessary, to distinguish between the two conditions. In the upper extremity, terminal latency index (TLI) allows comparative assessment of the conduction time along the distal (wrist to thenar) nerve segment with that of the intermediate segment (elbow to wrist). (17) The calculated formula is:(18) (Distance at terminal stimulation site)/(Terminal Latency) x (Conduction Velocity Across Forearm) Among other reported uses, it has been found to aid in the prognosis for different categories of CIDP (8)(20) to assist in differentiation between various forms of demyelinating neuropathies, specifically hereditary versus acquired, (21) and to have a high predictability for identifying those neuropathies that are associated with Anti-MAG activity.(18)(17)(19). The identification of an Anti- MAG and/or Anti-SGPG neuropathy is important as these conditions, often associated with an underlying IgM paraprotein, although distal predominant, are generally less responsive to standard immune modulating therapy and typically run a slowly progressive course.(18) Of more profound significance is that there may be a greater chance of an underlying malignant gammopathy or Waldenstrom’s disease in Anti-MAG/SGPG patients.(19) Kuwabara et al (8) and Mygland et al(20) each demonstrated that patients having CIDP and a low TLI, which is indicative of a distal predominance of demyelination, showed a more favorable prognosis. In evaluating a group of patients with various forms of demyelinating neuropathy in comparison to normal controls Attarian et al(21) found that the TLI was decreased 21/25 patients with Anti- MAG/SGPG, normal or increased in Charcot-Marie-Tooth 1A(CMT 1A), and normal or increased in 16/19 CIDP patients. That study, further reinforced what had been detected in earlier work by Kaku at al(22) who found that 16/21 nerves studied in patients with Anti-MAG/SGPG neuropathy had a TLI <.25 as compared to only 2/195 nerves studied in CMT 1A and 3/49 nerves in CIDP. Vitale’s group(17) recently provided additional support for the prior studies by showing that Anti-MAG/SGPG patients consistently had a Median TLI <.26 as compared to CMT 1A patients with a TLI >.32. Patients having intermediate Median TLI (between .26 and >32) often required further testing for confirmatory diagnosis. Mygland(19) did point out that a low TLI in his CIDP patients could be a factor of the timing of the elctrodiagnostic assessment, noting that this was found primarily in patients studied early in the course of the disease process. Thus, this may provide some reconciliation with Attarian et al and Kaku et al’s finding of CIDP patients having a normal to increased TLI. DECISION MAKING AND ADDITIONALWORK UP In a patient exhibiting the clinical and electrodiagnostic features which have been illustrated, the possibility of an underlying toxic, infectious, systemic, or paraneoplastic etiology warrants consideration, specifically seeking those disorders associated with a demyelinating neuropathy. A toxic neuropathy was felt to be very unlikely due to the absence of any neurotoxic medications and lack of known exposure to industrial/environmental agents. As such, no further work was performed in this area. Although most neurotoxins manifest as an axonopathy(23), there are several that can cause demyelinating disease. Potential medicinal toxins in this category include chloroquine, tacrolimus, hexachlorophene, perhexillene, muzolimine, procainimide, tellurium, zimeldine, suramin, amiodarone, cytarabine, and streptokinase.(24)(25)(26). Although predominantly causing an axon loss neuropathy, arsenic intoxication has been associated with a Guillain Barre type of syndrome(27). A sub-acute neuropathy with primary demyelinating features has also been attributed to n-hexane secondary to either occupational exposure or recreational glue sniffing.(28)(29) Although unlikely to be seen in an office setting due to the abrupt and severe evolution of symptoms, marine toxins such as tetrodotoxin, saxitoxin, and ciguotoxin result in prominent deymelinating features, primarily through their effects on ion channels(25)(30)(31)(32). Symptoms typically develop within 2-3 hours after ingestion, usually beginning with oro-lingual and acroparesthesia, breathlessness, vertigo, nausea, and vomiting. Eliciting a history of fish ingestion , particularly shellfish, shortly prior to the onset of symptoms, in the presence of rapidly progressive neurologic signs and symptoms is the key to diagnosis. Similar to toxic substances, infectious neuropathies typically manifest as a sensori-motor axonal neuropathy. Levin(25) has listed several of these as potential etiologies in the presence of an acute, rapidly progressive, motor or motor/sensory syndrome. Of those listed, Diptheria and HIV are associated with segmental demyelination. The patient had no other clinical stigmata of either condition. Specific to HIV, the patient was currently in a monogamous relationship and had a past history that placed him at low risk for this disorder. HIV testing was offered, but declined by the patient. Tropical Spastic Paraparesis is a disorder more common in the equatorial regions and associated with HTLV-1 infection. Peripheral neuropathic features can occur, usually as a mixture of axonal and demyelinating characteristics but there is also the common finding of prominent upper motor neuron signs such as spasciticy and a neurogenic bladder, sometimes accompanied by a cerebellar ataxic syndrome and/or cranial nerve involvement.(115) (116)(117) Paraneoplastic syndromes are neurologic disorders, associated remotely with a cancer, that often become symptomatic before the cancer is diagnosed, evolve subacutely over days or weeks then stabilize, and usually have caused substantial disability at the time of a patient’s initial examination. (33) A discussion of the wide variety of onoco-neural antibodies used for detection and their related paraneoplastic syndromes is beyond the scope of this presentation. Peripheral nerve manifestations of paraneoplastic syndromes are usually axonal, sensory or sensori-motor, and associated with Anti-Hu and/or Anti-CV2 antibodies, often due to an underlying small cell lung cancer. (34), (35), (36). However, Jean-Christope’s study (36) further pointed out that, although patients who were positive for Anti-Hu and/or Anti-CV2 onco-neuronal antibodies usually had the axonal sensori-motor phenotype, several patients were discovered exhibiting primary demyelinating characteristics. A paraneoplastic demyelinating phenotype associated with Anti-Hu antibody was also exhibited in a case report by Eggers et al. (37) Not strictly within the defined category of a paraneoplastic syndrome, myelodysplastic disorders (38) lymphomas, (39),(40),(41), solitary osteosclerotic plasmacytomas, (42),(43), and various other paraproteinemias (44), (45), (46) including multiple myeloma (47),(48) and Waldenstrom’s macroglobulinemia (49), (50) are associated with demyelinating neuropathies. In fact, a fairly recent study, seeking to characterize neuropathies associated with elevated serum IgM levels found that 73% of the patients with elevated serum IgM levels fulfilled at least one published criteria for CIDP. (51) Despite the fact that our patient was otherwise healthy, and did not exhibit the progressive or severe neurologic disability that is generally associated with underlying metastatic disorders, it was felt prudent to still exclude those conditions associated with demylinating neurophysiologic features which, if present but undiagnosed, would pose dire consequences. Furthermore, the phenotype of this patient’s neuropathy, exhibiting a clear distal predominance, is one that is often found with an underlying IgM paraproteinemia and associated Anti-MAG and Anti-SGPG antibodies. (17),(22). Somewhat incongruous, however, with the classic presentation of an Anti-MAG/SGPG neuropathy is that our patient did not have the profound low extremity sensory loss that is typically seen and the onset was more abrupt. Additionally, from a prognostic standpoint, Anti-MAG/SGPG neuropathies do not respond to treatment as readily as do other dysimmune neuropathies but the overall progression of the disease is very slow. (18) Based upon the preceding thought process and diagnostic concerns, additional testing was performed including; CBC, ESR, Comprehensive metabolic panel, T4, TSH, Serum and Urine Immunoelectrophoresis, Anti-Hu and Anti-CV2 antibodies. Anti-MAG antibodies were also obtained as, occasionally, these can be seen in the absence of a measurable M-protein. (58),(59),(60) Serum levels of vitamin E, B12, and Folic Acid were obtained. Vitamin E deficiency can cause a demyelinating neuropathy and is usually associated with intestinal malabsorbtion,(53) although isolated deficiencies and an associated neuropathy have also been seen. (54),(55). Deficiencies of vitamin B12, characteristically associated with a sensori-motor axonal neuropathy and/or myeloneuropathy, has also been shown to cause isolated peripheral neuropathy with primary demyelinating features. (56),(57) A chest x-ray was obtained to evaluate the mediastinal lymph nodes. All of the preceding testing was found to be normal. Based upon the normalcy of all test results, it was not felt necessary to undertake an extensive skeletal survey for a solitary osteosclerotic lesion, although these lesions have been reported to occur even in the absence of a monoclonal protein on immunoelectrophoresis.(118) The patient was offered CSF analysis but declined as, shortly after his incident visit, he had reported a noticeable reduction in his paresthesias, had not developed any significant motor weakness, and had a lessening of his diffuse musculoskeletal pain. DISCUSSION: The idiopathic inflammatory neuropathies are a heterogenous group of disorders sharing the common presumption of an immune mediated attack on the peripheral nervous system but differing in the temporal profile of their onset and ultimate rate and degree of progression.(61) The peripheral nervous system serves as the target for an immune attack mediated by T-cells, B-cells, and macrophages and the interaction of these factors with the structural components of the nervous system may determine the extent of inflammation and possibly repair mechanisms.(94) Diffuse pain and/or fatigue although not invariably present, are common concomitants to the neurologic involvement. (62)(63) Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is characterized by a greater than 2 month progression of weakness and sensory loss with associated hyporeflexia and demyelinating features on electrophysiologic testing. (84). In the classic presentation, large diameter motor and sensory fibers are involved and weakness is evident, usually symmetrically, in distal and proximal muscles.(20) Numerous atypical presentations have been described including a multifocal sensori-motor variant termed Lewis-Sumner syndrome,(85) distal acquired demyelinating sensorimotor neuropathy (DADSM), often associated with a paraproteinemia and Anti-MAG reactivity, (86)(22)(18)(19) pure sensory variants, (87)(88) and a pure motor neuropathy that can often be confused with motor neuron disease unless electrodiagnostic evidence of conduction block or serologic evidence of Anti-GM1 or Anti-GD1a antibodies is present. (89)(90). Based upon the temporal profile exhibited by our patient, that being a rapid onset, with maximum neurologic deficit reached by 4 weeks, CIDP was not favored as a diagnosis. However, it is necessary to recognize that an acute presentation of CIDP, with similar maximum deficit achieved within 4 weeks, can occur.(92) In Mygland’s series of 44 CIDP patients, 3 exhibited such a presentation. (20). Odaka et al. (91) reported that in a series of 663 GB patients, 11 were eventually reclassified as CIDP based upon symptomatic relapses which occurred between 4-8 weeks after diagnosis. Recognizing that it is often difficult to differentiate acute onset CIDP (A-CIDP) from a GB treated related failure (GBS-TRF), Ruts et al., after studying 13 patients with A-CIDP, in comparison to 11 patients with GBS-TRF (93) opined that acute CIDP should be suspected when a patient with GBS deteriorates after 9 weeks from onset or when deterioration occurs three times or more. Guillain Barre syndrome is best viewed as a having at least two primary clinical subtypes, the commonest of which is that of an acute, acquired, demyelinating polyradiculopathy at one end of the spectrum and, at the other end, an acute motor axonal neuropathy.(61) Between those two ends are several variants, each of which share the abrupt onset of neurologic dysfunction, but differ in the location and symmetry of the disease process. Levin’s paper describes the currently recognized atypical forms as; asymmetric, pure motor, pure sensory, pure autonomic, and regional variants that include Miller-Fisher Syndrome, pharyngeal-cervical-brachial, paraparetic, and facial diplegia with paresthesia (25). Somarajan described a GB variant presenting with acute quadriparesis, brisk tendon reflexes, and electrophysiologic evidence of conduction block and temporal dispersion in multiple nerves, stating that the presence of brisk reflexes does not necessarily exclude GB as a diagnosis.(64). Hamidon described a case of GB presenting with only an acute bulbar palsy, manifesting with a nasal voice and difficulty swallowing, which showed rapid recovery. Although no other peripheral symptoms were present, the clinical examination showed generalized areflexia and NCV studies exhibited a demyelinating peripheral neuropathy (65) Mori et al., in their series of 464 consecutive GB patients, found that in 33 of those, hand weakness, clumsiness, and paresthesia were the initial symptoms and that the symptoms remained restricted to the hands in 4. (66) Bickerstaff’s Brainstem Encephalitis is a rare disorder presenting with acute opthalmoplegia, ataxia, disturbed consciousness, hyper-reflexia, and other signs of CNS involvement that may overlap with GB showing peripheral electrodiagnostic features of a predominantly motor axonal neuropathy. (67) Several antecedent infectious processes, usually respiratory or gastrointestinal, have come to be associated with the acute immune-mediated inflammatory neuropathties, which are felt to develop due to a process of “molecular mimicry” in which the antigenic properties of the infecting microorganism share similar epitopes with gangliosides within the human peripheral nervous system, thereby precipitating an immune reaction against normal nervous tissue components.(68)Antibodies to over 20 different glycolipids have been identified and associated with a range of acute and chronic neuropathic syndromes and it is hypothesized that the location of a particular glycolipid structure within the nerve, and the immunologic insult to that structure, plays a role in influencing the clinical presentation of the illness (73) Infections with Campylobacter jejuni, Cytomegalovirus, Epstein-Barr, and mycoplasma are thought to be the triggering agents in a majority of cases. (69),(70),(71). A recent study utilizing a more highly specific assay based upon C. jejuni genes Cj0017 and Cj01113 found serologic evidence of C. jejuni as the triggering agent in 80.6% of their GB patients and in only 3.5% of controls.(72) Other antecedent events have included immunizations, surgery, epidural anesthesia, and drugs.(96)(97) A recent case report by de Freitas et al. (98) noted the development of GB 15 days after brachial plexus trauma, further discussing two prior cases that had been reported secondary to acute head trauma. From a clinical standpoint, Guillain Barre and its variants are separated from the other inflammatory demyelinating neuropathies by a temporal profile exhibiting an acute onset with the attainment of maximum disability usually occurring within 4 weeks in 98% of the cases. (74). Diagnostic criteria has been published by Asbury and Cornblath that, while specific, may not be sensitive to atypical or mild forms. (100) Complete recovery reportedly occurs in 75%-87% of afflicted patients(75),(76),(77), although there are also reports illustrating a less favorable outcome, noting that up to 49% of patients can continue to experience disturbing residuals and only 33% felt completely cured one year after the onset of their illness. (95) The results of studies which have evaluated prognostic indicators have been somewhat inconsistent as well. Kaur et al noted that an adverse prognosis was expected when a patient exhibited a long interval between peak deficit and onset of recovery(> 3 weeks), and a coexistent reduced motor NCV associated with evidence of denervation.(106). However, it should be noted that this investigation took place prior to the more contemporary treatments for immune mediated neuropathies. Acute motor axonal neuropathy (AMAN), characterized by primary axonal damage and the associated low compound motor action potentials was once felt to carry a poor prognosis.(78) However, several studies have illustrated that certain patients with AMAN may actually improve more quickly than those with demyelinating GB.(79),(80) Kuwabara et al evaluated 80 consecutive GB patients finding that predictors of a rapid recovery included preservation of deep tendon reflexes at nadir of disease progression and serologic evidence of H influenza infection.(81) In this study, evidence of prior C. jejuni infection correlated with a poor prognosis in those patients with the axonal subtype. Other authors have also illustrated that an antecedent gastroenteritis illness and serologic evidence of C. jenjui correlated with a poorer prognosis, especially in the acute axonal varieties. (82)(74)(83). In the Italian Guillain-Barre Study Group, features, in addition to an antecedent gastroenteritis, which predicted a tendency towards a poor outcome included old age, short latency to nadir, and electrophysiologic features of axonopathy.(74) As an illustration of the lack of consensus regarding prognostic factors, Ng et al’s study reported that age had no bearing on prognosis, and that a longer time to nadir adversely influenced prognosis.(99). This preceding study did, however, confirm that those who had an antecedent C. jejuni illness fared worse than those who did not. A more recent study, evaluating 41 GB patients, described factors associated with a delayed mean recovery time (> 6-8 weeks) as being as being associated with any of; predominant distal low extremity weakness, proximal upper limb weakness, autonomic disturbance, and an axonal pattern on EMG.(107) Contrary to the preceding, Sing et al, in their study of 24 GB patients found no association between autonomic disturbance and prognosis. They did find that poor outcomes correlated with a prolonged peak of paralysis, lasting more than 2 weeks and delayed onset of recovery, not commencing within 3 weeks from the onset of the illness, additionally noting that bulbar paralysis and respiratory involvement were also adverse to a good recovery. (108) Electrodiagnostic findings in the acute inflammatory neuropathies will vary depending on the timing of the study and the neural substrates involved.(101) Neuropysiologic criteria for demyelination may not be met for those AIDP patients encountered early in their illness when the only abnormalities may be absent H- reflexes, abnormal F-waves, and a Sural sparing sensory pattern. (102) Gordon and Wilbourn evaluated the electrodiagnostic findings in 31 AIDP patients seen within the first week of their symptoms finding an absent H-reflex in 30, low amplitude or absent upper extremity SNAP in 19, Sural sparing pattern in 15, prolonged distal latency in 20, slow NCV in 16, prolonged F-waves in 25, reduced compound muscle action potential in 22, and motor conduction block in 4. They concluded that an absent H-response, abnormal F-wave, and a Sural sparing pattern are characteristic of early GB.(103). A higher rate of conduction block (CB), possibly due to a different operant definition of such, was found in Atanasova et al’s study which showed CB present in 81.2% of the 16 GB patients seen within the third day of their illness, being most commonly identified in the Peroneal > Tibial > Ulnar/Median nerves.(105) Other papers have also illustrated that the Sural sparing pattern is suggestive of GB and that the reverse of the Sural sparing pattern (abnormal or reduced Sural as compared to relatively normal upper extremity SNAP) may help to differentiate between GB, CIDP, and axonopathies. (4)(7) Further studying the Sural sparing pattern, otherwise known as “abnormal median-normal sural” response, Bromberg revealed that while this pattern is only seen in 3% of healthy controls, it is not necessarily specific to AIDP being seen in 39% of AIDP patients, 28% in CIDP patients, 14-23% of diabetic neuropathies, and even 22% of motor neuron disease patients.(5) As discussed earlier, Cleland et al have surmised that the identification of a distal CMAP of > 8.5 msec in duration, in the appropriate clinical context, is, as a sole criterion, both sensitive and specific for an early diagnosis of AIDP.(12) Subacute Inflammatory Demyelinating Polyneuropathy (SIDP) was first reported by Oh in 1978 as being a steroid responsive demyelinating neuropathy with a nadir to short to be diagnostic of CIDP and to long to fit criteria for AIDP.(109). This original report was expanded upon in 2003 based upon the author’s personal experience with 45 patients over a 32 year period.(110) Definite SIDP met the following: 1) progressive motor and/or sensory dysfunction consistent with neuropathy in more than one limb with time to nadir between 4-8 weeks. 2) electrophysiologic evidence of demyelination in at least two nerves, 3) no known etiology of neuropathy other than associated diseases, and 4) no relapse over a minimum 2 year follow up period. Criteria for probable SIDP were those meeting the first three standards, but with a less than 2 year follow up period to insure a relapse which would then re-classify the patient into a diagnosis of CIDP. Of the 45 patients, 16 were categorized as “definite” SIDP and were found to have a favorable response to prednisone, in contrast to AIDP patients whose response to prednisone is generally lacking. They were also noted to have a much better long term outcome that those patients who would eventually be classified as having CIDP. Oh felt that, based upon SIDP patients showing a more beneficial response to steroids than AIDP, the antecedent infection rate residing between AIDP and CIDP, the time frame of evolving neurologic dysfunction, and the outcomes and monophasic course which were closer to AIDP than to CIDP, that this entity stands on its own as a separately identifiable disorder bridging the gap between the true acute and chronic neuropathies. Although “probable” SIDP was considered in the diagnosis of our patient, it was excluded based upon the impression that our patient had reached the peak of neurologic dysfunction within a 4 week time frame. FINAL DIAGNOSIS: Our patient was diagnosed with a mild form of AIDP or demyelinating phenotype of Guillain-Barre syndrome, with a clear distal predominance. Asbury and Cornblath’s(100) published criteria for a diagnosis of Guillain-Barre syndrome are as follows: I. Features required for diagnosis: a. Progressive motor weakness of more than one limb b. Areflexia II. Features strongly supportive of the diagnosis: a. Progression within 4 weeks b. Relative symmetry c. Mild sensory symptoms or signs d. Cranial nerve involvement e. Recovery within four weeks of progression stopping f. Autonomic dysfunction g. Absence of fever at onset h. Raised CSF protein i. CSF mononuclear leucocyte count less than 10/mm/3 j. Electrodiagnostic features strongly supportive of the diagnosis (nerve conduction slowing or block) III. Features casting doubt on the diagnosis a. Pronounced persistent asymmetry of weakness b. Persistent bowel or bladder dysfunction c. Bladder of bowel dysfunction at onset d. More than 50 mononuclear leucocytes/mm/3 e. Presence of polymorphonuclear leucocytes in CSF f. Sharp sensory level. IV. Features that rule out the diagnosis. a. Current history of hexacarbon misuse b. Abnormal porphyrin metabolism c. Recent diptheritic infection d. Features clinically consistent with lead neuropathy e. Purely sensory syndrome. f. Definite diagnosis of poliomyelitis, botulism, hysterical paralysis, or toxic neuropathy. As illustrated previously, it can be seen that our patient met several criteria proposed by the above referenced authors, specifically pertaining to the tempo of maximum neurologic dysnfunction, the initiation of recovery within 4 weeks, the demyelinating features on electrophysiologic testing, and the lack of an alternative explanation for his symptoms. Although CSF studies were not performed, based upon the patient declining such testing in view of his improvement, it is unlikely that, considering his improvement, any evidence of a conflicting disease would have been present. Although porphyria can present acutely, it was not felt necessary to exclude this as a there were no other stigmata of this disease such as abdominal pain or psychosis. The neuropathy of acute porphyria also typically presents with asymmetric weakness and an EMG pattern of axonal involvement. (111) For similar reasons, primarily the acuteness of onset, lack of laboratory or symptomatic evidence of systemic disease, and the strongly demyelinating pattern on electrodiagnostic testing, the exclusionary criteria listed above were not felt relevant to this case. Mild cases of Guillain-Barre syndrome, usually classified as such based upon the ability to walk at nadir of progression, have been reported in the literature.(112)(113)(74). In the Italian study,(74) 32 out of 239 diagnosed cases of Guillain-Barre syndrome were categorized as mild at initial presentation, 29 of which showed no further progression of the disease. Green and Roper’s cohort of 254 GB cases exhibited 12 in the mild category.(112) Comparing these to the remaining patients with more severe deficits revealed no important clinical or electrodiagnostic differences except for the mild group showing a lesser percentage, and when present, degree, of denervation. Van Koningsveld et al, in two studies found that serologic evidence of infection with C. jejuni, cytomegalovirus, EBV, or M. pneumonia was found more frequently in the severely affected group, additionally noting that anti-ganglioside antibodies were also less frequently found in those less severely afflicted.(113)(114) Despite a fairly comprehensive literature search, I was unable to identify any prior reports devoted to the specific phenotype of AIDM that is illustrated in this paper; that being of an acute onset, distal predominant, demyelinating neuropathy, with minimal symptoms, and rapid neurologic recovery. It is interesting to speculate on whether or not this patient would have exhibited serologic evidence of a specific antecedent infection or anti-ganglioside antibody profile and further if this phenotype would correlate with such evidence and possibly be identified as a new sub-category of GB which exhibits an excellent overall prognosis, even without therapeutic intervention. REFERENCES: 1. Oh SJ. Clinical Electromyography: Nerve Conduction Studies. 2nd Ed. Williams and Wilkins. 1993 2. Albers et al. Sequential electrodiagnostic abnormalities in acute inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 1985;8:528-539 3. Cornblath D. Electrophysiology in Guillain-Barre Syndrome. Ann Neurol 1990;27 (suppl): S17-S20 4. Bansal et al. Pattern of sensory conduction in Guillain-Barre syndrome. Electro Myogr Clin Neurophysiol. 2001;41:433-437 5. Bromberg et al. Patterns of sensory nerve conduction abnormalities in demyelinating and axonal peripheral nerve disorders. 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