Acute Inflammatory Demyelinating Polyradiculoneuropathy Research Articles

Utility of neurophysiological criteria in Guillain Barre΄ syndrome: Subtype spectrum from a tertiary referral hospital in India

The Guillain Barre' syndrome (GBS) is a heterogeneous disease with various subtypes, the prevalence of which would depend on the geographic region. Recognition of these subtypes is of clinical importance since each subtype has an independent pathogenesis and different type of pathology and prognosis. To study the various subtypes of GBS using the various published electrophysiological criteria. Retrospective descriptive study. In a tertiary care hospital setting, the study compared the various published criteria for demyelination in GBS. The charts of 115 consecutive patients referred for electrodiagnostic evaluation to the Electromyography laboratory between July 2000 and June 2006 were reviewed. Of the 115 patients, 51 (44.4%) patients had axonal forms of GBS and 44 (38.2%) patients had acute inflammatory demyelinating polyradiculoneuropathy (AIDP). Applying the various published criteria, the number of patients categorized under the AIDP subtype ranged between 23.4% and 67.2%. In this study 44% patients had axonal forms of the disease, 38.2% patients had AIDP subtype and 17% remained unclassified. The most sensitive criteria to identify AIDP were the criteria proposed by Albers and colleagues and the Dutch group.

Clinical, electrophysiological subtypes and antiganglioside antibodies in childhood Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) has been the most common cause of flaccid paralysis in children after the decline in the incidence of poliomyelitis. There are not any published data from the Indian subcontinent documenting electrophysiological patterns and antiganglioside antibodies in pediatric GBS. The study population included children with GBS referred for electrodiagnostic evaluation and also children with GBS admitted to our institute between August 2006 and July 2007. Nerve conduction studies were done to determine GBS subtypes and serum antiganglioside antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and electrophysiological features were correlated with antiganglioside antibody results. Of the 43 (male to female ratio = 2.1:1) children studied, 97.6% had motor weakness, 76.7% had cranial nerve palsies, 13.9% had autonomic disturbances and respiratory paralysis was found in 9.3% children. Antecedent illness was recorded in 69.8% children. The GBS subtype distribution was as follows: acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in 21 (48.8%), acute motor axonal neuropathy (AMAN) in 19 (44.2%), and 3 (6.9%) children were unclassified. The severity of illness was similar in both AMAN and AIDP subtypes and the recovery in both the subtypes was complete without any significant difference in the duration of recovery. Preceding diarrheal illness was more common in AMAN subtype as compared to AIDP subtype (57.9% vs. 4.7%, P = 0.007). Sensory symptoms were more common in AIDP subtype than in AMAN subtype (66.6% vs. 21%, P = 0.03}. The commonest ganglioside antibody was IgM GM2. Anti GM3 antibodies were exclusively seen in children with AMAN and IgG GD1b was significantly associated with (36.7 vs. 4%; P = 0.007) AMAN subtype. IgG GT1b was identified in 50% of patients with AIDP as compared to 22.7% in patients with AMAN. In this study, AMAN subtype accounted for a significant proportion of pediatric GBS. AMAN was associated with diarrhea and specific antiganglioside antibodies. Recovery in children with GBS was complete, irrespective of the subtype.

Campylobacter jejuni infection in Guillain-Barré syndrome: A prospective case control study in a tertiary care hospital

Guillain-Barré syndrome (GBS), is a common post-infectious polyradiculoneuropathy worldwide. The commonest implicated causative organism the world over is Campylobacter jejuni (C. jejuni). This study was carried out to determine the relationship between C. jejuni infection and GBS in an Indian setting. This prospective study was carried out on a cohort of 50 patients with GBS who were treated in a tertiary care hospital in India. Based on electrophysiological findings the patients were divided into various subtypes. Serology for C. jejuni (Immunoglogulin G, IgG and Immunoglogulin, IgM) using an enzyme-linked immunosorbent assay method (ELISA) was done both in patients and 40 age, sex and geographically matched controls. Evidence of recent C. jejuni infection was present in 30% of GBS patients compared to 8% of controls (15/50 vs. 3/40 P<0.005). Eight (47%) C. jejuni-positive patients reported symptoms of gastroenteritis 4-30 days (mean 13 days) prior to onset of GBS. Of the 15 patients with evidence of C. jejuni infection, 10 (67%) patients had axonal type of GBS. Axonal variety of GBS presented in a younger age group compared to acute inflammatory demyelinating polyradiculoneuropathy (AIDP) patients (mean age: axonal vs. AIDP: 30.11 + 13.73 vs. 40.2 + 18.77). C. jejuni-positive patients presented mainly in spring and winter and had a similar age and sex incidence as compared to the rest of the GBS patients. Preceding C. jejuni infection is common among GBS patients and is often associated with the axonal variety of GBS. Axonal variety of GBS generally presents in a younger age group as compared to AIDP.

Approach to acute or subacute myelopathy

Improved understanding of the differential diagnosis and improved investigative techniques, particularly neuroimaging and serologic testing, have facilitated the diagnosis of patients with acute and subacute myelopathy and reduced the proportion of patients who are labeled as having “idiopathic transverse myelitis.” Additionally, these advances have identified subgroups of patients in whom progression of deficit or future relapses are anticipated, allowing intervention and prophylaxis as appropriate. However, early management remains empiric and consists of high-dose corticosteroids for most patients. In the event of an inadequate response to corticosteroids or a subsequent atypical course, further investigations to detect diagnoses other than “transverse myelitis” should be considered and additional treatments, such as plasmapheresis, may be appropriate. Individualized diagnosis and treatment is more feasible now than in the past. Localizing an acute neurologic process to the spinal cord is often, but not always, straightforward (table 1). The ascending sensory symptoms of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) may confuse the diagnosis, as this complaint is also highly associated with acute myelopathy. Unequivocal upper motor neuron signs exclude AIDP, but are often not apparent in the early stages of a spinal cord insult. Although not invariably present, an unequivocal sensory level on the torso, sensory loss indicating involvement of spinal tracts (e.g., spinothalamic modality impairment contralateral to motor findings), or urinary retention localize to the spinal cord. Myopathy or neuromuscular junction disorders may be mistaken for myelopathy, particularly if the lower limbs are predominantly affected, but the absence of any sensory abnormality should suggest the correct localization. Bilateral mesial frontal lobe lesions (e.g., bilateral anterior cerebral artery distribution infarcts) could mimic a myelopathy, although abulia or other signs of frontal lobe dysfunction typically coexist. Autoimmune or paraneoplastic muscle stiffness syndromes, such as stiff-person syndrome associated with glutamic acid decarboxylase or amphiphysin autoantibodies, may be confused with spasticity …

Pitfalls in electrodiagnosis of Guillain–Barré syndrome subtypes

ObjectiveTo electrophysiologically classify an Italian Guillain–Barré syndrome (GBS) population into demyelinating and axonal subtypes, to investigate how serial recordings changed the classification and to underline the pitfalls in electrodiagnosis of...

Inflammatory Neuropathies

Inflammatory neuropathies are acquired disorders of peripheral nerves and occasionally of the central nervous system that can affect individuals at any age. The course can be monophasic, relapsing, or progressive. Inflammatory neuropathies are classified as acute or chronic. The acute form reaches a nadir by 4 weeks and the chronic form over 8 weeks or greater. The most common example of an acute inflammatory neuropathy is acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is part of the Guillain-Barré syndrome (GBS). The most common chronic inflammatory neuropathy is chronic inflammatory demyelinating polyradiculopathy (CIDP). Other chronic inflammatory neuropathies are multifocal motor neuropathy (MMN) and the Lewis-Sumner syndrome. The Fisher syndrome and Bickerstaff brainstem encephalitis occur acutely and have clinical overlap with AIDP.

Could Helicobacter pylori play an important role in axonal type of Guillain-Barré Syndrome pathogenesis?

In this case-control study, ELISA and Western blot with whole bacterial protein lysate were performed on serum and cerebrospinal fluid (CSF) of 15 controls and 15 patients. According to Griffin subtypes, 10 of our patients were in acute inflammatory demyelinating polyradiculoneuropathy (AIDP) group, 3 in acute motor axonal neuropathy (AMAN) group, and 2 in acute motor sensory axonal neuropathy (AMSAN) subtype. 86.6% of patients were positive for Helicobacter pylori ( H. pylori) IgG. Serum anti- H. pylori IgG of patients and controls were significantly different. CSF anti- H. pylori IgG was significantly higher in patients than controls. In patients, the titer of anti- H. pylori IgG in serum was significantly higher than CSF, which may indicate extra-neural antibody synthesis. CSF IgG titer was higher in patients having axonal pattern. Western blot was positive in CSF of 13 patients and negative in all controls. There was a correlation between the number of antibody types against H. pylori particles and the titer of anti- H. pylori IgG in CSF and serum. Also, antibody against cytotoxin associated protein (CagA) was associated with primary axonal pattern. The association between the presence of anti-CagA and primary axonal pattern, is in favor of the relation between axonal neuropathy and H. pylori infection.

Electrodiagnostic and Clinical Aspects of Guillain-Barré Syndrome: An Analysis of 142 Cases

The incidence of Guillain-Barré syndrome (GBS) and its subtypes varies throughout the world. We present a retrospective analysis of 142 GBS cases, treated at our center, aimed at classifying GBS electrophysiologically, to study the sequential electrophysiological changes in cases with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), and to look for any clinical and cerebrospinal fluid parameters that can also help in distinguishing the subtypes. One hundred twenty-one (85.2%) cases had AIDP, 15 (10.6%) had acute motor axonal neuropathy, and 6 (4.2%) were unclassifiable. Motor conduction blocks and temporal dispersion could be observed from days 3 and 5 onward, respectively. Progression of motor conduction slowing in AIDP was most impressive in the median nerves. Varying affection of deep tendon reflexes, cranial nerves, and cerebrospinal fluid albuminocytological dissociation can also help make a distinction between AIDP and acute motor axonal neuropathy. Sural sparing, a marker of demyelinating neuropathy, is more commonly seen in later than in early stages of AIDP.

The role of IL‐12 and TNF‐α in AIDP and AMAN

Background: Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) have been described as two major subtypes of Guillain‐Barré syndrome (GBS); however, the possible difference of their immune‐inflammatory pathogenesis remains unclear.Methods: In this study, by using FACS and enzyme‐linked immunosorbent assays analyses, the role of Th1 cytokines tumour necrosis factor‐α (TNF‐α), interleukin‐12 (IL‐12) and their receptors on peripheral blood mononuclear cells (PBMCs) and in serum concentrations were investigated in AIDP and AMAN.Results: The results showed enhanced IL‐12, IL‐12R1 in AIDP and TNF‐α in AMAN during the acute phase, as well as increased TNF‐α and TNFR1 during the plateau phase of AIDP. Intravenous high dose immunoglobulin decreased IL‐12R1 expression on cells in AIDP, but increased TNF‐α and TNFR2 in AMAN.Discussion: Our data suggest that IL‐12 promotes disease development in AIDP and in contrast to previously inflammatory assumptions, TNF‐α may play double roles in GBS. The anti‐inflammatory role of TNF‐α realized through TNFR2 in AMAN is possibly a therapeutic mechanism in the IVIg treatment of AMAN.

Acute motor conduction block neuropathy pattern occurring in the course of an acute inflammatory demyelinating polyradiculoneuropathy

To describe the case of a young woman with the diagnosis of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), who during the course of the disease developed an electrophysiologic pattern of acute motor conduction block neuropathy (AMCBN). Electrophysiologic techniques including needle EMG, standard motor and sensory nerve conductions studies, and somatosensory evoked potentials were carried out over the four months after symptom onset. The results of four neurophysiological studies, performed on Days 14, 26, 35 and 125 after symptomatic onset are reported. All immunological determinations including antiganglioside antibodies (GM1, GM2, GM3, asialoGM1, GD1a, GD1b, GD3, GQ1b and GT1b) were negative. The patient had a favorable evolution following treatment with intravenous immunoglobulins (IVIg). We conclude that the electrophysiologic hallmark of AMCBN may occur in the course of AIDP. Serial investigation including proximal, intermediate and distal segments of all nerves from upper and lower limbs is essential for its detection.

Mechanical allodynia and spinal up-regulation of P2X4 receptor in experimental autoimmune neuritis rats

Experimental autoimmune neuritis (EAN) is the animal model of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) that is the most common subtype of Guillain-Barre syndrome (GBS). While neuropathic pain is a common symptom of GBS, its underlying mechanisms remain elusive. Central sensitization, particularly spinal glia (microglia and astrocytes) activation, is important for the initiation and maintenance of neuropathic pain. P2X4 receptor (P2X4R) is an ATP-gated ion channel and its spinal up-regulation has been found to be crucial for the development of neuropathic pain following peripheral nerve injury. The initiation of mechanical allodynia in rat EAN was observed at day 9 before the onset of neurological signs. Maximal level of mechanical allodynia was observed from days 17–19 and then a slow recovery, long after the cessation of typical neurological signs of EAN, until day 37 was observed. Expression of P2X4R in lumbar spinal cords was studied by immunohistochemistry. P2X4R immunoreactivity (IR) was mainly seen in gray matter, particularly in the dorsal horn. Accumulation of P2X4R+ cells in the lumbar dorsal horn was observed at day 9, reached the maximal level at day 17 and remained elevated until day 37 after immunization. Furthermore, a negative correlation between the density of P2X4R+ cells in the lumbar dorsal horn with mean hind-paw withdrawal threshold in EAN rats was seen, indicating that P2X4R might contribute to EAN mechanical allodynia. Double staining revealed that almost all P2X4R+ cells co-expressed CD68, a marker for reactive microglia, but not the astrocyte marker, glial fibrillary acidic protein (GFAP). Our data demonstrate that EAN induces mechanical allodynia and P2X4R expression in spinal microglia, suggesting that EAN is a good animal model for neuropathic pain in polyneuropathy and spinal microglia activation might participate in EAN-induced neuropathic pain.

Myasthenia gravis.

Myasthenia gravis (MG) is a rare, autoimmune neuromuscular junction disorder. Contemporary prevalence rates approach 1/5,000. MG presents with painless, fluctuating, fatigable weakness involving specific muscle groups. Ocular weakness with asymmetric ptosis and binocular diplopia is the most typical initial presentation, while early or isolated oropharyngeal or limb weakness is less common. The course is variable, and most patients with initial ocular weakness develop bulbar or limb weakness within three years of initial symptom onset. MG results from antibody-mediated, T cell-dependent immunologic attack on the endplate region of the postsynaptic membrane. In patients with fatigable muscle weakness, the diagnosis of MG is supported by: 1. pharmacologic testing with edrophonium chloride that elicits unequivocal improvement in strength; 2. electrophysiologic testing with repetitive nerve stimulation (RNS) studies and/or single-fiber electromyography (SFEMG) that demonstrates a primary postsynaptic neuromuscular junctional disorder; and 3. serologic demonstration of acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) antibodies. Differential diagnosis includes congenital myasthenic syndromes, Lambert Eaton syndrome, botulism, organophosphate intoxication, mitochondrial disorders involving progressive external ophthalmoplegia, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), motor neuron disease, and brainstem ischemia. Treatment must be individualized, and may include symptomatic treatment with cholinesterase inhibitors and immune modulation with corticosteroids, azathioprine, cyclosporine, and mycophenolate mofetil. Rapid, temporary improvement may be achieved for myasthenic crises and exacerbations with plasma exchange (PEX) or intravenous immunoglobulin (IVIg). Owing to improved diagnostic testing, immunotherapy, and intensive care, the contemporary prognosis is favorable with less than five percent mortality and nearly normal life expectancy.

Guillain-Barré syndrome

As in so many areas of scientific inquiry, the path to a mechanistic understanding of the pathobiology of Guillain-Barre syndrome (GBS) begins with phenomenology. A group of phenotypes fall under of the rubric of GBS, some with a very similar appearance and others quite disparate. The question of whether they represent a common pathogenic process with diverse clinical manifestations, or are distinct disease entities, awaits a definitive answer. Guillain, Barre, and Stroll initiated the debate in the early 20th century, insisting that their eponymous disorder was comparatively benign and, therefore, different from that described by Landry some 60 years earlier. The archetypal descriptor “ascending paralysis” remains applicable in characterizing the clinical features of most GBS subcategories. The term GBS, however, has taken on more generic connotations and has been largely supplanted by a more complex nosology based on the neurobiology of the disease. Contemporary electrophysiologic techniques have played a large role in the subclassification of GBS by permitting characterization of the pathologic processes affecting peripheral nerves, and the selective subpopulations of axons involved in these GBS variants. There is general consensus regarding the taxonomy of these GBS species with the most common entities including acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor and sensory axonal neuropathy (AMSAN), and acute motor axonal neuropathy (AMAN), all of which are phenomenologically more similar than not, along with Fisher syndrome, which is characterized by its strikingly distinctive features. While GBS has traditionally been conceptualized as an autoimmune disorder …

Association of Tumor Necrosis Factor Polymorphisms with Guillain-Barré Syndrome

It has been reported that the tumor necrosis factor (TNF)α promoter polymorphism is associated with autoimmune disease and inflammatory disease. It has also been claimed that this polymorphism may affect TNFα expression. We investigated the TNFα –308 polymorphism and TNFα levels in 79 unrelated Chinese patients with Guillain-Barré syndrome (GBS) and 78 healthy controls using PCR-RFLP and ELISA assay. Patients with GBS were divided into 2 subgroups, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), based on electrophysiological information. We found that the TNFα2 allele was associated with increased risk of GBS (OR = 1.876, 95% CI = 1.144–3.075, p = 0.008), particularly for AMAN, the main subtype (OR = 2.914, 95% CI = 1.412–6.015, p = 0.004), but there was no association between TNFα polymorphism and AIDP. We also found that carriers of the TNFα2 allele had significantly higher TNFα2 levels than TNFα1 homozygotes (p < 0.05). These data indicate that TNFα promoter polymorphism is responsible for susceptibility to GBS, especially to AMAN. The TNFα2 allele is associated with higher levels of TNFα.

Motor recovery after Guillain-Barré syndrome in childhood

Purpose. To determine the clinical factors that modify the recovery time for gait after Guillain-Barré syndrome (GBS) in childhood.Method. Medical records of patients admitted to Instituto de Ortopedia Infantil Roosevelt (IOIR) between years 1991 and 2001, were reviewed. Age, sex, cranial nerve impairment, requirement of assisted ventilation, number of days of assisted ventilation, muscular strength at day 10 of the disease, presence of quadriplegia, intravenous infusion of human gamma globulins (IVIG), were taken as independent variables. The number of needed days to reach Hughes State III was taken as the major outcome. First, univariate analysis was performed and with the factors that showed a statistically significant association with recovery time, multiple linear regression analysis and Cox regression were also performed.Results. Data of 332 children under 15 years old was collected. (Mean age: 7.1 years). A sample of 215 children was gathered for the study, all of them were regarded as functional states IV or V. Acute Motor Axonal Neuropathy (AMAN) was found in 30% of all cases. In the univariate analysis Cranial nerve impairment, requirement of assisted ventilation, presence of quadriplegia and presence of non-excitable motor nerves were associated with delayed motor recovery time. Patients who received IVIG reached Hughes state III faster than those who received only support treatment. This finding, that was more important in the presence of Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP), lost its value in the Cox regression analysis. In the multivariate analysis, muscular strength, assessed at day 10 of the disease was the most important predictor to determine motor recovery. The presence of quadriplegia was strongly associated with a delayed recovery time. Relative risk: 3.3 (95% Confidence Interval 2.1 – 5.2).Conclusions. Muscular strength at day 10 of the disease is the most useful clinical factor to determine prognosis of motor recovery in children who have suffered Guillain-Barré syndrome.

Therapeutic apheresis in the Philippines

The statistics for this report were obtained from a current survey being conducted by the Philippine Society for Hematology and Blood Transfusion for the purpose of organizing a national apheresis registry. Preliminary data coming from 8 of 10 medical centers included 194 patients and 735 procedures from 1994 to 2004. Eighty percent of patients belonged to ASFA indication Category I with a predominance of neurologic and hematologic disorders. Five most common indications were acute inflammatory demyelinating polyradiculoneuropathy (AIDP), multiple sclerosis (MS), thrombotic thrombocytopenic purpura (TTP), leucocytosis/thrombocytosis (L/T), and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A rise from 5% to 20% was noted in procedures for TTP in this 10-year period. Favorable response is noted in the use of therapeutic apheresis (TA) for the removal of antibodies in presensitized patients prior to kidney transplantation to prevent rejection. Complete recovery was seen in 2 of 4 patients with fulminant hepatic failure. Two patients with idiopathic thrombocytopenia (ITP) treated by plasma exchange were classified under Category IV due to unavailability of affinity columns. Negative results reported in controlled studies for the treatment of systemic lupus erythematosus account for the limited use of TA in this disease. Factors affecting the progress of TA in the country were cited. The organization of a national registry for apheresis may improve the practice of TA in the Philippines.

Association between Helicobacter pylori infection and acute inflammatory demyelinating polyradiculoneuropathy

The aim of this study was to investigate a possible association between Helicobacter pylori infection and acute inflammatory demyelinating polyradiculoneuropathy (AIDP). Of 17 consecutive patients with Guillain-Barre syndrome (GBS), 13 patients (six females; mean age 50 +/- 24 years) with AIDP were investigated. Clinical status was evaluated according to Hughes' score, and electrophysiological tests were performed within 2 weeks from disease onset. Helicobacter pylori infection was detected histologically and serum H. pylori-specific IgG antibodies were analysed by ELISA. Twenty asymptomatic patients (12 females; mean age 63 +/- 8 years), undergoing upper gastrointestinal endoscopy for investigation of mild iron deficiency anaemia, served as controls. Helicobacter pylori was found in 12 of 13 AIDP patients (92%), and in 10 of 20 controls (50%), (P = 0.02). Electrophysiological studies showed demyelination in all AIDP patients. High levels of anti-H. pylori IgG antibodies correlated with advanced clinical status. Five of seven AIDP patients with high levels of anti-H. pylori IgG antibodies had delayed F-wave latencies, indicating affection of proximal segments of peripheral nerves. Helicobacter pylori infection seems to be more frequent in AIDP patients. Anti-H. pylori titre might reflect advanced clinical status. Anti-H. pylori IgG antibodies are also associated with involvement of the proximal parts of peripheral nerves in AIDP.

Neurophysiologic findings in early acute inflammatory demyelinating polyradiculoneuropathy

Background: Patients with early acute inflammatory demyelinating polyradiculoneuropathy (AIDP) may not meet the current neurophysiologic criteria. Objective: To document neurophysiologic findings in early AIDP. Methods: Clinical and neurophysiologic data from 38 AIDP patients, assessed within 10 days of symptom onset were reviewed. Results: In addition to absent H reflexes and abnormal F-wave responses in the acute stage of AIDP, abnormalities of blink reflexes, upper limb sensory responses abnormalities with spared sural responses, presence of distal CMAP dispersion, and A-waves were frequently observed. Established demyelinating neurophysiologic parameters were infrequently seen. Conclusions: Abnormalities of H reflexes and F responses were most frequently noted in early AIDP. Additionally, distal temporal dispersion, prolonged or absent blink reflexes, and A-waves were often present in the acute stage of AIDP when classic diagnostic criteria of AIDP were not satisfied. Significance: Neurophysiologic studies in early AIDP frequently reveal abnormalities that are not specific of primary demyelinating neuropathy.

MANAGEMENT OF INFLAMMATORY NEUROPATHIES

Inflammatory neuropathies are uncommon but important to diagnose because they are treatable. This review summarises the clinical approach to diagnosis and treatment of Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy...

Acute inflammatory demyelinating polyradiculoneuropathy associated with perforin‐deficient familial haemophagocytic lymphohistiocytosis

This study reports the first paediatric case of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) associated with a fatal haemophagocytic lymphohistiocytosis (HLH). The patient developed progressive weakness of the lower limbs in the context of a picture of infectious mononucleosis and Epstein-Barr virus (EBV) infection. After an apparent improvement, a fulminant hepatic failure and pancytopenia ensued, leading to death. Molecular genetic studies documented a compound heterozygosity for two mutations in the perforin (PRF1) gene as the background defect for a familial haemophagocytic lymphohistiocytosis (FHL). In this patient EBV infection triggered both AIDP and FHL. The latter condition was due to PRF1 deficiency. Two novel mutations in the PRF1 gene were concomitantly present in the patient. The first caused an amino acid change, while the second introduced a stop codon in the sequence which resulted in a truncated protein.