Gross Motor Function Measure Evolution Ratio: Use as a Control for Natural Progression in Cerebral Palsy.

OBJECTIVE: To develop a new way to interpret Gross Motor Function Measure (GMFM-66) score improvement in studies conducted without control groups in children with cerebral palsy (CP). DESIGN: The curves, which describe the pattern of motor development according to the children's Gross Motor Function Classification System level, were used as historical control to define the GMFM-66 expected natural evolution in children with CP. These curves have been modeled and generalized to fit the curve to particular children characteristics. SETTING: Research center. PARTICIPANTS: Not applicable. INTERVENTIONS: Not applicable. MEAN OUTCOME MEASURES: Not applicable. RESULTS: Assuming that the GMFM-66 score evolution followed the shape of the Rosenbaum curves, by taking into account the age and GMFM-66 score of children, the expected natural evolution of the GMFM-66 score was predicted for any group of children with CP who were <8 years old. Because the expected natural evolution could be predicted for a specific group of children with CP, the efficacy of a treatment could be determined by comparing the GMFM-66 score evolution measured before and after treatment with the expected natural evolution for the same period. A new index, the Gross Motor Function Measure Evolution Ratio, was defined as follows: Gross Motor Function Measure Evolution Ratio=measured GMFM-66 score change/expected natural evolution. CONCLUSIONS: For practical or ethical reasons, it is almost impossible to use control groups in studies evaluating effectiveness of many therapeutic modalities. The Gross Motor Function Measure Evolution Ratio gives the opportunity to take into account the expected natural evolution of the gross motor function of children with CP, which is essential to accurately interpret the therapy effect on the GMFM-66.

Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans.

An increasing number of genes required for mitochondrial biogenesis, dynamics, or function have been found to be mutated in metabolic disorders and neurological diseases such as Leigh Syndrome. In a forward genetic screen to identify genes required for neuronal function and survival in Drosophila photoreceptor neurons, we have identified mutations in the mitochondrial methionyl-tRNA synthetase, Aats-met, the homologue of human MARS2. The fly mutants exhibit age-dependent degeneration of photoreceptors, shortened lifespan, and reduced cell proliferation in epithelial tissues. We further observed that these mutants display defects in oxidative phosphorylation, increased Reactive Oxygen Species (ROS), and an upregulated mitochondrial Unfolded Protein Response. With the aid of this knowledge, we identified MARS2 to be mutated in Autosomal Recessive Spastic Ataxia with Leukoencephalopathy (ARSAL) patients. We uncovered complex rearrangements in the MARS2 gene in all ARSAL patients. Analysis of patient cells revealed decreased levels of MARS2 protein and a reduced rate of mitochondrial protein synthesis. Patient cells also exhibited reduced Complex I activity, increased ROS, and a slower cell proliferation rate, similar to Drosophila Aats-met mutants.

Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.

Little is known about the genetics of nonsyndromic intellectual disability (NSID). We hypothesized that de novo mutations (DNMs) in synaptic genes explain an important fraction of sporadic NSID cases. In order to investigate this possibility, we sequenced 197 genes encoding glutamate receptors and a large subset of their known interacting proteins in 95 sporadic cases of NSID. We found 11 DNMs, including ten potentially deleterious mutations (three nonsense, two splicing, one frameshift, four missense) and one neutral mutation (silent) in eight different genes. Calculation of point-substitution DNM rates per functional and neutral site showed significant excess of functional DNMs compared to neutral ones. De novo truncating and/or splicing mutations in SYNGAP1, STXBP1, and SHANK3 were found in six patients and are likely to be pathogenic. De novo missense mutations were found in KIF1A, GRIN1, CACNG2, and EPB41L1. Functional studies showed that all these missense mutations affect protein function in cell culture systems, suggesting that they may be pathogenic. Sequencing these four genes in 50 additional sporadic cases of NSID identified a second DNM in GRIN1 (c.1679_1681dup/p.Ser560dup). This mutation also affects protein function, consistent with structural predictions. None of these mutations or any other DNMs were identified in these genes in 285 healthy controls. This study highlights the importance of the glutamate receptor complexes in NSID and further supports the role of DNMs in this disorder.

An atypical case of SCN9A mutation presenting with global motor delay and a severe pain disorder.

INTRODUCTION: Erythromelalgia due to heterozygous gain-of-function SCN9A mutations usually presents as a pure sensory-autonomic disorder characterized by recurrent episodes of burning pain and redness of the extremities. METHODS: We describe a patient with an unusual phenotypic presentation of gross motor delay, childhood-onset erythromelalgia, extreme visceral pain episodes, hypesthesia, and self-mutilation. The investigation of the patient's motor delay included various biochemical analyses, a comparative genomic hybridization array (CGH), electromyogram (EMG), and muscle biopsy. Once erythromelalgia was suspected clinically, the SCN9A gene was sequenced. RESULTS: The EMG, CGH, and biochemical tests were negative. The biopsy showed an axonal neuropathy and neurogenic atrophy. Sequencing of SCN9A revealed a heterozygous missense mutation in exon 7; p.I234T. CONCLUSIONS: This is a case of global motor delay and erythromelalgia associated with SCN9A. The motor delay may be attributed to the extreme pain episodes or to a developmental perturbation of proprioceptive inputs.

Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy.

Although many genes that predispose for epilepsy in humans have been determined, those that underlie the classical syndromes of idiopathic generalized epilepsy (IGE) have yet to be identified. We report that an Ala322Asp mutation in GABRA1, encoding the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A (GABA(A)), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABA(A) receptors that contain the mutant subunit show a lesser amplitude of GABA-activated currents in vitro, indicating that seizures may result from loss of function of this inhibitory ligand-gated channel. Our results confirm that mutation of GABRA1 predisposes towards a common idiopathic generalized epilepsy syndrome in humans.

Transient creatine phosphokinase elevations in children: a single-center experience.

OBJECTIVES: To determine the etiologies and evolution of rhabdomyolysis in children. STUDY DESIGN: We performed a retrospective study of patients with rhabdomyolysis who were seen in our tertiary care university-affiliated pediatric hospital. Patients in outpatient clinics, seen in the emergency department, or admitted from 2001 to 2002 were selected. With a standardized case report form, we collected predetermined data from each patient's chart. RESULTS: A total of 130 patients with rhabdomyolysis were included in the study (male, 56%; mean age, 7.5 ± 5.9 years). The median elevation of creatine phosphokinase was 2207 IU/L (range, 1003 to 811 428 IU/L). The most frequent diagnoses were viral myositis (29, 22.3%), trauma (24, 18.4%), surgery (24, 18.4%), hypoxia (12 , 9.2%), and drug reaction (8, 6.2%). Metabolic myopathy was found only in one patient (0.8%). In 17 patients (13.1%), no definite diagnosis could be made. CONCLUSIONS: Etiologies of rhabdomyolysis in children are varied and differ from those reported in adults. In most patients, rhabdomyolysis is benign and without recurrence. In our series, rhabdomyolysis was the initial symptom of a metabolic myopathy in only one patient.

Tremor-ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3-10q23.31.

Leukodystrophies are a heterogeneous group of disorders associated with abnormal central nervous system white matter. The clinical features invariably include upper motor neuron signs and developmental regression with or without other neurological manifestations. The objective of this study was to characterize clinically and genetically a new form of childhood-onset leukodystrophy with ataxia and tremor. We recruited seven French-Canadian cases belonging to five families affected by an unknown form of childhood-onset leukodystrophy. Genome-wide scans (GWS) were performed using the Illumina Hap310 or Hap610 Bead Chip to identify regions of shared homozygosity that were further studied for linkage with STS markers. All cases presented between the ages of 1 and 5 years with spasticity along with other upper motor neuron signs, prominent postural tremor, and cerebellar signs. Though motor regression is a constant feature, cognitive functions are relatively preserved, even late in the course of the disease. The higher frequency of founder diseases in the French-Canadian population and the segregation in pedigrees are suggestive of a recessive mode of inheritance. By homozygosity mapping, we established linkage to a 12.6-Mb SNP-haplotyped region on chromosome 10q22.3-10q23.31 (maximum LOD score: 5.47). We describe an autosomal recessive childhood-onset leukodystrophy with ataxia and tremor mapping to a 12.6 Mb interval on chromosome 10q22.3-10q23.31. Identification of the mutated gene will allow precise diagnosis and genetic counseling and shed light on how its perturbed function leads to white matter abnormalities.

Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Although several clinical trials have evaluated the impact of n-3 polyunsaturated fatty acid (PUFA) on patients with attention-deficit hyperactivity disorder (ADHD), changes in plasma PUFA composition were not always assessed following n-3 supplementation. Furthermore, no reports are available on the efficacy of n-3 PUFA in Canadian youth with ADHD. OBJECTIVES: To determine fatty acid (FA) composition, and the efficacy and safety of n-3 PUFA supplementation on ADHD clinical symptoms in French Canadian primary school children. PATIENTS AND METHODS: The Strengths and Weaknesses in ADHD and Normal Behaviors (SWAN) and Conners' questionnaires were used to assess changes in ADHD symptoms in 37 children (only 26 children completed the study from zero to 16 weeks). They were divided into two groups (A and B), and participated in a 16-week, double-blind, one-way, crossover randomized study. In the first phase, group A received the n-3 PUFA supplement and group B received n-6 PUFA (sunflower oil) as a placebo. During the second phase, group B received the active n-3 PUFA supplement that was continued in group A. FA composition and lipid profile were assessed during the phases of the study. RESULTS: FA differences between groups were observed in the 26 patients. Supplementation with n-3 PUFA resulted in significant increases in eicosapentaenoic and docosahexaenoic acids in group A, while group B was enriched with alpha-linolenic, gamma-linolenic and homo-gamma-linolenic acids. The n-3 PUFA supplement was tolerated without any adverse effects. A statistically significant improvement in symptoms was noted based on the parent version of the Conners' questionnaire from baseline to the end of phase 1, and this amelioration continued from phases 1 to 2, although the latter changes from phases 1 and 2 were not statistically significant in any of the subscales except for the subscale measuring inattention in group B. The improvement was greater in patients from group A in phase 1 and in patients from group B in phase 2. A subgroup of eight patients (four in each group) displayed a statistically significant clinical improvement following the administration of the n-3 PUFA supplement, particularly for the inattention and global Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, total Conners' subscales. CONCLUSIONS: A subgroup of children with ADHD who used n-3 PUFA supplements achieved and maintained symptom control. The data of the present study also supported n-3 PUFA safety and tolerability, but limited changes were noted in the FA profile in French Canadians with ADHD.

Founder SH3TC2 mutations are responsible for a CMT4C French-Canadians cluster.

Charcot-Marie-Tooth polyneuropathies (CMT) are clinically and genetically heterogeneous. We describe a French-Canadian cluster of 17 recessive CMT cases belonging to 10 families with variable early-onset CMT and scoliosis. The patients demonstrate great intra- and inter-familial variability. Linkage analysis confirmed that all families are linked to CMT4C locus on chromosome 5q32 (multipoint LOD score of 9.06). Haplotype analysis suggests that two SH3TC2 mutations are present in this cohort. The majority of carrier chromosomes, 26 of 34 (76%), carry the c.2860C-->T mutation. Despite extensive sequencing, the other mutation is not yet uncovered. This study demonstrates that the clinical variability observed in CMT4C is due to other factors than the nature of the mutation and that further work is needed to better define the SH3TC2 gene to ensure the identification of all CMT4C mutations.

Lipid profile, fatty acid composition and pro- and anti-oxidant status in pediatric patients with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent behavioral disorder in children and the pathophysiology remains obscure. In addition to the pharmacotherapy, which is the primary treatment of ADHD, nutritional intervention may have a significant impact on ADHD symptoms. We studied lipid and lipoprotein profiles, fatty acid (FA) composition, and oxidant-antioxidant status in 37 pediatric ADHD patients and 35 healthy control subjects. Our results show that plasma triacylglycerols and phospholipids were lower, whereas free cholesterol, HDL, and apolipoprotein A-I were higher in ADHD patients compared with controls. The proportion of plasma EPA and DHA was higher, but that of oleic and alpha-linolenic (ALA) acids was lower. As expected from these findings, the proportions of both total saturates and polyunsaturates fatty acids (PUFA) were higher and lower, respectively, in ADHD patients than in controls, which led to a significant decrease in the PUFAs/saturates ratio. On the other hand, the ratios of eicosatrienoic acid to arachidonic acid and of palmitoleic acid to linoleic acid, established indexes of essential fatty acid (EFA) status remained unchanged revealing that EFA did not affect ADHD patients. Similarly, the activity of delta-6 desaturase, estimated by the ratio of 18:2(n-6)/20:4(n-6), was found unaffected, whereas ALA/EPA was diminished. Lessened lipid peroxidation was noted in ADHD subjects as documented by the diminished values of plasma malondialdehyde accompanied by increased concentrations of gamma-tocopherol. In conclusions, significant changes occur in the lipid and lipoprotein profiles, as well as in the oxidant-antioxidant status of ADHD patients, however, the FA distribution does not reflect n-3 FA deficiency.

Congenital axonal neuropathy and encephalopathy.

Congenital axonal neuropathy associated with encephalopathy appears to be very rare. Only a few cases have been reported in the literature. In the last 25 years, we have seen seven patients affected by congenital axonal neuropathy with encephalopathy. Biopsies of their sural nerves revealed axonal atrophy and loss of large-diameter nerve fibers. All of these patients presented at birth or soon thereafter with hypotonia associated with distal weakness and diffuse areflexia. Central nervous system manifestations included microcephaly, seizures, and developmental delay. Outcomes were poor. Four children died before age 3 years from respiratory insufficiency or aspiration pneumonia. The three surviving patients manifested severe developmental delay. In our most recent patient, Western-blot analysis of snap-frozen specimens of the temporal and cerebellar cortex demonstrated an absence or marked decrease of microtubule-associated protein types 1A and 2, compared with age-matched control subjects. Calloso-splenial hypogenesis and neurofilament swellings were also documented in the deep white matter and adjacent cortex. The absence or hypo-expression of central nervous system microtubule-associated proteins has never been reported in congenital neuropathies, and may represent a new clinicopathologic entity.

Deflazacort use in Duchenne muscular dystrophy: an 8-year follow-up.

Data reported here were collected over an 8-year period for 79 Duchenne muscular dystrophy patients, 37 of whom were treated with deflazacort. Mean length of treatment was 66 months. Treated boys stopped walking at 11.5 +/- 1.9 years, compared with 9.6 +/- 1.4 years for untreated boys. Cardiac function was better preserved with the use of deflazacort, as shown by a normal shortening fraction in treated (30.8 +/- 4.5%) vs untreated boys (26.6 +/- 5.7%, P < 0.05), a higher ejection fraction (52.9 +/- 6.3% treated vs 46 +/- 10% untreated), and lower frequency of dilated cardiomyopathy (32% treated vs 58% untreated). Scoliosis was much less severe in treated (14 +/- 2.5 degrees ) than in untreated boys (46 +/- 24 degrees ). No spinal surgery was necessary in treated boys. Limb fractures were similarly frequent in treated (24%) and untreated (26%) boys, but vertebral fractures occurred only in the treated group (7/37) (compared with zero for the untreated group). In both groups, body weight excess tripled between the ages of 8 and 12 years. All untreated patients grew normally (>4 cm/year), as opposed to only 15% of treated boys. Deflazacort improves cardiac function, prolongs walking, and seems to eliminate the need for spinal surgery, although vertebral fractures and stunted growth occur. The overall impact on quality of life appears positive.

Acute combined central and peripheral nervous system demyelination in children.

Reports of acute combined central and peripheral nervous system acquired inflammatory demyelination are rare in children. This study aimed to (1) define the clinical features and prognoses of patients with this entity; and (2) compare these patients with children presenting isolated acute central or peripheral nervous system demyelination. A retrospective chart review of 523 children with central or peripheral nervous system demyelination hospitalized between 1993-2006 was undertaken. Among these, 93 fulfilled criteria (clinical features and positive magnetic resonance imaging or electromyography/nerve conduction studies) for either acute central (n = 37; 39.8%) or peripheral (n = 43; 46%) nervous system demyelination, or a combination of the two (n = 13; 14%). Significant differences between groups were evident for age (median, 10 versus 7 versus 11 years, respectively; P = 0.047), admission to pediatric intensive care unit (8% versus 30% versus 58%, respectively; P = 0.001), length of hospital stay (median, 8 versus 9 versus 29 days, respectively; P < 0.001), treatment with steroids (52% versus 7% versus 75%, respectively; P < 0.001) and immunoglobulins (11% versus 81% versus 75%, respectively; P < 0.001), and poor evolution (3% versus 12% versus 54%, respectively; P = 0.002). This entity in children is not rare, and has a poorer outcome than isolated central or peripheral nervous system demyelination. Assessment is needed for a better understanding of risk factors, etiologies, management, and prognosis.

Health-Related Quality of Life for Patients With Genetically Determined Leukoencephalopathy.

BACKGROUND: We attempted to characterize the health-related quality of life in patients with genetically determined leukoencephalopathies as it relates to the severity of clinical features and the presence or absence of a precise molecular diagnosis. METHODS: Health-related quality of life was assessed using the Pediatric Quality of Life Inventory model (Pediatric Quality of Life Inventory 4.0 Self- and Proxy-reports) on 59 patients diagnosed with genetically determined leukoencephalopathies. In total, 38 male and 21 female patients ranging from one to 32 years of age (mean nine years), as well as their parents, completed the Pediatric Quality of Life Inventory health-related quality of life measures. In addition, participants completed detailed standardized clinical assessments or questionnaires. The correlation between health-related quality of life results and the severity of the clinical features, as well as the presence or absence of a molecular diagnosis, were analyzed. RESULTS: Patients with more severe clinical features showed statistically significant lower total Pediatric Quality of Life Inventory scores. More specifically, lower health-related quality of life was noted in children with sialorrhea, gastrostomy, and dystonia and in children who use a wheelchair. CONCLUSIONS: Patients with more severe clinical features experience a lower quality of life. Our study further highlights the importance of addressing both physical and psychosocial issues and discussing perception of quality of life with both parents and children. A larger multicenter prospective study will be needed to further define the burden of these diseases and to identify modifiable factors.

A newborn with spinal muscular atrophy type 0 presenting with a clinicopathological picture suggestive of myotubular myopathy.

We report a male term newborn with genetically confirmed spinal muscular atrophy type 0, presenting with arthrogryposis and severe generalized weakness and requiring ventilatory support. Muscle biopsy revealed fibers with central nuclei resembling myotubes and negative myotubularin immunohistochemical staining compared with a control muscle biopsy. The absence of myotubularin associated with survival motor neuron protein deficiency suggests that survival motor neuron protein may have a role in muscle fiber maturation and myotubularin expression. Studying the pathology of this rare and lethal neonatal form of spinal muscular atrophy may further our understanding of spinal muscular atrophy pathogenesis.

Evolution and treatment of childhood chronic inflammatory polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy is a rare disease in pediatric patients. The disease usually responds well to standard therapies including immunoglobulins, corticosteroids, and plasmapheresis. However, a minority of cases appear refractory to standard treatments. This report presents the evolution of 13 patients with chronic inflammatory demyelinating polyneuropathy monitored in our pediatric neurology clinic between 1975 and 2005, including two recent patients with refractory diseases. The literature regarding treatment of refractory cases in adults and children is also reviewed.

Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy.

OBJECTIVE: To assess safety and efficacy of deflazacort (DFZ) and prednisone (PRED) vs placebo in Duchenne muscular dystrophy (DMD). METHODS: This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated muscle strength among 196 boys aged 5-15 years with DMD during a 52-week period. In phase 1, participants were randomly assigned to receive treatment with DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, PRED 0.75 mg/kg/d, or placebo for 12 weeks. In phase 2, placebo participants were randomly assigned to 1 of the 3 active treatment groups. Participants originally assigned to an active treatment continued that treatment for an additional 40 weeks. The primary efficacy endpoint was average change in muscle strength from baseline to week 12 compared with placebo. The study was completed in 1995. RESULTS: All treatment groups (DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, and PRED 0.75 mg/kg/d) demonstrated significant improvement in muscle strength compared with placebo at 12 weeks. Participants taking PRED had significantly more weight gain than placebo or both doses of DFZ at 12 weeks; at 52 weeks, participants taking PRED had significantly more weight gain than both DFZ doses. The most frequent adverse events in all 3 active treatment arms were Cushingoid appearance, erythema, hirsutism, increased weight, headache, and nasopharyngitis. CONCLUSIONS: After 12 weeks of treatment, PRED and both doses of DFZ improved muscle strength compared with placebo. Deflazacort was associated with less weight gain than PRED. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for boys with DMD, daily use of either DFZ and PRED is effective in preserving muscle strength over a 12-week period.

Myelination Delay and Allan-Herndon-Dudley Syndrome Caused by a Novel Mutation in the SLC16A2 Gene.

Allan-Herndon-Dudley syndrome is an X-linked disease caused by mutations in the solute carrier family 16 member 2 (SLC16A2) gene. As SLC16A2 encodes the monocarboxylate transporter 8 (MCT8), a thyroid hormone transporter, patients with Allan-Herndon-Dudley syndrome present a specific altered thyroid hormone profile. Allan-Herndon-Dudley syndrome has been associated with myelination delay on the brain magnetic resonance imaging (MRI) of affected subjects. We report a patient with Allan-Herndon-Dudley syndrome characterized by developmental delay, hypotonia, and delayed myelination caused by a novel SLC16A2 mutation (p.L291R). The thyroid hormones profile in our patient was atypical for Allan-Herndon-Dudley syndrome. The follow-up examinations showed that the progression of the myelination was not accompanied by a clinical improvement. Our paper suggests that SLC16A2 mutations should be investigated in patients with myelination delay even when the thyroid function is not conclusively altered.

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single-centre study.

AIM: Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centre's experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epilepsy. METHODS: We retrospectively reviewed the medical records of 22 patients who received lacosamide from November 2009 to April 2014 at the CHU Ste-Justine, University of Montreal. Treatment responders were defined as children with a ≥50% reduction in seizure frequency compared to baseline, and this was determined three months after the initiation of treatment and at the last follow-up visit. RESULTS: We included 14 boys and eight girls with a mean age of 12.9 years (SD: 5.2; range: 5.2-20.7 years) at the initiation of treatment. The average length of follow-up was 11.9 months. Patients had previously received an average of 7.5 antiepileptic drugs. The mean number of concomitant antiepileptic drugs was 2.3. The mean initial and maintenance doses were 2.9 and 8.4 mg/kg/d, respectively. Thirteen (59%) and ten (45%) patients were responders after three months of treatment and at the last follow-up visit, respectively. One became seizure-free. Adverse effects were reported in 11 patients and none were severe. Responders and non-responders were identical with respect to all studied parameters except gender, with the proportion of responders being greater in girls than in boys (75% vs 29%; p=0.035). CONCLUSION: Our study adds evidence that lacosamide appears to be a safe and effective adjunctive therapy for children with refractory focal epilepsy.

Chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized clinically by a progressive symmetrical weakness evolving over a period of at least 2 months. There is increased CSF protein and conduction block, reduced nerve conduction velocities, increased distal latencies, and/or absent F wave or prolonged F wave latency in two or more nerves. Incidence is lower in children (10 times less) than in adults, and the condition presents in an acute or subacute manner with frequent relapses. It is not associated with other systemic diseases such as neoplasia, diabetes mellitus, or monoclonal gammopathies. It appears to be immune-related as a variety of humoral and cellular autoimmune mechanisms have been implicated. Treatment is based on results obtained in randomized clinical trials (RCTs) conducted in adults as such studies are lacking in the pediatric population. The evolution of CIDP is more favorable in children than in adults, with 80-100% response rates to standard treatments (steroids, intravenous immunoglobulins, and/or plasmapheresis) and excellent outcome with complete functional recovery in most patients. Cases refractory to standard therapies do exist in children, for which azathioprine, methotrexate, and mycophenolate mofetil alone or more often in association with other treatments have been used. However, safety and efficacy data are still insufficient to give specific recommendations regarding the optimal choice.