Demyelinating Polyneuropathy Research Articles

Guillain-barre syndrome: a paediatric case scenario in a tertiary care hospital at southern India

Background: During hospital ward rounds which was conducted as a part of Doctor of Pharmacy curriculum at Caritas Hospital, Thellakom, the first author got a chance to deal with a case of GBS. Case:12 year old female patient admitted with complaints of weakness on both legs; later diagnosed by the neurologist with demyelinating poly neuropathy and Guillain-Barre Syndrome. Aim: The aim of this particular study was to study more about Guillain-Barre Syndrome which is an auto immune disorder involving peripheral nervous system which usually occurring very rarely, affects 1.55 people per 100,000 in the world’s population, and is characterised by flaccid paralysis of limbs. It typically happens as a result of an earlier illness or other triggering events that excite the immune system of the body and result in the development of various antibodies. Materials and Methods: Analyse various case reports published in various scientific databases like PubMed, Medline, CrossRef etc. Results: This particular case was treated as follows: The treatment involves intravenous infusion of IVIg at a dose which varies according to the weight and severity of condition in each individual. Supplementation with Methyl cobalamin, Alpha lipoic acid, Levo-carnitine, and Vitamin E can improve the neural health and hasten the healing of nerve injuries. Conclusion: Data till now tells us that out of all GBS diagnosed population, 80% have recovered completely, 15% of patients have shown some neurological disabilities, and 5% have succumb to death. Here, the therapy was successful and the patient got discharged from hospital.

091 CIDP mimic in a patient with HIV; An unusual presentation of POEMS syndrome

A 37-year old woman with HIV on antiretrovirals (undetectable viral load; CD4 count 520) presented with a painful length dependant sensorimotor polyneuropathy. Investigations showed mild neutropenia, IgA 5.2g/L without paraprotein. Nerve conduction studies indicated a demyelinating polyneuropathy. CSF was acellular with protein 1193mg/L. Despite multiple courses of IVIg and subsequently pulsed IV and oral steroids, her power deteriorated considerably. A nerve biopsy showed loss of myelinated fibres with inflammation. On reinvestigation an IgA lambda paraprotein (5.2g/L) with raised VEGF (1190ng/L) was identified. Bone marrow demonstrated 8% plasma cells; a CT-PET was normal. A diagnosis of POEMS syndrome was made and chemotherapy commenced. A full VEGF response and resolution of neuropathic pain was seen 6-months post treatment initiation; however, treatment was complicated by venous sinus thrombosis and hypocortisolaemia.POEMS syndrome is a rare plasma cell dyscrasia with protean clinical manifestations, though all develop a progressive peripheral neuropathy. There is no reported association with HIV and POEMS, though HIV in association with CIDP has been reported and is usually responsive to treatment. It is important to challenge a CIDP diagnosis when refractory to treatment with atypical features, particularly severe neuropathic pain, and to repeat investigations if clinical suspicion is high.liamcarroll@nhs.net

Unusual clinical presentation of Guillain Barre syndrome: a case report

Background: Guillen barre syndrome is the most frequent cause of flaccid paralysis in the world, it is characterized by an acute demyelinating, autoimmune and multiple etiology polyneuropathy, among which are included infectious agents such as Campylobacter jejuni, Zika virus, of genetic and environmental factors.
 Case Report: We present the case of a 56-year-old Colombian male patient with a history of hypertension, who entered the intensive care unit with symptoms of atypical asymmetric motor neurological compromise, which rapidly progressed to ventilatory failure and subsequent confinement síndrome.
 Discussion: Guillen barre síndrome establishes a potentially fatal disease, the semiology of pain, paresthesia, symmetric-progressive, distal weakness, instability, hipo/areflexia, constitute a neurological emergency. There are Clinical variants establishing a great.

F27. Myoclonus in demyelinating polyneuropathies: Preliminary results

Introduction The reports on tremor and different types of polyneuropathies have been increasing and it was suggested to be associated with cerebellar involvement in chronic inflammatory demyelinating polyneuropathy (CIDP). Apart from specific syndromes, the co-existence of polyneuropathy and myoclonus is exceptional. We previously observed cortical myoclonus in cases with inflammatory polyneuropathy who were referred for tremor analysis and aimed to analyze presence of myoclonus and its relation with clinical features in demyelinating polyneuropathies. Methods We prospectively included all patients with inflammatory polyneuropathy who were admitted between January 2017 and June 2017 and had tremor-like, regular or irregular involuntary movements on clinical examination. All patients underwent neurological examination and multichannel surface electromyography which included upper extremity muscles as well as lower extremity and facial or neck muscles in selected cases. We also recorded long latency reflexes and somatosensory evoked potentials (SEPs) to categorize myoclonus. Results We identified eight patients with demyelinating polyneuropathy who matched the inclusion criteria: four patients with CIDP, three patients with Guillain–Barre syndrome and one patient with Charcot-Marie-Tooth disease. The mean age was 50.5 ± 19.6 years (range: 26–81 years) and there were seven male patients. Seven out of eight patients had myoclonus, two of which were in the form of polyminimyoclonus. Others had myoclonus on both proximal and distal parts of upper extremities. Negative myoclonus was observed in four of them. Duration of myoclonus was between 30 and 100 ms. only one had duration of 200 ms. Most patients (five out of seven) had cortical myoclonus (with high-amplitude C reflex or SEPs). Conclusion Myoclonus in the patients with polyneuropathy was irregular tremor-like, however, the electrophysiological characteristics was similar to a cortical subtype. Therefore, it would be interesting to investigate a bigger cohort of inflammatory polyneuropathies for the presence and subtypes of myoclonus and to determine associated clinical features.

Hereditary neuropathy with liability to pressure palsy (HNPP): report of a family with a new point mutation in PMP22 gene

BackgroundHereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder most commonly presenting with acute-onset, non-painful focal sensory and motor mononeuropathy. Approximately 80% of patients carry a 1.5 Mb deletion of chromosome 17p11.2 involving the peripheral myelin protein 22 gene (PMP22), the same duplicated in Charcot-Marie-Tooth 1A patients. In a small proportion of patients the disease is caused by PMP22 point mutations.Case presentationWe report on a familial case harbouring a new point mutation in the PMP22 gene.The proband is a 4-years-old girl with acute onset of focal numbness and weakness in her right hand. Electroneurography demonstrated transient sensory and motor radial nerves involvement. In her father, reporting chronic symptoms (cramps and exercise-induced myalgia), we uncovered mild atrophy and areflexia on clinical examination and a mixed (predominantly demyelinating) polyneuropathy with sensory-motor involvement on electrophysiological study.Both carried a nucleotidic substitution c.178 + 2 T > C on intron 3 of the PMP22 gene, involving the splicing donor site, not reported on databases but predicted to be likely pathogenic.ConclusionsWe described a previously unreported point mutation in PMP22 gene, which led to the development of a HNPP phenotype in a child and her father. In children evaluated for a sensory and motor transient episode, HNPP disorder due to PMP22 mutations should be suspected. Clinical and electrophysiological studies should be extended to all family members even in the absence of previous episodes suggestive for HNPP.

FV 7. Nerve ultrasound protocol in differentiating chronic neuritis

Introduction The aim of this study was to evaluate the applicability of a neuritis ultrasound protocol (NUP) in differentiating chronic neuritis. Methods The neuritis ultrasound protocol underwent prospective evaluation overall in 110 patients, that were divided into four groups, presenting with chronic symmetric or asymmetric neuritis of demyelinating or axonal type. Results The neuritis ultrasound protocol led overall to a correct classification in 42/49 (85.7%) of the CIDP, 13/15 (86.9%) of the MMN and 5/5 (100%) of the MADSAM cases. The neuritis ultrasound protocol showed a >80% sensitivity and specificity in distinguishing CIDP, MMN and MADSAM both in symmetric and asymmetric demyelinating and axonal polyneuropathies ( Table 1 , Table 2 ). Conclusions The neuritis ultrasound protocol seems to be a useful addition in the differential diagnostic of chronic neuritis in everyday practice.

Usefulness of cervical root magnetic stimulation in assessing proximal motor nerve conduction

Objectives: To evaluate the reliability and utility of cervical root magnetic stimulation in exploring proximal motor conduction. Methods: In 20 patients with demyelinating polyneuropathy (DPN), 20 patients with amyotrophic lateral sclerosis (ALS) and 25 healthy subjects, evoked compound muscle action potentials (CMAPs) were recorded from abductor digiti minimi muscle in response to electrical stimulation up to Erb’s point and magnetic stimulation up to the cervical roots. Results: In all healthy and ALS subjects, magnetic root stimulation confirmed the absence of conduction abnormalities, including those in whom supramaximal responses at Erb’s point were not achieved. In the DPN group, conduction block and/or temporal dispersion was revealed by magnetic root stimulation in 9 out of 20 patients (45%), 3 more than those detected at Erb’s point. Conclusions: Cervical root stimulation allowed clear distinction between motor neuronopathy and DPN. It is recommended as part of the routine evaluation of patients suspected of having DPN, especially when distal nerve studies are inconclusive.

Correlation between compound muscle action potential amplitude and duration in axonal and demyelinating polyneuropathy

ObjectiveTo get a better understanding of pathophysiology in polyneuropathies (PNPs) by correlating compound muscle action potential (CMAP) amplitude with duration. MethodsA total of 145 motor nerve conduction studies (MNCS) in 53 axonal and 132 MNCS in 45 demyelinating PNPs were analyzed. Peroneal and tibial MNCS were done by surface stimulation while for median and ulnar nerves near nerve or surface stimulations were used. CMAP amplitude and duration were compared in axonal and demyelination PNPs. Relationships between amplitude and duration of distally and proximally evoked CMAP were examined using regression analysis. ResultsCMAP amplitude was lower and duration was increased in all examined nerves in demyelinating PNPs than in axonal PNPs. In demyelinating PNPs, an inverse linear correlation between amplitude and duration was seen in distally and proximally evoked CMAP in all examined nerves. In axonal PNPs, there was no correlation in any of the nerves neither in distally nor in proximally evoked CMAP. ConclusionsDistal CMAP duration and the relationship between CMAP amplitude and duration show supplementary electrodiagnostic potential in demyelinating PNPs. SignificanceMore knowledge about the relation between amplitude and duration in axonal lesions and demyelination may help to reveal the pathophysiology in PNPs. Significant correlation between amplitude and duration in demyelination may suggest that the severe decrease in amplitude in demyelinating PNPs is probably due to the increase in duration secondary to temporal dispersion.

Clinical analysis and outcomes of amyotrophic lateral sclerosis with demyelinating polyneuropathy

Abnormalities of both motor and sensory nerve action potentials, similar to those found in demyelinating polyneuropathy, may occur in patients with amyotrophic lateral sclerosis (ALS). We analyzed the clinical features of unusual ALS patients with demyelinating polyneuropathy (DPN) to delineate the characteristics and outcomes of this rare condition. We reviewed three ALS patients with DPN who were confirmed to meet the electrophysiological nerve conduction criteria for DPN among 157 patients with ALS. At the initial neurological examination, one patient had both subjective sensory symptoms and abnormal results of sensory examinations, and one patient had sensory symptoms. Motor weakness of the limbs was present in all patients, and fasciculation was present in two patients. Anti-GalNAc-GD1a IgG antibodies were evident in one. Sural nerve biopsy showed a moderate, marginal reduction in myelin thickness, and teased fiber analysis revealed segmental demyelination and remyelination, but axonal degeneration was found in one patient. The mean interval from disease onset to respiratory failure or death in our three patients and seven previously documented ALS patients with DPN was 43.1 ± 18.7 months. Our findings suggest that survival in ALS with DPN is similar to that in classic ALS.

Remission of Demyelinating Polyneuropathy With Immunoadsorption, Low Dose Corticosteroids and Anti‐CD20 Monoclonal Antibody

Demyelinating polyneuropathy with anti-myelin associated glycoprotein (anti-MAG) antibodies is an immune mediated disorder characterized by proximal and distal symmetric weakness. Electrophysiological measurements depict features characteristic for demyelination, including prolonged distal latency, retarded conduction velocity, delayed or absent F-waves, and, rarely, partial conduction block. We report on a 65-year-old patient who was diagnosed with demyelinating polyneuropathy and anti-MAG antibodies five years before admission. Despite immunosuppressive agents and extracorporeal therapy (plasmapheresis) the disease progressed as assessed by clinical symptoms and neurological tests. Laboratory results showed an increase of serum immunoglobulin M and anti-MAG antibodies over time. Because of progressive disease we decided to treat the patient with immunoadsorption followed by application of the anti-CD20 antibody, rituximab. Six cycles of selective immunoadsorption were performed over three-weekly intervals with a repetitively used column (Globaffin); each cycle consisted of four consecutive daily treatments. Starting at cycle 4 the anti-CD20 antibody rituximab was administered with 375 mg/m(2) after immunoadsorption. The pretreatment anti-MAG antibody level of 10,000 U/mL, indicating disease activity, initially increased during treatment to a maximum of 30,559 U/mL. However, after completion of the six cycles, the anti-MAG level had decreased to 2348 U/mL; 16 months after the last immunoadsorption cycle the anti-MAG level had increased to 4134 U/mL, while the conduction velocity and compound motor action potentials remained stabile. Immunoadsorption in combination with a monoclonal anti-CD20 antibody in patients with demyelinating polyneuropathy with anti-MAG is effective and can be used an alternative treatment option in patients with progressive disease.

Neuropathy in lymphoma: a relationship between the pattern of neuropathy, type of lymphoma and prognosis?

Background:Neuropathies associated with lymphoma (NAL) are rare and present a great clinical heterogeneity, making them difficult to diagnose and worsening their prognosis.Objectives:(1) To report the different patterns of NAL and...

Neurologic and hematologic response to fludarabine treatment in IgM MGUS polyneuropathy

We studied the efficacy of fludarabine in 16 patients with immunoglobulin M monoclonal gammopathy of unknown significance polyneuropathy in a prospective uncontrolled trial. The modified Rankin scale improved in 5/16 patients, all of whom had a demyelinating polyneuropathy. The motor conduction velocity improved by more than 10% in two or more nerves for four of five of these patients. Hematologic response in bone marrow occurred in three of five of these patients, whereas two of five already had small polyclonal B cell populations. There were no serious side effects.

Hereditary motor and sensory neuropathy associated with auditory neuropathy in a Gypsy family

In a Slovene Gypsy family of 19 subjects from four generations three patients with clinical characteristics compatible with hereditary motor and sensory neuropathy - Lom (HMSNL). were found They had severe distal and milder proximal muscle atrophy and weakness with areflexia of myotatic jerks. Two had facial weakness at the time when already wheelchair bound. All sensory modalities were affected distally in the limbs. Sluggish pupillary responses to light and convergence were found. They had skeletal abnormalities. One patient had polydactily on the hand. Nerve conduction studies were compatible with demyelinative polyneuropathy. Nerve biopsy showed mainly axonal loss without hypertrophic changes. Auditory neuropathy was diagnosed in all of them. None of the patients had duplication of 17p1.2-12 or point mutations in the Protein zero. Peripheral myelin protein and Connexin32 genes. Similar disorder that mapped to 8q24 was previously described in some Bulgarian and Italian Gypsy families. Members of our family may suffer from the same hereditary disease and may carry the same ancestor mutation, which was in the past spread in European Gypsy populations.

MAY ELECTROPHYSIOLOGY DIFFERENTIATE CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY (CIDP) AND POLINEUROPATHY WITH ANTI‐SGPG ANTIBODIES?

Demyelinating polyneuropathy with anti‐MAG/SGPG ab is elecrophysiologically characterized by a disproportionate distal slowing of motor conductions. A terminal latency index TLI = 0.25 in at least two nerves has been proposed to differentiate polyneuropathy with anti‐MAG/SGPG ab from other chronic demyelinating disorders (Kaku et al. 1994).We reviewed and compared the electrophysiogical studies of 18 patients with CIDP and 8 with polyneuropathy anti‐SGPG antibodies. The Anti‐SGPG group showed: (1) lower CMAP amplitudes and longer motor distal latencies; (2) lower TLI and longer F wave latencies; (3) higher percentages of nerves with TLI = 0.25; (4) much fewer conduction blocks; (5) more frequent absent SAPs.CIDP and polyneuropathy with anti‐MAG/SGPG seems to be, as groups, electrophysiologically different. However, three patients with CIDP showed at least 2 nerves with TLI = 0.25 and one, although displaying all the additional electrophysiological features characteristic of anti‐MAG/SGPG polyneuropathy, was negative for ab search at diagnosis and one year later, and did not have immunoglobulin deposits in sural nerve. On the other hand, one patient with anti‐SGPG antibodies did not have distal disproportionate slowing of motor conduction velocities.In conclusion, demyelination seems to be in anti‐MAG/SGPG polyneuropathy a length‐dependent process, whereas in CIDP it tends to be patchy and multifocal, which strengthens the view that these are two different pathophysiological entities. Electrophysiological findings can suggest an anti‐SGPG polyneuropathy and address the search of ab, but they are not pathognomonic in the individual patient.

Hereditary motor and sensory neuropathy associated with auditory neuropathy in a Gypsy family.

In a Slovene Gypsy family of 19 subjects from four generations three patients with clinical characteristics compatible with hereditary motor and sensory neuropathy -Lom (HMSNL), were found. They had severe distal and milder proximal muscle atrophy and weakness with areflexia of myotatic jerks. Two had facial weakness at the time when already wheelchair bound. All sensory modalities were affected distally in the limbs. Sluggish pupillary responses to light and convergence were found. They had skeletal abnormalities. One patient had polydactily on the hand. Nerve conduction studies were compatible with demyelinative polyneuropathy. Nerve biopsy showed mainly axonal loss without hypertrophic changes. Auditory neuropathy was diagnosed in all of them. None of the patients had duplication of 17pl.2-12 or point mutations in the Protein zero, Peripheral myelin protein and Connexin32 genes. Similar disorder that mapped to 8q24 was previously described in some Bulgarian and Italian Gypsy families. Members of our family may suffer from the same hereditary disease and may carry the same ancestor mutation, which was in the past spread in European Gypsy populations.

Diagnostic value of myotactic reflexes in axonal and demyelinating polyneuropathy.

In 11 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 11 patients with chronic idiopathic axonal polyneuropathy (CIAP), absent myotatic reflexes were significantly associated more often with CIDP than with CIAP, an absent biceps-reflex having the highest sensitivity and specificity for the diagnosis of CIDP. In CIDP, the latencies of electromyographically recorded myotatic reflexes often indicated demyelination, notwithstanding normal clinically assessed myotatic reflexes. Myotatic reflexes may therefore be useful for the distinction between axonal and demyelinating polyneuropathy.

Mitochondrial myopathy with demyelination polyneuropathy

Mitochondrial myopathy with demyelination polyneuropathy

Immunofixation superior to plasma agarose electrophoresis in detecting small M-components in patients with polyneuropathy

Monoclonal immunoglobulins (M-components) in blood are found in some patients with polyneuropathy and are thought to be of pathogenetic importance, especially if the M-component is of IgM isotype. As the finding of an M-component may indicate a treatable polyneuropathy, the potential of the method to uncover an M-component is of importance. Cellulose acetate or agarose electrophoresis used in routine practice may miss small M-components covered by other proteins. We therefore applied the uncovering and specific method of immunofixation in comparison with agarose electrophoresis on patients investigated for polyneuropathy. Of 83 consecutive patients, 5 had M-components. Two of these 5 patients, one with an axonal polyneuropathy and the other with a lower motor neuron syndrome, had extra bands on agarose electrophoresis, verified as IgG M-components by immunofixation. In the 3 additional patients an M-component was uncovered only by immunofixation, not seen in the agarose electrophoresis of plasma; 2 of them were of IgM isotype and one was of IgG isotype. These 3 patients were diagnosed as having a demyelinating (i.e., possibly immune-mediated) polyneuropathy by means of neurophysiology and in one by means of nerve biopsy. A 6th patient had 2 small bands in the gamma region on the agarose electrophoresis, verified as oligoclonal bands of IgG isotype by immunofixation but was not judged as an M-component. Three out of the 83 patients, were judged as having motor neuron diseases. All remaining 80 were found to have polyneuropathy. In 38 (47.5%) of these 80 patients the polyneuropathy was associated with other diseases or deficiency states whereas in 42 (52.5%) no obvious cause was found. The prevalence of M-components in patients without obvious associated diseases or laboratory evidence of deficiency states (i.e., idiopathic polyneuropathy) was 7% (3 out of 42 patients). In conclusion, immunofixation was superior to agarose electrophoresis of plasma in detecting “hidden” small M-components in patients with “idiopathic” demyelinating polyneuropathy.

Peripheral neuropathy as a component of the neuroleptic malignant syndrome

The neuroleptic malignant syndrome, an idiosyncratic reaction to antipsychotic medication, is defined by the tetrad of autonomic dysfunction, rigidity, fever, and altered mental status. Two patients in whom this syndrome developed acquired severe peripheral neuropathies during the course of their illness. This demyelinative polyneuropathy has not been reported previously as occurring in the neuroleptic malignant syndrome.