Demyelinating Sensorimotor Polyneuropathy Research Articles

Anti-myelin-associated glycoprotein polyneuropathy coexistent with CREST syndrome

Clinical involvement of the peripheral nervous system in the calcinosis cutis, raynaud's phenomenon, esophageal dismotility, sclerodactyly and telangiectasia (CREST) variant of systemic sclerosis occurs infrequently and is characterized by axonal degeneration due to necrotizing vasculitis. We report a female patient with a known history of CREST syndrome, which developed a slowly progressive, distal symmetric demyelinating sensorimotor polyneuropathy (PN), with tremor and ataxia as prominent features, compatible with anti-myelin associated glycoprotein (MAG) PN. The diagnosis of PN was established by the presence of monoclonal immunoglobulin M anti-MAG antibodies (Thin-Layer Chromatography, Western Blot and enzyme-linked immunoabsorbent assay). Given the evidence that in CREST activation of T-helper cells is observed and that anti-MAG antibodies, despite the fact that they are T-cell-independent, may be influenced by an increase in T-helper function, the coexistence of these two rare autoimmune disorders in the same patient may not be incidental but related to the underlying immunological mechanisms involved.

Intractable Epilepsy, Audio-Visual Hallucinations and Charcot-Marie-Tooth Disease 1A in an African-American Boy

Charcot-Marie-Tooth disease 1A (CMT1A) is the most common autosomal dominant demyelinating sensorimotor polyneuropathy. A few patients with Charcot-Marie-Tooth disease were reported in the literature to have epilepsy. We report on an African-American boy with CMT1A, with duplication of peripheral myelin protein 22 gene, who also developed intractable generalized tonic-clonic seizures and audiovisual hallucinations.

POEMS: A Rare Cause of Low SAAG Refractory Ascites

Purpose: Clinical Case: 67yo WF with no known liver disease presented with refractory ascites, LE edema, and acute renal failure. Six months before admission she developed peripheral neuropathy, ascites, right-sided pleural effusion and shortness of breath. Diuretic therapy led quickly to renal dysfunction requiring diuretic discontinuation and a requirement for serial therapeutic paracenteses. She underwent pleurodesis for her pleural effusion. A right heart catheterization revealed mild pulmonary hypertension but normal cardiac function. PMHx: hypothyroidism. SocHx: no alcohol. FHx: no liver disease. PE: cachectic-appearing, no jaundice or scleral icterus, no stigmata of chronic liver disease. Abd: distended, moderate ascites, NT, no palpable hepatosplenomegaly. Ext: 1+ edema to knees bilaterally. Neuro: significantly decreased lower extremity vibratory and pinprick sensation. Labs: WBC 3,500/mL, HCT 31%, Plt 224,000/mL, alb 2.6 g/dL; liver function tests were normal. Diagnostic paracentesis performed on admission revealed a SAAG of 0.4. CEA, CA 19-9, CA-125 and ascitic cytology, AFB stain, and amylase were all normal. CT of chest/abd/pelvis done to screen for malignancy and/or carcinomatosis showed hepatosplenomegaly and sclerotic bone lesions of sternum, clavicle, and iliac wings. EGD and colonoscopy were nondiagnostic, including small bowel biopsies for celiac disease and rectal biopsies for amyloid. An SPEP and IFE showed a monoclonal M spike of 0.5g/dL with lambda light chain present. Nerve conduction studies confirmed a severe diffuse demyelinating sensorimotor polyneuropathy in the lower extremities. Further testing showed low levels of FSH and LH. Severe symptomatic bradydysrhythmias with syncope in the hospital required pacemaker implantation. Given her polyneuropathy, hepatosplenomegaly, endocrinopathy, monoclonal gammapathy and sclerotic bone changes, concern for POEMS syndrome was raised. A bone marrow biopsy was consistent with multiple myeloma. She was discharged home with plans to initiate therapy for multiple myeloma. Discussion: POEMS syndrome is a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia. It is associated with polyneuropathy, organomegaly, endocrinopathy of various forms, monoclonal gammopathy, and skin changes. The acronym POEMS captures several dominant features of the syndrome but other important features may include elevated levels of VEGF, sclerotic bone lesions, ascites, pulmonary hypertension, and cardiac conduction disturbances. Treatment is directed at the underlying plasma cell dyscrasia. In this case, ascites was one of the main presenting features. Therefore, POEMS syndrome needs to be included in the differential diagnosis of low SAAG ascites.

Mutations in ABHD12 Cause the Neurodegenerative Disease PHARC: An Inborn Error of Endocannabinoid Metabolism

Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a neurodegenerative disease marked by early-onset cataract and hearing loss, retinitis pigmentosa, and involvement of both the central and peripheral nervous systems, including demyelinating sensorimotor polyneuropathy and cerebellar ataxia. Previously, we mapped this Refsum-like disorder to a 16 Mb region on chromosome 20. Here we report that mutations in the ABHD12 gene cause PHARC disease and we describe the clinical manifestations in a total of 19 patients from four different countries. The ABHD12 enzyme was recently shown to hydrolyze 2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that acts on cannabinoid receptors CB1 and CB2. Our data therefore represent an example of an inherited disorder related to endocannabinoid metabolism. The endocannabinoid system is involved in a wide range of physiological processes including neurotransmission, mood, appetite, pain appreciation, addiction behavior, and inflammation, and several potential drugs targeting these pathways are in development for clinical applications. Our findings show that ABHD12 performs essential functions in both the central and peripheral nervous systems and the eye. Any future drug-mediated interference with this enzyme should consider the potential risk of long-term adverse effects.

Tacrolimus-Induced Polyneuropathy After Heart Transplantation

Tacrolimus has been often described to induce neuropathy in liver-, pancreas-, and renal-transplanted patients. Here, we report the first case of a 56-year-old woman who developed a progressive symmetric demyelinating sensorimotor polyneuropathy in the distal muscles of the lower limbs after therapy with tacrolimus because of heart transplantation. This condition suddenly reverted after the tacrolimus was stopped.

Asymmetric Phenotype Associated With Rare Myelin Protein Zero Mutation

Myelin protein zero (MPZ) mutations cause demyelinating neuropathies that range from severe neonatal to milder adult forms. We report a 36-year-old man who developed weakness of his left little finger adduction 3 years earlier. The weakness progressed to his other limbs. Examination revealed mildly high-arched feet with asymmetric weakness of ulnar-innervated muscles (left > right) and asymmetric weakness of peroneal-innervated muscles (right > left). Motor nerve conduction velocities ranged from 18.4 to 24.4 m/s in the upper extremities and from 14.8 to 22.7 in the lower extremities. Left median partial motor conduction block was noted at the forearm segment. Genetic testing demonstrated MPZ mutation with ARG98HIS amino acid change. The patient's father is a 68-year-old man who was asymptomatic and who was noticed to have high-arched feet and asymmetric leg muscle atrophy and weakness (right > left). The patient's 2-year-old son is "clumsy" with history of neonatal laryngomalacia. He has flat feet, areflexia, and difficulty standing on individual right versus left leg. The patient's paternal grandfather had high-arched feet and hearing loss. We conclude that ARG98HIS MPZ mutation may cause hereditary and relatively mild and asymmetric demyelinating sensorimotor polyneuropathy.

Polyneuropathy and Cerebral Infarction Complicating Scrub Typhus

We describe a 64-year-old man with scrub typhus who presented with both polyneuropathy and cerebral infarction. A eurological examination revealed a confused mental state, stiff neck, hearing impairment, symmetric weakness, sensory loss, and ataxia. Electrophysiologic studies showed demyelinating sensorimotor polyneuropathy and sensorineural hearing loss. Brain magnetic resonance imaging showed multiple infarctions. Brain involvement or polyneuropathy associated with scrub typhus has been rarely reported, and the pathogenic mechanism underlying the multiple neurological complications remains to be elucidated.

Diethylene Glycol: Widely Used Solvent Presents Serious Poisoning Potential

Objective: To describe the serious toxicity of a readily available solvent, diethylene glycol (DEG). We describe a case of intentional ingestion of a wallpaper stripper containing DEG resulting in severe multi-system organ failure. Case Report: A 27-year-old male presented to the Emergency Department (ED) one day after ingesting wallpaper stripper containing DEG. He developed acidosis, renal cortical necrosis, hepatocellular injury, and severe neurologic sequelae, including cranial neuropathies and peripheral demyelinating sensori-motor polyneuropathy. His neurologic function improved over 5 months. Discussion: Our case demonstrates the severe toxicity of DEG. DEG is present in numerous formulations, often without proper protective packaging. DEG has been associated with severe epidemic poisonings in the past and with the availability of safer alternatives, DEG in consumer products should be eliminated. Conclusion: DEG is found in numerous products. Delays in treatment can have devastating results, resulting in death or permanent disability. The pervasive use of this compound makes further human exposures likely.

Radiology–Pathology Conference: pulmonary hyalinizing granuloma associated with lupus-like anticoagulant and Morvan's Syndrome

Pulmonary hyalinizing granulomata are rare, noninfectious, fibrosing lesions of the lung, which can mimic metastatic disease radiographically. Their etiology is unknown, but they may be caused by an exaggerated immune response. We report the radiology, long clinical course, and pathology of a patient with pulmonary hyalinizing granuloma who presented with initially asymptomatic pulmonary nodules. Over a 10-year period, the patient developed multiple insidious autoimmune phenomena, including lupus anticoagulant, neuromyotonia, demyelinating sensorimotor polyneuropathy, and eventually, Morvan's syndrome. Such an association has not been previously published to our knowledge.

Mitochondrial Neurogastrointestinal Encephalomyopathy: Evidence of Mitochondrial DNA Depletion in the Small Intestine

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease clinically defined by gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy, white-matter changes in brain magnetic resonance imaging, and mitochondrial abnormalities. Loss-of-function mutations in thymidine phosphorylase gene induce pathologic accumulations of thymidine and deoxyuridine that in turn cause mitochondrial DNA (mtDNA) defects (depletion, multiple deletions, and point mutations). Our study is aimed to define the molecular basis of gastrointestinal dysmotility in a case of MNGIE. By using laser capture microdissection techniques, we correlated histologic features with mtDNA abnormalities in different tissue components of the gastrointestinal wall in a MNGIE patient and ten controls. The patient's small intestine showed marked atrophy and mitochondrial proliferation of the external layer of muscularis propria. Genetic analysis revealed selective depletion of mtDNA in the small intestine compared with esophagus, stomach, and colon, and microdissection analysis revealed that mtDNA depletion was confined to the external layer of muscularis propria. Multiple deletions were detected in the upper esophagus and skeletal muscle. Site-specific somatic point mutations were detected only at low abundance both in the muscle and nervous tissue of the gastrointestinal tract. Analysis of the gastrointestinal tract from 10 controls revealed a non-homogeneous distribution of mtDNA content; the small intestine had the lowest levels of mtDNA. Atrophy, mitochondrial proliferation, and mtDNA depletion in the external layer of muscularis propria of small intestine indicate that visceral myopathy is responsible for gastrointestinal dysmotility in this MNGIE patient.

A novel PMP22 mutation Ser22Phe in a family with hereditary neuropathy with liability to pressure palsies and CMT1A phenotypes.

We describe a Cypriot family in which some family members presented with episodes of pressure palsies, while other family members had a slowly progressive chronic polyneuropathy typical of the Charcot-Marie-Tooth type 1 phenotype. All family members were evaluated clinically, with nerve conduction studies, and with genetic testing. In all affected individuals there was clinical and electrophysiological evidence of diffuse demyelinating sensorimotor polyneuropathy and a novel point mutation in the PMP22 gene (Ser22Phe) was identified.

Acute demyelinating sensorimotor polyneuropathy in B‐cell lymphoma with IGM autoantibodies against glycolipid GD1B

We report the case of an acute demyelinating sensorimotor polyneuropathy in a patient with IgM autoantibody against peripheral nerve myelin glycolipid GD1b produced by a B‐cell lymphoma. A 76‐year‐old woman presented with one month history of weight loss, paresthesias at the distal extremities of the four limbs followed by progressive and diffuse motor weakness. Neurological examination showed sensory ataxia, marked motor deficit (4 at MRC scale in proximal and distal muscle districts of limbs), superficial and proprioceptive sensory deficit with a stocking‐glove distribution, areflexia at lower limbs. Electroneurography documented absent sensory action potentials, prolonged distal latencies of motor action potentials, markedly slowed motor conduction velocities and evidence of conduction block and temporal dispersion of motor action potentials. Diagnosis of acute demyelinating sensorimotor polyneuropathy was established. CSF examination showed a slight increase of protein concentration. Haematological screening revealed a monoclonal gammopathy with high serum IgM (1151 mg/dL) and light chain kappa proteinuria. A total body CT scan evidenced a pelvic mass identified as low grade B‐cell lymphoma by rectal biopsy. Research for antiganglioside autoantibodies evidenced the presence of IgM antibodies against glycolipid GD1b. Autoantibodies anti‐Mag, anti‐Hu, anti‐Yo and anti‐Ri were negative. The pathogenetic role of serum autoantibodies against glycolipid GD1b in the development of demyelinization in the peripheral nervous system has already been documented either clinically in post‐infective polyneuropathies or experimentally in animal research. This is the first report of selective positivity of anti‐GD1b in polyneuropathy associated to B‐cell lymphoma supporting the possible paraneoplastic significance of these serum autoantibodies.

Clinical progression and genetic analysis in hereditary spastic paraplegia with thin corpus callosum in spastic gait gene 11 (SPG11).

Hereditary spastic paraplegia (HSP) with thin corpus callosum (CC) is a rare neurodegenerative disorder classified as a complicated form of spastic paraplegia. Some patients with HSP with thin CC have previously been described in Japanese families, and the genetic locus was linked to chromosome 15q13-15. Our objective was to further clinically and genetically characterize HSP with thin CC. We describe the clinical, structural, and functional follow-up and the genetic characterization of 2 sisters aged 26 and 31 years who had severe spastic paraplegia and cognitive impairment. Magnetic resonance imaging revealed a thin CC with progressing frontoparietal cortical atrophy paralleled by cognitive decline. Using transcranial magnetic stimulation, we delineated a lack of transcallosal inhibition. Images obtained with(18)fluorodeoxyglucose positron emission tomography showed reduced cortical and thalamic hypometabolism that decreased further within 4 years. Additionally, combined axonal loss and demyelinating sensorimotor polyneuropathy were present. Because other family members were not affected, autosomal recessive inheritance was considered likely. Genetic analysis of this autosomal recessive HSP was consistent with the linkage to 15q13-15 (markers D15S971, D15S118, D15S994, and D15S659). No mutation was found within the SLC12A6 gene. Progressive axonal degeneration occurs in the corticocortical projections, corticospinal tract, and peripheral nerves in HSP with thin CC linking to chromosome 15q13-15 in a German pedigree.

Poster 172: Return of muscle strength and function after use of intravenous immunoglobulin for Lyme disease-associated acute demyelinating polyneuropathy.

Setting: Tertiary care hospital acute rehabilitation unit. Patient: A 58-year-old man with babesiosis and Lyme disease. Case Description: The patient, who had a history of splenectomy, was admitted with diffuse myalgias, fevers, and chills. He had a history of foreign and domestic travel 6 weeks prior. He was diagnosed with babesiosis. The patient’s muscle strength on admission was 5/5 throughout, but declined during his acute care stay. The patient was transferred to the acute rehabilitation floor, where he demonstrated noted weakness primarily in the lower extremities. Through his first week of rehabilitation, he became significantly weaker in hip flexors and knee extensors (to 2+/5) as well as developed proximal upper-extremity weakness (to 3+/5) for shoulder flexion. An electromyogram (EMG) on day 14 showed primary demyelinating sensorimotor polyneuropathy. Sural nerve biopsy was unremarkable. Western blot for Lyme disease returned positive. He was started on intravenous ceftriaxone, yet deterioration of muscle strength and function was noted. An EMG on day 30 showed continued evidence of demyelinating polyneuropathy with significantly prolonged F-wave latencies in the upper extremities and moderate worsening in conduction velocities in 3 of 4 nerves. He was started on intravenous immunoglobulin (IVIG) on day 33 and received a total of 5 doses over 5 days. Assessment/Results: Patient was discharged on day 38 with improving muscle strength and he was able to ambulate 150ft using a wheeled walker with supervision. At follow-up 8 weeks later, muscle strength had fully returned. Discussion: This case illustrates that Lyme disease-associated demyelinating polyneuropathy may be treated with IVIG. The potential use of IVIG in this population is based on its efficacy in those with acute demyelinating neuropathy of alternative etiologies. Conclusion: IVIG can be considered as a treatment option for demyelinating polyneuropathy associated with Lyme disease.

Amiodarone-Induced Neuromyopathy: Three Cases and a Review of the Literature

To better characterize the clinical, electrodiagnostic, and pathologic aspects of amiodarone-induced neuromyopathy. We reviewed medical records, performed electrodiagnostic studies, and examined histopathologic specimens of muscle and nerve in three patients with amiodarone-induced neuromuscular toxicity, as well as summarized the relevant literature. Two patients had a slightly asymmetric, mixed, but primarily demyelinating sensorimotor polyneuropathy. One also had a substantial myopathy. The third had an acute neuropathy resembling Guillain-Barré syndrome. Seemingly, creatine kinase levels did not correlate with clinical or electromyographic evidence of myopathy. Histologic evaluations of peripheral nerves revealed demyelination, some axon loss, and a variable number of characteristic lysosomal inclusions. Muscle specimens from two patients showed evidence of a vacuolar myopathy. After discontinuation of amiodarone, two patients improved and one died of cardiac arrhythmia. Although the clinical features and onset times vary, amiodarone neuromuscular toxicity manifests as a mixed polyneuropathy, vacuolar myopathy, or both. Creatine kinase levels may not correlate with the degree of myopathy. Variable numbers of lysosomal inclusions in peripheral nerve, endothelial cells, and muscle are characteristic.

Neuropatía hereditaria con parálisis sensible a la presión (neuropatía tomacular). Estudio clínico, electrofisiológico y molecular de dos familias afectadas

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder of peripheral myelin characterized by episodes of recurrent mononeuropathies usually involving nerves at common sites of entrapment and compression. Additional features include evidence of a diffuse demyelinating sensorimotor polyneuropathy on nerve conduction studies, focal myelin thickening (tomacula) on sural nerve biopsy, and a 1.5 Mb deletion on 17p11.2 encompassing the peripheral myelin protein 22 (PMP22) gene in most families. Two girls, aged 10 and 12 years, presented with peroneal nerve palsy and peroneal nerve palsy plus tibial nerve palsy, respectively. In none case, a clear causal factor was recognizable. Neurophysiological studies: both cases showed diffuse sensory and motor nerve conduction velocity slowing and prolongation of distal motor latencies. In addition, features of focal entrapment neuropathy were obtained at proximal peroneal nerve level. Sural nerve biopsy: large axons demyelination, redundant myelin and intraaxonal looping (case 1) and tomaculas (case 2). Molecular genetics: 17p12-p11 deletion was demonstrated in both affected girls, the mother and two maternal uncles of case 1 and in the father, paternal grandfather and two paternal uncles of case 2. NHPP should be suspected in cases of peripheral neuropathy without clearly recognizable cause. Electrophysiological and molecular studies permit both delineation of the condition and identification of otherwise clinically normal family members.

Chronic demyelinating sensorimotor polyneuropathy with serum antibodies to sulfatide: description of a case

Chronic demyelinating sensorimotor polyneuropathy with serum antibodies to sulfatide: description of a case

Demyelinating sensorimotor polyneuropathy after administration of FK506.

Demyelinating sensorimotor polyneuropathy after administration of FK506.