Mixed Polyneuropathy Research Articles

A case of cerebrotendinous xanthomatosis with brain and spinal involvement without tendon xanthomas: Identification of a novel mutation of the CYP27A1 gene

Cerebrotendinous xanthomatosis (CTX) is a rare inherited disorder of the alternative pathway of bile acid biosynthesis, due to mutation(s) of the gene CYP27A1, leading to sterol 27-hydroxylase deficiency. The latter results in a systematic deposition of cholestanol and cholesterol to the central nervous system and tendons, premature cataract, as well as the manifestation of systematic symptoms, such as chronic diarrhea, osteoporosis, and premature atherosclerosis. Due to its marked clinical heterogeneity, prompt diagnosis of this disorder is challenging. We present a case of a 38-year-old male with gait difficulty, a progressive deterioration in ambulation, several episodes of vertigo and episodic diarrhea. Clinical history revealed neonatal jaundice, juvenile bilateral cataracts, borderline intellectual capacity, hypothyroidism, testicular cancer. Magnetic resonance imaging demonstrated increased T2-weighted signal in internal capsules, midbrain, cerebellum, and spinal cord. Electrodiagnostic study showed mixed polyneuropathy. Genetic analysis revealed a novel, biallelic, most likely pathogenic mutation, in gene CYP2A1 (c.1410_1411del). Plasma sterol profiling confirmed the diagnosis of CTX. Our patient was treated with chenodeoxycholic acid and one year later, he shows a progressive improvement of gait, normalization of plasma sterol biochemistry and electrophysiological parameters. This case highlights the importance of maintaining a high index of suspicion as the key to an early diagnosis of CTX, taking into consideration its clinical variability and, if promptly identified, the good response to treatment.

Clinical and electromyography characteristics of chemotherapy-induced polyneuropathy in children with acute lymphoblastic leukemia

Background. The Hemoblastoses are one of the urgent problems of oncohematology. Modern methods for the treatment of hemoblastoses have improved the prognosis significantly. However, the use of chemotherapy is accompanied by a high frequency of drug complications, including those associated with neurotoxicity. The addition of neurological symptoms to the main clinical picture of the disease significantly aggravates the patients condition, affects the prognosis and quality to life.
 Aim. Compare clinical picture and neurophysiological signs of chemo-induced polyneuropathy in children with acute lymphoblastic leukemia.
 Materials and methods. Neurological examination and electromyography (EMG), were conducted in 21 children aged 3 to 17 years in Regional Children Clinical Hospital of Yekaterinburg from 2019 to 2020.
 Results. In the study group, the signs of peripheral polyneuropathy, were revealed in almost all patients receiving induction chemotherapy (95.2%) while clinical neurological symptoms were found in 25% patients. During a 4-month follow-up, all children with subclinical signs of peripheral nerve damage developed corresponding neurological symptoms. According to EMG, the number of patients with mixed polyneuropathy increased by 1.7 times. In every third child, the amplitude of the M-response and nerve conduction velocity, were decreased.
 Conclusions. Therefore, neurophysiological examination should be performed at an early stage to identify high-risk groups for neurotoxic complications in children with acute lymphoblastic leukemia receiving chemotherapy as timely administration of therapeutic treatment is required.

Transthyretin -Related Familial Amyloid Polyneuropathy (TTR-FAP) Polineuropathy – Challenge Diagnosis and Case Presentation

Abstract Introduction Transthyretin -Related Familial Amyloid Polyneuropathy (TTR-FAP) is a rare cause of polyneuropathy, mainly in Romania, but also in other geographic area of Europe, Japan and north America. Polyneuropathies are common in neurology practice, but prevalence and incidence are not known, usually are underreported and misdiagnosis. Almost one third of polyneuropathies remain idiopathic, in spite of extensive work-out to identify etiology. Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is a multisystemic disease neurological manifestation caused by the accumulation of amyloidogenic transthyretin (TTR) protein in tissues. It is an autosomal dominant syndrome, and there are more than 100 forms of TTr associated with FAP. The disease is characterized by progressive peripheral and autonomic neuropathy, and visceral amyloid involvement like cardiac amyloidosis. Case presentation We present the case of a male, aged 48, who experienced from 18 month paresthesias of distal inferior limb and fatigue, with an important weight loss. The patient was diagnosed with mixed polyneuropathy, and he was extensively investigated. Etiology was not established. He began to feel dizziness and faints several times, and these new features lead to our final diagnosis. Conclusions Etiology of a polyneuropathy case could be very challenging for general neurologist due to a numerous causes. A large variety of signs and symptoms lead the clinician to a narrow diagnostic possibilities and still this might take a long time. Polyneuropathy and cardiac involvement make a mark for life threatening disease but potentially curable

Clinical and neurophysiological spectrum of polyneuropathies in children

Peripheral neuropathy is a disorder of the peripheral nerves and results from a disturbance of structure and/or function of the peripheral sensory, motor and/or autonomic neurons. The possible aetiology of peripheral neuropathies is diverse, but inflammatory and hereditary diseases of the peripheral nerves predominate in childhood. The aim of this study was to determine the clinical and electrophysiological profile of large nerve fibre neuropathy detected by nerve conduction studies (NCS) in children over a 10-year period at the Children's Clinical University Hospital in Latvia. Based on NCS findings, 165 children between 2008 and 2018 were diagnosed with polyneuropathy. In our study, the majority of children had peripheral neuropathy due to acquired causes, mostly due to diabetes mellitus; roughly one in five of the patients had hereditary neuropathy. Almost half of the patients had motor deficits, which were more prevalent in toxic and inflammatory neuropathies. A little less than a third of patients complained of pain as well as presenting with autonomic dysfunction symptoms. The NCS demonstrated a demyelinating neuropathy in 52 cases (31%), an axonal neuropathy in 34 cases (21%), and mixed polyneuropathy in 79 cases (48%). Our study investigated the clinical and electrophysiological characteristics of polyneuropathies diagnosed with NCS in children. Most of the polyneuropathies in our study were hereditary and diabetic neuropathies with combined (myelin and axon) damage to nerve fibres. Almost all clinical symptoms of polyneuropathy were present in all aetiological groups.

P88-T Clinical and neurophysiologic characterization of the diabetic truncal mononeuropathy

Background Thoraco-abdominal or truncal nerves can be selectively affected in diabetic patients. The clinical picture shows predominantly sensory symptoms like pain, paresthesia, and occasional motor involvement. This mononeuropathy can be misdiagnosed with different thoracic-abdominal conditions (herpes zoster, angor pectoris, acute abdomen, intraabdominal tumours,…). It usually occurs between the 5th and 6th decades, with an insidious or subacute onset. We present a series of 4 cases in which electrodiagnostic testing was decisive for the diagnosis. Material and methods All the patients presented a long history of type 2 diabetes, and complained of poorly defined abdominal pain, without finding a cause that justified the symptoms in a prior extensive clinical investigation (including analytics and imaging studies). The neurophysiologic study consisted on motor and sensory conduction studies and quantitative needle electromyography of the rectus abdominis and external abdominal oblique muscles. Results In every case electromyography showed a subacute-chronic neurogenic pattern, characterized by complex and long-duration motor unit potentials, with an increased percentage of polyphasic potentials. In three cases we found spontaneous activity (fibrillation potentials or positive sharp waves). The study was compatible with the diagnosis of truncal neuropathy/radiculopathy. In half of the patients it was associated with a mixed sensory-motor polyneuropathy. Conclusions Truncal mononeuropathy in diabetic patients is most likely underdiagnosed, probably because the unspecific clinical presentation, including very variable sensory symptoms that mimic other conditions. Once the diagnosis of presumption is stablished, it is easily confirmed neurophysiologically, with electromyography being the technique that provides the most information for the diagnosis.

Clinical spectrum of POEMS-associated multicentric Castleman disease with renal involvement: a diagnostic challenge

Background: Castleman disease (CD) is a rare and heterogeneous lymphoproliferative disorder with a wide variety of clinical presentations and outcomes. Human herpesvirus-8 (HHV-8) related CD corresponds to the most common subtype of the multicentric Castleman disease (MCD). However, if HHV-8 is negative, POEMS (peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) associated with MCD or idiopathic MCD are the cause in a subgroup of patients. Considering the rarity of POEMS and MCD association, we herein describe a patient with a typical presentation based on clinical, laboratory and tissue biopsy data. Case Presentation: We report a diabetic patient who presented with asthenia, edema, skin lesions manifested by scarring in chiropodactyls, multiple lymph node enlargement in the neck, armpits and inguinal areas, splenomegaly, severe anemia, thrombocytopenia, and mixed polyneuropathy. Hematuria and proteinuria were detected. The patient developed progressive renal failure requiring dialysis. Renal biopsy showed mesangial expansion with mesangial hypercellularity, and lymphoplasmacytoid cells focally distributed in tubules and interstitium, which were compatible with acute tubulointerstitial nephritis. In immunofluorescence, no deposits of IgG, IgA, IgM, C1q, C3 or fibrinogen were found, and kappa and lambda were also negative. Lymph node biopsy revealed lymphoid tissue with follicular hyperplasia, sinusoidal and medullary infiltration of plasma cells. Immunohistochemistry confirmed positivity for B lymphocytes, T lymphocytes, and plasma cells in sub-capsular and para-follicular areas. The patient was diagnosed as POEMS-associated MCD variant, and chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone was started. The patient did not recover renal function and remained dialysis-dependent. Conclusions: To date, the renal involvement in MCD and POEMS syndrome seems to be uncommon as reported in few case series. Its pathophysiology is not well understood. In the spectrum of MCD, decreased renal function may have impact in patient survival. Early diagnosis and treatment are needed to control the systemic manifestations, and most importantly to avoid chronic organ damage.

Postinfectious (Varicella Zoster) myositis and mixed polyneuropathy

We present a case of a 21-year-old male with weakness of all four limbs after primary episode of chicken pox. Nerve conduction studies and magnetic resonance imaging dorsal spine with whole spine and brain screening confirmed polyneuropathy and myositis, respectively. He responded well to intravenous steroids, with complete reversal of symptoms. This case shows that primary varicella zoster infection is a sufficient stimulus to drive antibody generation and precipitate clinical complications.

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.

Hypereosinophilic Syndrome - A Case with Churg Strauss Vasculitis

The hypereosinophilic syndromes represent a group of disorders marked by the sustained overproduction of eosinophils, with eosinophilic infiltration of tissues and mediator release, leading to multiple organic damages. Churg-Strauss syndrome is a rare disorder characterized by systemic small vessel vasculitis, extra vascular granulomas and hypereosinophilia, characteristically occurring in people with background late-onset asthma and allergic rhinitis. Its annual incidence is between 0 and 4 per million of population. The authors present the case of a 72 year old Caucasian female patient, admitted at the Hygeia Hospital Tirana due to a hypereosinophilic syndrome. The thorax CT scan verified bilateral pseudo nodular pulmonary infiltrates; the head MRI showed vascular bilateral lesions in periventricular white matter and centrum semiovale, right internal capsule and left caudate nucleus, and the nerve conduction study (NCS) revealed a distal mixed polyneuropathy. A fibro-gastroscopy with biopsy suggested an atrophic gastritis. The patient underwent a course of treatment with intravenous methylprednisolone, tapered thereafter to oral prednisone together with cyclophosphamide, with a prompt improvement of the clinical picture.

Liver transplantation as treatment of familial amyloid polyneuropathy in patients older than 60 years

Background and objectiveFamilial amyloid polyneuropathy (FAP) is the most prevalent type of hereditary systemic amyloidosis. It is an autosomal dominant disease characterized by the deposition of an abnormal variant transthyretin. It has a worldwide distribution, with localized endemic areas in Portugal, Sweden and Japan. In Spain there is an endemic focus, located in Mallorca. Liver transplantation is the only curative option for patients with FAP. The aim of this study was to describe the clinical and demographic characteristics of patients transplanted with a diagnosis of PAF. Material and methodSix patients with PAF underwent liver transplantation between April 1986 and December 2012. ResultsThe mean age was 57.7+16 years, patients of Spanish origin were older than 60 years. All patients had progressive symptoms as mixed polyneuropathy. In 2 patients, combined heart–liver transplants sequentially were performed. Patient survival and graft was 80% at 1, 3 and 5 years. ConclusionsThe only effective treatment for etiologic PAF is liver transplantation. Early detection is the key to the treatment and control, avoiding the irreversible organ damage.

Pharmacological approach for the management of patient with carpal tunnel syndrome associated to diabetic polyneuropathy. Case report

BACKGROUND AND OBJECTIVES: Peripheral neuropathy and carpal tunnel syndrome are debilitating diseases associated to diabetes mellitus in 12 to 21% of cases. There are no significant evidences of the clinical differentiation between such painful syndromes and their specific management. This study aimed at reporting the clinical presentation of a patient with peripheral polyneuropathy associated to carpal tunnel syndrome, focusing on therapeuthic approaches and discussing clinical differentiation between both diseases. CASE REPORT: Male patient, 68 years old, married, retired, who looked for medical assistance complaining of burning pain, especially in left upper limb. He also referred pain in lower limbs with night exacerbation, in addition to numbness in extremities and pain intensity of 6 in the visual analog scale. Presence of trigger- points in trapezius and levator scapulae muscles. Patient was submitted to decompression surgery due to carpal tunnel syndrome diagnosis two years ago, however without postoperative improvement. Patient refers pain in upper and lower limbs, with nocturnal exacerbation, numbness and pain in extremities. He has history of hypertension, diabetes mellitus type 2 and leprosy. At physical evaluation: painful boot and glove hypoesthesia and possible motor deficit in C6 and C7. Electromyography showed mixed peripheral polyneuropathy of lower limbs and median carpal syndrome to the left. There has been movement amplitude improvement in myotomes C6 and C7. Pain decreased to 3 in the visual analog scale after two weeks under gabapentin and duloxetine. CONCLUSION: It is difficult to clinically differentiate between neuropathy of different etiology and peripheral polyneuropathy. The proposed treatment has provided 50% improvement in the visual analog scale two weeks later. Lidocaine infusion at 5% has provided acute improvement of patient’s pain.

An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs.

An inherited polyneuropathy (PN) observed in Leonberger dogs has clinical similarities to a genetically heterogeneous group of peripheral neuropathies termed Charcot-Marie-Tooth (CMT) disease in humans. The Leonberger disorder is a severe, juvenile-onset, chronic, progressive, and mixed PN, characterized by exercise intolerance, gait abnormalities and muscle atrophy of the pelvic limbs, as well as inspiratory stridor and dyspnea. We mapped a PN locus in Leonbergers to a 250 kb region on canine chromosome 16 (Praw = 1.16×10−10, Pgenome, corrected = 0.006) utilizing a high-density SNP array. Within this interval is the ARHGEF10 gene, a member of the rho family of GTPases known to be involved in neuronal growth and axonal migration, and implicated in human hypomyelination. ARHGEF10 sequencing identified a 10 bp deletion in affected dogs that removes four nucleotides from the 3′-end of exon 17 and six nucleotides from the 5′-end of intron 17 (c.1955_1958+6delCACGGTGAGC). This eliminates the 3′-splice junction of exon 17, creates an alternate splice site immediately downstream in which the processed mRNA contains a frame shift, and generates a premature stop codon predicted to truncate approximately 50% of the protein. Homozygosity for the deletion was highly associated with the severe juvenile-onset PN phenotype in both Leonberger and Saint Bernard dogs. The overall clinical picture of PN in these breeds, and the effects of sex and heterozygosity of the ARHGEF10 deletion, are less clear due to the likely presence of other forms of PN with variable ages of onset and severity of clinical signs. This is the first documented severe polyneuropathy associated with a mutation in ARHGEF10 in any species.

Trasplante hepático como tratamiento de la polineuropatía amiloidótica familiar en pacientes mayores de 60 años

Background and objectiveFamilial amyloid polyneuropathy (FAP) is the most prevalent type of hereditary systemic amyloidosis. It is an autosomal dominant disease characterized by the deposition of an abnormal variant transthyretin. It has a worldwide distribution, with localized endemic areas in Portugal, Sweden and Japan. In Spain there is an endemic focus, located in Mallorca. Liver transplantation is the only curative option for patients with FAP. The aim of this study was to describe the clinical and demographic characteristics of patients transplanted with a diagnosis of PAF. Material and methodSix patients with PAF underwent liver transplantation between April 1986 and December 2012. ResultsThe mean age was 57.7+16 years, patients of Spanish origin were older than 60 years. All patients had progressive symptoms as mixed polyneuropathy. In 2 patients, combined heart-liver transplants sequentially were performed. Patient survival and graft was 80% at one, 3 and 5 years. ConclusionsThe only effective treatment for etiologic PAF is liver transplantation. Early detection is the key to the treatment and control, avoiding the irreversible organ damage.

Long Term Follow-Up of Clinical and Electromyoneurographical Abnormalities in Eight Croatian Patients with Triple A Syndrome (P01.126)

Objective: To analyse long term follow up of neurological abnormalities (during 2 years to 23 years) in eight Croatian patients with triple A syndrome. Background The triple A syndrome is caused by autosomal recessively inherited mutation in AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN. This multisystem disease is characterized by achalasia, alacrimia, adrenal insufficiency and neurological impairment. Design/Methods: Clinical examination, electromyoneurography (EMNG) and molecular genetic analysis were performed in eight patients with triple A syndrome (five males and three females). Results: At the time of diagnosis all patients (aged 2 years to 8 years) presented with alacrimia, latent or manifest adrenal insufficiency, anisocoria in 2, optic atrophy in 4, motor and sensory polyneuropathy on the first exam in 2 siblings, muscle weakness and hypotrophy of distal muscle groups, cavus feet, hyperreflexia but absent triceps surae jerks, talocrural joints contractures, tremor and dysmetria in 5 patients. First EMG findings were normal at the age 6-11 years in 6/8 patients. The follow up EMG showed chronic partial denervation in all patients. Spontaneous activity (fibrillations) was registered in 3/8, compound muscle action potentials (CMAP) were polyphasic in 6/8 patients. Absent or low CMAP amplitude (0-0,5mV) was obtained in 6/8, decreased motor conduction velocity (29-40 m/s) in 8/8, absent F-wave potentials in 7/8, absent neural potentials in 5/8, and proximal conduction block in 5 patients. Mutation pSer263Pro was identified in 5 of 8 patients. One is homozygous and four are compound heterozygous for this mutation. Genotype/phenotype analysis confirmed lack of correlation in patients with triple A syndrome. Conclusions: Long term follow up neurography in patients with triple A syndrome showed progressive mixed motor and sensory polyneuropathy development with signs of pronounced demyelination and/or probably secondary axonal damage. Molecular results support the hypothesis that the pSer263Pro mutation is founder mutation in Slavic population. Disclosure: Dr. Barisic has nothing to disclose. Dr. Dumic has nothing to disclose. Dr. Kusec has nothing to disclose. Dr. Stingl has nothing to disclose. Dr. Lehman has nothing to disclose. Dr. Bunoza has nothing to disclose. Dr. Grdan has nothing to disclose. Dr. Koehler has nothing to disclose. Dr. Heubner has nothing to disclose.

A Deletion in the N-Myc Downstream Regulated Gene 1 (NDRG1) Gene in Greyhounds with Polyneuropathy

The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre teasing and electron microscopy. A severe chronic progressive mixed polyneuropathy was observed. Seven affected and 17 related control dogs were genotyped on the 50k canine SNP chip. This allowed us to localize the causative mutation to a 19.5 Mb interval on chromosome 13 by homozygosity mapping. The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D). Therefore, we considered NDRG1 a positional and functional candidate gene and performed mutation analysis in affected and control Greyhounds. A 10 bp deletion in canine NDRG1 exon 15 (c.1080_1089delTCGCCTGGAC) was perfectly associated with the polyneuropathy phenotype of Greyhound show dogs. The deletion causes a frame shift (p.Arg361SerfsX60) which alters several amino acids before a stop codon is encountered. A reduced level of NDRG1 transcript could be detected by RT-PCR. Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease. Selection against this mutation can now be used to eliminate polyneuropathy from Greyhound show dogs.

PO32-FR-22 A glue sniffer with mixed polyneuropathy: a case report

PO32-FR-22 A glue sniffer with mixed polyneuropathy: a case report

MYELOMA-ASSOCIATED POLYNEUROPATHY RESPONDING TO LENALIDOMIDE

In recent years, thalidomide has emerged as an important treatment for multiple myeloma, but its usefulness is limited by the occurrence of a toxic axonal polyneuropathy in many patients.1 Lenalidomide, a structural derivative of thalidomide with much lower neurotoxicity, is also effective in controlling myeloma, and has begun to be used as a first-line treatment.2 This article describes a patient with myeloma who presented with a severe demyelinating polyneuropathy that responded poorly to standard immunotherapy, but improved remarkably during treatment with lenalidomide. ### Case report. In March 2005, a 38-year-old woman developed numbness in her hands and feet and increasing limb weakness, worse in her arms. Within 6 months, she was unable to walk without support and could hardly feed herself. Nerve conduction studies performed elsewhere showed a mixed demyelinating and axonal polyneuropathy with markedly prolonged distal motor and sensory latencies and F wave latencies in many nerves (table). Needle EMG was normal in proximal and distal extremities. The spinal fluid contained 1 white blood cell per mm3 and protein 48 mg/dL. Serum immunofixation electrophoresis showed a monoclonal IgA-lambda paraprotein; total gamma globulin was 2.17 g/dL. Fasting blood glucose, antinuclear antibodies, rheumatoid …

The Fourth Dorsal Interosseus Pedis Muscle: A Useful Muscle in Routine Electromyography

The aim of the study was to assess the utility of needle examination of the fourth dorsal interosseus pedis (FDIP) muscle in routine EMG. FDIP is an easily accessible muscle and may be less prone to blunt trauma as compared with the other foot muscles but despite its potential utility in electrophysiology, little if any data are available on the FDIP muscle. Detailed neurologic examination, nerve conduction, and needle EMG studies were performed in 118 individuals referred to the EMG laboratory of a tertiary referral center. The FDIP was studied by inserting a needle obliquely at an angle of about 30 degrees immediately proximal to the fourth and fifth metatarsal heads. In 44 subjects (patients/volunteers) with normal studies, <5% had increased insertional activity (IA) in the FDIP, but none had sustained spontaneous activity (SA). Among 32 patients with mixed sensorimotor polyneuropathy, FDIP showed abnormal SA in >90%. In patients with S1 root compromise, 66% had sustained SA in FDIP but none with involvement of L3, L4, or L5 nerve root alone. Two of the four patients with tibial and one of five with peroneal neuropathies had increased SA in this muscle; none with other lower limb focal neuropathies. In patients with lumbosacral plexopathy, FDIP showed denervation potentials with diffuse plexus involvement but not with upper plexopathy. Almost all patients tolerated the FDIP needle examination well. End plates were frequently encountered in the FDIP muscle. We concluded that in normal feet, the FDIP muscle has a low incidence of sustained SA. Abnormal SA in FDIP correlates well with the overall neurologic condition, and it may be a useful muscle to include in routine electrodiagnostic evaluation.

The spectrum of transthyretin gene mutations in italy: a report

Transthyretin gene mutations causing autosomal dominant familial amyloidotic polyneuropathy (FAP) are often associated with cardiomyopathy. More than 80 amino acid variations have been described until now, showing a high allelic heterogeneity. We screened for TTR mutations 55 patients with mixed polyneuropathy with variable cardiac involvement. By means of direct sequencing of the full coding region we identified the following 26 genotypes: 2 Ser6 (polymorphism), 3 Met30, 4 Gln89, 2 Leu64 (TTT &gt; TTG) and 7 Leu64 (TTT &gt; CTT), 2 Ala49, 2 Leu68, 1 Thr34, 1 Arg50, 1 Glu53 and 1 Asn90. Interestingly, two Leu64 variants were due to a novel nucleotide variation TTT to TTG in codon 64 and 1 Asn90 mutation was found to co‐segregate with a FAP phenotype. Transthyretin mutations in hereditary amyloidosis deserve to be investigated in all cases of mixed polyneuropathy with cardiomyopathy both familial and sporadic. A marked allelic heterogeneity in Italy has been further confirmed by this study and PCR and direct sequencing seems to represent the more appropriate diagnostic tool for this pathology.

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.