RESUMO
BACKGROUND: Mutations of myelin protein zero (MPZ) may cause inherited neuropathy with variable expression. OBJECTIVE: To report phenotypic variability in a large American kindred with MPZ mutation His39Pro. PATIENTS: Genetic testing was performed on 77 family members and 200 controls. Clinical and electrophysiological field study assessments were available for review in 47 family members. RESULTS: His39Pro was found in all 10 individuals prospectively identified with neuropathy. 200 normal controls were without mutation. Symptoms of neuropathy began in adulthood and were slowly progressive except for one acute-onset painful sensory neuropathy. Associated features included premature hearing loss (n = 7), nocturnal restless leg symptoms (n = 8) and multiple sclerosis in one. CONCLUSIONS: MPZ mutation His39Pro may be associated with acute-onset neuropathy, early-onset hearing loss and restless legs. The relationship with multiple sclerosis in the proband remains uncertain.
Assuntos
Perda Auditiva/genética , Esclerose Múltipla/genética , Proteína P0 da Mielina/genética , Adulto , Idade de Início , Pré-Escolar , Análise Mutacional de DNA , Feminino , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Histidina , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Prolina , Síndrome das Pernas Inquietas/genéticaRESUMO
Fifty-seven patients with biopsy-proven sarcoidosis causing limb neuropathy were reviewed in order to delineate the characteristic symptoms, impairments, disability, course, outcome and response to corticosteroid treatment of limb sarcoid neuropathy. Typically the neuropathy had a definite date of symptomatic onset. Prominent were positive neuropathic sensory symptoms (P-NSS), especially pain, overshadowing weakness and sensory loss. P-NSS were the main cause of disability. Almost always the pattern was asymmetric and not length-dependent (unlike distal polyneuropathy). We inferred (from kind and distribution of symptoms, signs and electrophysiologic and other test results) that the pathologic process was focal or multifocal, involving most classes of nerve fibers and variable levels of proximal to distal levels of roots and peripheral nerves. Additional features aiding in diagnosis were: systemic symptoms such as fatigue, malaise, arthralgia, fever and weight loss; involvement of multiple tissues (i.e. skin, lymph nodes and eye); the patterns of neuropathy; MRI features; and ultimately tissue diagnosis. Axonal degeneration predominated, although an acquired demyelinating process was observed in 3 patients. For most cases, the disease had a chronic, monophasic course. MRI studies done in later years of affected neural structures were helpful in identifying leptomeningeal thickening, hilar adenopathy; and enlargement and T2 enhancement of nerve roots, plexuses, and limb nerves. Corticosteroid treatment appeared to ameliorate symptoms more than impairments. Several variables were associated with neuropathic improvement: CSF pleocytosis, short duration between symptom onset and treatment, and a higher grade of disability at first evaluation-a possible rationale for future earlier diagnosis and treatment.
Assuntos
Nervos Periféricos/fisiopatologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/fisiopatologia , Sarcoidose/complicações , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Axônios/patologia , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/fisiopatologia , Avaliação da Deficiência , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/etiologia , Neuralgia/fisiopatologia , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/etiologia , Prognóstico , Estudos Retrospectivos , Transtornos de Sensação/etiologia , Transtornos de Sensação/fisiopatologia , Raízes Nervosas Espinhais/patologia , Raízes Nervosas Espinhais/fisiopatologia , Resultado do Tratamento , Degeneração Walleriana/etiologia , Degeneração Walleriana/fisiopatologiaRESUMO
BACKGROUND AND OBJECTIVES: The association between prediabetes and distal polyneuropathy (DPN) remains controversial. Here we test whether the prevalence of small fiber sensory distal polyneuropathy is increased in prediabetes. METHODS: Prospectively recruited cohorts of healthy subjects and those with prediabetes from Olmsted County, Minnesota, were assessed for positive neuropathic sensory symptoms, or pain symptoms characteristic of small fiber sensory DPN. Hyperalgesia and hypoalgesia were assessed by "smart" quantitative sensation testing (QST). The prevalence of symptoms and QST abnormalities were compared among the groups. RESULTS: There was no significant increase in the prevalence of positive neuropathic sensory or pain symptoms, nor of hyper- or hypoalgesia in the prediabetes group. There was an increased prevalence of hypoalgesia of the foot only in newly diagnosed diabetes. CONCLUSIONS: Based on positive sensory and pain symptoms and QSTs, we did not find an increase in small fiber sensory DPN in prediabetes. Recognizing that obesity and diabetes mellitus are implicated in macro- and microvessel complications, physicians should encourage healthy living and weight loss in patients with prediabetes. In medical practice, alternate causes should be excluded before concluding that small fiber sensory distal neuropathy is secondary to prediabetes.
Assuntos
Eritromelalgia/etiologia , Estado Pré-Diabético/complicações , Estudos de Coortes , Eritromelalgia/diagnóstico , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Medição da Dor , Limiar da Dor/fisiologiaRESUMO
Protein stabilization and oligonucleotide therapies are being tested in transthyretin amyloid polyneuropathy (TTR FAP) trials. From retrospective analysis of 97 untreated TTR FAP patients, we test the adequacy of Neuropathy Impairment Score+7 tests (NIS+7) and modifications to comprehensively score impairments for use in such therapeutic trials. Our data confirms that TTR FAP usually is a sensorimotor polyneuropathy with autonomic features which usually is symmetric, length dependent, lower limb predominant and progressive. NIS+7 adequately assesses weakness and muscle stretch reflexes without ceiling effects but not sensation loss, autonomic dysfunction or nerve conduction abnormalities. Three modifications of NIS+7 are suggested: 1) use of Smart Somatotopic Quantitative Sensation Testing (S ST QSTing); 2) choice of new autonomic assessments, e.g., sudomotor testing of distributed anatomical sites; and 3) use of only compound muscle action potential amplitudes (of ulnar, peroneal and tibial nerves) and sensory nerve action potentials of ulnar and sural nerve - than the previously recommended attributes suggested for the sensitive detection of diabetic sensorimotor polyneuropathy. These modifications of NIS+7 if used in therapeutic trials should improve characterization and quantification of sensation and autonomic impairment in TTR FAP and provide better nerve conduction tests.
Assuntos
Neuropatias Amiloides Familiares/diagnóstico , Vias Autônomas/fisiopatologia , Exame Neurológico , Adulto , Idoso , Neuropatias Amiloides Familiares/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Neurofisiologia , Adulto JovemRESUMO
OBJECTIVES: Autonomic deficits in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have not been adequately quantitated. The Composite Autonomic Severity Score (CASS) is a validated instrument for laboratory quantitation of autonomic failure derived from standard autonomic reflex tests. We characterized dysautonomia in CIDP using CASS. METHODS: Autonomic function was retrospectively analyzed in 47 patients meeting CIDP criteria. CASS ranges from 0 (normal) to 10 (pandysautonomia), reflecting summation of sudomotor (0-3), cardiovagal (0-3), and adrenergic (0-4) subscores. Severity of neurologic deficits was measured with Neuropathy Impairment Score (NIS). Degree of small fiber involvement was assessed with quantitative sensation testing. Thermoregulatory sweat test (TST) was available in 8 patients. RESULTS: Patients (25 men) were middle-aged (45.0 ± 14.9 years) with longstanding CIDP (3.5 ± 4.3 years) of moderate severity (NIS, 46.5 ± 32.7). Autonomic symptoms were uncommon, mainly gastrointestinal (9/47; 19%) and genitourinary (8/47; 17%). Autonomic deficits (CASS ≥1) were frequent (22/47; 47%) but very mild (CASS, 0.8 ± 0.9; CASS ≤3, all cases). Deficits were predominantly sudomotor (16/47; 34%) and cardiovagal (10/47; 21%) with relative adrenergic sparing (4/47; 9%). TST was abnormal in 5 of 8 patients (anhidrosis range, 2%-59%). Sudomotor impairment was predominantly distal and postganglionic. Somatic deficits (disease duration, severity, small fiber deficits) did not predict presence of autonomic deficits. CONCLUSION: Our data characterize the autonomic involvement in classic CIDP as mild, cholinergic, and predominantly sudomotor mainly as a result of lesions at the distal postganglionic axon. Extensive or severe autonomic involvement (CASS ≥4) in suspected CIDP should raise concern for an alternative diagnosis.
Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Adulto , Regulação da Temperatura Corporal/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Sudorese/fisiologiaRESUMO
BACKGROUND: The reported prevalence of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) varies greatly, from 1.9 to 7.7 per 100,000. CIDP is reported to occur more commonly in patients with diabetes mellitus (DM) but has not been rigorously tested. OBJECTIVES: To determine the incidence (1982-2001) and prevalence (on January 1, 2000) of CIDP in Olmsted County, Minnesota, and whether DM is more frequent in CIDP. METHODS: CIDP was diagnosed by clinical criteria followed by review of electrophysiology. Cases were coded as definite, probable, or possible. DM was ascertained by clinical diagnosis or current American Diabetes Association glycemia criteria. RESULTS: One thousand five hundred eighty-one medical records were reviewed, and 23 patients (10 women and 13 men) were identified as having CIDP (19 definite and 4 probable). The median age was 58 years (range 4-83 years), with a median disease duration at diagnosis of 10 months (range 2-64 months). The incidence of CIDP was 1.6/100,000/year. The prevalence was 8.9/100,000 persons on January 1, 2000. Only 1 of the 23 CIDP patients (4%) also had DM, whereas 14 of 115 age- and sex-matched controls (12%) had DM. CONCLUSIONS: 1) The incidence (1.6/100,000/year) and prevalence (8.9/100,000) of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are similar to or higher than previous estimates. 2) The incidence of CIDP is similar to that of acute inflammatory demyelinating polyradiculoneuropathy within the same population. 3) Diabetes mellitus (DM) is unlikely to be a major risk covariate for CIDP, but we cannot exclude a small effect. 4) The perceived association of DM with CIDP may be due to misclassification of other forms of diabetic neuropathies and excessive emphasis on electrophysiologic criteria.
Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Comorbidade , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatologia , Eletrodiagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Minnesota , Condução Nervosa/fisiologia , Nervos Periféricos/metabolismo , Nervos Periféricos/patologia , Nervos Periféricos/fisiopatologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Prevalência , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: The variable clinical features of hereditary sensory and autonomic neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory neuropathy could be caused by missense mutations of SPTLC1 and RAB7 and not be recognised as familial. OBJECTIVE: To screen persons with dominantly inherited HSAN I and others with idiopathic sensory neuropathies for known mutations of SPTLC1 and RAB7. PATIENTS: DNA was examined from well characterised individuals of 25 kindreds with adult onset HSAN I for mutations of SPTLC1 and RAB7; 92 patients with idiopathic sensory neuropathy were also screened for known mutations of these genes. RESULTS: Of the 25 kindreds, only one had a mutation (SPTLC1 399T-->G). This kindred, and 10 without identified mutations, had prominent mutilating foot injuries with peroneal weakness. Of the remainder, 12 had foot insensitivity with injuries but no weakness, one had restless legs and burning feet, and one had dementia with hearing loss. No mutation of RAB7 was found in any of these. No known mutations of SPTLC1 or RAB7 were found in cases of idiopathic sensory neuropathy. CONCLUSIONS: Adult onset HSAN I is clinically and genetically heterogeneous and further work is required to identify additional genetic causes. Known SPTLC1or RAB7 mutations were not found in idiopathic sensory neuropathy.
Assuntos
Aciltransferases/genética , Análise Mutacional de DNA , Genes Dominantes , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Proteínas rab de Ligação ao GTP/genética , Adulto , Primers do DNA/genética , Diagnóstico Diferencial , Éxons , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Feminino , Triagem de Portadores Genéticos , Genótipo , Neuropatias Hereditárias Sensoriais e Autônomas/diagnóstico , Humanos , Masculino , Dados de Sequência Molecular , Fases de Leitura Aberta , Linhagem , Polineuropatias/diagnóstico , Polineuropatias/genética , Análise de Sequência de DNA , Serina C-Palmitoiltransferase , proteínas de unión al GTP Rab7RESUMO
BACKGROUND: Chronic inflammatory neuropathies can present with a sensory ataxia due to involvement of dorsal root ganglia (DRG) or sensory nerves. Selective inflammatory involvement of sensory nerve roots proximal to the DRG has been postulated. METHODS: The authors identified 15 patients with a sensory syndrome and normal nerve conduction studies. Sensory nerve root involvement was suggested by either somatosensory evoked potential (SSEP) or imaging abnormalities. CNS disease was excluded. RESULTS: All patients had gait ataxia, large fiber sensory loss, and paresthesias, and nine had frequent falls. The disease course was chronic and progressive (median duration 5 years, range 3 months to 18 years). Sural sensory nerve action potential amplitudes were preserved and SSEP abnormalities were consistent with sensory nerve root involvement. Five patients had enlargement of lumbar nerve roots on MRI with enhancement in three. The CSF protein was elevated in 13 of 14 patients tested. Three patients had lumbar sensory rootlet biopsies that showed thickened rootlets, decreased density of large myelinated fibers, segmental demyelination, onion-bulb formation, and endoneurial inflammation. Six patients who required aids to walk were treated with immune modulating therapy and all had marked improvement with four returning to normal ambulation. CONCLUSION: Based on the described clinical features, normal nerve conduction studies, characteristic somatosensory evoked potential (SSEP) abnormality, enlarged nerve roots, elevated CSF protein, and inflammatory hypertrophic changes of sensory nerve rootlet tissue, we suggest the term chronic immune sensory polyradiculopathy (CISP) for this syndrome. This condition preferentially affects large myelinated fibers of the posterior roots, may respond favorably to treatment, and may be a restricted form of chronic inflammatory demyelinating polyradiculoneuropathy.
Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Adulto , Idoso , Potenciais Somatossensoriais Evocados , Feminino , Marcha Atáxica/diagnóstico , Marcha Atáxica/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Raízes Nervosas Espinhais/patologia , Raízes Nervosas Espinhais/ultraestruturaRESUMO
BACKGROUND: Although peripheral neuropathy (PN) occurs after bariatric surgery (BS), a causal association has not been established. OBJECTIVES: To ascertain whether PN occurs more frequently following BS vs another abdominal surgery, to characterize the clinical patterns of PN, to identify risk factors for PN, and to assess if nerve biopsy provides pathophysiologic insight. METHODS: Retrospective review identified patients with PN after BS. The frequency of PN was compared with that of an age- and gender-matched, retrospectively evaluated cohort of obese patients undergoing cholecystectomy. RESULTS: Of 435 patients who had BS, 71 (16%) developed PN. Patients developed PN more often after BS than after cholecystectomy (4/126; 3%) (p < 0.001). The clinical patterns of PN were polyneuropathy (n = 27), mononeuropathy (n = 39), and radiculoplexus neuropathy (n = 5). Risk factors included rate and absolute amount of weight loss, prolonged gastrointestinal symptoms, not attending a nutritional clinic after BS, reduced serum albumin and transferrin after BS, postoperative surgical complications requiring hospitalization, and having jejunoileal bypass. Most risk factors were associated with the polyneuropathy group. Sural nerve biopsies showed prominent axonal degeneration and perivascular inflammation. CONCLUSIONS: Peripheral neuropathy (PN) occurs more frequently after bariatric surgery (BS) than after another abdominal surgery. The three clinical patterns of PN after BS are sensory-predominant polyneuropathy, mononeuropathy, and radiculoplexus neuropathy. Malnutrition may be the most important risk factor, and patients should attend nutritional clinics. Inflammation and altered immunity may play a role in the pathogenesis, but further study is needed.
Assuntos
Cirurgia Bariátrica/efeitos adversos , Trato Gastrointestinal/cirurgia , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/patologia , Adulto , Idoso , Anemia Ferropriva/complicações , Anemia Ferropriva/etiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Trato Gastrointestinal/fisiopatologia , Humanos , Derivação Jejunoileal/efeitos adversos , Masculino , Desnutrição/complicações , Desnutrição/etiologia , Desnutrição/fisiopatologia , Pessoa de Meia-Idade , Neurite (Inflamação)/etiologia , Neurite (Inflamação)/patologia , Neurite (Inflamação)/fisiopatologia , Nervos Periféricos/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Polineuropatias/etiologia , Polineuropatias/patologia , Polineuropatias/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismo , Nervo Sural/patologia , Nervo Sural/fisiopatologia , Transferrina/metabolismoRESUMO
OBJECTIVE: To study the role of mechanical, infectious, and inflammatory factors inducing neuropathic attacks in hereditary brachial plexus neuropathy (HBPN), an autosomal dominant disorder characterised by attacks of pain and weakness, atrophy, and sensory alterations of the shoulder girdle and upper limb muscles. METHODS: Four patients from separate kindreds with HBPN were evaluated. Upper extremity nerve biopsies were obtained during attacks from a person of each kindred. In situ hybridisation for common viruses in nerve tissue and genetic testing for a hereditary tendency to pressure palsies (HNPP; tomaculous neuropathy) were undertaken. Two patients treated with intravenous methyl prednisolone had serial clinical and electrophysiological examinations. One patient was followed prospectively through pregnancy and during the development of a stereotypic attack after elective caesarean delivery. RESULTS: Upper extremity nerve biopsies in two patients showed prominent perivascular inflammatory infiltrates with vessel wall disruption. Nerve in situ hybridisation for viruses was negative. There were no tomaculous nerve changes. In two patients intravenous methyl prednisolone ameliorated symptoms (largely pain), but with tapering of steroid dose, signs and symptoms worsened. Elective caesarean delivery did not prevent a typical postpartum attack. CONCLUSIONS: Inflammation, probably immune, appears pathogenic for some if not all attacks of HBPN. Immune modulation may be useful in preventing or reducing the neuropathic attacks, although controlled trials are needed to establish efficacy, as correction of the mutant gene is still not possible. The genes involved in immune regulation may be candidates for causing HBPN disorders.
Assuntos
Neuropatias do Plexo Braquial/complicações , Neuropatias do Plexo Braquial/genética , Doenças do Sistema Nervoso Periférico/etiologia , Adolescente , Adulto , Idade de Início , Anti-Inflamatórios/administração & dosagem , Neuropatias do Plexo Braquial/tratamento farmacológico , Neuropatias do Plexo Braquial/patologia , Neuropatias do Plexo Braquial/fisiopatologia , Criança , Eletrofisiologia , Feminino , Humanos , Inflamação/etiologia , Inflamação/patologia , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Linhagem , Doenças do Sistema Nervoso Periférico/patologia , Gravidez , Complicações na Gravidez/etiologiaRESUMO
BACKGROUND: Hereditary motor and sensory neuropathy type 2C (HMSN2C, Charcot-Marie-Tooth 2C [CMT2C]) is an autosomal dominant motor and sensory neuropathy involving limb, diaphragm, vocal cord, and intercostal muscles. OBJECTIVE: To identify the chromosome localization for this disorder in one large American family of English and Scottish ethnicity. METHODS: Variable clinical severity led the authors to combine several approaches to accurately identify affected patients. Genome-wide two-point linkage analysis, high-definition mapping, and multipoint and recombinant haplotype analyses were performed. Mutation analysis of the triplet repeat region of ataxin-2 was also carried out. RESULTS: The initial genome-wide scan identified a region at 12q24, and fine mapping provided a maximal lod score of 4.73 (D12S1645 and D12S1583 at theta = 0.01 and 0, respectively). With multipoint analysis, a higher lod score of 5.17 was obtained and localized to the same region at 119.0 cM. Haplotype analysis narrowed the region to approximately 5.0 cM between D12S1646,D12S1330 and D12S105,D12S1339 (12q23.3-24.21). Ataxin-2, the gene responsible for spinocerebellar ataxia type 2 (SCA2), localizes to this region, but no triplet repeat expansion or point mutations within the repeat were found. CONCLUSIONS: The gene for HMSN2C maps to 12q23-24. This region is associated with SCA2, scapuloperoneal spinal muscular atrophy, and congenital distal spinal muscular atrophy. Further studies are needed to demonstrate the specific gene alteration and its relationship with nearby genes.