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Biomedical subjects

P J Dyck

Publications and source records attributed to P J Dyck.

At least 19 recordsLinked to original sources
PubMed2006

The natural history and long-term outcome of 57 limb sarcoidosis neuropathy cases.

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.

Adrenal Cortex Hormones↗
PubMed2006

Myelin protein zero mutation His39Pro: hereditary motor and sensory neuropathy with variable onset, hearing loss, restless legs and multiple sclerosis.

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.

Adult↗
PubMed2005

Sudden cardiac death in diabetes mellitus: risk factors in the Rochester diabetic neuropathy study.

OBJECTIVES: To determine risk factors for sudden cardiac death and the role of diabetic autonomic neuropathy (DAN) in the Rochester diabetic neuropathy study (RDNS). METHODS: Associations between diabetic and cardiovascular complications, including DAN, and the risk of sudden cardiac death were studied among 462 diabetic patients (151 type 1) enrolled in the RDNS. Medical records, death certificates, and necropsy reports were assessed for causes of sudden cardiac death. RESULTS: 21 cases of sudden cardiac death were identified over 15 years of follow up. In bivariate analysis of risk covariates, the following were significant: ECG 1 (evolving and previous myocardial infarctions): hazard ratio (HR) = 4.4 (95% confidence interval (CI), 1.6 to 12.1), p = 0.004; ECG 2 (bundle branch block or pacing): HR = 8.6 (2.9 to 25.4), p<0.001; ECG 1 or ECG 2: HR = 4.2 (1.3 to 13.4), p = 0.014; and nephropathy stage: HR = 2.1 (1.3 to 3.4), p = 0.002. Adjusting for ECG 1 or ECG 2, autonomic scores, QTc interval, high density lipoprotein (HDL) cholesterol, 24 hour microalbuminuria, and 24 hour total proteinuria were significant. However, adjusting for nephropathy, none of the autonomic indices, QTc interval, HDL cholesterol, microalbuminuria, or total proteinuria was significant. At necropsy, all patients with sudden cardiac death had coronary artery or myocardial disease. CONCLUSIONS: Sudden cardiac death was correlated with atherosclerotic heart disease and nephropathy, and to a lesser degree with DAN and HDL cholesterol. Although DAN is associated with sudden cardiac death, it is unlikely to be its primary cause.

Aged↗
PubMed2005

SPTLC1 and RAB7 mutation analysis in dominantly inherited and idiopathic sensory neuropathies.

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.

Acyltransferases↗
PubMed2003

The gene for HMSN2C maps to 12q23-24: a region of neuromuscular disorders.

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.

Age of Onset↗
PubMed2002

Inflammation and neuropathic attacks in hereditary brachial plexus neuropathy.

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.

Adolescent↗
PubMed2001

Increased weakness after pancreas and kidney transplantation.

BACKGROUND: Already there is evidence that simultaneous pancreas and kidney (SPK), or pancreas after kidney (PAK) transplantation, in patients with type 1 diabetes mellitus and end-stage kidney disease prevents worsening of diabetic polyneuropathy, but neuropathic improvement is delayed and incomplete. METHODS: In 85 patients with type 1 diabetes mellitus who underwent SPK or PAK transplantations, we performed sequential neuromuscular evaluations before, every 3 months after, and yearly after transplantation, quantitating muscle weakness separately from overall severity of polyneuropathy. RESULTS: We found that, on average, the weakness subscore of the Neuropathy Impairment Score of the lower limbs [NIS(LL)-W] was significantly worse at 3, 6, 9, and 12 months (by about 5 points) than at baseline. By contrast, for these times after transplantation, a composite score of nerve conduction abnormalities, an independent measure of severity of polyneuropathy, was not significantly worse and, in fact, was significantly improved. In multivariate analysis, length of hospital stay correlated with the increased weakness. CONCLUSIONS: We conclude that: (1) increased neuromuscular impairment after transplantation is mainly due to muscle weakness and not to worsening polyneuropathy; (2) in multivariate analysis, duration of hospitalization after transplantation was significantly associated with this increased weakness; (3) increased weakness is probably due to development of myopathy, which may be related to graft rejection, immunosuppression, sepsis, and intercurrent infections; (4) in future transplantation trials, weakness should be evaluated separately from neuropathic status, and the lowest efficacious dosages of immunotherapy should be used; and (5) essentially all diabetic patients reported that SPK or PAK transplantation was worthwhile because it freed them from diabetic lifestyle concerns.

Adolescent↗
PubMed2001

Diagnostic accuracy and certainty from sequential evaluations in peripheral neuropathy.

Three masked neuromuscular experts analyzed the contribution of the data from sequential evaluations in predicting specific varieties of peripheral neuropathy in 72 patients. The largest improvement (16%) in diagnostic accuracy resulted from presentation of neurologic history. By contrast, diagnostic confidence increased gradually with presentation of additional medical information. Therefore, the authors conclude that for diagnostic accuracy and certainty, expert neuromuscular judgment and extensive characterizing or discriminative testing are needed.

Cohort Studies↗
PubMed2001

Methylprednisolone may improve lumbosacral radiculoplexus neuropathy.

OBJECTIVE: To report on an open trial of intravenous methylprednisolone (IV MP) in nondiabetic lumbosacral radiculoplexus neuropathy (LSRPN). BACKGROUND: Lumbosacral radiculoplexus neuropathy is a subacute, unilateral or asymmetric syndrome of pain, weakness, and paresthesia of the lower extremity, which is attributed to ischemic injury from microvasculitis in lumbosacral roots, plexus, and nerves. METHODS: Eleven nondiabetic patients with worsening LSRPN were treated - ten with infusions of IV MP (1 gm/wk) for 8 to 16 weeks and one with an equivalent dosage of oral prednisone. The main endpoints evaluated were: 1) the Neuropathy Impairment Score (NIS), and 2) the Neuropathy Symptoms and Change (NSC) scores. RESULTS: The median age of our patients was 67 years, range 49 to 86 years. Seven patients were women. All 11 patients reported improvement during treatment--nine reported marked improvement. The median NIS improved from 42 points (range 9 to 106 points) before treatment, to 20 points (range 5 to 57 points) (p = 0.005) after treatment. Pain was completely resolved in four patients and much improved in seven. The change subscore and the severity subscore of the NSC were statistically significantly improved after treatment. Prior to treatment, all patients had significant weakness with six confined to wheelchairs and four using mechanical devices to aid in ambulation. After treatment, the weakness was markedly improved in nine patients; only one still required a wheelchair and six walked independently (p = 0.03). CONCLUSIONS: 1) In LSRPN, pain and neurological deficits improved (often dramatically) with IV MP treatment. 2) Although our results should be interpreted with caution since this trial is uncontrolled, IV MP may favorably affect the natural history of LSRPN. 3) The results are sufficiently promising to provide a rationale for prospective, sham controlled, double blind trials.

Aged↗
PubMed2001

Non-diabetic lumbosacral radiculoplexus neuropathy: natural history, outcome and comparison with the diabetic variety.

Diabetic lumbosacral radiculoplexus neuropathy (DLSRPN) (other names include diabetic amyotrophy) is well recognized, unlike the non-diabetic lumbosacral radiculoplexus neuropathy (LSRPN), which has received less attention. Our objective was to characterize the natural history and outcome of LSRPN and to assess whether it is similar to the diabetic variety in its symptoms, course, electrophysiological features, quantitative sensory and autonomic findings, and the underlying pathophysiology. We studied 57 patients with LSRPN and 33 patients with DLSRPN. We found that the age of onset, course, kind and distribution of symptoms and impairments, laboratory findings and outcomes are essentially alike. Both disorders are a lumbosacral plexus neuropathy associated with weight loss, often beginning focally or asymmetrically in the thigh or leg but usually progressing to involve the initially unaffected segment and the contralateral side. Both have prolonged morbidity due to pain, paralysis, autonomic involvement and sensory loss. In biopsied distal LSRPN nerves, we found changes similar to those found in DLSRPN-alterations typical of ischaemic injury and of microvasculitis. The long-term outcome was determined in 42 LSRPN patients: two had become diabetic, seven had relapsed and only three had recovered completely, although all had improved. We conclude that: (i) LSRPN is a subacute, asymmetrical, painful and debilitating neuropathy of the lower limbs associated with weight loss, and we think it is under-recognized; (ii) recovery from the long-term impairments of LSRPN is usually delayed and incomplete and only a small minority of patients develop diabetes mellitus; (iii) LSRPN mirrors the diabetic variety in its clinical features, course, pathological findings (ischaemic injury from microvasculitis) and long-term outcome; and (iv) LSRPN should be set apart from chronic inflammatory demyelinating polyradiculoneuropathy and from systemic necrotizing vasculitis. We infer an autoimmune basis for LSRPN and emphasize the need for controlled trials of immune-modulating therapy.

Adult↗
PubMed2000

Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy: A randomized controlled trial. rhNGF Clinical Investigator Group.

CONTEXT: Nerve growth factor is a neurotrophic factor that promotes the survival of small fiber sensory neurons and sympathetic neurons in the peripheral nervous system. Recombinant human nerve growth factor (rhNGF) has demonstrated efficacy as treatment for peripheral neuropathy in experimental models and phase 2 clinical trials. OBJECTIVE: To evaluate the efficacy and safety of a 12-month regimen of rhNGF in patients with diabetic polyneuropathy. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial conducted from July 1997 through May 1999. SETTING: Eighty-four outpatient centers throughout the United States. PATIENTS: A total of 1019 men and women aged 18 to 74 years with either type 1 or type 2 diabetes and a sensory polyneuropathy attributable to diabetes. INTERVENTIONS: Patients were randomly assigned to receive either rhNGF, 0.1 microg/kg (n = 504), or placebo (n = 515) by subcutaneous injection 3 times per week for 48 weeks. Patients were assessed at baseline, 12 weeks, 24 weeks, and 48 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was a change in neuropathy between baseline and week 48, demonstrated by the Neuropathy Impairment Score for the Lower Limbs, compared between the 2 groups. Secondary outcome measures included quantitative sensory tests using the CASE IV System, the Neuropathy Symptom and Change questionnaire, the Patient Benefit Questionnaire (PBQ), and a global symptom assessment, as well as nerve conduction studies and occurrence of new plantar foot ulcers. Patients also were evaluated for presence of adverse events. RESULTS: Among patients who received rhNGF, 418 (83%) completed the regimen compared with 461 (90%) who received placebo. Administration of rhNGF was safe, with few adverse events attributed to treatment apart from injection site pain/hyperalgesia and other pain syndromes. However, neither the primary end point (P =.25) nor most of the secondary end points demonstrated a significant benefit of rhNGF. Exceptions were the global symptom assessment (P =.03) and 2 of 32 comparisons within the PBQ, which showed a modest but significant benefit of rhNGF (P =.05 for severity of pain in the legs and P =.003 for 6-month symptoms in the feet and legs). CONCLUSION: Unlike previous phase 2 trials, this phase 3 clinical trial failed to demonstrate a significant beneficial effect of rhNGF on diabetic polyneuropathy. JAMA. 2000;284:2215-2221.

Activities of Daily Living↗
PubMed2000

Hereditary motor and sensory neuropathy type 2C is genetically distinct from types 2B and 2D.

BACKGROUND: Linkage analysis studies have identified 3 genetically different varieties of hereditary motor and sensory neuropathy type 2 (HMSN 2, also called Charcot-Marie-Tooth disease type 2, or CMT 2): HMSN 2A (linked to 1p35-p36), 2B (to 3q13-q22), and 2D (to 7p14). Hereditary motor and sensory neuropathy type 2C is characterized by diaphragmatic and vocal cord paresis; its disease locus has not been mapped. OBJECTIVE: To determine whether the HMSN 2C phenotype, previously shown not to be linked to the HMSN 2A locus, is linked to the HMSN 2B or HMSN 2D loci. DESIGN: Linkage analysis. SETTING AND PATIENTS: Thirty-three subjects, including 12 affected individuals and 11 individuals at risk, in a large family with HMSN 2C. RESULTS: Evidence was found against linkage of HMSN 2C phenotype to either the HMSN 2B or the 2D loci. CONCLUSIONS: HMSN 2C is genetically distinct from HMSN 2A, 2B, and 2D. We think that at least 4 genetically distinct varieties of autosomal dominant HMSN 2 exist.

Alleles↗
PubMed2000

Natural history of 46 patients with multifocal motor neuropathy with conduction block.

We studied 46 consecutive patients with multifocal motor neuropathy with conduction block (MMN-CB). Typically, asymmetric weakness and atrophy of the hands or arms developed insidiously, but spontaneous improvement (without treatment) or death from this disease did not occur and 94% remained employed. For 18 patients examined on multiple occasions using the weakness subscore of the neuropathy impairment score [NIS(W)] for a median time of 2.3 years, worsening of 1.3 points per year was observed; many patients, however, had received intensive immunomodulating therapy. Median worsening to our first evaluation (generally without treatment) was estimated at 4.2 points per year, perhaps suggesting that treatment had influenced course. Three criteria for conduction block (CB) were compared, but the least stringent was sensitive for the diagnosis. Conduction block accompanied by weakness and atrophy typically affected only motor fibers, especially of midforearm nerves, and these sites of dysfunction persisted for months or years. Neurological signs and electrodiagnostic features were consistent with CB, axonal degeneration, a variable degree of reinnervation, and segmental demyelination. Although this study did not focus on therapy, intravenous gammaglobulin and cyclophosphamide appeared to be associated with neurological improvement, which was seldom complete or sustained. Axonal degeneration and faulty regeneration may in part explain this muted response. Possibly, treatment must be earlier, more intense, or different.

Action Potentials↗