A review on the investigation of peripheral neuropathy at Mater Dei Hospital

The term peripheral neuropathy encompasses a wide range of disorders. The underlying causes of peripheral neuropathy are diverse. It is very difficult to ascertain the incidence of peripheral neuropathy with any degree of certainty, but it is a manifestation of several common multisystem disorders, whose incidence is on the rise, such as diabetes and Human Immunodeficiency (HIV) virus infection. Worldwide, the population prevalence is about 2,400 per 100,000 (2.4%), rising with age to 8,000 per 100,000 (8%).1 Peripheral neuropathy can significantly impact an individual's quality of life especially if undiagnosed and untreated. Investigation of peripheral neuropathy is expensive and time consuming, and is best performed in a stepwise approach. Even in the best of circumstances, an aetiological diagnosis is not always achieved. At present, the existing guidelines deal with the treatment of peripheral neuropathy but there are none on how patients with peripheral neuropathy should be investigated.peer-reviewe

Vascular risk factors and diabetic neuropathy

Background: Other than glycemic control, there are no treatments for diabetic neuropathy. Thus, identifying potentially modifiable risk factors for neuropathy is crucial. We studied risk factors for the development of distal symmetric neuropathy in 1172 patients with type 1 diabetes mellitus from 31 centers participating in the European Diabetes (EURODIAB) Prospective Complications Study. Methods: Neuropathy was assessed at baseline (1989 to 1991) and at follow-up (1997 to 1999), with a mean (±SD) follow-up of 7.3±0.6 years. A standardized protocol included clinical evaluation, quantitative sensory testing, and autonomic-function tests. Serum lipids and lipoproteins, glycosylated hemoglobin, and the urinary albumin excretion rate were measured in a central laboratory. Results: At follow-up, neuropathy had developed in 276 of 1172 patients without neuropathy at baseline (23.5 percent). The cumulative incidence of neuropathy was related to the glycosylated hemoglobin value and the duration of diabetes. After adjustment for these factors, we found that higher levels of total and low-density lipoprotein cholesterol and triglycerides, a higher body-mass index, higher von Willebrand factor levels and urinary albumin excretion rate, hypertension, and smoking were all significantly associated with the cumulative incidence of neuropathy. After adjustment for other risk factors and diabetic complications, we found that duration of diabetes, current glycosylated hemoglobin value, change in glycosylated hemoglobin value during the follow-up period, body-mass index, and smoking remained independently associated with the incidence of neuropathy. Cardiovascular disease at baseline was associated with double the risk of neuropathy, independent of cardiovascular risk factors. Conclusions: This prospective study indicates that, apart from glycemic control, the incidence of neuropathy is associated with potentially modifiable cardiovascular risk factors, including a raised triglyceride level, body-mass index, smoking, and hypertension

Vascular risk factors and diabetic neuropathy

Background: Other than glycemic control, there are no treatments for diabetic neuropathy. Thus, identifying potentially modifiable risk factors for neuropathy is crucial. We studied risk factors for the development of distal symmetric neuropathy in 1172 patients with type 1 diabetes mellitus from 31 centers participating in the European Diabetes (EURODIAB) Prospective Complications Study. Methods: Neuropathy was assessed at baseline (1989 to 1991) and at follow-up (1997 to 1999), with a mean (±SD) follow-up of 7.3±0.6 years. A standardized protocol included clinical evaluation, quantitative sensory testing, and autonomic-function tests. Serum lipids and lipoproteins, glycosylated hemoglobin, and the urinary albumin excretion rate were measured in a central laboratory. Results: At follow-up, neuropathy had developed in 276 of 1172 patients without neuropathy at baseline (23.5 percent). The cumulative incidence of neuropathy was related to the glycosylated hemoglobin value and the duration of diabetes. After adjustment for these factors, we found that higher levels of total and low-density lipoprotein cholesterol and triglycerides, a higher body-mass index, higher von Willebrand factor levels and urinary albumin excretion rate, hypertension, and smoking were all significantly associated with the cumulative incidence of neuropathy. After adjustment for other risk factors and diabetic complications, we found that duration of diabetes, current glycosylated hemoglobin value, change in glycosylated hemoglobin value during the follow-up period, body-mass index, and smoking remained independently associated with the incidence of neuropathy. Cardiovascular disease at baseline was associated with double the risk of neuropathy, independent of cardiovascular risk factors. Conclusions: This prospective study indicates that, apart from glycemic control, the incidence of neuropathy is associated with potentially modifiable cardiovascular risk factors, including a raised triglyceride level, body-mass index, smoking, and hypertension

Cardiovascular autonomic neuropathy among non- insulin dependent diabetics patients

Background and Objective: Cardiovascular autonomic neuropathy (CAN) is the most common and important type of diabetic autonomic neuropathy. Silent myocardial infarction, respiratory failure and increased mortality are the outcomes of CAN. This study was carried out to screen the cardiovascular autonomic neuropathy in non- insulin dependent diabetics patients. Method: This descriptive - analytic study was carried on 70 (22 males, 48 females) non- insulin dependent diabetics’ patients. Resting heart rate, heart rate variability, orthostatic changes in heart rate, blood pressure and corrected QT interval were recorded for each subject. The final findings were categorized as follow: 0=normal, 1=borderline and 2=CAN positive. Results: 10 (14.3%) of patients were normal, 35 (50%) of patients were borderline and 25 (35.7%) of patients were considered cardiovascular autonomic neuropathy positive. There was significant differences between duration of diabetes and three CAN scores (P<0.05). The systolic blood pressure alterations showed the maximum correlation with CAN scores (r=0.509). Conclusion: In our study, the rate of cardiovascular autonomic neuropathy was higher than other reports. The most important risk factor for cardiovascular autonomic neuropathy was more than 10 years history of diabetes mellitus. Keywords: Diabetes mellitus, Cardiovascular autonomic neuropathy, Hypertensio

Sciatic neuropathy with preserved sensory nerve action potentials, a case series

Background: Sciatic neuropathy is differentiated from lumbosacral radiculopathy based on the finding of abnormal sensory nerve action potentials (SNAPs). Cases of sciatic neuropathy with intact SNAPS have not been well described. Methods: A retrospective analysis of 12 patients with sciatic neuropathy in a single institution. Results: We describe 12 patients in whom a sciatic neuropathy was diagnosed based on a combination of history, physical exam, radiological and electrodiagnostic (EDX) findings. Lower extremity SNAPs were found to be within normal range in all patients, although SNAP amplitude asymmetry between both sides was observed in 3. Included patients were young (mean age of 40.3 years) and mostly female (9 patients). Conclusions: Sciatic neuropathy may occur with a relative sparing of sensory fibers. Recognition of this group of patients should help to avoid making a misdiagnosis of lumbosacral radiculopathy

Severe acute axonal neuropathy following treatment with arsenic trioxide for acute promyelocytic leukemia: a case report

Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide

Neuropathy - gait changes in the diabetic foot

Motor neuropathy in patients with diabetes can lead to weakness in the muscles of the foot and lower leg, which in turn can lead to characteristic changes to the structure of the foot, such as an altered arch profile. Such structural changes often occur at sites of abnormally high pressure, which can result in tissue breakdown and ulceration particularly in individuals who also have sensory neuropathy

CEDNIK: Phenotypic and molecular characterization of an additional patient and review of the literature

Synaptosomal-associated protein 29 (SNAP29) is a t-SNARE protein that is implicated in intracellular vesicle fusion. Mutations in the SNAP29 gene have been associated with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome (CEDNIK). In patients with 22q11.2 deletion syndrome, mutations in SNAP29 on the nondeleted chromosome are linked to similar ichthyotic and neurological phenotypes. Here, the authors report a patient with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome who presented with global developmental delay, polymicrogyria, dysgenesis of the corpus callosum, optic nerve dysplasia, gaze apraxia, and dysmorphic features. He has developed ichthyosis and palmoplantar keratoderma as he has grown. Exome sequencing identified a homozygous nonsense mutation in SNAP29 gene designated as c.85C>T (p.Arg29X). The authors compare the findings in the proband with previously reported cases. The previously unreported mutation in this patient and his phenotype add to the characterization of cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome and the accumulating scientific evidence that implicates synaptic protein dysfunction in various neuroectodermal conditions

Progressive auditory neuropathy in patients with Leber's hereditary optic neuropathy

Objective: To investigate auditory neural involvement in patients with Leber's hereditary optic neuropathy (LHON).Methods: Auditory assessment was undertaken in two patients with LHON. One was a 45 year old woman with Harding disease (multiple-sclerosis-like illness and positive 11778mtDNA mutation) and mild auditory symptoms, whose auditory function was monitored over five years. The other was a 59 year old man with positive 11778mtDNA mutation, who presented with a long standing progressive bilateral hearing loss, moderate on one side and severe to profound on the other. Standard pure tone audiometry, tympanometry, stapedial reflex threshold measurements, stapedial reflex decay, otoacoustic emissions with olivo-cochlear suppression, auditory brain stem responses, and vestibular function tests were undertaken.Results: Both patients had good cochlear function, as judged by otoacoustic emissions ( intact outer hair cells) and normal stapedial reflexes ( intact inner hair cells). A brain stem lesion was excluded by negative findings on imaging, recordable stapedial reflex thresholds, and, in one of the patients, olivocochlear suppression of otoacoustic emissions. The deterioration of auditory function implied a progressive course in both cases. Vestibular function was unaffected.Conclusions: The findings are consistent with auditory neuropathy - a lesion of the cochlear nerve presenting with abnormal auditory brain stem responses and with normal inner hair cells and the cochlear nucleus (lower brain stem). The association of auditory neuropathy, or any other auditory dysfunction, with LHON has not been recognised previously. Further studies are necessary to establish whether this is a consistent finding

An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed

Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population