Satyan M Rajbhandari

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

Aims/hypothesisThe early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy.MethodsTwelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7±0.6 years later.ResultsAt baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p<0.001), segmental demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration. Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell hyperplasia (p<0.004) and a reduction in luminal area (p<0.007).Conclusions/interpretationThe early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.

Charcot neuroarthropathy in diabetes mellitus.

Abstract. Charcot neuroarthropathy has been recognised for over 130 years and yet it remains a major cause of morbidity for patients with diabetes mellitus and a continuing challenge for physicians. It is rare but it seems to be increasing in prevalence and this provides hope that with larger studies it will soon be possible to clarify the natural history and optimal treatment regimens. The underlying cause is thought to be trauma in a neuropathic foot that leads to a complex series of pathological processes culminating in bone and joint destruction and subsequent deformity. The acute reaction is often misdiagnosed and many patients present late with established deformity. Even when the diagnosis is considered at an early stage there are no definitive criteria or tests to confirm charcot neuroarthropathy and a high index of suspicion is necessary in any diabetic patient with a swollen warm foot in the presence of somatic or autonomic neuropathy. Treatment has traditionally involved the use of various methods to avoid weight bearing but recent work has begun to suggest that bisphosphonates might be able to arrest the acute process. In the long term, treatment involves a multidisciplinary approach aimed at providing appropriate footwear to reduce plantar pressures and avoid foot ulceration; in some circumstances this involves surgical correction of deformities before adequate footwear can be supplied. Further studies of the emerging treatments for Charcot neuroarthropathy are needed to provide long-term outcome data on morbidity and deformity.

Spinal-cord involvement in diabetic peripheral neuropathy

The pathogenesis of diabetic distal symmetrical polyneuropathy (DSP) is poorly understood but there is some evidence that the disease process might extend beyond peripheral nerves. We used magnetic-resonance imaging to measure spinal-cord cross-sectional area in diabetic patients with and without DSP and in healthy controls. There were significant differences in cord area between the groups at C4/5 and T3/4 (p=0.004 and p=0.033, respectively), with a smaller cord area in those with DSP compared with controls (p=0.001 and p=0.016 for C4/5 and T3/4, respectively). These results indicate that DSP is not simply a disease of the peripheral nerve and that there is substantial involvement of the spinal cord.

'Sausage toe': a reliable sign of underlying osteomyelitis.

Aims To follow‐up patients with a ‘sausage’ deformity of the toe associated with local neuropathic ulceration to confirm the diagnosis of underlying osteomyelitis. This was based on our observation that some diabetic patients with suspected pedal osteomyelitis with a local neuropathic ulcer have a ‘sausage’ deformity of a toe.

Digital imaging: an accurate and easy method of measuring foot ulcers.

Aims A progressive reduction in the area of foot ulcer on serial measurement is traditionally done by tracing the margin of the ulcer on a transparent film and counting the number of squares on a graph paper underneath. We set out to use and validate the measurement of foot ulcers using a digital imaging technique and compare this with the traditional method.

A new minimally invasive technique to show nerve ischaemia in diabetic neuropathy.

Aims/hypothesis. Experimental studies have shown that abnormalities of nerve microcirculation are important factors in the pathogenesis of diabetic neuropathy but there have been few clinical studies. We have applied microlightguide spectrophotometry to measure intravascular oxygen saturation (HbO2%) and blood flow in human sural nerve. Methods. We studied ten patients with mild-moderate sensory motor diabetic neuropathy, nine patients without neuropathy and nine control subjects. We took 300 measurements of oxygen saturation under direct visual control through a 1.9 mm rigid endoscope over three regions of the nerve. Spectrophotometric measurements of nerve fluorescence were taken after an intravenous injection of sodium fluorescein and the rate of increase in nerve fluorescence (rise time) was used as an indicator of nerve blood flow. Results. Nerve oxygen saturation was reduced in patients with neuropathy compared with control subjects (67.1 ± 2.2 % vs 76.7 ± 2.1 %, p = 0.006). Fluorescein rise time was prolonged in patients with neuropathy compared with the control group (48.5 ± 7.0 s vs 14.0 ± 3.1 s, p = 0.001) suggesting impaired nerve blood flow. There was a correlation between rise time, nerve oxygen saturation, glycaemic control and sural nerve sensory conduction velocity (p < 0.01). Conclusion/interpretation. The combination of microlight-guide spectrophotometry and micro-endoscopy provides a valuable minimally invasive technique for clinical investigation of nerve microcirculation. We have shown reduced nerve oxygenation and impaired blood flow in diabetic neuropathy and these findings strongly support a central role of microvascular disease in the pathogenesis of diabetic neuropathy. [Diabetologia (1999) 42: 737–742]

Unusual infections in diabetes

Infection with rare organisms or at unusual sites occur more frequently in people with diabetes. If not recognised and treated promptly, morbidity and mortality are high in such cases. Here we report cases of necrotising fascitis, malignant otitis externa, Fourniers gangrene and psoas abscess occurring in diabetics that needed intensive treatment with antibiotics, surgical debridement and insulin. Literature reviews suggest that cellular defence mechanisms may be impaired in people with diabetes.

Central pontine myelinolysis and ataxia: an unusual manifestation of hypoglycaemia.

Hypoglycaemia is common in people with diabetes who aim to achieve good blood glucose control. Severe hypoglycaemia presents with evidence of neurological dysfunction, such as inability to concentrate, confusion, siezures, and coma. Such disturbances are reversible on correction of the hypoglycaemia. Infrequently there may be a focal neurological deficit and we report one such case presenting with cerebellar symptoms following an episode of severe hypoglycaemia. A magnetic resonance scan showed features consistent with the presence of central pontine myelinolysis. The symptoms resolved within a few months with only minimal residual neurological deficit.

Diabetic neuropathic pain in a leg amputated 44 years previously

The mechanism of neuropathic pain in the diabetic limb is far from clear. Phantom limb pain likewise is of obscure aetiology. The development of typical pain in an absent leg in a patient with diabetes many years after the amputation stimulates thought as to the mechanism, not only of neuropathic pain, but also of phantom limb pain. A 58-year-old man was diagnosed with type 2 diabetes 44 years after having undergone left below knee amputation for congenital AV malformation, at the age of 13. Eight months before the diagnosis of diabetes he began to complain of pain in the leg on the amputated side-pain very similar to that described in typical diabetic neuropathy. This was followed by similar pain in the right leg. MR scan of the spine revealed a small syringohydromyelia of the thoracic cord in addition to a prolapse of disc at L(5)/S(1) level on the left side, which was first noted 5 years previously. There were no other features of S(1) compression. The typical neuropathic character of the pain involving both the amputated and the intact limbs that developed with the diagnosis of type 2 diabetes suggest that the neuropathic pain may originate from centres higher than peripheral nerves.