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Clinical and Pathological Study of Ischaemic Neuropathy

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Clinical and Pathological Study of Ischaemic Neuropathy J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.30.3.215 on 1 June 1967. Downloaded from J. Neurol. Neurosurg. Psychiat., 1967, 30, 215 Clinical and pathological study of ischaemic neuropathy ROSEMARY A. EAMES AND L. S. LANGE From the Department ofAnatomy, St. Mary's Hospital Medical School, and the Department of Neurology, St. Mary's Hospital, Paddington, London For many years a number of workers have studied (Joffroy and Achard, 1889; Woltman and Wilder, the relation between arterial occlusion or com- 1929). Cottrell (1940) found occlusive changes pression in man, produced by various pathological present in the vasa nervorum of the aged. Detailed processes, and peripheral nerve abnormality. The examination of the smaller vessels has, however, whole subject was authoritatively reviewed by been neglected both by workers on nerve ischaemia Richards (1951). There is ample evidence, clinical, and by those studying arteriosclerosis. histological, and electrical, that ischaemia of a nerve It has been shown that there are two types of has an adverse effect upon it. Persisting nerve degenerative change that occur in nerve fibres: damage from ischaemia may be produced by arterial Wallerian degeneration and segmental demyelina- injury (Tinel, 1917; Holmes, Highet and Seddon, tion (Gombault, 1880; Vizoso and Young, 1948; 1944), by embolism (Blackwood, 1944; Haimovici, Thomas and Young, 1949; Vizoso, 1950; Lubin'ska, Protected by copyright. 1950), by chronic occlusive arterial disease (Joffroy 1958 and 1959). It is a common clinical experience and Achard, 1889; Priestley, 1931; Hutchinson and to find abolition of vibration sensitivity and Liversedge, 1956; Gairns, Garven, and Smith, 1960), diminution or loss of ankle jerks in the feet of the by polyarteritis nodosa (Kemohan and Woltman, aged (Pearson, 1928; Critchley, 1931). Lascelles and 1938), and by other, rarer, causes. Experimentally Thomas (1966) studied isolated nerve fibres from the ischaeiia has been produced in animal nerves by sural nerves of subjects of various ages, and found variou means (Adams 1943; Roberts, 1948) and degenerative changes present in those over the age electrical studies have been carried out on ischaemic of 65 years, segmental demyelination being the nerves (Bentley and Schlapp, 1943; Porter and predominant abnormality. They suggested a possible Wharton, 1949). Lewis, Pickering, and Rothschild relationship between these clinical findings and (1931) showed in their classical experiments that nerve changes and atheromatous occlusion of the changes may be produced in nerve function by vasa nervorum. ischaemia. The present investigation was designed to The histological changes described in the nerves determine the degree of neurological abnormality, have been fairly consistent and non-specific, and as assessed clinically, in the affected limbs of patients involve patchy degeneration in nerve fibres together with chronic occlusive arterial disease of the legs. http://jnnp.bmj.com/ with endoneurial fibrosis. However, many reports This was combined with a study of the pathological have not distinguished between changes occurring in changes in sensory nerves from the affected limbs, nerves after an acute ischaemic episode and those by both light and electron microscopy, with particular resulting from chronic longstanding ischaemia, and reference to the alterations in the vasa nervorum no attempt has been made to determine the type of and the detailed study of the nerve fibres themselves. degeneration in ischaemic nerve fibres by individual In of the earlier reports MATERIALS AND METHODS examination. addition, many on September 29, 2021 by guest. on nerves in arteriosclerotic limbs were from cases complicated by diabetes mellitus. Some of the studies CLINICAL SURVEY Thirty-two patients with clear clinical on but it has and arteriographic evidence of peripheral arterial disease also were carried out digital nerves, of the lower limbs were studied. Two patients were been shown (Gairns et al., 1960) that the digital suffering from Buerger's disease, with histories dating nerves even of healthy young subjects may reveal back 27 and 13 years respectively, and the other 30 damage due to repeated minor injuries. patients had arteriosclerotic obliterative disease. All were The state of the vasa nervorum in peripheral in-patients, admitted under the care of the Surgical Unit arteriosclerosis has been commented upon incident- for surgery (endarterectomy, sympathectomy, by-pass ally by a few authors while studying the nerves procedures, or amputation). Their ages ranged from 215 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.30.3.215 on 1 June 1967. Downloaded from 216 Rosemary A. Eames and L. S. Lange 43 to 71 years, 28 patients falling into the 50-to-70-year and exclusions were made on the same basis as for the range (Table I). Twenty-six patients were smokers, and, patients with vascular disease. with one exception, all were male. LIGHT AND ELECTRON MICROSCOPY Eight of the 32 patients with arterial disease had amputations at the TABLE I knee joint while in hospital. All eight were biopsied for AGES OF PATIENTS AND DURATION OF SYMPTOMS OF electron microscopy; five of these also had pieces of nerve PERIPHERAL ARTERIAL DISEASE taken for light microscopy. At operation a 2 in. incision Patient Duration ofSymptoms Age (years) was made 1 in. behind the lateral malleolus immediately (years) before the leg was amputated. A small piece of sural nerve was removed and divided into three portions. a solution of 4% 2 2 The larger piece was placed in 3 2 formaldehyde in 09% sodium chloride for four days. 4 27 It was then transferred to a solution of 1% osmium 5 washed in distilled water, and 6 tetroxide for 24 hours, 7 3 macerated in a solution of 2:1 glycerol and water for three 8 13 days. Individual fibres were teased out in pure glycerol 9 4 with mounted needles under a dissecting microscope and 10 3 11 1 transferred to a few drops of creosote on a slide. For 12 1 1 each case, the first 45 fibres covering the range of fibre 13 7 diameter were teased out, no effort being made to obtain 14 2 fibres. The nerve fibres were 15 10 particularly pathological 16 3 arranged in parallel rows, and, after draining off the 17 3 creosote, mounted in Canada balsam. 18 5 Internodal length and fibre diameter were measured 19 7 was 7 using a micrometer eyepiece; each diameter recorded 20 Protected by copyright. 21 1 the mean of five measurements made along the internode. 22 For each case, internodal lengths were plotted against 23 5 of the widest internode on a given fibre, and 24 l the diameter 25 7 the points joined bya vertical line, accordingto themethod 26 5 suggested by Fullerton, Gilliatt, Lascelles, and Morgan- 27 2 Hughes (1965). 28 4 The second piece of sural nerve obtained at amputation 29 1* 30 II was placed in Flemming's fixative for 24 hours and, after 31 2i washing and dehydration in alcohols, embedded in 32 3 paraffin wax. Transverse sections were cut at 5p and stained in Kulschitsky's stain for myelin by the method of Every effort was made to exclude patients with other Gutmann and Sanders (1943). possible causes of peripheral neuropathy or myelopathy, The smallest piece of nerve obtained was placed particularly diabetes, carcinoma, collagen diseases, a immediately in ice-cold 2% osmium tetroxide, buffered history of alcoholism or of neurotoxic drugs, vitamin at pH 7 4, for electron microscopy. Within 10 minutes of deficiencies, and lumbar disc prolapse. In addition being placed in the fixative, the nerve was teased into patients with a recent cerebrovascular accident or a individual fascicles with a sharp scalpel blade. After family history of neurological disease were excluded. two to three hours of fixation, the pieces were placed in http://jnnp.bmj.com/ Apart from exclusions on those grounds no selection 70% alcohol for 12 hours, dehydrated in absolute alcohol, was made. and embedded in Araldite. A few fascicles from each case Each patient was carefully examined by one of us, were stained in bulk in 1 % phosphotungstic acid in 95% particular attention being paid to the peripheral nervous alcohol before dehydrating. system. Careful note was made of complaints of Sections were cut using a Cambridge ultramicrotome, paraesthesiae or leg weakness, and the sensory exam- mounted on unfilmed copper grids, and examined in a ination was made as objectively as possible, in most cases Siemens Elmiskop I. Sections from those blocks which the findings being confirmed on more than one occasion. had not been stained in bulk were treated with lead Gangrenous areas were excluded from sensory testing. hydroxide on the grid before examination. on September 29, 2021 by guest. Intermittent claudication was severe in all the patients, the least affected being able to walk a distance of up to RESULTS 200 yards before pain forced them to stop. Thirteen patients had gangrene of the toes or feet, and 16 patients CLINICAL FINDINGS Table II summarizes the had pain at rest. abnormalities found, and shows a correlation Twelve control patients were also examined. These were in a between the incidence of neurological abnormalities were in hospital for various reasons. They All with similar age range to the patients with arterial disease. and the severity of ischaemia. patients None had any evidence of ischaemia of the lower limbs, claudication distances of less than 100 yards showed J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.30.3.215 on 1 June 1967. Downloaded from Clinical andpathological study of ischaemic neuropathy 217 TABLE II some neurological abnormalities, which were severest SUMMARY OF CLINICAL FINDINGS in those who had pain at rest and claudication 20 or less. Patient Leg Pulses Sensory Ankle Motor distances of yards Present' Deficit2 Jerks3 Signs' The presence of palpable pulses distal to the femoral pulse in these patients was usually associated R F a + L F a with more minor degrees ofneurological abnormality, 2 R All a or none at all.
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