Chronic immune sensory polyradiculopathy: a possibly treatable sensory ataxia.

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.

Microvasculitis in non-diabetic lumbosacral radiculoplexus neuropathy (LSRPN): similarity to the diabetic variety (DLSRPN).

Diabetic lumbosacral radiculoplexus neuropathy (DLSRPN) has been shown to be due to ischemic injury from microvasculitis. The present study tests whether ischemic injury and microvasculitis are the pathologic cause of non-diabetic lumbosacral radiculoplexus neuropathy (LSRPN), and whether the pathologic alterations are different between LSRPN and DLSRPN. We studied distal cutaneous nerve biopsies of 47 patients with LSRPN and compared findings with those of 14 age-matched healthy controls and 33 DLSRPN patients. In both disease conditions, we found evidence of ischemic injury (multifocal fiber degeneration and loss, perineurial degeneration and scarring, characteristic fiber alterations, neovascularization, and injury neuroma) that we attribute to microvasculitis (mural and perivascular mononuclear inflammation of microvessels, inflammatory separation, fragmentation and destruction of mural smooth muscle, and previous microscopic bleeding [hemosiderin]). Teased nerve fibers in LSRPN showed significantly increased frequencies of axonal degeneration, segmental demyelination, and empty nerve strands. The segmental demyelination appeared to be clustered on fibers with axonal dystrophy. The nerves with abnormal frequencies of demyelination were significantly associated with nerves showing multifocal fiber loss. We reached the following conclusions: 1) LSRPN is a serious condition with much morbidity that mirrors DLSRPN. 2) Ischemic injury from microvasculitis appears to be the cause of LSRPN. 3) Axonal degeneration and segmental demyelination appear to be linked and due to ischemia. 4) The pathologic alterations in LSRPN and DLSRPN are indistinguishable, raising the question whether these 2 conditions have a common underlying mechanism, and whether diabetes mellitus contributes to the pathology or is a risk factor in DLSRPN. 5) Both LSRPN and DLSRPN are potentially treatable conditions.

No evidence for axonal atrophy in human diabetic polyneuropathy.

In rats with streptozin-induced diabetes mellitus, the caliber of distal myelinated fiber (MF) axons in relation to the number of myelin lamellae is smaller than in controls. This finding usually has been attributed to axonal atrophy, but shrinkage or maldevelopment has also been considered. For human diabetic polyneuropathy (DP), axonal atrophy has been assumed by some investigators, but convincing evidence has not been demonstrated. We morphometrically evaluated transverse sections of 33 sural nerves from carefully evaluated diabetic patients > or = 30 years old without (8 patients) or with (25 patients) DP and compared them with 24 nerves from healthy subjects > or = 30 years old. Nerves from diabetic patients and controls were obtained under identical conditions and processed and evaluated in the same way, using an observer blind to the disease condition. Using computer digitization of electron micrographs, we evaluated the axonal area, perimeter, index of circularity, number of myelin lamellae, and frequency of adaxonal sequestration of 50.4 (mean) +/- 5.8 (SD) MF per sural nerve for healthy subjects and diabetic patients > or = 30 years old. The regression lines of the natural log (In) of axonal area on number of myelin lamellae of diabetic patients (with or without DP) were not significantly different from the regression lines of nerves of healthy subjects for large MFs-the most reliable group in which to recognize atrophy. Likewise, the regression lines of index of circularity (IC) (an index that is decreased with atrophy or shrinkage) on number of myelin lamellae for large fibers was not significantly different between the disease and control groups. The rate of adaxonal sequestration was not significantly higher in DP than in healthy subjects. These results do not support the hypothesis that axonal atrophy occurs in human DP. For small MF, or all MF, some significant differences in regression lines of In axonal area or IC on number of lamellae were found, but these changes are probably explained by events of remyelination and axonal regeneration, which can affect these relationships and are known to occur in DP.

[Alcohol--no universal drug against heart disease]. / Alkohol--ingen universalmedisin mot hjertesykdom.

Alcohol is part of the normal culture for a majority of the population in western countries. Few investigators or clinicians disagree with the contention that there is a positive relationship between cardiovascular disease and mortality in the upper part of the alcohol consumption curve. No such general agreement exists when infrequent users and non-users are studied. Epidemiological evidence of the relationship between cardiovascular mortality and levels of alcohol consumption is scrutinized, with emphasis on how alcohol anamnestic data are collected, the characterization of non-users, and the authors' definition of moderate consumers. The results indicate that there is hardly any evidence to advocate moderate consumption of alcohol as a health-promoting activity. On the other hand there seems to be a positive relationship between moderation in many aspects of lifestyle and some health gain.

Neuropathologic and morphometric effects of aminoguanidine on rat nerves.

Aminoguanidine prevents some pathophysiologic changes typical of streptozocin diabetes and, therefore, might be efficacious in prevention or treatment of human diabetic polyneuropathy. In order to evaluate the possible toxicity of aminoguanidine on peripheral nerves, Sprague-Dawley rats received aminoguanidine intraperitoneally in dosages of 0, 50, 100, and 300 mg/kg per day for 3 months. Only rats receiving the highest dosages developed acute and chronic behavioral changes and had decreased weight gain. Minor hepatic dysfunction also was observed in this group. Teased-fiber abnormalities were not significantly more frequent in the highest dosage group than in controls. Likewise, a significant morphometric abnormality was not found for the peroneal nerve. Mild changes were found in the highest dosage group compared to the control group in the sural nerve (increased fiber density, decreased myelin area). We interpret the small morphometric differences for the sural nerve as due to maldevelopment. We found no evidence that aminoguanidine at a high dosage (300 mg/kg per day) caused fiber degeneration or demyelination.

Structural alterations of nerve during cuff compression.

Whether compression nerve injury is due to ischemia, direct mechanical injury, or both remains unsettled. To assess structural changes of nerve during compression, peroneal nerves of rats were compressed at various pressures for different times, and the structural alterations were stopped by simultaneous in situ and perfusion fixation. The structural changes observed during a few minutes of compression cannot be explained by ischemic injury because the pathologic alterations characteristic of ischemia take many hours to develop and in any case are different from the ones found here. The pressure- and time-related structural changes observed in the present study under the cuff were (i) decrease in fascicular area and increase in fiber density due to expression of endoneurial fluid; (ii) compression and expression of axoplasm, sometimes to the point of fiber transection; (iii) lengthening of internodes; and (iv) obscuration of nodes of Ranvier due to cleavage and displacement of myelin and overlapping of nodes by displaced loops of myelin. At the edges of the cuff the changes were (i) increase of fascicular area probably from expressed endoneurial fluid; (ii) widening of nodal gaps, perhaps mainly from translocated axonal fluid; and (iii) disordered structure of axoplasm. We suggest that the process of paranodal demyelination and axonal transection are linked, occur during the act of compression, and are due to shear forces. The initial event is expression of endoneurial fluid, followed by compression and expression of axoplasm and cleavage and displacement of layers of myelin. Conceivably, with prolonged cuff compression ischemic injury might be found to be superimposed on mechanical injury.

Resistance to axonal degeneration after nerve compression in experimental diabetes.

To determine the effect of diabetes on the development of axonal degeneration after acute nerve compression, the mobilized peroneal nerves of rats with streptozotocin-induced diabetes and of control rats were compressed at 150 mmHg (1 mmHg = 133 Pa) for 30 min by using specially devised cuffs. At three intervals after compression--3 days, rats diabetic for 31 wk; 14 days, diabetic for 6 wk; and 24 days, diabetic for 31 wk--groups of nerves were studied to assess numbers and sizes of fibers above, at, and below the cuff and to assess frequency of fiber degeneration in teased fibers from nerve distal to the cuff. Teased fibers with pathologic abnormalities were more frequent in nerves from controls than in nerves from diabetic rats in all three groups but the difference was statistically significant only at 3 and 14 days after compression. The lack of significant difference at 24 days may be explained by higher rates of disappearance of degenerating products and of fiber regeneration at 24 than at 3 and 14 days. This study provides evidence that in addition to delaying the reported functional deficit of vibratory detection threshold and conduction block during nerve compression, diabetes also may partially prevent axonal injury. Low nerve myo-inositol concentration did not predispose diabetic nerve to acute compression injury. If these results also apply to human diabetes and if repeated acute compression is involved in the genesis of fiber degeneration in entrapment, then a higher frequency of entrapment neuropathy among diabetics might be due to mechanisms other than increased susceptibility of fibers to acute compression--e.g., possibly to greater constriction of nerve due to pathologic alterations of the carpal ligament.

The spatial distribution of fiber loss in diabetic polyneuropathy suggests ischemia.

Characterization and quantitation of the spatial distribution of pathological abnormalities along the length of nerves may be helpful in understanding the underlying mechanisms of diabetic polyneuropathy. To this end, by examining transverse sections of nerve roots and proximal-to-distal levels of lower limb nerves in 9 controls and 15 diabetic patients with polyneuropathy, we have determined the myelinated fiber (MF) number, size distribution, median diameter, and variability of density (MFs/mm2) among frames and among fascicles. Even in cases with mild polyneuropathy, fiber loss, a decrease in the median diameter, and an increase in the variability of density among frames and among fascicles began in proximal nerve and extended to distal levels. Multifocal fiber loss along the length of nerves and sprouting provide the best explanation for these findings. The pattern is dissimilar from that observed in diffuse metabolic disease of Schwann cells, neuronal degeneration, and dying-back neuropathy, but like that found in experimental ischemic neuropathy induced by embolization of nerve capillaries.