Peripheral neuropathy in essential mixed cryoglobulinemia

Sixteen patients with essential mixed cryoglobulinemia were studied and followed up clinically and electrophysiologically for 4.2 years. Peripheral neuropathy was diagnosed in seven cases. Five of these patients had distal symmetrical sensorimotor polyneuropathy. Nerve conduction velocities were normal and therefore indicative of pure axonal neuropathy. Sural nerve biopsy showed moderate loss of myelinated axons in two patients and severe loss in one. This patient also had necrotizing arteritis. The remaining two had both clinical and electrophysiologic signs of overlapping mononeuritis multiplex with severe denervation in the territory of the involved nerves, but normal conduction velocities. Sural nerve biopsy in one of these two patients showed marked loss of myelinated fibers and signs of vasculitis. Two types of neuropathy were noted: (1) a mild distal neuropathy with relatively minor neurologic deficit, probably due to vasa nervorum microcirculation occlusion caused by intravascular deposits of cryoglobulins and (2) a severe distal symmetrical sensorimotor neuropathy or overlapping mononeuritis multiplex, associated with necrotizing vasculitis.     

Inherited early onset severe axonal polyneuropathy with respiratory failure and autonomic involvement

We report dizygotic twins who first presented at the age of 6 months with severe diaphragmatic weakness and marked abnormalities of autonomic function. A female sibling had earlier died from a disorder with similar clinical features. Both twins had a severe axonal polyneuropathy with generalized hypotonic limb weakness together with diaphragmatic paralysis resulting in respiratory failure. Associated features were tachycardia, increased sweating, elevated body temperature, and hypertension, suggesting autonomic dysfunction. Nerve conduction studies indicated an axonopathy affecting both motor and sensory nerve fibres. Sural nerve biopsy in one twin performed at the age of 7 months showed a reduced population of myelinated nerve fibres, particularly those of larger diameter, with no indication of hypomyelination, demyelination or axonal atrophy. Examples of axonal forms of hereditary motor and sensory neuropathy (HMSN) with onset in infancy are very rare and autonomic involvement associated with this condition has not so far been described.     

Peripheral neuropathy associated with mitochondrial myopathy

Twenty patients with mitochondrial myopathy were investigated for the presence of peripheral neuropathy. There were clinical features of a mild sensorimotor neuropathy in 5 patients (25%) and nerve conduction studies were abnormal in 10 patients (50%). Electrophysiological studies of the whole group showed significant impairment of motor and sensory conduction, compared with controls. Sural nerve biopsy and morphometric studies were performed on 4 patients with clinical neuropathy. There was a reduction in density of myelinated fibers and electron microscope features of axonal degeneration affecting myelinated and unmyelinated fibers. Abnormal mitochondria containing paracrystalline inclusions were seen in the Schwann cell cytoplasm of two nerves.     

Peripheral neuropathy associated with chronic natural killer cell lymphocytosis

We report a patient with steroid-responsive peripheral neuropathy which developed with chronic natural killer cell lymphocytosis (CNKL). A 70-year-old female with a 2-week history of progressive motor and sensory neuropathy showed a marked increase of natural killer (NK) cells in the blood, and was diagnosed as having CNKL. Nerve conduction studies (NCS) revealed a mixed axonal and demyelinating neuropathy. A sural nerve biopsy revealed infiltration of NK cells into the nerve fascicles, and demyelinating changes with axonal degeneration. The infiltrating NK cells were adjacent to myelinated fibers, showing damage of Schwann cell membrane. Treatment with oral prednisolone resulted in rapid improvement of the sensory disturbance and weakness with a significant decrease of NK cells in the blood and disappearance of the conduction blocks in NCS. This is the first case of CNKL associated neuropathy in which infiltration of NK cells was demonstrated in the nerve fascicles. Our observations suggest that the infiltrating NK cells may directly damage myelin and Schwann cells, thus causing demyelination.     

Chronic inorganic mercury induced peripheral neuropathy

We report the clinical features, electrophysiological studies, and morphometric analysis of sural nerve pathology in a patient with polyneuropathy due to inorganic mercury intoxication. He developed slowly progressive generalized paralysis of all limbs after 3 months ingestion of herb drugs which contained mercuric sulfate. Electrophysiologic studies revealed axonal polyneuropathy involving both motor and sensory fibers. Sural nerve biopsy demonstrated axonal degeneration with demyelination and a predominant loss of large myelinated fibers. His muscle strength showed only mild improvement after 2 years' follow-up. We concluded that inorganic mercury exposure may induce severe axonal sensorimotor polyneuropathy in humans and that neurological deficits may persist in severe cases.     

Rheumatoid neuropathy: a histological and electrophysiological study

Peripheral nerves in five patients with rheumatoid neuropathy were examined electrophysiologically and by sural nerve biopsy. There was close correlation between the clinical severity of the disease and the degree of nerve damage found histologically and by EMG. Group 1 patients with a mild distal sensory neuropathy showed varying degrees of axonal degeneration in the large myelinated fibres and some segmental demyelination. Group 2 patients with a severe, rapidly progressive sensori-motor neuropathy had extensive loss of myelinated fibres. In one case all the large fibres had degenerated. The second case had lost both large and small myelinated fibres together with many of the non-myelinated axons. The major nerve damage in both groups appeared to be axonal degeneration but some segmental demyelination was detected. Occlusive vascular disease in the vasa nervorum was considered to be the major cause of the nerve damage.     

Xeroderma pigmentosum: neurological, neurophysiological and morphological studies

In 3 cases of xeroderma pigmentosum showing signs of peripheral neuropathy, electrophysiological studies were made. In one of them, a sural nerve biopsy was performed. MCV obtained from the lower limbs were moderately reduced in all cases, and SCV could be obtained in only 1 case from the median nerve. Auditory brain stem responses were not obtainable in all cases. Sural nerve biopsy revealed a marked decrease of myelinated fibers and also suggested severe damage in both myelinated and unmyelinated fibers. Teased fiber study showed myelin ovoids and indicated axonal degeneration. Sensory nerves including the acoustic nerve may suffer damage earlier than the motor nerve. In all cases CT scans revealed brain atrophy and thickening of the skull.     

Giant axonal swelling in "huffer's" neuropathy.

A young man with a long history of "huffing" of lacquer thinner developed toxic peripheral neuropathy. Clinical improvement occurred several weeks after cessation of exposure. Substantial slowing in nerve conduction was noted. Sural nerve biopsy specimen showed (1) giant axonal swelling, (2) axonal degeneration, and (3) an increased paranodal gap. We believe that "huffer's" neuropathy is a primary axonal neuropathy with secondary demyelination.     

Neuropathy caused by cisplatin. Clinical, electrophysiological and morphological study

Seven patients with cancer presented a sensory peripheral neuropathy induced by cisplatinum. This drug was used alone in 1 case and, in 6 other cases it was associated with drugs without any toxicity for the peripheral nervous system. Every patient had an electromyogram and motor and sensory nerve conduction studies. A sural nerve biopsy was performed in 5 cases for light and electron microscopic studies as well as for teasing and quantitative studies. Electromyograms and motor nerve conductions were normal. Sensory nerve conductions were slowed with very low amplitude sensory action potentials. Such results suggested axonal changes. Nerve biopsies showed typical axonopathic changes with secondary demyelination. Morphometric studies confirmed a loss of myelinated fibers affecting the large fibers in all cases, according to the slowed sensory nerve conductions. This study confirmed that the cisplatinum-induced neuropathy is a new form of toxic distal axonal neuropathy. The hypothesis of a primary demyelination of peripheral nerves, which has been proposed, could not be retained.     

Acute presentation of Tangier polyneuropathy: a clinical and morphological study

Summary We describe a patient with Tangier disease and a peripheral neuropathy with an unusual acute onset. The morphological studies of sural nerve biopsy revealed both axonal degeneration and demyelination, and the fiber loss was preferentially restricted to two of ten nerve fascicles. The cytoplasm of Schwann cells, fibroblasts, macrophages and pericytes were vacuolated because of the presence of numerous lipid droplets. The clinical and morphological findings are consistent with the possibility that ischemia plays a major role in causing this neuropathy.Supported by grants from Istituto Scientifico S. Raffaele, Milan     

Hereditary motor and sensory neuropathy with optic atrophy. Ultrastructural and morphometric observations on nerve fibers, mitochondria, and dense-cored vesicles

Nerve biopsy specimens from three cases of hereditary motor and sensory neuropathy with optic atrophy were studied by light and electron microscopy and by morphometry. All cases had a chronic neuropathy of the neuronal/axonal type with little, presumably secondary, demyelination. There was predominant reduction of the large-caliber population of myelinated and unmyelinated nerve fibers. The number of dense-cored vesicles in unmyelinated and small myelinated fibers was increased. Abnormal mitochondria in Schwann cells with paracrystalline inclusions, prominent cristae including paracrystalline material (cases 1 and 2), and axonal mitochondria with presumable hydroxyapatite crystals (case 3) were found. The morphologic results suggest that hereditary motor and sensory neuropathy with optic atrophy should be regarded as a separate entity within the hereditary motor and sensory neuropathy group.     

Motor-sensory neuropathy without minifascicles in a patient with 46XY gonadal dysgenesis

We report a 36-year-old patient with 46XY pure gonadal dysgenesis (GD), who manifested a syndrome of progressive motor-sensory neuropathy. Sural nerve biopsy showed severe axonal neuropathy. Since reported cases of chronic motor-sensory neuropathy and pure gonadal dysgenesis have been characterized by nerve biopsy evidence of minifascicle formation, we suggest that this clinical association may be a new type of hereditary motor-sensory neuropathy, not necessarily associated with minifascicle formation.     

The clinical and pathological features of peripheral neuropathy accompanied with HTLV-I associated myelopathy

We describe the clinical and pathological studies in HTLV-I associated myelopathy (HAM)/tropical spastic paraparesis (TSP) patients with peripheral neuropathy as proven by sural nerve biopsy. Sural nerve pathology in HAM/TSP patients revealed that the most common type of pathologic change is a combination of both demyelination and remyelination and axonal degeneration and regeneration, and this change is modified by the complications. The pathologic changes were correlated with neither the duration of disease nor human T lymphotropic virus type I (HTLV-I) proviral load. This study suggests that peripheral nerves could be involved in HAM/TSP.     

Conduction block in vasculitic neuropathy

Vasculitis involving peripheral nerves usually presents as an acute asymmetrical axonal neuropathy. We report a 67-year-old man with a symmetrical subacute neuropathy in which nerve conduction studies showed prominent conduction block, a finding indicative of demyelination. Sural nerve biopsy showed a vasculitic neuropathy with invasion of blood vessel walls by inflammatory cells and a mixture of nerve fiber loss and demyelination. The demyelination in this case was presumably a consequence of subinfarctive nerve ischemia. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:1084–1088, 1998.     

Relapsing ophthalmoparesis-sensory neuropathy syndrome

We studied two patients with recurrent sensory neuropathy and weakness of extraocular muscles. There was electrophysiologic evidence of multifocal demyelination of sensory nerves, with relative sparing of somatic motor nerves. Sural nerve biopsy in one patient showed segmental demyelination. We believe that these patients had an unusual form of inflammatory polyneuropathy--possibly a relapsing variant of the Miller-Fisher syndrome of acute idiopathic polyneuritis.     

Tangier disease. A case with sensorimotor distal polyneuropathy and lipid accumulation in striated muscle and vasa nervorum

Summary A 65-year-old man with Tangier disease (analphalipoproteinemia) had had a progressive sensorimotor distal neuropathy with sensory ataxia for 1 year. Muscle biopsy demonstrated excess lipid vacuoles on histochemical and electron-microscopic techniques. Sural nerve biopsy showed a marked loss of large fibers and an increase in small myelinated fibers, with presence of remyelinating fibers and clusters of regeneration; a few aspects of active demyelination and some onion-like formations were also present. Lipid accumulation chiefly affected the Schwann cells of unmyelinated fibers and, to a lesser degree, of myelinated fibers, endoneurial fibroblast, and vasa nervorum. Teased fibers showed prevalent aspects of de-/remyelination and, often in association, marked myelin wrinkling suggesting axonal atrophy.This Tangier patient differs from known cases for the presence of a distal symmetrical sensorimotor polyneuropathy (not previously reported in Tangier disease) and because of the morphological findings of de-/remyelination coexisting with aspects of axonal atrophy and previous degeneration, and of lipid accumulation within striated muscle and vasa nervorum. This latter finding contrasts with the assumption that in Tangier disease vessel walls are not a site of lipid storage: probably the vasa nervorum are different, in this respect, from other vessels, because of the intense lipid metabolism of the nervous tissue. Thus we suggest that involvement of vasa nervorum in Tangier disease may be more important than previously suspected, possibly playing a role in the causation of neuropathy.     

Progressive centripetal degeneration in polyneuropathies (author's transl)

This is a clinicopathologic report on three patients with sensory polyneuropathies of different origin. Sensory loss involved all four limbs reaching the upper third of the thighs and the elbow level or higher, in all three patients. In addition to the limbs the central region of the anterior aspect of the trunk, from lower abdomen up to level T2, and on the top of the scalp were involved. There was minimal weakness. This pattern of sensory deficit can best be explained by a length dependent degeneration of fibers. Familial amyloidosis, Portugese type, was responsible for the neuropathy in the first patient, diabetes mellitus in the second and alcoholism in the third one. On teased nerve fiber study, single regenerating fibers were isolated on sural nerve biopsy specimens from patients 1 and 2. Segmental demyelination and/or remyelination occurred in 11 per cent of the fibres in patient 1, in 36 per cent in patient 2 and in 4 of the 19 fibres isolated in patient 3. On cross sections of nerve specimens embedded in Epon there was a striking loss of myelinated fibres which was less important and predominated on smaller fibres in patients 1 and 2. On electron microscopic examination loss of unmyelinated fibres was conspicuous in all three patients. On single fiber studies as well as on sections of embedded specimens, myelinated fibres occasionally showed demyelination in contact to amyloid deposits. The present study demonstrates that in this pattern of neuropathy degeneration of myelinated fibers begins in the distal part of longest axons and may be associated with axonal sprouting in more proximal parts of degenerating axons. As the neuropathy progresses axons of shorter and shorter length become involved.     

Familial multiple symmetric lipomatosis with peripheral neuropathy

We describe coexisting peripheral neuropathy and multiple symmetric lipomatosis in 4 of 7 siblings. The absence of either condition in 3 other generations of this family suggests autosomal recessive inheritance. None of the affected siblings were alcoholic, a factor some have proposed to explain the frequent occurrence of peripheral neuropathy in sporadic multiple symmetric lipomatosis. Serum lipid studies, including apoprotein A levels, were normal. Sural nerve biopsy from 1 patient showed nerve fiber loss, predominantly affecting large myelinated fibers. The relationship between myelin sheath thickness and axon diameter was normal, arguing that this neuropathy is not due to primary axonal atrophy.     

Severe axonal polyneuropathy with onset in the postpartum period

We report two patients who presented severe polyneuropathy in the postpartum period. Electrophysiological studies evidenced an axonal process which was associated with proximal demyelination in the second patient. In both cases, a peripheral nerve biopsy showed severe axonal Wallerian-like degeneration and no feature of demyelination. The first patient had a dramatic loss of myelinated fibres, and severe disability persisted for several months. These two patients are different from cases of acute or chronic inflammatory demyelinating polyradiculoneuropathy previously reported in relation with pregnancy.     

Giant axonal neuropathy: report on a case with focal fiber loss

Summary We report on a 5 1/2 year-old boy with chronic progressive polynèuropathy, ataxia, and pyramidal signs. His hair was not curled. Sural nerve biopsy disclosed many axons enlarged by accumulation of 10-nm neurofilaments and a marked variability in the number of myelinated fibers as well as in the amount of axonal enlargements among different fascicles. These findings and the electrophysiological data were consistent with a giant axonal polyneuropathy with a multifocal fiber loss.