Mitochondrial paracrystalline inclusions in the peroneus brevis muscle of patients with peripheral neuropathy.

In a series of 50 consecutive biopsies of peroneus brevis muscle (PBm) taken from patients with ascertained or suspected polyneuropathy in the course of sural nerve biopsy, we found a high incidence (26%) of intramitochondrial paracrystalline inclusions (MPI). Five out of these 13 patients were also submitted to an additional biopsy of a proximal muscle, which in no case confirmed the finding of MPI. Six out of the 13 patients with MPI were affected by diseases with a presumably important ischemic component. The mean age of patients with MPI was quite elevated (60.7), and the difference in distribution of age between patients with and without MPI was statistically significant. No significant difference in histochemical changes was found between the group of MPI patients and a control group of age-matched patients without MPI, thus excluding that MPI in the PBm are specifically associated with other neurogenic or myopathic aspects. We conclude that aging and, probably, ischemia are largely responsible for the frequent presence of MPI in the PBm. In addition, factors intrinsic to the muscle itself, possibly related to morphological, physiological, or biochemical peculiarities, may also influence the development of MPI.

Abnormal muscle mitochondria in ischemic claudication.

The gastrocnemius and quadriceps muscles findings in 18 patients with chronic arterial insufficiency were reviewed with regard to mitochondrial changes. Prominent mitochondrial alterations were present in eight out of 18 patients. The comparison of clinical data between patients with and without mitochondrial changes revealed that in this latter group all patients were at stage IV, whereas the degree of ischemic disease was milder in the other group: the difference in distribution of patients at stage IV between the two groups was statistically significant. This supports the view that mitochondrial changes are expression of adaptive modification rather than damage.

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

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.

Skeletal muscle and peripheral nerve changes caused by chronic arterial insufficiency--significance and clinical correlations--histological, histochemical and ultrastructural study.

A histological, histochemical and ultrastructural study on muscle changes in chronic arterial insufficiency has been carried out in 40 patients. Muscle biopsy probes were taken in each patient either from the gastrocnemius or rectus femoris. In 7 patients submitted for amputation of a lower limb due to a more severe vascular disease, specimens were also obtained from both the sciatic and sural nerve for light and electron microscopic study. Our findings confirm the previous histological, histochemical and ultrastructural data on chronic ischemia of the skeletal muscle, suggesting that muscle damage is mainly based on a neurogenic noxa initiated by an ischemic peripheral neuropathy. In addition, many morphologic features also show the presence of a primary myopathic noxa, possibly depending on the direct damage of the mitochondrial respiratory chain by the deficit of the muscle blood supply.

Pathological study of the sural nerve in Fabry's disease.

A man with Fabry's disease, who died at 52, suffered from lancinating limb pains between the age of 20 and 27, and from severe arthralgia between 20 and 40. The sural nerve showed a severe loss of fibers (1,614 myelinated fibers/mm2), chiefly affecting the small myelinated fibers. Inclusions of both homogeneous and lamellated appearance were present in the perineurial cells, fibroblasts and vessel walls. Teased fibers displayed moderate remyelination, regeneration and the presence of globular focal myelin thickening. The transient time course of painful manifestations in this case is stressed in view of a possible pathogenesis of pain in Fabry's disease. It appears that small-fiber neuropathy is not directly related to the occurrence of pain symptoms, since the prevalent loss of small myelinated fibers was seen in the absence of actual pain. The small sensory neurons in the dorsal root ganglia, that are especially affected by lipid accumulation, probably give rise to abnormal discharges producing pain via the prevalence of the small-fiber versus the large-fiber input to the dorsal horn of the spinal cord (gate control theory). Thus pain fits may spontaneously abate, as in our case, if degeneration and loss of the small sensory neurons overstep a critical level.

Immunological abnormalities in a family with progressive external ophthalmoplegia.

The authors report the muscular and humoral immunological abnormalities found in a family with progressive external ophthalmoplegia (PEO) of the "pure" form. Serum circulating immune complexes as determined by the polyethylen glycol (PEG) test and double radial immunodiffusion (DRID) were positive for IgG in both cases studied and for IgM and Clq for the propositus. In the latter circulating auto-antibodies against smooth muscle were also present. Immunohistochemical studies on striated muscle of the propositus showed positive perivascular IgG and IgM staining and IgG in the sarcolemma basement membrane complex. It is suggested that in this family a genetically inherited abnormal immune response to the muscular blood vessel wall has induced vascular injury and ultimately chronic ischemic muscular damage. This is consistent with the view that PEO is a clinical syndrome, i.e. the expression of various defects affecting primarily or secondarily the energy metabolism of the muscular tissue.

Localized nodular myositis and the diagnosis of the localized muscle mass.

Localized nodular myositis (LNM) is a rare variant of polymyositis beginning with inflammatory nodules within muscles. Only seven cases have so far been reported in the literature. We describe a probable further case of LNM in a 67-year-old man with ischemic claudication of the left leg for three years who presented with painful nodules in the left gastrocnemius muscle and signs of systemic disease; a complete follow-up was not possible, because the patient died after only two months and autopsy was not performed. Muscle biopsy showed localized areas of necrotic and inflammatory pleomorphic changes, in keeping with the features of the other known cases. The ultrastructural findings (not previously reported in this disease) were characterized by marked changes of endomysial capillaries, with fibroblastic metamorphosis of the endothelial cells, and by the presence of filamentous inclusions in the myonuclei. The differential diagnosis of LNM from other localized muscle masses, chiefly from muscle infarct, is discussed.

Ultrastructural findings of uraemic muscular damage: functional implications.

The ultrastructure (US) of the skeletal muscle from 10 patients on conservative treatment (PCT) and 10 haemodialysed patients (HP) was studied. The two groups exhibited no qualitative differences but quantitative alterations of the mitochondrial apparatus and capillary vessels were more impressive in the HP group. Disarray and loss of the myofibrillar sarcoplasm was the most obvious change in the uraemic muscle. The US findings are consistent with a neurogenic atrophy of the uraemic skeletal muscle but other features indicate a primary myopathic damage probably caused by a deficit of muscle microcirculation and by changes in the mitochondrial respiratory chain.

[Histopathologic and ultrastructural study of various amputation neuromas]. / Studio istopatologico ed ultrastrutturale in alcuni neuromi da amputazione.

The results of a light and electron microscopy study of seven amputation neuromas are presented. The neuromas were removed during surgery for traumatic lesions of limbs. The histological study showed a complete disappearance of the nerve architecture at the neuroma level, where the fibres are collected in small bundles, enveloped in an abnormal perineural sheath, surrounded by an overgrowing connective tissue. In two cases a partial and incomplete reinnervation of the distal stump was found. The ultrastructural study shows abnormalities of the nervous fibers, both of the axon and of the relationships between the axonal part and the Schwann cell. The results of our data in man are compared to nerve regeneration patterns recently investigated in experimental models.

Polyneuropathy in progressive external ophthalmoplegia.

A case of progressive external ophthalmoplegia (PEO) in association with peripheral neuropathy and other neural and visceral manifestations is reported. Pathological studies of the sural nerve demonstrated loss of large myelinated fibers, segmental demyelination with remyelination, and excess of zebra bodies in the Schwann cells on electron microscopy. Peripheral neuropathy in the course of PEO is regarded as a further although rare aspect of a multisystem disease.