Diffuse axonal injury without direct head trauma and with delayed onset of coma.

A 16-year-old female was involved in a jet ski (water craft) accident resulting in bilateral lower extremity fractures but no loss of consciousness or any other evidence of head trauma. Thirty hours later she became comatose. Magnetic resonance imaging was consistent with diffuse axonal injury. She recovered after several weeks without any clinical sequelae. This patient demonstrates an unusual example of diffuse axonal injury without direct head trauma and with delayed onset of symptoms. The authors recommend that patients involved in high-velocity accidents, even without immediate evidence of head injury, be observed for signs of diffuse axonal injury.

The effects of acetyl-L-carnitine and sorbinil on peripheral nerve structure, chemistry, and function in experimental diabetes.

Nerve conduction velocity (NCV) increased with age in nondiabetic male Wistar rats for the first 26 weeks of life. The NCV of animals made hyperglycemic at age 6 weeks by administration of streptozotocin (STZ) also increases, but at a slower rate. Animals with 4 weeks of hyperglycemia and reduced NCV treated with an aldose reductase inhibitor (sorbinil) or a short-chain acyl-carnitine (acetyl-L-carnitine [ALC]) daily for 16 weeks showed an improvement in NCV. Morphometric studies of tibial nerves collected from animals after 20 weeks of hyperglycemia (age 26 weeks) showed a consistent reduction in the width of the myelin sheath and little change in axon area. The number of large myelinated fibers (>6.5 microns) found in nerves collected from hyperglycemic animals was less than the number found in nondiabetic animals. Treatment of hyperglycemic rats with either sorbinil or ALC was associated with increased NCV, myelin width, and large myelinated fibers. The apparent metabolic effect of these agents was similar for fatty acid metabolism, but different for polyol pathway activity. We conclude that in animals hyperglycemic long enough to slow NCV, sorbinil and/or ALC treatment reduces the functional, structural, and biochemical changes associated with hyperglycemia that occur in the myelin sheath.

Nerve and muscle damage after experimental thrombosis of large artery. Electrophysiology and morphology.

The effect of the terminal aorta thrombosis on the spinal cord and hind limb nerves and muscles morphology, and the sciatic-tibial motor nerve conduction was studied in cats. The effect of the iliac and femoral artery thrombosis on nerve morphology and conduction was also examined. Aortic thrombosis usually caused severe nerve and muscle lesions while spinal cord was spared. Nerve and muscle damage was strikingly more extensive and severe after aortic thrombosis than ligation. Nerve damage was also seen after the iliac or femoral artery thrombosis but not after ligation of these arteries. The tibial and peroneal nerve segments at the calf level were most vulnerable to ischemic damage. The nerve conduction studies (NCS) localized nerve lesions and indicated severity of the morphologic changes. The nerve conduction changes after arterial thrombosis reached a nadir at more variable time than in other experimental models of peripheral nerve ischemia. The markedly delayed development of maximal nerve dysfunction in some cases, if confirmed in humans, may present a rationale for aggressive medical or surgical intervention even several hours after acute arterial thrombosis.

The effect of hyperglycemia on nerve conduction and structure is age dependent.

The nerve conduction velocity (NCV) of nondiabetic male Wistar rats continues to increase until approximately 26 weeks of age. Rats made hyperglycemic at 6 weeks of age manifest reduced NCV by 10 weeks of age and show morphological differences in the sciatic tibial nerve after 5 months of hyperglycemia when compared with age-matched controls. Fiber diameter, myelin width, and the number of large myelinated fibers were decreased in the tibial nerves of the hyperglycemic animals. Rats made hyperglycemic at 26 weeks of age had elevated glycosylated hemoglobin and sciatic nerve sorbitol levels but maintained normal NCVs and had little change in morphology after 7 months of hyperglycemia. Thus, animals with maturing peripheral nerve structure and function exposed to chronic hyperglycemia manifest greater pathological alterations than those that occur when more matured nerves are exposed to similarly elevated glucose concentrations for an even greater duration. We suggest that immature animal models commonly used to study diabetic peripheral neuropathy may not be appropriate for understanding a process that commonly develops in humans who become hyperglycemic after maturation of the peripheral nerves.

Acetyl-L-carnitine corrects the altered peripheral nerve function of experimental diabetes.

Acetyl-L-carnitine (ALC) has been shown to facilitate the repair of transected sciatic nerves. The effect of ALC (50 mg/kg/d) on the diminished nerve conduction velocity (NCV) of rats with streptozotocin (STZ)-induced hyperglycemia of 3 weeks' duration was evaluated. The aldose reductase inhibitor, sorbinil, which is reported to normalize the impaired NCV associated with experimental diabetes, was used as a positive control. Aldose reductase inhibitors are thought to have an effect by decreasing peripheral nerve sorbitol content and increasing nerve myo-inositol. Treatment of STZ-diabetic rats with either ALC or sorbinil resulted in normal NCV. Sorbinil treatment was associated with normalized sciatic nerve sorbitol and myo-inositol; ALC treatment did not reduce the elevated sorbitol levels, but sciatic nerve myo-inositol content was no different from nondiabetic levels. Both ALC and sorbinil treatment of STZ-diabetic rats were associated with a reduction in the elevated malondialdehyde (MDA) content of diabetic sciatic nerve, indicating reduced lipid peroxidation. The beneficial effects of sorbinil and ALC on the altered peripheral nerve function associated with diabetes were similar, but their effects on the polyol pathway (frequently implicated in the pathogenesis of peripheral neuropathy) were different.

Infantile progressive striato-thalamic degeneration in two siblings: a new syndrome.

The clinical features, neuroimaging, and neuropathologic findings of a new syndrome, characterized by onset in early infancy, progressive course, choreiform movements, hypotonia, and dysphagia, are described in 2 siblings originating from a consanguineous marriage. The serial neuroimaging studies indicated progressive loss of volume of both caudate nuclei and change in signal intensity in putamina. Pathologically, there was severe neuronal loss and gliosis in the striatum and thalamus. This pathologic pattern in association with clinical and radiologic correlates, to our knowledge, has not been previously described. It appears that this syndrome is an autosomal recessive disorder.

Perineurial hemorrhage in ischemic nerve after anticoagulation.

We report a 29-year-old woman who developed severe left leg ischemia after aortic dissection and left common iliac artery occlusion. Light microscopic studies revealed severe nerve and muscle ischemic changes at the calf level. Nerves also showed extensive perineurial hemorrhage, most likely secondary to heparin administration. Perineurial hemorrhage should be considered as one of the possible complications of anticoagulant therapy.

Progression of regeneration after nerve infarction.

We performed morphologic studies on the progression of regeneration in cat hind limb nerves after acute ischemic injury. None of the damaged nerve trunks showed a major increase in endoneurial connective tissue. Despite this fact, regeneration of nerve with transfascicular infarct was far from complete even 16 months after injury as manifested by a striking increase in the small myelinated fibers (MF) number and decrease in large MF number. Restoration of infarcted nerves was less complete than that previously reported after a nerve crush. Changes in the necrotic nerve segment and difficulty in making target contact with muscle and other tissues damaged by ischemia may be limiting factors in the regeneration of infarcted nerves.

Improvement in peripheral nerve function after one year of Sorbinil.

The effect of 250 mg day-1 of the aldose reductase inhibitor, Sorbinil, upon peripheral nerve function was assessed in 23 adult diabetics with clinical neuropathy. Sorbinil was given for 4 weeks to 10 subjects, while 13 received placebo in this double-blind study. Open label treatment with Sorbinil was then continued for 52 weeks in 10 of the 23 subjects. Red cell sorbitol, hemoglobin A1c, vibratory sensation, median nerve sensory and motor conduction velocities were measured at 0, 4 and 52 weeks. There were no measurable changes in peripheral nerve function after 4 weeks of Sorbinil treatment. After 52 weeks significant improvement was found in the median nerve motor and sensory conduction velocities. This was associated with no change in blood glucose control but a reduction of erythrocyte sorbitol levels.

Eosinophilia-myalgia syndrome with myoclonic jerks.

A patient while using L-tryptophan had typical features of the eosinophilia-myalgia syndrome and in addition myoclonic jerks which are unusual for this syndrome.

Muscle vulnerability to ischemic damage is decreased in experimental diabetes mellitus.

The severity of necrotic muscle and nerve lesions in the ischemic hind limbs of diabetic and nondiabetic rats was compared. Chronic limb ischemia was induced by repetitive, daily for up to 8 weeks, intraperitoneal injections of serotonin in rats with ligated right femoral artery. Light microscopic examination and lesion severity grading was performed on sections taken from several right hind limb muscles and the right tibial nerve. Overall, muscle was less damaged in diabetic than in nondiabetic rats. However, muscle was damaged more than nerve in all but diabetic rats with severe chronic ischemia. Muscle vulnerability to ischemic damage is decreased in diabetes, presumably due to abundance of glucose and other energy substrates which can be utilized during ischemia.

Distribution of nerve lesions in serotonin-induced acute ischemic neuropathy.

We have developed a new model of an acute ischemic nerve injury in rat produced by the combined effects of right femoral artery ligation and intraperitoneal injection of serotonin. Light microscopic studies were performed on the right sciatic, tibial, plantar and sural nerves dissected from rats 7 days to 6 months after serotonin injection. Ischemic lesions occurred mostly in the middle tibial nerve and involved either a part or the whole transverse nerve section. Partial tibial nerve lesions appeared mainly as small subperineurial or large wedge-shaped areas of fiber loss or regeneration. No well-delineated central fascicular lesions were seen. Sural nerves were less damaged than tibial nerves. The predominantly subperineurial fascicular distribution of ischemic lesions seen in the present model differs from the central fascicular distribution found in previous experimental studies on nerve ischemia. The different distribution of lesions is probably related to the small fascicular size and local microvascular architecture of the affected nerve segment, as well as to the method of producing ischemia.

Nerve regeneration patterns after acute ischemic injury.

We performed morphologic studies on regeneration of the cat's hind limb nerves, following simultaneous ligation of the aorta and right femoral artery. There were 2 regeneration patterns depending on the extent of ischemic necrosis. When nerve infarcts were limited only to intrafascicular regions, there was no basic change of nerve microarchitecture during regeneration. Extension of the necrosis to the perineurium resulted in replacement of the original fascicle by a collection of small fascicles, many of which were surrounded by their own perineurium. These minifascicles formed within the boundaries of the old perineurium.

Intima of epineurial arterioles is increased in diabetic polyneuropathy.

Epineurial arteriolar wall components in sural nerves of 45 diabetics (39 with and six without neuropathy) were measured and compared with those of 34 healthy subjects. Intimal area and numbers of intimal nuclei were significantly greater in diabetics than in controls. Regression lines relating intimal to medial area in diabetics and controls had a common slope, but the line for diabetics was at a higher intercept. We found no direct association between increase of intima and severity of nerve fiber degeneration. These studies indicate that intima is increased in arterioles in diabetes, due primarily to proliferation of intimal cells. The increased intima, and possible resulting decrease of nerve perfusion, may contribute to development of diabetic polyneuropathy.

Carnitine palmityltransferase deficiency with permanent weakness.

A 16-year-old male had a history of muscle pain and exercise intolerance from the age of six years. At 14 years of age, he experienced the first episode of myoglobinuria and has had eight episodes subsequently. The longest interval between episodes was 14 months. Between attacks he manifested permanent, mild proximal limb weakness, elevated serum creatine kinase activity, and myopathic features indicated by electromyography and muscle biopsies. The muscle carnitine palmityltransferase activity was 30% of normal. This patient demonstrates that carnitine palmityltransferase deficiency can be a progressive disorder leading to permanent weakness. The need for early diagnosis and treatment is stressed.

Progressive necrotizing myelopathy associated with leukemia: clinical, pathologic, and MRI correlation.

We describe a patient with progressive, irreversible, necrotizing myelopathy associated with myelomonocytic leukemia. The neuropathologic lesions consisted of diffuse necrosis, most pronounced in the cervical cord and affecting both the gray and white matter. These areas corresponded to areas of increased T2 on magnetic resonance imaging scans of the patient. We felt that there was no causal relationship of these lesions to any single antileukemic agent the patient received, and no other local or systemic causes were found to explain the lesions at necropsy. It is suggested that our case is an example of paraneoplastic necrotizing myelopathy. To our knowledge, this is the third case of necrotizing myelopathy associated with leukemia reported in the English medical literature, and the first one demonstrating usefulness of magnetic resonance imaging in diagnosis of necrotizing myelopathy.