Patient self-management of continuous subcutaneous insulin infusion.

Continuous subcutaneous insulin infusion (CSII) is one of the ways to control blood glucose for prolonged periods. This study was undertaken to establish the long-term feasibility and efficacy of CSII with patient self-management. Patients were instructed to maintain their calorie and carbohydrate intake. Basal infusion of insulin, representing 50% of the total pre-CSII dose, was supplemented by boluses of insulin based on carbohydrate intake for each meal. With this type of regimen, blood glucose and M-values were easily normalized during the physician-directed periods. This study demonstrated that near-normalization of blood glucose, M-values, and glycosylated hemoglobin was maintained after a 1 1/2-yr period of patient self-management. We attributed this successful management in part to the protocol used, in which boluses were related solely to carbohydrate intake while basal insulin was adjusted according to fasting blood glucose. The chronic normalization of blood glucose resulted in improvement of platelet function as witnessed by responsiveness to antiaggregating (PGE1) and aggregating (epinephrine) agents. An improvement was noticed in doppler measurement of ankle-arm blood pressure and a near-normalization of nerve latency and conductivity was observed.

Myoclonus in familial restless legs syndrome.

Eighteen members of a family were affected over a span of five generations with the restless legs syndrome, transmitted as an autosomal dominant trait. Ten patients had myoclonus. The propositus, a 57-year-old man, suffered from repeated, intense, asymmetric flexion jerks of the lower extremities, alternating with fidgeting and friction movements of the legs; all occurred at night prior to sleep and severely interfering with it. The patient's movements ceased with the onset of stage 1 sleep, while in his brother, the motor activity persisted in stages 1 and 2 of sleep.

Sensory neuropathy associated with primary biliary cirrhosis. Histologic and morphometric studies.

Sensory symptoms can develop in the course of primary biliary cirrhosis. They have been attributed to xanthomatous infiltrates of the nerves. We report a case of a young woman suffering from pure sensory neuropathy starting at a time when evidence of liver disease was minimal. Histologic and morphometric studies of sural nerve biopsy specimens obtained from calf and ankle showed a dying-back type of axonal degeneration predominantly affecting large myelinated fibers. No lipid-containing cells were seen, which raises the possibility that other mechanisms related to primary biliary cirrhosis are involved in the pathogenesis of the neuropathy.

Schwann cell internuclear distances in developing rat unmyelinated nerve fibers.

The interrelation of Schwann cells in developing rat cervical sympathetic trunk was studied by measuring distances between consecutive Schwann cell nuclei in teased unmyelinated nerve fiber bundles (Remak fibers). From 300 to 400 inter-nuclear Schwann cell distances (INDs) were measured at ten days and 2, 4, 5, 6, 8, 12, and 16 weeks after birth. Median INDs increased from 54mum at ten days to reach adult values (90mum to 100mum) at 16 weeks of age. Mean axonal diameters measured in the contralateral cervical sympathetic trunk increased from 0.57mum to 0.69mum during the same period. Developmental changes in median INDs of Schwann cells correlated significantly with age but did not parallel increases in axonal diameter.

Type I fiber atrophy and internal nuclei. A form of centronuclear myopathy?

A 6-year-old boy had a myopathy characterized by central nuclei with type I muscle fiber atrophy and preponderance. Study of the family members demonstrated no abnormalities with the exception of an unusually high incidence of centrally located muclei in the muscle biopsy specimen of the mother. A review of the literature disclosed a limited number of cases with identical morphological abnormalities, suggesting that they constitute a form of centronuclear myopathy with some distinctive clinical features.

Polyneuropathy and folate deficiency.

We studied five patients (two men and three women, age between 58 and 76 years) with clinical and electrophysiological signs of polyneuropathy. Routine neurological, hematological, and gastroenterological studies as well as procedures to test fat malabsorption were performed. Folate determinations were done using both radioactive and Lactobacillus casei methods. Two patients displayed the signs of subacute combined degeneration of the spinal cord with polyneuropathy, while three had only signs of neuropathy. All had low serum folate concentration, long-standing gastrointestinal disease, and deficient folate intake. The D-xylose absorption test gave values in all patients, while none displayed the classical malabsorption syndrome. The patients had substantial improvement or recovered (according to clinical and electrophysiological measurements) after periods ranging from 9 to 39 months of folate therapy. Such acquired folate-responsive polyneuropathy has two principal characteristics: mixed sensorimotor with mainly sensory deficits, and involvement of one or both of the lower extremities much more extensively than the upper extremities.

Vasculitic neuropathy in rheumatoid disease and Sjögren syndrome.

Two patients with rheumatoid arthritis and one with Sjögren syndrome had a severe sensorimotor neuropathy preceding or up to 5 years after the onset of the disease. Electrophysiologic and sural nerve biopsy studies revealed an axonal neuropathy. Myelinated fibers were affected to a greater extent than unmyelinated axons. Peripheral nerve damage was related to occlusion of the vasa nervorum, since vasculitic involvement of epineurial vessels was observed in all patients. Despite the severity of the neuropathy, it may recover, because, compared with axons, Schwann cells are perhaps less vulnerable to ischemia.

Decreased horseradish peroxidase labeling in deafferented spinal motoneurons of the rat.

It has been suggested that the incorporation and retrograde transport of horseradish peroxidase (HRP) were linked to the level of neuronal activity. Therefore one could postulate that the motor impairment resulting from dorsal rhizotomy affects the HRP labeling of spinal motoneurons in the absence of morphological damage to the motor system. This hypothesis was tested in the adult rat by sectioning bilaterally the L3-L5 dorsal roots. 2-18 months after surgery, the L4 radicular nerve was immersed in a solution of HRP. Labeled motoneurons were counted together with the motor axons of the L4 ventral root and results were compared with values obtained in paired controls. Deafferentation resulted in a crippling deficit of lower limb movements with disuse atrophy of muscle fibers but had no effect on the fiber population of the sciatic nerve and the L4 ventral root. Whereas in normal animals the L4 HRP-labeled motoneurons represented 71.9-98.3% (average 85.4) of the motor axonal counts, in animals studied 4, 12 and 18 months after dorsal rhizotomy, the number of motoneurons containing HRP granules constituted only 20.1-55.7% (average 46.2) of the number of motor axons and many of the labeled cells were faintly stained. These findings, which may reflect either a decreased retrograde transport of HRP in deafferented motoneurons or an increased turnover of the enzyme in the cell body, call attention to the possibility that the degree of activity in neuronal pathways influences HRP labeling.

Motor, sympathetic and sensory innervation of rat skeletal muscles.

This study reports on the location, number and size of motor, sympathetic and sensory neurons innervating the following muscles of rat: quadriceps femoris (QF), tibialis anterior (TA), extensor digitorum longus (EDL), peroneus longus (PL), gastrocnemius medius (GM) and soleus (SOL). Cells were labelled by application of horseradish peroxidase (HRP) to transected muscle nerves. Counts of neurons were compared with counts of myelinated (MF) and unmyelinated (UMF) fibers in normal, deafferented and chemically sympathectomized nerves. The topographical arrangement of spinal motor nuclei resembled that reported previously in other mammals and birds. Sensory somata were aggregated without precise somatotopic organization, preferentially in one of the lumbar dorsal root ganglia at a segmental level corresponding to that of the motor innervation. Because lumbar sympathetic ganglia were often poorly circumscribed, the segmental position of sympathetic ganglion cells could not be localized with certainty. Sensory and sympathetic somata demonstrated a unimodal size-frequency distribution, while QF, TA and PL motoneurons could be subdivided according to size in alpha and gamma cells. For all muscles except unsuccessfully deafferented QF, counts of motor fibers after deafferentation correlated closely with counts of labelled motoneurons. Similarly, estimates of sympathetic axons, averaging 30,7% of the UMF, in most instances exceeded only marginally the ganglion cell population. In contrast, the number of peripheral afferent fibers outnumbered markedly that of sensory cell bodies, with an average of 2.8 axons per ganglion cell.

Differences in horseradish peroxidase labeling of sensory, motor and sympathetic neurons following chronic axotomy of the rat sural nerve.

In an attempt to clarify the ultimate fate of permanently axotomized adult primary neurons, horseradish peroxidase (HRP) was used as a cell marker to label the motor, sensory and postganglionic sympathetic neurons of rat sural nerves which had been sectioned at the ankle and prevented from regenerating for periods of up to 80 weeks. Axotomy did not affect sympathetic neurons, but resulted 4 weeks later in a sudden reduction in the number of labeled sensory and motor cells which persisted to the end of the study. The missing neuronal population amounted to 44.4% and 45.9% respectively of the normal sensory and motor contingent and included most of the large afferent and efferent neurons. However, examination of sural nerves at the thigh, 30 mm proximal to the neuroma, revealed marked axonal atrophy but no change in the number of myelinated and unmyelinated fibers up to 52 weeks after axotomy. Such prolonged survival of the peripheral processes is indirect evidence that axotomized neurons can endure long-term detachment from their end organs and suggests that the lack of HRP labeling in certain sensory and motor neurons does not imply their degeneration, but expresses one of many retrograde dysfunctions triggered by axotomy.

A comparative study of the effects of chronic axotomy, crush lesion and re-anastomosis of the rat sural nerve on horseradish peroxidase labelling of primary sensory neurons.

Chronic axotomy is detrimental to the incorporation of horseradish peroxidase (HRP) by neurons of the central and peripheral nervous system. Using the rat sural nerve as a model, this study aimed to determine the effects of other types of nerve injury on the peroxidase labelling of dorsal root ganglion (DRG) cells. Compared to the decreased labelling occurring shortly after permanent transection of the sural axons at the ankle, crush injury of the nerve had no effect on the number and size distribution of peroxidase-stained cells. Re-anastomosing the sural nerve to its own distal segment or to the tibial nerve delayed the changes in HRP neuronal labelling, which subsequently were less severe in neurons allowed to reinnervate their own nerve. It also sustained the incorporation of HRP by many large DRG neurons, a function which is lost shortly after these cells are chronically axotomized. Nerve re-anastomosis also prevented the retrograde atrophy of myelinated and unmyelinated nerve fibers which is triggered by permanent transection. Based on the preservation of fiber counts in the sural nerves proximal to the site of surgery, with no evidence of degeneration, our observations possibly reflect alterations in the peroxidase metabolism of DRG neurons depending on the type of axonal injury they sustained and the possibility they had upon regeneration to contact endoneurial tubes and ultimately their original end-organs.

Carbonic anhydrase and horseradish peroxidase: double labelling of rat dorsal root ganglion neurons innervating motor and sensory peripheral nerves.

Dorsal root ganglion neurons supplying peroneus longus, soleus and gastrocnemius medius muscles and the sural nerve of the rat were labelled with horseradish peroxidase and analysed for their carbonic anhydrase content. Staining of the sections was done either on the same or on alternate slides. Both methods led to the same results, despite a slight fading of the carbonic anhydrase reaction in double-stained sections. The data indicated that the muscles under study were supplied by approximately the same number of horseradish peroxidase-labelled cells, irrespective of their differences in size. 74.9% of these labelled neurons had diameters exceeding 30 microns and 52.4% of them also stained for carbonic anhydrase. The double-labelled cells represented 66.9% of the population of large neurons (greater than 30 microns) and comprised most of those measuring over 47.5 microns. Richness in carbonic anhydrase of the large muscle afferent neurons may be linked to their innervation of the stretch receptors, as components of an active apparatus which includes the gamma motor axons which also stain positively for carbonic anhydrase. In contrast, the ganglion cells supplying the sural nerve were almost totally devoid of carbonic anhydrase, as only 6.4% showed double labelling. This contingent possibly represents the muscle afferents of the small motoneural population which supplies, through this nerve, part of the foot musculature of the rat.

The neuropathy of Charlevoix-Saguenay ataxia: an electrophysiological and pathological study.

Two female patients aged 30 and 40 years with the Charlevoix-Saguenay ataxia were studied. Both had absent sensory action potentials in upper and lower extremities but, unlike typical cases of Friedreich's ataxia, they displayed a marked slowing of motor conduction velocities. Sural nerve biopsies taken from calf and ankle revealed a severe loss of large myelinated axons contrasting with a normal myelinated fiber density. Evidence for active axonal degeneration was scarce, with no indication of axonal regeneration. Teased myelinated fibers revealed an increased variability of internodal length but no evidence for myelin breakdown. These findings support, as a primary defect, a developmental abnormality of peripheral nerve, namely a lack of maturation of large myelinated axons and possibly a faulty myelination of nerve fibers. We think it is unlikely to represent a progressive axonal atrophic or dystrophic process, as suggested in Friedreich's ataxia.

Nerve conduction studies and electromyography in Friedreich's ataxia.

Twenty-six of 50 patients were investigated with nerve conduction studies and electromyography using a standard protocol and were compared to the findings in 50 normal control subjects. Almost all cases of typical Friedreich's ataxia had absent sensory action potentials (SAP) in the digital (92%) or sural (96%) nerves. The others had markedly decreased S.A.P's. In these same patients motor conduction velocities were either normal or only slightly decreased. In the second, atypical group of 9 patients, the motor conduction velocities were considerably decreased. Because of the absence of sensory action potentials in Friedreich's ataxia, and that the absence was noted in our very mild cases, it is proposed that this measure be used to facilitate early diagnosis.

Motoneuronal and motor axonal innervation in the rat hindlimb: a comparative study using horseradish peroxidase.

In order to validate the horseradish peroxidase (HRP) technique as a quantitative method for assessing neuronal pools, we compared counts of labeled motoneurons to numbers of corresponding motor axons. Rat spinal motoneurons were labeled by immersing in HRP either the L4 radicular nerve or the normal or deafferented nerve to the tibialis anterior muscle (TA). The technique slightly under-valued the L4 motoneuronal population estimated by counting ventral root motor fibres, while in deafferented TA, counts of labeled neurons closely reflected numbers of motor axons. Measurements of neuron and nerve fibre diameters revealed good correlations of alpha and gamma motor estimates at spinal cord and nerve levels. Values were considered representative because of the approximation obtained in HRP-estimates between control and deafferented animals, indicating no significant damage from the surgical deafferentation.

Motor and sensory neurons of the rat sural nerve: a horseradish peroxidase study.

Neurons of origin of the rat sural nerve were labelled with horseradish peroxidase. Dorsal root ganglionic cells were located in the L4 and L5 ganglia, and occasionally at the L6 level. Most of these sensory neurons measured under 35 microns in diameter. In keeping with previous electrophysiological studies suggesting the presence of motor fibers to plantar muscles in the rat sural nerve, motoneurons were identified at the caudal end of the L5 spinal segment, intermingled in the posterior aspect of the ventral horn with posterior tibial motor cells supplying the foot muscles. A quantitative analysis of HRP-labelled motoneurons revealed no difference between normal (average 67) and deafferented animals (average 70), the values being only marginally lower than counts of motor axons in deafferented sural nerves (average 80).

Muscle reorganization after partial denervation and reinnervation.

The normal rat tibialis anterior (TA) muscle was found to be innervated by approximately 154 spinal motor cells of which 95 are alpha motoneurons. Most of these axons ran in the L4 root and connected with glycolytic type 2B muscle fibers. The L5 root supplied 8.4% to 14.7% of the motor axons of TA muscle and innervated type 1 and 2A muscle fibers rich in oxidative enzymes. Two months after section of the peroneal nerve, there was marked fiber-type grouping and compact rearrangement of the L4 and L5 motor units. After section of the L4 radicular nerve, the TA muscle remained atrophic with no evidence of fiber-type grouping until 3 months when the L4 regenerating axons reached the muscle. Similar results were obtained after ligation of the divided ends of the L4 radicular nerve, which delayed but did not prevent reinnervation. These data suggest that, after partial denervation, muscle reinnervation by collateral sprouting is a slowly developing process.