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A case of hyperparathyroidism, who presented with unusual complex neurological symptomatology is reported. Mental confusion, asterixis and elevated cerebrospinal fluid protein with marked pleocytosis dominated the neurological picture. All these findings subsided upon correction of hypercalcemia, suggesting direct relationship between cerebrospinal fluid abnormalities, asterixis and this metabolic disturbance.

— The diagnostic yield of sural nerve biopsy was evaluated in 120 peripheral neuropathy patients. In 58 (48%) a final diagnosis was reached without biopsy, while 14 (11.5%) remained undiagnosed. Nerve biopsy contributed to the final diagnosis in 20 of the 53 biopsies (38%). In patients with motor conduction velocity below 30 m/s, sural nerve histology was helpful in 65% of biopsies. In patients with milder reduction in conduction biopsy contributed in only 11%. It is concluded that in general neurological population, nerve biopsy is of limited value as a routine diagnostic procedure. However, in patients with marked slowing of conduction velocity, in whom the diagnosis is not immediately apparent, sural nerve biopsy is indicated.

31P nuclear magnetic resonance studies of a patient with phosphofructokinase deficiency in muscle provided the following new findings: First, ATP metabolism is disturbed at rest and during exercise. At rest, ATP levels are lower than normal and continue to decline during exercise. Second, exercise kinetics are normal, suggesting a normal mitochondrial fuel supply although glycolysis is blocked. Third, no "phosphate trapping" is observed during prolonged low-level exercise. Fourth, postexercise recovery is abnormally prolonged by the slow dephosphorylation of sugar phosphates, which has an in vivo half-life of about nine minutes. These findings demonstrate how muscle tissue adapts to a block in a major bioenergetic pathway.

• Ampicillin trihydrate aggravated the symptoms of two myasthenic patients. One patient had severe temporary weakness after an ampicillin sodium challenge. Ampicillin increased the preexisting electrical decrement in three rabbits with experimental autoimmune myasthenia gravis while the drug had no deleterious effects in less affected or normal animals. Myasthenic patients receiving ampicillin should be closely monitored for possible acute exacerbations.

Using in vivo 31P NMR spectroscopy, the authors compared the NMR spectra of the flexor muscles of the forearm from 13 humans characterized as MH susceptible on the basis of in vitro caffeine/halothane contracture tests with those from 25 normal controls. The levels of phosphocreatine (PCr), inorganic phosphate (Pi), and ATP during rest, graded exercise, and post-exercise recovery were measured in their forearms. MH susceptible subjects had significantly (P less than 0.001) higher Pi/PCr values (0.222 +/- 0.009) at rest than did normal controls (0.140 +/- 0.004). In addition, a significantly (P less than 0.01) slower post-exercise recovery rate was found in the MH-susceptible group. There was no significant difference between the two groups in the relationship of work rate to Pi/PCr. These data suggest that unchallenged MH susceptible patients can be distinguished from normals using 31P NMR spectroscopy. The potential use of this technique as a non-invasive tool in determining MH susceptibility is discussed, as well as the possible mechanisms underlying the observed 31P NMR abnormalities.

Of a series of 16 cases with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 14 patients were treated with high-dose steroid therapy (HDST, 1.0-1.5 mg/kg/day of prednisone). The average functional disability score (FDS) before treatment was 3.06 +/- 0.11 (maximum FDS = 4). There was a significant improvement under this treatment (FDS = 1.43 +/- 1.12, p less than 0.001). Maximal improvement appeared in 10 patients after 4 weeks of HDST. Following improvement, repeated attempts were made to taper off HDST in 9 patients, 8 of them developed 26 relapses. In most of the patients medium-dose steroid therapy (MDST) with 0.5-0.75 mg/kg/day of prednisone was continued, sometimes with addition of other immunosuppressive medication. The duration of HDST + MDST was between 0.5 and 6.0 years (average 2.6). The following factors were found to correlate with better response to HDST: shorter duration of CIDP, milder neurological deficit, milder decrease of nerve conduction velocity, younger age and being female. Global distribution of weakness, muscle atrophy and a positive Babinski sign were predictive of poor prognosis. Involvement of cranial nerves and level of protein in the cerebrospinal fluid did not correlate with the results of HDST. The risk of relapse was higher with shorter periods of HDST and with more rapid tapering off of HDST. The results indicate that treatment with HDST should be initiated as early as possible, a period of stability of remission is needed before tapering off, and lowering of HDST must be very gradual.

– Acute appearance of hemiparesis or hemiplegia with initial marked spasticity was observed in 8 stroke patients. All had intracerebral hematomas and in 7 it was located in the region of the basal ganglia. By contrast, none of 121 hemiplegic patients with hemispheric ischemic stroke hospitalized during the same period had increased muscle tone in the involved limbs at stroke onset. Study indicates that association of hemiplegia with immediate spasticity at stroke onset is a clinical clue to a possible deeply located intracerebral hematoma.

Strenuous exercise can result in muscle injury that may persist for 2 weeks. Our purpose was to determine if muscle injury can be detected with 31-P magnetic resonance spectroscopy. Normal subjects performed repeated lengthening contractions with either arms or legs designed to result in mild muscle injury. One hour after the arm exercise, there was a significant increase in the inorganic phosphate to phosphocreatine ratio (Pi/PCr), with the maximum increase in Pi/PCr occurring 1 day postexercise (0.12 +/- 0.01 to 0.21 +/- 0.05). Pi/PCr remained elevated for 3-10 days. Similar results were seen following the leg exercise protocol. ATP/(Pi + PCr) decreased in all the arm exercised subjects. Exercise protocols that did not contain lengthening contractions did not result in changes of Pi/PCr or ATP/(Pi + PCr). Patients with various neuromuscular diseases with evidence of muscle damage (elevated CK, muscle soreness, and histopathological findings) also showed increased Pi/PCr at rest. We conclude that elevated Pi/PCr at rest can reflect nonspecific muscle damage in normal and diseased subjects.

Five patients with McArdle's syndrome were examined by phosphorus magnetic resonance spectroscopy (31P-NMR). Adenosine triphosphate (ATP) levels at rest were reduced by 22%, but did not fall further during exercise or contracture. The slope of work rate versus inorganic phosphate/phosphocreatine (Pi/PCr) was 42 +/- 8 joules/min/Pi/PCr in three patients without muscle wasting, compared with 13 and 16 in patients with atrophy (normal, 30 to 50 joules/min/Pi/PCr). Recovery from exercise showed similar rates in patients (postischemic exercise 1.03 +/- 0.17, post-aerobic 1.63 +/- 0.17 PCr/Pi units per minute) and controls (1.0 +/- 0.2 and 1.8 +/- 0.2, respectively) independent of intracellular pH. Infusion of glucose improved exercise kinetics by 163 to 190%, but an oral load of protein had no effect. We conclude that (1) muscle mitochondria operate normally in vivo in this glycogenolytic disorder, suggesting a sufficient alternate fuel supply. (2) Blood-borne glucose may serve as one alternate fuel for the "second wind" phenomenon. (3) ATP control mechanisms are altered only at rest. (4) Recovery from exercise is relatively pH-independent.

In vivo 31phosphorus nuclear magnetic resonance spectroscopy (P-NMR) of the anterior tibialis muscle was used to investigate the metabolic myopathy of inherited muscle-type phosphofructokinase (PFK) deficiency in four (homozygous) dogs who had mild exercise intolerance, rare muscle cramps, increased serum creatine kinase activity, but no myoglobinuria. During isometric muscle work induced by indirect electrical stimulation, and subsequent recovery, changes in the ratio of phosphocreatine (PCr) and inorganic phosphates (Pi) were comparable in muscle of PFK-deficient and normal dogs and indicated a large capacity for arobic oxidative phosphorylation in canine muscle. The progressive accumulation of sugar phosphates (PME) during graded exercise clearly demonstrated the glycolytic block in PFK-deficient dogs. During a muscle contracture, induced by acute muscle stimulation, PFK-deficient muscle became completely depleted of PCr and ATP, accumulated large amounts of PME, and recovered very slowly. We conclude that PFK-deficient dogs have a metabolic myopathy that demonstrated some but not all the features recognized in the human disorder.

In vivo phosphorus nuclear magnetic resonance spectroscopy of muscle was performed at rest, during work and during postexercise recovery in rats injected with iodo-acetate (IA) (35-40 mg.kg-1, intra-arterially), in order to follow bio-energetic changes in muscle with acute glycolytic block. Three animals with contracture had very low ratios of phosphocreatine:inorganic phosphate (PCr:Pi) at rest (0.5-0.9). The PCr:Pi were normal at rest (6.9 +/- 2.0, +/- 2 SD) in all other rats. Exercise-induced continuous accumulation of phosphomonoesters (PME), the characteristic finding of glycolytic block, was observed. The end-exercise levels of PME correlated with the degree of block measured in vitro. During steady-state work, induced by nerve stimulation at four frequencies, PCr:Pi values were significantly lower (p less than 0.02) than the control values at 0.25, 1.0 and 2.0 Hz. The ATP levels fell during exercise to reach 75% +/- 7% of initial values. The recovery of PCr:Pi from exercise and the disappearance of PME were slow. Two animals which survived the IA injection demonstrated much lower PME accumulation 18 h later. It is concluded that in acute muscle glycolytic block: (1) energy metabolism is impaired during exercise and also at rest, (2) accumulating PME can serve as an indicator of the degree of glycolytic block, (3) ATP levels fall during work, and (4) postexercise recovery is slow. The findings are compared with 31P-NMR observations in chronic muscle glycolytic disorders.

Skeletal muscle bioenergetics of dystrophic hamsters (DH) were studied by in vivo 31P-NMR in order to evaluate possible metabolic impairment. 31P-NMR data were obtained during rest, during muscle work that was induced by nerve stimulation at 3 frequencies (0.2, 0.4 and 1.0 Hz) and during postexercise recovery. At rest, phosphocreatine-to-inorganic phosphate ratio (PCr/Pi) was significantly (P less than 0.02) lower in adult DH (5.3 +/- 1.1; +/- 2 SD) compared with control hamsters (6.55 +/- 0.5). An increased PCr depletion was found in DH muscle during nerve stimulation and the steady-state PCr/Pi was significantly (P less than 0.05) lower at 0.4 and 1.0 Hz. Slow PCr/Pi recovery was observed in DH (0.5 +/- 0.2 units per min compared with 1.42 +/- 0.28 for control, +/- 2 SD, P less than 0.02). These findings suggest a significant in vivo mitochondrial malfunction in DH muscle that may result from either mitochondrial abnormalities or cardiac insufficiency or a combination of both.

• In vivo phosphorus magnetic resonance spectroscopy was used to evaluate the changes in muscle bioenergetics in a patient with a partial glycolytic block. Phosphoglycerate mutase-deficient muscle showed the following evidence: (1) Abnormal accumulation of sugar phosphates does occur, even when 6% enzyme activity is present. (2) The elimination of sugar phosphates was faster than in complete glycolytic blocks. (3) Mild intracellular acidosis occurred during ischemic exercise. (4) The energy state was slightly low at rest but not during exercise. (5) Postexercise recovery was mildly slowed. These findings suggest that phosphorus magnetic resonance spectroscopy can detect partial defects, as well as full glycolytic blocks, in muscle metabolism.

• Histometric data on muscle fiber types were studied in two cases of congenital myotonic dystrophy (CMD); one underwent biopsy at the age of 5 months and the other at the age of 10 years. A previously unreported severe deficiency of type IIB fibers were found in both cases. In addition, in the first case, there was type I fiber preponderance and hypotrophy as described in cases of congenital fiber type disproportion (CFTD). It is suggested that an abnormality of motor unit maturation may be common to CMD and to CFTD, and that this results from a disorder of neural trophic influences during muscle development.

Theoretical consideration and experimental findings of 31P nuclear magnetic resonance spectroscopy (NMR) studies of exercising human muscle suggest that a graded, steady-state work protocol is highly suitable for performance evaluation in health and disease. We describe a similar rat model for repeated 31P-NMR studies that follows many of the 31P-NMR features observed in normal human controls. Calf muscles of rats anesthetized with chloral hydrate were indirectly stimulated at four frequencies (0.25, 0.5, 1.0, and 2.0 Hz). It was found that 1) several steady states can be briefly maintained in this model; 2) work-induced phosphocreatine (PCr) fall and inorganic phosphate (Pi) rise is stoichiometric; 3) a linear relationship between stimulation rate and Pi/PCr was obtained, with a slope of 2.01 +/- 0.4 (+/- 2SD, n = 15); 4) no significant drop in ATP was observed, allowing the estimation of phosphorylation potential (PP) changes during this range of muscle work (PP at rest was 61,603 +/- 25,100 M-1 and fell to 6,700 +/- 900 M-1 at the end of exercise); and 5) poststimulation recovery was rapid, with a rate of 2.27 +/- 0.5 PCr/Pi U/min. This simple model can be used for prolonged studies of chronic animal muscle disorders.

Guillain-Barré syndrome (GBS) appeared in four patients 1 to 2 weeks after epidural anesthesia. In all patients, clinical diagnosis was confirmed by CSF findings and nerve conduction velocity studies. Although epidural anesthesia has not been listed as an antecedent event in GBS, evidence for the relationship has been previously reported. Interaction between the anesthetic agents and peripheral nervous system myelin or local trauma to roots may initiate a cascade of immunologic events that result in the demyelinating neuropathy.

Twelve adults with mitochondrial myopathies were studied by phosphorus magnetic resonance spectroscopy of muscle. All 12 had abnormal 31 P-NMR findings; recovery from exercise was abnormal in 11 patients. At rest, the ratio of phosphocreatine to inorganic phosphate was reduced in 10. Exercise transfer characteristics were abnormal in all five patients who could exercise. Exercise-induced intracellular acidosis was subnormal in nine patients. The range of abnormalities indicates biochemical heterogeneity, with two possible groups: (1) primary defects of energy metabolism with marked 31 P-NMR abnormalities, and (2) secondary, less specific 31 P-NMR abnormalities.

Four members of a family had an adult form of hexosaminidase A deficiency. The clinical picture was predominated by selective proximal muscle weakness in the legs and stuttering speech. Two of these patients had children with Tay-Sachs disease.